[Prognostic value of histologic classifications of advanced stomach cancer: comparative study of Lauren's and Goseki's classifications].
Controversy exists about the prognostic value of the histological classifications of gastric cancer commonly used. Recently Goseki proposed a new classifying system based on intracellular mucus production and the degree of tubular differentiation. The aim of this study was to compare Lauren and Goseki classifications with particular emphasis on their prognostic significance. Eighty-nine patients, who underwent potentially curative resections (RO) and radical lymphadenectomy for advanced gastric cancer from September 1988 to April 1996 were analysed. Cox regression model was used to evaluate the prognostic significance of Goseki classification, Lauren classification, age, sex, type of lymphadenectomy, depth of tumour invasion (T), node metastases (N) and number of metastatic nodes. A statistically significant correlation between the different Goseki grades and histology according to Lauren was found (p < 0.001). By multivariate analysis the only parameters predictive of long term outcome were depth of tumour invasion, nodal status and histology according to the Lauren classification. Also after excluding the Lauren classification from the analysis, the Goseki histological grading system did not affect survival independently. This study on advanced gastric cancer patients identified depth of invasion, lymph node metastases and Lauren classification as significant independent pathological variables influencing survival. The classification proposed by Goseki did not add anything further to the prognostic informations provided by TNM staging and Lauren classification.


Further characterization of the in vitro tumoricidal activity of staphylococcal protein A.
Treatment of plasma or serum from leukemic patients with solid phase staphylococcal Protein A induced leukemic blast cell lysis in vitro, but this effect was relatively independent of the amount of immunoglobulin G (IgG) removed. Samples with approximately equal cytotoxic activity contained markedly different IgG levels, while samples with similar IgG levels had a wide range of tumoricidal activity. Assays of plasma samples collected during a perfusion of one plasma volume through a Protein A-Sepharose column indicated that the duration of the procedure had a greater effect on cytotoxic activity than did the amount of IgG removed. Neither added leukemic nor normal IgG significantly improved blast cell viability in treated serum. Cytotoxic activity was not dialyzable and concentrated in the Mr less than 100,000 fraction of samples separated by filtration. Treated cytotoxic serum samples did not have important Clq binding activity. These results suggest that the in vitro tumoricidal activity of solid phase Protein A is probably due to a toxic substance added to serum during immunoadsorption rather than to its immunoadsorptive capacity.


Identification of a p-coumarate degradation regulon in Rhodopseudomonas palustris by Xpression, an integrated tool for prokaryotic RNA-seq data processing.
High-throughput sequencing of cDNA prepared from RNA, an approach known as RNA-seq, is coming into increasing use as a method for transcriptome analysis. Despite its many advantages, widespread adoption of the technique has been hampered by a lack of easy-to-use, integrated, open-source tools for analyzing the nucleotide sequence data that are generated. Here we describe Xpression, an integrated tool for processing prokaryotic RNA-seq data. The tool is easy to use and is fully automated. It performs all essential processing tasks, including nucleotide sequence extraction, alignment, quantification, normalization, and visualization. Importantly, Xpression processes multiplexed and strand-specific nucleotide sequence data. It extracts and trims specific sequences from files and separately quantifies sense and antisense reads in the final results. Outputs from the tool can also be conveniently used in downstream analysis. In this paper, we show the utility of Xpression to process strand-specific RNA-seq data to identify genes regulated by CouR, a transcription factor that controls p-coumarate degradation by the bacterium Rhodopseudomonas palustris.


Nocturnal intermittent hypoxia and metabolic syndrome; the effect of being overweight: the CIRCS study.
We investigated whether nocturnal intermittent hypoxia, a surrogate marker for obstructive sleep apnea, is associated with metabolic syndrome and its components among Japanese. We examined 1,710 male and 2,896 female community-dwelling Japanese aged 40 to 69, who participated in annual cardiovascular examinations and investigations of sleep. Nocturnal intermittent hypoxia was estimated based on a 3% oxygen desaturation index measured with pulse-oximetry during sleep. No, mild and moderate-to-severe nocturnal intermittent hypoxia were defined by <5, 5 to <15 and >or=15 events/hour, respectively. Metabolic syndrome was defined by modified criteria of the Adult Treatment Panel III guidelines. Compared with no nocturnal intermittent hypoxia, the multivariable odds ratio of metabolic syndrome was 1.9 (95% confidence interval: 1.6-2.4) for mild and 3.2 (2.2-4.7) for moderate-to-severe nocturnal intermittent hypoxia among men; 2.6 (2.1-3.4) and 5.8 (3.4-9.8) among women, respectively. When stratified by overweight status (body mass index >or=25 kg/m(2)), the multivariable odds ratio of two or more metabolic risk factors (other than overweight) associated with moderate-to-severe nocturnal intermittent hypoxia was 1.9 (1.2-3.1) among non-overweight subjects and 1.4 (0.9-2.1) among overweight subjects (p for interaction=0.002). Nocturnal intermittent hypoxia was associated with the accumulation of metabolic risk factors, especially among non-overweight individuals.


Bioinks-materials used in printing cells in designed 3D forms.
Use of materials to activate non-functional or damaged organs and tissues goes back to early ages. The first materials used for this purpose were metals, and in time, novel materials such as ceramics, polymers and composites were introduced to the field to serve in medical applications. In the last decade, the advances in material sciences, cell biology, technology and engineering made 3D printing of living tissues or organ models in the designed structure and geometry possible by using cells alone or together with hydrogels through additive manufacturing. This review aims to give a brief information about the chemical structures and properties of bioink materials and their applications in the production of 3D tissue constructs.


Microtubule motor protein Kar3 is required for normal mitotic division and morphogenesis in Candida albicans.
The kinesin-related protein Kar3 is a minus end-directed molecular motor that plays a multifunctional role in microtubule-directed nuclear movement. Previously, it was shown that Candida albicans Kar3p is critical for nuclear fusion during mating as kar3 mutants were defective in karyogamy. In this study, we confirm that Kar3p is required for nuclear congression in mating but that neither Kar3p nor the dynein motor protein Dyn1p is required for nuclear migration in the mating projection prior to cell fusion. In addition, we show that C. albicans Kar3p plays an important role in the cell and colony morphology of mitotically dividing cells, as evidenced by diminished filamentation of kar3 cells on Spider medium and an increased tendency of mutant cells to form pseudohyphal cells in liquid culture. Loss of Kar3p also led to defects in nuclear division, causing cells to grow slowly and exhibit reduced viability compared to wild-type cells. Slow growth was due, at least in part, to delayed cell cycle progression, as cells lacking Kar3p accumulated in anaphase of the cell cycle. Consistent with a role in mitotic division, Kar3 protein was shown to localize to the spindle pole bodies. Finally, kar3 cells exhibited unstable or aberrant mitotic spindles, a finding that accounts for the delay in cell cycle progression and decreased viability of these cells. We suggest that the altered morphology of kar3 cells is a direct consequence of the delay in anaphase, and this leads to increased polarized growth and pseudohypha formation.


In vitro and in vivo effect of human lactoferrin on glioblastoma growth.
Human lactoferrin (HLF) is a natural protein with antitumor activity. The aim of this study was to investigate the effects of HLF alone and in combination with temozolomide (TMZ), a conventional chemotherapeutic, on human glioblastoma (GBM) cells. The authors cultured fresh human primary cell lines NMD and FN and the continuous cell line U87MG to evaluate proliferation in the presence of HLF alone at different doses (1, 10, and 100 mg/ml, and 1 mg/ml) and in combination with TMZ. In in vivo experiments they assessed tumor size reduction in CD1 nude mice carrying an orthotopic GBM xenograft and orally treated with HLF. Lactoferrin causes growth inhibition in the NMD and FN primary cell lines and in the U87MG continuous cell line. This inhibition seemed to be modulated by the downregulation of cyclin D1 and D4. Western blot and fluorescence-activated cell sorting analysis showed inhibition of the cell cycle in G0/G1 and G2 phases. When administered in nude mice, HLF (60 mg/kg/day) decreased tumor size about 30%, as shown in both histological analyses and high-field brain MRI. Administration of HLF with TMZ enhanced the effect of chemotherapy both in vitro and in vivo. This study demonstrated that HLF can inhibit GBM cell growth, suggesting that this nontoxic substance may have a role in potentiating the effect of current TMZ treatment of GBM.


Ventilatory efficiency in combination with peak oxygen uptake improves risk stratification in patients undergoing lobectomy.
We aimed to evaluate whether or not using the slope of the increase in minute ventilation in relation to carbon dioxide (VE/VCo2-slope), with a cutoff value of 35, could improve risk stratification for major pulmonary complications or death following lobectomy in lung cancer patients at moderate risk (Vo2peak = 10-20 mL/kg/min). Single center, retrospective analysis of 146 patients with lung cancer who underwent lobectomy and preoperative cardiopulmonary exercise testing in 2008-2020. The main outcome was any major pulmonary complication or death within 30 days of surgery. Patients were categorized based on their preoperative cardiopulmonary exercise testing as: low-risk group, peak oxygen uptake >20 mL/kg/min; low-moderate risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope <35; and moderate-high risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope ≥35. The frequency of complications between groups was compared using χ2 test. Logistic regression was used to calculate the odds ratio with 95% CI for the main outcome based on the cardiopulmonary exercise testing group. Overall, 25 patients (17%) experienced a major pulmonary complication or died (2 deaths). The frequency of complications differed between the cardiopulmonary exercise testing groups: 29%, 13%, and 8% in the moderate-high, low-moderate, and low-risk group, respectively (P = .023). Using the low-risk group as reference, the adjusted odds ratio for the low-moderate risk group was 3.44 (95% CI, 0.66-17.90), whereas the odds ratio for the moderate-high risk group was 8.87 (95% CI, 1.86-42.39). Using the VE/VCo2-slope with a cutoff value of 35 improved risk stratification for major pulmonary complications following lobectomy in lung cancer patients with moderate risk based on a peak oxygen uptake of 10 to 20 mL/kg/min. This suggests that the VE/VCo2-slope can be used for preoperative risk evaluation in lung cancer lobectomy.


Deformation of a micro-torque swimmer.
The membrane tension of some kinds of ciliates has been suggested to regulate upward and downward swimming velocities under gravity. Despite its biological importance, deformation and membrane tension of a ciliate have not been clarified fully. In this study, we numerically investigated the deformation of a ciliate swimming freely in a fluid otherwise at rest. The cell body was modelled as a capsule with a hyperelastic membrane enclosing a Newtonian fluid. Thrust forces due to the ciliary beat were modelled as torques distributed above the cell body. The effects of membrane elasticity, the aspect ratio of the cell's reference shape, and the density difference between the cell and the surrounding fluid were investigated. The results showed that the cell deformed like a heart shape, when the capillary number was sufficiently large. Under the influence of gravity, the membrane tension at the anterior end decreased in the upward swimming while it increased in the downward swimming. Moreover, gravity-induced deformation caused the cells to move gravitationally downwards or upwards, which resulted in a positive or negative geotaxis-like behaviour with a physical origin. These results are important in understanding the physiology of a ciliate's biological responses to mechanical stimuli.


A core-brush 3D DNA nanostructure: the next generation of DNA nanomachine for ultrasensitive sensing and imaging of intracellular microRNA with rapid kinetics.
A highly loaded and integrated core-brush three-dimensional (3D) DNA nanostructure is constructed by programmatically assembling a locked DNA walking arm (DA) and hairpin substrate (HS) into a repetitive array along a well-designed DNA track generated by rolling circle amplification (RCA) and is applied as a 3D DNA nanomachine for rapid and sensitive intracellular microRNA (miRNA) imaging and sensing. Impressively, the homogeneous distribution of the DA and HS at a ratio of 1 : 3 on the DNA track provides a specific walking range for the DA to avoid invalid and random self-walking and notably improve the executive ability of the core-brush 3D DNA nanomachine, which easily solves the major technical challenges of traditional Au-based 3D DNA nanomachines: low loading capacity and low executive efficiency. As a proof of concept, the interaction of miRNA with the 3D DNA nanomachine could initiate the autonomous and progressive operation of the DA to cleave the HS for ultrasensitive ECL detection of target miRNA-21 with a detection limit as low as 3.57 aM and rapid imaging in living cells within 15 min. Therefore, the proposed core-brush 3D DNA nanomachine could not only provide convincing evidence for sensitive detection and rapid visual imaging of biomarkers with tiny change, but also assist researchers in investigating the formation mechanism of tumors, improving their recovery rates and reducing correlative complications. This strategy might enrich the method to design a new generation of 3D DNA nanomachine and promote the development of clinical diagnosis, targeted therapy and prognosis monitoring.


Synergistic Activity of Clofazimine and Clarithromycin in an Aerosol Mouse Model of Mycobacterium avium Infection.
Infections with nontuberculous mycobacteria (NTM) have a poor prognosis in patients with underlying respiratory diseases. Clofazimine (CFZ) showed both experimental and clinical promising results against clinically relevant NTM. However, there are no data on CFZ in combination with the current recommended treatment; therefore, we aimed to study its in vivo activity in an aerosol mouse model of Mycobacterium avium In an aerosol infection BALB/c mouse model using M. avium strain Chester, we treated 58 mice with four combinations of rifampin (RIF) at 10 mg/kg, CFZ at 25 mg/kg, and clarithromycin (CLR) and ethambutol (EMB) at 100 mg/kg. Treatment efficacy was assessed on the basis of lung CFU counts after 2 (M2) and 4 (M4) months of treatment. At M2, CLR-RIF-EMB was slightly but significantly more efficient than CFZ-RIF-EMB (3.02 ± 0.12 versus 3.55 ± 0.28, respectively, P < 0.01), whereas CLR-CFZ-EMB and CLR-CFZ-RIF-EMB dramatically decreased lung CFU counts by 4.32 and 4.47 log10, respectively, compared to untreated group. At M4, CLR-RIF-EMB was significantly more efficient than CFZ-RIF-EMB (2 ± 0.53 versus 2.66 ± 0.22, respectively, P = 0.01). The addition of CLZ to CLR dramatically decreased the lung CFU count, with CFU counts 5.41 and 5.79 log10 lower in the CLR-CFZ-EMB and CLR-CFZ-RIF-EMB groups, respectively, than in the untreated group. The addition of CFZ to CLR seems to improve the efficacy of CLR as early as M2 and was confirmed at M4. CFZ, in addition to RIF and EMB, on the other hand, is less effective than CLR-RIF-EMB. These results need to be confirmed by similar studies along with CFZ potential for shortening treatment.


Occurrence of NKX3.1 C154T polymorphism in men with and without prostate cancer and studies of its effect on protein function.
NKX3.1, a member of the NK class of homeodomain proteins, is expressed primarily in the adult prostate and has growth suppression and differentiating effects in prostate epithelial cells. A C-->T polymorphism at nucleotide 154 (NKX3.1 C154T) is present in approximately 11% of healthy men with equal distribution among whites and blacks. In a cohort of 1253 prostate cancer patients and age-matched controls, the presence of the polymorphism was associated with a 1.8-fold risk of having stage C or D prostate cancer or Gleason score > or =7 (confidence interval, 1.01-3.22). The NKX3.1 C154T polymorphism codes for a variant protein that contains an arginine-to-cysteine substitution at amino acid 52 (R52C) adjacent to a protein kinase C phosphorylation site at serine 48. Substitution of cysteine for arginine 52 or of alanine for serine 48 (S48A) reduced phosphorylation at serine 48 in vitro and in vivo. Phosphorylation of wild-type NKX3.1, but not of NKX3.1 R52C or NKX3.1 S48A, diminished binding in vitro to a high-affinity DNA binding sequence. NKX3.1 also serves as a transcriptional coactivator of serum response factor. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate to phosphorylate NKX3.1 had no effect on NKX3.1 coactivation of serum response factor. Neither the R52C nor the S48A substitution affected serum response factor coactivation by NKX3.1 We conclude that the polymorphic NKX3.1 allele codes for a variant protein with altered DNA binding activity that may affect prostate cancer risk.


Development of differentiation between writing and drawing systems.
When does a writing system emerge out of children's drawing to separate (a) script processing and production from (b) picture processing and production? And does one system's activation help or hinder the other system's operation? Children 4-12 years of age wrote repeated Os and Vs and drew matching shapes, in the contexts of script and of pictures. The technique elicits matching products in order to identify differences between production kinematics in different contexts. A transition occurred around age 6 in which (a) production was more fluent for writing than drawing and (b) activation of one system interfered with the other. Modeling the consolidation of both phenomena generated testable parameters for the slow approach to the adult steady state, involving increasing specialization and the waning of the need for suppression of the two systems' interference.


Combined pharmacotherapy-multimodal psychotherapy in children with Disruptive Behavior Disorders.
Although multi-component psychotherapeutic interventions are first-line treatments for Disruptive Behavior Disorders (DBD), pharmacotherapy is often associated for more severe patients. Our aim was to explore effectiveness of an associated pharmacotherapy in referred children with DBD receiving a one-year psychotherapeutic intervention. Aggression, callous unemotional (CU) traits and emotional dysregulation were outcome measures. The sample included 144 children, aged 8-12 years, 41 (29%) with an ADHD comorbidity. Fifty-five (38%) patients received an additional pharmacotherapy with one medication, methylphenidate, a second generation antipsychotic, or a mood stabilizer. Data were collected before and after the one-year treatment. According to the Child Behavior Checklist (CBCL), aggressive behaviors, rule-breaking behaviors and emotional dysregulation improved in the whole group, as well as parent- and child-reported CU traits. The hierarchical regression model showed that additional pharmacotherapy significantly predicted lower scores at the CBCL aggressive behaviors and emotional dysregulation, but not CU traits at the end of the treatment. The interaction between methylphenidate and ADHD comorbidity predicted lower aggressive behaviors after the treatment. In summary, this naturalistic investigation suggest that an additional pharmacotherapy significantly improved aggression and emotional dysregulation, but not CU traits. When ADHD was comorbid, methylphenidate was more effective than antipsychotics or mood stabilizers in reducing aggression.


Exportin-5 mediates nuclear export of SRP RNA in vertebrates.
The signal recognition particle is a ribonucleoprotein complex that is essential for the translocation of nascent proteins into the endoplasmic reticulum. It has been shown that the RNA component (SRP RNA) is exported from the nucleus by CRM1 in the budding yeast. However, how SRP RNA is exported in higher species has been elusive. Here, we show that SRP RNA does not use the CRM1 pathway in Xenopus oocytes. Instead, SRP RNA uses the same export pathway as pre-miRNA and tRNA as showed by cross-competition experiments. Consistently, the recombinant Exportin-5 protein specifically stimulated export of SRP RNA as well as of pre-miRNA and tRNA, whereas an antibody raised against Exportin-5 specifically inhibited export of the same RNA species. Moreover, biotinylated SRP RNA can pull down Exportin-5 but not CRM1 from HeLa cell nuclear extracts in a RanGTP-dependent manner. These results, taken together, strongly suggest that the principal export receptor for SRP RNA in vertebrates is Exportin-5 unlike in the budding yeast.


A detailed analysis of chromosomal changes in heritable and non-heritable retinoblastoma.
Full cytogenetic analysis of 27 different retinoblastoma tumors is presented. Gross aneuploidy of chromosome arms 6p and 1q were very common, being observed in 15/27 and 21/27 tumors, respectively. However, we found that chromosome 13 was rarely missing: only 3/27 had a detectable monosomy affecting 13q14. Monosomy of chromosome 13 by small deletion or rearrangement was also not observed in any of 12 retinoblastoma tumor lines analyzed detail at the 300-400 chromosome band level. A novel observation in retinoblastoma was the discovery of non-random translocations at three specific breakpoints, 14q32 (4/12), 17p12 (5/12), and 10q25 (3/12). Genomic rearrangements similar to those described involving C-myc in Burkitt lymphoma 14q+ cells could not be demonstrated in the four 14q+ retinoblastoma lines using molecular techniques, and a probe mapping to the site implicated to have an activating role in lymphoma. These data suggest that there is a target for rearrangement at 14q32 but it is not the same sequence used in some Burkitt lymphomas. Two other breakpoints (2p24 and 8q24) coincided with the mapped position of cellular oncogenes, but also failed to show a molecular rearrangement with the oncogene probes. The breakpoints, 10q25 and 17p12, are constitutional fragile sites which may predispose these regions to act as acceptors of translocations in malignant cells. One line had double minute chromosomes, and was the only one of 16 (6%) tested with the N-myc probe which had an amplification. Different tumors from single patients with multifocal heritable retinoblastoma showed independent karyotype evolution. Unilateral non-heritable tumors exhibited a high level of karyotype stability throughout both in vivo and in vitro growth. The various common patterns of aneuploidy and translocations probably confer an early selective advantage to malignant cells, rather than induce malignant transformation.


Effect of age, sex, and sites on the cellularity of the adipose tissue in mice and rats rendered obese by a high-fat diet.
Cell size and number of parametrial fat pads were determined in Swiss mice made obese by means of a high-fat diet (40% lard w/w) given ad lib. This diet and a control were introduced to two groups of mothers during gestation and lactation, and sucklings were given the same diets as their mothers at weaning and throughout life.2-wk old mice suckled by mothers fed a high-fat diet have fatter parametrial pads. This difference is due solely to an increase in fat cell size. After weaning, until the 18th wk, the two groups differed with a striking fat cell enlargement seen in the obese group. Later on, whereas cell numbers did not change in the control group, a constant and uninterrupted increase in number is shown in those of obese mice until the 52nd wk. Hyperplasia was observed only in adults. When the high-fat diet was introduced to adult rats it also triggered an increase in fat cell number. Three sites of fat pads were compared in both sexes at 32 wk of age. All sites increased in weight in the high-fat fed group. This was due to: hyperplasia in perirenal site, hypertrophy in epididymal and subcutaneous sites, and hyperplasia plus hypertrophy in the parametrial one. So, in each sex, adipose sites in the obese mice reacted to the diet in a site-specific way. It was concluded that the level of fat in a diet is involved in both formation and maturation of new fat cells and in the regulation of fat cell lipid content. The two processes may be separated or may act together according to the adipose tissue site.


A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs.
Patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant/intolerant to ≥2 tyrosine kinase inhibitors (TKIs) are at high risk of experiencing poor outcomes because of disease biology and inadequate efficacy and/or safety of current therapies. Asciminib, a first-in-class BCR-ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to approved TKIs. In this phase 3, open-label study, patients with CML-CP previously treated with ≥2 TKIs were randomized (2:1) to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily. Randomization was stratified by major cytogenetic response (MCyR) status at baseline. The primary objective was to compare the major molecular response (MMR) rate at week 24 for asciminib vs bosutinib. A total of 233 patients were randomized to asciminib (n = 157) or bosutinib (n = 76). Median follow-up was 14.9 months. The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% confidence interval, 2.19-22.30; 2-sided P = .029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib. The study showed a superior efficacy of asciminib compared with that of bosutinib, together with a favorable safety profile. These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant/intolerant to ≥2 prior TKIs. This trial was registered at www.clinicaltrials.gov as #NCT03106779.


Double-face augmentation urethroplasty for bulbar urethral strictures: Analysis of short-term outcomes.
To present our initial experience with double-face augmentation urethroplasty for near-obliterative bulbar urethral strictures and analyze the short-term outcomes. We retrospectively evaluated a prospectively maintained database of patients with near-obliterative bulbar urethral strictures (>2 cm), who underwent double-face augmentation urethroplasty. The patients' demographic characteristics, clinical data, and data regarding the investigations conducted were analyzed. Near-obliterative urethral stricture was defined as lumen <6 Fr. Double-face urethroplasty was performed using a ventral approach, during which dorsal inlay and ventral onlay buccal mucosal graft (BMG) augmentation were performed. A successful outcome was defined as normal voiding without the need for any instrumentation to improve the urinary flow rate. A total of 37 patients with a mean age of 50±11.7 years, who underwent this procedure were included in the study. The mean stricture length was 5.2±0.95 cm. The mean length of the dorsal inlay BMG augmentation was 3.1±0.5 cm and that of the ventral onlay BMG augmentation was 6.3±1.2 cm. Post-void dribbling (18.9%) was the most commonly reported complication. The maximum flow rates and symptom scores significantly improved in both groups compared with the preoperative parameters (p<0.001). The incidence of both erectile dysfunction and ejaculatory failure was reported in 6 (16.2%) patients; respectively. The overall success rate was 86.5% at a median follow-up period of 36 months (IQR: 26.5-43). Double-face augmentation urethroplasty is a safe and feasible option for near-obliterative bulbar urethral strictures, and our study showed satisfactory short-term outcomes for the same.


OmpR phosphorylation regulates ompS1 expression by differentially controlling the use of promoters.
The Salmonella enterica ompS1 gene encodes a quiescent porin that belongs to the OmpC/OmpF family. In the present work we analysed the regulatory effects of OmpR phosphorylation on ompS1 expression. We found that in vivo, OmpR in its phosphorylated form (OmpR-P) was important in the regulation of the two ompS1 promoters: OmpR-P activated the P1 promoter and repressed the P2 promoter in an EnvZ-dependent manner; expression occurs from the P2 promoter in an ompR mutant. In vitro, OmpR-P had a higher DNA-binding-affinity to the ompS1 promoter region than OmpR and OmpRD55A, showing an affinity even higher than that of equivalent DNA regions in the 5'-upstream regulatory sequence of the major porin-encoding genes ompC and ompF. By analysing different environmental conditions, we found that glucose and glycerol enhanced ompS1 expression in the wild-type strain. Interestingly the stimulation by glycerol was OmpR-dependent while the effect of glucose was still observed in the absence of OmpR. Acetyl phosphate produced by the AckA-Pta pathway did not influence ompS1 regulation. These data indicate the important role of the phosphorylation in the activity of OmpR on the differential regulation of both ompS1 promoters and its impact on the pathogenesis.


Focus on early-career GPs: qualitative evaluation of a multi-faceted educational intervention to improve antibiotic prescribing.
We conducted an educational intervention emphasizing rational antibiotic prescribing in early-career General Practitioners (GP) in vocational training (trainees). The intervention consisted of an online introduction module, an online communication training module, face-to-face workshops, and cases to be discussed one-on-one by the trainee-supervisor dyad during regular scheduled education sessions. To explore the participants' experiences with the intervention. A qualitative study of 14 GP trainees and supervisors. Interviews followed a semi-structured interview guide, were transcribed and analysed using concurrent thematic analysis. Overall, the intervention was well received. Resources were not often used in practice, but GP trainees used the information in communicating with patients. The intervention improved trainees' confidence and provided new communication strategies, e.g. explicitly asking about patients' expectations and talking patients through the examination to form an overall clinical picture. Trainees seemed eager to learn and adapt their practice, whereas GP supervisors rather commented that the intervention was reinforcing. None of the participants reported prescribing conflicts between trainee and supervisor. However, most participants identified conflicts within the GP practice or with specialists: other doctors who prescribe more antibiotics perpetuate patients' ideas that antibiotics will fix everything, which in turn causes conflict with the patient and undermines attempts to improve antibiotic prescribing. The educational intervention was received positively. Early-career GPs thought it influenced their prescribing behaviour and improved their confidence in non-prescribing. Interventions that target teams (e.g. entire practice) could minimize conflict, ensure consistency of messages and support overall antibiotic stewardship in primary care.


Influence of Abutment Fabrication Method on 3D Fit at the Implant-Abutment Connection.
To three-dimensionally evaluate the internal fit at the implant-abutment interface of abutments fabricated with different workflows using a combination of the silicone replica technique and microcomputed tomography (μCT). Thirty abutments were fabricated to restore internal-connection implants and were divided into three groups according to fabrication method: (1) full digital (abutment machined using CAD/CAM system); (2) Ti-Base (prefabricated standard Ti-Base abutments); and (3) UCLA (UCLA-type abutments) (n = 10/group). Linear and volume measurements were performed to assess the internal misfit using a silicone replica of the implant-abutment interface misfit area, which was three-dimensionally reconstructed after μCT. The internal discrepancies in three different regions of interest (Gapsuperior, Gapmarginal, and Gapcenter) were assessed. Data were statistically evaluated using ANOVA and Tukey test (P < .05). Ti-Base and UCLA abutments presented significantly lower misfit volume (0.49 mm3, 95% CI: ± 0.045 mm3 and 0.48 mm3, 95% CI: ± 0.045 mm3, respectively) and mean internal gap (25.20 μm, 95% CI: ± 3.14 μm and 27.97 μm, 95% CI: ± 3.14 μm, respectively) than the full digital group (0.70 mm3, 95% CI: ± 0.045 mm3; 34.90 μm, 95% CI: ± 3.14 μm) (P < .001), but did not differ from each other (P = .825). While Gapcenter was significantly higher in the full digital group (P < .001), Gapsuperior and Gapmarginal did not demonstrate significant differences among groups. All regions were statistically similar within groups, except for Gapcenter in the full digital group, which exhibited higher mean values compared to the other regions (P = .000). The 3D measurements for quantification of internal discrepancy were strongly associated with the 2D measurements. Ti-Base and UCLA abutments exhibited better internal fit at the implant-abutment interfaces compared to a fully digitalized workflow (CAD/CAM custom abutments).


The relationship between adult reactive and proactive aggression, hostile interpretation bias, and antisocial personality disorder.
Reactive aggression (RA) refers to angry responses to provocation or frustration, while proactive aggression (PA) denotes nonemotional, instrumental, and unprovoked aggression. The current study examined personality-related and cognitive correlates of both aggressive types. Respectively, the predictive values of antisocial personality disorder (ASPD), and of hostile interpretation bias, which is the tendency to interpret ambiguous stimuli in a hostile manner, were studied. The sample consisted of n = 37 male adult patients with mixed diagnoses and n = 29 male nonpatients that responded to vignettes and pictures of ambiguous situations, using both open and closed answer formats. ASPD was assessed by means of the Structured Clinical Interview for DSM-IV Axis II disorders (SCID-II), and the Reactive Proactive Questionnaire (RPQ) measured RA and PA. Results showed that although both RA and PA types were predicted by ASPD traits, RA was additionally predicted by a hostile interpretation bias. These findings suggest that reducing hostile bias is a promising avenue for clinical treatment of ASPD-patients high in RA.


[Dynamics of the biosynthesis of nystatin components by Act. noursei, strain 153 under controlled culture conditions].
The ratio of the nystatin components produced under various cultivation conditions was studied. It was found to change during the greater part of the fermentation period and depend on the carbohydrate content in the medium. Under the conditions of the uncontrolled batch process the ratio of components A1 and A2 during the first 36 hours of the cultivation changed from 7.2 to 6.2. When the rate of the antibiotic synthesis was maximum (42 - 72 hours), the ratio of A1 and A2 components was practically constant and equal to 5.5 - 5.2. Beginning from the 72nd hour, when the rate of nystatin synthesis decreased, the ratio of A1 and A2 components increased up to 6.6 - 9.0. Periodical addition of high amounts of glucose during the idiophase promoted activation of the synthesis of the less active A1 component. On momentous addition of glucose in the amounts of 1, 2 and 3 per cent the ratio of A1 and A2 components increased by the end of the process up to 14.3, 16.6 and 22.4 respectively. The data suggest that the nystatin components and especially the active A2 component which is more stable on storage are sensitive to accumulation of glucose catabolites.


Coupled-resonator-induced plasmonic bandgaps.
By drawing an analogy with the conventional photonic crystals, the plasmonic bandgaps have mainly employed the periodic metallic structures, named as plasmonic crystals. However, the sizes of the plasmonic crystals are much larger than the wavelengths, and the large sizes considerably decrease the density of the photonic integration circuits. Here, based on the coupled-resonator effect, the plasmonic bandgaps are experimentally realized in the subwavelength waveguide-resonator structure, which considerably decreases the structure size to subwavelength scales. An analytic model and the phase analysis are established to explain this phenomenon. Both the experiment and simulation show that the plasmonic bandgap structure has large fabrication tolerances (>20%). Instead of the periodic metallic structures in the bulky plasmonic crystals, the utilization of the subwavelength plasmonic waveguide-resonator structure not only significantly shrinks the bandgap structure to be about λ2/13, but also expands the physics of the plasmonic bandgaps. The subwavelength dimension, together with the waveguide configuration and robust realization, makes the bandgap structure easy to be highly integrated on chips.


Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of lymphoma.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is highly accurate in diagnosing mediastinal lymphadenopathies of lung cancer and benign disorders. However, the utility of EBUS-TBNA in the diagnosis of mediastinal lymphomas is unclear. The aim of this study was to determine the diagnostic value of EBUS-TBNA in patients with suspected lymphoma. Sixty-eight patients with isolated mediastinal lymphadenopathy and suspected of lymphoma were included in the study. EBUS-TBNA was performed on outpatients under moderate sedation. The sensitivity, specificity, negative predictive value and diagnostic accuracy of EBUS-TBNA were calculated. Sixty-four patients were diagnosed by EBUS-TBNA, but four patients with non-diagnostic EBUS-TBNA required surgical procedures. Thirty-five (51.5%) patients had sarcoidosis, six (8.8%) had reactive lymphadenopathy, nine (13.3%) had tuberculosis, one (1.5%) had squamous cell carcinoma, two (2.9%) had sarcoma and fifteen (22%) had lymphoma (follicular center cell, large B-cell primary, and Hodgkin lymphomas in three, two, and ten, respectively). Of the 15 lymphoma patients, thirteen were diagnosed by EBUS and two by thoracotomy and mediastinoscopy. The sensitivity, specificity, negative predictive value, and diagnostic accuracy of EBUS-TBNA for the diagnosis of lymphoma were calculated as 86.7%, 100%, 96.4%, and 97%, respectively. EBUS-TBNA can be employed in the diagnosis of mediastinal lymphoma, instead of more invasive surgical procedures.


Thrombocytopenia associated with antithrombotic therapy in patients with cardiovascular diseases: diagnosis and treatment.
Agents with antiplatelet and anticoagulant activity have been proved to be effective in reducing the incidence of complications following acute coronary syndrome, percutaneous coronary intervention, and cardiopulmonary bypass. However, these agents, including heparin, glycoprotein IIb/IIIa receptor inhibitors, and thienopyridines, are associated with increased risk of bleeding and thrombocytopenia and have been administered together with increasing frequency in a variety of cardiovascular settings. Therefore, clinicians must be familiar with the safety and rational use of these potent antithrombotic agents. Clinical features of thrombocytopenia range from bleeding to thrombosis, even death, and therapy is very different depending on the underlying cause. Additionally, patients may sometimes need urgent intervention or surgery. Thus, it is essential to quickly discriminate the etiology and start appropriate therapy. This review highlights the pathogenesis, clinical and laboratory manifestation, differential diagnosis, and treatment of antithrombotic drug-induced thrombocytopenia in cardiovascular diseases.


Evaluation of or staffing and postoperative patient outcomes.
The purpose of this cross-sectional cohort study was to evaluate the relationship between the number of OR personnel involved in a surgery and subsequent postoperative outcomes. We collected data from a sample of general surgery patients (N = 911) by using the American College of Surgeons National Surgical Quality Improvement Project processes. Data obtained from electronic medical records about the number of different personnel involved in the surgeries were used to create total OR staffing and nurse staffing variables for each surgery. Two associations approached statistical significance after we controlled for significant risk factors, including OR duration. A higher number of total nursing personnel involved in a surgical procedure was associated with any postoperative complication at the P = .095 level. A higher number of total OR personnel was associated with surgical site infections at the P = .057 level. We recommend further evaluation of these measures in multiple hospital settings.


Effects of intraperitoneal bevacizumab administration on colonic anastomosis and early postoperative adhesion formation.
The purpose of this study is to investigate the effect of intraperitoneal (IP) bevacizumab on colonic anastomosis and evaluate the effects on early postoperative adhesion formation. A total of 24 mature female Sprague-Dawley rats were used for this study. Rats were randomly assigned to a control group that received saline (n = 8) or to experimental groups (n = 8 each) that received bevacizumab at a dose of 2.5 mg/kg (group 1) or 5 mg/kg (group 2). Animals were killed humanely on the seventh day after operation, and measurements of anastomotic strength and biochemical variables were performed. The mean adhesion grade was 2.63 ± 0.92, and 1 ± 0.93 and 0.75 ± 0.71 for the control and test groups, respectively. Bevacizumab significantly reduced adhesion formation in both low-dose and high-dose IP applications (P < .05). When all groups were compared, it was found that VEGF levels decreased significantly only in the tissue (P = .001), whereas there was no significant difference in the blood and the IP fluid (P = .73 and .08, respectively). We evaluated hydroxyproline levels, anastomosis bursting pressure, and histopathological healing scores. When each of these parameters were examined, there was statistical difference between groups (P = .01, .004, and .01, respectively). It was found that these parameters significantly decreased depending on increasing drug dose. IP administration of bevacizumab effectively reduced the formation of adhesions and caused significant impairment of anastomotic wound healing when standard doses were administered (5 mg/kg), but the 2.5-mg/kg dosage did not affect the anastomotic wound healing and also effectively reduced the formation of adhesions.


Hydrous silica coatings: occurrence, speciation of metals, and environmental significance.
Si-enriched coatings form on the surface of silicate minerals under acidic conditions. Although they are often only a few nanometers thick, their large specific surface area may control the interaction between silicate minerals in acidic soils, aquifers, and mine tailings. Micrometer thick, hydrous-silica coatings occur on the surface of a granite outcrop in contact with acidic pond water at the Coppercliff mine-tailings area in the Greater City of Sudbury, Ontario, and are ideal to study the concentration and speciation of metals and metalloids inside Si-enriched coatings. These coatings have higher average concentrations of Cr, Mn, Co, Ni, Cu, Zn, and Pb than coatings composed of schwertmannite, Fe(8)O(8)(OH)(4.4)(SO(4))(1.8) (H(2)O)(8.4). Microscopic and spectroscopic examination of the hydrous-silica coating indicates the occurrence of Fe- and Cu-Zn-oxy-hydroxide particles, tetrahedrally coordinated Fe(3+) and a high proportion of M-O-Si bonds (M = metal). These observations suggest that metals occur either finely distributed in the hydrous-silica matrix or in oxy-hydroxide particles. The latter particles are products of the diffusion of metals into the hydrous silica and the subsequent nucleation of oxy-hydroxide phases.


Ruxolitinib in combination with lenalidomide as therapy for patients with myelofibrosis.
Ruxolitinib and lenalidomide may target distinct clinical and pathological manifestations of myelofibrosis and prevent therapy-related worsening of blood cell counts. To determine the efficacy and safety of the combination in patients with myelofibrosis, patients were given 15 mg ruxolitinib orally twice daily in continuous 28-day cycles, plus 5 mg lenalidomide orally once daily on days 1-21. Thirty-one patients were treated, with a median followup of 28 months (range, 12 - 35+). Due to failure to meet the predetermined efficacy rules for treatment success the study was terminated early. Simultaneous administration of ruxolitinib and lenalidomide was difficult: 20 of the 23 dose interruptions occurred within the first 3 months of therapy. Lenalidomide was interrupted in all 20 cases. Fourteen patients (45%) were completely off lenalidomide within 3 months of initiation. Responses were noted in 17 patients (55%). The median time to response was 1.8 months (range, 0.4 - 31). All responses were International Working Group for Myelofibrosis Research and Treatment-defined clinical improvement in palpable spleen size. One spleen responder also met the criteria for clinical improvement in hemoglobin. The response rate was higher (73%) among patients who did not require early dose interruption than among those who required early interruption (45%). Improvements in bone marrow fibrosis and serial reductions in lactate dehydrogenase >50% were noted in 17% and 50% of evaluable responders, respectively. Alternate approaches such as sequential dosing need to be evaluated when considering novel combination strategies for myelofibrosis. This trial was registered with clinicaltrials.gov identifier: NCT01375140.


Optimally coordinated traffic diversion by statistical physics.
Road accidents or maintenance often lead to the blockage of roads, causing severe traffic congestion. Diverted routes after road blockage are often decided individually and have no coordination. Here, we employ the cavity approach in statistical physics to obtain both analytical results and optimization algorithms to optimally divert and coordinate individual vehicle routes after road blockage. Depending on the number and the location of the blocked roads, we found that there can be a significant change in traveling path of individual vehicles, and a large increase in the average traveling distance and cost. Interestingly, traveling distance decreases but traveling cost increases for some instances of diverted traffic. By comparing networks with different topology and connectivity, we observe that the number of alternative routes plays a crucial role in suppressing the increase in traveling cost after road blockage. We tested our algorithm using the England highway network and found that coordinated diversion can suppress the increase in traveling cost by as much as 66% in the scenarios studied. These results reveal the advantages brought by the optimally coordinated traffic diversion after road blockage.


Country of birth is associated with very low food security among Mexican American older adults living in colonias along the south Texas border with Mexico.
The availability of an adequate household food supply is critical for the older population. There is little work that has examined food security and the influence of nativity on food security among older Mexican Americans living along the Texas-Mexico border. Using data from 140 older women (age ≥ 50 y) who participated in the 2009 Colonia Household and Community Food Resource Assessment (C-HCFRA), we examined demographic characteristics, health characteristics, food access and mobility, federal and community food and nutrition assistance programs, quality of food environment, food security, eating behaviors, and alternative food sources. 77% of participants experienced food insecurity, with 68% experiencing very low food security. Very low food security was associated with being born in Mexico, adjusting for household income and food assistance program participation. This article provides compelling evidence for enhanced research efforts that will better understand coping strategies and the use of food and nutrition assistance programs for reducing hardship associated with very low food security among older U.S.- and Mexico-born Mexican American women.


Allelopathic Mechanisms in Camellia oleifera-Arachis hypogaea L. Intercropping.
Tree-crop intercropping is of great significance in food security, land protection, and sustainable agriculture. However, the mechanisms of allelopathy between plant species during intercropping are still limited. This study focuses on the allelopathic effects in the intercropping between Camellia oleifera and Arachis hypogaea L. in southern China. We use different parts of the C. oleifera extract to evaluate their impact on peanut seed germination. The results showed that it has inhibitory effects on peanut germination and growth, with the fruit shell having the strongest inhibitory effect. Three main allelopathic substances affecting A. hypogaea germination and growth were identified using gas chromatography-mass spectrometry (GC-MS) analysis, namely, 2,4-di-tert-butylphenol, hexanal, and benzaldehyde. Transcriptomics and metabolomics analyses revealed their effects on glutathione metabolism pathways and specific gene expression. In summary, this study reveals the allelopathic interaction mechanism between C. oleifera and A. hypogaea, which helps to better understand the role of allelopathy in intercropping practices between trees and crops.


Fecal-Derived Phenol Induces Egg-Laying Aversion in Drosophila.
Feces is an abundant, rich source of energy, utilized by a myriad of organisms, not least by members of the order Diptera, i.e., flies. How Drosophila melanogaster reacts to fecal matter remains unclear. Here, we examined oviposition behavior toward a range of fecal samples from mammals native to the putative Southeast African homeland of the fly. We show that D. melanogaster display a strong oviposition aversion toward feces from carnivorous mammals but indifference or even attraction toward herbivore dung. We identify a set of four predictor volatiles, which can be used to differentiate fecal from non-fecal matter, as well as separate carnivore from herbivore feces. Of these volatiles, phenol-indicative of carnivore feces-confers egg-laying aversion and is detected by a single class of sensory neurons expressing Or46a. The Or46a-expressing neurons are necessary and sufficient for oviposition site aversion. We further demonstrate that carnivore feces-unlike herbivore dung-contain a high rate of pathogenic bacteria taxa. These harmful bacteria produce phenol from L-tyrosine, an amino acid specifically enriched in high protein diets, such as consumed by carnivores. Finally, we demonstrate that carnivore feces, as well as phenol, is also avoided by a ball-rolling species of dung beetle, suggesting that phenol is a widespread avoidance signal because of its association with pathogenic bacteria.


Free fatty acids and skeletal muscle insulin resistance.
Acute exposure to fatty acids causes insulin resistance in muscle, and excess dietary lipid and obesity are also strongly associated with muscle insulin resistance. Relevant mechanisms, however, are still not fully elucidated. Here we examine the latest evidence as to why lipids might accumulate in muscle and the possible mechanisms for lipid-induced insulin resistance. Muscle lipid metabolites such as long chain fatty acid coenzyme As, diacylglycerol and ceramides may impair insulin signalling directly. Crosstalk between inflammatory signalling pathways and insulin signalling pathways, mitochondrial dysfunction and oxidative stress have also been put forward as major contributors to the development or maintenance of lipid-induced insulin resistance in muscle. Several animal models with gene deletions in pathways of fatty acid synthesis and storage also show increased metabolic rate, reduced intramuscular lipid storage and improved insulin action when challenged with a high lipid load. Studies in genetic and dietary obese animal models, genetically modified animals and humans with obesity or type 2 diabetes suggest plausible mechanisms for effects of fatty acids, lipid metabolites, inflammatory pathways and mitochondrial dysfunction on insulin action in muscle. Many of these mechanisms, however, have been demonstrated in situations in which lipid accumulation (obesity) already exists. Whether the initial events leading to muscle insulin resistance are direct effects of fatty acids in muscle or are secondary to lipid accumulation in adipose tissue or liver remains to be clarified.


Migraine improvement during short lasting ketogenesis: a proof-of-concept study.
Ketogenesis is a physiological phenomenon due to starvation or a ketogenic diet (KD), a drastic restricted carbohydrate dietary regimen that induces lipid metabolism and ketone body synthesis. Two patients whose migraines disappeared only during, and not outside, cycles of very-low-calorie KD performed to reduce their weight were recently observed. To confirm our observation, in a dietitian clinical setting two parallel groups of migraineurs, one receiving a 1-month very-low-calorie KD prescription followed by a 5-month standard low-calorie diet (SD) and the other a 6-month SD, were followed. Ninety-six overweight female migraineurs were enrolled in a diet clinic and blindly received a KD (n = 45) or an SD (n = 51) prescription. Mean monthly attack frequency, number of days with headaches and tablet intake were assessed before and 1, 2, 3 and 6 months after diet initiation. In the KD group, the baseline attack frequency (2.9 attacks per month), number of days with headaches (5.11 days per month) and tablet intake (4.91 doses per month) were significantly reduced after the first month of diet (respectively 0.71, 0.91, 0.51; overall, KD versus baseline, P < 0.0001). During the transition period (first versus second month), the KD group showed a transient worsening of each clinical headache variable (respectively 2.60, 3.60, 3.07), despite being improved compared with baseline, with continuous improvement up to month 6 (respectively 2.16, 2.78, 3.71). In the SD group, significant decreases in the number of days with headaches and tablet intake were observed only from month 3 (P < 0.0001), and in attack frequency at month 6 (P < 0.0001). The underlying mechanisms of KD efficacy could be related to its ability to enhance mitochondrial energy metabolism and counteract neural inflammation.


Replicated, replicable and relevant-target engagement and pharmacological experimentation in the 21st century.
A pharmacological experiment is typically conducted to: i) test or expand a hypothesis regarding the potential role of a target in the mechanism(s) underlying a disease state using an existing drug or tool compound in normal and/or diseased tissue or animals; or ii) characterize and optimize a new chemical entity (NCE) targeted to modulate a specific disease-associated target to restore homeostasis as a potential drug candidate. Hypothesis testing necessitates an intellectually rigorous, null hypothesis approach that is distinct from a high throughput fishing expedition in search of a hypothesis. In conducting an experiment, the protocol should be transparently defined along with its powering, design, appropriate statistical analysis and consideration of the anticipated outcome (s) before it is initiated. Compound-target interactions often involve the direct study of phenotype(s) unique to the target at the cell, tissue or animal/human level. However, in vivo studies are often compromised by a lack of sufficient information on the compound pharmacokinetics necessary to ensure target engagement and also by the context-free analysis of ubiquitous cellular signaling pathways downstream from the target. The use of single tool compounds/drugs at one concentration in engineered cell lines frequently results in reductionistic data that have no physiologically relevance. This overview, focused on trends in the peer-reviewed literature, discusses the execution and reporting of experiments and the criteria recommended for the physiologically-relevant assessment of target engagement to identify viable new drug targets and facilitate the advancement of translational studies.


Multiple Skip Incisions Versus Single Long Incision for Single-stage Basilic Transposition Arteriovenous Fistula: A Cohort Study.
Basilic vein transposition via single long incision is a renowned technique despite its known wound-related complications. Contrary to that, multiple skip incisions technique is thought to have relatively lower wound-related complications. But to the best of our knowledge, these 2 techniques have never been formally compared. Therefore, we conducted this study to compare both. This was a retrospective cohort study. Patients who underwent basilic vein transposition arteriovenous fistula (AVF) from January 2011 till May 2016 at Aga Khan University Hospital, Pakistan were eligible for inclusion in the study. Study population was divided into 2 groups; one group comprising of patients who underwent fistula formation through single long incision and the other group had the procedure carried out via multiple skip incisions. Wound-related complications including wound infection and dehiscence, fistula maturation time, duration of surgery, and primary patency at a follow-up of 12 months were recorded. Both the groups were comparable regarding baseline variables. Incidence proportion of wound infection, hematoma, and dehiscence was higher in long incision group; however, it was statistically insignificant. Primary patency at 12 months in skip versus long incision group was 73.0% vs. 69.7% (P-value: 0.62). The mean maturation time for fistula was 42.8 ± 9.5 days and 44.3 ± 10.4 days in skip and long incision group, respectively (P-value:0.31). Duration of surgery was comparable in both. Although skip technique does not have significant benefit over long incision technique based on these results, but it is a valid alternative. Randomized control trial is required to better differentiate between these two.


Releasing the "GENI": integrating authentic microbial genomics research into the classroom through GENI-ACT.
The integration of genomics research into the undergraduate biology curriculum provides students with the opportunity to become familiar with bioinformatics tools and answer original research questions. Our purpose with this research project was to upscale the research experience through integration with classroom experience giving students access to authentic research projects. Students annotated 60 predicted ABC genes of Methanothermobacter thermautotrophicus and Methanobacterium sp. SWAN-1, and they were required to present a research poster to demonstrate their understanding of the project. During this research project a number of tests, assessments and surveys were conducted to assess familiarity with technical and conceptual understanding of genome annotation, satisfaction with annotation instruction, gain in bioinformatics research skills, scientific communications skills and increased student interest in research. We found that students gained significant skills in bioinformatics, specifically genome annotation skills and also gained confidence in their abilities to carry out scientific research. As a result of this authentic undergraduate research experience under-represented students were motivated to pursue future careers in STEM fields.


AC-coupled front-end for biopotential measurements.
AC coupling is essential in biopotential measurements. Electrode offset potentials can be several orders of magnitude larger than the amplitudes of the biological signals of interest, thus limiting the admissible gain of a dc-coupled front end to prevent amplifier saturation. A high-gain input stage needs ac input coupling. This can be achieved by series capacitors, but in order to provide a bias path, grounded resistors are usually included, which degrade the common mode rejection ratio (CMRR). This paper proposes a novel balanced input ac-coupling network that provides a bias path without any connection to ground, thus resulting in a high CMRR. The circuit being passive, it does not limit the differential dc input voltage. Furthermore, differential signals are ac coupled, whereas common-mode voltages are dc coupled, thus allowing the closed-loop control of the dc common mode voltage by means of a driven-right-leg circuit. This makes the circuit compatible with common-mode dc shifting strategies intended for single-supply biopotential amplifiers. The proposed circuit allows the implementation of high-gain biopotential amplifiers with a reduced number of parts, thus resulting in low power consumption. An electrocardiogram amplifier built according to the proposed design achieves a CMRR of 123 dB at 50 Hz.


Simultaneous measurement of intracellular pH and Ca2+ in insulin-secreting cells by spectral imaging microscopy.
Described is a microscopic spectral imaging approach to monitor pH and Ca2+ simultaneously from combined spectra of multiple ion indicators. Emitted light from a cell is focused onto a grating spectrograph and spectra are imaged with a cooled charge-coupled device camera. The combined spectral output of fura 2 and SNARF-1 was analyzed to follow changes in intracellular Ca2+ concentration ([Ca2+]i) and intracellular pH (pHi) simultaneously and to correct the Ca2+ signal for concurrent changes in pHi. Responses of individual hamster insulinoma (HIT-T15) cells to effectors of ion homeostasis were heterogeneous. Treatment with NH4Cl increased pHi and transiently increased [Ca2+]i. Removal of NH4Cl induced cytosolic acidification concomitant with either no change or sustained increases in [Ca2-]i. Glucose treatment generally resulted in rapid and sustained increases in both [Ca2+]i and pHi but also heterogeneous pHi and [Ca2+]i responses. Corrections of the fura 2 signal for pH were important for following Ca2+ transitions elicited by NH4Cl but were less important for glucose-induced responses. The spectral imaging microscope provides a sensitive method for simultaneous measurements of pHi and [Ca2+]i in single cells.


Iterated crowdsourcing dilemma game.
The Internet has enabled the emergence of collective problem solving, also known as crowdsourcing, as a viable option for solving complex tasks. However, the openness of crowdsourcing presents a challenge because solutions obtained by it can be sabotaged, stolen, and manipulated at a low cost for the attacker. We extend a previously proposed crowdsourcing dilemma game to an iterated game to address this question. We enumerate pure evolutionarily stable strategies within the class of so-called reactive strategies, i.e., those depending on the last action of the opponent. Among the 4096 possible reactive strategies, we find 16 strategies each of which is stable in some parameter regions. Repeated encounters of the players can improve social welfare when the damage inflicted by an attack and the cost of attack are both small. Under the current framework, repeated interactions do not really ameliorate the crowdsourcing dilemma in a majority of the parameter space.


Mycobacterium tuberculosis heat shock fusion protein enhances class I MHC cross-processing and -presentation by B lymphocytes.
Exogenous heat shock protein (HSP):peptide complexes are processed for cross-presentation of HSP-chaperoned peptides on class I MHC (MHC-I) molecules. Fusion proteins containing HSP and Ag sequences facilitate MHC-I cross-presentation of linked antigenic epitopes. Processing of HSP-associated Ag has been attributed to dendritic cells and macrophages. We now provide the first evidence to show processing of HSP-associated Ag for MHC-I cross-presentation by B lymphocytes. Fusion of OVA sequence (rOVA, containing OVA(230-359) sequence) to Mycobacterium tuberculosis HSP70 greatly enhanced rOVA processing and MHC-I cross-presentation of OVA(257-264):K(b) complexes by B cells. Enhanced processing was dependent on linkage of rOVA sequence to HSP70. M. tuberculosis HSP70-OVA fusion protein enhanced cross-processing by a CD91-dependent process that was independent of TLR4 and MyD88. The enhancement occurred through a post-Golgi, proteasome-independent mechanism. These results indicate that HSPs enhance delivery and cross-processing of HSP-linked Ag by B cells, which could provide a novel contribution to the generation of CD8(+) T cell responses. HSP fusion proteins have potential advantages for use in vaccines to enhance priming of CD8(+) T cell responses.


Of cardiovascular illness and diversity of biological response.
Noise in gene expression (stochastic variation in the composition of the transcriptome in response to stimuli) may play an important role in maintaining robustness and flexibility, which ensure the stability of normal physiology and provide adaptability to environmental changes for the living system. Broad-based technologies have allowed us to study with unprecedented accuracy the molecular profiles of various states of health and cardiovascular disease. In doing so, we have observed a correlation between the degree of variation in gene expression and the state of health. Specifically, the stochastic variation in gene expression in response to environmental and physiological factors is found in healthy mice, and tends to disappear in mice with advanced disease states. Although further evidence is needed to draw a solid conclusion with respect to the significance of decreased transcriptional noise in the disease state as a whole, it is tantalizing to introduce the concept that stochasticity may be linked to the organism's adaptability to a changing environment, and the "quiet" states of gene expression may indicate the loss of diversity in the organism's response.


The personal assistant--a new option for home care.
One agency has tapped middle-aged women as resources for home care aides--specifically as personal assistants. This approach has fine results and may prove a good model for addressing the normally high-turnover rate this position accrues.


Intestinal barrier disruption and dysregulated mucosal immunity contribute to kidney fibrosis in chronic kidney disease.
Emerging evidence suggests that intestinal dysbiosis is associated with diverse pathological processes. In this study we demonstrated intestinal barrier disruption and aberrant mucosal immunity in 5/6 nephrectomized mice and the effect of probiotics on chronic kidney disease (CKD). CKD was induced in 6-week-old mice by 5/6 nephrectomy. They were fed a lactobacilli mixture for 8 weeks. Serum, urine and stool samples were collected for renal function assessments and gut microbiome analyses. Gut permeability, colon heat shock protein 70 (HSP70) and colon epithelial integrity were evaluated and cytokine levels in colon and kidney were measured. Colon leukocytes were analyzed by flow cytometry and bone marrow-derived cells were cocultured with lactobacilli mixture. In CKD mice, 'leaky gut' was accompanied by decreased colon HSP70 and claudin-1 expression, whereas it increased pore-forming claudin-2 expression and apoptosis. Although the percentage of regulatory T cells did not differ between CKD and control mice, cytokine expression and the ratio of CX3CR1intermediate:CX3CR1high pro-inflammatory/resident macrophages increased in the colon of CKD mice. Orally administered lactobacilli partially mitigated the CKD-induced 'leaky gut'; restored colon epithelial HSP70, claudin-1 and claudin-2 expression and decreased apoptosis. Probiotic treatment also restored the CX3CR1intermediate:CX3CR1high macrophage ratio and increased circular dichroism (CD)103+CD11c+ regulatory dendritic cells in the colon. These changes suppressed systemic inflammation and kidney fibrosis. Our results suggest that intestinal dysbiosis-associated gut barrier disruption and aberrant mucosal immunity are important for the systemic inflammation and progressive fibrosis of CKD. Targeting the intestine might provide novel therapeutic opportunities for CKD.


Glenohumeral dysplasia changes after tendon transfer surgery in children with birth brachial plexus injuries.
This study hypothesizes that children with glenohumeral dysplasia secondary to birth brachial plexopathy treated with tendon transfer surgery at a younger age will show greater radiographic improvement than those treated at an older age. Twenty-six children treated with latissimus dorsi and teres major tendon transfer had preoperative and 1 year postoperative computed tomography (CT) scans at an average follow-up of 17 months (10 to 46 mo). Average age at surgery was 44 months (10 to 134 mo). CT scans were measured for glenoid version and percent humeral head anterior to the midscapular line (PHHA). Shoulders were classified as dislocated (PHHA 0%), subluxed (PHHA 1% to 35%), or normal positioning (>35%). Two age groups were compared: 24 months or less at the time of surgery (n=11); and greater than 2 years (n=15). Concomitant surgical techniques were also evaluated. For the 11 children treated at 24 months of age or less, PHHA averaged 13% preoperatively (range: 0% to 54%) and postoperatively 42% (range: 25% to 51%); glenoid version averaged -25 degrees preoperatively (range: -36 to -11 degrees) and postoperatively -14 degrees (range: -31 to -2 degrees); and preoperatively 5 shoulders were dislocated, 5 subluxed, and 1 normal; whereas postoperatively 0 shoulders were dislocated, 2 subluxed, and 9 normally positioned. For the 15 children treated at greater than 2 years of age, PHHA averaged 30% preoperatively (range: 0% to 53%) and postoperatively 33% (range: 0% to 57%); glenoid version averaged -17 degrees preoperatively (range: -27 to -4 degrees) and postoperatively -16 degrees (range: -31 to -2 degrees); and preoperatively 2 shoulders were dislocated, 6 subluxed, and 7 normal; whereas postoperatively 2 shoulders were dislocated, 5 subluxed, and 8 normally positioned. Eleven children treated at 24 months of age or less had significantly greater improvement in the CT scan radiographic measurements of glenohumeral dysplasia, than the 15 children treated at greater than 2 years of age. The effect of age had greater correlation with improvement than open reduction. For children undergoing tendon transfer for lack of active external rotation due to brachial plexus birth injury, improvement in glenohumeral dysplasia can be achieved if the surgery is performed before 2 years of age. Level IV, case controlled series.


In vitro digestibility and glycemic response of potato starch is related to granule size and degree of gelatinization.
Starch granule microstructure affects the digestion of starch and its nutritional impact; however, the exact relationship between both factors is not clear. This study reports quantitative relationships between granule size (length and polygonal area), degree of gelatinization (DG), in vitro digestibility (by enzymatic methods), and glycemic response of potato starch granules gelatinized to various extents by heating at several constant temperatures in the range of 55 to 65 degrees C. DG measured by differential scanning calorimetry was closely related with heating temperature (R(2)= 0.997), size parameters of granules (measured by image analysis), in vitro digestion, and in vivo glycemic response (R(2) of adjusted models > 0.9); shape parameters of granules (measured by image analysis) were not related with DG. Results demonstrate that DG of starch strongly affects its digestibility in vitro, and may influence the postpandrial glycemic response. Future studies should be performed to investigate the effect of potato starch gelatinization on the nutritional impact at other temperatures and in more complex matrices.


Research Advance in Intestinal Mucosal Barrier and Pathogenesis of Crohn's Disease.
To date, the etiology and pathogenesis of Crohn's disease (CD) have not been fully elucidated. It is widely accepted that genetic, immune, and environment factors are closely related to the development of CD. As an important defensive line for human body against the environment, intestinal mucosa is able to protect the homeostasis of gut bacteria and alleviate the intestinal inflammatory and immune response. It is evident that the dysfunction of intestinal mucosa barriers plays a crucial role in CD initiation and development. Yet researches are insufficient on intestinal mucosal barrier's action in the prevention of CD onset. This article summarizes the research advances about the correlations between the disorders of intestinal mucosal barriers and CD.


Review article: leaving the emergency department without being seen.
Patients who leave the ED without being seen (LWBS) are unlikely to be satisfied with the quality of the service provided and might be at risk from conditions that have not been assessed or treated. We therefore examined the available research literature to inform the following questions: (i) In patients who attend for ED care, what factors are associated with the decision to LWBS? (ii) In patients who attend for ED care, are there adverse health outcomes associated with the decision to LWBS? (iii) Which interventions have been used to try to reduce the number of patients who attend for ED care and LWBS? From the available literature, there was insufficient evidence to draw firm conclusions; however, the literature does suggest that patients who LWBS have conditions of lower urgency and lower acuity, are more likely to be male and younger, and are likely to identify prolonged waiting times as a central concern. LWBS patients generally have very low rates of subsequent admission, and reports of serious adverse events are rare. Many LWBS patients go on to seek alternative medical attention, and they might have higher rates of ongoing symptoms at follow-up. Further research is recommended to include comprehensive cohort or well-designed case-control studies. These studies should assess a wide range of related factors, including patient, hospital and other relevant factors. They should compare outcomes for groups of LWBS patients with those who wait and should include cross-sectoral data mapping to truly detect re-attendance and admission rates.


Effect of ultrasonic waves on the heat resistance of Bacillus cereus and Bacillus licheniformis spores.
Heat resistance of Bacillus cereus and Bacillus licheniformis spores in quarter-strength Ringer solution decreases markedly after ultrasonic treatments which are unable to kill a significant proportion of the spore population. This effect does not seem to be caused by a loss of Ca(2+) or dipicolinic acid. The use of ultrasonics to eliminate vegetative cells or to break aggregates in Bacillus spore suspensions to be used subsequently in heat resistance experiments appears to be unadvisable.


Post-Treatment/Pre-operative PET Response Is Not an Independent Predictor of Outcomes for Patients With Gastric and GEJ Adenocarcinoma.
To determine whether changes in positron emission tomography (PET) avidity correlated with histologic response and were independently associated with outcome. The implications of metabolic response to neoadjuvant therapy as measured by repeat PET imaging remain ill-defined for patients with gastric and gastroesophageal junction (GEJ) cancers. We identified patients with gastric and GEJ adenocarcinoma who were evaluated with PET imaging before and following neoadjuvant treatment, and subsequently underwent curative resections. Spearman rank correlation and Cox proportional hazards regression were used to evaluate standardized uptake value (SUV) and histologic response, pathologic parameters, and disease-specific survival (DSS). From 2002 to 2013, 192 patients met our inclusion criteria. The median SUVmax response was 57.3% (range: -110% to 100%) for patients with GEJ cancers, with a corresponding median pathologic treatment response of 80% (range: 0% to 100%). The median SUVmax response was 32.5% (-230% to 100%) for patients with gastric cancers, with a corresponding median pathologic treatment response of 35% (range: 0% to 100%). The Spearman correlation between SUVmax response and histologic response was significant for patients with GEJ (rho = 0.19, P = 0.04) and gastric (rho = 0.44, P < 0.0001) cancers. For patients with GEJ (P <0.0001 to 0.046) and gastric cancers (P = 0.0003 to 0.016), histopathologic response and tumor staging predicted DSS. SUVmax response failed to demonstrate a relationship with DSS when entered into multivariable models containing conventional pathologic variables. Following completion of neoadjuvant therapy for gastric and GEJ adenocarcinoma, histopathologic staging remains the best predictor of outcome. Repeat post-treatment/preoperative PET imaging for the purpose of prognostication is of limited value.


Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats.
Iron (Fe) deficiency anemia is a global health concern and Fe fortification and supplementation are common corrective strategies. Fe is essential not only for the human host but also for nearly all gut bacteria. We studied the impact of Fe deficiency and Fe repletion on the gut microbiota in rats. Weanling rats were fed an Fe-deficient diet for 24 d and then repleted for 13 d with FeSO₄ (n = 15) or electrolytic Fe (n = 14) at 10 and 20 mg Fe · kg diet⁻¹. In addition, one group of rats (n = 8) received the Fe-deficient diet and one group (n = 3) received a Fe-sufficient control diet for all 37 d. Fecal samples were collected at baseline and after the depletion and repletion periods, and colonic tissues were examined histologically. Microbial metabolite composition in cecal water was measured and fecal samples were analyzed for microbial composition with temporal temperature gradient gel electrophoresis and qPCR. Compared to Fe-sufficient rats, Fe-deficient rats had significantly lower concentrations of cecal butyrate (-87%) and propionate (-72%) and the abundance of dominant species was strongly modified, including greater numbers of lactobacilli and Enterobacteriaceae and a large significant decrease of the Roseburia spp./E. rectale group, a major butyrate producer. Repletion with 20 mg FeSO₄ · kg diet⁻¹ significantly increased cecal butyrate concentrations and partially restored bacterial populations compared to Fe-deficient rats at endpoint. The effects on the gut microbiota were stronger in rats repleted with FeSO₄ than in rats repleted with electrolytic Fe, suggesting ferrous Fe may be more available for utilization by the gut microbiota than elemental Fe. Repletion with FeSO₄ significantly increased neutrophilic infiltration of the colonic mucosa compared to Fe-deficient rats. In conclusion, Fe depletion and repletion strongly affect the composition and metabolic activity of rat gut microbiota.


Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs.
Effect sizes are the most important outcome of empirical studies. Most articles on effect sizes highlight their importance to communicate the practical significance of results. For scientists themselves, effect sizes are most useful because they facilitate cumulative science. Effect sizes can be used to determine the sample size for follow-up studies, or examining effects across studies. This article aims to provide a practical primer on how to calculate and report effect sizes for t-tests and ANOVA's such that effect sizes can be used in a-priori power analyses and meta-analyses. Whereas many articles about effect sizes focus on between-subjects designs and address within-subjects designs only briefly, I provide a detailed overview of the similarities and differences between within- and between-subjects designs. I suggest that some research questions in experimental psychology examine inherently intra-individual effects, which makes effect sizes that incorporate the correlation between measures the best summary of the results. Finally, a supplementary spreadsheet is provided to make it as easy as possible for researchers to incorporate effect size calculations into their workflow.


Screening for Depression in Cardiovascular Patients in Albania: Findings from the Country Check-Up Program.
This is a retrospective study conducted in Vlora from January 2016 to April 2017 and the aim was to report the prevalence of depression in cardiovascular (CVD) patients. Depression assessment was done using the Patient Health Questionnaire (PHQ)-9 (PHQ-9). Data were derived from the patient records and the standard recommended cut-off point of PHQ-9 ≥ 10 was used. In total, data of 300 patients were analyzed. Depressive symptoms (PHQ-9 ≥ 10) were observed at 6% of the participants. Trouble falling asleep or staying asleep or sleeping too much, feeling tired or having little energy and having little interest or pleasure in doing things were the most common symptoms reported. In multivariate analysis, only family status showed statistical significance. Unmarried (mean rank = 207.22) are more likely to have moderate or severe depression level (OR 3.529; C.I. 95% 1.017-12.238). Future research should focus on the needed actions after depression screening (i.e. referral, treatment etc.).


Tumor-growth-promoting cyclooxygenase-2 prostaglandin E2 pathway provides medulloblastoma therapeutic targets.
Prostaglandin E(2) (PGE(2)) has been shown to play important roles in several aspects of tumor development and progression. PGE(2) is synthesized from arachidonic acid by cyclooxygenases (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4). In this study, we show for the first time that medulloblastoma (MB), the most common malignant childhood brain tumor, expresses high levels of COX-2, microsomal prostaglandin E synthase-1, and EP(1) through EP(4) and secretes PGE(2). PGE(2) and the EP(2) receptor agonist butaprost stimulated MB cell proliferation. Treatment of MB cells with COX inhibitors suppressed PGE(2) production and induced caspase-dependent apoptosis. Similarly, specific COX-2 silencing by small interfering RNA inhibited MB cell growth. EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth. Administration of COX inhibitors at clinically achievable nontoxic concentrations significantly inhibited growth of established human MB xenografts. Apoptosis was increased, proliferation was reduced, and angiogenesis was inhibited in MBs treated with COX inhibitors. This study suggests that PGE(2) is important for MB growth and that therapies targeting the prostanoid metabolic pathway are potentially beneficial and should be tested in clinical settings for treatment of children with MB.


[Some results of the trematode fauna investigation in the freshwater mollusk Melanopsis praemorsa (L.) from water bodies of Azerbaijan. 2. New species of virgulate cercaria].
Two closely related forms of virgulate cercaria, Cercaria agstaphensis 9 and C. agstaphensis 10 of the superfamily Lecithodendroidea from water bodies of Azerbaijan are described. Morphological data, including chaetotaxic traits, fugures, and differential diagnoses are provided. Descriptions of armature, glandular apparatus, excretory and digestive systems, inclusions of parenchyma, and other structures of the cercaria, characteristic for the superfamily, are presented.


Progressive resistance training and mobility-related function in young people with cerebral palsy: a randomized controlled trial.
The aim of this study was to investigate whether individualized resistance training improves the physical mobility of young people with cerebral palsy (CP). Forty-eight participants with spastic diplegic CP (26 males, 22 females; mean age 18y 1mo, SD 1y 11mo) classified as level II or III on the Gross Motor Function Classification System were allocated randomly to progressive resistance training or usual-care control. Resistance training was completed twice weekly for 12 weeks at a community gymnasium under the supervision of a physiotherapist. Exercises were based on instrumented gait analysis and targeted muscles contributing to walking difficulties. Outcomes at 12 weeks and 24 weeks included objective measures of mobility (6-min walk test, instrumented gait analysis, and Gross Motor Function Measure dimensions D and E), participant-rated measures of mobility (Functional Mobility Scale and Functional Assessment Questionnaire), and muscle performance. The strength of targeted muscles increased by 27% (95% CI 8-46%) compared with control group. There were no between-group differences in any objective measure of mobility at 12 weeks (6-min walk test: mean difference 0.1m; 95% CI -21 to 21m) or at 24 weeks. Participant-rated mobility improved (Functional Mobility Scale at 5m: mean 0.6 units; 95% CI 0.1-1.1 units; Functional Assessment Questionnaire: 0.8 units; 95% CI 0.1-1.6 units) compared with control group at 12 weeks. Individualized progressive resistance training increased strength in adolescents and young adults with spastic diplegic CP. Despite participant-rated benefits, the increased strength did not result in objective improvements in mobility.


Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris.
Psoriasis is a chronic inflammatory skin disease characterized by dysregulated keratinocyte differentiation, but oxidative stress also plays an important role in the pathogenesis of this disease. Here, we examined the effect of cannabidiol (CBD), a phytocannabinoid with antioxidant and anti-inflammatory properties, on the redox balance and phospholipid metabolism in UVA/UVB-irradiated keratinocytes isolated from the skin of psoriatic patients or healthy volunteers. CBD accumulates mainly in membrane keratinocytes, especially from patients with psoriasis. This phytocannabinoid reduces the redox imbalance observed in the UV-irradiated keratinocytes of healthy subjects. It does so by decreasing reactive oxygen species (ROS) generation, increasing the Trx-dependent system efficiency, and increasing vitamin A and E levels. Consequently, a reduction in lipid peroxidation products, such as 8-isoprostanes and 4-hydroxynonenal, was also observed. Moreover, CBD modifies redox balance and lipid peroxidation in psoriatic patient keratinocytes following UV-irradiation. Interestingly, these changes are largely in the opposite direction to the case of keratinocytes from healthy subjects. CBD also regulates metabolic changes by modulating the endocannabinoid system that is disturbed by psoriasis development and UV irradiation. We observed a decrease in anandamide level in the UV-irradiated keratinocytes of healthy controls following CBD treatment, while in keratinocytes from patients treated with CBD, anandamide level was increased. However, the level of palmitoylethanolamide (PEA) was decreased in both groups treated with CBD. We further demonstrate that CBD increases CB1 receptor expression, primarily in the keratinocytes of patients, and increases CB2 receptor expression in both the psoriatic and control groups. However, CBD decreases CB2 receptor expression in UV-irradiated keratinocytes taken from patients. The UV- and psoriasis-induced activity of transmembrane transporters (Multidrug-Resistance (MDR) and breast cancer resistance protein (BCRP)) is normalized after CBD treatment. We conclude that CBD partially reduces oxidative stress in the keratinocytes of healthy individuals, while showing a tendency to increase the oxidative and inflammatory state in the keratinocytes of patients with psoriasis, especially following UV-irradiation.


Experimental constraints on the theory of high-tc superconductivity.
Analysis of the many experiments on high-temperature superconductivity indicate several essential aspects of any theory. The conductivity and other transport properties as a function of disorder, temperature, and frequency point to a non-Fermi liquid-like behavior, whereas photoemission experiments and magnetic properties indicate the presence of a Fermi surface in momentum space. To reconcile this apparent contradiction, a new type of electron liquid, called a Luttinger liquid, has been postulated, and the present article aims to show the need for this postulate. Theory and experiment indicate that the suitable phenomenological electronic structure model of the CuO layers is that of the one-band Hubbard model. It is also argued that experiment clearly indicates that interlayer interactions strongly affect the superconducting transition temperature, T(c), consistent with the fact that no theoretical calculations on two-dimensional Hubbard models have resulted in the prediction of high transition temperatures, and that anyon models are not favored by experiment.


Histology Shift in Esophageal Cancer Between Biopsies and Resections After Neoadjuvant Therapy: A Pilot Study.
Preoperative neoadjuvant therapy followed by resection is the mainstay treatment for locally advanced esophageal adenocarcinoma. We recently observed the histology shift from predominant esophageal adenocarcinoma in the biopsy to neuroendocrine neoplasm with or without adenocarcinoma in the post-treatment resection. The underlying mechanism of this finding is uncertain, and there is limited information in the literature. A total of 11 patients were identified: 10 patients received presurgical chemoradiation and 1 with chemotherapy. All biopsies were diagnosed with adenocarcinoma. When neuroendocrine immunomarkers were retrospectively performed on 5 biopsies, 2 showed focal positivity, although the classic neuroendocrine morphology was not readily appreciated. All resections contained neuroendocrine neoplasm, including 8 of well-differentiated type and 3 of neuroendocrine carcinomas. Two post-treatment esophagectomies consisted of neuroendocrine neoplasm only without residual adenocarcinoma. Upon follow-up, 8 patients died of the disease (median survival = 26 months), and 3 patients were alive after a median follow-up of 14 months. The overall median survival time was better than the reported esophageal neuroendocrine carcinoma (15 months). The 5-year observed survival rate was 11.3%, which was lower than the Surveillance, Epidemiology, and End Results 5-year survival rate of adenocarcinoma (21.8%). We reported a small series of esophageal adenocarcinoma that showed histology shift between biopsy and esophagectomy after neoadjuvant therapy. Our limited data suggest that prognosis of this group is different than the conventional adenocarcinoma. Awareness of this morphological change reminds pathologists to examine the biopsy specimens thoroughly, because recognition of neuroendocrine neoplasm, especially high-grade neuroendocrine component, might potentially affect pre- and post-surgical regimens.


[The influence of zoledronic acid on proliferation, migration and apoptosis of fibroblasts].
Bisphosphonates are commonly used to treat bone-derived malignant tumors currently. In recent years, with the widespread use of these drugs, reports on the difficulty of wound healing (DWH) increase remarkably. However, the mechanism is still unclear. The soft tissue injury was suspected to cause DWH in many recent reports. This experiment was designed to explore the influence of zoledronic acid on fibroblast, and investigate the possible mechanisms leading to DWH. NIH 3T3 fibroblasts were routinely cultured in vitro. The influence of zoledronic acid on apoptosis, proliferation and migration of fibroblast were tested with flow cytometry, MTT and cell migration assay, respectively. The results of each experimental group were compared with the control group using SPSS 17.0 software package. At a concentration of 5-50 μmol/L, zoledronic acid could dose-dependently inhibit the activity of fibroblast proliferation and migration, and up-regulate apoptosis with significant difference (P<0.05). Zoledronic acid can up-regulate cell apoptosis, inhibit proliferation and migration of fibroblast, suggesting that soft tissue impairment might contribute to the occurrence of DWH.


Wound healing process in post-bariatric patients: an experimental evaluation.
Bariatric surgery is the most effective treatment for morbid obesity. Despite this, side effects are recorded. One of them is redundant skin hanging from the patients' body causing both aesthetical and functional deformities. They can only be corrected with body contouring surgery, whose wound complication rate is very high in previously obese population. Despite several hypotheses, an adequate explanation is still awaited. The aim of our study was to evaluate the wound healing process in post-bariatric patients. Seven patients, six women and one man, were enrolled. They all were nonsmokers and nondiabetic. They all underwent biliopancreatic diversion (BPD). After 36 months, abdominoplasty was performed. Biochemical parameters before and after bariatric surgery were evaluated. The content of total protein and hydroxyproline was assessed in multiple scar biopsies before and after BPD. Abdominoplasty horizontal scar skin samples were subjected to histological evaluation with Weigert-Van Gieson stain for elastic fibers and connectivum. All biochemical parameters analyzed were reduced post-BPD compared to the preoperative period. Tissue proteins were significantly reduced after BPD both in their totality and as hydroxyproline and hydroxyproline/total tissue protein. Histological evaluation revealed abnormal dermal elastic and collagen fibers. The cause of aberrant healing in massive weight loss body contouring is likely multifactorial. A relationship between nutritional state, wound collagen accumulation, and elastic fiber content seems to be only partially involved. The high mechanical stress of tissues before BPD probably influences the wound healing process after BPD.


Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells.
CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) mediated genome editing is a powerful approach for loss of function studies. Here we report that lentiviral CRISPR/Cas9 vectors are highly efficient in introducing mutations in the precursor miRNA sequence, thus leading to the loss of miRNA expression and function. We constructed four different lentiviral CRISPR/Cas9 vectors that target different regions of the precursor miR-21 sequence and found that these lentiviral CRISPR/Cas9 miR-21 gRNA vectors induced mutations in the precursor sequences as shown by DNA surveyor mutation assay and Sanger sequencing. Two miR-21 lentiviral CRISPR/Cas9 gRNA vectors were selected to probe miR-21 function in ovarian cancer SKOV3 and OVCAR3 cell lines. Our data demonstrate that disruption of pre-miR-21 sequences leads to reduced cell proliferation, migration and invasion. Moreover, CRISPR/Cas9-mediated miR-21 gene editing sensitizes both SKOV3 and OVCAR3 cells to chemotherapeutic drug treatment. Disruption of miR-21 leads to the inhibition of epithelial to mesenchymal transition (EMT) in both SKOV3 and OVCAR3 cells as evidenced by the upregulation of epithelial cell marker E-cadherin and downregulation of mesenchymal marker genes, vimentin and Snai2. The miR-21 target genes PDCD4 and SPRY2 were upregulated in cells transduced with miR-21gRNAs compared to controls. Our study indicates that lentiviral CRISPR/Cas9-mediated miRNA gene editing is an effective approach to address miRNA function, and disruption of miR-21 inhibits EMT in ovarian cancer cells.


Comparative Study on Flow-Accelerated Corrosion and Erosion-Corrosion at a 90° Carbon Steel Bend.
Electrochemical measurements and surface analysis are performed to comparatively study flow-accelerated corrosion (FAC) and erosion-corrosion (E-C) behavior at a 90° carbon steel bend. The corrosion rates are higher under FAC conditions than those under E-C conditions. For FAC, the corrosion is more serious at the inside wall. However, corrosion is exacerbated at the outside wall under E-C conditions. No erosion scratches are observed under FAC conditions and at the inside wall under E-C conditions, while remarkable erosion scratches appear at the outside wall under E-C conditions. The dominant hydrodynamics affecting FAC and E-C are remarkably different.