Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu's Arteritis.
To explore the relationships between Toll-like receptors (TLRs) and the activation and differentiation of T-cells in Takayasu's arteritis (TAK), using real-time fluorescence quantitative polymerase chain reaction, mRNA abundance of 29 target genes in peripheral blood mononuclear cells (PBMCs) were detected from 27 TAK patients and 10 healthy controls. Compared with the healthy control group, the untreated TAK group and the treated TAK group had an increased mRNA level of TLR2 and TLR4. A sample-to-sample matrix revealed that 80% of healthy controls could be separated from the TAK patients. Correlation analysis showed that the inactive-treated TAK group exhibited a unique pattern of inverse correlations between the TLRs gene clusters (including TLR1/2/4/6/8, BCL6, TIGIT, NR4A1, etc) and the gene cluster associated with T-cell activation and differentiation (including TCR, CD28, T-bet, GATA3, FOXP3, CCL5, etc). The dynamic gene co-expression network indicated the TAK groups had more active communication between TLRs and T-cell activation than healthy controls. BCL6, CCL5, FOXP3, GATA3, CD28, T-bet, TIGIT, IκBα, and NR4A1 were likely to have a close functional relation with TLRs at the inactive stage. The co-expression of TLR4 and TLR6 could serve as a biomarker of disease activity in treated TAK (the area under curve/sensitivity/specificity, 0.919/100%/90.9%). The largest gene co-expression cluster of the inactive-treated TAK group was associated with TLR signaling pathways, while the largest gene co-expression cluster of the active-treated TAK group was associated with the activation and differentiation of T-cells. The miRNA sequencing of the plasma exosomes combining miRDB, DIANA-TarBase, and miRTarBase databases suggested that the miR-548 family miR-584, miR-3613, and miR-335 might play an important role in the cross-talk between TLRs and T-cells at the inactive stage. This study found a novel relation between TLRs and T-cell in the pathogenesis of autoimmune diseases, proposed a new concept of TLR-co-expression signature which might distinguish different disease activity of TAK, and highlighted the miRNA of exosomes in TLR signaling pathway in TAK.


Synthesis and Antitumor Activity of New Group 3 Metallocene Complexes.
The quest for alternative drugs with respect to the well-known cis-platin and its derivatives, which are still used in more than 50% of the treatment regimens for patients suffering from cancer, is highly needed. In this context, organometallic compounds, which are defined as metal complexes containing at least one direct covalent metal-carbon bond, have recently been found to be promising anticancer drug candidates. A series of new metallocene complexes with scandium, yttrium, and neodymium have been prepared and characterized. Some of these compounds show a very interesting anti-proliferative activity in triple negative breast cancer cell line (MDA.MB231) and the non-hormone sensitive prostate cancer cell line (DU145). Moreover, the interaction of some of them with biological membranes, evaluated using liposomes as bio-membrane mimetic model systems, seems to be relevant. The biological activity of these compounds, particularly those based on yttrium, already effective at low concentrations on both cancer cell lines, should be taken into account with regard to new therapeutic approaches in anticancer therapy.


Latent Subtype of Cognitive Frailty among Multimorbidity Older Adults and Their Association with Social Relationships.
This study aimed to explore all the relevant subtypes of cognitive frailty among Japanese community-dwelling older adults with multimorbidity. Moreover, it examined the associations between these potential subtypes of cognitive frailty and social relationships. This study targeted relevant cross-sectional data regarding community-based older adults with multimorbidity. It employed a person-centered method to perform a latent class analysis and explore the subtypes of cognitive frailty among older adults. Moreover, a multinominal logistic regression analysis was employed to examine the association between potential subtypes of cognitive frailty and social relationships. Data for 396 participants (mean age, 75.8 [SD, 7.3] years; 51.3% females) were analyzed. Three cognitive frailty subtypes were subsequently revealed: the robust group (42.0%), the group with partial cognitive frailty (38.6%), and the group with cognitive frailty (19.4%). People with high levels of social relationships were more likely to be in the robust and the partial cognitive frailty groups. This study identified different subtypes of cognitive frailty among multimorbid older adults and highlighted the significance of social relationships. These findings could serve as a reference for conceptualizing cognitive frailty through the person-centered method. Promoting a high level of social relationships could be useful to prevent the cognitive frailty among older adults with multimorbidity.


Self-Assembled Multivalent Aptamer Drug Conjugates: Enhanced Targeting and Cytotoxicity for HER2-Positive Gastric Cancer.
Antibody drug conjugates (ADCs) have shown promise to be the mainstream chemotherapeutics for advanced HER2-positive cancers, yet the issues of poor drug delivery efficiency, limited chemotherapeutic effects, severe immune responses, and drug resistance remain to be addressed before the clinical applications of ADCs. The DNA aptamer-guided drug conjugates (ApDCs) are receiving growing attention for specific tumors due to their excellent tumor affinity and low cost. Therefore, developing a multivalent ApDC nanomedicine by combining anti-HER2 aptamer (HApt), tetrahedral framework nucleic acid (tFNA), and deruxtecan (Dxd) together to form HApt-tFNA@Dxd might help to address these concerns. In this study, the HER2-targeted DNA aptamer modified DNA tetrahedron (HApt-tFNA) was employed as a system for drug delivery, and the adoption of tFNA could effectively enlarge the drug-loading rate compared to aptamer-guided ApDCs previously reported. Compared with free Dxd and tFNA@Dxd, HApt-tFNA@Dxd showed better structural stability, excellent targeted cytotoxicity to HER2-positive gastric cancer, and increased tissue aggregation ability in tumors. These features and superiorities make HApt-tFNA@Dxd a promising chemotherapeutic medicine for HER2-positive tumors. Our work developed a new targeting nanomedicine by combining DNA nanomaterials and chemotherapeutic agents, which represents a critical advance toward developing novel DNA-based nanomaterials and promoting their potential applications for HER2-positive cancer therapy.


Current guidance for communicating with refugee and asylum seeker patients: An environmental scan of online resources.
Primary healthcare practitioners (PHPs) are often the first point of care for people seeking refuge or asylum in Australia. Communication plays a vital part in their care. The aim of this study was to identify, appraise and synthesise online resources that aim to support communication during consultations with these patients. A systematic environmental scan of online Australian resources, using the Google search engine, was conducted. The resources were appraised and rated using a validated purpose taxonomy as well as the Patient Education Materials Assessment Tool for Printed Materials to determine understandability and actionability. A total of 32 unique resources were identified. On average, the resources scored better on understandability (mean 64%) than actionability (mean 49%). The resources each had between two and five purpose taxonomy types, and the proportion of the content relevant to communication ranged from 5% to 100%. There are multiple resources available to PHPs to improve their communication with refugee and asylum seeker patients. Those that were rated better overall identified the population group and had practical suggestions to help operationalise their content. This article synthesises the online resources with practical suggestions regarding continuity of care, language barriers and PHPs' responsiveness to individual and cultural considerations.


Transcatheter arterial embolization for upper gastrointestinal tract bleeding.
Transcatheter arterial embolization is a possible treatment for patients with recurrent bleeding from the upper gastrointestinal tract after failed endoscopic management and is also an alternative to surgical treatment. To analyze the outcomes of transcatheter arterial embolization and identify the clinical and technical factors that influenced the rates of morbidity and mortality. A retrospective analysis was carried out, based on the data of 36 patients who underwent transcatheter arterial embolization for acute nonvariceal upper gastrointestinal bleeding in 2013 to 2015 in our center. An analysis was performed between early rebleeding rates, mortality and the following factors: patient sex, age, number of units of packed red blood cells and packed plasma administered to the patients, length of hospital stay, therapeutic or prophylactic embolization. The technical success rate of the embolization procedure was 100%. There were 15 (41.70%) therapeutic embolizations and 21 (58.3%) prophylactic embolizations. There was a 77.8% clinical success rate. Following embolization, 10 (27.80%) patients had repeated bleeding and 9 (25.0%) patients died. Significant associations were found between rebleeding and prophylactic embolization (OR = 10.53; p = 0.04) and between mortality and prophylactic embolization (OR = 10.53; p = 0.04) and units of packed red blood cells (OR = 1.25; p < 0.01). In our experience, transcatheter arterial embolization is a safe treatment method for acute nonvariceal upper gastrointestinal bleeding and a possible alternative to surgery for high-risk patients.


[Differential expression of Notch1 and Notch2 in astrocytoma and medulloblastoma].
To detect the differential expression of Notch1 and Notch2 in human astrocytoma and medulloblastoma; and to study the role of Notch1 and Notch2 in the development of both tumors. Immunohistochemical staining (SP method) and Western blot analysis were used to detect Notch1 and Notch2 expression in tissue arrays and freshly resected samples of normal brain tissue, astrocytoma and medulloblastoma. Notch1 and Notch2 were negative in normal human brain tissue. Notch1 was highly expressed (total positive rate 80.0%, 48/60) while Notch2 was not detected in grade IV astrocytomas and sporadically observed in lower grade astrocytomas (total positive rate 10.0%, 6/60). The percentage of positive tumor cells and expression level of Notch1 increased with higher histologic grade (r = 0.859, P < 0.05). On the other hand, overexpression of Notch2 was detected in medulloblastoma (9/10) in contrast with lower expression of Notch1 (2/10). Notch1 and Notch2 show differential expression in astrocytoma and medulloblastoma. This may be related to their different functional activities during the process of brain development.


Cell wall proteins of Candida albicans.
Proteins were solubilized from cell wall fractions of Candida albicans and separated by polyacrylamide gel electrophoresis. Cell walls were isolated from 25 and 37 degrees C growing and stationary phase yeast cultures and from germ tubes. The 42 protein bands detected by dye binding were observed in all wall extracts, regardless of the temperature, growth state, or morphology of the culture. The carbohydrate content of most bands was below the detectable limit of the periodic acid Schiff reagent. The protein complement revealed by autoradiography of radiolabeled proteins was half that detected by staining. Two bands showed greater intensity from cultures grown at 37 degrees C. The radio-labeled pattern was similar with both [35S]methionine-and [14C]leucine-labeled proteins and either pulse- or continuous-labeled proteins.


Differential gene expression in the otic capsule and the middle ear--an annotation of bone-related signaling genes.
A number of bone-related genes may be responsible for the unique suppression of perilabyrinthine bone remodeling. Bone remodeling is highly inhibited around the inner ear space most likely because of osteoprotegerin (OPG), which is a well-known potent inhibitor of osteoclast formation and function. However, other signaling molecules may also be responsible for the inhibition of bone remodeling within the otic capsule. Microarray technology was used to determine bone-related genes differentially expressed between the lining tissues of the otic capsule (spiral ligament and stria vascularis) and the lining tissues from the middle ear of the rat. Data was analyzed with statistical bioinformatics tools. Gene expression levels of selected genes were validated using quantitative polymerase chain reaction. A total of 413 genes were identified when young inner bulla (growing) were compared with young otic capsule and 358 genes were identified when adult inner bulla (quiescent) were compared with adult otic capsule. Fourteen genes were involved in bone metabolism of which four genes have been previously discussed in the literature of perilabyrinthine bone biology. The gene expression of the otic capsule was significantly different from that of the middle ear. This study identified a number of differentially expressed bone-related mRNAs of potential significance and confirmed the OPG/receptor activator of nuclear factor kappa-B (RANK)/RANK ligand (RANKL) pathway as the key signaling system for the unique behavior of bone cells within the otic capsule. No differentially expressed up- or downstream messengers in the OPG/RANK/RANKL pathway were found.


Scaling of the glassy dynamics of soft repulsive particles: a mode-coupling approach.
We combine the hypernetted chain approximation of liquid state theory with the mode-coupling theory of the glass transition to analyze the structure and dynamics of soft spheres interacting via harmonic repulsion. We determine the locus of the fluid-glass dynamic transition in a temperature--volume fraction phase diagram. The zero-temperature (hard-sphere) glass transition influences the dynamics at finite temperatures in its vicinity. This directly implies a form of dynamic scaling for both the average relaxation time and dynamic susceptibilities quantifying dynamic heterogeneity. We discuss several qualitative disagreements between theory and existing simulations at equilibrium. Our theoretical results are, however, very similar to numerical results for the driven athermal dynamics of repulsive spheres, suggesting that "mean-field" mode-coupling approaches might be good starting points to describe these nonequilibrium dynamics.


The relationship between cannabis and anorexia nervosa: a scoping review.
Relapse rates in Anorexia Nervosa (AN) remain high, warranting exploration of further treatments. Cannabinoid agonists are of interest as they have shown successful outcomes in the treatment of associated conditions, such as post-traumatic stress disorder. This scoping review explores the endocannabinoid system (ECS), benefits/harms/null effects of cannabinoid treatment, and harms of cannabis use in AN. PubMed, PsycINFO, Cochrane, and Web of Science were searched for studies published between 2010 and August 2023, with human participants that explored the ECS, cannabinoid treatment, or cannabis use, and included 1 or more keywords for both cannabis and AN in the title and or abstract. Reports describing secondary anorexia, reports not available in English, grey literature, reports combining data from AN with other conditions, and reports only reporting the prevalence of cannabis abuse/dependence were excluded. Data were extracted from 17 reports (n = 15 studies). For the ECS, outcomes included genetics such as allele expression related to the ECS, cannabinoid receptor availability, and circulating levels of endocannabinoids. For benefits/harms/null effects of cannabinoid treatment, outcomes included changes in weight, eating disorder (ED) symptoms, physical activity (PA), and hormones. For harms of cannabis use, outcomes included genetics related to cannabis use disorder and associations between cannabis use and ED symptoms. Eight studies (n = 8 reports) found abnormalities in the ECS in AN including expression of related alleles, genotypes, and haplotypes, availability of cannabinoid receptors, and levels of endocannabinoids. Three studies (n = 5 reports) found benefits/harms/null effects of cannabinoid treatment. Benefits included weight gain, improved ED symptoms and reduced PA, while null effects included no changes in weight or ED symptoms, and harms included increased PA and lowered adipose hormones. Four studies (n = 4 reports) expanded upon harms of cannabis use, including genetic predispositions to cannabis use disorder, and compensatory behaviors related to cannabis use. Limited evidence suggests that abnormalities in the ECS in AN may render cannabis a potential treatment for weight restoration and associated symptoms. Future research may wish to investigate individualized dosing approaches to maximize beneficial effects while minimizing harms. Level II Evidence: Scoping Review.


Farmers' exposure to airborne microorganisms in composting swine confinement buildings.
Farmers' exposure to airborne microorganisms was studied in 12 composting swine confinement buildings and in 7 buildings with traditional slatted-floor pit systems. Airborne cultivable mesophilic, xerophilic, and thermotolerant fungi, mesophilic bacteria, and thermophilic actinobacteria were determined with a six-stage impactor. Furthermore, the total concentrations of microorganisms were determined with filter sampling and direct count using a microscope. In swine confinement buildings where the composting system was functioning properly, the concentrations of microorganisms were 10-1000 times higher than in traditional swine buildings. High concentrations of thermotolerant fungi and thermophilic actinobacteria (up to 10(5) CFU/m(3)), which have been considered to be the main causative agents of farmer's lung, were found in the composting swine confinement buildings that were studied. The conclusion was reached that farmers are exposed to high concentrations of fungal and actinobacterial spores also in swineries, at least in composting confinement buildings. Therefore, personal protection is strongly recommended in composting swineries, especially during the turning of the compost bed.


[Staphylococcus and its counter-measures against epidermal antimicrobial peptides].
Staphylococci are microorganisms often involved in a colonization process on muco-cutaneous sites. They are responsible for various nosocomial and community-associated skin infections. The methicillin-resistant staphylococci are particularly involved in various aspects of pathology. Epidermal antimicrobial peptides are part of the host defense mechanisms corresponding to the innate immunity. They may limit the extent in colonization. However, some staphylococci are able to bypass the antimicrobial peptides released by the host.


Novel crown ether and salen metal chelation driven molecular pincers.
The synthesis of novel metal chelation driven molecular pincers based on crown ether and salen ligand substructures are described. Their functionality was monitored by fluorescence spectroscopy using pyrene groups as fluorescence probes. The pincer was shown to function reversibly with respect to metal chelation with Zn2+ and also to chelate ditopically with 100 mol % of Zn2+ and 100 mol % Li+ or 200 mol % of Li+ ion.


Preparation and mechanical properties of rubber composites reinforced with carbon nanohorns.
Nitrile butadiene rubber (NBR) composites with single-wall carbon nanohorns (SWNHs, or simply NHs), hole-opened NHs (h-NHs), and carbon black (CB), the most commonly used nanocarbon rubber filler, were prepared, and their mechanical properties were compared. The NBR composites with h-NHs (NBR/h-NH) showed higher tensile strength than those with NHs (NBR/NH), and the tensile strength of NBR/h-NH or NBR/NH was much greater than those of the NBR composites with CB (NBR/CB). At 5 parts per hundred of rubber (phr), the tensile stresses at break of NBR/h-NH was about 1.8 times larger than those of NBR/CB, and the strain at the break, 1.2 times larger. Similarly, at 20 phr, both the tensile strength and strain at the break of NBR/h-NH were 1.4 times larger than those of NBR/CB. NBR/NH showed the highest hardness while having the smallest specific gravity. The present results indicate that NHs and h-NHs have much superior reinforcement effects to CB for NBR rubber matrix.


Purification and characterization of extracellular 1,2-alpha-L-fucosidase from Bacillus cereus.
Bacillus cereus isolated from a soil sample, inductively produced alpha-L-fucosidase in culture medium containing porcine gastric mucin (PGM). The production of the enzyme was also weakly induced by L-fucose and D-arabinose, but not by other sugars including glucose. The enzyme was purified 61-fold with an overall recovery of 1.8% from the culture fluid supplemented with PGM by ammonium sulfate precipitation, acetone fractionation, and subsequent column chromatography. The purified enzyme was found homogeneous by SDS-PAGE and its molecular mass was estimated to be approximately 196,000 kDa. Its optimum pH was 7.0 and it was stable in the pH range of 5.0 to 9.0. The enzyme hydrolyzed the alpha-(1-->2)-L-fucosidic linkage in oligosaccharides such as Fucalpha1-2Galbeta1-4Glc (2'-fucosyllactose), Fucalpha1-2Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc (lacto-N-fucopentaose I), and the glycoprotein PGM. The enzyme was inactive on p-nitrophenyl alpha-L-fucoside, the alpha-(1-->3)-L-fucosidic linkages in Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3Galbeta1-4Glc (lacto-N-fucopentaose III) and orosomucoid, the alpha-(1-->4)-L-fucosidic linkage in Galbeta1-3(Fucalpha1-4)GlcNAcbeta1-3Galbeta1-4Glc (lacto-N-fucopentaose II), and the alpha-(1-->6)-L-fucosidic linkage in thyroglobulin.


Mechanistic Insight into Age-Related Macular Degeneration (AMD): Anatomy, Epidemiology, Genetics, Pathogenesis, Prevention, Implications, and Treatment Strategies to Pace AMD Management.
One of the most complicated eye disorders is age-related macular degeneration (AMD) which is the leading cause of irremediable blindness all over the world in the elderly. AMD is classified as early stage to late stage (advanced AMD), in which this stage is divided into the exudative or neovascular form (wet AMD) and the nonexudative or atrophic form (dry AMD). Clinically, AMD primarily influences the central area of retina known as the macula. Importantly, the wet form is generally associated with more severe vision loss. AMD has a systemic component, where many factors, like aging, genetic, environment, autoimmune and non-autoimmune disorders are associated with this disease. Additionally, healthy lifestyles, regular exercise, maintaining a normal lipid profile and weight are crucial to decreasing the risk of AMD. Furthermore, therapeutic strategies for limiting AMD should encompass a variety of factors to avoid and improve drug interventions, and also need to take into account personalized genetic information. In conclusion, with the development of technology and research progress, visual impairment and legal blindness from AMD have been substantially reduced in incidence. This review article is focused on identifying and developing the knowledge about the association between genetics, and etiology with AMD. We hope that this review will encourage researchers and lecturers, open new discussions, and contribute to a better understanding of AMD that improves patients' visual acuity, and upgrades the quality of life of AMD patients.


Phage-inactivating Effect of Iron(II)-Ascorbate Complex.
The effect of iron(II)-ascorbate complex on various phages was investigated. At 10- (6) M, the complex inactivated all nine phages examined. The mechanism of the inactivation was studied with phage J1, the most sensitive to the complex. The addition of H2O2 or Cu(2+) to the reaction mixture increased the inactivation. Bubbling of nitrogen through the reaction mixture and the addition of Fe(3+), a reducing agent, a chelating agent, or a radical scavenger prevented inactivation. These findings suggest the involvement of oxygen radicals in the inactivation. The complex had no effects on the SDS-PAGE pattern or amino acid composition of bovine serum albumin, or the structural protein of phage J1. The complex nicked the supercoiled form of pUC18 DNA, giving first single-stranded breaks (the open circular form) and then double-stranded breaks (the linear form). Strands of M13mp8 DNA, λDNA, and J1 DNA were also broken. The breaks could account for the inactivation.


The association between sleep duration and physical performance in Chinese community-dwelling elderly.
Physical performance is an important healthy factor in elder people. Good living habits, which include sleep, can maintain physical strength and physical performance. The aim of the present study was to conduct a cross-sectional study to determine the association between total sleep duration and physical performance. Our study population comprised residents of the township central hospital in the suburban of Tianjin, China. We measured muscle strength, walk speed and balance function by grip, 4-m walk test and timed up and go test (TUGT). We divided sleep duration into four groups <7h, 7-8h, >8-9h, >9h. A total 898 participants had completed data (392 men and 506 women, mean age 67.71 years). In man, adjusted sleep duration was associated with lower grip in > 9 h group, the mean value (95% CI) was 0.429 (0.409, 0.448), and longer TUGT time was also associated with long sleep duration, 10.46s (9.97 s, 10.95 s). In women, adjusted slower 4-m walk speed present an inverse U-shaped relation with sleep duration, by 0.93 m/s (0.86 m/s, 0.98 m/s), 0.97 m/s (0.96 m/s, 1.00 m/s), 0.97 m/s (0.95 m/s, 0.99 m/s) and 0.92 m/s (0.89 m/s, 0.96 m/s); longer TUGT time were associated with long sleep duration (> 9 h), by 11.23 s (10.70 s, 11.77 s). In Chinese community-dwelling elderly, lower muscle strength and lower balance function were associated with long sleep duration in men. Slower walk speed and lower balance function were associated with long sleep duration in women.


Relevance of secretor status genotype and microbiota composition in susceptibility to rotavirus and norovirus infections in humans.
Host genetic factors, such as histo-blood group antigens (HBGAs), are associated with susceptibility to norovirus (NoV) and rotavirus (RV) infections. Recent advances point to the gut microbiome as a key player necessary for a viral pathogen to cause infection. In vitro NoV attachment to host cells and resulting infections have been linked to interactions with certain bacterial types in the gut microbiota. We investigated the relationship between host genotype, gut microbiota, and viral infections. Saliva and fecal samples from 35 adult volunteers were analysed for secretor status genotype, the gut microbiota composition by 16S rRNA gene sequencing, and salivary IgA titers to NoV and RV. Higher levels of IgA against NoV and RV were related to secretor-positive status. No significant differences were found between the FUT2 genotype groups, although the multivariate analysis showed a significant impact of host genotype on specific viral susceptibilities in the microbiome composition. A specific link was found between the abundance of certain bacterial groups, such as Faecalibacterium and Ruminococcus spp., and lower IgA titers against NoV and RV. As a conclusion, we can state that there is a link between host genetics, gut microbiota, and susceptibility to viral infections in humans.


Structural organization and processing of the genetic transcript in the cellular slime mold Dictyostelium discoideum.
The organization of the genome and the synthesis and processing of heterogeneous nuclear RNA (HNRNA) in the cellular slime mold Dictysotelium discoideum have been analyzed. Approximately 60-70% of the genome of Dictyostelium consists of interspersed reiterated and single-copy sequences. The interspersed reiterated sequences have an average length of 250-400 nucleotides. Approximately 50% of the reiterated DNA sequences consist of long noninterspersed sequences. The results of analyses of ynRNA synthesis and processing have been incorporated into a model. According to the model the primary genetic transcript of Dictyostelium is synthesized as a molecule that is 25% larger than mRNA. The bulk of the hnRNA is synthesized from a unit consisting of a short reiterated DNA sequence transcript at the 5' end of the molecule and a single-copy sequence of approximately 1,200 nucleotides in length. In the processing of the mRNA precursor, there appears to be a loss of the majority of the repetitive sequence at the 5' end. The genome contains interspersed sequences of poly (dT)25. These sequences, which appear to be at the 3' terminus of the transcription unit, are transcribed directly into the heterogenous nuclear RNA and are contained within the messenger RNA. During the processing of the heterogeneous nuclear RNA, a poly (A) sequence of approximately 125 nucleotides in length is added posttranscriptionally to the 3' end of the molecule.


A projection-based reformulation of the coincident site lattice Σ for arbitrary bicrystals at finite temperature.
The coincident site lattice and, specifically, the `Σ value' of a grain boundary are a ubiquitous metric for experimental classification of grain boundaries. However, the mathematical nature of Σ - a pathological function taking values of either an integer or infinity - has been relatively unexplored. This work presents a framework for interpreting Σ as the inverse of a projection defined using the standard L2 inner product over continuous fields that represent lattices. `Pre-mollifiers' are used to introduce thermal regularization in the context of the inner product, and a closed-form analytic result is derived. For all nonzero values of the regularization parameters, the formulation is mathematically smooth and differentiable, providing a tool for computationally determining experimental deviation from measured low-Σ boundaries at finite temperatures. It is verified that accurate Σ values are recovered for sufficiently low Σ boundaries, and that the numerical result either converges towards an integer value or diverges to infinity.


Baseline soil-transmitted helminth and schistosome infection in the Geshiyaro project, Ethiopia: A unique transmission interruption project using biometric fingerprinting for longitudinal individual analysis.
The Geshiyaro project aims to assess the feasibility of interrupting transmission of soil-transmitted helminths (STH) and schistosome (SCH) infection in the Wolaita zone of southern Ethiopia through high coverage community-wide mass drug administration (MDA), in combination with improved water, sanitation, and hygiene services and behaviour change communication delivered through the existing health care infrastructure. To accurately measure treatment coverage a population census was conducted enrolling individuals with biometric fingerprinting and barcoded ID cards. This paper details the baseline census and parasitology surveys conducted before the start of any interventions. The census was conducted in five of the 15 Wolaita districts between October 2018 and December 2019, enrolling all consenting participants from every household. Simultaneously, a cross-sectional parasitology survey was conducted in 130 out of 361 randomly selected communities from all 15 districts, with 100 individuals across all age groups (infant to adult) per community providing stool and urine for analysis by duplicate Kato-Katz and a point-of-care circulating cathodic antigen (POC-CCA) to test for Schistosoma mansoni and STH, and microhaematuria and urine filtration for Schistosoma haematobium. Of the 130 communities, 30 were randomly selected for annual, longitudinal parasitological monitoring, with 150 randomly selected individuals from infant to adult providing two days of stool and urine samples for analysis by the same diagnostic tests per community. In total 97,919 households participated in the baseline census enrolling 466,071 individuals, with parasitological data obtained from 10,785 people. At baseline, 15.5% were infected with at least one STH species, with Ascaris lumbricoides (9.5%), followed by hookworm (7.2%) and Trichuris trichiura (1.8%). Substantial heterogeneity in STH prevalence was observed between communities ranging from 0% to 61% where most infections were low intensity. Schistosoma mansoni infection was the dominant schistosome infection (0.85% by Kato-Katz and 13.3% by POC-CCA trace negative and 21.5% trace positive), with few Schistosoma haematobium infections identified (2.77% haematuria positive and 0.13% positive by urine filtration). While the national control program in Ethiopia has made good progress in reducing prevalence of STH and SCH in Wolaita since it was launched in 2015, there remain areas of persistent infection suggesting the existence of environmental or behavioural risk factors that contribute to ongoing transmission. This project aims to identify the most efficient intervention strategies to reduce community burden and reach interruption of transmission.


A Novel Intraoperative Transient Variant of Immune Thrombocytopenia.
Immune thrombocytopenia, also known as immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a very low number of platelets and associated excessive bleeding. Primary ITP is a diagnosis of exclusion and secondary causes of ITP including lymphoproliferative disorders, medications, and certain infections must be ruled out during workup. This is the first report to highlight intraoperative ITP or an ITP-like novel variant in the perioperative setting leading to increased bleeding. The patient's extensive workup failed to reveal any secondary causative factors. The clinical presentation of ITP was transient. She received tranexamic acid (TXA), intravenous steroids, and intravenous immunoglobulins (IVIG) and recovered without complication. This case report explores a potentially underreported cause for intraoperative and postoperative hemorrhage in surgical patients.


Special symposium issue: slipped capital femoral epiphysis (SCFE).
Up-date on the pathogenesis, epidemiology, pathology, histopathology, clinical findings, diagnosis & classification, imaging modalities and all treatment options in slipped capital femoral epiphysis. This symposium issue of JCO is based on lectures presented at the Pre-Course at the 35th Annual Congress of the European Paediatric Orthopaedic Society (EPOS) in 2016.


Magnetic properties of bcc Iron surfaces and the influence of the chemical environment: electronic structure calculations.
We have investigated the magnetic properties of low-indexed iron surfaces and the influence of the chemical environment on these properties. We have considered the (1 0 0), (1 1 0), (1 1 1), (2 1 1) and (3 1 0) surfaces, both, bare and with the presence of adsorbates. These were chosen to mimic realistic chemical synthesis environments, being H, Cl, HCl, NH3, NH4Cl, or CH3COOH. We have found an increased magnetization at all bare surfaces. Upon H adsorption the magnetization is generally reduced, but still above the bulk value. All other ligands and their dissociated parts alter the magnetic properties of the surfaces only weakly. Our calculations do not indicate that ligands are responsible for experimental observations of Fe nanoparticles with average magnetizations below the bulk value.


The untold saga of chromotherapy in dentistry.
Being a centuries-old concept and used successfully over years, chromotherapy is the method of treating diseases using coloured food, coloured clothing, colour saturated oils, coloured water and visible spectrum of electromagnetic radiation. The basis of chromotherapy depends on the fact that illness is caused by an imbalance in the basic chakras of the body. Colour therapy rebalances the chakras using specific colours. Being a part of complementary and alternative medicine systems, it proves to be effective for various systems of the body and affects neurohormonal pathways. Based on the available literature, this review documents the scientific evolution of colour therapy in medicine and dentistry and its various applications. Future studies will establish exactly how chromotherapy promotes wellbeing, owing to technical advancements and the scientific approach. Till then, it is a low-cost, non-invasive treatment option that is worth a go.


Frontal brain deactivation during a non-verbal cognitive judgement bias test in sheep.
Animal welfare concerns have raised an interest in animal affective states. These states also play an important role in the proximate control of behaviour. Due to their potential to modulate short-term emotional reactions, one specific focus is on long-term affective states, that is, mood. These states can be assessed by using non-verbal cognitive judgement bias paradigms. Here, we conducted a spatial variant of such a test on 24 focal animals that were kept under either unpredictable, stimulus-poor or predictable, stimulus-rich housing conditions to induce differential mood states. Based on functional near-infrared spectroscopy, we measured haemodynamic frontal brain reactions during 10 s in which the sheep could observe the configuration of the cognitive judgement bias trial before indicating their assessment based on the go/no-go reaction. We used (generalised) mixed-effects models to evaluate the data. Sheep from the unpredictable, stimulus-poor housing conditions took longer and were less likely to reach the learning criterion and reacted slightly more optimistically in the cognitive judgement bias test than sheep from the predictable, stimulus-rich housing conditions. A frontal cortical increase in deoxy-haemoglobin [HHb] and a decrease in oxy-haemoglobin [O2Hb] were observed during the visual assessment of the test situation by the sheep, indicating a frontal cortical brain deactivation. This deactivation was more pronounced with the negativity of the test situation, which was reflected by the provenance of the sheep from the unpredictable, stimulus-poor housing conditions, the proximity of the cue to the negatively reinforced cue location, or the absence of a go reaction in the trial. It seems that (1) sheep from the unpredictable, stimulus-poor in comparison to sheep from the predictable, stimulus-rich housing conditions dealt less easily with the test conditions rich in stimuli, that (2) long-term housing conditions seemingly did not influence mood--which may be related to the difficulty of tracking a constant long-term state in the brain--and that (3) visual assessment of an emotional stimulus leads to frontal brain deactivation in sheep, specifically if that stimulus is negative.


Evaluation of the free-radical scavenging and antioxidant activities of Chilauni, Schima wallichii Korth in vitro.
Free radicals are an outcome of various metabolic activities and their excess production leads to many diseases. Therefore, it is necessary to neutralize excess free radicals. Free-radical scavenging activity of various extracts of Schima wallichii was evaluated using standard protocols. Chloroform, ethanol and aqueous extracts of S. wallichii scavenged DPPH, hydroxyl, superoxide, nitric oxide and ABTS free radicals and increased ferric-reducing antioxidant potential in a concentration-dependent manner. A total of 1000 μg/ml of all the extracts and ethanol extract showed highest total flavonoids and phenol contents, respectively. The different extracts of S. wallichii scavenged different free radicals efficiently due to the presence of flavonoids and polyphenols and may be helpful in free radical-induced diseases.


Johrei family healing: a pilot study.
Johrei is a form of spiritual healing comprising "energy channelling" and light massage given either by a trained healer or, after some basic training, by anyone. This pilot trial aimed to identify any potential benefits of family-based Johrei practice in childhood eczema and for general health and to establish the feasibility of a subsequent randomised controlled trial. Volunteer families of 3-5 individuals, including at least one child with eczema were recruited to an uncontrolled pilot trial lasting 12 months. Parents were trained in Johrei healing and then practised at home with their family. Participants kept diaries and provided questionnaire data at baseline, 3,6 and 12 months. Eczema symptoms were scored at the same intervals. Scepticism about Johrei is presently an obstacle to recruitment and retention of a representative sample in a clinical trial, and to its potential use in general practice. The frequency and quality of practise at home by families may be insufficient to bring about the putative health benefits. Initial improvements in eczema symptoms and diary recorded illness, could not be separated from seasonal factors and other potential confounders. There were no improvements on other outcomes measuring general health and psychological wellbeing of family members.


Identification of tri-phosphatase activity in the biogenesis of retroviral microRNAs and RNAP III-generated shRNAs.
Transcripts possessing a 5'-triphosphate are a hallmark of viral transcription and can trigger the host antiviral response. 5'-triphosphates are also found on common host transcripts transcribed by RNA polymerase III (RNAP III), yet how these transcripts remain non-immunostimulatory is incompletely understood. Most microRNAs (miRNAs) are 5'-monophosphorylated as a result of sequential endonucleolytic processing by Drosha and Dicer from longer RNA polymerase II (RNAP II)-transcribed primary transcripts. In contrast, bovine leukemia virus (BLV) expresses subgenomic RNAP III transcripts that give rise to miRNAs independent of Drosha processing. Here, we demonstrate that each BLV pre-miRNA is directly transcribed by RNAP III from individual, compact RNAP III type II genes. Thus, similar to manmade RNAP III-generated short hairpin RNAs (shRNAs), the BLV pre-miRNAs are initially 5'-triphosphorylated. Nonetheless, the derivative 5p miRNAs and shRNA-generated 5p small RNAs (sRNAs) possess a 5'-monophosphate. Our enzymatic characterization and small RNA sequencing data demonstrate that BLV 5p miRNAs are co-terminal with 5'-triphosphorylated miRNA precursors (pre-miRNAs). Thus, these results identify a 5'-tri-phosphatase activity that is involved in the biogenesis of BLV miRNAs and shRNA-generated sRNAs. This work advances our understanding of retroviral miRNA and shRNA biogenesis and may have implications regarding the immunostimulatory capacity of RNAP III transcripts.


Genetic and Morphological Evidence Implies Existence of Two Sympatric Species in Cyathopharynx furcifer (Teleostei: Cichlidae) from Lake Tanganyika.
Although the cichlid fishes from Lake Tanganyika are treated as a textbook example of adaptive radiation, many taxonomic problems remain unresolved. Cyathopharynx furcifer, which belongs to the currently monospecific genus Cyathopharynx, contains two colour morphs at the southern end of the lake: one has a yellow anal fin, and the other has a black anal fin. Some books for hobbyists of ornamental fish treat these morphs as different species, but taxonomic studies have neither mentioned the existence nor addressed the status of these colour morphs. In the present paper, we analysed these two colour morphs using mitochondrial, microsatellite, morphometric, and meristic data sets. Both molecular and morphological data allowed clear discrimination between these morphs, suggesting the existence of two distinct sympatric species. Three taxonomic species have been described in this genus, and only C. furcifer is currently considered valid. Observations of type specimens of these three nominal species will be needed to determine the scientific names of these colour morphs.


Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein that block processing to gp85 and gp37.
We have investigated the specificity of the proteolytic cleavage of the Rous sarcoma virus glycoprotein precursor by introducing two mutations into the putative cleavage region (Arg-Arg-Lys-Arg). We show that neither a deletion of the cleavage sequence nor a glutamic acid for lysine substitution altered intracellular transport or surface expression of the env gene products. However, both the four-amino-acid deletion and the glutamic acid substitution block processing of the env precursor. Susceptibility of the glutamic acid-substituted env precursor to proteases indicated that tertiary protein structure was unaffected. While inhibitor experiments suggested that more than one endopeptidase might be capable of mediating the proteolytic cleavage, the results presented here point to the presence in the Golgi apparatus of a novel endopeptidase, required for retroviral glycoprotein cleavage, that has a high specificity for lysine-containing peptides.


High Fluoroquinolone Resistant Strains of Helicobacter pylori in the Golden triangle
Background and aims: Helicobacter pylori (H. pylori) infections, associated with fatal GI diseases such as gastric cancer and MALT lymphoma, remain a major health problem in ASEAN countries. The Golden triangle has long been known as one of Asia's main opium-producing areas. There have been no prior studies of H. pylori infection in this area. The major objectives of this project were therefore to establish prevalence, antibiotic resistance patterns and associated predictive in the Golden triangle. Methods: We recruited dyspeptic patients in Chiang khong and Chiang saen districts, Chiangrai province of Thailand. All subjects underwent gastroscopy, and 3 antral gastric biopsies were collected for rapid urease tests and H. pylori culture. E-tests were used to evaluate the MICs for metronidazole (MNZ), levofloxacin (LVX), ciprofloxacin (CIP), amoxicillin(AMX), tetracycline (TET) and clarithromycin (CLR). Results: Total of 148 patients was included. H. pylori infection was present in 36.3%(37/102) of Chiang khong and 34.8 % (16/46) of Chiang saen subjects and the overall H. pylori infection rate was 35.8% (53/148). Antibiotic resistance was demonstrated in 44%, including 2% for CLR and 26% for MNZ, whereas fluoroquinolone resistance was demonstrated to be as high as 25% in Chiang khong. Multi-drug resistant H. pylori was detected in 4%. There was no AMX and TET resistance in this study. The prevalence of CLR resistance on a background of gastritis was significantly higher than peptic ulcer disease in the golden triangle area (100%vs 0%: P= 0.04). Conclusions: H. pylori remains a common infection in the Golden triangle. MNZ resistance appears to be high, whereas fluoroquinolone resistance is prevalent and is becoming a significant problem in this area. Diagnosis of gastritis might be a predictor of CLR resistance in the Golden triangle. H. pylori eradication with an appropriate regimen by using the local antibiotic resistant pattern is a key important tool to reduce H. pylori associated GI diseases in this particular part of the world.


The kinetics of intravenously administered methyl mercury in man.
We describe a compartmental pharmacokinetic model for methyl mercury and its metabolite mercuric mercury in humans. A tracer dose of 203Hg-labeled methyl mercury was administered iv to seven healthy young adult male volunteers. Blood samples were obtained periodically and urine and feces were collected throughout the 70 days of the study. The blood contained predominantly methyl mercury, while the excreta contained principally inorganic mercury. The behavior of both methyl mercury and inorganic mercury in the body was modeled with the simplest compartmental model which fit the data. This five-compartment model shows that inorganic mercury accumulates in the body and at longer times is the predominant form of mercury present. The biological half-life of methyl mercury in the body is 44 days and 1.6% of the body burden is lost each day by both metabolism and excretion. This rate of loss is 60% greater than that currently accepted (1.0% per day). Thus, the risk associated with dietary methyl mercury may have been overestimated.


Intraoperative cochlear nerve monitoring in vestibular schwannoma surgery--does it really affect hearing outcome?
The objective of this study was to examine the usefulness of intraoperative cochlear nerve monitoring (ICNM) in the preservation of normal and social hearing in vestibular schwannoma (VS) removal. A retrospective chart review was conducted. Of 1315 patients operated for VS between June 1988 and December 2005, 150 patients were subjected to hearing preservation surgery. Among these, 99 patients with preoperative normal and social hearing (class A and B in the modified Sanna classification) and with a small tumor <1.5 cm in size were included in the analysis. The difference in hearing preservation rates between patients operated with and without ICNM was statistically examined using Fisher's exact test. An initial analysis was conducted for the total group. Patients were then divided into two subgroups according to the surgical approach (middle cranial fossa and retrosigmoid-retrolabyrinthine). The effectiveness of ICNM in each subgroup was analyzed. The hearing preservation rate was 26.7% in cases operated with ICNM and 20.8% in cases without ICNM. The difference did not reach statistical significance (p = 0.79). In subgroup analyses, the ICNM did not prove to contribute to the significantly higher hearing preservation rate. ICNM did not increase the ratio of patients with postoperative normal and social hearing in VS surgery.


Cloning and characterization of the gene for Escherichia coli tryptophanyl-transfer ribonucleic acid synthetase.
From a Clark-Carbon plasmid containing trpS, the structural gene for the tryptophanyl-transfer ribonucleic acid synthetase of Escherichia coli, we subcloned a 2.6-kilobase fragment that has trpS and its neighboring regions. The location and orientation of trpS in the deoxyribonucleic acid insert was determined by deoxyribonucleic acid sequencing. In vitro transcription experiments and S1 nuclease mapping studies with in vivo message established that transcription is initiated at the same site in vivo and in vitro, approximately 58 base pairs upstream from the trpS coding region. We also describe the construction of an inphase trpS-lacZ gene fusion that is under the control of the trpS promoter and encodes a hybrid protein with beta-galactosidase activity.


Effect of the Interlayer Ordering on the Fermi Surface of Kagome Superconductor CsV_{3}Sb_{5} Revealed by Quantum Oscillations.
The connection between unconventional superconductivity and charge density waves (CDWs) has intrigued the condensed matter community and found much interest in the recently discovered superconducting Kagome family of AV_{3}Sb_{5} (A=K, Cs, Rb). X-ray diffraction and Raman spectroscopy measurements established that the CDW order in CsV_{3}Sb_{5} comprises of a 2×2×4 structure with stacking of layers in a star-of-David (SD) and inverse-star-of-David (ISD) pattern along the c-axis direction. Such interlayer ordering will induce a vast normalization of the electronic ground state; however, it has not been observed in Fermi surface measurements. Here we report quantum oscillations of CsV_{3}Sb_{5} using tunnel diode oscillator frequency measurements. We observed a large number of frequencies, many of which were not reported. The number of frequencies cannot be explained by DFT calculations when only SD or ISD distortion is considered. Instead, our results are consistent with calculations when interlayer ordering is taken into account, providing strong evidence that the CDW phase of CsV_{3}Sb_{5} has complicated structure distortion which in turn has dramatic effects on the Fermi surface properties.


Sensitization of keloid fibroblasts by quercetin through the PI3K/Akt pathway is dependent on regulation of HIF-1α.
Keloids are raised, red, hard and irregular tumors that are prone to extend beyond the wound borders. Surgical excision is not sufficient to eradicate a keloid. Adjuvant therapy with radiation is a recommended treatment that reportedly achieves improved efficacy. However, radiation does not only kill cells in the keloid tissue but also stimulates their resistance, and intractable cases can display continuous recurrence. Quercetin was initially extracted from natural products and is used as a dietary supplement. The role of quercetin as an oxidant scavenger has been highlighted in many studies and has drawn interest to the application of ionizing radiation (IR) sensitization. In this study, we first demonstrate that keloid fibroblasts acquire resistance after IR treatment, and this can be relieved by treatment with quercetin. Further, we showed that hypoxia-inducible factor 1 (HIF-1), a prognostic marker used in clinical practice after radiation therapy, was associated with stronger radioresistance in keloid fibroblasts, which was downregulated after quercetin treatment. The inhibition of HIF-1 expression by quercetin was found to be dependent on the phosphatidylinositol-3-kinase (PI3K)/Akt pathway. Quercetin has been reported to reduce the phosphorylation of Akt. Taken together, we revealed one mechanism underlying the suppression of radioresistance by quercetin, which involved the regulation of HIF-1α by the PI3K/Akt pathway. Our study provides a molecular basis for the application of quercetin in radiation sensitization in the treatment of keloids.


Protecting PTEN in the Nucleus.
A recent study shows that the transport receptor Importin-11 relocates PTEN, a tumor suppressor, to the nucleus, preventing its degradation in the cytoplasm. Mice lacking Importin-11 are prone to lung cancers, and its absence in human prostate and lung tumors signals a poorer prognosis.


Obstructive Sleep Apnea: Epidemiology and Portuguese patients profile.
Obstructive Sleep Apnea (OSA) is characterized by recurrent episodes of apnea and hypopnea, secondary to collapse of the upper airways during sleep. OSA is frequently associated to cardiovascular complications. In Portugal, its magnitude is unknown. In 2014 a cross-sectional study was performed using the Portuguese General Practitioner (GP) Sentinel Network (Rede Médicos Sentinela). Participants GP reported all OSA cases diagnosed and registered in their lists of users on the 31 December 2013. Frequency of OSA has been estimated by sex and age. OSA patients were also characterized by method of diagnosis, treatment, and underlying conditions. Association between risk factors and severe OSA (odds ratio) was calculated using a logistic regression model adjusting confounding. Prevalence of OSA on the population aged 25 years or more was 0.89% (95 CI: 0.80-1.00%); it was higher in males 1.47% (95 CI: 1.30-1.67%) and in those aged between 65 and 74 (2.35%). Most had severe OSA (48.4%). Hypertension (75.9%), obesity (74.2%) and diabetes mellitus (34.1%) were the most frequent comorbidities. Being a male (OR: 2.6; 95 CI: 1.2-5.8) and having obesity (OR: 4.0; 95 CI: 1.8-8.6) were associated with an increased risk of severe OSA. Found frequency of OSA was lower than other countries estimates, which may be explained by differences on case definition but can also suggest underdiagnosis of this condition as reported by other authors.


Job-sharing: the key to flexible working?
Job-sharing appears to be on the increase in nursing and may represent an important step in meeting equal opportunity goals for women. This article discusses the potential for this form of employment in the NHS.


Using Passive Infrared Detectors to Record Group Activity and Activity in Certain Focus Areas in Fattening Pigs.
Animal behavior is an important aspect in the assessment of animal welfare. Passive infrared detectors (PID), detecting thermal changes to measure activity, have already been used to record data on the behavior of groups of animals. Within this study, the suitability of these detectors for the collection of activity profiles for focused areas is further investigated. The aim was to record the activity of a group of eleven fattening pigs in a pen, as well as the activity in the five functional areas for resting, feeding, drinking, exploration, and elimination. In order to evaluate the data obtained, the behavior was video recorded for visual assessment. In addition, relevant indoor environment parameters were recorded (ammonia, air temperature, and relative humidity). For the measurement of activity by PID, strong correlations from up to r = 0.87 (p < 0.01) could be found compared to visual assessment. The results indicate that activity changes during the day and activity in defined functional areas can be recorded using PIDs. These data combined with data of climate-related sensors could serve the farmer as a monitoring tool for early detection of behavioral changes or serve as partial aspect within a Weak Point Analysis within external on-farm consulting.


Neurosteroids as regenerative agents in the brain: therapeutic implications.
Regenerative therapeutics hold the promise of self-renewal and repair. Ageing and age-associated neurodegenerative diseases are marked by a decline in self-renewal and repair, but a capacity for regeneration is retained. The challenge faced by researchers developing molecular therapeutics to promote self-renewal in the nervous system is to activate regenerative and repair pathways often in the context of progressive degeneration. Neurosteroids regulate both regeneration and repair systems in the brain, and among this class of molecules, allopregnanolone has been broadly investigated for its role to promote regeneration in both the central and peripheral nervous systems. In the brain, allopregnanolone induced generation and survival of new neurons in the hippocampus of both aged mice and mice with Alzheimer disease, accompanied by restoration of associative learning and memory function. In the brain of mice with Alzheimer disease, allopregnanolone increased liver X receptor and pregnane X receptor expression, reduced amyloid-β and microglial activation, and increased markers of myelin and white matter generation. Therapeutic windows for efficacy of allopregnanolone were evident in the brains of mice with both normal ageing and Alzheimer disease. Allopregnanolone dose and a regenerative treatment regimen of intermittent allopregnanolone exposure were determining factors regulating therapeutic efficacy. Allopregnanolone serves as proof of concept for therapeutics that target endogenous regeneration, windows of therapeutic opportunity for regeneration, and critical system biology factors that will determine the efficacy of regeneration.


Malignant minor salivary gland carcinomas of the larynx.
To explore the clinical characteristics and treatment of malignant minor salivary gland carcinomas of the larynx. Clinical patient information regarding presentation, pathology, treatment and outcome was obtained through a review of patient charts. Malignant minor salivary carcinomas in the larynx were confirmed pathologically in 15 patients (11 males, 4 females) between 2003 and 2010 in our hospital; 6 patients had mucoepidermoid carcinoma (MEC; 40%), 6 had adenoid cystic carcinoma (ACC; 40%) and 3 had adenocarcinoma (20%). The most common tumour location was the subglottis (60%), followed by the supraglottis (33%). In total, 13 patients underwent surgery, of which 10 (77%) had positive/insufficient resection margins. The mean follow-up time was 42.3 months, with a range of 8-129 months. The 3- and 5-year overall survival rates were 46.7 and 20%, respectively. Malignant minor salivary gland carcinoma of the larynx is a rare disease that showed male predominance in our study. The carcinomas were most often localised in the subglottic region, and the most common histological types were ACC and MEC. Wide-margin surgery with postoperative radiotherapy is advocated. The overall prognosis is poor compared to squamous cell carcinomas of the same location and tumour stage.


A Narrative Review of Clinical Decision Support for Inpatient Clinical Pharmacists.
Increasingly, pharmacists provide team-based care that impacts patient care; however, the extent of recent clinical decision support (CDS), targeted to support the evolving roles of pharmacists, is unknown. Our objective was to evaluate the literature to understand the impact of clinical pharmacists using CDS. We searched MEDLINE, EMBASE, and Cochrane Central for randomized controlled trials, nonrandomized trials, and quasi-experimental studies which evaluated CDS tools that were developed for inpatient pharmacists as a target user. The primary outcome of our analysis was the impact of CDS on patient safety, quality use of medication, and quality of care. Outcomes were scored as positive, negative, or neutral. The secondary outcome was the proportion of CDS developed for tasks other than medication order verification. Study quality was assessed using the Newcastle-Ottawa Scale. Of 4,365 potentially relevant articles, 15 were included. Five studies were randomized controlled trials. All included studies were rated as good quality. Of the studies evaluating inpatient pharmacists using a CDS tool, four showed significantly improved quality use of medications, four showed significantly improved patient safety, and three showed significantly improved quality of care. Six studies (40%) supported expanded roles of clinical pharmacists. These results suggest that CDS can support clinical inpatient pharmacists in preventing medication errors and optimizing pharmacotherapy. Moreover, an increasing number of CDS tools have been developed for pharmacists' roles outside of order verification, whereby further supporting and establishing pharmacists as leaders in safe and effective pharmacotherapy.


The dynein adaptor Hook2 plays essential roles in mitotic progression and cytokinesis.
Hook proteins are evolutionarily conserved dynein adaptors that promote assembly of highly processive dynein-dynactin motor complexes. Mammals express three Hook paralogs, namely Hook1, Hook2, and Hook3, that have distinct subcellular localizations and expectedly, distinct cellular functions. Here we demonstrate that Hook2 binds to and promotes dynein-dynactin assembly specifically during mitosis. During the late G2 phase, Hook2 mediates dynein-dynactin localization at the nuclear envelope (NE), which is required for centrosome anchoring to the NE. Independent of its binding to dynein, Hook2 regulates microtubule nucleation at the centrosome; accordingly, Hook2-depleted cells have reduced astral microtubules and spindle positioning defects. Besides the centrosome, Hook2 localizes to and recruits dynactin and dynein to the central spindle. Dynactin-dependent targeting of centralspindlin complex to the midzone is abrogated upon Hook2 depletion; accordingly, Hook2 depletion results in cytokinesis failure. We find that the zebrafish Hook2 homologue promotes dynein-dynactin association and was essential for zebrafish early development. Together, these results suggest that Hook2 mediates assembly of the dynein-dynactin complex and regulates mitotic progression and cytokinesis.


Everyday executive function in focal onset pediatric epilepsy on the parent-report BRIEF2.
Executive function (EF) difficulties are a core neuropsychological feature of pediatric epilepsy, and parent-report measures of EF concerns are an important complement to task-based EF measures. The Behavior Rating Inventory of Executive Function (BRIEF) has shown sensitivity to parent-reported EF concerns in epilepsy and other pediatric populations. We compared profiles of parent-reported EF concerns using the BRIEF and its revision, the BRIEF2, in 117 pediatric patients with focal onset epilepsy to examine the clinical utility of the revised scale. We then compared BRIEF2 profiles between patients and age- and gender-matched healthy controls. Among patients, profiles on the BRIEF did not globally differ from the BRIEF2, and agreement was very good across scales. Patients and controls differed significantly on the BRIEF2, with patients showing higher EF difficulties reported by parents across most scales. High rates of clinical elevation among patients emerged on the Task Monitor, Plan/Organize, Working Memory, and Shift scales. Younger age of epilepsy onset, chronic epilepsy, and right hemisphere seizure focus were associated with higher parent-reported EF concerns. Findings suggest that the BRIEF2 demonstrates similar performance to the BRIEF among pediatric patients with focal onset epilepsy who are most at risk in the areas of task monitoring, working memory, planning and organization, and flexibility. These findings are informative when comparing literature across versions and provide additional insight into the nature of parent-reported EF difficulties among children with focal onset epilepsy.


Maximal, Not Habitual, Walking Velocity is More Highly Correlated to Functional Fitness of Community-Dwelling Older Adults.
The aim of this investigation was to determine the relationship between usual and maximal walking velocities with measures of functional fitness (FF). Fifty-seven older adults (78.2 ± 6.6 years) were recruited from a local retirement community. All participants completed the following assessments: 10-m usual and maximal walk, Short Physical Performance Battery (SPPB), 6-min walk (6MW), 8-foot up-and-go (UPGO), and 30-s chair stand. Based on their SPPB performance, low (≤ 9) and high (≥ 10) FF groups were formed. Among all participants, maximal walking velocity, not usual walking velocity, was significantly correlated with SPPB (r = .35; p < .05 and r = .19; p > .05, respectively). In the high functioning group, both maximal and usual walking velocities were correlated, but correlation coefficients were stronger for all variables for maximal walking velocity. These results suggest different walking conditions may be necessary to use for high and low functioning older adults; specifically, maximal walking velocity may be a preferred measure among high functioning older adults.


Effects of arbuscular mycorrhizal fungi and soil nutrient addition on the growth of Phragmites australis under different drying-rewetting cycles.
The frequency of soil drying-rewetting cycles is predicted to increase under future global climate change, and arbuscular mycorrhizal fungi (AMF) are symbiotic with most plants. However, it remains unknown how AMF affect plant growth under different frequencies of soil drying-rewetting cycles. We subjected a clonal wetland plant Phragmites australis to three frequencies of drying-rewetting cycles (1, 2, or 4 cycles), two nutrient treatments (with or without), and two AMF treatments (with or without) for 64 days. AMF promoted the growth of P. australis, especially in the 2 cycles of the drying-rewetting treatment. AMF had a significant positive effect on leaf mass and number of ramets in the 2 cycles of the drying-rewetting treatment with nutrient addition. In the 2 cycles of drying-rewetting treatment without nutrient addition, AMF increased leaf area and decreased belowground to aboveground biomass ratio. These results indicate that AMF may assist P. australis in coping with medium frequency of drying-rewetting cycles, and provide theoretical guidance for predicting how wetland plants respond to future global climate change.


A20 alleviates the vascular remodeling induced by homocysteine.
Hyperhomocysteinemia is an independent risk factor for multiple cardiovascular diseases. The pathogenesis of homocysteine-induced vascular remodeling has not yet been elucidated. In vivo, we established hyperhomocysteinemia model with high L-methionine diet and found that the accumulation of macrophages, proliferation of VSMCs and decreased expression of A20 in the aorta of mice fed with high methionine diet. In vitro, we found that the overexpression of A20 suppressed the nuclear translocation of NF-kappaB p65 and attenuated homocysteine-induced proliferation and migration of VSMCs. However, down-regulation of A20 reversed the protective effects above. Moreover, A20 attenuated homocysteine-induced vascular remodeling by alleviating the activation of inflammation and suppressing the proliferation and migration of VSMCs through enhanced nuclear translocation of IRF3 and binding to PPAR-γ.


Antibacterial, antitumor and hemolytic activities of alpha-helical antibiotic peptide, P18 and its analogs.
The alpha-helical antibiotic peptide (P18: KWKLFKKIPKFLHLAKKF-NH2) designed from the cecropin A(1-8)-magainin 2 (1-12) hybrid displayed strong bactericidal and tumoricidal activity without inducing hemolysis. The effect of the Pro9 residue at central position of P18 on cell selectivity was investigated by Pro9 --> Leu or Pro9 --> Ser substitution. Either substitution markedly reduced the antibacterial activity of P18 and increased hemolysis, although it did not significantly affect cytotoxicity against human transformed tumor and normal fibroblast cells. These results suggest that a proline kink in alpha-helical antibiotic peptide P18 serves as a hinge region to facilitate ion channel formation on bacterial cell membranes and thus plays an important role in providing high selectivity against bacterial cells. Furthermore, to investigate the structure-antibiotic activity relationships of P18, a series of N- or C-terminal deletion and substitution analogs of P18 were synthesized. The C-terminal region of P18 was related to its antibiotic activity and alpha-helical conformation on lipid membranes rather than N-terminal one. Higher alpha-helicity of the peptides was involved in the hemolytic and antitumor activity rather than antibacterial activity. Except for [L9]-P18 and [S9]-P18, all the designed peptides containing a Pro residue showed potent antibacterial activity, although they did not induce a cytolytic effect against human erythrocyte and normal fibroblast cells at the concentration required to kill bacteria. In particular, P18 and some analogs (N-1, N-2, N-3, N-3L and N-4L) with potent bactericidal and tumoricidal activity and little or no normal cell toxicity may serve as an attractive candidate for the development of novel anti-infective or antitumor agents.


Nitrifying Kinetics and the Persistence of Nitrite in the Seine River, France.
Although a higher oxidation rate for nitrite than for ammonia generally prevents nitrite accumulation in oxic waters, nitrite concentrations in the Seine River (1-31 μM) exceed European norms. We investigated the kinetics of in situ ammonia- and nitrite-oxidizing communities in river water and wastewater treatment plant (WWTP) effluents to determine the role of pelagic nitrification in the origin and persistence of nitrite downstream of Paris. The main source of nitrite is the major Parisian WWTP, and its persistence, up to tens of kilometers downstream of the plant, is explained by low ammonia and nitrite oxidation rates and high river flow. Furthermore, similar nitrite and ammonia oxidation rates preclude a rapid consumption of both preexisting nitrite and nitrite produced by ammonia oxidation. Maximum ammonia oxidation rates are two to three times higher downstream than upstream of the WWTP, indicating the input of ammonia oxidizers and ammonia from the WWTP. In both river water and WWTP effluents, nitrite oxidizers were unable to oxidize all available nitrite. In the human-impacted Seine River, this phenomenon might be due to mixotrophy. This study highlights the low resilience of the river to nitrite contamination as well as the importance of managing nitrite, nitrifiers, and organic matter concentrations in WWTP effluents to avoid nitrite persistence in rivers.


Smart tetrazole-based antibacterial nanoparticles as multifunctional drug carriers for cancer combination therapy.
Due to multidrug resistance of cancer tissues and immune-suppression of cancerous patients during chemotherapy in one hand and the use of tetrazole derivatives in medicine because of its anticancer, antifungal, and antiviral properties, on the other, we were encouraged to design novel smart antibacterial nanocomposites-based polymer of tetrazole as dual anticancer drug delivery systems. The structures of nanocomposites characterized by FTIR, 1H NMR, FESEM-EDX, and TGA analyzes and antibacterial activity of smart carriers were evaluated by determination of minimum inhibitory concentration (MIC) values against some bacteria and fungi. Then, the pH-responsive manner of both nanocomposites was proved by checking their release profiles at pH of the physiological environment (pH 7.4) and pH of tumor tissues (mildly acidic). Finally, the potential antitumoral activity of these nanocomposite systems against MCF7 cell lines was evaluated by MTT assay and cell cycle studies. The results demonstrated that the novel developed nanocomposites not only meet our expectations about simultaneous release of two anticancer drugs according to the predicted profile but also showed antibacterial and anticancer properties in vitro experimental. Moreover, it was proved that these carriers have tremendous potential in multifunctional drug delivery in cancer therapy.


Both chloroplastic and cytosolic phosphofructoaldolase isozymes are present in the pea leaf nucleus.
In higher plants, fructose bisphosphate aldolase (EC 188.8.131.52) occurs in chloroplast, cytosol, and nucleus. Immunocytolocalization experiments with isozyme-directed antibodies indicate that both chloroplastic and cytosolic aldolase isoforms are present in the pea (Pisum sativum L.) leaf nucleus.


Evidence of a field effect associated with mammary cancer chemoprevention by methylseleninic acid.
In the present study, the molecular effects of methylseleninic acid in cancer chemoprevention was evaluated using two closely related sets of targets. The first approach examined the modulation of biomarkers in pathologically-defined premalignant lesions of the rat mammary gland. The second approach involved the use of cDNA microarray technology to characterize the profile of gene expression changes in the whole mammary tissue. Treatment with methylseleninic acid led to quantifiable changes in the expression of selective cell cycle and apoptosis regulatory proteins in the premalignant lesions. The biomarkers in the panel included cyclin A, cyclin D1, p21, p27, bcl-2 and bax. These were found to be modulated in a manner that was consistent with a reduction in the development of premalignant lesions by methylseleninic acid. Microarray analysis using RNA isolated from the whole mammary gland provided highly suggestive clues that methylseleninic acid was able to produce a widespread effect on gene expression in adipocytes and stromal cells, which are present in abundance in the mammary tissue. Thus, epithelial cells may not be the only targets for the action of selenium, even though the focus of selenium chemoprevention is to inhibit premalignant lesions and cancers arising from the epithelial cells. In view of the fact that adipocytes and stromal cells are known to play an important role in the growth and differentiation of their neighboring epithelial cells, the concept of a field effect in selenium chemoprevention is proposed as a new frontierforfuture research endeavors.


[Clinical symptoms and treatment of cervicofacial actinomycosis. Literature survey and case report].
Actinomycosis is a chronic, specific inflammation which is characterized by suppuration, abscess formation, tissue fibrosis and granuloma formation. Actinomycosis has three main forms (cervicofacial, which is the most frequent, approximately 60%, pulmonary and abdominal), but other regions of the body can be involved, too (e.g. neck, ovaries, bones), that is why its differential diagnosis becomes more and more relevant. Regarding its treatment, the majority of authors recommends the combination of surgical and antibiotic treatment. The authors of this article present a typical case of cervicofacial actinomycosis, in which the authors used the combination of surgical and antibiotic treatment. As a result of the treatment the healing process was completed successfully and without complications.


Aggressive clinical course of primary invasive vaginal carcinoma associated with type 61 HPV: a case report.
Primary invasive vaginal cancer is one of the rarest malignant processes in the female genital tract. The etiology has not been identified, but the strongest association is with HPV infection and subtypes 16 and 18 have the highest oncogenic potential. We present the case of a young woman diagnosed with metastatic squamous cell carcinoma of the vagina associated with HPV type 61, a non-oncogenic HPV type. We report the propensity of a primary vaginal neoplasm to spread to lymphatic vessels early and the unresponsive aggressive behavior to multimodal therapy.


Eyelid basal cell carcinoma with neuroendocrine differentiation: a case report and literature review.
Basal cell carcinoma (BCC) is the most common type of malignant tumor in the periocular region. BCCs with neuroendocrine differentiation in the periocular region, however, have not been described in the literature.We present a retrospective case review of a patient with an eyelid BCC with neuroendocrine differentiation. Demographical, clinical, radiological, surgical, histological, and follow-up data are presented.The patient presented with a slow-growing lesion of the eyelid with associated epiphora and dull ache. Initial incisional biopsy of the lesion revealed an infiltrating carcinoma composed of epithelial cells. Immunohistochemistry showed that the tumor was positive for p40, Ber-Ep4, neuron specific enolase (NSE), chromogranin A, CD56 (NCAM), and synaptophysin. The pathology from the margin-controlled excision showed basosquamous cell carcinoma with neuroendocrine differentiation. Tumor recurrence was not detected clinically at the post-operative six-month review.BCC with neuroendocrine marker positivity represents an important diagnostic differential for rare eyelid carcinomas such as primary cutaneous neuroendocrine carcinoma and metastatic small cell carcinoma that have a poor prognosis. The prognostic importance of neuroendocrine marker positivity in BCCs is uncertain. The present case provides further evidence for neuroendocrine differentiation in BCCs.


FASD Prevalence among Schoolchildren in Poland.
Prenatal Alcohol Exposure is a major cause of brain damage and developmental delay, known as Fetal Alcohol Spectrum Disorders (FASD) but in Poland is rarely diagnosed and the scale of problem is not known. An active case ascertainment approach was applied to estimate the prevalence of FASD among 7-9 years olds. Pre-screening was conducted in 113 randomly selected regular and special schools. In the screening phase participated 280 children (54% from the risk group, 60% boys). The entire number of eligible students (N = 2500) was taken as a denominator. The prevalence of FASD is not lower than 2%, including 0.4% of Fetal Alcohol Syndrome. Neurodevelopmental disorders associated with PAE are a serious challenge for the public health system. Development of procedures and services to diagnose and to support individuals affected by PAE and their families is an urgent need in Poland.


Guanylate-binding protein 2 orchestrates innate immune responses against murine norovirus and is antagonized by the viral protein NS7.
Noroviruses are the main causative agents of acute viral gastroenteritis, but the host factors that restrict their replication remain poorly identified. Guanylate-binding proteins (GBPs) are interferon (IFN)-inducible GTPases that exert broad antiviral activity and are important mediators of host defenses against viral infections. Here, we show that both IFN-γ stimulation and murine norovirus (MNV) infection induce GBP2 expression in murine macrophages. Results from loss- and gain-of-function assays indicated that GBP2 is important for IFN-γ-dependent anti-MNV activity in murine macrophages. Ectopic expression of MNV receptor (CD300lf) in human HEK293T epithelial cells conferred susceptibility to MNV infection. Importantly, GBP2 potently inhibited MNV in these human epithelial cells. Results from mechanistic dissection experiments revealed that the N-terminal G domain of GBP2 mediates these anti-MNV effects. R48A and K51A substitutions in GBP2, associated with loss of GBP2 GTPase activity, attenuated the anti-MNV effects of GBP2. Finally, we found that nonstructural protein 7 (NS7) of MNV co-localizes with GBP2 and antagonizes the anti-MNV activity of GBP2. These findings reveal that GBP2 is an important mediator of host defenses against murine norovirus.


Meaning of death among care workers of geriatric institutions in a death-avoidant culture: Qualitative descriptive analyses of in-depth interviews by Buddhist priests.
Care workers' views of clients' death have not been explored in Japan because of a cultural tendency to avoid talking openly about death. However, given the arising problems in end-of-life care settings, such as abuse and burnout, understanding care workers' views regarding death is essential for designing effective interventions. We had two main research questions: Do care workers in Japan have their own ideas about death after working in the landscape of dying and death? Do these ideas influence care workers' professional lives? We recruited interviewees based on a quantitative survey of care workers at 10 geriatric institutions in Tokyo. Among the 323 respondents, 23 survey respondents were willing to participate in an interview. After the scheduling process, nine individuals were able to participate in an in-depth interview. To overwhelm cultural avoidance regarding death that prevents care workers from talking openly about death, Buddhist priests conducted interviews in the current study. Physicians and researchers assisted the interviews. Because this was exploratory studies in which little is known about the topic in question, we adapted a qualitative descriptive approach. Thematic analysis revealed that: 1) care workers had clear views about conditions of clients' good death after working in the field of dying and death; 2) care workers were motivated by past experiences of being close to dying themselves; and 3) care workers regarded their care for the dying as an experience that enriched their lives. In addition, the results revealed that the concept of spiritual care in Japan is still its infancy among care workers because of its vague definition. Care workers were willing to work for dying people with their view of death, and regarded their jobs as important opportunities for personal growth through caring for the dying.


Tools of genomic medicine for clinical practice: The example of psychiatry.
Most psychiatric disorders are moderate to highly heritable, often with different genetic architectures. Although genetic research in psychiatry has progressed, its findings, interpretation, and impact on clinical psychiatry are unknown to most mental healthcare professionals. This article addresses key genetic concepts to understand some clinical entities, emphasizing genetic terminology and types of mutations. Particularly, we describe the role of heritability in the early days of psychiatry genetic research, the most used study designs, and their main objectives. On the other hand, we review some genetic and genomic databases useful for clinical practice. These include Online Mendelian Inheritance in Man, ClinVar, Ensembl, and The Single Nucleotide Polymorphism Database. Finally, a clinical vignette is presented in which we can apply genomic medicine tools. Since the evidence in psychiatric genetics is based on studies carried out in European or North American ancestral populations, we must develop local studies to increase the knowledge and application of genomic medicine on underrepresented populations.


Routine intrauterine insemination and the effect of spermatozoal washing as assessed by computer-assisted semen analyzer.
We present the results from 283 cycles of intrauterine insemination (IUI) performed on 237 patients. Their indications for treatment included cervical factor infertility, spermatozoal antibodies, idiopathy, poor postcoital test, and oligozoospermia. Pregnancies arose in all groups, with 28 pregnancies from natural cycles, and 17 from clomiphene citrate-supplemented cycles. A live birth rate per cycle of 12.7% (36/283) was achieved following nine miscarriages. A further 133 patients, with only cervical factor or idiopathic infertility, underwent 144 cycles of IUI in natural cycles; this more homogeneous group had their spermatozoal performance monitored by a computer-assisted semen analyzer (CASA) before and after spermatozoal washing for IUI. All factors in the spermatozoal profile changed significantly after washing. Twelve clinical pregnancies resulted from these 144 cycles of IUI, and a comparison was made between the spermatozoal profiles, as assessed by CASA, of conceptual and nonconceptual cycles. Post-wash spermatozoal concentration was slightly greater (P less than .1) in the conceptual cycles, whilst spermatozoal velocity was significantly less (P less than .005). The relevance of these findings to the definition of a "hyperactivational" state for human spermatozoa is discussed, and the general applicability of IUI as a "frontline" treatment for nontubal infertility is proposed.


Therapy and prevention of gastric ulcer.
After establishing the benign nature of a gastric ulcer, the treatment is primarily medical. This medical therapy is aimed to alleviate symptoms, to heal the ulcer and to prevent relapses. Based on the history of non-steroidal anti-inflammatory drugs (NSAIDs) and the Helicobacter pylori-status, gastric ulcer patients can be divided into four categories (1) H. pylori positive plus NSAID-use, (2) H. pylori positive without NSAID use, (3) NSAID use with negative H. pylori-status, (4) Negative H. pylori-status and no NSAID use. Patients taking NSAIDs should stop this therapy if possible. Patients with gastric H. pylori infection should be treated by a regimen of a proton pump inhibitor with at least two appropriate antibiotics. This treatment will result in early alleviation of symptoms, rapid healing of the ulcer and prophylaxis of ulcer relapse. In patients with gastric ulcer who cannot stop NSAIDs, maintenance therapy with prostaglandins or potent antisecretory drugs should be considered. The few patients with gastric ulcer who do not take NSAIDs and do not have gastric H. pylori infection should be treated by antisecretory drugs, and they should be carefully followed endoscopically to exclude malignant (carcinoma, lymphoma) or non-peptic (Crohn's disease) disease. All patients with gastric ulcer should be re-endoscoped to verify complete ulcer healing. Surgery may be considered in gastric ulcer patients with complications, in those with severe dysplasia of the gastric mucosa, and in those who are not able or willing to take the medication.


Role of Thiolate Ligand in Spin State and Redox Switching in the Cytochrome P450 Catalytic Cycle.
The catalytic cycle of cytochrome P450 involves a change from the resting-state, water-bound, six-coordinated form (1, low-spin state) to a five-coordinated form (2, high-spin state) upon binding of a hydrophobic substrate. Here, we used a heme-thiolate model complex (SR complex) with THF as a model of nonionic H2O to address the question of whether or not coordination of nonionic water is sufficient to induce the low-spin state. Measurements of electronic absorption spectra and magnetic properties confirmed that five-coordinated SR complex has a high-spin state, and THF-bound, six-coordinated SR has a low-spin state in dichloromethane at ambient temperature. The redox potential E1/2 (FeII/FeIII) of THF-bound SR was 80-90 mV more negative than that of five-coordinated SR. These properties indicate SR is a good model of P450. Our results suggest that thiolate coordination plays a key role in setting the low energy barrier between the high-spin and low-spin states.


Development of a Global Subjective Skin Aging Assessment score from the perspective of dermatologists.
Several skin aging assessment scales exist but no standard scale is widely used. Dermatologists may be the most appropriate persons for skin assessment but their perceptions regarding the signs of skin aging are unexplored. To develop a simple global skin aging assessment score from the perspective of dermatologists, an online questionnaire, the Thai Dermatologist Survey of Skin Aging Assessment, was conducted from October to December, 2016. Twenty-nine signs with published evidence of their relevancy to skin aging were included. Certified dermatologists were asked to score each sign using a 5-point Likert scale. Descriptive statistics and exploratory factor analysis (EFA) were used for data analysis. Of 213 randomly selected dermatologists, 145 responded to the survey. EFA revealed 3 important factors related to skin aging: Factor 1 comprised 8 signs related to atrophy (deep/superficial wrinkles, eye bags, lax appearance, etc.); Factor 2 comprised 7 signs related to discoloration (freckles, lentigines, melasma, etc.); and Factor 3 comprised 3 malignant skin lesions. The Global Subjective Skin Aging Assessment (GS2A2) score is a simple numerical score that can be used to evaluate the anti-aging effects of a cosmetic product or dermatologic intervention. This score should be tested further for validity and reliability.


Septic Embolism Associated With Periodontal Disease: A Case Report.
Parvimonas micra and Provetella oralis are two commensal anaerobic bacteria of the human oral cavity. Anaerobic bacteria infections are uncommon and require a high index of suspicion and a quick start of appropriate treatment. We present a patient with multifocal infiltrates compatible with septic embolism (lung, liver, and spleen emboli) and polymicrobial bacteremia with Parvimonas micra and Provetella oralis. Periodontal disease appears to be the main cause of this disseminated infection.


MicroRNAs 155-5p, 122-5p, and 181a-5p Identify Patients With Graft Dysfunction Due to T Cell-Mediated Rejection After Liver Transplantation.
MicroRNAs (miRNAs) are small noncoding RNAs that can be detected in plasma and whose expression is associated with pathological processes. The role of miRNAs in the noninvasive diagnosis of T cell-mediated rejection (TCMR) after liver transplantation (LT) is unclear. Thus, we aimed to assess the effectiveness of a panel of 4 miRNAs (155-5p, 122-5p, 181a-5p, and 148-3p) in diagnosing TCMR in LT recipients with graft dysfunction (GD), and we compared its accuracy with previously published tests for diagnosing TCMR based on routine laboratory parameters. From a prospective cohort of 145 patients followed during the first year after transplant, 49 developed GD and underwent a liver biopsy and plasma collection for miRNA analysis using quantitative real-time polymerase chain reaction. Patients with GD due to TCMR (n = 21) exhibited significantly higher (P < 0.001) expression of miRNA 155-5p (2.05 versus 0.07), 122-5p (19.36 versus 1.66), and 181a-5p (1.33 versus 0.37) compared with those with GD from other causes (n = 28). The area under the receiver operating characteristic curve of miRNAs 155-5p, 122-5p, and 181a-5p for the diagnosis of TCMR was 0.87, 0.91, and 0.89, respectively, significantly higher than those of the other noninvasive tests (P < 0.001). Furthermore, miRNA 155-5p identified all patients who presented TCMR during the first 2 weeks after transplant. miRNA plasmatic expression differentiates TCMR from other causes of GD in patients who have undergone LT and may be a useful tool in clinical practice.


Trafficking of plant plasma membrane aquaporins: multiple regulation levels and complex sorting signals.
Aquaporins are small channel proteins which facilitate the diffusion of water and small neutral molecules across biological membranes. Compared with animals, plant genomes encode numerous aquaporins, which display a large variety of subcellular localization patterns. More specifically, plant aquaporins of the plasma membrane intrinsic protein (PIP) subfamily were first described as plasma membrane (PM)-resident proteins, but recent research has demonstrated that the trafficking and subcellular localization of these proteins are complex and highly regulated. In the past few years, PIPs emerged as new model proteins to study subcellular sorting and membrane dynamics in plant cells. At least two distinct sorting motifs (one cytosolic, the other buried in the membrane) are required to direct PIPs to the PM. Hetero-oligomerization and interaction with SNAREs (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptors) also influence the subcellular trafficking of PIPs. In addition to these constitutive processes, both the progression of PIPs through the secretory pathway and their dynamics at the PM are responsive to changing environmental conditions.


Vestibular schwannoma management: current practice amongst UK otolaryngologists--time for a national prospective audit.
It is generally agreed that the successful management of a vestibular schwannoma (VS) usually involves close collaboration between a neuro-otologist and neurosurgeon. In addition, it is accepted that the experience of the team managing such tumours is one of the key determinants of outcome after surgical intervention. The aim of this study was to identify current practice in the management of such tumours amongst otolaryngologists in the UK and to observe whether such collaborative working practices exist. A cross sectional postal questionnaire survey of consultant members of the British Association of Otorhinolaryngologists-Head and Neck Surgeons (n = 542). A total of 336 replies were received (62%). Of respondents, 299 consultants referred their patients to another surgeon for further management; 242 referred to another ENT surgeon (80.9%), 29 to a neurosurgeon (9.7%) and 28 to a combined team (9.4%). Twenty-eight of the responding otolaryngologists (8.6%) managed the tumours themselves, of whom 22 worked with a neurosurgeon. Of these 28 neuro-otologists, nearly two-thirds (64%) had been undertaking VS surgery for more than 10 years. The total number of patients with a VS referred to these 28 consultants during 2001 was 775, with a mean caseload of 29.8, median 23 and a range of 4 to 102 per surgeon. Seven of the 28 otolaryngologists chose their surgical approach entirely based on the size of the tumour. Eight consultants preferred the sub-occipital (SO) approach, 10 the translabyrinthine (TL) approach, three chose between SO and TL approaches. The majority of surgeons had a prospective, computer-based data collection and were willing to give further information about their outcomes and complications. Amongst the otolaryngologists surveyed in the UK, we have identified 28 neuro-otologists who undertake VS surgery. The majority work with neurosurgical colleagues, confirming collaborative practice. The wide range in caseload raises the issue of training and maintaining standards and in the first instance we recommend a prospective national audit of VS management and outcomes with our neurosurgical colleagues. This would also be of value in manpower planning particularly if a minimum caseload could be identified below which results were seen to be less good.


Developing a Problem-Based Learning Approach to the Integration of Environmental and Occupational Health Topics into Medical School Curriculum.
A pilot study incorporating environmental and occupational health (EOH) learning objectives into medical school curriculum using problem-based learning approach. One hundred eight-four Case Western Reserve University medical students participated in problem-based learning curriculum emphasizing EOH topics. Multiple choice (MCQ), short essay (SEQ), and summative short essay (SSEQ) questions assessed student knowledge. Two rating scale questions and one open-ended question determined student attitudes and confidence. Eighty percent of students answered 10 of 12 MCQs correctly. Students scored 70% on three of four SEQs and averaged 95.2% and 88.5% on two final SSEQs demonstrating improvement in student knowledge. Students rated the importance of and confidence in EOH topics as 4.4 and 3.9, respectively. Problem-based learning facilitated inclusion of new EOH content in pre-clerkship curriculum leading to achievement of students' cognitive objectives, positive attitudes, and improved confidence in EOH topics.


Association between being overweight and oral health in Serbian schoolchildren.
Childhood obesity, dental caries, and periodontal disease are major public health problems due to their adverse impact on the growth and development of children. To examine the association between nutritional status, oral health, and lifestyle habits among schoolchildren in Serbia. This cross-sectional study assessed 422 children and adolescents aged 6-18 years with the following dental indexes analyzed: DMF/dmf (decayed, missed, and filled teeth), plaque index (PI), and gingival index (GI). Depending on their nutritional status, the subjects were categorized, as being 'normal weight,' 'at risk of overweight,' and 'overweight.' Logistic regression was applied to study the association between the dental indexes and independent variables: gender, age, toothbrushing, nutritional status, and lifestyle factors. Being overweight positively correlated with GI, but negatively correlated with the DMF/dmf index among the participants. Multivariate analysis showed a strong association between the weight category and toothbrushing with GI and PI. Overweight children (6-11 years) were less likely to have caries, whereas in older children/adolescents (12-18 years), caries was associated with the intake of sugar-sweetened juices. Being overweight was found to be significantly associated with a higher probability of developing gingivitis and negatively associated with caries prevalence in Serbian children and adolescents.