Revisiting the relationship between carbon emission, renewable energy consumption, forestry, and agricultural financial development for China.
Globally, the use of modern technologies is increasing along with carbon emission due to the consumption of fossil fuels to operate modern technologies. Therefore, in this study, we aimed to investigate the relationship between carbon emission, renewable energy consumption, forestry, and agricultural value added per capita from 1998 to 2018. The auto-regressive distribution lag model was estimated for long-run and short-run correlation analysis. The results of this study revealed that carbon emission decreases owed increases in forest areas in the long and well as short-run nexus. Furthermore, in the short run, carbon emission decreases due to an increase in renewable energy consumption. In addition, the carbon emission was run in an upward direction parallel to agricultural financial development. Furthermore, this study confirmed that the unidirectional causality between variables by estimating the non-Granger causality test. Therefore, this study suggests that to combat carbon emissions with carbon emission, it is necessary to switch from nonrenewable energy to renewable energies and organic fertilizer consumption along with afforestation to make the climate free from carbon.


A new idiocerine leafhopper genus, Dianica, from China (Hemiptera: Cicadellidae).
The new idiocerine leafhopper genus Dianica gen. nov. is described and illustrated based one species, Dianica rugulosa sp. nov. from southwestern China. A diagnosis of the new genus is given and compared to the related genera. In addition, a key to genera and a checklist of species for Tasnimocerus group are also provided.


C-reactive protein increases plasminogen activator inhibitor-1 expression in human endothelial cells.
C-reactive protein (CRP) is an inflammatory marker which predicts cardiovascular disease. However, it is not fully understood whether CRP has direct effects on endothelial functions and gene expression. The purpose of current study was to determine the effects and molecular mechanisms of CRP on the expression of plasminogen activator inhibitor-1 (PAI-1) in human endothelial cells. Human coronary artery endothelial cells (HCAEC) were treated with CRP at clinically relevant concentrations for different durations. PAI-1 mRNA, protein and enzyme activities were studied. The effects of CRP on MAPK p38 phosphorylation was also studied by Bio-Plex luminex immunoassay. In addition, other types of human endothelial cells isolated from umbilical vein, skin, and lung microvessels were tested. CRP significantly increased PAI-1 mRNA levels in a time- and concentration-dependent manner. The protein level and enzyme activity of PAI-1 in the supernatant of CRP-treated HCAEC cultures were significantly increased. Anti-CD32 antibody effectively blocked CRP-induced PAI-1 mRNA expression. In addition, CRP significantly increased CD32 mRNA levels and enhanced phosphorylation of MAPK p38. Furthermore, antioxidant curcumin dramatically inhibited CRP-induced PAI-1 mRNA expression. The effect of CRP on PAI-1 expression was also confirmed in other types of human endothelial cells. In conclusion, CRP significantly increased the expression of PAI-1 in HCAEC and other human endothelial cells. CRP also increased its receptor CD32 expression which may further enhance its action. CRP-induced PAI-1 expression may be mediated by oxidative stress and p38 signal pathway as antioxidant effectively blocks the effect of CRP on HCAEC.


Vitamin E affects lung biochemical and morphologic response to hyperoxia in the newborn rabbit.
The effects of parenteral vitamin E treatment on aspects of the pulmonary biochemical and morphologic response to 100% oxygen were studied in newborn rabbits manifesting chemical evidence of vitamin E deficiency. Pups treated with 2 mg/100 g body weight increased serum vitamin E levels from 0.39 to 2.17 mg/dl by 72 hr and lung tissue vitamin E content from 3.52 to 17 mg/mg wet weight of lung. In vitro lipid peroxidation in lung homoginates of animals in 100% oxygen for 72 hr was inhibited by approximately 80% in animals receiving 100% oxygen plus vitamin E. Hyperoxia-induced increases in the pulmonary antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and glutathione reductase were diminished by vitamin E administration. Lungs from vitamin E-treated animals did not show the early lung epithelial injury seen in animals exposed to 100% oxygen but not treated with vitamin E. Mophometric analysis of lungs of animals in room air for 72 hr showed 81.6% of lung to be normal as compared with 43.3% normal lung in the group maintained in 100% oxygen for 72 hr. In the group treated with oxygen plus vitamin E, the lungs were similar to room air controls (82.6% normal). This study thus provides further evidence for a direct antioxident affect of vitamin E in lung.


Thin-layer electrophoresis with PhastSystem facilitates analysis of phosphoamino acids from proteins bound to Immobilon.
A modification of thin-layer electrophoresis of phosphoamino acids on miniplates, using the PhastSystem (Pharmacia) is described. This method not only reduces the amount of radioactivity required but also the radioactive waste. In addition, it also decreases the handling of hazardous substances and takes only a fraction of the time required for the standard procedure.


Menstrual blood-derived endometrial stem cells alleviate neuroinflammation by modulating M1/M2 polarization in cell and rat Parkinson's disease models.
Neuroinflammation is closely related to the development of Parkinson's disease (PD). Because of the extensive sources, non-invasive and periodical collection method, human menstrual blood-derived endometrial stem cells (MenSCs) have been explored as a promising tool for treatment of PD. This study aimed to investigate if MenSCs could inhibit neuroinflammation in PD rats by regulating M1/M2 polarization and to excavate the underlying mechanisms. MenSCs were co-cultured with 6-OHDA-exposed microglia cell lines. Then the morphology of microglia cells and the level of inflammatory factors were assessed by immunofluorescence and qRT-PCR. After MenSCs were transplanted into the brain of PD rats, animal motor function, the expression of tyrosine hydroxylase, and the level of inflammatory factors in the cerebrospinal fluid (CSF) and serum were detected to evaluate the therapeutic potential of MenSCs. Meanwhile, the expression of M1/M2 phenotype related genes was detected by qRT-PCR. One protein array kit containing 1000 kinds of factors was used to detect the protein components in the conditioned medium of MenSCs. Finally, bioinformatic analysis was performed to analyze the function of factors secreted by MenSCs and the signal pathways involved in. MenSCs could suppress 6-OHDA-induced microglia cell activation and significantly decrease inflammation in vitro. After transplantation into the brain of PD rats, MenSCs improved animal motor function, which was indicated by the increased movement distance, ambulatory episodes, exercise time on the rotarod, and less contralateral rotation. Additionally, MenSCs reduced the loss of dopaminergic neurons and down-regulated the level of pro-inflammatory factors in the CSF and serum. Moreover, q-PCR and WB results showed the transplantation of MenSCs significantly down-regulated the expression of M1 phenotype cell markers and meanwhile up-regulated the expression of M2 phenotype cell markers in the brain of PD rats. 176 biological processes including inflammatory response, negative regulation of apoptotic process, and microglial cell activation were enriched by GO-BP analysis. 58 signal pathways including PI3K/Akt and MAPK were enriched by KEGG analysis. In conclusion, our results provide preliminary evidence for the anti-inflammation capacity of MenSCs by regulating M1/M2 polarization. We firstly demonstrated the biological process of factors secreted by MenSCs and the signal pathways involved in using protein array and bioinformatic analysis.


Reducing asthma hospitalisations in at-risk children: A systematic review.
To identify interventions that reduce hospitalisations and improve related outcomes in children at risk of asthma hospital admissions. Medline, Embase, Pubmed and Cochrane Library search from January 2002 to April 2020. randomised controlled trials of any intervention for children with asthma who are at risk of hospitalisations. hospitalisation (primary outcome), rescue oral corticosteroid use, school absences, quality of life and cost-effectiveness. Twelve randomised controlled trials were conducted with 2719 participants. Due to heterogeneity of interventions and reporting of outcomes, a meta-analysis was not conducted. Multi-modal interventions comprising caregiver education, reduction of home environmental allergens and regular follow-up reduced hospitalisations, rescue corticosteroid use and improved quality of life. Cost-effectiveness was not reported. Three studies scored an overall low risk of bias, and nine had some concerns. Multi-modal interventions can be effective in reducing hospitalisations, rescue oral corticosteroid use and quality of life but cost-effectiveness is unknown.


Anti-S-100 serum blocks long-term potentiation in the hippocampal slice.
S-100 is a calcium-binding, glial protein which has been shown to be involved in behavioral learning and memory tasks. Long-term potentiation (LTP) in the hippocampus is a long-lasting enhancement of synaptic efficacy evoked by repetitive afferent stimulation. When anti-S-100 serum is applied by pressure ejection onto the stratum radiatum of area CA1 of the hippocampal slice, the amplitude of the extracellularly recorded population spike is not affected. However, repetitive stimulation of the afferents during S-100 application failed to produce LTP. At a distant site in the same slice, LTP occurs normally. Preimmune normal rabbit serum had no effect on the development of LTP. It appears that S-100 protein is involved in the establishment of LTP.


Use of laser-assisted intracytoplasmic sperm injection (ICSI) in patients with a history of poor ICSI outcome and limited metaphase II oocytes.
In this study, laser-assisted intracytoplasmic sperm injection (ICSI) improved the fertilization rate and the embryo quality in patients with a history of poor ICSI outcome and with limited metaphase II oocytes. This technique is less traumatic to the oocytes during the procedure, and the use of the technique may be expanded.


The Short-term Effects of Temperature on Infectious Diarrhea among Children under 5 Years Old in Jiangsu, China: A Time-series Study (2015-2019).
The association between meteorological factors and infectious diarrhea has been widely studied in many countries. However, investigation among children under 5 years old in Jiangsu, China remains quite limited. Data including infectious diarrhea cases among children under five years old and daily meteorological indexes in Jiangsu, China from 2015 to 2019 were collected. The lag-effects up to 21 days of daily maximum temperature (Tmax) on infectious diarrhea were explored using a quasi-Poisson regression with a distributed lag non-linear model (DLNM) approach. The cases number of infectious diarrhea was significantly associated with seasonal variation of meteorological factors, and the burden of disease mainly occurred among children aged 0-2 years old. Moreover, when the reference value was set at 16.7°C, Tmax had a significant lag-effect on cases of infectious diarrhea among children under 5 years old in Jiangsu Province, which was increased remarkably in cold weather with the highest risk at 8°C. The results of DLNM analysis implicated that the lag-effect of Tmax varied among the 13 cities in Jiangsu and had significant differences in 8 cities. The highest risk of Tmax was presented at 5 lag days in Huaian with a maximum RR of 1.18 (95% CI: 1.09, 1.29). Suzhou which had the highest number of diarrhea cases (15830 cases), had a maximum RR of 1.04 (95% CI:1.03, 1.05) on lag 15 days. Tmax is a considerable indicator to predict the epidemic of infectious diarrhea among 13 cities in Jiangsu, which reminds us that in cold seasons, more preventive strategies and measures should be done to prevent infectious diarrhea.


Computer-generated pulse sequences for 1H-15N and 1Hα-13Cα separated local-field experiments.
High-resolution separated local field (SLF) experiments are employed in oriented-sample solid state NMR to measure angular-dependent heteronuclear dipolar couplings for structure determination. While traditionally these experiments have been designed analytically by determining cycles of pulses with specific phases and durations to achieve cancellation of the homonuclear dipolar terms in the average Hamiltonian, recent work has introduced a computational approach to optimizing linewidths of the 1H-15N dipolar resonances. Accelerated by GPU processors, a computer algorithm searches for the optimal parameters by simulating numerous 1H-15N NMR spectra. This approach, termed ROULETTE, showed promising results by developing a new pulse sequence (ROULETTE-1.0) exhibiting 18% sharper mean linewidths than SAMPI4 for an N-acetyl Leucine (NAL) crystal. Herein, we expand on this previous work to improve the performance of the 1H-15N SLF experiment and extend the work beyond the original approach to new SLF experiments. The new algorithm, in addition to finding pulse durations and phases, now searches for the optimal on/off application scheme of radio frequency irradiation on each channel. This constitutes true de novo optimization, effectively optimizing every aspect of a pulse sequence instead of just phases and durations. With an improved ROULETTE algorithm, we have found a new 1H-15N pulse sequence, termed ROULETTE-2.0, yielding 32% sharper mean linewidths than SAMPI4 for NAL crystal at 500 MHz 1H frequency. Whereas both SAMPI4 and ROULETTE-1.0 have a window where the rf power on the I-channel is turned off, the new pulse sequence is entirely windowless. Furthermore, the reliability of the algorithm has been greatly improved in terms of avoiding false positives, i.e. well-performing pulse sequences in silica that fail to render narrow resonances in experiment. The program has been extended to the 13Cα-1Hα SLF experiments, using a 6 subdwell architecture similar to the 1H-15N optimization. Compared to the PISEMA pulse sequence, the mean 13Cα-1Hα linewidth is 17% sharper for the new pulse sequence, termed ROULETTE-CAHA. In addition to superior performance, the work demonstrates the broad applicability of the algorithm and its adaptability to different NMR experiments and spin systems.


Kinetic evidence for three photolyzable taxonomic conformational substates in oxymyoglobin.
The kinetics of oxygen geminate binding with the taxonomic substates of MbO2 are reported. The maximum entropy method was used to analyze the rebinding kinetics of MbCO and MbO2 monitored in the Soret. The resulting rate distributions were found to consist of a small number of overlapping bands. A global parametric fit of a series of rate distributions recorded at several temperatures was performed using a Gaussian basis set to resolve the individual enthalpy distributions P(H). This approach was first validated by showing that the well-documented taxonomic substates of MbCO could be recovered. The method was then applied to MbO2. Three taxonomic substates were identified at pH 4.8, whereas only two of them contribute to oxygen geminate rebinding at pH 7.0. These findings show that, similarly to MbCO, MbO2 also exists as three photolyzable and kinetically different taxonomic substates and suggest reconsidering the issue of the photolysis quantum yield of MbO2.


Allosteric activation of Hsp70 reduces mutant huntingtin levels, the clustering of N-terminal fragments, and their nuclear accumulation.
Huntington's disease (HD) is caused by a mutant huntingtin protein that misfolds, yields toxic N-terminal fragments, aggregates, and disrupts proteostasis. The Hsp70 chaperone is a potential therapeutic target as it prevents proteotoxicity by favouring protein folding, disaggregation, or degradation. We tested the hypothesis that allosteric Hsp70 activation with a pharmacological mimetic of the Hsp70 co-chaperone Hip, YM-1, could modulate huntingtin proteostasis. We used HD cell models expressing either N-terminal or full-length huntingtin. Using single-cell analysis we studied huntingtin aggregation in different cellular compartments by fluorescence microscopy. Protein interaction was evaluated by immunoprecipitation, while protein levels were quantified by immunofluorescence and western-blot. N-terminal huntingtin interacted with Hsp70 and increased its levels. Treatment with YM-1 reduced N-terminal huntingtin clustering and nuclear aggregation. Full-length mutant huntingtin also interacted with Hsp70, and treatment with YM-1 reduced huntingtin levels when combined with Hsp70 induction by heat shock. Mechanistically, YM-1 increases the Hsp70 affinity for substrates, promoting their proteasomal degradation. Consistently, YM-1 reduced the levels of ubiquitinated proteins. Interestingly, YM-1 accumulated in mitochondria, interfered with its Hsp70 isoform involved in protein import, and increased NRF1 levels, a regulator of proteasome genes. We thus suggest that YM-1 may trigger the coordination of mitochondrial and cytosolic proteostasis, enhancing protein degradation. Our findings show that the strategy of allosteric Hsp70 activation holds potential for HD. While drug efficacy may be limited to tissues with elevated Hsp70, combined therapies with Hsp70 elevating strategies could harness the full potential of allosteric Hsp70 activators for HD.


Working memory components as predictors of children's mathematical word problem solving.
This study determined the working memory (WM) components (executive, phonological loop, and visual-spatial sketchpad) that best predicted mathematical word problem-solving accuracy of elementary school children in Grades 2, 3, and 4 (N=310). A battery of tests was administered to assess problem-solving accuracy, problem-solving processes, WM, reading, and math calculation. Structural equation modeling analyses indicated that (a) all three WM components significantly predicted problem-solving accuracy, (b) reading skills and calculation proficiency mediated the predictive effects of the central executive system and the phonological loop on solution accuracy, and (c) academic mediators failed to moderate the relationship between the visual-spatial sketchpad and solution accuracy. The results support the notion that all components of WM play a major role in predicting problem-solving accuracy, but basic skills acquired in specific academic domains (reading and math) can compensate for some of the influence of WM on children's mathematical word problem solving.


Protective effect of prostaglandin A2 against menadione-induced cell injury in cultured porcine aorta endothelial cells.
Prostaglandin A2 (PGA2) stimulates the biosynthesis of gamma-glutamylcysteine synthetase and elevates glutathione (GSH) contents in cultured mammalian cells. To clarify the importance of gamma-glutamylcysteine synthetase induction in the defence of endothelial cells against oxidative stress, the effect of PGA2 on menadione (2-methyl-1,4-naphthoquinone)-induced cell injury was examined. Incubation of porcine aorta endothelial cells with menadione produced marked loss of cellular GSH and protein sulfhydryl groups, followed by leakage of lactic dehydrogenase (LDH) into the culture medium. The LDH leakage and modification of protein thiol was, however, completely prevented by pretreatment of the cells with PGA2. The protective effect of PGA2 was more potent than that of cysteine delivery agents such as methionine, N-acetylcysteine or 2-oxo-4-thiazolidine carboxylic acid (OTC). The results suggest that cellular GSH plays an important role in the defence against oxidative stress, and induction of gamma-glutamylcysteine synthetase is effective for protecting vascular endothelial cells.


Identification of differentially expressed genes associated with semigamy in Pima cotton (Gossypium barbadense L.) through comparative microarray analysis.
Semigamy in cotton is a type of facultative apomixis controlled by an incompletely dominant autosomal gene (Se). During semigamy, the sperm and egg cells undergo cellular fusion, but the sperm and egg nucleus fail to fuse in the embryo sac, giving rise to diploid, haploid, or chimeric embryos composed of sectors of paternal and maternal origin. In this study we sought to identify differentially expressed genes related to the semigamy genotype by implementing a comparative microarray analysis of anthers and ovules between a non-semigametic Pima S-1 cotton and its doubled haploid natural isogenic mutant semigametic 57-4. Selected differentially expressed genes identified by the microarray results were then confirmed using quantitative reverse transcription PCR (qRT-PCR). The comparative analysis between isogenic 57-4 and Pima S-1 identified 284 genes in anthers and 1,864 genes in ovules as being differentially expressed in the semigametic genotype 57-4. Based on gene functions, 127 differentially expressed genes were common to both semigametic anthers and ovules, with 115 being consistently differentially expressed in both tissues. Nine of those genes were selected for qRT-PCR analysis, seven of which were confirmed. Furthermore, several well characterized metabolic pathways including glycolysis/gluconeogenesis, carbon fixation in photosynthetic organisms, sesquiterpenoid biosynthesis, and the biosynthesis of and response to plant hormones were shown to be affected by differentially expressed genes in the semigametic tissues. As the first report using microarray analysis, several important metabolic pathways affected by differentially expressed genes in the semigametic cotton genotype have been identified and described in detail. While these genes are unlikely to be the semigamy gene itself, the effects associated with expression changes in those genes do mimic phenotypic traits observed in semigametic plants. A more in-depth analysis of semigamy is necessary to understand its expression and regulation at the genetic and molecular level.


Development of alginate-based hydrogels: Crosslinking strategies and biomedical applications.
Natural polysaccharide-based hydrogels have drawn much concern in the biomedical fields. Among them, alginate, a natural polyanionic polysaccharide, has become one of the research hotspots, because of its abundant source, biodegradability, biocompatibility, solubility, modification flexibility, and other characteristics or physiological functions. Recently, through adopting various physical or chemical crosslinking strategies, selecting suitable crosslinking or modification reagents, precisely controlling the reaction conditions, or introducing organic or inorganic functional materials, a variety of alginate-based hydrogels with excellent performance have been continuously developed, considerably expanding the breadth and depth of their applications. Here, various crosslinking strategies in the preparation of alginate-based hydrogels are comprehensively introduced. The representative application progress of alginate-based hydrogels in drug carrier, wound dressing and tissue engineering is also summarized. Meanwhile, the application prospects, challenges and development trends of alginate-based hydrogels are discussed. It is expected to provide guidance and reference for the further development of alginate-based hydrogels.


The experience of headache pain--an assessment of the qualities of tension headache pain.
The subjective component of headache pain has been neglected in headache research. In this study of 65 chronic headache sufferers, assessment of the subjective component was amplified using the McGill Pain Questionnaire (MPQ) as well as headache diaries. The overall level of pain experienced was as high as that previously reported for cancer and phantom-limb patients. Assessment of sensory pain qualities (MPQ) revealed differences between tension and migraine headache types; tension headaches were felt to be "tight", while migraines were experienced as "sharp", "blinding", "nauseating" and "sickening". The results thus support a dichotomous rather than a continuum model of headache. The relationship between the subjective experience of headache and mood (Wakefield Depression Scale) and personality (EPQ) was examined. Pain intensity and affective reactions to pain were associated with general mood state; however, no subjective measures correlated with personality indices. It was argued that the MPQ provided valuable additional information to be used with headache diaries, particularly in the assessment of sensory qualities and affective reactions to pain.


Platelet adenylate cyclase and phospholipase C activity in posttraumatic stress disorder.
Adenylate cyclase and phospholipase C activity were examined in platelet membranes obtained from 19 male subjects with combat-related posttraumatic stress disorder (PTSD) and 35 age- and gender-matched healthy controls. Basal and forskolin-stimulated adenylate cyclase activity were significantly lower in the PTSD group whereas aluminum chloride plus sodium fluoride (AlCl3/NaF)- and prostaglandin E1 (PGE1)-stimulated responses were normal. There was no difference in phospholipase C activity between the two groups. The lower basal and forskolin-stimulated adenylate cyclase responses replicate a previous report and suggest that PTSD may be associated with an abnormality of the catalytic subunit of the receptor-adenylate cyclase complex.


Deiodination in the presence of Dehalococcoides mccartyi strain CBDB1: comparison of the native enzyme and co-factor vitamin B12.
Triiodinated benzoic acid derivatives are widely used as contrast media for medical examinations and are found at high concentrations in urban aquatic environments. During bank filtration, deiodination of iodinated contrast media has been observed under anoxic/anaerobic conditions. While several bacterial strains capable of dechlorination and debromination have been isolated and characterized, deiodination has not yet been shown for an isolated strain. Here, we investigate dehalogenation of iodinated contrast media (ICM), triiodobenzoic acids (TIBA), and analogous chlorinated compounds by Dehalococcoides mccartyi strain CBDB1 and its corrinoid co-factor vitamin B12. No cell growth of CBDB1 was observed using iodinated compounds as electron acceptor. Only negligible deiodination occurred for ICM, whereas 2,3,5-TIBA was nearly completely deiodinated by CBDB1 without showing cell growth. Furthermore, TIBA inhibited growth with hexachlorobenzene which is usually a well-suited electron acceptor for strain CBDB1, indicating that TIBA is toxic for CBDB1. The involvement of CBDB1 enzymes in the deiodination of TIBA was verified by the absence of deiodination activity after heat inactivation. Adding iodopropane also inhibited the deiodination of TIBA by CBDB1 cells, indicating the involvement of a corrinoid-enzyme in the reductive TIBA deiodination. The results further suggest that the involved electron transport is decoupled from proton translocation and therefore growth. Graphical abstract.


[How to diagnose and treat psoriasis of the nails].
Psoriasis is an inherited chronic hyper proliferative autoimmune disease. Nail involvement is common and is found in 61% of cases of cutaneous psoriasis, with lifetime incidence of 90%; 80 to 90% in patients with psoriatic arthritis. Classical manifestations on the nail apparatus are correlated with the origin site of the disease. The proximal matrix produces pitting, trachyonychia and Beau's lines, transverse grooves. The distal matrix (lunula) may appear spotted or erythematous in color. Inflammation of the mid or distal matrix causes leuconychia due to nail incorporation of parakeratotic cells. Nail bed and hyponychium can show onycholysis, oil drops (salmon patches) subungual hyperkeratosis and at the distal nail bed splinter hemorrhages. Induction or severe exacerbation of psoriasis may be due to drugs, such as β-blockers, lithium, antimalarial agents, anti-TNF and interferon.


Effect of addition of Nano hydroxyapatite particles on wear of resin modified glass ionomer by tooth brushing simulation.
Recently, incorporation of nanohydroxyapatite (NHA) has been suggested to improve the mechanical properties of glass ionomers (GIs). This study aimed to assess the effect of addition of NHA on wear of resin modified glass ionomer (RMGI) by tooth brushing simulation. In this in vitro, experimental study, NHA in 1, 2, 5, 7 and 10wt% concentrations was added to Fuji II LC RMGI powder, and 48 samples (5×5mm) in five experimental and one control group (n=8) were fabricated. After polishing, cleaning and incubation at 37°C for three weeks, the samples were weighed and subjected to tooth brushing simulation in a toothpaste slurry according to ISO14569-1. Then, they were weighed again and the weight loss was calculated. The data were analyzed using one-way ANOVA and Tukey's test. The highest and the lowest weight loss was found in the 0% NHA (-1.052±0.176) and 5% NHA (-0.370±0.143) groups, respectively. Wear was significantly higher in 0% NHA group (P<0.05). No difference was detected in wear between 2 and 5wt% NHA or among 1, 7 and 10wt% NHA groups. Significant differences were noted in wear between 2 and 5wt% NHA and 1, 7 and 10wt% NHA groups (P<0.001). Incorporation of up to 10wt% of NHA increases the wear resistance of Fuji II LC RMGI. This increase was the highest when 2 and 5wt% NHA were added. Key words:Glass ionomer, hydroxyapatites, nanoparticles, dental restoration wear.


Potentials and limitations of peripheral nerve injury models in rodents with particular reference to the femoral nerve.
Restoration of function after peripheral nerve repair in humans is unsatisfactory. Various causes of poor recovery have been proposed. Still, we do not understand which of these potential factors are indeed detrimental and do not know how to manipulate them experimentally in a clinically feasible way. Future success largely depends on methodological improvement in rodent models. An example of recent progress is the introduction of new functional and anatomical outcome measures in the facial nerve injury paradigm which led to novel insights into facial nerve regeneration and a new therapeutic concept. Less success can be ascribed to the use of the classical spinal nerve model, the sciatic nerve paradigm, not least because of its anatomical and functional complexity making assessment of recovery challenging. A simpler alternative to the sciatic nerve is the femoral nerve model. It offers, alongside with its known usefulness for studies on precision of motor reinnervation, the possibility of reliable functional assessments and a straightforward search of anatomical substrates of dysfunction. The structure-function approach in the femoral nerve paradigm has been useful for testing of novel therapeutic means and analyses of regeneration in mutant mice. The potential of the method has still not been really exploited and its more extensive use may contribute to better understanding of nerve regeneration.


Fingolimod.
In the absence of a better alternative, subcutaneous interferon beta is the standard first-line treatment for relapsing-remitting multiple sclerosis. Fingolimod, an oral immunosuppressant that reduces the circulating lymphocyte count, is in the process of receiving marketing authorisation for this use in the European Union. Initial clinical evaluation is based on 2 trials. In a 12-month, comparative, double-blind, randomised trial including 1292 patients daily treatment with oral fingolimod (0.5 mg or 1.25 mg) modestly prolonged the interval between exacerbations compared to weekly intramuscular injections of interferon beta-1a: about one exacerbation prevented every 6 years. No tangible impact on progression of disability was observed. A double-blind placebo-controlled trial that lasted 2 years also showed a statistically significant reduction in the annual frequency of exacerbations. There was no firm evidence that fingolimod had a tangible effect on progression of disability. An indirect comparison suggests that the impact of fingolimod on exacerbations is roughly similar to that of cladribine, another oral immunosuppressant that received a negative opinion in this indication from the European Medicines Agency. Several short-term adverse effects consistent with the pharmacological action of fingolimod and the results of animal pharmacology studies were observed in clinical trials, including infections (especially herpetic), pulmonary disorders, cardiac conduction disorders and macular oedema. A risk of lymphoma and heart failure is possible in the longer term. Given the modest gain in efficacy compared with interferon beta (based on weak supporting evidence) and the major adverse effects of fingolimod, it is better to continue to use interferon beta for initial treatment of relapsing-remitting multiple sclerosis, and to reserve fingolimod for use in clinical trials in which patients are closely monitored.


Neural differentiation of amphibian gastrula ectoderm exposed to phorbol ester.
Ectoderm from early gastrula stages of amphibians was isolated and treated with phorbol 12-myristate 13-acetate. The ectoderm formed neural tissue and in a few cases also mesenchyme and melanophores. The control explants formed atypical epidermis. In explants treated with phorbol 12-myristate 13-acetate the mitotic rate was increased.


MALDI imaging mass spectrometry of N-linked glycans on formalin-fixed paraffin-embedded murine kidney.
Recent developments in spatial proteomics have paved the way for retrospective in situ mass spectrometry (MS) analyses of formalin-fixed paraffin-embedded clinical tissue samples. This type of analysis is commonly referred to as matrix-assisted laser desorption/ionization (MALDI) imaging. Recently, formalin-fixed paraffin-embedded MALDI imaging analyses were augmented to allow in situ analyses of tissue-specific N-glycosylation profiles. In the present study, we outline an improved automated sample preparation method for N-glycan MALDI imaging, which uses in situ PNGase F-mediated release and measurement of N-linked glycans from sections of formalin-fixed murine kidney. The sum of the presented data indicated that N-glycans can be cleaved from proteins within formalin-fixed tissue and characterized using three strategies: (i) extraction and composition analysis through on-target MALDI MS and liquid chromatography coupled to electrospray ionization ion trap MS; (ii) MALDI profiling, where N-glycans are released and measured from large droplet arrays in situ; and (iii) MALDI imaging, which maps the tissue specificity of N-glycans at a higher resolution. Thus, we present a complete, straightforward method that combines MALDI imaging and characterization of tissue-specific N-glycans and complements existing strategies.


Polarised cell migration: intrinsic and extrinsic drivers.
Cell polarity arises out of asymmetry of the distribution and organisation of cell contents. Polarity is an important feature of all living organisms and much energy is devoted to breaking symmetry and establishing polarity. Recent developments in our understanding of how the budding yeast Saccharomyces cerevisiae establishes and maintains polarity for cell division shed light on universal mechanisms that may be relevant to both asymmetric cell division and polarised cell migration in other organisms. Here, we summarise some of the recent developments in our understanding of polarity of the cytoskeleton and associated signalling molecules as it relates to cell migration. Parallels are drawn between planar cell polarity and apical-basal polarity in epithelial tissues and front-back polarity in migrating cells.


Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease.
To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease. Eighteen persons at risk for Huntington's disease had two positron emission tomographic glucose metabolic studies and two magnetic resonance imaging scans separated by 42 (+/- 9) months. Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology. Seven of the individuals were Huntington' disease gene negative by testing at the polymorphic DNA loci D4S10, D4S43, and D4S125; the remainder were gene positive by genetic testing or onset of chorea after study entry. None. Onset of chorea and imaging results. The gene-positive group demonstrated a significant 3.1% loss of glucose metabolic rate per year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48) compared with the gene-negative group. There was a 3.6% per year increase in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a linear measure of caudate atrophy. The rate of change in caudate size did not correlate with the rate of change in caudate metabolism, suggesting that metabolic loss and atrophy may develop independently. The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism.


Parent-Reported Strengths and Positive Qualities of Adolescents and Adults with Autism Spectrum Disorder and/or Intellectual Disability.
Despite increasing attention to understanding strengths in those on the autism spectrum, few studies have explored this in older individuals. The present study provides a qualitative analysis of parent-reported strengths and positive qualities of 68 15-30-year-olds with autism and/or intellectual disability (ID). Most parents (97%) reported at least one positive quality. Themes were consistent with previous studies; Personality characteristics (82%) and Sociability (53%) were reported most frequently. A Work Ethic/Motivation category not previously reported emerged. Autistic individuals (with/without ID) were more likely than those with ID-only to have a Specific Skill. Findings highlight the importance of recognizing strengths of autistic adults. Research is needed to understand how to best leverage positive qualities to promote goal achievement and quality of life.


Cyclic Tetrapyrrolic Photosensitisers from the leaves of Phaeanthus ophthalmicus.
Twenty-seven extracts from 26 plants were identified as photo-cytotoxic in the course of our bioassay guided screening program for photosensitisers from 128 extracts prepared from 64 terrestrial plants in two different collection sites in Malaysia - Royal Belum Forest Reserve in the State of Perak and Gunung Nuang in the State of Selangor. One of the photo-cytotoxic extracts from the leaves of Phaeanthus ophtalmicus was further investigated. The ethanolic extract of the leaves from Phaeanthus ophtalmicus was able to reduce the in vitro viability of leukaemic HL60 cells to < 50% when exposed to 9.6 J/cm2 of a broad spectrum light at a concentration of 20 μg/mL. Dereplication of the photo-cytotoxic fractions from P. ophthalmicus extracts based on TLC Rf values and HPLC co-injection of reference tetrapyrrolic compounds enabled quick identification of known photosensitisers, pheophorbide-a, pheophorbide-a methyl ester, 132-hydroxypheophorbide-a methyl ester, pheophytin-a and 151-hydroxypurpurin 7-lactone dimethyl ester. In addition, compound 1 which was not previously isolated as a natural product was also identified as 7-formyl-151-hydroxypurpurin-7-lactone methyl ester using standard spectroscopic techniques. Our results suggest that the main photosensitisers in plants are based on the cyclic tetrapyrrole structure and photosensitisers with other structures, if present, are present in very minor amounts or are not as active as those with the cyclic tetrapyrrole structure.


Acral persistent papular mucinosis: A case report and summary of 24 Japanese cases.
Acral persistent papular mucinosis is a rare subtype of localized lichen myxedematosus. We report a case of a 41-year-old woman with acral persistent papular mucinosis. She had a 5-year history of multiple, scattered, whitish papules, on the back of both hands, of 2-5 mm in diameter. Histopathological examination revealed a focal, fairly circumscribed area with sparse collagen fibers in the upper and middle dermis. The circumscribed area was positively stained with Alcian blue. The papules were clinically and histologically diagnosed as acral persistent papular mucinosis. We also summarized 24 Japanese acral persistent papular mucinosis cases, including ours. Although acral persistent papular mucinosis occurs predominantly in women according to overseas reports, the male : female ratio is 5:7 in Japan. It has been reported that tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) was effective in two Japanese cases. In our case, the patient had been treated with tranilast for 2 months without improvement. Further studies are required to confirm the efficacy of tranilast for acral persistent papular mucinosis.


Simulated annealing coupled replica exchange molecular dynamics--an efficient conformational sampling method.
Molecular dynamics simulated annealing (SA-MD) simulations are frequently used for refinement and optimization of peptide and protein structures. Depending on the simulation conditions and simulation length SA-MD simulations can be trapped in locally stable conformations far from the global optimum. As an alternative replica exchange molecular dynamics (RexMD) simulations can be used which allow exchanges between high and low simulation temperatures at all stages of the simulation. A significant drawback of RexMD simulations is, however, the rapid increase of the replica number with increasing system size to cover a desired temperature range. A combined SA-MD and RexMD approach termed SA-RexMD is suggested that employs a small number of replicas (4) and starts initially with a set of high simulation temperatures followed by gradual cooling of the set of temperatures until a target temperature has been reached. The protocol has been applied for the folding of several peptide systems and for the refinement of protein model structures. In all the cases, the SA-RexMD method turned out to be significantly more efficient in reaching low energy structures and also structures close to experiment compared to continuous MD simulations at the target temperature and to SA-MD simulations at the same computational demand. The approach is well suited for applications in structure refinement and for systematic force field improvement.


Decolonizing Zemiology: Outlining and Remedying the Blindness to (Post)colonialism Within the Study of Social Harm.
This paper hosts the first meaningful dialogue between two important epistemic movements for criminology: zemiology and decolonisation. I identify that zemiology has a disciplinary blindness to colonialism and explain this using Gurminder K. Bhambra's scholarship-and cognate scholarship-as a frame. Three cases-Pemberton's Harmful Societies, Grenfell, and Border Zemiology-are selected for their critical importance within zemiology. They are used to argue that zemiology works within a standard narrative of modernity characterised by capitalist nation-states, which does not recognise the colonial foundations of both of these. Capitalist modernity is, however, a colonial formation. Recognising this allows for a better understanding for a wide range of harms. I then discuss future directions for decolonial zemiology, advocating not for expansion of repertoire, but canonical revision so that colonialism is afforded space as an explanatory frame and zemiology can better explain social harm on a global level.


[Determination of the antihistaminic properties of histidine derivatives on models of guinea pig T- and B-lymphocyte rosette formation].
It was found that carnosine, like metiamide, an H-2 antagonist of histamine, is capable of inhibiting the histamine caused suppression of T rosette-formation by guinea-pig blood and spleen lymphocytes. The other histidine derivatives, imidazole lactate, imidazole pyruvate and N-acetyl histidine did not exhibit such properties. The data obtained allow classifying carnosine with H-2-histamine blockers and serve as one of the explanations of the mechanism of its antiallergic action.


Departures from Cost-Effectiveness Recommendations: The Impact of Health System Constraints on Priority Setting.
Abstract-The methods and application of cost-effectiveness analysis have reached an advanced stage of development. Many decision makers consider cost-effectiveness analysis (CEA) to be a valid and feasible approach toward setting health priorities, and it has been extensively applied in evaluating interventions and developing evidence-based clinical guidelines. However, the recommendations arising from cost-effectiveness analysis are often not implemented as intended. A fundamental reason for the failure to implement is that CEA assumes a single constraint, in the form of the budget constraint, whereas in reality decision makers may be faced with numerous other constraints. The objective of this article is to develop a typology of constraints that may act as barriers to implementation of cost-effectiveness recommendations. Six categories of constraints are considered: the design of the health system; costs of implementing change; system interactions between interventions; uncertainty in estimates of costs and benefits; weak governance; and political constraints. Where possible-and if applicable-for each class of constraint, the article discusses ways in which these constraints can be taken into account by a decision maker wishing to pursue the principles of cost-effectiveness.


Seasonal variation in rates of emergency room visits and acute admissions following recommended infant vaccinations in Ontario, Canada: a self-controlled case series analysis.
To determine if birth month has an effect on the incidence of adverse events following the 2- and 12-month recommended vaccinations. Using health administrative databases, we conducted a population-based retrospective cohort study and employed a self-controlled case series analysis approach. We included children born in Ontario, Canada between April 1st 2002 and March 31st 2010 who received the diphtheria, tetanus, pertussis, inactivated poliovirus and Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine recommended at 2 months and/or the measles, mumps, and rubella vaccine recommended at 12 months. We calculated the relative incidence (RI) of hospitalizations and emergency room visits within a pre-specified risk period compared to a control period following vaccination. We measured the effect of birth month using relative incidence ratios (RIRs) to compare the RI for infants born in each month to that for the month having the lowest RI. For the 2-month vaccination, we observed the lowest and highest RIs for infants born in October and April, respectively. The RIR (95% CI) for April compared to October was 2.06 (1.59-2.67, p<0.0001), consistent with a strong seasonal effect. For the 12-month vaccination, November births had the lowest RI, whereas August births had the highest. The RIR (95% CI) for August compared to November was 1.52 (1.30-1.77, p<0.0001). Our findings suggest a seasonal effect on susceptibility to adverse events following vaccination exists. Further study will be important to elucidate potential biological and/or behavioral explanations for the seasonal effect we observed.


Efficient multiwave mixing in the ultraslow propagation regime and the role of multiphoton quantum destructive interference.
We analyze a lifetime-broadened four-state four-wave-mixing (FWM) scheme in the ultraslow propagation regime and show that the generated FWM field can acquire the same group velocity and pulse shape as those of an ultraslow pump field. We show that a new type of induced transparency resulted from multiphoton destructive interference that significantly reduced the pump field loss. Such induced transparency based on multphoton destructive interference may have important applications in other nonlinear optical processes.


BOugie or stylet in patients UnderGoing Intubation Emergently (BOUGIE): protocol and statistical analysis plan for a randomised clinical trial.
Intubation-related complications are less frequent when intubation is successful on the first attempt. The rate of first attempt success in the emergency department (ED) and intensive care unit (ICU) is typically less than 90%. The bougie, a semirigid introducer that can be placed into the trachea to facilitate a Seldinger-like technique of tracheal intubation and is typically reserved for difficult or failed intubations, might improve first attempt success. Evidence supporting its use, however, is from a single academic ED with frequent bougie use. Validation of these findings is needed before widespread implementation. The BOugie or stylet in patients Undergoing Intubation Emergently trial is a prospective, multicentre, non-blinded randomised trial being conducted in six EDs and six ICUs in the USA. The trial plans to enrol 1106 critically ill adults undergoing orotracheal intubation. Eligible patients are randomised 1:1 for the use of a bougie or use of an endotracheal tube with stylet for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is severe hypoxaemia, defined as an oxygen saturation less than 80% between induction until 2 min after completion of intubation. Enrolment began on 29 April 2019 and is expected to be completed in 2021. The trial protocol was approved with waiver of informed consent by the Central Institutional Review Board at Vanderbilt University Medical Center or the local institutional review board at an enrolling site. The results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences. ClinicalTrials.gov Registry (NCT03928925).


Psychophysiological analysis of atopic dermatitis.
Ten atopic dermatitis (AD) patients with active symptomatology and ten control subjects matched for age, sex and race were administered a stress test. AD subjects had greater EMG and heart rate activity as well as higher anxiety scores on the Symptom Checklist-90R. These results suggest that AD may have a psychophysiological component.


Role of beta adrenergic receptor polymorphisms in heart failure: systematic review and meta-analysis.
Heart Failure (HF) is a common disorder associated with substantial morbidity and mortality. beta adrenergic receptors (betaAR) are the primary pathway through which cardiac function is influenced. Chronic beta(1)AR activation is implicated in the pathogenesis of HF and betaAR blockade improves survival in left ventricular systolic dysfunction. Common functional polymorphisms in beta adrenergic receptor genes (ADRB) have been associated with HF phenotypes, and with pharmacogenetic interaction with beta adrenergic receptor blockers (beta blockers). However, these associations have not been consistently replicated. The evidence for ADRB variant involvement in pathogenesis, progression and response to beta blockers in HF is reviewed. In addition, a meta-analysis of three studies analysing the effect of ADRB1 Arg389Gly polymorphism on left ventricular remodelling with the use of beta blockers, demonstrating a 5% improvement in left ventricular ejection fraction in Arg389 homozygotes, is presented. There is now accumulating molecular evidence for a different functional response to beta blockers associated with this polymorphism. In the future, confirmed genotypic associations may enable patients to be identified who are either at greater risk of developing HF, whose HF may rapidly progress, or who are unlikely to benefit from beta blockers, and such patients may benefit from targeted aggressive therapy.


Fitting of normal tissue tolerance data to an analytic function.
During external beam radiotherapy, normal tissues are irradiated along with the tumor. Radiation therapists try to minimize the dose of normal tissues while delivering a high dose to the target volume. Often this is difficult and complications arise due to irradiation of normal tissues. These complications depend not only on the dose but also on volume of the organ irradiated. Lyman has suggested a four-parameter empirical model which can be used to represent normal tissue response under conditions of uniform irradiation to whole and partial volumes as a function of the dose and volume irradiated. In this paper, Lyman's model has been applied to a compilation of clinical tolerance data developed by Emami et al. The four parameters to characterize the tissue response have been determined and graphical representations of the derived probability distributions are presented. The model may, therefore, be used to interpolate clinical data to provide estimated normal tissue complication probabilities for any combination of dose and irradiated volume for the normal tissues and end points considered.


Dichlorvos-induced hepatotoxicity in rats and the protective effects of vitamins C and E.
Dichlorvos is an organophosphate insecticide that is widely used in pest control. Vitamin C (200mg/kg)+vitamin E (200mg/kg), dichlorvos (1.6mg/kg), or a combination of vitamin C (200mg/kg)+vitamin E (200mg/kg)+dichlorvos (1.6mg/kg) was given to rats via oral gavage for 7 weeks. When rats of the dichlorvos-treated group and the vitamins+dichlorvos-treated group were compared with the control group, body weights were decreased and liver weights were increased significantly at the end of the 4th and 7th week. Serum total protein, albumin, triglyceride, low density lipoprotein-cholesterol (VLDL-cholesterol) levels were decreased, and serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl-transferase (GGT), lactate dehydrogenase (LDH), and total cholesterol levels were increased significantly at the end of the 4th and 7th week in the dichlorvos- and vitamins+dichlorvos-treated rats. There was a statistically significant difference for all biochemical parameters when the vitamins+dichlorvos-treated group was compared with the dichlorvos-treated group at the end of the 4th and 7th week. In an electron microscopic investigation, swelling of mitochondria and dilatation of endoplasmic reticulum were observed in liver cells of the dichlorvos- and vitamins+dichlorvos-treated rats at the end of the 4th and 7th week. As a result, vitamins C and E reduced dichlorvos hepatotoxicity, but vitamins C and E did not confer complete protection.


Drivers of Under-Five Stunting Trend in 14 Low- and Middle-Income Countries since the Turn of the Millennium: A Multilevel Pooled Analysis of 50 Demographic and Health Surveys.
Understanding the drivers contributing to the decreasing trend in stunting is paramount to meeting the World Health Assembly's global target of 40% stunting reduction by 2025. We pooled data from 50 Demographic and Health Surveys since 2000 in 14 countries to examine the relationships between the stunting trend and potential factors at distal, intermediate, and proximal levels. A multilevel pooled trend analysis was used to estimate the association between the change in potential drivers at a country level and stunting probability for an individual child while adjusting for time trends and child-level covariates. A four-level mixed-effects linear probability regression model was fitted, accounting for the clustering of data by sampling clusters, survey-rounds, and countries. Stunting followed a decreasing trend in all countries at an average annual rate of 1.04 percentage points. Among the distal factors assessed, a decrease in the Gini coefficient, an improvement in women's decision-making, and an increase in urbanization were significantly associated with a lower probability of stunting within a country. Improvements in households' access to improved sanitation facilities and drinking water sources, and children's access to basic vaccinations were the important intermediate service-related drivers, whereas improvements in early initiation of breastfeeding and a decrease in the prevalence of low birthweight were the important proximal drivers. The results reinforce the need for a combination of nutrition-sensitive and -specific interventions to tackle the problem of stunting. The identified drivers help to guide global efforts to further accelerate stunting reduction and monitor progress against chronic childhood undernutrition.


Cardiovascular responses of conscious DOCA-salt hypertensive rats to acute intracerebroventricular and intravenous administration of captopril.
The effect on blood pressure and heart rate, following administration of the same intracerebroventricular (ivt) and intravenous (iv) doses of captopril, was compared in freely moving DOCA-salt hypertensive rats, with chronically implanted ivt, iv and intraarterial cannulae. Ivt captopril (500 micrograms) in DOCA-salt rats showed an initial pressor response followed by a long lasting hypotensive effect. The ivt effect was greater than that following iv administration. No effect was observed in normotensive controls either ivt or iv. ASA or naloxone pretreatments significantly lowered the captopril hypotensive effect, thus suggesting an involvement of prostaglandin and opioid systems in blood pressure elevation in "non renin dependent" hypertension.


Life-history constraints on maximum population growth for loggerhead turtles in the northwest Atlantic.
Conservation planning for protected species often relies on estimates of life-history parameters. A commonly used parameter is the instantaneous maximum population growth rate (r max) that can be used to limit removals and design recovery targets. Estimation of r max can be challenging because of limited availability of species- and population-specific data and life-history information. We applied a method proposed by Neil and Lebreton, originally developed for birds, to loggerhead turtles. The method uses age-at-first-reproduction and adult survival to estimate r max. We used a variety of datasets and matrix population models to confirm an allometric assumption required by the method, and to generate estimates of age-at-first-reproduction and adult survival. A meta-analysis was applied to parameters from reported growth curves, which were then combined with the size distribution of neophyte nesters to derive estimates of age-at-first-reproduction. Adult survival rates were obtained from an existing matrix population model. Monte Carlo simulation was then used to combine the estimates of the allometric coefficients, age-at-first-reproduction, and adult survival to obtain a probability distribution of approximate r max values. Estimated annual maximum population growth rates averaged 0.024, with a mode of 0.017 and a 95% highest density interval of 0.006-0.047. These estimates were similar to values reported by others using different methods and captured the variability in positive, annual change estimates across nesting beach sites for the northwest Atlantic loggerhead population. The use of life-history parameters has a long history in wildlife and fisheries management and conservation planning. Our estimates of r max, while having some biases and uncertainty, encompassed values presently used in recovery planning for loggerhead turtles and offer additional information for the management of endangered and threatened species.


Mutagenicity of N-ethyl-N-nitrosourea, N-methyl-N-nitrosourea, methyl methanesulfonate and ethyl methanesulfonate in the developing Syrian hamster fetus.
N-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU) are well-known direct-acting transplacental mutagens and carcinogens. Methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) are also direct-acting but more stable compounds and form a different proportion of the various methyl and ethyl DNA adducts. The transplacental mutagenicity and carcinogenicity of MMS and EMS have not been well characterized. We tested the mutagenicity to the developing Syrian hamster by these compounds under identical conditions and with a range of dose. Mutant fetal cells were selected for diphtheria toxin resistance. All four compounds were significantly mutagenic. MNU was the most active and MMS the least active of the compounds. ENU and MNU demonstrated linear dose-response curves, whereas that for EMS seemed to be supralinear over the range 0.125-0.5 mmol/kg. At its highest dose, EMS was comparable to ENU in mutagenicity. In view of a recent accidental exposure of pregnant women and others to EMS, further studies of this compound in animal models may be warranted.


Tracing recent outdoor geolocation by analyzing microbiota from shoe soles and shoeprints even after indoor walking.
The microbial communities on shoe soles and shoeprints could carry microbial information about where someone walked. This is possible evidence to link a suspect in a crime case to a geographic location. A previous study had shown that the microbiota found on shoe soles depend on the microbiota of the soil on which people walk. However, there is a turnover of microbial communities on shoe soles during walking. The impact of microbial community turnover on tracing recent geolocation from shoe soles has not been adequately studied. In addition, it is still unclear whether the microbiota of shoeprints can be used to determine recent geolocation. In this preliminary study, we investigated whether the microbial characteristics of shoe soles and shoeprints can be used to trace geolocation and whether this information can be destroyed by walking on indoor floors. In this study, participants were asked to walk outdoors on exposed soil, then walk indoors on a hard wood floor. High-throughput sequencing of the 16S rRNA gene was performed to characterize the microbial communities of shoe soles, shoeprints, indoor dust, and outdoor soil. Samples of shoe soles and shoeprints were collected at steps 5, 20, and 50 while walking indoors. The PCoA result showed that the samples were clustered by geographic origin. The shoeprint showed a more rapid turnover of microbial community than the shoe sole during indoor walking. The result of FEAST showed that the microbial communities of shoe sole and shoeprint were mainly (shoe sole, 86.21∼92.34 %; shoeprint, 61.66∼90.41 %) from the soil of the outdoor ground where the individual recently walked, and a small portion (shoe sole, 0.68∼3.33 %; shoeprint, 1.43∼27.14 %) from the indoor dust. Based on the matching of microbial communities between geolocation and shoe sole or shoeprint, we were able to infer the recent geolocation of the individual with relatively high accuracy using the random forest prediction model (shoe sole: 100.00 %, shoeprint: 93.33∼100.00 %). Overall, we are able to accurately infer the geolocation of an individual's most recent outdoor walk based on the microbiota of shoe sole and shoeprint, even though these microbiotas show a turnover when walking indoor floor. The pilot study was expected to provide a potential method for tracing recent geolocation of suspects.


Precuneus degeneration and isolated apathy in patients with Parkinson's disease.
To investigate isolated apathy in a set of consecutively enrolled Parkinson's disease (PD) patients without dementia, depression, and significant motor response fluctuations, by conducting neuropsychological and neuroimaging analyses. One hundred twenty-four patients were eligible for inclusion in this study. Clinical information and data were collected from a predefined neuropsychological test battery, including the mini-mental status examination, apathy scale, geriatric depression scale, digit span test, Boston naming test, Seoul verbal learning test, controlled oral word association test, go-no-go test, and the Rey figure copy test. From matched groups of 10 non-apathetic and 12 apathetic patients in the initial cohort and 9 healthy controls, [18F]fluorodeoxyglucose positron emission tomography and volumetric magnetic resonance images were acquired. Apathy was detected in 59.7% of the initial cohort. Apathetic patients had lower scores in the digit span forward, digit span backward, and immediate recall of verbal learning tests than did those without apathy (p <0.05). The results were unaffected by parkinsonian motor severity and medication dose. Neuroimaging analyses revealed precuneus atrophy and hypometabolism in patients with isolated apathy. These precuneus changes were well-correlated with apathy severity (p <0.001). Apathy severity was also positively correlated with gray matter volume in the superior frontal gyrus and cerebellar vermis, and with metabolism in the medial frontal and anterior cingulate regions (p < 0.001). PD patients with isolated apathy showed attention and working memory dysfunction, and precuneus degeneration might be related to this distinctive nonmotor symptom in PD.


Updates on Topical and Local Anesthesia Agents.
Use of topical and local anesthesia (LA) is the workhorse of all aspects of dentistry. There was a time in the past when dentistry was performed without any local pain control. Owing to this there are patients with dental anxiety and fear of a dental office. The media portraying dentistry as being painful, or showing a dentist with needles, enlists fear and distrust of dentists. In contrast, pain is what brings the patient to the dental office and with local pain control measures a dentist is able to alleviate the patient's cause of pain.


Sagittal split osteotomy fixed with biodegradable, self-reinforced poly-L-lactide screws. A pilot study in sheep.
Self-reinforced poly-L-lactide (SR-PLLA) screws were used to fix bilateral mandibular sagittal split osteotomies (SSO) in six sheep. No intermaxillary fixation was used postoperatively. The follow-up time was 16 weeks, after which the sheep were killed. Both sides of the mandible were photographed and radiographed. The bending strength of the osteotomy was measured on the left side of the mandible. Histological and microradiographic studies were performed on the right side of the mandible. The results showed that the SR-PLLA screws were strong enough to fix the SSO rigidly. The bending force needed to break the bone was greater than that for the average unoperated mandible. The histological and microradiographic studies showed uneventful healing of the osteotomies in all six sheep. The results indicate that this method should be suitable for rigid fixation of SSO and fractures of the mandible in human beings.


A bilayer "artificial skin" capable of sustained release of an antibiotic.
The most frequent complication of the bilayer "artificial skin", composed of a silicone sheet and collagen sponge described in a previous paper, was infection beneath it. This paper describes a new type of "artificial skin" in which microspheres containing antibiotics were installed beneath the silicone sheet, allowing a continuous release of antibiotics.


Can MRCP replace the diagnostic role of ERCP for patients with choledochal cysts?
MRCP is rapidly replacing diagnostic ERCP in various pancreaticobiliary diseases. This study was designed to evaluate the accuracy of MRCP in detecting and determining the extent of choledochal cysts, as well as associated ductal anomalies or lesions. The study design was an 8-year retrospective survey conducted at a tertiary referral center, Asan Medical Center (University of Ulsan College of Medicine, Seoul, Korea). There were 72 patients with choledochal cysts. All patients underwent both MRCP and ERCP. MRCP findings were compared with those of ERCP as the criterion standard. The overall detection rate of MRCP for choledochal cysts was 96% (69/72). The sensitivity, the specificity, the positive predictive value, and the negative predictive value of MRCP for classifying choledochal cysts according to Todani's classification were 81%, 90%, 86%, and 86% in type I, respectively; 73%, 100%, 100, and 95% in type III, respectively; 83%, 90%, 80%, and 91% in type IVa, respectively; 100%, 100%, 100%, and 100% in type IVb, respectively; and 100%, 100%, 100%, and 100% in type V, respectively. The sensitivity, the specificity, and the accuracy of MRCP for detecting ductal anomalies were 83%, 90%, and 86%, respectively. The detection rate of MRCP for concurrent cholangiocarcinoma and choledocholithiasis was 87% (13/15) and 100% (8/8), respectively. MRCP showed overall good accuracy in the detection and the classification of choledochal cysts and revealed associated cholangiocarcinoma and choledocholithiasis with excellent accuracy. MRCP, therefore, may supersede the diagnostic role of ERCP for the patients with choledochal cysts. However, MRCP showed limited capacity to detect minor ductal anomalies or small choledochocele.


Perceptions of difference between aging and disability service systems consumers: implications for policy initiatives to rebalance long-term care.
This study explores service professionals' perceptions of how and why older adults and younger persons with disabilities are different consumers and clients within the long-term care service sector. Data are from 2004, early in the history of federal long-term care rebalancing initiatives, reflecting perceptions at that time. Findings suggest professionals working within aging, developmental disability, and physical disability service networks believe significant distinctions exist related to age of clients and nature of service required and how it is delivered. Overall need for greater professional and organizational capacity to support provision of service to both aging and disability populations is reported.


Microbial contamination of pharmaceutical products in the home.
One thousand, nine hundred and seventy-seven pharmaceutical products used in the home were examined for microbial contamination. Viable micro-organisms were recovered from 14.0% of samples. Medicines used in the home are apparently not exposed to the same opportunities for contamination as those used in hospital.


The need to protect cancer nurses from exposure to hazardous drugs.
Freelance medical writer Christine Clark (email@example.com) reports on an online meeting held in May 2022 as part of a series on the risks of exposure to hazardous drugs for nurses working in oncology.


Perceived discrimination, emotion dysregulation and loss of control eating in young men.
Experiences with discrimination may account, in part, for race-related disparities in obesity. Yet, there is minimal understanding of the link between perceived discrimination and health behaviors that contribute to obesity. This study examined the link between perceived discrimination and loss of control (LOC) eating in 798 African American, Asian/Asian American, and Hispanic/Latino men (18-30y; M = 24.0 ± 3.6). Emotion dysregulation was examined as a moderator. Participants completed an online survey assessing perceived discrimination; emotion dysregulation; and LOC eating frequency in the last 28 days. Negative binomial regression models were conducted within each racial/ethnic group, as each group completed different measures of perceived discrimination. In Hispanic/Latino men, perceived ethnic discrimination was positively associated with LOC eating frequency (p < .001). In African American men, perceived daily discrimination was positively associated with LOC eating frequency (p < .001). In Asian/Asian American men, neither perceived racial microaggressions nor racism were associated with frequency of LOC eating. Emotion dysregulation did not significantly moderate any of these associations. Findings highlight another detrimental correlate of perceived discrimination among some ethnic minority men - LOC eating. Future research should examine whether other identity- and culture-specific factors serve to exacerbate or mitigate the effects of discrimination on the health and health behaviors of ethnic minority men.


Clonal relationship of tumor nodules in hepatocellular carcinoma: a hierarchical clustering analysis of comparative genomic hybridization data.
Information on the clonal relationship between tumor nodules in patients diagnosed with hepatocellular carcinoma (HCC) holds prognostic significance in the prediction of recurrence and postoperative treatment. Here, we investigated the clonal relationships in 11 focal nodules from 5 patients with HCC by comparative genomic hybridization (CGH) and spectral karyotyping. CGH analysis indicated tumor nodules in 5 (100%) of 5 cases to share similar patterns of genomic imbalances, suggesting nodules to be clonally related. This clonal relationship was further substantiated in 2 cases, where spectral karyotyping analysis indicated identical structural rearrangements between focal tumors. Few studies have attempted to differentiate multicentric growth from intrahepatic dissemination in HCC using CGH analysis; however, data interpretation remained subjective. In this study, we have extended our data to include published CGH findings on 57 nodules derived from 19 HCC cases. Simulation of CGH findings by unsupervised 2-way hierarchical clustering indicated tumor nodules in 20 (83.3%) of 24 cases to cluster concordantly, signifying a high incidence of clonal similarity. In sum, bioinformatic analysis of genomic profiles may represent a reliable research tool in analyzing clonal relationships among tumor nodules.


Molecular and immune interactions between β- and γ-herpesviruses in the immunocompromised host.
β- and γ-herpesviruses persistently infect most of the world population, largely without clinical manifestations. However, in immunosuppressive settings like transplantation, these viruses are often jointly reactivated, associating with graft dysfunction/rejection, HCMV disease, and lymphoproliferation. In HIV/AIDS, direct interaction mechanisms have been described for EBV and KSHV in primary effusion lymphoma, demonstrating that the cooperation between both viruses enhances lymphomagenesis. Here, we discuss the clinical evidence supporting that the simultaneous reactivation of these viruses increases the probability of mutual interactions, also providing a conceptual framework explaining how one virus can influence another. Specifically, we propose mechanisms of indirect communication through immune soluble mediators, mainly cytokines, chemokines, and IFN regulatory molecules, based on common features of their infectious cycles and the convergent need on immunomodulatory mechanisms. This latter point should be experimentally addressed in feature research.


Improved prediction of subcellular location for apoptosis proteins by the dual-layer support vector machine.
Apoptosis proteins play an important role in the development and homeostasis of an organism. The accurate prediction of subcellular location for apoptosis proteins is very helpful for understanding the mechanism of apoptosis and their biological functions. However, most of the existing predictive methods are designed by utilizing a single classifier, which would limit the further improvement of their performances. In this paper, a novel predictive method, which is essentially a multi-classifier system, has been proposed by combing a dual-layer support vector machine (SVM) with multiple compositions including amino acid composition (AAC), dipeptide composition (DPC) and amphiphilic pseudo amino acid composition (Am-Pse-AAC). As a demonstration, the predictive performance of our method was evaluated on two datasets of apoptosis proteins, involving the standard dataset ZD98 generated by Zhou and Doctor, and a larger dataset ZW225 generated by Zhang et al. With the jackknife test, the overall accuracies of our method on the two datasets reach 94.90% and 88.44%, respectively. The promising results indicate that our method can be a complementary tool for the prediction of subcellular location.


Statistical learning of music- and language-like sequences and tolerance for spectral shifts.
In our previous study (Daikoku, Yatomi, & Yumoto, 2014), we demonstrated that the N1m response could be a marker for the statistical learning process of pitch sequence, in which each tone was ordered by a Markov stochastic model. The aim of the present study was to investigate how the statistical learning of music- and language-like auditory sequences is reflected in the N1m responses based on the assumption that both language and music share domain generality. By using vowel sounds generated by a formant synthesizer, we devised music- and language-like auditory sequences in which higher-ordered transitional rules were embedded according to a Markov stochastic model by controlling fundamental (F0) and/or formant frequencies (F1-F2). In each sequence, F0 and/or F1-F2 were spectrally shifted in the last one-third of the tone sequence. Neuromagnetic responses to the tone sequences were recorded from 14 right-handed normal volunteers. In the music- and language-like sequences with pitch change, the N1m responses to the tones that appeared with higher transitional probability were significantly decreased compared with the responses to the tones that appeared with lower transitional probability within the first two-thirds of each sequence. Moreover, the amplitude difference was even retained within the last one-third of the sequence after the spectral shifts. However, in the language-like sequence without pitch change, no significant difference could be detected. The pitch change may facilitate the statistical learning in language and music. Statistically acquired knowledge may be appropriated to process altered auditory sequences with spectral shifts. The relative processing of spectral sequences may be a domain-general auditory mechanism that is innate to humans.


[Comparative study of research methods to assess water pollution of the fecal origin in the rural Sudan-Western Sahara environment].
In the assessment of the bacteriological quality of water from 1,500 drills World has not in Burkina-Faso, three methods have been analyzed comparatively. The first, relying upon bacterial production of H2S as indicator of faecal pollution and proposed by Indian workers, has been found unreliable for determining water potability. The second, based upon the nitrate content of water, is unable to reveal water contamination by human and animal excreta. The third method, employing a membrane filtration, is to be commended since it is well adapted to the Sahelian conditions. Simple, reliable, of low cost, this method is providing the quality assurance of water potability, a requirement which must accompany the drilling programs.


Effects of Compliance With the Early Management Bundle (SEP-1) on Mortality Changes Among Medicare Beneficiaries With Sepsis: A Propensity Score Matched Cohort Study.
US hospitals have reported compliance with the SEP-1 quality measure to Medicare since 2015. Finding an association between compliance and outcomes is essential to gauge measure effectiveness. What is the association between compliance with SEP-1 and 30-day mortality among Medicare beneficiaries? Studying patient-level data reported to Medicare by 3,241 hospitals from October 1, 2015, to March 31, 2017, we used propensity score matching and a hierarchical general linear model (HGLM) to estimate the treatment effects associated with compliance with SEP-1. Compliance was defined as completion of all qualifying SEP-1 elements including lactate measurements, blood culture collection, broad-spectrum antibiotic administration, 30 mL/kg crystalloid fluid administration, application of vasopressors, and patient reassessment. The primary outcome was a change in 30-day mortality. Secondary outcomes included changes in length of stay. We completed two matches to evaluate population-level treatment effects. In standard match, 122,870 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (21.81% vs 27.48%, respectively), yielding an absolute risk reduction (ARR) of 5.67% (95% CI, 5.33-6.00; P < .001). In stringent match, 107,016 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (22.22% vs 26.28%, respectively), yielding an ARR of 4.06% (95% CI, 3.70-4.41; P < .001). At the subject level, our HGLM found compliance associated with lower 30-day risk-adjusted mortality (adjusted conditional OR, 0.829; 95% CI, 0.812-0.846; P < .001). Multiple elements correlated with lower mortality. Median length of stay was shorter among cases whose care was compliant (5 vs 6 days; interquartile range, 3-9 vs 4-10, respectively; P < .001). Compliance with SEP-1 was associated with lower 30-day mortality. Rendering SEP-1 compliant care may reduce the incidence of avoidable deaths.


Usefulness of laboratory mental stress test in patients with stable coronary artery disease.
Many episodes of ischemia in daily life are silent occurring during sedentary activities and may be related to mental stress. In 35 patients with stable angina and positive exercise test awaiting bypass surgery, we investigated whether laboratory mental stress tests would trigger ischemia of a comparable severity to that occurring in daily life and attempted to elucidate some of the underlying mechanisms. All patients underwent exercise testing, personality assessment, 2-day Holter monitoring, and laboratory mental stress tests while on their usual medications. Only four patients (12%) had positive mental stress test (ST depression > or = 0.1 mV). All episodes were silent and usually associated with fast heart rate (> 90 beats/min). In contrast, ambulatory ischemia was common (average duration of 51 min per 24 h), and at least one episode was recorded in 27 patients (77%) including the 4 with positive test. Patients with positive mental stress test had a higher heart rate during testing (124 +/- 24 vs. 86 +/- 16 beats/min, p < 0.01), and a shorter exercise time and time to 1 mm ST depression on cycle ergometry than those with negative mental stress test. None of the four patients were on beta blockers. There was no difference in personality inventory between the two groups. Comparisons between patients with and without positive mental stress test revealed no difference in the duration and frequency of ambulatory ischemia, or in the occurrence of silent ischemia. However, the heart rate at onset of ambulatory ischemia tended to be higher in the patients with positive mental stress test (96 +/- 9 vs. 62 +/- 43, p = 0.07). Further subgroup analysis in patients without beta blockers (4 mental stress test positive and 18 negative) showed similar results. Laboratory mental stress test is a weak inducer of ischemia detected by electrocardiographic monitoring in patients with frequent ambulatory ischemia. Wall motion evaluation during mental stress test may improve sensitivity. While larger scale studies may determine its clinical role, the present study illustrated that patients with heightened heart rate response to mental stress were identified in whom beta blockers could be the drug of choice.


A systematic review and meta-analysis of deep brain stimulation for depression.
Deep brain stimulation is increasingly being used for treatment-resistant depression. Blinded, randomized controlled trials of active versus sham treatment have been limited to small numbers. We performed a systematic review and meta-analysis on the effectiveness of deep brain stimulation (DBS) in depression. Cochrane Central Register of Controlled Trials, PubMed/Medline, Embase and PsycINFO, Chinese Biomedical Literature Service System, and China Knowledge Resource Integrated Database were searched for single- or double placebo-controlled, crossover, and parallel-group trials in which DBS was compared with sham treatment using validated scales. Ten papers from nine studies met inclusion criteria, all but two of which were double-blinded RCTs. The main outcome was a reduction in depressive symptoms. It was possible to combine data for 190 participants. Patients on active, as opposed to sham, treatment had a significantly higher response (OR = 5.50; 95% CI = 2.79, 10.85; p < .0001) and reductions in mean depression score (SMD = -0.42; 95% CI = -0.72, -0.12; p = .006). However, the effect was attenuated on some of the subgroup and sensitivity analyses, and there were no differences for most other outcomes. In addition, 84 participants experienced a total of 131 serious adverse effects, although not all could be directly associated with the device or surgery. Finally, publication bias was possible. DBS may show promise for treatment-resistant depression but remains an experimental treatment until further data are available.


Flow cytometry Coulter volume analysis of lead- and cadmium-induced cellular alterations in bone marrow obtained from young adult and aged Balb/c mice.
Flow cytometry Coulter volume analysis was used to examine the effects of an acute exposure to cadmium or lead on subpopulations of Balb/c bone marrow cells. A significant shift in the volume of Balb/c bone marrow cells was detected in response to a single i.p. injection of cadmium acetate (Cd) or lead acetate (Pb) compared to sodium acetate (Na)-treated mice. An increase in the relative number or size of myeloid/monocytic cells was noted in the bone marrow of cadmium or lead-treated mice. This effect was more pronounced in aged Balb/c mice than in young adults. These studies suggest the flow cytometry Coulter volume analysis may be a useful and sensitive technique for the assessment of cellular changes that occur in the bone marrow in response to xenobiotic exposure.


The Role of Antigen-presenting Cells in HIV Pathogenesis.
The study of antigen-presenting cells (APC) in HIV pathogenesis has been ongoing for almost 20 years. The initial studies recognized the important role of APC as targets for HIV infection and their ability to serve as reservoirs of virus, particularly in tissues. The issue of whether HIV impacts the functional competency of APC has been more controversial, with some studies showing reduced expression of important costimulatory molecules on APC, but others showing the functional capacity of APC to be normal. The study of APC has advanced with recent interest in one class of APC, namely the dendritic cell. These cells have been shown to consist of numerous subsets and serve an important role in bridging innate and adaptive immune responses. The impact of HIV infection on dendritic cells has recently been characterized, as well as the critical functional role of these cells in host defenses in HIV-infected patients. One of the more exciting recent advances in APC biology is the ability to manipulate APC ex vivo for therapeutic purposes in an attempt to restore immune responses in HIV-infected persons. This review covers many of the advances of the field of APC biology and puts them into perspective with HIV pathogenesis.


Dihydromyricetin ameliorates the oxidative stress response induced by methylglyoxal via the AMPK/GLUT4 signaling pathway in PC12 cells.
Dihydromyricetin (DMY), the major bioactive flavonoid ingredient extracted from the leaves of Ampelopsis grossedentata (Hand.-Mazz) W.T. Wang, displays multiple pharmacological activities, including oxidation resistance, antitumor properties and free radical scavenging capacities. However, the role of DMY in methylglyoxal (MG)-induced diabetes-associated cognitive decline and its underlying molecular mechanisms are unclear. The aim of the present study was to evaluate the effects of DMY on oxidative stress and glucose transport activity in a MG-induced PC12 cell line and to explore the related mechanisms. The effects of DMY on cell survival and apoptosis were examined, and the dysregulation of intracellular Ca(2+) was determined. Oxidative stress was evaluated by monitoring ROS production and the glutathione to glutathione disulfide ratio. The effects of DMY on glucose metabolism were investigated using a fluorescently labeled deoxyglucose analog and by measuring ATP and lactate production. Western blot analysis was performed to examine the protein levels of glyoxalase I (Glo-1), glucose transporter 4 (GLUT4), AMP-activated protein kinase (AMPKα) and phosphorylated AMPKα (p-AMPKα). The results revealed that DMY suppressed cellular oxidative stress in PC12 cells and balanced glucose metabolism. Additionally, DMY reduced GLUT4 translocation dysfunction and increased Glo-1 and p-AMPKα expression. We found that DMY protected PC12 cells against MG-induced apoptosis and glycometabolic disorders, at least in part by restraining the hyperactivation of p-AMPK activity and normalizing the translocation of GLUT4 from the intracellular compartment, resulting in a balance in glucose uptake. This result indicates that DMY may serve as a novel and effective candidate agent to treat diabetic encephalopathy by reducing the toxicity of MG.


Parental waivers to enable adolescent participation in certain forms of health research: lessons from a South African case study.
The South African legal framework requires mandatory parental/legal guardian consent for all research with children. Ethics guidelines provide some reprieve by allowing RECs to grant waivers of parental or guardianship consent in certain defined circumstances. In the first instance, consent may be provided by a proxy when parents or guardians are unavailable, for example with orphaned children. In the second instance, guidelines permit adolescent self-consent when the nature of the study justifies this approach, for example, research on sensitive issues like sexual behaviour or substance use. South African guidelines set several conditions that must be met for waivers to be granted. These norms overlap with those in international guidelines. However, the ethical norms, especially related to self-consent are sometimes vague. This article critically evaluates the consent norms in the national ethics guidelines and makes recommendations for reform to ethics guidelines in a way that recognises the value of child participation in research, their evolving decision-making capacity and their best interests. Recommendations are made to harmonise ethics guidelines and law in a way that promotes child participation in research, to ensure additional protections for adolescents when self-consent is allowed, and to withdraw procedural requirements for the community endorsement of self-consent strategies.


Osteoid osteoma: an evaluation of diagnostic modalities.
Significant delays still occur in the diagnosis of osteoid osteoma yet in two-thirds of cases the plain films show the characteristic features; unfortunately, early changes may be overlooked. A diagnostic approach is proposed for the investigation of focal bone pain in young individuals. Plain radiography is followed by isotope bone scanning with, if possible, a bone blood flow study. Tomography is sometimes helpful in atypical cases. CT scanning is valuable in foci in the axial skeleton including the pelvis. Lesions in the appendages of the vertebrae should be sought in patients with painful scoliosis or lordosis of relatively recent onset.


Investigation of the antimony fractions and indigenous microbiota in aerobic and anaerobic rice paddies.
The accumulation of antimony (Sb) by rice is a severe threat to exposed populations. Previous studies demonstrated that, compared to flooded (anaerobic) water management, dry cultivation management (aerobic) could substantially decrease As, an analog of Sb, uptake by rice. However, the effects of different water management strategies on the accumulation of Sb by rice are less understood. It is proposed that microorganisms play an important role in regulating Sb mobility in rice paddies. Hence, the current study compared the microbial communities in rice paddies receiving different water management, i.e., flooded (anaerobic) and dry (aerobic)) rice cultivation. Significant decrease in Sb uptake by rice, in both the roots and grains, was observed under the aerobic compared to the anaerobic conditions. This could partially be attributed to the differences in the microbial communities as shaped by the redox environment. In aerobic soils, the gene responsible for Sb oxidation (i.e., aioA) was significantly, while in anaerobic soils the gene responsible for Sb reduction (i.e., arrA) was enriched, suggesting that variation in redox conditions may trigger different microbial responses. Accordingly, geochemical analysis indicated that accumulation of Sb(III) was only observed under anaerobic conditions, but not under aerobic conditions. The environment-microbe interactions were distinct between the two treatments with a greater number of interactions between Sb fractions and the microbial assemblage under anaerobic conditions, while Eh was the most influential geochemical parameter under aerobic conditions. Finally, the presence of a core microbiome under the two conditions suggested the possibility of microorganisms that support rice growth, nutrition, and health. The reduction of Sb in rice grain significantly decreases Sb exposure to the residents in Sb contaminated regions, and should be considered for future rice cultivation practices.


HIV-1 nucleotide mixture detection in the virco(®)TYPE HIV-1 genotyping assay: a comparison between Sanger sequencing and 454 pyrosequencing.
HIV-1 Protease (PR) and Reverse Transcriptase (RT) genotyping is well established for the management of antiretroviral (ARV) drug therapy, as it is able to detect gene mutations encoding resistance to ARV compounds or drug classes, that are associated with reduced drug susceptibility (i.e. phenotype). A correct phenotypic interpretation from the derived PR-RT genotype (i.e. virtual phenotype), requires a well characterized geno-phenotype correlative database and appropriate statistical predictive models. The applicability of the virtual phenotype for the patient, will, however, not only depend on the accuracy of the statistical models and the database they rely on, but also depend largely on the sequence information that is provided. Since HIV-1 evolves as a complex of closely related but non-identical viral genomes (i.e. quasispecies) it is crucial that the sequencing method used, is able to characterize most of the genetic mixtures that make up the different quasispecies within a single patient. US regulatory agencies require that developers of HIV-1 genotyping assays, determine and report the HIV-1 mixture detection level of their assay. Hence, the mixture scoring sensitivity of the population-based Sanger sequencing method, along with the defined mixture scoring rules, used to drive the virco(®)TYPE HIV-1 virtual phenotype, was investigated by comparing it to the 454 pyrosequencing technique, which is able to generate the complete viral population sequence. To this end the PR-RT coding sequence of 20 clinical isolates was determined by both sequencing methodologies. The genotyping assay which feeds the virco(®)TYPE HIV-1 virtual phenotype was able to call automatically 97.5% (i.e. 268 mixtures) and 95.3% (i.e. 326 mixtures) of the mixtures that were present between 25 and 75% and between 20 and 80% in the viral population, as detected by 454. From the not called mixtures, all but one did present a mixture sequence in the Sanger DNA chromatograms, however, with a peak surface area for the second peak that was below the threshold setting for automatic mixture calling in the basecaller software (i.e. 25%). Viral loads ranged from 470 to 629,000 copies/mL and exerted no effect on the mixture calling relationship between both sequencing methodologies (R(2)=0.92). In some occasions (i.e. 55 mixtures) the genotyping assay would detect automatically mixtures that were present below 20% in the viral population, when measured by 454. Hence, the mixture scoring sensitivity of the automated high throughput virco(®)TYPE HIV-1 genotyping assay is currently set at 97.5% and 95.3%, for mixtures present at 25 and 20% in the viral population and may identify occasionally mutations that are present at lower frequencies. These findings were not influenced by the viral load of the examined samples.


Drought-induced increase in water-use efficiency reduces secondary tree growth and tracheid wall thickness in a Mediterranean conifer.
In order to understand the impact of drought and intrinsic water-use efficiency (iWUE) on tree growth, we evaluated the relative importance of direct and indirect effects of water availability on secondary growth and xylem anatomy of Juniperus thurifera, a Mediterranean anisohydric conifer. Dendrochronological techniques, quantitative xylem anatomy, and (13)C/(12)C isotopic ratio were combined to develop standardized chronologies for iWUE, BAI (basal area increment), and anatomical variables on a 40-year-long annually resolved series for 20 trees. We tested the relationship between iWUE and secondary growth at short-term (annual) and long-term (decadal) temporal scales to evaluate whether gains in iWUE may lead to increases in secondary growth. We obtained a positive long-term correlation between iWUE and BAI, simultaneously with a negative short-term correlation between them. Furthermore, BAI and iWUE were correlated with anatomical traits related to carbon sink or storage (tracheid wall thickness and ray parenchyma amount), but no significant correlation with conductive traits (tracheid lumen) was found. Water availability during the growing season significantly modulated tree growth at the xylem level, where growth rates and wood anatomical traits were affected by June precipitation. Our results are consistent with a drought-induced limitation of tree growth response to rising CO2, despite the trend of rising iWUE being maintained. We also remark the usefulness of exploring this relationship at different temporal scales to fully understand the actual links between iWUE and secondary growth dynamics.


Disaster medicine: the caring contradiction.
The nature of mankind is a concern for those in need. Disasters, both natural and manmade, have been with us since the beginning of recorded history but media coverage of them is a relatively new phenomenon. When these factors come together, there is great potential to both identify and serve the sick and injured. However, the mass media by its nature tends to enhance the humanistic aspect of rescue while minimizing the practical problems involved. We describe a recent scenario in Haiti that puts some of these complications into a practical perspective.