Contaminants of emerging concerns in recycled water: Fate and risks in agroecosystems.
Recycled water (RW) has been increasingly recognized as a valuable source of water for alleviating the global water crisis. When RW is used for agricultural irrigation, many contaminants of emerging concern (CECs) are introduced into the agroecosystem. The ubiquity of CECs in field soil, combined with the toxic, carcinogenic, or endocrine-disrupting nature of some CECs, raises significant concerns over their potential risks to the environment and human health. Understanding such risks and delineating the fate processes of CECs in the water-soil-plant continuum contributes to the safe reuse of RW in agriculture. This review summarizes recent findings and provides an overview of CECs in the water-soil-plant continuum, including their occurrence in RW and irrigated soil, fate processes in agricultural soil, offsite transport including runoff and leaching, and plant uptake, metabolism, and accumulation. The potential ecological and human health risks of CECs are also discussed. Studies to date have shown limited accumulation of CECs in irrigated soils and plants, which may be attributed to multiple attenuation processes in the rhizosphere and plant, suggesting minimal health risks from RW-fed food crops. However, our collective understanding of CECs is rather limited and knowledge of their offsite movement and plant accumulation is particularly scarce for field conditions. Given a large number of CECs and their occurrence at trace levels, it is urgent to develop strategies to prioritize CECs so that future research efforts are focused on CECs with elevated risks for offsite contamination or plant accumulation. Irrigating specific crops such as feed crops and fruit trees may be a viable option to further minimize potential plant accumulation under field conditions. To promote the beneficial reuse of RW in agriculture, it is essential to understand the human health and ecological risks imposed by CEC mixtures and metabolites.


p53 protein expression in grade II astrocytomas: immunohistochemical study of 100 cases with long-term follow-up.
p53 protein expression was evaluated by immunohistochemistry in a homogeneous series of 100 supratentorial grade II astrocytomas with long-term follow-up. The staining was positive in 72 cases. The proportion of p53 positive tumors was slightly higher in younger patients. The tumor regrowths which derived from p53 positive tumors were themselves p53 positive, and this p53 immunopositivity was often stronger than in the initial tumors. All of the 10 gemistocytic astrocytomas included in our series were p53 positive, and age more than histological type appeared decisive in prognosis. p53 protein expression did not quite reach statistical significance as an independent predictive variable in multivariate analysis, whereas survival was related with age, mass effect, surgery and tumor location. Only a tendency to a longer survival was observed on the curves in younger patients with mildly positive tumors.


In vitro changes in back vertex distance of chick and pigeon lenses: species differences and the effects of aging.
We have used a scanning laser technique to measure in vitro changes in back vertex distance of chick and pigeon lenses. Enucleated eyes were dissected, leaving the lens naturally suspended by the ciliary body and intraocular muscles. Ray tracing techniques were used to measure the resting back vertex distance of the lenses by passing a laser beam through the lens and scanning it across the pupillary aperture. The pupil diameter was measured videographically. The measurements were repeated while the intraocular muscles were pharmacologically stimulated with increasing concentrations of either nicotine or carbachol. Drug stimulation caused changes in pupil diameter and changes in the back vertex distance of the lenses. These experiments were conducted on the eyes of young chicks, young pigeons, and on the eyes of three pigeons older than 10 yr. The lenses from the eyes of the old pigeons had the greatest resting back vertex distance, followed by those of the young pigeons and finally those of the young chicks. Lenses from the eyes of young chicks and young pigeons underwent similar drug-induced changes in back vertex distance, but the lenses from old pigeon eyes showed an almost complete absence of such changes. Further, we demonstrated that, just as in the chick eye, lenticular changes in pigeon eyes are due to a contraction of the iris muscle. This is evident because after the iris has been removed the lens undergoes no change in back vertex distance during stimulation. We conclude with a discussion of the lenticular accommodative ability of the pigeon eye with reference to the recently reported accommodative mechanism of the chick eye and a comparison of chick and pigeon iris morphology.


Dynamisation and early weight-bearing in tibial reamed intramedullary nailing: its safety and effect on fracture union.
To compare the safety and effect on tibial diaphyseal fracture bone union of two intramedullary nailing techniques: (1) dynamic locking with early, full weight bearing, and (2) static locking with delayed weight bearing until bone union. This is a retrospective case-control study of closed or type I open tibial diaphyseal fractures (types A and B according to the AO classification) treated with dynamic nailing (32 cases) or static nailing (35 cases). The type of intramedullary nail, the surgical technique and the postoperative protocol were similar for both groups, with the exception of the locking mode and the time of weight bearing. Time to union, mechanical and biological complications, and the number and type of re-operations needed until union were recorded and analysed. Mean union time was 21 weeks in the dynamic group and 26 in the static group (p = 0.051). In both groups 3 cases of nonunion were noted. In the dynamic group there was 1 case of delayed union and 1 case of malunion. In the static group, 5 cases of delayed union and 5 cases of malunion were found. Four reoperations were required in the dynamic group, whereas 10 were needed in the static group (p >0.05). Initial degree of interfragmentary gaps had an impact on the mean time to union and the appearance of biological complications in both groups. Dynamic nailing assembly in intramedullary nailing in closed or type I open tibial diaphyseal fractures with limited comminution (types A and B according to the AO classification) is safe when used for these fracture types. A dynamic mode of nailing should be encouraged in these fracture patterns.


Changes in transepithelial electrical resistance and intracellular ion concentration in TGF-β-induced epithelial-mesenchymal transition of retinal pigment epithelial cells.
This study aimed to investigate the changes in transepithelial electrical resistance (TEER) and ion concentrations, and their relationship in TGF-β-induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. RPE cell line ARPE-19 was employed and treated with 10 ng/ml TGF-β1 and TGF-β2 to establish the EMT model in vitro. The EMT markers fibronectin, N-cadherin, occludin, zona occludens 1(ZO-1) and claudin-19 were investigated by western blot and immunofluorescence. CellZscope system was used to monitor the TEER values. Fluorescent probe, flow cytometry and automatic microplate reader were employed to detect the changes of Ca2+, Mg2+, Zn2+, Na+ and K+ in ARPE-19 cells. The TGF-β1-induced EMT of ARPE-19 cells was marked by the disruption of the distribution of occludin, ZO-1, and claudin-19. The development of TEER was significantly disturbed in both TGF-β1 and TGF-β2 treatment groups. Also, the time course of the maximum slope indicated that the fastest decrease in TEER values occurred after 36 hours. The concentrations of Ca2+, Mg2+, Zn2+, and K+ increased in TGF-β1- and TGF-β2-treated ARPE-19 cells, while the concentration of Na+ decreased. Significant inverse correlations were detected between the concentrations of Ca2+, Mg2+, Zn2+, and K+ and TEER values in ARPE-19 cells treated with TGF-β1. The Na+ concentration and TEER values showed a positive correlation. Similar results were observed in the TGF-β2 treatment group. The time-effect analysis showed that the concentrations of Ca2+, Mg2+, Zn2+ and K+ increased and peaked after 72, 72, 48, and 72 h, respectively, with the extension of TGF-β1 treatment time. In the TGF-β2 treatment group, the Ca2+, Mg2+, Zn2+, and K+ concentrations were also upregulated and reached their highest after 72, 72, 72, and 36 h, respectively. In contrast, the concentration of Na+ decreased and reached the lowest after 48 h in the TGF-β1 treatment group and after 72 h in the TGF-β2 treatment group. TGF-β1 and TGF-β2 disrupted the ARPE-19 cell monolayer, disturbed TJs integrity, downregulated TEER values, and changed intracellular ion permeability. These findings might help further understand the EMT of RPE cells during PVR.


Quasi-non-linear deformation modeling of a human liver based on artificial and experimental data.
Researchers working on error-prevention theories have shown that the use of replica models within simulation systems has improved operating skills, resulting in better patient outcomes. This study aims to provide material test data specifically for a human liver to validate the accuracy of viscoelastic soft tissue models. This allows the validation of virtual surgery simulators by comparison with physical test data obtained from material tests on a viscoelastic silicone gel pad. The results proved that stress behavior and relaxation curves of Aquaflex® experiment and FEM simulation are close if average liver response and respective material parameters and model are used. The precise representation of manipulated tissues used in virtual surgery trainers involves the accurate characterization of mechanical properties of the tissue. Consequently, successful implementations of these mechanical properties in a mathematical model of the deforming organ are of major importance. Copyright © 2015 John Wiley & Sons, Ltd.


Immunotherapy resistance driven by loss of NY-ESO-1 expression in response to transgenic adoptive cellular therapy with PD-1 blockade.
The tumor antigen NY-ESO-1 has been shown to be an effective target for transgenic adoptive cell therapy (ACT) for the treatment of sarcoma and melanoma. However, despite frequent early clinical responses, many patients ultimately develop progressive disease. Understanding the mechanisms underlying treatment resistance is crucial to improve future ACT protocols. Here, we describe a novel mechanism of treatment resistance in sarcoma involving loss of expression of NY-ESO-1 in response to transgenic ACT with dendritic cell (DC) vaccination and programmed cell death protein-1 (PD-1) blockade. A HLA-A*02:01-positive patient with an NY-ESO-1-positive undifferentiated pleomorphic sarcoma was treated with autologous NY-ESO-1-specific T-cell receptor (TCR) transgenic lymphocytes, NY-ESO-1 peptide-pulsed DC vaccination, and nivolumab-mediated PD-1 blockade. Peripheral blood reconstitution with NY-ESO-1-specific T cells peaked within 2 weeks of ACT, indicating rapid in vivo expansion. There was initial tumor regression, and immunophenotyping of the peripheral transgenic T cells showed a predominantly effector memory phenotype over time. Tracking of transgenic T cells to the tumor sites was demonstrated in on-treatment biopsy via both TCR sequencing-based and RNA sequencing-based immune reconstitution, and nivolumab binding to PD-1 on transgenic T cells was confirmed at the tumor site. At the time of disease progression, the promoter region of NY-ESO-1 was found to be extensively methylated, and tumor NY-ESO-1 expression was completely lost as measured by RNA sequencing and immunohistochemistry. ACT of NY-ESO-1 transgenic T cells given with DC vaccination and anti-PD-1 therapy resulted in transient antitumor activity. NY-ESO-1 expression was lost in the post-treatment sample in the setting of extensive methylation of the NY-ESO-1 promoter region. Antigen loss represents a novel mechanism of immune escape in sarcoma and a new point of improvement in cellular therapy approaches. NCT02775292.


High-cholesterol diets induce changes in lipid composition of rat erythrocyte membrane including decrease in cholesterol, increase in alpha-tocopherol and changes in fatty acids of phospholipids.
Effects of high dietary cholesterol on erythrocyte membrane lipids were studied. Feeding rats with a diet containing 0.5% cholesterol and 0.15% sodium cholate for two weeks induced changes in erythrocyte membrane lipids including a decrease in cholesterol, an increase in alpha-tocopherol (alpha-Toc) and changes in the fatty acid composition of phospholipids. Oleic acid and linoleic acid increased, while arachidonic acid decreased in phosphatidylcholine. Saturated fatty acids decreased and unsaturated fatty acids increased in phosphatidylethanolamine. Almost the same changes in membrane lipids were also noted after six weeks of feeding rats with the diet. A diet containing 0.5% cholesterol but without sodium cholate caused a decrease in erythrocyte cholesterol and an increase in erythrocyte alpha-Toc after two weeks of feeding, as compared to the basal diet, indicating that high dietary cholesterol, but not sodium cholate, was responsible for these changes in the erythrocyte membrane.


Disability and use of healthcare resources in Brazilian patients with Parkinson's disease.
To assess disability and healthcare resource use in Parkinson's disease (PD) patients. A cross-sectional survey of 144 Brazilian PD patients consecutively admitted at a Neurological outpatient clinic. Clinical evaluation was done using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn & Yahr staging (H&Y). The Schwab and England (SE) activity of daily living (ADL) scale was used to assess the level of dependence in the ADL. Information about the utilization of health resources was obtained interviewing the patient by means of a structured questionnaire. A total of 66% of patients (mean age 62 years; males, 53%) had a Hoehn & Yahr stage < or = 2. Mean UPDRS score was 46.2, and median SE scale score was 80. Disabled PD patients significantly received more visits by a general practitioner (p < 0.001). Patients with comorbid conditions significantly used more domiciliary nurse care and physiotherapist assistance (p < 0.01). The most frequent reason for hospitalization was the treatment of clinical complications and drug dose adjustment. Pharmacological treatment costs were associated with the severity of the disease (p < 0.05). Utilization of healthcare resources was influenced by functional status and comorbid conditions.


New method for immobilising diverse proteins onto cubic micro-protein polyhedrin crystals.
Cypovirus is an insect virus that is encapsulated in stable cubic protein crystals composed of polyhedrin protein produced in virus-infected cells. Molecular technology developed over the last decade is now able to immobilise proteins of interest on polyhedrin crystals. Modified polyhedrin crystals can be used in cell cultures for implantation in animals and vaccines, among other applications. However, this technique does not work for some proteins. Here, we developed and tested an alternative approach for immobilising foreign proteins in polyhedrin crystals using a linker method; diverse proteins, such as fluorescent proteins, enzymes, antibodies, and streptavidin were successfully contained. The immobilised antibodies retained their binding activity on filter paper, implying their potential for new immunochromatography applications. Moreover, this immobilisation method allows enzymes to be collected from one reaction reagent and transferred to another reagent. These results demonstrate the potential of this immobilisation method and the likelihood of expanding the applications of polyhedrin crystals using this approach.


A putative role for ALDH inhibitors and chemoprevention of BRCA-mutation-driven tumors.
Aldehyde dehydrogenase (ALDH) enzymatic activity is a marker of cancer-initiating cells (CIC) in many tumor types. Our group and others have found that ALDH1A family inhibitors (ALDHi) can preferentially induce death of ovarian CIC in established ovarian cancer. We sought to determine if ALDHi, by targeting CIC at the time of tumor initiation, could function as a chemopreventive for ovarian cancer. As BRCA1/2 mutation carriers represent a population who could benefit from an ovarian cancer chemopreventive, we focused on BRCA mutation-associated tumor cell lines and murine tumor models. We found that, compared to BRCA wild-type cells, BRCA mutant ovarian cancer cells are more sensitive to the ALDHi673A. Similarly, while 673A treatment of wild-type fallopian tube epithelial (FTE) cells is non-toxic, 673A induces death in FTE cells with BRCA1 knockdown. Using a murine fallopian tube organoid model of ovarian carcinogenesis, we show that 673A reduced organoid complexity and significantly reduce colony formation of BRCA-mutant cells. Organoids that persisted after 673A treatment were predominantly BRCA1wt, but NF1 mutant, suggesting a resistance mechanism. Finally, using the BPRN (Brca1, Trp53, Rb1, Nf1 inactivated) mouse model of tubo-ovarian cancer, we evaluated the impact of intermittent 673A therapy on carcinogenesis. 673A treatment resulted in a significant reduction in serous tubal intraepithelial carcinoma (STIC) lesions and carcinomas. Collectively, the findings suggest that ALDHi, such as 673A, could serve as chemopreventive agents for BRCA1/2 mutation carriers.


Avifauna conservation and disturbance ecology in a coastal freshwater lagoon.
This work was developed in Barrinha de Mira Coastal Lagoon, Portugal. The lagoon belongs to the Natura 2000 network. Its main objectives were to monitor aquatic bird species before, during, and after a desorption intervention on this lagoon. Monitoring of waterfowl was carried out to evaluate the monthly variation of birds in Barrinha, in order to obtain useful information for region's management and planning, as well as for species preservation. In experimental design, it was decided to perform four counts per month in each pond (weekly), to evaluate the effect of increased monitoring effort in relation to previous years. The results revealed that the study area has a significant importance as a wintering zone for water birds. Some species have stable resident populations which, seasonally, see their numbers vary with migratory birds arrival and departure. Another purpose was to verify the influence of desorption intervention on the usual number of individuals by species. The results show that during and after intervention, there was a reduction of birds in the order of 89%, being more visible in the populations of Anas platyrhynchos and Fulica atra.


KIT Exon 11 Codons 557-558 Deletion Mutation Promotes Liver Metastasis Through the CXCL12/CXCR4 Axis in Gastrointestinal Stromal Tumors.
KIT mutations, the most prevalent genetic event in gastrointestinal stromal tumors (GIST), are associated with malignant features and poor prognosis. Aggressive GISTs possess a high propensity to spread to the liver. This study aimed to explore the role of KIT mutations in GIST liver metastasis. A total of 170 GISTs were used to determine the association between KIT mutations and liver metastasis. Immunohistochemistry was performed to assess the correlation of KIT mutations with CXCR4 and ETV1 expression. Genetic and pharmacologic methods were used to study the regulation of CXCR4 and ETV1 by KIT mutations. Codons 557 and 558 in KIT exon 11 were deletion hot spots in GISTs. KIT exon 11 deletions involving codons 557-558 were highly associated with liver metastasis. Overexpression of mutant KIT with exon 11 codons 557-558 deletion (KIT Δ557-558) increased GIST cell motility and liver metastasis. Mechanistically, overexpression of KIT Δ557-558 in GIST cells increased ETV1 and CXCR4 expression. CXCR4 knockdown counteracted KIT Δ557-558-mediated cell migration. Moreover, KIT Δ557-558-induced CXCR4 expression could be abolished by silencing ETV1. The chromatin immunoprecipitation assay showed that ETV1 directly bound to the CXCR4 promoter. After ERK inhibitor PD325901 treatment, the upregulation of ETV1 by KIT Δ557-558 was prevented. In addition, KIT exon 11 codons 557-558 deletion enhanced CXCL12-mediated GIST cell migration and invasion. KIT exon 11 557-558 deletion upregulates CXCR4 through increased binding of ETV1 to the CXCR4 promoter in GIST cells, which thus promotes liver metastasis. These findings highlighted the potential therapeutic targets for metastatic GISTs. Clin Cancer Res; 22(14); 3477-87. ©2016 AACR.


Platelet activation and red blood cell phosphatidylserine exposure evaluated by flow cytometry in patients with Behçet's disease: are they related to thrombotic events?
Behçet's disease (BD) is associated with an increased risk of venous and arterial thromboses that are associated with morbidity and mortality increase, although the mechanisms are not well established. In the present study, we used whole blood cytometry to determine the exposure of CD62 on the surface of platelets and the expression of phosphatidylserine (PS) on the surface of circulating red blood cells. Microparticle and microaggregate formation from platelets were also determined in a well-classified group of 72 patients (39 males, 33 females, aged 46.5 +/- 12.5 years) with BD, in comparison with a well-matched control group of 72 healthy volunteers. Results showed no differences in the above-mentioned parameters when BD patients and controls were compared. However, when we compared BD patients with/without thrombosis using these parameters, there were significant differences between both groups. BD patients with previous thrombosis had a higher percentage of circulating CD62-positive platelets and a higher number of circulating microaggregates than those without thrombosis, suggesting that platelet activation may be involved in the development of thrombotic events in these patients.


An unusual primary malignant tumor of the stomach: fetal gutlike gastric adenocarcinoma with "blastoma"-like component.
An unusual case of a polypoid, malignant gastric tumor in a 62-year-old man is presented. Endoscopy and subsequent polypectomy revealed an 8.5 × 6.5 × 4.5-cm lesion in the body of the stomach. Microscopy showed surface dysplasia with an invasive adenocarcinoma displaying prominent tubulopapillary areas composed of large vacuolated cells, pleomorphic nuclei, and occasional cytoplasmic hyaline globules. This component then blended with tubular structures lined by more primitive-appearing vacuolated cells embedded within a stroma made up of cellular primitive, high-grade blastemalike areas and less cellular, more pleomorphic foci with spindle and several bizarre, large cells. Immunohistochemistry showed the adenocarcinoma and primitive tubules to be strongly SALL4 and epithelial marker positive but with only focal expression of α-fetoprotein and glypican-3. The stromal component made up of blastemalike areas displayed strong immunoreactivity for glypican-3. The pleomorphic stromal areas were negative for all markers, including epithelial and muscle markers. The overall morphology and expression of primitive oncofetal proteins, especially SALL4 and glypican-3, are in keeping with this being a primitive adenocarcinoma showing fetal gutlike differentiation with an accompanying blastomalike component, a combination not previously described in a primary gastric cancer.


Copy number aberrations in circulating tumor DNA enables prognosis prediction and molecular characterization of breast cancer.
Low-pass whole-genome sequencing (LP-WGS)-based circulating tumor DNA (ctDNA) analysis is a versatile tool for somatic copy number aberration (CNA) detection, and this study aims to explore its clinical implication in breast cancer. We analyzed LP-WGS ctDNA data from 207 metastatic breast cancer (MBC) patients to explore prognostic value of ctDNA CNA burden and validated it in 465 stage II-III triple-negative breast cancer (TNBC) patients who received neoadjuvant chemotherapy in phase III PEARLY trial (NCT02441933). The clinical implication of locus level LP-WGS ctDNA profiling was further evaluated. We found that a high baseline ctDNA CNA burden predicts poor overall survival and progression-free survival of MBC patients. The post hoc analysis of the PEARLY trial showed that a high baseline ctDNA CNA burden predicted poor disease-free survival independent from pathologic complete response (pCR), validating its robust prognostic significance. The 24-month disease-free survival rate was 96.9% and 55.9% in [pCR(+) and low I-score] and [non-pCR and high I-score] patients, respectively. The locus-level ctDNA CNA profile classified MBC patients into 5 molecular clusters and revealed targetable oncogenic CNAs. LP-WGS ctDNA and in vitro analysis identified the BCL6 amplification as a resistance factor for CDK4/6 inhibitors. We estimated ctDNA-based homologous recombination deficiency status of patients by shallowHRD algorithm, which was highest in the TNBC and correlated with platinum-based chemotherapy response. These results demonstrate LP-WGS ctDNA CNA analysis as an essential tool for prognosis prediction and molecular profiling. Particularly, ctDNA CNA burden can serve as a useful determinant for escalating or de-escalating (neo)adjuvant strategy in TNBC patients.


Novel Imaging of Prostate Cancer with MRI, MRI/US, and PET.
Imaging of prostate cancer presents many challenges to the imaging community. There has been much progress in this space in large part due to MRI and PET radiopharmaceuticals. Though MRI has been focused on the evaluation of local disease and PET on the detection of metastatic disease, these two areas do converge and will be complementary especially with the growth of new PET/MRI technologies. In this review article, we review novel MRI, MRI/US, and PET radiopharmaceuticals which will offer insight into the future direction of imaging in prostate cancer.


Sleep structure in patients with psychogenic nonepileptic seizures.
Psychogenic nonepileptic seizures (PNES) are a significant public health problem, occurring in perhaps 25% of patients admitted to epilepsy monitoring units. Additional distinguishing characteristics for these patients would be helpful from both a clinical and a scientific standpoint. This study examines sleep structure by polysomnography in patients with PNES compared with patients with epileptic seizures (ES). ES and PNES were verified by video-EEG monitoring. All patients with PNES were evaluated by a psychiatrist. Eight female patients with PNES were compared with 10 female ES patients in the same age group. Percentage REM sleep was significantly greater for women with PNES (23+/-1%) than for those with ES (18+/-1%). There were no differences in other sleep stages, total sleep time, or sleep efficiency. REM latency was less in PNES patients although not significantly. The study suggests that patients with PNES have a sleep architecture similar to that found in major depression, known to be associated with increased REM sleep.


Effect of pacing method on risk of sudden death after atrioventricular node ablation and pacemaker implantation in patients with atrial fibrillation.
Sudden death may occur after radiofrequency catheter ablation of the atrioventricular node (AVN) and permanent pacemaker implantation. It is unclear whether a faster initial heart rate with gradual rate reduction decreases the risk of sudden death. To evaluate the effects of initial pacing at a faster rate after AVN ablation, with a gradual rate decrease over 3 months, on the rate of sudden death in patients with atrial fibrillation. We compared the rate of likely or possible procedure-related sudden death in 2 groups of patients who had AVN ablation and pacemaker implantation. The study cohort was treated between January 2005 and December 2009, and pacemakers were programmed to a lower rate of 90 beats/min after the procedure, with a monthly decrement of 10 beats/min until 60 beats/min was reached. The control group was treated between July 1990 and December 1998 when pacemakers were programmed to a lower rate of 60 beats/min immediately after ablation. The study cohort included 520 patients (mean age 73.6 ± 10.3 years), and the control cohort comprised 334 patients (mean age 68.1 ± 1.1 years). Sudden death deemed likely or possibly related to ablation and pacemaker implantation occurred in 1 patient in the study cohort (0.2%) and in 7 patients (2.1%) in the control group (P = .007). Sudden death was significantly decreased in the study cohort compared to controls. The faster lower pacing rate immediately after AVN ablation with a gradual decrease is a plausible mechanism for the improved clinical outcome.


Photoelectrochemical degradation of selected organic substances on Fe2O3 photoanodes: a comparison with TiO2.
The photoelectrochemical degradation of selected aromatic substances, acid orange 7 (AO7), salicylic acid (SA), benzoic acid (BA), and 4-chlorophenol (4-CP) was studied on hematite (α-Fe2O3) and compared with titanium dioxide (TiO2), both deposited as thin films on conducting substrates (FTO/glass). Batch type reactors were used under backside and front side illumination. Electrical bias was applied on the semiconducting electrodes, such that only valence band processes leading to oxidative pathways were followed. The initial Faradaic efficiency, f0, of degradation processes was determined from the UV-Vis absorbance decrease of the starting materials. f0 for 1 mM AO7 degradation in 0.01 M sulphuric acid was found to be 7.5%. When the pH of the solution was neutral (pH 7.2) or alkaline (pH 13), f0 decreased to 1.7%. For 1 mM SA, f0 was 6.2% on hematite photoanodes and 6.1% on titanium dioxide. For 1 mM benzoic acid and 4-chlorophenol, f0 was an order of magnitude lower, but only on hematite. This is ascribed to the lack of OH· radical formation on hematite, which seems to be essential for the photooxidation of these compounds.


A randomized controlled trial to optimize indocyanine green-augmented diode laser therapy of capillary malformations.
Indocyanine green (ICG)-augmented diode laser therapy (ICG + DL) represents a new treatment modality for capillary malformations (CM). However, an increase of the ICG-concentration or the use of an intense pulsed light (IPL) device as light source may further optimize treatment outcomes in CM. This proof-of-concept trial including 15 patients (skin type II to III) with CM evaluated the efficacy and safety of ICG-augmented diode laser therapy (808 nm) at a total dose of 4 mg/kg body weight (b.w.). Additionally, five patients with extensive CM received IPL therapy before and after ICG-administration (ICG + IPL). ICG was intravenously administered to 15 patients with CM at a total dose of 4 mg/kg b.w. Immediately after ICG injection, diode laser pulses with different radiant exposures (20-110 J/cm(2) ) were applied as one single treatment. Five patients with extensive CM additionally received IPL (555-950 nm) therapy. Safety and efficacy were assessed both 1 and 3 months after the single treatment by a blinded investigator and the patient. Furthermore, color of the CM was objectively measured by means of a color meter (colorStriker™, Eduard Mathai GmbH, Hannover, Germany). Treatment with the flashlamp-pumped pulsed dye laser (FPDL) and the IPL alone (five patients) served as reference treatment. According to the assessment by the patients and the blinded investigator, the clearance rate was slightly better after ICG + DL therapy than after FPDL treatment (P = 0.1, P = 0.8). In one out of five patients, IPL with and without ICG injection induced poor to moderate clearance of CM and persisting erythema in another patient. The correlation between the visual assessment by the blinded investigator and the colorimetric measurements was poor. A minority of patients with CM may benefit from ICG + DL therapy, but efficacy cannot be improved by higher ICG doses.


All-cause Mortality Due to Bacteremia during a 60-Day Non-Physician Healthcare Worker Strike.
This study explored all-cause mortality of bacteremia diagnosed during a 60-day non-physician healthcare worker strike in 2008. A significant change, with 5.0% (95% confidence interval [CI] 1.2-8.7%, P < .01) absolute risk increase, was seen in 90-day mortality during the strike (n = 598) compared with the rest of the study period 2000-2015 (n = 75 647).


Is bisphosphonate therapy compromised by the emergence of adverse bone disorders?
Bisphosphonates (BPs) are the preferred class of antiresorptive agents used for the treatment of osteoporosis and bone metastases. Recently, an increasing number of clinical reports concerning osteonecrosis of the jaw and atypical fractures have suggested a link between prolonged use of BPs and these adverse bone events, which are exceptionally difficult to treat. Even though these side effects were mainly observed in patients with metastases, osteoporotic patients might become increasingly affected by these conditions with the increasing use of injectable BPs. Could these severe adverse bone events compromise the use of BPs? The development of these unfavorable conditions as a consequence of oversuppression of bone resorption could raise concern regarding the use of therapeutic strategies involving antiresorptive drugs.


The case for patch test readings beyond day 2. Notes from the lost and found department.
Additional patch test readings taken after 2 days (48 hours) are valuable in distinguishing false-positive reactions, which may occur up to 22% of the time. Second readings taken on days 3 through 7 may detect an additional 34% positive reactivity. Those reactions, both lost (initially positive, later negative) and found (initially negative, later positive) by delayed readings, require clinical correlation for relevance as do the readings that persist at and beyond day 2 (positive at both readings).


Clinical effectiveness of decoction form of herbal medicine in primary care treatment of allergic rhinitis: A retrospective cohort study.
The decoction form of herbal medicine (D-HM) is mainly prescribed to patients with allergic rhinitis (AR) in Korean Medicine (KM) clinics in the Republic of Korea; however, it is difficult to conduct clinical trials of D-HM due to regulatory issues. This study investigated the clinical safety and effectiveness of D-HM combination therapy for the treatment of AR by analyzing the AR outpatient data from 17 KM clinics. This retrospective cohort study included patients who visited KM clinics for AR treatment from January 1, 2021, to March 31, 2022. Cases were collated using structured case report forms and divided into the D-HM with KM usual care group (D-HM group) and the KM usual care group (UC group). Since D-HM therapy could not be randomly assigned to the study population, we used optimal propensity score (PS) matching to investigate the effectiveness and safety of D-HM combination therapy in the treatment of AR. Data from 228 patients were collected. After PS matching, 144 patients were finally analyzed. The total nasal symptom score (TNSS) and mini-rhinoconjunctivitis quality of life questionnaire (mini-RQLQ) were significantly improved in the D-HM group compared with those in the UC group (TNSS: p=0.02; mini-RQLQ: p=0.04). Four patients in the D-HM group experienced minor adverse events that were mild and resolved within 15 days. D-HM combination therapy may be beneficial in the management of symptoms and rhinitis-associated quality of life and potentially useful in clinical practice. However, randomized placebo-controlled clinical trials are required to confirm their effectiveness. This study has been registered at Clinical Research Information Service (KCT0007242).


Directional Janus Metasurface.
Janus monolayers, a class of two-faced 2D materials, have received significant attention in electronics, due to their unusual conduction properties stemming from their inherent out-of-plane asymmetry. Their photonic counterparts recently allowed for the control of hydrogenation/dehydrogenation processes, yielding drastically different responses for opposite light excitation spins. A passive Janus metasurface composed of cascaded subwavelength anisotropic impedance sheets is demonstrated. By introducing a rotational twist in their geometry, asymmetric transmission with the desired phase function is realized. Their broken out-of-plane symmetry realizes different functions for opposite propagation directions, enabling direction-dependent versatile functionalities. A series of passive Janus metasurfaces that enable functionalities including one-way anomalous refraction, one-way focusing, asymmetric focusing, and direction-controlled holograms are experimentally demonstrated.


Down-modulation of CD4 antigen during programmed cell death in U937 cells.
It has been hypothesized that programmed cell death (PCD), an active cell suicide process occurring in place of necrosis, can be associated with the pathogenesis of acquired immunodeficiency syndrome (AIDS). The entry of human immunodeficiency virus (HIV) into competent cells is mediated by the CD4 molecule present on the surface of certain lymphocyte subpopulations as well as on some cultured cell lines, e.g. U937 myelomonocytic cells. The present paper focuses on some specific aspects of PCD induced by the cytokine tumor necrosis factor (TNF). The results obtained indicate that the exposure of U937 cells to cycloheximide facilitates TNF-mediated PCD via a short term cell death program and modifies the expression of CD4 surface molecules. This change in surface antigen expression, manifested by internalization of the CD4 molecule, occurs in cells in which apoptosis has been triggered, but not in cells undergoing necrosis. These results indicate that the progression of cell death could be associated with specific alterations of certain surface molecules and could have a role in the entry of HIV into cells.


Final-year nursing students called to work: Experiences of a rushed labour insertion during the COVID-19 pandemic.
The first COVID-19 case was confirmed in China in December 2019, and countries around the world rapidly diagnosed new cases from January 2020 onwards. The World Health Organization (WHO) declared an international emergency, characterising it as a pandemic in March 2020. In Spain, final-year Medicine and Nursing students were recruited to reinforce the healthcare system. Using a qualitative phenomenological approach we aimed to clarify the experiences of these final-year year nursing students employed to provide nursing care during the COVID-19 pandemic in Spain. A total of 20 interviews were conducted with final-year students from six universities who were employed by Catalan Hospitals. Data was analyzed using Colaizzi's method. Analysis identified the meta-category 'feeling the commitment' from the interaction of two categories, 'facing the unknown' and 'being and feeling like a nurse', and five subcategories. Students felt highly committed to fighting the COVID-19 pandemic, volunteering to work as nurses despite facing the unknown and not yet having finished their studies. Future Spanish nursing programmes should include 'pandemic and disaster management' content to increase students' preparedness for such scenarios.


Multiple stakeholders' perspectives on patient and public involvement in community mental health services research: A qualitative analysis.
Patient and public involvement (PPI) has become essential in health research. However, little is known about multiple stakeholders' perspectives on the implementation of PPI in community mental health research settings. The present study aimed to qualitatively analyse multiple stakeholders' views on PPI, including potential concerns, barriers and approaches. This study involved conducting focus group interviews and collecting qualitative data from 37 participants in multiple stakeholder groups (patients = 6, caregivers = 5, service providers = 7, government staff = 5 and researchers = 14) in the community mental health field. The data were qualitatively analysed using a data-driven approach that derived domains, themes and subthemes related to perspectives on PPI and to specific challenges and approaches for implementing PPI. The qualitative analysis identified four domains. The 'Positive views and expectations regarding PPI' domain consisted of themes related to supportive views of PPI in a mental health service research setting and improvements in the quality of research and service. The 'General concerns about PPI' domain included themes concerning the need for non-PPI research and tokenism, excessive expectations concerning social changes and use of evidence from PPI research, and heavy burdens resulting from PPI. The 'Specific issues regarding the implementation of PPI' domain consisted of four themes, including academic systems, selection methods (e.g., representativeness and conflict of interest issues), relationship building, and ambiguous PPI criteria. In particular, all stakeholder groups expressed concerns about relational equality during PPI implementation in Japan. The 'Approaches to PPI implementation' domain included themes such as facilitating mutual understanding, creating a tolerant atmosphere, establishing PPI support systems (e.g., training, ethics and human resource matching) and empowering patient organizations. The study replicated most of the barriers and approaches to PPI reported by qualitative research in Western counties. However, utilization of evidence produced by PPI research and partnership in the PPI process may be particularly serious issues in Japan. Future PPI studies should carefully address solutions that fit each culture. A patient-researcher was involved in all stages of this project, from development of the research topic and the protocol to manuscript preparation.


Cognitive development in offspring of untreated and preconceptionally treated maternal phenylketonuria.
A survey is given of literature reports on the effect of performance in offspring from 26 maternal PKU pregnancies treated prior to conception. The survey includes two women who were referred to us for genetic counselling because they had both given birth to microcephalic, mentally retarded children. The women were discovered to suffer from unrecognized maternal PKU with fasting phenylalanine concentration of 1.1-1.5 mmol/L. A strict diet was introduced prior to planned pregnancy and after some months on diet (phenylalanine concentrations less than 0.6 mmol/L) they became pregnant again. Serum phenylalanine levels were monitored weekly throughout pregnancy, and adjustments in the diet were made to keep serum phenylalanine concentration within the range of 0.18-0.42 mmol/L. The outcome of the pregnancies were healthy children who have developed normally. Their IQs are 105 and 119 at ten and four years of age, respectively and their head circumferences are normal. Our data show that the effect of preconceptional dietary treatment was children with a normal performance, contrary to their older siblings born following untreated pregnancies. These results are in agreement with the survey of ten years' promising experiences with preconceptional treatment in maternal PKU. The data may help to motivate young PKU women to accept planned pregnancies and to encourage them to return to the strict diet, which has prevented them from being retarded.


Importance of attenuating quadriceps activation deficits after total knee arthroplasty.
Total knee arthroplasty (TKA) is associated with persistent quadriceps dysfunction. Because quadriceps dysfunction impairs functional performance, minimizing quadriceps dysfunction by attenuating central activation deficits early after surgery may improve function later in life. Rehabilitation strategies incorporating neuromuscular electrical stimulation and early, aggressive quadriceps strengthening may prove beneficial. Furthermore, surgical approaches, such as minimally invasive TKA, may minimize postoperative quadriceps dysfunction.


Pre-Sleep Arousal and Fear of Sleep in Trauma-Related Sleep Disturbances: A Cluster-Analytic Approach.
Trauma-related sleep disturbances constitute critical symptoms of posttraumatic stress disorder (PTSD), but sleep symptoms often reside even after successful trauma-focused psychotherapy. Therefore, currently unattended factors - like fear of sleep (FoS) - might play a crucial role in the development and maintenance of residual sleep disturbances. However, it is unclear whether trauma-exposed individuals exhibit different symptomatic profiles of sleep disturbances that could inform individualized therapeutic approaches and eventually enhance treatment efficacy. In a large online study, a two-step cluster analysis and a hierarchical cluster analysis using Ward's method were performed to explore subgroups among trauma-exposed individuals (N = 471) in terms of FoS, different aspects of trauma-related sleep disturbances (e.g., insomnia symptoms, nightmares, arousal), and PTSD symptoms. These variables were compared between resulting clusters using ANOVAs and Scheffé's post-hoc tests. The hierarchical cluster analysis supported 3- and 4-cluster solutions. The 3-cluster solution consisted of one "healthy" (n = 199), one "subclinical" (n = 223), and one "clinical" (n = 49) cluster, with overall low, medium, and high symptomatology on all used variables. In the 4-cluster solution, the clinical cluster was further divided into two subgroups (n = 38, n = 11), where one cluster was specifically characterized by elevated somatic pre-sleep arousal and high levels of FoS. A subgroup of trauma-exposed individuals with PTSD and sleep disturbances suffers from increased pre-sleep arousal and FoS, which has been suggested as one possible explanation for residual sleep disturbances. In these patients, FoS might be a relevant treatment target.


Case competition sessions: a global education and academic engagement tool.
Radiology virtual teaching sessions utilize live video conferencing to promote collaborative learning and engagement by discussing radiology cases. Because of its convenience and flexibility, this mode of education has gained popularity, particularly after the corona virus disease 2019 pandemic. We describe our experience in organizing a series of "Global Health Imaging Case Competitions" for trainees in low- and middle-income countries (LMICs). These competitions provide the trainees with an opportunity to present unique radiology cases, network with radiologists, learn about various radiology topics, win prizes and potentially publish their case reports in a peer-reviewed journal. Planning and execution of the competition involves several steps. First, trainees are invited to participate and submit abstracts discussing unique cases. The organizing committee grades these abstracts; the authors of the 20 abstracts with the highest scores are asked to submit a video presentation of their cases to be presented during the live webinar. During this webinar, presentations are displayed and graded to select winners. Additionally, the audience votes to choose a participant as the people's favorite. We have completed four cycles (Africa, Latin America and the Caribbean, Africa and the Middle East and Asia) and will continue in the same order of rotation. Attendance totalled 2,510 participants from 50 countries. Pediatric cases represented the majority of cases among finalists. Feedback was positive; 26 out of 29 (90%) participants surveyed indicated that the webinar was "very good" to "excellent" with well-organized and challenging cases. Diversity of participating countries was noted. Limitations included technology barriers such as internet connectivity. This innovative approach emphasizing audience participation engaged trainees from LMICs and fostered locoregional collegiality and mentoring.


Assessment of splenic function.
Hyposplenic patients are at risk of overwhelming post-splenectomy infection (OPSI), which carries mortality of up to 70%. Therefore, preventive measures are warranted. However, patients with diminished splenic function are difficult to identify. In this review we discuss immunological, haematological and scintigraphic parameters that can be used to measure splenic function. IgM memory B cells are a potential parameter for assessing splenic function; however, more studies are necessary for its validation. Detection of Howell-Jolly bodies does not reflect splenic function accurately, whereas determining the percentage of pitted erythrocytes is a well-evaluated method and seems a good first-line investigation for assessing splenic function. When assessing spleen function, (99m)Tc-labelled, heat-altered, autologous erythrocyte scintigraphy with multimodality single photon emission computed tomography (SPECT)-CT technology is the best approach, as all facets of splenic function are evaluated. In conclusion, although scintigraphic methods are most reliable, they are not suitable for screening large populations. We therefore recommend using the percentage of pitted erythrocytes, albeit suboptimal, as a first-line investigation and subsequently confirming abnormal readings by means of scintigraphy. More studies evaluating the value of potentially new markers are needed.


Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir- vs. efavirenz-based antiretroviral therapy.
Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.


Graduating midwifery students' preferred model of practice and first job decisions: A qualitative study.
To explore and describe the preferred model of practice and first job decisions of final stage midwifery students from three Western Australian universities. Qualitative descriptive. Three Western Australian (WA) universities offering courses leading to registration as a midwife. Twenty-seven midwifery students from undergraduate and postgraduate (pre-registration) courses. Data were collected from recorded interviews and focus groups. Thematic analysis of interview transcripts was used to identify commonalities. Data saturation guided when recruitment ceased and final sample size was achieved. Participants' preferred model of maternity care was influenced by learning about and witnessing both autonomous midwifery practice and collaborative care during their studies. The greatest influence was clinical experience, with most preferring a continuity of midwifery model (CoM) but first consolidating their practice in a public hospital. Most students reported that they would not choose a private hospital as their first option. Work/life balance was also considered, with some accepting that family commitments and a need to work close to home may prevent them from choosing a CoM model. Although many Australian midwifery students start their midwifery course with preconceived ideology of their eventual workplace, the influences of their educators, clinical placement environment, preceptors and continuity of care experience relationships with women helped determine their final direction. To provide students with the experiences to become woman-centred autonomous practitioners it is important for universities and all maternity care providers to carefully consider their responsibility in how they influence midwifery students in education and practice.


Perceived Neighborhood Safety and Depressive Symptoms: The Role of Perceived Neighborhood Cohesion and Perceived Control.
Few have examined mechanisms explaining the link between perceived neighborhood unsafety, neighborhood social processes, and depressive symptoms for Black adolescents. The goal of this study was to examine the role of perceived control as a mechanism linking perceptions of neighborhood unsafety and depressive symptoms, and neighborhood cohesion as a protective factor. Participants were 412 Black adolescents living in a major Mid-Atlantic urban center in the United States (49% female, Mage = 15.80, SD = 0.36). Participants reported perceptions of neighborhood unsafety at grade 10, neighborhood cohesion at grade 10, perceived control at grades 10 and 11 and depressive symptoms in grades 10 and 12. High neighborhood unsafety was associated with low perceived control and in turn high depressive symptoms only when neighborhood cohesion was high. The results highlight the role of neighborhood unsafety and perceived control in the development of depressive symptom and the possible downsides of neighborhood social factors.


Overview of emergency nursing in Australasia.
Emergency nursing practice has been shaped by many factors. These factors include advances in resuscitation and technology, recognition of emergency as a specialty practice, increased consumer expectation, increased number of patient presentations and changing case mix. These factors and the growing demand on the healthcare system have increased the complexity and demands experienced in emergency nursing. The current focus on emergency care provides an opportunity for nurses to collectively drive the healthcare agenda, management focus, policy direction and research agenda.


Comparison of surgical correction rates between titanium and cobalt-chrome-alloy as rod materials in adolescent idiopathic scoliosis.
Numerous biomechanical studies comparing titanium (Ti) and cobalt-chrome-alloy (CCM) rods are described in the literature. However, there is a dearth of literature comparing the two rod materials in adolescent idiopathic scoliosis (AIS). Therefore, the purpose of this study is to compare the correction rates of Ti and CCM rods in the treatment of AIS with double major curves. We enrolled 45 patients with AIS who underwent surgery between 2009 and 2012. We divided patients into two groups, Group A (n = 29) treated with six-millimeter Ti rods and Group B (n = 16) treated with six-millimeter CCM rods. The rod-derotation maneuver was used for correction. We measured pre- and postoperative indices of coronal alignment (Cobb's angle, coronal balance, T1-tilt, clavicle angle) and sagittal alignment (sagittal vertical axis, thoracic kyphosis, lumbar lordosis). In our study, there were no significant differences between the two groups with respect to demographics or curve characteristics (P > 0.05). In Group A, thoracic and lumbar curvature correction rates were 71.2% and 66.8% respectively, and in Group B they were 71.2% and 73.3%, respectively (P = 0.664 and 0.09). There were no significant differences between the two groups in coronal or sagittal factors (P > 0.05) except for greater postoperative lumbar lordosis in the CCM group (P < 0.001). In conclusion, Ti and CCM rods showed similar correction rates in the sagittal and coronal planes for the surgical correction of AIS with double major curves. Biomechanical studies of Ti and CCM rods in vitro is different in biological condition.


Monte Carlo methods for light propagation in biological tissues.
Light propagation in turbid media is driven by the equation of radiative transfer. We give a formal probabilistic representation of its solution in the framework of biological tissues and we implement algorithms based on Monte Carlo methods in order to estimate the quantity of light that is received by a homogeneous tissue when emitted by an optic fiber. A variance reduction method is studied and implemented, as well as a Markov chain Monte Carlo method based on the Metropolis-Hastings algorithm. The resulting estimating methods are then compared to the so-called Wang-Prahl (or Wang) method. Finally, the formal representation allows to derive a non-linear optimization algorithm close to Levenberg-Marquardt that is used for the estimation of the scattering and absorption coefficients of the tissue from measurements.


An efficient synthesis of polyguanylic acid by a thermophilic polynucleotide phosphorylase.
Polyguanylic acid (poly(G)) was synthesized from GDP in a yield of 60-75% by Thermus thermophilus polynucleotide phosphorylase (polyribonucleotide: orthophosphate nucleotidyltransferase, EC 18.104.22.168) at 70 degrees C, pH 8.5 in the presence of Mg2+. The yield was dependent on the ratio of GDP to Mg2+, but was independent of the concentrations of enzyme or substrate. The maximal rate of GDP polymerization was obtained when the ratio of GDP to Mg2+ was 3:1. However, by prolonged incubation, the higher initial ratio of over 4:1 was preferred because of the rapid consumption of GDP in the reaction mixture. Poly(G) prepared by 1 h incubation was heterogeneous in size from 5 S to over 23 S, but by prolonged incubation of 19 h the size of product converged to 9 S as judged by sucrose density gradient centrifugation. Its chain length was determined by terminal nucleoside analysis to be 200 nucleotides long.


Mini-cholecystectomy under local anaesthesia.
Reports of mini-cholecystectomy (MC) under general anaesthesia in the surgical treatment of gallbladder disease are common, but those of MC under local anaesthesia are much more limited. We report our experience of MC under local anaesthesia. Forty-two patients with gallstone disease scheduled for MC under local anaesthesia were included in this study. Twenty-seven were female, with a median age of 54.5 years (range, 29-71) and median body mass index (BMI) of 20.5 (range, 17.6-23.4). None of the patients had evidence of acute cholecystitis on admission or previous upper abdominal surgery. MC was performed by a standardized technique and under the combination of local anaesthesia (1% xylocaine with adrenaline) and intravenous administrations of fentanyl (0.001-0.002 mg/kg) and midazolam (0.05-0.1 mg/kg). The median operative time was 40 minutes (range, 35-64). Local anaesthesia was converted to general anaesthesia in two patients owing to the discomfort caused by lysis of dense adhesions around the gallbladder, giving a success rate of 95%. MC was done successfully in all patients without any postoperative complications. The median hospital stay was 5 days (range, 2-7). MC under local anaesthesia is an effective surgical procedure for patients with BMI of less than 24, who have no evidence of acute inflammation of the gallbladder and no previous upper abdominal surgery.


Ethyl (6aRS,8RS,12bRS)-6-oxo-8-phenyl-6a,7,8,12b-tetrahydro-6H-benzo[b]naphtho[1,2-d]pyran-6a-carboxylate.
In the title compound, C(26)H(22)O(4), the pyranone ring adopts a twisted boat conformation, while the cyclohexane ring is close to an envelope conformation. The dihedral angle between the mean planes of the coumarin and naphthalene systems is 78.8(1) degree. The attached phenyl ring is in an equatorial position with respect to the cyclohexane ring.


Spatial heterogeneity of crenarchaeal assemblages within mesophilic soil ecosystems as revealed by PCR-single-stranded conformation polymorphism profiling.
Microbial ecologists have discovered novel rRNA genes (rDNA) in mesophilic soil habitats worldwide, including sequences that affiliate phylogenetically within the division Crenarchaeota (domain Archaea). To characterize the spatial distribution of crenarchaeal assemblages in mesophilic soil habitats, we profiled amplified crenarchaeal 16S rDNA sequences from diverse soil ecosystems by using PCR-single-stranded-conformation polymorphism (PCR-SSCP) analysis. PCR-SSCP profiles provide a measure of relative microbial diversity in terms of richness (number of different phylotypes as estimated from the number of unique PCR-SSCP peaks) and evenness (abundance of each phylotype as estimated from the relative area under a peak). Crenarchaeal assemblages inhabiting prairie, forest, turf, and agricultural soils were characterized at six sampling locations in southern and central Wisconsin. Phylotype richness was found to be more stable than evenness among triplicate samples collected within 30 cm at each sampling location. Transformation of the PCR-SSCP data by principal-component analysis, followed by statistical testing (analysis of variance [P < 0.0001] and least-significant-difference analysis [alpha = 0.5]), supported the conclusion that each location exhibited a unique profile. To further characterize the spatial distribution of crenarchaeal assemblages at one location, additional soil samples (a total of 30) were collected from agricultural field plots at the Hancock Agricultural Research Station. PCR-SSCP revealed a patchy spatial distribution of crenarchaeal assemblages within and between these plots. This mosaic of crenarchaeal assemblages was characterized by differences in phylotype evenness that could not be correlated with horizontal distance (15 to 30 m) or with depth (0 to 20 cm below the surface). Crenarchaeal 16S rDNA clone libraries were produced and screened for unique SSCP peaks. Clones representing the dominant phylotypes at each location were identified, sequenced, and found to group phylogenetically with sequences in crenarchaeal clade C1b.


Recovery of single word comprehension: CT-scan correlates.
9tory comprehension for single words, as measured by the BDAE Word Discrimination subtest, was studied longitudinally in a group of 37 aphasic patients. The majority of the patients had impaired performance at 1 month postonset, but recovery by Month 6 postonset was quite striking. Damage to Wernicke's area did not preclude recovery of single word comprehension to within the normal range. Only patients with very extensive left hemisphere lesions had incomplete recovery of single word comprehension.


[Prevalence of adverse and victimization experiences in adult people with severe mental illness in Barcelona].
To describe the extension of the adverse experiences, including victimization, lived in childhood and adulthood in a sample of people with severe mental illness residing in Barcelona, Spain. Descriptive, quantitative and cross-sectional study. Adverse and victimization experiences were assessed using 26 items from the Adverse Childhood Experiences Questionnaire (ACE-IQ). Items were included obtain information regarding victimization during adulthood. Seventy-four people with severe mental illness were interviewed (median age: 42.03 years; standard deviation: 9.60). All participants reported at least two victimization experiences throughout their lifetime. The most frequent experiences were conventional crimes (87.8%) and victimization by caregivers (86.5%). Before age 18, half of the participants reported having experienced physical violence by their caregivers (52.7%) and almost one out of three reported to have been victim of sexual abuse (32.4%). Women were almost 13 times more likely to experience sexual victimization than men throughout their lifetime (odds ratio: 12.75; 95% confidence interval: 4.19-38.71). Victimization experienced by people with severe mental illness is a widespread problem that has received little attention. The results of this study are consistent with those obtained in previous investigations and underscore the need to translate this knowledge into medical practice into medical practice, considering them in order to develop treatments with a comprehensive approach to mental health.


Involvement of the ventromedial and anterior hypothalamic nuclei in the hormonal induction of receptivity in the female rat.
Bilateral lesions of the ventromedial hypothalamic area virtually eliminated the estrogen-induced display of sexual receptiveness in the female rat. Such lesions usually diminished sexual responsiveness to combined estrogen-progresterone stimulation, although not all lesions were equally effective in this regard. Damage to the anterior hypothalamic area was without apparent effect on the hormonally-induced display of receptivity, suggesting that previous observations to this effect are probably related to incicental damage to the ventromedial hypothalamic area incurred during placement of the lesions. This study complements other work indicating that the ventromedial hypothalamic area is relatively rich in estradiol concentrating cells and that estrogen implants to this area induce sexual receptivity in spayed female rats. Together, these studies affirm that the ventromedial hypothalamic area plays a critical role in the hormonal induction of receptivity in female rats.


Prevention of muscarinic acetylcholine receptor down-regulation by chloroquine: antilysosomal or antimuscarinic mechanisms.
The effect of the antimalarial drug chloroquine on the carbachol-induced down-regulation of muscarinic acetylcholine receptors (mAChRs) was studied in the neuroblastoma-glioma hybrid NG108-15 cells. Chloroquine, which is proposed to have both antilysosomal and antimuscarinic effects (4,11), blocked the loss of both cell surface and total mAChRs as monitored by [3H]N-methyl-scopolamine (NMS) and [3H] quinuclidinyl benzilate (QNB) bindings respectively. To the contrary, NH4Cl, only an antilysosomal agent, had no effect on the loss of surface receptors, but blocked degradation of internalized receptors following the effect of carbachol. These findings demonstrate that chloroquine prevents the agonist-induced mAChR down-regulation in NG108-15 cells by both its antilysosomal and antimuscarinic effects.


Sacral nerve stimulation in patients with severe constipation.
Constipation is frequently a multifactorial disease. This study was designed to evaluate the potential effects of sacral nerve stimulation for patients suffering from severe chronic constipation. Nineteen patients suffering from pathologic colonic transit time or rectal outlet obstruction were included. Only patients with severe rectal outlet obstruction who needed digital manipulation for defecation or patients suffering from pathologic colonic transit constipation with less than two bowel movements per week were regarded as candidates. A temporary stimulation lead was implanted into the sacral foramen that showed the best muscular response. After an evaluation period, the stimulation electrode was removed. An improvement in constipation (more than 2 bowel movements per week or defecation without digital manipulation, respectively) during the test stimulation, as well as a recurrence of prestimulation constipation symptoms during the following surveillance period of three weeks were prerequisites for implanting the permanent sacral nerve stimulating system. All of the patients showed a positive motor response to acute needle stimulation. After the evaluation period, eight patients (42 percent) reported an improvement of constipation, and permanent systems were implanted successfully. During the median follow-up of 11 (range, 2-20) months, a significant improvement in the Wexner constipation score was observed compared with the preoperative baseline level (baseline: median: 23, range, 18-27; 12 months after implantation: median, 8, range, 4-13). After successful sacral nerve stimulation, patients also showed a significant improvement in their quality of life. Patients suffering from severe constipation are a new challenge for sacral nerve stimulation but further research on pelvic floor function is needed.


Sizing up the threat: the envisioned physical formidability of terrorists tracks their leaders' failures and successes.
Victory in modern intergroup conflict derives from complex factors, including weaponry, economic resources, tactical outcomes, and leadership. We hypothesize that the mind summarizes such factors into simple metaphorical representations of physical size and strength, concrete dimensions that have determined the outcome of combat throughout both ontogenetic and phylogenetic experience. This model predicts that in the aftermath of tactical victories (e.g., killing an enemy leader), members of defeated groups will be conceptualized as less physically formidable. Conversely, reminders that groups possess effective leadership should lead their members to be envisioned as more physically formidable. Consonant with these predictions, in both an opportunistic study conducted immediately after Osama bin Laden's death was announced (Study 1) and a follow-up experiment conducted approximately a year later (Study 2), Americans for whom the killing was salient estimated a purported Islamic terrorist to be physically smaller/weaker. In Studies 3 and 4, primes of victorious terrorist leaders led to inflated estimates of terrorists' physical attributes. These findings elucidate how the mind represents contemporary military power, and may help to explain how even largely symbolic victories can influence reasoning about campaigns of coalitional aggression.


Removal of heavy metal ions by capacitive deionization: Effect of surface modification on ions adsorption.
Activated carbon cloth (ACC) coated with zinc oxide (ZnO) nanoparticles (NPs) have been used as electrodes in flow-by capacitive deionization (CDI) system. Aqueous solution of individual Pb2+ and Cd2+ ions and mixed Pb2+ and Cd2+ ions were used as test contaminant in CDI system to study the effect of surface modification upon ions removal efficiency. Due to the aggregated structure of ZnO NPs on ACC surface, the modified ACC electrodes develop the additional surface area as well as dielectric barrier therefore resulting in higher specific capacitance. In addition, coating with ZnO NPs effectively reduced physical adsorption whereby enhanced the ions adsorption rate and capacity during electrosorption process. Upon incorporating with ZnO NPs, the electrosorption efficiency was enhanced from 17% to 33% for Pb2+, from 21% to 29% for Cd2+ and from 21% to 35% for mixed Pb2+ and Cd2+ ions. The power consumption of individual ions and mixed ions removal process for ACC and ZnO NPs modified ACC were also discussed. Furthermore, used ACC electrodes surfaces were examined using photoelectron spectroscopy (XPS) and results were also conferred. The CDI ACC electrodes with ZnO NPs showed a promising and an effective way for heavy metal removal applications.


Cloning and expression of alpha class glutathione S-transferase gene from the small hermaphroditic fish Rivulus marmoratus (Cyprinodontiformes, Rivulidae).
In order to assess its potential as a biomarker of aquatic pollution, an alpha class glutathione S-transferase gene (GSTalpha gene) was cloned from the small hermaphroditic fish Rivulus marmoratus. The R. marmoratus GSTalpha gene spanned 1.3 kb, consisting of 6 exons encoding 221 amino acid residues. It showed high similarity to zebrafish GST. We named this R. marmoratus GSTalpha gene as rm-GSTalpha. The cDNA of the rm-GSTalpha gene was also investigated for its phylogeny, tissue-specific and chemical-induced expression. Rm-GSTalpha was subcloned into a 6 x His-tagged pCRT7 TOPO TA expression vector to produce the recombinant 6 x His-tagged rm-GST protein. This will be used in future to raise an rm-GSTalpha antibody for use in the study of phase II metabolism involved in detoxification. We also exposed R. marmoratus to 300 microg/l of 4-nonylphenol in water, and found approximately 4-fold induction of R. marmoratus GSTalpha mRNA in the treated animals. In this paper, we discuss the characteristics of the R. marmoratus GSTalpha gene as well as its potential use in relation to environmental pollution.


Impact of Pain on Postoperative Recovery and Participation in Care Following Knee Arthroplasty Surgery: A Qualitative Descriptive Study.
Patient participation in care is key to optimising postsurgical outcomes and the quality of acute care delivery. This study explored patient perceptions of the impact of pain on acute recovery following Total Knee Arthroplasty (TKA), and barriers and facilitators to participating in pain management. An exploratory-descriptive qualitative study involving semi-structured interviews. A private-sector health service. Participants were adults undergoing TKA allocated to the control ward of a cluster randomised controlled trial who received standard care. To allow adequate opportunity for participation in their care, interview and pain data were collected on postoperative Day 3. Acute pain was assessed using an 11-point Numerical Rating Scale (NRS). Interviews were analysed using combined qualitative thematic analysis and quantitative content analysis. Overall, 120 patients, 69 females (50.4%) and 68 males, were interviewed (mean age = 66.8 years, stadard deviation [SD] = 8.5). Most reported severe (NRS 7-10), day 3 pain (n = 76, 63.3%). Two themes emerged from interviews: (1) participants' postoperative pain experience; and (2) participation in postoperative pain management was limited. Pain experience was characterised by variation in pain and its qualities, having uncontrolled pain and distress, and influence from preoperative expectations. Patient participation was characterized by reliance upon prior staff instruction, barriers from limited knowledge, inconsistent promotion of non-pharmacologic strategies, and suboptimal clinician-patient communication. Regular analgesia was identified to facilitate participation. Despite the known benefits of patient participation in pain management, gaps remain in providing patients with the knowledge and opportunity to take an active role in their recovery. Interventions to overcome identified barriers need to be developed and evaluated.


Comparing the pRIFLE, AKIN, KDIGO, and modified KDIGO criteria in neonates after cardiac surgery.
While several standardized criteria for acute kidney injury (AKI) have been studied, there is no consensus on which criteria to use in neonates after cardiac surgery. The goal of this research was to compare the AKI incidence and outcomes according to the pediatric Risk, Injury, Failure and Loss, and End-Stage (pRIFLE), AKI Network (AKIN), Kidney Disease Improving Global Outcomes (KDIGO), and modified KDIGO (mKDIGO) criteria in neonates following congenital cardiac surgery. A clinical database of all neonates undergoing congenital cardiac surgery admitted to the Cantonese cardiac center from 2014 to 2020 was retrospectively analyzed. AKI was based on the pRIFLE, AKIN, KDIGO, and mKDIGO classification. The predictive abilities for postoperative outcomes were compared by receiver operating curves, and multivariate logistic regression analysis was used to assess the association of AKI definitions with postoperative outcomes. In the study population of 522 patients, 177, 110, 131, and 114 neonates had AKI according to the pRIFLE, AKIN, KDIGO, and mKDIGO criteria, respectively. After multivariate analysis, all definitions were found to be significant predictors of increased mortality. The AUCs for mortality were substantially different with pRIFLE (AUC, 0.795), AKIN (AUC, 0.724), KDIGO (AUC, 0.819), and mKDIGO (AUC, 0.831) (P < 0.01) across the entire population, whereas the mKDIGO system was more accurate than the pRIFLE, AKIN, and KDIGO systems. The incidence of AKI varied across all definitions. However, the mKDIGO system was more accurate in predicting in-hospital mortality than the pRIFLE, AKIN, and KDIGO systems in neonates after heart surgery.


An effector of 'Candidatus Liberibacter asiaticus' manipulates autophagy to promote bacterial infection.
Autophagy functions in plant host immunity responses to pathogen infection. The molecular mechanisms and functions used by the citrus Huanglongbing (HLB)-associated intracellular bacterium 'Candidatus Liberibacter asiaticus' (CLas) to manipulate autophagy are unknown. We identified a CLas effector, SDE4405 (CLIBASIA_04405), which contributes to HLB progression. 'Wanjincheng' orange (Citrus sinensis) transgenic plants expressing SDE4405 promotes CLas proliferation and symptom expression via suppressing host immunity responses. SDE4405 interacts with the ATG8-family of proteins (ATG8s), and their interactions activate autophagy in Nicotiana benthamiana. The occurrence of autophagy is also significantly enhanced in SDE4405-transgenic citrus plants. Interrupting NbATG8s-SDE4405 interaction by silencing of NbATG8c reduces Pseudomonas syringae pv. tomato strain DC3000ΔhopQ1-1 (Pst DC3000ΔhopQ1-1) proliferation in N. benthamiana, and transient overexpression of CsATG8c and SDE4405 in citrus promotes Xanthomonas citri subsp. citri (Xcc) multiplication, suggesting that SDE4405-ATG8s interaction negatively regulates plant defense. These results demonstrate the role of the CLas effector protein in manipulating autophagy, and provide new molecular insights into the interaction between CLas and citrus hosts.


Reversal of dementia associated with Whipple's disease by trimethoprim-sulfamethoxazole, drugs that penetrate the blood-brain barrier.
A previously healthy 67-yr-old man presented with progressive dementia over an 11-mo period. Evaluation revealed evidence of malabsorption. Jejunal biopsy established the diagnosis of Whipple's disease. No other etiology for the patient's dementia was uncovered. Treatment with trimethoprim-sulfamethoxazole resulted in rapid elimination of Whipple's bacilli from the jejunum and complete reversal of the patient's dementia over a 6-mo period. Significant levels of trimethoprim and sulfamethoxazole were easily quantitated in the cerebrospinal fluid during therapy. There is increasing recognition of progressive neurologic disease in patients with Whipple's disease who were treated with tetracycline. The reversal of presumed central nervous system disease in this case suggests that drugs that penetrate the blood-brain barrier might be preferable for the initial treatment of Whipple's disease.


First Detection in Helicobacter suis of a Mutation Conferring Resistance to Clarithromycin in Helicobacter pylori: Case Report and Review of the Literature.
Helicobacter pylori and non-H. pylori Helicobacter (NHPH) are associated with gastritis, ulcer, and gastric neoplasia. Because of the impossibility to culture them, diagnosis remains based on microscopic examination and molecular analysis of biopsies. Owing to the lack of data concerning antibiotic resistance of NHPH, infected patients are usually treated using antibiotics, including clarithromycin. Herein, we describe, for the first time a human infection by Helicobacter suis harboring a mutation associated to clarithromycin resistance in H. pylori. Eradication was successful with a metronidazole-based treatment. This observation highlights the benefit to use genotypic detection of resistance to improve therapeutic management of NHPH infections.


Evolutionary optimisation of antibiotic dosing regimens for bacteria with different levels of resistance.
Antimicrobial resistance is one of the biggest threats to global health, food security, and development. Antibiotic overuse and misuse are the main drivers for the emergence of resistance. It is crucial to optimise the use of existing antibiotics in order to improve medical outcomes, decrease toxicity and reduce the emergence of resistance. We formulate the design of antibiotic dosing regimens as an optimisation problem, and use an evolutionary algorithm suited to continuous optimisation (differential evolution) to solve it. Regimens are represented as vectors of real numbers encoding daily doses, which can vary across the treatment duration. A stochastic mathematical model of bacterial infections with tuneable resistance levels is used to evaluate the effectiveness of evolved regimens. The objective is to minimise the treatment failure rate, subject to a constraint on the maximum total antibiotic used. We consider simulations with different levels of bacterial resistance, two ways of administering the drug (orally and intravenously), as well as coinfections with two strains of bacteria. Our approach produced effective dosing regimens, with an average improvement in lowering the failure rate 30%, when compared with standard fixed-daily-dose regimens with the same total amount of antibiotic.


Automated assessment of ovarian follicles using a novel three-dimensional ultrasound software.
To evaluate the accuracy, efficiency, and applicability of a new automated method of follicular assessment. Retrospective review of three-dimensional ultrasonographic ovarian volumes. Academic center. Three-dimensional ovarian volumes from patients undergoing IVF. Three-dimensional volumes of gonadotropin-stimulated ovaries and simulated ovarian follicles (SOFs) of known volume were evaluated with the new automated follicular assessment software (SonoAVC). [1] Maximum absolute error for the SonoAVC in assessing the volumes of the SOFs; [2] correlations between the automated and manual follicular measurements; [3] time required to analyze all of the follicles in a given ovarian volume. The SOF of 4, 6, and 10 mm were evaluated. The SonoAVC's maximum absolute error for the volumes of the 4, 6, and 10 mm SOFs was 0 (0%), 0.01 (8.3%), and 0.02 (3.8%) cc, respectively. Three hundred forty-seven follicles, ranging in diameter from 2.3-32 mm, were evaluated. The correlation coefficient for the SonoAVC-generated relaxed follicular diameter and the manual measured mean follicular diameter was 0.99. The time required to analyze all of the follicles in a given ovarian volume for the automated and manual method was 133 versus 361 seconds, respectively. The SonoAVC proved to be a very accurate and efficient way to measure ovarian follicles. The measurements obtained by the SonoAVC correlated extremely well with the manual measurements we obtained.


The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation.
Exit from mitosis requires the inactivation of mitotic cyclin-dependent kinases (CDKs) by an unknown mechanism. We show that the Cdc14 phosphatase triggers mitotic exit by three parallel mechanisms, each of which inhibits Cdk activity. Cdc14 dephosphorylates Sic1, a Cdk inhibitor, and Swi5, a transcription factor for SIC1, and induces degradation of mitotic cyclins, likely by dephosphorylating the activator of mitotic cyclin degradation, Cdh1/Hct1. Feedback between these pathways may lead to precipitous collapse of mitotic CDK activity and help coordinate exit from mitosis.


Growth hormone induces resistance to the mitogenic action of insulin through local IGF-I. Studies in normal and Pygmy T-cell lines.
Growth hormone (GH) and insulin have both mitogenic and metabolic actions. The growth-promoting effects of GH in vivo are thought to be mediated by insulin-like growth factor-I (IGF-I), whereas the metabolic effects of GH are thought to be either direct or mediated by factors other than IGF-I. In previous studies using HTLV-II-transformed T-lymphoblast cell lines established from normal individuals, we have shown that GH preincubation induces resistance to the growth-promoting (mitogenic) action of insulin. In this study, using T-cell lines from 3 American control subjects, 1 African control subject, and 1 African Pygmy (the latter previously shown to be resistant to the growth-promoting actions of both IGF-I and GH), we examined the role of local IGF-I in the mediation of GH-induced resistance to the mitogenic action of insulin. In these studies, we quantified the stimulation of T-cell colony formation in response to insulin in the presence and absence of either GH or IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)


Filipin fluorescence quenching by spin-labeled probes: studies in aqueous solution and in a membrane model system.
A detailed photophysical study of the fluorescence quenching (transient and steady state) of the macrolide antibiotic filipin by nitroxide-substituted fatty acids and a cholesterol derivative was carried out, aimed at determining its transverse position in a model system of membranes (multilamellar vesicles of dipalmitoylphosphatidylcholine). Filipin partitions efficiently into membranes (Kp = (5.0 +/- 1.0).10(3), 20 degrees C) and it was concluded that the antibiotic is buried in the membrane, away from the lipid-water interface. In addition, information on the organization of the quenchers was also obtained. The 5-nitroxide derivative of the fatty acid is essentially randomly distributed, while the 16-nitroxide is aggregated at concentrations higher than approximately 5% molar. For the cholesterol compound the results point to a phase separation at concentrations higher than 3% molar (below this limit concentration filipin associates with the derivatized sterol with KA = 20 M-1, assuming a 1:1 interaction). We propose that this phase separation and the aggregation state of filipin in the aqueous solution may be key processes in the antibiotic mode of action. A systematic and general approach to fluorescence quenching data analysis in complex (e.g., biochemical) systems is also presented.


Prolene-Monocryl-composite meshes do not increase microvascular Staphylococcus aureus adherence and do not sensitize for leukocytic inflammation.
Mesh implantation for hernia repair bears the risk of bacterial mesh infection. In this study, we analyzed whether this complication is supported by an increased interaction of bacteria and leukocytes with the microvascular endothelium at the implantation site. Ultrapro meshes were implanted into the dorsal skinfold chamber of Syrian golden hamsters. After 12 days, fluorescein isothiocyanate (FITC)-labeled staphylococci were injected in the animals. Subsequently, we analyzed bacterial adherence, leukocyte-endothelial cell interaction, and microhemodynamics in venules of the mesh border zone and of distant control tissue under baseline conditions and during TNF-alpha-induced inflammation using intravital fluorescence microscopy. The results were compared to animals which did not receive any bacteria. Under baseline conditions, leukocyte-endothelial cell interaction and bacterial adherence were not affected by the implanted biomaterial. TNF-alpha-induced inflammation significantly increased numbers of adherent leukocytes and bacteria in venules located in direct vicinity to the mesh however without any differences to control tissue. Comparable results were found for the leukocyte-endothelial cell interaction when animals were not exposed to bacteria. Implanted Ultrapro meshes do neither increase microvascular Staphylococcus aureus adherence nor sensitize for leukocytic inflammation. Thus, we suggest that a mesh-induced increase of bacterial adherence in vessels of the implantation site cannot be considered as a primary cause for the development of mesh infection.


Modification of microridge pattern in teleost (Pimelodus maculatus) epidermal cells induced by NaCl.
When NaCl is added to the aqueous environment, the fingerprint-like pattern showed by microridges of epidermal superficial cells of the teleost Pimelodus maculatus is modified. This modification probably occurs consequently the rearrangement of cytoplasmic filaments.


Butafenacil: A positive control for identifying anemia- and variegate porphyria-inducing chemicals.
Butafenacil is an herbicide that inhibits protoporphyrinogen oxidase (PPOX), an enzyme that catalyzes oxidation of protoporphyrinogen IX to protoporphyrin IX during chlorophyll and heme biosynthesis. Based on a high-content screen, we previously identified butafenacil as a potent inducer of anemia in zebrafish embryos. Therefore, the objective of this study was to begin investigating the utility of butafenacil as a positive control for identifying anemia- and variegate porphyria-inducing chemicals. Static exposure to butafenacil from 5 to 72 h post-fertilization (hpf) in glass beakers resulted in a concentration-dependent decrease in arterial circulation at low micromolar concentrations. At 72 hpf, the magnitude of butafenacil-induced anemia was similar when embryos were exposed in the presence or absence of light, whereas protoporphyrin accumulation and acute toxicity were significantly lower or absent when embryos were exposed under dark conditions. To identify sensitive developmental windows, we treated embryos to butafenacil from 5, 10, 24, or 48 hpf to 72 hpf in the presence of light, and found that anemia and protoporphyrin accumulation were present at 72 hpf following initiation of exposure at 5 and 10 hpf. On the contrary, protoporphyrin accumulation - but not anemia - was present following initiation of exposure at 24 hpf. Lastly, protoporphyrin accumulation at 72 hpf after exposure from 24 to 48 hpf suggests that protoporphyrin was not eliminated over a 24-h recovery period. Collectively, our data suggests that butafenacil may be a reliable positive control for identifying anemia- and variegate porphyria-inducing chemicals.


Switches in species-specific codon preferences: the influence of mutation biases.
A model of synonymous codon usage is developed in which the most frequent codons are selectively advantageous because of their coadaptation with tRNA abundances. Random drift opposes the progress of this coevolution by pushing codon frequencies in the direction of the frequency that would result from mutation in the absence of selection. It is predicted that, within a certain range, an increased mutation bias away from an advantageous codon has little influence on its usage in highly expressed genes. However, a subsequent small increase in mutation bias over a critical range leads to a large reduction in the frequency of the codon. The switch in preference from one synonym to another is a sharp transition, with no stable intermediate state in which neither codon is advantageous. Codon usage patterns were compared among three related bacterial species of differing genomic G & C contents, Escherichia coli, Serratia marcescens, and Proteus vulgaris. It was found that although changes in mutation biases do not always result in switches in codon preferences, some switches have occurred in the direction of species-specific mutation biases. Fluctuating mutation biases may therefore be the main cause of differences between species in their codon preferences.


Increased semaphorin 3c expression promotes tumor growth and metastasis in pancreatic ductal adenocarcinoma by activating the ERK1/2 signaling pathway.
Pancreatic cancer is characterized by neural alterations and aberrant expression of neural-specific factors. Semaphorins have been recognized as key contributors in axon guidance, the immune response and tumor progression. Recent studies have suggested the involvement of Semaphorin 3c (sema3c) in tumorigenesis and metastasis in numerous types of cancer, however, the clinical significance of sema3c and its role in the growth and metastasis of pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we found that aberrant sema3c expression was positively associated with a particular tumor stage and correlated with poor survival of PDAC patients. Knockdown of sema3c attenuated proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in a pancreatic cancer cell line and reduced PDAC cell tumorigenesis upon xenotransplantation into NOD/SCID mice. Overexpression of sema3c produced the opposite effects and promoted the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Overall, our findings demonstrate that aberrant expression of sema3c is correlated with poor prognosis of PDAC patients and promotes tumor growth and metastasis by activating ERK1/2 signaling pathway.


Evaluation of the Hepatitis C Testing Strategy for Human Immunodeficiency Virus-Positive Men Who Have Sex With Men at the Sexually Transmitted Infections Outpatient Clinic of Amsterdam, the Netherlands.
As the incidence of hepatitis C virus (HCV) infections remains high among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) an HCV testing strategy was introduced at the sexually transmitted infections (STI) clinic in Amsterdam in 2017. We aimed to evaluate this HCV testing strategy. The HIV-positive MSM and transgender women (TGW) were eligible for HCV testing (anti-HCV and HCV ribonucleic acid) at the STI clinic if they did not visit their HIV clinician in the 3 months before the consultation and had not been tested for HCV at the STI clinic in the previous 6 months. All eligible individuals were administered the 6 questions on risk behavior of the HCV-MSM observational study of acute infection with hepatitis C (MOSAIC) risk score; a risk score of 2 or greater made a person eligible for testing. From February 2017 through June 2018, 1015 HIV-positive MSM and TGW were eligible for HCV testing in 1295 consultations. Eleven active HCV infections (HCV ribonucleic acid positive) were newly diagnosed (positivity rate, 0.9%; 95% confidence interval [CI], 0.4-1.5%). Sensitivity and specificity of the HCV-MOSAIC score for newly diagnosed active HCV infections were 80.0% (95% CI, 49.0-94.3%) and 53.7% (95% CI, 50.8-56.5%), respectively. If an HCV-MOSAIC score of 2 or greater were used to determine whom to test, 46.6% of individuals currently tested for HCV would be eligible for testing. Using the new HCV testing strategy, HCV testing was done in 1295 consultations with HIV-positive MSM and TGW in 17 months. We newly diagnosed 11 active HCV infections. The HCV-MOSAIC risk score could reduce the number of tests needed, but some active HCV infections will be missed.


External and iatrogenic trauma of the urinary bladder: a survey in Poland.
To assess incidence of urinary bladder injuries (frequently associated with pelvic trauma and often iatrogenic) in Poland. The records and details of urinary bladder injuries treated between 1995 and 1999 were analysed for 61 urological departments in Poland. During the 5-year period 512 patients had urinary bladder injuries; in 210 (41%) the injury was caused by a road traffic accident, in eight (2%) by compression (crushing injury) within the limits of the pelvic bones, in 40 (8%) by a fall from a height, in three by a gunshot wound and in the remaining 251 (49%) the injury was iatrogenic. Among the 261 bladder injuries that were not iatrogenic, 41 (16%) were associated with pelvic bone trauma. In 36 patients there was simultaneous injury of the urinary bladder and posterior urethra, constituting 14% of such injuries and 7% of all trauma cases. The iatrogenic injuries were in 98 patients (39%) in urological departments, in 130 (52%) women in gynaecological departments and in 23 (9%) on surgical wards. The injury was open in 102 patients (20%) and closed in 372 (73%); there was bladder contusion in 38 patients (7%). The injuries were intraperitoneal in 225 patients (44%) and extraperitoneal in 287 (56%). For diagnosis, abdominal ultrasonography was used in 455 (89%) patients, intravenous pyelography in 266 (52%), cystography in 388 (76%) and computed tomography in 15 (3%). The delay between trauma and diagnosis was 0.5-124 h. Surgical treatment of the injury comprised a monolayer suture of the bladder wall in 51 patients (10%), a two-layered suture in 461 (90%), perivesical drainage in 468 (91%) and inspection of the peritoneal cavity in 232 (45%). The mean (range) interval between diagnosis and treatment was 14 (7-70) days. Seven patients died after the treatment failed. Almost half the patients had iatrogenic injuries, of which over half occurred in gynaecological and maternity wards. Thus it is important teach the basic range of urological operations to trainee doctors. The commonest diagnostic method was not ascending cystography but ultrasonography; we recommend ascending cystography be used with at least two views after filling the urinary bladder with approximately 300 mL of contrast medium, with an additional film after emptying the contrast medium. In patients with pelvic bone trauma it is reasonable to use spiral computed tomography with virtual analysis before surgery. A two-layered suture of the bladder wall with perivesical drainage should be used.


Repair of Scars and Tissue Deficiency With Free Grafts of Full-thickness Scalp in Secondary Unilateral Cleft Lip Deformity.
Although surgical techniques have developed, the incidence of secondary cleft lip deformities after the primary repair is still high. Asymmetry of Cupid's bow and philtrum is a common presentation and a technical challenge to reconstruct the upper lip. The authors introduce a technique to use the free grafts of the full-thickness scalp for the correction of scars and tissue deficiency in secondary unilateral cleft lip deformity. Thirty-seven patients with a prominent scar, tight upper lip, deformed Cupid's bow and philtrum, and irregular vermillion border were included in this study. The specific points of interest were assessed before and after surgery by independent examiners with both subjective and objective methods. All surgeries were successfully completed, and the assessment results were satisfactory. The rating scores of philtrum improvement was 1.6±0.4, the POSAS result of patient scales was 13.48±3.21, and the observer scale result was 11.98±3.88. The asymmetry of Cupid's bow was corrected ( P =0.004), the central tubercle of vermilion was more natural ( P =0.001), and the irregular vermillion border was improved ( P =0.015). The results presented significant differences before and after surgery. This method could be an optional treatment for repairing scars and tissue deficiency in secondary unilateral cleft lip deformity.