IPr3 Si3 Cl5 (+) : A Highly Reactive Cation with Silanide Character.
The reaction of a metastable SiCl2 solution with the sterically less-demanding carbene N,N-diisopropylimidazo-2-ylidene (IPr) yields the salt [(IPr3 Si3 Cl5 )(+) ]Cl(-) (1-Cl), containing a silyl cation with a Si3 backbone. Salt 1 is highly reactive, but it can be used as a reagent in deuterated dichloromethane, whereby dehalogenation with Me3 SiOTf (OTf=O3 SCF3 ) gives the dicationic silyl halide [(IPr3 Si3 Cl4 )](2+) 2. Quantum chemical calculations show that the HOMO is localized at the negatively charged central silicon atom of 1 and 2, and thus although both compounds are cations they are better described as silanides, which was also corroborated by NMR investigations.


Service provider attitudes regarding conversational rule violations in three public settings.
Previous research identified an attitudinal hierarchy of conversational tradeoff choices among public service providers involving utterance-based augmentative and alternative communication (AAC) systems in a bookstore context. The purpose of the current research was to determine if there was a hierarchy of choices in three additional settings (i.e., movie theater, convenience store, hair salon), if these hierarchies would be the same, and if there were attitude differences in terms of participant gender and that of the person using AAC. In each of two experiments, 80 service providers viewed scripted, video-recorded conversations between a customer using AAC and a nonvisible provider in each setting, and completed an attitude questionnaire. A hierarchy of tradeoffs was found in each setting, although not the same hierarchy. No gender differences were found. As in the bookstore, messages with repetitive information were consistently rated the highest, messages with partly relevant information were consistently rated the lowest and messages with a delay in delivery were consistently rated in the middle of the hierarchies across the current settings, while messages with either inadequate or excessive information were more context-sensitive. The findings may direct individuals in message choice selections that yield the most positive evaluations by service providers and in designing technology to optimize these choices.


Antinociceptive Effects of Prim-O-Glucosylcimifugin in Inflammatory Nociception via Reducing Spinal COX-2.
We measured anti-nociceptive activity of prim-o-glucosylcimifugin (POG), a molecule from Saposhnikovia divaricate (Turcz) Schischk. Anti-nociceptive or anti-inflammatory effects of POG on a formalin-induced tonic nociceptive response and a complete Freund's adjuvant (CFA) inoculation-induced rat arthritis pain model were studied. Single subcutaneous injections of POG produced potent anti-nociception in both models that was comparable to indomethacin analgesia. Anti-nociceptive activity of POG was dose-dependent, maximally reducing pain 56.6% with an ED50 of 1.6 mg. Rats given POG over time did not develop tolerance. POG also time-dependently reduced serum TNFα, IL-1β and IL-6 in arthritic rats and both POG and indomethacin reduced spinal prostaglandin E2 (PGE2). Like indomethacin which inhibits cyclooxygenase-2 (COX-2) activity, POG dose-dependently decreased spinal COX-2 content in arthritic rats. Additionally, POG, and its metabolite cimifugin, downregulated COX-2 expression in vitro. Thus, POG produced potent anti-nociception by downregulating spinal COX-2 expression.


EchinoDB: an update to the web-based application for genomic and transcriptomic data on echinoderms.
Here we release a new version of EchinoDB, EchinoDB v2.0 ( https://echinodb.uncc.edu ). EchinoDB is a database of genomic and transcriptomic data on echinoderms. The initial database consisted of groups of 749,397 orthologous and paralogous transcripts arranged in orthoclusters by sequence similarity. The updated version of EchinoDB includes two new major datasets: the RNA-Seq data of the brittle star Ophioderma brevispinum and the high-quality genomic assembly data of the green sea urchin Lytechinus variegatus. In addition, we enabled keyword searches for annotated data and installed an updated version of Sequenceserver to allow Basic Local Alignment Search Tool (BLAST) searches. The data are downloadable in FASTA format. The first version of EchinoDB appeared in 2016 and was implemented in GO on a local server. The new version has been updated using R Shiny to include new features and improvements in the application. Furthermore, EchinoDB now runs entirely in the cloud for increased reliability and scaling. EchinoDB serves a user base drawn from the fields of phylogenetics, developmental biology, genomics, physiology, neurobiology, and regeneration. As use cases, we illustrate the function of EchinoDB in retrieving components of signaling pathways involved in the tissue regeneration process of different echinoderms, including the emerging model species Ophioderma brevispinum. Moreover, we use EchinoDB to shed light on the conservation of the molecular components involved in two echinoderm-specific phenomena: spicule matrix proteins involved in the formation of stereom endoskeleton and the tensilin protein that contributes to the capacity of the connective tissues to quickly change its mechanical properties. The genes involved in the former had been previously studied in echinoids, while gene sequences involved in the latter had been previously described in holothuroids. Specifically, we ask (a) if the biomineralization-related proteins previously reported only in sea urchins are also present in other, non-echinoid, echinoderms and (b) if tensilin, the protein responsible for the control of stiffness of the mutable collagenous tissue, previously described in sea cucumbers, is conserved across the phylum.


Synthesis of 6-formylpterin nucleoside analogs and their ROS generation activities in the presence of NADH in the dark.
We demonstrated previously that 3-position-modified 6-formylpterin (6FP) derivatives produce reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) from oxygen in the presence of NADH in the dark. It has been shown that 6FP derivatives markedly generate ROS, which gives rise to their particular physiological activities, such as induction of apoptosis in cellular and living systems, suggesting that such compounds provide a hint for the design of a ROS controlling agent in vivo. However, it is not well understood why such unique activities appear on chemical modification. In the present study, in order to see the effect on ROS generation activity in the dark by the modification of the 1-position in 6FP, we have developed a new synthetic procedure for nucleoside analogs of 6FP and prepared 1-(beta-d-ribofuranosyl)-2-(N,N-diethylaminomethyleneamino)-6-formylpteridin-4-one (RDEF) and 1-(beta-d-ribofuranosyl)-2-(piperidine-1-ylmethyleneamino)-6-formylpteridin-4-one (RPIF) in which the 1-position of 6FP is glycosylated. At pH 7.4, NADH was spontaneously oxidized to NAD(+) in the presence of RDEF in the dark. Using electron paramagnetic resonance analysis coupled with the spin trapping technique, we show that O(2) was converted to H(2)O(2)via superoxide anion radical ( O(2)(-)) during this reaction. The modification of the 1-position of 6FP did not cancel ROS generation activities, which were demonstrated in 3-position-modified 6FPs. Since the 6FP derivatives developed in the present study have a ribose moiety, these compounds can be subjected to further derivatization, such as incorporation into oligonucleotides, oligosaccharides, proteins, or any other compounds that recognize and interact with specific biomolecules, and therefore would be useful in pharmaceutical investigations that need generation of appropriate and controllable amounts of ROS in vivo.


Neurobiology of Comorbid Substance Use Disorders and Psychiatric Disorders: Current State of Evidence.
"Dual disorder" or "dual diagnosis" refers to the co-occurrence of substance use disorder and psychiatric disorders. Prospective studies have shown that treatment outcomes, such as symptom levels, hospitalization rates, housing stability, and functional status, are worse among the patients with dual disorders as compared with those who have either of these disorders. The current article is aimed at reviewing the current state of evidence on neurobiology of dual disorders. Given the high prevalence of co-occurrence of substance use disorder and psychiatric disorders, it is important to explore the various facets of this association. The current review assimilates the information on neurobiological research on dual disorders and helps the readers gain insights into the current understanding on this theme. The electronic database of PubMed was searched for relevant publications. The studies included in the review belonged to various domains of neurobiology including neuropathology, structural neuroimaging, functional neuroimaging, genetics, neurochemicals/neuroreceptors, and neuroendocrinology. Forty studies were included in the review. Most of the issues related to the neurobiology of dual disorders remain inadequately studied. However, the current evidence suggests that the individuals with co-occurring disorders are likely to differ from those with either substance use disorders or psychiatric disorders alone on various neurobiological aspects. Hence, it is imperative to systematically study the various neurobiological aspects of dual disorders in the future.


Shoshin beriberi: a rare diagnostic problem.
A 30 year old man with a 15 year history of alcohol abuse presented with symptoms and signs of circulatory shock, severe disturbances of renal and liver functions, and metabolic acidosis. The cardiovascular and metabolic features were attributable to Shoshin beriberi. He recovered completely after treatment with thiamine.


Service support, work engagement and psychological wellbeing: validating an index of resource and infrastructure support for the delivery of CBT.
Effective dissemination of cognitive behavioural therapy (CBT) has been assisted by clearly defined competencies, skills and activities, and validated scales used to measure therapist competence and adherence. However, there is no validated measure of the resource and infrastructure support therapists require to enable them to deliver CBT in line with best practice. This study aimed to validate an index of resource infrastructure and support for the delivery of CBT. This study took an existing questionnaire developed by Groom and Delgadillo () and aimed to establish its psychometric properties through expert review and a pilot study. This resulted in a shorter questionnaire with good content validity, internal consistency (α = 0.80) and temporal stability (r = 0.74, p < .00). The index consists of six components, and construct validity was demonstrated through positive association with measures of work engagement (r = 0.31, p < .00) and practitioner wellbeing (r = 0.47, p < .00). The questionnaire provides a valid and reliable index of service support for delivering CBT, and is positively related to engagement and wellbeing among CBT practitioners.


Regioisomeric structure determination of alpha- and gamma-linolenoyldilinoleoylglycerol in blackcurrant seed oil by silver ion high-performance liquid chromatography and mass spectrometry.
Gamma-linolenic acid (Gla) and oils containing Gla have evident positive effects on a variety of disorders, and therefore, the structure of triacylglycerols (TAGs) containing Gla is of special interest. The regioisomeric structures of TAGs 18:3(n-3)/18:2/18:2 (Ala/L/L) and 18:3(n-6)/18:2/18:2 (Gla/L/L) in blackcurrant seed oil were determined by Ag-HPLC/APCI-MS and Ag-HPLC/ESI-MS/MS techniques. In the latter, silver ion adducts were prepared by adding silver nitrate to the postcolumn flow. A new Ag-HPLC solvent system containing nonchlorinated solvents for the separation of Gla- and Ala-containing TAGs is introduced. Ag-HPLC separation of Ala/L/L and Gla/L/L was sufficient and regioisomers sn-LnLL + sn-LLLn and sn-LLnL (Ln, linolenic acid) could be differentiated well with the MS methods used. No discrimination was made between the sn-1 and sn-3 positions. The results show that the methods used are suitable to discriminate and determine the regioisomeric structure of TAGs. The regioisomeric structure of TAG with the fatty acid combination Gla/L/L in blackcurrant seed oil was considered to be practically random (32.7-37.8% of sn-LGlaL). In the fatty acid combination Ala/L/L, the regioisomeric structure is nonrandom (7.3-12.1% of sn-LAlaL) with Ala preferentially in a primary position. It can be concluded that the positional distribution of Ala and Gla is different in Ln/L/L TAGs of blackcurrant seed oil.


High-Yielding Syntheses of Crown Ether-Based Pyridyl Cryptands.
Pyridinium bis(trifluoromethylsulfonyl)imide (PyTFSI)-templated syntheses of 2,6-pyridyl cryptands of cis(4,4')-dibenzo-30-crown-10 (3a), the p-bromobenzyloxy derivative 3b, bis(m-phenylene)-32-crown-10 (5), cis(4,4')-dibenzo-27S-crown-9 (7), cis(4,4')-dibenzo-27L-crown-9 (9), and cis(4,4')-dibenzo-24-crown-8 (11) are reported. Here we provide a fast (12 h), high-yielding (89%, 74%, 80%, and 62% for 3a, 3b, 5, and 9, respectively) templation method without the use of a syringe pump. The yields for 7 (19%) and 11 (26%) were lower than with the previous pseudo-high-dilution method, indicating ineffective templation in these cases. Coupled with our previously developed templated syntheses of dibenzo crown ethers, this protocol makes powerful cryptand hosts readily available in gram quantities in good yields from methyl 4(or 3)-hydroxy-3(or 4)-benzyloxybenzoate.


The Springtime Influence of Natural Tropical Pacific Variability on the Surface Climate of the Ross Ice Shelf, West Antarctica: Implications for Ice Shelf Thinning.
Observational records starting in the 1950s show West Antarctica is amongst the most rapidly warming regions on the planet. Together with increased intrusions of warm circumpolar deep water (CDW) onto the continental shelf due to local wind forcing (the primary mechanism in recent decades), this has resulted in enhanced surface and basal melting of floating ice shelves and an associated acceleration and thinning of West Antarctic outlet glaciers, increasing the rate of global sea level rise. In this study, it is shown that during the austral spring season, significant surface warming across West Antarctica has shifted westward to the Ross Ice Shelf in recent decades in response to enhanced cyclonic circulation over the Ross Sea. These circulation changes are caused by a Rossby wave train forced by increasing sea surface temperatures in the western tropical Pacific, which is tied to the springtime shift of the Interdecadal Pacific Oscillation (IPO) to its negative phase after 1992. While the local wind trends enhance warm air advection and surface warming across the Ross Ice Shelf, the strong easterly component of the wind trends reduces the likelihood for intrusions of CDW onto the continental shelf in this region. This suggests that during spring there are competing mechanisms of surface and basal melting of the Ross Ice Shelf, both of which are closely tied to natural tropical Pacific decadal variability. Moreover, that the projected transition of the IPO back to its positive phase in the coming decade, though likely to reduce surface warming on the Ross Ice Shelf, could increase the risk of disintegration of Ross Sea ice shelves due to increased intrusions of CDW and enhanced basal melting.


Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection.
Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection. Despite low or lack of CD4 receptor expression on Vδ2 T cells, infection of these cells has previously been reported. We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo. We assessed the presence of latent HIV infection by measurements of DNA and outgrowth assays within Vδ2 cells in 18 aviremic patients on long-standing antiretroviral therapy. In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.


Fullerene C60 films cross-linked with octane-1,8-dithiol: preparation, characterization and the use as template for chemical deposition of gold nanoparticles.
We report on the preparation of fullerene C60 thin films chemically cross-linked with octane-1,8-dithiol, which are capable of binding gold nanoparticles. The formation of a polymer was directly proved by means of laser desorption/ionization time-of-flight mass spectra, in which we observed the cleavage of fullerene-dithiol polymer at different bonds. Fourier-transform infrared, Raman and UV-visible spectra of the functionalized films exhibited notorious changes due to the formation of new covalent bonds between C60 molecules and bifunctional thiol. We further demonstrated that the dithiol-functionalized fullerene can be employed as a support for stable and homogeneous deposition of gold nanoparticles. Their average size is about 5 nm according to high-resolution transmission electron microscopy observations, and up to 20 nm, as found from scanning tunneling microscopy images. The proposed binding mechanism is through a strong coordination attachment between Au nanoclusters and sulfur donor atoms of the functionalized fullerene, as supported by density functional theory calculations.


Developing a framework of quality indicators for healthcare business cases: a qualitative document analysis consolidating insight from expert guidance and current practice.
Business cases are used to provide a structured justification in favour of investing in new projects, services or interventions. Despite the use of business cases in determining how limited resources will be allocated within England's National Health Service (NHS), guidance concerning how to develop and evaluate business cases in the context of healthcare is inconstant and of varying relevance. This study aimed to develop a new framework of quality indicators for healthcare-related business cases by analysing the content of expert guidance documents and a sample of NHS business cases. Qualitative document analysis was conducted on guidance documents (n = 7) and existing NHS business case documents (n = 18). Documents were purposefully sampled using criteria to ensure the framework reflected a diverse spread of expert opinion, and a varied sample of example business cases from current practice. Data were analysed using thematic and content analysis, and are presented in a visualised framework. Seven themes were identified within the qualitative document analysis (purpose, strategic priorities, options, benefits, costs, risks and evaluation). These themes were described and presented with a framework of quality indicators for healthcare-related business cases. To ou`r knowledge, this is the first framework of business case quality indicators designed specifically for use in a healthcare context. The framework presented in this study has implications for how business cases are developed and evaluated by decision makers. In the future it would be beneficial to investigate how the framework could be used in practice as a tool for critical appraisal.


Phytoplankton Biological Pump Controls the Spatiotemporal Bioaccumulation and Trophic Transfer of Antibiotics in a Large Subtropical River.
The spatiotemporal bioaccumulation, trophic transfer of antibiotics, and regulation of the phytoplankton biological pump were quantitatively evaluated in the Pearl River, South China. The occurrence of antibiotics in organisms indicated a significant spatiotemporal trend associated with the life cycle of phytoplankton. Higher temporal bioaccumulation factors (BAFs) were found in phytoplankton at the bloom site, while lower BAFs of antibiotics in organisms could not be explained by phytoplankton biomass dilution but were attributed to the low bioavailability of antibiotics, which was highly associated with distribution coefficients (R2 = 0.480-0.595, p < 0.05). Such lower BAFs of antibiotics in phytoplankton at higher biomass sites hampered the entry of antibiotics into food webs, and trophic dilutions were subsequently observed for antibiotics except for ciprofloxacin (CFX) and sulfamerazine (SMZ) at sites with blooms in all seasons. Distribution of CFX, norfloxacin (NFX), and sulfapyridine (SPD) showed further significant positive relationships with the plasma protein fraction (R2 = 0.275-0.216, p < 0.05). Both mean BAFs and trophic magnification factors (TMFs) were significantly negatively correlated with phytoplankton biomass (R2 = 0.661-0.741, p < 0.05). This study highlights the importance of the biological pump in the regulation of spatiotemporal variations in bioaccumulation and trophic transfer of antibiotics in anthropogenic-impacted eutrophic rivers in subtropical regions.


Characterization of Black Pigmenturia in a Cat with Apocrine Gland Cystadenocarcinoma.
An 8-year-old neutered female domestic shorthair cat was presented for further management of an apocrine gland cystadenocarcinoma. Extensive nodal metastasis was diagnosed and the cat was humanely destroyed 2 months after presentation. Post-mortem histopathology of the cystadenocarcinoma revealed areas of yellow-brown granular pigmentation on light microscopy, staining positively for reducing substances with Schmorl's stain and demonstrating autofluorescence on confocal microscopy. The cat's urine was black and also exhibited autofluorescence, and further analysis revealed increased free pentosidine. Based on these findings, it was presumed that the apocrine gland cystadenocarcinoma was producing lipofuscin-like pigments and that the characteristics of the urine were at least partially secondary to advanced glycation end-products.


Hospital Variation in Mortality After Inpatient Pediatric Surgery.
The aim was to determine the association between risk adjusted hospital perioperative mortality rates, postoperative complications, and failure to rescue (FTR) after inpatient pediatric surgery. FTR has been identified as a possible explanatory factor for hospital variation in perioperative mortality in adults. However, the extent to which this may be the case for hospitals that perform pediatric surgery is unclear. The Pediatric Health Information System database (2012-2020) was used to identify patients who underwent one of 57 high-risk operations associated with significant perioperative mortality (n=203,242). Academic, pediatric hospitals (n=48) were stratified into quintiles based on risk adjusted inpatient mortality [lower than average, quintile 1 (Q1); higher than average, quintile 5 (Q5)]. Multivariable hierarchical regression was used to evaluate the association between hospital mortality rates, complications, and FTR. Inpatient mortality, complication, and FTR rates were 2.3%, 8.8%, and 8.8%, respectively. Among all patients who died after surgery, only 34.1% had a preceding complication (Q1, 36.1%; Q2, 31.5%; Q3, 34.7%; Q4, 35.7%; Q5, 32.2%; trend test, P =0.49). The rates of observed mortality significantly increased across hospital quintiles, but the difference was <1% (Q1, 1.9%; Q5; 2.6%; trend test, P <0.01). Relative to Q1 hospitals, the odds of complications were not significantly increased at Q5 hospitals [odds ratio (OR): 1.02 (0.87-1.20)]. By comparison, the odds of FTR was significantly increased at Q5 hospitals [OR: 1.60 (1.30-1.96)] with a dose-response relationship across hospital quintiles [Q2-OR: 0.99 (0.80-1.22); Q3-OR: 1.26 (1.03-1.55); Q4-OR: 1.33 (1.09-1.63)]. The minority of pediatric surgical deaths are preceded by a postoperative complication, but variation in risk adjusted mortality across academic, pediatric hospitals may be partially explained by differences in the recognition and management of postoperative complications. Additional work is needed to identify children at greatest risk of postoperative death from perioperative complications as opposed to those at risk from pre-existing chronic conditions.


Selective killing of cancer cells by a small molecule targeting the stress response to ROS.
Malignant transformation, driven by gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes, results in cell deregulation that is frequently associated with enhanced cellular stress (for example, oxidative, replicative, metabolic and proteotoxic stress, and DNA damage). Adaptation to this stress phenotype is required for cancer cells to survive, and consequently cancer cells may become dependent upon non-oncogenes that do not ordinarily perform such a vital function in normal cells. Thus, targeting these non-oncogene dependencies in the context of a transformed genotype may result in a synthetic lethal interaction and the selective death of cancer cells. Here we used a cell-based small-molecule screening and quantitative proteomics approach that resulted in the unbiased identification of a small molecule that selectively kills cancer cells but not normal cells. Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death in both cancer cells and normal cells engineered to have a cancer genotype, irrespective of p53 status, but it has little effect on either rapidly or slowly dividing primary normal cells. Significant antitumour effects are observed in piperlongumine-treated mouse xenograft tumour models, with no apparent toxicity in normal mice. Moreover, piperlongumine potently inhibits the growth of spontaneously formed malignant breast tumours and their associated metastases in mice. Our results demonstrate the ability of a small molecule to induce apoptosis selectively in cells that have a cancer genotype, by targeting a non-oncogene co-dependency acquired through the expression of the cancer genotype in response to transformation-induced oxidative stress.


Natural variation in food acquisition mediated via a Drosophila cGMP-dependent protein kinase.
In natural environments where food abundance and quality can change drastically over time, animals must continuously alter their food acquisition strategies. Although genetic variation contributes to this plasticity, the specific genes involved and their interactions with the environment are poorly understood. Here we report that natural variation in the Drosophila gene, foraging (for), which encodes a cGMP-dependent protein kinase (PKG), affects larval food acquisition in an environmentally dependent fashion. When food is plentiful, the wild-type rover (for(R)) allele confers lower food intake and higher glucose absorption than both the wild-type sitter (for(s)) allele and the mutant for(s2) allele. When food is scarce, for(R), for(s) and for(s2) larvae increase food intake to a common maximal level, but for(R) larvae retain their increased absorption efficiency. Changes in for expression can induce corrective behavioral modifications in response to food deprivation. When reared in environments with low food levels, for(R) larvae have higher survivorship and faster development than for(s) and for(s2) larvae. Together, these results show that natural variation in for has far reaching implications affecting a suite of phenotypes involved in the regulation of food acquisition.


Spontaneous ovarian neoplasms of the laboratory rat.
A wide range of spontaneous tumors of the ovary are reported in a group of 5903 aged female Sprague-Dawley rats of the CD and CFY strains examined since 1978 in this laboratory. The most commonly observed tumor was the tubular adenoma. Others recorded were tubular adenocarcinoma, papillary cystadenoma, papillary cystadenocarcinoma, a Sertoli's cell tumor, benign and malignant granulosa cell tumors, benign thecal cell tumors, and classical mesotheliomas of ovarian origin. A system of classification and nomenclature of the ovarian tumors from this group is advanced.


Genetic heterogeneity: implications and methods of detection.
Genetic heterogeneity is highly pervasive in genetic disorders. The need to identify its existence is reflected in the potentially different treatments, prognoses, and recurrence risks associated with each disease entity. Of the 3 major approaches to its detection, biochemical methods are better than pedigree, and pedigree methods are better than clinical in their ability to pinpoint the underlying defect, but each plays an important role in the discovery process. With the advent of several new highly specific biochemical techniques, the next decade promises to show major advances in this area of genetics.


Introduction of an adaptor to fix Y/Z slides during Leksell gamma knife radiosurgery to treat concomitant bilateral far-lateral lesions.
The authors develop and introduce an adaptor in gamma knife radiosurgery to fix the Y/Z slides inside the Leksell coordinate G frame for the treatment of concomitant bilateral far-lateral intracranial lesions. The new adaptor was used to treat a 60-year-old woman with renal cell carcinoma and multiple brain metastases. She experienced sudden onset of left-sided weakness and disturbed consciousness. Brain computed tomographic scans showed a large right temporal intracerebral hematoma. After a craniectomy for the removal of the hematoma, she received a complete course of whole brain radiotherapy. However, several new tumors were detected on the follow-up brain magnetic resonance imaging scan. The longest distance of these far-lateral lesions on the x axis was approximately 108 mm. It was not possible to treat some of these tumors in one session with the normal use of the Y/Z slides in the trunnions mode. We developed a new adaptor to fix the Y/Z slides inside the G frame. By using the adaptor, the far-lateral located tumors were treated successfully in a single session. This newly developed adaptor can fix the Y/Z slides inside the G frame. It increases the range of the coordinates on the x axis from 52 to 148 mm to 30 to 170 mm. Using the adapter, gamma knife radiosurgery is a simple and accurate procedure for the treatment of bilateral far-lateral lesions in one session, particularly for lesions that cannot be approached with the normal use of the Y/Z slides in the trunnions mode.


Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function.
Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.


Serum uric acid is associated with better executive function in men but not in women: Baseline assessment of the ELSA-Brasil study.
Serum uric acid (SUA) may protect against free radical stress damage and was previously linked to cognitive impairment in older adults, but evidence in middle-aged adults is scarce. We sought to analyze whether SUA is associated with cognitive performance in apparently healthy middle-aged participants in the ELSA-Brasil cohort study. We excluded participants older than age 65, those taking allopurinol, benzbromarone, or medications that could impair cognitive performance, those with previous stroke, and those with incomplete data on cognitive tests or SUA. The Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Test (CERAD-WLMT), the Semantic Fluency Test (SFT), and the Trail Making Test version B (TMT) were used as dependent variables. Sex-specific linear regression models were used to assess the association between SUA and cognitive tests, adjusted by age, education, hypertension, dyslipidemia, diabetes, smoking, alcohol consumption, body mass index, coronary heart disease, renal function, depression, aspirin use, thyroid function, and menopausal status (in women). We used the Bonferroni procedure to control for the false discovery rate associated with multiple comparisons. We analyzed cross-sectional data from 6751 women and 5464 men. Mean age and standard deviation (SD) of the sample was 49.6 (SD 7.4) years for men and 49.9 (SD 7.3) years for women. The majority of men (52%) and women (51%) were white. Mean SUA value was 4.75 (SD 1.16) mg/dL in women and 6.44 (SD 1.39) mg/dL in men. Multivariate linear models showed no association in women and a significant inverse association between SUA levels and TMT (β=-3.106, 95% CI=-4.594; -1.618, p=0.0004) in men. In a middle-aged subset population, SUA is associated with better performance on an executive function test in men, but not in women in the ELSA-Brasil cohort study.


DJ-1 plays a neuroprotective role in SH-SY5Y cells by modulating Nrf2 signaling in response to lidocaine-mediated oxidative stress and apoptosis.
To investigate the effects of DJ-1 on lidocaine-induced cytotoxicity in neurons and the link with Nrf2 signaling, SH-SY5Y cells were treated with 1, 4, 8, and 16 mM lidocaine. Cell viability was measured by MTT assay, and apoptosis was measured by flow cytometry analysis. The mitochondrial membrane potential, reactive oxygen species (ROS) levels, lipid peroxidation (MDA), and GSH/GSSG ratio were determined with specific kits. Expression of DJ-1, Nrf2, and Nrf2 downstream signaling proteins (glutathione peroxidase [GPx], heme oxygenase-1 [HO-1], catalase [CAT], and glutathione reductase [GR]), was determined by western blot and qRT-PCR. The cell viability was dramatically decreased, while levels of apoptosis, ROS and Cys106-oxidized DJ-1 were significantly enhanced following treatment with lidocaine (concentration 4-16 mM), and increases were observed in a dose-dependent manner. After treatment with 8 mM lidocaine, DJ-1, and nuclear Nrf2, as well as antioxidative stress-related proteins, GPx, GR, HO-1, and CAT, were all significantly inhibited. Overexpression of DJ-1 suppressed lidocaine-induced apoptosis and oxidative stress in SH-SY5Y cells and activated Nrf2 signalling at the same time, and these effects were reversed by the inhibition of Nrf2. DJ-1 could protect SH-SY5Y cells from lidocaine-induced apoptosis through inhibition of oxidative stress via Nrf2 signaling.


Cryptic speciation and recombination in the fungus Paracoccidioides brasiliensis as revealed by gene genealogies.
Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, a disease confined to Latin America and of marked importance in the endemic areas due to its frequency and severity. This species is considered to be clonal according to mycological criteria and has been shown to vary in virulence. To characterize natural genetic variation and reproductive mode in this fungus, we analyzed P. brasiliensis phylogenetically in search of cryptic species and possible recombination using concordance and nondiscordance of gene genealogies with respect to phylogenies of eight regions in five nuclear loci. Our data indicate that this fungus consists of at least three distinct, previously unrecognized species: S1 (species 1 with 38 isolates), PS2 (phylogenetic species 2 with six isolates), and PS3 (phylogenetic species 3 with 21 isolates). Genealogies of four of the regions studied strongly supported the PS2 clade, composed of five Brazilian and one Venezuelan isolate. The second clade, PS3, composed solely of 21 Colombian isolates, was strongly supported by the alpha-tubulin genealogy. The remaining 38 individuals formed S1. Two of the three lineages of P. brasiliensis, S1 and PS2, are sympatric across their range, suggesting barriers to gene flow other than geographic isolation. Our study provides the first evidence for possible sexual reproduction in P. brasiliensis S1, but does not rule it out in the other two species.


Hypoxia induces the synthesis of tropomyosin in cultured porcine pulmonary artery endothelial cells.
The present study examined the effect of hypoxia on protein synthesis by porcine pulmonary artery endothelial cells (PAEC). Hypoxia decreased protein synthesis in PAEC, but two-dimensional gel electrophoresis of [35S]methionine-labeled PAEC proteins demonstrated the increased synthesis of a set of proteins having molecular masses (M(r)) of 35, 36.5, 45, 116, and 205 kDa. The synthesis of the 35-, 36.5-, and 45-kDa proteins was increased in preconfluent and postconfluent cells. The 35- and 45-kDa proteins were not induced by hyperthermia, whereas the 36.5-kDa protein was induced slightly by hyperthermia. Induction of the 36.5- and 45-kDa proteins required a minimum of 8 h of hypoxia, whereas induction of the 35-kDa protein required only 4 h of exposure to hypoxia. The upregulated synthesis of the 35-, 36.5-, and 45-kDa proteins was reversible with return to normoxia. Actinomycin D, an inhibitor of transcription, did not block the hypoxic induction of the 35- and 36.5-kDa proteins but did block induction of the 45-kDa protein. The partial amino acid sequence of the 35-kDa protein obtained from cyanogen bromide cleavage of the molecule was Asp-Ala-Ile-Lys-Lys-Lys-Met-Gln-Met-Leu-Lys-Leu-Asp-Lys-Glu. This partial sequence of the 35-kDa protein identically matches the sequence of tropomyosin. Amino acid composition data and the isoelectric point (4.8) were also typical of tropomyosin. Finally, specific cross-reactivity was detected between the 35-kDa protein and a monoclonal antibody to chicken gizzard tropomyosin on immunoblot. Thus hypoxia induces the synthesis of tropomyosin, a major microfilament-associated protein, in porcine PAEC in monolayer culture.


Minimum GC-rich sequences for overlap extension PCR and primer annealing.
PCR is a common method to produce desired DNA fragments from templates. The oligonucleotide primers used for PCR must contain annealing sequences that are usually 20-30 nucleotides long and identical to a part of template DNA. However, primers often contain additional sequences at their 5' ends, which are restriction enzyme sites, recombination targeting sequences, or overlap sequences for fusion PCR. When these additional sequences are attached to their annealing sequences, the annealing sequences can be shortened. Here, we describe universal GC-rich annealing sequences useful for overlap extension PCR and simple in-frame addition of desired sequences.


Network pharmacology study on the mechanism of the Chinese medicine Radix Isatidis (Banlangen) for COVID-19.
Radix Isatidis (Banlangen) is a well-known traditional Chinese medicine for the treatment of different diseases and prevention of many body disorders. Besides, it also plays a pivotal role in novel coronavirus pneumonia, coronavirus disease 2019 (COVID-19). However, few researchers know its active ingredients and mechanism of action for COVID-19. To find whether Banlangen has a pharmacological effect on COVID-19. In this research, we systematically analyze Banlangen and COVID-19 through network pharmacology technology. A total of 33 active ingredients in Banlangen, 92 targets of the active ingredients, and 259 appropriate targets of COVID-19 were obtained, with 11 common targets. The analysis of the biological process of gene ontology and the enrichment of Kyoto Encyclopedia of Genes and Genomes signaling pathway suggests that Banlangen participated in the biological processes of protein phosphatase binding, tetrapyrrole binding, the apoptotic process involving cysteine-type endopeptidase activity, etc. The COVID-19 may be treated by regulating advanced glycation end products/a receptor for advanced glycation end products signaling pathway, interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, sphingolipid signaling pathway, and p53 signaling pathway. Banlangen has a potential pharmacological effect on COVID-19, which has the value of further exploration in the following experiment and clinical application.


Immunogenicity and safety of high-dose hepatitis B vaccine among drug users: A randomized, open-labeled, blank-controlled trial.
Due to the low uptake, adherence, and completion of vaccination among drug users, and their compromised immune responses to hepatitis B vaccination, the current practice of hepatitis B vaccination may not provide optimal protection. The aim of this study was to evaluate the immunogenicity and safety of 60 µg and 20 µg hepatitis B vaccines among drug users. A randomized, open-labeled, blank-controlled trial was conducted among drug users at 2 drug rehabilitation centers in China. The eligible participants were drug users who were serologically negative for the hepatitis B surface antigen (HBsAg) and the hepatitis B surface antibody (anti-HBs). Participants were randomized in a ratio of 1:1:1 to receive 20 µg (IM20 group) or 60 µg (IM60 group) of hepatitis B vaccine or blank control at months 0, 1, and 6, and followed at months 6, 7, and 12. Seroconversion rates of 94.7% and 92.6% were observed in IM20 and IM60 groups at month 7, and correspondingly decreased to 89.5% and 91.7% respectively at month 12. The IM60 group showed significantly higher geometric mean concentrations (GMCs) of anti-HBs (2022.5 and 676.7 mIU mL-1) than the IM20 group did (909.6 and 470.5 mIU mL-1) at months 7 and 12 (P < 0.05). No safety concerns associated with vaccination were noted. Three-dose intramuscular immunization with hepatitis B vaccines showed good immunogenicity among the drug users.


Relationship between fibronectin and lymphoid cells in buccal mucosa, labial salivary glands and palatine tonsil.
The distribution of fibronectin in human buccal mucosa and labial salivary glands and its relationship to lymphoid cells was studied using an immunoperoxidase technique and monoclonal and polyclonal antibodies. In all specimens fibronectin was associated with basement membranes of epithelia, vascular endothelium and perineural sheaths. In histologically normal areas of buccal mucosa fibronectin was distributed as a sparse network in the superficial lamina propria. A more extensive network of fibronectin was found within the lamina propria of mucosal specimens infiltrated with T lymphocytes, whereas fibronectin was absent in areas occupied by B lymphocytes. A similar relationship between lymphocyte type and the presence of a fibronectin network was found in labial glands and palatine tonsil. Fibronectin was not detected within oral, salivary gland, tonsillar crypt or capsular epithelium.


Local health department effectiveness in addressing the core functions of public health.
Objective 8.14 of the Year 2000 National Health Objectives calls for 90 percent of the population to be served by a local health department effectively carrying out the three core functions of public health--assessment, policy development, and assurance. To provide a benchmark of local health department effectiveness in addressing the core functions and to assess implications for achieving the year 2000 target, a random national sample (stratified by jurisdiction and population base) of local health departments was surveyed to determine self-reported compliance with 10 public health practice performance measures that operationalize the core functions. Overall compliance with the 10 performance measures was 50 percent, based on weighted responses of 208 responding health departments. Compliance was highest for the practices related to the assurance function and least for practices related to the policy development function. Compliance was also high for departments serving a population of 50,000 or more and those smaller departments organized at the city and city-county levels. Using two different definitions developed by the investigators, 19 and 31 percent of the health departments were judged to be effective in addressing the core functions of public health. These data suggest that less than 40 percent of the U.S. population was served by a health department effectively addressing the core functions of public health in 1993. It appears that considerable capacity building within the public health system will be needed to achieve the year 2000 target of 90 percent.


Association between Normal Weight Obesity and Skeletal Muscle Mass Index in Female University Students with Past Exercise Habituation.
This study investigated the relationship between normal weight obesity (NW-O) and skeletal muscle mass index (SMI) in 120 female university students who participated in sporting activities during junior and senior high school. The current physical activity level (PAL) was estimated by a factorial method using 24-h physical activity recall. The body mass index (BMI) of the participants ranged from 18.5 to 24.9 kg/m2; their body fat (BF) was classified as NW-O if above the 75th percentile (28.9% BF), normal weight and lean (NW-L) if below the 25th percentile value (21.0%BF), and all others were normal weight (NW). PAL was significantly lower in NW-O than in NW-L. SMI was significantly lower in NW-O than in NW and NW-L, and 60% of NW-O had Low-SMI (<6.3 kg/m2). Although lower limb muscle mass was significantly lower in NW-O than in NW and NW-L, no significant differences were found in the upper limbs. These results suggest that the current PAL is associated with NW-O, and NW-O is associated with a lower SMI, even in young females with past exercise habits. Therefore, the prevention of NW-O in young females is important for the prevention of not only lifestyle-related diseases, but also future sarcopenia.


Effects of beta-adrenergic blocking agents on specific binding of [3H]D-Ala2-Met5-enkephalinamide and [3H]naloxone.
To gain further insight into the central nervous system (CNS)-action of beta-adrenergic blocking agents (beta-blockers), we examined the effects of various kinds of beta-blockers on opioid receptors (Op-Rs) using radiolabeled receptor assay (RRA). We demonstrated that beta-blockers are competitively bound to Op-Rs in the CNS. Sodium index of beta-blockers in [3H]naloxone binding study indicated that beta-blockers had the mixed agonist-antagonist activity of opiates. The relative potency of beta-blockers in opioid RRA was negatively correlated with their membrane stabilizing activity. Neither beta-blocking activity nor intrinsic sympathomimetic activity was correlated with IC50 values of beta-blockers in opioid RRA. While it is widely accepted that beta-blockers have a tranquilizing activity, a part of the tranquilizing action of beta-blockers may be mediated through Op-Rs in the CNS. Although beta-blockers may have effects on their own receptors (beta-receptors) in the CNS, the more precise mechanisms of central action of these drugs must be further investigated.


Glycan analysis of Prostate Specific Antigen (PSA) directly from the intact glycoprotein by HR-ESI/TOF-MS.
Glycans are important modulators of the biological function of proteins and are normally characterized from proteolytic glycopeptides or from (N-)glycans released enzymatically by glycosidase treatment or chemically by hydrazinolysis. We demonstrate that glycan compositions can easily be determined directly by LC-ESI/TOF-MS from intact glycoproteins even with a very complex glycosylation pattern. Interpretation of isotopically resolved mass spectra of prostate specific antigen (PSA) using bioinformatics tools gives within a few hours the glycan compositions of 38 glycoforms.


Post-operative outcomes after cleft palate repair in syndromic and non-syndromic children: a systematic review protocol.
There is a lack of high-level evidence on the surgical management of cleft palate. An appreciation of the differences in the complication rates between different surgical techniques and timing of repair is essential in optimizing cleft palate management. A comprehensive electronic database search will be conducted on the complication rates associated with cleft palate repair using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Two independent reviewers with expertise in cleft pathology will screen all appropriate titles, abstracts, and full-text publications prior to deciding whether each meet the predetermined inclusion criteria. The study findings will be tabulated and summarized. The primary outcomes will be the rate of palatal fistula, the incidence and severity of velopharyngeal insufficiency, and the rate of maxillary hypoplasia with different techniques and also the timing of the repair. A meta-analysis will be conducted using a random effects model. The evidence behind the optimal surgical approach to cleft palate repair is minimal, with no gold standard technique identified to date for a certain type of cleft palate. It is essential to appreciate how the complication rates differ between each surgical technique and each time point of repair, in order to optimize the management of these patients. A more critical evaluation of the outcomes of different cleft palate repair methods may also provide insight into more effective surgical approaches for different types of cleft palates.


Specific Enrichment of Peptides with N-Terminal Serine/Threonine by a Solid-Phase Capture-Release Approach for Efficient Proteomics Analysis.
A problem for "shot-gun" proteomics is that the peptides generated in the proteolysis step overwhelm the analytical capacity of current LC-MS/MS systems. A straightforward approach to overcome this problem is to reduce the sample complexity by isolating the representative peptides of each protein. In this study, we presented a facile solid-phase capture-release approach to selectively enrich the peptides with N-terminal serine/threonine from protein digests. This method exploited the highly efficient reaction between an aldehyde group and a hydrazine group. The excellent performance of this approach was validated using synthetic peptides as well as complex protein digests. It was found that high enrichment specificity could be obtained and the identifications for complex samples with and without enrichment were highly complementary. Besides, the enrichment of peptides with serine/threonine adjacent to different protease cleavage sites demonstrated that our method was able to enrich peptides from protein digests in a sequence specific way. As a result, this new approach provides a simple way to reduce sample complexity and facilitates the identification of low-abundance proteins.


X-ray diffraction from flight muscle with a headless myosin mutation: implications for interpreting reflection patterns.
Fruit fly (Drosophila melanogaster) is one of the most useful animal models to study the causes and effects of hereditary diseases because of its rich genetic resources. It is especially suitable for studying myopathies caused by myosin mutations, because specific mutations can be induced to the flight muscle-specific myosin isoform, while leaving other isoforms intact. Here we describe an X-ray-diffraction-based method to evaluate the structural effects of mutations in contractile proteins in Drosophila indirect flight muscle. Specifically, we describe the effect of the headless myosin mutation, Mhc (10) -Y97, in which the motor domain of the myosin head is deleted, on the X-ray diffraction pattern. The loss of general integrity of the filament lattice is evident from the pattern. A striking observation, however, is the prominent meridional reflection at d = 14.5 nm, a hallmark for the regularity of the myosin-containing thick filament. This reflection has long been considered to arise mainly from the myosin head, but taking the 6th actin layer line reflection as an internal control, the 14.5-nm reflection is even stronger than that of wild-type muscle. We confirmed these results via electron microscopy, wherein image analysis revealed structures with a similar periodicity. These observations have major implications on the interpretation of myosin-based reflections.


Prognostic factors for alarm treatment.
A review of the literature concerning the use of enuresis alarms highlighted the lack of standardised definitions used to define enuresis and the insufficient understanding of the working mechanisms of alarms. Although first reported in 1904, enuresis alarms were not in routine use until the 1930's. Sensors in the bed or underwear, in conjunction with audible warning devices are the most common types of alarms. The alarm success rate of approximately 75% is independent of the type of alarm and there is a low relapse rate. In predicting alarm response, studies utilizing multivariate analysis techniques are superior to univariate techniques, but no one or combination of predictor variables is currently known to predict outcome accurately enough to alter standard clinical decision making. It is imperative that definitions are standardized and that study protocols are applied uniformly to well-defined populations that have a better potential response to enuresis alarms-the best intervention currently available.


Survey of scalp dermatophyte carriage in a Day Care Center in Turkey.
The prevalence of tinea capitis and the symptom-free colonisation of the scalp with dermatophytes were examined in 502 mentally retarded participants who attended day care centers in the Tarsus district, Mersin, Turkey. Between December 2006 and May 2007, a screening study was conducted in three centers on a total of 316 (62.9%) male and 186 (37.1%) female participants aged 12 +/- 6.2 years. The examinations were carried out in parallel with the hairbrush, toothbrush, and cotton swab methods by inoculation onto Sabouraud glucose agar. No participant was diagnosed with tinea capitis; however, we detected three carriers, all of whom were boys aged 2-16 years. The total prevalence of carrier state was 0.6%. Of three boys, T. tonsurans was seen in two cases (66.7%), and in one case a zoophilic variant of T. mentagrophytes (33.3%) was isolated. The diagnosis was made via the hairbrush method in all three carriers. We also did a screening study on ten households of the three asymptomatic carriers. T. mentagrophytes also was isolated in a 5-year-old sister of the boy with T. mentagrophytes colonisation. All the carriers were followed-up without any antimycotic treatment. In two of the participants, the carrier state persisted at the 13th and 17th week follow-ups, and mycological clearance was documented at the 20th and 24th week for these individuals. The third case and the household's culture were found negative at the 7- and 12-week follow-ups. Despite poor hygienic conditions and the participants' difficulties in performing basic hygiene practices, asymptomatic carriage was found to be surprisingly less prevalent among the mentally retarded individuals.


Evaluation of Silver Zeolites Sorbents Toward Their Ability to Promote Stable CH3I Storage as AgI Precipitates.
In this study, up to 13 different silver zeolites sorbents were prepared by repeated ion exchange from their parent structures (FAU X and Y, MOR, *BEA, MFI, FER), characterized, and evaluated for their ability to capture methyl iodide in the context of a nuclear severe accident. A novel methodology was implemented to establish structure-activity relationships between sorbent properties and iodine trapping stability. After saturation of the zeolite bed with CH3I during a dynamic breakthrough experiment at 100 °C, a two-step quantitative desorption method was elaborated with the aim to quantify separately the CH3I fractions trapped by physisorption, chemisorption, or reacted as AgI precipitates. Besides, an analysis of the mechanisms involved in CH3I sorption and decomposition processes was also carried out. Overall, Ag/Y zeolites displayed the highest fractions trapped as stable AgI precipitates, thanks to the presence of high amounts of dispersed silver species at accessible locations in the large supercages, and their low sodium content.


Studies on the hexose region of the lipopolysaccharide from a low virulence strain of Salmonella typhimurium.
The structure of the hexose region of the lipopolysaccharide from M206 strain, a mutant of Salmonella typhimurium having reduced virulence, was partially determined. Immunological tests indicated cross-reactions of anti-(M206) antiserum with wild-type C5 and Ra mutant strains. Data obtained on chemical composition, periodate oxidation, acetolysis, methylation and analysis by gas chromatography/mass spectrometry show that M206 type lipopolysaccharide contains the common core polysaccharide of Salmonella which was substituted in position 4 of the subterminal glucose unit by a disaccharide: D-glucosyl 1----3 D-galactose. This substitution is probably related to the slight virulence of M206 strain.


Tryptophan metabolism, growth responses, and postprandial insulin metabolism in weaned piglets according to the dietary provision of niacin (vitamin B) and tryptophan.
The present experiment aimed to determine if Trp metabolism and growth responses to dietary Trp are modulated by dietary niacin (B) in weanling piglets. Piglets weaned at 3 wk of age were distributed 1 wk later (7.6 kg of BW, SEM = 0.1) in 52 pens of 2 animals each. Pens were assigned to factorial dietary treatments with 2 additions of B, 15 mg/kg (LB3) vs. 45 mg/kg (HB3) and 2 additions of Trp, 0 mg/kg (-Trp) vs. 1 mg/kg (+Trp) for Trp to Lys ratios of 0.16 vs. 0.24, respectively. Growth performance was recorded every week from 4 to 10 wk of age. Fasting blood samples were taken at 4, 6, 8, and 10 wk of age. From 4 to 10 wk of age, ADFI tended to be greater ( = 0.10) in HB3 than in LB3 (1,031 vs. 1,003 g, SEM = 7), and this was reflected ( = 0.06) by ADG (642 vs. 623 g, SEM = 7). No treatment effect was observed on plasma Trp or kynurenine (Kyn), an intermediate metabolite of Trp catabolism. The response of plasma nicotinamide (Nam), a product of Trp catabolism and an indicator of B status, to dietary B differed according to treatments (interaction Trp × B, < 0.01) with values of 1.4, 3.3, 4.1, and 5.3 μM (SEM = 0.1) in LB3-Trp, HB3-Trp, LB3+Trp, and HB3+Trp, respectively. At 11 wk of age, postprandial blood samples were collected from 6 piglets per treatment for measurements of Trp and insulin metabolism. Postprandial plasma Trp (96.4 vs. 72.2 μ, SEM = 3.4) and Kyn (1.7 vs. 1.3 μ, SEM = 0.1) were greater ( < 0.01) in +Trp vs. -Trp. Postprandial plasma Nam was greater ( < 0.01) in +Trp vs. -Trp (3.4 vs. 1.9 µ, SEM = 0.3) and in HB3 vs. LB3 piglets (3.4 vs. 1.9 µ, SEM = 0.3). Postprandial peaks and areas under curves of C-peptide and glucose were not affected by treatments. However, for insulin, the postprandial peak was lower in +Trp vs. -Trp piglets in the LB3 group (interaction Trp × B, < 0.05); values were 1.3, 1.0, 0.7, and 1.0 n (SEM = 0.1) in LB3-Trp, HB3-Trp, LB3+Trp, and HB3+Trp, respectively. The peak value of the molar ratio insulin:C-peptide was lower ( < 0.02) in +Trp vs. -Trp piglets (0.56 vs. 0.73, SEM = 0.05). The responses observed on growth performance and plasma Nam suggest that the LB3 level was suboptimal. According also to plasma Nam, it appears that supplemental dietary B can attenuate Trp oxidation toward niacin metabolites. Postprandial profiles of insulin and C-peptide indicate that Trp action is exerted on insulin clearance rather than on insulin secretion in piglets, without apparent consequences on glucose utilization.


Hand effects on mentally simulated reaching.
Within the area of simulated (imagined) versus actual movement research, investigators have discovered that mentally simulated movements, like real actions, are controlled primarily by the hemispheres contralateral to the simulated limb. Furthermore, evidence points to a left-brain advantage for accuracy of simulated movements. With this information it could be suggested that, compared to left-handers, most right-handers would have an advantage. To test this hypothesis, strong right- and left-handers were compared on judgments of perceived reachability to visual targets lasting 150 ms in multiple locations of midline, right- and left-visual field (RVF/LVF). In reference to within group responses, we found no hemispheric or hand use advantage for right-handers. Although left-handers revealed no hemispheric advantage, there was a significant hand effect, favoring the non-dominant limb, most notably in LVF. This finding is explained in regard to a possible interference effect for left-handers, not shown for right-handers. Overall, left-handers displayed significantly more errors across hemispace. Therefore, it appears that when comparing hand groups, a left-hemisphere advantage favoring right-handers is plausible.


Positive Aging Effect of ZnO Nanoparticles Induced by Surface Stabilization.
For quantum-dot photodiodes comprising an electron-transporting layer assembled of ZnO nanoparticles, the light emitter/absorber generally exhibits enhanced optoelectronic performance after the device is shelf-aged. To understand the so-called positive aging effect, the optoelectronic properties of ZnO nanoparticles are investigated at the thin film and device level as a function of aging time. It is evidenced that the aging process is driven by a surface-stabilizing mechanism of ZnO nanoparticles, in which the active surface adsorption sites for oxygen are gradually but irreversibly stabilized, i.e.. with surface termination of HO-ZnO, leading to reduced nonradiative recombination and increased built-in potential in the adjacent photoactive layer. This work provides insight into new synthetic routes for minimizing the negative impact caused by the aging process.


Overview of health and development of children and their families: health and functional status of the elderly.
This paper provides an overview of two studies designed to establish data bases that would aid in describing the health and development of children and their families and the health and functioning of the elderly in a rural community in South Africa.


Scopolamine-Induced Memory Impairment Is Alleviated by Xanthotoxin: Role of Acetylcholinesterase and Oxidative Stress Processes.
Xanthotoxin, popularly occurring furanocoumarin, which can be found in plants from the Apiaceae family, was isolated from fruits of Pastinaca sativa L. by mean of high-performance countercurrent chromatography, and its effects on the scopolamine-induced cognitive deficits in male Swiss mice using the passive avoidance (PA) test were evaluated. To measure the acquisition of memory processes, xanthotoxin (1, 2.5, 5 mg/kg) was administered 30 min before PA test and scopolamine was administered 10 min after xanthotoxin. To measure the consolidation of memory processes, xanthotoxin (1 and 2.5 mg/kg) was injected immediately after removing the mouse from the apparatus and 10 min after scopolamine was administered. In subchronic experiments, mice were injected with xanthotoxin (1 mg/kg) or saline, 6 days, twice daily. At 24 h after the last injection of the drugs, the hippocampus and the prefrontal cortex were removed for biochemical assays. The results demonstrated that either single (2.5 and 5 mg/kg) or repeatable (1 mg/kg) administration of xanthotoxin significantly increased index of latency (IL) in both acquisition and consolidation of memory processes, showing some procognitive effects. The behavioral tests also showed that an acute (2.5 mg/kg) and subchronic (1 mg/kg) administration of xanthotoxin prevent memory impairment induced by injection of scopolamine (1 mg/kg). Observed effects could be due to the inhibition of acetylcholinesterase activities and amelioration of oxidative stress processes in the hippocampus and the prefrontal cortex. It was suggested that xanthotoxin could show neuroprotective effect in scopolamine-induced cognitive impairment connected to cholinergic neurotransmission and oxidative stress in the brain structures.


Biomechanical Changes After LASIK Flap Creation Combined With Rapid Cross-Linking Measured With Brillouin Microscopy.
To evaluate the biomechanical changes occurring after LASIK flap creation and rapid corneal cross-linking (CXL) measured with Brillouin light microscopy. Porcine eyes (n = 11) were evaluated by Brillouin light microscopy sequentially in the following order: virgin state, after LASIK flap creation, and after rapid CXL. Each eye served as its own control. Depth profile of the Brillouin frequency shift was computed to reveal the depth-dependent changes in corneal stiffness. There was a statistically significant reduction of Brillouin shift (reduced corneal stiffness) after LASIK flap creation compared to virgin corneas across total corneal thickness (-0.035 GHz, P = .0195) and within the anterior stromal region (-0.104 GHz, P = .0039). Changes in the central (-0.029 GHz, P = .0391) and posterior (-0.005 GHz, P = .99) stromal regions were not significant. There was a small increase in Brillouin shift after rapid cross-linking that was not statistically or clinically significant across total corneal thickness (0.006 GHz, P = .4688 for any specific stromal region; 0.002 to 0.009 GHz, P > .46 for all). LASIK flap creation significantly reduced Brillouin shift in the anterior third of the stroma in porcine eyes. Rapid corneal cross-linking had no significant effect on Brillouin shift after LASIK flap creation in porcine eyes. With further validation, non-contact, non-perturbative Brillouin microscopy could become a useful monitoring tool to evaluate the biomechanical impact of corneal refractive procedures and corneal cross-linking protocols. [J Refract Surg. 2017;33(6):408-414.].


Possible role of the first intron of c-H-ras in gene expression: anti-cancer elements in oncogenes.
When members of ras gene family, which encode structurally related proteins of approximately 21,000 daltons (p21), are activated by either structural mutations or enhanced promoter activities, immortalized mammalian cells can be transformed into malignant forms. The ras genes are classified as "housekeeping genes" which express relatively constantly at low levels in all tissues and throughout all developmental stages. It is therefore important to understand how regulatory, cis-acting in particular, elements of the genes control their expression. We have previously reported that the principal promoter, 51 bp long or less, located around 1370 bp upstream from the first coding ATG, plays the most important role for expression, though there seem to be residual promoter activities further downstream as well. The most upstream mRNA start site is located at the 3'-end of the principal promoter, which lies directly adjacent to the homologous sequence between human and rat c-H-ras 5'-flanking regions. It is therefore proposed that the c-H-ras gene may have a dispersed promoter in which the principal promoter and subpromoters may be distributed. On the other hand, the first intron region seems to contain two sets of positive and negative elements which appear to have, respectively, a positive and negative influence on the efficiency of focus formation with the activated c-H-ras oncogene. From testing done in our laboratory, it was further revealed that these cis-acting elements in the intron affect c-H-ras gene expression at the post-transcriptional level. The middle part of the first intron was in fact shown unusually conserved between human and rat DNA sequences. Moreover, computer analyses revealed that the intron sequences of various oncogenes (both human and rodent sequences available from GenBank DNA sequence data-bank) such as ras, fos, c-myc, N-myc and int-1, are in general significantly more highly conserved when compared with sequences of non-oncogene introns. The significance of this oncogene-related conserved sequence is discussed and the proposal is made that it may function as an "anti-cancer element" or "safety valve" against gene truncation/translocational activation of oncogenes.


Lipophilic oligopeptides for chemo- and enantioselective acyl transfer reactions onto alcohols.
Inspired by the extraordinary selectivities of acylases, we envisioned the use of lipophilic oligopeptidic organocatalysts for the acylative kinetic resolution/desymmetrization of rac- and meso-cycloalkane-1,2-diols. Here we describe in a full account the discovery and development process from the theoretical concept to the final catalyst, including scope and limitations. Competition experiments with various alcohols and electrophiles show the full potential of the employed oligopeptides. Additionally, we utilized NMR and IR-spectroscopic methods as well as computations to shed light on the factors responsible for the selectivity. The catalyst system can be readily modified to a multicatalyst by adding other catalytically active amino acids to the peptide backbone, enabling the stereoselective one-pot synthesis of complex molecules from simple starting materials.


[Beta-adrenergic receptor blockers in the treatment of chronic heart failure].
We present a current opinion about the management of chronic heart failure with beta-blocking agents. Pathophysiologic rationales for such treatment and clinical experience were analyzed. Most of the studies showed that long-term treatment of heart failure with beta-blockade produces improvement in symptoms, exercise tolerance, ejection fraction and central hemodynamics (CI, PCWP, MPAP, LVSWI, SVI). Treatment must be started at an extremely low dose and then must be increased gradually to therapeutic levels over several weeks. The titration phase must take place in the hospital. It was emphasized that the management of chronic heart failure with beta-blockers is not the routine management yet. Ongoing multicenters trials should finally determine the place of beta-blockers in the treatment of chronic heart failure.


Type-B ARABIDOPSIS RESPONSE REGULATORs Specify the Shoot Stem Cell Niche by Dual Regulation of WUSCHEL.
Plants are known for their capacity to regenerate the whole body through de novo formation of apical meristems from a mass of proliferating cells named callus. Exogenous cytokinin and auxin determine cell fate for the establishment of the stem cell niche, which is the vital step of shoot regeneration, but the underlying mechanisms remain unclear. Here, we show that type-B ARABIDOPSIS RESPONSE REGULATORs (ARRs), critical components of cytokinin signaling, activate the transcription of WUSCHEL (WUS), which encodes a key regulator for maintaining stem cells. In parallel, type-B ARRs inhibit auxin accumulation by repressing the expression of YUCCAs, which encode a key enzyme for auxin biosynthesis, indirectly promoting WUS induction. Both pathways are essential for de novo regeneration of the shoot stem cell niche. In addition, the dual regulation of type-B ARRs on WUS transcription is required for the maintenance of the shoot apical meristem in planta. Thus, our results reveal a long-standing missing link between cytokinin signaling and WUS regulator, and the findings provide critical information for understanding cell fate specification.


Common motifs in protein self-assembly.
The importance of misfolding proteins forming amyloid fibrils for the aetiology of many diseases, particularly those of old age, is well recognized. This phenomenon is now thought to be a universal property of proteins, as long as appropriate conditions for loosening the native folded structure can be found, which may be outside those of normal physiology. However, the beta-sheet-rich structure of the amyloid fibril does not need to exist in isolation. Recent work has shown that higher order assemblies of the fibrils occur into structures resembling spherulites found in common synthetic semi-crystalline polymers. In these, the fibrils grow outwards from an inner core, thought to be amorphous. Data will be presented on the kinetics of growth of these fibrils for different proteins, so that similarities and differences can be revealed, and related to subtle differences in appearance under the microscope. The in vitro assembly of amyloid fibrils is usually thought to occur well away from the isoelectric point of the protein, and these are the conditions under which they have most been studied. Around the isoelectric point, particulate self-assembly is known to occur for beta-lactoglobulin, and we can now show this is also a generic form of protein self-assembly once the net charge on the protein is close to zero. Nevertheless, the charge is not actually zero, and salt in the solution is found to have a significant effect on the growth of the particles. The use of SAXS, thioflavin T staining and FTIR also shows that within the particles there is also clear evidence for amyloid-like beta-sheet structure, particularly in the case when salt is absent, demonstrating that this particular motif underlies this very different form of protein self-assembly.


MiR-1-3p Suppresses the Proliferation, Invasion and Migration of Bladder Cancer Cells by Up-Regulating SFRP1 Expression.
Bladder cancer is of compelling morbidity and mortality due to its high recurrence rate. Little development has been made in the last decades in the therapy methods. Thus, the mechanism of its growth and invasiveness involving novel molecular targets are needed. Our research objective is to confirm the hypothesis that miR-1-3p suppresses the proliferation, invasion and migration of bladder cancer cells. The expression levels of miR-1-3p and SFRP1 were evaluated using RT-qPCR in bladder cancer tissues and cells as well as in normal tissues and cells. J82 cell lines were selected as experiment subjects due to their low expression levels of miR-1-3p. Plasmids carrying miR-1-3p mimics, miR-1-3p inhibitors and SFRP1 were transfected into the J82 cell lines. Subsequently, the protein expression of SFRP1 was detected using Western Blot analysis, and cell proliferation, apoptosis, invasion and migration ability was measured using MTT, the flow cytometry, the Transwell test and wound healing assays, respectively Results: Bladder cancer tissues and cells exhibited significant decrease in the expression of miR-1-3p and SFRP1 compared to normal tissues and cells, and human bladder cancer cell line J82 exhibited the most significant decrease in these expressions (P < 0.05). MiR-1-3p up-regulates SFRP1 expression in bladder cancer cells, and the over-expression of miR-1-3p can suppress the proliferation, invasion and migration ability of bladder cancer cells. This mechanism is similar to the effect of SFRP1 over-expression on bladder cancer cells. MiR-1-3p suppresses the proliferation, invasion and migration of bladder cancer cells by up-regulating SFRP1 expression.


Buprenorphine for the treatment of posttraumatic stress disorder.
The core pharmacological treatment of Post-Traumatic Stress Disorder (PTSD) is selective serotonin reuptake inhibitors (SSRIs), although remission is only around 30% with them. Many patients will self-treat with opioids and due to the opiate system involvement in dysphoric mood and anxiety/stress responses, it is likely that antagonism of the kappa opioid receptor (KOR) system represents a potential target for treatment of PTSD. The aim of this study is to compare response of PTSD symptoms when antagonizing KOR via buprenorphine/naloxone compared to SSRIs or opioid therapy. A retrospective chart review of patients in the MEDVAMC between June 1, 2010 and June 30, 2016 was conducted. Inclusion criteria included patients with a documented diagnosis of PTSD with at least two documented PTSD scores (either PCLC or PC-PTSD). Exclusion criteria included patients not prescribed one of the study medications (ie, buprenorphine, SSRI, or opiate for chronic pain), and patients not on the study medication for at least 30 days. Buprenorphine patients exhibited the lowest final average PTSD score (2.47) and the largest change from baseline (-24.0%) compared to opioids (-16.1%) or SSRIs (1.16%). The average buprenorphine dose was 23.3 mg/day, and the average length of therapy was 860 days. Buprenorphine may help decrease PTSD symptoms more than SSRIs or opioids alone. Prospective studies are needed to determine whether these effects are reproducible. Pharmacotherapy advancements in PTSD treatment have been limited and the kappa opioid receptor system presents a new target that warrants further research. (Am J Addict 2019;XX:1-6).


Effect of moderate-intensity aerobic exercise on glycosylated haemoglobin among elderly patients with type 2 diabetes & peripheral neuropathy.
Aerobic exercise has been known to improve glycosylated haemoglobin (HbA1c) levels and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). The present study was undertaken to evaluate the effect of eight week moderate-intensity aerobic (heart rate reserve 40-60%) exercise on glycaemic control in elderly patients with T2DM and diabetic peripheral neuropathy (DPN). The participants (n=87) were randomly assigned to an eight-week programme by a computer-generated random number table to the study or control group, respectively. There were 47 participants in the control group and 40 participants in the study group after randomization. There was a significant difference in the mean values of glycated haemoglobin (HbA1c) at baseline and 8th week between the two groups. Moderate-intensity aerobic exercise of eight weeks duration helped in achieving enhanced glycaemic control in the T2DM patients with DPN.


Expression of a kinase-dead form of CPK33 involved in florigen complex formation causes delayed flowering.
Regulation of flowering time is crucial for reproductive success of plants. FLOWERING LOCUS T (FT) protein is a central component of florigen and forms a ternary complex with 14-3-3 and FD, a basic leucine zipper transcription factor, in the shoot apex and promotes flowering. This complex formation requires phosphorylation of threonine residue at position 282 of FD. A calcium-dependent protein kinase CPK33 is responsible for the phosphorylation. However, possibly due to functional redundancy among calcium-dependent protein kinases, impact of the loss of CPK33 reported in the previous study was rather limited. Here, we report that expression of a kinase-dead form of CPK33 caused a clear delayed-flowering phenotype, supporting for an important role of CPK33 in florigen function through FD phosphorylation.


Autoregulatory capacity in renal and mesenteric vasculatures of mineralocorticoid hypertensive dogs.
Experiments were performed in seven conscious dogs to quantitate the renal and mesenteric autoregulatory capacity in deoxycorticosterone acetate (DOCA)-salt hypertensive dogs. Each dog was chronically instrumented for the measurement of aortic blood pressure and blood flows through the superior mesenteric and left renal arteries (Doppler measurements); a right nephrectomy was also performed. To induce hypertension, animals were administered 5 mg/kg DOCA each day and given 1% saline as a drinking solution. After arterial pressure had increased by 25% (8-14 days of DOCA), a large-bore catheter was positioned retrograde in the left common carotid artery for subsequent connection to a gravity reservoir system for acute control of arterial pressure. Autoregulatory capacity was evaluated by controlling arterial pressure via the gravity reservoir at hypertensive and then normotensive values for 15-min periods. In neurally intact animals the renal, but not the mesenteric, circulation displayed autoregulatory capacity; the closed-loop gain of renal flow control averaged 0.92 +/- 0.06. Inhibition of autonomic ganglionic transmission (hexamethonium) increased the gain of flow regulation in the mesenteric circulation, but mesenteric autoregulation was not manifest. Ganglionic blockade, inhibition of prostaglandin formation, or blockade of histamine or adenosine receptors did not significantly influence renal autoregulatory capacity. These data demonstrate that the kidney has a high capacity to autoregulate in DOCA hypertension and suggest that autoregulatory-mediated renal vasoconstriction contributes to the increased total peripheral resistance.


Grassroots Efforts To Quantify and Improve the Academic Climate of an R1 STEM Department: Using Evidence-Based Discussions To Foster Community.
Women and some racial and ethnic groups remain underrepresented in chemistry departments across the United States, and generally, efforts to improve representation have resulted in minimal or no improvements in the last 10 years. Here, we present the outcomes of a graduate-student-led initiative that sought to assess the issues affecting inclusivity, diversity, and wellness within the Department of Chemistry at the University of California, Berkeley. We report how the results of a department-tailored academic climate survey were used to develop a method to foster open, productive discussion among graduate students, postdoctoral researchers, and faculty. This event format led to an improved understanding of the challenges facing our community members, as well as the identification of strategies that can be used to make the Department of Chemistry more welcoming for all members. We report the success of this student-led effort to highlight the value of assessing diversity and inclusion at the department-level, as well as the benefits of using community data to stimulate productive, evidence-based discussions. Furthermore, we envision that these methods can be implemented within any research-focused academic community to promote positive cultural change.


Molecular Features for Probing Small Amphiphilic Molecules with Self-Assembled Monolayer-Protected Nanoparticles.
The sensing of small molecules poses the challenge of developing devices able to discriminate between compounds that may be structurally very similar. Here, attention has been paid to the use of self-assembled monolayer (SAM)-protected gold nanoparticles since they enable a modular approach to tune single-molecule affinity and selectivity simply by changing functional moieties (i.e., covering ligands), along with multivalent molecular recognition. To date, the discovery of monolayers suitable for a specific molecular target has relied on trial-and-error approaches, with ligand chemistry being the main criterion used to modulate selectivity and sensitivity. By using molecular dynamics, we showcase that either individual molecular characteristics and/or collective features such as ligand flexibility, monolayer organization, ligand local ordering, and interfacial solvent properties can also be exploited conveniently. The knowledge of the molecular mechanisms that drive the recognition of small molecules on SAM-covered nanoparticles will critically expand our ability to manipulate and control such supramolecular systems.


Inducible transcriptional activation of the human immunodeficiency virus long terminal repeat by protein kinase inhibitors.
The protein kinase inhibitor 2-aminopurine (2-AP) greatly stimulated expression in human promonocytes-macrophages of plasmid constructs carrying various reporter genes (chloramphenicol acetyltransferase, lacZ, firefly luciferase [luc], and Salmonella typhimurium histidinol dehydrogenase [his]) driven by the human immunodeficiency virus type 1 (HIV-1) long terminal repeat. Adenine, adenosine, and caffeine were also effective inducers, but other purine or pyrimidine derivatives were ineffective. Experiments with mutant derivatives of the HIV-1 long terminal repeat revealed no specific eukaryotic promoter elements necessary for 2-AP induction but indicated the need for some minimum combination of such elements. Induction of HIV-1-directed gene expression appeared not to require action of the transcription factor NF-kappa B. The mechanism of induction was investigated by using the luc and his genes linked to the HIV-1 long terminal repeat. 2-AP induced marked, steady rises in mRNA accumulation from both transfected and chromosomally integrated HIV-1 constructs but no increases from an endogenous gene encoding gamma-actin or glucose 6-phosphate dehydrogenase. Thus, induction is selective and not an artifact induced by transfecting DNA into cells. In run-on transcription experiments, the rates of transcription initiation of both transfected and integrated copies of the his gene increased about sixfold in cells treated with 2-AP. Thus, while increased initiation accounted for a portion of 2-AP induction, it could not cause the far greater increase in steady-state mRNA levels. 2-AP induction did not change mRNA decay rates and differed from the phorbol ester (phorbol myristate acetate)-induced activation of the protein kinase C-NF-kappa B pathway in its time course and in its requirement for new protein synthesis. Gel retardation assays showed that unlike phorbol myristate acetate induction, 2-AP induction is enhancer independent. Whereas many previous studies have implicated the activation of various protein kinases in gene induction, we here describe a mechanism of gene activation that appears to involve protein kinase inhibition as a component of the induction response.


The impact of different degrees of injured c7 nerve transfer: an experimental rat study.
Ipsilateral C7 nerve transfer is an available procedure in C5C6 2-root avulsion injury of the brachial plexus. However, concomitant injury of a normal-looking C7 cannot be ruled out. The efficiency of a concomitant injury of C7 transfer was investigated. Forty-two Sprague-Dawley rats were randomly assigned to 5 groups. They all underwent a 2-stage procedure. In the first stage from dorsal spine approach, left C5 and C6 roots were avulsed and C7 was crushed with jeweler's forceps with different degrees: group A (n = 6), C7 not injured; group B (n = 10), C7 crushed for 10 seconds; group C (n = 10), C7 crushed for 30 seconds; group D (n = 10), C7 doubly crushed for 60 seconds; and group E (n = 6), C7 transected and not repaired. Four weeks later in the second stage, the C7 was reexplored via volar approach, transected, and coapted to the musculocutaneous nerve. At 12 weeks following the nerve transfer, functional outcomes were assessed. Grooming test, muscle weight, electromyography, and muscle tetanic contraction force all showed that the biceps muscles were significantly worse in group C (moderate crush) and group D (severe crush). Group B (mild crush) and group A (uninjured) showed no difference. Group E (C7 cut and not repaired) was the worst. An injured but grossly normal-looking ipsilateral C7 can be used as a motor source but with variable results. The result is directly proportional to the severity of injury, potentially implying that better results will be achieved when longer regeneration time is allowed.


[Primary peritoneal tumors: report on a series of eight cases and review of the literature].
Primary peritoneal tumors are rare and yet not well-known malignancies. We report here the clinical cases of 8 patients who were referred to our institution with a primary peritoneal tumor, 4 serous carcinomas (PSC) and 4 malignant mesotheliomas (PMM). Diagnosis was available in all cases and reviewed by two pathologists. A battery of various immunomarkers contributed to confirm the morphological diagnosis. All patients underwent initial surgery with or without optimal debulking. All of them received a platinum-based systemic chemotherapy. Intraperitoneal treatment with cisplatin and hyperthermia was performed in two cases. Four patients are dead (3 PSC, 1 PMM), two are alive (one in partial remission (1 PSC) and one is having treatment (1 PMM)), one is in complete remission (1 PMM) and one is lost to follow up (1 MMP). PSC and PMM are difficult to distinguish since they share the embryonic cOElomic epithelium as a common origin. The clinical presentations are similar and usually include the detection of a pelvic mass and/or diffuse peritoneal carcinomatosis with or without malignant ascites. Therefore, the accuracy and reliability of the initial histological examination is of crucial importance. Further attempts will be required to better identify the most active therapeutic post-surgical combinations, especially for PMM.


Solid-phase extraction of small biologically active peptides on cartridges and microelution 96-well plates from human urine.
Currently liquid chromatography - mass spectrometry (LC-MS) analysis after solid-phase extraction (SPE) on weak cation-exchange cartridges is a method of choice for anti-doping analysis of small bioactive peptides such as growth hormone releasing peptides (GHRPs), desmoporessin, LHRH, and TB-500 short fragment. Dilution of urine samples with phosphate buffer for pH adjustment and SPE on weak cation exchange microelution plates was tested as a means to increase throughput of this analysis. Dilution using 200 mM phosphate buffer provides good buffering capacity without affecting the peptides recoveries. SPE on microelution plates was performed on Waters Positive Pressure-96 Processor with subsequent evaporation of eluates in nitrogen flow. Though the use of smaller sample volume decreases the pre-concentration factor and increases the limits of detection of 5 out of 17 detected peptides, the recovery, linearity, and reproducibility of the microelution extraction were comparable with cartridge SPE. The effectiveness of protocols was confirmed by analysis of urine samples containing ipamorelin, and GHRP-6 and its metabolites. SPE after urine sample dilution with buffer can be used for faster sample preparation. The use of microelution plates decreases consumption of solvents and allows processing of up to 96 samples simultaneously. Cartridge SPE with manual рН adjustment remains the best option for confirmation. Copyright © 2015 John Wiley & Sons, Ltd.


Whole-Genome Sequencing of a 900-Year-Old Human Skeleton Supports Two Past Migration Events from the Russian Far East to Northern Japan.
Recent studies on paleogenomics have reported some Paleolithic and Neolithic genomes that have provided new insights into the human population history in East and Northeast Asia. However, there remain some cases where more recent migration events need to be examined to elucidate the detailed formation process of local populations. Although the area around northern Japan is one of the regions archaeologically suggested to have been affected by migration waves after the Neolithic period, the genetic source of these migrations are still unclear. Thus, genomic data from such past migrant populations would be highly informative to clarify the detailed formation process of local populations in this region. Here, we report the genome sequence of a 900-year-old adult female (NAT002) belonging to the prehistoric Okhotsk people, who have been considered to be the past migrants to northern Japan after the Neolithic period. We found a close relationship between NAT002 and modern Lower Amur populations and past admixture events between the Amur, Jomon, and Kamchatka ancestries. The admixture dating suggested migration of Amur-related ancestry at approximately 1,600 BP, which is compatible with the archaeological evidence regarding the settlement of the Okhotsk people. Our results also imply migration of Kamchatka-related ancestry at approximately 2,000 BP. In addition, human leukocyte antigen (HLA) typing detected the HLA-B*40 allele, which is reported to increase the risk of arthritis, suggesting the genetic vulnerability of NAT002 to hyperostosis, which was observed around her chest clavicle.


Xeroderma Pigmentosum - Facts and Perspectives.
Ultraviolet (UV)-induced DNA lesions are almost exclusively removed by the nucleotide excision repair (NER) pathway, which is essential for prevention of skin cancer development. Patients with xeroderma pigmentosum (XP) are extremely sun sensitive due to a genetic defect in components of the NER cascade. They present with first signs of premature skin aging at an early age, with a considerably increased risk of developing UV-induced skin cancer. XP belongs to the group of DNA repair defective disorders that are mainly diagnosed in the clinic and in hindsight confirmed at the molecular level. Unfortunately, there are no causative treatment options for this rare, autosomal-recessive disorder, emphasizing the importance of an early diagnosis. Subsequently, UV-protective measures such as the reduction of exposure to environmental UV and regular skin cancer screenings should be undertaken to substantially improve prognosis as well as the disease course.


Engineering a freestanding biomimetic cardiac patch using biodegradable poly(lactic-co-glycolic acid) (PLGA) and human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs).
Microgrooved thin PLGA film (≈30 μm) is successfully fabricated on a Teflon mold, which could be readily peeled off and is used for the construction of a biomimetic cardiac patch. The contraction of it is studied with optical mapping on transmembrane action potential. Our results suggest that steady-state contraction could be easily established on it under regular electrical stimuli. Besides, the biomimetic cardiac patch recapitulates the anisotropic electrophysiological feature of native cardiac tissue and is much more refractory to premature stimuli than the random one constructed with non-grooved PLGA film, as proved by the reduced incidence of arrhythmia. Considering the good biocompatibility of PLGA as demonstrated in our study and the biodegradability of it, our biomimetic cardiac patch may find applications in the treatment of myocardial infarction. Moreover, the Teflon mold could be applied in the fabrication of various scaffolds with fine features for other tissues.


Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes.
Several natural compounds have been identified for the treatment of leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones, and saponins. The new compound reported here, 7-geranyloxycoumarin, called aurapten, belongs to the chemical class of the coumarins and has a molecular weight of 298.37. The compound was extracted from the Rutaceae species Esenbeckia febrifuga and was purified from a hexane extract starting from 407.7 g of dried leaves and followed by four silica gel chromatographic fractionation steps using different solvents as the mobile phase. The resulting compound (47 mg) of shows significant growth inhibition with an LD50 of 30 microM against the tropical parasite Leishmania major, which causes severe clinical manifestations in humans and is endemic in the tropical and subtropical regions. In the present study, we investigated the atomic structure of aurapten in order to determine the existence of common structural motifs that might be related to other coumarins and potentially to other identified inhibitors of Leishmania growth and viability. This compound has a comparable inhibitory activity of other isolated molecules. The aurapten is a planar molecule constituted of an aromatic system with electron delocalization. A hydrophobic side chain consisting of ten carbon atoms with two double bonds and negative density has been identified and may be relevant for further compound synthesis.


[Expression of cytokeratin19, galectin-3 and HBME-1 in thyroid lesions and their differential diagnoses].
To study immunohistochemical expression of cytokeratin19 (CK19), galectin-3 (Gal-3) and HBME-1 in thyroid lesions and to assess their usefulness as markers in the differential diagnoses of thyroid nodular lesions. Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue of 21 cases of nodular goiters, 14 cases of toxic goiters, 15 cases of follicular adenomas (FA), 13 cases of follicular carcinomas (FC), 13 cases of follicular variant papillary carcinomas (FVPC) and 48 cases of classic papillary carcinomas (CPC). All three markers were expressed in the cytoplasm with no or weak expression in benign lesions and diffuse and strong in malignant cases. Positive expressions of CK19, Gal-3 and HBME-1 were present in 11of 21, two of 21, four of 21 in nodular goiters, seven of 14, one of 14, one of 14 in toxic goiters, nine of 15, two of 15, two of 15 in FA, 10 of 13, eight of 13, seven of 13 in FC, 13 of 13, 11 of 13, 12 of 13 in FVPC, and 48 of 48, 45 of 48, 46 of 48 in CPC. The expression rates of the three markers between benign lesions (nodular goiters, toxic goiters and FA) and malignant lesions (FA, FVPC and CPC) were statistically significant. Among the three follicular lesions (FA, FC and FVPC), the differences were statistically significant as well. Nine, seven and six cases were negative for all three markers in nodular goiters, toxic goiters and FA, respectively. Only one case in FC was negative for all three markers, no case was all negative in FVPC and CPC; the rate of one case with two or more positive marker expression in nodular goiters, toxic goiters, FA, FC, FVPC and PC was 14.2% (3/21), 21.43% (3/14), 20.0% (3/15), 69.2% (9/13), 92.3% (12/13), 100.0% (48/48), the differences between benign lesions and malignant lesions and between FA, FC and FVPC were also statistically significant. Immunohistochemical stains of CK19, Gal-3 and HBME-1, especially when used in combination, can be an important adjunct to the histopathological diagnoses of thyroid lesions.