Design, Synthesis, and Evaluation of Antifungal Bioactivity of Novel Pyrazole Carboxamide Thiazole Derivatives as SDH Inhibitors.
Agricultural production is seriously threatened by plant pathogens. The development of new fungicides with high efficacy and low toxicity is urgently needed. In this study, a series of pyrazole carboxamide thiazole derivatives were designed, synthesized, and evaluated for their antifungal activities against nine plant pathogens in vitro. Bioassay results showed that most compounds (3i, 5i, 6i, 7i, 9i, 12i, 16i, 19i, and 23i) exhibited good antifungal activities against Valsa mali. In particular, compounds 6i and 19i exhibited better antifungal activities against Valsa mali with EC50 values of 1.77 and 1.97 mg/L, respectively, than the control drug boscalid (EC50 = 9.19 mg/L). Additionally, compound 23i exhibited excellent inhibitory activity against Rhizoctonia solani, with an EC50 value of 3.79 mg/L. Compound 6i at 40 mg/L showed a satisfactory in vivo protective effect against Valsa mali. Scanning electron microscopy analyses revealed that compound 6i could significantly damage the surface morphology to interfere with the growth of Valsa mali. In molecular docking, the results showed that compound 6i interacts with TRP O: 173, SER P: 39, TYR Q: 58, and ARG P: 43 of succinate dehydrogenase (SDH) through hydrogen bonding and σ-π interaction, and its binding mode is similar to that of boscalid and SDH. The enzyme activity experiment also further verified its action mode. Our studies suggested that pyrazole carboxamide thiazole derivative 6i provided a valuable reference for the further development of succinate dehydrogenase inhibitors.


[Application of tendon-derived stem cells and bone marrow-derived mesenchymal stem cells for tendon injury repair in rat model].
To evaluate the application of tendon-derived stem cells (TDSC) and bone marrow-derived mesenchymal stem cells (BMSC) for patellar tendon injury repair in rat model. TDSCs and BMSCs were isolated from patellar tendons or bone marrow of healthy SD rats. The patellar tendon injury model was induced in 60 SD rats, then the animals were divided into 3 groups with 20 in each group: rats in TDSC group received transplantation of TDSC with fibrin glue in defected patellar tendon, rats in BMSC group received BMSC with fibrin glue for transplantation and those in control group received fibrin glue only. The gross morphology, histology and biomechanics of the patellar tendon were examined at 1, 2, 4, 6 and 8 weeks after the treatment. Gross observation showed that the tendon defects in TDSC group and BMSC group almost disappeared in week 8, while the boundary of tendon defects in control group was still visible. Histology examination showed that the neo-tendon formation in TDSC group and BMSC group was observed at week 8, while there was no neo-tendon formation in control group. Biomechanics study showed that the ultimate stress and Young Modulus, relative ultimate stress and relative Young Modulus increased with the time going in all groups(all P<0.05); the ultimate stress and Young Modulus, relative ultimate stress and relative Young Modulus of TDSC and BMSC groups were significantly higher than those in control group at week 4, 6 and 8(all P<0.05). There was no difference in ultimate stress and Young Modulus between TDSC group and BMSC group(P>0.05), however, the relative Young Modulus of TDSC group was significantly higher than that in BMSC group at week 8(P<0.05). Allogeneic TDSC and BMSC transplantation facilitates the repair of tendon injury and improves the biomechanics of tendon. TDSC is more suitable for in vivo tendon regeneration than BMSC.


Validation of the Persian version of the Burn Specific Health Scale-Brief.
The Burns Specific Health Scale-Brief (BSHS-B) is easy to apply, can be self-administered, and is considered a suitable instrument to measure general health and the physical, mental, and social aspects of burn victims' life. The purpose of this study was to translate and culturally adapt the BSHS-B into the Persian language and to investigate its psychometric properties. The BSHS-B was translated and adapted for Iranian patients. 200 patients (94.34%) filled out the questionnaire. The psychometric properties of the scale, including its internal consistency, test-retest reliability, and construct validity through the known-groups technique were evaluated. The Cronbach's alpha coefficient of total scores of the questionnaire was 0.94, demonstrating reasonable internal consistency of the instrument. The test-retest coefficients were reported to be between 0.81 and 0.96. The scale's construct validity was statistically significant. Principal components' factor analysis was used to derive an instrument called the Burn Specific Health Scale-Brief in eight domains. The domains described patients' functions in terms of "Heat sensitivity", "Affect", "Hand function & simple abilities", "Treatment regimens", "Work", "Sexuality", "Interpersonal relationships", and "Body image". The reliability and validity of the adapted version of the BSHS-Brief was shown to be satisfactory. Thus, it can be used to investigate quality of life of Iranian patients suffering from burn.


Comparison of Failure and Complication Risks of Porcelain Laminate and Indirect Resin Veneer Restorations: A Meta-Analysis.
To evaluate and compare the failure and complication risks of porcelain laminate and indirect resin veneer restorations (VRs) by means of a meta-analysis. An electronic database search was performed in MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane Central Register of Controlled Trials (CENTRAL) databases, and a gray literature search was performed on OpenGrey. All database searches were completed by March 2018. Two authors individually screened the literature according to the inclusion and exclusion criteria. The quality and risk of bias of the included studies were evaluated using the Newcastle-Ottawa scale (NOS) and the Cochrane Handbook for Systematic Reviews of Interventions (CHSRI). The Mantel-Haenszel method was used to synthesize the data of the included studies. All statistical analyses were performed using the software Stata 14.0, and the results were expressed as risk ratio (RR) with 95% confidence interval (CI). Five studies-two randomized controlled trials (RCTs) and three clinical controlled trials (CCTs)-were included in this review. Of the three CCTs, two were assessed to be low quality, and the third was considered high quality. The two RCTs were rated as unclear risk of bias. The meta-analysis results showed the risk of failure for indirect resin VRs was higher than for porcelain laminate VRs (RR: 0.15, 95% CI: 0.06-0.40; P = .000). Fracture and debonding were the main complications leading to failure. For risk of fracture, an RR of 0.18 (95% CI: 0.04-0.71) and a statistically significant difference (P = .015) were found in favor of porcelain laminate VRs. For risk of debonding, there was no statistically significant difference (P = .108) found between the two types of VRs. The results of the sensitivity analysis (RR: 0.09, 95% CI: 0.02-0.45; P = .004) suggested that this conclusion was reliable. The survival rate of porcelain laminate VRs was higher than indirect resin VRs, and the latter had a higher risk of fracture. However, there was no statistically significant difference in the risk of debonding between the two types of VRs. Porcelain laminate VRs have a better prognosis compared to indirect resin VRs, which provides an evidence-based reference for the selection of VRs in clinical practice.


Surface Pressures in Lower Extremity Splints: A Biomechanical Study.
Though ubiquitously used in orthopaedic trauma, lower extremity splints may have associated iatrogenic risk of morbidity. Although clinicians pad bony prominences to minimize skin pressure, the effect of joint position on skin pressure and, more specifically, changing joint position, is understudied. The purpose of this biomechanical study is to determine the effect of various short-leg splint application techniques on anterior ankle surface pressure in the development of iatrogenic skin pressure ulcers. Various constructs of lower extremity, short-leg splints were applied to 3 healthy subjects (6 limbs total) with an underlying pressure transducer (Tekscan I-Scan system) on the skin surface centered on the tibialis anterior tendon at the level of the ankle. All subjects underwent anterior ankle surface pressure assessment when padding was applied in maximum plantar flexion and neutral position for conventional short-leg splints application in clinically relevant patient scenarios. Percentage change from initial contact pressure centered on the tibialis anterior with cast padding were calculated. The percentage change in anterior ankle contact pressure when padding was applied in maximum plantar flexion (PF) and then definitively placed in neutral was increased at least 2-fold without the addition of plaster in lower extremity short-leg splints. Removing anterior ankle padding following final splint application in neutral reduced contact forces at the anterior ankle 46% and 59% in splints applied in maximum PF and neutral ankle position, respectively. The present study is the first of its kind to underscore and quantify clinically relevant technical pearls that can be useful in reducing risk of iatrogenic risk of skin breakdown at the anterior ankle when placing short-leg splints, mainly, that it is imperative to apply padding in the intended final splint position and to remove anterior ankle padding following splint application when able. Level IV, biomechanical study with clear hypothesis.


Grafting of mesenchymal stem cell-seeded small intestinal submucosa to repair the deep partial-thickness burns.
Regenerative medicine provides many treatments for burn wounds, of which cell-seeded substitutes are encouraging for large and deep burns. To assess the feasibility of mesenchymal stem cell (MSC)-seeded small intestinal submucosa (SIS) to repair the deep partial-thickness burns, a rat study was performed. The burn model was created by contacting the dorsal surface directly with boiled water for 10 seconds. MSCs at passage 3 were seeded on the SIS before implantation. Three days after burn injury, the grafts were implanted onto the burn area. At 3, 7, 14 and 21 days post implantation, gross observation and histological assessments were performed. SIS alone and MSC-seeded SIS were able to accelerate the burn wound closure by enhancing granulation tissue formation, increasing wound maturity, improving revascularization, and inducing the proliferation of neo-epidermal cells. Additionally, MSC-seeded SIS was much more effective than SIS alone for the repair of deep partial-thickness burns. Both SIS and MSC-seeded SIS were able to repair the large and deep burn wounds and the loaded MSCs possessed positive effects to accelerate the wound closure in a rat model.


Survival by radiation therapy oncology group recursive partitioning analysis class and treatment modality in patients with brain metastases from malignant melanoma: a retrospective study.
In a population of patients with brain metastases from melanoma, the authors sought to determine whether various therapies provided any benefit at all, whether local therapy was better than whole brain radiotherapy (WBRT), and whether combined local therapy and WBRT provided any advantage over local therapy alone. They also analyzed survival according to a Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) to determine how well the RTOG RPA classes predicted survival in this patient population and whether treatments varied in effectiveness from category to category. A total of 74 patients with brain metastases from melanoma were treated at The Cleveland Clinic Foundation between 1984 and 1998. For this study, the authors reviewed patient charts and confirmed survival status. Survival was compared by treatment modality (surgical resection, WBRT, stereotactic radiosurgery, or WBRT combined with local therapy). Survival also was compared according to the RTOG RPA prognostic classes (Class 1, Class 2, or Class 3), which has not been validated previously in patients with malignant melanoma. The median survival was 5.5 months for all patients. Survival varied significantly by RTOG prognostic class; The median survival was 10.5 months (range, 2.2-99.2 months) for patients in Class 1, 5.9 months (range, 0.2-43.9 months) for patients in Class 2, and 1.8 months (range, 0.1-6.9 months) for patients in Class 3 (P < 0.0001). Survival analysis showed that combined treatment offered significantly better survival (P < 0.0001; combined vs. other). The median survival was 8.8 months (range, 1.8-99.2 months) for the combined therapy group, 4.8 months (range, 1.2-27.8 months) for the local therapy alone group, 2.3 months (range, 0.2-9.6 months) for the WBRT alone group, and 1.1 months (0.1-3.0 months) for the group that received no therapy. Adding WBRT to local therapy may improve survival in this group of patients: Combined therapy was superior to WBRT alone. The RPA classification scheme likely has prognostic value for patients with brain metastases from malignant melanoma. Prospective studies are required to overcome selection bias and confirm these results.


Extending chestnut blight hypovirus host range within diaporthales by biolistic delivery of viral cDNA.
Biolistic bombardment was used to successfully transform three phytopathogenic fungal species with an infectious cDNA clone of the prototypic hypovirus, CHV1-EP713, a genetic element responsible for the virulence attenuation (hypovirulence) of the chestnut blight fungus, Cryphonectria parasitica. The fungal species included two strains each of C. parasitica and Valsa ceratosperma, as well as one strain of Phomopsis G-type (teleomorph Diaporthe Nitschke); all are members of the order Diaporthales but classified into three different genera. A subset of transformants for each of the fungal species contained CHV1-EP713 dsRNA derived from chromosomally integrated viral cDNA. As has been reported for CHV1-EP713 infection of the natural host C parasitica, biolistic introduction of CHV1-EP713 into the new fungal hosts V ceratosperma and Phomopsis G-type resulted in altered colony morphology and, more importantly, reduced virulence. These results suggest a potential for hypoviruses as biological control agents in plant-infecting fungal pathogens other than the chestnut blight fungus and closely related species. In addition, the particle delivery technique offers a convenient means of transmitting hypoviruses to potential host fungi that provides new avenues for fundamental mycovirus research and may have practical applications for conferring hypovirulence directly on infected plants in the field.


Decentralized fuzzy Hinfinity filtering for nonlinear interconnected systems with multiple time delays.
In general, due to the interaction among subsystems, it is difficult to design an Hinfinity filter for nonlinear interconnected systems. This paper introduces a decentralized Hinfinity fuzzy filter design for nonlinear interconnected systems with multiple time delays via T-S fuzzy models. The T-S fuzzy model consists of N time-delay T-S fuzzy subsystems. The decentralized Hinfinity filter is designed based on this model, which the asymptotic stability and a prescribed Hinfinity performance index are guaranteed for the overall filtering error system. A sufficient condition for the existence of such a filter is established by using linear matrix inequalities that are numerically feasible. A simulation example is given to show the effectiveness of this approach.


[Possibilities for detection of homebound elderly people through the welfare commissioner (Minsei-iin)].
The purposes of this study were (1) to evaluate the percentage of homebound elderly people that could actually be detected through commissioners who consciously tried to detect and provide information regarding these people, and (2) to identify difficulties that commissioners experienced when attempting to detect and provide information about such people. This study was conducted in one of the districts of a city in Kanto area. The percentage of detection of homebound elderly people was calculated by following the 3 steps described below. First, the number of homebound elderly people was estimated by using the probability sample survey on elderly people living in the district. Second, detection and information activities were conducted by the commissioner in the district over a 2-month period. Finally, the detection rate through the commissioner's efforts was calculated. The detection rate was calculated by dividing the number of homebound elderly people detected through commissioners by the estimated number of homebound elderly people in the district. The difficulties that commissioners experienced were analyzed by using the KJ method to analyze qualitative data obtained from focus group interview surveys for commissioners. The commissioners actually detected and reported 1.4% of homebound elderly people. The difficulties in detection and reporting included the lack of opportunities for detection and hesitation in providing information about homebound elderly people. Although the commissioners are not completely responsible for detection of homebound elderly people, the rate of detection through these commissioners can be higher. To improve this rate of detection, the commissioner's other responsibilities need to be limited and the anonymity of the commissioners who provided information regarding homebound elderly people should be restricted to avoid harming their relationships with the elderly.


New developments of the Gas Research Institute method for the permeability measurement of porous media.
This work reports on new developments of an unsteady-state method to measure the permeability and porosity of permeable porous materials, extending the so-called Gas Research Institute method beyond its classical use. These extensions allow one to carry out measurements on samples having a cylindrical shape in the case of one- or three-dimensional (or axisymmetric) flows. They rely on the derivation of the quasi-analytical solutions that are required to interpret the experimental data by solving an inverse problem. The only simplifying assumption is that the compressibility of the probing gas can be treated as a constant over the range of pressure variations during measurement. The relevance of the method, together with the validity of this hypothesis, is checked over a wide range of porosity and permeability values through a sensitivity analysis and a comparison with direct numerical simulations of the complete initial boundary value problem. The efficiency of the method is further illustrated with experiments performed on four different porous materials in one-dimension and axisymmetric configurations for permeabilities ranging between 10-14 and 10-19 m2. The potential capability of diagnosing heterogeneous and/or anisotropic materials is highlighted. These new developments open the way for further extensions to samples of arbitrary shapes or partially saturated by a trapped fluid.


Adaptive optimization of the OXPHOS assembly line partially compensates lrpprc-dependent mitochondrial translation defects in mice.
Mouse models of genetic mitochondrial disorders are generally used to understand specific molecular defects and their biochemical consequences, but rarely to map compensatory changes allowing survival. Here we took advantage of the extraordinary mitochondrial resilience of hepatic Lrpprc knockout mice to explore this question using native proteomics profiling and lipidomics. In these mice, low levels of the mtRNA binding protein LRPPRC induce a global mitochondrial translation defect and a severe reduction (>80%) in the assembly and activity of the electron transport chain (ETC) complex IV (CIV). Yet, animals show no signs of overt liver failure and capacity of the ETC is preserved. Beyond stimulation of mitochondrial biogenesis, results show that the abundance of mitoribosomes per unit of mitochondria is increased and proteostatic mechanisms are induced in presence of low LRPPRC levels to preserve a balance in the availability of mitochondrial- vs nuclear-encoded ETC subunits. At the level of individual organelles, a stabilization of residual CIV in supercomplexes (SCs) is observed, pointing to a role of these supramolecular arrangements in preserving ETC function. While the SC assembly factor COX7A2L could not contribute to the stabilization of CIV, important changes in membrane glycerophospholipid (GPL), most notably an increase in SC-stabilizing cardiolipins species (CLs), were observed along with an increased abundance of other supramolecular assemblies known to be stabilized by, and/or participate in CL metabolism. Together these data reveal a complex in vivo network of molecular adjustments involved in preserving mitochondrial integrity in energy consuming organs facing OXPHOS defects, which could be therapeutically exploited.


Life event stress is associated with blunted cardiovascular responding to both personally salient and personally non-salient laboratory tasks.
Life event stress has been associated with blunted cardiovascular reactivity to acute psychological stress. However, recent studies have suggested that blunted reactivity to stress only arises when the laboratory tasks are not personally salient to the individual. We re-analyzed data from 136 healthy young adults where we had previously reported a negative association between life event stress and cardiovascular reactivity to two combined stressors. Participants completed a mental arithmetic task and a personally salient speech task, following a formal baseline period with Finometer-assessed cardiovascular parameters. The reanalyses examined reactivity to the verbal mental arithmetic (personally non-salient) and speech (personally salient) tasks separately and found that life event stress was negatively associated with diastolic blood pressure reactivity, to both the personally non-salient, β = -.20, p = .023, and personally salient stressors, β = -.24, p = .004. Life event stress was negatively associated with systolic blood pressure reactivity to the personally salient stressor only, β = -.20, p = .021, and was not associated with heart rate reactivity. This study provides evidence against the argument that blunted reactivity to stress emerges as a result of stressor context, with findings indicating that low reactors show lower reactivity to both personally salient and personally non-salient stress.


Antibody to intermediate filaments of the cytoskeleton in the sera of patients with acute malaria.
Sera from 78 patients with acute malaria were tested for antibodies to intermediate filaments (IFs) by indirect immunofluorescence. Eighty-two per cent of the sera contained antibody which stained the IFs in human fetal skin fibroblasts and/or HEp2 cells. In contrast, only 8% of sera taken from blood donors gave weak positive staining of IFs and no staining was observed with 42 myeloma sera which were also tested as controls. In most cases autoantibodies were of the IgM class. Erythrocytes parasitized with Plasmodium falciparum failed to stain when reacted with non-malarial anti-IF antibody positive serum.


RotaRod and acoustic startle reflex performance of two potential mouse models for Meniere's disease.
Meniere's disease (MD) is a disorder of the inner ear characterized by chronic episodes of vertigo, tinnitus, increased aural pressure, and sensorineural hearing loss. Causes of MD are unknown, but endolymphatic hydrops is a hallmark. In addition, 5%-15% of MD cases have been identified as familial. Whole-genome sequencing studies of individuals with familial MD identified DTNA and FAM136A as candidate genes for autosomal dominant inheritance of MD. Although the exact roles of these genes in MD are unknown, FAM136A encodes a mitochondrial protein, and DTNA encodes a cytoskeletal protein involved in synapse formation and maintenance, important for maintaining the blood-brain barrier. It is also associated with a particular aquaporin. We tested vestibular and auditory function in dtna and fam136a knockout (KO) mice, using RotaRod and startle reflex-based clicker tests, respectively. Three-factor analysis of variance (ANOVA) results indicated that sex, age, and genotype were significantly correlated with reduced mean latencies to fall ("latencies") for male dtna KO mice, while only age was a significant factor for fam136a KO mice. Fam136a KO mice lost their hearing months before WTs (9-11 months vs. 15-20 months). In male dtna KO mice, divergence in mean latencies compared with other genotypes was first evident at 4 months of age, with older males having an even greater decrease. Our results indicate that fam136a gene mutations generate hearing problems, while dtna gene mutations produce balance deficits. Both mouse models should help to elucidate hearing loss and balance-related symptoms associated with MD.


ERP characterization of sustained attention effects in visual lexical categorization.
As our understanding of the basic processes underlying reading is growing, the key role played by attention in this process becomes evident. Two research topics are of particular interest in this domain: (1) it is still undetermined whether sustained attention affects lexical decision tasks; (2) the influence of attention on early visual processing (i.e., before orthographic or lexico-semantic processing stages) remains largely under-specified. Here we investigated early perceptual modulations by sustained attention using an ERP paradigm adapted from Thierry et al. [1]. Participants had to decide whether visual stimuli presented in pairs pertained to a pre-specified category (lexical categorization focus on word or pseudoword pairs). Depending on the lexical category of the first item of a pair, participants either needed to fully process the second item (hold condition) or could release their attention and make a decision without full processing of the second item (release condition). The P1 peak was unaffected by sustained attention. The N1 was delayed and reduced after the second item of a pair when participants released their attention. Release of sustained attention also reduced a P3 wave elicited by the first item of a pair and abolished the P3 wave elicited by the second. Our results are consistent with differential effects of sustained attention on early processing stages and working memory. Sustained attention modulated early processing stages during a lexical decision task without inhibiting the process of stimulus integration. On the contrary, working memory involvement/updating was highly dependent upon the allocation of sustained attention. Moreover, the influence of sustained attention on both early and late cognitive processes was independent of lexical categorization focus.


shRNA targeting Bmi1 impedes the self-renewal of cisplatin-enriched stem-like cells in human A549 cells.
It has been hypothesized that cancer stem-like cells are responsible for tumor recurrence following chemotherapy. Evidence on the mechanisms through which drug-resistant stem-like cells recapitulate the tumor mass has not been definitively reported. Based on this information, we investigated the enrichment ability of a population of stem-like cells following treatment with cisplatin in human A549 cells and focused on the molecular mechanisms regulating the self-renewal of stem-like cells. A population of stem-like cells was enriched following cisplatin treatment and was defined phenotypically and functionally based on the expression of certain stem cell markers, sphere-forming ability, multipotent differentiation and induction of xenograft tumors in vivo. For various types of differentiated cells, Bmi1 has been reported to be important for cell proliferation and for the self-renewal of stem cells. The high expression of Bmi1 in cisplatin-enriched stem-like cells was shown using Q-PCR and western blotting; therefore, the role of Bmi1 was investigated in cisplatin-enriched stem-like cells by infecting cisplatin-enriched stem-like cells with Bmi1-targeted RNAi lentiviruses. Cell proliferation, tumor sphere formation and xenograft formation was reduced following knockdown of Bmi1. Based on our results, we propose that, after cisplatin treatment, Bmi1 is required for the self-renewal of stem-like cells that are important for the expansion of the stem-like cell pool in human A549 cells and that targeting Bmi1 slows down the formation of tumors in vivo.


Management of hand dermatitis.
Ill-defined endogenous factors are important in many cases of hand dermatitis; however, these factors are difficult to identify, and, ultimately, there is little the physician can do to alter a patient's constitution. Because of this, therapy of hand dermatitis focuses on identifying exogenous factors and avoiding these where possible. Steroids are invaluable, but gentle skin care remains the basis of treating hand dermatitis. Recalcitrant hand dermatitis, especially potential occupational cases, requires the involvement of a dermatologist.


A case of recurrent acute encephalopathy with febrile convulsive status epilepticus with carnitine palmitoyltransferase II variation.
Acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) is the most common type of acute encephalopathy in childhood in Japan, which develops with prolonged febrile convulsion, followed by mild unconsciousness. It is generally sporadic and nonrecurrent. In this report, a 1-year-old girl showed signs of AEFCSE triggered by respiratory syncytial virus infection. Two years later, she presented with AEFCSE triggered by influenza virus infection, resulting in severe neurologic sequelae. The patient had a thermolabile genotype of carnitine palmitoyltransferase II (CPT II) variations consisting of three single nucleotide polymorphisms in exons 4 [1055T > G/F352C and 1102G > A/V368I] and 5 [1939A > G/M647V]. The polymorphism has been identified as a genetic predisposition for acute encephalopathy. This report presents the first case of recurrent encephalopathy with CPT II variations that may partially associate with pathogenesis of recurrent AEFCSE.


Blood concentrations of synthetic cannabinoids.
Synthetic cannabinoids (SCs) are the largest and most diverse group of new psychoactive substances. Their influence on organism is unpredictable and often lead to intoxications, including fatal poisonings. The interpretation of blood concentrations of detected SC although complicated, can help to determine the effects of an administered drug. The interpretation of one's own results usually requires a comparison to previously published cases, therefore, a referenced compilation of concentration ranges would be useful. The data collection was based on a search of PubMed and Google search engine. All the available data from articles and reports where SCs concentrations have been measured in whole blood, serum or plasma were included in the data analysis. Presented table lists the observed concentrations in fatal and non-fatal cases involving 65 SCs. A reference list with original papers has been added for each compound, which makes it easy to find the source data. The observed concentrations of SCs vary widely and often have overlapping ranges for fatal and non-fatal cases. Conclusions regarding the cause of death are difficult based upon the concentrations alone and should include knowledge of the clinical situation in each case.


Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.
Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally co-exists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared to concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathological heterogeneity between IDC-P and PAC. Compared to co-existing PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 metastatic prostate cancer patients revealed that IDC-P carriers with lower risk ISUP grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P.


Continuous contact- and contamination-free ultrasonic emulsification-a useful tool for pharmaceutical development and production.
A novel concept was developed here for the continuous, contact- and contamination-free treatment of fluid mixtures with ultrasound. It is based on exciting a steel jacket with an ultrasonic transducer, which transmitted the sound waves via pressurised water to a glass tube installed inside the jacket. Thus, no metallic particles can be emitted into the sonicated fluid, which is a common problem when a sonotrode and a fluid are in direct contact. Moreover, contamination of the fluid from the environment can be avoided, making the novel ultrasonic flow-through cell highly suitable for aseptic production of pharmaceutical preparations. As a model system, vegetable oil-in-water emulsions, fed into the cell as coarse pre-emulsions, were studied. The mean droplet diameter was decreased by two orders of magnitude yielding Sauter diameters of 0.5 microm and below with good repeatability. Increasing the residence time in the ultrasonic field and the sonication power both decreased the emulsion mean diameter. Furthermore, the ultrasonic flow-through cell was found to be well suited for the production of nanoparticles of biodegradable polymers by the emulsion-solvent extraction/ evaporation method. Here, perfectly spherical particles of a volume mean diameter of less than 0.5 microm could be prepared. In conclusion, this novel technology offers a pharmaceutically interesting platform for nanodroplet and nanoparticle production and is well suited for aseptic continuous processing.


Degenerative Joint Disease After Meniscectomy.
The meniscus has an important role in stabilizing the knee joint and protecting the articular cartilage from shear forces. Meniscus tears are common injuries and can disrupt these protective properties, leading to an increased risk of articular cartilage damage and eventual osteoarthritis. Certain tear patterns are often treated with arthroscopic partial meniscectomy, which can effectively relieve symptoms. However, removal of meniscal tissue can also diminish the ability of the meniscus to dissipate hoop stresses, resulting in altered biomechanics of the knee joint including increased contact pressures. This makes meniscal repair an important treatment consideration whenever possible. Understanding the incidence and mechanism of osteoarthritis development after arthroscopic partial meniscectomy as it relates to different tear morphologies and other treatment alternatives (ie, meniscus repair) is important to appropriately treat meniscus tears.


A study of pharyngeal symptoms caused by bronchofiberscopy.
We investigated the occurrence of pharyngeal symptoms in 100 patients who had undergone bronchofiberscopies by conducting a post-examination survey of the patients. Eighty-four patients complained of having a problem. Seventy-five patients, including 26 with dysphagia, complained of pharyngeal symptoms. The proportion with pharyngeal symptoms whose symptoms appeared on the day of examination was a high 89.4%. In 70.6% of cases, the duration of symptoms was less than four days. The pharyngeal symptoms were particularly common among patients who had undergone a bronchofiberscopy on a previous occasion or whose examination lasted for 15 min or more. A greater dysphagia incidence was noted among patients who had required an endotracheal tube (P = 0.03) and among those whose examination had lasted for 15 min or more (P = 0.01). Based on the results, we are now studying methods of alleviating pharyngeal symptoms, including dysphagia.


Bacteria associated with crabs from cold waters with emphasis on the occurrence of potential human pathogens.
A diverse array of bacterial species, including several potential human pathogens, was isolated from edible crabs collected in cold waters. Crabs collected near Kodiak Island, Alaska, contained higher levels of bacteria than crabs collected away from regions of human habitation. The bacteria associated with the crabs collected near Kodiak included Yersinia enterocolitica, Klebsiella pneumoniae, and coagulase-negative Staphylococcus species; the pathogenicity of these isolates was demonstrated in mice. Although coliforms were not found, the bacterial species associated with the tissues of crabs collected near Kodiak indicate possible fecal contamination that may have occurred through contact with sewage. Compared with surrounding waters and sediments, the crab tissues contained much higher proportions of gram-positive cocci. As revealed by indirect plate counts and direct scanning electron microscopic observations, muscle and hemolymph tissues contained much lower levels of bacteria than shell and gill tissues. After the death of a crab, however, the numbers of bacteria associated with hemolymph and muscle tissues increased significantly. Microcosm studies showed that certain bacterial populations, e.g., Vibrio cholerae, can be bioaccumulated in crab gill tissues. The results of this study indicate the need for careful review of waste disposal practices where edible crabs may be contaminated with microorganisms that are potential human pathogens and the need for surveillance of shellfish for pathogenic microorganisms that naturally occur in marine ecosystems.


Behavioral and physiological indicators of stress coping styles in larval zebrafish.
Different individuals cope with stressors in different ways. Stress coping styles are defined as a coherent set of individual behavioral and physiological differences in the response to a stressor which remain consistent across time and context. In the present study, we have investigated coping styles in larval zebrafish (Danio rerio) at 8 days post-fertilization. Larvae were separated into two groups, according to the emergence sequence from a darkened into a novel well-lit environment, early (EE) and late (LE) emergers. We used brief periods of netting as a stressor. Swimming behavior and kinematics before and after netting stress were analyzed, as were whole-body cortisol levels before and at 10, 30 and 60 min after the stress event. The results show that general swimming activity was different between EE and LE larvae, with lower baseline cumulative distance and more erratic swimming movements in EE than in LE larvae. EE larvae showed a faster recovery to baseline levels after stress than LE larvae. Cortisol baseline levels were not different between EE and LE larvae, but peak levels after stress were higher and the recovery towards basal levels was faster in EE than in LE larvae. This study shows that coping styles are manifest in zebrafish larvae, and that behavior and swimming kinematics are associated with different cortisol responses to stress. A better understanding of the expression of coping styles may be of great value for medical applications, animal welfare issues and conservation.


Inhibition of N-glycan processing modulates the network of EDEM3 interactors.
We present here data on EDEM3 network of ER resident interactors and the changes induced upon this network by perturbing the early ER N-glycan processing with mannosidase and glucosidase inhibitors. By coupling immunoprecipitation with mass spectrometry we identified EDEM3 interactors and assigned statistical significance to those most abundant ER-residents that might form functional complexes with EDEM3. We further show that this ER interaction network changes in both content and abundance upon treatment with kifunensine (kif) and N-butyldeoxynojirimycin (NB-DNJ) which suggests that when interfering with the N-glycan processing pathway, the functional complexes involving EDEM3 adapt to maintain the cellular homeostasis. In order to increase the scope of EDEM3 network contenders, the set of MS identified species was further supplemented with putative interactors derived from in silico simulations performed with STRING. Finally, the most interesting candidates to this network were further validated by immunoprecipitation coupled with Western Blotting, which strengthened the confidence in the inferred interactions. The data corroborated herein suggest that besides ER residents, EDEM3 interacts also with proteins involved in the ERAD cargo recognition and targeting to degradation translocation into the cytosol, including UBA1 and UBA2 ubiquitinating enzymes. In addition, the results indicate that this network of EDEM3 interactors is highly sensitive to interfering with early ER N-glycan processing.


The effect of biosilver nanoparticles on different bacterial strains' metabolism reflected in their VOCs profiles.
The use of silver nanoparticles has become in recent years a growing interest for many researchers, due to their bacteriostatic and bactericidal properties and synergetic effects when they are used together with antibiotics, for an increased efficiency and less adverse reactions in the treatment of bacterial infections. Gas chromatography coupled with mass spectrometry (GC-MS), which is considered 'the golden standard' in chemical analysis, has proven to be a reliable instrument, perfectly suitable for clinical analysis. In this work, three bacterial strains, Escherichia coli (E. coli), Klebsiella oxytoca (K. oxytoca) and Staphylococcus saccharolyticus (S. saccharolyticus) were treated with biosilver nanoparticles (bioAgNPs). Headspace and GC-MS analysis was used for the detection of volatile metabolites. We observed decreased amounts of alcohols and carbonyl components (mainly ketones) in K. oxytoca and S. saccharolyticus bacteria incubated with silver. In contrast, biosilver nanoparticles added to E. coli increased the amount of VOCs, mainly hydrocarbons and alcohols. Our results have successfully demonstrated that the treatment of bacterial strains with bioAgNPs has a direct influence on their VOC profiles, by modifying the number of metabolic markers. Connected with this, the inhibition of bacteria is supposed, and consequently both the bacteriostatic and/or bactericidal effects of bioAgNPs on all three bacterial strains investigated were revealed.


Reduced expression of PTPRD correlates with poor prognosis in gastric adenocarcinoma.
PTPRD, encoding protein tyrosine phosphatases receptor type D, is located at chromosome 9p23-24.1, a loci frequently lost in many types of tumors. Recently, PTPRD has been proposed to function as a tumor suppressor gene. The current study aimed to investigate PTPRD expression and its prognostic significance in primary gastric adenocarcinoma. Quantitative real time reverse transcription PCR (qRT-PCR) and western blotting were used to examine PTPRD expression in paired gastric tumourous and paracancerous tissues. Compared with the matched normal gastric mucosa tissues, both the mRNA (P = 0.0138) and protein (P = 0.0093) expression of PTPRD in fresh surgical specimens were significantly reduced. Clinicopathological and prognostic roles of PTPRD in gastric adenocarcinoma were investigated using immunohistochemistry with 513 paraffin-embedded gastric adenocarcinoma tissue blocks. Statistical analysis revealed that reduced PTPRD expression was significantly associated with T stage (P = 0.004), TNM stage (P<0.001) and tumor size (P = 0.003). Furthermore, Kaplan-Meier survival analysis revealed that low expression of PTPRD significantly correlated with poor survival of gastric cancer patients (P<0.001). Cox regression analysis confirmed PTPRD expression as independent predictor of the overall survival of gastric cancer patients. The MTT assay determined the effects of PTPRD on cell proliferation of MGC803 and GES1 cell lines. Restoring PTPRD expression in MGC803 cells significantly inhibited their growth rate. Silencing PTPRD expression by siRNA treatment in GES1 significantly enhanced cell proliferation compared with mock siRNA treatment. Methylation analysis of PTPRD promoter CpG island in 3 primary GC samples showed one case with partial methylation. These results indicated that PTPRD is a candidate tumour suppressor in gastric cancer. Thus, PTPRD may play an important role in gastric tumorigenesis and serve as a valuable prognostic marker of gastric adenocarcinoma.


Validation of quantitative fluorescent-PCR for rapid prenatal diagnosis of common aneuploidies in the Chinese population.
Quantitative fluorescent polymerase chain reaction (QF-PCR) is an accurate and reliable method for rapid detection of aneuploidy; however, it is not routinely used in China. We aimed to validate QF-PCR as a means for prenatal common aneuploidy screening and to analyze the heterozygosities of short tandem repeat (STR) markers in the Chinese population. The sequences of 19 STR markers in chromosomes 21, 18, 13, X, and Y were designed; three kinds of fluoresceins were used to label the primers, and the QF-PCR detecting conditions were explored and optimized. The results of analysis of 210 prenatal samples by multiplex QF-PCR were compared with karyotyping analysis. All cases were successfully tested by QF-PCR and conventional cytogenetic analysis. QF-PCR results were consistent with the results of cytogenetic analyses, with the exception of two cases. The sensitivity and specificity of QF-PCR to diagnose common aneuploidies were 94.74 and 100%, respectively. The heterozygosities of most of the markers were lower than reported for Western populations, but relatively similar to those of other Asian populations. We conclude that QF-PCR is able to detect the common aneuploidies for prenatal diagnosis with high detection efficacy; therefore it is suitable for rapid prenatal diagnosis and for large-scale testing in laboratories. However, we need to add new STR markers or to find alternative STR markers with high heterozygosity in order to make this technique useful for routine diagnosis.


Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans.
Skeletal muscle homeostasis depends on muscle growth (hypertrophy), atrophy and regeneration. During ageing and in several diseases, muscle wasting occurs. Loss of muscle mass and function is associated with muscle fiber type atrophy, fiber type switching, defective muscle regeneration associated with dysfunction of satellite cells, muscle stem cells, and other pathophysiological processes. These changes are associated with changes in intracellular as well as local and systemic niches. In addition to most commonly used rodent models of muscle ageing, there is a need to study muscle homeostasis and wasting using human models, which due to ethical implications, consist predominantly of in vitro cultures. Despite the wide use of human Myogenic Progenitor Cells (MPCs) and primary myoblasts in myogenesis, there is limited data on using human primary myoblast and myotube cultures to study molecular mechanisms regulating different aspects of age-associated muscle wasting, aiding in the validation of mechanisms of ageing proposed in rodent muscle. The use of human MPCs, primary myoblasts and myotubes isolated from adult and aged people, provides a physiologically relevant model of molecular mechanisms of processes associated with muscle growth, atrophy and regeneration. Here we describe in detail a robust, inexpensive, reproducible and efficient protocol for the isolation and maintenance of human MPCs and their progeny - myoblasts and myotubes from human muscle samples using enzymatic digestion. Furthermore, we have determined the passage number at which primary myoblasts from adult and aged people undergo senescence in an in vitro culture. Finally, we show the ability to transfect these myoblasts and the ability to characterize their proliferative and differentiation capacity and propose their suitability for performing functional studies of molecular mechanisms of myogenesis and muscle wasting in vitro.


A glycerol assisted light-emitting diode-induced fluorescence detector for capillary flow systems.
A glycerol assisted light-emitting diode (LED)-induced fluorescence detector (IF) for capillary flow systems was constructed and evaluated. A blue LED was used as the excitation source, and optical fibers (OF) were used to transmit the excitation light and collect the fluorescence. A commercial available 5-port manifold was used as detection cell, where the capillary tube and the OF were fixed into the manifold. The precision of the holes on the manifold ensured a self-alignment of optical path. A refractive index matching fluid (RIMF)-glycerol was used to eliminate the interfaces between the OF and the LED, as well as between the fused silica capillary and the transmitting/collecting fiber. The enhancement of excitation light led to 2.8-folds improvement on the signal-to-noise ratio. The use of RIMF also eliminates focusing effect of the capillary wall and reduces both the excitation light directed to the detection cell and background signal, resulting in reduction in the fluorescence intensity and noise level. The intensity was reduced to 47-63% for laser and 60-77% for LED, respectively, for capillaries with i.d. from 50 to 250 microm; while the noise level was reduced to 1/3 when RIMF was used for both laser and LED on the tested capillaries. About 5.6-fold enhancement in signal-to-noise ratio was obtained in total. The detection limit of the LED-IF for fluorescein isothiocyanate (FITC) was 4 nM. Application of the LED-IF for the analysis of FITC-labeled amino acids by electrophoresis was demonstrated.


Exploring the relationship between α-actinin-3 deficiency and obesity in mice and humans.
Obesity is a worldwide health crisis, and the identification of genetic modifiers of weight gain is crucial in understanding this complex disorder. A common null polymorphism in the fast fiber-specific gene ACTN3 (R577X) is known to influence skeletal muscle function and metabolism. α-Actinin-3 deficiency occurs in an estimated 1.5 billion people worldwide, and results in reduced muscle strength and a shift towards a more efficient oxidative metabolism. The X-allele has undergone strong positive selection during recent human evolution, and in this study, we sought to determine whether ACTN3 genotype influences weight gain and obesity in mice and humans. An Actn3 KO mouse has been generated on two genetic backgrounds (129X1/SvJ and C57BL/6J) and fed a high-fat diet (HFD, 45% calories from fat). Anthropomorphic features (including body weight) were examined and show that Actn3 KO 129X1/SvJ mice gained less weight compared to WT. In addition, six independent human cohorts were genotyped for ACTN3 R577X (Rs1815739) and body mass index (BMI), waist-to-hip ratio-adjusted BMI (WHRadjBMI) and obesity-related traits were assessed. In humans, ACTN3 genotype alone does not contribute to alterations in BMI or obesity.


Excitation of whispering gallery modes with a "point-and-play," fiber-based, optical nano-antenna.
We demonstrate the excitation and detection of whispering gallery modes in optical microresonators using a "point-and-play," fiber-based, optical nano-antenna. The coupling mechanism is based on cavity-enhanced Rayleigh scattering. Collected spectra exhibit Lorentzian dips, Fano shapes, or Lorentzian peaks, with a coupling efficiency around 13%. The spectra are characterized by the coupling gap, polarization, and fiber tip position. The coupling method is simple, low-cost and, most importantly, the Q-factor can be maintained at 108 over a wide coupling range, thereby making it suitable for metrology, sensing, or cavity quantum electrodynamics experiments.


Lanthanum Complexes with a Diimine Ligand in Three Different Redox States.
The reduction of 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene (dpp-Bian) with an excess of La metal in the presence of iodine (dpp-Bian/I2 = 2/1) in tetrahydrofuran (thf) or dimethoxyethane (dme) affords lanthanum(III) complexes of dpp-Bian dianion: deep blue [(dpp-Bian)2-LaI(thf)2]2 (1, 84%) was isolated by crystallization of the product from hexane, while deep green [(dpp-Bian)LaI(dme)2] (2, 93%) precipitated from the reaction mixture in the course of its synthesis. A treatment of complex 1 with 0.5 equiv of I2 in thf leads to the oxidation of the dpp-Bian dianion to the radical anion and results in the complex [(dpp-Bian)1-LaI2(thf)3] (3). Addition of 18-crown-6 to the mixture of 1 and NaCp* (Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl) in thf affords ionic complex [(dpp-Bian)2-La(Cp*)I][Na(18-crown-6)(thf)2] (4, 71%). In the absence of crown ether the alkali metal salt-free complex [(dpp-Bian)2-LaCp*(thf)] (5, 67%) was isolated from toluene. Reduction of complex 1 with an excess of potassium produces lanthanum-potassium salt of the dpp-Bian tetra-anion {[(dpp-Bian)4-La(thf)][K(thf)3]}2 (6, 68%). Diamagnetic compounds 1, 2, 4, 5, and 6 were characterized by NMR spectroscopy, while paramagnetic complex 3 was characterized by the electron spin resonance spectroscopy. Molecular structures of 2-6 were established by single-crystal X-ray analysis.


[The effects of amiodaron on the thyroid function].
The use of several groups of medications may result in thyroid dysfunction including thyrotoxicosis or hypothyroidism of various degree (from subclinical to full-clinical syndrome). The mentioned disturbances may develop either on the basis of normal euthyroid gland or may overlap the previously-existing oceult changes (first of all different forms of autoimmune thyroiditis). Amiodarone is a widely used anti-arrythmic drug with considerable potential to cause thyroid dysfunction because of its 35% iodine content. Besides amiodarone particles are known to inhibit T4 to T3 conversion, they work as inhibitors of nuclear receptors for thyroid hormones, exert cytotoxic effect and induce immune/inflammatory process in thyroid gland. Both thyrotoxicosis (AIT - amiodarone induced thyrotoxicosis) and hypothyroidism (AIH - amiodarone induce hypothyroidism) may develop during amiodarone therapy. AIT appears to occur more frequently in geographical areas with low iodine intake, whereas AIH is more frequent in iodine-sufficient areas. Two forms of AIT are known. Their differentiation is very important for further therapeutical procedures. Because thyrotoxicosis and hypothyroidism symptoms during amiodarone therapy are scanty, there is need for periodic determination of thyroid function. Normal ranges for amiodarone patients differ from those for the rest of population. They are presented in this review. Treatment of AIT is very complicated. Sometimes there is need to use few methods together, especially when amiodarone treatment can not be stopped.


GABAB receptors-mediated tonic inhibition of glutamate release from Aβ fibers in rat laminae III/IV of the spinal cord dorsal horn.
Presynaptic GABAB receptors (GABABRs) are highly expressed in dorsal root ganglion neurons and spinal cord dorsal horn. GABABRs located in superficial dorsal horn play an important antinociceptive role, by acting at both pre- and postsynaptic sites. GABABRs expressed in deep dorsal horn could be involved in the processing of touch sensation and possibly in the generation of tactile allodynia in chronic pain. The objective of this study was to characterize the morphological and functional properties of GABABRs expressed on Aβ fibers projecting to lamina III/IV and to understand their role in modulating excitatory synaptic transmission. We performed high-resolution electron microscopic analysis, showing that GABAB2 subunit is expressed on 71.9% of terminals in rat lamina III-IV. These terminals were engaged in axodendritic synapses and, for the 46%, also expressed glutamate immunoreactivity. Monosynaptic excitatory postsynaptic currents, evoked by Aβ fiber stimulation and recorded from lamina III/IV neurons in spinal cord slices, were strongly depressed by application of baclofen (0.1-2.5 µM), acting as a presynaptic modulator. Application of the GABABR antagonist CGP 55845 caused, in a subpopulation of neurons, the potentiation of the first of two excitatory postsynaptic currents recorded with the paired-pulse protocol, showing that GABABRs are endogenously activated. A decrease in the paired-pulse ratio accompanied the effect of CGP 55845, implying the involvement of presynaptic GABABRs. CGP 55845 facilitated only the first excitatory postsynaptic current also during a train of four consecutive stimuli applied to Aβ fibers. These results suggest that GABABRs tonically inhibit glutamate release from Aβ fibers at a subset of synapses in deep dorsal horn. This modulation specifically affects only the early phase of synaptic excitation in lamina III-IV neurons.


Gaps in international nutrition and child feeding guidelines: a look at the nutrition and young child feeding education of Ghanaian nurses.
To examine the nutrition and young child feeding (YCF) education and training of nurses in public health clinics of Ghana's Komenda-Edina-Eguafo-Abrem region (KEEA) in relation to global health guidelines, and how nurses served as educators for caregivers with children aged 0-5 years. A qualitative study of semi-structured one-on-one and group interviews (n 21) following a questionnaire of closed- and open-ended questions addressing child feeding, nutrition and global health recommendations. Interviews were conducted in English, audio-recorded, transcribed and coded. Descriptive data were tabulated. Content analysis identified themes from open-ended questions. KEEA public health clinics (n 12). Nurses (n 41) purposefully recruited from KEEA clinics. A model capturing nurses' nutrition and YCF education emerged with five major themes: (i) adequacy of nurses' basic knowledge in breast-feeding, complementary feeding, iron-deficiency anaemia, YCF and hygiene; (ii) nurses' delivery of nutrition and YCF information; (iii) nurses' evaluation of children's health status to measure education effectiveness; (iv) nurses' perceived barriers of caregivers' ability to implement nutrition and YCF education; and (v) a gap in global health recommendations on YCF practices for children aged 2-5 years. Nurses demonstrated adequate nutrition and YCF knowledge, but reported a lack of in-depth nutrition knowledge and YCF education for children 2-5 years of age, specifically education and knowledge of YCF beyond complementary feeding. To optimize child health outcomes, a greater depth of nutrition and YCF education is needed in international health guidelines.


Fiber optic sensor for the measurement of concentration of silica in water with dual wavelength probing.
The design, development, and characterization of a fiber optic evanescent wave based sensor with selectivity suitable for concentration measurement are presented. The sensor that is made up of a step index plastic multimode fiber can be used for the measurement of silica in water. Generally evanescent wave fiber optic sensors employ a single source and detector that show change in output optical power irrespective of the interacting species, i.e., they lack selectivity. This design employing two sources provides excellent selectivity, and the differential arrangement further enhances sensitivity and repeatability. Advantages of this design include the use of inexpensive and easily available light-emitting diode sources that match the analytical wavelength of the samples. The use of dual wavelength probing topology enhances the selectivity, sensitivity, and repeatability, which cannot be achieved by single source evanescent wave fiber optic sensors.


Age-Dependent Changes in Resting Energy Expenditure (REE): Insights from Detailed Body Composition Analysis in Normal and Overweight Healthy Caucasians.
Age-related changes in organ and tissue masses may add to changes in the relationship between resting energy expenditure (REE) and fat free mass (FFM) in normal and overweight healthy Caucasians. Secondary analysis using cross-sectional data of 714 healthy normal and overweight Caucasian subjects (age 18-83 years) with comprehensive information on FFM, organ and tissue masses (as assessed by magnetic resonance imaging (MRI)), body density (as assessed by Air Displacement Plethysmography (ADP)) and hydration (as assessed by deuterium dilution (D₂O)) and REE (as assessed by indirect calorimetry). High metabolic rate organs (HMR) summarized brain, heart, liver and kidney masses. Ratios of HMR organs and muscle mass (MM) in relation to FFM were considered. REE was calculated (REEc) using organ and tissue masses times their specific metabolic rates. REE, FFM, specific metabolic rates, the REE-FFM relationship, HOMA, CRP, and thyroid hormone levels change with age. The age-related decrease in FFM explained 59.7% of decreases in REE. Mean residuals of the REE-FFM association were positive in young adults but became negative in older subjects. When compared to young adults, proportions of MM to FFM decreased with age, whereas contributions of liver and heart did not differ between age groups. HOMA, TSH and inflammation (plasma CRP-levels) explained 4.2%, 2.0% and 1.4% of the variance in the REE-FFM residuals, but age and plasma T3-levels had no effects. HMR to FFM and MM to FFM ratios together added 11.8% on to the variance of REE-FFM residuals. Differences between REE and REEc increased with age, suggesting age-related changes in specific metabolic rates of organs and tissues. This bias was partly explained by plasmaT3-levels. Age-related changes in REE are explained by (i) decreases in fat free mass; (ii) a decrease in the contributions of organ and muscle masses to FFM; and (iii) decreases in specific organ and tissue metabolic rates. Age-dependent changes in the REE-FFMassociation are explained by composition of FFM, inflammation and thyroid hormones.


In-house validation of a liquid chromatography/electrospray tandem mass spectrometry method for confirmation of chloramphenicol residues in muscle according to Decision 2002/657/EC.
In this work we present an in-house validation study for the confirmatory analysis of chloramphenicol (CAP) in muscle according to the Commission Decision 2002/657/EC requirements. CAP is extracted in acetonitrile and after liquid-liquid partitioning with n-hexane is identified and quantitatively determined by ion trap liquid chromatography/electrospray ionisation tandem mass spectrometry (LC/ESI-MS/MS) analysis in the negative ion mode. CAP was identified using the precursor ion and at least two product ions, meeting the qualitative and quantitative criteria set by the European Commission in the Decision 2002/657/EC for confirmation of prohibited veterinary drug residues. We calculated mean drug recoveries, CCalpha and CCbeta of the method, and reported data on specificity, ruggedness and within-laboratory reproducibility. Finally, we point out and discuss some problems and questions arising from controversy about the application of Decision 2002/657/EC.


Treatment of diabetic coma with small intravenous insulin boluses.
The clinical efficacy of small intravenous boluses of insulin in treating diabetic decompensation was tested in 23 patients presenting in either a ketoacidotic or a nonketotic diabetic coma. In addition to the usual ionic and fluid replacement, the patients received hourly intravenous injections of insulin 5 IU. This dose lowered blood glucose levels in all but two patients. In the patients who responded the percentage decrease in glycaemia was similar whatever the initial glucose concentration and averaged (+/-SE of mean) 50+/-3% in five hours. Close monitoring of insulin and glucose concentrations after intravenous insulin in three patients showed that despite the short half life of insulin the effect of the intravenous bolus lasted for about 60 minutes. The overall clinical effectiveness of this type of treatment is comparable to that of the other low-dose regimens. Owing to its simplicity, this technique of insulin administration seems most suitable for the routine treatment of diabetic coma.


Time trends of process and impact indicators in Italian mammography screening programmes--1996-2004.
Since 1990, the Italian Group for Mammography Screening (GISMa) has been promoting the development of new organised programmes and performing a yearly systematic survey of data activity. The screening extension has increased over time, reaching an overall 76.4% of coverage in 2005. The geographical extension is still heterogeneous, with a higher distribution in Northern and Central Italy compared with Southern and Insular Italy, where the screening activity was implemented only recently. Notwithstanding the continuity in implementation, the actual coverage reached only 50.3% of the target population, due to a reduced flow of invitations over time as a consequence of a chronic lack of invested resources and of well-plannedpolicies. The overall Italian rate for crude attendance was above the acceptable 50% standard even though a North-South trend is still confirmed; in Southern/Insular Italy participation was still inadequate (<40%) and did not reach the standard considered acceptable. Participation was higher in centralised programmes compared with those without regional coordination (+5-8%). The time trends for the other key performance indicators showed good average performance: the benign/malignant surgical biopsy ratio (B/M ratio) progressively decreased, reaching an 0.25 ratio (both for first and subsequent screening) in 2004; overall detection rate, detection rate for in situ and small cancers (< or =10 mm) showed a good trend, reaching 6.7% per hundred, 0.7% per hundred, and 1.6% per hundred, respectively, for the first screening, and 5.1% per hundred, 0.9% per hundred, and 1.7% per hundred for the subsequent screening in 2004. The only exception was the referral rate (RR) at first screening, which exceeded standards (> 7% in 2002-2004). Data comparing activity volume and programme duration were also analysed. In programmes with greater activity (average test number: 22,506) the referral rate for the first screening was higher, but still within acceptable standards. 6.3% per hundred; RR: 1.01 (0.98-1.04). This performance is compensated by better specificity and sensitivity: Positive Predictive Value (PPV). 12.8; RR:1.16 (1.05-1.27); overall detection rate: 8.1% per hundred, RR 1.19 (1.07-1.31). An improvement in quality with the increase of programme experience is evident. programmes with more than 6 years of activity, compared with newer programmes, show a recall rate in first screening of 6.5%; RR. 0.87 (0.84-0.89), a PPV of 1.7, RR:1.61 (1.48-1.75) andan overall detection rate of 7.6% per hundred, RR:1.41 (1.29-1.55). These results are consistent with those observed in other European programmes and encourage to explore new analysis strategies. The website of the National Centre for Screening Monitoring (ONS) is http://www.osservatorionazionalescreening.it.


Evaluation of five commercial kits to detect dsDNA antibodies.
Experiments were performed to evaluate five commercial kit assays used for the detection of antibodies to dsDNA. The kits were compared using a performance index score as recommended by the guidelines of the European Committee for Clinical Laboratory Standards. The highest performance score was obtained using the radioimmunoassay from Immunodiagnostic Services Ltd, with the Amersham kit second, the immunofluorescence test using Crithidia luciliae third, the Walker ELISA kit fourth, and the haemagglutination assay fifth. The results showed that none of the kits was outstanding, each appeared to detect a different anti-DNA antibody type as different results were obtained using each kit in assays of quality control sera, linearity of the method, antibody detection in various patient groups, and interference by various substances. It is suggested that laboratories using commercial assay kits for the detection of antibodies to dsDNA should decide which is the most appropriate to their particular needs and that a performance index scoring system may be useful in the comparison of assay evaluations between different laboratories.


[Electrochemical deposition of copper by using ionic liquids as additive and its surface-enhanced Raman scatting effect].
The use of room-temperature ionic liquids (RTILs) as green media for electrochemical application has attracted great attention recently. However, the effects of RTILs used as additives for electrodeposition of metals have hardly been explored. In the present work, the electrochemical deposition of copper was investigated on a pure copper plate from acid cupric sulfate solutions in the presence of RTILs (1-butyl-3-methylimidazolium tetrafluoroborate, [bmim] BF4) additive by cyclic voltammetric technique, scanning electron microscope (SEM), and X-ray diffraction (XRD). For comparison, the electrodeposition of copper from acid cupric sulfate solutions was also investigated. The voltammograms showed that the cathodic peak potential shifted toward more negative potential and cathodic peak current increased when 1.0 x 10(-4) mol x L(-1) [bmim] BF4 was added into acid cupric sulfate solutions. SEM images indicated that the shinning electrodeposits of copper were lamellar structure and the size of layered grain decreased with addition of [bmim]BF4 additive. The XRD results indicated that copper deposits exhibited face-centered cubic structure and (220) highly preferred orientation. The surface-enhanced Raman scattering (SERS) activities of copper deposits were measured by using methyl orange (MO) as the probe molecules. The copper electrodeposit obtained in acid cupric sulfate solutions with [bmim]BF4 is shown to be excellent substrate for SERS measurements, demonstrating significant enhancement and good stability. The enhancement factor was calculated to be up to 4.7 x 10(5). It was also found that copper electrodeposit stored for 60 days in air shows no significant degradation in its sensitivity.


Generalized logistic functions in modelling emergence of Brassica napus L.
The objective of this study was to determine whether generalized logistic functions (Richards model with time shift) may be used to predict emergence of winter rapeseed (Brassica napus L.) after its seed treatment with plant extracts from Taraxacum officinale roots under controlled environment conditions. Emergence analyses were conducted for winter rape whose seeds were treated with a plant extract and for the non-treated seeds sown to the soil at the site of earlier point application of the extract. Curves were plotted for experimental data by minimizing the square sum of differences between the experimental data and the mathematical model. To evaluate model fit, the mean squared error was divided into four factors. Computing modelling efficiency coefficients were also introduced to enable complete analysis. Results of simulation research demonstrate that the determined parameters of curves (e.g. values of growth parameters, time shift or the upper limit of population) describing the number of seedlings in the function of time stayed compliant to the interpretation with regard to the biology of the analyzed processes. The proposed mathematical description based on generalized logistic functions showed extraordinary fit (r = 0.999) to the experimental data, which makes it highly useful in predictive control of rapeseed emergence. In addition, the study enabled concluding that plant extracts application to the soil allowed achieving a higher maximal emergence rate compared to the control sample. The application of the plant extracts increased the final population of rapeseed and significantly accelerated the occurrence of the maximal emergence rate.


Impact of the Surveillance Interval on the Survival of Patients Who Undergo Curative Surgery for Gastric Cancer.
For patients who undergo gastrectomy for gastric cancer, systematic follow-up evaluation to detect recurrent lesions is recommended, although the benefits of a surveillance program using short-term imaging studies have not been evaluated. This study reviewed the clinical data of patients who underwent curative surgery for gastric cancer using a prospective database. Patients with recurrence were classified according to surveillance interval as follows: ≤3, 3-6, and 6-12 months. Of the 2785 patients who underwent curative surgery for gastric cancer, 376 (13.5 %) had intraabdominal recurrences, excluding the stomach. Multivariable analysis showed that a short surveillance interval did not increase the post-recurrence survival duration (with 6-12 months as the reference: ≤3 months: hazard ratio [HR] 0.954; 95 % confidence interval [CI] 0.689-1.323; 3-6 months: HR 0.994, 95 % CI 0.743-1.330). In addition, short surveillance intervals did not increase overall survival (with 6-12 months as the reference: ≤3 months: HR 0.969; 95 % CI 0.699-1.342; 3-6 months: HR 0.955; 95 % CI 0.711-1.285). In contrast to the surveillance interval, age, cancer stage, symptoms at recurrence, and recurrence time after gastrectomy were factors associated with both post-recurrence survival and overall survival. Although the detection of recurrence before symptoms helped to prolong both post-recurrence survival and overall survival, shortening the surveillance interval to less than 6 months did not improve either the patient's post-recurrence survival or overall survival. Hence, it is not recommended that asymptomatic patients undergo surveillance involving imaging studies more often than once a year.


Patients' memories of events during general anaesthesia.
Awareness remains a serious complication of general anaesthesia with potential adverse psychological sequelae. Even during seemingly adequate general anaesthesia, implicit memory may be retained along with the ability to subconsciously process auditory stimuli. As a result behaviour may be modified and postoperative progress influenced. We shall discuss the structure of memory and the effects of increasing doses of general anaesthesia on cognitive processes. In addition methods of assessing the depth of anaesthesia will be reviewed.


Polaris and Polycystin-2 in dorsal forerunner cells and Kupffer's vesicle are required for specification of the zebrafish left-right axis.
Recently, it has become clear that motile cilia play a central role in initiating a left-sided signaling cascade important in establishing the LR axis during mouse and zebrafish embryogenesis. Two genes proposed to be important in this cilia-mediated signaling cascade are polaris and polycystin-2 (pkd2). Polaris is involved in ciliary assembly, while Pkd2 is proposed to function as a Ca(2+)-permeable cation channel. We have cloned zebrafish homologues of polaris and pkd2. Both genes are expressed in dorsal forerunner cells (DFCs) from gastrulation to early somite stages when these cells form a ciliated Kupffer's vesicle (KV). Morpholino-mediated knockdown of Polaris or Pkd2 in zebrafish results in misexpression of left-side-specific genes, including southpaw, lefty1 and lefty2, and randomization of heart and gut looping. By targeting morpholinos to DFCs/KV, we show that polaris and pkd2 are required in DFCs/KV for normal LR development. Polaris morphants have defects in KV cilia, suggesting that the laterality phenotype is due to problems in cilia function per se. We further show that expression of polaris and pkd2 is dependent on the T-box transcription factors no tail and spadetail, respectively, suggesting that these genes have a previously unrecognized role in regulating ciliary structure and function. Our data suggest that the functions of polaris and pkd2 in LR patterning are conserved between zebrafish and mice and that Kupffer's vesicle functions as a ciliated organ of asymmetry.


Gonadal regulation of hypothalamic gonadotropin-releasing hormone release in primates.
This review has examined, in primates, the action of sex steroids on the neural timing mechanism that governs the intermittent release of GnRH by the hypothalamus, the so-called GnRH pulse generator. Determinants of hypothalamic GnRH pulse generator frequency have generally been examined indirectly by monitoring moment to moment fluctuations in circulating LH concentrations. Studies using this approach have led to the hypothesis that negative feedback control of LH secretion by the testes is mediated by the action of T, or of one of its metabolites, to retard the frequency of the GnRH pulse generator. P also appears capable of decelerating GnRH pulse frequency during the luteal phase of the menstrual cycle, but the physiological significance of this phenomenon remains to be clarified. To date, a cognate action of E2 on the GnRH pulse generator has not been described. Because of limitations in contemporary technology, the factors underlying amplitude modulation of the GnRH pulse generator are less well understood. In addition to the ability of certain sex steroids to decelerate the frequency of pulsatile GnRH discharge, E2 and P appear capable of facilitating the secretion of this hypothalamic releasing factor. However, the increase in GnRH pulse frequency and/or GnRH pulse amplitude that must underlie these stimulatory actions remains to be fully defined. An inhibitory action of high levels of circulating cortisol on the hypothalamic GnRH pulse generator has also been noted.


Unveiling the irreversible performance degradation of organo-inorganic halide perovskite films and solar cells during heating and cooling processes.
While organo-inorganic halide perovskite solar cells show great potential to meet future energy needs, their thermal instability raises serious questions about their commercialization viability. At present, the stability of perovskite solar cells has been studied under various environmental conditions including humidity and temperature. Nonetheless, understanding of the performance of CH3NH3PbI3-xClx perovskite solar cells is limited. This study reports the irreversible performance degradation of CH3NH3PbI3-xClx perovskite solar cells during the heating and cooling processes under AM 1.5 and unveils what triggers the irreversible performance degradation of solar cells. Particularly, the primary cause of the irreversible performance degradation of CH3NH3PbI3-xClx is quantitatively analyzed by monitoring in real time the development of deteriorated crystallinity, charge trapping/detrapping, trap depth, and the PbI2 phase, namely a critical signal of perovskite degradation while varying the temperature of the perovskite films and solar cells. Most surprisingly, it is revealed that the degradation of both perovskite films and solar cells was triggered at ∼70 °C. Remarkably, even after the device temperature cooled down to room temperature, the degraded performance of the solar cells persisted with increasing charge trapping and further development of the PbI2 phase. Identification of the irreversible performance degradation of perovskite solar cells provides guidance for future development of more stable perovskite solar cells.


Limitations of recognition of modified-self by alloantigen-activated cytotoxic T lymphocytes.
Alloantigen-activated CTL from CBA (H-2k), but not from C57BL/6 (H-2b), mice were able to lyse autologous cells modified by incubation with TNP-HSA. Moreover, allogeneic CTL of the H-2k haplotype lysed syngeneic cells modified with high or low concentrations of TNBS. Allogeneic CTL of the H-2b haplotype, however, did not lyse autologous cells modified with low concentrations of TNBS, even though they lysed syngeneic cells modified with high concentrations of TNBS. These limitations of recognition by the different H-2 haplotypes paralleled the restrictions evident for MHC-restricted, TNBS-specific CTL. It was thus apparent that alloantigen-activated CTL are governed by the same limitations of recognition operant for the MHC-restricted, TNBS-specific CTL.


Zeatin and zeatin riboside from a mycorrhizal fungus.
The puffball fungus Rhizopogon roseolus produces and releases three cytokinins when it is cultured in liquid media. Two of these compounds have been isolated in crystalline form from such media and were found to have properties identical to those of synthetic zeatin and zeatin riboside.


[Chinese expert consensus on the use of topical timolol maleate treatment of infantile hemangiomas].
Non-selective β-blocker propranolol has been proved by FDA as the first-line agent for infantile hemangioma (IH) with dramatic response. To reduce the side effects caused by systemic administration of propranolol, timolol maleate treatment has been increasingly used as an alternative to systemic β-blockers and watchful waiting for many IH patients in recent years. However, the appropriate indications, drug dosage, dosing regimen, time for initiation, optimal duration, monitoring for side effects still remains controversial. To standardize the use of topical timolol in treating IH, avoid overtreatment or under-treatment, as well as minimize complications, a Chinese expert consensus on the use of topical timolol treatment of IH has been approved and written by a multidisciplinary experts group based on an up-to-date literature review and repeated discussion, which can be used to reduce inappropriate variations in clinical practice and to promote the delivery of high quality, evidence-based health care for IH patients.


Simple and Efficient Ruthenium-Catalyzed Oxidation of Primary Alcohols with Molecular Oxygen.
Oxidative transformations utilizing molecular oxygen (O2 ) as the stoichiometric oxidant are of paramount importance in organic synthesis from ecological and economical perspectives. Alcohol oxidation reactions that employ O2 are scarce in homogeneous catalysis and the efficacy of such systems has been constrained by limited substrate scope (most involve secondary alcohol oxidation) or practical factors, such as the need for an excess of base or an additive. Catalytic systems employing O2 as the "primary" oxidant, in the absence of any additive, are rare. A solution to this longstanding issue is offered by the development of an efficient ruthenium-catalyzed oxidation protocol, which enables smooth oxidation of a wide variety of primary, as well as secondary benzylic, allylic, heterocyclic, and aliphatic, alcohols with molecular oxygen as the primary oxidant and without any base or hydrogen- or electron-transfer agents. Most importantly, a high degree of selectivity during alcohol oxidation has been predicted for complex settings. Preliminary mechanistic studies including (18) O labeling established the in situ formation of an oxo-ruthenium intermediate as the active catalytic species in the cycle and involvement of a two-electron hydride transfer in the rate-limiting step.


Compliance With American Urological Association Guidelines for Nonmuscle Invasive Bladder Cancer Remains Poor: Assessing Factors Associated With Noncompliance and Survival in a Rural State.
To identify factors associated with nonmuscle invasive bladder cancer (NMIBC) American Urological Association (AUA) guideline compliance in a rural state, to evaluate compliance rates over time, and to assess the impact of patient and provider rurality on delivery of NMIBC care. We identified 847 Iowans in Surveillance, Epidemiology, and End Results-Medicare from 1992 to 2009 with high-grade NMIBC who survived 2 years and were not treated with cystectomy or radiation during this period. Compliance with AUA guidelines was assessed over time and compared to patient demographic, tumor, and treatment institution variables. Impact of rurality was analyzed using Surveillance, Epidemiology, and End Results ZIP code data travel distance of patient to nearest urologist practice location. Overall compliance with AUA guidelines was low (<1%), and did not markedly improve over the study period. In the multivariable model, only care at an academic medical center (OR 11.68, 95% CI 7.07-19.29) and tumor stage (Tis; OR 3.24, 95% CI 1.86-5.63) increased the odds of compliance. Patients living closer (<10 miles) to their urologists underwent more cystoscopies than patients living further (>30 miles) but distance did not affect compliance with other measures. Compliance was not associated with cancer-specific survival. Compliance with post-Transurethral Resection of Bladder Tumor (TURBT) NMIBC treatment guidelines has improved but remains suboptimal in our rural state, and is highly associated with treatment at an academic cancer center for reasons that could not be fully explained with these data.


[The quality institute for doctors].
The mission of the Quality Institute, which is part of the Dutch National Health Care Institute, is to promote quality of healthcare. It is cooperating with all parties within healthcare to improve quality and insight into quality. Input from all stakeholders, including healthcare providers, clients, and providers of healthcare insurance, is important for the realisation of quality standards and measuring instruments. The starting point is the demands of the client. The Quality Institute has drawn up a framework to test criteria with which quality standards and measuring instruments must comply. This promotes the development of good quality standards and measuring instruments that deliver useful and reliable information. The current practice of parallel registration of patient data, for the care process and to deliver quality-information, causes high administrative burdens and is not future-proof. For that reason the Quality Institute, together with other parties in healthcare, is developing the concept of an 'information standard'. This should eventually lead to multiple use of unambiguous data registered at source.


Lower hybrid drift instability in a neutral sheet with O+ ions.
The electromagnetic lower-hybrid drift instability (LHDI) in the intermediate-wavelength regime k_(y)sqrt[rho_(i)rho_(e)] approximately 1 , where k_(y) and rho_(e,i) are the wave vector and the electron and ion gyroradii, respectively, in a thin plasma sheet containing electrons and H+ and O+ ions is examined using kinetic theory. It is shown that the growth rate of the LHDI first decreases and then increases with increase in the O+ content and temperature, with a minimum at a moderate level of the latter. The results can be relevant to understanding magnetic reconnection in the presence of LHDI.


Subsequent primary malignancies after diffuse large B-cell lymphoma in the modern treatment era.
With the addition of rituximab and other treatment advances, survival after diffuse large B-cell lymphoma (DLBCL) has improved, but subsequent primary malignancies (SPMs) have emerged as an important challenge for DLBCL survivorship. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPMs among 23 879 patients who survived at least 1 year after a first primary DLBCL diagnosed during 1989-2012, compared to the general population in California. Cumulative incidence (CMI) of SPMs, accounting for the competing risk of death, also was calculated. We found that the incidence of acute myeloid leukaemia (AML) nearly doubled in the post-rituximab era [SIR (95% CI) 4·39 (2·51-7·13) pre- (1989-2000) and 8·70 (6·62-11·22) post-rituximab (2001-2012)]. Subsequent thyroid cancer was rare pre-rituximab, but increased substantially after 2001 [0·66 (0·08-2·37) vs. 2·27(1·44-3·41)]. The 5-year CMI for all SPMs (4·77% pre- vs. 5·41% post-rituximab, P = 0·047), AML (0·15% vs. 0·41%, P = 0·003), thyroid cancer (0·03% vs. 0·15%, P = 0·003) and melanoma (0·25% vs. 0·42%, P = 0·020) were greater in DLBCL patients diagnosed in the post- versus pre-rituximab period. This study provides insight into the changing pattern of SPM occurrence after the introduction of rituximab, which may elucidate the aetiology of SPMs and should guide future cancer surveillance efforts among DLBCL patients.


Scoring radiographic progression in ankylosing spondylitis: should we use the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) or the Radiographic Ankylosing Spondylitis Spinal Score (RASSS)?
Radiographic damage is one of the core outcomes in axial SpA and is usually assessed with the modified Stoke Ankylosing Spondylitis (AS) Spine Score (mSASSS). Alternatively, the Radiographic AS Spinal Score (RASSS) is proposed, which includes the lower thoracic vertebrae, under the hypothesis that most progression occurs in these segments. We aimed to compare the mSASSS and RASSS with regard to performance. Two-yearly spinal radiographs from patients followed in the Outcome in AS International Study (OASIS) were used (scored independently by two readers). A total of 195 patients had at least one radiograph (12-year follow-up) to be included. We assessed the accessibility of vertebral corners (VCs) for scoring, as well as status and 2-year progression scores of both scoring methods. To assess the potential additional value of including the thoracic segment in the score, the relative contribution (in %) to the 2-year total RASSS progression of each spinal segment (cervical, thoracic and lumbar) was determined, and compared to the expected contribution, under the assumption that a balanced segmental progression would occur, proportional to the number of sites per segment. The mSASSS could be scored in a total of 809 radiographs and the RASSS in 78% of these. In 58% of the latter, the score was based on one to two available thoracic VCs scores, and the remaining two to three were imputed because they were missing. There were 520 two-year mSASSS intervals available, and in 63% of them RASSS progression could be assessed. The mean (SD) 2-year interval progression score (330 intervals) was 2.0 (3.6) for the mSASSS and 2.4 (4.4) for the RASSS, yielding a similar effect size (mSASSS 0.57 and RASSS 0.55). Exclusive progression of the thoracic segment occurred in only 5% of the cases. There was no significant difference between the observed (14%) and expected (16%) contribution to progression of the thoracic segment (P=0.70). The determination of RASSS for radiographic damage of the spine is frequently impossible or strongly influenced by non-contributory imputation. In comparison to the mSASSS, the contribution of thoracic VCs in the RASSS method is negligible, and does not justify the additional scoring efforts.


[Study on the determinants of prevalence in persons with overweight and obesity in rural areas of Kunming].
This study was to explore the prevalence of overweight and obesity,and the effects of contextual and individual level determinants on them in the rural areas of Kunming city, China. Shilin County was selected as the study site. Probability Proportional to Size (PPS) sampling method was used to select representative sample of 6006 residents aged 45 years and over from Shilin. Information was obtained from a cross-sectional survey on health. Data was analyzed using a multilevel logistic modeling. The prevalence rates of overweight and obesity were 12.10% and 2.15% in the study area. Males had a higher prevalence of overweight than females (13.60% vs. 10.71%). Similar situation was seen in the prevalence of obesity (2.82% vs. 1.52%). Both village level and individual level variables were associated with obesity, whereas only individual level variables were related to overweight. Elderly had lower probability of being overweight and obese than younger people with odds ratio (OR) as 0.95 (95% CI:0.83-0.97) and 0.93 (95% CI: 0.82-0.96), respectively. Males had higher probability of being overweight and obese than females: OR of 0.89 (95% CI:0.78-0.98) and OR of 0.87 (95% CI: 0.78-0.97),respectively. Individuals with lower family income had increased probability of having obesity (OR = 0.81, 95% CI: 0.73-0.95). Factor as living in a higher income village was associated with lower prevalence of obesity (OR = 0.92, 95% CI: 0.85-0.98). Interventions at village level on obesity in parallel with those at individual level were needed. Prevention and intervention on obesity should be emphasized in villages with higher income.


Unraveling the metabolic effects of benzophenone-3 on the endosymbiotic dinoflagellate Cladocopium goreaui.
As a well-known pseudo-persistent environmental pollutant, oxybenzone (BP-3) and its related organic ultraviolet (UV) filters have been verified to directly contribute to the increasing mortality rate of coral reefs. Previous studies have revealed the potential role of symbiotic Symbiodiniaceae in protecting corals from the toxic effects of UV filters. However, the detailed protection mechanism(s) have not been explained. Here, the impacts of BP-3 on the symbiotic Symbiodiniaceae Cladocopium goreaui were explored. C. goreaui cells exhibited distinct cell growth at different BP-3 doses, with increasing growth at the lower concentration (2 mg L-1) and rapid death at a higher concentration (20 mg L-1). Furthermore, C. goreaui cells showed a significant BP-3 uptake at the lower BP-3 concentration. BP-3 absorbing cells exhibited elevated photosynthetic efficiency, and decreased cellular carbon and nitrogen contents. Besides, the derivatives of BP-3 and aromatic amino acid metabolism highly responded to BP-3 absorption and biodegradation. Our physiological and metabolic results reveal that the symbiotic Symbiodiniaceae could resist the toxicity of a range of BP-3 through promoting cell division, photosynthesis, and reprogramming amino acid metabolism. This study provides novel insights into the influences of organic UV filters to coral reef ecosystems, which urgently needs increasing attention and management.


The Consequences of a Disruption in Cyto-Nuclear Coadaptation on the Molecular Response to a Nitrate Starvation in Arabidopsis.
Mitochondria and chloroplasts are important actors in the plant nutritional efficiency. So, it could be expected that a disruption of the coadaptation between nuclear and organellar genomes impact plant response to nutrient stresses. We addressed this issue using two Arabidopsis accessions, namely Ct1 and Jea, and their reciprocal cytolines possessing the nuclear genome from one parent and the organellar genomes of the other one. We measured gene expression, and quantified proteins and metabolites under N starvation and non-limiting conditions. We observed a typical response to N starvation at the phenotype and molecular levels. The phenotypical response to N starvation was similar in the cytolines compared to the parents. However, we observed an effect of the disruption of genomic coadaptation at the molecular levels, distinct from the previously described responses to organellar stresses. Strikingly, genes differentially expressed in cytolines compared to parents were mainly repressed in the cytolines. These genes encoded more mitochondrial and nuclear proteins than randomly expected, while N starvation responsive ones were enriched in genes for chloroplast and nuclear proteins. In cytolines, the non-coadapted cytonuclear genomic combination tends to modulate the response to N starvation observed in the parental lines on various biological processes.


Motor restlessness, sleep disturbances, thermal sensory alterations and elevated serum iron levels in Btbd9 mutant mice.
Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sensory-motor neurological disorder with a circadian component. RLS is characterized by uncomfortable sensations in the extremities, generally at night or during sleep, which often leads to an uncontrollable urge to move them for relief. Recently, genomic studies identified single-nucleotide polymorphisms in BTBD9, along with three other genes, as being associated with a higher risk of RLS. Little is known about the function of BTBD9 or its potential role in the pathophysiology of RLS. We therefore examined a line of Btbd9 mutant mice we recently generated for phenotypes similar to symptoms found in RLS patients. We observed that the Btbd9 mutant mice had motor restlessness, sensory alterations likely limited to the rest phase, and decreased sleep and increased wake times during the rest phase. Additionally, the Btbd9 mutant mice had altered serum iron levels and monoamine neurotransmitter systems. Furthermore, the sensory alterations in the Btbd9 mutant mice were relieved using ropinirole, a dopaminergic agonist widely used for RLS treatment. These results, taken together, suggest that the Btbd9 mutant mice model several characteristics similar to RLS and would therefore be the first genotypic mouse model of RLS. Furthermore, our data provide further evidence that BTBD9 is involved in RLS, and future studies of the Btbd9 mutant mice will help shine light on its role in the pathophysiology of RLS. Finally, our data argue for the utility of Btbd9 mutant mice to discover and screen novel therapeutics for RLS.


A Simple and Label-Free Detection of As3+ using 3-nitro-L-tyrosine as an As3+-chelating Ligand.
A simple and rapid As3+ detection method using 3-nitro-L-tyrosine (N-Tyr) is reported. We discovered the specific property of N-Tyr, which specifically chelates As3+. The reaction between As3+ and N-Tyr induces a prompt color change to vivid yellow, concomitantly increasing the absorbance at 430 nm. The selectivity for As3+ is confirmed by competitive binding experiments with various metal ions (Hg2+, Pb2+, Cd2+, Cr3+, Mg2+, Ni2+, Cu2+, Fe2+, Ca2+, Zn2+, and Mn2+). Also, the N-Tyr binding site, binding affinity, and As3+/N-Tyr reaction stoichiometry are investigated. The specific reaction is utilized to design a sensor that enables the quantitative detection of As3+ in the 0.1-100 μM range with good linearity (R2 = 0.995). Furthermore, the method's applicability for the analysis of real samples, e.g., tap and river water, is successfully confirmed, with good recoveries (94.32-109.15%) using As3+-spiked real water samples. We believe that our discovering and its application for As3+ analysis can be effectively utilized in environmental analyses such as those conducted in water management facilities, with simplicity, rapidity, and ease.