Dual-process model in semantic priming: A functional imaging perspective.
In this positron emission tomography study, we investigated the neural correlates of semantic priming, where response to a word is facilitated when preceded by a semantically related word. Nine normal subjects were scanned while performing a lexical decision task. Within this condition, the proportion of related prime-target word pairs was varied across scans from 0 to 100%. The control task involved letter decision on consonant letter strings, controlling orthographic processing and response selection. First, lexical decision (relative to letter decision) activated regions previously observed in lexicosemantic tasks, i.e., the left anterior and inferior temporal lobe and left inferior frontal gyrus. Behavioral analysis confirmed significant facilitation of lexical decision to related targets (mean priming effect 68 ms). It also suggested the contribution of both automatic and strategic processes, consistent with theoretical accounts of priming. Automatic priming was indicated by consistent RTs to related targets irrespective of the proportion of related word pairs per scan. Strategic processing was indicated by decreases in RTs to nonwords as the proportion of related targets increased. Nonlinear correlational analysis of cerebral activity during lexical decision revealed a neurophysiological correlate of these behavioral effects in (i) the left anterior temporal lobe (BA 38), a region involved in lexicosemantic processing; (ii) the anterior cingulate cortex, right premotor region (BA 6), and right superior parietal lobe (BA 7), regions associated with attentional processes. We conclude that in this experimental context, semantic priming involves both automatic and strategic processing.


Integrated Analyses of Mouse Stem Cell Transcriptomes Provide Clues for Stem Cell Maintenance and Transdifferentiation.
In vivo cell fate reprogramming has emerged as a new method for understanding cell plasticity and as potential treatment for tissue regeneration. Highly efficient and precise reprogramming requires fully understanding of the transcriptomes which function within different cell types. Here, we adopt weighted gene co-expression network analysis (WGCNA) to explore the molecular mechanisms of self-renewal in several well-known stem cell types, including embryonic stem cells (ESC), primordial germ cells (PGC), spermatogonia stem cells (SSC), neural stem cells (NSC), mesenchymal stem cells (MSC), and hematopoietic stem cells (HSC). We identified 37 core genes that were up-regulated in all of the stem cell types examined, as well as stem cell correlated gene co-expression networks. The validation of the co-expression genes revealed a continued protein-protein interaction network that included 823 nodes and 3113 edges. Based on the topology, we identified six densely connected regions within the continued protein-protein interaction network. The SSC specific genes Itgam, Cxcr6, and Agtr2 bridged four densely connected regions that consisted primarily of HSC-, NSC-, and MSC-correlated genes. The expression levels of identified stem cell related transcription factors were confirmed consistent with bioinformatics prediction in ESCs and NSCs by qPCR. Exploring the mechanisms underlying adult stem cell self-renewal will aid in the understanding of stem cell pool maintenance and will promote more accurate and efficient strategies for tissue regeneration and repair.


ERISA in 2015.
The federal Employee Retirement Income Security Act (ERISA) helps medical practices make carriers pay on claims that are now being denied, delayed, and recouped. Only a small percentage of practices understand how ERISA works. Yet with appropriate guidance, ERISA could possibly become a practice's best friend! Practices are in the dark when it comes to understanding how to protect their rights in collecting the monies owed them. ERISA regulates the practice's health benefits, health benefit payments, explanations of benefits, and, most importantly, appeal rights. This article covers ERISA in 2015 and how practices can capture the thousands of dollars that carriers currently are unfairly denying. This overview will empower the reader to stop the unfair recoupments and the timely filing and improper appeal periods that carriers mistakenly quote to physicians and hospital offices.


Prevalence of occupational asthma and respiratory symptoms in foundry workers.
This cross-sectional study was conducted in a foundry factory to assess the prevalence of respiratory symptoms and occupational asthma in foundry workers. Physical examination, spirometric evaluation, chest radiograph, and a questionnaire related to respiratory symptoms were performed. Monitoring of peak expiratory flow rates, spirometric reversibility test, and high-resolution computed tomographies were performed for the participants having respiratory symptoms and/or impaired respiratory function test. A total of 347 participants including 286 workers from production department and 61 subjects who worked in nonproduction departments were enrolled in this study. It is found that phlegm (n: 71, 20.46%) and cough (n: 52, 14.98%) were the most frequent symptoms. The other symptoms were breathlessness (n: 28, 8.06%), chest tightness (n: 14, 4.03%), and wheezing (n: 7, 2.01%) . The prevalence of occupational asthma was found to be more frequent among the subjects who worked in the production department (n: 48, 16.78% ) than the other persons who worked in the nonproduction department (n: 3, 4.91%) by chi-square test (P: 0.001). To prevent hazardous respiratory effects of the foundry production, an early diagnosis of occupational asthma is very important. Cessation of cigarette smoking and using of protective masks during the working time should be encouraged.


Pharmacokinetics of plasma-derived and recombinant factor IX: using population pharmacokinetics with sparse sampling data needs further study.
The concept of using pharmacokinetics for prophylactic dose tailoring with limited blood sampling in clinical practice has been demonstrated for factor VIII but not for factor IX. The pharmacokinetics of factor IX are more complicated than for factor VIII and also differ between plasma-derived and recombinant factor IX. Therefore, the pharmacokinetics of factor IX need to be further explored in clinical trials including comparative studies of prophylaxis with different factor IX concentrates. These are the main conclusions drawn from two of the last manuscripts written by Professor Sven Björkman and published in Haemophilia. Professor Björkman suddenly and unexpectedly died last summer. Thanks to the academic network created around his skill and through his enthusiasm for the pharmacokinetics of clotting factors and ability to convey his wisdom to others, this work will continue. Sven Björkman opened a new era in hemophilia prophylaxis.


The effect of instrumentation with two different file types, each with 2.5% NaOCl irrigation on the microhardness of root dentin.
The aim of this study was to measure root-dentin microhardness after instrumentation with two types of files and using irrigation with 2.5% sodium hypochlorite. Thirty roots were instrumented with irrigation: 10 roots had the pulp extirpated only; 10 roots were instrumented with stainless steel files, and 10 roots were instrumented with rotary nickel-titanium (NiTi) files. Additionally, five roots were extirpated only without irrigation and served as a control. The roots were sliced and root-dentin microhardness was determined at depths of 500 microm and 1000 microm from the pulp-dentin interface. Significant differences were found between the microhardness at 500 microm and 1000 microm (p < 0.001) in all groups. Instrumentation with NiTi rotary files affected dentin microhardness significantly to a lesser extent.


Skeletal efficacy with parathyroid hormone in rats was not entirely beneficial with long-term treatment.
We report the consequences of prolonged treatment with recombinant human parathyroid hormone (1-34) (PTH) in male and ovariectomized female rats with mature skeletons. Intact male and osteopenic, ovariectomized, female F-344 rats were evaluated after 1 year of treatment with 0, 8, or 40 microg/kg/day s.c. PTH. Males and females were about 6 months of age at study initiation; females were ovariectomized (Ovx) for 5 weeks before initiation of PTH treatment. PTH did not affect the survival of either intact males or ovariectomized females. Qualitative histopathology showed expected changes associated with aging in kidneys and proximal tibiae, with no treatment-related anomalies after 1 year of PTH administration. PTH slightly increased the femoral length of ovariectomized females but not that of males. No significant differences in femoral length were observed between sham and Ovx controls. Proximal femora of the males and ovariectomized females given the high dose of 40 microg/kg showed 211 and 186% greater trabecular bone area, 118 and 94% greater cortical thickness, 170 and 189% greater trabecular number, and 321 and 404% greater connectivity (node-to-node struts) compared with respective vehicle controls. Increased trabecular and endocortical surface apposition coincided with a 78 and 70% loss of marrow space for males and females treated with PTH, respectively. Biomechanical strength (ultimate load) of the femoral neck increased by 73 and 76%, respectively, in males and ovariectomized females. Cortical bone analyses of the femoral midshaft showed 105 and 72% increases in bone mineral content, 67 and 55% increases in bone mineral density, and 22 and 10% increases in cross-sectional area for males and ovariectomized females, respectively, with altered shape of femora. Biomechanical analyses of the midshaft showed substantial increases in strength and stiffness but a reduction in ultimate strain, which was likely due to the altered geometry of the midshaft for PTH groups. Aging effects on strength of vertebra and femoral midshaft were reversed by PTH treatment. In summary, the 1-year treatment duration, which represents about 50% of lifetime, did not affect survival and was not associated with any treatment-related anomalies in the kidney or skeleton. PTH reversed the aging process in bones but not kidneys and substantially increased bone mass and strength to well beyond normally attained levels. However, compared with short-term studies reported previously, there seemed to be no advantages to extending PTH treatment to 12 months in rat bones.


Morphological abnormalities in mitochondria of the skin of patients with sporadic amyotrophic lateral sclerosis.
Mitochondrial dysfunction has been reported in the central nervous system, hepatocytes and peripheral blood lymphocytes from patients with sporadic amyotrophic lateral sclerosis (SALS). However, the status of skin mitochondria has not been reported, in spite of the fact that SALS patients present skin abnormalities. The objective of the present study was to compare mitochondrial ultrastructural parameters in keratinocytes from patients with SALS and healthy controls. Our study was based on the analysis of 112 skin mitochondria from 5 SALS patients and 99 organelles from 4 control subjects by electron microscopy. Computerized image analysis showed that mitochondrial major axis length, area and perimeter of the organelle were significantly smaller in SALS respect of healthy control subjects. Morphologically, SALS mitochondria presented cristolysis and breakage of the outer membrane. Mitochondrial dysfunction in the skin may possibly reflect changes occurring in mitochondria of the central nervous system. The analysis of mitochondrial morphology in this tissue may be of value to follow disease progression and, eventually, the effectiveness of current therapies for SALS.


From the philosophy auditorium to the neurophysiology laboratory and back: from Bergson to Damasio.
Henri Bergson (1859-1941) was probably the most influential French philosopher at the turn of the twentieth century. In 1927 he was awarded the Nobel Prize for literature. Far beyond the restricted academic philosophical milieu, the impact of his thinking reached personalities as diverse as Claude Debussy, Marcel Proust, George Bemard Shaw, and the impressionists. His essay The Laughter (Le Rire) is one of the most profound and original ever written on the sense of humor. Bergson's opinions, with their emphasis on life, instinct and intuition, represented a deviation from the rationalist mainstream of western philosophical tradition. In some circles he was received with skepticism and irony, as in Bertrand Russel's History of Western Philosophy. Today, unbiased by theoretical "bergsonism," neurophysiologic research--as undertaken mainly by Antonio Damasio's team at Iowa University--confirms many of his hypotheses and elucidates their mechanisms. In this new light, intuition and "recognition by the body" should not be seen as the personal fantasy of an original thinker but as fundamental cognitive tools.


Excimer laser phototherapeutic keratectomy for granular and lattice corneal dystrophy: a comparative study.
To compare the visual and refractive outcome after excimer laser phototherapeutic keratectomy (PTK) for superficial comeal opacities in granular and lattice dystrophy. Phototherapeutic keratectomy was performed in 62 eyes of 40 patients (granular dystrophy [n = 50] and lattice dystrophy [n = 12]) after epithelial debridement and pannus removal. Data regarding pre-and postoperative best spectacle-corrected visual acuity, changes in spherical equivalent of manifest refraction, Zeiss keratometry, astigmatism, and corneal topography were analyzed and compared between granular and lattice dystrophy. Recurrence, if any, was noted during a mean follow-up of 3.0 +/- 2.7 years. Best spectacle-corrected visual acuity improved in 79% and 62% of eyes with granular and lattice dystrophy, respectively. Spherical equivalent refraction increased by a mean of 1.3 +/- 1.7 diopters (D) (median: 1.0 D) for granular dystrophy and a mean of 1.0 +/- 1.8 D (median: 0.5 D) for lattice dystrophy. The keratometric central power decreased by a mean of -0.8 +/- 4.3 D (median: -1.6 D) for granular dystrophy and a mean of -0.3 +/- 1.6 D (median: -0.7 D) for lattice dystrophy. No significant changes were noted regarding keratometric astigmatism in either granular or lattice dystrophy. The proportion of "regular" and "mild irregular" keratometry mires increased (39% vs 67% for granular dystrophy and 0% vs 50% for lattice dystrophy). In granular dystrophy, the surface regularity index/surface asymmetry index (SRI/SAI) decreased significantly from 2.14/2.24 preoperatively to 1.31/0.80 postoperatively (P = .006/P = .01). In contrast, decrease of SRI/SAI from 1.97/1.65 preoperatively to 1.35/1.16 postoperatively did not reach statistical significance in lattice dystrophy. Recurrences were observed in 10 (20%) eyes with granular dystrophy and 2 (17%) eyes with lattice dystrophy. Our results suggest that PTK may be tried in all patients with superficially accentuated opacities in granular and lattice dystrophy before undergoing a more invasive procedure, such as lamellar or penetrating keratoplasty.


[Experimental study about intra-ocular penetration of ammonia].
The seriousness of ocular alkali burn depends on low quick the alkali to enter the eye. We report the results of an experimental study on intra-ocular penetration of ammonia. This study included 23 eyes of New Zealand albino rabbits, burned for 1 minute by 100 microl of a solution titrating 15.3% ammonia. An pH meter probe inserted into the anterior chamber measured pH every 5 seconds. Experiment were carried out within 1, 3, 5, 10 and 30 minutes. An anterior chamber puncture was performed at the end of experiments, after of 1, 3, 5, and 10 minutes, for measuring the ammonia concentration in the anterior chamber. PH increased 1 to 3 minutes after applying of ammonia on the cornea, until a maxima 10, 5 to 6 minutes later, followed by an exponential decrease. After 30 minutes, pH was still higher than physiological pH, and the ammonia concentration was low. The penetration-ratio of ammonia through cornea was about 11%. Measured pH differed from pH calculated from the concentration of ammonia. The difference between measured and calculated pH evidences chemical reactions. The two pH increases interspersed with a plateau prove the existence of 2 successive acido-basic chemical reactions between ammonia and 2 sorts of acid. Also, the density of protein uptake can be calculated from ammonia. This suggests an interesting avenue of research as protein density can be related in the eye with the pK of the base, and thus foresee the potential danger of a base to biological tissues.


[Incidence of infectious spondylitis in the province of Albacete (Spain)].
Infectious spondylitis (IS) is an infrequent disease, although there are few data on its real incidence. To date, only one study, carried out in Denmark, that rigorously assesses the incidence of this disease has been published. To determine the incidence of IS in the nonpediatric population of the province of Albacete, and to analyze differences according to etiology, age, sex, and geographical area. We carried out a retrospective search of all the IS cases diagnosed in the province of Albacete during the period 1990-2002 and calculated the adjusted incidence rates using census data. The incidence of IS was 2.40 cases/10(5) inhabitants/year. Brucellar spondylitis had an incidence of 1.18 cases/10(5) inhabitants/year, with a predominance in the rural area and in men. Distribution by age was bimodal, with a first peak around 40 years old and a second peak around 60 years old. The incidence has significantly decreased in the last few years. Pyogenic spondylitis (incidence of 0.64 cases/10(5) inhabitants/year) showed a maximum incidence at around 60 years old, while its distribution by sex and geographical area was more uniform. Tuberculous spondylitis had an incidence of 0.45 cases/10(5) inhabitants/year and its frequency increased with age. The incidence rates of IS were higher than those reported in most previous studies, although they were similar to those observed in the most rigorous reports. These findings suggest that the frequency of IS could have been underestimated. The three etiologic groups analyzed showed distinct epidemiological profiles.


Edge absorption and pure spin current in a 2D topological insulator in the Volkov-Pankratov model.
Light absorption due to transitions between the edge and two-dimensional (2D) states of a 2D topological insulator (TI) is considered in the Volkov-Pankratov model. It is shown that the transitions are allowed only for the in-plane electric field orthogonal to the TI edge. It is found that the absorption is accompanied by pure spin photocurrent along the TI edge. A possibility of spin current measurement using polarized luminescence from 2D TI quantum dots is discussed.


[A patient with middle bile duct cancer who showed rapid obstruction on contrast radiographs 1 week after insertion of a non-covered stent, but this case obtained a long-term stent opening and long survival after re-insertion of a covered stent].
A 73-year-old female with jaundice was referred to our department and admitted. Blood examination on admission showed an abnormal liver function and an increase in CA19-9. Ultrasonography of the abdomen revealed a well-delineated round mass in the middle bile duct. After admission, PTBD was performed, and a complete obstruction was observed in the middle bile duct. Cytological examination of the bile demonstrated adenocarcinoma. Based on these findings, a diagnosis of middle bile duct cancer was made. Because of delirium and frequent wandering during the night due to dementia, a radical operation was abandoned, and a non-covered stent was placed. However, since 1 week after insertion of a non-covered stent, contrast radiography showed tumor protrusion (rapid obstruction) in the stent, and a covered stent was placed in the stent. The stent was open for 486 days after stent re-insertion. PTBD was performed for re-obstruction, but she died 596 days after admission. In patients for whom surgery is impossible for reasons other than tumor factors, internal fistula construction using a metallic stent, which neither impairs QOL nor shorten survival, can be indicated.


Numerical studies of nitric oxide formation in nanosecond-pulsed discharge-stabilized flames of premixed methane/air.
A simulation is developed to investigate the kinetics of nitric oxide (NO) formation in premixed methane/air combustion stabilized by nanosecond-pulsed discharges. The simulation consists of two connected parts. The first part calculates the kinetics within the discharge while considering both plasma/combustion reactions and species diffusion, advection and thermal conduction to the surrounding flow. The second part calculates the kinetics of the overall flow after mixing the discharge flow with the surrounding flow to account for the effect that the discharge has on the overall kinetics. The simulation reveals that the discharge produces a significant amount of atomic oxygen (O) as a result of the high discharge temperature and dissociative quenching of excited state nitrogen by molecular oxygen. This atomic oxygen subsequently produces hydroxyl (OH) radicals. The fractions of these O and OH then undergo Zel'dovich reactions and are found to contribute to as much as 73% of the total NO that is produced. The post-discharge simulation shows that the NO survives within the flow once produced.


Surface Functionalization of Orthopedic Titanium Implants with Bone Sialoprotein.
Orthopedic implant failure due to aseptic loosening and mechanical instability remains a major problem in total joint replacement. Improving osseointegration at the bone-implant interface may reduce micromotion and loosening. Bone sialoprotein (BSP) has been shown to enhance bone formation when coated onto titanium femoral implants and in rat calvarial defect models. However, the most appropriate method of BSP coating, the necessary level of BSP coating, and the effect of BSP coating on cell behavior remain largely unknown. In this study, BSP was covalently coupled to titanium surfaces via an aminosilane linker (APTES), and its properties were compared to BSP applied to titanium via physisorption and untreated titanium. Cell functions were examined using primary human osteoblasts (hOBs) and L929 mouse fibroblasts. Gene expression of specific bone turnover markers at the RNA level was detected at different intervals. Cell adhesion to titanium surfaces treated with BSP via physisorption was not significantly different from that of untreated titanium at any time point, whereas BSP application via covalent coupling caused reduced cell adhesion during the first few hours in culture. Cell migration was increased on titanium disks that were treated with higher concentrations of BSP solution, independent of the coating method. During the early phases of hOB proliferation, a suppressive effect of BSP was observed independent of its concentration, particularly when BSP was applied to the titanium surface via physisorption. Although alkaline phosphatase activity was reduced in the BSP-coated titanium groups after 4 days in culture, increased calcium deposition was observed after 21 days. In particular, the gene expression level of RUNX2 was upregulated by BSP. The increase in calcium deposition and the stimulation of cell differentiation induced by BSP highlight its potential as a surface modifier that could enhance the osseointegration of orthopedic implants. Both physisorption and covalent coupling of BSP are similarly effective, feasible methods, although a higher BSP concentration is recommended.


Osteonecrosis of the jaw in a patient on raloxifene: a case report.
Osteonecrosis of jaws (ONJ) is a chronic disease characterized by necrotic bone from any number of causes. ONJ can also occur due to several systemic and local factors which compromise blood flow within the bone. Among anti-resorptive medications, a very low risk of ONJ development is associated with oral bisphosphonates used for the management of osteopenia, osteoporosis, and Paget's disease. Raloxifene is a nonsteroidal benzothiophene which is classified as a selective estrogen receptor modulator (SERM). It is commonly used for the prevention and the treatment of osteoporosis in postmenopausal women and was recently approved to reduce the risk of breast cancer. Raloxifene is regarded as a safe alternative in the management of osteoporosis in terms of ONJ development. This report presents a case of ONJ in a patient receiving raloxifene, who presented with existing comorbidities and a history of discontinued oral bisphosphonates use. The clinical report is followed by a discussion aimed to clarify how the general practitioner should consider similar cases.


Restriction enzyme evidence for Alu sequence-mediated dispersion of microinjected genes in transgenic mice.
A human bacteriophage clone containing adult beta-globin genes with four Alu sequences was microinjected to produce transgenic mice. Southern blot analysis on the spleen of a transgenic mouse revealed an unusual hybridization pattern that suggested extensive dispersion of human DNA throughout the mouse genome. This pattern was reproducible using several restriction enzymes, including a noncutting enzyme. The hybridization pattern was not observed in other tissues, and sequences were not detected in progeny using the bacteriophage probe. However, hybridization of spleen DNA of offspring against a human Alu probe revealed genetic transmission of human Alu sequences. The results suggest dispersion of microinjected Alu sequences throughout the genome.


Cationic Vacancies in Anatase (TiO2): Synthesis, Defect Characterization, and Ion-Intercalation Properties.
As one of the most studied materials, research on titanium dioxide (TiO2) has flourished over the years owing to technological interest ranging from energy conversion and storage to medical implants and sensors, to name a few. Within this scope, the development of synthesis routes enabling the stabilization of reactive surface structure has been frequently investigated. Among these routes, solution-based synthesis has been utilized to tailor the material's properties spanning its atomic structural arrangement, or morphological aspects. One of the most investigated methods of stabilizing crystals with tailored facets relies on the use of fluoride-based precursors. Fluoride ions not only provide a driving force for the stabilization of metastable/reactive surface structures but also alter the reactivity of titanium molecular precursors and in turn the structural features of the stabilized crystals. Here, we review recent progress in the solution-based synthesis of anatase (one of the polymorphs of TiO2) employing a fluoride precursor, with an emphasis on how cationic vacancies are stabilized by a charge-compensating mechanism and the resulting structural features associated with these defects. Finally, we will discuss the ion-intercalation properties of these sites with respect to lithium and polyvalent ions such as Mg2+ and Al3+. We will discuss in more detail the relevant parameters of the synthesis that allow controlling the phase composition with the coexistence of oxide, fluoride, and hydroxide ions within the anatase framework. The mechanism of formation of defective anatase nanocrystals has highlighted a solid-state transformation mostly implying an oxolation reaction (the condensation of hydroxide ions) that results in a decrease in the vacancy content, which can be synthetically controlled. The investigation of local fluorine environments probed by solid-state 19F NMR revealed up to three coordination modes with different numbers of coordinated Ti4+ and vacancies. It further revealed the occurrence of single and adjacent pairs of vacancies. These different host sites including native interstitial (and single/paired vacancies) display different ion-intercalation properties. We notably discussed the influence of the local anionic environments of vacancies on the thermodynamics of intercalation properties. The selective intercalation of polyvalent cations such as Mg2+ and Al3+ further supports the beneficial uses of defect chemistry for developing post-lithium-ion batteries. It is expected that the ability to characterize the local structure of defects is key to the design of unique, tailored-made materials.


Effect of toothpaste with natural calcium carbonate/perlite on extrinsic tooth stain.
The current study was designed to determine the effect of natural calcium carbonate toothpaste containing Perlite and microgranules (Whitening toothpaste) on extrinsic tooth stain compared to a standard commercial toothpaste formulation with precipitated calcium carbonate (PCC) as abrasive and a commercial toothpaste with dicalcium phosphate dihydrate (DCPD) as abrasive. The toothpastes were evaluated in a double blind, three-cell, stratified (tobacco use; baseline tooth stain level), parallel group design study involving 600 subjects with extrinsic tooth stain. Subjects brushed twice daily with their allocated toothpaste for four weeks. Extrinsic tooth stain was measured using the Macpherson modification of the Lobene stain index. ANCOVA showed significant differences between toothpastes (p=0.037). Subsequent multiple comparisons using pairwise t-tests, showed the Whitening toothpaste to be superior to the DCPD toothpaste (p=0.014) and the PCC toothpaste (p=0.067). When a Box-Cox transformation was made to the data (y0.6) to improve normality, these two differences were more accurately estimated at p=0.004 and p=0.03 respectively. The Whitening toothpaste has been shown to be significantly more effective in tooth stain removal than the two standard commercial toothpaste formulations.


Ares-GT: Design of guide RNAs targeting multiple genes for CRISPR-Cas experiments.
Guide RNA design for CRISPR genome editing of gene families is a challenging task as usually good candidate sgRNAs are tagged with low scores precisely because they match several locations in the genome, thus time-consuming manual evaluation of targets is required. To address this issues, I have developed ARES-GT, a Python local command line tool compatible with any operative system. ARES-GT allows the selection of candidate sgRNAs that match multiple input query sequences, in addition of candidate sgRNAs that specifically match each query sequence. It also contemplates the use of unmapped contigs apart from complete genomes thus allowing the use of any genome provided by user and being able to handle intraspecies allelic variability and individual polymorphisms. ARES-GT is available at GitHub (https://github.com/eugomin/ARES-GT.git).


Assessment of maternal-fetal status of some essential trace elements in pregnant women in late gestation: relationship with birth weight and placental weight.
The status of the essential trace elements copper (Cu), iron (Fe), zinc (Zn), selenium (Se) and molybdenum (Mo) has been investigated in maternal and umbilical cord blood in control, uncomplicated pregnancies at term, and the possibility assessed of a relationship between blood levels of these trace elements and newborn weight and placental weight. Fetal-maternal ratios of the elements were also computed to establish baseline values for the Kuwaiti obstetric population. Blood samples were collected from a maternal vein, the umbilical artery and umbilical vein of normal pregnant women at the time of spontaneous delivery or Cesarean section, and the concentrations of various trace elements determined by atomic absorption spectrophotometry. The concentration of Cu, Fe, Mo, Se and Zn averaged 2406.1, 3252.1, 11.6, 107.3 and 696.2 microg/l, respectively, in maternal venous blood in the pregnant women (n=39) at term. Umbilical venous/maternal venous ratios of Cu, Fe, Mo, Se and Zn averaged 0.32, 1.96, 1.03, 0.83 and 1.55, respectively. Neonatal birth weight did not correlate with maternal blood levels of the trace elements (p>0.05) in the mother-child pairs studied. However, neonatal weight correlated negatively (p<0.05) with umbilical venous Cu level. Placental weight correlated positively (p<0.05) with Fe and Mo levels and negatively with Zn level in umbilical venous blood. Our results indicate an active placental transport for Fe and Zn, while Cu, Mo and Se appear to be exchanged passively between mother and fetus. Evaluation of Fe, Mo, Se and Zn levels in maternal and umbilical cord blood does not appear to be useful in the assessment of fetal growth.


Advances in lipid-based nanocarriers for breast cancer metastasis treatment.
Breast cancer (BC) is the most common cancer affecting women worldwide, with over 2 million women diagnosed every year, and close to 8 million women currently alive following a diagnosis of BC in the last 5-years. The side effects such as chemodrug toxicity to healthy tissues and drug resistance severely affect the quality of life of BC patients. To overcome these limitations, many efforts have been made to develop nanomaterial-based drug delivery systems. Among these nanocarriers, lipid-based delivery platforms represented one of the most successful candidates for cancer therapy, improving the safety profile and therapeutic efficacy of encapsulated drugs. In this review we will mainly discuss and summarize the recent advances in such delivery systems for BC metastasis treatment, with a particular focus on targeting the common metastatic sites in bone, brain and lung. We will also provide our perspectives on lipid-based nanocarrier development for future clinical translation.


Impact of implant size on cement filling in hip resurfacing arthroplasty.
Larger proportions of cement within femoral resurfacing implants might result in thermal bone necrosis. We postulate that smaller components are filled with proportionally more cement, causing an elevated failure rate. A total of 19 femoral heads were fitted with polymeric replicas of ReCap (Biomet) resurfacing components fixed with low-viscosity cement. Two specimens were used for each even size between 40 and 56 mm and one for size 58 mm. All specimens were imaged with computed tomography, and the cement thickness and bone density were analyzed. The average cement mantle thickness was 2.63 mm and was not correlated with the implant size. However, specimen with low bone density had thicker cement mantles regardless of size. The average filling index was 36.65% and was correlated to both implant size and bone density. Smaller implants and specimens with lower bone density contained proportionally more cement than larger implants. According to a linear regression model, bone density but not implant size influenced cement thickness. However, both implant size and bone density had a significant impact on the filling index. Large proportions of cement within the resurfacing head have the potential to generate thermal bone necrosis and implant failure. When considering hip resurfacing in patients with a small femoral head and/or osteoporotic bone, extra care should be taken to avoid thermal bone necrosis, and alternative cementing techniques or even cementless implants should be considered. This study should help delimiting the indications for hip resurfacing and to choose an optimal cementing technique taking implant size into account.


Templer's Death Anxiety Scale revisited: the Dutch version.
The aim of the present study was twofold, to present and analyse a Dutch version of Templer's Death Anxiety Scale and to explore further the scale's factor structure. Subjects were 179 Dutch freshmen in psychology who filled out the scale during a group test-session. Mean scale scores, standard deviations, and internal consistency were comparable to data reported in earlier studies. A principal components analysis identified five factors with eigenvalues larger than one. The first factor appeared to be an underlying primary dimension on which all items except Item 10 loaded substantially. It is suggested to change the response format form a dichotomous to a 5-point scale and to accept the Dutch version of the Death Anxiety Scale as a reliable measure of death anxiety.


Resolving the subtle details of human DNA alkyltransferase lesion search and repair mechanism by single-molecule studies.
SignificanceWe directly visualize DNA translocation and lesion recognition by the O6-alkylguanine DNA alkyltransferase (AGT). Our data show bidirectional movement of AGT monomers and clusters on undamaged DNA that depended on Zn2+ occupancy of AGT. A role of cooperative AGT clusters in enhancing lesion search efficiencies by AGT has previously been proposed. Surprisingly, our data show no enhancement of DNA translocation speed by AGT cluster formation, suggesting that AGT clusters may serve a different role in AGT function. Our data support preferential cluster formation by AGT at alkyl lesions, suggesting a role of these clusters in stabilizing lesion-bound complexes. From our data, we derive a new model for the lesion search and repair mechanism of AGT.


Genome-Wide Association Study to Identify Candidate Loci for Biomass Formation Under Water Deficit in Perennial Ryegrass.
Global warming is predicted to impact many agricultural areas, which will suffer from reduced water availability. Due to precipitation changes, mild summer droughts are expected to become more frequent, even in temperate regions. For perennial ryegrass (Lolium perenne L.), an important forage grass of the Poaceae family, leaf growth is a crucial factor determining biomass accumulation and hence forage yield. Although leaf elongation has been shown to be temperature-dependent under normal conditions, the genetic regulation of leaf growth under water deficit in perennial ryegrass is poorly understood. Herein, we evaluated the response to water deprivation in a diverse panel of perennial ryegrass genotypes, employing a high-precision phenotyping platform. The study revealed phenotypic variation for growth-related traits and significant (P < 0.05) differences in leaf growth under normal conditions within the subgroups of turf and forage type cultivars. The phenotypic data was combined with genotypic variants identified using genotyping-by-sequencing to conduct a genome-wide association study (GWAS). Using GWAS, we identified DNA polymorphisms significantly associated with leaf growth reduction under water deprivation. These polymorphisms were adjacent to genes predicted to encode for phytochrome B and a MYB41 transcription factor. The result obtained in the present study will increase our understanding on the complex molecular mechanisms involved in plant growth under water deficit. Moreover, the single nucleotide polymorphism (SNP) markers identified will serve as a valuable resource in future breeding programs to select for enhanced biomass formation under mild summer drought conditions.


Password-only authenticated three-party key exchange proven secure against insider dictionary attacks.
While a number of protocols for password-only authenticated key exchange (PAKE) in the 3-party setting have been proposed, it still remains a challenging task to prove the security of a 3-party PAKE protocol against insider dictionary attacks. To the best of our knowledge, there is no 3-party PAKE protocol that carries a formal proof, or even definition, of security against insider dictionary attacks. In this paper, we present the first 3-party PAKE protocol proven secure against both online and offline dictionary attacks as well as insider and outsider dictionary attacks. Our construct can be viewed as a protocol compiler that transforms any 2-party PAKE protocol into a 3-party PAKE protocol with 2 additional rounds of communication. We also present a simple and intuitive approach of formally modelling dictionary attacks in the password-only 3-party setting, which significantly reduces the complexity of proving the security of 3-party PAKE protocols against dictionary attacks. In addition, we investigate the security of the well-known 3-party PAKE protocol, called GPAKE, due to Abdalla et al. (2005, 2006), and demonstrate that the security of GPAKE against online dictionary attacks depends heavily on the composition of its two building blocks, namely a 2-party PAKE protocol and a 3-party key distribution protocol.


Management of dysfunctional uterine bleeding.
DUB is a common symptom which is mainly due to disorders of ovulation and local endometrial dysfunction. The diagnosis should be made only after excluding organic pelvic disease. Anaemia and other endocrine and systemic causes of DUB must be treated promptly. Spontaneous cure is also possible. However, in patients in whom the symptoms persist, drug treatment with combined oestrogen-progestogen, anti-prostaglandin and anti-fibrinolytic agents is often effective. Hysterectomy and hysteroscopic endometrial ablation are contemplated only in persistent DUB in older and parous women and radiotherapy has no place amongst the modern modalities of management.


Mental measurement of line length: the role of the standard.
Reaction times were examined for magnitude estimates of line length. In the first two experiments, reaction times increased linearly with judged length. This result is consistent with the hypothesis the judgments are made by laying off a mental image of the standard along the line to be judged. The slope of the function relating judged length to reaction time was not affected by the length of the standard line, suggesting that the rate at which the image of the standard is laid off is not a function of the length of the standard. Reaction time also increased linearly with judged length when subjects judged line length when the standard of 1 in. was suggested but not provided as well as when no standard was suggested. The hypothesized laying-off process was compared to other cognitive manipulations, such as mental rotation and size scaling. Equivalence of judgments based on the representation of the standard in perceptual memory and in imagination is discussed.


SUBTHRESHOLD MICROPULSE DIODE LASER VERSUS CONVENTIONAL LASER PHOTOCOAGULATION FOR DIABETIC MACULAR EDEMA: A Meta-Analysis of Randomized Controlled Trials.
To evaluate the relative efficacy of subthreshold micropulse diode laser versus conventional laser photocoagulation for the treatment of diabetic macular edema. A comprehensive literature search was conducted to find relevant randomized controlled trials (RCTs). Efficacy estimates were determined by comparing weighted mean differences of the mean change of best-corrected visual acuity and central macular thickness from baseline. Six RCTs were selected for this meta-analysis, including 398 eyes (203 eyes in the subthreshold micropulse diode laser group and 195 eyes in the conventional laser group). Subthreshold micropulse diode laser was superior to conventional laser in terms of mean change of logMAR best-corrected visual acuity at 3, 9, and 12 months after treatment (P = 0.02; P = 0.04, and P = 0.03, respectively), and it showed a similar trend at 6 months (P = 0.05). Although, there was no significant difference in terms of mean change in central macular thickness from baseline to 3, 6, 9, or 12 months (P = 0.80; P = 0.20; P = 0.88, and P = 0.86, respectively). Subthreshold micropulse diode laser treatment resulted in better visual acuity compared with conventional laser, although the differences before 12 months are likely to be too small to be of clinical relevance and may be dependent on baseline best-corrected visual acuity. The two types of treatment seem to have similar anatomical outcome.


Covid-19 Presenting as Acute Limb Ischemia.
Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a potentially fatal disease. COVID-19 is associated with a hypercoagulable state leading to increased incidence of venous thromboembolism. Arterial thrombosis has been reported, but the prevalence is not known. Herein, we report an unusual presentation of a 77-year-old male who presented with dyspnea and pain in left leg and was found to have acute limb ischemia. Our case adds to the limited literature regarding arterial thrombosis in COVID-19.


Increased neural activity during high working memory load predicts low relapse risk in alcohol dependence.
Working memory (WM) impairments are often observed in alcohol-dependent individuals, especially in early abstinence, which may contribute to an increased relapse risk after detoxification. Brain imaging studies on visuospatial WM in alcohol-dependent patients compared to controls indicate that information processing requires compensatory increased neural activation to perform at a normal level. However, to date, no study tested whether such increased neural WM activation patterns or the lack thereof predict relapse behavior in alcohol-dependent individuals, and whether such differences persist when adequately correcting for individual grey matter differences. We combined analyses of neural activation during an n-back task and local grey matter volumes using Biological Parametric Mapping in 40 detoxified alcohol-dependent patients and 40 matched healthy controls (HC), and assessed prospective relapse risk during a 7-month follow-up period. Despite equal task performance, we found increased functional activation during high versus low cognitive WM load (2-back-0-back) in bilateral rostral prefrontal cortex (BA10) and bilateral ventrolateral prefrontal cortex (BA45,47) in prospective abstainers versus relapsers, and further in left/right lateral/medial premotor cortex (BA6,8) in abstainers versus HC. In prospective abstainers, but not relapsers, subtle cognitive impairment was associated with increased neural task activity in the premotor cortex. These findings suggest that in prospective abstainers, higher functional engagement of presumably less impaired neural resources in executive behavioral control brain areas (BA10, 45, 47, 6, 8) may constitute a resilience factor associated with good treatment outcome.


Cyanobacterial metallochaperone inhibits deleterious side reactions of copper.
Copper metallochaperones supply copper to cupro-proteins through copper-mediated protein-protein-interactions and it has been hypothesized that metallochaperones thereby inhibit copper from causing damage en route. Evidence is presented in support of this latter role for cyanobacterial metallochaperone, Atx1. In cyanobacteria Atx1 contributes towards the supply of copper to plastocyanin inside thylakoids but it is shown here that in copper-replete medium, copper can reach plastocyanin without Atx1. Unlike metallochaperone-independent copper-supply to superoxide dismutase in eukaryotes, glutathione is not essential for Atx1-independent supply to plastocyanin: Double mutants missing atx1 and gshB (encoding glutathione synthetase) accumulate the same number of atoms of copper per cell in the plastocyanin pool as wild type. Critically, Δatx1ΔgshB are hypersensitive to elevated copper relative to wild type cells and also relative to ΔgshB single mutants with evidence that hypersensitivity arises due to the mislocation of copper to sites for other metals including iron and zinc. The zinc site on the amino-terminal domain (ZiaA(N)) of the P(1)-type zinc-transporting ATPase is especially similar to the copper site of the Atx1 target PacS(N), and ZiaA(N) will bind Cu(I) more tightly than zinc. An NMR model of a substituted-ZiaA(N)-Cu(I)-Atx1 heterodimer has been generated making it possible to visualize a juxtaposition of residues surrounding the ZiaA(N) zinc site, including Asp(18), which normally repulse Atx1. Equivalent repulsion between bacterial copper metallochaperones and the amino-terminal regions of P(1)-type ATPases for metals other than Cu(I) is conserved, again consistent with a role for copper metallochaperones to withhold copper from binding sites for other metals.


Freezing injury and phospholipid degradation in vivo in woody plant cells: I. Subcellular localization of phospholipase d in living bark tissues of the black locust tree (robinia pseudoacacia L.).
The subcellular localization of phospholipase D in homogenates of living bark tissues of the black locust tree (Robinia pseudoacacia L.) was examined and found in both soluble and particulate fractions. At least some of the soluble enzyme was considered to be compartmentalized in vacuoles. Considerable amounts of phospholipase D seemed to be tightly bound on several membranes such as endoplasmic reticulum, tonoplast, and a membrane associated with potassium-stimulated ATPase (pH 6.1). The mitochondrial fraction banding at the 40 to 43% (w/w) sucrose layer, however, had the lowest specific activity. The soluble and the particulate phospholipase D were considered to be similar in nature. It is possible that the particulate enzyme, as a part, may be derived from the coexisting nonvesiculated materials visualized in the electron micrograph of each membrane fraction. An involvement of the soluble or the presumed membrane-bound phospholipase D in phospholipid degradation in vivo during freezing at sublethal temperatures was discussed with special reference to freezing injury of plant cells.


Quantitative competitive polymerase chain reaction for accurate quantitation of HIV DNA and RNA species.
Inherent features of the PCR make this procedure suboptimal for quantitative applications. For typical clinical specimens, the absolute amount of product derived from PCR does not always bear a consistent relationship to the amount of target sequence present at the start of the reaction. Competitive PCR approaches to quantitation of nucleic acid sequences overcome the limitations of basic PCR methods for quantitation. We have developed a competitive PCR method known as quantitative competitive PCR for quantitation of HIV DNA and RNA sequences. Key features of the technique include quantitation, based on the relative amounts of products produced from the target sequence and a competitive template introduced into test specimens, and stringent internal control of all reactions, including the reverse transcription step in RNA PCR. The method is suitable for analysis of clinical specimens and may be particularly valuable for accurate quantitation of viral load in patients undergoing treatment with experimental therapies.


Novel technique: radiofrequency coagulation--a treatment alternative for early-stage hemorrhoids.
For early-stage hemorrhoids, in which bleeding is the primary symptom, conventional approaches to management include injection of sclerosing solutions, band ligation, and infrared coagulation. In our study, we used the radiofrequency coagulation technique as an alternative strategy to treat early-stage hemorrhoids. A total of 210 patients with bleeding hemorrhoids were treated with radiofrequency coagulation at the Gupta Nursing Home in Nagpur, India. Follow-up was at 2 weeks, 3 months, and 12 months after procedure. Results were recorded as follows: (1) Bleeding--Twenty-eight (13%) patients had recurrence of bleeding during the observation period. (2) Pain--Some degree of discomfort was reported by all patients within the first 48 hours. (3) Retention of urine--Only 1 patient had retention of urine; this patient was 74 years old and had an enlarged prostate. (4) Discharge--Thirty-four (16%) patients complained of discharge in the first 2 weeks after procedure. (5) Return to work--Seventy percent (n = 145) of patients resumed their duties after 48 hours; the remainder required 1 additional day. (6) Sepsis--There were no reports of postprocedure sepsis. (7) Sphincter function--None of the patients experienced problems with continence or stenosis. Overall patient satisfaction was 84% (n = 177). Although these initial results of coagulation of hemorrhoids by radiofrequency appear quite exciting and encouraging, long-term follow-up is needed to assess the duration of relief and potential side effects. Continued work in this area will likely provide promising new dimensions in the effective management of early-stage hemorrhoids in which bleeding is the main symptom. A separate, randomized trial was carried out to assess the difference in efficacy between infrared coagulation and radiofrequency coagulation in 100 patients with early-stage hemorrhoids. Radiofrequency coagulation was found to be more effective than infrared coagulation in terms of recurrence of bleeding, asymptomatic recurrences of hemorrhoids, and overall satisfaction of technique.


Increases in smoking cessation interventions after a feedback and improvement initiative using electronic health records -- 19 community health centers, New York City, October 2010-March 2012.
Quitting smoking substantially reduces smokers' risk for smoking-related morbidity and mortality and can increase life expectancy by up to a decade. Most smokers want to quit and make at least one medical provider visit annually. Health care providers can play an important role in helping smokers quit by documenting patients' tobacco use, advising smokers to quit, and providing evidence-based cessation treatments or referrals for treatment, but many providers and practices do not regularly take these actions. Systems to increase provider screening and delivery of cessation interventions are available; in particular, electronic health records (EHRs) can be powerful tools to facilitate increased cessation interventions. This analysis reports on an EHR-based pay-for-improvement initiative in 19 community health centers (CHCs) in New York City (NYC) that sought to increase smoking status documentation and cessation interventions. At the end of the initiative, the mean proportion of patients who were documented as smokers in CHCs had increased from 24% to 27%, whereas the mean proportion of documented smokers who received a cessation intervention had increased from 23% to 54%. Public health programs and health systems should consider implementing strategies to equip and train clinical providers to use information technology to increase delivery of cessation interventions.


Diode-pumped passively Q-switched Nd:Gd0.5Y0.5VO4 laser at 1.34 microm with V3+:YAG as the saturable absorber.
The performance of a diode-pumped passively Q-switched Nd:Gd(0.5)Y(0.5)VO(4) laser at 1.34 microm with V(3+):YAG as the saturable absorber was demonstrated for the first time to the best of our knowledge. The focal lengths of thermal lens in the diode-end-pumped Nd:Gd(0.5)Y(0.5)VO(4) laser for the 1.34 microm transition was experimentally investigated, with the corresponding proportion constant estimated to be approximately1.5x10(4) W/mm. For the passive Q-switching operation, the maximum average output power of 0.96 W was achieved under the pump power of 7.28 W, corresponding to optical-to-optical conversion and slope efficiency of 13.2% and 17.6%, respectively. The minimum pulse width attained was 47.8 ns with the pulse repetition frequency of 76 kHz, with the single pulse energy and peak power estimated to be 8.7 microJ and 182 W, respectively.


A systematic approach of method development for analysis of multiple classes of emerging contaminants in wastewater: a case study of a biological nutrient removal based plant.
Pharmaceuticals, personal care products, synthetic hormones, and industrial manufacturing additives are used worldwide, and their residues are frequently detected in wastewater. In this study, a sensitive and selective method was developed and validated for the detection and quantification of 14 Emerging Contaminants (ECs) with various physico-chemical properties frequently found in wastewater. Solid Phase Extraction (SPE) allowed for extraction and concentration of the compounds. Liquid chromatography-mass spectrometry in both positive and negative electrospray ionization mode was used for the analysis. Three different combinations of mobile phase, water + 0.1% formic acid : acetonitrile + 0.1% formic acid (3 compounds), water + 0.1% formic acid : methanol (5) and 10 mM ammonium acetate buffer : acetonitrile + 0.1% formic acid (6) gave the best chromatographic conditions to analyze the contaminants in real wastewater samples. Four different eluents at acidic and basic sample pH values were tested to optimize the SPE methodology, and three different dilution ratios (1 : 1, 2 : 1, and 5 : 1) were tested to reduce the matrix effect. Data validation was conducted using linearity, intra and inter-day repeatability, LOD/LOQ, percentage recovery, and percentage process efficiency studies. As a case study, a biological nutrient removal (BNR) based plant was tested for the presence of ECs using the developed method. Removal efficiency at different treatment stages was assessed. Most of the treatment occurred at the secondary treatment stage, whereas primary treatment and disinfection had little effect on removal. All the contaminants were found in the inlet wastewater. Estrone (E1), an endocrine disrupting compound, was reported for the first time in Indian wastewater at 376.2 ng L-1. Seven, four, and two ECs were removed at high, medium, and low efficiencies, respectively. Carbamazepine showed negative removal. This study enhanced our understanding of the occurrence and fate of several ECs in BNR based treatment systems.


Daily use of protective behavioral strategies and alcohol-related outcomes among college students.
The purpose of the present study was to examine associations between use of protective behavioral strategies (PBS) and alcohol-related outcomes (alcohol consumption, negative alcohol consequences, and positive alcohol consequences) using a daily diary approach. This approach is less affected by retrospective memory biases than typical self-reports of alcohol-related variables and allows the examination of both between-subjects and within-person effects. Using hierarchical linear modeling of data from 40 subjects who completed daily dairies for up to 15 days, we found significant within-person variation in PBS use over time, and each type of PBS had unique relationships with alcohol-related outcomes. For example, within-person variation in Serious Harm Reduction, one form of PBS, predicted increased daily alcohol use, negative consequences, and positive consequences. Our findings suggest the importance of intensive longitudinal methods to examine both between-subjects and within-subjects effects of PBS use and alcohol-related outcomes.


Gender and palliative care: a call to arms.
There has been a systematic and largely unconscious neglect of gender in palliative care research, practice and policy. This is despite significant, although previously uncollated, evidence that gender influences almost all aspects of end-of-life preferences, experiences and care. The social situations of women, transgender people and men often differ from one another while also intersecting in complex ways with sex differences rooted in biology. If palliative care is to meet its aspiration of providing universal benefit, it urgently needs to address a range of gender inequalities currently (re)produced at the level of the laboratory all the way through to government departments. In this call to arms, we spotlight specific instances where gender inequalities have been documented, for example, regarding end-of-life caregiving, end-of-life intervention and palliative care access and benefit. We highlight how gender inequalities intersect with other social determinants of health including ethnicity and economic status to exacerbate situations of marginality. We conclude by offering some practical steps that can be taken to support the discipline to adopt a more critical gender lens to support more equitable research, policy and practice.


A review on effective soil health bio-indicators for ecosystem restoration and sustainability.
Preventing degradation, facilitating restoration, and maintaining soil health is fundamental for achieving ecosystem stability and resilience. A healthy soil ecosystem is supported by favorable components in the soil that promote biological productivity and provide ecosystem services. Bio-indicators of soil health are measurable properties that define the biotic components in soil and could potentially be used as a metric in determining soil functionality over a wide range of ecological conditions. However, it has been a challenge to determine effective bio-indicators of soil health due to its temporal and spatial resolutions at ecosystem levels. The objective of this review is to compile a set of effective bio-indicators for developing a better understanding of ecosystem restoration capabilities. It addresses a set of potential bio-indicators including microbial biomass, respiration, enzymatic activity, molecular gene markers, microbial metabolic substances, and microbial community analysis that have been responsive to a wide range of ecosystem functions in agricultural soils, mine deposited soil, heavy metal contaminated soil, desert soil, radioactive polluted soil, pesticide polluted soil, and wetland soils. The importance of ecosystem restoration in the United Nations Sustainable Development Goals was also discussed. This review identifies key management strategies that can help in ecosystem restoration and maintain ecosystem stability.


HIV infection in women: do sex and gender matter?
At least half of all HIV infections occur in women. Most women are of childbearing potential; therefore, issues encompassing reproduction and mother-to-child transmission are critical in the management of this population. The efficacy of antiretroviral therapy (ART) is similar in men and women, although rates of adverse events or toxicity may be higher in women, which, in turn, may be related to higher antiretroviral drug levels documented in pharmacokinetic studies. A substantial proportion of women may not derive the benefit of highly active ART because nonsuppressive regimens are commonly used, especially in resource-limited settings, to decrease mother-to-child transmission. The likely emergence of resistant virus can have long-term sequelae for the mother, child, and other exposed individuals. Additional studies are needed of sex/gender-related issues including antiretroviral toxicities, pharmacokinetic profiles of approved and novel agents, ART strategies during pregnancy to minimize HIV resistance, and determination of optimal antiretroviral regimens for women.


Neuroimaging-based approaches in the brain-computer interface.
Techniques to enable direct communication between the brain and computers/machines, such as the brain-computer interface (BCI) or the brain-machine interface (BMI), are gaining momentum in the neuroscientific realm, with potential applications ranging from medicine to general consumer electronics. Noninvasive BCI techniques based on neuroimaging modalities are reviewed in terms of their methodological approaches as well as their similarities and differences. Trends in automated data interpretation through machine learning algorithms are also introduced. Applications of functional neuromodulation techniques to BCI systems would allow for bidirectional communication between the brain and the computer. Such bidirectional interfaces can relay information directly from one brain to another using a computer as a medium, ultimately leading to the concept of a brain-to-brain interface (BBI).


Preparation of tethered aldehyde ynoates and ynones by ring fragmentation of cyclic gamma-oxy-beta-hydroxy-alpha-diazo carbonyls.
Cyclic gamma-oxy-beta-hydroxy-alpha-diazo carbonyls undergo Lewis acid induced ring fragmentation to provide either ynoates or ynones tethered to an aldehyde, ketone, or ester. The fragmentation precursors are convenient to prepare by adding lithiated alpha-diazo carbonyls to alpha-oxy ketones. The fragmentation appears general and provides a variety of functional group-rich products in good to excellent yield.


Digit ratio (2D:4D) and handedness: A meta-analysis of the available literature.
The Geschwind-Behan-Galaburda and sexual differentiation models predict an association between elevated foetal androgen exposure and left-handedness whereas the callosal hypothesis predicts the opposite. We present a meta-analysis of correlations between handedness and digit ratio (2D:4D), a putative marker of prenatal testosterone. Left-handedness predicted low (male-typical) right-hand digit ratio (R2D:4D), high (female-typical) left-hand digit ratio (L2D:4D), and low R2D:4D-L2D:4D directional asymmetry (D[R-L]). Effect sizes were extremely small and not moderated by sex or method of measuring handedness or 2D:4D. The same general pattern was observed after excluding the very large study (110,329 males, 90,412 females) of Manning and Peters ([2009]. Digit ratio (2D:4D) and hand preference for writing in the BBC Internet Study. Laterality: Asymmetries of Body, Brain and Cognition, 14(5), 528-540. doi:10.1080/13576500802637872); however, no significant effects for R2D:4D were observed once these samples were removed. The results do not confirm any theory linking prenatal androgens with handedness, so we speculate they instead reflect the mechanical action of writing causing subtle changes in the musculature and/or fat pads of the fingers. Gripping a pen/pencil might cause an increase in 2D relative to 4D (and/or decrease in 4D relative to 2D) resulting in higher ratios on the writing-hand; furthermore, this could differ between left- and right-handers due to writing in the left-to-right direction (as in English) having asymmetrical effects depending on which hand is used.


[Two cardiac tumors with left ventricular location: myxoma and papillary fibroelastoma].
We report 2 clinical cases of cardiac tumors, myxoma and papillary fibroelastoma, with unusual ventricular location. The clinical manifestations of these entities are not well described. Usually the patients are asymptomatic even if they have a high risk for cardiac and systemic embolic events so that these neoplasms are recognized during life more often in patients evaluated for embolic events of unclear pathology. The routine use of echocardiography has increased the detection of these tumors in living patients. In the surgical treatment, the approach should allow minimal manipulation of the tumors, inspection of all four cardiac chambers to overlook if tumors are multifocal and provide adequate exposure for complete resection. In our experience, we used two surgical approaches, via the left ventricle and via the aortic valve.


3,4-Dimethyl-4-(3-hydroxyphenyl)piperidines: opioid antagonists with potent anorectant activity.
A series of (3R*,4R*)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists with varying substituents on the nitrogen were evaluated for their effect on food consumption in obese Zucker rats. Opioid affinity (mu, kappa, and delta for selected compounds) and opioid antagonist activity (mu and kappa) were characterized and compared to effects on food consumption. No compounds with high selectivity for either mu or kappa receptors were discovered. However, compounds in the series had exceptional potency as opioid antagonists and in reducing food consumption in the obese Zucker rat. In contrast, a few compounds with high potency as opioid antagonists had much weaker potency for inhibiting food consumption. (3R,4R)-3,4-Dimethyl-1-[(3S)-3- hydroxy-3-cyclohexyl-propyl]-4-(3-hydroxyphenyl)piperidine (11,LY255582) emerged as having the best activity profile, both in reducing food consumption and as an opioid antagonist. Compound 11 is a highly potent mu, kappa-, and delta-opioid antagonist with possible clinical utility as an appetite suppressant for weight loss.


PPARβ activation restores the high glucose-induced impairment of insulin signalling in endothelial cells.
PPARβ enhances insulin sensitivity in adipocytes and skeletal muscle cells, but its effects on insulin signalling in endothelial cells are not known. We analysed the effects of the PPARβ/δ (PPARβ) agonists, GW0742 and L165041, on impaired insulin signalling induced by high glucose in HUVECs and aortic and mesenteric arteries from diabetic rats. Insulin-stimulated NO production, Akt-Ser(473) and eNOS-Ser(1177) phosphorylation, and reactive oxygen species (ROS) production were studied in HUVECs incubated in low- or high-glucose medium. Insulin-stimulated relaxations and protein phosphorylation in vessels from streptozotocin (STZ)-induced diabetic rats were also analysed. HUVECs incubated in high-glucose medium showed a significant reduction in insulin-stimulated production of NO. High glucose also reduced insulin-induced Akt-Ser(473) and eNOS-Ser(1177) phosphorylation, increased IRS-1-Ser(636) and ERK1/2-Thr(183) -Tyr(185) phosphorylation and increased ROS production. The co-incubation with the PPARβ agonists GW0742 or L165041 prevented all these effects induced by high glucose. In turn, the effects induced by the agonists were suppressed when HUVEC were also incubated with the PPARβ antagonist GSK0660, the pyruvate dehydrogenase kinase (PDK)4 inhibitor dichloroacetate or after knockdown of both PPARβ and PDK4 with siRNA. The ERK1/2 inhibitor PD98059, ROS scavenger catalase, inhibitor of complex II thenoyltrifluoroacetone or uncoupler of oxidative phosphorylation, carbonyl cyanide m-chlorophenylhydrazone, also prevented glucose-induced insulin resistance. In STZ diabetic rats, oral GW0742 also improved insulin signalling and the impaired NO-mediated vascular relaxation. PPARβ activation in vitro and in vivo restores the endothelial function, preserving the insulin-Akt-eNOS pathway impaired by high glucose, at least in part, through PDK4 activation.


The ceramide [NP]/[NS] ratio in the stratum corneum is a potential marker for skin properties and epidermal differentiation.
Specific species of ceramides (Cer), major constituents of lipids in the stratum corneum (SC), are decreased and are correlated with SC barrier and water-holding functions in the skin of patients with atopic dermatitis (AD) or psoriasis (Pso). However, possible correlations between Cer subclass ratios and skin properties in barrier-disrupted skin and in healthy skin remain unclear. The objective of this study was to identify a new marker to evaluate skin properties and epidermal differentiation in SC not only in barrier-disrupted skin but also in healthy skin. The Cer subclass ratios in the SC of healthy control subjects and in patients with AD or Pso were evaluated. Correlations with candidate markers and facial skin features of healthy Japanese females (20-74 years old, n = 210) were investigated. Variations of markers during epidermal differentiation were studied in human epidermis and in cultured keratinocytes. The ratios of Cer [NP]/[NS], Cer [NH]/[NS], Cer [NP]/[AS], Cer [NH]/[NS], Cer [NDS]/[AS], Cer [AH]/[AS] and Cer [EOP]/[AS] showed significant differences between non-lesional skin of AD patients and normal skin of healthy control subjects, as well as Pso patients and their healthy control subjects. The Cer [NP]/[NS] ratio was correlated with SC functional parameters (transepidermal water loss and capacitance) and with skin appearance (texture, scaling and color) even in the cheek skin of healthy female subjects. The Cer [NP]/[NS] ratio in the SC was approximately 18-times higher than in living keratinocytes, and it increased as they differentiated. The Cer [NP]/[NS] ratio in the SC is a potential marker for skin properties and epidermal differentiation in barrier-disrupted skin as well as in healthy skin.


Development of cranial muscles in the actinopterygian fish Senegal bichir, Polypterus senegalus Cuvier, 1829.
Polypterus senegalus Cuvier, 1829 is one of the most basal living actinopterygian fish and a member of the Actinopterygii. We analyzed the spatial and temporal pattern of cranial muscle development of P. senegalus using whole-mount immunostaining and serial sectioning. We described the detailed structure of the external gill muscles which divided into dorsal and ventral parts after yolk exhaustion. The pattern of the division is similar to that of urodeles. We suggest that, the external gill muscles of P. senegalus are involved in spreading and folding of the external gill stem and the branches. The fibers of the external gill muscles appear postero-lateral to the auditory capsule. In addition, the facial nerve passes through the external gills. Therefore, the external gill muscles are probably derived from the m. constrictor hyoideus dorsalis. In contrast to previous studies, we described the mm. interhyoideus and hyohyoideus fibers as independent components in the yolk-sac larvae. The m. hyohyoideus fibers appear lateral to the edge of the ventral portion of the external gill muscles, which are probably derived from the m. constrictor hyoideus dorsalis. These findings suggest that the m. hyohyoidues is derived from the m. constrictor hyoideus dorsalis in P. senegalus. In other actinopterygians, the m. hyohyoideus is derived from the m. constrictor hyoideus ventralis; therefore, the homology of the m. hyohyoidues of P. senegalus and other actinopterygians remains unclear. J. Morphol. 278:450-463, 2017. © 2017 Wiley Periodicals, Inc.


Portal hypertension. Update on pathophysiology and management.
A lot has been learned about the pathophysiology of portal hypertension and its complications. This knowledge has led to vast advancements in therapy for this serious disease. I believe the future will carry more breakthroughs in therapy intercepting earlier steps in the disease process such as arresting fibrogenesis, inducing fibrinolysis or possibly targeting vascular remodeling and neovessel formation or employing hepatocytes transplantation.


[Side effects of anti-arrhythmia drugs].
Since there are no antiarrhythmic drugs with selective effect on the removal of pathologic rhythms without influence on the formation of normal stimuli and the conduction system, which are free from cardiac and extracardiac side effects, in the application of an antiarrhythmic drug apart from an indication which is strictly to be established it must equivalently be taken into consideration which systemic and genuine side effects, pharmacokinetic problems and drug interactions must be taken into account. An unavoidable risk (systemic side effects) is to be put up with. Existing contraindications sometimes bring about the renunciation of therapy. Side effects are avoidable, when they are strictly controlled, since they are then recognized in time and lead to the interruption of therapy.


The risk trajectory between preoperative fasting glucose and common digestive tract cancer-specific mortality in the FIESTA cohort involving 6865 Chinese patients.
Backgrounds: High blood glucose or hyperglycemia is an established risk factor for the development and progression of cancer at many sites, whereas data on the relevance between low blood glucose or hypoglycemia and cancer survival are lacking. Aims: We aimed to assess the shape of risk trajectory between preoperative fasting glucose and postoperative digestive cancer-specific mortality in Chinese. Methods: In total, 6865 patients who underwent radical surgery for esophageal cancer (n=2535), gastric cancer (n=3012) and colorectal cancer (n=1318) during 2000-2010 were followed up as of December 2015. All patients received neither chemotherapy nor radiotherapy before and after the surgery. Optimal cutoff points were determined using survival tree analysis. Results: The median follow-up time was 44.9 months (range: 0.5-188.9 months), with 1065 deaths from esophageal cancer, 1331 from gastric cancer and 412 from colorectal cancer. Using fasting glucose (4.36, 6.09] mmol/L as the reference group, hazard ratios for fasting glucose ≤4.36, (6.09, 8.95], (8.95, 11.5] and >11.5 mmol/L were 1.35 (95% confidence interval: 1.19, 1.54), 2.82 (2.57, 3.11), 3.56 (3.10, 4.08) and 4.27 (3.67, 4.97), respectively (p<0.001). Conclusions: Our findings indicate a U-shaped risk trajectory between preoperative fasting glucose and digestive tract cancer-specific mortality in Chinese. Further external validation is warranted.


Use of a light-induced respiratory transient to measure the optical cross section of photosystem I in chlorella.
A method has been developed whereby the magnitude of a transient in O(2) uptake attributable to photosystem (PS) I activity, following single-turnover laser flashes of varying energy, can be used to measure the optical cross section of PSI. As measurements are made under the identical physiological conditions for which the cross section of PSII has previously been determined (AC Ley, DC Mauzerall 1982 Biochim Biophys Acta 680: 96-105), it is now possible to simultaneously measure the cross section of both photosystems in intact, photosynthetically competent cells, without the use of inhibitors or artificial mediators of electron transport. Plots of light-saturation behavior of the respiratory oscillation following pulses at 596 nanometers indicate a mean optical cross section similar to that of PSII at this wavelength, but suggest significant heterogeneity in the cross section of PSI. If this method measures only PSI activity, this result implies that there exist units with different numbers of identical chromophores, or units having populations of chromophores with different absorption spectra.


The Dichotic Word Listening Test: preliminary observations in American and Canadian samples.
The present article describes observations of 670 American and Canadian child and adult control subjects on the recently developed Dichotic Word Listening Test (DWLT). The task was also administered to a sample of American children with traumatic brain injuries (n=21) of varying severity and a sample of American adults with mild traumatic injuries (n=36). The conceptual focus in this line of research was on using normative observations to identify clinically defective channels of auditory processing among patients. The principal findings were as follow: 1) the DWLT was sensitive to the effects of cerebral dysfunction following traumatic brain injury; 2) differences among normal samples with different demographic backgrounds were frequently observed, arguing for the development of local norms; 3) a shorter form of the DWLT task (DWLT30) can be used for screening purposes with relatively little reduction in sensitivity to cerebral dysfunction; 4) there appeared to be considerable improvement of DWLT performance between the ages of five and seven, due largely to higher scores from the left auditory channel; and 5) there were indications that use of French (rather than English) as one's native language before age six can negatively influence performance in adulthood on an English version of the DWLT. In general, the present findings suggest that the DWLT is likely to have relatively broad applicability for neuropsychological assessment across the life-span.


Utility of entomological indices for predicting transmission of dengue virus: secondary analysis of data from the Camino Verde trial in Mexico and Nicaragua.
Dengue vector entomological indices are widely used to monitor vector density and disease control activities. But the value of these indices as predictors of dengue infection is not established. We used data from the impact assessment of a trial of community mobilization for dengue prevention (Camino Verde) to examine the associations between vector indices and evidence of dengue infection and their value for predicting dengue infection levels. In 150 clusters in Mexico and Nicaragua, two entomological surveys, three months apart, allowed calculation of the mean Container Index, Breteau index, Pupae per Household Index, and Pupae per Container Index across the two surveys. We measured recent dengue virus infection in children, indicated by a doubling of dengue antibodies in paired saliva samples over the three-month period. We examined the associations between each of the vector indices and evidence of dengue infection at household level and at cluster level, accounting for trial intervention status. To examine the predictive value for dengue infection, we constructed receiver operating characteristic (ROC) curves at household and cluster level, considering the four vector indices as continuous variables, and calculated the positive and negative likelihood ratios for different levels of the indices. None of the vector indices was associated with recent dengue infection at household level. The Breteau Index was associated with recent infection at cluster level (Odds ratio 1.36, 95% confidence interval 1.14-1.61). The ROC curve confirmed the weak predictive value for dengue infection of the Breteau Index at cluster level. Other indices showed no predictive value. Conventional vector indices were not useful in predicting dengue infection in Mexico and Nicaragua. The findings are compatible with the idea of sources of infection outside the household which were tackled by community action in the Camino Verde trial.


Droplet and bone dust contamination from high-speed drilling during mastoidectomy.
The aim of this study was to examine contamination from otolaryngologic procedures involving high-speed drilling, specifically mastoid surgery, and to assess the adequacy of PPE in such procedures. Mastoid surgery was simulated in a dry laboratory using a plastic temporal bone, microscope and handheld drill with irrigation and suction. Comparisons of distance of droplet and bone dust contamination and surgeon contamination were made under differing conditions. Irrigation speed, use of microscope and drill burr size and type were compared. Measurement of the distance of field contamination while performing simulated mastoidectomy and location of surgeon contamination. There was a greater distance field contamination and surgeon contamination without the use of the microscope. Contamination was reduced by using a smaller drill burr and by using a diamond burr when compared to a cutting burr. The use of goggles and a face mask provided good protection for the surgeon. However, the microscope alone may provide sufficient protection to negate the need for goggles. While the risks of performing mastoid surgery during the coronavirus pandemic cannot be completely removed, they can be mitigated. Such factors include using the microscope for all drilling, using smaller size drill burrs and creating a safe zone around the operating table.


Effect of feeding allowance level on embryonic survival, IGF-1, insulin, GH, leptin and progesterone secretion in early pregnancy gilts.
The present experiment was conducted to evaluate the effects of feeding allowance level on embryonic survival, uterine development and reproductive hormone secretion in early gestation gilts. A total of 54 F1 crosses of Landrace x Large white gilts were randomly allocated to three treatment groups of high (H, 2 x maintenance), medium (M, 1.2 x maintenance) and low (L, 0.6 x maintenance) feeding level after mating. Blood samples and uterine flushings were collected on day 12, 25 and 35 of pregnancy, and embryonic survival rate was estimated. Concentrations of insulin-like growth factor I (IGF)-1, insulin, growth harmone (GH), leptin and progesterone in serum and uterine flushings were determined by enzyme-linked immunosorbent assay. Embryonic survival was affected by dietary treatment; total number of viable embryos and embryo survival of group M were higher than other groups in the early pregnancy (p < 0.05). Greater foetal weight in M gilts was achieved when gestation advanced to day 35 (p < 0.05), though there was no difference on day 25 of pregnancy among treatments. No appreciable differences were observed in the crown-rump length on day 25 and 35 of pregnancy among groups. Greater weight of uterus and products of conception were identified in M gilts compared with group H and L (p = 0.024 and p = 0.005, respectively) on day 25 of pregnancy. The hormone level was greatly affected by feeding allowance level. In serum, concentrations of IGF-1, leptin and insulin tended to be greater in H than in M and L during the early gestation, while concentrations of GH were greater in M and progesterone were the lowest in H. At the same time, feed allowance level affected the concentration of IGF-1, insulin, GH, leptin and progesterone in uterine flushings. These data demonstrated that feed allowance level after mating has important consequence on embryo survival, embryo development and uterine development, possibly mediated by nutrition level inducing changes in concentrations of reproductive hormones and/or intermediary metabolites in early pregnancy.


How "should" we write guideline recommendations? Interpretation of deontic terminology in clinical practice guidelines: survey of the health services community.
To describe the level of obligation conveyed by deontic terms (words such as "should", "may", "must" and "is indicated") commonly found in clinical practice guidelines. Cross-sectional electronic survey. A clinical scenario was developed by the researchers, and recommendations containing 12 deontic terms and phrases were presented to the participants. All 1332 registrants of the 2008 annual conference of the US Agency for Healthcare Research and Quality. Participants indicated the level of obligation they believed guideline authors intended by using a slider mechanism ranging from "No obligation" (leftmost position recorded as 0) to "Full obligation" (rightmost position recorded as 100.) 445/1332 registrants (36%) submitted the on-line survey; 254/445 (57%) reported that they have experience in developing clinical practice guidelines; 133/445 (30%) indicated that they provide healthcare. "Must" conveyed the highest level of obligation (median = 100) and least amount of variability (interquartile range = 5.) "May" (median = 37) and "may consider" (median = 33) conveyed the lowest levels of obligation. All other terms conveyed intermediate levels of obligation characterised by wide and overlapping interquartile ranges. Members of the health services community believe guideline authors intend variable levels of obligation when using different deontic terms within practice recommendations. Ranking of a subset of terms by intended level of obligation is possible. Matching deontic terminology to the intended recommendation strength can help standardise the use of deontic terminology by guideline developers.


Vitamin D deficiency in school-age Iranian children with attention-deficit/hyperactivity disorder (ADHD) symptoms: A critical comparison with healthy controls.
The associations between serum vitamin D levels and the severity of attention-deficit/hyperactivity disorder (ADHD) symptoms were assessed among Iranian hospitalized children (50 ADHD cases and 50 healthy (non-ADHD) controls) during 2014-2015. Levels of ADHD severity and serum 25-hydroxyvitamin D (25OHD) were determined by the Conners' Parent Rating Scale (CPRS) test and an ELISA kit, respectively. The serum 25OHD concentrations of <10, 10-29, and >30 ng/mL were respectively considered as deficient (severe deficiency), insufficient (mild deficiency), and sufficient levels of vitamin D. The association of nutrient bioavailability with ADHD was evaluated by statistical and regression analyses.There was no significant difference in the mean of socio-demographic variables (e.g., gender, age, weight, BMI, daily intake of dairy products, and daily sunlight exposure) between ADHD and non-ADHD subjects. The mean serum 25OHD concentration (16.57 ± 9.09 ng/mL) was found to be significantly lower in ADHD children with more parathyroid hormone (PTH) levels as compared to controls (22.01 ± 12.67ng/mL). The sufficient 25OHD concentration was more predominant in the controls than the cases (p = 0.002). A severe deficiency of vitamin D was more found in children with ADHD (3.36 times). There was a negative and significant association between the participants' age and their serum 25OHD levels. Although 25OHD levels in boys were significantly more than those in girls, the reduction of serum 25OHD concentration among boys with ADHD was more severe compared to the patient girls(p = 0.014). The results support the importance of vitamins D role in ADHD patients through the regular monitoring of serum 25OHD levels.


Consistency and change in club drug use by sexual minority men in New York City, 2002 to 2007.
We used repeated cross-sectional data from intercept surveys conducted annually at lesbian, gay, and bisexual community events to investigate trends in club drug use in sexual minority men (N = 6489) in New York City from 2002 to 2007. Recent use of ecstasy, ketamine, and γ-hydroxybutyrate decreased significantly. Crystal methamphetamine use initially increased but then decreased. Use of cocaine and amyl nitrates remained consistent. A greater number of HIV-positive (vs HIV-negative) men reported recent drug use across years. Downward trends in drug use in this population mirror trends in other groups.


Physical activity: perspectives of Mexican American and Anglo American midlife women.
Despite the well-known health benefits of physical activity (PA), most midlife and older adults lead sedentary lifestyles. Anglo American women and Mexican Americans of both genders are two of the least physically active groups. We conducted three focus groups to identify attitudes and beliefs about PA among Mexican American and Anglo American midlife women. Our long-term goal was to identify culture-specific interventions that promote long-term PA continuation. Significant differences were found between the two groups. While Anglo American women valued individual outcomes, and spoke of personal factors promoting or preventing exercise, Mexican American women viewed PA as prescriptive, important for restoring health, and cited family responsibilities and family attitudes as factors that promoted or prevented them from exercising. We found that in order for PA interventions to be successful in each group, they must be tailored to the values of each cultural group.


Degradation of microplastic seed film-coating fragments in soil.
Encapsulating fungicides and/or insecticides in film-coatings applied to agronomic seeds has become a widely accepted method for enhancing seed germination and overall seedling health by protecting against many diseases and early-season insect pests. Despite advancements in seed film-coating technologies, abrasion of the seed coating can occur during handling and mechanical planting operations, resulting in variable amounts of detached fragments entering the soil. The present study investigated the degradation in soil of these plastic-like, small-sized fragments, referred to here as microplastic coating fragments. Degradation of microplastic coating fragments in soil was found to be highly variable. The lowest degradation rate (≤48 days) was observed in fragments detached from seeds coated with a commercial polymer mixture, while fragments from a biodegradable plastic formulation degraded completely within 32 days. When spores of the plant growth-promoting bacterium, Bacillus subtilis, were incorporated into the bioplastic, degradation was even more rapid (≤24 days). The fragment degradation rate was unaffected by incorporating two commonly used neonicotinoid insecticides, imidacloprid or thiacloprid, into either coating formulations, but insecticide dissipation rates in soil were more rapid when added associated with seed coating fragments than when spiked in directly. Half-lives of these two insecticides were reduced by up to 27% in fragments from bioplastic-coated seeds. These results are consistent with variable and not easily predicted soil degradation rates for seed coating fragments, with enhanced dissipation of coating-entrapped pesticides and with a higher degradation rate for biodegradable seed coating incorporating selected microbial strains.


Error analysis for determination of accuracy of an ultrasound navigation system for head and neck surgery.
The use of conventional CT- or MRI-based navigation systems for head and neck surgery is unsatisfactory due to tissue shift. Moreover, changes occurring during surgical procedures cannot be visualized. To overcome these drawbacks, we developed a novel ultrasound-guided navigation system for head and neck surgery. A comprehensive error analysis was undertaken to determine the accuracy of this new system. The evaluation of the system accuracy was essentially based on the method of error definition for well-established fiducial marker registration methods (point-pair matching) as used in, for example, CT- or MRI-based navigation. This method was modified in accordance with the specific requirements of ultrasound-guided navigation. The Fiducial Localization Error (FLE), Fiducial Registration Error (FRE) and Target Registration Error (TRE) were determined. In our navigation system, the real error (the TRE actually measured) did not exceed a volume of 1.58 mm(3) with a probability of 0.9. A mean value of 0.8 mm (standard deviation: 0.25 mm) was found for the FRE. The quality of the coordinate tracking system (Polaris localizer) could be defined with an FLE of 0.4 +/- 0.11 mm (mean +/- standard deviation). The quality of the coordinates of the crosshairs of the phantom was determined with a deviation of 0.5 mm (standard deviation: 0.07 mm). The results demonstrate that our newly developed ultrasound-guided navigation system shows only very small system deviations and therefore provides very accurate data for practical applications.


Change in cytokine levels after administration of saikokaryuukotsuboreito or testosterone in patients with symptoms of late-onset hypogonadism.
The purpose of this study was to evaluate plasma cytokine levels after treatment with saikokaryukotsuboreito (SKRBT), which is a herbal medicine, or androgen replacement treatment (ART), for patients with late-onset hypogonadism (LOH)-related symptoms. Thirty-one patients over 40 years of age with LOH-related symptoms were included in this study. SKRBT was given orally three times daily to a total of 7.5 g/day for 15 eugonadal patients and ART was give to 16 hypogonadal patients by intramuscular injection of testosterone enanthate at 125 mg each time every 2 weeks. Plasma levels of testosterone and 18 cytokines, as well as LOH-related symptoms scored according to the Aging Males' Symptoms (AMS) scale, were compared before and more than 2 months after treatment. In the ART group, the total AMS score was decreased and testosterone was increased significantly after treatment. No cytokine variables were altered significantly after the treatment. In the SKRBT group, although the total AMS score was significantly decreased, testosterone did not change. From the evaluation of cytokines, a significant increase was found in interleukin (IL)- 8, IL-13, interferon-gamma and tumour necrosis factor-alpha. We conclude that SKRBT might improve LOH-related symptoms in eugonadal patients through the beneficial effect of cytokines, a mechanism that is quite different from ART.


Experiences of Young People and Their Caregivers of Using Technology to Manage Type 1 Diabetes Mellitus: Systematic Literature Review and Narrative Synthesis.
In the last decade, diabetes management has begun to transition to technology-based care, with young people being the focus of many technological advances. Yet, detailed insights into the experiences of young people and their caregivers of using technology to manage type 1 diabetes mellitus are lacking. The objective of our study was to describe the breadth of experiences and perspectives on diabetes technology use among children and adolescents with type 1 diabetes mellitus and their caregivers. This systematic literature review used integrated thematic analysis to guide a narrative synthesis of the included studies. We analyzed the perspectives and experiences of young people with type 1 diabetes mellitus and their caregivers reported in qualitative studies, quantitative descriptive studies, and studies with a mixed methods design. Seventeen articles met the inclusion criteria, and they included studies on insulin pump, glucose sensors, and remote monitoring systems. The following eight themes were derived from the analysis: (1) expectations of the technology prior to use, (2) perceived impact on sleep and overnight experiences, (3) experiences with alarms, (4) impact on independence and relationships, (5) perceived usage impact on blood glucose control, (6) device design and features, (7) financial cost, and (8) user satisfaction. While many advantages of using diabetes technology were reported, several challenges for its use were also reported, such as cost, the size and visibility of devices, and the intrusiveness of alarms, which drew attention to the fact that the user had type 1 diabetes mellitus. Continued use of diabetes technology was underpinned by its benefits outweighing its challenges, especially among younger people. Diabetes technologies have improved the quality of life of many young people with type 1 diabetes mellitus and their caregivers. Future design needs to consider the impact of these technologies on relationships between young people and their caregivers, and the impact of device features and characteristics such as size, ease of use, and cost.


The dynamic nitric oxide pattern in developing cuttlefish Sepia officinalis.
Nitric oxide (NO) is implied in many important biological processes in all metazoans from porifera to chordates. In the cuttlefish Sepia officinalis NO plays a key role in the defense system and neurotransmission. Here, we detected for the first time NO, NO synthase (NOS) and transcript levels during the development of S. officinalis. The spatial pattern of NO and NOS is very dynamic, it begins during organogenesis in ganglia and epithelial tissues, as well as in sensory cells. At later stages, NO and NOS appear in organs and/or structures, including Hoyle organ, gills and suckers. Temporal expression of NOS, followed by real-time PCR, changes during development reaching the maximum level of expression at stage 26. Overall these data suggest the involvement of NO during cuttlefish development in different fundamental processes, such as differentiation of neural and nonneural structures, ciliary beating, sensory cell maintaining, and organ functioning.


Solitary plasmacytoma of the jaw occurring in an elderly woman affected by hepatitis C virus infection: a case report.
Solitary plasmacytoma accounts for a small percentage of plasma cell neoplasms. The disease often affects older people and is potentially curable. Only a few cases of solitary jaw plasmacytoma have been described in the literature. Here we report the case of a 76-year-old woman affected by chronic hepatitis C infection and isolated plasmacytoma of the left jaw. Plasmacytoma was diagnosed in January 2001, but the swelling of the mandible had been present since 1993. Two different pathologists made the diagnosis on the basis of biopsy material from the mandibular swelling.