Mechanism of action of nonsteroidal anti-inflammatory drugs.
After more than a century of use, pharmacologists thought they had discovered the mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) when their inhibitory action on the production of prostaglandins was described. This action was located at the inhibition of the enzyme responsible for the conversion of arachidonic acid to prostaglandins, namely cyclo-oxygenase. More recently, it has been recognized that more than one isoform of the enzyme exists. The two forms of cyclo-oxygenase described are widely different in their location, activity, and role, especially because the COX-1 isoenzyme seems to be mainly a constitutive enzyme whereas the COX-2 isoenzyme is inducible. This separation of activity appears to be correlated with the separation of function of the various prostaglandins, whereas the constitutive form is associated with "physiologic" functions and the inducible form with inflammatory responses. Recent advances have included the development of drugs with a high specificity toward the inducible enzyme (COX-2) to focus on the anti-inflammatory actions, because many of the unwanted side effects of NSAIDs have been associated with inhibition of the constitutive isoform (COX-1). Other recent developments in studies of the NSAIDs have included potential therapeutic actions in other degenerative conditions.


CFD Modeling of Methanol to Light Olefins in a Sodalite Membrane Reactor using SAPO-34 Catalyst with In Situ Steam Removal.
In this work, the performance of a sodalite membrane reactor (MR) in the conversion of methanol to olefins (MTO process) was evaluated for ethylene and propylene production with in situ steam removal using 3-dimensional CFD (computational fluid dynamic) technique. Numerical simulation was performed using the commercial CFD package COMSOL Multiphysics 5.3. The finite element method was used to solve the governing equations in the 3- dimensional CFD model for the present work. In the sodalite MR model, a commercial SAPO-34 catalyst in the reaction zone was considered. The influence of key operation parameters, including pressure and temperature on methanol conversion, water recovery, and yields of ethylene, propylene, and water was studied to evaluate the performance of sodalite MR. The local information of component concentration for methanol, ethylene, propylene, and water was obtained by the proposed CFD model. Literature data were applied to validate model results, and a good agreement was attained between the experimental data and predicted results using CFD model. Permeation flux through the sodalite membrane was increased by an increase of reaction temperature, which led to the enhancement of water stream recovered in the permeate side. The CFD modeling results showed that the sodalite MR in the MTO process had higher performance in methanol conversion compared to the fixed-bed reactor (methanol conversion of 97% and 89% at 733 K for sodalite MR and fixed-bed reactor, respectively).


Prevalence and implications of type D personality in patients with alopecia areata: A marker of quality-of-life impairment and mood status disturbances, a comparative study.
Distressed personality (or Type D personality, TDp) is a personality trait that has been associated with poor quality of life in patients suffering from a variety of skin diseases such as psoriasis or urticaria. To date the potential association between Alopecia areata (AA) and TDp has not been studied. The aim of this study was to compare the prevalence of TDp between patients with AA and controls, and to analyse the impact of TDp on patients with AA regarding mood status disturbances, quality of life and sexuality. Cross-sectional study includes patients suffering from mild-to-severe AA and sex- and age-matched healthy controls. Socio-demographic and clinical variables, quality of life, sexual disfunction, anxiety, depression and TDp were collected using validated questionnaires. A total of 120 participants (60 patients and 60 controls) were included. Patients with AA showed higher prevalence of TDp than controls (35% vs. 15% p = 0.01), as well as higher rates of anxiety, depression and sexual dysfunction (p < 0.05). TDp was found to be linked to disease severity (p = 0.04), anxiety and depression scores (p < 0.001) and worse quality of life (p = 0.001). No relationship was found between TDp and sexual dysfunction. Type D personality prevalence is higher in patients with AA than in controls. It is associated with higher rates of anxiety, depression and worse quality of life. Screening for this type of personality could be useful to detect patients who could benefit from additional psychological support as a complement to their medical treatment.


[Progressive multifocal leucoencephalopathy. Observation with predominant pontocerebellar lesions and association with congenital immune deficiency].
A young woman presented a mixed congenital and familial immunodeficiency syndrome consisting in an absence of IgA and lowered levels of IgG and IgM, with a defect in cellular immunity. She had a mild malabsorption syndrome with slight alterations of the jejunal mucosa. Non-caseating tuberculoid granulomata were found in skin lesions, in lymph nodes and in the spleen. At age 27 the patient died of a neurological disease of 4 months duration. Autopsy revealed a very widespread demyelinating process involving mainly the right cerebellar hemisphere but also most of the pons and left cerebellum, with the typical morphologic characters of PML. In the hemispheres lesions were limited to microscopical "microglial nodules" with discrete demyelination. A review of 86 published cases of PML revealed 9 other cases in which lesions showed a strong predilection for the subtentorial territories. This sampling allows for tha assumption that some 11% of the cases of PML have this particular lesion distribution. Other pertinent features of this case are briefly discussed.


Principal component analysis-based unsupervised feature extraction applied to in silico drug discovery for posttraumatic stress disorder-mediated heart disease.
Feature extraction (FE) is difficult, particularly if there are more features than samples, as small sample numbers often result in biased outcomes or overfitting. Furthermore, multiple sample classes often complicate FE because evaluating performance, which is usual in supervised FE, is generally harder than the two-class problem. Developing sample classification independent unsupervised methods would solve many of these problems. Two principal component analysis (PCA)-based FE, specifically, variational Bayes PCA (VBPCA) was extended to perform unsupervised FE, and together with conventional PCA (CPCA)-based unsupervised FE, were tested as sample classification independent unsupervised FE methods. VBPCA- and CPCA-based unsupervised FE both performed well when applied to simulated data, and a posttraumatic stress disorder (PTSD)-mediated heart disease data set that had multiple categorical class observations in mRNA/microRNA expression of stressed mouse heart. A critical set of PTSD miRNAs/mRNAs were identified that show aberrant expression between treatment and control samples, and significant, negative correlation with one another. Moreover, greater stability and biological feasibility than conventional supervised FE was also demonstrated. Based on the results obtained, in silico drug discovery was performed as translational validation of the methods. Our two proposed unsupervised FE methods (CPCA- and VBPCA-based) worked well on simulated data, and outperformed two conventional supervised FE methods on a real data set. Thus, these two methods have suggested equivalence for FE on categorical multiclass data sets, with potential translational utility for in silico drug discovery.


Safety assessment of anticancer drugs in association with radiotherapy in metastatic malignant melanoma: a real-life report : Radiation/systemic drug combo in metastatic melanoma.
To assess the safety of the association of radiotherapy (RT) and systemic treatments for patients with metastatic malignant melanoma (mMM). A retrospective analysis included consecutive patients treated with palliative RT, and at least one line of systemic therapy for mMM between 2001 and 2016. Treatments were defined as sequential or concomitant when RT and the systemic drug were administered, respectively, at more or less than five half-lives from each other. 92 patients were included. They had 110 palliative RT treatments. RT was delivered with a "conventional" chemotherapy (mainly fotemustine and/or dacarbazine) and a "modern" systemic therapy (BRAF inhibitors, association of BRAF and MEK inhibitors, immunotherapy), respectively, in 88 (80%) and 22 (20%) cases. Systemic treatments and RT were mainly concurrently performed (n = 61, 55.5%). Regarding acute grade ≥ 3 toxicity, no difference was reported between sequential and concomitant groups either in the whole cohort (p = 1) or in the subgroup of patients receiving "modern" systemic therapies (p = 1). Acute and late grade ≥ 3 toxicities only occurred with vemurafenib. BRAF inhibitors and RT produced more severe infield adverse events than other associations (p = 0.001) with two deaths. In our series, compared to sequential administration, concomitant association of systemic anticancer drugs and palliative RT did not increase toxicity in mMM patients. BRAF inhibitors and RT produced severe infield toxicities. Prospective studies are needed to better characterize the toxicity of each association.


In situ production of bacterial cellulose/xanthan gum nanocomposites with enhanced productivity and properties using Enterobacter sp. FY-07.
While bacterial cellulose (BC) is a widely used, high-value product, its industrial production is hindered by the limited properties and productivity. Herein, by combining optimized fermentation methods and adding XG for in situ modification during submerged fermentation of Enterobacter sp. FY-07 (FY-07), homogeneously modified BC/xanthan gum (XG) nanocomposites with enhanced productivity and properties were obtained. The relationship between BC productivity and the contact area between the bacteria and objects was explored. The productivity of BC reached 3.2 g/L/d under optimal conditions. Compared to BC, the BC/XG nanocomposite exhibited coarser fibers along with significantly higher hardness, chewiness, resilience, and tensile strength, making the nanocomposite more suitable for food and other applications. The findings provide a low-cost, simple, and efficient strategy to improve the properties and productivity of BC. This work has significant implications for the in situ modification and production of BC in the biopolymer industry.


COVID-19 Interpretable Diagnosis Algorithm Based on a Small Number of Chest X-Ray Samples.
The COVID-19 medical diagnosis method based on individual's chest X-ray (CXR) is achieved difficultly in the initial research, owing to difficulties in identifying CXR data of COVID-19 individuals. At the beginning of the study, infected individuals' CXRs were scarce. The combination of artificial intelligence and medical diagnosis has been advanced and popular. To solve the difficulties, the interpretability analysis of AI model was used to explore the pathological characteristics of CXR samples infected with COVID-19 and assist medical diagnosis. The dataset was expanded by data augmentation to avoid overfitting. Transfer learning was used to test different pre-trained models and the unique output layers were designed to complete the model training with few samples. In this study, the output results of four pre-trained models were compared in three different output layers, and the results after data augmentation were compared with the results of the original dataset. The control variable method was used to conduct independent tests of 24 groups. Finally, 99.23% accuracy and 98% recall rate were obtained, and the visual results of CXR interpretability analysis were displayed. The network of COVID-19 interpretable diagnosis algorithm has the characteristics of high generalization and lightweight. It can be quickly applied to other urgent tasks with insufficient experimental data. At the same time, interpretability analysis brings new possibilities for medical diagnosis.


Barriers to care among people with schizophrenia attending a tertiary psychiatric hospital in Nigeria.
Individuals with schizophrenia in low- and middle-income countries and their caregivers face multiple barriers to care-seeking and continuous engagement with treatment services. Identifying specific barrier patterns would aid targeted interventions aimed at improving treatment access. The aim of this study was to determine stigma- and non-stigma-related barriers to care-seeking among persons with schizophrenia in Nigeria. This study was conducted at the Outpatient Clinics of the Federal Neuro-Psychiatric Hospital, Benin City, Nigeria. A cross-sectional study of a dyad of persons with schizophrenia and caregivers (n = 161) attending outpatient services at a neuro-psychiatric hospital in Nigeria. Stigma- and non-stigma-related barriers were assessed using the 30-item Barriers to Access to Care Evaluation (BACE) scale. Lack of insight, preference for alternative care, illness severity and financial constraints were common barriers to care-seeking among persons with schizophrenia. Females were significantly more likely to report greater overall treatment barrier (p < 0.01) and stigma-related barriers (p < 0.02). This study shows that attitudinal barriers impede care access and engagement among persons with schizophrenia in Nigeria.


Optic disc and peripapillary morphology in unilateral nonarteritic anterior ischemic optic neuropathy and age- and refraction-matched normals.
To compare optic disc morphologic features and peripapillary retinal nerve fiber layer (RNFL) thickness between the unaffected eyes of patients with unilateral nonarteritic anterior ischemic optic neuropathy (NAION) and their affected eyes and the eyes of age- and refraction-matched normal control subjects. Cross-sectional comparative study. Thirty-one patients with unilateral NAION and 62 age- and refraction-matched normal control subjects. Optic disc morphologic features and peripapillary RNFL thickness were evaluated in both eyes of patients with unilateral NAION and in one randomly chosen eye of the normal control subjects. Optic disc and cup parameters were measured using the Heidelberg Retina Tomograph II (Heidelberg Engineering GmbH, Dossenheim, Germany), and RNFL thickness was measured by scanning laser polarimetry with variable corneal compensation (GDx VCC; Carl Zeiss Meditec, Dublin, CA). There was no significant difference in the disc area between the NAION affected eyes and the unaffected fellow eyes. The cup area, cup-to-disc area ratio, cup volume, and cup shape measure were greater, whereas the peripapillary RNFL thickness was smaller in the former than the latter (P = 0.001 to approximately 0.043). When the unaffected eyes of patients with NAION and the age- and refraction-matched normal control eyes were compared, the disc area, cup area, cup-to-disc area ratio, cup volume, mean cup depth, and cup shape measure were smaller in the former (P = 0.0006 to approximately 0.03); there was no significant difference in the RNFL thickness between the two (P>0.06). A comparison of the eyes with NAION and the fellow eyes indicated that the cup was slightly larger in the former than in the latter, suggesting the acquired enlargement of the cupping after NAION develops. A comparison of the unaffected fellow eyes in patients with NAION and the age- and refraction-matched normal control eyes suggested that a smaller disc area and smaller cupping were predisposing risk factors for the development of NAION.


Development of cholesteryl peptide micelles for siRNA delivery.
Despite the rapid progress in the siRNA field, developing a safe and efficient delivery system of siRNA remains to be an obstacle in the therapeutical application of siRNA. The purpose of this study is to develop an efficient peptide-based siRNA delivery system for cancer therapy. To this end, cholesterol was conjugated to a series of peptides composed of lysine and histidine residues. The resultant cholesteryl peptides were characterized, and their potential for siRNA delivery was evaluated. Our results indicate that short peptides (11-21 mer) composed of various numbers of lysine and histidine residues alone are not sufficient to mediate efficient siRNA delivery. However, the amphiphilic cholesteryl peptides can self-assemble to form a micelle-like structure in aqueous solutions, which significantly promotes the siRNA condensation capability of the peptides. The cholesteryl peptides form stable complex with siRNA and effectively protect siRNA from degradation in rat serum up to three days. Furthermore, the cholesteryl peptides efficiently transfect siRNA into different cancer cells and trigger potent gene silencing effect, whereas peptides without cholesterol modification cannot deliver siRNA into the cells. In addition, one of the cholesteryl peptides Chol-H3K2s displays comparable cellular uptake and gene silencing effect but less cytotoxicity compared with branched polyethylenimine (bPEI) and Lipofectamine-2000. Our results reveal that the cholesteryl peptides possess great potential as an efficient siRNA delivery system.


Induction of labor and cervical ripening with oral PGE2 in risk pregnancies. A placebo-controlled study.
A double-blind, placebo-controlled study was undertaken to evaluate the priming effect on the cervix and also the effect on the subsequent induction of labor. 0.5 mg oral PGE2 or placebo was given hourly for two 12-h periods. A total of 191 women with risk pregnancies and Bishop score less than or equal to 5 were studied. The induction of labor was carried out with oxytocin or oral PGE2 in a randomized manner. Labor was induced in 39% of the women during the PGE2 priming. The best result, 71% vaginal deliveries, was achieved with the combination of PGE2 priming and induction of labor with oxytocin.


Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel.
Flux-dependent inactivation that arises from functional coupling between the inner gate and the selectivity filter is widespread in ion channels. The structural basis of this coupling has only been well characterized in KcsA. Here we present NMR data demonstrating structural and dynamic coupling between the selectivity filter and intracellular constriction point in the bacterial nonselective cation channel, NaK. This transmembrane allosteric communication must be structurally different from KcsA because the NaK selectivity filter does not collapse under low-cation conditions. Comparison of NMR spectra of the nonselective NaK and potassium-selective NaK2K indicates that the number of ion binding sites in the selectivity filter shifts the equilibrium distribution of structural states throughout the channel. This finding was unexpected given the nearly identical crystal structure of NaK and NaK2K outside the immediate vicinity of the selectivity filter. Our results highlight the tight structural and dynamic coupling between the selectivity filter and the channel scaffold, which has significant implications for channel function. NaK offers a distinct model to study the physiologically essential connection between ion conduction and channel gating.


Riddles in the dark: Decoding the relationship between neuromelanin and neurodegeneration in locus coeruleus neurons.
The noradrenergic locus coeruleus (LC) is among the first regions of the brain affected by pathology in both Alzheimer's disease (AD) and Parkinson's disease (PD), but the reasons for this selective vulnerability are not completely understood. Several features of LC neurons have been proposed as contributing factors to this dysfunction and degeneration, and this review will focus on the presence of neuromelanin (NM). NM is a dark pigment unique to catecholaminergic cells that is formed of norepinephrine (NE) and dopamine (DA) metabolites, heavy metals, protein aggregates, and oxidated lipids. We cover what is currently known about NM and the limitations of historical approaches, then discuss the new human tyrosinase (hTyr) model of NM production in rodent catecholamine cells in vivo that offers unique opportunities for studying its neurobiology, neurotoxicity, and potential of NM-based therapeutics for treating neurodegenerative disease.


[Sequential MRI imaging of progressive bilateral rostro-caudal medullary infarction].
Bilateral medial medullary infarction is exceptional. Initial symptoms can be misleading, even for a trained neurologist. We report two patients who presented progressive quadriplegia, anarthia and dysphagia. Sequential MRI showed progressive constitution of the characteristic "heart appearance" sign.


[Placental site trophoblastic tumor of the uterus after in vitro fertilization. A case report with initial vaginal metastasis].
We report the first case of placental site trophoblastic tumor following in vitro fertilization. A 32-year-old woman presented with a vaginal polyp diagnosed 11 months after a successful fertilization, resulting in the delivery of a term male baby, but followed by persistent amenorrhea. The diagnosis of PSTT was done on examination of the vaginal polyp and the curettage specimen and was confirmed after hysterectomy. The patient was well 30 months later. The value of initial metastases limited to the pelvis and the role of in vitro fertilization in the pathogenesis of the tumor are discussed.


It's what's inside that counts: egg contaminant concentrations are influenced by estimates of egg density, egg volume, and fresh egg mass.
In egg contaminant studies, it is necessary to calculate egg contaminant concentrations on a fresh wet weight basis and this requires accurate estimates of egg density and egg volume. We show that the inclusion or exclusion of the eggshell can influence egg contaminant concentrations, and we provide estimates of egg density (both with and without the eggshell) and egg-shape coefficients (used to estimate egg volume from egg morphometrics) for American avocet (Recurvirostra americana), black-necked stilt (Himantopus mexicanus), and Forster's tern (Sterna forsteri). Egg densities (g/cm(3)) estimated for whole eggs (1.056 ± 0.003) were higher than egg densities estimated for egg contents (1.024 ± 0.001), and were 1.059 ± 0.001 and 1.025 ± 0.001 for avocets, 1.056 ± 0.001 and 1.023 ± 0.001 for stilts, and 1.053 ± 0.002 and 1.025 ± 0.002 for terns. The egg-shape coefficients for egg volume (K v ) and egg mass (K w ) also differed depending on whether the eggshell was included (K v = 0.491 ± 0.001; K w = 0.518 ± 0.001) or excluded (K v = 0.493 ± 0.001; K w = 0.505 ± 0.001), and varied among species. Although egg contaminant concentrations are rarely meant to include the eggshell, we show that the typical inclusion of the eggshell in egg density and egg volume estimates results in egg contaminant concentrations being underestimated by 6-13 %. Our results demonstrate that the inclusion of the eggshell significantly influences estimates of egg density, egg volume, and fresh egg mass, which leads to egg contaminant concentrations that are biased low. We suggest that egg contaminant concentrations be calculated on a fresh wet weight basis using only internal egg-content densities, volumes, and masses appropriate for the species. For the three waterbirds in our study, these corrected coefficients are 1.024 ± 0.001 for egg density, 0.493 ± 0.001 for K v , and 0.505 ± 0.001 for K w .


Information Needs in Higher Education Institutions: Stock Valuation or Decision-Making?
Numerous higher education institutions apply a full costing system in their accounting model due to the imposition of formal agents (governments/funding institutions), or by suggestion of informal agents (associations). This paper analyzes whether the rationale applied by these agents to justify the use of the full costing rather than the direct/variable system is consistent with the theoretical bases underlying both costing systems. Methodologically, we review the mainstream literature that explores the links between the management accounting model and the use of its informative outcomes for the decision-making in higher education institutions. We conclude that there exists a gap between the theory-based statements and the information needs of these institutions. Remarkably, the full costing system falls short of adequateness for these institutions, which need information for their managerial decision-making process rather than for other industries' decisions such as stock valuation. Thus, this paper contributes to a critical view on the use of full costing systems and calls for redirecting current practices towards other more effective partial costing systems. Our findings have implications for academic, managers and policymakers interested on the implementation and improvement of managerial accounting in public higher education institutions.


Giant moving vortex mass in thick magnetic nanodots.
Magnetic vortex is one of the simplest topologically non-trivial textures in condensed matter physics. It is the ground state of submicron magnetic elements (dots) of different shapes: cylindrical, square etc. So far, the vast majority of the vortex dynamics studies were focused on thin dots with thickness 5-50 nm and only uniform across the thickness vortex excitation modes were observed. Here we explore the fundamental vortex mode in relatively thick (50-100 nm) dots using broadband ferromagnetic resonance and show that dimensionality increase leads to qualitatively new excitation spectra. We demonstrate that the fundamental mode frequency cannot be explained without introducing a giant vortex mass, which is a result of the vortex distortion due to interaction with spin waves. The vortex mass depends on the system geometry and is non-local because of important role of the dipolar interaction. The mass is rather small for thin dots. However, its importance increases drastically with the dot thickness increasing.


Outcome of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Patients With Intermediate SYNTAX II Score.
Patients with intermediate SYNTAX II score have been representing a confusion in our daily practice for interventional cardiologists whether to treat them by percutaneous coronary intervention (PCI) using second generation drug eluting stents or by coronary artery bypass grafting (CABG). We enrolled 214 consecutive patients with intermediate SYNTAX II score to undergo revascularization (109 patients underwent PCI and 105 patients underwent CABG) after Heart Team discussion. We compared both procedures with respect to the primary composite end point of major adverse cardiac or cerebrovascular events (all-cause mortality, myocardial infarction, target vessel revascularization or stroke) at 40 months post procedure. At 40 months post revascularization procedure, the primary end-point occurred in 22 patients and 15 patients in the PCI and CABG groups, respectively (hazard ratio, 1.65; 95% confidence interval, 0.87-3.14; P = 0.13). No significant differences were detected between both groups regarding the composite incidence of all-cause mortality, myocardial infarction, target vessel revascularization, and stroke. CABG significantly provided better quality of life than PCI for patients with intermediate SYNTAX II score. In patients with intermediate SYNTAX II score, there was no statistically significant difference between the PCI using second generation drug eluting stents and CABG with respect to the incidence of MACCE at 40 months post revascularization procedure.


Subgradient ellipsoid method for nonsmooth convex problems.
In this paper, we present a new ellipsoid-type algorithm for solving nonsmooth problems with convex structure. Examples of such problems include nonsmooth convex minimization problems, convex-concave saddle-point problems and variational inequalities with monotone operator. Our algorithm can be seen as a combination of the standard Subgradient and Ellipsoid methods. However, in contrast to the latter one, the proposed method has a reasonable convergence rate even when the dimensionality of the problem is sufficiently large. For generating accuracy certificates in our algorithm, we propose an efficient technique, which ameliorates the previously known recipes (Nemirovski in Math Oper Res 35(1):52-78, 2010).


Stem cells in natural product and medicinal plant drug discovery-An overview of new screening approaches.
Natural products remain a rich source of new drugs, and the search for bioactive molecules from nature continues to play an important role in the development of new medicines. Also, there is increasing use of herbal medicines for the treatment of a plethora of diseases, and demands for more scientific evidence for their efficacy and safety remains a huge challenge. The propensity of stem cells to differentiate into almost every cell type not only holds promise for the delivery of cell-based therapies for currently incurable diseases or a useful tool in studying cell physiology and pathophysiology. Increasingly, stem cells are becoming an important tool in preclinical drug screening and toxicity testing. In this review, we examine the scientific advances made towards the use of pluripotent stem cells as a model for the screening of plant-based medicines. The combination of well-established in vitro electrophysiological and a plethora of toxicogenomic technologies, together with the optimisation of culture methods of herbal plants and pluripotent stem cells can be explored to establish the basis for efficacy, and tissue/organ-based toxicities of many currently used medicinal plants whose efficacies and toxicities remain unknown.


Decreased peripheral dendritic cell numbers in dengue virus infection.
Laboratory predictors of severe forms of dengue virus (DENV) infection are needed. These clinical forms seem to be associated with high viremia, stressing the importance of immune responses, which could involve dendritic cells (DC). Yet, very few studies have evaluated DC after DENV infection. We assessed peripheral blood DC subset numbers in mild and severe forms of dengue in 44 patients, older than 15 years old, infected with serotypes DENV-2, 3 or 4. Patients were divided in high, intermediate and no detectable viremia according to results of molecular biology amplification of DENV. Serological status of anti-DENV IgG or IgM determined primary or secondary infections. Plasmacytoid and myeloid DC absolute and relative numbers were reduced in infected patients when compared to an age-matched healthy control group, but no significant differences in DC numbers were observed between mild or severe forms of disease. A severe disease was more frequent in patients infected with DENV-2 serotype and with secondary infection but no significant differences in DC subset numbers were found related to these variables. Viremia levels did not correlate to disease severity yet were associated to lower DC numbers. Plasmacytoid DC numbers were significantly lower in high and intermediate viremia groups compared to non-infected controls, but not in no detectable viremia patients. Myeloid DC numbers were also significantly lower than controls, even in no detectable viremia patients. These results confirm that circulating DC subset numbers are reduced after DENV infection, although this is not a biomarker of severe forms of dengue in adults.


The effects of ultraviolet and ionizing radiation on herpesviruses, SV40 and adenoviruses in relation to the small-plaque effect.
The small-plaque effect occurs with a wide range of herpesviruses following irradiation with ultraviolet light. The 37 per cent survival (D37) values, or dose required for one lethal hit (e-1), for herpes simplex, pseudorabies and pigeon herpesviruses in different cells indicate a broad spectrum of host-cell repair capacity. Other DNA-containing viruses such as SV40 and adenoviruses, which also replicate in the cell nucleus, show the small-plaque effect. Ionizing irradiation of herpes simplex virus type 1 (HSV-1) showed but little reduction in plaque-size.


Copper (II)-ploy-L-histidine functionalized multi walled carbon nanotubes as efficient mimetic enzyme for sensitive electrochemical detection of salvianic acid A.
In this work, carboxylated multi walled carbon nanotubes (CMWCNTs) were firstly prepared and functionalized with poly-L-histidine (PLH), which were then chelated with copper (II) ions to from the nanocomposites of Cu(II)-PLH-CMWCNTs. The nanocomposites could be exploited as an efficient mimic enzyme for sensitive electrochemical detection of salvianic acid A (SAA). Cu(II)-PLH-CMWCNTs owned good charge transfer property and excellent synergetic catalytic effect between the overoxidized imidazole groups and the copper redox-active units. Therefore, highly sensitive electrochemical response to SAA was achieved under optimum experimental conditions. A good linear relationship between differential pulse voltammetry (DPV) peak current and the SAA concentration was established in the range of 0.4-1000 μM. A low detection limit of 0.037 μM and a sensitivity of 0.27 μA μM-1 cm-2 were achieved. The developed biosensor also had advantages of good repeatability, stability and high selectivity, thus, it was successfully applied to the determination of SAA in real samples with satisfactory results, which may have great potential for further exploitation of electroanalysis applications.


Beneficial effects of ginsenosides on diabetic nephropathy: A systematical review and meta-analysis of preclinical evidence.
Ginseng is one of the most widely used herbs in the world for the treatment of various diseases, and ginsenoside is the representative bioactive component in ginseng. There have been many in vivo studies on ginsenoside for the treatment of diabetic nephropathy (DN), the most common diabetic microvascular complication and the main cause of diabetic morbidity and mortality. The purpose of this study is to evaluate the efficacy of ginsenosides on DN by preclinical evidence and meta-analysis. Meanwhile, the main possible action mechanisms of ginsenosides against DN were also summarized. We systematically searched PubMed, WOS, Embase, Cochrane, WanFang, Cqvip, CNKI and CBM databases from January 1, 2000, to November 15, 2021, to evaluate the animal experiments of ginsenosides for the treatment of DN. Finally, 30 animal experiments were included. Twelve outcome measures, including renal function indicators (24-h urine protein, serum creatinine, urea nitrogen, creatinine clearance, uric acid, urinary albumin to creatinine ratio), oxidative stress biomarkers (GPX, MDA, SOD), inflammatory factors (IL-1, IL-6, TNF-α) were obtained by using RevMan 5.4 software for meta-analysis. The results showed that except for no significant difference in CCr, other indicators such as 24h UP, SCr, blood urea nitrogen, uric acid and UACR were significantly decreased. It showed that ginsenoside could improve renal function in diabetes. Meanwhile ginsenoside significantly up-regulated antioxidant enzymes SOD and GPX, down-regulated MDA and inflammatory factors IL-1, IL-6 and TNF-α, indicating that ginsenoside may have antioxidant and anti-inflammatory effects. Ginsenoside can protect against the renal failure in diabetes through anti-inflammation, anti-oxidation, anti-renal fibrosis, anti-apoptosis/pyroptosis, regulation of blood glucose/lipid metabolism, etc. Which provides preclinical evidence for the application of ginsenoside in the treatment of DN.


Safety of Contrast Material Use During Pregnancy and Lactation.
The use of contrast media to image patients who are pregnant has increased during the past decades worldwide. Their use in pregnancy and in patients who are lactating remains a challenging issue for radiologists and other physicians. This article addresses the different types of contrast media that may be used in such patients according to the imaging modality (iodinated contrast media, barium, gadolinium-based, and ultrasound contrast agents), focusing on their adverse effects, potential teratogenic effects, strategies to minimize risks, and current clinical recommendation.


Calbindin-D28k immunoreactivity in the spinal cord of Xenopus laevis and its participation in ascending and descending projections.
Immunohistochemistry for calbindin-D28k (CB) revealed that the spinal cord of Xenopus laevis possess a large number of CB-containing neurons widely distributed in both the dorsal and ventral horns, including areas which possess long ascending projections to supraspinal structures. In addition, the presence of CB-immunoreactive axons in the spinal funiculi suggested that descending projections containing this calcium binding protein may originate in different brainstem nuclei. Apart from mapping CB-containing elements in the spinal cord, a double labeling approach was used that combined the retrograde transport of dextran amines with CB immunohistochemistry. Thus, dextran amine injections into the lateral reticular region of the rhombencephalon, the parabrachial region, the mesencephalon and the dorsal thalamus revealed many retrogradely labeled cells in the spinal cord, a few number of which were double labeled for CB and found in the superficial dorsal horn and in the ventral medial region of the ventral horn. Their axons passed mainly via the lateral funiculus. Tracer application into the cervical spinal cord, combined with CB immunohistochemistry, resulted in retrogradely labeled cells throughout the brain, five groups of which showed CB immunoreactivity: (1) the mesencephalic trigeminal nucleus, (2) the laterodorsal tegmental nucleus, (3) the raphe nucleus, (4) the middle reticular nucleus and (5) the inferior reticular nucleus. The presence of CB in spinal pathways suggests that CB may play a role in controlling spinal cells, mainly subserving visceroceptive and nociceptive information to supraspinal levels, and might also modulate reticulospinal pathways.


Effect of bevacizumab on intracranial meningiomas in patients with neurofibromatosis type 2 - a retrospective case series.
The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS). Approximately 80% of NF2 patients also have intracranial meningiomas. Vascular endothelial growth factor (VEGF) is expressed in both NF2-related and sporadic occurring meningiomas and anti-VEGF therapy (bevacizumab) may, therefore, be beneficial in NF2-related meningiomas. The purpose of the study was to report the effect of bevacizumab on meningiomas in NF2 patients. We retrospectively reviewed the effect of bevacizumab on the cross-sectional area (CSA) of 14 intracranial meningiomas in 7 NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every two weeks for six months and 15 mg/kg every three weeks thereafter. Patients were evaluated according to the modified Macdonald criteria with repeated magnetic resonance (MR) scans. The median duration of therapy was 27 months (range 16-34) and 42 MR scans (median 8, range 4-11) were reviewed. The median annual change in meningioma CSA prior to bevacizumab was 2% (range -4%-+76%). During treatment, a decrease in meningioma CSA was observed in 5 of 14 meningiomas (36%) in 5 of 7 patients (71%). The median decrease in CSA was -10% (range -3%--25%). One meningioma (7%) progressed and the remaining (93%) had stable disease. Bevacizumab may slow or reverse the growth of some NF-related meningiomas. However, we have previously reported a fatal case of intracerebral hemorrhage following bevacizumab in NF2 patients, wherefore, this effect needs to be balanced carefully against the risk of side effects.


Signaling systems, guided cell migration, and organogenesis: insights from genetic studies in Drosophila.
During development, cells change their position extensively. Although the basic cellular mechanisms involved in cell locomotion have been studied mostly in cultured cells, genetic and molecular approaches using model organisms are starting to shed light on the complex events influencing cell migration during development. Recent technical advances in following and analyzing migrating cells inside the living embryo offer the possibility of understanding how different signaling systems regulate the fundamental cellular processes underlying guided cell migration in vivo. In Drosophila melanogaster, studies of migrating cells have concentrated mainly on hemocytes, germ cells, border cells, and tracheal cells. Interestingly, most of these cells were recently shown to make different cellular extensions and to use receptor tyrosine kinases to sense the chemoattractive signal. This review describes our current understanding of how different signaling networks control guided migration in these four systems and discusses the impact of novel imaging techniques on the study of guided cell migration during development.


Modulation of lipopolysaccharide-induced proinflammatory cytokine production in vitro and in vivo by the herbal constituents apigenin (chamomile), ginsenoside Rb(1) (ginseng) and parthenolide (feverfew).
Dietary supplements are not subject to the same pre-market approval as conventional drugs, thus the true efficacy and, in cases, safety of these products is not known. The objective of this study was to evaluate the potential anti-inflammatory properties of three herbal constituents, apigenin (chamomile), ginsenoside Rb(1) (ginseng) and parthenolide (feverfew) on lipopolysaccaharide (LPS)-induced proinflammatory cytokine production, and to determine if effects in cell culture could predict results in an intact animal model. Murine macrophage cells and mice were treated with the stimulant LPS and herbal constituents, and resultant culture supernatant and serum, respectively, were evaluated for interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha by ELISA. All three constituents inhibited LPS-induced IL-6 and/or TNF-alpha production in culture. Inhibition of these two cytokines was observed in mice, but did not display the same patterns of inhibition as cell culture data. The results suggest that all three constituents possessed anti-inflammatory properties, but that cell culture data can only be used to approximate potential effects in animals, and must be confirmed using appropriate animal models.


Chemical profiles of mated and virgin queens, egg-laying intermorphs and workers of the ant Crematogaster smithi.
Many colonies of the North American ant Crematogaster smithi contain a "third female caste" in addition to queens and workers. These "intermorphs" are morphological intermediate of queens and workers and have well-developed ovaries but lack a spermatheca for the storage of sperm. They are specialised for laying large numbers of unfertilised, viable eggs, most of which serve as food for larvae and adults, though a few may eventually develop into males. Based on the assumption that cuticular hydrocarbons (CHCs) in social insects honestly signal the reproductive status of an individual we investigated the CHC of mated mature queens, virgin queens, intermorphs and workers. We expected intermorphs to show chemical profiles intermediate between those of mated queens and non-reproductive workers. A discriminant analysis of the chemical profiles reliably separated queens, virgin queens, and workers, but failed to distinguish between queens and intermorphs even though workers were apparently capable of doing so.


Low dose epidural morphine does not affect non-nociceptive spinal reflexes in patients with postoperative pain.
In order to determine the selectivity of the antinociceptive effect of epidural morphine, the electrophysiological features of a monosynaptic reflex were investigated before and after epidural morphine (2-3 mg) required for pain relief, in 4 patients suffering from postoperative pain. The reflex tested was the H reflex from the soleus muscle. Not only the classical Hmax/Mmax ratio, but also the threshold and the slope of the rising phase of the recruitment curve of H and M responses were analyzed. It was found that epidural morphine did not change significantly any of these parameters, at least during the 60 min post-injection period. By contrast, as usually observed clinically, epidural morphine produced an onset of pain relief by the 25th-30th min following injection. These data support the hypothesis that epidural morphine produced a 'selective spinal analgesia in man.'


Synthesis, antimicrobial and antioxidant activity of triazole, pyrazole containing thiazole derivatives and molecular docking studies on COVID-19.
New series of biologically active triazole and pyrazole compounds containing 2, 4-disubstituted thiazole analogues (12a-l) were synthesized from p-hydroxy benzaldehyde and phenyl hydrazine in excellent yields and purity. All the synthesized compounds were unambiguously identified based on their spectral data analyses (IR, 1H-NMR, 13C-NMR spectra, and HRMS). The final derivatives were evaluated for their in vitro anti-microbial activity after thorough purification. Among all the tested compounds, the compound 12e, 12f and 12 k possess the highest growth inhibitory activity at MIC values of 4.8, 5.1 and 4.0 μg/ml respectively. The antioxidant properties of these compounds demonstrated and revealed remarkable activity compared to the standard antioxidant by using the DPPH free radical-scavenging assay. Moreover, molecular docking studies to evaluate the probable interactions with the catalytic domain of the gram-positive S. aureus topoisomerase IV enzyme may provide new insights for developing these new hybrids as potential antimicrobial agents. The binding affinities of compounds 12a-l were ranging from - 10.0 to - 11.0 kcal/mol with topoisomerase IV enzyme and with COVID-19 main protease binding affinities are ranging from - 8.2 to - 9.3 kcal/mol. These docking studies reveal that the compounds 12a-l could be the best inhibitors for the novel SARS Cov-2 virus and have more future in discovery of potent drug candidates.


Atomimetic Mechanical Structures with Nonlinear Topological Domain Evolution Kinetics.
A mechanical metamaterial, a simple, periodic mechanical structure, is reported, which reproduces the nonlinear dynamic behavior of materials undergoing phase transitions and domain switching at the structural level. Tunable multistability is exploited to produce switching and transition phenomena whose kinetics are governed by the same Allen-Cahn law commonly used to describe material-level, structural-transition processes. The reported purely elastic mechanical system displays several key features commonly found in atomic- or mesoscale physics of solids. The rotating-mass network shows qualitatively analogous features as, e.g., ferroic ceramics or phase-transforming solids, and the discrete governing equation is shown to approach the phase field equation commonly used to simulate the above processes. This offers untapped opportunities for reproducing material-level, dissipative and diffusive kinetic phenomena at the structural level, which, in turn, invites experimental realization and paves the road for new active, intelligent, or phase-transforming mechanical metamaterials bringing small-scale processes to the macroscopically observable scale.


Do quantitative and qualitative shear wave elastography have a role in evaluating musculoskeletal soft tissue masses?
To determine if quantitative and qualitative shear wave elastography have roles in evaluating musculoskeletal masses. 105 consecutive patients, prospectively referred for biopsy within a specialist sarcoma centre, underwent B-mode, quantitative (m/s) and qualitative (colour map) shear wave elastography. Reference was histology from subsequent biopsy or excision where possible. Statistical modelling was performed to test elastography data and/or B-mode imaging in predicting malignancy. Of 105 masses, 39 were malignant and 6 had no histology but benign characteristics at 12 months. Radiologist agreement for B-mode and elastography was moderate to excellent Kw 0.52-0.64; PABAKw 0.85-0.90). B-Mode imaging had 78.8% specificity, 76.9% sensitivity for malignancy. Quantitatively, adjusting for age, B-mode and lesion volume there was no statistically significant association between longitudinal velocity and malignancy (OR [95% CI] 0.40[0.10, 1.60], p=0.193), but some evidence that higher transverse velocity was associated with decreased odds of malignancy (0.28[0.06, 1.28], p=0.101). Qualitatively malignant masses tended to be towards the blue spectrum (lower velocities); 39.5% (17/43) of predominantly blue masses were malignant, compared to 14.3% (1/7) of red lesions. Quantitatively and qualitatively there is no statistically significant association between shear wave velocity and malignancy. There is no clear additional role to B-mode imaging currently. • Correlation between shear wave velocity and soft tissue malignancy was statistically insignificant • B-mode ultrasound is 76.9 % sensitive and 78.8 % specific • Statistical models show elastography does not significantly add to lesion assessment.


Unexpected capacity for organic carbon assimilation by Thermosynechococcus elongatus, a crucial photosynthetic model organism.
Genetic modification of key residues of photosystems is essential to identify functionally crucial processes by spectroscopic and crystallographic investigation; the required protein stability favours use of thermophilic species. The currently unique thermophilic photosynthetic model organism is the cyanobacterial genus Thermosynechococcus. We report the ability of Thermosynechococcus elongatus to assimilate organic carbon, specifically D-fructose. Growth in the presence of a photosynthesis inhibitor opens the door towards crucial amino acid substitutions in photosystems by the rescue of otherwise lethal mutations. Yet depression of batch-culture growth after 7 days implies that additional developments are needed.


The vascular prosthesis without pseudointima prepared by antithrombogenic phospholipid polymer.
On the luminal surface of the common synthetic vascular prostheses, blood coagulation can occur and a thrombus membrane is formed when blood flow passes through it. The thrombus membrane should be organized according to the wound healing process and it becomes a pseudointima which could serve as a blood conduit. However, the small-diameter vascular prosthesis may be quickly occluded by the initial thrombus. Therefore, no clinically applicable small-diameter prostheses have been developed to date. 2-Methacrylovloxyethyl phosphoryleholine (MPC) polymers resemble the structure of an outer cell membrane similar to the fluid mosaic model and demonstrate excellent antithrombogenicity. The purpose of this study is to develop a clinically applicable small-diameter prosthesis based on the new concept of the MPC polymer. We prepared vascular prostheses (2mm ID) from polymer blend composed of segmented polyurethane and the MPC polymer. The prostheses were placed in rabbit carotid arteries. The luminal surface retrieved at eight weeks after implantation was clear without thrombus and pseudointima. We now realize that the vascular prosthesis having the MPC polymer can be applied as a small-diameter prosthesis because it functions without thrombus and pseudointima formation.


Visual loss and perimetric sensitivity in eyes with retinitis pigmentosa.
To investigate the various perimetric parameters that best predict reduction of best-corrected visual acuity (BCVA) to worse than 0.5 in the near future in eyes with retinitis pigmentosa (RP). The most recent records obtained by Humphrey Field Analyzer (HFA) central 10-2 perimetry were studied for the right eyes of 123 patients (60 men and 63 women) with typical RP. The correlation between various parameters of perimetric sensitivity and BCVA was retrospectively studied. The receiver operating characteristic (ROC) curves were used to find the best parameter to discriminate eyes with BCVA ≥0.5 from those with BCVA <0.5. Spearman rank correlation coefficients with logMAR BCVA were the highest for the foveal threshold (FT) and mean sensitivity of the test points within 1.4° of the fixation point (MS1.4). The ROC curve analysis revealed that the area under the curve was the largest for the MS1.4 among all the perimetric parameters for discriminating eyes with BCVA ≥0.5 from those with BCVA <0.5. The cutoff value of 30 dB showed 100 % specificity and 57 % sensitivity. The risk of vision decreasing below 0.5 in the near future may be predicted when the mean sensitivity within 1.4° of the fixation point in the HFA 10-2 reaches 30 dB in eyes with RP.


Smoking cessation, clonidine, and vulnerability to nicotine among dependent smokers.
This study examines the efficacy of clonidine in smoking cessation and the influence of gender, history of major depression, and measures of nicotine dependence. The study was designed as a 10-week double-blind randomized comparison stratified for gender and major depression. Three hundred subjects who smoked cigarettes heavily were enrolled in the study. Abstinence from smoking was evaluated by self-report and verified by serum cotinine levels. Gender, major depression recurrent type, and measures of nicotine addiction were risk factors for treatment failure. There was no clonidine effect in men, but there was a modest effect in women (odds ratio, 2.01; 95% confidence interval, 1.00 to 4.10) that was most pronounced (odds ratio, 8.5; 95% confidence interval, 1.67 to 43.62) among women with the highest risks. Measures of addiction and major depression predict treatment failure. Together they are stronger predictors of outcome than drug. Clonidine is a limited aid in cessation, and drug effects come primarily from women at high risk for treatment failure. An increased risk for psychiatric complications after smoking cessation was apparent among smokers with histories of major depression, particularly bipolar disease.


Influenza A virus (H1N1) increases airway epithelial cell secretion by up-regulation of potassium channel KCNN4.
Influenza infects the epithelial cells lining the airways. Normally epithelial cells move solutes through ion channels to create the osmotic drive to hydrate the airways. Viral alteration of this process could explain, in part, the fluid imbalance in the lungs and the resulting pulmonary edema that occurs during severe influenza infections. Using western blot and RT-qPCR, we measured ion channel and cytokine expression in the Calu3 airway cell line after infection with influenza virus (H1N1) for 48 h. We simultaneously measured chloride and potassium channel function by means of a short-circuit current (I(sc)) produced in an Ussing chamber. At a multiplicity of infection (MOI) of 10, viral M1 protein and pro-inflammatory cytokine expression was observed 24h post-infection, despite a lack of measurable change in Isc. However, we observed a decreased secretory response in cAMP- and calcium-induced Isc 48 h post-infection. This correlated with a decrease in CFTR and KCNN4 protein levels. Interestingly, a viral dose of an MOI 0.6 revealed an increased secretory response that correlated with pro-inflammatory cytokine expression. This increased secretory response seemed to be primarily driven through KCNN4. We detected an increase in KCNN4 mRNA and protein, while CFTR function and expression remained unchanged. Furthermore, inhibition of the KCNN4-stimulated I(sc) with TRAM-34, a specific inhibitor, ameliorated the response, implicating KCNN4 as the main driving force behind the secretory phenotype.


Single cells and rapid inward sodium current.
This chapter presents a brief review of measurements of rapid inward sodium current in single cardiac cells. It is shown that the simplified morphology of the individual cells, with a lack of restricted extracellular space, has been exploited to provide improved spatial and temporal voltage control, resulting in the first recordings of both the activation and inactivation phases of rapid inward sodium current. It is to be expected that future research will produce much interesting data on this component of membrane current, which will have direct relevance to many processes concerned with cardiac function at the cellular level.


[Transcanalicular microendoscopic laser DCR: technique and results].
Transcanalicular microendoscopic diode laser DCR combined with 5-mm balloon dacryoplasty is an innovative procedure in lacrimal surgery. This procedure is minimally invasive and provides the possibility to fill the gap between the first step procedures (LDP, MDP) and external or internal DCR.


Interrelationships between the autonomic nervous system and atrial fibrillation.
Mechanisms responsible for atrial fibrillation are not completely understood but the autonomic nervous system is a potentially potent modulator of the initiation, maintenance, termination and ventricular rate determination of atrial fibrillation. Complex interactions exist between the parasympathetic and sympathetic nervous systems on the central, ganglionic, peripheral, tissue, cellular and subcellular levels that could be responsible for alterations in conduction and refractoriness properties of the heart as well as the presence and type of triggered activity, all of which could contribute to atrial fibrillation. These dynamic inter-relationships may also be altered dependent upon other neurohumoral modulators and cardiac mechanical effects from ventricular dysfunction and congestive heart failure. The clinical implications regarding the effects of the autonomic nervous system in atrial fibrillation are widespread. The effects of modulating ganglionic input into the atria may alter the presence or absence of atrial fibrillation as has been highlighted from ablation investigations. This article reviews what is known regarding the inter-relationships between the autonomic nervous system and atrial fibrillation and provides state of the art information at all levels of autonomic interactions.


Chemical composition, antibacterial efficacy, and antioxidant capacity of essential oil and oleoresin from Monodora myristica and Tetrapleura tetraptera in Southeast Nigeria.
Specific to the West African sub-region, previous studies involving fruit, stem, and bark of Tetrapleura tetraptera as well as seeds of Monodora myristica have largely focused on phytochemical properties of aqueous and methanolic and ethanolic extracts. To supplement existing information, the chemical composition, antibacterial efficacy (tested against Escherichia coli and Staphylococcus aureus), and antioxidant capacity (1,1-diphenyl-2-picrylhydrazyl (DPPH∙) radical scavenging, ferric reducing power, and total antioxidant capacity) of essential oil and oleoresin extracted from T. tetraptera fruit and M. myristica seeds cultivated in Southeast Nigeria, were studied. Essential oil and oleoresin were respectively extracted by steam distillation and aqueous maceration. By way of gas chromatograph mass spectrometry (GC-MS) analysis, the chemical compounds from essential oil and oleoresin from M. myristica and T. Tetraptera samples totaled 6 and 5, as well as 27 and 16, respectively. Besides the oleoresin of M. myristica and the essential oil of T. tetraptera showing some resistance against S. aureus, the oleoresins seemed highly susceptible to E. coli-all of which demonstrated concentration-dependence to the antibacterial inhibition zone. Scavenging DPPH radical, reduction power activity, and total antioxidant capacity increased with essential oil and oleoresin extracts' concentrations, which positions M. myristica and T. tetraptera spices as very promising for food preservation, especially against autoxidation and microbial spoilage.


High AIECL performance of tetraphenylethene derivatives originated from the linear increasing of benzene ring and solvent regulation for sensitive measurement of melatonin.
The efficiency of aggregation-induced electrochemiluminescence (AIECL) in tetraphenylethene (TPE) derivatives were significantly enhanced by combining the regulation of molecular structure and solvent. Firstly, the linear increase of the benzene ring resulted in enhanced molecular aggregation and promoted the electrochemical reaction of the anode, due to increased molecular conjugation and higher lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO). The ECL efficiency of 4,4,4,4-(Ethene-1,1,2,2-tetrayl) tetrakis (([1,1,4,1-terphenyl]-4-carbaldehyde)) (T3) nanoparticles (NPs) with more benzene rings were 5558 times that of 4,4,4,4-(ethene-1,1,2,2-tetrayl) tetrabenzaldehyde (T1) NPs, and its relative ECL efficiency of T3 NPs reached 55.58% compared to the [Ru (bpy)3]2+/tripropylamine (TPrA) system. Furthermore, solvents with different polarities played a crucial role in modulating the degree of molecular aggregation, which also effectively facilitated the AIE process and reduced the aggregation-caused quenching (ACQ) effect caused by excessively dense aggregation. This aspect had often been overlooked in previous AIECL studies. T3 NPs demonstrated optimal ECL performance at fw = 70% (fw was the H2O content in tetrahydrofuran (THF)/H2O), and its ECL efficiency was 232 times greater than fw = 100% and 1853 times greater than fw = 0%. Additionally, it was found that melatonin (MT), one of the hormones widely used to treat insomnia, exhibited antioxidant and free radical scavenging properties, which exerted a significant quenching effect on the ECL of the T3 NPs/TPrA system. Consequently, a sensitive sensing platform was developed for MT with a low detection limit of 8.78 × 10-10 mol L-1, which promoted the application of AIECL in efficient ultra-sensitive biosensing.


Discrimination in hiring under the Americans with Disabilities Act: an overview of the National EEOC ADA Research Project.
This article is intended to provide an overview of the National EEOC ADA Research Project. It also previews four subsequent articles pertaining to the issue of hiring discrimination involving Americans with disabilities.


Collaborative eye tracking: a potential training tool in laparoscopic surgery.
Eye-tracking technology has been shown to improve trainee performance in the aircraft industry, radiology, and surgery. The ability to track the point-of-regard of a supervisor and reflect this onto a subjects' laparoscopic screen to aid instruction of a simulated task is attractive, in particular when considering the multilingual make up of modern surgical teams and the development of collaborative surgical techniques. We tried to develop a bespoke interface to project a supervisors' point-of-regard onto a subjects' laparoscopic screen and to investigate whether using the supervisor's eye-gaze could be used as a tool to aid the identification of a target during a surgical-simulated task. We developed software to project a supervisors' point-of-regard onto a subjects' screen whilst undertaking surgically related laparoscopic tasks. Twenty-eight subjects with varying levels of operative experience and proficiency in English undertook a series of surgically minded laparoscopic tasks. Subjects were instructed with verbal queues (V), a cursor reflecting supervisor's eye-gaze (E), or both (VE). Performance metrics included time to complete tasks, eye-gaze latency, and number of errors. Completion times and number of errors were significantly reduced when eye-gaze instruction was employed (VE, E). In addition, the time taken for the subject to correctly focus on the target (latency) was significantly reduced. We have successfully demonstrated the effectiveness of a novel framework to enable a supervisor eye-gaze to be projected onto a trainee's laparoscopic screen. Furthermore, we have shown that utilizing eye-tracking technology to provide visual instruction improves completion times and reduces errors in a simulated environment. Although this technology requires significant development, the potential applications are wide-ranging.


Fast pulse train control using filled-aperture coherent beam combining for high-average-power laser systems.
This study demonstrates fast pulse train switching using a coherent polarization beam combiner with a phase difference detection (PDD) algorithm. Based on the highly stable feedback control obtained with the PDD algorithm, stable burst-mode extraction with an arbitrary duty cycle was achieved with a contrast ratio of 800:1 for a third-harmonic light (347 nm) of a 5 MHz pulsed Yb-doped fiber laser. The proposed method can be effectively used for high-speed switching in high-average-power pulsed laser systems.


[Selective electric-current inhibition of signals from the C fibers in nerve fiber microbundles: a method for identifying A and C afferents].
Direct electric current of 3 microA applied through platinum electrode during 10 s to a fine strand teased mechanically from saphenous nerve, inhibits selectively C-fibre spikes in the strand and does not inhibit A-fiber spikes. The selective inhibition of C-fibers spikes in a fine strand is proposed as a method to identify a type of a single nerve fiber.


A reversible radioligand specific for the ETB receptor: [125I]Tyr13-Suc-[Glu9,Ala11,15]-endothelin-1(8- 21), [125I]IRL 1620.
Suc-[Glu9,Ala11,15]-endothelin(ET)-1(8-21), IRL 1620, is a linear ET-analog specific for the ET-isopeptide-nonselective ETB receptor. The radio-iodinated analog, [125I]IRL 1620, showed a single class of saturable binding to the ETB receptors in porcine lung membranes with a Kd of 18 pM and a Bmax of 930 fmol/mg protein, which are almost comparable to the values obtained with [125I]ET-3 (6 pM and 900 fmol/mg protein). In competitive binding assays with [125I]IRL 1620, unlabeled ET-1, ET-3, IRL 1620 and [monoiodo-Tyr13]-IRL 1620 showed almost identical displacement curves with Ki of 8 to 16 pM. However, [125I]IRL 1620 was dissociated from the binding sites by addition of an excess amount (100 nM) of any of these unlabeled peptides, each with the same t1/2 of 100 min. This was in marked contrast to [125I]ET-3 which was hardly dissociated from the binding sites.


A novel device for removal of the gastric remnant after intragastric balloon implantation for obesity.
A new system for endoscopic removal of a gastric prosthesis for treatment of obesity is presented. This technique permits rapid deflation of intragastric balloons as well as safe endoscopic removal of the gastric remnant. The method has been successfully employed in 26 patients, i.e. 74 events of balloon extraction.


Direct sensitive immunocharacterization of gangliosides on plastic thin-layer plates using peroxidase staining.
A technique for the immunocharacterization of gangliosides on thin-layer plates using a peroxidase-labelled anti-Ig antibody is described. The technique uses plastic plates and does not necessitate any transfer of the antigen onto nitrocellulose for immunodetection. Being extremely sensitive, it permits the characterization of gangliosides which cannot be detected by classical densitometric techniques and allows the detection of gangliosides even in trace amounts in ganglioside mixtures. It appears to be useful for the screening of monoclonal antibodies because of its rapidity. Its specificity was found to be analogous to other immunological techniques such as complement fixation and agglutination.


Effective generation of transgenic pigs and mice by linker based sperm-mediated gene transfer.
Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT) that greatly improves the production efficiency of large transgenic animals. The linker protein, a monoclonal antibody (mAb C), is reactive to a surface antigen on sperm of all tested species including pig, mouse, chicken, cow, goat, sheep, and human. mAb C is a basic protein that binds to DNA through ionic interaction allowing exogenous DNA to be linked specifically to sperm. After fertilization of the egg, the DNA is shown to be successfully integrated into the genome of viable pig and mouse offspring with germ-line transfer to the F1 generation at a highly efficient rate: 37.5% of pigs and 33% of mice. The integration is demonstrated again by FISH analysis and F2 transmission in pigs. Furthermore, expression of the transgene is demonstrated in 61% (35/57) of transgenic pigs (F0 generation). Our data suggests that LB-SMGT could be used to generate transgenic animals efficiently in many different species.


7beta-Hydroxycholesterol and 25-hydroxycholesterol-induced interleukin-8 secretion involves a calcium-dependent activation of c-fos via the ERK1/2 signaling pathway in THP-1 cells: oxysterols-induced IL-8 secretion is calcium-dependent.
Oxysterols found in oxidized low-density lipoproteins are probably involved in the appearance of atheroma; some are cytotoxic and some able to induce cytokine secretion. An oxysterol-induced interleukin-8 (IL-8) secretion in human monocytes/macrophages has been previously noticed, but the mechanisms remained unclear. In this paper, we investigated the signaling pathways leading to the induction of IL-8 secretion in monocytic THP-1 cells treated with 7beta-hydroxycholesterol, a cytototoxic oxysterol, or with 25-hydroxycholesterol, an oxysterol non-cytotoxic toward this cell line. The oxysterol-induced IL-8 secretion appears to be a calcium-dependent phenomenon as shown by the use of calcium channel blockers, which strongly decreased IL-8 secretion and IL-8 messenger RNA (mRNA) levels. Fluo-3 staining used in flow cytometry and video microscopy revealed an oxysterol-induced Ca(2+) influx, varying according to the oxysterol studied, leading to the activation of the MEK/ERK1/2 pathway as demonstrated by Western blot analysis. ERK activation led to an increase of c-fos mRNA and/or an activation of c-fos. Luciferase reporter gene assay using constructs of the human IL-8 gene promoter and Transam assay revealed the involvement of the AP-1 transcription factor in oxysterol-dependent IL-8 secretion. These results demonstrate that oxysterol-induced IL-8 secretion is a calcium-dependent phenomenon involving the MEK/ERK1/2 pathway leading to the activation of IL-8 gene via AP-1 (c-fos).


Writing of strain-controlled multiferroic ribbons into MnWO4.
Local and low-dimensional structures, such as interfaces, domain walls and structural defects, may exhibit physical properties different from the bulk. Therein, a wide variety of local phases were discovered including conductive interfaces, sheet superconductivity, and magnetoelectric domain walls. The confinement of combined magnetic and electric orders to spatially selected regions may be particularly relevant for future technological applications because it may serve as basis of electrically controllable magnetic memory devices. However, direct observation of magnetoelectric low-dimensional structures cannot readily be done partly because of the lack of experimental techniques locally probing their physical nature. Here, we report an observation of multiferroic ribbon-like domains in a non-multiferroic environment in MnWO4. Using optical second harmonic generation imaging, we reveal that a multiferroic phase is stabilized by locally generated strain while the bulk magnetic structure is non-multiferroic. We further find that the confined multiferroic state retains domains with different directions of electric polarization and we demonstrate deterministic writing of a multiferroic state embedded in a non-multiferroic environment.


Differential effect of type I and type II interferons on neopterin production and amino acid metabolism in human astrocyte-derived cells.
Intrathecal production of neopterin, a pteridine produced by interferon (IFN)-gamma-stimulated monocyte-derived macrophages, is associated with neurological disorders and infections. We investigated whether IFN-alpha/beta, IFN-gamma, or human immunodeficiency virus (HIV) induce neopterin production by human astroglioma cells. IFN-alpha/beta and IFN-gamma, but not HIV, induced neopterin. Interestingly, IFN-gamma, but not IFN-alpha/beta, increased expression and activity of the tryptophan-catabolizing enzyme indoleamine (2,3)-dioxygenase. In contrast, IFN-alpha/beta, but not IFN-gamma, reduced the uptake of three aromatic amino acids in U87MG and U138 astroglioma cells. Thus type I and type II IFN stimulate astrocyte-derived cells to produce neopterin and exert differential effects on amino acid metabolism.


Dechlorination of carbon tetrachloride by the catalyzed Fe-Cu process.
The electrochemical reduction characteristics of carbon tetrachloride (CT) were investigated using cyclic voltammetry in this study. In addition, the difference in reduction mechanisms of CT between Master Builders' iron and the catalyzed Fe-Cu process was discussed. The results showed that CT was reduced directly on the surface of copper rather than by atomic hydrogen produced at the cathode in the catalyzed Fe-Cu process. The reduction was realized largely by atomic hydrogen in Master Builders' iron. The entire CT in 350 ml aqueous solution with 320 mg/L was reduced to trichloromethane and dichloromethane in 2.25 h when 100 g of scrap iron with Fe/Cu ratio of 10:1 (w/w) were used. Moreover, the reduction rate slowed with time. CT could be reduced at acidic, neutral and alkaline pH from solution by Fe-Cu bimetallic media, but the mechanisms were different. The degradation rate was not significantly influenced by pH in the catalyzed Fe-Cu process; in Master Builders' iron it clearly increased with decreasing pH. The kinetics of the reductions followed pseudo-first order in both cases. Furthermore, the reductions under acidic conditions proceeded faster than that under the neutral and alkaline conditions. The catalyzed Fe-Cu process was superior to Master Builders' iron in treating CT-containing water and this advantage was particularly noticeable under alkaline conditions. The reduction was investigated in the cathode (Cu) and anode (Fe) compartments respectively, the results showed that the direct reduction pathway played an important role in the reduction by the catalyzed Fe-Cu process. The catalyzed Fe-Cu process is of practical value.


Optimization and characterization of freeze-dried multilamellar liposomes incorporating different standardized allergen extracts.
Desensitization therapy for type I allergy is now current practice. Liposomes have been proposed as a support for allergens to improve safety and effectiveness. The aim of this work was to optimize liposomal formulations of three different standardized allergen extracts and to test their allergenicity in vitro and in a preclinical trial. Allergen extracts (Dactylis glomerata, Dermatophagoides pteronyssinus, and cat hair and dander) were associated with multilamellar liposomes of varying compositions at different pH. Liposome-bound allergens were quantified by RAST inhibition after ultracentrifugation, and analyzed qualitatively by SDS-PAGE followed by immunoblotting. Their allergenicity was assessed by basophil degranulation in vitro, as compared with the allergenicity of an aqueous extract, and by skin tests in allergic subjects. The best association, about 50% of the added allergen, was obtained with negatively charged liposomes, when the pH of the allergen solution was adjusted so as to impart a net positive charge to the proteins. One-third of the liposome-associated allergens was located on the surface of the liposomes and was free to interact with antibody, as shown by RAST inhibition assays and the basophil degranulation test; the remaining two-thirds was encapsulated within the liposomes. All the major immunoreactive proteins in the extract were included. These liposomes could be readily freeze-dried and reconstituted without changing their properties. This study reveals the allergenic characteristics of liposomes and suggests their potential use in the treatment of allergic patients.


Familial recurrence of gastroschisis: literature review and data from the population-based birth registry "Mainz Model".
Familial forms of gastroschisis are considered rare. A search for these forms in a population-based birth registry in 1993 found a recurrence risk of 3.5% among first-degree relatives. Since then, similar investigations in population-based registries have led to contradictory results. A search of the population-based birth registry "Mainz Model" for familial cases of gastroschisis and a systematic review of the literature were performed. The Mainz Model database yielded 1 familial recurrence out of 27 gastroschisis cases. From the literature, 37 affected families could be retrieved. Among 412 gastroschises from population-based registries, 10 familial recurrences have been found. These translate into a recurrence risk of 2.4%, with a strong tendency toward underestimation. The existing data support the hypothesis that familial recurrence of gastroschisis is much more likely than previously thought.


Advances in the Detection, Mechanism and Therapy of Chronic Kidney Disease.
Chronic Kidney Disease (CKD) is characterized by the gradual loss of renal mass and functions. It has become a global health problem, with hundreds of millions of people being affected. Both its incidence and prevalence are increasing over time. More than $20,000 are spent on each patient per year. The economic burden on the patients, as well as the society, is heavy and their life quality worsen over time. However, there are still limited effective therapeutic strategies for CKD. Patients mainly rely on dialysis and renal transplantation, which cannot prevent all the complications of CKD. Great efforts are needed in understanding the nature of CKD progression as well as developing effective therapeutic methods, including pharmacological agents. This paper reviews three aspects in the research of CKD that may show great interests to those who devote to bioanalysis, biomedicine and drug development, including important endogenous biomarkers quantification, mechanisms underlying CKD progression and current status of CKD therapy.


Expenditure of biological drugs for rheumatoid arthritis treatment in the Brazilian public health system.
This work aims to analyze the quantity and expenses related to biological drugs used for the treatment of rheumatoid arthritis (RA) in outpatient public care within the Brazilian Unified Health System (SUS). It is a cross-sectional descriptive study based on secondary data from a historical series, referring to the purchase, volume, and the number of patients treated with different biological drugs (infliximabe, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab, and certolizumab pegol) for RA treatment in outpatient care from 2012 to 2017. The data were extracted from the SUS Outpatient Information System database-SIA/SUS and included ten drugs used for RA treatment. The study assessed the quantity and expenditure of these drugs, the number of RA patients treated, and the expenditure by RA subtypes. The National Broad Consumer Price Index was used to adjust the expenditures for December 2017. The Ministry of Health allocated approximately $500 million to provide about 2 million units of biological drugs for RA patients from 2012 to 2017. The supply of adalimumab 40 mg and etanercept 50 mg accounted for 68.3% of the total expenditure. The subtypes "other rheumatoid arthritis with rheumatoid factor" (ICD-10 M05.8), "rheumatoid arthritis without rheumatoid factor" (ICD-10 M06.0), and "Felty's syndrome" (M05. 0) represented 84.5% of the total expenditures. The proportion of patients treated with biological drugs increased by 33.0%. There was a significant 83.0% increase in the number of patients using biological drugs compared to the overall number of RA patients treated during the study period. The results obtained allow us to draw a more recent profile of expenditure on RA treatment and indicate trends in the use of biological drugs for this condition, generating data that can support management decisions in public health policies.


Resistance assessment of pyraoxystrobin in Magnaporthe oryzae and the detection of a point mutation in cyt b that confers resistance.
Pyraoxystrobin is a new QoI fungicide developed in China. The present study was aimed at determining the baseline sensitivity of M. oryzae to pyraoxystrobin and investigating the potential resistance risk and resistance mechanism of pyraoxystrobin in M. oryzae. The results showed that the mean EC50 of 109 M. oryzae isolates to pyraoxystrobin was 0.0094 μg/mL and the sensitivity exhibited a unimodal distribution. The established baseline sensitivity could provide critical data for monitoring sensitivity changes of M. oryzae to pyraoxystrobin in rice fields. The potential resistance risk was assessed by investigating the biological characteristics of the resistant mutants obtained by fungicide adaptation. The results indicated that the resistance risk of pyraoxystrobin in M. oryzae was medium to high with positive cross-resistance between pyraoxystrobin and azoxystrobin, but without cross resistance between pyraoxystrobin and carbendazim, isoprothiolane, and prochloraz. Further investigation revealed that the pyraoxystrobin-resistant mutants had a G143S mutation in the cyt b protein. Molecular docking confirmed that the G143S substitution conferred high resistance to pyraoxystrobin in M. oryzae. Collectively, the results of this study provided essential data for monitoring the emergence of resistance and developing resistance management strategies for pyraoxystrobin.


5α-reductase 1 regulates spinal cord testosterone after morphine administration.
The enzyme 5alpha-reductase 1 (5α-R(1)) that converts testosterone (T) to dihydrotestosterone (DHT) is present in many mammalian tissues including the spinal cord. It is established that morphine administration decreases spinal cord T levels, but the mechanism is still undetermined. Here, we investigated the link between T and the enzyme 5α-R(1) in the spinal cord after morphine administration. For spinal cord steroid extraction, all the animals were killed 30 min, 2 h (acute) and 14 days (chronic) after first drug injection by decapitation. The whole spinal cord was removed and kept frozen at -20°C until T and DHT extraction. The effects of acute and chronic morphine administration on 5α-R(1) expression in the adult male rat spinal cord were evaluated using RT-PCR. Spinal cord T and DHT levels were measured using radioimmunoassay before and after the morphine exposure. Morphine significantly reduced the T concentration after acute and chronic exposure in the spinal cord. In contrast, the 5α-R(1) expression and of course DHT levels increased the following chronic morphine administration. One important reason for the decreasing effect of morphine exposure on the spinal cord T level is due to an increase in the 5α-R(1) levels. We suggest that morphine plays a regulatory role in metabolism of neurosteroids, especially T in the spinal cord via 5α-R(1).


Ghrelin-leptin network influences serum chitinase 3-like protein 1 (YKL-40) levels in obese prepubertal children.
This study aimed to investigate any possible interactions between hormonal regulators of weight gain and markers of subclinical inflammation in childhood obesity. Forty-one obese prepubertal children and 41 age- and gender-matched lean controls were included. Children were classified as obese or non-obese according to international age- and gender-specific body mass index (BMI) cutoff points defined by the International Obesity Task Force to define childhood obesity. Anthropometric measurements, serum insulin, chitinase 3-like protein (YKL-40), ghrelin and leptin levels as well as plasma glucose in the fasting state were determined. Obese children as compared with controls had higher YKL-40 (50.7±15.2 vs 41.0±10.5 ng/ml, p=0.003), higher leptin (33.8±16.0 vs 9.7±7.5 ng/ml, p<0.001) and lower ghrelin serum levels (871.4±368.0 vs 1417.6±387.3 pg/ml, p<0.001). The obese children with ghrelin levels above median (43.8±10.2 ng/ml) as compared to those with ghrelin below median (57.2±16.6 ng/ml) presented lower serum YKL-40 levels (p=0.009), indicating more severe inflammation with lower levels of ghrelin. By contrast, although the obese children with leptin levels above median (49.7±16.3 ng/ml) presented lower serum YKL-40 levels as compared to those with leptin levels below median (51.6±14.6 ng/ml), this difference did not reach the level of statistical significance (p=0.726). Moreover, serum YKL-40 levels were significantly correlated with ghrelin (r=-0.359, p=0.014) but not with leptin levels (r=0.169, p=0.261). A significant negative correlation between ghrelin and leptin levels was also found (r=-0.276, p=0.041). These findings remained unchanged for obese, when analyses were done separately, whereas the significance of correlations was lost for non-obese subjects. Ghrelin-leptin network had an impact on serum YKL-40 levels in obese prepubertal children; upregulation of YKL-40 secretion seems to be a consequence of reduced ghrelin rather than elevated leptin concentrations.


Anthropometric predictors of geometric indices of hip bone strength in a group of Lebanese postmenopausal women.
The effects of anthropometric characteristics on hip bone strength in postmenopausal women are not completely elucidated. The aim of this study was to investigate the influence of anthropometric characteristics on geometric indices of hip bone strength using the hip structure analysis (HSA) program in a group of Lebanese postmenopausal women. This study included 109 postmenopausal women (aged 64--84yr). Age and years since menopause were recorded. Body composition and bone mineral density were assessed by dual-energy X-ray absorptiometry (DXA). To evaluate hip bone strength, DXA scans were analyzed at the femoral neck (FN), the intertrochanteric (IT), and the femoral shaft (FS) by the HSA program. Cross-sectional area (CSA), an index of axial compression strength, section modulus (Z), an index of bending strength, and buckling ratio (BR), an estimate of cortical stability in buckling, were measured from bone mass profiles. Using univariate analysis, weight, height, body mass index (BMI), lean mass, and fat mass were positively correlated to CSA and Z of the FN, IT, and FS. Weight, BMI, fat mass, and fat mass percentage were negatively correlated to BR of the FN, IT, and FS. Multiple linear regression analysis showed that lean mass was a stronger determinant of FN CSA, FN Z, IT Z, and FS Z than fat mass, whereas fat mass was a stronger determinant of IT CSA, FS CSA, IT BR, and FS BR than lean mass. This study suggests that, in postmenopausal women, fat mass is a strong predictor of hip axial compression strength and cortical stability in buckling, and lean mass is a strong predictor of hip bending strength.


Bu Yang Huan Wu decoction prevents reperfusion injury following ischemic stroke in rats via inhibition of HIF-1 α, VEGF and promotion β-ENaC expression.
Bu Yang Huan Wu Decoction (BYHW) is a famous traditional Chinese medicine (TCM) formula used in China for the treatment of cerebral ischemic stroke. But the protective effects and underlining mechanisms of BYHW remain unclear. This study was designed to investigate the protective effects and underlining signaling mechanisms of BYHW on brain tissues in a rat model of cerebral ischemic reperfusion (I/R) injury. Liquid chromatography was used to verify the composition of BYHW. The cerebral edema and infarct volume were measured by magnetic resonance imaging (MRI). The morphology and ultrastructure of ischemic penumbra brain tissues were observed by hematoxylin-eosin (HE) and transmission electron microscopy (TEM). The expression levels of HIF-1 α, VEGF and β-ENaC were tested using immunohistochemistry technique, western blot and quantitative PCR analysis, respectively. Administration of BYHW significantly decreased cerebral edema, rat neurological function scores, reduced brain infarct volume. At the same time, BYHW had protective effect on the blood-brain barrier (BBB), which improved the morphology and ultrastructure of ischemic penumbra brain tissues. BYHW treatment significantly decreased the protein and mRNA levels of HIF-1 α and VEGF compared with the model treatment. In addition, BYHW treatment significantly up-regulated the protein and mRNA levels of β-ENaC. BYHW protected against cerebral I/R injury in MCAO rats through inhibiting the activation of the HIF-1 α /VEGF pathway and stabilizing ion channel of β-ENaC in brain, indicating that BYHW shows potential for stroke treatment in acute stage.


Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia.
Through in silico and other analyses, we identified FOXC1 as expressed in at least 20% of human AML cases, but not in normal hematopoietic populations. FOXC1 expression in AML was almost exclusively associated with expression of the HOXA/B locus. Functional experiments demonstrated that FOXC1 contributes to a block in monocyte/macrophage differentiation and enhances clonogenic potential. In in vivo analyses, FOXC1 collaborates with HOXA9 to accelerate significantly the onset of symptomatic leukemia. A FOXC1-repressed gene set identified in murine leukemia exhibited quantitative repression in human AML in accordance with FOXC1 expression, and FOXC1(high) human AML cases exhibited reduced morphologic monocytic differentiation and inferior survival. Thus, FOXC1 is frequently derepressed to functional effect in human AML.


Nonphysician Clinicians in the Follow-Up of Resected Patients with Colorectal Cancer.
The 5-year postoperative follow-up for patients undergoing curative treatment for colorectal cancer (CRC) is labour intensive. We assessed the added value of a dedicated nonphysician clinician (NPC) in the follow-up of patients after resection for CRC. Patients were divided into 2 groups as defined by the number of follow-up visits in the first year, including intensive (≥3×) and minimal (≤2×). Involvement of an NPC, diagnosis of disease recurrence and the course of the disease were determined. Of the 681 patients, 79.9% belonged to the "intensive" and 21.1% to the "minimal" group. Involvement of an NPC resulted in a higher adherence to follow-up (84.3 vs. 73.9%, p = 0.001). Overall, patients in regular follow-up less often had multifocal recurrence (47.1 vs. 73.7%, p = 0.04), and a better survival after recurrence (SAR; hazard ratio [HR] 3.604, p < 0.001). The "intensive" group had a significantly better overall survival compared to the "minimal" group (HR 1.71, p = 0.013). Adherence to surveillance programs after resection for CRC is better in hospitals with a dedicated NPC. Overall, patients' adherence to follow-up resulted in less multifocal disease recurrence at the time of diagnosis as compared to patients presenting with symptoms and a better 3-year SAR.


Interaction of nerve growth factor with tubulin. Studies on binding and induced polymerization.
The interaction of the nerve growth factor with the neurotubule protein has been studied with the aim of elucidating the nature of the large complexes that they form when incubated together and the factors and control this event. The results show that the binding of nerve growth factor to tubulin is followed by the formation of large structures that, in certain experimental conditions, accelerate the rate of tubulin polymerization to form microtubules or catalyze their assembly in conditions where this process does not occur spontaneously. The formation of large nerve growth factor-tubulin complexes starts to occur only at a molar ratio of 1.0-1.5 NaCL or GTP strongly inhibit this proceed without a detectable effect on NGF binding. Two hypotheses are postulated explain these findings. Firstly, that tubulin has two sites with different affinity for nerve growth factor and the polymerization occurs only when the second NGF molecule has interacted with the microtubule protein. Alternatively, free tubulin in solution is the polymerization by hindering site of tubulin-factor complexes present in solution at a 1.1 molar ratio. In both cases, GTP, Na-+ or H-+ will affect the formation of large unsoluble, tubulin-NGF complexes, by changing their conformation or by decreasing electrostatic interactions.


Further studies on the response of a cytochemical bioassay to thyroid stimulators, using reference preparations of thyrotropin and long acting thyroid stimulator.
The fundamental response of this assay is shown to be a shortening of a latency period prior to a peak of staining after tissue sections have been exposed to either TSH or LATS. The magnitude of the peak for a given tissue is both stimulator and dose independent. Simultaneous exposure to a combined dose of the two stimulator resulted in a further shortening of the latency period, and no evidence of two peaks was observed in the presence of both stimulators. Dose-response curves after exposure to reference preparations of the two stimulators for the same time period (180 s.) were parallel: this indicates that given incremental doses of either stimulator result in indistinguishable increases in the fundamental response of this assay.


A randomized controlled trial of a parent training and emotion socialization program for families of hyperactive preschool-aged children.
The present study evaluated the effectiveness of a parent training and emotion socialization program designed specifically for hyperactive preschoolers. Participants were 31 preschool-aged children whose parents were randomly assigned to a parent training (PT) or waitlist (WL) control group. PT parents took part in a 14-week parenting program that involved teaching parenting strategies for managing hyperactive and disruptive behavior as well as emotion socialization strategies for improving children's emotion regulation. Compared to WL mothers, PT mothers reported significantly less child inattention, hyperactivity, oppositional defiance, and emotional lability; were observed using significantly more positive and less negative parenting; and reported significantly less maternal verbosity and unsupportive emotion socialization practices. Results provide some support for the effectiveness of this parenting program for reducing attention-deficit hyperactivity disorder (ADHD) symptoms and associated problems in preschool-aged children.


Unusual rRNA-linked complex of 50S ribosomal subunits isolated from an Escherichia coli RNase III mutant.
We have isolated and characterized complexes of ribosomal subunits from Escherichia coli mutant AB301-105 connected by strands of unprocessed RNA. By electron microscopy of these complexes, the location of the 5' end of 5S RNA was established and the location of the 3' end of 23S RNA was confirmed. We also note that in these complexes insertion of 5S rRNA can proceed without the 23S-5S spacer having been processed.


P110α inhibitor alpelisib exhibits a synergistic effect with pyrotinib and reverses pyrotinib resistant in HER2+ breast cancer.
Human epidermal growth factor receptor 2 (HER2) plays a critical role in breast cancer progression in patients with HER2 overexpression, thereby driving the development of targeted drugs and advancing therapy strategies targeting this gene. Pyrotinib is a novel irreversible pan-ErbB kinase inhibitor, primarily suppresses the downstream MAPK and PI3K/AKT pathways. Alpelisib, a selective PI3K p110α inhibitor, has been approved for clinical application in HR+, HER2-, PIK3CA mutated breast cancers and is also being developed for use in other breast cancer subtypes. In this study, we hypothesised that combining pyrotinib with alpelisib would yield superior results compared to single-drug treatment. Our data demonstrated that the combination of alpelisib and pyrotinib exhibited a synergistic effect in HER2+ breast cancer both in vitro and in vivo. This combination led to decreased cell proliferation and migration, G0-G1 cell cycle arrest, and increased apoptosis rates. Additionally, the deactivation of ErbB receptors and sustained activation of PI3K/AKT pathway by upstream compensatory pathways induced acquired pyrotinib resistant cells resistant to pyrotinib treatment, thus alpelisib combined with pyrotinib showed a tremendous synergistic effect and reverse pyrotinib resistance in acquired pyrotinib resistant cells by suppressing the activated PI3K/AKT pathway. Our results revealed a combination of pyrotinib and alpelisib as an effective therapeutic strategy in treating HER2+ breast cancer, whether sensitive or resistant to pyrotinib treatment.


One-Pot Synthesis of Arylketones from Aromatic Acids via Palladium-Catalyzed Suzuki Coupling.
A palladium-catalyzed one-pot procedure for the synthesis of aryl ketones has been developed. Triazine esters when coupled with aryl boronic acids provided aryl ketones in moderate to excellent yields (up to 95%) in the presence of 1 mol % Pd(PPh3)2Cl2 for 30 min.


Herpes simplex virus encephalitis in children.
Herpes simplex encephalitis (HSE) is an uncommon disease, yet 25 to 30 per cent of cases involve children. The initial clinical findings are nonspecific (fever, altered mental status), but most cases evolve to demonstrate focal neurologic signs and symptoms. The CSF is abnormal in over 90 per cent of cases. The EEG, CT, and MRI will further help in detecting focal encephalitis. The clinician caring for a child with focal encephalitis should institute broad-spectrum antimicrobial therapy plus acyclovir, pending definitive diagnosis by ancillary tests or brain biopsy, which is positive for HSE 33 to 55 per cent of the time and is diagnostic for other treatable conditions 10 to 20 per cent of the time. Acyclovir is the drug of choice for HSE and substantially reduces mortality and morbidity. The management of HSE in a child requires an experienced team of specialists and laboratory support in a tertiary intensive care setting.