Advances in collaborative evaluation.
Collaborative evaluation is an approach that offers, among others, many advantages in terms of access to information, quality of information gathered, opportunities for creative problem-solving, and receptivity to findings. In the last decade, collaborative evaluation has grown in popularity along with similar participatory, empowerment, and utilization-focused evaluation approaches. Increasingly, it has brought together evaluators and stakeholders from different sectors, disciplines, and cultures to exchange knowledge on how collaboration can be used as a strategic tool for fostering and strengthening evaluation practice. O'Sullivan (2004) and Rodríguez-Campos (2005, 2008) brought forward collaborative evaluation conceptual frameworks that distinguished it from other approaches. This article updates those conceptual frameworks and discusses key collaborative evaluation advances in order to further clarify and facilitate engagement in sound practice.


Binding of fullerol to human serum albumin: spectroscopic and electrochemical approach.
The potential impact of human exposure to carbonaceous nanomaterials in the environment becomes a concerning issue. Here we report on the interaction of fullerol with human serum albumin (HSA) using spectroscopic and electrochemical methods. The water-soluble fullerene derivative (fullerol) was synthesized and characterized by IR, (1)H NMR, TG-DSC, XRD, HR-TEM, etc. The spectroscopic methods show that the fluorescence quenching of HSA by fullerol is the result of the formation of an HSA-fullerol complex. Binding parameters such as ΔG, ΔH and ΔS were calculated, and the quenching constant K(a) at different temperatures was determined using the modified Stern-Volmer equation. The electrochemical experiments further confirmed the conclusions. In addition, the influences of coexisting heavy metal ions have also been studied in the present system. The circular dichroism spectra (CD), 3D fluorescence spectra and FT-IR spectra results suggest that the secondary structure of HSA was changed by fullerol. Based on the site marker competitive experiments, we can predict the possible binding position of fullerol on the HSA was located at the site of sub domain II A. Furthermore, the distance r between donor (HSA) and acceptor (fullerol) was obtained according to the famous fluorescence resonance energy transfer (FRET) mechanism.


Creation and characterization of a recombinant mammalian orthoreovirus expressing σ1 fusion proteins encoding human epidermal growth factor receptor 2 peptides.
Mammalian orthoreovirus (MRV) is an oncolytic virus that has been tested in over 30 clinical trials. Increased clinical success has been achieved when MRV is used in combination with other onco-immunotherapies. This has led the field to explore the creation of recombinant MRVs which incorporate immunotherapeutic sequences into the virus genome. This work focuses on creation and characterization of a recombinant MRV, S1/HER2nhd, which encodes a truncated σ1 protein fused in frame with three human epidermal growth factor receptor 2 (HER2) peptides (E75, AE36, and GP2) known to induce HER2 specific CD8+ and CD4+ T cells. We show S1/HER2nhd expresses the σ1 fusion protein containing HER2 peptides in infected cells and on the virion, and infects, replicates in, and reduces survival of HER2+ breast cancer cells. The oncolytic properties of MRV combined with HER2 peptide expression holds potential as a vaccine to prevent recurrences of HER2 expressing cancers.


Effect of multiple applications of compound 48/80 on mast cells of rat conjunctiva.
We sought to determine the effect on rat conjunctival mast cells of chronic exposure to a degranulating agent. Compound 48/80 (250 micrograms in 10 microliter) was applied daily to the ocular surface of rats for a total of 13 treatments administered in 17 days. A single application of compound 48/80 was given to rats for comparison. Four groups of animals (6 in each group) were evaluated 1 or 48 h after the last application of compound 48/80 in both chronic exposure and single exposure studies. Although a single exposure to compound 48/80 induced significant degranulation of mast cells in animals observed 1 h after treatment, no significant degranulation of mast cells was observed 1 h after the last dose of compound 48/80 was given to rats whose conjunctiva had been chronically exposed to this degranulating agent. Thus, multiple applications of compound 48/80 attenuated the mast cell response to compound 48/80. This acquired tolerance to compound 48/80 was reflected in the lessened clinical signs in rats receiving repeated applications compared with those given a single application.


Evaluating steroid hormone receptor interactions using the live-cell NanoBRET proximity assay.
Steroid hormone receptors play a crucial role in the development and characterization of the majority of breast cancers. These receptors canonically function through homodimerization, but physical interactions between different hormone receptors play a key role in cell functions as well. The estrogen receptor (ERα) and progesterone receptor (PR), for example, are involved in a complex set of interactions known as ERα/PR crosstalk. Here, we developed a valuable panel of nuclear receptor expression plasmids specifically for use in NanoBRET assays to assess nuclear receptor homo- and heterodimerization. We demonstrate the utility of this assay system by assessing ERα/PR physical interaction in the context of the endocrine therapy resistance-associated ERα Y537S mutation. We identify a role of the ERα Y537S mutation beyond that of constitutive activity of the receptor; it also increases ERα/PR crosstalk. In total, the NanoBRET assay provides a novel avenue for investigating hormone receptor crosstalk. Future research may use this system to assess the effects of other clinically significant hormone receptor mutations on hormone receptor crosstalk.


Dentists and ethnic minority communities.
It is estimated that 4.5% of the UK population originates from the New Commonwealth and Pakistan (NCWP). However, the distribution is not equal. For instance, two-thirds of all young children in the inner wards of Birmingham, and one-third of those in inner London, have parents who were born in the NCWP. Uptake of dental services is reported to be low in some inner city areas. There, as elsewhere, dental care needs to be accessible, acceptable and appropriate. But how are these objectives best achieved?


Mangrove forest: An important coastal ecosystem to intercept river microplastics.
The research on transportation of river microplastics (MPs) mainly focuses on the estimations of the total contents of river MPs entering the ocean, while the related transportation processes and influence factors were still largely unknown. In our study, the role of mangrove forest, a special tropical ecosystem in the estuary, on the transportations of MPs from rivers to ocean was explored. Except for the ND river with the absence of mangrove forest, the MPs collected from the water sample of the river upstream were much higher than their corresponding downstream (p < 0.05), with the interception rate of riverine MPs by mangrove forests ranging from 12.86% to 56% in dry season and 10.57%-42% in rainy season. The MPs with the characteristics of high density, larger size and regular shape were more easily intercepted. Furthermore, the combined effects of ecological indicators, the properties of mangrove and the hydrodynamic factors jointly determined the interception rates of MPs. This study provides a new perspective and data support for quantifying mangrove forests intercepting MPs in rivers as a factor of MPs retention in global rivers.


Oral and Maxillofacial Imaging.
This article provides the reader with the knowledge and skills of identification and diagnostic interpretative skills using planar images, tomographic images, CBCT, MDCT, pertinent MR images, as well as bone scans and PET images. The goal is to provide sufficient in-depth knowledge of the technique, anatomy, and radiographic identifiers for the diagnosis of local and systemic pathoses. The information will train the reader to be an advocate of selection criteria as well as a follower of the "Image Gently" campaign and philosophy supported by the organized dentistry in the United States, especially in Diagnostic Radiology.


Role of excitatory amino acids in the ventral tegmental area for central actions of non-competitive NMDA-receptor antagonists and nicotine.
The putative role of non-NMDA excitatory amino acid (EAA) receptors in the ventral tegmental area (VTA) for the increase in dopamine (DA) release in the nucleus acumbens (NAC) and the behavioural stimulation induced by systemically administered dizocilpine (MK-801) was investigated. Microdialysis was utilized in rats with probes in the VTA and NAC. The VTA was perfused with the AMPA and kainate receptor antagonist CNQX (0.3 or 1.0 mM) or vehicle and dialysates from the NAC were analyzed with high-performance liquid chromatography for DA. Forty min after onset of CNQX or vehicle perfusion of the VTA MK-801 (0.1 mg/kg) was injected subcutaneously (s.c.). Subsequently, typical MK-801 induced behaviours were assessed. The MK-801 induced hyperlocomotion was associated with a 50% increase of DA levels in NAC dialysates. Both the MK-801 evoked hyperlocomotion and DA release in the NAC were effectively antagonized by CNQX perfusion of the VTA. However, by itself the CNQX or vehicle perfusion of the VTA did not affect DA levels in NAC or the rated behaviours. The results indicate that MK-801 induced hyperlocomotion and increased DA release in the NAC are largely elicited within the VTA via activation of non-NMDA EAA receptors, tentatively caused by locally increased EAA release. In contrast, the enhanced DA output in the NAC induced by systemic nicotine (0.5 mg/kg s.c.) was not antagonized by intra VTA infusion of CNQX (0.3 or 1.0 mM), but instead by infusion of the NMDA receptor antagonist AP-5 (0.3 or 1.0 mM) into the VTA, which by itself did not alter DA levels in the NAC. Thus, the probably indirect, EAA mediated activation of the mesolimbic DA neurons in the VTA by MK-801 and nicotine, respectively, seems to be mediated via different glutamate receptor subtypes.


A preliminary map of the salivary gland chromosomes of Aedes (stegomyia) aegypti (Culicadae, Diptera).
A preliminary map of the polytene chromosomes in Aedes aegypti has been prepared. The preparations were made from the salivary glands of the late 4th instar larvae reared at low temperature. The entire chromosome complement was divided into 45 zones. The chromosomes showed a meshwork of the contents wherein they have a tendency to adhere to each other so as to form a single chromatic mass. The technical difficulties encountered in obtaining suitable preparations have partially been overcome. The banding pattern of Aedes aegypti seems to be quite independent and may be considered as unique for Aedes.


Characterisation of core-shell latexes by flow field-flow fractionation with multi-angle light scattering detection.
Flat channel asymmetrical flow field-flow fractionation with multi-angle light scattering (MALS) detection was used to study the swelling behaviour of core-shell particles with either carboxylated or hydroxylated shells as a function of pH and ionic strength. The equilibration time of the most heavily carboxylated core-shells appeared to be of the order of several hours. At low ionic strength (5 mM), the carboxylated core-shells showed a definite swelling response to a change in pH in the range from 5 to 10, ranging from a hydrodynamic radius increase of 24 to 118%, depending on the degree of carboxylation. A much milder response was found for the change of the root mean square (r.m.s.) radius as measured with MALS, indicating that the scattering plane is moving inwards during the swelling process due to a decreasing density of the shell. The hydroxylated core-shells appeared to be inert to a change in pH. Also the response of two expanded (pH 10) carboxylated core-shells on increasing ionic strength was studied. Comparison of the results of these ionic strength experiments with theoretical predictions based on Donnan equilibrium led us to the conclusion that a significant amount of counter-ion condensation may take place in the shells.


Predicting anaplastic lymphoma kinase rearrangement status in patients with non-small cell lung cancer using a machine learning algorithm that combines clinical features and CT images.
To develop an appropriate machine learning model for predicting anaplastic lymphoma kinase (ALK) rearrangement status in non-small cell lung cancer (NSCLC) patients using computed tomography (CT) images and clinical features. This study included 193 patients with NSCLC (154 in the training cohort, 39 in the validation cohort), 68 of whom tested positive for ALK rearrangements and 125 of whom tested negative. From the nonenhanced CT scans, 157 radiomic characteristics were extracted, and 8 clinical features were collected. Five machine learning (ML) models were assessed to find the best classification model for predicting ALK rearrangement status. A radiomic signature was developed using the least absolute shrinkage and selection operator (LASSO) algorithm. The predictive performance of the models based on radiomic features, clinical features, and their combination was assessed by receiver operating characteristic (ROC) curves. The support vector machine (SVM) model had the highest AUC of 0.914 for classification. The clinical features model had an AUC=0.805 (95% CI 0.731-0.877) and an AUC=0.735 (95% CI 0.566-0.863) in the training and validation cohorts, respectively. The CT image-based ML model had an AUC=0.953 (95% CI 0.913-1.0) in the training cohort and an AUC=0.890 (95% CI 0.778-0.971) in the validation cohort. For predicting ALK rearrangement status, the ML model based on CT images and clinical features performed better than the model based on only clinical information or CT images, with an AUC of 0.965 (95% CI 0.826-0.882) in the primary cohort and an AUC of 0.914 (95% CI 0.804-0.893) in the validation cohort. Our findings revealed that ALK rearrangement status could be accurately predicted using an ML-based classification model based on CT images and clinical data.


Red mud modified sludge biochar for the activation of peroxymonosulfate: Singlet oxygen dominated mechanism and toxicity prediction.
In this paper, red mud-sewage sludge derived biochar (RSDBC) was synthesized and employed as the heterogenous activator of peroxymonosulfate (PMS) for sulfamethoxazole (SMX) degradation. With the incorporation of red mud, 82.5% degradation of SMX was achieved by RSDBC/PMS system in a process dominated by 1O2, which was attributed to the participation of oxygen vacancy, ketone groups and graphitic carbon. On the other hand, in the absence of red mud, OH and SO4•- were dominantly accounted for SMX degradation in sewage sludge derived biochar (SDBC)/PMS system. In this case heterogeneous Fe species, ketone groups and graphitic carbon were responsible for PMS activation. Due to the different Reactive Oxygen Species (ROS), effects of reaction conditions including initial pH, common anions and natural organic matter (NOM) were not in full accord. Besides, Fe leaching from RSDBC (0.67 ppm) was much lower than that of SDBC (3.07 ppm), leading to a better reuse ability for RSDBC. Less degradation intermediates were disclosed in RSDBC/PMS system, along with lower residual toxicity. In addition, eco-toxicity of all the intermediates was predicted by ECOSAR program for the further understanding of the detoxification of SMX. Advantages of RSDBC/PMS system as disclosed in this paper further suggest its potential full-scale application of environmental remediation.


Immunocytochemistry and in situ hybridisation of epidermal growth factor receptor and relation to prognostic factors in breast cancer.
The breast tumour distribution of epidermal growth factor receptor (EGFR) was studied in 193 patients with primary breast cancer by immunocytochemistry on frozen sections. EGFR was correlated (P = 0.0009) with growth fraction assessed by Ki-67, and negatively correlated with oestrogen receptor (ER, P = 0.0001) and progesterone receptor (PR, P = 0.0001) status. In 47 patients, in-situ hybridisation for EGFR mRNA showed good agreement with the immunocytochemically assessed EGFR protein. There were, however, several tumours in which EGFR mRNA could be detected in the absence of EGFR protein and there were differences between the ER and PR status of those tumours in which translation of EGFR mRNA was not seen. The cause of these differences is unclear, but these findings may represent a clue as to the differential control of breast cancer cell receptors.


Relationship between blood test values and blood lead (Pb) levels in Black-headed gull (Chroicocephalus ridibundus: Laridae).
Few studies have evaluated immunosuppression due to lead accumulation below the overt toxicity threshold. If low levels of lead accumulation cause immunosuppression in birds, those birds could become more susceptible to pathogens. We aimed to determine if low levels of lead accumulation lead to immunosuppression in Black-headed gulls (Chroicocephalus ridibundus). Gulls were captured in Tokyo-bay and Mikawa-bay from January to April 2019. Their blood samples were analyzed for eight items. The data were analyzed to evaluate the correlation between lead concentrations and the variables from each bay. Lead was positively correlated with the percentage of heterophils and heterophil and lymphocyte ratio and negatively with lymphocytes. Thus, low lead accumulation levels may induce changes in percentage of the heterophils and lymphocyte.


Avoidance as a strategy of (not) coping: qualitative interviews with carers of Huntington's Disease patients.
Since Huntington's Disease (HD) is a familial disease with an average onset in the mid-thirties, one might expect that spousal carers are concerned with providing care for off-spring who may turn out to be affected. This study involved ten face-to-face interviews with carers of spouses affected by HD in Northeast Scotland. Carers were recruited through two channels: a genetic clinic and the Scottish Huntington's Association (SHA). Interviews were conducted in carers' own homes. A thematic analysis of the transcripts was conducted. Although carers did worry about their children, they did not envisage being involved in their care. Many avoided talking about the disease, both within and outwith their family; this may have greatly reduced the level of support provided by family members. Conversely, avoidance was often accompanied by symptom-spotting. For example, several people had given up driving, before they were incapable of doing so. The explanation appears to be that they avoided getting into situations in which HD may express itself. Support meetings seem to be valued amongst patients with other serious diseases and their carers, however, although all participants had had contact with the SHA, only one regularly attended meetings. It was felt that seeing others with HD provided a constant reminder of the possible effect of HD on the wider family, which seemed to outweigh the benefit of attending. Overall, the analysis highlighted 'avoidance' as a key theme. Many denied symptoms of HD in their spouses, pre-diagnosis. All had pretended at some point that it was not happening, through ignoring early signs and 'obvious' symptoms. Some partners had refused to go to the doctor until it was no longer possible to deny symptoms. Formal health and social care seemed to play a very small role compared to informal care arrangements.


[Degenerative changes in the knee joints caused by stress syndromes in floorers and roofers].
The problem of early degenerative lesions of knee joints in occupational groups of floorers and roofers has been presented. The major pathogenic factor was regarded to be overload occurring during the performance of static and dynamic work in the kneeling position. Over twofold rate of knee joints degeneration and its earlier occurrence were found as compared to controls. It was concluded that an extensive prophylaxis should be introduced.


Atrial Fibrillation Incidence Associated With Exposure to Anticancer Drugs Used as Monotherapy in Clinical Trials.
The incidence of atrial fibrillation (AF) associated with anticancer drugs in cancer patients remains incompletely defined. The primary outcome was the annualized incidence rate of AF reporting associated with exposure to 1 of 19 anticancer drugs used as monotherapy in clinical trials. The authors also report the annualized incidence rate of AF reported in the placebo arms of these trials. The authors systematically searched ClinicalTrials.gov for phase 2 and 3 cancer trials studying 19 different anticancer drugs of interest used as monotherapy, up to September 18, 2020. The authors performed a random-effects meta-analysis to compute summary AF annualized incidence rate with its 95% CI using log transformation and inverse variance weighting. A total of 191 clinical trials (47.1% were randomized) of 16 anticancer drugs across 26,604 patients were included. Incidence rates could be calculated for 15 drugs administered singly as monotherapy. Summary annualized incidence rates of AF reporting associated with exposure to 1 of the 15 anticancer drugs used as monotherapy were derived; these ranged from 0.26 to 4.92 per 100 person-years. The 3 highest annualized incidence rates of AF reporting were found for ibrutinib 4.92 (95% CI: 2.91-8.31), clofarabine 2.38 (95% CI: 0.66-8.55), and ponatinib 2.35 (95% CI: 1.78-3.12) per 100 person-years. Summary annualized incidence rate of AF reporting in the placebo arms was 0.25 per 100 person-years (95% CI: 0.10-0.65). AF reporting is not a rare event associated with anticancer drugs in clinical trials. A systematic and standardized AF detection should be considered in oncological trials, particularly those studying anticancer drugs associated with high AF rates. (Incidence of atrial fibrillation associated with anticancer drugs exposure in monotherapy, A safety meta-analysis of phase 2 and 3 clinical trials; CRD42020223710).


Glycan engineering of proteins with whole living yeast cells expressing rat liver alpha2,3-sialytransferase in the porous cell wall.
The N-glycans of recombinant proteins produced via the secretory pathway of cultured mammalian cells are often undersialylated, and insect cells lack sialytransferases. Undersialylated glycoproteins are rapidly cleared from the circulation, compromising the effect of pharmaceuticals. We show that incubation with living Saccharomyces cerevisiae cells expressing the catalytic ectodomain of rat liver alpha2,3-sialyltransferase (ST3Ne) in the porous cell wall resulted in sialylation of glycoproteins. The Km values of the yeast enzyme for several substrates were similar to those of recombinant ST3Ne from insect cells and of authentic ST3N. The yeast strain provides an inexpensive self-perpetuating source of ST3N activity for glycan engineering of recombinant proteins.


Perventricular device closure of a doubly committed juxtaarterial ventricular septal defect through a left parasternal approach: midterm follow-up results.
It is infeasible to occlude a doubly committed juxtaarterial ventricular septal defect (DCVSD) percutaneously. The previous perventricular device closure technique was performed through an inferior median sternotomy approach. The purpose of this study is to evaluate the feasibility, safety and efficacy of perventricular device closure of DCVSDs through a left parasternal approach. Sixty-two patients, with the DCVSD of less than 6 mm in diameter, were enrolled in this study. The pericardial space was approached through a left parasternal mini-incision without entering into the pleural space. Two parallel pursestring sutures were placed on the right ventricular outflow tract for puncture. Under transesophageal echocardiographic guidance, a new delivery sheath loaded with the device was inserted into the right ventricle and advanced through the defect into the left ventricle. The device, connected with a device stay suture, was deployed subsequently. Successful device closure of the defects was achieved in 58/62 patients (94 %). The DCVSD failed to close in 4 (6 %) patients due to device-related aortic regurgitation and device migration. The mean DCVSD diameter was 3.4 ± 1.0 mm (range, 2.0 to 6.0 mm). The implanted device size was 5.2 ± 1.3 mm (range, 4 to 8 mm). Forty-four out of 58 patients (76 %) was implanted with an eccentric occluder. The mean intracardiac manipulation time was 14 ± 13 min (range, 2 to 60 min). The procedure time was 66 ± 15 min (range, 42 to 98 min). During the follow-up period of 180 to 1860 (median 880) days, new mild pulmonary regurgitation occurred in 2 patients. No other device-related complications were found. The complete closure rate was 95 % at discharge, 98 % at 1-, 6- and 12-month, 96 % at 2-year, and 100 % at 3-year follow-up. Perventricular device closure of a DCVSD through a left parasternal approach is feasible, safe, and efficacious in selected patients. This minimally invasive technique permits easy defect crossing and accurate device positioning.


Inappropriate implantable cardioverter defibrillator shocks in fractured Sprint Fidelis leads associated with 'appropriate' interrogation.
We present two patients with fractures within the pace-sense circuit of their Medtronic Sprint Fidelis leads who received inappropriate shocks from their Medtronic defibrillators during device interrogation. This was not simply a coincidence, but due to electromagnetic interference induced within the Sprint Fidelis lead by the device programmer during two-way communication with the defibrillator. Our subsequent investigations have uncovered at least two other similar incidents in Canada. We have also discovered that the Medtronic 'Auto-resume' feature may leave future patients uniquely vulnerable to such inappropriate shocks in the future.


Highly selective microbiosensors for in vivo measurement of glucose, lactate and glutamate.
An alternative approach to production of amperometric microbiosensors, which combines electrochemical electrometallization and electropolymerisation of phenylene diamine film with covalent binding enzymes, is presented. In this respect, for a sensitive detection of hydrogen peroxide (HP) at +0.4V versus Ag/AgCl (detection limit of 0.5 microM, s/n=3), carbon fiber microelectrodes (30 microm in diameter and 500 microm long) were covered with ruthenium. To obtain a highly selective detection of HP, in the presence of different interfering compounds (ascorbic acid, uric acid, etc.), an additive semi-permeable polymer film was formed on the top of the ruthenium layer by electropolymerisation of m-phenylene diamine (m-PD). The enzymatic selective layers were formed by covalent cross-linking the enzymes (glucose oxidase, lactate oxidase or glutamate oxidase) with BSA by glutaraldehyde in the presence of ascorbate oxidase. An additional polymeric layer based on polyurethane and Nafion was deposited on the top of the enzymatic membrane (glucose oxidase, lactate oxidase, or glutamate oxidase) in order to extend the dynamic range of biosensors up to 4mM for glucose (R=0.997; Y[nA]=-0.22+9.68x[glucose, mM]), 1.75mM for lactate (R=0.991; Y[nA]=0.43+15.36x[lactate, mM]) and 0.25 mM for glutamate (R=0.999; Y[nA]=0.02+29.14x[glutamate, mM]). The developed microbiosensors exhibited also negligible influences from interfering compounds at their physiological concentrations. Microbiosensors remained stable during 10h in a flow injection system at 36 degrees C and pH 7.4. The microbiosensors developed are now used in vivo and, as an example, we report here the data obtained with the glucose biosensor.


Blood-Based Biomarkers in Afp Normal/Stable Hepatocellular Carcinoma: Diagnostic and Prognostic Relevance of Mir-10b for Patients on Liver Transplant List.
As a diagnostic criteria of hepatocellular carcinoma (HCC), the exact threshold of alpha-fetoprotein (AFP) is controversial. In additional, not all HCC tumors are AFP positive or secrete elevated amounts of AFP into the serum. However, the diagnosis of HCC is quite important on the liver transplant list. Therefore, the purpose of this study was to investigate the expression of circulating micro RNAs (miRNAs) in AFP-stable HCC patients. Thus, we aimed to determine a diagnostic biomarker in these patients. Sixteen miRNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction system in AFP-stable HCC and AFP-trending HCC patients. In our study, 46.7% (n = 28) of the patients diagnosed with HCC had stable/normal AFP levels. We detected that high expression of miR-24, miR-10b and the low expression of miR-143 were independently and significantly associated with HCC in AFP-stable compared with AFP trending (P < .05). Additionally, we demonstrated that the overexpression of miR-10b was associated with poor disease-free survival in HCC (P = 0.001). Although more clinical validations are needed for the diagnosis of HCC, our current results indicate that the coexistence of high expression of miR-10b and miR-24 may help clinicians adjust in the diagnosis of HCC in patients who are on the liver transplant list but awaiting biopsy for the diagnosis of HCC.


Proposal of a prediction score for hematoma expansion after intracerebral hemorrhage.
To propose and validate a prediction score for intracerebral hemorrhage (ICH) patients at risk of hematoma expansion (HE). A retrospective observational study was designed to propose and validate the score. Sanxiang Road branch and Xuguan branch belonging to the Second Affiliated Hospital of Soochow University (China). A total of 317 ICH patients in Sanxiang Road branch were registered as the development cohort, and 109 ICH patients in Xuguan branch were enrolled as the validation cohort. Independent risk factors for HE were identified using multiple logistic regression analysis. A prediction score was then proposed based on β coefficients and preliminarily verified in the validation cohort. All clinical data of the patients were compiled from the electronic medical records. Hematoma expansion was defined as an increase in hematoma volume >33% or absolute hematoma growth >6ml from the initial scan. Specific non-contrast CT(NCCT) signs were identified by two observers independently. Our score demonstrated satisfactory discrimination ability for HE (area under the ROC curve 0.854 in the development cohort versus 0.893 in the validation cohort). Appropriate calibration was found in the development cohort, whereas calibration in the validation cohort was slightly lower but still within the accuracy range (maximum deviation, average deviation and P were 0.070, 0.028, 0.773, respectively, versus 0.114, 0.056, 0.156). Decision curve analysis of the score from two samples were both far from the curve of treat all and curve of treat none, which verified its security and reliability. Patients with a total score ≥4.5 were at greatest risk of HE. The score may provide some reference and help in accurately identifying individuals at high risk of HE, allowing rapid guidance of clinical management and also serving as an aid in clinical trials.


Assessment the effect of vitamin D supplementation on plasma vitamin D levels, inflammation, and oxidative stress biomarkers based on vitamin D receptor genetic variation in breast cancer survivors: a protocol for clinical trial.
Both human genes and environmental exposures, due to complex interplay, play important role in the cancer etiology. Vitamin D is associated with a reduced risk of incidence and mortality of several human cancers. This study will aim to investigate the possible effects of individual polymorphisms in vitamin D receptor (VDR) as well as effects of VDR haplotypes on response to vitamin D supplementation in breast cancer survivors. This is an interventional study in which the effects of vitamin D supplementation on plasma vitamin D levels, inflammatory and antioxidant biomarkers and factors associated with cell proliferation, differentiation, damage, and apoptosis will be investigated stratified by variations in VDR genotype. The present study will be conducted on breast cancer survivors referred to the Shohadaye Tajrish hospital and its associated clinics. One hundred ninety-eight breast cancer survivors will receive 4000 IU of vitamin D3 daily for 12 weeks. VDR Fok1, ApaI, TaqI, BsmI, and Cdx-2 genotype will be determined at the end of the study and responses to vitamin D supplements (inflammatory, antioxidant, cell proliferation, differentiation, damage, and apoptosis biomarkers) will be compared between the three subgroups of each VDR polymorphism as well as different VDR haplotype categories. Genetic variation is a fundamental factor influencing individuals' divergent responses to diet, nutritional status, metabolic response, and diet-related health disorders. Furthermore, studies of gene and environment interactions will provide a precise and accurate assessments of individuals' dietary requirements by considering both the genetic and environmental aspects simultaneously. The results of the current study, to some extent, will highlight the discrepancies existing in the findings of different studies regarding vitamin D, VDR, and cancer by considering both the genetic and environmental aspects simultaneously. If responses to vitamin D supplementation could be modified by VDR SNPs, determining the distribution of VDR polymorphisms in both breast cancer survivors and healthy populations will provide a new insight into the vitamin D requirements of individuals to prevent cancer and its related mortality based on their genotypes. Trial registration This trial has been registered on Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153.


Data on distribution of heat transfer coefficient and profiles of velocity and turbulent characteristics behind a rib in pulsating flows.
The paper presents experimental data on heat transfer and kinematic structure of steady and pulsating flows behind a rib. Several forcing frequencies and one non-dimensional amplitude of pulsation are considered. Distributions of heat transfer coefficient were obtained in the separation region. Optical measurements yielded the profiles of velocity and turbulent characteristics of flow at representative coordinates of the separation region. .


Urinary Retention is Rare After Total Joint Arthroplasty When Using Opioid-Free Regional Anesthesia.
Postoperative urinary retention (POUR) is a relatively common complication after total joint arthroplasty (TJA). Based on the findings of a randomized, prospective study from our institution, we abandoned the routine use of indwelling urinary catheters in patients undergoing elective TJA using opioid-free spinal anesthesia. The aim of this study was to determine the incidence of and the risk factors for POUR in this patient population. A total of 842 consecutive patients underwent TJA between January 2012 and September 2014 using opioid-free spinal anesthesia in whom indwelling urinary catheters were not used. Postoperative urinary retention was defined as the inability of a patient to void that necessitated the placement of either an indwelling urinary catheter or straight catheterization. Multivariate logistic regression analysis was used to determine risk factors for developing POUR. In this cohort, 79 patients (79/842; 9.3%) developed POUR. Independent risk factors for POUR were history of a benign prostatic hyperplasia (P = .02), renal disease (P = .001), longer operative time (P = .003), and age older than 67 years (P = .02). No patients in this cohort developed neurogenic bladder. This study confirms that the routine use of indwelling urinary catheters for patients undergoing TJA using an opioid-free spinal anesthesia may not be warranted. Urinary catheters may be used selectively in patients at risk for subsequent urinary retention.


Improvement in the outcomes of mantle cell lymphoma in the last decade: a real-life non interventional study of the Croatian Cooperative Group for Hematologic Diseases.
To compare the outcomes of Croatian patients with mantle cell lymphoma (MCL) who started treatment in 2007 and 2008 (historical cohort) and of those who started treatment between 2015 and 2017 (recent cohort). The historical cohort consisted of 40 patients who started treatment with rituximab in 2007 and 2008. Data on the recent cohort, consisting of 89 patients, were collected retrospectively from the electronic databases of Croatian hospitals with hematology units. Demographic characteristics and data on induction regimens, autologous stem cell transplantation (ASCT), and rituximab maintenance in the first remission, event-free survival (EFS), and overall survival (OS) were available for both cohorts, and data on cell morphology, mantle cell international prognostic index (MIPI), and Ki67 expression only for the recent cohort. The recent cohort had significantly better two-year EFS and OS (EFS 58% vs 40%, P=0.014; OS 80% vs 56%, P=0.009), especially in patients below 65. In univariate analysis, induction regimen, ASCT, and maintenance were significant prognostic factors for EFS and the former two for OS. In the multivariate analysis, only ASCT remained significant. Bendamustine+rituximab (BR) induction improved the outcomes of non-transplantable patients over R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, steroid). Blastoid morphology and high MIPI were adverse prognostic factors for EFS and OS. In the last decade, the outcome of newly diagnosed MCL patients improved. ASCT in the first remission was the main contributor in transplantable patients and BR in non-transplantable. Regularly updated national guidelines may help in a timely adoption of new treatments, thus improving the results.


The solubilization of the L and M antigens from sheep red cell membranes.
The Lp, L1 and M antigens from sheep red cells were solubilized using the non-ionic detergent Triton X-100 in the presence of dithiothreitol. Recovery rates were improved when membranes were sonicated at 4 degrees C in the presence of the detergent; values in the range 16-25% (M) and 9-17% (Lp and L1) were achieved for recovery.


Modulation of physical and biological properties of a composite PLLA and polyaspartamide derivative obtained via thermally induced phase separation (TIPS) technique.
In the present study, blend of poly l-lactic acid (PLLA) with a graft copolymer based on α,β-poly(N-hydroxyethyl)-dl-aspartamide and PLA named PHEA-PLA, has been used to design porous scaffold by using Thermally Induced Phase Separation (TIPS) technique. Starting from a homogeneous ternary solution of polymers, dioxane and deionised water, PLLA/PHEA-PLA porous foams have been produced by varying the polymers concentration and de-mixing temperature in metastable region. Results have shown that scaffolds prepared with a polymer concentration of 4% and de-mixing temperature of 22.5°C are the best among those assessed, due to their optimal pore size and interconnection. SEM and DSC analysis have been carried out respectively to study scaffold morphology and the influence of PHEA-PLA on PLLA crystallization, while DMF extraction has been carried out in order to quantify PHEA-PLA into the final scaffolds. To evaluate scaffold biodegradability, a hydrolysis study has been performed until 56days by incubating systems in a media mimicking physiological environment (pH7.4). Results obtained have highlighted a progressive increase in weight loss with time in PLLA/PHEA-PLA scaffolds, conceivably due to the presence of PHEA-PLA and polymers interpenetration. Viability and adhesion of bovine chondrocytes seeded on the scaffolds have been studied by MTS test and SEM analysis. From results achieved it appears that the presence of PHEA-PLA increases cells affinity, allowing a faster adhesion and proliferation inside the scaffold.


Comparative proteomic analysis reveals differential protein expression of Hypsizygus marmoreus in response to different light qualities.
Light is important environmental stress that influences the growth, development, and metabolism of Hypsizygus marmoreus (white var.). However, the molecular basis of the light effect on H. marmoreus remains unclear. In this study, a label-free comparative proteomic analysis was applied to investigate the global protein expression profile of H. marmoreus mycelia growing under white, red, green, and blue light qualities and darkness (control). Among 3149 identified proteins in H. marmoreus, 2288 were found to be expressed in all tested conditions. Data of Each light quality was compared with darkness for further analysis, numerous differentially expressed proteins (DEPs) were identified and the white light group showed the most. All the up-regulated and down-regulated DEPs were annotated and analyzed with the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The KEGG enrichment analysis revealed that light stress was associated with primary metabolism, glycolysis/gluconeogenesis, MAPK, proteasome, and carbohydrate-active enzyme pathways. This study advances valuable insights into the molecular mechanisms underlying the role of different light qualities in mushroom growth and development.


Does drug decriminalization increase unintentional drug overdose deaths?: Early evidence from Oregon Measure 110.
This paper evaluates the causal effect of drug decriminalization on unintentional drug overdose deaths in a context with relatively poor access to drug treatment services. Using the synthetic control method, I find that when Oregon decriminalized small amounts of drugs in February 2021, it caused 182 additional unintentional drug overdose deaths to occur in Oregon in 2021. This represents a 23% increase over the number of unintentional drug overdose deaths predicted if Oregon had not decriminalized drugs.


Regulation of α-secretase ADAM10 expression and activity.
The amyloid precursor protein (APP) has a pivotal role in pathogenesis of Alzheimer's disease (AD) via its beta- and gamma-secretase-derived cleavage products--the A-beta peptides. An alternative processing pathway provided by the alpha-secretase prevents formation of those toxic peptides and gives rise to the neurotrophic and neuroprotective cleavage product APPs-alpha. The molecular identity of the alpha-secretase has been confirmed recently, and there is consistency about ADAM10 being the most relevant and physiological enzyme of this class. It is not clear to what extent a deficiency in the catalytic activity of ADAM10 contributes to AD pathology and whether a decline occurs in aging humans. Nevertheless, ADAM10 has been suggested as a valuable target for prevention and/or for treatment of Alzheimer's disease. This review focuses on our knowledge about regulation of ADAM10 on different levels of cell physiology, such as transcription and translation, as well as protein-protein interactions and how this especially in the case of transcriptional regulation by retinoic acids might lead to the development of new therapeutic approaches.


[Severe hypertension (grade III and grade IV). A study on the clinical course in 117 patients in Landspítalinn Medical Department 1957-1971. 1974].
The aim of this study was to evaluate the incidence, complications, survival time and causes of death of patients with severe hypertension (S.H.) (grade III and grade IV) who were admitted to Landspítalinn (The University Hospital in Reykjavík med. Depart.) during the years 1957-1971. During this period 117 patients were found to have S.H. according to the grading of Keith and Wagener (20 patients with grade IV end 97 with grade III). It was found that relatively fewer patients with S.H. were admitted during the last 5 year period (1967-1971) compared to the two previous 5 year-period (1957-1966). The cases were analysed according to sex and age distribution, blood urea, electrocardiographic changes, heart size (by x-ray) and blood pressure readings at the time of admission. In relation to the above mentioned factors the incidence and type of complications, survival time and causes of death were evaluated. The main causes of death were cerebrovascular accidents (26,6%), myocardial infarction (22,8%) and uremia (22,8%). The survival calculations were done by the decremental method aim taken from patient age less than 66 years. Approximately 50% of the men and 60% of the women had a 5 year survival. Elevated blood urea values and signs of left ventricular hypertrophy in the electrocardiogram at the time of diagnosis of S.H. had an unfavorable influence on length of survival.


Long non-coding RNA NEAT1 and its targets (microRNA-21 and microRNA-125a) in rheumatoid arthritis: Altered expression and potential to monitor disease activity and treatment outcome.
The present study aimed to explore the association of long non-coding RNA nuclear-enriched abundant transcript 1 (lnc-NEAT1) with inflammation, disease activity, treatment outcome, and its targets (microRNA [miR]-21 and miR-125a) in patients with rheumatoid arthritis (RA). Peripheral blood mononuclear cells were sampled from 130 RA patients at baseline, week (W) 6, and W12, as well as from 60 healthy controls (HCs) after enrollment. Meanwhile, the expressions of lnc-NEAT1, miR-21, and miR-125a were detected by reverse transcription-quantitative polymerase chain reaction. lnc-NEAT1 was elevated, but miR-21 and miR-125a were declined in RA patients compared with HCs (all p < 0.001); meanwhile, lnc-NEAT1 was negatively correlated with miR-21 and miR-125a (both p < 0.05) in RA patients. Besides, elevated lnc-NEAT1 but declined miR-21 and miR-125a were correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein and the 28-joint Disease Activity-ESR score (all p < 0.05) in RA patients. Moreover, lnc-NEAT1 was declined from baseline to W12 in RA patients (p < 0.001). Additionally, lnc-NEAT1 at W12 was declined in response patients compared with non-response patients (p = 0.006), and also decreased in remission patients compared with non-remission patients (p < 0.001). lnc-NEAT1 and its targets (miR-21 and miR-125a) correlate with RA risk and disease activity, and declined lnc-NEAT1 associates with better treatment outcome to some extent in RA patients, suggesting that lnc-NEAT1 might be a potential biomarker to monitor disease activity and treatment outcome in RA.


Microstructure and properties of thermomechanically processed chitosan citrate-based materials.
The traditional solvent casting method for preparing chitosan-based materials has limited productivity relative to the productivity of thermomechanical processing. Consequently, the thermomechanical processing technique was evaluated as a way to increase chitosan production. The role of citric acid (CA) as a destructuring and crosslinking agent during such processing was examined. SEM images revealed robust fibers that were associated with a superior mechanical strength (145%), which were produced after thermomechanical processing of chitosan in the presence of CA. Based on articles reviewed, this is the first time that this structure has been closely observed in the microstructure of chitosan-based materials. FTIR and XRD characterization showed the occurrence of chemical crosslinking and the successful destructuring of chitosan powder by CA during processing. Compared to acetic acid, the use of CA led to the development of materials with a homogeneous morphology and good physicochemical and mechanical properties that are suitable for biomedical applications.


Enhancing clinical communication in dermatologists: a personalized educational intervention.
Effective communication is a vital component of patient-centered consultations with favorable treatment outcomes. This study aimed in testing the effectiveness of a personalized, communication training program for dermatologists in their practices. Fifteen dermatologists were offered the educational intervention NO.TE.S. (Non-Technical Skills). Depending on the dermatologists' needs, seven to nine sessions with a 60-min duration were performed, focusing on: patient-centered care, principles of Neurolinguistic Programming, a guide to the medical interview, principles of motivational interviewing and self-care. After the program's completion, participants completed anonymously an 18-item evaluation questionnaire. All 14 participants would suggest NO.TE.S to a colleague. According to the main themes identified, their participation led to (i) re-consideration of the physician-patient relationship, (ii) more conscious application of the patient-centered model, (iii) improvement in communication skills, (iv) awareness of medical interview guides, (v) increase in self-confidence, and (vi) techniques of self-care. Eleven physicians (78.6%) declared improvement in patients' satisfaction, 14 (100%) in their own satisfaction, seven (50%) in adherence to therapeutic plan and seven (50%) in treatment outcomes. The one-to-one coaching is a convenient and well-received personalized means of enhancing clinical communication in dermatologists, leading to more patient-centered medical encounters with better treatment outcomes.


Cosmetic Use in Nigeria May Be Safe: A Human Health Risk Assessment of Metals and Metalloids in Some Common Brands.
Twenty different brands of cosmetic products were purchased from supermarkets in Port Harcourt, Rivers State, Nigeria, with the aims to determine the levels of metals and assess the health risk to humans through long-term usage. The concentration of metals (arsenic, lead, mercury, cadmium, and nickel) in the cosmetic samples was measured with atomic absorption spectrophotometry after acid digestion. The concentration of metals in these brands of cosmetic studied ranged from As: 0.001-0.0161 mg/kg, Pb: 0.289-2.873 mg/kg, Hg: 0.001-0.0014 mg/kg, Cd: 0.001-0.334 mg/kg, and Ni: 0.007-2.748 mg/kg. The metal and metalloid contents were less than the regulatory limits set for both metal impurities and as color additives. The target hazard quotient, hazard index, and cancer risk were less than the acceptable limit, indicating a measure of safety. Cosmetics sold in Nigeria may not add to the body burden of metals and metalloids.


Displacement of peer play by screen time: associations with toddler development.
Young children's digital media use may adversely affect child development, but the mechanisms of this association are unclear. We evaluated whether screen time displaces reading and peer play time, which are subsequently associated with child development. When children were 12, 18, 24, 30, and 36 months, mothers (n = 3894) reported the time their children spent on screens, being read to by an adult, and playing with other children. At 36 months, mothers completed the Ages and Stages Questionnaire©, an assessment of their child's developmental status. In unadjusted models, screen time from 12 to 36 months was not associated with reading but was associated with less time engaging in play with peers. In adjusted models accounting for developmental delay at 12 months, family and child characteristics, screen time was not directly associated with developmental delay. More peer play time was associated with a lower likelihood of developmental delay, and having higher screen time increased the likelihood of developmental delay indirectly through reduced peer play time. Results were similar for developmental delays in fine and gross motor, communication, and personal-social domains. Screen time in early childhood did not displace reported time spent reading, but did displace reported peer play time. Among children 1-3 years of age, more screen time was associated with less time engaged in peer play but not less reading with an adult. Having higher screen time from 1 to 3 years increased the odds of developmental delay indirectly through reduced peer play time. Ensuring that children engage in adequate time playing with peers may offset the negative associations between screen time and child development.


Characterization of therapeutic antibodies and related products by two-dimensional liquid chromatography coupled with UV absorbance and mass spectrometric detection.
The development of analytical tools for the characterization of large biomolecules is an emerging and rapidly evolving area. This development activity is motivated largely by the current trend involving the increase in development and use of large biomolecules for therapeutic uses. Given the inherent complexity of these biomolecules, which arises from their sheer size and possibilities for chemical modification as well as changes over time (e.g., through modification in solution, aggregation), two-dimensional liquid chromatography (2D-LC) has attracted considerable interest as an analytical tool to address the challenges faced in characterizing these materials. The immediate potential benefits of 2D-LC over conventional one-dimensional liquid chromatography in this context include: (1) higher overall resolving power; (2) complementary information gained from two dimensions of separation in a single analysis; and (3) enabling indirect coupling of separation modes that are inherently incompatible with mass spectrometric (MS) detection (e.g., ion-exchange, because of high-salt eluents) to MS through a more compatible second dimension separation such as reversed-phase LC. In this review we summarize the work in this area, most of which has occurred in the past five years. Although the future is bright for further development in this area, some challenges have already been addressed through new 2D-LC methods. These include: (1) deep characterization of monoclonal antibodies to understand charge heterogeneity, glycosylation patterns, and other modifications; (2) characterization of antibody-drug conjugates to understand the extent and localization of small molecule conjugation; (3) detailed study of excipients in protein drug formulations; and (4) detection of host-cell proteins on biotherapeutic molecule preparations. We fully expect that in the near future we will see this list expanded, and that continued development will lead to methods with further improved performance metrics.


HIF-1α-regulated lncRNA-TUG1 promotes mitochondrial dysfunction and pyroptosis by directly binding to FUS in myocardial infarction.
Myocardial infarction (MI) is a fatal heart disease that affects millions of lives worldwide each year. This study investigated the roles of HIF-1α/lncRNA-TUG1 in mitochondrial dysfunction and pyroptosis in MI. CCK-8, DHE, lactate dehydrogenase (LDH) assays, and JC-1 staining were performed to measure proliferation, reactive oxygen species (ROS), LDH leakage, and mitochondrial damage in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Enzyme-linked immunoassay (ELISA) and flow cytometry were used to detect LDH, creatine kinase (CK), and its isoenzyme (CK-MB) levels and caspase-1 activity. Chromatin immunoprecipitation (ChIP), luciferase assay, and RNA-immunoprecipitation (RIP) were used to assess the interaction between HIF-1α, TUG1, and FUS. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to measure HIF-1α, TUG1 and pyroptosis-related molecules. Hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC), and terminal deoxynucleotidyl transferase dUTP risk end labelling (TUNEL) staining were employed to examine the morphology, infarction area, and myocardial injury in the MI mouse model. Mitochondrial dysfunction and pyroptosis were induced in H/R-treated cardiomyocytes, accompanied by an increase in the expression of HIF-α and TUG1. HIF-1α promoted TUG1 expression by directly binding to the TUG1 promoter. TUG1 silencing inhibited H/R-induced ROS production, mitochondrial injury and the expression of the pyroptosis-related proteins NLRP3, caspase-1 and GSDMD. Additionally, H/R elevated FUS levels in cardiomyocytes, which were directly inhibited by TUG1 silencing. Fused in sarcoma (FUS) overexpression reversed the effect of TUG1 silencing on mitochondrial damage and caspase-1 activation. However, the ROS inhibitor N-acetylcysteine (NAC) promoted the protective effect of TUG1 knockdown on H/R-induced cardiomyocyte damage. The in vivo MI model showed increased infarction, myocardial injury, ROS levels and pyroptosis, which were inhibited by TUG1 silencing. HIF-1α targeting upregulated TUG1 promotes mitochondrial damage and cardiomyocyte pyroptosis by combining with FUS, thereby promoting the occurrence of MI. HIF-1α/TUG1/FUS may serve as a potential treatment target for MI.


Optical resolution of 1,16-dihydroxytetraphenylene by chiral gold(iii) complexation and its applications as chiral ligands in asymmetric catalysis.
We report herein a novel approach involving optical resolution of (±)-1,16-dihydroxytetraphenylene (DHTP) by chiral gold(iii) complexation. This method features several key advantages, i.e., recyclability of chiral resolution reagents, feasibility of scaling up to gram quantities, and operational simplicity. On the basis of this method, which led to optically pure DHTP, a library of 2,15-diaryl (S)-DHTPs and several (S)-DHTP-derived phosphoramidite ligands were synthesized. Finally, the superior performance of a (S)-DHTP phosphoramidite ligand was demonstrated by efficient iridium-catalyzed asymmetric allylic alkynylation reactions.


Deep venous thrombosis and pulmonary embolisms in adult patients undergoing craniotomy for brain tumors.
The development of venothromboembolisms (VTEs), including deep vein thrombosis (DVT) and pulmonary emboli (PE), is common in brain tumor patients. Their development can be catastrophic. Studies evaluating pre-operative clinical factors that predispose patients to the development of VTE are few and limited. An understanding may help risk stratify patients and guide subsequent therapy aimed at reducing the risk of DVTs/PEs. All adult patients who underwent surgery for an intracranial tumor at an academic tertiary care institution between 1998 and 2008 were retrospectively reviewed. Stepwise multivariate logistical regression analysis was used to identify pre-operative factors associated with the development of peri-operative (within 30 days of surgery) DVTs/PEs among patients who underwent surgery of their intracranial tumor. Of the 4293 patients in this study, 126 (3%) patients developed DVT and/or PE in the peri-operative period. The pre-operative factors independently associated with the development of DVTs/PEs were: poorer Karnofsky performance scale (KPS) [odds ratio (OR), 1·040; 95% confidence interval (CI), 1·026-1·052; P<0·0001], high grade glioma (OR, 1·702; 95% CI, 1·176-2·465; P = 0·005), older age (OR, 1·033; 95% CI, 1·020-1·046; P<0·0001), hypertension (OR, 1·785; 95% CI, 1·180-2·699; P = 0·006), and motor deficit (OR, 1·854; 95% CI, 1·244-2·763; P = 0·002). Eighty six per cent of the patients with DVTs/PEs were treated with either unfractionated or low molecular weight heparin, and 4% of these patients developed intracranial hemorrhage. The present study found that poorer functional status, older age, pre-operative motor deficit, high grade glioma, and hypertension each independently increased the risk of developing peri-operative DVTs/PEs. These findings may provide patients and physicians with prognostic information that may guide therapies aimed at minimizing the development of peri-operative DVTs/PEs.


Increasing incidence of recent hepatitis C virus infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan.
The incidence of hepatitis C virus (HCV) infection among HIV-negative men who have sex with men (MSM) is rarely investigated in the Asia-Pacific region. We aimed to estimate the incidence rate of and factors associated with recent HCV infection among the clients seeking voluntary counselling and testing (VCT) services for HIV in Taiwan. During 2006-2013, 12 143 clients sought VCT services for HIV. Clients with subsequent follow-up tests at an interval of 6 months or longer were included to estimate the incidence rate of HCV seroconversion. Phylogenetic analysis of HCV sequences from VCT clients and HIV-positive patients was performed. The overall HCV seroprevalence at baseline was 0.3%. Of 2150 clients testing negative for anti-HCV antibody at baseline with a total of 5074.99 person-years of follow-up (PYFU), 17 (0.8%) developed HCV seroconversion, leading to an overall incidence rate of 3.35 per 1000 PYFU (95% CI 1.76 to 4.94), which increased from 2.28 (95% CI 0.05 to 4.51) in 2006-2009, to 3.33 (95% CI 0.86 to 5.80) in 2010 to 2011 and 4.94 per 1000 PYFU (95% CI 0.99 to 8.99) in 2012-2013; the incidence of early syphilis increased from 11.91 to 13.28 and 31.78 per 1000 PYFU in the three corresponding periods. In multivariate analysis, having HIV-positive partners (adjusted HR (AHR) =3.756; 95%CI 1.180 to 11.955) and developing a rapid plasma reagin titre of 4 or greater (AHR=9.978; 95% CI 1.550 to 64.233) were significantly associated with HCV seroconversion. An increasing trend of recent HCV infection occurs among individuals seeking VCT services in Taiwan. Having HIV-positive partners and having syphilis are independently associated with recent HCV seroconversion.


Combined treatment for limited small cell lung cancer.
Radiation therapy is an important component for the management of limited small cell lung cancer (SCLC) in addition to systemic treatment. The role of surgery is limited for SCLC because of the nature of the disease, which often spreads to regional lymph nodes or spreads distantly. There have been major advances in the treatment of limited-stage SCLC during the past decade because of early application of thoracic radiation therapy (TRT) with concurrent chemotherapy, accelerated TRT, the application of prophylactic cranial irradiation for patients who achieved complete response to concurrent chemotherapy and TRT, and the improvement in supportive care such as discontinuation of tobacco smoking after the diagnosis of SCLC, nutritional support, pain control, granulocyte colony-stimulating factor, erythropoietin, and adequate antibiotics. It is important to select patients with limited SCLC who are able to tolerate concurrent chemotherapy and accelerated TRT.


Sites for xenobiotic activation and detoxication within the respiratory tract: implications for chemically induced toxicity.
Results of in situ immunohistochemical investigations on several enzymes which participate in the bioactivation and detoxication of xenobiotics and of histochemical studies on aryl hydrocarbon hydroxylase activity summarized in this report clearly demonstrate that there are numerous sites within the respiratory tract at which xenobiotics can be bioactivated and detoxicated. The data presented, however, also reveal that xenobiotic-metabolizing enzymes and benzo[a]pyrene hydroxylase activity may not be distributed uniformly within individual segments (e.g., the nasal mucosa) of this organ system. Thus, it should be apparent from these findings that one cannot generalize as to how a given xenobiotic-metabolizing enzyme or xenobiotic monooxygenase activity normally is distributed either within or among the different segments of the respiratory tract. Additionally, since enzymes catalyzing the bioactivation and detoxication of xenobiotics usually are present within the same respiratory tract cells, it obviously is difficult to predict from these results which cell types within individual segments of this organ system most likely would be damaged as a consequence of exposure to xenobiotics which are biotransformed into cytotoxic metabolites by cytochrome(s) P-450. Although the cellular localizations and intercellular distributions of cytochromes P-450 BNF-B and MC-B parallel those of benzo[a]pyrene hydroxylase activity within the different segments of the respiratory tract in untreated rats, immunohistochemical findings on the inductions of these cytochrome P-450 isozymes are not entirely consistent with histochemical observations on the enhancement of benzo[a]pyrene hydroxylase activity by Aroclor 1254 within the nasal mucosa and by both Aroclor 1254 and 3-methylcholanthrene within the lung. It must be appreciated, however, that other cytochrome P-450 isozymes undoubtedly are present and inducible in the nasal mucosa and lung and, further, that these hemeproteins, although being immunochemically unrelated to the cytochrome P-450 isozymes studied, also could catalyze aryl hydrocarbon hydroxylase activity. Nevertheless, these immunohistochemical and histochemical findings do demonstrate that one cannot generalize as to how chemicals which induce the same xenobiotic-metabolizing enzyme will affect that enzyme within different segments of the respiratory tract and, moreover, that inducers of cytochromes P-450 can alter differentially the extents to which different cells within a given segment of the respiratory tract (e.g., the nasal mucosa) participate in the oxidative metabolism of xenobiotics.


Trends of PCDD/F and PCB concentrations and depositions in ambient air in Northwestern Germany.
Time series of polychlorinated dioxins and furans (PCDD/F) and polychlorinated biphenyls (PCB) in ambient air of a large conurbation in North-Western Germany are presented and analyzed. The trend of PCDD/F concentrations, starting from as early as 1988, shows a pronounced decrease by at least one order of magnitude, demonstrating that the emission reductions were effective. The PCDD/F depositions also have decreased by a factor of 5 since 1992. However, both trends have leveled out since 2005. Time series of PCB concentrations and depositions starting in 1994 show only slight decreases for the concentrations and almost no decrease for the depositions. From the decay rates following first order kinetics, half-lives in the order of 5-15 years for the PCDD/F and 15-31 years for the sum of the six indicator PCB could be calculated, which are much longer than the half-lives estimated from their reactivity towards the OH radical. Apparently, small fresh emissions (PCDD/F), considerable secondary emissions and evaporation from contaminated soils slow down their decay in the atmosphere of big conurbations. Analyzing the decay rates of individual PCB congeners shows that the lower chlorinated and more volatile ones are removed faster than the higher chlorinated congeners, probably via gas phase reactions with the OH radical. It can be concluded from the present study that the input of PCDD/F and PCB into the food chain via the air path will continue for another one or two decades in big conurbations.


Continual transcranial Doppler in the monitoring of hemodynamic change following aneurysmal subarachnoid hemorrhage.
To analyze and compare the value of different treatment methods for acute aneurysmal subarachnoid hemorrhage (aSAH)-related vasospasm. Cerebral hemodynamic variables' changes were evaluated by transcranial Doppler (TCD) in aSAH patients within 14 days after onset. Thirty aSAH patients were enrolled in the study within 72 h after onset. Baseline CT and TCD were used for assessment. Patients were divided into three groups according to SAH severity and patients' discretion: nonsurgical group, endovascular coiling, and neurosurgical clipping. TCD hemodynamic parameters were measured and Lindegaard index was calculated daily from onset to 14th day after SAH. The group mean cerebral blood velocity (MBFV) and Lindegaard index were compared using repeated measures analysis of variance (reANOVA). Least Significant Difference (LSD) test was used for post hoc comparison. All 30 patients were followed for 90 days after onset for outcome assessment. The values of MBFV and Lindegaard index of anterior cerebral artery (ACA)/middle cerebral artery (MCA) from high to low is nonsurgical group, clipping and coiling (ACA: P= 0.0001/P= 0.006; MCA: P= 0.243/P= 0.317). These results indicate that both neurosurgical clipping and endovascular coiling management may relieve the severity of cerebral vasospasm in acute aSAH.


Bernthsen synthesis, antimicrobial activities and cytotoxicity of acridine derivatives.
The condensation reaction of diphenylamine with 2-oxo-2H-(substituted chromen)-4-yl acetic acid in presence of anhydrous zinc chloride afford 4-(acridine-9-ylmethyl)-2H-(substituted chromen)-2-one. The synthesized compounds were characterized by spectral studies and elemental analysis and screened for their in vitro antibacterial activity against Staphylococcus aureus, Staphylococcus pyogenes (gram +ve), Escherichia coli, Pseudomonas aeruginosa (gram -ve) and antifungal activity against Aspergillus niger and anticancer activity (HL-60, Hep-2 & HEK293T) by MTT assay. Chloro substituted compounds showed antimicrobial and anticancer activity with IC(50) values in the low micromolar range.


Fine structure of axons associated with the salivary apparatus of the cockroach, Nauphoeta cinerea.
Previous studies have shown that the neurotransmitter at the salivary gland of the cockroach is probably dopamine. An ultrastructural study of the innervation of these glands was made. It was concluded that there are two types of axon present designated type A and type B. Type A axons possess small agranular eliptical vesicles and large granular vesicles, whereas type B possess only large granular vesicles of larger diameter than those found in type A. The relationship of these types of axon to the cells of the acini is discussed. It is concluded that type A axons are catecholaminergic.


Analysis of squash smear cytology of ependymomas.
Ependymomas constitute 8-10 and 1-3% of central nervous system tumors in children and adults, respectively. Though intraoperative squash smear cytology is well documented, grading is rarely described. (1) To assess cytomorphology and grade ependymomas in squash smears. (2) To compare utility of hematoxylin and eosin (H&E) and toluidine blue (TB) staining. Ependymomas diagnosed from 2004 to 2010 were retrieved from pathology records. Intraoperative squash smears stained with TB and H&E were studied. Histological sections of 29 ependymomas were graded according to WHO 2007 classification. There were 3 myxopapillary (grade I), 13 grade II, and 13 grade III (anaplastic) ependymomas. Perivascular pseudorosettes were seen in 23 smears, and 11 showed rosettes. Less cohesive cells at the periphery of fragments with unipolar cytoplasmic processes were seen in all smears. The background was fibrillary in all except in myxopapillary ependymoma. Metachromatic material was seen in myxopapillary ependymoma around vessels and in globi. The nucleus was round with stippled chromatin and 1-2 small nucleoli could be seen. All smears of grade III ependymomas showed pleomorphism, mitoses, microvascular proliferation and necrosis. Ependymomas can be diagnosed and graded reliably by squash smear. Myxoid stroma was better appreciated by TB staining. TB and H&E complement each other in squash smears for cytomorphology.


WR2721 as a modulator of cisplatin- and carboplatin-induced side effects in comparison with other chemoprotective agents: a molecular approach.
Cisplatin is an active cytostatic that became successful in the treatment of several types of solid tumours after its nephrotoxic potential was controlled by hydration and diuresis. Thiol compounds were tested to reduce further cisplatin-induced nephrotoxicity. Thiosulphate is rapidly excreted by the kidneys and protects against cisplatin-induced nephrotoxicity by inactivating reactive platinum species in the kidney. Due to inactivation of cisplatin in the circulation, thiosulphate also interferes with its antitumour activity. Therefore, it is mainly used in two-route schedules, whereby cisplatin is delivered locally to the tumour (i.p. or i.a.) while systemic (i.v.) thiosulphate protects the kidneys. Diethyldithiocarbamate was shown to protect against cisplatin-induced nephrotoxicity in several animal models by reversing cellular damage. However, in the clinic it has been less successful, partly due to its central nervous system toxicity. The endogenous thiol compounds glutathione and metallothionein have been shown to reduce cisplatin-induced toxicity both in animal models and in clinical trials. However, the results are rather preliminary and a reduction in therapeutic efficacy may be expected, for both glutathione and metallothionein have been reported to be involved in platinum resistance. The thioether methionine has been shown to reduce cisplatin-induced nephrotoxicity in animal models but it has not yet been tested in the clinic. Cisplatin-induced acute emesis can be sufficiently controlled with a new class of 5-hydroxytryptamine-3 (5HT3)-receptor blockers, but delayed emesis remains a problem. High-dose cisplatin regimens with protection of the kidneys induces ototoxicity, peripheral neuropathy and myelotoxicity, which become dose-limiting. Neurotoxicity was partly reversed by the neurogenerative agent ORG2766, but this agent does not reduce other cisplatin-induced toxicities. Therefore, an agent capable of protecting multiple non-tumour tissues is needed. Carboplatin is a second-generation analogue of cisplatin with less nephro-, neuro- and ototoxicity. Carboplatin is at least as active as cisplatin at its maximum tolerated dose, which is defined by its myelotoxicity. Protection from carboplatin-induced myelotoxicity may be controlled by autologous bone marrow transplantation and/or hematopoietic growth factor infusions. High-dose carboplatin schedules may cause nephrotoxicity, neurotoxicity and ototoxicity. Again, the protection of multiple non-tumour tissues is needed. WR2721 appears to be such a modulating agent capable of protecting multiple non-tumour tissues. It was shown to be preferentially metabolized and taken up as the thiol metabolite WR1065 by non-tumour tissues as compared with (hypoxic) solid tumours. It was shown to protect mice from cisplatin-induced nephrotoxicity and from cisplatin- and carboplatin-induced myelotoxicity without interfering with the antitumour activity.(ABSTRACT TRUNCATED AT 400 WORDS)


Heavy-tailed fractional Pearson diffusions.
We define heavy-tailed fractional reciprocal gamma and Fisher-Snedecor diffusions by a non-Markovian time change in the corresponding Pearson diffusions. Pearson diffusions are governed by the backward Kolmogorov equations with space-varying polynomial coefficients and are widely used in applications. The corresponding fractional reciprocal gamma and Fisher-Snedecor diffusions are governed by the fractional backward Kolmogorov equations and have heavy-tailed marginal distributions in the steady state. We derive the explicit expressions for the transition densities of the fractional reciprocal gamma and Fisher-Snedecor diffusions and strong solutions of the associated Cauchy problems for the fractional backward Kolmogorov equation.


Effect of the introducer technique compared with the pull technique on the peristomal infection rate in PEG: a meta-analysis.
Peristomal infection is a main complication of PEG. The pull technique appears to be associated with higher infection rates compared with the introducer technique, although published results are controversial. To determine which technique is associated with a higher risk of infection. Systematic review and meta-analysis. Studies reporting rates of peristomal infection after PEG performed by either the pull or introducer technique. This study involved 2336 patients from 6 comparative and 10 observational studies. Public MEDLINE (National Library of Medicine journal articles database), Excerpta Medica Database, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Center on Health Sciences Information databases and proceedings of two meetings, Digestive Disease Week and United European Gastroenterology Week, were searched. Both comparative and observational studies were included and analyzed separately. Effect measures from each comparative study were reported as the odds ratio (OR). The pooled effect was then calculated. The infection rate in each observational study was also calculated, and a summary effect was then determined. In comparative studies, the risk of infection was significantly higher with the pull technique (OR 13.0; 95% confidence interval [CI], 4.6-36.8; P < .0001). Similarly, observational studies also reported higher infection rates with the pull technique (10.7%; 95% CI, 4.9-21.8 with the pull technique vs 0.9%; 95% CI, 0.2-4.5 with the introducer technique). Few studies were available for inclusion, and there was a high risk of bias among the comparative studies. The pull technique appears to be associated with a significantly higher risk of infection compared with the introducer technique.


Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration.
Microglia are the resident innate immune cells in the brain with a major role in orchestrating immune responses. They also provide a frontline of host defense in the central nervous system (CNS) through their active phagocytic capability. Being a professional phagocyte, microglia participate in phagocytic and autophagic clearance of cellular waste and debris as well as toxic protein aggregates, which relies on optimal lysosomal acidification and function. Defective microglial lysosomal acidification leads to impaired phagocytic and autophagic functions which result in the perpetuation of neuroinflammation and progression of neurodegeneration. Reacidification of impaired lysosomes in microglia has been shown to reverse neurodegenerative pathology in Alzheimer's disease. In this review, we summarize key factors and mechanisms contributing to lysosomal acidification impairment and the associated phagocytic and autophagic dysfunction in microglia, and how these defects contribute to neuroinflammation and neurodegeneration. We further discuss techniques to monitor lysosomal pH and therapeutic agents that can reacidify impaired lysosomes in microglia under disease conditions. Finally, we propose future directions to investigate the role of microglial lysosomal acidification in lysosome-mitochondria crosstalk and in neuron-glia interaction for more comprehensive understanding of its broader CNS physiological and pathological implications.


Species-specific debromination of BDE99 in teleost fish: The relationship between debromination ability and bioaccumulation patterns of PBDEs.
Polybrominated diphenyl ethers (PBDEs) are known to be broken down by debromination reactions in the natural environment, such as by photolysis, microbial and metabolic processes. Although species-specific debromination of PBDEs by fish has also been reported, it has only rarely been studied from the phylogenetic perspective. The objective of this study is to reveal the factors affecting species-specific debromination through validation between the bioaccumulation of PBDEs in muscle tissue and the ability to debrominate BDE99. As environmental observations, PBDE concentrations in muscle tissues were analyzed in 25 wild fish (Cyprinidae, Gobiidae and others). As in vitro experiments, debromination experiments were conducted using the hepatic microsomes of 21 fish species. Significant amounts of BDE99 were detected in almost none of the Cyprinidae. A relatively higher debromination ability was confirmed in the Cyprinidae in in vitro experiments. The Cyprinidae thus appears to be a family with high debromination ability. BDE99 has been detected in some goby species but not others. This pattern was also seen in in vitro experiments, suggesting that debromination ability is not consistent within the Gobiidae. In further quantitative comparisons, kinetic parameters such as Km and vmax were determined for selected fish species. The common carp (Cyprinus carpio) and the Japanese crucian carp (Carassius cuvieri), both Cyprinidae, showed higher vmax values, whereas vmax values among three Gobiidae diverged widely. A comparison of field observations and in vitro experiments, revealed the bioaccumulation ratio of BDE99 to be affected by the BDE99 debromination ability of each fish species. This is the first report on classification of BDE99 accumulation ratio by debromination ability and a phylogenetic species comparison based on kinetic parameters for debromination reactions of PBDEs by fish.


Effect of plaque compositions on fractional flow reserve in a fluid-structure interaction analysis.
Coronary artery disease involves the reduction of blood flow to the myocardium due to atherosclerotic plaques. The findings of myocardial ischemia may indicate severe coronary stenosis, but many studies have demonstrated a mismatch between lumen stenosis and fractional flow reserve (FFR). Recently, some clinical studies have found that the composition of atherosclerotic plaques may be a potential missing link between stenosis and ischemia. To investigate the relationship between myocardial ischemia and plaque composition, we have developed and adopted a new fluid-structure interaction (FSI) patient-specific coronary plaque model, based on computed tomography angiography data, to assess the impact on FFR as a biomechanical indicator of ischemia. A total of 180 analyses have been performed in 3D-FSI coronary artery disease models based on plaque compositions, plaque location, and stenosis degree. Hemodynamic analysis of simulation results and comparisons with other methods has been conducted to validate our models. Our results have successfully verified that the different compositions of plaques have resulted in differences in the calculated FFR. The mean FFR values with lipid plaques are [Formula: see text] as compared to the mean FFR values in lesions with fibrous plaques [Formula: see text] and calcified plaques [Formula: see text]. Besides, FFR differences between the three different plaque compositions have been shown to increase as the diameter stenosis increased. Plaque composition affects vascular stiffness and vascular dilation ability, and thereby affects the stenosis degree, resulting in abnormal FFR leading to myocardial ischemia. This interrelationship can help to diagnose the cause of high-risk coronary artery disease, leading to myocardial ischemia.


Modifying Pavlovian-to-instrumental transfer by approach avoidance training in healthy subjects: a proof of concept study.
The modulation of instrumental action by conditioned Pavlovian cues is hypothesized to play a role in the emergence and maintenance of maladaptive behavior. The Pavlovian to Instrumental transfer task (PIT) is designed to examine the magnitude of the influence of cues on behavior and we aim to manipulate the motivational value of Pavlovian cues to reduce their effect on instrumental responding. To this end, we utilized a joystick-based modification of approach and avoidance propensities that has shown success in clinical populations. To examine changes in PIT, we subjected 35 healthy participants to a series of experimental procedures: (1) Instrumental training was followed by (2) Pavlovian conditioning of neutral stimuli that were associated with monetary reward or loss. (3) In a subsequent joystick task, approach and avoidance tendencies toward conditioned cues were assessed. (4) In a transfer test, the PIT effect as the impact of conditioned cues on instrumental behavior was measured. (5) The explicit knowledge of cue-reward contingencies was assessed in a forced-choice phase. (6, 7) systematic joystick training was followed by a posttest (8) the transfer task and forced-choice test were repeated. We found no effect of training on approach-avoidance propensities in the context of this proof of concept study. A higher response rate towards negative stimuli during PIT after systematic training compared to sham training was seen. On the other hand, we saw an increased PIT effect after sham training. These results contribute to the understanding of the strength of the influence of cues on instrumental behavior. Our findings further stress the importance of context, instructions and operationalization of instrumental behavior in the framework of transfer effects.


Retrograde aortic dissection during cardiopulmonary bypass: "nonoperative" management.
Seven patients are reported in whom retrograde aortic dissection occurred, 2 during valve replacement and 5 during coronary artery bypass, among 770 patients perfused through the common femoral artery. Successful management included : (1) immediate cessation of cardiopulmonary bypass; (2) removal of the arterial cannula and its replacement in the ascending aorta, usually through both lumens of the dissection; (3) completion of the operation by suturing the proximal ends of saphenous vein grafts to both lumens of the dissection in the ascending aorta; and (4) no treatment of the dissection itself. One patient died of other causes 30 days postoperatively. Follow-up from 2 to 3 1/2 years in 6 long-term survivors has revealed no complications related to the dissection. Saphenous vein graft function is apparently satisfactory.


Fournier's gangrene in hypersensitivity vasculitis.
Fournier's gangrene in IgE positive hypersensitivity vasculitis demands concurrent high dose immunosuppression, radical surgery and intensive treatment of septic sequelae. Even extended autologous skin grafting is possible with immunosuppression. A case of fulminant necrotizing infection of the genitalia, perineum and abdominal wall during the acute generalization phase of IgE positive hypersensitivity vasculitis is described. Apart from the radical surgical approach, medical treatment demands a different strategy than in classical Fournier's gangrene. The favorable outcome in a 21-year-old man after several months of intensive care could be realized only by close cooperation of internal specialists, urologists and plastic surgeons.


Isovaline, a rare amino acid, has anticonvulsant properties in two in vitro hippocampal seizure models by increasing interneuronal activity.
We investigated whether RS-isovaline, a unique amino acid found in carbonaceous meteorites and presumed extraterrestrial, has anticonvulsant properties in rat hippocampal slices in vitro. Extracellular recordings were obtained in the rat hippocampal CA1 pyramidal layer in two in vitro seizure models: perfusion of low (0.25 mm) Mg(2+) and high (5 mm) K(+) (LM/HK), or 100 μm 4-aminopyridine (4-AP). To investigate the underlying mechanisms of isovaline action, whole-cell recordings were obtained from CA1 pyramidal neurons and stratum oriens interneurons during 4-AP blockade of K(+) channels. Perfusion of LM/HK produced seizure-like events (SLEs) or stimulus-evoked primary afterdischarges (PADs) with amplitudes of 0.9 ± 0.1 mV lasting 80 ± 14 s. Application of isovaline (250 μm) for 20-30 min abolished SLEs and PADs or attenuated seizure amplitude and duration by 57.0 ± 9.0% and 57.0 ± 12.0%, respectively. Similar effects were seen with isovaline in the 4-AP seizure model. Isovaline alone increased interneuronal spontaneous spiking from 0.9 ± 0.3 to 3.2 ± 0.9 Hz, increased input resistance by 21.6 ± 8.1%, and depolarized the resting membrane potential by 8.0 ± 1.5 mV; no changes in the firing or electrical properties of pyramidal neurons were observed. Coapplication of 4-AP and isovaline increased interneuronal spontaneous spiking from 1.0 ± 0.6 to 2.6 ± 0.8 Hz, whereas pyramidal neuronal spiking activity decreased from 0.6 ± 0.4 to 0.2 ± 0.1 Hz. Isovaline exhibited anticonvulsant properties in two hippocampal seizure models. This may lead to the development of a new class of anticonvulsants based on an unusual mechanism of action of this presumed extraterrestrial amino acid.


Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 17. Photosensitizing properties and cellular effects of ZnII octacationic and ZnII/PtII hexacationic macrocycles in aqueous media: Perspectives of multimodal anticancer potentialities.
The photosensitizing activity of two multiply charged porphyrazine derivatives, i.e. the ZnII species [(CH3)8LZn]8+ and the ZnII/PtII heterobimetallic complex [(PtCl2)(CH3)6LZn]6+ (neutralized byI- ions; L=tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazinato dianion) has been examined in the water medium in the presence of SDS under experimental conditions in which the two species are present exclusively in their monomeric form. The determined quantum yield values (ΦΔ) for both complexes, of interest in photodynamic therapy (PDT), are 2.3-2.5 higher than that of the aluminium compound PcAlSmix (Photosens®) used as the reference standard, an encouraging result for the application of the two cationic species as anticancer curative drugs in PDT. Investigation was also extended to explore the cellular effects on the melanoma C8161 and the oral squamous carcinoma CA-1 cell lines like viability, cellular uptake, cell death modality and cell cycle distribution experiments. The IC50 values for the ZnII and ZnII/PtII cations are consistently lower than those of the reference standard, thus the degree of efficiency as anticancer agents being in the order octacation≫hexacation>PcAlSmix. A large prevalence of apoptosis with respect to necrosis is observed for both charged complexes. Thus, all achieved information from photoactivity and in vitro tests in water solution further enhance perspectives for the application of the two ZnII cation [(CH3)8LZn]8+ and the related ZnII/PtII analog [(PtCl2)(CH3)6LZn]6+ as potential bi-multimodal anticancer drugs.


Ilizarov callus distraction produces systemic bone cell mitogens.
We tested the hypothesis that the application of strain during callus distraction induces systemic osteoblast stimulating factors that enhance osteoblast activity both locally and systemically. To study the systemic occurence of strain-induced osteoblast stimulating factor during callus distraction, we investigated the mitogenic capacity of sera from 12 patients who had undergone callus distraction on the osteoblastic cell line SaOS-2 (part I). Serum samples from six patients who had undergone rigidly fixed high tibial osteotomy (i.e., without distraction) served as controls. The sera were assayed for platelet-derived growth factor and transforming growth factor-beta. In part II of the study, the in vitro effects of mechanical strain were investigated in a simplified model by cyclic stimulation of osteoblast cultures isolated from cortical bone explants from the same patients; a specially developed apparatus was used for cell-stretching. Sera taken during the third to fourth week of callus distraction demonstrated a significant increase in proliferation of SaOS-2 cells (p < 0.005). In contrast, sera from patients who had had an osteotomy failed to induce or decreased the mitogenic capacity of SaOS-2 cells. The concentration of platelet-derived growth factor increased significantly (p < 0.01) in sera from both the patients who had undergone callus distraction and the controls who had had osteotomy. However, the level of transforming growth factor-beta was increased (p < 0.05) in the sera from the patients who had distraction (sera that stimulated proliferation of SaOS-2 cells), but the level was not increased in the sera from patients who had osteotomy.(ABSTRACT TRUNCATED AT 250 WORDS)


Chemokines as organizers of primary and secondary lymphoid organs.
Lymphoid organs represent highly specialized tissues enabling the development and activation of B and T lymphocytes. Contact between lymphoid and parenchymal cells in bone marrow and thymus is a prerequisite for proper development of B and T cells, respectively, while secondary lymphoid organs, such as spleen and lymph nodes are the places where B and T cells get into contact with antigen presenting cells in order to initiate an adaptive immune response. Recent evidence suggests that few constitutively produced chemokines are essentially required to allow for the correct positioning and interaction of lymphoid and non-lymphoid cells thus creating microenvironments for efficient development and activation of the immune system at multiple stages.


Development of a sensitive gene expression reporter system and an inducible promoter-repressor system for Clostridium acetobutylicum.
A sensitive gene expression reporter system was developed for Clostridium acetobutylicum ATCC 824 by using a customized gusA expression cassette. In discontinuous cultures, time course profiles of beta-glucuronidase specific activity reflected adequately in vivo dynamic up- and down-regulation of acidogenesis- and/or solventogenesis-associated promoter expression in C. acetobutylicum. Furthermore, a new inducible gene expression system was developed in C. acetobutylicum, based on the Staphylococcus xylosus xylose operon promoter-repressor regulatory system.


Proteinase yscD. Purification and characterization of a new yeast peptidase.
A newly recognized peptidase, designated proteinase yscD, was purified from the yeast Saccharomyces cerevisiae. The enzyme cleaves the Pro-Phe bond of the synthetic peptide substrate Bz-Pro-Phe-Arg-4-nitroanilide and the Ala-Ala bond of Ac-Ala-Ala-Pro-Ala-4-nitroanilide, Ac-Ala-Ala-Pro-Phe-4-nitroanilide, and MeO-Suc-Ala-Ala-Pro-Met-4-nitroanilide with high efficiency (Bz-, Ac-, and MeO-Suc are defined as benzoyl, acetyl, and methoxy-succinyl, respectively). [3H]Methylcasein does not serve as a substrate. Optimum pH for cleavage of Bz-Pro-Phe-Arg-4-nitroanilide is in the range of 6.5 to 7; for Ac-Ala-Ala-Pro-Ala-4-nitroanilide the range is between 5.75 and 6. For MeO-Suc-Ala-Ala-Pro-Met-4-nitroanilide the pH optimum was found to be 5.5. The purified enzyme has an apparent Stokes radius of Rs = 37.9 A as judged by gel chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates a molecular weight of approximately 83,000 for the enzyme. Mercurials and EDTA were found to be potent inhibitors of proteinase yscD activity.


[Towards a better assessment of child and adolescent mental health status. Polish version of strengths and difficulties questionnaire. Experiences from two population studies].
There is a need for a brief validated instrument, that could be used in Poland in population studies to monitor mental health problems in children and adolescents. Goodman's Strengths and Difficulties Questionnaire (SDQ) has been used in epidemiological studies in many countries, to our knowledge, not yet in Poland. SDQ has 25 items and a supplement on the impact of these difficulties for the child and the family. Scoring system includes one total score generated on the basis of 20 main items, and partial scores for four subscales concerning: emotional symptoms, conduct problems, hyperactivity and peer problems. THE AIM of this study was: to evaluate the Polish version of SDQ on the basis of two large population studies, to assess the prevalence of mental health problems in youth and to discuss existing norms. For the first time self-reported and proxy (parents) SDQ was used in Poland in a national mail survey conducted in 2003 within the KIDSCREEN project. In the present study a subsample of 774 children in average age 14.3 years was considered. For the second time, an improved self-reported version of SDQ was used in a school-based survey carried out in 2006 within HBSC project on the representative sample of 5270 pupils in comparable average age of 14.0 years. Factor analysis, performed on the basis of the second survey, suggested a four-component structure of SDQ-20, however it was different than in the original scale. Only peer subscale was fully replicated. Emotional subscale could include in Polish version more than five original items, while hyperactivity and conduct subscales had less than five items with high enough factor loadings. The internal consistency of the full questionnaire was much better than for four subscales. Distributions of total SDQ scores were similar in both surveys. According to the HBSC study, borderline or noticeable scores were reported by 17.7% young respondents, according to previous KIDSCREEN study by 14.9% adolescents and 18.8% parents as proxy respondents. SDQ is a promising instrument for monitoring mental health problems in children and adolescents, however the Polish adaptation is still not as reliable as could be expected. To complete the validation process, especially convergent validity in comparison to other instruments measuring the same concept should be conducted, as well as discriminative validity studies in clinical settings.


Chronic and Recurrent Sinusitis in Children, as Manifestation of Immune Dysfunction and Atopic Background.
Rhinosinusitis in children, as in adults, can be classified by duration (acute, recurrent, and chronic) and by cause (viral, bacterial, and inflammatory) and needs to be treated accordingly after careful investigation which include through clinical history, laboratory tests, and, if necessary, nasal endoscopy and imaging studies.


Dental cleaning behavior and related factors among hemodialysis patients in the West of Iran: A cross-sectional study.
Oral health-related behaviors in hemodialysis patients are reduced, potentially leading to adverse consequences. The aim of the present study was to evaluate dental cleaning behavior (DCB) and related factors among hemodialysis patients. This cross-sectional study was carried out in Sanandaj city, in the west of Iran in 2022. Using the census method, 115 hemodialysis patients from the dialysis center of Tohid Hospital were recruited. Data were gathered by a three-section questionnaire. The first section included demographic characteristics, the second section involved variables related to the health belief model (HBM), and the third section assessed stages of DCB change based on the trans-theoretical model. Analysis of data was done by assessing frequency, descriptive and inferential statistics such as t test, correlation coefficient, and regression. Only 26.1% of participants reported DCB, defined as tooth brushing at least twice daily; 30.4% were in the precontemplation stage, 26.1% in contemplation, and 17.4% in the preparation stage. Perceived self-efficacy was lower among patients who did not perform DCB. The odds of DCB increased with perceived self-efficacy (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.19-1.92, p < .05), cues to action (OR = 1.63, 95% CI = 1.03-2.55, p < .05), and decreased with perceived barriers (OR = 0.68, 95% CI = 0.47-0.97, p < .01). DCB of patients on hemodialysis requires improvement. Perceived self-efficacy, cues to action, and perceived barriers constructs of the HBM should be considered in interventional programs targeting to increase oral health as well as in future research in the field.