Development of transgenic mice that inducibly express an active form of c-Src in the epidermis.
Recent work from our laboratory has shown that elevated src kinase activity enhances tumor promotion, malignant progression, and metastasis during multistage skin carcinogenesis. In this study, we have generated "gene-switch" src(530) transgenic mice to further analyze the role of this nonreceptor tyrosine kinase in multistage carcinogenesis. Target transgenic mice that have an activated form of the human c-src (src(530)) gene fused with GAL4 binding sites upstream of the thymidine kinase (TK) promoter were generated. Two lines of epidermis-specific transactivator mice were used that targeted the expression of GLVPc or GLp65 transactivators, fusion molecules containing a truncated progesterone receptor with a GAl4-DNA binding domain, with either a mouse loricrin (ML) or human keratin 14 (HK14) promoter, respectively. The transactivator mice (ML.GLVPc or HK14.GLp65) and the target mice (TK.src(530)) were mated to generate bitransgenic mice, and src(530) transgene expression was induced by topical application of RU486 (mifepristone, a progesterone receptor antagonist). In both ML.GLVPc/TK.src(530) and HK14.GLp65/TK.src(530) bitransgenic mice, histological analysis revealed that only the bitransgenic mice had marked epidermal hyperplasia and hyperkeratosis after treatment with RU486. Neither the nontransgenic mice nor the mice hemizygous for either the transactivator transgene or the target transgene alone showed any response to treatment with RU486. In addition, no differences were observed in the skin of the bitransgenic mice versus nontransgenic littermates without treatment of RU486. Interestingly, in HK14.GLp65/TK.src(530) bitransgenic mice, squamous cell carcinomas (SCCs) arose along the periphery of the area of the punch biopsies in 25% of the bitransgenic mice several weeks after taking the biopsy and subsequent to RU486 treatment. Collectively, the data support a role of c-src activation in epidermal hyperproliferation. Furthermore, the data support the conclusion that src activation can substitute for an initiating event in the presence of a tumor promoting stimulus (i.e., wounding). Finally, inducible src(530) transgenic mice provide a new tool for dissecting the role of src activation in multistage carcinogenesis by allowing temporal control of the expression of this oncogene.


Are the therapeutic effects of homeopathy attributed to the consultation, the homeopathic remedy, or both? A protocol for a future exploratory feasibility trial in patients with rheumatoid arthritis.
Systematic reviews suggest that homeopathy has a greater effect than placebo, however, the mechanisms of its action are unknown. The clinical effects of homeopathy could be attributed to the specific effects of the remedy and/or to the contextual effects of the consultation process; these factors have not been critically evaluated. We have developed a model that attempt to separate the consultation effects from the specific effects because of the remedy. We propose to investigate this design in a chronic condition, rheumatoid arthritis, for which previous research has evaluated both classical and complex homeopathic interventions. The following protocol describes the study design. The aims of this exploratory trial are to assess the feasibility of the study design, identify effect sizes of the consultation, the complex treatment, and the individualized remedy, as well as possibly efficacy, for the two types of homeopathic treatment and the homeopathic consultation. Data collection will take place in 2004.


Tailoring Phosphonium Ionic Liquids for a Liquid-Liquid Phase Transition.
The existence of more than one liquid state in a single-component system remains the most intriguing physical phenomenon. Herein, we explore the effect of cation self-assembly on ion dynamics in the vicinity of liquid-liquid and liquid-glass transition of tetraalkyl phosphonium ([Pmmm,n]+, m = 4, 6; n = 2-14) ionic liquids. We found that nonpolar local domains formed by 14-carbon alkyl chains are crucial in obtaining two supercooled states of different dynamics within a single ionic liquid. Although the nano-ordering, confirmed by Raman spectroscopy, still occurs for shorter alkyl chains (m = 6, n < 14), it does not bring calorimetric evidence of LLT. Instead, it results in peculiar behavior of ion dynamics near the liquid-glass transition and 20-times smaller size of the dynamic heterogeneity compared to imidazolium ionic liquids. These results represent a crucial step toward understanding the nature of the LLT phenomenon and offer insight into the design of efficient electrolytes based on ionic liquids revealing self-assembly behavior.


Cognitive -behavioral therapy for managing depressive and anxiety symptoms after stroke: a systematic review and meta-analysis.
Post-stroke anxiety and depression can be disabling and result in impaired recovery. Cognitive-behavioral therapy (CBT) has been demonstrated to be effective for anxiety and depression; however, determining its efficacy among those with stroke is warranted. Our objectives to evaluate CBT for anxiety and depression post-stroke . This review was registered with PROSPERO (REG# CRD42020186324). Medline, PsycInfo, and EMBR Cochrane were used to locate studies published before May 2020, using keywords such as stroke and CBT. A study was included if: (1) interventions were CBT-based, targeting anxiety and/or depression; (2) participants experienced a stroke at least 3 months previous; (3) participants were at least 18 years old. Standardized mean differences ± standard errors and 95% confidence intervals were calculated, and heterogeneity was determined. The Cochrane Risk of Bias tool was used. The search yielded 563 articles, of which 10 (N = 672) were included;6 were randomized controlled trials. Primary reasons for exclusion included: (1) wrong population (2) insufficient data provided for a meta-analysis; (3) wrongoutcomes. CBT showed large effects on reducing overall anxiety (SMD ± SE: 1.01 ± 0.32, p < .001) and depression (SMD ± SE: 0.95 ± 0.22, p < .000) symptoms at the end of the studies. CBT moderately maintained anxiety (SDM ± SE: 0.779 ± 0.348, p ˂.025) and depression (SDM ± SE: 0.622 ± 0.285, p ˂ .029) scores after 3-months. Limitations included small sample size, limited comparators, and lack of follow-up data. The results of this meta-analysis provide substantial evidence for the use of CBTto manage post-stroke anxiety and depression.


Accuracy of mean grey density values obtained with small field of view cone beam computed tomography in differentiation between periapical cystic and solid lesions.
To determine if small and medium field of view (FOV) cone beam computed tomography (CBCT) adjusted grey density values can be used to distinguish between periapical cystic and solid lesions. Fifty-seven patients with periapical lesions having retrievable small or medium FOV CBCT images and biopsy samples were included. Two oral and maxillofacial pathologists examined the biopsy samples to provide the gold standard diagnosis of cystic or solid lesion. From the CBCT images, two independent examiners recorded the minimum adjusted grey density value of each lesion twice. Intra-examiner and inter-examiner reliability of the measurements were analysed, and sensitivity, specificity and accuracy of the minimum grey values in distinguishing a solid from cystic lesion were calculated. A receiver operating curve for diagnostic ability of adjusted grey density values to differentiate between periapical cystic and solid lesions was obtained, and the area under the curve (AUC) was calculated. The intra- and inter-examiner reliability of the grey density values of the lesions and dentine were excellent. The AUC was 0.44 (P-value = 0.45). The adjusted grey density value with the greatest accuracy for differentiating between cystic and solid lesions had an accuracy, sensitivity and specificity of 0.54, 1.00 and 0.075, respectively. Small FOV CBCT adjusted grey density values obtained by the device used in the study could not distinguish between periapical cystic and solid lesions. Further developments in CBCT devices are needed to improve the accuracy of grey density measurements.


Naloxone reverses pattern of obstruction of the distal common bile duct induced by analgesic narcotics in hepatobiliary imaging.
It is widely known that narcotics, such as morphine, cause spasm of the sphincter of Oddi, increasing pressure in the common bile duct. This pharmacologic effect has been applied to hepatobiliary scintigraphy in patients with chronic cholecystitis or cholestasis to reducing the time required for a diagnostic study. However, this feature of narcotics could result in delayed or nonvisualization of the small bowel, simulating a distal common bile duct obstruction, in patients requiring parenteral narcotic analgesics who must undergo hepatobiliary scintigraphy. We report on three patients where administration of intravenous naloxone hydrochloride (Narcan), a narcotic antagonist, was helpful in distinguishing narcotic-induced spasm of the sphincter of Oddi from true obstruction of the common bile duct.


Ingestion of subthreshold doses of environmental toxins induces ascending Parkinsonism in the rat.
Increasing evidence suggests that environmental neurotoxicants or misfolded α-synuclein generated by such neurotoxicants are transported from the gastrointestinal tract to the central nervous system via the vagus nerve, triggering degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and causing Parkinson's disease (PD). We tested the hypothesis that gastric co-administration of subthreshold doses of lectins and paraquat can recreate the pathology and behavioral manifestations of PD in rats. A solution containing paraquat + lectin was administered daily for 7 days via gastric gavage, followed by testing for Parkinsonian behavior and gastric dysmotility. At the end of the experiment, brainstem and midbrain tissues were analyzed for the presence of misfolded α-synuclein and neuronal loss in the SNpc and in the dorsal motor nucleus of the vagus (DMV). Misfolded α-synuclein was found in DMV and SNpc neurons. A significant decrease in tyrosine hydroxylase positive dopaminergic neurons was noted in the SNpc, conversely there was no apparent loss of cholinergic neurons of the DMV. Nigrovagally-evoked gastric motility was impaired in treated rats prior to the onset of parkinsonism, the motor deficits of which were improved by l-dopa treatment. Vagotomy prevented the development of parkinsonian symptoms and constrained the appearance of misfolded α-synuclein to myenteric neurons. These data demonstrate that co-administration of subthreshold doses of paraquat and lectin induces progressive, l-dopa-responsive parkinsonism that is preceded by gastric dysmotility. This novel preclinical model of environmentally triggered PD provides functional support for Braak's staging hypothesis of idiopathic PD.


A three-year experience with the argon laser in dermatotherapy.
Since January 1980, 477 patients were treated with an argon laser, 337 afflicted with vascular lesions and 140 with nonvascular lesions. Laser therapy of portwine stains gave good results in 70% of the adult patients, but it was disappointing in patients younger than 18 years of age. Other vascular lesions, such as telangiectasia, venous lake, angiofibroma, lymphangioma, and cherry angioma, were also treated with success. For the removal of tattoos the argon laser is not an optimal modality. In our experience it should only be used in skin areas, where dermabrasion cannot be performed. Therapy of epidermal nevi, xanthelasma of the eyelids, verrucae, vulgares , and sebaceous gland hyperplasia gave preliminary promising results in some patients.


Modeling cancer driver events in vitro using barrier bypass-clonal expansion assays and massively parallel sequencing.
The information on candidate cancer driver alterations available from public databases is often descriptive and of limited mechanistic insight, which poses difficulties for reliable distinction between true driver and passenger events. To address this challenge, we performed in-depth analysis of whole-exome sequencing data from cell lines generated by a barrier bypass-clonal expansion (BBCE) protocol. The employed strategy is based on carcinogen-driven immortalization of primary mouse embryonic fibroblasts and recapitulates early steps of cell transformation. Among the mutated genes were almost 200 COSMIC Cancer Gene Census genes, many of which were recurrently affected in the set of 25 immortalized cell lines. The alterations affected pathways regulating DNA damage response and repair, transcription and chromatin structure, cell cycle and cell death, as well as developmental pathways. The functional impact of the mutations was strongly supported by the manifestation of several known cancer hotspot mutations among the identified alterations. We identified a new set of genes encoding subunits of the BAF chromatin remodeling complex that exhibited Ras-mediated dependence on PRC2 histone methyltransferase activity, a finding that is similar to what has been observed for other BAF subunits in cancer cells. Among the affected BAF complex subunits, we determined Smarcd2 and Smarcc1 as putative driver candidates not yet fully identified by large-scale cancer genome sequencing projects. In addition, Ep400 displayed characteristics of a driver gene in that it showed a mutually exclusive mutation pattern when compared with mutations in the Trrap subunit of the TIP60 complex, both in the cell line panel and in a human tumor data set. We propose that the information generated by deep sequencing of the BBCE cell lines coupled with phenotypic analysis of the mutant cells can yield mechanistic insights into driver events relevant to human cancer development.


Thermal response to firefighting activities in residential structure fires: impact of job assignment and suppression tactic.
Firefighters' thermal burden is generally attributed to high heat loads from the fire and metabolic heat generation, which may vary between job assignments and suppression tactic employed. Utilising a full-sized residential structure, firefighters were deployed in six job assignments utilising two attack tactics (1. Water applied from the interior, or 2. Exterior water application before transitioning to the interior). Environmental temperatures decreased after water application, but more rapidly with transitional attack. Local ambient temperatures for inside operation firefighters were higher than other positions (average ~10-30 °C). Rapid elevations in skin temperature were found for all job assignments other than outside command. Neck skin temperatures for inside attack firefighters were ~0.5 °C lower when the transitional tactic was employed. Significantly higher core temperatures were measured for the outside ventilation and overhaul positions than the inside positions (~0.6-0.9 °C). Firefighters working at all fireground positions must be monitored and relieved based on intensity and duration. Practitioner Summary: Testing was done to characterise the thermal burden experienced by firefighters in different job assignments who responded to controlled residential fires (with typical furnishings) using two tactics. Ambient, skin and core temperatures varied based on job assignment and tactic employed, with rapid elevations in core temperature in many roles.


Purification and Valorization of Waste Cotton Seed Oil as an Alternative Feedstock for Biodiesel Production.
This article is focused on the production of biodiesel from the waste cotton seed oil (WCSO), after purification, as an alternative to fossil fuels. Waste oil was collected from Sodecoton, a factory producing cotton seed oil in the Far North Cameroon. The WCSO was subjected to purification using activated coal, followed by transesterification under basic conditions (potassium hydroxide (KOH)), using methanol and ethanol. Some physico-chemical properties of biodiesel, such as absorbance of waste and purified oil, density, viscosity, water content, acid value, and its energy content were determined. The result of treating the WCSO with activated coal indicated that purification efficiency of activated coal increased with the contact time and the mass of the absorbent. Absorbance results directly proved that activated coal removed unwanted components. In the same way, activated coal concentration and exposure time influenced the level of free fatty acids of WCSO. The yield of methyl ester was 97%, while that of ethyl ester was 98%. The specific gravity at 25 °C was 0.945 ± 0.0601. An evaluation of the lower calorific value (PCI) was done in order to study the energy content of biodiesel. This was found to be a value of 37.02 ± 3.05 MJ/kg for methyl ester and 36.92 ± 7.20 MJ/kg for ethyl ester. WCSO constitutes feedstock for high volume, good quality, and sustainable production of biodiesel, as well as a realistic means of eliminating the pollution resulting from the indiscriminate disposal of waste oils from both household and industrial users.


Effect of alpha-ketoglutarate and N-acetyl cysteine on cyanide-induced oxidative stress mediated cell death in PC12 cells.
Cyanide is a mitochondrial poison, which is ubiquitously present in the environment. Cyanide-induced oxidative stress is known to play a key role in mediating the neurotoxicity and cell death in rat pheochromocytoma (PC12) cells. PC12 cells are widely used as a model for neurotoxicity assays in vitro. In the present study, we investigated the protective effects of alpha-ketoglutarate (A-KG), a potential cyanide antidote, and N-acetyl cysteine (NAC), an antioxidant against toxicity of cyanide in PC12 cells. Cells were treated with various concentrations (0.625-1.25 mM) of potassium cyanide (KCN) for 4 hours, in the presence or absence of simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM). Cyanide caused marked decrease in the levels of cellular antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Lipid peroxidation indicated by elevated levels of malondialdehyde (MDA) was found to be accompanied by decreased levels of reduced glutathione (GSH) and total antioxidant status (TAS) of the cells. Cyanide-treated cells showed notable increase in caspase-3 activity and induction of apoptotic type of cell death after 24 hours. A-KG and NAC alone were very effective in restoring the levels of GSH and TAS, but together they significantly resolved the effects of cyanide on antioxidant enzymes, MDA levels, and caspase-3 activity. The present study reveals that combination of A-KG and NAC has critical role in abbrogating the oxidative stress-mediated toxicity of cyanide in PC12 cells. The results suggest potential role of A-KG and NAC in cyanide antagonism.


Epidermal growth factor (urogastrone)-mediated phosphorylation of a 35-kDa substrate in human placental membranes: relationship to the beta subunit of the guanine nucleotide regulatory complex.
We have identified a component of about 35 kDa (pp35), present in human placental membrane preparations, that is a substrate for epidermal growth factor (urogastrone) [EGF(Uro)]-mediated phosphorylation. The EGF(Uro)-stimulated phosphorylation of pp35 was calcium-dependent and was markedly enhanced in membranes prepared in the presence (but not in the absence) of calcium. The phosphate incorporated into pp35 in the presence of EGF(Uro) was alkali-stable and was present as O4-phosphotyrosine. Under identical conditions, insulin did not stimulate pp35 phosphorylation. Either in its native or in its phosphorylated form, pp35 could be released from the membranes in the presence of calcium-chelating agents (EDTA/EGTA); and EGF(Uro)-stimulated phosphorylation was reconstituted by adding back EDTA/EGTA eluates to EDTA/EGTA-washed membranes in the presence of calcium. The properties of pp35 were similar if not identical to those of beta-35, a 35-kDa polypeptide similar to the beta subunit of the guanine nucleotide-binding oligomers that stimulate (Gs) or inhibit (Gi) the adenylate cyclase system. As with pp35, EGF(Uro)-stimulated phosphorylation of isolated rabbit liver beta-35 was observed in a reconstituted system using either EDTA/EGTA-washed placental membranes or solubilized EGF(Uro) receptor immobilized on concanavalin A-agarose. In contrast, the addition of beta subunits derived from rabbit liver Gi or bovine transducin did not result in phosphorylation of a 35-kDa substrate in the reconstituted system. Further, a 35-kDa protein released from placental membranes crossreacted with an anti-transducin antibody that can recognize the beta subunit isolated from a variety of sources. We conclude that the human placental pp35 substrate likely represents the placental equivalent of the beta-35 protein. Our data point to a possible link between those receptors involved in growth-factor action and the regulatory systems that utilize GTP-binding proteins as transducing elements.


Uprighting mesially impacted mandibular permanent second molars.
Impaction of permanent teeth is a relatively common occurrence and can involve any tooth in the dental arch. Impacted mandibular second molars are relatively rare, but when they occur they may present a clinical problem for the orthodontist and oral surgeon. A typical case of bilaterally impacted mandibular second molars is illustrated, with orthodontic and surgical treatment options presented. Emphasis is placed on early diagnosis and initiation of corrective orthodontic therapy.


Program Obesity Zero (POZ)--a community-based intervention to address overweight primary-school children from five Portuguese municipalities.
Results of the WHO European Childhood Obesity Surveillance Initiative indicated that on average one out of four primary-school children is overweight or obese. Portugal presented one of the highest prevalences of obesity. Childhood obesity prevention and treatment should be a top priority. The aim of the present study was to evaluate the effectiveness of Program Obesity Zero (POZ), a multi-component, community-, family- and school-based childhood obesity intervention. Parents and children attended four individual nutrition and physical activity counselling sessions, a one-day healthy cooking workshop and two school extracurricular sessions of nutrition education. Waist circumference, BMI, physical activity level, sedentary behaviours, and nutrition and physical activity knowledge, attitudes and behaviour were assessed at baseline and after 6 months. Diet was assessed using two 24 h recalls, at baseline and at 6 months. Five Portuguese municipalities and local communities. Two hundred and sixty-six overweight children (BMI ≥ 85th percentile) aged 6-10 years, from low-income families in five Portuguese municipalities, were assigned to the intervention. Children showed reductions in waist circumference (-2.0 cm; P < 0.0001), mean BMI (-0.7 kg/m2; P < 0.0001) and BMI-for-age percentile (-1.7; P < 0.0001) at 6 months. Overall, children's intake of fruit and vegetables was <400 g/d throughout the intervention. After 6 months, higher fibre consumption and an apparent decrease in sugary soft drinks intake to a quarter of that observed at baseline (mean intake: 198 ml/d at baseline), with improvements in physical activity levels and screen time <2 h/d, were also observed. The findings suggested that POZ is a promising intervention programme, at municipality level, to tackle childhood overweight and obesity.


Identification and evaluation of flavone-glucosides isolated from barley sprouts and their inhibitory activity against bacterial neuraminidase.
Neuraminidase (NA) is one of the key enzymes responsible for bacterial infection and pathogenesis. This study aimed to gain deeper insights into the inhibitory effects of flavone-glucosides (1-9) isolated from barley sprouts (BS) on neuraminidase activity. The isolated compounds were identified as, lutonarin (1), saponarin (2), isoorientin (3), orientin (4), isovitexin (5), isoscoparin-7-O-[6-sinapoyl]-glucoside (6), isoscoparin-7-O-[6-feruloyl]-glucoside (7), isovitexin-7-O-[6-sinapoyl]-glucoside (8), and isovitexin-7-O-[6-feruloyl]-glucoside (9). Among them, compounds 1-5 exhibited neuraminidase-inhibitory activities in a dose-dependent manner, with IC50 values ranging from 20.1 to 32.7 μM, in a non-competitive inhibition mode according to kinetic studies. Moreover, the individual flavone-glucoside levels differed notably, in particular, lutonarin (1) and saponarin (2) were shown to be present in the greatest amounts, according to UPLC analysis. Consequently, our results suggest that BS may be utilized as an effective NA inhibitor in human health food, additives, and feed.


[The galenic pharmacy in the development of new drugs].
After having regarded the drug dosage form as a simple presentation of the active substance, the pharmaceutical world is convinced that the drug substance activity is not only controlled by its molecular structure but also by the galenical formulation as well as the manufacturing methods of the drug dosage forms. The galenical research in universities and in pharmaceutical companies gave rise to a new generation of dosage forms called "drug delivery systems" which have often taken advantage of the potential of new administration routes and have definitely found an important place in both human and veterinary therapeutics.


Quantitative tools for implementing the new definition of significant portion of the range in the U.S. Endangered Species Act.
In 2014, the Fish and Wildlife Service (FWS) and National Marine Fisheries Service announced a new policy interpretation for the U.S. Endangered Species Act (ESA). According to the act, a species must be listed as threatened or endangered if it is determined to be threatened or endangered in a significant portion of its range (SPR). The 2014 policy seeks to provide consistency by establishing that a portion of the range should be considered significant if the associated individuals' "removal would cause the entire species to become endangered or threatened." We reviewed 20 quantitative techniques used to assess whether a portion of a species' range is significant according to the new guidance. Our assessments are based on the 3R criteria-redundancy (i.e., buffering from catastrophe), resiliency (i.e., ability to withstand stochasticity), and representation (i.e., ability to evolve)-that the FWS uses to determine if a species merits listing. We identified data needs for each quantitative technique and considered which methods could be implemented given the data limitations typical of rare species. We also identified proxies for the 3Rs that may be used with limited data. To assess potential data availability, we evaluated 7 example species by accessing data in their species status assessments, which document all the information used during a listing decision. In all species, an SPR could be evaluated with at least one metric for each of the 3Rs robustly or with substantial assumptions. Resiliency assessments appeared most constrained by limited data, and many species lacked information on connectivity between subpopulations, genetic variation, and spatial variability in vital rates. These data gaps will likely make SPR assessments for species with complex life histories or that cross national boundaries difficult. Although we reviewed techniques for the ESA, other countries require identification of significant areas and could benefit from this research.


[Isothermal amplification technology based on microfluidic chip].
Polymerase chain reaction (PCR) is the gold standard for nucleic acid amplification in molecular diagnostics. The PCR includes multiple reaction stages (denaturation, annealing, and extension), and a complicated thermalcycler is required to repetitively provide different temperatures for different stages for 30-40 cycles within at least 1-2 hours. Due to the complicated devices and the long amplification time, it is difficult to adopt conventional PCR in point-of-care testing (POCT). Comparing to conventional PCR, isothermal amplification is able to provide a much faster and more convenient nucleic acid detection because of highly efficient amplification at a constant reaction temperature provided by a simple heating device. When isothermal amplification is combined with microfluidics, a more competent platform for POCT can be established. For example, various diagnosis devices based on isothermal amplification have been used to rapidly and conveniently detect SARS-CoV-2 viruses. This review summarized the recent development and applications of the microfluidics-based isothermal amplification. First, different typical isothermal amplification methods and related detection methods have been introduced. Subsequently, different types of microfluidic systems with isothermal amplification were discussed based on their characteristics, for example, functionality, system structure, flow control, and operation principles. Furthermore, detection of pathogens (e.g. SARS-CoV-2 viruses) based on isothermal amplification was introduced. Finally, the combination of isothermal amplification with other new technologies, e.g. CRISPR, has been introduced as well.


Elimination of undifferentiated human embryonic stem cells by cardiac glycosides.
An important safety concern in the use of human pluripotent stem cells (hPSCs) is tumorigenic risk, because these cells can form teratomas after an in vivo injection at ectopic sites. Several thousands of undifferentiated hPSCs are sufficient to induce teratomas in a mouse model. Thus, it is critical to remove all residue-undifferentiated hPSCs that have teratoma potential before the clinical application of hPSC-derived cells. In this study, our data demonstrated the cytotoxic effects of cardiac glycosides, such as digoxin, lanatoside C, bufalin, and proscillaridin A, in human embryonic stem cells (hESCs). This phenomenon was not observed in human bone marrow mesenchymal stem cells (hBMMSCs). Most importantly, digoxin and lanatoside C did not affect the stem cells' differentiation ability. Consistently, the viability of the hESC-derived MSCs, neurons, and endothelium cells was not affected by the digoxin and lanatoside C treatment. Furthermore, the in vivo experiments demonstrated that digoxin and lanatoside C prevented teratoma formation. To the best of our knowledge, this study is the first to describe the cytotoxicity and tumor prevention effects of cardiac glycosides in hESCs. Digoxin and lanatoside C are also the first FDA-approved drugs that demonstrated cytotoxicity in undifferentiated hESCs.


Ginsenoside Rb2 suppresses cellular senescence of human dermal fibroblasts by inducing autophagy.
Ginsenoside Rb2, a major active component of Panax ginseng, has various physiological activities, including anticancer and anti-inflammatory effects. However, the mechanisms underlying the rejuvenation effect of Rb2 in human skin cells have not been elucidated. We performed a senescence-associated β-galactosidase staining assay to confirm cellular senescence in human dermal fibroblasts (HDFs). The regulatory effects of Rb2 on autophagy were evaluated by analyzing the expression of autophagy marker proteins, such as microtubule-associated protein 1A/1B-light chain (LC) 3 and p62, using immunoblotting. Autophagosome and autolysosome formation was monitored using transmission electron microscopy. Autophagic flux was analyzed using tandem-labeled GFP-RFP-LC3, and lysosomal function was assessed with Lysotracker. We performed RNA sequencing to identify potential target genes related to HDF rejuvenation mediated by Rb2. To verify the functions of the target genes, we silenced them using shRNAs. Rb2 decreased β-galactosidase activity and altered the expression of cell cycle regulatory proteins in senescent HDFs. Rb2 markedly induced the conversion of LC3-Ⅰ to LC3-Ⅱ and LC3 puncta. Moreover, Rb2 increased lysosomal function and red puncta in tandem-labeled GFP-RFP-LC3, which indicate that Rb2 promoted autophagic flux. RNA sequencing data showed that the expression of DNA damage-regulated autophagy modulator 2 (DRAM2) was induced by Rb2. In autophagy signaling, Rb2 activated the AMPK-ULK1 pathway and inactivated mTOR. DRAM2 knockdown inhibited autophagy and Rb2-restored cellular senescence. Rb2 reverses cellular senescence by activating autophagy via the AMPK-mTOR pathway and induction of DRAM2, suggesting that Rb2 might have potential value as an antiaging agent.


Proteome analysis of differential protein expression in cervical cancer cells after paclitaxel treatment.
It is well known that infection with HPV (human papillomavirus) is the main cause of cervical cancer and certain types of HPV are recognized as carcinogens. At present, there is little information regarding the antineoplastic mechanism of paclitaxel against cervical carcinoma cells. We thus tried to analyze differential protein expression and antineoplastic mechanism-related proteins after paclitaxel treatment on cervical cancer cells by using a proteomic analysis and to investigate the mechanism of action. Using proteomics analysis including 2-DE and MALDI-TOF-MS, we detected the antineoplastic mechanism-related proteins. Then, we performed western blot analysis for apoptosis- and transformation-related proteins to confirm expression patterns derived from proteome analysis after paclitaxel treatment. We identified several cellular proteins that are responsive to paclitaxel treatment in HeLa cells using proteomics methods. Paclitaxel treatment elevated mainly apoptosis, immune response and cell cycle check point-related proteins. On the other hand, paclitaxel treatment diminished growth factor/oncogene-related proteins and transcription regulation-related proteins. Also, in the HPV-associated cervical carcinoma cells, paclitaxel demonstrated anti-proliferative activity through the membrane death receptor-mediated apoptotic pathway and the mitochondrial-mediated pathway. Identification and characterization of functionally modulated proteins involved in anti-cancer regulatory events should lead to a better understanding of the long-term actions of paclitaxel at the molecular level and will contribute to the future development of novel therapeutic drug treatments based upon current therapies.


[Proximal autosomal recessive types of spinal muscular atrophy].
One hundred and three patients with spinal muscular atrophy (SMA) were registered in a population medical genetic study of autosomal recessive childhood proximal SMA in Saratov region. Twenty-five patients were investigated complexly, using biochemical analysis of some enzymes, electroneuromyography, magnetic resonance imaging of spinal cord, muscle biopsy and molecular genetic testing. Pronounced clinical polymorphism and genetic heterogeneity of the disease were revealed.


Bilayer Hydrogel Composed of Elastin-Mimetic Polypeptides as a Bio-Actuator with Bidirectional and Reversible Bending Behaviors.
Biologically derived hydrogels have attracted attention as promising polymers for use in biomedical applications because of their high biocompatibility, biodegradability, and low toxicity. Elastin-mimetic polypeptides (EMPs), which contain a repeated amino acid sequence derived from the hydrophobic domain of tropoelastin, exhibit reversible phase transition behavior, and thus, represent an interesting starting point for the development of biologically derived hydrogels. In this study, we succeeded in developing functional EMP-conjugated hydrogels that displayed temperature-responsive swelling/shrinking properties. The EMP-conjugated hydrogels were prepared through the polymerization of acrylated EMP with acrylamide. The EMP hydrogel swelled and shrank in response to temperature changes, and the swelling/shrinking capacity of the EMP hydrogels could be controlled by altering either the amount of EMP or the salt concentration in the buffer. The EMP hydrogels were able to select a uniform component of EMPs with a desired and specific repeat number of the EMP sequence, which could control the swelling/shrinking property of the EMP hydrogel. Moreover, we developed a smart hydrogel actuator based on EMP crosslinked hydrogels and non-crosslinked hydrogels that exhibited bidirectional curvature behavior in response to changes in temperature. These thermally responsive EMP hydrogels have potential use as bio-actuators for a number of biomedical applications.


Effect of Motion Perception on Intertemporal Choice Is Associated With the Altered Time Perception.
Intertemporal choice refers to the choice between receiving a small immediate reward or a large delayed one. Previous studies have indicated that time perception plays a critical role in the intertemporal choice, and it could be affected by the features of the target stimulus in the time reproduction task, such as speed of movement and state of motion. However, there is no evidence about whether backward or forward motion perception could alter the intertemporal choice. Thus, in our current study, 29 participants were asked to perform two tasks in a random order. One was the intertemporal choice task after viewing videos containing moving elements with forward/backward directions as well as stationary ones, and another was the time perception task. We found that the discounting rate in intertemporal choice was significantly larger in backward motion condition than in both forward motion and stationary conditions, indicating that backward motion perception made participants more myopic (specifically, more likely to choose the smaller immediate reward instead of the large delayed one) during their decision-makings. Meanwhile, participants overestimated the temporal duration in a time perception task in backward motion condition compared to the other two conditions. Furthermore, the Pearson's correlation analysis showed that the changes of the intertemporal choice induced by backward motion perception could be associated with the altered time perception. As far as we know, we provide the first evidence on influence of motion perception on the intertemporal choice as well as its possible cognitive correlates, which extend previous studies on cognitive basis of the intertemporal choices.


Long-term growth hormone treatment in a boy with 45,X/46,X,idic(Yp) mixed gonadal dysgenesis: comparison with growth pattern of an untreated patient.
Mixed gonadal dysgenesis (MGD) is a rare disorder. Short stature is a well known feature of this condition. Although growth hormone (GH) treatment has been suggested to treat growth impairment, conflicting data surround this issue. We report on long-term growth hormone (GH) therapy at pharmacological doses (0.33 mg/kg/week) in a boy (age 4.6 years) with MGD [karyotype 45,X/46,X,idic(Yp)]. An untreated boy of similar karyotype and growth delay served as control. The treated boy showed a progressive improvement of stature during GH administration. His height completely normalized after 6.5 years of treatment and he reached his target height centile before puberty onset. In the untreated boy, no improvement of growth pattern was found. We conclude that short boys with MGD and 45,X/46,X,idic(Yp) karyotype may benefit from early GH therapy at pharmacological doses. Evaluation of larger patient samples and additional follow-up till final height are needed to reach definitive conclusions as to the optimal growth-promoting therapy for this disorder of sex development.


The Proton Pump Inhibitors Use and COVID-19 from Prior to Vaccination Perspective: A Review.
The coronavirus infectious disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been a huge challenge, affecting directly or indirectly the human race worldwide. Many COVID-19-related risk factors have been identified. Various drugs, including proton pump inhibitors (PPIs), have been claimed to increase the risk of acquiring or affecting the outcome of COVID-19 prior to the availability of vaccines. The aim of this review was to summarize the uncertain role of PPI use on the SARS-CoV-2 infection and COVID-19 clinical course, including both some well-established and presumptive indications to these potent inhibitors of gastric acid secretion, before vaccinations against COVID-19 were implemented on a massive scale. Although iatrogenic hypochlorhydria alters human microbiota and impairs the nonspecific innate immunity, increasing the likelihood of gastrointestinal and pulmonary infections, published data on the relationship between SARS-CoV-2 positivity and clinical manifestations of COVID-19 are quite inconclusive. On the contrary, the beneficial role of PPI use in the prevention of the upper gastrointestinal bleeding, particularly in at-risk patients receiving dual antiplatelet treatment and/or concomitant anticoagulation, constituting a significant proportion of COVID-19 patients, has been well-documented. Furthermore, PPIs have been marked as a potential antiviral remedy, just like many already existing repurposed drugs, that merit further studies in search of successful anti-CO-VID-19 pharmacotherapy. The controversial role of PPIs on the SARS-CoV-2 infection and COVID-19 severity propounded in the past should not prevent the use of these potent inhibitors of gastric acid secretion in well-established clinical indications.


Silica Source in Soil Solutions.
Heat of solution of silica in soil saturation pastes was calculated from silica solubilities and agreed with values for solid silicic acid. The immediate source of silica in soil solutions apparently is solid silicic acid. The solution of silica from soils exhibited three stages of constant silica solubility.


Unexpected positive cultures including isolation of Propionibacterium acnes in revision shoulder arthroplasty.
Little information is available to guide treatment strategies regarding patients with unexpected positive cultures (UPC), including Propionibacterium acnes (PA), without overt signs of infection in revision shoulder arthroplasty (RSA). The purpose of our study was to analyze the prevalence, clinical meaning, treatment and prognosis of UPC in RSA. We performed a systematic review of the literature between 1950 and 2013 for all studies reporting on UPC for PA. Studies with the prevalence and prognosis of patients with UPC in RSA were analyzed. Six studies meeting our inclusion criteria yielded data for 1 402 patients who underwent a total of 1405 RSA. Based on the available data, following RSA 235 shoulders had UPCs with a pooled percentage of 16.7% (235/1405). The most commonly isolated bacteria from shoulders following RSA with UPCs was PA with pooled percentages of 63.4% (149/235). Occurrence of true infection from UPCs after RSA was seen in 24 shoulders (24/235, 10.2%). Antibiotic use did not influence the rate of the occurrence of true infection from UPCs (P = 0.498). Our study showed a low risk of having a true infection from UPCs after RSA without clinical signs of preoperative infection at the time of the surgery. Therefore, prolonged antibiotic therapy may not be necessary in these patients.


Neurochemical Basis of Inter-Organ Crosstalk in Health and Obesity: Focus on the Hypothalamus and the Brainstem.
Precise neural regulation is required for maintenance of energy homeostasis. Essential to this are the hypothalamic and brainstem nuclei which are located adjacent and supra-adjacent to the circumventricular organs. They comprise multiple distinct neuronal populations which receive inputs not only from other brain regions, but also from circulating signals such as hormones, nutrients, metabolites and postprandial signals. Hence, they are ideally placed to exert a multi-tier control over metabolism. The neuronal sub-populations present in these key metabolically relevant nuclei regulate various facets of energy balance which includes appetite/satiety control, substrate utilization by peripheral organs and glucose homeostasis. In situations of heightened energy demand or excess, they maintain energy homeostasis by restoring the balance between energy intake and expenditure. While research on the metabolic role of the central nervous system has progressed rapidly, the neural circuitry and molecular mechanisms involved in regulating distinct metabolic functions have only gained traction in the last few decades. The focus of this review is to provide an updated summary of the mechanisms by which the various neuronal subpopulations, mainly located in the hypothalamus and the brainstem, regulate key metabolic functions.


A spiking neural network model of the midbrain superior colliculus that generates saccadic motor commands.
Single-unit recordings suggest that the midbrain superior colliculus (SC) acts as an optimal controller for saccadic gaze shifts. The SC is proposed to be the site within the visuomotor system where the nonlinear spatial-to-temporal transformation is carried out: the population encodes the intended saccade vector by its location in the motor map (spatial), and its trajectory and velocity by the distribution of firing rates (temporal). The neurons' burst profiles vary systematically with their anatomical positions and intended saccade vectors, to account for the nonlinear main-sequence kinematics of saccades. Yet, the underlying collicular mechanisms that could result in these firing patterns are inaccessible to current neurobiological techniques. Here, we propose a simple spiking neural network model that reproduces the spike trains of saccade-related cells in the intermediate and deep SC layers during saccades. The model assumes that SC neurons have distinct biophysical properties for spike generation that depend on their anatomical position in combination with a center-surround lateral connectivity. Both factors are needed to account for the observed firing patterns. Our model offers a basis for neuronal algorithms for spatiotemporal transformations and bio-inspired optimal controllers.


Allergic bronchopulmonary aspergillosis and fungoses.
ABPA is more common than was once suspected, while it remains likely that ABPF is rare. The spectrum of ABPA ranges from mild asthma to end-stage fibrotic lung disease. The episodes of chest roentgenographic infiltrates may be associated with little symptomatology and their detection is made by serial measurement of total serum IgE. A useful serodiagnostic aid for identification of early cases of ABPA is the demonstration of elevated IgE and IgG antibodies to Af compared with patients with asthma who do not have ABPA. Such assays are helpful in childhood cases of ABPA and in cystic fibrosis where no other test is as sensitive and specific. Prednisone remains the treatment of choice and, in many cases, its use can be intermittent.


Soluble mannose receptor as a predictor of prognosis of hepatitis B virus-related acute-on-chronic liver failure.
Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a syndrome with a high short-term mortality rate, and it is crucial to identify those patients at a high mortality risk clinically. To investigate the clinical value of soluble mannose receptor (sMR) in predicting the 90-day mortality of HBV-ACLF patients. A total of 43 patients were diagnosed with HBV-ACLF between October 2017 and October 2018 at the Second Hospital of Anhui Medical University, and all of them were enrolled in this retrospective study. Their serum sMR levels were determined using an enzyme-linked immunosorbent assay. Demographic and clinical data, including gender, age, albumin level, total bilirubin (TBIL) level, international normalized ratio, HBV-DNA level, HBV serological markers, procalcitonin level, interleukin-6 level, and model for end-stage liver disease (MELD) score were accessed at the time of diagnosis of HBV-ACLF. A multivariate logistic regression analysis was used to analyze the independent risk factors for mortality. Serum sMR level was significantly increased in HBV-ACLF patients compared with chronic hepatitis B patients and healthy controls (P < 0.01). When compared with surviving patients, it was higher in those patients who succumbed to HBV-ACLF (P < 0.05). Serum sMR level was positively correlated with MELD score (r s = 0.533, P = 0.001), HBV-DNA level (r s = 0.497, P = 0.022), and TBIL level (r s = 0.894, P < 0.001). Serum sMR level (odds ratio = 1.007, 95% confidence interval: 1.004-1.012, P = 0.001) was an independent risk factor for the 90-day mortality in the HBV-ACLF cases. The patients with HBV-ACLF were stratified into two groups in accordance with their serum sMR levels at the baseline (low risk: < 99.84 pg/mL and high risk: ≥ 99.84 pg/mL). The 90-day mortality rates were 27.3% in the low-risk group and 87.5% in the high-risk group. Furthermore, sMR level apparently improved the performance of MELD score for predicting the prognosis of patients with HBV-ACLF. Serum sMR level may be a predictor of the prognosis of HBV-ACLF patients.


Unique behavioral change with cinepazide in parkinsonism. A case report.
A 56-year-old male parkinsonian patient developed a unique behavioral change following the oral administration of cinepazide, a cerebral vasodilator. This behavior consisted of an apparent infatuation with a ward nurse, which ceased after medication was discontinued.


Molecular typing of Clostridium perfringens toxins recovered from Central Saudi Arabia.
This study reports on comparisons between polymerase chain reaction (PCR) and conventional diagnostic methods for typing Clostridium perfringens toxins collected from Central Saudi Arabia. Fecal samples from 150 animals showing signs of enterotoxaemia were collected from 24 April 2009 to 25 September 2009, from different farms located in Riyadh, Kingdom of Saudi Arabia. Twenty-seven toxigenic strains of Clostridium perfringens were recovered from 150 fecal and intestinal content samples were identified and typed by conventional methods. All the strains were analyzed by PCR using specific primers for alpha, beta, epsilon and iota toxin genes. The experimental work was carried out at the Center of Excellence in Biotechnology, King Saud University, Riyadh, Kingdom of Saudi Arabia. The results revealed alpha toxin gene Clostridium perfringens type A in 22 (81.5%) strains out of 27 toxigenic strains, however, only 20 (74.1%) of them were identified previously as type A by classical method. One strain (3.7%) was identified as type C and 3 strains (11.1%) were identified as D by PCR typing. Moreover, PCR results confirmed the traditional methods in typing one strain as type B (3.7%). Also, PCR method can detect 2 other strains of type A directly from the feces and intestinal contents of the examined chicken, which provide negative results in bacteriological examination. Polymerase chain reaction technique can be used as an alternative diagnostic method for detection and typing of Clostridium perfringens.


Fine particulate chemical composition and light extinction at Meadview, AZ.
The concentration of fine particulate nitrate, sulfate, and carbonaceous material was measured for 12-hr day-night samples using diffusion denuder samplers during the Project Measurement of Haze and Visibility Effects (MOHAVE) July to August 1992 Summer Intensive study at Meadview, AZ, just west of Grand Canyon National Park. Organic material was measured by several techniques. Only the diffusion denuder method measured the semivolatile organic material. Fine particulate sulfate and nitrate (using denuder technology) determined by various groups agreed. Based on the various collocated measurements obtained during the Project MOHAVE study, the precision of the major fine particulate species was +/- 0.6 microg/m3 organic material, +/- 0.3 microg/m3 ammonium sulfate, and +/- 0.07 microg/m3 ammonium nitrate. Data were also available on fine particulate crustal material, fine and coarse particulate mass from the Interagency Monitoring of Protected Visual Environments sampling system, and relative humidity (RH), light absorption, particle scattering, and light extinction measurements from Project MOHAVE. An extinction budget was obtained using mass scattering coefficients estimated from particle size distribution data. Literature data were used to estimate the change in the mass scattering coefficients for the measured species as a function of RH and for the absorption of light by elemental carbon. Fine particulate organic material was the principal particulate contributor to light extinction during the study period, with fine particulate sulfate as the second most important contributor. During periods of highest light extinction, contributions from fine particulate organic material, sulfate, and light-absorbing carbon dominated the extinction of light by particles. Particle light extinction was dominated by sulfate and organic material during periods of lowest light extinction. Combination of the extinction data and chemical mass balance analysis of sulfur oxides sources in the region indicate that the major anthropogenic contributors to light extinction were from the Los Angeles, CA, and Las Vegas, NV, urban areas. Mohave Power Project associated secondary sulfate was a negligible contributor to light extinction.


Management of incidental gallbladder cancer in a national cohort.
Incidental gallbladder cancer is a rare event, and its prognosis is largely affected by the tumour stage and treatment. The aim of this study was to analyse the management, treatment and survival of patients with incidental gallbladder cancer in a national cohort over a decade. Patients were identified through the Swedish Registry of Gallstone Surgery (GallRiks). Data were cross-linked to the national registry for liver surgery (SweLiv) and the Cancer Registry. Medical records were collected if registry data were missing. Survival was measured as disease-specific survival. The study was divided into two intervals (2007-2011 and 2012-2016) to evaluate changes over time. In total, 249 patients were identified with incidental gallbladder cancer, of whom 92 (36·9 per cent) underwent re-resection with curative intent. For patients with pT2 and pT3 disease, median disease-specific survival improved after re-resection (12·4 versus 44·1 months for pT2, and 9·7 versus 23·0 months for pT3). Residual disease was present in 53 per cent of patients with pT2 tumours who underwent re-resection; these patients had a median disease-specific survival of 32·2 months, whereas the median was not reached in patients without residual disease. Median survival increased by 11 months for all patients between the early and late periods (P = 0·030). Re-resection of pT2 and pT3 incidental gallbladder cancer was associated with improved survival, but survival was impaired when residual disease was present. A higher re-resection rate and more R0 resections in the later time period may have been associated with improved survival.


Lung fluid balance in hypoxic lambs.
In spontaneously breathing newborn lambs, alveolar hypoxia increases lung microvascular pressure, which causes lung lymph flow to increase and the concentration of protein in lymph to decrease. To see if this response derives from hypoxia itself rather than from the change in breathing pattern that occurs during hypoxia, we measured lung vascular pressures, pleural pressure, cardiac output, and lung lymph flow in 12 anesthetized lambs that were ventilated at a fixed rate and tidal volume, first with air, then with 10-14% O2 in nitrogen. Alveolar hypoxia did not affect pleural pressure, but pulmonary arterial pressure increased from 19 to 32 torr, lung lymph flow increased from 2.20 to 3.83 ml/h and lymph protein concentration decreased from 3.4 to 2.8 g/dl. To be certain that the increased lymph flow associated with hypoxia is not simply the result of an acute release of fluid from the lungs and to assess the effects of carbon dioxide on lymph flow during hypoxia, we next studied six unanesthetized lambs kept hypoxic for a total of 12 h. After a 2-4-h period in air the lambs breathed 9-11% O2 in nitrogen for 2-4 h, then 8-11% O2 and 3-5% CO2 in nitrogen for 8-10 h. In these lambs we injected intravenously radioactive albumin and measured its uptake in lymph to see if sustained hypoxia alters microvascular permeability to protein in the lungs. In these experiments pulmonary arterial pressure increased from 17 to 37 torr, lung lymph flow increased from 1.74 to 3.28 ml/h, and lymph protein concentration decreased from 3.8 to 3.1 g/dl during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)


A Content Analysis of How Sexual Behavior and Reproductive Health are Being Portrayed on Primetime Television Shows Being Watched by Teens and Young Adults.
Television is a leading source of sexual education for teens and young adults, thus it is important to understand how sexual behavior and reproductive health are portrayed in popular primetime programming. This study is a media content analysis of the 19 top-rated scripted English-language primetime television shows aired between January 1, 2015 and May 31, 2015, and viewed by American youth audiences 12-24 years of age. The purpose of this study is to assess how sex/sexuality and reproductive health are being portrayed in a popular medium that reaches many adolescent and young adult audiences. Themes used for this analysis include youth pregnancy/parenting, mentoring/guidance of youth regarding sexual behavior, sex/sexuality, body image/identity, sexual violence/abuse/harassment, gender identity/sexual orientation, and reproductive health. Themes have been classified in one of the following six categories: visual cues, brief mentions, dialogue, minor storylines, major storylines, and multi-episode storylines. Our findings indicate that narratives providing educational information regarding the risks and consequences of sexual behavior were missing from the television shows we analyzed and that storylines promoting low risk sexual behavior were rare. Sexual violence and abuse, casual sex among adults, lack of contraception use, or no portrayal of consequences of risky behaviors were common. Compared to prior research, we found an emergent theme normalizing non-heterosexual gender identity and sexual orientation. Our findings have important implications as exposure to popular media shapes the perceptions and behaviors of teens and young adults. This study has the potential to shed light on the need to create stories and narratives in television shows watched by American teens and young adults with educational messages regarding the risks and consequences of sexual behavior.


Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016.
The purpose of this study is to estimate the national prevalence of parent-reported attention deficit/hyperactivity disorder (ADHD) diagnosis and treatment among U.S. children 2-17 years of age using the 2016 National Survey of Children's Health (NSCH). The NSCH is a nationally representative, cross-sectional survey of parents regarding their children's health that underwent a redesign before the 2016 data collection. It included indicators of lifetime receipt of an ADHD diagnosis by a health care provider, whether the child currently had ADHD, and receipt of medication and behavioral treatment for ADHD. Weighted prevalence estimates were calculated overall and by demographic and clinical subgroups (n = 45,736). In 2016, an estimated 6.1 million U.S. children 2-17 years of age (9.4%) had ever received an ADHD diagnosis. Of these, 5.4 million currently had ADHD, which was 89.4% of children ever diagnosed with ADHD and 8.4% of all U.S. children 2-17 years of age. Of children with current ADHD, almost two thirds (62.0%) were taking medication and slightly less than half (46.7%) had received behavioral treatment for ADHD in the past year; nearly one fourth (23.0%) had received neither treatment. Similar to estimates from previous surveys, there is a large population of U.S. children and adolescents who have been diagnosed with ADHD by a health care provider. Many, but not all, of these children received treatment that appears to be consistent with professional guidelines, though the survey questions are limited in detail about specific treatment types received. The redesigned NSCH can be used to annually monitor diagnosis and treatment patterns for this highly prevalent and high-impact neurodevelopmental disorder.


Prefrontal activity predicts individual differences in optimal attentional strategy for preventing motor performance decline: a functional near-infrared spectroscopy study.
Directing attention to movement outcomes (external focus; EF), not body movements (internal focus; IF), is a better cognitive strategy for motor performance. However, EF is not effective in some healthy individuals or stroke patients. We aimed to identify the neurological basis reflecting the individual optimal attentional strategy using functional near-infrared spectroscopy. Sixty-four participants (23 healthy young, 23 healthy elderly, and 18 acute stroke) performed a reaching movement task under IF and EF conditions. Of these, 13 healthy young participants, 11 healthy elderly participants, and 6 stroke patients showed better motor performance under EF conditions (EF-dominant), whereas the others showed IF-dominance. We then measured prefrontal activity during rhythmic hand movements under both attentional conditions. IF-dominant participants showed significantly higher left prefrontal activity than EF-dominant participants under IF condition. In addition, receiver operating characteristic analysis supported that the higher activity in the left frontopolar and dorsolateral prefrontal cortices could detect IF-dominance as an individual's optimal attentional strategy for preventing motor performance decline. Taken together, these results suggest that prefrontal activity during motor tasks reflects an individual's ability to process internal body information, thereby conferring IF-dominance. These findings could be applied for the development of individually optimized rehabilitation programs.


Fluorodeoxyglucose uptake and glucose transporter expression in experimental inflammatory lesions and malignant tumours: effects of insulin and glucose loading.
The expression of glucose transporters (GLUTs) and its relationship to fluorodeoxyglucose accumulation in malignant tumours have been well investigated, while such a relation has not been studied in inflammatory lesions. The aim of the present study was to investigate the effects of insulin and glucose loading on the expression of GLUTs in inflammatory lesions and compare them with those in malignant tumours in relation to fluorodeoxyglucose accumulation. All tissue specimens used in this study were obtained in our previous study, in which rats were inoculated with allogenic hepatoma cells (KDH-8), Staphylococcus aureus, or turpentine oil into the left calf muscle and divided into three subgroups: insulin loaded, glucose loaded, and control groups. The expression of glucose transporters (GLUT-1 to GLUT-5) was investigated by immunostaining the lesions (n=5-6, for each group). In all control groups, the expression levels of GLUT-1 and GLUT-3 were significantly higher than those of GLUT-2, GLUT-4 and GLUT-5. Insulin loading did not significantly affect the expression levels of GLUT-1 and GLUT-3 in these lesions except for a significant but slight decrease in the GLUT-1 expression level in the inflammatory lesion of non-infectious origin (89% of the control value). Glucose loading significantly decreased the expression level of GLUT-1 in the inflammatory lesion of non-infectious origin (70% of the control value, P<0.01), and that of GLUT-3 in the inflammatory lesion of infectious origin (70% of the control value, P<0.05), while the expression levels of GLUT-1 and GLUT-3 in the tumour were not significantly affected. These results demonstrate the effects of insulin and glucose loading on the expression level of a molecule (GLUT proteins). The decreased GLUT-1 and GLUT-3 expression levels induced by glucose loading may partly explain the impaired FDG uptake observed in our previous study.


Proteome Analysis of Vacuoles Isolated from Fig (Ficus carica L.) Flesh during Fruit Development.
Fruit flesh cell vacuoles play a pivotal role in fruit growth and quality formation. In the present study, intact vacuoles were carefully released and collected from protoplasts isolated from flesh cells at five sampling times along fig fruit development. Label-free quantification and vacuole proteomic analysis identified 1,251 proteins, 1,137 of which were recruited as differentially abundant proteins (DAPs) by fold change ≥ 1.5, P < 0.05. DAPs were assigned to 10 functional categories; among them, 238, 186, 109, 93 and 90 were annotated as metabolism, transport proteins, membrane fusion or vesicle trafficking, protein fate and stress response proteins, respectively. Decreased numbers of DAPs were uncovered along fruit development. The overall changing pattern of DAPs revealed two major proteome landscape conversions in fig flesh cell vacuoles: the first occurred when fruit developed from late-stage I to mid-stage II, and the second occurred when the fruit started ripening. Metabolic proteins related to glycosidase, lipid and extracellular proteins contributing to carbohydrate storage and vacuole expansion, and protein-degrading proteins determining vacuolar lytic function were revealed. Key tonoplast proteins contributing to vacuole expansion, cell growth and fruit quality formation were also identified. The revealed comprehensive changes in the vacuole proteome during flesh development were compared with our previously published vacuole proteome of grape berry. The information expands our knowledge of the vacuolar proteome and the protein basis of vacuole functional evolution during fruit development and quality formation.


Promising new suprapubic catheter.
The author describes his first-hand experience of a technique to keep patients with a suprapubic catheter free from urine leakage. He modified a suprapubic catheter by adding an external phalange to secure the catheter and balloon placement within the bladder. To date, this modification has prevented leakage around the catheter site for all patients in which it was used. In a followup article, the author will explain how he obtained a patent for the new design and worked with companies to manufacture the new product.


A syndrome of misinterpreting role changes as changes of person.
A syndrome is described in three elderly women who all suffered from cerebral arteriosclerosis, and who in their dependent condition were looked after by their daughters. These women accepted their daughters as their daughters when carrying out directly caring tasks related to them, but spoke of them and addressed them as different women, with the same forenames as their daughters, when their daughters were engaged in other duties. This syndrome is compared with the syndromes of Capgras and similar conditions. It is likely to be detected with increasing frequency as psychiatrists become involved in the community aspects of the speciality.


Alveolar bone graft resorption associated with abnormal dental follicle.
An unusual case of an alveolar bone graft that underwent almost complete resorption in association with a large radiolucent lesion around the erupting canine is reported. Clinical and radiographic follow-up after grafting is important to detect and manage any pathologic changes which might occur. Early detection of any abnormal radiologic changes and surgical intervention to excise the lesion could prevent further destruction of the grafted bone.


Focusing on the Differences of Resting-State Brain Networks, Using a Data-Driven Approach to Explore the Functional Neuroimaging Characteristics of Extraversion Trait.
In recent years, functional magnetic resonance imaging (fMRI) has been widely used in studies that explored the personality-brain association. Researches on personality neuroscience have the potential to provide personality psychology with explanatory models-that is, why people differ from each other rather than how they differ from each other (DeYoung and Gray, 2009). As one of the most important dimensions of personality traits, extraversion is the most stable core and a universal component in personality theory. The aim of the present study was to employ a fully data-driven approach to study the brain mechanism of extraversion in a sample of 111 healthy adults. The Eysenck Personality Questionnaire (EPQ) was used to measure the personality characteristics of all the subjects. We investigated whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their intrinsic connectivity networks (ICNs). The resultant subjects communities and the representative characteristics of ICNs were then associated to personality concepts. Finally, we found one ICN (salience network) whose subject community profiles exhibited significant associations with Extraversion trait.


Selective calculation of high-intensity vibrations in molecular resonance Raman spectra.
We present an intensity-driven approach for the selective calculation of vibrational modes in molecular resonance Raman spectra. The method exploits the ideas of the mode-tracking algorithm [M. Reiher and J. Neugebauer, J. Chem. Phys. 118, 1634 (2003)] for the calculation of preselected molecular vibrations and of Heller's gradient approximation [Heller et al., J. Phys. Chem. 86, 1822 (1982)] for the estimation of resonance Raman intensities. The gradient approximation allows us to construct a basis vector for the subspace iteration carried out in the mode-tracking calculation, which corresponds to an artificial collective motion of the molecule that contains the entire intensity in the resonance Raman spectrum. Subsequently, the algorithm generates new basis vectors from which normal mode approximations are obtained. It is then possible to provide estimates for (i) the accuracy of the normal mode approximations and (ii) the intensity of these modes in the final resonance Raman spectrum. This approach is tested for the examples of uracil and a structural motif from the E colicin binding immunity protein Im7, in which a few aromatic amino acids dominate the resonance Raman spectrum at wavelengths larger than 240 nm.


[Effect of a simple kidney cyst on renal function].
Renal cysts are a common disease that occurs at a rate of 7-10%. Currently there are no clinical recommendations for the treatment of patients with simple renal cysts. In the current literature there is some evidence that a simple renal cyst has negative effects on renal function. Decreased renal function occurs due to partial atrophy and loss of the renal parenchyma (in the "crater" area at the base of the cyst) caused by compression. Therefore, the efforts to analyze the effect of simple kidney cysts on kidney function and identify the characteristics of the cyst that affect renal function to determine the indications for surgical treatment remains a substantial task. The aim of the study was to analyze the effect of simple renal cysts on renal function, to investigate the relationship between cyst size, atrophied parenchyma volume, and renal function, and to determine indications for surgical treatment of simple renal cysts. We conducted a prospective cohort study. The study included 109 patients with simple renal cysts. Patients with a solitary cyst of the right or left renal kidney, grade I-II according to Bosniak classification, were included in the study. The estimated glomerular filtration rate (eGFR) of the patients was calculated using various formulas. A contrast CT scan of the urinary tract was also performed to determine the maximum size of the cyst, calculate the volume of the renal parenchyma, and the volume of the lost (atrophied) parenchyma. Patients underwent renal scintigraphy with calculation of total GFR and split renal function. We analyzed the symmetry of the function of both kidneys by comparing the GFR of the affected and healthy kidneys, analyzed the relationship between the presence of a kidney cyst and a decrease in GFR, between the maximum size of a renal cyst and a decrease in its function compared with that of a healthy kidney. We also analyzed the correspondence of total GFR values obtained in renal scintigraphy and GFR values calculated according to the formulas. Data from 109 patients were available for analysis; the mean blood creatinine was 87.4 mol/L. The median maximum cyst size was 80 mm. The median baseline volume of the affected kidney parenchyma was 174 ml, the median volume of the lost parenchyma was 49 ml, and the median proportion of the lost parenchyma was 28%. The median total GFR was 77.07 ml/min. The median GFR of the healthy kidney was 45.49 mL/min, and the median GFR of the kidney affected by the cyst was 34.46 mL/min. The median difference in GFR of the healthy and affected kidney units was 11 mL/min and was statistically significant. Comparison of the eGFR values obtained by the formulas with the reference values of GFR obtained by scintigraphy showed that the Cockcroft-Gault formula with standardization on the body surface area calculated closest eGFR values to the reference ones. Correlation analysis revealed a statistically significant association between the proportion of lost parenchyma volume and the maximum cyst size: =0.37 with 95% CI [0.20; 0.52] (p-value = 0). A multivariate logistic regression model revealed that a statistically significant factor influencing the probability of a significant decrease in GFR was the percent of lost renal parenchyma volume (OR=1,13; =0). Our study showed that growth of renal cysts associated with renal parenchyma atrophy and decrease of GFR of the affected kidney. An increase in the volume of atrophied parenchyma leads to the decrease in GFR of the affected kidney. The obtained data suggest that performing dynamic renal scintigraphy to assess the decrease in affected renal function and determine the indications for surgical treatment of renal cysts is a reasonable recommendation. According to the results of the study, the loss of 20% of the renal parenchyma can be considered an indication for renal scintigraphy. The Cockcroft-Gault formula with standardization on the body surface area allows to calculate closest GFR values to those obtained by scintigraphy and, therefore, can be recommended as the optimal formula for calculating eGFR in daily clinical practice.


A novel C-type lectin from Trichinella spiralis mediates larval invasion of host intestinal epithelial cells.
The aim of this study was to investigate the characteristics of a novel type C lectin from Trichinella spiralis (TsCTL) and its role in larval invasion of intestinal epithelial cells (IECs). TsCTL has a carbohydrate recognition domain (CRD) of C-type lectin. The full-length TsCTL cDNA sequence was cloned and expressed in Escherichia coli BL21. The results of qPCR, Western blotting and immunofluorescence assays (IFAs) showed that TsCTL was a surface and secretory protein that was highly expressed at the T. spiralis intestinal infective larva (IIL) stages and primarily located at the cuticle, stichosome and embryos of the parasite. rTsCTL could specifically bind with IECs, and the binding site was localized in the IEC nucleus and cytoplasm. The IFA results showed that natural TsCTL was secreted and bound to the enteral epithelium at the intestinal stage of T. spiralis infection. The rTsCTL had a haemagglutinating effect on murine erythrocytes, while mannose was able to inhibit the rTsCTL agglutinating effect for mouse erythrocytes. rTsCTL accelerated larval intrusion into the IECs, whereas anti-rTsCTL antibodies and mannose significantly impeded larval intrusion in a dose-dependent manner. The results indicated that TsCTL specifically binds to IECs and promotes larval invasion of intestinal epithelium, and it might be a potential target of vaccines against T. spiralis enteral stages.


Seasonal variation and intra urban heterogeneity of the entomological risk of transmission of dengue and yellow fever in Abidjan, Côte d'Ivoire.
Dengue and yellow fever are prevalent in Côte d'Ivoire and Aedes (Stegomyia) aegypti (Linnaeus), (Diptera: Culicidae), is known as the main vector. We aimed to assess seasonal variation and spatial heterogeneity in the transmission of both arbovirus diseases in Abidjan. Entomological surveys targeting larvae of A. aegypti, were carried out between November 2015 and August 2016 covering the four climatic seasons including a cohort of 100 houses randomly selected in three neighbourhoods. A. aegypti was the predominant species (96.6%) of mosquitoes resulting from the rearing of harvested larvae, and the only vector of dengue and yellow fever recorded during the study period. The highest proportion of water storage containers (45.5%) which represented the major breeding sites infested by the larvae of A. aegypti, was observed in Anoumabo. The house indices >5% and/or Breteau indices >20 recorded in each neighbourhood, during the different climatic seasons, indicated that there was, a high and permanent, heterogeneity in the transmission risk of dengue and yellow fever between the three neighbourhoods. In terms of transmission risk, Anoumabo was the neighbourhood with the highest risk compared to the two others, then, particular attention should be paid to this site in terms of surveillance by vector control programme in Abidjan.


[Research progress of nanosecond pulsed electric field applied to intracellular electromanipulation].
In recent years, many experts have done some researches on experiment and mechanism of intracellular electromanipulation (IEM) under nanosecond pulsed electric field (nsPEF). The experiment results have shown that nsPEF could not induce electroporation of cell membrane, but could induce intracellular effects such as apoptosis, calcium release, enhancement of gene expression, and fragmentation of DNA and chromosome. In order to account for the phenomenon, researchers believe that when the pulse width of the pulsed electric field is larger than the charging time of plasma membrane, the pulsed electric field mainly targets on the outer membrane of cell; and that the effect of the pulsed electric field on nucleus and nuclear membrane increases with the decrease of the pulse width. It is also believed that the effect of electroporation changes from the outer membrane to intracellular electromanipulation when the pulse width decreases to a value being smaller than the charging time of plasma membrane.


Hepatitis B surface antigen (HBsAg)-fibrinogen interaction.
Deparaffinized sections of hepatitis B surface antigen (HBsAg) positive liver biopsies, when incubated in a human fibrinogen solution, reveal a strong labelling of ground-glass hepatocytes with fibrinogen. This implies an interaction between HBsAg and fibrinogen. The binding of fibrinogen to HBsAg is thought to be mediated by the protein moiety of HBsAg, since its binding capacity is destroyed by trypsin digestion, and to occur through formation of disulphide bridges because the binding can be disrupted by the reducing effect of 2-mercapto-ethanol. Not all ground-glass hepatocytes exhibit fibrinogen binding. The reason for this is at present unclear. No relationship between serum HBeAg positivity and binding of HBsAg to fibrinogen was observed. Preincubation in a fibrinogen solution did not alter the immunoreactivity of HBsAg. We conclude that there is a striking analogy between the interaction of HBsAg with polymerized human serum albumin and its interaction with fibrinogen.


Structural and catalytic properties of the four phenylalanine ammonia-lyase isoenzymes from parsley (Petroselinum crispum Nym.).
Near-full-length cDNAs for the four phenylalanine ammonia-lyase (PAL) isoenzymes in parsley (Petroselium crispum Nym.) were cloned and the complete amino acid sequences deduced. Fusion proteins with glutathione S-transferase were expressed in Escherichia coli, purified and cleaved. All of the resulting phenylalanine ammonia-lyase proteins, as well as the fusion proteins, were catalytically active. The turnover number of one selected isoenzyme, PAL-1, was estimated to be around 22 s-1 for each active site. In contrast to a certain degree of differential expression in various parts of parsley plants, the four phenylalanine ammonia-lyase isoenzymes exhibited very similar apparent Km values for L-phenylalanine (15-24.5 microM) as well as identical temperature (58 degrees C) and pH (8.5) optima. All of them were competitively inhibited by (E)-cinnamate with similar efficiency (Ki values: 9.1-21.5 microM), lacked cooperative behaviour, and accepted L-tyrosine as a substrate with low affinity (Km values: 2.6-7.8 mM). These results suggest that the occurrence of multiple gene copies has a function other than encoding isoenzymes with different enzyme kinetic properties.


Research highlights from the 2017 ERS International Congress: airway diseases in focus.
For another year, high-quality research studies from around the world transformed the annual ERS International Congress into a vivid platform to discuss trending research topics, to produce new research questions and to further push the boundaries of respiratory medicine and science. This article reviews only some of the high-quality research studies on asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and chronic cough that were presented during the congress through the Airway Diseases Assembly (ERS Assembly 5) and places them into the context of current knowledge and research challenges.


Near- and far-ultraviolet circular dichroism of the catalytic subunit of adenosine cyclic 5'-monophosphate dependent protein kinase.
The circular dichroism spectrum of the catalytic subunit of cAMP-dependent protein kinase was measured in the far-UV (190-240 nm) and near-UV (250-300 nm) region. Data from the far-UV spectra were processed with the CONTIN program for estimation of globular protein secondary structure [ Provencher , S. W. (1982) CONTIN (Version 2) User's Manual, European Molecular Biology Laboratory, Heidelberg, West Germany]. The composition of the protein determined by this method was 49 +/- 2% alpha-helix, 20 +/- 4% beta-sheet, and 31 +/- 3% remainder. This composition changes when the protein is allowed to bind Kemptide , a synthetic peptide substrate, with more than half of the disordered portion of the protein taking the form of beta-sheet. A certain portion of the alpha-helical structure also appears to move into a beta-sheet form. The near-UV CD spectrum of catalytic subunit shows changes in aromatic amino acid dichroism associated with substrate binding. These changes can be ascribed with a fair degree of certainty to alterations in the orientation of a tyrosine residue at the surface of the protein. These findings are discussed in terms of previous work on induced dichroism in this enzyme with regard to control mechanisms operating at the active site.


[Stability and variation of the maximal ventilation and maximal expiratory volume ratios].
The level of stability of the ratio (alpha coefficient) of maximal ventilation (MBC) over maximal expiratory volume per second (FEV1) was continued statistically for its practical value in estimating the respiratory functional incapacity. Three observations were made: --the mean value of the alpha coefficient=MBC/FEV1 is independent of the sex, age, size or weight in the normal subject; alpha was slightly higher than that found from theoretical values of MBC (CECA) and FEV1 (BALDWIN and COURNAND); --the alpha coefficient varied with the vital capacity (VC) and with FEV1; --there was a particularly simple relation between alpha and VC: alpha decreased from 38 to 30 when VC increased from 1 to 6 litres.


Large-scale analysis of microRNA evolution.
In animals, microRNAs (miRNA) are important genetic regulators. Animal miRNAs appear to have expanded in conjunction with an escalation in complexity during early bilaterian evolution. Their small size and high-degree of similarity makes them challenging for phylogenetic approaches. Furthermore, genomic locations encoding miRNAs are not clearly defined in many species. A number of studies have looked at the evolution of individual miRNA families. However, we currently lack resources for large-scale analysis of miRNA evolution. We addressed some of these issues in order to analyse the evolution of miRNAs. We perform syntenic and phylogenetic analysis for miRNAs from 80 animal species. We present synteny maps, phylogenies and functional data for miRNAs across these species. These data represent the basis of our analyses and also act as a resource for the community. We use these data to explore the distribution of miRNAs across phylogenetic space, characterise their birth and death, and examine functional relationships between miRNAs and other genes. These data confirm a number of previously reported findings on a larger scale and also offer novel insights into the evolution of the miRNA repertoire in animals, and it's genomic organization.


Intestinal T-cell responses in celiac disease - impact of celiac disease associated bacteria.
A hallmark of active celiac disease (CD), an inflammatory small-bowel enteropathy caused by permanent intolerance to gluten, is cytokine production by intestinal T lymphocytes. Prerequisites for contracting CD are that the individual carries the MHC class II alleles HLA-DQ2 and/or HLA-DQ8 and is exposed to gluten in the diet. Dysbiosis in the resident microbiota has been suggested to be another risk factor for CD. In fact, rod shaped bacteria adhering to the small intestinal mucosa were frequently seen in patients with CD during the "Swedish CD epidemic" and bacterial candidates could later be isolated from patients born during the epidemic suggesting long-lasting changes in the gut microbiota. Interleukin-17A (IL-17A) plays a role in both inflammation and anti-bacterial responses. In active CD IL-17A was produced by both CD8(+) T cells (Tc17) and CD4(+) T cells (Th17), with intraepithelial Tc17 cells being the dominant producers. Gluten peptides as well as CD associated bacteria induced IL-17A responses in ex vivo challenged biopsies from patients with inactive CD. The IL-17A response was suppressed in patients born during the epidemic when a mixture of CD associated bacteria was added to gluten, while the reverse was the case in patients born after the epidemic. Under these conditions Th17 cells were the dominant producers. Thus Tc17 and Th17 responses to gluten and bacteria seem to pave the way for the chronic disease with interferon-γ-production by intraepithelial Tc1 cells and lamina propria Th1 cells. The CD associated bacteria and the dysbiosis they might cause in the resident microbiota may be a risk factor for CD either by directly influencing the immune responses in the mucosa or by enhancing inflammatory responses to gluten.


Photoaffinity labeling of human placental NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase with [alpha-32P]2N3NAD+. Identification of a peptide in the adenine ring binding domain.
Oxidation of many prostaglandins at C-15 results in the formation of 15-keto metabolites, which have reduced biological activity. This reaction is catalyzed by NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase. Using the photoaffinity analog of NAD+, [alpha-32P]nicotinamide-2-azidoadenine dinucleotide, we have identified a peptide in the adenine ring binding domain of the NAD+ binding site of 15-hydroxyprostaglandin dehydrogenase. The specificity of photolabeling was demonstrated by saturation and protection experiments. Saturation of photolabeling was observed at approximately 45-50 microM with an apparent Kd of 8-10 microM. Approximately 90% of photolabeling could be protected by 200 microM NAD+ when the protein was photolyzed in the presence of 10 microM probe. The photolabeled protein was digested with Staphylococcus aureus V8 or chymotrypsin, and the photolabeled peptides were purified by either boronate affinity chromatography or Fe+3 chelate chromatography followed by reverse phase HPLC. The photolabeled peptide region was identified to be Val32-Glu40.


Metabolic network reconstruction of Euglena gracilis: Current state, challenges, and applications.
A metabolic model, representing all biochemical reactions in a cell, is a prerequisite for several approaches in systems biology used to explore the metabolic phenotype of an organism. Despite the use of Euglena in diverse industrial applications and as a biological model, there is limited understanding of its metabolic network capacity. The unavailability of the completed genome data and the highly complex evolution of Euglena are significant obstacles to the reconstruction and analysis of its genome-scale metabolic model. In this mini-review, we discuss the current state and challenges of metabolic network reconstruction in Euglena gracilis. We have collated and present the available relevant data for the metabolic network reconstruction of E. gracilis, which could be used to improve the quality of the metabolic model of E. gracilis. Furthermore, we deliver the potential applications of the model in metabolic engineering. Altogether, it is supposed that this mini-review would facilitate the investigation of metabolic networks in Euglena and further lay out a direction for model-assisted metabolic engineering.


Effect of Hypnosis on Anxiety: Results from a Randomized Controlled Trial with Women in Postmenopause.
Anxiety is common, yet often under-treated, among women in postmenopause. This study examined the effect of a hypnotic intervention designed to reduce hot flashes, on anxiety levels of postmenopausal women. Anxiety was assessed using the State-Trait Anxiety Inventory, the Hospital Anxiety and Depression Scale-Anxiety subscale, and a visual analog scale. Additionally, hypnotizability was tested as a moderator of anxiety reductions. Significant reductions in anxiety were found from baseline to endpoint and follow-up and hypnosis was superior to the control condition. Additionally, ratings of Current Anxiety decreased from pre-session to post-session at each weekly visit and the pre-session scores reduced continuously. Hypnotizability was found to moderate anxiety reductions, but regardless of hypnotizability level participants, on average, experienced significant symptom improvement from baseline scores. These data provide initial support for the use of hypnosis to reduce symptoms of anxiety among postmenopausal women.Trial registration: This study was registered at ClinicalTrials.gov on February 11, 2011 under Identifier number NCT01293695 ( https://clinicaltrials.gov/ct2/show/NCT01293695?term=Elkins&cond=hot+flashes&draw=2&rank=2 ).


Epidemiological features of amyotrophic lateral sclerosis in a large clinic-based African American population.
Our objective was to identify the main clinical and epidemiological features of ALS in a large cohort of African American (AA) patients and compare them to Caucasian (CA) patients in a clinic-based population. We retrospectively identified 207 patients who were diagnosed with ALS based on the revised El Escorial criteria (60 AA and 147 CA subjects). Patients were seen in the Neuromuscular Division at the University Medical Center. We compared epidemiological and clinical features of these two groups, focusing on age of onset and diagnosis, clinical presentation and survival. Results showed that AA patients had a significantly younger age of disease onset (55 years vs. 61 years for CA, p = 0.011) and were diagnosed at an earlier age (56 years vs. 62 years, p = 0.012). In younger ALS patients (< 45 years of age), there was a significant difference in gender frequency, with females predominating in the AA population and males in the CA population (p = 0.025). In a multivariable Cox proportional hazard model, survival rates were not different between the groups. In both groups, survival significantly increased with younger age. In conclusion, AA patients presented at an earlier age, but there was no difference in survival compared to CA patients. A gender reversal occurred in younger ALS patients, with AA patients more likely to be female and CA patients more likely to be male.


Scanning electron microscopy of in vitro serum-mediated destruction of juvenile Fasciola hepatica.
The tegumental surface of immature Fasciola hepatica was damaged when incubated in vitro with serum collected from an experimentally infected calf. Degeneration of the tegumental surface was observed by scanning electron microscopy (SEM) at 4 hr. after incubation. Decomposition was observed 8 to 12 hr after incubation and complete destruction of the tegument occurred by 16 hr. The flukes became inactive after 8 to 12 hr of incubation. None of the above findings were observed for the tegument of flukes incubated in tissue culture media or in media containing normal calf serum and the trematodes remained motile throughout the incubation period. Latex particles were used as an immunological marker for SEM studies to determine if gamma globulin could be responsible for the observed changes and, if so, the site of antibody attachment. The coated latex particles covered the entire surface of flukes recovered from mice 5 days after infection with metacercariae. In contrast, latex particles coated with either normal gamma globulin or gamma globulin from serum of the experimentally infected calf that had been adsorbed with disrupted adult flukes were not attached to the surface of the flukes. Absorption of the serum with disrupted, adult flukes decreased the concentrations of immunoglobulins (Ig)G1 and G2 whereas IgA and IgM were apparently not affected.


Machiavelli's advice to the hospital chief executive officer.
Hospital chief executive oficers (CEOs) have demanding jobs in which they must, at tims, function as if they are potentates of small principalities. Their ability to elicit loyalty and allegiance, hand out discipline and praise, foster alliances with other organizations, and commit the occasional hostile yet (it is hoped) successful foray onto a competitor's turf are skills that must be mastered for success and longevity. We have taken the thoughts and strategies of the Renaissance political master, Niccolo Machiavelli, and applied them to the modern hospital CEO for whom we feel they still hold elements of wisdom and guidance.


A Review of Applications and Intracellular Mechanisms of Intense Pulsed Light in Eyelid Inflammatory Diseases.
Objective: To evaluate relevant clinical outcomes and conclude possible mechanisms of intense pulsed light (IPL) in eyelid inflammation. Background: IPL devices were primarily applied in cutaneous vascular malformations and have been used in ocular diseases for about 20 years, mostly including meibomian gland dysfunction (MGD), blepharitis, and ocular rosacea. Recent findings: Seventy-two original clinical researches were included, 57 for MGD, 4 for blepharitis or blepharitis-related keratoconjunctivitis, and 11 for rosacea. Dry eye symptoms, (tear) break-up time (BUT), and meibomian structure and/or functions were improved in most patients, but production of reactive oxygen species is an important link in the photobiomodulation mediated by IPL, which can influence numerous signal pathways to achieve anti-inflammatory, anti-infective, and prodifferentiation effects. Conclusions: The evidence suggests that IPL is an effective therapeutic tool for most patients with MGD, but more clinical evidence is needed for other indications.


Assessment of drug activity and proliferation ex vivo for prediction of outcome in aggressive non-Hodgkin's lymphomas.
The activity of cytotoxic drugs and tumour cell proliferation rate were assessed ex vivo using the fluorometric microculture cytotoxicity assay (FMCA) and stainings for Ki67 and mitosis in 40 patients with aggressive non-Hodgkin's lymphomas (NHL). The findings were correlated to clinical response and survival. Twenty-three patients had a complete remission and 10 a partial remission. A drug sensitivity index based on the cell survival for three major drugs in NHL treatment was derived empirically and proliferation was expressed as low-, intermediate- or high. In 5 out of 8 drugs tested, cell survival ex vivo was higher in clinical non-responders than that in responders. Using the median drug sensitivity index as a cut-off, the sensitivity and specificity for tumour response were 58% and 100%, respectively, and was similar for the proliferation index. Both indices combined increased the sensitivity to 73% at retained specificity. Intermediate/high proliferation was significantly associated with impaired survival, whereas the drug sensitivity index was not predictive of survival. Thus, ex vivo assessments of drug sensitivity and proliferation seem to provide prognostic information in aggressive NHL.


[Polyradiomodification as component of combined treatment of rectal cancer: rationale and results].
The report discusses our 30-year experience with surgical and combined treatment of rectal cancer. In cases of preoperative radiotherapy, loco-regional frequency of relapse dropped to 9.6% as compared with surgery (16.3%). After preoperative thermoradiotherapy it fell to 4.6%; polyradiomodification - 0.5% (3-year follow-up). Distant metastasis formation rates were: after polyradiomodification--1.5%, radiotherapy--9.6%, and thermo-radiotherapy--6%. Recurrence-free survival rates (3 years) were: polyradiomodification--97.3%, thermo-radiotherapy--75.9%, radiotherapy--71.1%, and surgery--58%. Data on regimens and dosage of polyradiomodification alongside radiation damage for different combinations of treatment are presented.