Semimetal-Semiconductor Transitions for Monolayer Antimonene Nanosheets and Their Application in Perovskite Solar Cells.
Antimonene-based 2D materials are attracting increasing research interest due to their superior physicochemical properties and promising applications in next-generation electronics and optoelectronics devices. However, the semiconductor properties of antimonene are still at the theoretical simulation stage and are not experimentally verified, significantly restricting its applications in specific areas. In this study, the semiconductor properties of monolayer antimonene nanosheets are experimentally verified. It is found that the obtained semiconductive antimonene nanosheets (SANs) exhibit indirect bandgap properties, with photoluminescence (PL) bandgap at about 2.33 eV and PL lifetime of 4.3 ns. Moreover, the obtained SANs are ideal for the hole extraction layer in planar inverted perovskite solar cells (PVSCs) and significantly enhance the device performance due to fast hole extraction and efficient hole transfer at the perovskite/hole transport layer interface. Overall, these findings look promising for the future prospects of antimonene in electronics and optoelectronics.


Factors Affecting the Outcomes of Double-Bundle Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocations Evaluated by Multivariate Analysis.
Many factors are involved in causing patellar instability or recurrent patellar dislocations. However, factors affecting the outcomes of anatomic medial patellofemoral ligament (MPFL) reconstruction have not been fully documented. To evaluate the rate of recurrent patellar instability after isolated MPFL reconstruction and to elucidate factors affecting the outcomes of isolated MPFL reconstruction using multivariable statistics. Case-control study; Level of evidence, 3. A total of 42 patients (44 knees) who underwent isolated, anatomic MPFL reconstruction using a semitendinosus autograft without any additional patellar stabilization procedures for treating recurrent patellar dislocations were included in this study. All patients were followed for more than 2 years; the mean follow-up period was 3.2 years (range, 2-9 years). Postoperative patellofemoral instability was diagnosed when the patient complained of recurrent patellar subluxations or dislocations or had a positive apprehension sign during follow-up. Preoperative radiographic findings were obtained using plain radiography and computed tomography. Femoral tunnel positions were assessed on postoperative radiographs. The strength of the relationship between postoperative patellofemoral instability and potential risk factors such as preoperative age, sex, body mass index, patellar type, sulcus angle, congruence angle, lateral tilt angle, patellar height, tibial tubercle-trochlear groove (TT-TG) distance, degree of trochlear dysplasia, and femoral bone tunnel position were evaluated by univariate and multivariate logistic regression analyses. At follow-up, 2 knees had experienced a redislocation (4.5%). A positive apprehension sign was still evident in 8 knees (18.2%). Three factors, including the sulcus angle, the congruence angle, and trochlear dysplasia, were extracted by single linear regression analysis. Univariate logistic regression analysis showed that the sulcus angle (odds ratio [OR], 1.11; 95% CI, 1.01-1.22; P = .04) and trochlear dysplasia (OR, 3.04; 95% CI, 1.39-6.63; P = .01) were associated with postoperative patellofemoral instability. Trochlear dysplasia was independently associated with postoperative patellofemoral instability by multivariable logistic regression analysis (P < .05). An increased TT-TG distance exerted a significant effect on the outcomes of MPFL reconstruction, particularly in patients with type D trochlea. Severe trochlear dysplasia is the most important predictor of residual patellofemoral instability after isolated MPFL reconstruction. In addition, an increased TT-TG distance affected the outcomes in patients with type D trochlea. Additional patellar stabilization procedures should be considered for patients with severe trochlear dysplasia and an increased TT-TG distance.


[Anatomical basis of ultrasonography of the knee].
Authors show the structures of the knee joint that can be demonstrated by ultrasound. It is stated that in normal circumstances the tendons, the collateral ligaments, the bursae and Hoffa's fat tissue can be easily brought in the visual field. The demonstration of the single parts of the menisci and the cruciate ligaments is more difficult in certain cases (bulky knee, contracture, progressed gonarthrosis). Corresponding to the literary data and on the basis of their results they conclude that the ultrasound is suitable to the correct demonstration of the complicated anatomy of the knee. The examination is noninvasive, it can be repeated any time and with adequate experience it gives possibility to recognise the changes in the knee joint.


Changes in growth, photosynthetic activities, biochemical parameters and amino acid profile of Thompson Seedless grapes (Vitis vinifera L.).
The study on photosynthetic activity and biochemical parameters in Thompson Seedless grapes grafted on Dog Ridge rootstock and its impact on growth, yield and amino acid profile at various stages of berry development was conducted during the year 2012-2013. Leaf and berry samples from ten year old vines of Thompson Seedless were collected at different growth and berry developmental stages. The analysis showed difference in photosynthetic activity, biochemical parameters and amino acid status with the changes in berry development stage. Higher photosynthetic rate of 17.39 umol cm(-2) s(-1) was recorded during 3-4mm berry size and the lowest (10.08 umol cm(-2) s(-1)) was recorded during the veraison stage. The photosynthetic activity showed gradual decrease with the onset of harvest while the different biochemical parameters showed increase and decrease from one stage to another in both berry and leaves. Changes in photosynthetic activity and biochemical parameters thereby affected the growth, yield and amino acid content of the berry. Positive correlation of leaf area and photosynthetic rate was recorded during the period of study. Reducing sugar (352.25 mg g(-1)) and total carbohydrate (132.52 mg g(-1)) was more in berries as compared to leaf. Amino acid profile showed variations in different stages of berry development. Marked variations in photosynthetic as well as biochemical and amino acid content at various berry development stages was recorded and thereby its cumulative effect on the development of fruit quality.


Evaluation of contaminated drinking water and preterm birth, small for gestational age, and birth weight at Marine Corps Base Camp Lejeune, North Carolina: a cross-sectional study.
Births during 1968-1985 at Camp Lejeune were exposed to drinking water contaminated with trichloroethylene (TCE), tetrachloroethylene (PCE), and benzene. We conducted a cross-sectional study to evaluate associations between residential prenatal exposure to contaminated drinking water at Camp Lejeune during 1968-1985 and preterm birth, small for gestational age (SGA), term low birth weight (TLBW), and mean birth weight (MBW) deficit. Birth certificates identified mothers residing at Camp Lejeune at delivery. We analyzed exposure data for the entire pregnancy and individual trimesters. For each period examined, births were categorized as unexposed if mothers did not reside at Camp Lejeune or if their residence on base received uncontaminated drinking water. Ground water contaminant fate/transport and distribution system models provided monthly estimated contaminant levels at residences. For PCE and TCE, the exposed group was divided into four levels: < median value, ≥ median value, ≥75th percentile, and ≥90th percentile. For benzene, the exposed group was categorized as <1 part per billion (ppb) versus ≥1 ppb because of sparse data. Magnitude of effect estimates and exposure response relationships were used to assess associations. Confidence intervals (CIs) indicated precision of estimates. For the highest TCE exposure category during the entire pregnancy, odds ratios (ORs) were 1.5 (95% CI: 1.2, 1.9) and 1.3 (95% CI: 0.8, 2.2) for SGA and TLBW, respectively, and reduced MBW β = -78.3 g (95% CI: -115.0, -41.7). The OR =1.3 (95% CI: 1.0, 1.6) for preterm birth and the highest PCE exposure category during the entire pregnancy. Monotonic exposure-response relationships were observed for benzene exposure during the entire pregnancy and TLBW (highest category OR =1.5, 85% CI: 0.9, 2.3). Although a monotonic association between benzene and adjusted MBW difference was also observed (highest category β = -36.2 g, 95% CI: -72.3, -0.1), the association disappeared when TCE was also added to the model. We found no evidence suggesting any other associations between outcomes and exposures. Findings suggested associations between in utero exposures to TCE and SGA, TLBW and reduced MBW; benzene and TLBW; and PCE and preterm birth.


The development of skin cancer is closely related to high exposure to UV radiation. Lifeguards are at an increased risk of excessive sun exposure. Objectives The main objective of this study was to measure the exposure of Barcelona's beach lifeguards to UV radiation. Measurements in the work chair were taken every 30 minutes on a typical working day from 10:45 am to 19:15 pm. These measurements were carried out on four different days. These data were used to calculate the erythematous doses received during working hours, as well as those potentially received throughout the summer season. Vitamin D production was also estimated for the four days that the radiation received was measured, and the amount generated was calculated for the entire summer season. Exposure to UV radiation among Barcelona lifeguards far exceeds safety limits. In some locations, the exposure to UVB radiation is more than 16 times the minimum erythematous dose for phototype II skin. This study assessed the radiation received during only four days. However, is a much higher number than most of the published papers. Conclusion Although the health risks of excessive exposure to UV radiation are known, Barcelona's beach lifeguards are insufficiently protected.


Visible-Light Transparent, Ultrastretchable, and Self-Healable Semicrystalline Fluorinated Ionogels for Underwater Strain Sensing.
The development of ultrastretchable ionogels with a combination of high transparency and unique waterproofness is central to the development of emerging skin-inspired sensors. In this study, an ultrastretchable semicrystalline fluorinated ionogel (SFIG) with visible-light transparency and underwater stability is prepared through one-pot copolymerization of acrylic acid and fluorinated acrylate monomers in a mixed solution of poly(ethylene oxide) (PEO) and fluorinated ionic liquids. Benefiting from the formation of the PEO-chain semicrystalline microstructures and the abundant noncovalent interactions (reversible hydrogen bonds and ion-dipole interactions) in an ionogel, SFIG is rendered with room-temperature stable cross-linking structures, providing high mechanical elasticity as well as high chain segment dynamics for self-healing and efficient energy absorption during the deformation. The resultant SFIG exhibits excellent stretchability (>2500%), improved mechanical toughness (7.4 MJ m-3), and room-temperature self-healability. Due to the high compatibility and abundance of hydrophobic fluorinated moieties in the ionogel, the SFIG demonstrates high visible-light transparency (>97%) and excellent waterproofness. Due to these unique advantages, the as-prepared SFIG is capable of working as an ultrastretchable ionic conductor in capacitive-type strain sensors, demonstrating excellent underwater strain-sensing performances with high sensitivity, large detecting range, and exceptional durability. This work might provide a straightforward and efficient method for obtaining waterproof ionogel elastomers for application in next-generation underwater sensors and communications.


Methods for the detection of paxillin post-translational modifications and interacting proteins by mass spectrometry.
Methods for the simultaneous identification of interacting proteins and post-translational modifications of the focal adhesion adapter protein, paxillin, are presented. The strategy includes (1) lower-level, transient transfection of FLAG-GFP-Paxillin into HEK293 cells, (2) incubation of cells with phosphatase inhibitors prior to lysis, (3) purification of paxillin by anti-FLAG immunoprecipitation, (4) analysis of peptides generated from on-beads digestion using LTQ-FT or LTQ-ETD mass spectrometry, and (5) enrichment of phosphopeptide methyl esters with IMAC. Using the above strategies, we identify 29 phosphorylation sites (19 novel and 10 previously reported) and a novel glycosylation site on Ser 74. Furthermore, with this method, we simultaneously detect 10 co-purifying proteins which are present in focal adhesion complexes. Extension of these methods to other substrates should facilitate generation of global phosphorylation maps and protein-protein interactions for any protein of interest.


Inflammatory breast cancer: current understanding.
Inflammatory breast cancer is a highly aggressive variant of locally advanced breast cancer that carries a significantly worse prognosis. The purpose of this review is to highlight recent advances in the molecular modus operandi of this particular form of breast cancer. Studies on tumor cell emboli, E-cadherin, chemokine receptors, steroid hormone receptor, angiogenesis, lymphangiogenesis and gene expression all suggest significant differences with noninflammatory breast cancer and are clearly in line with a different pathogenesis of the condition. This comprehensive review will hopefully allow for better treatment modalities with targeted approaches as suggested by the early data on anti-vascular endothelial growth factor treatment in inflammatory breast cancer.


A rapid DNA digestion system.
This paper presents a novel microfluidic DNA digestion system incorporating a high performance micro-mixer. Through the appropriate control of fixed and periodic switching DC electric fields, electrokinetic forces are established to mix the DNA and restriction enzyme samples and to drive them through the reaction column of the device. The experimental and numerical results show that a mixing performance of 98% can be achieved within a mixing channel of length 1.6 mm when a 150 V/cm driving voltage and a 5 Hz switching frequency are applied. The relationship between the mixing performance, switching frequency, and main applied electric field is derived. It is found that the optimal switching frequency depends upon the magnitude of the main applied electric field. The successful digestion of lambda-DNA using Eco RI restriction enzyme is demonstrated. The DNA-enzyme reaction is completed within 15 min in the proposed microfluidic system, compared to 50 min in a conventional large-scale system. Hence, the current device provides a valuable tool for rapid lambda-DNA digestion, while its mixer system delivers a simple yet effective solution for mixing problems in the micro-total-analysis-systems field.


PINK1 rendered temperature sensitive by disease-associated and engineered mutations.
Mutations in Parkin or PINK1 are the most common cause of recessively inherited parkinsonism. Parkin and PINK1 function in a conserved mitochondrial quality control pathway, in which PINK1, a putative mitochondrial kinase, directs Parkin, a cytosolic E3 ubiquitin ligase, selectively to dysfunctional mitochondria to promote their isolation, immobilization and degradation by macroautophagy (hereafter, mitophagy). As Parkin recruitment to mitochondria is robustly induced by PINK1 expression on the outer mitochondrial membrane, Parkin recruitment to mitochondria was used as an assay for PINK1 function. Unexpectedly, mutation of serine residues within the activation segment of PINK1 uncovered a temperature-sensitive variant of PINK1 (tsPINK1). tsPINK1 allowed for the first time the disassociation of PINK1 activity from its expression and localization. Additionally, extensive mutagenesis identified three disease-associated variants in the activation segment and one in an α-helix N-terminal to kinase domain (Q126P) that are similarly thermally labile, suggesting that their activity could be restored post-translationally (e.g. by reducing the temperature or by a chemical or pharmacologic chaperone). Together, these findings suggest that tsPINK1 may represent a valuable tool for the analysis of the PINK1/Parkin pathway in human cells; additionally, as the serine residue promoting thermal lability is conserved among Mus musculus, Danio rerio, Drosophila melanogaster and Caenorhabditis elegans, it may serve as the basis for developing other temperature-sensitive models for the study of recessive parkinsonism and mitophagy. Finally, these results suggest that PINK1 kinase function could be restored for a subset of patients with PINK1 mutations, and perhaps alter the course of their disease.


Comparison of three techniques for the diagnosis of urinary tract infections in dogs with urolithiasis.
To identify an appropriate sampling technique(s) to accurately detect the bacteria causing urinary tract infections in dogs with urolithiasis. Twenty-one dogs with urolithiasis were included in the study. Three types of samples were taken from each dog. Urine was collected by cystocentesis, and a urinary bladder mucosal biopsy and urolith were retrieved during cystotomy. The samples were then cultured on blood agar and MacConkey's agar to identify the bacteria associated with urinary tract infections. Bacterial urinary tract infection was found in 16 cases (76.19 per cent). The most prevalent bacteria found to cause urinary tract infection were Escherichia coli (n=7), followed by coagulase-positive Staphylococcus species (n=4), Klebsiella pneumoniae (n=2), Pseudomonas aeruginosa (n=2) and Proteus mirabilis (n=1). In the case of a positive urine culture, the same bacteria were also cultured from the urinary bladder mucosal biopsy alone or from both the urinary bladder mucosal biopsy and urolith. However, in the case of a negative urine culture, bacteria were found to be present in the urinary bladder mucosal biopsy or urolith cultures in 23.81 per cent of dogs. The uroliths that gave positive culture results were either infection-induced uroliths composed of struvite and calcium carbonate phosphate, ammonium acid urate only or metabolic uroliths composed of calcium oxalate and calcium phosphate, or calcium phosphate only. All the uroliths that gave negative culture results were metabolic uroliths composed of calcium oxalate and/or calcium phosphate, and uric acid and calcium phosphate. When the culture from the urine obtained by cystocentesis is negative, cultures of urinary bladder mucosal biopsy and urolith are recommended in dogs with urolithiasis in order to accurately assess the microbiological status of the urinary tract.


The prognostic significance of high/positive expression of tissue VEGF in ovarian cancer.
At present, numerous reports have shown that high/positive expression of tissue vascular endothelial growth factor (VEGF) may be associated with the prognosis of patients with ovarian cancer. However, their results still remained controversy. Thus, this meta-analysis was designed to analyze and assess the prognostic value of tissue VEGF expression in patients with ovarian cancer. We searched PubMed, Embase, Cochrane Library and Web of Science to October, 2017. Hazard Ratio (HR) with its 95% confidence intervals (CIs) was used to evaluate the association between high/positive expression of tissue VEGF and the prognosis of ovarian cancer patients. All statistical analyses were performed using standard statistical procedures provided in RevMan 5.2. A total of 18 studies (including 1145 patients) were included for this meta-analysis. The positive/high expression of tissue VEGF had an obvious association with overall survival (OS) (HR 2.24, 95% CI 1.36-3.70; P=0.002), progression-free survival (PFS) (HR 1.60, 95% CI 1.11-2.31; P=0.01) and disease-free survival (DFS) (HR 3.49, 95% CI 1.27-9.56; P=0.02) of patients with ovarian cancer respectively. The present meta-analysis indicated that positive/high expression of tissue VEGF may have a close association with survival of ovarian cancer.


[Interobserver diagnostic agreement on digital images of hysteroscopic studies].
Hysteroscopic studies are of the most used methods to examine the uterine cavity in patients that present abnormal uterine hemorrhage as well as those patients with infertility. The use of hysteroscopic studies during reproductive cycles has increased the successful of pregnancy rates. Up to date, there are not many studies evaluating the inter-observer agreement in the diagnosis of different uterine pathology when using a hysteroscopic study. To evaluate the inter-observer agreement in the diagnosis of uterine pathology when using digitalized images in hysteroscopic studies made by residents of gynecological endoscopy. A cross-sectional, descriptive and observational study was made including 28 images of hysteroscopic studies selected by at least two of three experts in hysteroscopy, who determined that they were adequate to do a diagnostic impresion. From a total of four residents, two were selected using a randomized sampling. The images were shown to each resident in a randomized presentation and the diagnosis agreement was evaluated. Kappa test was used to evaluate the interobserver agreement with 95% confidence interval. The interobserver agreement obtained by Kappa test for different images for diagnosis of uterine pathology were: normal uterine cavity (κ = 0.81 with CI 95%, 0.56-1.00), endometrial polypus (κ = 0.71 with CI 95%, 0.33-1.00), submucous myoma (κ = 0.71 with Cl 95%, 0.33- 1.00), intrauterine adherences (κ = 0.84 with Cl 95%, 0.52-1.00), uterine septum (κ = 0.76 with CI 95%, 0.43-1.00) and endometrial hyperplasia or potential endometrial cancer (κ = 0.87 with Cl 95%, 0.61-1.00). The interobserver agreement using digitalized images in the diagnosis of different uterine pathology from hysteroscopic studies made by residents of endoscopic surgery was high and very high in all cases.


China's Actions to Achieve Universal Health Coverage for Children.
The United Nations General Assembly adopted the 2030 Sustainable Development Goals (SDGs) in September 2015. Through this, governments have also committed to universal health coverage (UHC) as a development sub-goal within the SDG health field (1-2). In its effort to fully safeguard universal child health, China has established a management system for child healthcare to provide all children with continuous healthcare services starting at birth. Since 1950, China has implemented a system of local physicians who take responsibility for child healthcare services within their areas. Under the three-tier management system at the county, township, and village levels, every newborn is included in the child health management system starting immediately after birth. The urban and rural community-based health facilities in the area provide unified, standardized, and systematic healthcare services. Moreover, since 2009, child health management has been included in the National Essential Public Health Service Program, which mandates that community-based primary health facilities provide free health management services for children 0-6 years old in their area. This has led to equitable and comprehensive coverage of health services for these children. When children enter school at the age of six, they receive an annual routine physical examination at school. In 2020, the national coverage for neonatal visits, the health management rate for children under 3 and the health management rate for children under 7 all surpassed 92%, while the prevalence of stunting among children under 5 continued to decline. In addition, urban-rural disparities in major child health indicators have also narrowed significantly. Moreover, the inoculation rate of children in National Immunization Programme Vaccines has remained over 99% since 2011 (3).


Biology, staging, and treatment of breast cancer during pregnancy: reassessing the evidences.
Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Here, we review the management of women with breast cancer during pregnancy (BCP), focusing on biology, diagnosis and staging, local and systemic treatments, obstetric care and long-term follow-up of children with prenatal exposure to anticancer treatments.


Validation of endogenous controls for quantitative gene expression analysis: application on brain cortices of human chronic alcoholics.
Real-time PCR is frequently used for gene expression quantification due to its methodological sensitivity and reproducibility. The gene expression is quantified by normalization to one or more reference genes, usually beta-actin (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPD) or to ribosomal RNA (18S). However, different environmental or pathological conditions might also influence the expression of normalizing genes, which could severely skew the interpretation of quantitative results. This study evaluates whether 16 genes frequently used as endogenous controls in expression studies, can serve as such for comparison of human brain tissues of chronic alcoholics and control subjects. The prefrontal and motor cortices that are affected differently by chronic alcohol consumption were analyzed. The reference genes that have no or small differences in expression in alcoholics and control subjects, were found to be specific for each region: beta-actin (ACTB) and ribosomal large P0 (RPLP0) for the prefrontal cortex while importin 8 (IPO8) and RNA polymerase II (POLR2A) for the motor cortex. Four out of sixteen analyzed genes demonstrated significant differences in expression between alcoholics and controls: phosphoglycerate kinase (PGK1), hypoxanthine phosphoribosyl transferase (HPRT1) and peptidylprolyl isomerase A (PPIA) in the motor cortex and beta-2-microglobulin (B2M) in the prefrontal cortex. Our study demonstrates the importance of validation of endogenous control genes prior to real-time PCR analysis of human brain tissues. Prescribed and non-prescribed drugs, pathological or environmental conditions along with alcohol abuse may differentially influence expression of reference genes.


How should worsening in osteoarthritis be defined? Development and initial validation of preliminary criteria for clinical worsening in knee and hip osteoarthritis.
There is a need to define and validate measures of clinical worsening in knee and hip osteoarthritis (OA). The objectives of this exploratory project were: (i) to characterize worsening criteria in knee and hip OA using psychometric methods; (ii) to estimate their sensitivity and specificity; and (iii) to validate and compare these criteria with worsening criteria previously described in the literature. An Expert Group reached consensus on 10 sets of worsening criteria to be tested in observational data sets of patients with knee or hip OA who received multimodal conservative treatment. These sets included 219 patients (derivation cohort) and 296 patients (validation cohort). We estimated minimal clinically important worsening (MCIW) values for pain, function, stiffness, and patient global assessment, and tested candidate worsening criteria in the derivation cohort. Finally, using patient judgement, we examined the sensitivity and specificity of literature-based as well as candidate worsening criteria in the validation cohort. Literature-based worsening criteria were found to have high specificity (range 60-92%) but low sensitivity (range 22-59%). Two out of 10 candidate worsening criteria constructed by the Expert Group showed an acceptable combination of sensitivity and specificity in the derivation cohort, which was confirmed in the validation cohort (ranging from 54% to 65% and 67% to 74%, respectively). This is the first study to describe symptomatic worsening criteria based on expert consensus after examining the performance of candidate criteria derived from the literature applied to data in an observational study. The newly proposed worsening criteria show an acceptable combination of sensitivity and specificity.


Hepatoprotective Effect of Actinidia deliciosa against Streptozotocin-Induced Oxidative Stress, Apoptosis, and Inflammations in Rats.
The present research intended to assess the possible protective and hypoglycemic effect of Actinidia deliciosa fruit aqueous extract (ADAE) in diabetic rats. The scavenging antioxidant capabilities of ADAE were evaluated using GC-MS analysis. In addition, rats were divided into four groups: control, ADAE, streptozotocin-induced DM (STZ), and STZ-treated rats + ADAE in an in vivo investigation. GC-MS analysis of ADAE was shown to include major components with high total phenolic contents and high DPPH scavenging activity. In diabetic rats, significant elevation in blood glucose level, lipid peroxidation, bilirubin, and lactate dehydrogenase activity as well as a change in lipid profile was observed, while insulin, body and liver weights, enzymatic and nonenzymatic antioxidants, liver function biomarkers, and protein content were significantly decreased. Furthermore, changes in the expression of the peroxisome proliferator-activated receptor (PPAR-γ), apoptotic, and inflammation-related genes were found. In addition, histological differences in rat liver tissue architecture were discovered, corroborating the biochemical modifications. However, consuming ADAE alone reduced lipid peroxidation and improved antioxidant status. Furthermore, diabetic rats given ADAE showed significant reductions in oxidative stress indicators and biochemical parameters, as well as improved tissue structure, when compared to the diabetic rats' group. Also, ADAE supplementation protects diabetic rats' hepatic tissue by upregulating PPAR-γ and downregulating apoptotic and inflammatory-related gene expression. In conclusion, A. deliciosa has beneficial protective effects so, it might be used as a complementary therapy in diabetes mellitus.


Mitochondrial complex I deficiency leads to the retardation of early embryonic development in Ndufs4 knockout mice.
The NDUFS4 gene encodes an 18-kD subunit of mitochondria complex I, and mutations in this gene lead to the development of a severe neurodegenerative disease called Leigh syndrome (LS) in humans. To investigate the disease phenotypes and molecular mechanisms of Leigh syndrome, the Ndufs4 knockout (KO) mouse has been widely used as a novel animal model. Because the homozygotes cannot survive beyond child-bearing age, whether Ndufs4 and mitochondrial complex I influence early embryonic development remains unknown. In our study, we attempted to investigate embryonic development in Ndufs4 KO mice, which can be regarded as a Leigh disease model and were created through the CRISPR (clustered regularly interspaced short palindromic repeat) and Cas9 (CRISPR associated)-mediated genome editing system. We first designed a single guide RNA (sgRNA) targeting exon 2 of Ndufs4 to delete the NDUFS4 protein in mouse embryos to mimic Leigh syndrome. Then, we described the phenotypes of our mouse model by forced swimming and the open-field test as well as by assessing other behavioral characteristics. Intracytoplasmic sperm injection (ICSI) was performed to obtain KO embryos to test the influence of NDUFS4 deletion on early embryonic development. In this study, we first generated Ndufs4 KO mice with physical and behavioral phenotypes similar to Leigh syndrome using the CRISPR/Cas9 system. The low developmental rate of KO embryos that were derived from knockout gametes indicated that the absence of NDUFS4 impaired the development of preimplantation embryos. In this paper, we first obtained Ndufs4 KO mice that could mimic Leigh syndrome using the CRISPR/Cas9 system. Then, we identified the role of NDUFS4 in early embryonic development, shedding light on its roles in the respiratory chain and fertility. Our model provides a useful tool with which to investigate the function of Ndufs4. Although the pathological mechanisms of the disease need to be discovered, it helps to understand the pathogenesis of NDUFS4 deficiency in mice and its effects on human diseases.


Binding of cytochrome c to liposomes as revealed by the quenching of fluorescence from pyrene-labeled phospholipids.
Resonance energy transfer from pyrene-fatty acid containing phospholipid derivatives to the heme of cytochrome c (cyt c) was used to observe the binding of this protein to liposomal membranes. Liposomes were formed of egg yolk phosphatidic acid (PA) and either egg yolk phosphatidylcholine or dipalmitoylphosphatidylcholine with 1 mol % of the fluorescent lipid. Binding of cyt c to liposomes was monitored by measuring the decrease either in the fluorescence intensity or in the lifetime of pyrene emission. The requirement for the presence of the acidic phospholipid in the membrane for the binding of cyt c could be reconfirmed. Below 5 mol % of phosphatidic acid in the membrane, no significant attachment of cyt c to liquid-crystalline bilayers was evident whereas upon increasing the concentration of PA further the association of cyt c progressively increased until a saturation was reached at about 30 mol % of phosphatidic acid. Addition of NaCl caused the fluorescence intensity and lifetimes to return to values observed in the absence of cyt c, thus revealing the dissociation of the protein from the membrane. The pyrene-labeled phosphatidic acid derivatives PPHPA and PPDPA were quenched more effectively than the corresponding phosphatidylcholines, apparently due to the direct involvement of the acidic head group in binding cyt c. When dipalmitoylphosphatidylcholine (DPPC) with 5 mol % of phosphatidic acid was used, no binding of cyt c to the liposomes above the phase transition temperature of the former lipid could be demonstrated whereas below the transition temperature (Tm) binding did take place.(ABSTRACT TRUNCATED AT 250 WORDS)


Distance recovery via swept frequency mixing for data-efficient FMCW LiDAR.
We propose a novel, to the best of our knowledge, distance recovery method via swept frequency mixing for frequency-modulated continuous wave (FMCW) light detection and ranging (LiDAR) to overcome the Nyquist limit and obtain high data efficiency. A one dimensional (1D) experiment was conducted to recover the optical fiber length; in addition, a 3D image was obtained by recovering the distances of several targets in free space. Compared to conventional methods based on fast Fourier transform (FFT), beat frequency up to 14 times the Nyquist limit for sampling frequency was successfully measured without aliasing. The proposed method dramatically increases the data efficiency in FMCW LiDAR by reducing the number of complex algorithms and experimental resources required.


Hepatitis B virus HBx protein activates Ras-GTP complex formation and establishes a Ras, Raf, MAP kinase signaling cascade.
Hepatitis B virus produces a small (154-amino acid) transcriptional transactivating protein, HBx, which is required for viral infection and has been implicated in virus-mediated liver oncogenesis. However, the molecular mechanism for HBx activity and its possible influence on cell proliferation have remained obscure. A number of studies suggest that HBx may stimulate transcription by indirectly activating transcription factors, possibly by influencing cell signaling pathways. We now present biochemical evidence that HBx activates Ras and rapidly induces a cytoplasmic signaling cascade linking Ras, Raf, and mitogen-activated protein kinase (MAP kinase), leading to transcriptional transactivation. HBx strongly elevates levels of GTP-bound Ras, activated and phosphorylated Raf, and tyrosine-phosphorylated and activated MAP kinase. Transactivation of transcription factor AP-1 by HBx is blocked by inhibition of Ras or Raf activities but not by inhibition of Ca(2+)- and diacylglycerol-dependent protein kinase C. HBx was also found to stimulate DNA synthesis in serum-starved cells. The hepatitis B virus HBx protein therefore stimulates Ras-GTP complex formation and promotes downstream signaling through Raf and MAP kinases, and may influence cell proliferation.


Components of "authority" as determinants of compliance.
This study investigated factors affecting compliance, to orders from a formal authority. The design created a two-level status hierarchy in which subjects occupied identical low-status positions and responded to demands from a simulated high-status leader. Four components of authority-normativity,coervice power, collective justification, and success-failure-were manipulated as independent variables. Another component, the endorsement accorded the leader, was included in the design as a measured variable. Results indicated that compliance increased significantly when coervice power was high (rather than low), when justification was collective (rather than partisan), and when demands were normative (rather than counternormative). Contary ti the theoretical expectation, endorsement did not affect compliance by low-status members. The findings show that the normative aspect of legitimacy serves as a compliance-gaining base even when stripped of enforcing sanctions and under-lying goals and that the distinction between normativity and endorsement is valid for research on social power.


Cancer Microenvironment: What Can We Learn from the Stem Cell Niche.
Epidermal stem cells (ESCs) are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle-also known as the bulge region. ECS are also found between basal cells of the interfollicular epidermis or mucous membranes. The non-epithelial elements such as mesenchymal stem cell-like elements of dermis or surrounding adipose tissue can also contribute to this niche formation. Cancer stem cells (CSCs) participate in formation of common epithelial malignant diseases such as basal cell or squamous cell carcinoma. In this review article, we focus on the role of cancer microenvironment with emphasis on the effect of cancer-associated fibroblasts (CAFs). This model reflects various biological aspects of interaction between cancer cell and CAFs with multiple parallels to interaction of normal epidermal stem cells and their niche. The complexity of intercellular interactions within tumor stroma is depicted on example of malignant melanoma, where keratinocytes also contribute the microenvironmental landscape during early phase of tumor progression. Interactions seen in normal bulge region can therefore be an important source of information for proper understanding to melanoma. The therapeutic consequences of targeting of microenvironment in anticancer therapy and for improved wound healing are included to article.


IN VIVO CARBON TETRACHLORIDE-INDUCED HEPATOPROTECTIVE AND IN VITRO CYTOTOXIC ACTIVITIES OF GARCINIA HOMBRONIANA (SEASHORE MANGOSTEEN).
Garcinia hombroniana, known as "manggis hutan" (jungle mangosteen) in Malaysia, is distributed in tropical Asia, Borneo, Thailand, Andaman, Nicobar Islands, Vietnam and India. In Malaysia, its ripened crimson sour fruit rind is used as a seasoning agent in curries and culinary dishes. Its roots and leaves decoction is used against skin infections and after child birth. This study aimed to evaluate in vivo hepatoprotective and in vitro cytotoxic activities of 20% methanolic ethyl acetate (MEA) G. hombroniana bark extract. In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl4)/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl4. Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1H, 13C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract. In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (p<0.05) potency. In cytotoxicity study, MEA extract was more toxic towards MCF-7 and DBTRG cell lines causing 78.7% and 64.3% cell death, respectively. MEA extract in 1H, 13C-NMR, and IR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents. From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra.


Inhibitors of epidermal cell DNA synthesis in surviving pig skin in vitro.
Keratome slices of domestic pig skin were used to study the DNA synthesis phase of epidermal cell DNA synthesis. Cyclic AMP and agents which elevate intracellular concentrations of cyclic AMP have no direct effect on the "S" phase of DNA synthesis. Theophylline, isobutylmethylxanthine, and adenosine inhibit DNA synthesis immediately by a mechanism which is reversible and is not dependent on cyclic AMP. This inhibition is not associated with an increase in intracellular thymidine phosphates. Hydroxyurea, however, inhibits DNA synthesis immediately and does produce an elevated pool of thymidine phosphates.


Isotope tracing enhancement of chemiluminescence assays for nitric oxide research.
Chemiluminescence assays are used widely for the detection of nitric oxide (NO)-derived species in biological fluids and tissues. Here, we demonstrate that these assays can be interfaced with mass-sensitive detectors for parallel determination of isotopic abundance. Results obtained with tri-iodide and ascorbic acid-based reductive assays indicate that mass spectrometric detection enables NO isotope-tracing experiments to be carried out to a limit of detectability of a few picomoles, a sensitivity similar to that of standard gas phase chemiluminescence methods. The advantage afforded by mass spectrometric detection is demonstrated using the murine macrophage cell line J774, which is shown here to reduce 15NO3- to 15NO2- under anoxic conditions. The particular combination of an analytical and cellular system described here may hold promise for future characterization of the enzymatic pathways contributing to mammalian nitrate reductase activity, without background interference from 14NO2- derived from other sources.


Calibration and field application of a Sierra Model 235 cascade impactor.
A Sierra Model 235 slotted impactor was used to measure the particle size distribution of ore dust in uranium concentrating mills. The impactor was calibrated at a flow rate of 0.21 m3/min, using solid monodisperse particles of methylene blue and an impaction surface of Whatman #41 filter paper soaked in mineral oil. The reduction from the impactor's design flow rate of 1.13 m3/min (40 cfm) to 0.21 m3/min (7.5 cfm), a necessary adjustment because of the anticipated large particles sizes of ore dust, increased the stage cut-off diameters by an average factor of 2.3. Evaluation of field test results revealed that the underestimation of mass median diameters, often caused by the rebound and reentrainment of solid particles from dry impaction surfaces, was virtually eliminated by using the oiled Whatman #41 impaction surface.


Non-canonical DNA transcription enzymes and the conservation of two-barrel RNA polymerases.
DNA transcription depends on multimeric RNA polymerases that are exceptionally conserved in all cellular organisms, with an active site region of >500 amino acids mainly harboured by their Rpb1 and Rpb2 subunits. Together with the distantly related eukaryotic RNA-dependent polymerases involved in gene silencing, they form a monophyletic family of ribonucleotide polymerases with a similarly organized active site region based on two double-Psi barrels. Recent viral and phage genome sequencing have added a surprising variety of putative nucleotide polymerases to this protein family. These proteins have highly divergent subunit composition and amino acid sequences, but always contain eight invariant amino acids forming a universally conserved catalytic site shared by all members of the two-barrel protein family. Moreover, the highly conserved 'funnel' and 'switch 2' components of the active site region are shared by all putative DNA-dependent RNA polymerases and may thus determine their capacity to transcribe double-stranded DNA templates.


Topical negative pressure versus closed surgical wound drainage: a difference in philosophy.
Vacuum force (suction) is commonly used in wound management strategies. Topical negative pressure wound therapy and closed surgical wound drainage both use vacuum force but each have different modus operandi.


A phyletically rare gene promotes the niche-specific fitness of an E. coli pathogen during bacteremia.
In bacteria, laterally acquired genes are often concentrated within chromosomal regions known as genomic islands. Using a recently developed zebrafish infection model, we set out to identify unique factors encoded within genomic islands that contribute to the fitness and virulence of a reference urosepsis isolate-extraintestinal pathogenic Escherichia coli strain CFT073. By screening a series of deletion mutants, we discovered a previously uncharacterized gene, neaT, that is conditionally required by the pathogen during systemic infections. In vitro assays indicate that neaT can limit bacterial interactions with host phagocytes and alter the aggregative properties of CFT073. The neaT gene is localized within an integrated P2-like bacteriophage in CFT073, but was rarely found within other proteobacterial genomes. Sequence-based analyses revealed that neaT homologues are present, but discordantly conserved, within a phyletically diverse set of bacterial species. In CFT073, neaT appears to be unameliorated, having an exceptionally A+T-rich composition along with a notably altered codon bias. These data suggest that neaT was recently brought into the proteobacterial pan-genome from an extra-phyletic source. Interestingly, even in G+C-poor genomes, as found within the Firmicutes lineage, neaT-like genes are often unameliorated. Sequence-level features of neaT homologues challenge the common supposition that the A+T-rich nature of many recently acquired genes reflects the nucleotide composition of their genomes of origin. In total, these findings highlight the complexity of the evolutionary forces that can affect the acquisition, utilization, and assimilation of rare genes that promote the niche-dependent fitness and virulence of a bacterial pathogen.


Induction of apoptosis by tomato using space mutation breeding in human colon cancer SW480 and HT-29 cells.
As far as we know, there have been no reports concerning the functional characteristics of tomatoes using space mutation breeding. The aim of this study was to evaluate the anti-colon cancer effect of tomatoes M1 and M2 using space mutation breeding. In the present study, obvious anti-cancer activity was shown with tomato juice of M1 and M2 and their parent CK treatment in colon cancer cell lines SW480 and HT-29 in cell growth inhibition. In addition, SW480 cells were more sensitive to M1 and M2 than HT-29 cells in cell apoptosis. Furthermore, M1 and M2 induced cell cycle arrest both in G0-G1 and G2/M phases. These data suggest that consumption of tomato using space mutation breeding may provide benefits to inhibit growth of colon cancer cells. Therefore, tomato production using space mutation breeding may be a good candidate for development as a dietary supplement in drug therapy for colon cancer.


Monitoring the fate and behavior of TiO2 nanoparticles: Simulated in a WWTP with industrial dye-stuff effluent according to OECD 303A.
The use of nanoparticles (NPs) in several consumer products has led to them finding their way into wastewater treatment plants (WWTPs). Some of these NPs have photocatalytic properties, thus providing a possible solution to textile industries to photodegrade dyes from their wastewater. Thus, the interaction of NPs with industrial dye effluents is inevitable. The Organization for Economic Co-operation and development (OECD) guideline for testing of chemical 303A was employed to study the fate and behaviour of TiO2 NPs in industrial dye-stuff effluent. This was due to the unavailability of NPs' fate and behaviour test protocols. The effect of TiO2 NPs on the treatment process was ascertained by measuring chemical oxygen demand (COD) and 5-day biological oxygen demand (BOD5). Inductively coupled plasma optical emission spectroscopy (ICP-OES) was used to study the fate and behavior of TiO2 NPs. Acclimatization of bacteria to target pollutants was a crucial factor for the treatment efficiency of activated sludge in a simulated wastewater treatment plant (SWTP). The acclimatization of the activated sludge to the synthetic industrial dye-stuff effluent was successfully achieved. Effect of TiO2 NPs on the treatment process efficiency was then investigated. Addition of TiO2 NPs had no effect on the treatment process as chemical oxygen demand (COD) removal remained >80%. Measured total plate count (TPC) affirmed that the addition of TiO2 NPs had no effect on the treatment process. The removal of total nitrogen (TN) was not efficient as the treatment system was required to have an oxic and anoxic stage for efficient TN removal. Results from X-ray powder diffraction (XRD) confirmed that the anatase phase of the added TiO2 NPs remained unchanged even after exposure to the treatment plant. Removal of the NPs from the influent was facilitated by biosorption of the NPs on the activated sludge. Nanoparticles received by wastewater treatment plants will therefore reach the environment through sludge waste dumped in landfill. About 90% of TiO2 was retained in the activated sludge, and 10-11% escaped with the treated effluents. Scanning electron microscope (SEM) mapping micrographs together with an energy dispersive X-ray spectroscopy (EDS) confirmed the presence of Ti in the sludge.


Cloning and heterologous expression of glycosidase genes from Saccharomyces cerevisiae.
Genomic clones were isolated that code for three glycosidases proposed to be involved in the catabolism of cell wall components in Saccharomyces cerevisiae. alpha-Mannosidase (AMS1), exoglucanase (BGL1), and endochitinase (CTS1) genes were isolated with the aid of filter assays based on the hydrolysis of 4-methylumbelliferyl glycosides, which permitted the in situ monitoring of these glycosidase activities in yeast colonies. Uracil prototrophs resulting from transformation with a multicopy YEp24 yeast genomic library were screened, leading to the identification of transformants possessing high levels of glycosidase activity. Restriction maps of plasmids from multiple isolates were used to localize glycosidase-overproduction genes, which were subcloned into a Schizosaccharomyces pombe/S. cerevisiae shuttle vector. Transformation of Sch. pombe with BGL1 and CTS1 subclones resulted in the appearance of these activities in this organism, and an AMS1 plasmid caused a 2-fold increase in endogenous alpha-mannosidase levels. Insertion of the marker gene LEU2 into putative AMS1 sequences disrupted plasmid-encoded alpha-mannosidase overproduction. S. cerevisiae strains that incorporated a restriction fragment containing ams1::LEU2 into their chromosomal DNA by homologous recombination expressed no detectable alpha-mannosidase activity in either the haploid or homozygous recessive diploid states, whereas heterozygous and wild-type cells exhibited levels proportional to AMS1 gene dosage. No readily apparent phenotype was associated with the alpha-mannosidase deficiency; however, labeling experiments utilizing [2-3H]mannose suggest that alpha-mannosidase may function in mannan turnover.


Performance characteristics of a real-time RT-PCR assay for quantification of hepatitis C virus RNA in patients with genotype 1 and 2 infections.
Polymerase chain reaction (PCR) methods play an essential role in providing data relating to diagnosis, monitoring and treatment of hepatitis C virus (HCV) infection. The real-time reverse transcription PCR (RT-PCR) assay is an established and promising tool in terms of quantifying HCV RNA for clinical application. This study aimed to evaluate the performance characteristics of a real-time RT-PCR-based test in a clinical setting. Validation and reproducibility tests were performed using a standard panel. Sera from 197 chronic HCV patients were analyzed by the real-time RT-PCR assay and the results were compared with the Versant bDNA3.0 assay (bDNA3.0). The real-time RT-PCR assay showed an acceptable linear response (r2=0.989-0.995) in the serial dilutions regarding genotypes 1b, 2a, 2b and 1b+2a. HCV viral loads were quantifiable in all 197 patients (100%) by the real-time RT-PCR assay and in 194 (98.5%) by the bDNA3.0. HCV RNA quantification values measured by the real-time RT-PCR and bDNA3.0 assays were positively correlated (Pearson's correlation coefficient r=0.734, p<0.001). The real-time RT-PCR assay values were on average 0.13 logs higher than the bDNA3.0 results. The correlation coefficients with genotypes 1b, 2a, 2b and mixed were 0.737, 0.711, 0.791 and 0.766, respectively (p<0.01). The real-time RT-PCR assay showed comparable performance with bDNA3.0 regarding quantification of HCV viral loads with genotype 1 and 2 HCV infections.


Comparative study of crystallization process in metallic melts using ab initio molecular dynamics simulations.
The crystallization process of liquid metals is studied using ab initio molecular dynamics simulations. The evolution of short-range order during quenching in Pb and Zn liquids is compared with body-centered cubic (bcc) Nb and V, and hexagonal closed-packed (hcp) Mg. We found that the fraction and type of the short-range order depends on the system under consideration, in which the icosahedral symmetry seems to dominate in the body-centered cubic metals. Although the local atomic structures in stable liquids are similar, liquid hcp-like Zn, bcc-like Nb and V can be deeply supercooled far below its melting point before crystallization while the supercooled temperature range in liquid Pb is limited. Further investigations into the nucleation process reveal the process of polymorph selection. In the body-centered cubic systems, the polymorph selection occurs in the supercooled state before the nucleation is initiated, while in the closed-packed systems it starts at the time of onset of crystallization. Atoms with bcc-like lattices in all studied supercooled liquids are always detected before the polymorph selection. It is also found that the bond orientational ordering is strongly correlated with the crystallization process in supercooled Zn and Pb liquids.


One-year rehospitalisation after percutaneous coronary intervention: a retrospective analysis.
The aim of the study was to evaluate the incidence and causes of rehospitalisation within one year after percutaneous coronary intervention (PCI) in a country where the National Health Service provides universal tax-supported healthcare, guaranteeing residents free hospital access. Between January 2010 and September 2014, 17,111 patients were treated with PCI in two University Hospitals in Western Denmark. Patients who were readmitted within one year after PCI were identified. The overall one-year readmission rate was 50.4%. The cause was angina/myocardial infarction (MI) in 4,282 patients (49.7%), and other reasons in 4,334 (50.3%). Predictors of angina/MI-related readmissions were female gender (odds ratio [OR] 1.15, 95% confidence interval [CI]: 1.07-1.25), diabetes (OR 1.14, 95% CI: 1.04-1.26), age (per 10-year increase) (OR 0.86, 95% CI: 0.83-0.88), and indication for index PCI (stable angina pectoris as reference): ST-segment elevation myocardial infarction (OR 1.34, 95% CI: 1.23-1.47) and non-ST-segment elevation myocardial infarction (OR 1.18, 95% CI: 1.08-1.29). Predictors for other readmissions were female gender (OR 1.09, 95% CI: 1.01-1.18), diabetes (OR 1.29, 95% CI: 1.18-1.42), age (OR 1.30, 95% CI: 1.26-1.34) and Charlson comorbidity index ≥3 (OR 3.03, 95% CI: 2.71-3.27). In an unselected patient cohort treated with PCI, half of the patients were rehospitalised within one year, highlighting the impact of comorbidity in patients with ischaemic heart disease.


The Optical Signature of Charges in Conjugated Polymers.
Electrical charge flowing through organic semiconductors drives many of today's mobile phone displays and television screens, suggesting an internally consistent model of charge-carrier properties in these materials to have manifested. In conjugated polymers, charges give rise to additional absorption of light at wavelengths longer than those absorbed by the electrically neutral species. These characteristic absorption bands are universally being related to the emergence of localized energy levels shifted into the forbidden gap of organic semiconductors due to local relaxation of the molecular geometry. However, the traditional view on these energy levels and their occupation is incompatible with expected changes in electron removal and addition energies upon charging molecules. Here, I demonstrate that local Coulomb repulsion, as captured by nonempirically optimized electronic-structure calculations, restores compatibility and suggests a different origin of the charge-induced optical transitions. These results challenge a widely accepted and long-established picture, but an improved understanding of charge carriers in molecular materials promises a more targeted development of organic and hybrid organic/inorganic (opto-)electronic devices.


[Early and late results after coating intracranial aneurysms with biobond (author's transl)].
Fifteen patients with intracranial aneurysms have been treated by coating the aneurysms with Biobond. Three patients died in the postoperative period. Only one patient had recurrent haemorrhage one year after operation. In this case the sac had not been wrapped completely at operation. Histological examination of this aneurysm revealed macrophage reaction and signs of slow disappearance of the plastic. Ten patients, who were followed up for a period of 3 to 8 years after operation, had no recurrent haemorrhage and were in good clinical condition, 8 of them doing full-time work. No complications caused by the material have been encountered. In 5 patients carotid angiography was performed after operation. In 2 cases the size of the aneurysm was diminished and in 3 cases was unchanged. There were no signs of thrombosis or narrowing of the adjacent arteries. We believe that Biobond is suitable for coating intracranial aneurysms that cannot be treated by clipping or ligature. As Biobond in vivo seems partially to disappear after long periods, it should be applied in thick layers.


Microcystins Presence in Mussels (M. galloprovincialis) and Water of Two Productive Mediterranean's Lagoons (Sardinia, Italy).
Microcystins (MCs) are hepatotoxins harmful for animal and human health. The most toxic type between them is MC-LR whose presence has been investigated in different reservoirs all around the world. In this work microcystins were monitored in spring and summer in water and mussels (Mytilus galloprovincialis) of two Sardinia lagoons: Cabras and Calich lagoons. A Solid Phase Extraction method was developed to clean and concentrate samples before the Enzyme Linked Immunosorbent Assay (ELISA) and the following Mass Spectrometry detection. MCs presence was detected using the screening ELISA test in both lagoons. MCs peak was revealed in July for water and mussels belonging to Cabras lagoon (0.75 ± 0.07 ng/L in water and 0.12 ± 0.04 ng/g ww in mussels). In water of Calich lagoon there was a constant trend in the concentration of MCs during the considered months, while there was a MCs peak in July (0.6 ± 0.5 ng/g ww) in mussels. The following LC-MS/MS analysis did not reveal MC-LR presence in all analyzed samples. These results can be useful to enrich knowledge on public health and consumer's safeguard.


miR-144-3p Induces Cell Cycle Arrest and Apoptosis in Pancreatic Cancer Cells by Targeting Proline-Rich Protein 11 Expression via the Mitogen-Activated Protein Kinase Signaling Pathway.
microRNAs (miRNAs) have been proved to be involved in many events of tumor development and progression, including cell proliferation, cell apoptosis, and cell cycle arrest. However, the potential role of miR-144-3p in pancreatic cancer (PC) remains elusive. In this study, we demonstrated that miR-144-3p was decreased in PC tissues and PANC-1 cells, whereas proline-rich protein 11 (PRR11) was remarkably increased. miR-144-3p mimics were discovered to inhibit cell proliferation by arresting cells at the S-phase of the cell cycle, and inducing cell apoptosis in PANC-1 cells. The effects of miR-144-3p on cell proliferation and cell apoptosis were reversed after treatment with the miR-144-3p inhibitor. Furthermore, a luciferase activity assay indicated that miR-144-3p directly targeted PRR11 3'-UTR. Moreover, transfection with miR-144-3p mimics inhibited the expression of PRR11. miR-144-3p mimics also upregulated the expression of p-JNK and p-p38, whereas they downregulated the expression of p-ERK. The effects of miR-144-3p on mitogen-activated protein kinase pathway proteins were reversed by the miR-144-3p inhibitor. PRR11 overexpression attenuated the effect of miR-144-3p mimics on cell apoptosis and cell cycle arrest. The expression of caspase-3 was decreased by enhanced PRR11. In summary, our findings indicated that miR-144-3p induced cell cycle arrest and apoptosis in PC by targeting PRR11. Therefore, the targeting of miR-144-3p could serve as a potential therapeutic strategy for the treatment of PC.


Myeloid cells in Alzheimer's disease: culprits, victims or innocent bystanders?
Several recent genome-wide association studies (GWAS) in patients with neurodegenerative disorders have shed new light on the brain immune system, suggesting that it plays a pivotal role in disease pathogenesis. Mononuclear phagocytes are blatantly involved in Alzheimer's disease (AD) of the central nervous system (CNS), but the specific functions of resident microglia, perivascular or meningeal macrophages, and circulating myeloid cells have not yet been fully resolved. Next-generation sequencing, high-throughput immune profiling technologies, and novel genetic tools have recently revolutionized the characterization of innate immune responses during AD. These studies advocate selective and non-redundant roles for myeloid subsets, which could be a target for novel disease-modifying therapies in AD.


Two cases of low back pain of unknown etiology diagnosed as multiple myeloma.
We report two cases of patients complaining of lumbar back pain of unknown etiology which were finally diagnosed as multiple myeloma. The first case was a woman in her 80s with a chief complaint of lumbar back pain. The second case was a male in his 70s. He also consulted our institution because his pain did not subside despite receiving increased doses of oral medication and nerve blocks from his previous doctor. Both patients presented with compression fractures on plain radiography, and additionally with cytopenia, hyperproteinemia, and hypoalbuminemia in blood tests. Further tests were conducted due to suspected multiple myeloma, revealing a punched-out legion in the skull and elevated levels of β2 microglobulin and Immunoglobulin G. Subsequently, both patients were transferred to the hematology department. In these two cases, we had predicted the presence of multiple myeloma from the results of initial testing and subsequently successfully provided definitive diagnoses following additional examinations.


Prebrief Time for Immersive Virtual and Augmented Reality Simulation: An Integrative Review.
Virtual reality and augmented technology are rapidly advancing and hold the potential to transform nursing education by offering a convenient, efficient, learner-centered way to educate students. A comprehensive and time-oriented prebrief is essential to the process. This review analyzes the status of scientific exploration regarding the prebrief and time allotments for virtual and augmented reality simulation. Whittemore and Knafl's 5-stage method guided this integrative review. The authors searched 6 databases and selected 7 articles based on inclusion criteria. The findings from this review demonstrated objectives, a safe learning environment, orientation, preparation materials, and time in the prebrief; yet, inconsistencies persist in the virtual and augmented reality prebrief. Defining a comprehensive and consistent prebrief is essential for high-quality simulation. A more standardized process, including time allotments, must be established for virtual and augmented reality.


Functional and morphological evolution of remnant pancreas after resection for pancreatic adenocarcinoma.
Functional and morphological evolution of remnant pancreas after resection for pancreatic adenocarcinoma is investigated.The medical records of 45 patients who had undergone radical resection for pancreatic adenocarcinoma from March 2010 to September 2013 were reviewed retrospectively. There were 34 patients in the pancreaticoduodenectomy (PD) group and 10 patients in the distal pancreatectomy (DP) group. One patient received total pancreatectomy. The endocrine function was measured using the glucose tolerance index (GTI), which was derived by dividing daily maximum serum glucose fluctuation by daily minimum glucose. Remnant pancreas volume (RPV) was estimated by considering pancreas body and tail as a column, and head as an ellipsoid, respectively. The pancreatic atrophic index (PAI) was defined as the ratio of pancreatic duct width to total pancreas width. Representative indices of each patient were compared before and after resection up to 2 years postoperatively.The area under receiver operating characteristic curve of GTI for diagnosing DM was 0.823 (95% confidence interval, 0.699-0.948, P < .001). Overall, GTI increased on postoperative day 1 (POD#1, mean ± standard deviation, 1.79 ± 1.40 vs preoperative, 1.02 ± 1.41; P = .001), and then decreased by day 7 (0.89 ± 1.16 vs POD#1, P < .001). In the PD group, the GTI on POD#14 became lower than preoperative (0.51 ± 0.38 vs 0.96 ± 1.37; P = .03). PAI in the PD group was significantly lower at 1 month postoperatively (0.22 ± 0.12 vs preoperative, 0.38 ± 0.18; P < .001). In the PD group, RPV was significantly lower at 1 month postoperatively (25.3 ± 18.3 cm vs preoperative, 32.4 ± 20.1 cm; P = .02), due to the resolution of pancreatic duct dilatation. RPV of the DP group showed no significant change. GTI was negatively related to RPV preoperatively (r = -0.317, P = .04), but this correlation disappeared postoperatively (r = -0.044, P = .62).Pancreatic endocrine functional deterioration in pancreatic adenocarcinoma patients may in part be due to pancreatic duct obstruction and dilatation caused by the tumor. After resection, this proportion of endocrine insufficiency is corrected.


A well-defined monomeric aluminum complex as an efficient and general catalyst in the Meerwein-Ponndorf-Verley reduction.
The metal-catalyzed Meerwein-Ponndorf-Verley (MPV) reduction allows for the mild and sustainable reduction of aldehydes and ketones but has not found widespread application in organic synthesis due to the high catalyst loading often required to obtain satisfactory yields of the reduced product. We report here on the synthesis and structure of a sterically extremely overloaded siloxide-supported aluminum isopropoxide capable of catalytically reducing a wide range of aldehydes and ketones (52 examples) in excellent yields under mild conditions and with low catalyst loadings. The unseen activity of the developed catalyst system in MPV reductions is due to its unique monomeric nature and the neutral donor isopropanol weakly coordinating to the aluminum center. The present work implies that monomeric aluminum alkoxide catalysts may be attractive alternatives to transition-metal-based systems for the selective reduction of aldehydes and ketones to primary and secondary alcohols.


Frequency and outcomes of obinutuzumab-induced thrombocytopenia.
Obinutuzumab is a third-generation anti-CD20 monoclonal antibody widely used in the treatment of B-lymphoproliferative disorders but infrequently associated with severe thrombocytopenia, which can be life-threatening. The pathophysiology is unclear, but platelet clearance can be extremely rapid (usually within 24 h). In a retrospective case series, we have identified four cases among 149 recipients of obinutuzumab-containing chemotherapy regimens between 2015 and 2022 treated for haematological malignancies in Canberra, Australia (frequency 2.7%). We illustrate four cases of obinutuzumab-induced thrombocytopenia with a review of the literature. Research is required to identify the pathophysiology and improve early recognition and management of the condition in the context of multiagent chemotherapy.


The role of Candida albicans in root caries biofilms: an RNA-seq analysis.
Objective This study sought to analyze the gene expression of Candida albicans in sound root surface and root caries lesions, exploring its role in root caries pathogenesis. Methodology The differential gene expression of C. albicans and the specific genes related to cariogenic traits were studied in association with samples of biofilm collected from exposed sound root surface (SRS, n=10) and from biofilm and carious dentin of active root carious lesions (RC, n=9). The total microbial RNA was extracted, and the cDNA libraries were prepared and sequenced on the Illumina Hi-Seq2500. Unique reads were mapped to 163 oral microbial reference genomes including two chromosomes of C. albicans SC5314 (14,217 genes). The putative presence of C. albicans was estimated (sum of reads/total number of genes≥1) in each sample. Count data were normalized (using the DESeq method package) to analyze differential gene expression (using the DESeq2R package) applying the Benjamini-Hochberg correction (FDR<0.05). Results Two genes (CaO19.610, FDR=0.009; CaO19.2506, FDR=0.018) were up-regulated on SRS, and their functions are related to biofilm formation. Seven genes ( UTP20 , FDR=0.018; ITR1 , FDR=0.036; DHN6 , FDR=0.046; CaO19.7197 , FDR=0.046; CaO19.7838 , FDR=0.046; STT4 , FDR=0.046; GUT1 , FDR=0.046) were up-regulated on RC and their functions are related to metabolic activity, sugar transport, stress tolerance, invasion and pH regulation. The use of alternative carbon sources, including lactate, and the ability to form hypha may be a unique trait of C. albicans influencing biofilm virulence. Conclusions C. albicans is metabolically active in SRS and RC biofilm, with different roles in health and disease.


Lack of expression of the EP2 but not EP3 receptor for prostaglandin E2 results in suppression of skin tumor development.
The EP2 receptor for prostaglandin E2 (PGE2) is a membrane receptor that mediates at least part of the action of PGE2. It has been shown that EP2 plays a critical role in tumorigenesis in mouse mammary gland and colon. However, the possibility that the EP2 receptor is involved in the development of skin tumors was unknown. The purpose of this study was to investigate the role of the EP2 receptor in mouse skin carcinogenesis. Unlike EP3 knockout mice, the EP2 knockout mice produced significantly fewer tumors and reduced tumor incidence compared with wild type (WT) mice in a 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) two-stage carcinogenesis protocol. EP2 knockout mice had significantly reduced cellular proliferation of mouse skin keratinocytes in vivo and in vitro compared with that in WT mice. In addition, the epidermis of EP2 knockout mice 48 hours after topical TPA treatment was significantly thinner compared with that of WT mice. The inflammatory response to TPA was reduced in EP2 knockout mice, based on a reduced number of macrophages in the dermis and a reduced level of interleukin-1alpha mRNA expression, compared with WT mice. EP2 knockout mice also had significantly reduced epidermal cyclic AMP levels after PGE2 treatment compared with WT mice. Tumors from WT mice produced more blood vessels and fewer apoptotic cells than those of EP2 knockout mice as determined by immunohistochemical staining. Our data suggest that the EP2 receptor plays a significant role in the protumorigenic action of PGE2 in skin tumor development.


Morphology and molecular phylogeny of two colepid species from China, Coleps amphacanthus Ehrenberg, 1833 and Levicoleps biwae jejuensis Chen et al., 2016 (Ciliophora, Prostomatida).
Two colepid ciliates, Coleps amphacanthus Ehrenberg, 1833 and Levicoleps biwae jejuensis Chen et al., 2016, were first recorded in China. Their living morphology, infraciliature and small subunit (SSU) rRNA gene sequences were determined using standard methods. The improved diagnosis of Coleps amphacanthus is as follows:cell size about 100×50 μm in vivo, barrel-shaped; 22-28 ciliary rows each composed of about 14-21 monokinetids and two perioral dikinetids; 5-10 caudal cilia; and one terminal contractile vacuole. Levicoleps biwae jejuensis was also investigated, with an improved diagnosis given based on previous and present work. The phylogenetic analyses based on SSU rRNA gene sequences revealed that all Coleps species were grouped together, except for Coleps amphacanthus, which was grouped into a clade of the genus Levicoleps.


Menthol-Based (Deep) Eutectic Solvents: A Review on Properties and Application in Extraction.
In the last 10 years the interest in deep eutectic solvents (DESs) as a new class of green solvents has considerably increased. The emergence of numerous of hydrophobic DESs has stimulated intensive research into their application in extraction technologies, including sample preparation. As the properties of such systems are highly dependent on the properties of their components (hydrogen bond donors and acceptors) and can be finely tuned, DESs can be successfully used for the extraction of both metal ions and organic substances, including biomolecules. Despite the rapidly increasing number of publications on the use of DESs as an extraction medium, including review articles, information on the extraction properties of DESs in terms of their chemical composition has not yet been summarized. This review covers available literature data on the physicochemical properties of menthol-based eutectic solvents and the results of their practical application as an extraction medium. Also, the appropriateness of using the term "DES" for all mixtures with melting points lower than the melting points of their components is discussed.


Perceived Impact of Digital Health Maturity on Patient Experience, Population Health, Health Care Costs, and Provider Experience: Mixed Methods Case Study.
Health care organizations understand the importance of new technology implementations; however, the best strategy for implementing successful digital transformations is often unclear. Digital health maturity assessments allow providers to understand the progress made toward technology-enhanced health service delivery. Existing models have been criticized for their lack of depth and breadth because of their technology focus and neglect of meaningful outcomes. We aimed to examine the perceived impacts of digital health reported by health care staff employed in health care organizations across a spectrum of digital health maturity. A mixed methods case study was conducted. The digital health maturity of public health care systems (n=16) in Queensland, Australia, was examined using the quantitative Digital Health Indicator (DHI) self-assessment survey. The lower and upper quartiles of DHI scores were calculated and used to stratify sites into 3 groups. Using qualitative methods, health care staff (n=154) participated in interviews and focus groups. Transcripts were analyzed assisted by automated text-mining software. Impacts were grouped according to the digital maturity of the health care worker's facility and mapped to the quadruple aims of health care: improved patient experience, improved population health, reduced health care cost, and enhanced provider experience. DHI scores ranged between 78 and 193 for the 16 health care systems. Health care systems in the high-maturity category (n=4, 25%) had a DHI score of ≥166.75 (the upper quartile); low-maturity sites (n=4, 25%) had a DHI score of ≤116.75 (the lower quartile); and intermediate-maturity sites (n=8, 50%) had a DHI score ranging from 116.75 to 166.75 (IQR). Overall, 18 perceived impacts were identified. Generally, a greater number of positive impacts were reported in health care systems of higher digital health maturity. For patient experiences, higher maturity was associated with maintaining a patient health record and tracking patient experience data, while telehealth enabled access and flexibility across all digital health maturity categories. For population health, patient journey tracking and clinical risk mitigation were reported as positive impacts at higher-maturity sites, and telehealth enabled health care access and efficiencies across all maturity categories. Limited interoperability and organizational factors (eg, strategy, policy, and vision) were universally negative impacts affecting health service delivery. For health care costs, the resource burden of ongoing investments in digital health and a sustainable skilled workforce was reported. For provider experiences, the negative impacts of poor usability and change fatigue were universal, while network and infrastructure issues were negative impacts at low-maturity sites. This is one of the first studies to show differences in the perceived impacts of digital maturity of health care systems at scale. Higher digital health maturity was associated with more positive reported impacts, most notably in achieving outcomes for the population health aim.


[Regulatory effect of Smad7 gene on MAPK signal pathway in malignant transformation of immortalized human bronchial epithelial BEP2D cells].
Smad7 is an inhibitor of transforming growth factor-beta (TGF-beta) signal pathway. TGF-beta could induce the expression of several genes through activating SMAD and ras/MEK/ERK pathways. This study was to determine whether Smad7 is involved in regulating mitogen-activated protein kinase (MAPK) signal pathway with TGF-beta in malignant transformation of human bronchial epithelial BEP2D cells. Immortalized BEP2D cells and malignant BERP35T2 cells were co-transfected with full-length Smad7 cDNA constructed pCISmad7.neo or Smad7 siRNA, transactivator vector pTet-Elk or pTet-Jun, and reporter vector pTRE-Luc, and stimulated with TGF-beta. The regulatory effect of Smad7 on MAPK signal pathway was investigated by standard luciferase assay. In BEP2D cells, when treated with TGF-beta1, phosphorylated activities of Elk and Jun were up-regulated (P(Elk)=0.033, P(Jun)=0.016); after co-transfection of Elk or Jun with pCISmad7.neo, phosphorylated activity of Elk was increased, and that of Jun was decreased (P(Elk)=0.017, P(Jun)=0.028); after co-transfection of Elk or Jun with Smad7 siRNA, phosphorylated activity of Elk was decreased, and that of Jun was increased (P(Elk)=0.018, P(Jun)=0.005). In BERP35T2 cells, when treated with TGF-beta1, phosphorylated activity of Elk was up-regulated (P=0.006); after co-transfection of Elk and Smad7 siRNA, phosphorylated activity of Elk was decreased (P=0.000); no activity of Jun was detected in BERP35T2 cells. In the process of malignant transformation of BEP2D cells, the intervention of Smad7 in MAPK signal pathway leads to the activity imbalance between extracellular signal-related protein kinase (ERK) and c-Jun NH2-terminal kinase (JNK), which in turn promotes cell proliferation. All these could contribute to further malignant transformation of these cells.


A detailed clinicopathologic study of ALK-translocated papillary thyroid carcinoma.
Pathogenic ALK translocations have been reported in papillary thyroid carcinoma (PTC). We developed and validated a screening algorithm based on immunohistochemistry (IHC), followed by fluorescence in situ hybridization (FISH) in IHC-positive cases to identify ALK-rearranged PTC. IHC and FISH were performed in a cohort of 259 thyroid carcinomas enriched for aggressive variants. IHC was positive in 8 cases, 6 confirmed translocated by FISH (specificity 75%). All 251 IHC-negative cases were FISH negative (sensitivity 100%). Having validated this approach, we performed screening IHC, followed by FISH in IHC-positive cases in an expanded cohort. ALK translocations were identified in 11 of 498 (2.2%) of all consecutive unselected PTCs and 3 of 23 (13%) patients with diffuse sclerosing variant PTCs. No ALK translocations were identified in 36 PTCs with distant metastases, 28 poorly differentiated (insular) carcinomas, and 20 anaplastic carcinomas. All 14 patients with ALK translocations were female (P=0.0425), and translocations occurred at a younger age (mean 38 vs. 48 y, P=0.0289 in unselected patients). ALK translocation was an early clonal event present in all neoplastic cells and mutually exclusive with BRAF mutation. ALK translocation was not associated with aggressive clinicopathologic features (size, stage, metastasis, vascular invasion, extrathyroidal extension, multifocality, risk for recurrence, radioiodine resistance). We conclude that 2.2% of PTCs are ALK-translocated and can be identified by screening IHC followed by FISH. ALK translocations may be more common in young females and diffuse sclerosing variant PTC but do not connote more aggressive disease.


Blood flow patterns in focal liver lesions at microbubble-enhanced US.
Noninvasive diagnosis of liver lesions is usually performed with contrast material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging and is based on enhancement features of the arterial and portal venous phases. Ultrasonography (US) is often limited in characterizing liver lesions because color and spectral Doppler US provide limited vascular information in large patients and in small or deep lesions. However, microbubble contrast agents, together with specialized US techniques, now allow diagnosis of liver lesions based on morphologic evaluation of lesion vascularity and visualization of specific enhancement features. Microbubble contrast agents are purely intravascular, easy to administer, and well tolerated and allow sensitive real-time evaluation of blood flow in hepatic lesions. During the portal venous phase, benign lesions (eg, hemangioma, focal nodular hyperplasia) typically enhance more than the liver, whereas malignant lesions (eg, hepatocellular carcinoma, metastases) enhance less. Microbubble-enhanced US allows characterization of very small lesions that may not be accurately characterized with CT or MR imaging. Findings from initial studies suggest that microbubble-enhanced US of the liver provides enhancement information comparable to that provided by contrast-enhanced CT and MR imaging, along with real-time morphologic evaluation of lesion vascularity.


A decision support system for phosphorus management at a watershed scale.
Phosphorus (P) is one of the main nutrients controlling algal production in aquatic systems. Proper management of P in agricultural production systems can greatly enhance our ability to combat pollution of aquatic environments. To address this issue, a decision support system (DSS) consisting of the Maryland Phosphorus Index (PI), diagnosis expert system (ES), prescription ES, and a nonpoint-source pollution model, Ground Water Loading Effects of Agricultural Management Systems (GLEAMS), was developed and applied to an agricultural watershed in southern Sweden. This system can identify critical source areas (CSAs) regarding phosphorus losses within the watershed, make a diagnosis of probable causes, prescribe the most appropriate best management practices (BMPs), and test the environmental effects of the applied BMPs. The PI calculations identified small parts of the watershed as CSAs. Only 10.4% of the total watershed area in 1995 and 5.2% of the total watershed area in 1996 were classed as "high potential P movement." Four probable causes (high P level in soil, excessive P fertilization, stream proximity, and subsurface drainage) and three BMPs (riparian buffer strips, reduced P fertilizer application, and P fertilizer incorporation) were identified by a diagnosis and prescription expert system. The GLEAMS simulations conducted for one selected CSA field for a 24-yr period showed that the recommended BMP reduced runoff P losses by 55% and sediment P losses by 71%, if applied from the first year. Results showed that using DSS may enable us to select a proper BMP implementation strategy and to realize the beneficial effect of BMPs on a long-term basis.


Toward alcohol synthesis from CO hydrogenation on Cu(111)-supported MoS2 - predictions from DFT+KMC.
In the quest for cheap and efficient catalysts for alcohol synthesis from syngas, a material of interest is single-layer MoS2 owing to its low cost, abundancy, and flexible structure. Because of the inertness of its basal plane, however, it is essential to find ways that make it catalytically active. Herein, by means of density functional theory based calculations of reaction pathways and activation energy barriers and accompanying kinetic Monte Carlo simulations, we show that while S vacancy row structures activate the MoS2 basal plane, further enhancement of chemical activity and selectivity can be achieved by interfacing the MoS2 layer with a metallic support. When defect-laden MoS2 is grown on Cu(111), there is not only an increase in the active region (surface area of active sites) but also charge transfer from Cu to MoS2, resulting in a shift of the Fermi level such that the frontier states (d orbitals of the exposed Mo atoms) appear close to it, making the MoS2/Cu(111) system ready for catalytic activity. Our calculated thermodynamics of reaction pathways lead to the conclusion that the Cu(111) substrate promotes both methanol and ethanol as the products, while kinetic Monte Carlo simulations suggest a high selectivity toward the formation of ethanol.


Quantum melting of the charge-density-wave state in 1T-TiSe2.
We report a Raman scattering study of low-temperature, pressure-induced melting of the charge-density-wave (CDW) phase of 1T-TiSe2. Our measurements reveal that the collapse of the CDW state occurs in three stages: (i) For P<5 kbar, the pressure dependence of the CDW amplitude mode energies and intensities are indicative of a "crystalline" CDW regime; (ii) for 5<P<25 kbar, there is a decrease in the CDW amplitude mode energies and intensities with increasing pressure that suggests a regime in which the CDW softens, and exhibits enhanced fluctuations; and (iii) for P>25 kbar, the absence of amplitude modes reveals a metallic regime in which the CDW has melted.


Preparation of collagen/polyurethane/knitted silk as a composite scaffold for tendon tissue engineering.
The main objective of this study was to prepare a hybrid three-dimensional scaffold that mimics natural tendon tissues. It has been found that a knitted silk shows good mechanical strength; however, cell growth on the bare silk is not desirable. Hence, electrospun collagen/polyurethane combination was used to cover knitted silk. A series of collagen and polyurethane solutions (4%-7% w/v) in aqueous acetic acid were prepared and electrospun. According to obtained scanning electron microscopy images from pure collagen and polyurethane nanofibers, concentration was set constant at 5% (w/v) for blend solutions of collagen/polyurethane. Afterward, blend solutions with the weight ratios of 75/25, 50/50 and 25/75 were electrospun. Scanning electron microscopy images demonstrated the smooth and uniform morphology for the optimized nanofibers. The least fibers diameter among three weight ratios was found for collagen/polyurethane (25/75) which was 100.86 ± 40 nm and therefore was selected to be electrospun on the knitted silk. Attenuated total reflectance-Fourier transform infrared spectra confirmed the chemical composition of obtained electrospun nanofibers on the knitted silk. Tensile test of the specimens including blend nanofiber, knitted silk and commercial tendon substitute examined and indicated that collagen/polyurethane-coated knitted silk has appropriate mechanical properties as a scaffold for tendon tissue engineering. Then, Alamar Blue assay of the L929 fibroblast cell line seeded on the prepared scaffolds demonstrated appropriate viability of the cells with a significant proliferation on the scaffold containing more collagen content. The results illustrate that the designed structure would be promising for being used as a temporary substitute for tendon repair.


Cross-polarization photography of the nerve fiber layer.
Cross-polarized photography was used to enhance the visibility of the arcuate bundles of the retinal nerve fiber layer ( NFL ). A fundus camera (Zeiss) was modified to accept a linear polarizing filter in front of the flash and another polarizing filter in front of the film plane. The azimuths of the two filters were kept at right angles to one another. Cross-polarized photographs were taken of the NFL of seven normal eyes and 18 eyes with ocular hypertension. The polarizers were rotated together to obtain four different orientations, equally spaced through 90 degrees. The manner in which visibility of the arcuate fibers was enhanced varied consistently with the orientation of the polarizing filters. Cross-polarization accentuated apparent defects in the NFL when compared with standard red-free illumination.


Indications for tocolytic therapy: incidence of true preterm labor with uterine contractions as the sole deciding factor.
To evaluate the maximal impact tocolytic therapy could exert on preterm delivery rate, we conducted a retrospective study of all births that took place at Aarbus Kommune-hospital during a 2-year period when the only therapeutic regimen used in threatened preterm labor was bed rest. All singleton pregnancies that were delivered before the 35th week of gestation were included in the study. Eighty (1.2%) of 6454 deliveries fulfilled these criteria. Thirty-seven (46%) of the preterm pregnancies were associated with complications in which tocolytic therapy is contraindicated. Forty-three (54%) of the preterm deliveries occurred in women without pregnancy-related complications. Primary rupture of the membranes occurred in 19 (24%) women who therefore were not candidates for tocolytic therapy. Spontaneous contractions without contraindications for tocolytic therapy and with a cervical dilation less than 5 cm were present in 15 women only. In this group one infant had nonsuspected severe congenital malformations. Thus, only 14 (17.5%) of the preterm deliveries could have been prevented by tocolytic therapy. Tocolytic therapy other than bed rest was therefore indicated in only 0.2% of all deliveries.


Incidence of epistaxis after endoscopic pituitary surgery: Proposed treatment algorithm.
Endoscopic transsphenoidal surgery for pituitary tumors is an increasingly common practice. Little has been reported on the incidence and treatment of postoperative epistaxis in this population. The aim of this study was to analyze the incidence of postoperative epistaxis and formulate a treatment algorithm based on our experience. We performed a case series with chart review. A total of 434 consecutive patients who had endoscopic transsphenoidal pituitary surgery were identified between April 2006 and November 2013. The incidence, clinical management, and outcomes were recorded. Based on the data, a treatment algorithm was constructed. Fifty-two percent of patients treated were female (mean age: 51.4 years). Tumor types included pituitary adenomas (73.3%), Rathke cleft cysts (19.6%), and other pathologies (6.7%). Eighteen patients reported an epistaxis event within 6 weeks of surgery (4.1%). Treatment included office cauterization in 7 (1.6%) patients, a return to the operating room for 5 (1.2%), nasal packing in 3 (0.7%), embolization in 2 (0.5%), and use of intranasal hemostatic agents in 1 (0.2%). Epistaxis after endoscopic pituitary surgery is concerning for rapid blood loss and risk of intracranial complications. Fortunately, in the absence of new cranial nerve palsy, most bleeding can be controlled with conservative measures such as topical cautery, hemostatic agents, and nasal packing. An algorithm is presented to help guide physician decision making in this clinical scenario.


Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition: The Big Step Forward in Lipid Control.
The breakthrough discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) 20 years ago revolutionised the current understanding of cholesterol homeostasis. Genetic studies have shown that gain-of-function mutations in PCSK9 lead to elevated LDL cholesterol and increased risk of atherosclerotic cardiovascular disease, while loss-of-function mutations in PCSK9 result in lifelong low levels of circulating LDL cholesterol and dramatic reduction in atherosclerotic cardiovascular disease. Therapies inhibiting PCSK9 lead to a higher density of LDL receptor on the surface of hepatocytes, resulting in greater ability to clear circulating LDL. Thus far, randomised controlled trials have shown that subcutaneous fully human monoclonal antibodies targeting PCSK9, evolocumab and alirocumab, and PCSK9 silencing with inclisiran result in drastic reductions in LDL cholesterol. Additionally, several novel strategies to target PCSK9 are in development, including oral antibody, gene silencing, DNA base editing and vaccine therapies. This review highlights the efficacy, safety and clinical use of these various approaches in PCSK9 inhibition.


Molecular basis of peptide recognition in metallopeptidase Dug1p from Saccharomyces cerevisiae.
Dug1p, a M20 family metallopeptidase and human orthologue of carnosinase, hydrolyzes Cys-Gly dipeptide, the last step of glutathione (GSH) degradation in Saccharomyces cerevisiae. Molecular bases of peptide recognition by Dug1p and other M20 family peptidases remain unclear in the absence of structural information about enzyme-peptide complexes. We report the crystal structure of Dug1p at 2.55 Å resolution in complex with a Gly-Cys dipeptide and two Zn(2+) ions. The dipeptide is trapped in the tunnel-like active site; its C-terminus is held by residues at the S1' binding pocket, whereas the S1 pocket coordinates Zn(2+) ions and the N-terminus of the peptide. Superposition with the carnosinase structure shows that peptide mimics the inhibitor bestatin, but active site features are altered upon peptide binding. The space occupied by the N-terminus of bestatin is left unoccupied in the Dug1p structure, suggesting that tripeptides could bind. Modeling of tripeptides into the Dug1p active site showed tripeptides fit well. Guided by the structure and modeling, we examined the ability of Dug1p to hydrolyze tripeptides, and results show that Dug1p hydrolyzes tripeptides selectively. Point mutations of catalytic residues do not abolish the peptide binding but abolish the hydrolytic activity, suggesting a noncooperative mode in peptide recognition. In summary, results reveal that peptides are recognized primarily through their amino and carboxyl termini, but hydrolysis depends on the properties of peptide substrates, dictated by their respective sequences. Structural similarity between the Dug1p-peptide complex and the bestatin-bound complex of CN2 suggests that the Dug1p-peptide structure can be used as a template for designing natural peptide inhibitors.


Highly asymmetric aldol reaction of isatins and ketones catalyzed by chiral bifunctional primary-amine organocatalyst on water.
Herein, we have reported an environmentally friendly asymmetric aldol reaction between isatins and ketones catalyzed by double-hydrogen-bonded primary amine organocatalysts on water under mild conditions. Enantioenriched 3-hydroxy-2-oxindoles were obtained in high yields (up to 99%) and excellent stereoselectivities (up to 99 : 1 dr and 99% ee) under optimal conditions. Furthermore, the model reaction involving isatin and cyclohexanone was successfully scaled to 10 mmol with no reduction in yield or stereoselectivity. In addition, the catalyst was recovered via simple filtration and was subsequently reused on water, which highlights its good application potential.


Runx1 Regulates Myeloid Precursor Differentiation Into Osteoclasts Without Affecting Differentiation Into Antigen Presenting or Phagocytic Cells in Both Males and Females.
Runt-related transcription factor 1 (Runx1), a master regulator of hematopoiesis, is expressed in preosteoclasts. Previously we evaluated the bone phenotype of CD11b-Cre Runx1(fl/fl) mice and demonstrated enhanced osteoclasts and decreased bone mass in males. However, an assessment of the effects of Runx1 deletion in female osteoclast precursors was impossible with this model. Moreover, the role of Runx1 in myeloid cell differentiation into other lineages is unknown. Therefore, we generated LysM-Cre Runx1(fl/fl) mice, which delete Runx1 equally (∼80% deletion) in myeloid precursor cells from both sexes and examined the capacity of these cells to differentiate into osteoclasts and phagocytic and antigen-presenting cells. Both female and male LysM-Cre Runx1(fl/fl) mice had decreased trabecular bone mass (72% decrease in bone volume fraction) and increased osteoclast number (2-3 times) (P < .05) without alteration of osteoblast histomorphometric indices. We also demonstrated that loss of Runx1 in pluripotential myeloid precursors with LysM-Cre did not alter the number of myeloid precursor cells in bone marrow or their ability to differentiate into phagocytizing or antigen-presenting cells. This study demonstrates that abrogation of Runx1 in multipotential myeloid precursor cells significantly and specifically enhanced the ability of receptor activator of nuclear factor-κB ligand to stimulate osteoclast formation and fusion in female and male mice without affecting other myeloid cell fates. In turn, increased osteoclast activity in LysM-Cre Runx1(fl/fl) mice likely contributed to a decrease in bone mass. These dramatic effects were not due to increased osteoclast precursors in the deleted mutants and argue that inhibition of Runx1 in multipotential myeloid precursor cells is important for osteoclast formation and function.