A case of acute calcium pyrophosphate arthritis in two rare sites of involvement: The cervical facet and atlantoaxial joint.
Calcium pyrophosphate dihydrate deposition (CPPD) disease, also known as pseudogout, in which crystals are deposited in the joints and/or soft tissues, leads to a variety of articular and periarticular disorders. Herein we report a 67-year-old female patient with neck pain who was diagnosed as CPPD disease of both the atlantoaxial joint and right C4-C5 facet joint with radiological findings. The combined use of computed tomography and magnetic resonance imaging can be helpful in establishing a diagnosis and providing the correct treatment.


Equilibration of Imine-Linked Polymers to Hexagonal Macrocycles Driven by Self-Assembly.
Macrocycles based on directional bonding and dynamic covalent bond exchange can be designed with specific pore shapes, sizes, and functionality. These systems retain many of the design criteria and desirable aspects of two-dimensional (2D) covalent organic frameworks (COFs) but are more easily processed. Here we access discrete hexagonal imine-linked macrocycles by condensing a truncated analogue of 1,3,5-tris(4-aminophenyl)benzene (TAPB) with terephthaldehyde (PDA). The monomers first condense into polymers but eventually convert into hexagonal macrocycles in high yield. The high selectivity for hexagonal macrocycles is enforced by their aggregation and crystallization into layered structures with more sluggish imine exchange. Their formation and exchange processes provide new insight into how imine-linked 2D COF simultaneously polymerize and crystallize. Solutions of these assembled macrocycles were cast into oriented, crystalline films, expanding the potential routes to 2D materials.


[Femoroacetabular impingement syndrome: first experience with surgical treatment].
Femoroacetabular impingement syndrome (FAI) represents a mechanical conflict between acetabulum and proximal part of the femur. This disorder may gradually result in the development of the hip osteoarthritis. FAI may be caused by an acetabular retroversion, rarely by coxa profunda or by asphericity of the femoral head and missing femoral head-neck offset respectively. However, a combination of both conditions is the most frequent. Before FAI treatment was adopted as a standard technique for hip preservation at our department, detailed cadaver studies of the vascular anatomy of the hip were performed and the relevant literature was reviewed. The aim of this study was to assess the efficiency of hip preserving surgery in relation to the technique used. We hypothesized that surgical intervention helped to alleviate pain and improve hip function. In the period from October 11, 2005 to June 30, 2012, a total of 168 patients (190 hips) had surgery for FAI. After we met exclusion criteria, 83 hips were treated by surgical hip dislocation (SHD) and 17 undergoing anterior minimally invasive surgery (AMIS). The minimum follow-up was 12 months, with an average of 3 years and 4 months, and a range of 12 months to 7 years and 8 months. The subjective evaluation by the patients and the functional hip assessment were based on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the non-Arthritic Hip Score (nAHS) questionnaires. To assess the efficiency of the techniques, the pre- and post-operative scores were compared in each group (SHD group, n=83; AMIS group, n=17). A comparison of pre- and post-operative data was also made for the groups joined together to evaluate the benefit of surgery as such in FAI treatment. The results were statistically analysed using the Wilcoxon test for paired samples; the level of significance was set at 0.05. There was a statistically significant increase in the scores obtained after surgery, as compared with the pre-operative data, in the SHD and AMIS groups and in all patients evaluated together. Hip survival without the necessity of conversion to total hip replacement was 96.4% (80/83 hips) in the SHD group and 94.1% (16/17 hips) in the AMIS group. no serious complications were recorded. DISCUSSIOn The rate of failure in the surgical treatment of FAI syndrome in our patients was in accordance with the literature data, as was the number of the patients requiring conversion to total hip replacement. Also the other results were comparable with those of relevant studies. Hip preservation surgery is an issue which has slowly been gaining consensus although opinions on it, including FAI surgical treatment, still vary. As FAI syndrome is a condition leading to degenerative changes in the hip, it is important to pay attention to a thorough diagnostic evaluation and a correct, though often long-term, therapy.


Criticality of an isotropic-to-smectic transition induced by anisotropic quenched disorder.
We report combined optical birefringence and neutron scattering measurements on the liquid crystal 12CB nanoconfined in mesoporous silicon layers. This liquid crystal exhibits strong nematic-smectic coupling responsible for a discontinuous isotropic-to-smectic phase transition in the bulk state. Confined in porous silicon, 12CB is subjected to strong anisotropic quenched disorder: a short-ranged smectic state evolves out of a paranematic phase. This transformation appears continuous, losing its bulk first-order character. This contrasts with previously reported observations on liquid crystals under isotropic quenched disorder. In the low temperature phase, both orientational and translational order parameters obey the same power law.


Prevalence of Panton-Valentine leucocidin and phenotypic and genotypic characterization of biofilm formation among Staphylococcus aureus strains isolated from children with adenoid hypertrophy.
Adenoids as a first line of host defense against respiratory microbes play an important role in majority of upper airway infectious and noninfectious illnesses. Bacterial pathogen can colonize on the adenoid tissue and probably act as a reservoir for them. To determine phenotypic and genotypic characterization of biofilm forming capacity of Staphylococcus aureus isolates from children with adenoid hypertrophy and prevalence of Panton-Valentine leukocidin (PVL) gene we collected 17 consecutive, clinically significant S. aureus isolates from children with adenoid hypertrophy undergoing adenoidectomy with one or more of the upper airway obstruction symptoms, nasal obstruction, mouth breathing, snoring, or sleep apnea. Biofilm formation was evaluated by colorimetric microtiter plate's assay. Gene encoding PVL and adhesion- or biofilm formation-encoding genes were targeted by polymerase chain reaction (PCR) assay. According to the results, all strains produced biofilm. Seven (41.2%) isolates produced strong biofilm whereas 7 (41.2%) isolates produced week and 3 (17.6%) isolates produced medium biofilm. Regarding the adhesion- or biofilm formation-encoding genes, 16 (94.1%) isolates were positive for the gene eno, 13(76.4%) for icaA, 13 (76.4%) for icaD, 10 (58.8%) for fib, 10 (58.8%) for fnbB, 4(23.5%) for can, and 1(5.8%) for fnbA. The high prevalence of genes encoding biofilms and adhesins and phenotypic ability to form a biofilm by S. aureus strains emphasizes the pathogenic character of strains isolated from children with adenoid hypertrophy.


Foot problems in the adolescent.
The treatment of foot problems in the adolescent should be nonsurgical whenever possible. Surgical treatment should be considered when medical treatment does not relieve pain. Surgical corrections to prevent problems in adulthood may cause complications and lead to an undesirable outcome. This article highlights treatment for overriding fifth toe, juvenile bunion, Morton toe, Freiberg infraction, stress fractures of metatarsals, accessory navicular, tarsal coalition, plantar fascitis, pes cavus, and pes planus. Significant deformities generally require treatment before ambulation, and innocent deformities usually resolve spontaneously.


Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs: Preparation, Identification, Antioxidant Activity, and Stability against Thermal, pH, and Simulated Gastrointestinal Digestion Treatments.
Cardiac arterial bulbs of Skipjack tuna (Katsuwonus pelamis) are rich in elastin, and its hydrolysates are high quality raw materials for daily cosmetics. In order to effectively utilizing Skipjack tuna processing byproducts-cardiac arterial bulbs and to prepare peptides with high antioxidant activity, pepsin was selected from six proteases for hydrolyzing proteins, and the best hydrolysis conditions of pepsin were optimized. Using ultrafiltration and chromatographic methods, eleven antioxidant peptides were purified from protein hydrolysate of tuna cardiac arterial bulbs. Four tripeptides (QGD, PKK, GPQ and GLN) were identified as well as seven pentapeptides (GEQSN, GEEGD, YEGGD, GEGER, GEGQR, GPGLM and GDRGD). Three out of them, namely the tripeptide PKK and the pentapeptides YEGGD and GPGLM exhibited the highest radical scavenging activities on 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and superoxide anion assays. They also showed to protect plasmid DNA and HepG2 cells against H2O2-induced oxidative stress. Furthermore, they exhibited high stability under temperature ranged from 20-100 °C, pH values ranged from 3-11, and they simulated gastrointestinal digestion for 240 min. These results suggest that the prepared eleven antioxidant peptides from cardiac arterial bulbs, especially the three peptides PKK, YEGGD, and GPGLM, could serve as promising candidates in health-promoting products due to their high antioxidant activity and their stability.


Effectiveness of protected areas for vertebrates based on taxonomic and phylogenetic diversity.
Establishing protected areas is the primary goal and tool for preventing irreversible biodiversity loss. However, the effectiveness of protected areas that target specific species has been questioned for some time because targeting key species for conservation may impair the integral regional pool of species diversity and phylogenetic and functional diversity are seldom considered. We assessed the efficacy of protected areas in China for the conservation of phylogenetic diversity based on the ranges and phylogenies of 2279 terrestrial vertebrates. Phylogenetic and taxonomic diversity were strongly and positively correlated, and only 12.1-43.8% of priority conservation areas are currently protected. However, the patterns and coverage of phylogenetic diversity were affected when weighted by species richness. These results indicated that in China, protected areas targeting high species richness protected phylogenetic diversity well overall but failed to do so in some regions with more unique or threatened communities (e.g., coastal areas of eastern China, where severely threatened avian communities were less protected). Our results suggest that the current distribution of protected areas could be improved, although most protected areas protect both taxonomic and phylogenetic diversity.


Worldwide spread of the Ponseti method for clubfoot.
The Ponseti method has become the gold standard for the treatment of idiopathic clubfoot. Its safety and efficacy has been demonstrated extensively in the literature, leading to increased use around the world over the last two decades. This has been demonstrated by the increase in Ponseti related PubMed publications from many countries. We found evidence of Ponseti activity in 113 of 193 United Nations members. The contribution of many organizations which provide resources to healthcare practitioners in low and middle income countries, as well as Ponseti champions and modern communication technology, have helped to spread the Ponseti method around the world. Despite this, there are many countries where the Ponseti method is not being used, as well as many large countries in which the extent of activity is unknown. With its low rate of complication, low cost, and high effectiveness, this method has unlimited potential to treat clubfoot in both developed and undeveloped countries. Our listing of countries who have not yet shown presence of Ponseti activity will help non-governmental organizations to target those countries which still need the most help.


Urban Health in Tanzania: Questioning the Urban Advantage.
How are health inequalities articulated across urban and rural spaces in Tanzania? This research paper explores the variations, differences, and inequalities, in Tanzania's health outcomes-to question both the idea of an urban advantage in health and the extent of urban-rural inequalities in health. The three research objectives aim to understand: what are the health differences (morbidity and mortality) between Tanzania's urban and rural areas; how are health inequalities articulated within Tanzania's urban and rural areas; and how are health inequalities articulated across age groups for rural-urban Tanzania? By analyzing four national datasets of Tanzania (National Census, Household Budget Survey, Demographic Health Survey, and Health Demographic Surveillance System), this paper reflects on the outcomes of key health indicators across these spaces. The datasets include national surveys conducted from 2009 to 2012. The results presented showcase health outcomes in rural and urban areas vary, and are unequal. The risk of disease, life expectancy, and unhealthy behaviors are not the same for urban and rural areas, and across income groups. Urban areas show a disadvantage in life expectancy, HIV prevalence, maternal mortality, children's morbidity, and women's BMI. Although a greater level of access to health facilities and medicine is reported, we raise a general concern of quality and availability in health services; what data sources are being used to make decisions on urban-rural services, and the wider determinants of urban health outcomes. The results call for a better understanding of the sociopolitical and economic factors contributing to these inequalities. The urban, and rural, populations are diverse; therefore, we need to look at service quality, and use, in light of inequality: what services are being accessed; by whom; for what reasons?


Correlation of serum creatinine concentration and amikacin half-life.
The half-life of amikacin in serum has been measured following the administration of a single intravenous injection of 7 mg/kg in nine adult patients with varying degrees of renal function impairment and in four patients with normal renal function. A linear relationship between the half-life and the serum concentration has been found, suggesting that half-life of amikacin in serum can be calculated by multiplying the serum creatinine (in mg/100 ml) by 3.


Effects of ghrelin on pGSK-3β and β-catenin expression when protects against neuropathic pain behavior in rats challenged with chronic constriction injury.
Ghrelin has been shown to alleviate neuropathic pain by inhibiting the release of proinflammatory cytokines. The purpose of this study was to investigate the role of GSK-3β/β-catenin signaling in mediating the effect of ghrelin on neuropathic pain and to understand the associated mechanisms. Chronic constriction injury (CCI) of the sciatic nerve was used to establish a rat model of neuropathic pain. Hyperalgesia and allodynia were evaluated by observing the mechanical withdrawal threshold and the thermal withdrawal latency. Wnt3a and β-catenin protein expression and GSK-3β phosphorylation were detected by western blotting analysis. The levels of tumor necrosis factor-α and IL-1β were determined using an enzyme-linked immunosorbent assay. In addition, we used immunohistochemical analysis to determine the levels of GSK-3β phosphorylation in the dorsal horn of the spinal cord. Intrathecal delivery of ghrelin effectively ameliorated CCI-induced mechanical allodynia and thermal hyperalgesia at 7 and 14 days and reduced the levels of tumor necrosis factor-α. Ghrelin inhibited CCI-induced GSK-3β activation and β-catenin overexpression in the spinal dorsal horn. Moreover, intrathecal injection of ghrelin suppressed the activation of GSK-3β in the spinal dorsal horn of CCI rats, as assessed by immunohistochemical analysis. Our data indicated that ghrelin could markedly alleviate neuropathic pain by inhibiting the expression of β-catenin, via the suppression of GSK-3β activation, in the spinal cord of CCI rats.


Alkali and Heavy Metal Copoisoning Resistant Catalytic Reduction of NOx via Liberating Lewis Acid Sites.
The catalyst deactivation caused by the coexistence of alkali and heavy metals remains an obstacle for selective catalytic reduction of NOx with NH3. Moreover, the copoisoning mechanism of alkali and heavy metals is still unclear. Herein, the copoisoning mechanism of K and Cd was revealed from the adsorption and variation of reaction intermediates at a molecular level through time-resolved in situ spectroscopy combined with theoretical calculations. The alkali metal K mainly decreased the adsorption of NH3 on Lewis acid sites and altered the reaction more depending on the formation of the NH4NO3 intermediate, which is highly related to NOx adsorption and activation. However, Cd further inhibited the generation of active nitrate intermediates and thus decreased the NOx abatement about 60% on potassium-poisoned CeTiOx catalysts. Physically mixing with acid additives for CeTiOx catalysts could significantly liberate the active Lewis acid sites from the occupation of alkali metals and relieve the high dependence on NOx adsorption and activation, thus recovering the NOx removal rate to the initial state. This work revealed the copoisoning mechanism of K and Cd on Ce-based de-NOx catalysts and developed a facile anti-poisoning strategy, which paves a way for the development of durable catalysts among alkali and heavy metal copoisoning resistant catalytic reduction of NOx.


[Headache attributed neurosurgical diseases].
When we see headache patients, it is most important thing that we rule out patients with intracranial diseases. Intracranial diseases with headache are so many. I'd like to emphasize some intracranial diseases with headache not to miss. Especially subarachnoid hemorrhage due to ruptured cerebral aneurysm is a serious disease not to miss. Recently the cases of dissecting cerebral aneurysm (vertebral artery) and venous/sinus thrombosis are increasing with spreading MRI/MRA examination. And brain tumors and chronic subdural hematoma is a serious disease not to miss in recent Japanese aging society. I'd like to mention these important diseases with headache.


Tunable Electronic Structure via DNA-Templated Heteroaggregates of Two Distinct Cyanine Dyes.
Molecular excitons are useful for applications in light harvesting, organic optoelectronics, and nanoscale computing. Electronic energy transfer (EET) is a process central to the function of devices based on molecular excitons. Achieving EET with a high quantum efficiency is a common obstacle to excitonic devices, often owing to the lack of donor and acceptor molecules that exhibit favorable spectral overlap. EET quantum efficiencies may be substantially improved through the use of heteroaggregates-aggregates of chemically distinct dyes-rather than individual dyes as energy relay units. However, controlling the assembly of heteroaggregates remains a significant challenge. Here, we use DNA Holliday junctions to assemble homo- and heterotetramer aggregates of the prototypical cyanine dyes Cy5 and Cy5.5. In addition to permitting control over the number of dyes within an aggregate, DNA-templated assembly confers control over aggregate composition, i.e., the ratio of constituent Cy5 and Cy5.5 dyes. By varying the ratio of Cy5 and Cy5.5, we show that the most intense absorption feature of the resulting tetramer can be shifted in energy over a range of almost 200 meV (1600 cm-1). All tetramers pack in the form of H-aggregates and exhibit quenched emission and drastically reduced excited-state lifetimes compared to the monomeric dyes. We apply a purely electronic exciton theory model to describe the observed progression of the absorption spectra. This model agrees with both the measured data and a more sophisticated vibronic model of the absorption and circular dichroism spectra, indicating that Cy5 and Cy5.5 heteroaggregates are largely described by molecular exciton theory. Finally, we extend the purely electronic exciton model to describe an idealized J-aggregate based on Förster resonance energy transfer (FRET) and discuss the potential advantages of such a device over traditional FRET relays.


Estimation of treatment effect in two-stage confirmatory oncology trials of personalized medicines.
A personalized medicine may benefit a subpopulation with certain predictive biomarker signatures or certain disease types. However, there is great uncertainty about drug activity in a subpopulation when designing a confirmatory trial in practice, and it is logical to take a two-stage approach with the study unless credible external information is available for decision-making purpose. The first stage deselects (or prunes) non-performing subpopulations at an interim analysis, and the second stage pools the remaining subpopulations in the final analysis. The endpoints used at the two stages can be different in general. A key issue of interest is the statistical property of the test statistics and point estimate at the final analysis. Previous research has focused on type I error control and power calculation for such two-stage designs. This manuscript will investigate estimation bias of the treatment effect, which is implicit in the adjustment of nominal type I error for multiplicity control in such two-stage designs. Previous work handles the treatment effect of an intermediate endpoint as a nuisance parameter to provide the most conservative type I error control. This manuscript takes the same approach to explore the bias. The methodology is applied to the two previously studied designs. In the first design, patients with different biomarker levels are enrolled in a study, and the treatment effect is assumed to be in an order. The goal of the interim analysis is to identify a biomarker cut-off point for the subpopulations. In the second design, patients with different tumour types but the same biomarker signature are included in a trial applying a basket design. The goal of the interim analysis is to identify a subset of tumour types in the absence of treatment effect ordering. Closed-form equations are provided for the estimation bias as well as the variance under the two designs. Simulations are conducted under various scenarios to validate the analytic results that demonstrated that the bias can be properly estimated in practice. Worked examples are presented. Extensions to general adaptive designs and operational considerations are discussed. Copyright © 2017 John Wiley & Sons, Ltd.


Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis.
PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis. PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22-24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0-4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs). In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22-24 of PEDFIC 2 in sBAs was -201 μmol/L (p <0.0001). For cohort 1B and cohort 2, mean changes from odevixibat initiation to weeks 22-24 in sBAs were -144 and -104 μmol/L, respectively. The proportion of positive pruritus assessments in the first 24-week period of PEDFIC 2 was 33%, 56%, and 62% in cohorts 1A, 1B, and 2, respectively. Most TEAEs were mild or moderate. No drug-related serious TEAEs occurred. Odevixibat in patients with progressive familial intrahepatic cholestasis was generally well tolerated and associated with sustained reductions in sBAs and pruritus. This study is registered at ClinicalTrials.gov (NCT03659916). Disrupted bile flow is a hallmark feature of patients with progressive familial intrahepatic cholestasis and can result in build-up of bile constituents in the liver with spill over into the bloodstream; other effects that patients can experience include extremely itchy skin, and because not enough bile reaches the gut, patients can have problems digesting food, which may lead to poor growth. Odevixibat is an orally administered medication that shunts bile acids away from the liver. The current study, called PEDFIC 2, suggested that odevixibat can improve the problematic signs and symptoms of progressive familial intrahepatic cholestasis and was generally safe for patients.


Recalcitrant nodular scabies showing excellent response to tofacitinib: five case reports.
Scabies is a contagious skin condition caused by Sarcoptes scabiei, and it is always associated with an intense, unbearable, nocturnal deteriorating itch. Its presentations include classic burrows, erythema, pruritic papules, pustules, vesicles, and inflammatory nodules, with diffuse or localized distribution on the finger webs, wrist flexors, elbows, axillae, buttocks, genitalia, and breasts. Nodular scabies is an uncommon clinical variant of scabies. Its management is still challenging for some patients up to date, although topical, intralesional or systemic corticosteroids, topical calcineurin inhibitors, and crotamiton as well as cryotherapy alone or in different combinations are used. We here report five male patients of nodular scabies, aged between 14 and 25 years, who had classical scabies that had been cured by sulfur ointment for at least 4 weeks except for their itching nodules, and their residual pruritic nodules also failed in previous treatments including antihistamines, topical applying and intralesional injection of steroids as well as topical tacrolimus in different combinations before being recruited to this study. The patients were administered tofacitinib 5 mg, twice a day, which led to excellent and rapid improvement for both lesions and symptoms after 1-4 weeks of treatment, respectively, without any associations. During 6 months of follow-up, only one had re-infection of scabies associated with nodules that were cured by sulfur ointment and tofacitinib again. No adverse reaction was observed. The present results suggested that tofacitinib might be a potential agent for nodular scabies with excellent response.


Calmodulin binds RalA and RalB and is required for the thrombin-induced activation of Ral in human platelets.
Ral GTPases may be involved in calcium/calmodulin-mediated intracellular signaling pathways. RalA and RalB are activated by calcium, and RalA binds calmodulin in vitro. It was examined whether RalA can bind calmodulin in vivo, whether RalB can bind calmodulin, and whether calmodulin is functionally involved in Ral activation. Yeast two-hybrid analyses demonstrated both Rals interact directly but differentially with calmodulin. Coimmunoprecipitation experiments determined that calmodulin and RalB form complexes in human platelets. In vitro pull-down experiments in platelets and in vitro binding assays showed endogenous Ral and calmodulin interact in a calcium-dependent manner. Truncated Ral constructs determined in vitro and in vivo that RalA has an additional calmodulin binding domain to that previously described, that although RalB binds calmodulin, its C-terminal region is involved in partially inhibiting this interaction, and that in vitro RalA and RalB have an N-terminal calcium-independent and a C-terminal calcium-dependent calmodulin binding domain. Functionally, in vitro Ral-GTP pull-down experiments determined that calmodulin is required for the thrombin-induced activation of Ral in human platelets. We propose that differential binding of calmodulin by RalA and RalB underlies possible functional differences between the two proteins and that calmodulin is involved in the regulation of the activation of Ral-GTPases.


A Prussian blue nanoparticles-based fluorescent nanoprobe for monitoring microRNA-92a and microRNA-21.
Since microRNA-92a (miR-92a) and microRNA-21 (miR-21) are crucial biomarkers for colorectal cancer (CRC), monitoring miR-92a and miR-21 in serum is very significant for the early diagnosis of CRC. In this work, we developed a simple and sensitive fluorescent biosensor for the detection of miR-92a and miR-21 based on the quenching ability of Prussian blue nanoparticles (PBNPs) to fluorophores. Carboxyl fluorescein (FAM)-modified ssDNA (P-92a) and Cyanine 5 (Cy5)-modified ssDNA (P-21) were completely complementary to miR-92a and miR-21 separately. They were adsorbed on PBNPs surface by the binding of PO43- in DNA and Fe3+ in PBNPs to fabricate the P-92a + P-21@PBNPs sensing system. The fluorescence responses from P-92a + P-21@PBNPs show good selection to miR-92a and a great linear process with the miR-92a concentration ranging from 1 to 30 nM (ΔF = 10.978 cmiR-92a + 71.457). Meanwhile, the fluorescence responses from P-92a + P-21@PBNPs is linearly relative to miR-21 from 3 to 30 nM; the linear equation is ΔF = 5.7560 cmiR-21 + 48.729. Furthermore, the detections of miR-92a and miR-21 added in serum samples were achieved. In summary, this method is sensitive, highly specific, time-saving, cost-effective and applicable for the detection of miR-92a and miR-21. Therefore, this present sensor was expected to be used in clinical applications, which lays a potential foundation for an early diagnosis of cancer.


Is it time to rethink our one-size-fits-all approach to nitrate toxicity thresholds in forages?
Annual forages provide a valuable grazing resource for cattle producers; however, annuals are prone to accumulating nitrate and have the potential to cause nitrate toxicity. Although these forages pose a risk of containing high nitrate concentrations, they can be a high-quality feed source. Understanding the factors that affect the potential for toxicity when using these forages is important to help nutritionists and producers make management decisions. This review describes the previous research, current guidelines for nitrate toxicity, and the potential for improvement in our current recommendations. Current extension toxicity guidelines appear to be founded primarily on drenching based studies and overestimate the nitrate toxicity potential of forages. Recommendations need to account for multiple factors that affect the threshold for toxicity. There is evidence that fresh forages have a lower risk of toxicity because of slower release of nitrate into the rumen and a slower rate of dry matter intake. Increased dietary energy and sulfur content reduce the potential for toxicity. Microbial adaptation can reduce the risk and allow use of potentially toxic forages. These factors should influence feeding recommendations. However, there is currently not enough data available to establish new guidelines that account for these main factors. Thus, there is a need for renewed research in this area. The limited number of studies grazing elevated nitrate forages seems to suggest that there is less risk in grazing situations, especially if animals graze selectively. There is a need to develop guidelines for nitrate toxicity and management recommendations when grazing. To accomplish this, there is a need for more studies to evaluate risk of toxicity in grazing situations. These grazing studies need to evaluate the effects of nitrate concentration, forage quality, and grazing management on the potential for nitrate toxicity. While the conservative guidelines that are currently in use reduce risk of nitrate toxicity, they may also cause a significant increase in feed costs for producers.


Clinical predictors of antipsychotic use in children and adolescents with autism spectrum disorders: a historical open cohort study using electronic health records.
Children with autism spectrum disorders (ASD) are more likely to receive antipsychotics than any other psychopharmacological medication, yet the psychiatric disorders and symptoms associated with treatment are unclear. We aimed to determine the predictors of antipsychotic use in children with ASD receiving psychiatric care. The sample consisted of 3482 children aged 3-17 with an ICD-10 diagnosis of ASD referred to mental health services between 2008 and 2013. Antipsychotic use outcome, comorbid diagnoses, and other clinical covariates, including challenging behaviours were extracted from anonymised patient records. Of the 3482 children (79 % male) with ASD, 348 (10 %) received antipsychotic medication. The fully adjusted model indicated that comorbid diagnoses including hyperkinetic (OR 1.44, 95 %CI 1.01-2.06), psychotic (5.71, 3.3-10.6), depressive (2.36, 1.37-4.09), obsessive-compulsive (2.31, 1.16-4.61) and tic disorders (2.76, 1.09-6.95) were associated with antipsychotic use. In addition, clinician-rated levels of aggression, self-injurious behaviours, reduced adaptive function, and overall parental concern for their child's presenting symptoms were significant risk factors for later antipsychotic use. In ASD, a number of comorbid psychiatric disorders are independent predictors for antipsychotic treatment, even after adjustment for familial, socio-demographic and individual factors. As current trial evidence excludes children with comorbidity, more pragmatic randomised controlled trials with long-term drug monitoring are needed.


Effects of malted and non-malted whole-grain wheat on metabolic and inflammatory biomarkers in overweight/obese adults: a randomised crossover pilot study.
Metabolic dysfunction in obesity may be attenuated by whole-grain intake, which has been attributed to synergistic actions of bioactive compounds. Germination/malting may increase grain bioactives, including polyphenols, however biological effects compared with non-germinated grains are unclear. Polyphenols and biological effects were compared between malted-wheat (MLT) and whole-grain wheat (CON) breakfast cereals. Polyphenol content and antioxidant activity were significantly higher (P<0.01 and P<0.05, respectively) in MLT. Corresponding obesity-related biomarkers were measured in 10 overweight/obese adults in a 2×4-week double-blind, randomised, crossover trial. Following both interventions, diastolic blood pressure reduced significantly with time (P<0.05) and low-density lipoprotein increased slightly (P<0.05) over time. A significant time*cereal effect (P<0.05) was found for insulin resistance, decreasing following CON and increasing with MLT. No other significant metabolic or inflammatory differences were found. Whilst MLT contained significantly increased polyphenols, cumulative effects in attenuating obesity-related metabolic dysfunction may require increased consumption.


Characterization of the binding interactions between EvaGreen dye and dsDNA.
Understanding the dsDNA·EG binding interaction is important because the EvaGreen (EG) dye is increasingly used in real-time quantitative polymerase chain reaction, high resolution melting analysis, and routine quantification of DNA. In this work, a binding isotherm for the interactions of EG with duplex DNA (poly-dA17·poly-dT17) has been determined from the absorption and fluorescence spectra of the EG and dsDNA·EG complex. The isotherm has a sigmoidal shape and can be modeled with the Hill equation, indicating positive cooperativity for the binding interaction. A Scatchard plot of the binding data yields a concave-down curve in agreement with the Hill analysis of the binding isotherm for a positive cooperative binding interaction. Analysis of the Scatchard plot with the modified McGhee and von Hippel model for a finite one-dimensional homogeneous lattice and nonspecific binding of ligands to duplex DNA yields the intrinsic binding constant, the number of lattice sites occluded by a bound ligand, and the cooperativity parameter of 3.6 × 105 M-1, 4.0, and 8.1, respectively. The occluded site size of 4 indicates that moieties of the EG intercalate into the adjacent base pairs of the duplex DNA with a gap of 1 intercalation site between EG binding sites, as expected for a bifunctional molecule. Interestingly, at high [EG]/[base pair], the intercalation is disrupted. A model is proposed based on the fluorescence spectrum where the formation of anti-parallel stacked chains of EGs bound externally to the duplex DNA occur at these high ratios.


COVID-19 and kidney: role of SARS-CoV-2 infection in the induction of renal damage.
SARS-CoV-2 causes acute respiratory disease, interstitial and alveolar pneumonia, and involves numerous organs and systems such as the kidney, heart, digestive tract, blood, and nervous system. We aimed to evaluate the incidence of renal manifestations in patients diagnosed with COVID-19 infection. We performed a monocentric, cross-sectional, observational study, conducted on 114 patients with SARS-CoV-2. Clinical and laboratory parameters [renal function, serum electrolytes, inflammatory state, blood gas analysis, Interleukin 6 (IL-6) and urinalysis] were evaluated. The same values were checked out after two months (T1), however after negativization. We enrolled 114 patients (59 males) with a mean age of 63.8 ± 13.9 years. We found hematuria in 48 patients (55.8%), proteinuria in 33 patients (38.4%), leukocyturia in 61 patients (70.9%), acute kidney injury (AKI) in 28 patients (24.6%), AKI in chronic kidney disease (CKD) in 24 patients (21.1%). Moreover, we found a significant increase of inflammatory indexes as C Reactive Protein (CRP), lactic dehydrogenase (LDH), alpha 1 and alpha 2 globulins with a subsequent reduction at T1 (p = 0.016, p < 0.001, p = 0.005, p = 0.007; respectively). Hemoglobin and erythrocyte values significantly decreased (p < 0.001, p = 0.003, respectively), and we found lymphopenia (p < 0.001). Also, we found elevated levels of the D-Dimer (p < 0.001) and a significant increase in the International Normalized Ratio (INR) (p = 0.038). We also showed a significant improvement after negativization in oxygen partial pressure (p = 0.001) and oxygen saturation (p < 0.001) and a significant increase in pH (p = 0.018) and bicarbonate concentration (p = 0.042). Moreover, we found a significant increase in IL-6 (p = 0.004). Also, we reported mild hyponatremia and hypokalemia with subsequent significant recovery (p < 0.001, p < 0.001, respectively) and mild hypochloremia with a recovery to the limits of statistical significance (p = 0.053). At the entrance, we found an increase in serum glucose with a significant reduction during recovery (p < 0.001). The prevalence of AKI and/or CKD and/or abnormal urinalysis in patients diagnosed with COVID-19 on admission seems to be high and appears as a negative prognostic factor. Urinalysis appears to be very useful in unveiling the potential kidney impairment of COVID-19 patients; therefore, urinalysis could be used to reflect and predict the disease severity. We also recommend a careful evaluation of metabolic alterations, inflammatory states, and electrolytic disorders in COVID-19 patients.


Increased risk of aortic aneurysm (AA) in relation to the severity of psoriasis: A national population-based matched-cohort study.
Inflammation of systemic and vascular tissues besides the skin in psoriasis is associated with cardiovascular morbidity and mortality. We sought to investigate whether or not patients with psoriasis have an increased risk of aortic aneurysm (AA). This population-based cohort study identified 34,301 patients with psoriasis in the Taiwan National Health Insurance Research Database during 2004 to 2006, who were matched for age and sex with 137,204 control subjects without psoriasis from the Taiwan Longitudinal Health Insurance Database 2000. Each individual was individually followed up for 5 years to identify those who subsequently developed AA. After adjusting for medical history and medication use, patients with psoriasis were at increased overall risk of AA (adjusted hazard ratio [HR] 1.80; 95% confidence interval 1.25-2.61). The risk for AA increased with the severity of psoriasis. The adjusted HRs were higher for male than female patients (adjusted HR 1.84 vs 1.56), and for patients younger than 50 years versus older patients (adjusted HR 2.81 vs 1.64). There is a lack of information regarding patients' Psoriasis Area and Severity Index score, daily tobacco use, or alcohol consumption. Patients with psoriasis are predisposed to developing AA: this risk increases with psoriasis severity and is independent of established cardiovascular risk factors.


Macaque CYP2C76 encodes cytochrome P450 enzyme not orthologous to any human isozymes.
Cynomolgus monkey is used in the study of drug metabolism and toxicity due to its evolutionary closeness to human as compared with other non-human primate species. However, it has become certain that drug metabolism in monkeys is different than in humans. Such species differences have not been fully investigated at a molecular level largely due to the scarcity of information on drug-metabolizing enzyme genes. In cynomolgus monkey, we have identified cDNAs for 21 kinds of cytochromes P450 (CYPs), among which CYP2C76 does not correspond to any human CYP isozymes and is partly responsible for the difference in pitavastatin metabolism between cynomolgus monkey and human. In cynomolgus monkey CYP2C76, we identified numerous genetic variants including a null genotype. Heterozygotes for this null genotype are expected to be poor metabolizers in CYP2C76-mediated drug metabolism. To provide new clues to CYP2C76 function, here, we have taken advantage of sequence information that has been recently deposited to public databases to assess the presence of CYP2C76 orthologs in primate species. In this assessment, we found the CYP2C76 cDNA sequence in rhesus monkey, and a gene sequence highly homologous to cynomolgus monkey CYP2C76 in the marmoset and orangutan genomes, raising the possibility that CYP2C76 could also play a role in these primate species. This review paper gives an overview of CYP2C76 from isolation to molecular characterization, and its implication in drug metabolism.


Ferrihydrite-Modified Ti-Fe2 O3 as an Effective Photoanode: The Role of Interface Interactions in Enhancing the Photocatalytic Activity of Water Oxidation.
Semiconductor electrodes integrated with cocatalysts are key components of photoelectrochemistry (PEC)-based solar-energy conversion. However, efforts to optimize the PEC device have been limited by an inadequate understanding of the interface interactions between the semiconductor-cocatalyst (sem|cat) and cocatalyst-electrolyte (cat|ele) interface. In our work, we used ferrihydrite (Fh)-modified Ti-Fe2 O3 as a model to explore the transfer process of photogenerated charge carriers between the Ti-Fe2 O3 -Fh (Ti-Fe2 O3 |Fh) interface and Fh-electrolyte (Fh|ele) interface. The results demonstrate that the biphasic structure (Fh/Ti-Fe2 O3 ) possesses the advantage that the minority hole transfer from Ti-Fe2 O3 to Fh is driven by the interfacial electric field at the Ti-Fe2 O3 |Fh interface; meanwhile, the holes reached at the surface of Fh can rapidly inject into the electrolyte across the Fh|ele interface. As a benefit from the improved charge transfer at the Ti-Fe2 O3 |Fh and Fh|ele interface, the photocurrent density obtained by Fh/Ti-Fe2 O3 can reach 2.32 mA cm-2 at 1.23 V versus RHE, which is three times higher than that of Ti-Fe2 O3 .


Evaluation of dysuria in adults.
Dysuria, defined as pain, burning, or discomfort on urination, is more common in women than in men. Although urinary tract infection is the most frequent cause of dysuria, empiric treatment with antibiotics is not always appropriate. Dysuria occurs more often in younger women, probably because of their greater frequency of sexual activity. Older men are more likely to have dysuria because of an increased incidence of prostatic hyperplasia with accompanying inflammation and infection. A comprehensive history and physical examination can often reveal the cause of dysuria. Urinalysis may not be needed in healthier patients who have uncomplicated medical histories and symptoms. In most patients, however, urinalysis can help to determine the presence of infection and confirm a suspected diagnosis. Urine cultures and both urethral and vaginal smears and cultures can help to identify sites of infection and causative agents. Coliform organisms, notably Escherichia coli, are the most common pathogens in urinary tract infection. Dysuria can also be caused by noninfectious inflammation or trauma, neoplasm, calculi, hypoestrogenism, interstitial cystitis, or psychogenic disorders. Although radiography and other forms of imaging are rarely needed, these studies may identify abnormalities in the upper urinary tract when symptoms are more complex.


Improved Survival of Cancer Patients Admitted to the Intensive Care Unit between 2002 and 2011 at a U.S. Teaching Hospital.
Cancer patients are at increased risk of treatment- or disease-related admission to the intensive care unit. Over the past decades, both critical care and cancer care have improved substantially. Due to increased cancer-specific survival, we hypothesized that the number of cancer patients admitted to the intensive care unit (ICU) and survival have increased. MIMIC-III was used to study trends and outcomes of cancer patients admitted to the ICU between 2002 and 2011. Multiple logistic regression analysis was performed to adjust for confounders of mortality. Among 41,468 patients analyzed, 1,083 were hemato-oncologic, 4,330 were oncologic and 66 patients had both a hematological and solid malignancy. Admission numbers more than doubled and the proportion of cancer patients in the ICU increased steadily from 2002 to 2011. In both the univariate and multivariate analyses, solid cancers and hematologic cancers were strongly associated with 28-day mortality. This association was even stronger for 1-year mortality, with odds ratios of 4.02 (95% confidence interval [CI], 3.69 to 4.38) and 2.25 (95% CI, 1.93 to 2.62), respectively. Over the 10-year study period, both 28-day and 1-year mortality decreased, with hematologic patients showing the strongest annual adjusted decrease in the odds of death. There was considerable heterogeneity among solid cancer types. Between 2002 and 2011, the number of cancer patients admitted to the ICU more than doubled, while clinical severity scores remained overall unchanged, suggesting improved treatment. Although cancer patients had higher mortality rates, both 28-day and 1-year mortality of hematologic patients decreased faster than that of non-cancer patients, while mortality rates of cancer patients strongly depended on cancer type.


Short Lingual Osteotomy Using a Piezosurgery Ultrasonic Bone-Cutting Device During Sagittal Split Ramus Osteotomy.
Short lingual osteotomy is a useful method for the performance of sagittal split ramus osteotomy involving interference between the proximal and distal bone fragments when lateral differences exist in the setback distance. However, this procedure occasionally results in abnormal fracture and nerve injury; expert surgical skill is thus required. We herein describe a novel technique involving the use of an ultrasonic bone-cutting device (Piezosurgery; Mectron Medical Technology, Carasco, Italy) for vertical osteotomy posterior to the mandibular foramen. Successful short lingual osteotomy was performed using this technique with avoidance of abnormal fracture and neurovascular bundle damage.


Quantifying long-range correlations and 1/f patterns in a minimal experiment of social interaction.
In recent years, researchers in social cognition have found the "perceptual crossing paradigm" to be both a theoretical and practical advance toward meeting particular challenges. This paradigm has been used to analyze the type of interactive processes that emerge in minimal interactions and it has allowed progress toward understanding of the principles of social cognition processes. In this paper, we analyze whether some critical aspects of these interactions could not have been observed by previous studies. We consider alternative indicators that could complete, or even lead us to rethink, the current interpretation of the results obtained from both experimental and simulated modeling in the fields of social interactions and minimal perceptual crossing. In particular, we discuss the possibility that previous experiments have been analytically constrained to a short-term dynamic type of player response. Additionally, we propose the possibility of considering these experiments from a more suitable framework based on the use and analysis of long-range correlations and fractal dynamics. We will also reveal evidence supporting the idea that social interactions are deployed along many scales of activity. Specifically, we propose that the fractal structure of the interactions could be a more adequate framework to understand the type of social interaction patterns generated in a social engagement.


Evaluating the Effect of Parkinson's Disease on Jitter and Shimmer Speech Features.
Parkinson's disease (PD) is a neurological disorder caused by decreasing dopamine in the brain. Speech is one of the first functions that are disrupted. Accordingly, speech features are a promising indicator in PD diagnosis for telemedicine applications. The purpose of this study is to investigate the impact of Parkinson's disease on a minimal set of Jitter and Shimmer voice indicators and studying the difference between male and female speech features in noisy/noiseless environments. Our data includes 47 samples from nursing homes and neurology clinics, with 23 patients and 24 healthy individuals. The optimal feature for each category is studied separately for the men's and women's samples. The focus here is on the phonation in which the vowel/a/is expressed by the participants. The main features, including Jitter and Shimmer perturbations, are extracted. To find an optimal pair under both noisy and noiseless circumstance, we use the Relief feature selection strategy. This research shows that the Jitter feature for men and women with Parkinson's is 21 and 33.4, respectively. While the Shimmer feature is 0.1 and 0.06. In addition, by using these two features alone, we reach a correct diagnosis rate of 79% and 81% for noisy and noiseless states, respectively. The PD effects on the speech features can be accurately identified. Evaluating the extracted features suggests that the absolute value of the selected feature in men with PD is higher than for healthy ones. Whereas, in the case of women, this is the opposite.


Clinical performance evaluation of a newly developed sock for people with diabetes.
Diabetes mellitus (DM) is a chronic disease that has become a global health problem. As the population of people with diabetes is growing worldwide, the prevalence of complications associated with DM, such as diabetic foot, also increases. Neuropathy and high plantar pressure are the two most frequent causes of foot ulceration. Since diabetic wounds tend to heal slowly, it is crucial to prevent diabetic foot ulcers before they occur. In this study, the efficacy of a sock developed for diabetes in the previous research of the authors was investigated in a clinical study with the participation of patients with diabetes over a 6-month period. At the end of the study, it was observed that none of the participants had experienced any new ulcers, bacterial or fungal infections, or callus formation during this research. Moreover, a slight decrease in pressure was observed for the first, second, and third metatarsal bones when the socks were worn on day 1. On the other hand, pressure reduction was identified for the fourth and fifth metatarsal bones in all following measurements. However, analyses revealed that duration of usage did not have a statistically significant effect on overall plantar pressure. It was also found that pressure on the fourth and fifth metatarsal bones significantly decreased. Assessment of wearing comfort revealed the satisfaction of the patients, as well. Based on the promising outcomes of this clinical evaluation, these socks developed for people with diabetes can be strongly expected to help avoid diabetic foot ulcers.


Human P2Y1 receptor: molecular modeling and site-directed mutagenesis as tools to identify agonist and antagonist recognition sites.
The molecular basis for recognition by human P2Y1 receptors of the novel, competitive antagonist 2'-deoxy-N6-methyladenosine 3', 5'-bisphosphate (MRS 2179) was probed using site-directed mutagenesis and molecular modeling. The potency of this antagonist was measured in mutant receptors in which key residues in the transmembrane helical domains (TMs) 3, 5, 6, and 7 were replaced by Ala or other amino acids. The capacity of MRS 2179 to block stimulation of phospholipase C promoted by 2-methylthioadenosine 5'-diphosphate (2-MeSADP) was lost in P2Y1 receptors having F226A, K280A, or Q307A mutations, indicating that these residues are critical for the binding of the antagonist molecule. Mutation of the residues His132, Thr222, and Tyr136 had an intermediate effect on the capacity of MRS 2179 to block the P2Y1 receptor. These positions therefore appear to have a modulatory role in recognition of this antagonist. F131A, H277A, T221A, R310K, or S317A mutant receptors exhibited an apparent affinity for MRS 2179 that was similar to that observed with the wild-type receptor. Thus, Phe131, Thr221, His277, and Ser317 are not essential for antagonist recognition. A computer-generated model of the human P2Y1 receptor was built and analyzed to help interpret these results. The model was derived through primary sequence comparison, secondary structure prediction, and three-dimensional homology building, using rhodopsin as a template, and was consistent with data obtained from mutagenesis studies. We have introduced a "cross-docking" procedure to obtain energetically refined 3D structures of the ligand-receptor complexes. Cross-docking simulates the reorganization of the native receptor structure induced by a ligand. A putative nucleotide binding site was localized and used to predict which residues are likely to be in proximity to agonists and antagonists. According to our model TM6 and TM7 are close to the adenine ring, TM3 and TM6 are close to the ribose moiety, and TM3, TM6, and TM7 are near the triphosphate chain.


Changes in Lolium perenne transcriptome during cold acclimation in two genotypes adapted to different climatic conditions.
Activation of numerous protective mechanisms during cold acclimation is important for the acquisition of freezing tolerance in perennial ryegrass (Lolium perenne L.). To elucidate the molecular mechanisms of cold acclimation in two genotypes ('Veyo' and 'Falster') of perennial ryegrass from distinct geographical origins, we performed transcriptome profiling during cold acclimation using RNA-Seq. We cold-acclimated plants from both genotypes in controlled conditions for a period of 17 days and isolated Total RNA at various time points for high throughput sequencing using Illumina technology. RNA-seq reads were aligned to genotype specific references to identify transcripts with significant changes in expression during cold acclimation. The genes induced were involved in protective mechanisms such as cell response to abiotic stimulus, signal transduction, redox homeostasis, plasma membrane and cell wall modifications, and carbohydrate metabolism in both genotypes. 'Falster' genotype, adapted to cold climates, showed a stronger transcriptional differentiation during cold acclimation, and more differentially expressed transcripts related to stress, signal transduction, response to abiotic stimulus, and metabolic processes compared to 'Veyo'. 'Falster' genotype also showed an induction of more transcripts with sequence homology to fructosyltransferase genes (FTs) and a higher fold induction of fructan in response to low-temperature stress. The circadian rhythm network was perturbed in the 'Veyo' genotype adapted to warmer climates. In this study, the differentially expressed genes during cold acclimation, potentially involved in numerous protective mechanisms, were identified in two genotypes of perennial ryegrass from distinct geographical origins. The observation that the circadian rhythm network was perturbed in 'Veyo' during cold acclimation may point to a low adaptability of 'Veyo' to low temperature stresses. This study also revealed the transcriptional mechanisms underlying carbon allocation towards fructan biosynthesis in perennial ryegrass.


Comparison of subgingival bacterial sampling with oral lavage for detection and quantification of periodontal pathogens by real-time polymerase chain reaction.
Saliva has been studied for the presence of subgingival pathogens in periodontitis patients. With the anaerobic culture technique, the discrepancy between salivary recovery and subgingival presence has been significant, which makes this approach not suitable for practical use in the microbial diagnosis of periodontitis patients. The real-time polymerase chain reaction (PCR) technique represents a very sensitive technique to detect and quantify bacterial pathogens. The aim of the study was to compare the presence and numbers of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensis, Prevotella intermedia, and Micromonas micros in subgingival plaque and mouthwash samples by the anaerobic culture and real-time PCR techniques. Pooled subgingival plaque samples and 10-ml mouthwash samples were collected from 21 adult patients with periodontitis and analyzed by quantitative anaerobic culture and real-time PCR for A. actinomycetemcomitans, P. gingivalis, T. forsythensis, P. intermedia, and M. micros. The detection frequency of A. actinomycetemcomitans, P. gingivalis, and T. forsythensis in subgingival plaque was identical by culture and real-time PCR and was higher for P. intermedia and M. micros by real-time PCR. The highest detection frequencies for the target bacteria were found in mouthwash samples by real-time PCR. The additional value of the real-time PCR to detect target bacteria was 38% for P. gingivalis, 73% for T. forsythensis, 77% for P. intermedia, and 71% for M. micros. The sensitivity to detect target species in mouthwash by real-time PCR was 100% for all test species except for P. intermedia (93.8%). Rapid detection and quantification of periodontal pathogens in mouthwash samples are possible by real-time PCR. The procedure is significantly less time-consuming than subgingival sampling with paper points. This approach to detect major periodontal pathogens in mouthwash samples may simplify microbial diagnosis in periodontitis patients and may be used to monitor periodontal treatment.


[New method for preparing proximal anastomotic system].
Heartstring is a useful device. However, the device failure at the time of loading the seal into the delivery device is a troublesome issue. To avoid this problem, we invent a new method using 2 tourniquets made of 5 mm-wide woven Teflon tapes and plastic tubes. Using our method, the loading procedure became easier and more reliable.


Association of socioeconomic stratification with plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children.
To establish association between socioeconomic status and plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children from the middle-class and in critical poverty. Cross-sectional study with a sample of 114 school-age children (aged 7-9). The socioeconomic status, dietary intake of macro and micro-nutrients, weight, height, lipid profile, indicators of lipid peroxidation and enzymatic and non-enzymatic antioxidants were determined. The daily average intake of energy, carbohydrates and vitamin A, and the percentage of energy obtained from carbohydrates was significantly higher in middle-class children compared to critical poverty children (p <0.05). The circulating oxidized low density lipoprotein (p <0.001) and the susceptibility of low density lipoproteins and very low density lipoproteins to oxidation in vitro (p <0.05) were significantly higher in middle-class children, while the critical poverty children showed significantly lower levels of Vitamin C and E in plasma (p <0.05). Non-enzymatic antioxidant levels were frequently deficient in both strata. The concentrations of circulating oxidized low density lipoprotein (OR: 1.09, CI 95%: 1.016-1.179; p= 0.017) and Vitamin C (OR: 3.21, CI 95%: 1.104-9.938; p= 0.032) were associated to the socioeconomic status independently of gender, family history of premature coronary artery disease, triglicerides, Vitamin C and E dietary intake and count of white blood cells. The socioeconomic status was associated to circulating oxidized low density lipoprotein and Vitamin C in Venezuelan school-age children, The results suggested the need to improve the dietary intake of antioxidants in both studied socioeconomic groups.


A combined experimental and computational investigation of the microscopic external heavy atom effect in van der Waals clusters.
We present a combined experimental and computational study of the external heavy atom effect in van der Waals clusters of para-difluorobenzene (pDFB) with rare-gas atoms. Experimentally, clustering with rare-gas atoms is observed to shorten significantly the S1 fluorescence lifetime compared with that of the pDFB monomer, an effect we interpret in terms of an enhancement of the S1-T1 intersystem crossing rate. In order to test the validity of this widely held assumption, we have calculated the S1-T1 spin-orbit coupling matrix elements in the X-pDFB complexes (X=Ne, Ar, Kr) using a multiconfigurational linear response approach.


The effect of ceruletide on tardive dyskinesia: a double-blind placebo-controlled study.
1. In a double-blind placebo-controlled study of 37 patients with tardive dyskinesia, the therapeutic effect of ceruletide was evaluated. 2. The patients were assigned at random to two groups that received either intramuscular injections of 0.8 micrograms/kg of ceruletide or placebo once weekly for 4 weeks. Conventional neuroleptic medication was not changed 3 weeks prior to and throughout the study period. Tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale over an 8-week period. 3. Ceruletide had a more pronounced effect on TD than the placebo however, because of the limited number of subjects examined, the difference between the two groups was not significant. Ceruletide was more effective than placebo in patients under 60 years of age (p less than 0.05) and whose antipsychotic medication was mainly butyrophenones. 4. No serious side effect was noted. 5. The findings suggested that ceruletide therapeutically benefits patients with tardive dyskinesia.


The Sophisticated Transcriptional Response Governed by Transposable Elements in Human Health and Disease.
: Transposable elements (TEs), which cover ~45% of the human genome, although firstly considered as "selfish" DNA, are nowadays recognized as driving forces in eukaryotic genome evolution. This capability resides in generating a plethora of sophisticated RNA regulatory networks that influence the cell type specific transcriptome in health and disease. Indeed, TEs are transcribed and their RNAs mediate multi-layered transcriptional regulatory functions in cellular identity establishment, but also in the regulation of cellular plasticity and adaptability to environmental cues, as occurs in the immune response. Moreover, TEs transcriptional deregulation also evolved to promote pathogenesis, as in autoimmune and inflammatory diseases and cancers. Importantly, many of these findings have been achieved through the employment of Next Generation Sequencing (NGS) technologies and bioinformatic tools that are in continuous improvement to overcome the limitations of analyzing TEs sequences. However, they are highly homologous, and their annotation is still ambiguous. Here, we will review some of the most recent findings, questions and improvements to study at high resolution this intriguing portion of the human genome in health and diseases, opening the scenario to novel therapeutic opportunities.


Calcifying pseudotumor of scrotum: a case report.
Calcifying fibrous pseudotumors of the testicular and paratesticular soft tissue are relatively rare. We would like to report the first documented case of calcifying fibrous pseudotumor of the tunica vaginalis in Indian medical literature. This is a case of a 55 year old male who presented with a painless scrotal mass of 10 years duration. Histological sections showed dense hyalinised bands of collagen with focal collections of plasma cells and lymphocytes. Multiple round to oval concentrically laminated psammomatous bodies were seen.


Application of the comparison approach to open TG-GATEs: A useful toxicogenomics tool for detecting modes of action in chemical risk assessment.
Mode of action information is one of the key components for chemical risk assessment as mechanistic insight leads to better understanding of potential adverse health effects of a chemical. This insight greatly facilitates assessment of human relevance and enhances the use of non-animal methods for risk assessment, as it ultimately enables extrapolation from initiating events to adverse effects. Recently, we reported an in vitro toxicogenomics comparison approach to categorize (non-)genotoxic carcinogens according to similarities in their proposed modes of action. The present study aimed to make this comparison approach generally applicable, allowing comparison of outcomes across different studies. The resulting further developed comparison approach was evaluated through application to toxicogenomics data on 18 liver toxicants in human and rat primary hepatocytes from the Open TG-GATEs database. The results showed sensible matches between compounds with (partial) overlap in mode of action, whilst matches for compounds with different modes of action were absent. Comparison of the results across species revealed pronounced and relevant differences between primary rat and human hepatocytes, underpinning that information on mode of action enhances assessment of human relevance. Thus, we demonstrate that the comparison approach now is generally applicable, facilitating its use as tool in mechanism-based risk assessment.


Multiphase Oscillatory Flow Strategy for in Situ Measurement and Screening of Partition Coefficients.
Taking advantage of the difference between the surface energies of aqueous and organic solvents on a Teflon substrate, a fully automated small-scale strategy is developed on the basis of gas-driven oscillatory motion of a biphasic slug for high-throughput in situ measurement and screening of partition coefficients of organic substances between aqueous and organic phases. The developed oscillatory flow strategy enables single partition coefficient data point measurement within 8 min (including the sample preparation time) which is 360 times faster than the conventional "shake-flask" method, while using less than a 30 μL volume of the two phases and 9 nmol of the target organic substance. The developed multiphase strategy is validated using a conventional shake-flask technique. Finally, the developed strategy is extended to include automated screening of partition coefficients at physiological temperature.


Contact allergy to chloroacetamide.
Chloroacetamide is an uncommon skin care product allergen. A case of allergic contact dermatitis to this preservative is described in a patient who reacted to an underarm deodorant.


High coverage of mass drug administration for lymphatic filariasis in rural and non-rural settings in the Western Area, Sierra Leone.
Lymphatic filariasis elimination programs are based upon preventative chemotherapy annually in populations with prevalence more than or equal to 1%. The goal is to treat 80% of the eligible, at risk population yearly, for at least 5 years, in order to interrupt transmission and prevent children from becoming infected. This level of coverage has been a challenge in urban settings. Assessing the coverage in a rapidly growing urban/non-rural setting with inadequate population data is also problematic. In Sierra Leone, a 5-day preventative chemotherapy campaign was carried out in the Western Area including the capital: Freetown. An intensive, social mobilization strategy combined traditional and modern communication channels. To aid dissemination of appropriate information Frequently Asked Questions were developed and widely circulated. The population of the Western Area has grown faster than projected by the 2004 National Census due to the post-war settlement of internally displaced persons. As a reliable denominator was not available, independent monitoring was adapted and performed "in process" to aid program performance and "end process" to assess final coverage. In 5 days 1,104,407 eligible persons were treated. Using the projected population from the 2004 census this figure represented coverage of 116% in the Urban Western Area and 129% in the Rural Western Area. Independent monitors interviewed a total of 9,253 persons during the 2 End Process days representing 1% of the projected population. Of these, 85.8% recalled taking both ivermectin and albendazole (Urban: 85.2%, Rural: 87.1%). No serious adverse drug reactions were reported. The paper presents the key elements of success of the social mobilization and implementation strategy and describes the independent monitoring used to estimate final coverage in this urban/non-rural setting where the current population size is uncertain. This implementation strategy and Independent Monitoring tool could be useful in similar, rapidly growing cities implementing lymphatic filariasis elimination programs.


Dynamic assembly of DNA and polylysine mediated by electric energy.
Under an electric field, the complexes formed by DNA and polylysine exhibit novel features, such as selective merging of particles, ejecting of daughter vehicles, and differentiation of particles of varying mobility. The mobility of the complex could be three times faster than that of free DNA.


T cells as mediators in renal ischemia/reperfusion injury.
Inflammation has been established to contribute substantially to the pathogenesis of ischemia/reperfusion (I/R) with a central role for particular cells, adhesion molecules, and cytokines. Until recently, most of the research trying to unravel the pathogenesis of I/R injury has been focused on the role of neutrophils. However, recent studies have brought evidence that T cells and macrophages are also important leukocyte mediators of renal and extrarenal (liver) I/R injury. In vivo depletion of CD4+ cells but not CD8+ cells in wild-type mice was protective in I/R of the kidney. A marked preservation of liver function was also found after I/R in T-cell deficient athymic mice. Blocking the b130/CD28 costimulatory pathway by CTLA-4 Ig (recombinant fusion protein) ameliorated renal dysfunction and decreased mononuclear cell infiltration in I/R of the kidney. b130-1 expression was found limited to the membrane of the endothelial cells of the ascending vasa recta, resulting in trapping of CD28-expressing CD4 T cells. This trapping of leukocytes results in the upstream congestion in the ascending arterial vasa recta, generating the since more than 150 years described medullary vascular congestion of the kidney soon after ischemic injury. It seems worthwhile to study a combination therapy using anti-inflammatory/anti-adhesion molecules in the early phase of I/R.


Dimension from covariance matrices.
We describe a method to estimate embedding dimension from a time series. This method includes an estimate of the probability that the dimension estimate is valid. Such validity estimates are not common in algorithms for calculating the properties of dynamical systems. The algorithm described here compares the eigenvalues of covariance matrices created from an embedded signal to the eigenvalues for a covariance matrix of a Gaussian random process with the same dimension and number of points. A statistical test gives the probability that the eigenvalues for the embedded signal did not come from the Gaussian random process.


Body dimensions of Québecois children.
The present study examined the impact of sociocultural factors upon the body dimensions of primary school children (age 6-12 years) living within a uniquely francophone region of Québec. Data was collected prospectively on 546 students, drawn in approximately equal numbers from the two sexes and from urban and rural environments. Habitual activity was modified by allocating a half of the sample to an experimental programme that incorporated an additional five hours of required endurance activity per week into the primary school curriculum. Body dimensions at any given age were less in rural than in urban Québec, probably because of continuing socio-economic constraints. However, an increase of habitual physical activity did not modify body size. Stature was comparable with Demirjian 's Montr eal sample of francophone children, but was less than for anglophone children. Our within-sample variance suggests that socio-economic factors could explain only a part of the discrepancy. Relative to Toronto students, other dimensions such as height were affected less than standing height.


Transitions between smooth and complex stick-slip sliding of surfaces.
Shear measurements were performed on mica surfaces with molecularly thin films of squalane (C30H62) confined between them. Squalane is a branched hydrocarbon liquid that can be in the liquid, glassy, or liquid-crystalline state under confinement. The friction forces, especially the transitions between smooth and intermittent (e.g., stick-slip) sliding, were measured over a wider range of applied loads (pressures), sliding velocities (shear rates), and temperatures than in previous studies. The results reveal that, depending on the conditions, qualitatively different behavior can arise in the same system. These include both abrupt and continuous transitions, both upper and lower critical transition temperatures, short and very long transient effects, and chaotic, sawtooth, or sinusoidal stick-slip that can slowly decay with time or distance sheared. The differences between these branched and simpler, e.g., spherical, unbranched molecules are compared, as well as with unlubricated (dry) surfaces and macroscopic (geological) systems.


Potential of Grape Wastes as a Natural Source of Bioactive Compounds.
Grapes are widely used in the wine and juice industries, which can lead to massive amounts of waste, mostly grape peels and seeds. The antioxidant capacities, total phenolic and flavonoid contents and phenolic profiles of peels and seeds from 30 grape varieties were systemically assessed. The antioxidant activities of fat-soluble, water-soluble and insoluble-bound fractions of grape peels and seeds were evaluated using ferric-reducing antioxidant power and Trolox equivalent antioxidant capacity assays, and their total phenolic contents and total flavonoid contents were determined by the Folin-Ciocalteu method and AlCl₃ colorimetry, respectively. It was found that the antioxidant capacities were diverse among different grape peels and seeds. Moreover, several phenolic compounds were identified and quantified, including gallic acid, cyanidin-3-glucoside, epicatechin, catechin gallate, ferulaic acid, rutin and resveratrol, which could contribute to the antioxidant capacities of these grape peels and seeds. Several grape wastes with strong antioxidant activity could be abundant sources of natural bioactive compounds, and have the potential for development into functional foods, food additives and pharmaceuticals.


Identification of a human enterocyte lipoxin A4 receptor that is regulated by interleukin (IL)-13 and interferon gamma and inhibits tumor necrosis factor alpha-induced IL-8 release.
Epithelial cells of the alimentary tract play a central role in mucosal immunophysiology. Pathogens and/or agonists that interact with mucosal surfaces often elicit epithelial responses that upregulate inflammation. Therefore, it was of interest to explore potential epithelial targeted antiinflammatory signals. Here we identified and sequenced a human enterocyte lipoxin (LX) A4 [5(S), 6(R),15(S)-trihydroxy-7,9,13-trans-11-cis eicosatetraenoic acid] receptor, and demonstrate that transcription of this receptor was controlled by cytokines, of which lymphocyte-derived interleukin (IL)-13 and interferon gamma were the most potent. When lipoxins and LXA4 stable analogs were evaluated for enterocyte functional as well as immune responses, lipoxins sharply inhibited TNF-alpha-induced IL-8 release but did not alter either barrier function or agonist-stimulated chloride secretion. 15R/S-methyl-LXA4 and 16-phenoxy-LXA4 each attenuated (IC50 approximately 10 nM) IL-8 release. Cyclooxygenase (COX) II is emerging as an important component in wound healing and proliferation in intestinal epithelia and when acetylated by acetylsalicylic acid (aspirin) initiates the biosynthesis of a LXA4 receptor ligand. We therefore determined whether colonic cell lines (HT-29 Cl.19A, Caco-2, or T84) express the COX II isozyme. Results for RT-PCR and Western blot analysis showed that COX I as well as an IL-1beta- and TNF-alpha-inducible COX II are expressed in HT-29 Cl.19A. In addition, aspirin-treated enterocytes generated 15R-HETE, a precursor of 15-epi-LXA4 biosynthesis, whose potent bioactions were mimicked by the stable analog 15R/S-methyl-LXA4. Taken together, these results identify an endogenous pathway for downregulating mucosal inflammatory events and suggest a potential therapeutic benefit for LXA4 stable analogs.


Physicochemical, structural analysis of coal discards (and sewage sludge) (co)-HTC derived biochar for a sustainable carbon economy and evaluation of the liquid by-product.
This study focused on the hydrothermal treatment (HTC) of coal tailings (CT) and coal slurry (CS) and the co-hydrothermal treatment (Co-HTC) of CT, CS and sewage sludge to assess the potential for increasing the carbon content of the hydrochar produced as an enabler for a sustainable carbon economy. The optimal combination methodology and response surface methodology were used to study the relationship between the important process parameters, namely temperature, pressure, residence time, the coal-to-sewage-sludge ratio, and the carbon yield of the produced hydrochar. The optimized conditions for hydrochar from coal tailing (HCT) and hydrochar from coal slurry (HCS) (150 °C, 27 bar, 95 min) increased fixed carbon from 37.31% and 53.02% to 40.31% and 57.69%, respectively, the total carbon content improved from 42.82 to 49.80% and from 61.85 to 66.90% respectively whereas the ash content of coal discards decreased from 40.32% and 24.17% to 38.3% and 20.0% when compared CT and CS respectively. Optimized Co-HTC conditions (208 °C, 22.5bars, and 360 min) for Hydrochar from the blend of coal discards and sewage sludge (HCB) increased the fixed carbon on a dry basis and the total carbon content from 38.67% and 45.64% to 58.82% and 67.0%, when compared CT and CS respectively. Carbonization yields for HCT, HCS, and HCB were, respectively, 113.58%, 102.42%, and 129.88%. HTC and Co-HTC increase the calorific value of CT and CS, to 19.33 MJ/kg, 25.79 MJ/kg, respectively. The results further show that under Co-HTC conditions, the raw biomass undergoes dehydration and decarboxylation, resulting in a decrease in hydrogen from 3.01%, 3.56%, and 3.05% to 2.87%, 2.98%, and 2.75%, and oxygen from 8.79%, 4.78, and 8.2% to 5.83%, 2.75%, and 6.00% in the resulting HCT, HCS, and HCB, respectively. HTC and Co-HTC optimal conditions increased the specific surface area of the feedstock from 6.066 m2/g and 6.37 m2/g to 11.88 m2/g and 14.35 m2/g, for CT and CS, respectively. Total pore volume rose to 0.071 cm3/g from 0.034 cm3/g, 0.048 cm3/g, and 0.09 cm3/g proving the ability of HTC to produce high-quality hydrochar from coal discards alone or in conjunction with sewage sludge as precursors for decontamination of polluted waters, soil decontamination applications, solid combustibles, energy storage, and environmental protection.


Birefringent optical fiber with dispersive orientation of polarization axes.
We demonstrate for the first time in optical fibers the "dispersion of the axes" phenomenon, which relies upon spectral dependence of polarization planes of the guided modes. This feature was achieved in a specially designed side-hole fiber by combining linear birefringence induced by a pair of holes located in the cladding and the elliptical core tilted with respect to the symmetry plane of the holes. We performed numerical simulations of this design properties. The side-hole fiber with a tilted core was fabricated and experimentally studied. The orientation of the principal polarization planes of the fundamental modes varied by 14.5° in the analyzed spectral range. This value is in a good agreement with the simulation results.


Acute and long-term NCX activation reduces brain injury and restores behavioral functions in mice subjected to neonatal brain ischemia.
Hypoxic-ischemic encephalopathy (HI) accounts for the majority of developmental, motor and cognitive deficits in children, leading to life-long neurological impairments. Since the plasmamembrane sodium/calcium exchanger (NCX) plays a fundamental role in maintaining ionic homeostasis during adult brain ischemia, in the present work we aimed to demonstrate (1)the involvement of NCX in the pathophysiology of neonatal HI and (2)a possible NCX-based pharmacological intervention. HI was induced in neonatal mice at postnatal day 7(P7) by unilateral cut of the right common carotid artery, followed by 60 min exposure to 8%O2. Expression profiles of NCX isoforms from embryos stage to adulthood was evaluated in the hippocampus of hypoxic-ischemic and control mice. To assess the effect of NCX pharmacological stimulation, brain infarct volume was evaluated in brain sections, obtained at several time intervals after systemic administration of the newly synthesized NCX activator neurounina. Moreover, the long term effect of NCX activation was evaluated in adult mice (P60) subjected to neonatal HI and daily treated with neurounina for three weeks. Hypoxic-ischemic insult induced a reduction of NCX1 and NCX3 expression starting from day 7 until day 60. Notably, 8 weeks after HI induction in P7 mice, NCX pharmacological stimulation not only reduced infarct volume but improved also motor behaviour, spatial and visual memory. The present study highlights the significant role of NCX in the evolution of neonatal brain injury and in the learning and memory processes that are impaired in mice injured in the neonatal period.


Knockdown of TBRG4 affects tumorigenesis in human H1299 lung cancer cells by regulating DDIT3, CAV1 and RRM2.
The transforming growth factor β regulator 4 (TBRG4) gene, located on the 7p14-p13 chromosomal region, is implicated in numerous types of cancer. However, the contribution(s) of TBRG4 in human lung cancer remains unknown. In the present study, the expression of TBRG4 mRNA was investigated in the H1299 lung cancer cell line using the quantitative polymerase chain reaction (qPCR) following the knockdown of TBRG4 by a lentivirus-mediated small interfering RNA (siRNA). Results identified that the expression of TBRG4 within H1299 cells was significantly suppressed (P<0.01) by RNA interference, and 586 genes were differentially expressed following TBRG4 silencing. Ingenuity Pathway Analysis (IPA) revealed that these genes were often associated with infectious diseases, organismal injury, abnormalities and cancer functional networks. Further IPA of these networks revealed that TBRG4 knockdown in H1299 cells deregulated the expression of 21 downstream genes, including the upregulation of DNA damage-inducible transcript 3 (DDIT3), also termed CCAAT/enhancer-binding protein homologous protein, and downregulation of caveolin 1 (CAV1) and ribonucleotide reductase regulatory subunit M2 (RRM2). Results were validated using qPCR and western blotting. Furthermore, immunohistochemical staining of TBRG4 protein identified that expression was markedly increased in carcinoma compared with in normal tissue. In conclusion, TBRG4 serves a role in the tumorigenesis of lung cancer via deregulation of DDIT3, CAV1 and RRM2. The results of the present study may be important in contributing to our understanding of TBRG4 as a target for lung cancer treatment.


Cdc2 kinase-dependent disassembly of endoplasmic reticulum (ER) exit sites inhibits ER-to-Golgi vesicular transport during mitosis.
We observed the disassembly of endoplasmic reticulum (ER) exit sites (ERES) by confocal microscopy during mitosis in Chinese hamster ovary (CHO) cells by using Yip1A fused to green fluorescence protein (GFP) as a transmembrane marker of ERES. Photobleaching experiments revealed that Yip1A-GFP, which was restricted to the ERES during interphase, diffused throughout the ER network during mitosis. Next, we reconstituted mitotic disassembly of Yip1A-GFP-labeled ERES in streptolysin O-permeabilized CHO cells by using mitotic L5178Y cytosol. Using the ERES disassembly assay and the anterograde transport assay of GFP-tagged VSVGts045, we demonstrated that the phosphorylation of p47 by Cdc2 kinase regulates the disassembly of ERES and results in the specific inhibition of ER-to-Golgi transport during mitosis.


Decoupling of folded-end dipole antenna elements of a 9.4 T human head array using an RF shield.
Dipole antennas have recently been introduced to the field of MRI and successfully used, mostly as elements of ultra-high field (UHF, ≥ 7 T) human body arrays. Usage of dipole antennas for UHF human head transmit (Tx) arrays is still under development. Due to the substantially smaller size of the sample, dipoles must be made significantly shorter than in the body array. Additionally, head Tx arrays are commonly placed on the surface of rigid helmets made sufficiently large to accommodate tight-fit receive arrays. As a result, dipoles are not well loaded and are often poorly decoupled, which compromises Tx efficiency. Commonly, adjacent array elements are decoupled by circuits electrically connected to them. Placement of such circuits between distantly located dipoles is difficult. Alternatively, decoupling is provided by placing passive antennas between adjacent dipole elements. This method only works when these additional components are sufficiently small (compared with the size of active dipoles). Otherwise, RF fields produced by passive elements interfere destructively with the RF field of the array itself, and previously reported designs have used passive dipoles of about the size of array dipoles. In this work, we developed a novel method of decoupling for adjacent dipole antennas, and used this technique while constructing a 9.4 T human head eight-element transceiver array. Decoupling is provided without any additional circuits by simply folding the dipoles and using an RF shield located close to the folded portion of the dipoles. The array reported in this work demonstrates good decoupling and whole-brain coverage.


The Haber-Weiss cycle--70 years later.
The chain reactions HO* + H2O2 --> H2O + O2*- + H+ and O2*- + H+ + H2O2 --> O2 + HO* + H2O, commonly known as the Haber-Weiss cycle, were first mentioned by Haber and Willstätter in 1931. George showed in 1947 that the second reaction is insignificant in comparison to the fast dismutation of superoxide, and this finding appears to have been accepted by Weiss in 1949. In 1970, the Haber-Weiss reaction was revived by Beauchamp and Fridovich to explain the toxicity of superoxide. During the 1970s various groups determined that the rate constant for this reaction is of the order of 1 M(-1) s(-1) or less, which confirmed George's conclusion. The reaction of superoxide with hydrogen peroxide was dropped from the scheme of oxygen toxicity, and superoxide became the source of hydrogen peroxide, which yields hydroxyl radicals via the Fenton reaction, Fe2+ + H2O2 --> Fe3+ + HO- + HO*. In 1994, Kahn and Kasha resurrected the Haber-Weiss reaction again, but this time the oxygen was believed to be in the singlet (1delta(g)) state. As toxicity arises not from a Fenton-catalysed Haber-Weiss reaction, but from the Fenton reaction, the Haber-Weiss reaction should not be mentioned anymore.


Applicability and Limitations of a Capillary-LC Column-Switching System Using Hybrid Graphene-Based Stationary Phases.
Graphene oxide sheets fixed over silica particles (SiGO) and their modification functionalized with C18 and endcapped (SiGO-C18ec) have been reported as sorbents for extraction and analytical columns in LC. In this study, a SiGO column was selected as the extraction column and a SiGO-C18ec as the analytical column to study the applicability and limitations of a column-switching system composed exclusively of columns packed with graphene-based sorbents. Pyriproxyfen and abamectin B1a were selected as the analytes, and orange-flavored carbonated soft drinks as the matrix. The proposed system could be successfully applied to the pyriproxyfen analysis in a concentration range between 0.5 to 25 µg/mL presenting a linearity of R2 = 0.9931 and an intra-day and inter-day accuracy of 82.2-111.4% (RSD < 13.3%) and 95.5-99.8% (RSD < 12.7%), respectively. Furthermore, the matrix composition affected the area observed for the pyriproxyfen: the higher the concentration of orange juice in the soft drink, the higher the pyriproxyfen the signal observed. Additionally, the SiGO extraction column presented a life use of 120 injections for this matrix. In contrast, the proposed system could not apply to the analysis of abamectin B1a, and the SiGO-C18ec analytical column presented significant tailing compared to a similar approach with a C18 analytical column.


Sleep disruption in spinocerebellar ataxia type 3: a genetic and polysomnographic study.
Sleep structure disruption and rapid eye movement (REM) sleep behavior disorders (RBD) have been previously reported in patients with neurodegenerative diseases. However, similar studies have rarely been quantitatively conducted in type 3 spinocerebellar ataxia (SCA3). Fifteen patients with SCA3 and 16 healthy controls were recruited and evaluated by clinical history, International Cooperative Ataxia Rating Scale (ICARS), Epworth sleepiness scale (ESS), and polysomnography. Patients with SCA3 had reductions in sleep efficiency and percentage of REM sleep, which were negatively correlated with the severity of ataxia as evaluated by ICARS. REM sleep reduction occurred regardless of the presence of RBD, and severe reduction of REM sleep may significantly disturb the assessment of RBD. Poor sleep efficiency and REM sleep aberrations are the characteristics of sleep structure disruption in SCA3 as the disease progresses. The incidence of respiratory disturbance during sleep or excessive daytime sleepiness was not significantly higher in SCA3 patients than controls.


Expression of p57/Kip2 protein in extrahepatic bile duct carcinoma and intrahepatic cholangiocellular carcinoma.
Evaluation of the biological character of carcinomas requires understanding of cell cycle regulators. P57 (Kip2) belongs to the Cip/Kip family and is known to be one of the universal negative regulators of cell cycle. In the present study, therefore, we investigated p57 expression in 37 extrahepatic bile duct carcinomas (BDC) and 28 intrahepatic cholangiocellular carcinomas (CCC). The average p57 labeling index (LI) in BDC and CCC were 60.8 +/- 7.9 and 58.6 +/- 18.6, respectively, which were significantly lower (p = 0.0008 and p = 0.0408, respectively) than those in normal duct epithelia (73.1 +/- 7.9, 70.4 +/- 8.2). p57 LI was significantly lower in BDC and CCC cases with biological aggressive phenotypes such as poor differentiation (p = 0.0260 and p = 0.0069), lymph node metastasis (p = 0.0274 and p = 0.0214), high Ki-67 LI (p = 0.0164 and p = 0.0343) and cyclin D1 overexpression (p = 0.0359 and p = 0.0255). These findings suggest that decreased p57 expression is related to the increased activity of cell proliferation and also the progression of these carcinomas.


Skilled deaf readers have an enhanced perceptual span in reading.
Recent evidence suggests that, compared with hearing people, deaf people have enhanced visual attention to simple stimuli viewed in the parafovea and periphery. Although a large part of reading involves processing the fixated words in foveal vision, readers also utilize information in parafoveal vision to preprocess upcoming words and decide where to look next. In the study reported here, we investigated whether auditory deprivation affects low-level visual processing during reading by comparing the perceptual span of deaf signers who were skilled and less-skilled readers with the perceptual span of skilled hearing readers. Compared with hearing readers, the two groups of deaf readers had a larger perceptual span than would be expected given their reading ability. These results provide the first evidence that deaf readers' enhanced attentional allocation to the parafovea is used during complex cognitive tasks, such as reading.


"There's got to be a better way": Global Perspectives of Medicolegal Environment and Neurosurgical Socioeconomics.
Neurosurgery is considered to have one of the greatest risks of medical malpractice claims. However, medicolegal issues in neurosurgery are often disregarded and underrated worldwide. Medical errors in the neurosurgical field can be attributed to multiple factors, including highly morbid pathologies, the technical difficulty of neurosurgical procedures, and the involvement and interaction of a multidisciplinary team in the care of neurosurgical patients. Health care providers worldwide are at risk of lawsuits, sometimes even when no deviation from the standard of care had occurred in a given case. Often, governments use additional tactics to decrease the burden on compensators and extrajudicial institutions and to decrease the court's flow of irrational litigation. Continuous amendments to health care acts and newer reforms to address these issues have materialized worldwide. In the present narrative review, we have reviewed the global perspectives of medicolegal issues, with a focus on neurosurgical discipline.


A pilot trial on pulmonary emphysema quantification and perfusion mapping in a single-step using contrast-enhanced dual-energy computed tomography.
To know whether contrast-enhanced dual-energy computed tomography angiography (DECTA) can be used for simultaneous assessment of emphysema quantification and regional perfusion evaluation. We assessed 27 patients who had pulmonary emphysema and no pulmonary embolism on visual assessment of CT images, among 584 consecutive patients who underwent DECTA for the evaluation of pulmonary embolism. Virtual noncontrast (VNC) images were generated by modifying the "Liver VNC" application in a dedicated workstation. Using in-house software, the low-attenuation area below 950HU (LAA950), the 15th percentile attenuation (15pctlVNC) and the mean lung attenuation (MeanVNC) were calculated. The "Lung PBV" application was used to assess perfusion, and the low-iodine area below 5HU (LIA5), the 15th percentile iodine (15pctlIodine), and the mean iodine value (MeanIodine) were calculated from iodine map images. The correlation between VNC parameters and pulmonary function test data (available in 22 patients) and the correlation between VNC and iodine map parameters (all included 27 patients) were assessed. Color-coded map of VNC image were compared with iodine map images for the evaluation of regional heterogeneity. We observed moderate correlations between LAA950 and predicted %FEV1 (rs = -0.47, P < 0.05), and 15pctlVNC and predicted %FEV1 (rs = 0.56, P < 0.05). We also observed significant correlations between LAA950 and LIA5 (rs = 0.48, P < 0.05), 15pctlVNC and 15pctlIodine (rs = 0.59, P = 0.001), and MeanVNC and MeanIodine (rs = 0.47, P < 0.05). On visual assessment of the regional heterogeneity, 82% of patients showed relatively good correlation between the areas of perfusion impairment on iodine map images and areas of emphysema on color-coded VNC images. We observed moderate correlations between quantitative parameters on VNC images and pulmonary function test data, and also observed moderate correlations between the severity of parenchymal destruction, as determined from VNC images, and perfusion status, as determined from iodine maps. Therefore, the contrast-enhanced DECTA can be used for the emphysema quantification and regional perfusion evaluation by using the VNC images and iodine map, simultaneously.


Role of miRNA in Lung Cancer-Potential Biomarkers and Therapies.
MicroRNAs (miRNAs) are small noncoding RNAs, which downregulate gene expression by repressing or degrading mRNA targets. Lung cancer (LC), together with liver and colorectal cancers are the three leading causes of cancer death worldwide, and 80% of LCs belong to non-small cell lung cancers (NSCLCs). Despite a great advancement in developing distinct and delicate tools for early diagnosis and targeted therapies over the last decade, only about 15% of the NSCLC patients eventually survived. MiRNAs are frequently dysregulated in carcinoma, including LC. Numerous lines of evidence have demonstrated various roles played by miRNAs in the development and progression of LC. In this review, we propose to summarize the current understanding of miRNAs in LC, with a particular focus on translational application of miRNAs as novel diagnostic and prognostic biomarkers and tools for treatment.