ACTG1 and TLR3 are biomarkers for alcohol-associated hepatocellular carcinoma.
Alcohol consumption is a risk factor for the development of hepatocellular carcinoma (HCC); however, the association between alcohol and HCC remains unknown. The present study aimed to identify key genes related to alcohol-associated HCC to improve the current understanding of the pathology of this disease. Alcohol-associated and non-alcohol-associated HCC samples in the GSE50579 dataset of the Gene Omnibus Database were analyzed to investigate altered gene expression. Integrated bioinformatics methods were employed to clarify the biological functions of the differentially expressed genes (DEGs), including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interactions (PPIs). The present study reported that candidate biomarker micro (mi)RNAs via TargetScan Human 7.1. DEGs and their associated miRNAs (according to bioinformatics analysis) were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, 284 EGs from the GSE50579 dataset were revealed. In GO term analysis, DEGs were closely associated with the 'regulation of nucleic acid metabolism'. KEGG pathway analysis indicated that the DEGs were tightly engaged in the 'VEGF and VEGF receptor signaling network', 'proteoglycan syndecan-mediated signaling events', 'erbB receptor signaling' and 'β1 integrin cell surface interactions'. According to the results of PPI and heat map analysis, the main hub genes were centrin 3 (CETN3), Toll-like receptor 3 (TLR3), receptor tyrosine-protein kinase (ERBB4), heat shock protein family member 8, actin γ1 (ACTG1) and α-smooth muscle actin. it was demonstrated that the ACTG1, TLR3, miR-6819-3p and miRΝΑ (miR)-6877-3P had undefined associations. Furthermore, RT-qPCR analysis revealed that miR-6819-3p and miR-6877-3P may enhance the expression levels of ACTG1 and inhibit the expression levels of TLR3 in alcohol-associated HCC tissues. TLR3 and ACTG1 were proposed as potential biomarkers of alcohol-associated HCC. Investigation into the regulatory functions of miR-6819-3p and miR-6877-3P may provide novel insights into the treatment of alcohol-associated HCC.


Profilin desensitization in two patients with plant-derived food allergy.
Profilins are "panallergens", responsible for many cross-reactivities between inhalant, latex and plant-derived food allergens. We evaluated the effectiveness and the safety of sublingual desensitization treatment (SLIT) in two patients with allergic respiratory and food diseases. Skin prick tests, IgE and IgG4 assays to pollens, some plant-derived foods, profilin, non-lipid specific transfer protein and PR 10 proteins were performed. The patients also underwent double-blind placebo-controlled challenge (DBPCFC) with the culprit foods and profilin and then a SLIT with it. Both the patients had positive SPT, specific IgE and DBPCFCs with profilin and some vegetables referred in anamnesis. They therefore underwent SLIT with profilin extract. At the end of treatment, the patients had negative DBPCFCs with culprit foods and a decrease of specific IgE levels for profilin and vegetable foods. Profilin desensitization allowed our patients to manage their diet without restriction, eating several foods previously not tolerated.


Modeling highly focused laser beam in optical tweezers with the vector Gaussian beam in the T-matrix method.
The vector Gaussian beam with high-order corrections is used to describe accurately the laser beam up to numerical aperture NA=1.20 in the optical tweezers for trapping nanoparticles. The beam is then expanded in the T-matrix method into the vector spherical wave function (VSWF) series using the point matching method with a new selection of the matching points. The errors in the beam description and in the VSWF expansion are much lower than those that occur in the paraxial Gaussian beam model.


Continuous Aspirin Use Does Not Increase Bleeding Risk of Split-Thickness Skin Transplantation Repair to Chronic Wounds.
Discontinuation of aspirin therapy before cutaneous surgery may cause serious complications. The aim of this prospective study was to evaluate the bleeding risk of split-thickness skin transplantation repair to chronic wounds in patients on aspirin therapy. A total of 97 patients who underwent split-thickness skin transplantation surgery of chronic wounds during a 2-year period were enrolled. They were categorized on the basis of aspirin therapies. The primary outcome was postoperative bleeding and bleeding complications. Univariate analysis was performed to examine the association between aspirin and bleeding complications. Among the 26 patients taking aspirin continuously in group A, there were 5 bleeding complications (19.23%). Among the 55 nonusers in group B, there were 10 bleeding complications (18.18%). Among the 16 discontinuous patients in group C, there were 3 bleeding complications (18.75%). No statistical differences were found among the groups ( P = .956). Univariate analysis showed that continuous aspirin use was not significantly associated with bleeding complications (odds ratio, 0.933; 95% confidence interval, 0.283-3.074; P = .910 in the aspirin and control groups) and that discontinuous aspirin use was not significantly associated with bleeding complications (odds ratio, 0.963; 95% confidence interval, 0.230-4.025; P = .959 in the aspirin and control groups; odds ratio, 0.969; 95% confidence interval, 0.198-4.752; P = .969 in the aspirin and discontinuous groups). Continuous aspirin use does not produce an additional bleeding risk in patients who undergo split-thickness skin transplantation repair of chronic wounds.


Constitutive expression of B-myb can bypass p53-induced Waf1/Cip1-mediated G1 arrest.
Overexpression of wild-type p53 protein has been shown to induce arrest in the G1 stage of the cell cycle and to transactivate expression of the gene that encodes the 21-kDa Waf1/Cip1 protein, a potent inhibitor of cyclin-dependent kinase activity. p53-dependent G1 arrest is accompanied by decreased expression of the B-myb gene, a relative of the c-myb cellular oncogene. In this study we show that B-myb expression is required for cells to progress from G1 into S phase and that high levels of ectopic B-myb expression uncoupled from cell cycle regulation rescues cells from p53-induced G1 arrest even in the presence of Waf1/Cip1 transactivation and inhibition of cyclin E/Cdk2 kinase activity. Cotransfection experiments with p53 expression plasmids and expression plasmids encoding in-frame deletion mutations in B-myb coding sequences indicate that the DNA-binding domain of the B-Myb protein is required for this activity. These results provide evidence of a bypass of p53-induced Waf1/Cip1-mediated cell cycle regulatory pathways by a member of the myb oncogene family.


Comparison Between Carbapenems and β-Lactam/β-Lactamase Inhibitors in the Treatment for Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis.
Carbapenems are widely used for the management of bloodstream infections (BSIs) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE). However, the wide use of carbapenems has been associated with carbapenem-resistant Enterobacteriaceae development. We searched the PubMed and Scopus databases (last search date was on June 1, 2016) looking for studies that reported mortality in adult patients with ESBL-PE BSIs that were treated with carbapenems or β-lactam/β-lactamase inhibitors (BL/BLIs). Fourteen studies reported mortality data in adult patients with ESBL-PE BSI that were treated with carbapenems or BL/BLIs. Among them, 13 studies reported extractable data on empiric therapy, with no statistically significant difference in mortality of patients with ESBL-PE BSI that were treated empirically with carbapenems (22.1%; 121 of 547), compared with those that received empiric BL/BLIs (20.5%; 109 of 531; relative risk [RR], 1.05; 95% confidence interval [CI], 0.83-1.37; I2 = 20.7%; P = .241). In addition, 7 studies reported data on definitive therapy. In total, 767 patients (79.3%) received carbapenems and 199 patients (20.6%) received BL/BLIs as definitive therapy, and there was again no statistically significant difference (RR, 0.62; 95% CI, 0.25-1.52; I2 = 84.6%; P < .001). Regarding specific pathogens, the use of empiric BL/BLIs in patients with BSI due to ESBL-Escherichia coli was not associated with a statistically significant difference in mortality (RR, 1.014; 95% CI, 0.491-2.095; I2 = 62.5%; P = .046), compared with the use of empiric carbapenems. These data do not support the wide use of carbapenems as empiric therapy, and BL/BLIs might be effective agents for initial/empiric therapy for patients with BSI caused by likely ESBL-PE, and especially ESBL-E coli.


Mosaicplasty with autogenous talar autograft for osteochondral lesions of the talus after failed primary arthroscopic management: a prospective study with a 4-year follow-up.
There have been limited data in the literature reporting the results of osteochondral autografting for osteochondral lesions of the talus that have failed arthroscopic treatment. Osteochondral autografting can produce significant clinical improvement and a high rate of healing of osteochondral defects of the talus that have failed arthroscopic treatment. Cohort study; Level of evidence, 4. Between 1998 and 2003, 35 patients (18 men, 17 women) with osteochondral talar lesions for which arthroscopic excision, curettage, and drilling had failed, underwent mosaicplasty with an osteochondral graft harvested from the ipsilateral talar articular facet. A malleolar osteotomy or a tibial wedge osteotomy was used for central or posterior lesions that could not otherwise be reached. The mean age of the patients was 30.9 years, and the mean follow-up was 48.9 months. The American Orthopaedic Foot and Ankle Society Ankle Hindfoot scale score in patients without osteotomy rose by 39 points (P = .0001); with malleolar osteotomy, by 30.1 points (P = .017); with tibial wedge osteotomy, by 34.9 points (P = .0002); and with the posterolateral approach, by 32 points. The Wilcoxon test revealed a significant difference between patients without and with osteotomy (P <or= .027) and between patients with malleolar and tibial wedge osteotomies (P = .046). There were no patients with nonunion or malunion in the osteotomy groups. The score values corresponded with the subjective patient evaluation. The Spearman coefficient of correlation was .89. Osteochondral autografting with tibial wedge osteotomy is a good alternative to malleolar osteotomy in osteochondral talar lesions that have failed arthroscopic treatment and that cannot be reached in spite of a forced plantar flexion of the ankle. Patients with small osteochondral lesions accessible through an anterior approach without additional osteotomy have the best prognostic factors.


Complement biomarkers reflect the pathological status of neuromyelitis optica spectrum disorders.
Complement is involved in the pathogenesis of neuroimmune disease, but the detailed pathological roles of the complement pathway remain incompletely understood. Recently, eculizumab, a humanized anti-C5 monoclonal antibody, has been clinically applied against neuroimmune diseases such as myasthenia gravis and neuromyelitis optica spectrum disorders (NMOSD). Clinical application of eculizumab is also being investigated for another neuroimmune disease, Guillain-Barré syndrome (GBS). However, while the effectiveness of eculizumab for NMOSD is extremely high in many cases, there are some cases of myasthenia gravis and GBS in which eculizumab has little or no efficacy. Development of effective biomarkers that reflect complement activation in these diseases is therefore important. To identify biomarkers that could predict disease status, we retrospectively analyzed serum levels of complement factors in 21 patients with NMOSD and 25 patients with GBS. Ba, an activation marker of the alternative complement pathway, was elevated in the acute phases of both NMOSD and GBS. Meanwhile, sC5b-9, an activation marker generated by the terminal complement pathway, was elevated in NMOSD but not in GBS. Complement factor H (CFH), a complement regulatory factor, was decreased in the acute phase as well as in the remission phase of NMOSD, but not in any phases of GBS. Together, these findings suggest that complement biomarkers, such as Ba, sC5b-9 and CFH in peripheral blood, have potential utility in understanding the pathological status of NMOSD.


Exiting homelessness: perceived changes, barriers, and facilitators among formerly homeless adults with mental disorders.
This study examines key themes from narrative interviews conducted with 43 homeless adults with mental disorders 18 months after random assignment to Housing First with intensive supports or to treatment as usual (no housing or supports through the study). Coding and thematic analysis of semistructured interviews was based on 2 research questions from participants' perspectives: (a) What changes were perceived over time? (b) What factors facilitated or hindered change? The majority of participants assigned to Housing First reported positive change across multiple domains as a result of stable housing; whereas the majority of treatment as usual participants reported negative or neutral change. Key themes included feelings of security and pride; adjusting to living alone; housing as a learning process; and developing meaningful activity. The sense of security associated with stable housing was the most influential factor that supported change. Factors that helped or hindered change clustered into 4 key themes: the type and quality of services; the cumulative effects of trauma; social ties; and concurrent substance use. Our findings provide important context to the emerging body of quantitative research on Housing First and recovery from homelessness. Participants' experiences of recovery, particularly as it relates to housing and supports, shifts in identity, and meaningful activity must be acknowledged and incorporated into the design and evaluation of public services, and policy and service reforms. (PsycINFO Database Record


Dispersibility and emulsion-stabilizing effect of cellulose nanowhiskers esterified by vinyl acetate and vinyl cinnamate.
The surface of cotton cellulose nanowhiskers (CNW's) was esterified by vinyl acetate (VAc) and vinyl cinnamate (VCin), in the presence of potassium carbonate as catalyst. Reactions were performed under microwave activation and monitored by Fourier transform infrared (FT-IR) spectroscopy. The supramolecular structure of CNW's before and after modification was characterized by X-ray diffraction (XRD) and atomic force microscopy (AFM). Distinctively from the acetylation treatment, an increase in particles dimensions was noted after esterification with VCin, which was assigned to π-π stacking interactions that may exist between cinnamoyl moieties. The dispersibility and emulsion stabilizing effect of acylated CNW's was examined in ethyl acetate, toluene, and cyclohexane, three organic solvents of medium to low polarity. The acylated nanoparticles could never be dispersed in toluene nor cyclohexane, but they formed stable dispersions in ethyl acetate while remaining dispersible in water. Stable ethyl acetate-in-water, toluene-in-water, and cyclohexane-in-water emulsions were successfully prepared with CNW's grafted with acetyl moieties, whereas the VCin-treated particles could stabilize only the cyclohexane-in-water emulsions. The impact of esterification treatment on emulsion stability and droplets size was particularly discussed.


Chronic binge ethanol consumption accelerates progression of simian immunodeficiency virus disease.
While alcohol consumption is known to increase the incidence and severity of infections, the impact of alcohol consumption on human immunodeficiency virus (HIV) disease progression has been difficult to assess. Therefore, we examined the effect of ethanol on simian immunodeficiency virus (SIV) disease progression in a well-defined model utilizing rhesus macaques. Alcohol was administered for 5 hours via an indwelling intragastric catheter to achieve an alcohol concentration of 50 to 60 mM for 4 consecutive days per week for the duration of the study. Control animals received isocaloric sucrose. After 3 months, animals were inoculated intravenously with 10,000 times the ID(50) of SIV(DeltaB670) and followed to end-stage disease. Plasma SIV ribonucleic acid (RNA) was higher in alcohol-consuming animals compared with sucrose-treated animals during the early asymptomatic stage of disease but not at later time points. This increase in viral set point was associated with more rapid progression to end-stage disease in macaques administered alcohol (median=374 days) compared with sucrose (median=900 days). The decline in blood CD4+ cells was similar in both groups of animals. This study indicates that frequent episodes of alcohol intoxication in SIV+ macaques increase viral set point in association with more rapid development of end-stage disease.


Human papillomavirus in cervical cancer and oropharyngeal cancer: One cause, two diseases.
Human papillomavirus (HPV) causes greater than 5% of cancers worldwide, including all cervical cancers and an alarmingly increasing proportion of oropharyngeal cancers (OPCs). Despite markedly reduced cervical cancer incidence in industrialized nations with organized screening programs, cervical cancer remains the second most common cause of death from cancer in women worldwide, as developing countries lack resources for universal, high-quality screening. In the United States, HPV-related OPC is only 1 of 5 cancers with a rising incidence since 1975 and now has taken over the cervix as the most common site of HPV-related cancer. Similar trends follow throughout North America and Europe. The need for early detection and prevention is paramount. Despite the common etiologic role of HPV in the development of cervical cancer and HPV-associated OPC, great disparity exists between incidence, screening modalities (or lack thereof), treatment, and prevention in these 2 very distinct cohorts. These differences in cervical cancer and HPV-associated OPC and their impact are discussed here. Cancer 2017;123:2219-2229. © 2017 American Cancer Society.


[Selective proximal vagotomy (SPV). Experience and technic using the LDS device].
In the period between January 1974 and 1977, a total of 358 selective proximal vagotomies were performed in patients with gastroduodenal ulcers avoiding pyloroplasty if possible. This report is concerned with intra- and postoperative experience with Burge's operating technique, incorporating LDS instruments from the USSC. The use of the instrument in preparing the proximal stomach is discussed. The instrument is recommended for reducing the time needed for emergency and simultaneous operations and for performing vagotomy in high risk patients.


Modelling of poliovirus. HIV-1 antigen chimaeras.
We have used laboratory-based molecular modelling to identify structural features of antigen chimaeras of poliovirus expressing epitopes from human immunodeficiency virus (HIV-1) that may affect virus viability. Chimaeras were constructed by replacement of antigenic site 1 of VP1 by sequences corresponding to epitopes from HIV-1. Loop volume, estimated by approximating the loop to an ellipsoid was significantly (P less than 0.001) lower in viable (2062.1 A3 +/- 400.2) than in non-viable (3617 A3 +/- 650.7) constructs. Our results suggest that viable virus will only be formed when antigen chimeras modified at antigenic site of VP1 have a loop occupying a similar volume in space to that occupied by the antigenic site 1 loop. In addition, the modified loop must fit with the peptide bond angles and distances at the top of the beta-barrel of VP1.


Salmonella Osteomyelitis in Previously Healthy Children: Report of 4 Cases and Review of the Literature.
Salmonella osteomyelitis in children is an uncommon condition, typically associated with hemoglobinopathies or other underlying disorders. Only few cases have been reported in children without predisposing factors. We describe 4 cases of Salmonella osteomyelitis in otherwise healthy children. Since treatment duration is expected to be prolonged, the practice of direct inoculation of aspirates into blood culture bottles appears to be essential for diagnosis and targeted therapy.


Comparison of autograft and allograft tendons in posterior cruciate ligament reconstruction: A meta-analysis.
The purpose of this meta-analysis of randomized controlled trials (RCTs) and non-RCTs was to compare the clinical outcomes of autograft versus allograft tendons in patients who underwent posterior cruciate ligament (PCL) reconstruction. We conducted a search of PubMed, EMBASE, The Cochrane Library, and Web of Science databases for RCTs and non-RCTs comparing autograft and allograft tendons in PCL reconstruction up to August 2016. The outcomes were Lysholm knee function score, postoperative objective and subjective International Knee Documentation Committee Score (IKDCS), Tegner activity scale, and knee posterior stability. Data analysis was performed using RevMan 5.3 software. One RCT and 4 non-RCTs met the inclusion criteria. The current meta-analysis indicated that there were no significant differences in the Lysholm knee function score (mean difference [MD] = -0.99, 95% confidence interval [CI]: -5.51 to 3.54, P = .67), Tegner activity scale (MD = 0.46, 95% CI: 0.03 to 0.90, P = .04), postoperative objective IKDCS (odds ratio [OR] = 1.66, 95% CI: 0.77 to 3.58, P = .20), postoperative subjective IKDCS (MD = 3.00, 95% CI: -0.29 to 6.29, P = .07), or knee posterior stability (MD = -0.45, 95% CI: -1.28 to 0.38, P = .29) between patients who received autograft tendons and those who received allograft tendons. The patients with autograft tendons had a higher Tegner activity scale (MD = 0.46, 95% CI: 0.03 to 0.90, P = .04) than those with allograft tendons. The present meta-analysis shows that there was insufficient evidence to indicate that allograft tendons were significantly better than autograft tendons for PCL reconstruction. Due to the limited quality and data in the studies currently available, in the future, more high-quality RCTs are required to answer this question more definitively.


Role of autoimmunity in primary biliary cirrhosis.
Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis. The pathogenesis of PBC involves environmental factors, genetic predisposition and loss of immune tolerance. In recent years, it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC. In this study, the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.


Drug-eluting embolic microspheres for local drug delivery - State of the art.
Embolic microspheres or beads used in transarterial chemoembolization are an established treatment method for hepatocellular carcinoma patients. The occlusion of the tumor-feeding vessels by intra-arterial injection of the beads results in tumor necrosis and shrinkage. In this short review, we describe the utility of using these beads as devices for local drug delivery. We review the latest advances in the development of non-biodegradable and biodegradable drug-eluting beads for transarterial chemoembolization. Their capability to load different drugs, such as chemotherapeutics and anti-angiogenic compounds with different physicochemical properties, like charge and hydrophilicity/hydrophobicity, are discussed. We specifically address controlled and sustained drug release from the microspheres, and the resulting in vivo pharmacokinetics in the plasma vs. drug distribution in the targeted tissue.


[A Patient Underwent Pancreaticoduodenectomy with Reconstruction of Replaced Right Hepatic Artery].
A 78 year-old man was diagnosed as a pancreatic cancer in department of gastroenterology in our hospital. Enhanced computed tomography demonstrated an aberrant right hepatic artery(ARHA)arising from superior mesenteric artery(SMA). We conducted sub-stomach preserving pancreaticoduodenectomy(SSPPD- II A-1). As the preoperative diagnosis, right hepatic artery(RHA)was arising from SMA and running through the tumor, and we resected the ARHA with the tumor and reconstructed RHA to gastroduodenal artery(GDA). Pathological diagnosis was non invasive tumor with neither lymph node metastasis nor invasion of the vasculature. We report a case of the patient underwent pancreaticoduodenectomy with reconstruction of aberrant right hepatic artery.


[Effects of dehydroepiandrosterone sulfate on mimetic aging actions of cerebral cortex of fetal rats in vitro].
The effects of dehydroepiandrosterone sulfate (DHEAS) on mimetic aging action of cultured neurons were studied in two models: the cultured cerebral cortex neurons were exposed to the xanthine oxidase-hypoxanthine(XO-HPX) system; serum free culture of cerebral cortex neurons. The results indicated that when cultured neurons were incubated for 6 h with XO-HPX system or 24 h serum free cultures, LDH release and MDA content increased while the number of surviving neurons decreased. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased and morphological injury developed. DHEAS (25, 50, 100 micrograms.L-1) concentration-dependently increased the number of surviving neurons and the activities of SOD and GSH-Px. It also inhibited the elevation of LDH and MDA induced by free radical and serum free cultures. The results suggest that DHEAS prevent the toxicity of free radical and serum free culture insults by suppressing the generation of lipid peroxide and increasing the activities of antioxidant enzymes.


Reduced clearance of penile human papillomavirus infection in uncircumcised men.
The relationship between circumcision and the acquisition and clearance of human papillomavirus (HPV) infection was examined in a cohort of 357 men followed up at 2-month intervals for an average of 431 days. There were no differences in HPV acquisition by circumcision status. Clearance of HPV infection, including infection with oncogenic types, was slower in the glans/coronal sulcus of the penis of uncircumcised men than circumcised men. The median duration of HPV infection of the glans/coronal sulcus was significantly longer in uncircumcised men (154 days) than circumcised men (91 days) (P=.04). Circumcision may protect against HPV-associated disease by enhancing the resolution of infection.


Trumping shame by blasts of noise: narcissism, self-esteem, shame, and aggression in young adolescents.
This experiment tested how self-views influence shame-induced aggression. One hundred and sixty-three young adolescents (M = 12.2 years) completed measures of narcissism and self-esteem. They lost to an ostensible opponent on a competitive task. In the shame condition, they were told that their opponent was bad, and they saw their own name at the bottom of a ranking list. In the control condition, they were told nothing about their opponent and did not see a ranking list. Next, participants could blast their opponent with noise (aggression measure). As expected, narcissistic children were more aggressive than others, but only after they had been shamed. Low self-esteem did not lead to aggression. In fact, narcissism in combination with high self-esteem led to exceptionally high aggression.


[Surveillance on Pseudomonas aeruginosa isolated in Gifu prefecture (2004)].
We analyzed Pseudomonas aeruginosa isolates in Gifu prefecture between September and October 2004. We conducted antimicrobial susceptibility test for 266 strains isolated from 8 medical institutes and 1 clinical laboratory, based on broth microdilution method. The MIC50 and MIC90 of piperacillin, amikacin, imipenem, and ciprofloxacin were 4 and 64, 4 and 8, 1 and 16, 0.25 and 8 microg/mL, respectively. The strains isolated from urine had higher MIC level in comparison with from sputum, which was remarkable in penicillins, cephalosporins and fluoroquinolones. We isolated 7 strains of multi-drug resistant Pseudomonas aeruginosa (MDRP), in which 3 strains showed under 16 microg/mL in MIC against anti-MRSA (methicillin-resistant Staphylococcus aureus) drug arbekacin. Continuous surveillance would be needed for antimicrobial resistance on P. aeruginosa in Gifu prefecture.


Overfishing and nutrient pollution interact with temperature to disrupt coral reefs down to microbial scales.
Losses of corals worldwide emphasize the need to understand what drives reef decline. Stressors such as overfishing and nutrient pollution may reduce resilience of coral reefs by increasing coral-algal competition and reducing coral recruitment, growth and survivorship. Such effects may themselves develop via several mechanisms, including disruption of coral microbiomes. Here we report the results of a 3-year field experiment simulating overfishing and nutrient pollution. These stressors increase turf and macroalgal cover, destabilizing microbiomes, elevating putative pathogen loads, increasing disease more than twofold and increasing mortality up to eightfold. Above-average temperatures exacerbate these effects, further disrupting microbiomes of unhealthy corals and concentrating 80% of mortality in the warmest seasons. Surprisingly, nutrients also increase bacterial opportunism and mortality in corals bitten by parrotfish, turning normal trophic interactions deadly for corals. Thus, overfishing and nutrient pollution impact reefs down to microbial scales, killing corals by sensitizing them to predation, above-average temperatures and bacterial opportunism.


Effects of embryo-derived exosomes on the development of bovine cloned embryos.
The developmental competence of in vitro cultured (IVC) embryos is markedly lower than that of their in vivo counterparts, suggesting the need for optimization of IVC protocols. Embryo culture medium is routinely replaced three days after initial culture in bovine, however, whether this protocol is superior to continuous nonrenewal culture method under current conditions remains unclear. Using bovine somatic cell nuclear transfer (SCNT) embryos as the model, our results showed that compared with routine renewal treatment, nonrenewal culture system significantly improved blastocyst formation, blastocyst quality (increased total cell number, decreased stress and apoptosis, enhanced Oct-4 expression and ratio of ICM/TE), as well as following development to term. Existence and function of SCNT embryo-derived exosomes were then investigated to reveal the cause of impaired development induced by culture medium replacement. Exosomes were successfully isolated through differential centrifugation and identified by both electron microscopy and immunostaining against exosomal membrane marker CD9. Supplementation of extracted exosomes into freshly renewed medium significantly rescued not only blastocyst formation and quality (in vitro development), but also following growth to term (in vivo development). Notably, ratio of ICM/TE and calving rate were enhanced to a similar level as that in nonrenewal group. In conclusion, our results for the first time indicate that 1: bovine SCNT embryos can secrete exosomes into chemically defined culture medium during IVC; 2: secreted exosomes are essential for SCNT blastocyst formation, blastocyst quality, and following development to term; 3: removal of exosomes induced by culture medium replacement impairs SCNT embryo development, which can be avoided by nonrenewal culture procedure or markedly recovered by exosome supplementation.


Effective patterning of metal nanoparticles on sapphire surface for aligned growth of single-walled carbon nanotubes.
We studied patterning of metal nanoparticle catalyst on sapphire (alpha-Al2O3) substrates to grow horizontally-aligned single-walled carbon nanotubes (SWNTs) from defined positions. Various modifications of sapphire surface were investigated for effective adsorption of iron oxide nanoparticles. We found that phosphoric acids bind to sapphire surface and enhance the adsorption of the nanoparticles. This surface modification enabled effective patterning of nanoparticle via electron beam lithography. The small nanoparticles with a mean diameter of 5 nm tended to diffuse at high temperature during the nanotube growth, while the large particles with 12 nm mean diameter mostly stayed at the same position giving aligned SWNTs grown from the catalyst pattern.


Development of High-Throughput Screening Assay for Antihantaviral Therapeutics.
Humans acquire hantavirus infection by the inhalation of aerosolized excreta of infected rodent hosts. There is no treatment for hantavirus diseases at present. Therapeutic intervention during early stages of viral infection can improve the outcome of this zoonotic viral illness. The interaction between an evolutionary conserved sequence at the 5' terminus of hantaviral genomic RNA and hantavirus nucleocapsid protein plays a critical role in the hantavirus replication cycle. This unique interaction is a novel target for therapeutic intervention of hantavirus disease. We developed a very sensitive, tractable, and cost-effective fluorescence-based assay to monitor the interaction between the nucleocapsid protein and the target RNA sequence. The assay was optimized for high-throughput screening of chemical libraries to identify molecules that interrupt this RNA-protein interaction. The assay was validated using a library of 6880 chemical compounds. This validation screen demonstrated the reproducibility and validity of required statistical criteria for high-throughput screening. The assay is ready to use for high-throughput screening of large chemical libraries to identify antihantaviral therapeutic molecules and can be amenable to similar targets in other viruses.


Dissection of lignin macromolecular configuration and assembly: comparison to related biochemical processes in allyl/propenyl phenol and lignan biosynthesis.
This comprehensive review describes the current status and knowledge of biochemical and molecular processes involved in allyl/propenyl phenol, lignan, norlignan and lignin biosynthesis. Recent advances made over the last decade are critically discussed, and placed in context with earlier studies largely dating back to the 1950s. Beginning with the recently established formation of phenylalanine in plants, each downstream biochemical conversion is described from the perspective of the mechanistic details known to this point. Particular emphasis is placed upon proteinaceous control of monolignol-derived radical-radical coupling processes, leading to lignans and lignins, as well as apparently related processes affording the various ellagitannins and phenolic terpenoids. The evidence for non-random macromolecular lignin assembly is discussed in detail, this being in contrast to earlier notions that such processes were random. The latter assumptions have largely resulted from a lack of robust analytical procedures and rigorous quantification, as well as a lack of incisive experimental design. In addition, the often-noted severe effects of modulating lignin compositions and contents on plant vascular tissue properties (i.e. in terms of compromised biophysical properties) are described herein, as well as the severe limitations as regards recent claims of compensatory 'combinatorial chemistry' lignin formation. Much of the latter confusion has also resulted from the serious deficiencies in current lignin analytical protocols and quantification, as well as in the general lack of experimental approaches/design to probe lignin primary structure(s).


Isolation of VIM-2-producing Pseudomonas monteilii clinical strains disseminated in a tertiary hospital in northern Spain.
We describe here the occurrence of blaVIM-2 in 10 carbapenem-resistant Pseudomonas monteilii strains isolated from different clinical samples from patients at the University Hospital Marqués de Valdecilla in northern Spain. All the blaVIM-2-harboring P. monteilii isolates possessed a class 1 integron, with the cassette array [intI1_blaVIM-2_aac(6')-Ib_qacEΔ1_sul1]. Our results show the emergence of VIM-2-producing multidrug-resistant species other than Pseudomonas aeruginosa or Pseudomonas putida in a Spanish hospital. P. monteilii, although sporadically isolated, should also be considered an important metallo-β-lactamase (MBL) reservoir.


Anal intraepithelial neoplasia: A review of diagnosis and management.
Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.


Preventing Adolescent Substance Use Through an Evidence-Based Program: Effects of the Italian Adaptation of Life Skills Training.
Evidence-based preventive interventions for adolescent substance use, violence, and mental health issues are increasingly being adapted and disseminated internationally. In the present paper, we report the results of an effectiveness study that was part of a comprehensive initiative by a coalition of health promotion organizations in the Lombardy region of Italy to select, culturally adapt, implement, evaluate, and sustain an evidence-based drug abuse prevention program developed in the USA. Findings are presented from a large-scale effectiveness study of the Life Skills Training prevention program among over 3000 students attending 55 middle schools in Italy. The prevention program taught drug refusal skills, antidrug norms, personal self-management skills, and general social skills. Relative to comparison group students, students who received the prevention program were less likely to initiate smoking at the post-test and 2-year follow-up, and less likely to initiate weekly drunkenness at the 1-year follow-up. The program had direct positive effects on several cognitive, attitudinal, and skill variables believed to play a protective role in adolescent substance use. The findings from this study show that a drug abuse prevention program originally designed for adolescents in the USA is effective in a sample of Italian youth when a rigorous and systematic approach to cultural adaptation is followed that incorporates the input of multiple stakeholders.


Assessing the need for native language in pharmacy education and practice: a survey in the UAE.
To evaluate pharmacists' opinions on the need for Arabic in pharmacy education and practice in the United Arab Emirates (UAE). A questionnaire was developed to address the study objectives and hand delivered to a stratified sample of community pharmacists and a convenience sample of pharmacists in other areas of practice in the UAE. Pharmacists' responses were measured on a 5-point Likert-type scale (strongly disagree to strongly agree) towards teaching of the following topics in Arabic: management of chronic diseases and minor ailments, screening for diseases and counselling on smoking cessation, exercise, weight management, diet and nutrition and complementary/alternative medicine. Topics related to communication skills were also assessed. Descriptive statistics on participant responses were calculated and chi-square test of independence examined inter-relationships among pharmacist and pharmacy variables. A total of 351 pharmacists completed the questionnaire. Almost 50% of pharmacists considered Arabic in health sciences education a cultural and/or practice necessity. In pharmacy undergraduate curricula, preferred topics to be taught in Arabic included counselling on complementary/alternative medicine (67.4%), management of cold/flu (65.5%), counselling on weight management (64.2%), communication in special situations (63.2%), vocabulary (63.2%) and listening and empathic responding (62.6%). For continuing education, topics included management of cold/flu (69.8%) and skin conditions (69.2%), counselling on smoking cessation (68.9%), communicating with physicians and other professionals (54.8%), communication in special situations (54.7%) and vocabulary (50.9%). For all assessed topics and communication skills, more than half of the pharmacists agreed that they needed to be included in pharmacy education. A blended learning approach that combines integrated content for native language within an English curriculum could be explored.


A kinetic model for enzyme interfacial activity and stability: pa-hydroxynitrile lyase at the diisopropyl ether/water interface.
A kinetic framework is developed to describe enzyme activity and stability in two-phase liquid-liquid systems. In particular, the model is applied to the enzymatic production of benzaldehyde from mandelonitrile by Prunus amygdalus hydroxynitrile lyase (pa-Hnl) adsorbed at the diisopropyl ether (DIPE)/aqueous buffer interface (pH = 5.5). We quantitatively describe our previously obtained experimental kinetic results (Hickel et al., 1999; 2001), and we successfully account for the aqueous-phase enzyme concentration dependence of product formation rates and the observed reaction rates at early times. Multilayer growth explains the early time reversibility of enzyme adsorption at the DIPE/buffer interface observed by both enzyme-activity and dynamic-interfacial-tension washout experiments that replace the aqueous enzyme solution with a buffer solution. The postulated explanation for the unusual stability of pa-Hnl adsorbed at the DIPE/buffer interface is attributed to a two-layer adsorption mechanism. In the first layer, slow conformational change from the native state leads to irreversible attachment and partial loss of catalytic activity. In the second layer, pa-Hnl is reversibly adsorbed without loss in catalytic activity. The measured catalytic activity is the combined effect of the deactivation kinetics of the first layer and of the adsorption kinetics of each layer. For the specific case of pa-Hnl adsorbed at the DIPE/buffer interface, this combined effect is nearly constant for several hours resulting in no apparent loss of catalytic activity. Our proposed kinetic model can be extended to other interfacially active enzymes and other organic solvents. Finally, we indicate how interfacial-tension lag times provide a powerful tool for rational solvent selection and enzyme engineering.


Prophylactic Administration of Vasopressors Prior to Emergency Intubation in Critically Ill Patients: A Secondary Analysis of Two Multicenter Clinical Trials.
Hypotension affects approximately 40% of critically ill patients undergoing emergency intubation and is associated with an increased risk of death. The objective of this study was to examine the association between prophylactic vasopressor administration and the incidence of peri-intubation hypotension and other clinical outcomes. A secondary analysis of two multicenter randomized clinical trials. The clinical effect of prophylactic vasopressor administration was estimated using a one-to-one propensity-matched cohort of patients with and without prophylactic vasopressors. Seven emergency departments and 17 ICUs across the United States. One thousand seven hundred ninety-eight critically ill patients who underwent emergency intubation at the study sites between February 1, 2019, and May 24, 2021. None. The primary outcome was peri-intubation hypotension defined as a systolic blood pressure less than 90 mm Hg occurring between induction and 2 minutes after tracheal intubation. A total of 187 patients (10%) received prophylactic vasopressors prior to intubation. Compared with patients who did not receive prophylactic vasopressors, those who did were older, had higher Acute Physiology and Chronic Health Evaluation II scores, were more likely to have a diagnosis of sepsis, had lower pre-induction systolic blood pressures, and were more likely to be on continuous vasopressor infusions prior to intubation. In our propensity-matched cohort, prophylactic vasopressor administration was not associated with reduced risk of peri-intubation hypotension (41% vs 32%; p = 0.08) or change in systolic blood pressure from baseline (-12 vs -11 mm Hg; p = 0.66). The administration of prophylactic vasopressors was not associated with a lower incidence of peri-intubation hypotension in our propensity-matched analysis. To address potential residual confounding, randomized clinical trials should examine the effect of prophylactic vasopressor administration on peri-intubation outcomes.


Establishing structure-function relationships for eumelanin.
The aggregation-dependent optical properties of eumelanin from human hair are examined. When aggregation is increased, the absorption spectrum extends to lower energy. The absorption spectra of oligomers isolated from black human hair and Sepia officinalis are comparable and are in quantitative agreement with the reported action spectra for photoinduced oxygen consumption and free-radical generation by eumelanin. The agreement between the optical properties of human hair and squid eumelanins suggests the fundamental molecular constituents of the pigments are similar and aggregation-dependent photophysical behavior is a general feature of all eumelanins.


Endospores of halophilic bacteria of the family Bacillaceae isolated from non-saline Japanese soil may be transported by Kosa event (Asian dust storm).
Generally, extremophiles have been deemed to survive in the extreme environments to which they had adapted to grow. Recently many extremophiles have been isolated from places where they are not expected to grow. Alkaliphilic microorganisms have been isolated from acidic soil samples with pH 4.0, and thermophiles have been isolated from samples of low temperature. Numerous moderately halophilic microorganisms, defined as those that grow optimally in media containing 0.5-2.5 Molar (3-15%) NaCl, and halotolerant microorganisms that are able to grow in media without added NaCl and in the presence of high NaCl have been isolated from saline environments such as salterns, salt lakes and sea sands. It has tacitly been believed that habitats of halophiles able to grow in media containing more than 20% (3.4 M) are restricted to saline environments, and no reports have been published on the isolation of halophiles from ordinary garden soil samples. We demonstrated that many halophilic bacteria that are able to grow in the presence of 20% NaCl are inhabiting in non-saline environments such as ordinary garden soils, yards, fields and roadways in an area surrounding Tokyo, Japan. Analyses of partial 16S rRNA gene sequences of 176 isolates suggested that they were halophiles belonging to genera of the family Bacillaceae, Bacillus (11 isolates), Filobacillus (19 isolates), Gracilibacillus (6 isolates), Halobacillus (102 isolates), Lentibacillus (1 isolate), Paraliobacillus (5 isolates) and Virgibacillus (17 isolates). Sequences of 15 isolates showed similarities less than 92%, suggesting that they may represent novel taxa within the family Bacillaceae. The numbers of total bacteria of inland soil samples were in a range from 1.4 x 10(7)/g to 1.1 x 10(6)/g. One tenth of the total bacteria was occupied by endospore-forming bacteria. Only very few of the endospore-forming bacteria, roughly 1 out of 20,000, are halophilic bacteria. Most of the halophilic bacteria were surviving as endospores in the soil samples, in a range of less than 1 to about 500/g soil. Samples collected from seashore in a city confronting Tokyo Bay gave the total numbers of bacteria and endospores roughly 1000 time smaller than those of inland soil samples. Numbers of halophilic bacteria per gram, however, were almost the same as those of inland soil samples. A possible source of the halophilic endospore originating from Asian dust storms is discussed.


Large porphyrin squares from the self-assembly of meso-triazole-appended L-shaped meso-meso-linked Zn(II)-triporphyrins: synthesis and efficient energy transfer.
meso-Triazolyl-appended Zn(II)-porphyrins were readily prepared by Cu(I)-catalyzed 1,3-dipolar cycloaddition of benzyl azide to meso-ethynylated Zn(II)-porphyrin (click chemistry). In noncoordinating CHCl(3) solvent, spontaneous assembly occurred to form tetrameric array (3)(2) from meso-meso-linked diporphyrins 3, and dodecameric porphyrin squares (4)(4) and (5)(4) from the L-shaped meso-meso-linked triporphyrins 4 and 5. The structures of these assemblies were examined by (1)H NMR spectra, absorption spectra, and their gel permeation chromatography (GPC) retention time. Furthermore, the structures of the dodecameric porphyrin squares (4)(4) and (5)(4) were probed by small- and wide-angle X-ray scattering (SAXS/WAXS) measurements in solution using a synchrotron source. Excitation-energy migration processes in these assemblies were also investigated in detail by using both steady-state and time-resolved spectroscopic methods, which revealed efficient excited-energy transfer (EET) between the meso-meso-linked Zn(II)-porphyrin units that occurred with time constants of 1.5 ps(-1) for (3)(2) and 8.8 ps(-1) for (5)(4).


Carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute spinal cord injury in rats.
Acute spinal cord injury (SCI) leads to permanent functional deficits via mechanical injury and secondary mechanisms, but the therapeutic strategy for SCI is limited. Carvedilol has been shown to possess multiple biological and pharmacological properties. The of the present study was to investigate the possible protective effect of carvedilol in SCI rats. An acute SCI rat model was established and neurological function was tested. After carvedilol (10 mg/kg, oral gavage) treatment for 21 days, the status of osteoporosis, neuron damage, astrocyte activation, inflammation, oxidative stress and apoptosis were evaluated in rats. Carvedilol significantly improved locomotor activity that was decreased by SCI. In addition, carvedilol promoted bone growth by regulating the expression of nuclear factor-κB ligand (receptor activator of nuclear factor-κB ligand; RANKL) and osteoprotegerin (OPG), inactivating osteoclasts and thereby increasing bone mineral density in tibias. In addition, carvedilol reduced SCI-induced neural damage, increased neuron number and reduced astrocyte activation in the spinal cord. Furthermore, the production and mRNA expression of tumour necrosis factor-α, interleukin (IL)-1β and IL-6 were significantly reduced, reduced glutathione content and superoxide dismutase activity were markedly increased and malondialdehyde content was markedly decreased in the spinal cords of carvedilol-treated rats. These results indicate that carvedilol exhibits anti-inflammatory and anti-oxidative effects in SCI rats. In addition, the expression of Fas and Fas ligand was reduced by carvedilol treatment, which, in turn, reduced cleaved caspase 3 expression and finally decreased the number of apoptotic cells in the spinal cord. In conclusion, carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute SCI in rats.


Vertebrobasilar infarction related to giant cell (temporal) arteritis: case report.
An 84-year-old male with a 3-month history of headache and elevated C-reactive protein levels was admitted for biopsy of the superficial temporal artery, which led to the diagnosis of giant cell arteritis (GCA). Two days after prednisolone therapy was initiated, the patient began to experience transient vertigo attacks. Two days later, dysarthria, left-sided hemiparesis, right abducens palsy, and horizontal nystagmus developed. Magnetic resonance (MR) imaging disclosed fresh infarctions in the vertebrobasilar territory. Since the patient became drowsy because of brainstem compression and hydrocephalus due to cerebellar swelling, emergency suboccipital decompression surgery and ventricular drainage were performed. Subsequently, the patient's consciousness levels improved. MR angiography revealed right vertebral artery (VA) occlusion and left VA stenosis due to arteritis. Ischemic stroke is a serious though relatively rare complication of GCA. Similar cases have been reported, in which ischemic stroke developed despite or possibly due to steroid therapy. To our knowledge, this is the first description of vertebrobasilar infarction associated with GCA in the Japanese population. The merits and potential demerits of steroid therapy are briefly discussed.


Autobiographical memory specificity among people with recovered memories of childhood sexual abuse.
Individuals who report to have recovered memories of childhood sexual abuse (CSA) almost by definition believe that these memories were previously inaccessible for them. We examined whether poor autobiographical memory specificity for all kinds of events (i.e., events not necessarily related to CSA) may underlie such impressions of amnesia. Thus, we examined whether people who report recovered memories of CSA (n=44) would exhibit more difficulty retrieving specific autobiographical memories compared to people who never forgot their abuse experiences (continuous memory group; n=42) and people without a history of abuse (controls; n=26). The standard Autobiographical Memory Test (AMT) was administered to these 3 groups along with measures of depression and posttraumatic stress disorder symptomatology. Controls were significantly better at retrieving specific autobiographical memories relative to individuals with continuous and recovered CSA memories, who did not differ from each other. Thus, reduced autobiographical memory specificity was not particularly pronounced in people with recovered memories of CSA. Poor autobiographical memory specificity is unlikely to explain the impression of amnesia reported by this group.


Genetic and genomic analysis of age at first insemination in Israeli dairy cattle.
We performed a genetic analysis of age at first insemination, including estimation of the heritability and genetic correlations with other economic traits, and the consequences of including this trait in the Israeli selection index. The genetic factors affecting age at first insemination were determined via GWAS. Five data sets were analyzed. Data sets 1, 2, and 3 were used to compute variance components among age at first insemination, first calving age, days from first insemination to calving, and the 9 traits included in the Israel breeding index. Heritabilities for age at first insemination, calving age, and days from first insemination to calving in Israeli Holsteins as computed by REML individual animal model analyses of 273,239 Israeli Holstein cows were 0.072, 0.042, and 0.014. The estimated genetic correlation between the first 2 traits was 0.88. In addition to the fact that heritability of age at first insemination is 1.7 times the heritability for calving, the former trait has the advantage that the number of records is greater, and the records are generated earlier. Absolute values of the genetic and residual correlations between age at first insemination and the 9 traits included in the Israeli index were all less than 0.2. Data set 4 included first insemination dates of 1,181,600 calves born from 1985 through 2018. Genetic evaluations were computed by a single trait animal model. Annual phenotypic and genetic trends for age at first calving for calves born since 1985 were "positive," that is, economically negative, at 0.320 ± 0.003 and 0.169 ± 0.005 d, respectively. Applying the GCTA-GREML software, 54% of variance in the transmitting ability of 1,585 sires could be explained by considering all 40,498 markers included in the GWAS analysis. The significant markers were mainly associated with milk production genes. The SNP UA-IFASA-8854 on chromosome 11 had the lowest probability value, 1.2 × 10-24. This marker is located between the genes RETSAT and ELMOD3, both of which are overexpressed in human mammary glands. The gene RETSAT is reported to be essential for lipid accumulation and adipogenesis promotion. Gene enrichment analysis found that genes in the genomic region flanking significant markers are associated with vasopressin receptor activity, which was shown to mediate puberty in humans. If age at first insemination is included in the index with a weighting to account for 9% of the index, reductions of 2.8 and 2.6 d for age at first insemination and first calving age after 10 yr of selection are predicted, as compared with reductions of 1.4 and 1.1 d with the current index. Gains for the other index traits are only marginally affected. We suggest selection on age at first insemination as an alternative to selection for early calving.


Microfluidic Control of Tumor and Stromal Cell Spheroids Pairing and Merging for Three-Dimensional Metastasis Study.
Three-dimensional cell culture provides an efficient way to simulate the in vivo tumorigenic microenvironment where tumor-stroma interaction intrinsically plays a pivotal role. Conventional three-dimensional (3D) culture is inadequate to address precise coexistential heterogeneous pairing and quantitative measurement in a parallel algorithm format. Herein, we implemented a set of microwell array microfluidic devices to study the cell spheroids-based tumor-stromal metastatic process in vitro. This approach enables accurate one-to-one pairing between tumor and fibroblast spheroid for dissecting 3D tumor invasion in the manner of high-content imaging. On one single device, 240 addressable tumor-stroma pairings can be formed with convenient pipetting and centrifugation within a small area of 1 cm2. Consequential confocal imaging analysis disclosed that the tumor spheroid could envelop the fibroblast spheroid. Specific chemicals can effectively hamper or promote this 3D metastasis. Due to the addressable time-resolved measurements of the merging process of hundreds of doublets, our approach allows us to decipher the metastatic phenotype between different tumor spheroids. Compared with traditional protocols, massive heterogeneous cellular spheroids pairing and merging using this method is well-defined with microfluidic control, which leads to a favorable high-content tumor-stroma doublet metastasis analysis. This simple technique will be a useful tool for investigating heterotypic spheroid-spheroid interactions.


Urinary porphyrin excretion in a human population highly exposed to hexachlorobenzene.
Data from an epidemic reported in Turkey (1955-1959) is the only information about the relationship between hexachlorobenzene (HCB) intake and porphyria cutanea tarda in humans. No information is available on the HCB threshold exposure level to induce porphyria cutanea tarda. To study HCB serum levels and urinary porphyrin excretion in the inhabitants of a village located near an organochlorine compound factory with high HCB concentrations in the air and to detect possible alterations in urinary porphyrin excretion and examine their relationship with HCB serum levels. Cross-sectional study. Unit of Porphyrias of a tertiary care facility in Barcelona, Spain. Six hundred four inhabitants of the village who were older than 14 years provided serum and urine samples (185 participants were factory workers). Serum HCB was analyzed by gas chromatography coupled to electron capture detection. Quantification of urinary total porphyrins was performed by spectrofluorimetry. Porphyrin profile was determined by high-pressure liquid chromatography. Hexachlorobenzene was detected in all serum samples (mean, 39.8 ng/mL; range, 1.1-1616.0 ng/mL), and levels were higher in factory workers. Mean +/- SD level urinary total porphyrin average concentration was 98 +/- 69 nmol/L (range, 9-1009 nmol/L). Only the urine sample with the highest porphyrin concentration showed an increase of highly carboxylated porphyrins, with a typical profile of porphyria cutanea tarda. In the remaining 603 urine samples, coproporphyrin was the predominant fraction. The airborne exposure to and increased body burden of HCB in the Flix village population are not enough to trigger a significant alteration of the heme biosynthesis pathway.


Two-dimensional Covalent Organic Frameworks for Electrochromic Switching.
The electrochromic materials have received immense attention for the fabrication of smart optoelectronic devices. The alteration of the redox states of the electroactive functionalities results in the color change in response to electrochemical potential. Even though transition metal oxides, redox-active small organic molecules, conducting polymers, and metallopolymers are known for electrochromism, advanced materials demonstrating multicolor switching with fast response time and high durability are of increasing demand. Recently, two-dimensional covalent organic frameworks (2D COFs) have been demonstrated as electrochromic materials due to their tunable redox functionalities with highly ordered structure and large specific surface area facilitating fast ion transport. Herein, we have discussed the mechanistic insights of electrochromism in 2D COFs and their structure-property relationship in electrochromic performance. Furthermore, the state-of-the-art knowledge for developing the electrochromic 2D COFs and their potential application in next-generation display devices are highlighted.


Switching the conformation of a DNA molecule with a chemical oscillator.
pH oscillations generated by a nonequilibrium chemical reaction are used to switch a pH-sensitive DNA structure between two distinct conformations. The utilization of a chemical oscillator represents a novel method for achieving autonomous motion in molecular devices. The oscillatory reaction is a variant of the Landolt reaction and produces pH variations in the range between pH 5 and 7. In this range, a cytosine-rich DNA strand can be switched between a random coil conformation and the folded i-motif structure. The conformational changes are monitored simultaneously with the pH value in fluorescence-resonance energy-transfer experiments.


A Three-Dimensional Molecular Perovskite Ferroelectric: (3-Ammoniopyrrolidinium)RbBr3.
It is known that CH3NH3PbI3 is particularly promising for next-generation solar devices; therefore, molecular perovskite structures have recently received extraordinary attention from the academic community because of their potential in producing unique physical properties. However, although great efforts have been made, molecular ferroelectrics with three-dimensional (3D) perovskite structures are still rare. So far, reported perovskite-like molecular ferroelectrics are basically one- or two-dimensional, significantly deviating from the inorganic perovskite ferroelectrics. Thus, their ferroelectric properties have to be greatly improved to meet the requirements of practical applications. Here, we report a 3D molecular perovskite ferroelectric: (3-ammoniopyrrolidinium)RbBr3 [(AP)RbBr3], with a high Curie temperature (Tc = 440 K) beyond that of BaTiO3. To the best of our knowledge, such above-room-temperature ferroelectricity in the 3D molecular perovskite compound is unprecedented. Furthermore, (AP)RbBr3 has great potential for applications due to its high thermal stability, ultrafast polarization reversal (greater than 20 kHz), and fascinating multiaxial characteristic. This finding opens a new avenue to the design and controllable synthesis of molecular ferroelectric perovskites, where the metal ion, halogen ion, and organic cation can be easily tuned.


Current status of kidney transplantation in HIV-infected patients.
To summarize the most current literature on transplant outcomes in HIV-infected kidney recipients. HIV-infected recipients overall have excellent patient and allograft outcomes. Acute rejection, delayed graft function, drug-drug interactions and limited access to organs have emerged as important issues for HIV-infected kidney transplant patients. The subset of patients who are coinfected with hepatitis C virus do not fare as well and improving their outcomes should be a focus of future research in the field. Renal transplantation remains the optimal treatment for end stage renal disease in the HIV-infected patient.


Redox-responsive theranostic nanoplatforms based on inorganic nanomaterials.
Spurred on by advances in materials chemistry and nanotechnology, scientists have developed many novel nanopreparations for cancer diagnosis and therapy. To treat complex malignant tumors effectively, multifunctional nanomedicines with targeting ability, imaging properties and controlled drug release behavior should be designed and exploited. The therapeutic efficiency of loaded drugs can be dramatically improved using redox-responsive nanoplatforms which can sense the differences in the redox status of tumor tissues and healthy ones. Redox-sensitive nanocarriers can be constructed from both organic and inorganic nanomaterials; however, at present, drug delivery nanovectors progressively lean towards inorganic nanomaterials because of their facile synthesis/modification and their unique physicochemical properties. In this review, we focus specifically on the preparation and application of redox-sensitive nanosystems based on mesoporous silica nanoparticles (MSNs), carbon nanomaterials, magnetic nanoparticles, gold nanomaterials and other inorganic nanomaterials. We discuss relevant examples of redox-sensitive nanosystems in each category. Finally, we discuss current challenges and future strategies from the aspect of material design and practical application.


Community-based lifestyle intervention for reducing blood pressure and glucose among middle-aged and older adults in China: a pilot study.
Although evidence suggests that lifestyle interventions can reduce blood pressure (BP) and glucose levels, there is little information about the feasibility of such interventions when implemented in community settings. This study evaluated the effectiveness of a community-based lifestyle intervention on BP and glucose in the middle-aged and older Chinese population. By using a cluster randomisation approach, 474 participants from two communities were assigned to the intervention group which received intensive health education and behavioural intervention, or the control group which received conventional education. Linear mixed models were used to compare between-group differences on change in BP and fasting glucose after 6, 12 and 24 months. At the 12-month follow-up, the intervention group experienced significantly reductions in systolic BP (-4.9 vs. 2.4 mmHg; mean difference [MD] -7.3 mmHg; p < 0.001), diastolic BP (-1.9 vs. 1.9 mmHg; MD -3.8 mmHg; p < 0.001) and fasting glucose (-0.59 vs. 0.08 mmol/L; MD -0.67 mmol/L; p < 0.001). These differences were sustained at the 24-month follow-up. With only two communities, it was not possible to adjust for potential clustering by site. This approach of lifestyle interventions conducted through primary care services may be a potential solution for combating hypertension and diabetes in a resource-limited country context in China.


Isolated intracranial myeloid sarcoma: report of a case and review of the literature.
Myeloid sarcoma is a rare malignant tumor of primitive myeloid cell origin often associated with hematologic disorders. The central nervous system is rarely involved and differentiating between myeloid sarcoma and other tumors is not possible on imaging. Here we present the rare case of an isolated intracranial myeloid sarcoma, initially misdiagnosed radiologically as a meningioma, treated with surgical total resection and subsequent chemotherapy, with no signs of any hematological disorder at follow up. Differential diagnosis and management strategies, as well as follow-up implications are discussed along with literature review, which pointed out that only five cases with no further signs of hematological disorders at follow up have been described in the literature so far and this case has the longest follow up of them at 9 years.


Carcinosarcoma and sarcomatoid carcinoma of the bladder: clinicopathological study of 41 cases.
Carcinosarcoma of the bladder is a rare neoplasm characterized by an intimate admixture of carcinoma and malignant soft tissue neoplasm. The clinical usefulness of separating carcinosarcoma (carcinoma with sarcomatous component) from sarcomatoid carcinoma (carcinoma with spindle cell carcinomatous component) is uncertain, and it comprises the subject of this report. We reviewed the clinical and pathological records of 10 men and 5 women a mean of 66 years old with carcinosarcoma, and 21 men and 5 women a mean of 66.5 years old with sarcomatoid carcinoma of the bladder, as documented in the files of the Mayo Clinic between 1936 and 1995. Of the 15 patients in the carcinosarcoma group 9 had urothelial carcinoma, small cell carcinoma, 3 had squamous cell carcinoma and 2 had more than 1 type. The sarcomatous component included chondrosarcoma in 3 cases, leiomyosarcoma in 3, malignant fibrous histiocytoma in 3, osteosarcoma in 2, fibrosarcoma in 1, rhabdomyosarcoma in 1 and more than 1 type in 2. All disease was high stage at presentation. Treatment included cystectomy in 11 patients with (4) and without (7) radiation therapy, and transurethral resection in 4 with (1) and without (3) radiation therapy. Mean followup available in 14 cases was 34 months (range 1 to 144). A total of 11 patients died of cancer at 1 to 48 months (mean 17.2) and 2 survived for 8 to 131 months. Of the 26 patients in the sarcomatoid carcinoma group 18 had urothelial carcinoma, 1 had squamous carcinoma, 2 had urothelial carcinoma combined with squamous cell carcinoma and 5 had spindle cells only with no recognizable epithelium. All but 1 case was high stage at diagnosis. Treatment included transurethral resection in 17 patients with (7) and without (10) radiation therapy, including 1 who also received chemotherapy, and only cystectomy in 5, including 2 who also underwent radiation therapy and 1 who also received chemotherapy. Mean followup available in 21 cases was 49 months (range 1 to 420). A total of 17 patients died of cancer at 1 to 73 months (mean 9.8), 1 was alive at 140 months and 3 died of unrelated causes. Carcinosarcoma and sarcomatoid carcinoma of the bladder are highly aggressive malignancies with a similar outcome regardless of histological findings and treatment. Pathological stage is the best predictor of survival.


Selective up-regulation of matrix metalloproteinase-9 expression in human erythema migrans skin lesions of acute lyme disease.
Despite the absence of enzymes that digest extracellular matrix, Borrelia burgdorferi spreads in the skin to form erythema migrans (EM) lesions and then disseminates to other organs. We studied the induction by bacteria of host matrix metalloproteinases (MMPs) in EM skin lesions of patients with acute Lyme disease. In blister fluid from the EM lesions, the expression of MMP-9 was selectively increased by 1900%+/-1037%, compared with blister fluid from the surrounding normal-appearing skin. The expression of all other MMP messenger RNAs was similar in the EM lesions and normal-appearing skin. Selective up-regulation of MMP-9 in the EM lesions was found. Fibroblasts and, to a lesser degree, mononuclear cells were the sources of local MMP-9 production. These results demonstrate specific up-regulation of MMP-9 in the EM skin lesions of patients with acute Lyme disease. Bacterial induction of host proteases may play a role in the dissemination of B. burgdorferi.


PROGNOSTIC INDICATORS OF VISUAL ACUITY AFTER OPEN GLOBE INJURY AND RETINAL DETACHMENT REPAIR.
To identify prognostic indicators of postoperative visual acuity and retinal detachment (RD) in open globe injuries. Retrospective review of 50 adult open globe injuries between September 2011 and March 2014. Hierarchical multivariable regression was used to evaluate relationships among injury characteristics, postoperative visual acuity, and RD after age adjustment. Mean participant age was 46.2 years, and mean follow-up was 1.2 years. Blunt trauma accounted for 58% of injuries (29/50), and the wound extended posteriorly into sclera in 64% of cases (32/50). The retinal detachment occurred in 40% of patients (20/50), 95% of whom had developed vitreous hemorrhage (19/20). Multivariable regression revealed that preoperative visual acuity (P = 0.0010), posterior wound extension (P = 0.022), and RD (P = 0.0038) independently predicted postoperative visual acuity. No other injury characteristic was related to postoperative visual acuity after adjustment for preoperative visual acuity. Vitreous hemorrhage predicted RD (P < 0.001), and further consideration of preoperative visual acuity and other variables did not improve model fit. Moreover, among patients who underwent RD repair (n = 13), earlier vitrectomy after vitreous hemorrhage diagnosis (≤12 days) was associated with fewer macula-off RDs (P = 0.018) and better postoperative visual acuity (P = 0.0055). Preoperative visual acuity, posterior wound extension, and RD significantly influenced postoperative visual acuity after open globe injury. Vitreous hemorrhage predicted RD, and prompt intervention after detection may improve visual outcomes.


Electronic neuron within a ganglion of a leech (Hirudo medicinalis).
We report the construction of an electronic device that models and replaces a neuron in a midbody ganglion of the leech Hirudo medicinalis. In order to test the behavior of our device, we used a well-characterized synaptic interaction between the mechanosensory, sensitive to pressure, (P) cell and the anteropagoda (because of the action potential shape) (AP) neuron. We alternatively stimulated a P neuron and our device connected to the AP neuron, and studied the response of the latter. The number and timing of the AP spikes were the same when the electronic parameters were properly adjusted. Moreover, after changes in the depolarization of the AP cell, the responses under the stimulation of both the biological neuron and the electronic device vary in a similar manner.


Clinical pathways in acoustic tumor management.
Clinical pathways are tools for cost containment and quality improvement in the managed care environment. This report describes our experience with developing and implementing a clinical pathway for acoustic neuroma surgery. Intensive care unit bed days and inpatient hospitalization days for cerebellopontine angle surgery significantly decreased during the months that the pathway was developed, and the incidence of complications was unchanged after adoption of the algorithm. We conclude that with joint neurootology and neurosurgery leadership clinical pathways can be a safe, cost-effective, and clinically useful technique in acoustic neuroma surgery in a managed care setting. As this management scheme evolves, surgeons must take the leadership to ensure that decisions are based on clinically relevant parameters.


Fentanyl Patches to Supplement Ultrasound-Guided Nerve Blocks for Improving Pain Control After Foot and Ankle Surgery: A Prospective Study.
The analgesic effects of preoperative ultrasound-guided nerve blocks wear off after about 12 hours, leaving some patients in substantial pain. Transdermal fentanyl concentrations peak at 12 to 24 hours after application and maintain this concentration for approximately 72 hours. We sought to determine whether combining the use of a transdermal fentanyl patch with either a sciatic or femoral-sciatic nerve block would improve pain control in patients undergoing foot and/or ankle surgery. Consecutive patients in the no-patch control group (n = 104) were enrolled from July 2011 to October 2011, and those in the treatment group (n = 232) were enrolled from November 2011 to May 2012 and received a transdermal patch (4.125 mg/7.5 cm(2) releasing 25 μg of fentanyl per hour) applied to their chest postoperatively. Pain was assessed using a visual analog scale at 6, 12, 24, and 48 hours after surgery. The primary outcome measure was the number of requests for additional postoperative pain medication. Additional postoperative analgesia was requested by 49 of the 104 control patients (47.1%) and 63 of the 232 treated patients (27.1%; p = .002). The mean pain scores were also lower in the treatment group, with a statistically significant difference (p < .05) at 12, 24, and 48 hours. Thus, patients receiving a fentanyl patch combined with an ultrasound-guided nerve block required less supplemental analgesia to maintain adequate pain control than did those receiving a nerve block alone. In conclusion, a fentanyl patch is a useful adjunct to an ultrasound-guided nerve block in foot and ankle surgery.


A personal series of 100 children operated for Cushing's disease (CD): optimizing minimally invasive diagnosis and transnasal surgery to achieve nearly 100% remission including reoperations.
Background Transnasal surgery (TNS) is the first choice in the treatment of pediatric Cushing's disease. The question is how can high remission rates be achieved with minimally invasive investigations and TNS whilst avoiding radiotherapy or bilateral adrenalectomy in children. Methods Data from a published series 1 (n=55) of surgeon DKL will be compared with his recent series 2 (n=45) until 2009. All patients were operated by direct transnasal microsurgery. Over time, inferior petrosal sinus sampling (IPSS) was replaced by cavernous sinus sampling (CSS), restricted to unclear cases without increase of salivary cortisol in corticotropin-releasing hormone-test, difficult sellar anatomy or negative magnetic resonance imaging (MRI). Multiple direct intra-operative micro-cytology, micro-doppler and adequate visualization techniques are described. Results In series 1, IPSS was performed in 13 (24%) of whom 46% had false adenoma lateralization. All adenomas could be removed with extensive pituitary exploration. Three patients had early successful re-surgery. In series 2, with more refined MRI and endocrinology, CSS was used in only seven patients (15%) and all micro-adenomas were correctly localized. In three of four patients with persistent cortisol excess, repeat-TNS was necessary and successful. Side effects of TNS were minimal. Recurrence rates were 16% and 11% in series 1 and 2, respectively. Only four of 100 children with invasive adenomas were irradiated, significantly less than in other experienced pediatric centers. Conclusions Thus, 98% remission rate could be achieved with fewer invasive pre-surgical investigations, such as central catheter studies, refined TNS and early repeat-TNS. Repeat-TNS in recurrences minimized the need for irradiation.


Reactivity of catecholamine-driven Fenton reaction and its relationships with iron(III) speciation.
Fenton reaction is the main source of free radicals in biological systems. The reactivity of this reaction can be modified by several factors, among these iron ligands are important. Catecholamine (dopamine, epinephrine, and norepinephrine) are able to form Fe(III) complexes whose extension in the coordination number depends upon the pH. Fe(III)-catecholamine complexes have been related with the development of several pathologies. In this work, the ability of catecholamines to enhance the oxidative degradation of an organic substrate (veratryl alcohol, VA) through Fenton and Fenton-like reactions was studied. The initial VA degradation rate at different pH values and its relationship to the different iron species present in solution were determined. Furthermore, the oxidative degradation of VA after 24 hours of reaction and its main oxidation products were also determined. The catecholamine-driven Fenton and Fenton-like systems showed higher VA degradation compared to unmodified Fenton or Fenton-like systems, which also showed an increase in the oxidation state of the VA degradation product. All of this oxidative degradation takes place at pH values lower than 5.50, where the primarily responsible species would be the Fe(III) mono-complex. The presence of Fe(III) mono-complex is essential in the ability of catecholamines to increase the oxidative capacity of Fenton systems.


trans-Dibromidobis(triphenyl-phosphane)platinum(II) chloro-form monosolvate.
Both the platininum complex and the solvent mol-ecule of the title compound, [PtBr(2)(C(18)H(15)P)(2)]·CHCl(3), are located on a twofold rotation axis. The CH unit and the Cl atoms of the CHCl(3) mol-ecule are disordered over two equally occupied positions. The complex shows a trans square-planar geometry about the Pt atom.


Simultaneous Visualization of Vessels and Brain Tumor with Contrast-enhanced Three-dimensional Phase-contrast MR Imaging.
The sequence for concurrently depicting engulfed vessels and a well-enhanced tumor in once-off scanning has never been reported for preoperative magnetic resonance imaging for brain tumor resection. Multimodal fusion techniques have been recently developed, but the risks of misregistration still remain. Here a case is reported where contrast-enhanced three-dimensional phase contrast sequence concurrently depicted an engulfed vessel and metastatic brain tumor in once-off scanning and related technical aspects are discussed.


[Interaction of triamcinolone acetonide with Morris hepatoma cells in the presence antibiotics--inhibitors of RNA synthesis].
Some regularities of [3H]triamcinolone acetonide (TA)binding to glucocorticoid-sensitive Morris hepatoma cell nuclei were studied. It was shown that part of the hormone incorporated into the nuclei form highly stable complexes with nuclear structures that are not destroyed during nuclei lysis with 0.25% SDS. Such complex formation is not practically suppressed by a 500-fold excess of non-labeled TA. As the time of incubation of Morris hepatoma cells with the hormone rises from 10 min to 24 hours, the specific binding of TA to the nuclei decreases, while the specific radioactivity of the [3H]TA-nuclei complexes resistant to 0.25% SDS increases. The stable complexes are eluted from Sepharose 6B together with the bulk of the nuclear proteins and do not contain DNA. Actinomycin D extrudes, to some extent, the [3H]TA from the complexes having specific binding sites that are localized in the nuclei and induces the accumulation of the steroid in the firmly bound nuclear complexes resistant to 0.25% SDS. The ability to suppress hormonal induction of tyrosine aminotransferase was detected only in the antibiotics with a high affinity for the GC-pairs of DNA. i.e., actinomycin D and mitramycin. It was assumed that high concentrations of TA specifically bound to the nuclei are necessary only at initial steps of hormonal induction. At later stages, gradual dissociation of the complexes takes place and the hormone is accumulation within the composition of the SDS-resistant firmly bound complexes.


Ligand-Orientation Based Fragment Selection in STD NMR Screening.
While saturation transfer difference (STD) is a widely used NMR method for ligand screening, the selection of specific binders requires the validation of the hits through competition experiments or orthogonal biophysical techniques. We show here that the quantitative STD analysis is a reliable and robust approach to discriminate between specific and nonspecific ligands, allowing selection of fragments that bind proteins with a privileged binding mode, in the absence of any structural data for the protein.


Prevalence of myotonic dystrophy in Guipúzcoa (Basque Country, Spain).
Prevalence figures for inherited neuromuscular disorders are important both for health care planning purposes and for evaluating the need for DNA diagnostic services for eugenic approaches. We screened for the prevalence of myotonic dystrophy (MyD) through extensive inquiry of neurologic and primary health services of Guipúzcoa (Basque Country, northern Spain) between 1989 and 1991. Typical adult-onset and neonatal cases and relatives at risk; suffering from a partial syndrome, were included. In the latter, molecular typing was performed with DNA probes close to the MyD gene to demonstrate the MyD gene carrier status. The high prevalence detected (26.5 cases per 100,000 population) could be explained by methodological factors, but intrinsic factors, such as a possible founder genetic effect or the quick growth of the Guipúzcoa population since the last century may contribute to one of the highest MyD prevalence in the world. In the future, the methodological basis for epidemiologic surveys of MyD must combine molecular technology with more-extensive family inquiries.


Reducing electron contamination for photon beam-quality specification.
The percentage depth dose at 10 cm in a 10 x 10-cm2 photon beam at an SSD of 100 cm, %dd(10), is a better beam-quality specifier for radiotherapy beams than the commonly used values of TPR10(20) or nominal accelerating potential. The presence of electron contamination affects the measurement of %dd(10) but can be removed by the use of a 0.1-cm lead filter, which reduces surface dose from contaminant electrons from the accelerator by more than 95% for radiotherapy beams with energies from 60Co to 50 MV. The filter performs best when it is placed immediately below the head. An electron-contamination correction factor is introduced to correct for electron contamination from the filter and air. It converts the %dd(10) which includes the electron contamination with the filter in place [hereafter %dd(10)m], into %dd(10) for just the photons in the filtered beam. The correction factor is a linear function of %dd(10)m for all filtered beams with %dd(10)m > 70%. A small correction for the photon filtering effect converts the pure photon %dd(10) for the filtered beam into that for the unfiltered beam, which can be used to determine stopping-power ratio. Calculations show that the values of water-to-air stopping power ratio in the unfiltered beam are related to the values of %dd(10)m in the filtered beam by a cubic function. The uncertainty of stopping-power ratios in unfiltered beams for the same value of the %dd(10)m is within 0.2% for all beams.


Environmental performance of collection boxes for end of life mobile phones.
Managing waste electrical and electronic equipment is currently one of the top priority challenges of waste management in the European Union. The collection and subsequent processing of waste electrical and electronic equipment are realized by means of the so-called collective systems that employ collection boxes varying in size and materials used for their production. This study focuses on quantifying and comparing environmental impacts of often-used collection boxes on the example of mobile phone collection. The comparison was based on volume (20 l, 60 l, and 70 l) and on the material used for the construction of the box (polypropylene, corrugated cardboard, and stainless steel). Other parameters, such as lifetime, material and energy performance for production, end of life stage, and waste generation were taken in account. The evaluation was carried out using the method of life cycle assessment with the characterization model CML 2001 created in GaBi 8. The goal of the study was to identify the box with the smallest environmental impact and to identify the hotspots in the life cycles of the individual collection boxes. The results of the study show that polypropylene boxes are the most environmentally suitable for collecting small waste electrical and electronic equipment as they produce the lowest environmental impacts in all of the impact categories evaluated, while boxes made of stainless steel have been found to represent the least environmentally friendly option. The results of the study provide and suggest to the collective system basic data for choosing the type of collection box.


Decision area and occupational independence of nurses in ambulatory health care. II.
Contrary to family nurses, practice nurses employed in outpatient departments did not change their scope of duties very much compared to the period prior to the reform of health care. The study presented the current and expected scope of tasks, with the consideration of the area of independent decision making in ambulatory health care. The dependent variable was the scope of nursing practice, which was analysed by means of the following indicators: the scope of duties realized, scope of independence at work, scope of responsibility, possibilities of occupational development and making decisions concerning the methods of work, the competence to make decisions. The study covered a group of 90 nurses employed in public and non-public health care units in Białystok and its area, and was conducted with the use of a questionnaire form. It was observed that practice nurses expected changes with respect to competence, and consequently increased responsibility and adjustment of tasks according to their qualifications. Nurses from public units had less favourable conditions for widening their decision area. The analysis of the study material showed that the regular scope of duties and responsibility in one third of nurses in both groups did not cover occupational competence. In order to independently plan and make decisions, nurses must be trained and improve their knowledge. In the opinion of 80% of respondents from public units and 60% of those employed in non-public units, nurses do not have sufficient possibilities for post-graduate education according to the needs.


Synthesis of the Photoaffinity-labeled Grayanotoxins for Studying the Gating Mechanism of Na Channel.
Grayanotoxin loosely binds to the neurotoxin receptor site 2 on Na channels. 14R-N-[4-(1-Azi-2, 2, 2-triftuoroethyl)]benzyliminograyanotoxane-3β, 5, 6β, 16-tetraol (4) and 17-N-[4-(1-azi-2, 2, 2-triftuoroethyl)]- benzyliminograyanotox-15-ene-3β, 5, 6β, 14R-tetraol (5) were synthesized and applied intracellularly to squid axons. On UV irradiation, their membrane potential produced by a dose of 4 or 5 rose to higher level than that in the dark. However, in the case of 5, even when the axons were internally perfused with toxin-free solution after the dose, the potential level did not fall in contrast to 4. It suggested that 5 covalently bound to the receptor involved in the gating mechanism of Na channels.


The Surgeon's Role in Addressing Racism and Achieving Health Equity.
In the United States, the nation's health is not an organic outcome. It is not a coincidence that certain groups of people living in the United States experience higher premature death rates or poorer health outcomes than others. For centuries, racial and ethnic as well as geographic differences in health outcomes have been part of the American landscape, so entrenched in society that many people fail to recognize that health inequities were intentionally derived. A national crisis tends to magnify inequities in our society, but even more alarming is the fact that as the country becomes more racially and ethnically diverse in the coming years, the health inequities are projected to worsen if we do not proactively and immediately address them. As we continue to grapple with the lasting impact of the pandemic, it is of vital importance that we utilize this time to acknowledge, understand, and seriously address the health inequities that have historically plagued the country for over 400 years. As the United States works overtime to stem the tide of the COVID-19 pandemic, it must also work equally hard to move in a more equitable, inclusive, and healthier direction, not only because of the more than 83 000 Americans dying prematurely each year but also because of the economic and national security toll it will have if not effectively addressed.


Recovery of amino acid neurotransmitters from the spinal cord during posterior epidural stimulation: a preliminary study.
Continuous posterior epidural spinal cord stimulation (SCS) has been an effective method for treating spasticity. The mechanisms of SCS include activation of inhibitory segmental neuronal systems and suprasegmental structures that produce inhibitory descending control. The neurochemical correlates of the mechanism of action have not been clearly defined. Microdialysis of the spinal cord extracellular space in an in vivo preparation during continuous epidural SCS was performed. The recovery of amino acid neurotransmitters, aspartate, glutamate, gamma-aminobutyric acid (GABA), glycine, and taurine from stimulated animals was compared to non-stimulated animals. Evoked potentials from the cortex and spinal cord of the stimulated animals were recorded to insure that there had been adequate epidural stimulation and normal segmental cord function. A significant increase in the concentration of glycine was seen after 90 minutes of continuous stimulation. The levels of the other amino acids were not significantly elevated. These results suggest that amelioration of spasticity with epidural SCS may involve enhanced glycine release, the major inhibitory neurotransmitter of the spinal cord.


Contribution of hypothermia and CB1 receptor activation to protective effects of TAK-937, a cannabinoid receptor agonist, in rat transient MCAO model.
Cannabinoid (CB) receptor agonists are expected to alleviate ischemic brain damage by modulating neurotransmission and neuroinflammatory responses via CB(1) and CB(2) receptors, respectively. In a previous study, TAK-937, a novel potent and selective CB(1) and CB(2) receptor agonist, was shown to exert significant cerebroprotective effects accompanied by hypothermia after transient middle cerebral artery occlusion (MCAO) in rats. Sustained hypothermia itself induces significant neuroprotective effects. In the present studies, we examined the relative contribution of hypothermia and CB(1) receptor activation to the cerebroprotective effects of TAK-937. Using a multichannel brain temperature controlling system we developed, the brain temperature of freely moving rats was telemetrically monitored and maintained between 37 and 38°C during intravenous infusion of TAK-937 (100 µg/kg/h) or vehicle for 24 h after 2 h MCAO. AM251, a selective CB(1) receptor antagonist, was administered intraperitoneally at 30 mg/kg 30 min before starting intravenous infusion of TAK-937 (100 µg/kg/h) for 24 h. Rats were sacrificed and their brains were isolated 26 h after MCAO in both experiments. When the hypothermic effect of TAK-937 was completely reversed by a brain temperature controlling system, the infarct-reducing effect of TAK-937 was attenuated in part, but remained significant. On the other hand, concomitant AM251 treatment with TAK-937 completely abolished the hypothermic and infarct-reducing effects of TAK-937. We conclude that the cerebroprotective effects of TAK-937 were at least in part mediated by induction of hypothermia, and mainly mediated by CB(1) receptor activation.


Interaction with the hERG channel and cytotoxicity of amiodarone and amiodarone analogues.
Amiodarone (2-n-butyl-3-[3,5 diiodo-4-diethylaminoethoxybenzoyl]-benzofuran, B2-O-CH(2)CH(2)-N-diethyl) is an effective class III antiarrhythmic drug demonstrating potentially life-threatening organ toxicity. The principal aim of the study was to find amiodarone analogues that retained human ether-a-go-go-related protein (hERG) channel inhibition but with reduced cytotoxicity. We synthesized amiodarone analogues with or without a positively ionizable nitrogen in the phenolic side chain. The cytotoxic properties of the compounds were evaluated using HepG2 (a hepatocyte cell line) and A549 cells (a pneumocyte line). Interactions of all compounds with the hERG channel were measured using pharmacological and in silico methods. Compared with amiodarone, which displayed only a weak cytotoxicity, the mono- and bis-desethylated metabolites, the further degraded alcohol (B2-O-CH(2)-CH(2)-OH), the corresponding acid (B2-O-CH(2)-COOH) and, finally, the newly synthesized B2-O-CH(2)-CH(2)-N-pyrrolidine were equally or more toxic. Conversely, structural analogues such as the B2-O-CH(2)-CH(2)-N-diisopropyl and the B2-O-CH(2)-CH(2)-N-piperidine were significantly less toxic than amiodarone. Cytotoxicity was associated with a drop in the mitochondrial membrane potential, suggesting mitochondrial involvement. Pharmacological and in silico investigations concerning the interactions of these compounds with the hERG channel revealed that compounds carrying a basic nitrogen in the side chain display a much higher affinity than those lacking such a group. Specifically, B2-O-CH(2)-CH(2)-N-piperidine and B2-O-CH(2)-CH(2)-N-pyrrolidine revealed a higher affinity towards hERG channels than amiodarone. Amiodarone analogues with better hERG channel inhibition and cytotoxicity profiles than the parent compound have been identified, demonstrating that cytotoxicity and hERG channel interaction are mechanistically distinct and separable properties of the compounds.