Strengthening effect of aluminum fluoride added to resin composites based on polyacid-containing polymer.
The study investigates the possible strengthening effect of aluminum ions liberated during long-time water storage of experimental resin composites containing a polymer with carboxylic acid groups. The organic part of the resin composites was formed by photopolymerization of methacrylate monomers. The monomer mixture was composed of UEDMA, HEMA or TEGDMA, and 0-40 mol% HEMAN (the adduct of HEMA and maleic anhydride). The filler part of the resin composites consisted of a conventional silanated glass filler and 1 or 5 wt% of AlF3 x 3H2O. The rupture strength and bending modulus were measured without water storage and after 1 month, 1 year, and 3 years of water storage at 37 degrees C of the resin composite. The experimental composites that had been stored in water had lower rupture strength and modulus than the composites that were tested without water storage. Specimens containing 30 or 40 mol% HEMAN increased in strength, and specimens containing 20, 30, or 40 mol% HEMAN increased in modulus during the period of water storage. Depending on composition, values for strength and modulus obtained after 3 years of water storage was up to 50% higher than the values obtained after 1 month. The strengthening effect of aluminum fluoride may be interpreted as the result of increased crosslinking by aluminum ions and carboxylate groups. The results may serve as a basis for the improvement of the mechanical properties of polyacid-modified resin composites.


Usability study of multiple vibrotactile feedback stimuli in an entire virtual keyboard input.
With advances in information technology, people spend more time on touchscreen-based virtual keyboards than physical keyboards. However, typing on touchscreens usually lacks informative tactile feedback and anchoring references to locate the right keys, and thus requires more visual attention. Most prior tactile keyboard research used single stimulus pattern, which was not enough to recognize different keys. The purpose of this study was to investigate the usability of multiple vibrotactile feedback patterns in an entire virtual QWERTY keyboard input. A set of highly discriminable vibration patterns was designed and associated with different regions of a virtual keyboard to help users to locate the right keys. However, the number of stimulus patterns might also affect the typing performance. A user study was conducted to evaluate the effectiveness of the multiple vibrotactile feedback. The results showed that an appropriate number of stimulus patterns provided higher typing speed, higher typing efficiency, and lower error rate.


Retracted: A Study on the Preventive Effect of Esketamine on Postpartum Depression (PPD) after Cesarean Section.
[This retracts the article DOI: 10.1155/2022/1524198.].


Transdiagnostic neurocognitive deficits in patients with type 2 diabetes mellitus, major depressive disorder, bipolar disorder, and schizophrenia: A 1-year follow-up study.
Neurocognition impairments are critical factors in patients with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), and also in those with somatic diseases such as type 2 diabetes mellitus (T2DM). Intriguingly, these severe mental illnesses are associated with an increased co-occurrence of diabetes (direct comorbidity). This study sought to investigate the neurocognition and social functioning across T2DM, MDD, BD, and SZ using a transdiagnostic and longitudinal approach. A total of 165 participants, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HC), were assessed twice at a 1-year interval using a comprehensive, integrated test battery on neuropsychological and social functioning. Common neurocognitive impairments in somatic and psychiatric disorders were identified, including deficits in short-term memory and cognitive reserve (p < 0.01, η²p=0.08-0.31). Social functioning impairments were observed in almost all the disorders (p < 0.0001; η²p=0.29-0.49). Transdiagnostic deficits remained stable across the 1-year follow-up (p < 0.001; η²p=0.13-0.43) and could accurately differentiate individuals with somatic and psychiatric disorders (χ² = 48.0, p < 0.0001). The initial sample size was small, and high experimental mortality was observed after follow-up for one year. This longitudinal study provides evidence of some possible overlap in neurocognition deficits across somatic and psychiatric diagnostic categories, such as T2DM, MDD, BD, and SZ, which have high comorbidity. This overlap may be a result of shared genetic and environmental etiological factors. The findings open promising avenues for research on transdiagnostic phenotypes of neurocognition in these disorders, in addition to their biological bases.


Selectivity of pirenzepine in the central nervous system. I. Direct autoradiographic comparison of the regional distribution of pirenzepine and carbamylcholine binding sites.
The binding capacities of the novel antagonist pirenzepine and the agonist carbamylcholine were examined autoradiographically to compare their abilities to reduce the binding of 1-[3H]quinuclidinyl benzilate ([3H]-1-QNB). This technique, which is applicable to any muscarinic ligand, permits a direct comparison between the binding of carbamylcholine and pirenzepine in the same assay. Analysis of the binding curves generated by standard scintillation counting of whole-brain slices indicated that the ligands bound heterogeneously to muscarinic receptors in the brain. Following apposition of slides to tritium-sensitive film, the binding profile for each ligand was examined visually and by microdensitometry. Regional analyses indicated that the agonist carbamylcholine displayed highest potency for thalamic nuclei, lower potency for cortical regions, and the lowest affinity for layers of the hippocampus. The M1-selective ligand pirenzepine displayed the highest potency for the dentate gyrus of the hippocampus, with lower inhibition levels in the cortex, and the lowest levels of inhibition found in the thalamus. The distribution of high affinity agonist sites was found to be distinct from the distribution of high-affinity antagonist binding sites. In a separate assay, the regional inhibition of pirenzepine and scopolamine was compared for the hippocampus and the forebrain. While scopolamine did not distinguish between muscarinic receptor sites in the hippocampus and cortex, pirenzepine inhibited [3H]-1-QNB labeling in the hippocampus significantly greater than in the cerebral cortex, providing additional evidence for the hypothesis that pirenzepine is a selective antagonist.


Mechanical feedback-loop regulation of morphogenesis in plants.
Morphogenesis is a highly controlled biological process that is crucial for organisms to develop cells and organs of a particular shape. Plants have the remarkable ability to adapt to changing environmental conditions, despite being sessile organisms with their cells affixed to each other by their cell wall. It is therefore evident that morphogenesis in plants requires the existence of robust sensing machineries at different scales. In this Review, I provide an overview on how mechanical forces are generated, sensed and transduced in plant cells. I then focus on how such forces regulate growth and form of plant cells and tissues.


Imaging Approach to Misplaced Central Venous Catheters.
Central venous catheters (CVCs) are commonly used in patients in a variety of clinical settings, including the intensive care unit, general ward, and outpatient settings. After placement, the radiologist is frequently requested to evaluate the location of CVCs and deem them suitable for use. An understanding of the ideal location of catheter tips as well as the approach to identifying malpositioned catheter tips is essential to prevent improper use, recognize and/or prevent further injury, and direct potential lifesaving care. An approach to CVC placement based on tip location can be helpful in localization and guiding management.


The ecology of Rhodococcus equi and physicochemical influences on growth.
Growth of Rhodococcus equi was studied in vitro. Optimal growth occurred under aerobic conditions between pH 7.0 and 8.5, at 30 degrees C. R. equi survived better in a neutral soil (pH 7.3) than it did in two acid soils (pH less than 5.5). It grew substantially better in soils enriched with faeces than in soils alone. Simple organic acids in horse dung, especially acetate and propionate, appear to be important in supporting growth of R. equi in the environment. The ecology of R. equi can be best explained by an environmental cycle allowing its proliferation in dung, influenced by management, grazing behaviour and prevailing climatic conditions. Preventive measures should be aimed at reducing or avoiding focal areas of faecal contamination in the environment.


Psychometric properties and cross-cultural comparison of the cognitive complaints in bipolar disorder rating assessment (COBRA) in Mexican patients with bipolar disorder.
Bipolar Disorder (BD) is a serious and frequent mental health condition that is sometimes fatal. Several longitudinal studies have found an important correlation between cognition and functionality in BD. Despite the known importance of cognitive symptoms in BD, evaluation of cognitive deficits is not routinely done in clinical settings, as assessment is time-consuming and requires neuropsychological testing. The aim was to evaluate the psychometric properties of the subjective cognitive deficits in bipolar disorder (COBRA) rating scale in a Mexican sample of patients with BD and perform a cross-cultural comparison with the results obtained in other cultures. Ninety-two Healthy Subjects and 80 euthymic patients with BD were asked to complete the COBRA rating scale. The psychometric properties found in Mexican population show a good internal consistency and good discriminant validity with control subjects. Adequate congruence coefficients were obtained between the COBRA analyses in Mexican population and Spanish population and acceptable when compared to Japanese population. The COBRA scale is a brief and valid measure of cognitive complaints in BD for use in Mexican population.


Spatially Localized Synthesis and Structural Characterization of Platinum Nanocrystals Obtained Using UV Light.
Platinum nanocrystals with a fine control of the crystal domain size in the range 1.0-2.2 nm are produced by tuning the NaOH concentration during the UV-induced reduction of H2PtCl6 in surfactant-free alkaline ethylene glycol. The colloidal solutions obtained are characterized by transmission electron microscopy and pair distribution function analysis, allowing analysis of both atomic and nanoscale structures. The obtained nanoparticles exhibit a face-centered cubic crystal structure even for the smallest nanoparticles, and the cubic unit cell parameter is significantly reduced with decreasing crystallite size. It is further demonstrated how the "UV-approach" can be used to achieve spatial control of the nucleation and growth of the platinum nanocrystals, which is not possible by thermal reduction.


Bills, babies, and (language) barriers: Associations among economic strain, parenting, and primary language during the newborn period.
The goal of this study was to examine associations among economic strain, parenting self-efficacy, parenting satisfaction, and parent primary language in a universally low-income sample of parents with newborns. Previous research links increased economic strain to lower levels of parenting self-efficacy and parenting satisfaction among socioeconomically diverse parents with older children. Little research has examined whether primary language shapes the associations among economic strain, parenting self-efficacy, and parenting satisfaction. Parents (n = 194, M age = 30.91) completed self-report surveys measuring economic strain, parenting self-efficacy, and parenting satisfaction. Parents' ethnic self-identification and primary language were used to stratify parents into three groups: Latinx Spanish speakers, Latinx English speakers, and non-Latinx English speakers. Regression analyses revealed that economic strain was negatively associated with both parenting self-efficacy and parenting satisfaction. Further, the negative association between economic strain and parenting self-efficacy was stronger for Latinx Spanish speakers. Economic strain may negatively influence parenting self-efficacy and parenting satisfaction during the newborn period. Parents whose primary language is Spanish may be disproportionately affected by economic strain. Parents of newborns may benefit from increased economic supports in linguistically responsive pediatric care and social service settings.


Are Orthopaedic Systematic Reviews Overly Prevalent?
Systematic Reviews (SRs) are becoming an increasingly utilized resource for readers that aims to answer a specific question by critically analyzing multiple research studies or papers on a topic. Although an SR can be extremely helpful to find an answer to a question, it may also be scrutinized, as the methodology is often not robust enough to adequately determine the outcome. This editorial serves to highlight the benefits of an SR, the methodology of a high-caliber SR, and some common pitfalls that may reduce the impact of an SR.


Surgical treatment of endemic goiter in a nonhospital setting without general anesthesia in Africa.
Endemic goiter remains a serious public health problem and 75 % of people affected live in underdeveloped countries where treatment is difficult for various reasons. The aim of this article is to report our experience in African countries with the management and surgical treatment of endemic goiter, performed in a nonhospital setting and without general anesthesia in the context of a collaborative development project by experienced endocrine surgeons. Fifty-six black African patients with a goiter were studied. Those in poor general health, the elderly, patients with either small goiters or clinical hyperthyroidism, and those presenting with an acute episode of malaria were excluded from the study. Cervical epidural anesthesia with spontaneous ventilation was used and a partial thyroidectomy was performed. The technique used, its immediate complications, and early and late follow-up were analyzed. Surgery was performed on 31 patients with grades 3 and 4 goiter without mortality and a morbidity rate of 11.9 %, with 97 % of all complications being minor. There were no instances of dysphonia or symptomatic hypocalcemia and the mean stay was 1.57 days (range 1.25-1.93). Follow-up in the first year was 71 % and no case of severe or recurrent hypothyroidism was detected. Surgery without general anesthesia performed in a nonhospital setting in underdeveloped countries in patients with goiter is a viable option with good results and low morbidity.


Long-term follow-up of a childhood amnesic syndrome.
In attempting to explain observed dissociations between impaired and preserved memory functioning in amnesia, various dichotomous memory systems (e.g., procedural versus declarative, episodic versus semantic, working versus reference memory) have often been employed. In such cases, the assumption has been that memory subserved by one system is preserved, while that of the other system is impaired. Cohen and Squire have suggested that in amnesia, declarative memory is impaired, although procedural memory is preserved. Long-term follow-up of a densely amnesic patient refutes this view by demonstrating significant anterograde learning of school subjects including reading, vocabulary, spelling, and arithmetic, all of which include some component of declarative memory. It appears that the procedural/declarative dichotomy is not adequate to explain preserved memory in amnesia.


Streamlined quantitative BOLD for detecting visual stimulus-induced changes in oxygen extraction fraction in healthy participants: toward clinical application in human glioma.
Monitoring brain oxygenation is critical in brain tumors, as low oxygenation influences tumor growth, pathological angiogenesis, and treatment resistance. This study examined the ability of the streamlined quantitative (sq)BOLD MRI technique to detect oxygenation changes in healthy individuals, as well as its potential application in a clinical setting. We used the asymmetric spin echo (ASE) technique with FLAIR preparation, along with model-based Bayesian inference to quantify the reversible transverse relaxation rate (R2') and oxygen extraction fraction (OEF) across the brain at baseline and during visual stimulation in eight healthy participants at 3T; and two patients with glioma at rest only. Comparing sqBOLD-derived parameters between baseline and visual stimulation revealed a decrease in OEF from 0.56 ± 0.09 at baseline to 0.54 ± 0.07 at the activated state (p = 0.04, paired t test) within a functional localizer-defined volume of interest, and a decline in R2' from 6.5 ± 1.3s-1 at baseline to 6.2 ± 1.4s-1 at the activated state (p = 0.006, paired t test) in the visual cortex. The sqBOLD technique is sensitive enough to detect and quantify changes in oxygenation in the healthy brain and shows potential for integration into clinical settings to provide valuable information on oxygenation in glioma.


Atrophic gastritis and intestinal metaplasia in Japan: results of a large multicenter study.
This study evaluated the relationship between Helicobacter pylori infection, atrophic gastritis and intestinal metaplasia in Japan. This was a multicenter study performed in 21 centers in Japan. A total of 2455 individuals were enrolled. H. pylori status was determined by validated ELISAs. Atrophic gastritis was diagnosed by histology, endoscopy with Congo Red dye scattering or the Kimura-Takemoto endoscopic classification. Atrophic gastritis increased from 9.4% in those less than 20 years of age to > 70% in those aged 60 or older and was strongly associated with H. pylori infection. The overall prevalence of atrophic gastritis in H. pylori infection was 82.9% (1272/1534) compared with 9.8% (90/921) among uninfected (OR = 44.8; 95% CI = 34.7-57.8). Intestinal metaplasia was present in 43.1% (542/1258) of H. pylori positive persons compared with 6.2% (51/823) among the uninfected (OR = 11.5; 95% CI = 8.5-15.5). Atrophic gastritis in H. pylori positive Japanese was very high in the younger generation (38.5% in those aged 20 or less and 58.5% in those 21-30). Atrophic gastritis and intestinal metaplasia were strongly associated with H. pylori and not with aging. The fall in prevalence of H. pylori in Japan has not been associated with a corresponding fall in the prevalence of atrophic gastritis among those with H. pylori infection. The high prevalence of the precursor lesion, atrophic gastritis with intestinal metaplasia, among those with H. pylori infection suggests that the risk of development of early gastric cancer will continue to remain high in Japan.


Side docking the robot for robotic laparoscopic radical prostatectomy.
Low lithotomy position with the robot between the legs for docking is a standard position for robotic radical prostatectomy. Its complications include occasional nerve injury and compartment syndrome. In some patients with conditions that limit hip abduction, this position may be infeasible. We report a docking technique that obviates stirrups and simplifies setup without altering surgical technique. A total of 100 consecutive patients underwent robotic radical prostatectomy for localized prostate cancer. Fifty patients (group 1) were in the standard lithotomy position, and the remaining 50 patients (group 2) were in slight trendelenburg position with the robot at the side of the bed - "side-docked." Setup and docking times were recorded and both groups were compared for differences in operative variables. Mean setup time for group 2 was 4.7 minutes shorter than for group 1 (p = 0.02). Docking time and other operative variables were statistically similar and not affected by the adoption of side-docking technique. However, overall surgical time was longer due to modifications in other aspects of the technique during the study period. Side-docking for robotic radical prostatectomy is associated with small but significant improvement in setup time and can be utilized in patients with limited hip abduction.


Implementation of a systematic comprehensive geriatric assessment for elderly patients suspected of pulmonary hypertension.
The phenotype of patients seen for a suspicion of pulmonary hypertension has changed, with an increasing age and frequency of comorbidities. Selection of elderly patients, in whom a classical work-up is mandatory, is challenging. Comprehensive geriatric assessment (CGA) has modified the management of elderly patients with cancer. Pulmonary hypertension (PH) shares with cancer a functional impact and may evolve rapidly, depending on the group of PH. We assessed the impact of a systematic CGA in patients over 70 years old referred for a suspicion of PH. A standardised CGA was performed on every patient older than 70 years old, referred for a PH suspicion, before considering invasive tests for diagnosis and treatment, between July 2014 and May 2019. Our primary aim was to describe the impact of CGA on the decision to stop or pursue the recommended diagnostic work-up for PH. Among the thirty-one patients evaluated [mean age 81,5 (72-91) years], a negative CGA leads to stop the diagnostic work-up in eleven patients. Among the nineteen remaining patients, sixteen had confirmed PH, with half being chronic thromboembolic pulmonary hypertension. Our study indicates that comprehensive geriatric assessment could be an excellent first screen for elderly patients referred for a PH suspicion. Involving a geriatric physician stopped the investigations in one third of patients. In patients with a favourable CGA, PH was confirmed in most of the cases, with chronic thromboembolic pulmonary hypertension being the first cause of PH.


Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT.
Late occurring CMV disease is an important problem after allogeneic SCT and has been associated with poor CMV-specific immunity. We conducted a prospective study of 58 patients studied at 3-6 months after allo-SCT, to base the antiviral therapy on monitoring of CMV-specific immunity. Reactivation of CMV was measured by quantitative PCR, and intracellular IFN-gamma production was analysed by FACS and enzyme-linked immunospot. Antiviral therapy was deferred in patients with documented CMV-specific immunity without symptoms of CMV disease or severe GVHD. Nineteen episodes of CMV reactivation were assessable. The strategy was correctly applied in 16/19 episodes. Therapy was deferred in 5/19 (none of these patients developed CMV disease) and was given according to the strategy in 11/19 episodes. Two patients received antiviral therapy despite having T cell-specific immunity. There was a tendency that patients with late CMV reactivation had weak CD8 T cell immunity at 3 months (P=0.06). The donors' serostatus influenced the strength of both CD4 and CD8 immunity at 3 months after SCT (P<0.01). There was no effect as regards the type of conditioning, donor type, stem cell source or acute GVHD. Monitoring the immunity of SCT patients may allow more targeted use of antiviral therapy.


Combined toxicity of zinc oxide nanoparticles and cadmium inducing root damage in Phytolacca americana L.
In recent years, nano-contamination in the soil environment has aroused concern. But it is still uncertain whether the interactions of nano- and metal-pollutants would have a combined toxic effect on plants. In this study, we investigated the effects of joint exposure to zinc oxide nanoparticles (ZnO NPs) and Cd on the root tissue of Phytolacca americana L. Spin-polarized density functional theory simulations assumed that the plant may undergo metal toxicity or acidosis upon joint exposure to ZnO NPs/Cd. Subsequently, experimental exposure of P. americana verified the combined toxic effects. The plant grew normally with a single treatment of ZnO NPs (500 mg/kg) or low doses of Cd (10 mg/kg). However, root growth was significantly inhibited with the combined treatments (up to 43% reduction); additionally, Cd ions were transported to the shoot, leading to shoot growth inhibition (translocation factor > 1). The antioxidant enzymes in the root (superoxide dismutase, peroxidase, and catalase) were highly activated to resist stress, accompanied by a greater than two-fold increase in thiobarbituric acid reactive substances. Corresponding to physiological indicators, biological transmission electron microscopy revealed severe damage to the root cells. Moreover, ZnO NPs/Cd accumulation was observed in the root cytoderm, which confirmed the toxicity of the combined effects. Our study provides insight into the potential combined toxicity of ZnO NPs and heavy metals in polluted environments, such as mining areas and electronic waste sites, and agricultural soils.


Evaluating the psychometric properties of the Arabic version of the Groningen Frailty Indicator among Lebanese elderly people.
The levels of frailty are anticipated to increase as a result of population aging. A valid instrument is required to detect individuals at high risk of frailty. The present research aimed to assess feasibility, reliability, and construct validity of the Arabic version of Groningen Frailty Indicator (GFI) in urban and rural populations in South Lebanon. During 2015, a cross-sectional study, which enrolled 390 community-dwelling individuals aged 65 years and above, was conducted in urban and rural areas in Nabatieh in South Lebanon. The survey included questions on sociodemographic and health-related characteristics, GFI, and Vulnerable Elders Survey-13 (VES-13). The translation and cultural adaptation of the GFI followed a standardized protocol. After that, the psychometric properties of the scale (i.e., feasibility, reliability, and validity) were evaluated. A total of 390 elderly filled out the questionnaire, of whom 51% were women and 70% lived in rural areas. 81.3% of elderly were identified as frail. The internal consistency of the GFI scale was high for all subscales (Cronbach's alpha > 0.70), except the social scale (0.56). The GFI yielded statistically significant scores for subgroup analysis (known-groups validity) as higher levels of frailty were seen in older people, women, those with morbidities, and those reported poor financial status. The construct validity of the scale was supported by the significant correlation with the VES-13 (r = 0.73; p = 0.001), quality of life (r = - 0.22; p = 0.001), and self-reported health status (r = - 0.66; p = 0.001). This study supports the feasibility, reliability, and validity of the GFI Arabic version as a screening tool for frailty among community-dwelling elderly in South Lebanon.


Campylobacter diarrhea in children in South Asia: A systematic review.
Campylobacter spp. are one of the commonest causes of diarrhea in children under five and in resource poor settings also lead to malabsorption and stunting. The purpose of this systematic review was to understand the burden of Campylobacter spp. associated diarrhea among children in the South Asian countries. This systematic review followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines. Databases were searched with defined keywords for publications from the years 1998-2018. Data on proportion of positive samples was extracted to compare the rates of Campylobacter infection among children (under the age of 19) from different study populations. Of the 359 publications screened, 27 eligible articles were included in this systematic review and categorized based on study design. In 8 case-control studies, Campylobacter spp. was detected more frequently among diarrheal cases (range, 3.2-17.4%) than non-diarrheal cases (0-13%). Although there were variations in the study population, overall, children under the age of two years experienced Campylobacter diarrhea more often than older children. Most studies reported stool culture as the method used to detect Campylobacter spp. however retesting using PCR-based methods significantly increased detection rates. Limited data were available on Campylobacter species. In 4 studies that provided species data, C. jejuni (3.2-11.2%) was shown to be the most common species, followed by C. coli. In South Asia, Campylobacter spp. are one of the most common bacterial diarrheal pathogens affecting children but there is a paucity of data on species, risk factors and attributable sources. Although a few studies were available, the epidemiology of campylobacteriosis remains uncertain. To understand the true burden and sources of infection, more detailed studies are needed collecting data from human, animal and environmental sources and using both culture and genomic tools.


Predator-mediated genotypic shifts in a prey population: experimental evidence.
We demonstrate the effect of fish predation on genotype frequencies in a laboratory population composed of two Daphnia magna clones, with historically contrasting exposures to fish predation. The two clones differed in their responsiveness to predation via differential avoidance/escape behavior. The clone which coexists with fish in nature is more responsive to the presence of a fish predator, while the clone not exposed to fish predation does not exhibit the defensive reaction. Fish caused a rapid (within 18 h) and significant shift in Daphnia clonal composition, from 1:1 to 8:1, in favor of the responsive clone. Genotype-specific defensive abilities (modus defendi) can contribute greatly to the phenomenon of genotype replacement under selective predation.


Correction to: Voice rehabilitation for laryngeal cancer after radiotherapy: a systematic review and meta-analysis.
In the original publication of the article, the reference 14 was published incorrectly. The correct reference is given below.


A chlorogenic acid-chitosan complex bifunctional coating for improving osteogenesis differentiation and bactericidal properties of zirconia implants.
Poor osteogenesis caused by limited bioactivity and peri-implantitis caused by bacterial colonization are the main challenges affecting the use of zirconia-based materials in dental implants. Accordingly, the development of a surface treatment method with an antibacterial effect and that promotes osteogenesis without damage to cells is crucial for yttrium-stabilized tetragonal zirconia (Y-TZP) implants. Herein, we have developed a functional surface modification strategy whereby a poly (ethylene imine)/hyaluronic acid /chitosan-chlorogenic acid (PEI/HA/CGA-CS) conjugate is deposited on a zirconia surface by the layer-by-layer (LBL) technique, enhancing its osteogenic differentiation and antibacterial activities. The results showed that the PEI/HA/CGA-CS coating improved the wettability of the zirconia surface and maintained stable release of CGA. The PEI/HA/CGA-CS functional coating was found to promote early cell adhesion, proliferation, differentiation, and calcification. The results of bacterial adhesion and activity tests showed that the coating effectively inhibits the proliferation and activity of Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) without impairing the biological activity of osteoblasts. In addition, we found that the PEI/HA/CGA-CS coating enhances the osteogenesis of MC3T3-E1 cells by promoting the protein expression of Nephronectin (NPNT) and activating the Wnt/β-catenin signaling pathway. The above results are of profound significance for the practical application of zirconia-based implants. DATA AVAILABILITY: Data will be made available on request.


Improving methane production from digested manure biofibers by mechanical and thermal alkaline pretreatment.
Animal manure digestion is associated with limited methane production, due to the high content in fibers, which are hardly degradable lignocellulosic compounds. In this study, different mechanical and thermal alkaline pretreatment methods were applied to partially degradable fibers, separated from the effluent stream of biogas reactors. Batch and continuous experiments were conducted to evaluate the efficiency of these pretreatments. In batch experiments, the mechanical pretreatment improved the degradability up to 45%. Even higher efficiency was shown by applying thermal alkaline pretreatments, enhancing fibers degradability by more than 4-fold. In continuous experiments, the thermal alkaline pretreatment, using 6% NaOH at 55°C was proven to be the most efficient pretreatment method as the methane production was increased by 26%. The findings demonstrated that the methane production of the biogas plants can be increased by further exploiting the fraction of the digested manure fibers which are discarded in the post-storage tank.


Is there an association between lifetime cumulative exposure and acute pulmonary responses to ozone?
To investigate the potential effects of lifetime cumulative ozone (O3) exposure on acute pulmonary responses to O3. Fifteen healthy subjects from a larger cohort of young adults were exposed to 200 ppb O3 for 4 hours followed by bronchoscopy and bronchoalveolar lavage 18 hours later. Lung function, symptom questionnaires, and blood samples were obtained before and after each exposure. Subjects' lifetime cumulative O3 exposures were estimated from residential histories and air-quality monitoring data. Acute exposure to O3 caused decrements in forced expiratory volume in 1 second (FEV1), maximal mid-expiratory flow rate (FEF25-75), and forced expiratory flow rate at 75% of forced vital capacity (FEF75), and an increase in plasma clara cell protein (CC16) level. Changes in CC16 and lower respiratory symptoms, but not in lung function, were positively correlated with lifetime cumulative O3 exposure. Higher lifetime cumulative O3 exposure was associated with airway injury and respiratory symptom responses, but not with airway inflammatory or lung function responses, to acute O3 exposure.


Regulation of the epithelial adhesion molecule CEACAM1 is important for palate formation.
Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at various developmental stages before, during, and after palate fusion using GeneChip® microarrays. Ceacam1 was one of the highly up-regulated genes during palate formation, and this was confirmed by quantitative real-time PCR. Immunohistochemical staining showed that CEACAM1 was present in prefusion palatal epithelium and was degraded during fusion. To investigate the developmental role of CEACAM1, function-blocking antibody was added to embryonic mouse palate in organ culture. Palatal fusion was inhibited by this function-blocking antibody. To investigate the subsequent developmental role of CEACAM1, we characterized Ceacam1-deficient (Ceacam1(-/-)) mice. Epithelial cells persisted abnormally at the midline of the embryonic palate even on day E16.0, and palatal fusion was delayed in Ceacam1(-/-) mice. TGFβ3 expression, apoptosis, and cell proliferation in palatal epithelium were not affected in the palate of Ceacam1(-/-)mice. However, CEACAM1 expression was retained in the remaining MEE of TGFβ-deficient mice. These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion.


Factors influencing the stability of ranitidine in TPN mixtures.
The stability of ranitidine in TPN mixtures has been widely studied with varying results. The evidence suggests that ranitidine is unstable and should be added within 24 h of administration, although other reports indicate ranitidine is stable for at least 14 days. The causes of ranitidine degradation in TPN mixtures were therefore studied in mixtures without fat emulsion using a stability-indicating HPLC method. The results indicated that the stability of ranitidine at 5 degrees C depended on the commercial source of amino acid, additives and type of bag used. The principle mechanism of degradation was identified as oxidation. Ranitidine was more stable in EVA bags in the absence of the trace element additive, which appeared to accelerate ranitidine oxidation. Ranitidine was most stable in mixtures compounded in multi-layered bags. The results suggest TPN mixtures with ranitidine in multi-layered bags could be assigned shelf lives of at least 14 days at 5 degrees C, depending on the amino acid infusion used in the regimen.


Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy.
To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta2 alpha-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.


Artemin-GFRα3 interactions partially contribute to acute inflammatory hypersensitivity.
The expression of artemin (ARTN), a glial cell line-derived neurotrophic factor (GDNF) family ligand, increases in pre-clinical models of nociception and recent evidence suggests this growth factor may play a causative role in inflammatory pain mechanisms. The aim of this study was to demonstrate functional inhibition of ARTN with monoclonal antibodies and to determine whether ARTN neutralisation could reverse inflammatory pain in mice. We show that monoclonal antibodies with high affinity to ARTN, completely inhibit ARTN-induced Ret and ERK activation in a human neuroblastoma cell line, and block capsaicin-induced CGRP secretion from primary rat DRG cultures. In addition, administration of anti-ARTN antibodies to mice provides a transient, partial reversal (41%) of FCA-induced mechanical hypersensitivity. Anti-ARTN antibodies had no effect on hypersensitivity in response to partial nerve ligation in mice. These data suggest that ARTN-GFRα3 interactions partially mediate early stage nociceptive signalling following an inflammatory insult.


Coulomb-bound four- and five-particle intervalley states in an atomically-thin semiconductor.
As hosts for tightly-bound electron-hole pairs carrying quantized angular momentum, atomically-thin semiconductors of transition metal dichalcogenides (TMDCs) provide an appealing platform for optically addressing the valley degree of freedom. In particular, the valleytronic properties of neutral and charged excitons in these systems have been widely investigated. Meanwhile, correlated quantum states involving more particles are still elusive and controversial despite recent efforts. Here, we present experimental evidence for four-particle biexcitons and five-particle exciton-trions in high-quality monolayer tungsten diselenide. Through charge doping, thermal activation, and magnetic-field tuning measurements, we determine that the biexciton and the exciton-trion are bound with respect to the bright exciton and the trion, respectively. Further, both the biexciton and the exciton-trion are intervalley complexes involving dark excitons, giving rise to emissions with large, negative valley polarization in contrast to that of the two-particle excitons. Our studies provide opportunities for building valleytronic quantum devices harnessing high-order TMDC excitations.


[Prenatal development of cerebral veins and sinuses with variants and dysplasias].
A review is given on the development of the cerebral veins and sinuses in man illustrated by schematic drawings and phlebograms of comparable embryos and fetuses of higher vertebrates. The system of venous sinuses arises early in development from three dural plexuses and the primary head sinus according to a constant pattern. The internal cerebral veins and particularly the temporo-basal veins arise at a later stage from longitudinal anastomoses of ventral segmental veins of the pial venous plexus of the brainstem. Accordingly they exhibit a high degree of variability in the adult.


A novel hybrid nano zerovalent iron initiated oxidation--biological degradation approach for remediation of recalcitrant waste metalworking fluids.
Disposal of operationally exhausted metal working fluids (MWF) through a biological route is an attractive option, since it is effective with relatively low energy demands. However, it is enormously challenging since these fluids are chemically complex, including the addition of toxic biocides which are added specifically to retard bio-deterioration whilst the fluids are operational. Nano-sized elemental iron represents a new generation of environmental remediation technologies. Laboratory scale batch studies were performed to test the degradation ability of a semi-synthetic metalworking fluid (MWF) wastewater (which was found to be resistant to initial bacterial treatment in specifically established bioreactors) by employing a novel hybrid approach. The approach was to combine the synergistic effects of nano zerovalent iron (nZVI) induced oxidation, followed by biodegradation, specifically for the remediation of recalcitrant components of MWF effluent. Addition of nZVI particles to oxygenated wastewater resulted in oxidation of organic contaminants present. Our studies confirmed 78% reduction in chemical oxygen demand (COD) by nZVI oxidation at pH 3.0 and 67% reduction in neutral pH (7.5), and 85% concurrent reduction in toxicity. Importantly, this low toxicity made the nZVI treated effluent more amenable for a second stage biological oxidation step. An overall COD reduction of 95.5% was achieved by the novel combined treatment described, demonstrating that nZVI oxidation can be exploited for enhancing the biodegradability of a recalcitrant wastewater in treatment processes.


Histopathological prognosticators in oral and oropharyngeal squamous cell carcinoma.
Histopathological assessment of the surgical resection specimen continues to provide information that is central to determining the post-operative treatment needs and prognosis for an individual patient with oral/oropharyngeal squamous cell carcinoma. This review describes the prognostic value of histopathological features related to the primary tumour and the cervical lymph nodes, and considers their relative merits. In addition, a brief overview of more general patient factors is included. Throughout the review, guidance is offered on practical aspects of the histopathological assessment together with brief mention of potential inaccuracies. Emphasis is given also to the importance of the partnership between the surgeon and the pathologist, the need for standardisation during all stages of the histopathological assessment, and the value of accurate documentation of the findings.


Image-guided neurosurgery for secondary operative removal of projectiles after missile injury of the brain.
The primary treatment of penetrating missile injuries of the brain includes debridement of the scalp, fractured skull, and necrotic brain parenchyma. It is acceptable to remove all bony and metallic fragments that are accessible without additional trauma to nondamaged brain regions. Therefore, bone chips and bullets are often initially retained in the brain and are supposedly responsible for delayed cerebral infections and posttraumatic seizures. We successfully operated on 3 patients electively to remove bony and metallic fragments secondarily after penetrating brain trauma. We used an electromagnetic neuronavigation system for preoperative planning and chose a less invasive approach for the exact intraoperative localization of the fragments. All fragments were extracted without any problems. No patients had any additional neurologic deficits, and no signs of cerebral infections or seizures occurred between 4 and 8 weeks after the operative revision. We recommend the implementation of neuronavigation techniques into the surgical strategy for secondary removal of retained missile fragments.


Effects of opiates and methionine-enkephalin on pontine and bulbar respiratory neurones of the cat.
The effects of microelectrophoretically applied opiate agonists and the antagonist naloxone have been investigated on extracellularly recorded neurones in pontine and bulbar respiratory centers of the cat. Morphine, levorphanol and methionine-enkephalin depressed the spontaneous discharge of respiration related units and the firing induced in these cells by phoretically applied L-glutamate. The rhythmic pattern of these neurones was modified, in such a way that basal activity was hardly affected while peak frequency was markedly reduced. These effects are mediated via stereospecific opiate receptors, since they were antagonized by naloxone and not mimicked by the D+ enantiomer of levorphanol, dextrophan. The few excitations observed following opiate agonist application were not antagonizable by naloxone. These data may provide a basis for the explanation of the depressant effect on central respiratory rhythm of systemically injected opiates which have been obtained in control experiments. The results are interpreted in terms of opiates lowering excitatory synaptic efficacy.


Kinetics of proton-hydroxyl transport across lecithin vesicle membranes as measured with a lipoid pH-indicator.
When unilamellar vesicles are prepared in the presence of 3-Palmitoyl-7-ocy-coumarin abbreviation 3P-UBF) this lipoid pH-Indicator is anchored by its fatty acid chain to the membrane and can be used to measure pH-changes at the outer and inner membrane surface (ranging from pH to pH 9.5). By rapidly changing the pH of the outer aqueous phase a pH-gradient is set up across the vesicle membrane. The rate of the subsequent H+ or OH- influx into the vesicles can be measured as a change of the 3P-UBF absorbance at 424 nm. This was done with a stopped-flow -spectrophotometer at temperatures between 10 degree C and 50 degree C. Suspensions of vesicles prepared from egg-lecithin or L-dipalmitoyl-lecithin were investigated in buffered salt solutions. The influence of Na+, K+, Cl-, SO2-(4) and valinomycin on the rate of absorbance changes was studied at different temperatures. It was found that the rate of the pH-equilibration between the aqueous phase outside and inside the vesicles depends on the direction of the pH-gradient. This new result together with a high H+/OH- permeability of vesicle membranes found in recent studies from other laboratories and confirmed by this investigation is interpreted to indicated a higher permeability of the vesicle membrance to OH--ions compared to H+-ions. (Calculated values are: POH = 1.4 x 10(-4) cm/s at pH9 and PH = 8.3 x 10 (-7) cm/s at pH 5 and 20 degree C.) All data described in the literature in detail agree with this suggestion but a pH-dependence of POH and PH cannot be excluded.


Individual differences in behavioral flexibility predict future volitional ethanol consumption in mice.
Cognitive control is key to regulating alcohol intake and preventing relapse. Behavioral inflexibility can prevent adaptive strategies such as mindfulness or other relapse-prevention behaviors. In a mouse model we investigated whether individual variability in behavioral flexibility (using attentional set-shifting task; ASST) predicts future alcohol intake. Adult male and female C57BL/6J mice were subjected to ASST using a bowl-digging paradigm where mice identify a baited bowl based on compound odor and textural cues. This was completed prior to any alcohol exposure. Individual performance across mice varied within the group. We integrated several metrics, specifically ASST stage completed, trials to completion, and errors performed to produce an individual performance index measure of behavioral flexibility. Afterward, ASST mice were trained to drink ethanol (15%, v/v, 1 h/day) for 3-4 weeks until intake stabilized. Using this prospective approach, we identified an inverse relationship between behavioral flexibility and drinking-less-flexible mice had a propensity to consume more alcohol. Similar relationships have been identified previously in non-human primates and rats. Our results show that the relationship between alcohol and behavioral flexibility is a robust trait that is conserved across species and can be used in mice to study neural substrates underlying these behaviors.


PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells.
Retention of long-term repopulating hematopoietic stem cells (LT-HSCs) in the bone marrow is essential for hematopoiesis and for protection from myelotoxic injury. We report that signaling cascades that are traditionally viewed as coagulation related also control retention of endothelial protein C receptor-positive (EPCR(+)) LT-HSCs in the bone marrow and their recruitment to the blood via two pathways mediated by protease activated receptor 1 (PAR1). Thrombin-PAR1 signaling induces nitric oxide (NO) production, leading to EPCR shedding mediated by tumor necrosis factor-α-converting enzyme (TACE), enhanced CXCL12-CXCR4-induced motility and rapid stem and progenitor cell mobilization. Conversely, bone marrow blood vessels provide a microenvironment enriched with activated protein C (aPC) that retains EPCR(+) LT-HSCs by limiting NO generation, reducing Cdc42 activity and enhancing integrin VLA4 affinity and adhesion. Inhibition of NO production by aPC-EPCR-PAR1 signaling reduces progenitor cell egress from the bone marrow, increases retention of bone marrow NO(low) EPCR(+) LT-HSCs and protects mice from chemotherapy-induced hematological failure and death. Our study reveals new roles for PAR1 and EPCR in controlling NO production to balance maintenance and recruitment of bone marrow EPCR(+) LT-HSCs, with potential clinical relevance for stem cell transplantation.


Two bombesin analogues discriminate between neuromedin B- and bombesin-induced calcium flux in a lung cancer cell line.
We examined the profile of two bombesin (BN) antagonists, (CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3] (ICI 216140) and [D-Phe6,des-Met14]BN(6-14)ethylamide (DPDM-BN EA), against neuromedin B-induced Ca2+ mobilization in the small cell lung cancer (SCLC) line NCI-H345. Neuromedin B (NMB), a BN-like peptide sharing sequence homology with ranatensin, elicited a concentration-dependent Ca2+ release (in part) from intracellular stores. Sequential addition of NMB attenuated Ca2+ mobilization. Desensitization occurred between BN and NMB; depletion of intracellular Ca2+ is a likely mechanism because thapsigargin stimulated Ca2+ release after a maximally desensitizing dose of NMB. ICI 216140 and DPDM-BN EA competitively inhibited BN-induced Ca2+ transients. In contrast, these compounds antagonized NMB-stimulated Ca2+ transients in a noncompetitive manner. The pharmacological profiles obtained support receptor heterogeneity for BN-like peptides on this SCLC line, underscoring the need for thorough examination of dose-response relationships when investigating effects of BN analogues on intact cells.


Spatial distribution of soil contamination by 137Cs and 239,240Pu in the village of Dolon near the Semipalatinsk nuclear test site: new information on traces of the radioactive plume from the 29 August 1949 nuclear test.
The village of Dolon located about 60 km northeast from the border of the Semipalatinsk Nuclear Test Site in Kazakhstan is one of the most affected inhabited settlements as a result of nuclear tests by the former USSR. Radioactive contamination in Dolon was mainly caused by the first USSR nuclear test on 29 August 1949. As part of the efforts to reconstruct the radiation dose in Dolon, Cs and Pu in soil samples collected from 26 locations in the vicinity of and within the village were measured to determine the width and position of the center-axis of the radioactive plume that passed over the village from the 29 August 1949 nuclear test. Measured soil inventories of Cs and Pu were plotted as a function of the distance from the supposed center-axis of the plume. A clear shape similar to a Gaussian function was observed in their spatial distributions with each maximum around a center-axis. It was suggested that the plume width that contaminated Dolon was at most 10 km and the real center-axis of the radioactive plume passed 0.7-0.9 km north of the supposed centerline. A peak-like shape with the maximum near the center-axis was also observed in the spatial distribution of the Pu/Cs activity ratio, which may reflect the fractionation effect between Pu and Cs during the deposition process. These results support the recently reported results. The data obtained here will provide useful information on the efforts to estimate radiation dose in Dolon as reliably as possible. Health Phys. 94(4):328-337; 2008.


Fractal temporal organisation of motricity is altered in major depression.
Motor changes in major depression (MD) may represent potential markers of treatment response. Physiological rhythms (heart rate/gait cycle/hand movements) have been recently shown to be neither random nor regular but to display a fractal temporal organisation, possibly reflecting a unique central "internal clock" control. Sleep and mood circadian rhythm modifications observed in MD also suggest a role for this "internal clock". We set out to examine the fractal pattern of motor activity in MD. Ten depressed patients (46±20 years) and ten age- and gender-matched healthy controls (48±21 years) underwent a 6-h ambulatory monitoring of spontaneous hand activity with a validated wireless device. Fractal scaling exponent (α) was analysed. An α value close to 1 means the pattern is fractal. Healthy controls displayed a fractal pattern of spontaneous motor hand activity (α: 1.0±0.1), whereas depressed patients showed an alteration of that pattern (α:1.2±0.15, p<0.01), towards a smoother organisation. The alteration of fractal pattern of hand activity by depression further supports the role of a central internal clock in the temporal organisation of movements. This novel way of studying motor changes in depression might have an important role in the detection of endophenotypes and potential predictors of treatment response.


l-Dopa-induced dyskinesia-clinical presentation, genetics, and treatment.
Levodopa-induced dyskinesia (LID) has been recognized since the introduction of levodopa for the management of Parkinson's disease (PD) and continues to be one of the most clinically challenging factors in long-term management of patients with PD. Most patients develop LID within 10 years of PD onset and the cause has been attributed to various factors including disease demographics, pharmacological, and possibly genetic causes. The clinical pattern of LID varies and shows intra and inter-patient variability and has been classified based upon phenomenology and relation to timing of levodopa. The potential armamentarium to address and manage LID has significantly increased in the last decade. This chapter addresses the current understanding of various clinical aspects and available therapeutics for LID.


Stressful life events and alcohol problems among women seen at a detoxication center.
No strong temporal associations were found between the occurrence of stressful life events and the onset of alcohol problems.


Sodium salicylate reduced mRNA abundance of hypoxia-associated genes in MAC-T cells.
Hypoxia is an oxygen deficiency commonly found in growing tissues and is speculated to occur in the rapidly developing mammary gland in peripartum dairy cattle. Low oxygen concentrations can activate hypoxia-inducible factor-1 (HIF-1), which increases transcription of genes involved in angiogenesis (VEGFA) and glucose transport (GLUT1), among other processes. The mRNA stability of these genes is positively regulated by heterogeneous nuclear ribonucleoprotein D (HNRNPD; also known as AUF1). In our previous research, postpartum administration of sodium salicylate (SS) increased whole-lactation milk yield in multiparous cows but tended to reduce milk yield in primiparous cows. Because rapid mammary tissue development likely occurs in cows approaching first lactation, we hypothesized that SS inhibited the activation of HIF-1α and decreased transcription of downstream targets. MAC-T cells were treated with SS (100 μM) or control medium before incubation under either hypoxic (1% O2) or normoxic conditions for 12 h. Additionally, cells were transfected with either HIF1A small interfering RNA (siRNA) or a scrambled siRNA negative control 48 h before hypoxia treatments. HIF1A, GLUT1, VEGFA, and HNRNPD were quantified relative to the internal control gene NENF. Transcript abundance was assessed using a linear mixed model with the fixed effects of SS, hypoxia, siRNA, and all 2- and 3-way interaction terms and the random effect of plate nested within hypoxia. Treatment with SS interacted with hypoxia for GLUT1, as SS reduced GLUT1 when MAC-T cells were cultured in normoxic conditions; however, no effect of SS was found in hypoxia-treated cells. Regardless of oxygen status, SS reduced HNRNPD and tended to decrease VEGFA mRNA relative to untreated cells. Hypoxia increased GLUT1, yet no effect was observed on VEGFA or HNRNPD. Small interfering RNA knocked down HIF1A, but no effect was found on GLUT1, VEGFA, or HNRNPD. In conclusion, SS reduced transcript abundance of genes involved with mammary gland development but generally did not interact with oxygen status.


Integrative clinical transcriptome analysis reveals TMPRSS2-ERG dependency of prognostic biomarkers in prostate adenocarcinoma.
In prostate adenocarcinoma (PCa), distinction between indolent and aggressive disease is challenging. Around 50% of PCa are characterized by TMPRSS2-ERG (T2E)-fusion oncoproteins defining two molecular subtypes (T2E-positive/negative). However, current prognostic tests do not differ between both molecular subtypes, which might affect outcome prediction. To investigate gene-signatures associated with metastasis in T2E-positive and T2E-negative PCa independently, we integrated tumor transcriptomes and clinicopathological data of two cohorts (total n = 783), and analyzed metastasis-associated gene-signatures regarding the T2E-status. Here, we show that the prognostic value of biomarkers in PCa critically depends on the T2E-status. Using gene-set enrichment analyses, we uncovered that metastatic T2E-positive and T2E-negative PCa are characterized by distinct gene-signatures. In addition, by testing genes shared by several functional gene-signatures for their association with event-free survival in a validation cohort (n = 272), we identified five genes (ASPN, BGN, COL1A1, RRM2 and TYMS)-three of which are included in commercially available prognostic tests-whose high expression was significantly associated with worse outcome exclusively in T2E-negative PCa. Among these genes, RRM2 and TYMS were validated by immunohistochemistry in another validation cohort (n = 135), and several of them proved to add prognostic information to current clinicopathological predictors, such as Gleason score, exclusively for T2E-negative patients. No prognostic biomarkers were identified exclusively for T2E-positive tumors. Collectively, our study discovers that the T2E-status, which is per se not a strong prognostic biomarker, crucially determines the prognostic value of other biomarkers. Our data suggest that the molecular subtype needs to be considered when applying prognostic biomarkers for outcome prediction in PCa.


Impact of late gadolinium enhancement extent, location, and pattern on ventricular tachycardia and major adverse cardiac events in patients with ischemic vs. non-ischemic cardiomyopathy.
Left ventricular late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) has been associated with increased risk for life-threatening ventricular tachyarrhythmias. The differences in association between LGE characteristics and prognosis in patients with ischemic (ICM) vs. non-ischemic (NICM) cardiomyopathy is incompletely understood. A total of 168 consecutive patients who underwent CMR imaging with either ICM or NICM were included in our study. LGE extent, location and pattern were examined for association to the primary endpoint of ventricular tachycardia (VT) and secondary endpoint of major adverse cardiac events (MACE). Of 68 (41%) patients with ICM and 97 (59%) patients with NICM, median LGE mass was 15% (IQR 9-28) for the ICM group and 10% (IQR 6-15) for the NICM group. On multivariate analysis for both groups, LGE characteristics were prognostic while LVEF was not. In patients with ICM, septal and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median) and inferior wall LGE independently predicted the primary endpoint. In patients with NICM, anterior, inferior and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median, number of LGE segments, LGE stratified per 5% increase) and midwall LGE were independent predictors of the primary endpoint. Although LGE was an independent predictor of prognosis in both groups, LGE extent, location, and pattern characteristics were more powerful correlates to worse outcomes in patients with NICM than ICM.


Cmr1 enables efficient RNA and DNA interference of a III-B CRISPR-Cas system by binding to target RNA and crRNA.
CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) systems provide adaptive immunity against invasive nucleic acids guided by CRISPR RNAs (crRNAs) in archaea and bacteria. Type III CRISPR-Cas effector complexes show RNA cleavage and RNA-activated DNA cleavage activity, representing the only known system of dual nucleic acid interference. Here, we investigated the function of Cmr1 by genetic assays of DNA and RNA interference activity in the mutants and biochemical characterization of their mutated Cmr complexes. Three cmr1α mutants were constructed including ΔβΔ1α, Δβ1α-M1 and Δβ1α-M2 among which the last two mutants carried a double and a quadruple mutation in the first α-helix region of Cmr1α. Whereas the double mutation of Cmr1α (W58A and F59A) greatly influenced target RNA capture, the quadruple mutation almost abolished crRNA binding to Cmr1α. We found that Cmr2α-6α formed a stable core complex that is active in both RNA and DNA cleavage and that Cmr1α strongly enhances the basal activity of the core complex upon incorporation into the ribonucleoprotein complex. Therefore, Cmr1 functions as an integral activation module in III-B systems, and the unique occurrence of Cmr1 in III-B systems may reflect the adaptive evolution of type III CRISPR-Cas systems in thermophiles.


Decerebration does not alter hypoxic sympathoexcitatory responses in rats.
In anesthetized, paralyzed and ventilated rats, hypoxia, produced by intratracheal administration of 100% N2 for 20 s, increases sympathetic nerve activity and produces cardiovascular responses. Acute midcollicular decerebration has no effect on these responses in chemo-innervated or chemo-denervated animals. Suprapontine neural structures are, therefore, not required for the rapid sympathetic and cardiovascular responses to acute hypoxia. The results support the view that sympathoexcitatory responses to acute hypoxia depend entirely on the functions of reticulospinal sympathoexcitatory vasomotor neurons of the rostral ventrolateral medulla (RVL).


Label-free chemiluminescent ATP aptasensor based on graphene oxide and an instantaneous derivatization of guanine bases.
In this work, a novel label-free chemiluminescent (CL) aptasensor has been developed for rapid and facile detection of adenosine triphosphate (ATP, as model analyte) using graphene oxide (GO) nano-platform. The strategy relies on the preferential binding of GO to single-stranded DNA (ssDNA) over rigid double-stranded DNA (dsDNA) or aptamer-target complexes, and the instantaneous derivative reaction between phenylglyoxal (PGO), a special CL reagent as the signaling molecule, and guanine nucleobases (G) of aptamer strands adsorbed on the surface of GO. In the absence of ATP, the aptamers adsorbed onto the surface of GO leading to a strong background CL signal. Conversely, in the presence of ATP, the aptamers formed the aptamer-ATP complexes which had weak binding ability to GO resulting in a significant CL signal decrease. The CL intensity was adversely related to the ATP concentration in the assay solution. The biosensor's signal decreased linearly with the logarithm of the concentration of ATP from 2 to 80 nmol with a detection limit of 1.4 nmol. The aptasensor also showed high selectivity against cytosine triphosphate (CTP), guanosine triphosphate (GTP), and uridine triphosphate (UTP). The method presented here holds the advantages of being label-free, cost effective, rapid, sensitive and selective, which would shows great promise for clinical application.


Exosomes are secreted at similar densities by M21 and PC3 human cancer cells and show paclitaxel solubility.
Exosomes are cell-secreted vesicles less than ≈150 nm in size that contain gene-encoding and gene-silencing RNA and cytosolic proteins with roles in intercellular communication. Interest in the use of exosomes as targeted drug delivery vehicles has grown since it was shown that they can bind specific cells and deliver intact genetic material to the cytosol of target cells. We isolated extracellular vesicles (EVs), consisting of a mixture of exosomes and microvesicles, from prostate (PC3) and melanoma (M21) cancer cell lines using serial ultracentrifugation. Interrogation via western blot analysis confirmed enrichment of CD63, a widely recognized EV surface protein, in the EV pellet from both cell lines. Nanoparticle tracking analysis (NTA) of EV pellets revealed that the two cell lines produced distinct vesicle size profiles in the ≈30 nm to ≈400 nm range. NTA further showed that the fraction of exosomes to all EVs was constant, suggesting cellular mechanisms that control the fraction of secreted vesicles that are exosomes. Transmission electron microscopy (TEM) images of the unmodified PC3 EVs showed vesicles with cup-like (i.e., nanocapsule) and previously unreported prolate morphologies. The observed non-spherical morphologies for dehydrated exosomal vesicles (size ≈30-100 nm) are most likely related to the dense packing of proteins in exosome membranes. Solubility phase diagram data showed that EVs enhanced the solubility of paclitaxel (PTX) in aqueous solution compared to a water-only control. Combined with their inherent targeting and cytosol delivery properties, these findings highlight the potential advantages of using exosomes as chemotherapeutic drug carriers in vivo.


Applications of Mouse Models to the Study of Food Allergy.
Mouse models of allergic disease offer numerous advantages when compared to the models of other animals. However, selection of appropriate mouse models is critical to advance the field of food allergy by revealing mechanisms of allergy and for testing novel therapeutic approaches. All current mouse models for food allergy have weaknesses that may limit their applicability to human disease. Aspects such as the genetic predisposition to allergy or tolerance from the strain of mouse used, allergen dose, route of exposure (oral, intranasal, intraperitoneal, or epicutaneous), damage of the epithelial barrier, use of adjuvants, food matrix effects, or composition of the microbiota should be considered prior to the selection of a specific murine model and contemplated according to the intended purpose of the study. This chapter reviews our current knowledge on the application of mouse models to food allergy research and the variables that may influence the successful development of each type of model.


A mutation in the gene for polynucleotide kinase of bacteriophage T4 K10 affects mRNA processing.
The bacteriophage T4 insertion-substitution (I/S) vector system has become one of the most important tools for the introduction of site-directed mutations into the T4 genome. In this study, we show that the I/S phage T4 K10 carries two point mutations within the gene for polynucleotide kinase pseT, resulting in amino acid substitutions G14D and R229H. The G14D mutation impairs 5'-kinase activity in vivo as well as in vitro and leads to diminished processing at secondary sites of several RegB-cleaved transcripts.


One-pot synthesis of polycyclic isoindolines using isoindole umpolung.
Using an isoindole umpolung strategy, a one-pot synthesis of polycyclic isoindolines was accomplished. In this reaction, the in situ-generated nucleophilic isoindoles were converted to electrophilic isoindoliums via protonation, which underwent a Pictet-Spengler-type cyclization to afford a variety of polycyclic isoindolines in good yields.


Association between hemogram‑derived indices and culture‑positive infections in intensive care population.
To investigate the relationship between hemogram parameters and bacterial growth in cultures of blood, urine or sputum in intensive care unit patients. This retrospective, observational, cross-sectional study was conducted in a tertiary referral hospital between March 2015 and December 2017. Baseline demographic and clinical characteristics, hemogram parameters and other laboratory test results of patients admitted to intensive care unit were recorded. Patients were divided into two groups as patients who were infected, and those who did not have any infectious agents grown in the culture dish, and then the groups were compared with each other. There were no significant differences between the groups in terms of baseline demographic and clinical characteristics. When the groups were compared in terms of hemogram parameters, the neutrophil‑to‑lymphocyte ratio (p < 0.001), platelet‑to‑lymphocyte ratio (p = 0.013), plateletcrit (p = 0.028) and mean platelet volume (p < 0.001) were significantly higher in infected patients than in non-infected patients. We suggest that neutrophil‑to‑lymphocyte ratio, platelet‑to‑lymphocyte ratio, plateletcrit, and mean platelet volume could be used as infection markers in the intensive care unit population (Tab. 1, Ref. 25).


Functional MR imaging of the uterus.
Recent developments in MR imaging techniques have enabled the functional assessment of the uterus. Cine MR imaging is a useful tool for evaluating uterine kinematic functions derived from myometrial contractility, and for investigating the alteration of uterine contractility in a variety of conditions and gynecologic disorders. Diffusion-weighted imaging can demonstrate abnormal signal in pathologic foci based on differences in molecular diffusion, and could provide useful information in evaluating malignant conditions. Dynamic contrast-enhanced MR imaging has the potential to improve tumor detection and local staging, and quantitative information may be useful for both monitoring therapeutic effects and predicting outcome. These state-of-the-art functional MR imaging techniques are beneficial for elucidating various uterine conditions when used appropriately, and the findings further provide the basis of future MR imaging investigations.


LY2228820 dimesylate, a selective inhibitor of p38 mitogen-activated protein kinase, reduces angiogenic endothelial cord formation in vitro and in vivo.
LY2228820 dimesylate is a highly selective small molecule inhibitor of p38α and p38β mitogen-activated protein kinases (MAPKs) that is currently under clinical investigation for human malignancies. p38 MAPK is implicated in a wide range of biological processes, in particular those that support tumorigenesis. One such process, angiogenesis, is required for tumor growth and metastasis, and many new cancer therapies are therefore directed against the tumor vasculature. Using an in vitro co-culture endothelial cord formation assay, a surrogate of angiogenesis, we investigated the role of p38 MAPK in growth factor- and tumor-driven angiogenesis using LY2228820 dimesylate treatment and by shRNA gene knockdown. p38 MAPK was activated in endothelial cells upon growth factor stimulation, with inhibition by LY2228820 dimesylate treatment causing a significant decrease in VEGF-, bFGF-, EGF-, and IL-6-induced endothelial cord formation and an even more dramatic decrease in tumor-driven cord formation. In addition to involvement in downstream cytokine signaling, p38 MAPK was important for VEGF, bFGF, EGF, IL-6, and other proangiogenic cytokine secretion in stromal and tumor cells. LY2228820 dimesylate results were substantiated using p38α MAPK-specific shRNA and shRNA against the downstream p38 MAPK effectors MAPKAPK-2 and HSP27. Using in vivo models of functional neoangiogenesis, LY2228820 dimesylate treatment reduced hemoglobin content in a plug assay and decreased VEGF-A-stimulated vascularization in a mouse ear model. Thus, p38α MAPK is implicated in tumor angiogenesis through direct tumoral effects and through reduction of proangiogenic cytokine secretion via the microenvironment.


The effect of greenness on allergic rhinitis outcomes in children and adolescents: A systematic review and meta-analysis.
The relationship between greenness and health emerges as new public health concern. More published studies from multiple areas have explored the relationship between greenness and allergic rhinitis (AR) in children and adolescents. This study aims to determine the association between greenness and allergic rhinitis by systematic review and meta-analysis, in order to provide a more comprehensive assessment of the impact of greenness on AR in children and adolescents. The relative literature was systematically searched in PubMed, Embase, and Web of science lastly on September 25, 2022. Terms related to greenness and allergic rhinitis were used for searching. Summary effect estimates of greenness on AR in children and adolescents were calculated for per 10 % increase of greenness exposure with different buffer sizes by random-effects model. A total of 579 studies were screened, and fourteen studies from Europe, Asia and North America were finally included. Most greenness exposure were measured by normalized difference vegetation index (NDVI). Enhanced vegetation index, outdoor-green environmental score and existed to measuring different greenness types. Greenness surrounding residences and schools were assessed. The overall effect of greenness on primary outcome was 1.00 (95%CI = 0.99-1.00). Most effect estimates of greenness were included in the NDVI-500 m group, and the pooled OR was 0.99 (95%CI = 0.97-1.01). No significant pooled estimates were found in analyses with study locations. This study indicates no significant association between greenness exposure and AR in children and adolescents. Various exposure measures and conversion of data may affect the results of this meta-analysis. More precise assessment of personal greenness exposure in well-designed prospective studies are vital for drawing a definite association in future. Furthermore, greenness exposure surrounding schools should be paid considerable attention for its effect on AR in school-aged children and adolescents.


Apoptotic Bodies of Cardiomyocytes and Fibroblasts - Regulators of Directed Differentiation of Heart Stem Cells.
We studied the effects of apoptotic bodies of cardiomyocytes (ApBc) and fibroblasts (ApBf) on myocardial regeneration and contractility in rats and the dynamics of RNA concentrations in cardiomyocytes and fibroblasts at different stages of apoptosis. ApBc increase the contractility of rat myocardium, while ApBf reduce it. ApBc stimulate the development of clones of cardiomyocyte precursors in the myocardium, while ApBf stimulate the formation of endothelial precursor clones. In doxorubicin cardiomyopathy, ApBc, similar to the reference drug (ACE inhibitor) improve animal survival, while ApBf produce no such effect. RNA concentrations in cardiomyocytes and fibroblasts before apoptosis and at the beginning of cell death significantly differed, while in apoptotic bodies of these cells, it was practically the same. It has been hypothesized that RNA complex present in ApBc and ApBf represents an "epigenetic code" of directed differentiation of cardiac stem cells.


Application of validated bleeding risk scores for atrial fibrillation in obscure gastrointestinal bleeding patients increases videocapsule endoscopy's diagnostic yield: a retrospective monocentric study.
Videocapsule endoscopy (VCE) is considered the gold standard for overt and obscure gastrointestinal bleeding (OGIB), after negative upper and lower endoscopy. Nonetheless, VCE's diagnostic yield is suboptimal, and it represents a costly, time-consuming, and often not easily available technique. In order to evaluate bleeding risk in patients with atrial fibrillation, several scoring systems have been proposed, but their utilization outside the original clinical setting has rarely been explored. The aim of the study is to evaluate potential role of bleeding risk scoring systems in predicting the occurrence of positive findings at VCE examination, and therefore in increasing VCE diagnostic yield. Data from consecutive patients undergoing VCE between April 2015 and June 2020 were retrospectively retrieved, and clinical and demographic characteristics were collected. HAS-BLED, ATRIA, and ORBIT scores were calculated, and patients were considered at low or high risk of bleeding accordingly. Discriminative ability of the scores for positive VCE findings has been evaluated by area under receiver operator characteristic curve (AUC) calculation. Diagnostic yield of scores in high- and low-risk patients was calculated. A total of 413 patients underwent VCE examination, among which 368 (89%) for OGIB. Positive findings were observed in 246 patients (67%), with angiodysplasias being the most frequent lesion (92%). The three scores displayed similar consistent discriminative ability for positive VCE findings (mean AUC = 0.69), and identified high-risk group of patients in which VCE has a higher diagnostic yield. In the present retrospective study, bleeding scores accurately discriminated patients with higher probability of positive findings at VCE examination. Bleeding scores utilization may help in the management of patients with OGIB, with a potential consistent resource optimization and cost-saving.


Targeted Alveolar Ridge Augmentation for Patient-Centered Dental Implant Site Development.
Guided bone regeneration (GBR) is the most commonly utilized procedure for augmenting deficient alveolar ridges in support of dental implant placement. In a GBR procedure, barrier membrane dimensions, bone graft volume, and surgical complexity may influence the risk of postsurgical morbidity. A 25-year-old female in good general health received GBR at two mandibular first molar sites exhibiting horizontal ridge deficiency. High-density polytetrafluoroethylene membranes were intentionally limited in size, and small-volume freeze-dried bone allografts were applied only where clinically beneficial for implant site development. Treatment resulted in clinically favorable ridge augmentation with no appreciable swelling and minimal postoperative discomfort. At dental implant sites exhibiting modest alveolar ridge deficiency, limiting GBR barrier membrane dimensions and bone graft volumes may enhance patient-centered outcomes while accomplishing clinical goals.


Immunomodulatory characteristics of a novel antiproliferative protein, suppressin.
We investigated the immunoregulatory properties of a recently described inhibitor of lymphocyte proliferation, suppressin (SPN). It was determined that preincubation of murine leukocytes with SPN enhances natural killer cell (NK) activity. In addition, SPN potentiates interferon-gamma (IFN-gamma) augmentation of NK activity. Furthermore, preincubation of murine leukocytes with SPN induces the production of IFN-alpha/beta. The IFN-alpha/beta produced is active in NK assays as well as vesicular stomatitis virus neutralization assays. In vivo, SPN increases the time of survival of C57BL/6 mice injected with EL-4 lymphoma cells. Interestingly, SPN inhibits immunoglobulin (IgA, IgG, and IgM) production in response to the mitogen, concanavalin A in a dose-dependent manner. Collectively, the above data indicate SPN may have numerous applications in clinical science including tumor surveillance and autoimmune diseases such as arthritis.


Reducing the public health risk of Escherichia coli O157 exposure by immunization of cattle.
The One Health approach investigates the complexities surrounding the interplay between the animal, human and environmental domains. Zoonotic pathogens, such as Escherichia coli (E. coli) O157, which have animal reservoirs, also have direct impact on public health. Cattle are the primary reservoir of E. coli O157, however infection with this bacterium is asymptomatic. Infected cattle appear healthy and have normal growth rates and milk production abilities. Each year, thousands of Canadians become ill following exposure to E. coli O157. To reduce this public health risk, immunization of cattle would be an effective intervention. Several models have shown that on-farm pathogen reduction programs would significantly reduce the risk of human illness.


Surgical treatment of intraventricular tumors associated with tuberous sclerosis.
Six children with intraventricular tumors associated with tuberous sclerosis (TS) were treated at the Children's Health Center, Department of Pediatric Neurosurgery, in the period 1987-1992. The age of the patients ranged from 7 to 15 years. TS was diagnosed according to Gomez diagnostic criteria. Computer tomography (CT) and magnetic resonance imaging showed intraventricular tumors associated with ventricular enlargement and multiple subependymal nodules commonly observed in cases of TS. All tumors were removed totally through frontal transcortical approach, with uneventful postoperative recovery. One patient, with two parallel tumors in the two frontal horns, underwent one-stage surgery with successful total removal. Histopathological examination in all cases showed subependymal giant cell astrocytoma (SGCA). The growth pattern of SGCA associated with TS, documented by sequential CT scans over several years, is described. The diagnosis and surgical treatment of the tumor are discussed, and periodic CT scanning, at least every 2 years, is recommended for patients with TS.


Clinical Trial on Mindfulness with Family Caregivers for Patients with Cancer.
To examine the effectiveness of a brief mindfulness-based interventions (MBIs) and educational interventions (EI) on self-efficacy and burden among family caregivers (FCs) of patients with cancer in Jordan. A quasi-experimental design was conducted. Two interventions were performed: the brief MBIs and the EIs were applied. A sampling of 138 FCs completed the study interventions. The FCs in the mindfulness group demonstrated a significant improvement in measures of self-efficacy and reduction in burden scores. Furthermore, in the EI group, only self-efficacy was significantly higher in the post-test. Burden reduction was significantly higher in the EI group than the mindfulness group. Appropriate supportive interventions should be directed to improve self-efficacy and reduce burden to assist FCs to carry out their crucial role in providing care for their patients.


Acute effect of methamphetamine on heme oxygenase activity and on cytochrome P-450 content in the liver of female rats.
After a single treatment with d-methamphetamine (philopon) at a dose of 8 mg/kg in 10 weeks old female Wistar rats, heme oxygenase activity was enhanced at 3 hr and reached it peak level at 12 hr, whereas cytochrome P-450 content showed the lowest level at 12 hr. However, activity of delta-aminolevulinic acid synthetase was not affected. Twenty-four hr later, all measured parameters returned to nearly initial levels at zero time. The pretreatment with cycloheximide blocked the increase of heme oxygenase activity in philopon-treated animals.


Preconceptional folic acid utilization in Israel: five years after the guidelines.
In Israel, a national survey was conducted in order to assess the efficacy of the ongoing national folic acid (FA) campaign launched in 2000. The Ministry of Health had issued official guidelines in August 2000 recommending daily FA supplementation for all childbearing age women. In 2005, structured interviews of pregnant and postpartum women were conducted by the nursing staff of the Maternal Child Health Clinics administered by the Public Health Service. The results of the 2005 survey are compared with similar surveys done in 2002 and 2000 (baseline). In the 2005 survey (n=1860), FA awareness, knowledge, timing knowledge and preconceptional utilization were 90.3%, 80.8%, 74.6% and 34.0%, respectively. Education was significantly associated with compliance: only 13.6% of women with <12 years of education utilized FA preconceptionally versus 48.1% of women with >or=16 years. In the 2002 survey (n=1661), FA awareness, knowledge, and preconceptional utilization were 85%, 77.7% and 30.5%, respectively. In the 2000 survey (n=1719), FA awareness was 54.6%, knowledge was 17.6% and preconceptional utilization was 5.2%. The national preconceptional FA campaign in Israel has resulted in significant increases in awareness, knowledge and preconceptional utilization.


Retinal detachment in young premature infants with acute retrolental fibroplasia. Thirty-two new cases.
Experience with scleral buckling for exudative and tractional retinal detachments in very young premature infants who have acute retrolental fibroplasia (RLF) is reported. In this series, surgery was successful in 24 of 32 eyes (75%) of 23 infants, (age at surgery ranged from 1.75 months to 6 months, average age of 3 months). We attribute the 15% improvement in the success rate over our 1979 series in part to closer screening with emphasis on the examination at age 8 weeks, to earlier referral for treatment, and to our observation that these fragile eyes can withstand reoperation if buckle revision is necessary to combat persistent retinal traction. We encountered no serious complications either at surgery or immediately after surgery. We stress that (1) because of the high incidence of spontaneous remission, buckling surgery should not be performed until the detachment has progressed well posterior to the equator and remission is obviously unlikely (Grade IV or V); (2) excessive cryotherapy and undue surgical trauma should be avoided; and (3) because scleral erosion is certain as the eyes grow, the encircling band should be transected six months to one year after surgery.


Helix bundle loops determine whether histidine kinases autophosphorylate in cis or in trans.
Bacteria frequently use two-component signal transduction pathways to sense and respond to environmental and intracellular stimuli. Upon receipt of a stimulus, a homodimeric sensor histidine kinase autophosphorylates and then transfers its phosphoryl group to a cognate response regulator. The autophosphorylation of histidine kinases has been reported to occur both in cis and in trans, but the molecular determinants dictating which mechanism is employed are unknown. Based on structural considerations, one model posits that the handedness of a loop at the base of the helical dimerization domain plays a critical role. Here, we tested this model by replacing the loop from Escherichia coli EnvZ, which autophosphorylates in trans, with the loop from three PhoR orthologs that autophosphorylate in cis. These chimeric kinases autophosphorylated in cis, indicating that this small loop is sufficient to determine autophosphorylation mechanism. Further, we report that the mechanism of autophosphorylation is conserved in orthologous sets of histidine kinases despite highly dissimilar loop sequences. These findings suggest that histidine kinases are under selective pressure to maintain their mode of autophosphorylation, but they can do so with a wide range of sequences.


High mortality rates among GHB abusers in Western Sweden.
GHB is a drug of abuse and acute poisonings have been an increasing medical problem over the last decade in Sweden. To document all cases of GHB poisonings in Gothenburg during 1995-2004 and to record drug-related deaths to compare the toxicity of GHB with other illicit drugs, such as heroin and amphetamine. The number of GHB-poisoned patients treated at the Sahlgrenska University Hospital has been recorded with the help of an in-house database. The number of deaths by illicit drugs was recorded during 2004. Seizures of the drugs GHB, 1,4-butanediol, and GBL were registered between 1996 and 2004. The number of poisoned patients was 259. The number of seizures with GHB was 743, GBL 343, and 1,4-butanediol 236. In 2004 the number of deaths was 6 with heroin, 7 with GHB, 32 with amphetamine, 6 with cocaine, and one with methadone. One patient with GHB poisoning died during hospital care. Intoxication by GHB has substantial morbidity and abuse of GHB has substantial mortality. The acute prognosis is good but long-term prognosis is insecure with an increased risk for drug dependency and an early death.


Depleted histone deacetylase 3 or restored microRNA-19b-1-5p facilitates recovery of spinal cord injury via inactivating JAK2/STAT3 signaling pathway.
We intended to discuss the influence of histone deacetylase 3 (HDAC3) on spinal cord injury (SCI) by regulating microRNA-19b-1-5p (miR-19b-1-5p) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. In a rat model, the role of HDAC3 and miR-19b-1-5p in SCI was identified through detecting motor function, serum inflammation, pathological damage, cell apoptosis and GFAP expression. Also, by measuring GFAP expression and migration of spinal cord astrocytes, the effects of HDAC3 and miR-19b-1-5p in SCI were identified in vitro. Restoration of miR-19b-1-5p or depletion of HDAC3 alleviated motor function, inflammation, relieved pathological damage and reduced apoptosis, and reduced GFAP expression in the spinal cord tissue of SCI rats. Up-regulating miR-19b-1-5p or down-regulating HDAC3 decreased migration and GFAP expression of injured astrocytes. Our study presents that down-regulated HDAC3 can facilitate the recovery of SCI via inhibiting the activation of JAK2/STAT3 pathway by up-regulating miR-19b-1-5p.


Schirmer test results: are they associated with topical or systemic medication?
To test whether Schirmer test (ST) results are associated with topical or systemic medication and to evaluate the distribution of tear fluid quantity in a 3-min and 5-min ST. The Gutenberg Health Study is a population-based, prospective, observational cohort study in Germany. ST was assessed in a sub-cohort of 1,999 participants. ST was performed under topical anesthesia for 5 min (ST-5) or of 3 min (ST-3). Anthropometric factors, systemic diseases, use of systemic and eye medications were recorded. We used multivariable quantile regression analysis to assess the influence on ST measurements. The length of wetting of the Schirmer strips for ST-5 was 23.2 ± 9.31 mm for right and 22.9 ± 9.0 mm for left eyes. In ST-3, the measurements were 20.0 mm in right and 19.1 mm in left eyes. The clinical cut off of 10 mm for ST-5 corresponded with an 8 mm cut off for ST-3. There was an association of smaller ST-5 measures with male sex, higher age, socioeconomic status and season (all p < 0.001), but not with diabetes or smoking. The use of prostaglandin or beta-blocker eye drops or oral non-steroidal anti-inflammatory drugs, drugs for peptic ulcer and gastro-oesophageal reflux disease, thyroid hormones, progesterone and estrogen combination drugs, and hypnotics and sedatives showed an association with smaller ST-5. For the first time we describe the distribution of tear fluid quantity by ST in a very large cohort of the general population. Furthermore, we found associations of ST measures with topical and systemic medication.


Carbon fibers coated with urchin-like copper sulfide for nonenzymatic voltammetric sensing of glucose.
Urchin-like CuS was grown on xanthan gum-derived carbon nanofibers to obtain a sensor for enzyme-free electrochemical sensing of glucose. The unique nanostructure of the sensor provides a large specific surface, more electrocatalytically active sites, and high electrical conductivity. The voltammetric response to glucose, best measured at around 57 mV (vs. Ag/AgCl (E/V)) in 0.1 M NaOH solution, covers two linear ranges, one from 0.1-125 μM, another from 0.16 to 1.2 mM. The sensitivity is quite high (23.7 μA mM-1 cm-2), and the detection limit is low (19 nM at S/N = 3). The sensor has high selectivity against potentially interfering molecules such as fructose, appreciable operational stability, excellent durability, and good repeatability (with relative standard deviations of 2.3%). It was successfully applied to the determination of glucose in diluted serum samples. Graphical abstractSchematic representation of electrochemical detection of glucose based on the use of a screen printed carbon electrode (SPCE) modified with CuS and xanthan gum-derived carbon nanofibers (XGCNFs).


Hermansky-Pudlak syndrome (HPS5) in a nonagenarian.
Hermansky-Pudlak syndrome (HPS) is an autosomal-recessive disorder clinically characterized by oculocutaneous albinism, bleeding diatheses, and lysosomal accumulation of ceroid lipofuscin, which in some cases may cause granulomatous colitis and pulmonary fibrosis. Any of these complications could result in a shortened life span for patients with HPS. We report a 92-year-old man with HPS 5 who, to our knowledge, is the oldest patient with HPS documented in the literature. This report highlights the importance of typing HPS to counsel patients regarding disease prognosis.


Implant Material Sciences.
In the past, the only way to replace missing teeth was to have a removable appliance. However, these days, dental implants are commonly being used to replace missing teeth. The dental implants are improving as a result of new technological and scientific advances. Different materials have been used in the past for dental implants such as lead, stainless steel, and gold. Currently, the focus is on using Roxolid, surface-modified titanium implants, and zirconia. These materials have superior esthetic and functional characteristics for dental implants.


Detection and modeling of anti-Leptospira IgG prevalence in cats from Lisbon area and its correlation to retroviral infections, lifestyle, clinical and hematologic changes.
Leptospirosis is a zoonosis of global importance caused by Leptospira species. Rodents are the main reservoirs, known to shed the bacteria in urine, thus contaminating water and soil and infecting other animals and people. Leptospirosis has been re-emerging in both developing and developed countries including Europe. It has been hypothesized that cats could be asymptomatic carriers of Leptospira. This study aims to evaluate cats' exposure to Leptospira in Lisbon, Portugal, by measuring IgG titres and correlating them with possible factors that may increase the risk of exposure in urban cats. Two hundred and forty-three samples were collected from the biobank. An ELISA test followed by a seroprevalence analysis using a finite mixture model was performed to detect and measure anti-Leptospira IgG antibodies titres. In parallel, a survey was conducted to identify possible risk factors for seropositivity. According to the ELISA test protocol, only twenty-three cats (9.5%; 95% CI =(6.1%;13.9%)) could be considered as seropositive to Leptospira antigens. However, when the same data were analysed by the best different mixture models, one hundred and forty-four cats (59.3%; 95%CI = (52.8%; 65.5%)) could be classified as intermediate and high antibody responders to Leptospira antigens. Seropositivity to Feline Immunodeficiency Virus infection (FIV) was found to be the only significant risk factor associated with anti-Leptospira IgG antibodies. In conclusion, the present studies raises the possibility of a higher exposure of cats to Leptospira than previously thought due to the identification of a subpopulation of cats with intermediate antibody levels.


Ultrasound diagnosis of extrahepatic portal vein obstruction in childhood. The sign of the subhepatic sponge-like mass.
Portal vein obstruction in childhood produces portal hypertension and hepatopetal collaterals surrounding the obstructed portal vein; this is the "cavernomatous transformation of the portal vein" which is a well defined angiographic entity. Clinically findings are the various manifestations of Banti's syndrome, especially splenomegaly and gastrointestinal bleeding. Ultrasonic diagnosis is possible on the associated findings of splenomegaly, normal liver, a subhepatic sponge like mass corresponding to the hepatopetal collaterals. These signs must be sought in the ultrasonic differential diagnosis of splenomegaly in pediatrics.