Modulation of ecto-5'-nucleotidase by phospholipids in human umbilical vein endothelial cells (HUVEC).
Ecto-5'-nucleotidase, the major enzyme controlling extracellular adenosine production, can be activated by phospholipids, e.g. lysophosphatidylcholine (LPC). This study examined the structural requirements of phospholipids to evoke this enzyme activation and figured out two new activators of ecto-5'-nucleotidase: platelet activating factor (PAF) and sphingosylphosphorylcholine (SPC). Potential signal transduction pathways including an involvement of protein kinase C and PAF-receptor were evaluated on the model of human umbilical vein endothelial cells (HUVEC). Cells were pre-incubated with 10 microM of various phospholipids including lysophosphatidylcholine, beta-arachidonyl-gamma-palmityl-alpha-phosphatidylcholine, beta,gamma-dipalmityl-alpha-phosphatidyl-choline, beta,gamma-dipalmityl-alpha-phosphatidylethanolamine, beta,gamma-dipalmityl-alpha-phosphatidylserine, gamma-acyl-beta-lyso-alpha-phosphatidylethanolamine, beta-acetyl-gamma-O-hexadecyl-alpha-phosphatidylcholine (platelet activating factor), lysophosphatidylic acid, sphingosine-1-phosphate and sphingosylphosphorylcholine. In the cell supernatant the extracellular dephosphorylation rate of the fluorescent AMP-analogue 1,N6-etheno-5'AMP to 1,N6-etheno-adenosine was measured by HPLC. Out of these ten structurally related phospholipids only lysophosphatidylcholine, sphingosylphosphatidylcholine and platelet activating factor dose-dependently increased the activity of ecto-5'-nucleotidase. Pharmacological blocking experiments revealed that neither the activation of PAF-receptor nor of protein kinase C were important for mediating the activation of ecto-5'-nucleotidase. Thus, using information on the known molecular structures of tested phospholipids, a phosphatidylcholine residue in alpha-position and a short chain length fatty acid esterified in beta-position seem essential for activation of ecto-5'-nucleotidase by glycerophospholipids. Since all tested phospholipids have similar fatty acid chain lengths and residues in alpha-position, they should act similarly on membrane fluidity. It is concluded that the observed effects are not based on changes in membrane fluidity by the added phospholipids, but rather involve a yet to be determined phospholipid-receptor.


Water-soluble Self-assembled {Pd84 }Ac Polyoxopalladate Nano-wheel as a Supramolecular Host.
Polyoxopalladates (POPs) are a class of self-assembling palladium-oxide clusters that span a variety of sizes, shapes and compositions. The largest of this family, {Pd84 }Ac , is constructed from 14 building units of {Pd6 } and lined on the inner and outer torus by 28 acetate ligands. Due to its high water solubility, large hydrophobic cavity and distinct 1 H NMR fingerprint {Pd84 }Ac is an ideal molecule for exploring supramolecular behaviour with small organic molecules in aqueous media. Molecular visualisation studies highlighted potential binding sites between {Pd84 }Ac and these species. Nuclear Magnetic Resonance (NMR) techniques, including 1 H NMR, 1 H Diffusion Ordered Spectroscopy (DOSY) and Nuclear Overhauser Spectroscopy (NOESY), were employed to study the supramolecular chemistry of this system. Here, we provide conclusive evidence that {Pd84 }Ac forms a 1 : 7 host-guest complex with benzyl viologen (BV2+ ) in aqueous solution.


Complex karyotypes in a series of pediatric osteosarcomas.
Cytogenetic analysis was performed on eight osteosarcomas, including six primary untreated biopsies, one second primary in a patient with a history of undifferentiated sarcoma, and one recurrent lung metastasis. Two primary tumors and the peripheral blood lymphocytes from all eight patients had normal karyotypes. Six of the tumors demonstrated extremely complex karyotypes, with modal numbers in the hypodiploid, triploid, and hypertetraploid ranges. The predominant types of structural abnormalities observed were nonreciprocal translocations and deletions, which differed between cases. A consistent loss of normal chromosome 13 homologs was evident in the six cases with abnormal tumor karyotypes; however, chromosomal loss was not restricted to #13. Molecular studies of osteosarcoma, especially with regard to the retinoblastoma locus on chromosome 13, should take into consideration the complex cytogenetic changes seen in this tumor.


Rat testis during 2,5-hexanedione intoxication and recovery. II. Dynamics of pyrrole reactivity, tubulin content, and microtubule assembly.
Charles River CD rats (200 g) were intoxicated with 1% 2,5-hexanedione (2,5-HD) in the drinking water for 5 weeks followed by a 17-week recovery period. Pyrrole reactivity of testis proteins increased early during intoxication and then returned toward normal during recovery. Testis tubulin content first increased as germ cells were lost and then fell over time while atrophy was maintained. Purified testis tubulin demonstrated a decreased nucleation time for microtubule assembly at 2 weeks, maintained this alteration throughout intoxication, and then returned to normal assembly kinetics during recovery. The assembly abnormality was accompanied by the presence of a unique crosslinked tubulin species. These findings support the hypothesis that alterations in Sertoli cell microtubules result in germ cell loss following 2,5-HD exposure.


Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway.
To identify the significantly altered circRNAs and mRNAs in thyroid cancer, investigate their target miRNAs and determine their biological functions. The differentially expressed circRNAs, mRNAs and pathways in thyroid cancer were identified by microarray analysis and gene set enrichment analysis (GSEA). The correlative circRNAs and mRNAs were found out through Pearson correlative analysis. The common target miRNAs of circNEK6 and FZD8 related to thyroid cancer was screened out through Targetscan, miRanda and HMDD analysis. The mRNA and protein expressions in thyroid cancer tissues and cells were detected by qRT-PCR and western blot. CircRNA was confirmed by the RNase R digestion and nucleic acid electrophoresis. The target relationships were verified by the dual luciferase reporter assay. Cell viability, invasion and apoptosis were determined by MTT assay, Transwell assay and flow cytometry, respectively. CircNEK6 and FZD8 were significantly up-regulated in thyroid cancer, with strong correlations. The Wnt signaling pathway was activated in thyroid cancer. MiR-370-3p was the common target miRNA of circNEK6 and FZD8, and it was down-regulated in thyroid cancer. Overexpression of circNEK6 and FZD8 could promote the growth and invasion of thyroid cancer cells, while up-regulation of miR-370-3p could suppress thyroid cancer progression and inhibit the Wnt signaling pathway. MiR-370-3p's effect on thyroid cancer cells could be rescued by circNEK6 or FZD8. CircNEK6 promoted the progression of thyroid cancer through up-regulating FZD8 and activating Wnt signaling pathway by targeting miR-370-3p.


Validity and reliability of the Internalized Stigma of Smoking Inventory: An exploration of shame, isolation, and discrimination in smokers with mental health diagnoses.
De-normalization of smoking as a public health strategy may create shame and isolation in vulnerable groups unable to quit. To examine the nature and impact of smoking stigma, we developed the Internalized Stigma of Smoking Inventory (ISSI), tested its validity and reliability, and explored factors that may contribute to smoking stigma. We evaluated the ISSI in a sample of smokers with mental health diagnoses (N = 956), using exploratory and confirmatory factor analysis, and assessed construct validity. Results reduced the ISSI to eight items with three subscales: smoking self-stigma related to shame, felt stigma related to social isolation, and discrimination experiences. Discrimination was the most commonly endorsed of the three subscales. A multivariate generalized linear model predicted 21-30% of the variance in the smoking stigma subscales. Self-stigma was greatest among those intending to quit; felt stigma was highest among those experiencing stigma in other domains, namely ethnicity and mental illness-based; and smoking-related discrimination was highest among women, Caucasians, and those with more education. Smoking stigma may compound stigma experiences in other areas. Aspects of smoking stigma in the domains of shame, isolation, and discrimination were related to modeled stigma responses, particularly readiness to quit and cigarette addiction, and were found to be more salient for groups where tobacco use is least prevalent. The ISSI measure is useful for quantifying smoking-related stigma in multiple domains.


Cerebellar hypoplasia in children with the carbohydrate-deficient glycoprotein syndrome.
We describe seven children with the carbohydrate-deficient glycoprotein syndrome, an autosomal recessive inborn error of protein glycosylation characterised by failure to thrive, neurological dysfunction and a unique pattern of physical abnormalities. Neuro-radiological investigations revealed cerebellar hypoplasia in all seven children. Two children also developed supratentorial atrophy following episodes of neurological deterioration.


Alkaline polyol pulping and enzymatic hydrolysis of softwood: effect of pulping severity and pulp properties on cellulase activity and overall sugar yield.
The saccharification of softwood using alkaline polyol pulping (AlkaPolP) and enzymatic hydrolysis was investigated. It will be demonstrated that the AlkaPolP process yields high quality pulps which can easily be hydrolyzed by cellulases. Temperature (180-230°C) and duration (15-60 min) of the alkaline glycerol pulping, expressed as pulping severity R0, were varied to find optimum reaction conditions. The obtained pulps were characterized regarding their residual lignin content, kappa number and crystallinity index. Thus, the dependencies of the conversion during enzymatic hydrolysis on severity, pulp composition and pulp characteristics could be observed. In further experiments it was investigated how the enzymatic hydrolysis is affected by pulp drying or by a reduction of enzyme loading. Up to 83% of the initial cellulose in wood and almost 97% of the cellulose in pulp were converted into glucose using cellulases from Trichoderma reesei and β-glucosidase from Aspergillus niger.


Development and validation of a management system and dataset quality assessment tool for the Radiology Common Data Model (R_CDM): A case study in liver disease.
The Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM), a distributed research network, has low clinical data coverage. Radiological data are valuable, but imaging metadata are often incomplete, and a standardized recording format in the OMOP-CDM is lacking. We developed a web-based management system and data quality assessment (RQA) tool for a radiology_CDM (R_CDM) and evaluated the feasibility of clinically applying this dataset. We designed an R_CDM with Radiology_Occurrence and Radiology_Image tables. This was seamlessly linked to the OMOP-CDM clinical data. We adopted the standardized terminology using the RadLex playbook and mapped 5,753 radiology protocol terms to the OMOP vocabulary. An extract, transform, and load (ETL) process was developed to extract detailed information that was difficult to extract from metadata and to compensate for missing values. Image-based quantification was performed to measure liver surface nodularity (LSN), using customized Wonkwang abdomen and liver total solution (WALTS) software. On a PACS, 368,333,676 DICOM files (1,001,797 cases) were converted to R_CDM chronic liver disease (CLD) data (316,596 MR images, 228 cases; 926,753 CT images, 782 cases) and uploaded to a web-based management system. Acquisition date and resolution were extracted accurately, but other information, such as "contrast administration status" and "photography direction", could not be extracted from the metadata. Using WALTS, 9,609 pre-contrast axial-plane abdominal MR images (197 CLD cases) were assigned LSN scores by METAVIR fibrosis grades, which differed significantly by ANOVA (p < 0.001). The mean RQA score (83.5) indicated good quality. This study developed a web-based system for management of the R_CDM dataset, RQA tool, and constructed a CLD R_CDM dataset, with good quality for clinical application. Our management system and R_CDM CLD dataset would be useful for multicentric and image-based quantification researches.


Variation in digestive performance between geographically disjunct populations of Atlantic salmon: countergradient in passage time and digestion rate.
European Atlantic salmon (Salmo salar) populations inhabit rivers from northern Portugal to northern Norway across a wide spectrum of environmental variability. To address whether single physical factors might lead to genetic divergence of isolated populations, we compared the digestive performances total digestibility, relative nitrogen digestibility, passage time, and digestion rate (g dry matter · h-1) - of northern (Scotland) and southern (Asturias, northern Spain) populations at three temperature regimes (5, 12, and 20° C). Total dry matter digestibilities increased directly with temperature but were similar for both populations at each of the three trials. Relative nitrogen digestibility did not differ between populations nor among temperature regimes. In contrast, passage time was significantly longer for low-than for high-latitude fish at both 5 and 20° C. When the percentage of food digested and the passage time were integrated as digestion rates (food digested per unit time), a significant population × temperature interaction consistent with a genotype × environment interaction was detected in addition to the population and temperature effects. This implies that not only is the digestive performance of the high-latitude population higher throughout the range of temperatures examined, but moreover the difference is reinforced at high temperatures, where the digestion rate of high-latitude fish was 1.6 times greater. Taken together, these two results provide preliminary evidence for countergradient variation in digestive rates of salmonids in response to variation in growth opportunity. The data support our previous work on the same two populations showing differences in growth rates, and underlie one of the possible mechnisms leading to more rapid growth of the high-latitude fish when both populations are reared in a common environment.


Implementation method for magneto-acoustic concentration tomography with magnetic induction (MACT-MI) based on the method of moments.
Magneto-acoustic concentration tomography of magnetic nanoparticles with magnetic induction (MACT-MI) is a new imaging technology that combines the advantages of the high sensitivity of magnetic particle imaging and the high resolution of ultrasonic imaging. This technique has broad application prospects in the biomedical and molecular imaging fields. In this study, a reconstruction algorithm based on the method of moments (MoM) is proposed for the MACT-MI inverse problem. Image reconstructions of the acoustic source and superparamagnetic nanoparticle (SPN) concentration were performed using different shape models, and the reconstructed images were analyzed. In addition, the effect of the radius of the tissue region loaded with SPNs on the quality of the reconstructed images was evaluated. The results demonstrated that the new method could reconstruct the SPN concentration distribution well, and a negative correlation existed between the radius of the imaging model and reconstructed image quality. The finding of this research can potentially contribute to the development of MACT-MI in medicine.


Is topical metronidazole effective in seborrheic dermatitis? A double-blind study.
Seborrheic dermatitis is a common, chronic, papulosquamous dermatosis. Although several types of treatment have been developed, repetitive treatment courses are often necessary. To perform a randomized, placebo-controlled, double-blind clinical study with metronidazole 0.75% gel in patients with mild to moderate seborrheic dermatitis of the face. Eighty-four patients (52 males and 32 females) with seborrheic dermatitis were enrolled in the study. Patients were randomly allocated to the application of metronidazole 0.75% gel or placebo to their facial lesions, twice daily for 8 weeks. Patients were scored with regard to the severity of the lesions at the initial evaluation and every 2 weeks for 2 months. All patients were evaluated for a final assessment of improvement at the end of the study. At baseline, both treatment groups were comparable in terms of demographic data and lesion severity score. Seventy-eight patients (48 males and 30 females), 48 (62%) in the metronidazole group and 30 (38%) in the placebo group, completed the study. Two patients in the metronidazole group and four patients in the placebo group left the study. There was no statistically significant difference in the change in the mean severity score between the two groups at the end of the study (P > 0.05). At the final evaluation of the response at 8 weeks, no statistically significant difference was found between the treatment groups (P > 0.05). Metronidazole gel was generally tolerated well during the study. Metronidazole 0.75% gel and placebo show similar efficacy in the treatment of seborrheic dermatitis.


Flow injection with in-line reduction column and conductometric detection for determination of total inorganic nitrogen in soil.
A cost effective flow injection (FI) conductometric system has been developed for determination of total inorganic nitrogen (TIN). The system is aimed for evaluation of nitrogen nutrient in soil for agricultural application. Inorganic nitrogen compounds were extracted from soil according to the standard method by using potassium chloride solution as an extractant, and the extracted solution was then injected into the FI system. Nitrate and nitrite are converted to ammonium ion by an in-line reduction column packed with a Devarda's alloy. A gas diffusion unit was incorporated into the FI system to separate ammonium ion from other ions in a donor stream by forming ammonia gas that can diffuse through a PTFE membrane to re-dissolve in an acceptor stream. Conductance of the acceptor stream was directly proportional to ammonium ion concentration. Various parameters affecting reduction efficiency of the column, e.g., column diameter, column packing procedure, and column length was investigated and optimized. A linear calibration graph in the range of 2.00-60.00 mg L(-1) N-NH4(+) (y=0.123x+0.039, R(2) =0.997) was obtained with a limit of detection of 0.47 mg L(-1). Sample throughput of 20 samples h(-1) was achieved. The result of developed method was correlated with total Kjeldahl nitrogen (TKN) obtained from the Kjeldahl digestion method. The proposed method could be used as an alternative method to the Kjeldahl method for determination of TIN in soil.


Disposition and toxicity of methylcyclopentadienyl manganese tricarbonyl in the rat.
The disposition and toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT) was studied in Sprague-Dawley rats after subcutaneous administration at a dose of 4 mg/kg. Blood, lung, liver and kidney Mn levels were increased between 1.5 and 96 h after MMT injection, with peak organ levels occurring at 3-6 h. At this time the MMT-derived Mn concentration in lung, liver and kidney averaged 13-, 4- and 4-fold higher, respectively, than in the blood, indicating the accumulation and retention of MMT (or metabolite) in these tissues. Maximal pulmonary toxicity, as assessed by pulmonary lavage protein levels, occurred 24-48 h after injection. Plasma urea and sorbitol dehydrogenase levels were not increased at any time after MMT, suggesting minimal or no hepatic or renal injury. That maximal pulmonary toxicity occurred after peak Mn accumulation, and that the organ-specific toxicity of MMT correlated with its accumulation and retention, suggests a causal relationship between tissue Mn accumulation and MMT-induced toxicity.


Experimental study on the impact of soiling on the modules temperature and performance of two different PV technologies under hot arid climate.
In this paper we conducted an experimental study to evaluate the impact of soiling on the temperature and electricity production of two photovoltaic technologies (Poly-Si and CdTe) under a hot semi-arid climate of Morocco. For this purpose, two modules -from each technology-were exposed for one year where one is cleaned every day and the other is left to accumulate soiling on its surface. In parallel, the electrical parameters, the weather data and the modules temperature were monitored using high precision instruments. Results show that the Poly-Si technology is highly affected by soiling in comparison to the CdTe where the measured daily Soiling ratio (SR) can reach 0.70 and 0.73 respectively. This values lead to a drop on the energy production of 15% for the Poly-Si and 13%. Regarding the modules temperature (Tm) results show that soiling has an impact on increasing the temperature for both technologies, but the Poly-Si module is more affected than the CdTe one, where the daily average temperature difference between the clean and the soiled modules is around 1.5 °C and 1.3 °C for both technologies, respectively.


Charged hadron fragmentation functions from collider data: NNPDF Collaboration.
We present NNFF1.1h, a new determination of unidentified charged-hadron fragmentation functions (FFs) and their uncertainties. Experimental measurements of transverse-momentum distributions for charged-hadron production in proton-(anti)proton collisions at the Tevatron and at the LHC are used to constrain a set of FFs originally determined from electron-positron annihilation data. Our analysis is performed at next-to-leading order in perturbative quantum chromodynamics. We find that the hadron-collider data is consistent with the electron-positron data and that it significantly constrains the gluon FF. We verify the reliability of our results upon our choice of the kinematic cut in the hadron transverse momentum applied to the hadron-collider data and their consistency with NNFF1.0, our previous determination of the FFs of charged pions, kaons, and protons/antiprotons.


Early life fluoxetine treatment causes long-term lean phenotype in skeletal muscle of rats exposed to maternal lard-based high-fat diet.
There is a concern about early life exposure to Selective Serotonin Reuptake Inhibitors (SSRI) in child development and motor system maturation. Little is known, however, about the interaction of environmental factors, such as maternal nutrition, associated with early exposure to SSRI. The increased maternal consumption of high-fat diets is worrisome and affects serotonin system development with repercussions in body phenotype. This study aimed to assess the short- and long-term effects of neonatal fluoxetine treatment on the body and skeletal muscle phenotype of rats exposed to a maternal lard-based high-fat (H) diet during the perinatal period. A maternal lard-based high-fat diet causes reduced birth weight, a short-term reduction in type IIA fibers in the soleus muscle, and in type IIB fibers in the Extensor Digitorum Longus (EDL) muscle, reducing Lactate Dehydrogenase (LDH) activity in both muscles. In the long-term, the soleus showed reduced muscle weight, smaller area and perimeter of muscle fibers, while the EDL muscle showed reduced Citrate Synthase (CS) activity in offspring from the rats on the maternal lard-based high-fat diet. Early-life exposure to fluoxetine reduced body weight and growth and reduced soleus weight and enzymatic activity in young rats. Exposure to neonatal fluoxetine in adult rats caused a decreased body mass index, less food intake, and reduced muscle weight with reduced CS and LDH activity. Neonatal fluoxetine in young rats exposed to a maternal lard-based high-fat diet caused reduced body weight and growth, reduced soleus weight as well as area and perimeter of type I muscle fibers. In adulthood, there was a reduction in food intake, increased proportion of IIA type fibers, reduced area and perimeter of type IIB, and reduction in levels of CS activity in EDL muscle. Neonatal fluoxetine treatment in rats exposed to a maternal lard-based, high-fat diet induces a reduction in muscle weight, an increase in the proportion of oxidative fibers and greater oxidative enzymatic activity in adulthood.


Child abuse disposition: concurrences and differences between a hospital team, child protection agency and the court.
Ninety-six children admitted to a pediatric ward for maltreatment are described statistically using variables characterizing the child, the family and the type of abuse. Recommendations of the hospital's child protection team in 81 cases are compared to those of the county childrens Services Board and the court. Multiple regression analysis is used to identify which variables influenced the decisions of these three agencies.


Characteristics of breast cancers detected by screening mammography in Taiwan: a single institute's experience.
Breast cancer is the most common female malignancy in the world. Nearly ninety percent of screening-detected breast cancers were diagnosed with earlier stages of 0 to II in Taiwan. It's widely acknowledged that mammography screening of breast cancer can achieve the goal of early diagnosis and treatment in terms of preventive task while neglected interval cancers are associated with unfavorable tumor characteristics and worse outcomes. The purpose of this study was to explore the characteristics of screening-detected breast cancers in Taiwan. Both screening and diagnostic mammography examinations with accompanied BI-RADS (breast imaging-reporting and data system) classification were extracted from the health information system and linked to cancer registry in Taiwan. Enrolled population included those attending their first mammography between 2012 and 2016, excluding subjects with previous breast cancer, or with missing or incomplete data. We compared treatment outcomes between breast cancers with either initial screening or diagnostic mammography (control group), and investigated the compositions of breast cancers detected by screening mammography through direct chart reviews. A total of 84,246 screening and 61,230 diagnostic mammography sessions were performed from 2010 to 2020. More positive results (BI-RADS 0, 3, 4 and 5) were observed for those attending the first diagnostic than the first screening mammography (43.58% versus 16.12%, p < 0.001). Earlier stages (0 and I) distribution (92% versus 81%, p < 0.0001), better survivorship (overall survival: 96.91% versus 92.17%, p = 0.007) and a lower HER2 (human epidermal growth factor receptor II) positive status and lower tumor grade were noted in breast cancers with initial screening rather than diagnostic mammography. Among 26,103 mammography screening invitees between 2012 and 2016, 325 breast cancers were ascertained from cancer registry. Of these, 234 had one, 72 had two and 19 had three episodes of mammography before cancer diagnosis. Extensive chart reviews revealed that women with and without breast symptoms constituted 29.9 and 70.1% of the 325 screening-detected breast cancers, with the latter further divided into false negative results (interval cancer), diagnosed at the first mammography, diagnostic at the secondary or subsequent mammography and those with a delayed biopsy or confirmatory imaging constituted (5.2, 47, 10.5 and 7.4%). Screening-detected breast cancers were a mixture of women with and without symptoms, those with a false negative result, true negative results with cancer detected at subsequent mammography and non-adherers. Despite this, efficacy of mammography screening was ascertained in Taiwan from this study. To further enhance earlier detection and decrease false negativity, the impact of repeated mammography, and additional sonography for symptomatic women, compliance following a positive screening mammography should not be overemphasized.


Predicting in-hospital outcomes of patients with acute kidney injury.
Acute kidney injury (AKI) is prevalent and a leading cause of in-hospital death worldwide. Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. We develop a deep learning model based on a nationwide multicenter cooperative network across China that includes 7,084,339 hospitalized patients, to dynamically predict the risk of in-hospital death (primary outcome) and dialysis (secondary outcome) for patients who developed AKI during hospitalization. A total of 137,084 eligible patients with AKI constitute the analysis set. In the derivation cohort, the area under the receiver operator curve (AUROC) for 24-h, 48-h, 72-h, and 7-day death are 95·05%, 94·23%, 93·53%, and 93·09%, respectively. For dialysis outcome, the AUROC of each time span are 88·32%, 83·31%, 83·20%, and 77·99%, respectively. The predictive performance is consistent in both internal and external validation cohorts. The model can predict important outcomes of patients with AKI, which could be helpful for the early management of AKI.


First report on interferon related developmental regulator-1 from Macrobrachium rosenbergii: bioinformatic analysis and gene expression.
This study reports the first full length gene of interferon related developmental regulator-1 (designated as MrIRDR-1), identified from the transcriptome of Macrobrachium rosenbergii. The complete gene sequence of the MrIRDR-1 is 2459 base pair long with an open reading frame of 1308 base pairs and encoding a predicted protein of 436 amino acids with a calculated molecular mass of 48 kDa. The MrIRDR-1 protein contains a long interferon related developmental regulator super family domain between 30 and 330. The mRNA expressions of MrIRDR-1 in healthy and the infectious hypodermal and hematopoietic necrosis virus (IHHNV) infected M. rosenbergii were examined using qRT-PCR. The MrIRDR-1 is highly expressed in hepatopancreas along with all other tissues (walking leg, gills, muscle, haemocyte, pleopods, brain, stomach, intestine and eye stalk). After IHHNV infection, the expression is highly upregulated in hepatopancreas. This result indicates an important role of MrIRDR-1 in prawn defense system.


Polymerase iota (POLI) confers radioresistance of esophageal squamous cell carcinoma by regulating RAD51 stability and facilitating homologous recombination.
Radiotherapy resistance is an important and urgent challenge in the clinical management of esophageal squamous carcinoma (ESCC). However, the factors mediating the ESCC resistance to radiotherapy and its underlying molecular mechanisms are not fully clarified. Our previous studies have demonstrated the critical role of DNA polymerase iota (POLI) in ESCC development and progression, here, we aimed to investigate the involvement of POLI in ESCC radiotherapy resistance and elucidate the underlying molecular mechanism. We found that highly expressed POLI was correlated with shorter overall survival of ESCC patients received radiotherapy. Down-regulation of POLI sensitized ESCC to IR, prolonged γH2AX foci in nuclei and comet tails after IR. HR but not NHEJ repair is inhibited in POLI-deficient ESCC cells. POLI stabilizes RAD51 protein via competitively binding with and blocking the interaction between RAD51 and E3 ligase XIAP and XIAP-mediated ubiquitination. Furthermore, loss of POLI leads to the activation of GAS signaling. Our findings provide novel insight into the role of POLI in the development of radioresistance mediated by stabilizing RAD51 protein in ESCC.


Autonomic markers of extubation readiness in premature infants.
In premature infants, extubation failure is common and difficult to predict. Heart rate variability (HRV) is a marker of autonomic tone. Our aim is to test the hypothesis that autonomic impairment is associated with extubation readiness. Retrospective study of 89 infants <28 weeks. HRV metrics 24 h prior to extubation were compared for those with and without extubation success within 72 h. Receiver-operating curve analysis was conducted to determine the predictive ability of each metric, and a predictive model was created. Seventy-three percent were successfully extubated. The success group had significantly lower oxygen requirement, higher sympathetic HRV metrics, and a lower parasympathetic HRV metric. α1 (measure of autocorrelation, related to sympathetic tone) was the best predictor of success-area under the curve (AUC) of .73 (p = 0.001), and incorporated into a predictive model had an AUC of 0.81 (p < 0.0001)-sensitivity of 81% and specificity of 78%. Extubation success is associated with HRV. We show an autonomic imbalance with low sympathetic and elevated parasympathetic tone in those who failed. α1, a marker of sympathetic tone, was noted to be the best predictor of extubation success especially when incorporated into a clinical model. This article depicts autonomic markers predictive of extubation success. We depict an autonomic imbalance in those who fail extubation with heightened parasympathetic and blunted sympathetic signal. We describe a predictive model for extubation success with a sensitivity of 81% and specificity of 78%.


The Effect of Melatonin on Analgesia, Anxiety, and Intraocular Pressure (IOP) in Cataract Surgery Under Topical Anesthesia.
This study investigated the effect of oral melatonin as a premedication before cataract surgery on pain score, anxiety, surgical conditions, and intraocular pressure (IOP) during cataract surgery with phacoemulsification under topical anesthesia. This randomized, double-blind prospective study was conducted among 120 patients aged 50 to 80. Patients were randomly assigned to receive either sublingual melatonin 3 mg or placebo 60 min before surgery. Verbal anxiety and pain scores, heart rate, systolic and diastolic blood pressure, intraocular pressure, and quality of surgical conditions were recorded. The results were analyzed using SPSS 23 software, and statistical analysis consisted of χ2 test and t-test, and a P value less than .05 was considered significant. There was a significant difference between the two groups regarding pain after the surgery before being discharged from the recovery room. The mean pain score in the melatonin group was lower than the placebo group in T4 (in the postoperative ward) (P < .05). The anxiety score of patients was lower in the melatonin group in T3 and T4 (during surgery and in the postoperative ward, respectively) (P < .05). IOP was significantly lower in the case group at the end of the surgery after receiving premedication (P = .021). This study showed that 3 mg Sublingual melatonin premedication for patients undergoing cataract surgery under topical anesthesia reduced patients' anxiety scores, pain score, and IOP.


Diagnostic accuracy of Gram staining when predicting staphylococcal hospital-acquired pneumonia and ventilator-associated pneumonia: a systematic review and meta-analysis.
There is no clear guidance on empirical antibiotic coverage against Staphylococcus aureus for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). To evaluate whether the presence of clusters of Gram-positive cocci in Gram staining of respiratory samples predicts S. aureus as HAP/VAP pathogen. Data sources were MEDLINE, PubMed, Embase, Scielo, CINAHL and Scopus, from inception to 15/07/2017 (update on 31/10/2019), and original data from a single-centre database (PROSPERO: CRD42017072138). We included studies reporting the diagnostic accuracy of a Gram-staining evaluation suggestive of Staphylococcus compared with a positive culture for S. aureus in any type of lower respiratory tract sample. Participants were adult patients with HAP/VAP. The index test was morphological evaluation of Gram staining of respiratory samples. We followed PRISMA guidelines and assessed risk of bias and applicability with the QUADAS-2 tool. We conducted a meta-analysis using a bivariate random effects model. We selected five studies that included only VAP and data from a single-centre database including VAP and HAP. We pooled six studies for VAP and analysed 1665 respiratory samples. Pooled sensitivity was 68% (95%CI 49-83 and specificity 95% (95%CI 86-98). The pooled positive likelihood ratio was 12.7 (95%CI 5.1-31.6), negative likelihood ratio 0.34 (95%CI 0.20-0.57), diagnostic odds ratio 38 (95%CI 13-106) and area under the summary receiver operating curve (SROC) 0.91 (95%CI 0.88-0.93). There was great heterogeneity between sensitivity and specificity. In scenarios in which the prevalence of S. aureus was between 5% and 20%, the positive and negative predictive values were 62% (95%CI 47-77) and 95% (95%CI 82-100), respectively. Detection of Gram-positive cocci in clusters in respiratory samples of patients with VAP has the potential to guide risk assessments of S. aureus for more personalized antibiotic coverage. Randomized clinical trials with patient-centred outcomes are needed for strong clinical recommendations.


Great expectations: views of genetic research participants regarding current and future genetic studies.
Recruitment of prior participants in genetic research is one strategy suggested to maximize efficient use of research dollars in gene-environment studies. We explored attitudes toward genetic research participation among people in a case-control genetic epidemiology study of colon cancer, the North Carolina Colorectal Cancer Study (NCCCS). Quantitative and qualitative cross-sectional analysis of 801 NCCCS participants. Participants were "very positive" (63%) or "positive" (32%) about genetic research, and "very likely" (49%) or "somewhat likely" (40%) to participate in future genetic research. Variables significantly associated with feeling "very positive" were white race, more education, nonreligious, hearing "a lot" about genetic research, and two measures of trust in medical research. Except for race and education, the same variables were significantly associated with being "very likely" to participate in future studies. Qualitatively, "good things" for self and family included discovering causes and cures for cancer, and the value of genetic information. Many could not list "bad things"; those who did mentioned anxiety, "knowing too much," losing confidentiality, or abuse of information. Despite very positive attitudes of these participants toward genetic research, there is significant variation based on participant characteristics. These findings should encourage and caution researchers attempting to recruit prior participants into genetic studies.


Three types of noncovalent interactions studied between pyrazine and XF.
Three types noncovalent interactions (type I, II and III) between pyrazine (C4H4N2) and XF (X = F, Cl, Br, and I) have been discovered at the MP2/aug-cc-pVTZ level. TypeI is σ-hole interaction between the positive site on the halogen X of XF and the negative site on one of the pyrazine nitrogens. Type II is counterintuitive σ-hole interaction driven by polarization between the positive site on the halogen X of XF and a portion of the pyrazine ring. Type III is an interaction between the lateral regions of the halogen X of XF and the position of the pyrazine ring. Through comparing the calculated interaction energy, we can know that the type II and type III interactions are weaker than the corresponding type I interactions, and type III interactions are weaker than the corresponding type II interactions in C4H4N2-XF complexes. SAPT analysis shows that the electrostatic energy are the major source of the attraction for the type I (σ-hole) interactions while the type III interactions are mainly dispersion energy. For the type II (counterintuitive σ-hole) interactions in C4H4N2-XF (X = F and Cl) complexes, electrostatic energy are the major source of the attraction, while in C4H4N2-XF (X = Br and I) complexes, the electrostatic term, induction and dispersion play equally important role in the total attractive interaction. NBO analysis, AIM theory, and conceptual DFT are also being utilized.


Comparison of DCE-MRI kinetic parameters and FMISO-PET uptake parameters in head and neck cancer patients.
Tumor hypoxia is a major cause of radiation resistance, often present in various solid tumors. Dynamic [18 F]-fluoromisonidazole (FMISO) PET imaging is able to reliably assess tumor hypoxia. Comprehensive characterization of tumor microenvironment through FMISO-PET and dynamic contrast enhanced (DCE) MR multimodality imaging might be a valuable alternative to the dynamic FMISO-PET acquisition. The aim of this work was to explore the correlation between the FMISO-PET and DCE-MRI kinetic parameters. This study was done on head and neck cancer patients (N = 6), who were imaged dynamically with FMISO-PET and DCE-MRI on the same day. Images were registered and analyzed for kinetics on a voxel basis. FMISO-PET images were analyzed with the two-tissue compartment three rate-constant model. Additionally, tumor-to-muscle ratio (TMR) maps were evaluated. DCE-MRI was analyzed with the extended Tofts model. Voxel-wise Pearson's coefficients were calculated for each patient to assess pairwise parameter correlations. Median correlations between FMISO uptake parameters and DCE-MRI kinetic parameters varied across the parameter pairs in the range from -0.05 to 0.71. The highest median correlation of r = 0.71 was observed for the pair Vb -vp , while the K1 -Ktrans median correlation was r = 0.45. Median correlation coefficients for the K1 -vp and the Ki -Ktrans pairs were r = 0.42 and r = 0.32, respectively. Correlations between FMISO uptake rate parameter Ki and DCE-MRI kinetic parameters varied substantially across the patients, whereas correlations between the FMISO and DCE-MRI vascular parameters were consistently high. Median TMR-K1 and TMR-Ktrans correlations were r = 0.52 and r = 0.46, respectively, but varied substantially across the patients. Based on this clinical evidence, we can conclude that the vascular fraction parameters obtained through DCE-MRI kinetic analysis or FMISO kinetic analysis measure the same biological property, while other kinetic parameters are unrelated. These results might be useful in the design of future clinical trials involving FMISO-PET/DCE-MR multimodality imaging for the assessment of tumor microenvironment.


A case of concomitant perforated acute cholecystitis and pancreatitis.
Introduction. Concomitant cholecystitis and gallstone pancreatitis is an infrequent clinical encounter, reported sparsely in the literature. Concurrent acute cholecystitis and pancreatitis complicated by gall bladder perforation has not been reported before. Presentation of Case. We report a 39-year-old female presenting with concomitant cholecystitis and acute pancreatitis, complicated by gallbladder perforation. Discussion. There is much controversy surrounding the timing of cholecystectomy following gallstone pancreatitis, with the recent literature suggesting that "early" operation is safe. In the current case, gallbladder perforation altered the "routine" management of gallstone pancreatitis and posed as a management dilemma. Conclusion. Clinical judgement dictated timing of operative management and ultimately cholecystectomy was performed safely.


Novel enzymes as reagents.
Enzymes are now used in a wide range of analytical methods, primarily for the measurement of substrates and as labels in immunoassays. Enzymes from microbial sources are becoming the preferred choice because of ease of extraction, catabolic activities and opportunities for enhancing yields. Protein engineering of bacterial enzymes will also play a role in future enzyme design with respect to improvements in specificity, reaction kinetics and stability.


Cytotoxic Flavokawain B Inhibits the Growth and Metastasis of Hepatocellular Carcinoma through UCK2 Modulation of the STAT3/Hif-1α/VEGF Signalling Pathway.
Hepatocellular carcinoma (HCC) is associated with a high mortality rate due to early recurrence and its metastasis features. To this day, effective treatment options for metastatic HCC remain a major challenge to patient treatment. Flavokawain B (FKB) is a naturally occurring chalcone molecule capable of providing effective therapy against this life-threatening disease. This study investigated the anti-metastatic effects of FKB on the growth and development of metastatic HCC. HepG2 cells were used in this study and a neutral red assay was performed to determine the IC50 value of FKB. Cell scratch and exclusion zone assays were performed to assess the rate of cell migration and invasion. Relative mRNA levels of UCK2, STAT3, VEGF and HIF-1α genes were quantified using RT-qPCR. FKB inhibited the proliferation of HepG2 cells at an IC50 value of 28 μM after 72 h of incubation. Its cytotoxic effect was confirmed to induce apoptosis through the phase-contrast inverted microscope. Cell migration and invasion were significantly inhibited at 7, 14, and 28 μM of FKB as compared to untreated cells. The inhibition in the cell migration significantly increased with the increasing concentrations of the bioactive compound. The relative expression levels of the UCK2 gene and its downstream genes, STAT3, VEGF and HIF-1α, were significantly downregulated after 72 h exposure to FKB treatment. Our data suggest that FKB inhibited HepG2 proliferation and further suppressed its metastasis partly by regulating the STAT3/Hif-1α/VEGF signalling pathway. FKB could be a potential alternative and viable strategy against HCC.


Pilot of a digital contact tracing card in a hospital setting in New Zealand, 2020.
Countries are rapidly developing digital contact tracing solutions to augment manual contact tracing. There is limited empirical evidence evaluating these tools. We conducted a feasibility study of a Bluetooth-enabled card with hospital staff in New Zealand (n = 42). We compared the card data against self-report contact surveys and a stronger Bluetooth device. The cards detected substantially more contacts than self-report contact surveys, while the concordance between Bluetooth devices was high, suggesting that the cards detected clinically relevant close contacts. There was high acceptability among participants, suggesting that their integration would be accepted by healthcare staff. As the pandemic shifts, there is a need to rapidly contact trace and conduct informed risk management, particularly in critical settings such as healthcare.


Monoclonal antibody CC3C195, which detects cancer-associated antigens in serum, binds to the human Lea blood group antigen and to its sialylated derivative.
Mouse monoclonal antibody CC3C195, which detects elevated levels of its antigen in sera from many patients with colon and pancreatic cancer, binds with high affinity to the sialylated human Lea blood group antigen NeuAc alpha 2-3Gal beta 1-3 [Fuc alpha 1-4]GlcNac . . . and with lower affinity to the Lea blood group antigen itself.


Improvement in the rate of inadequate pharmaceutical treatment by orthopaedic surgeons for the prevention of a second fracture over the last 10 years.
We have previously reported that the low rate of osteoporosis patients treated with anti-osteoporotic drugs following surgical treatment for the first fragility fractures by orthopaedic surgeons during 3 years from 2000 to 2003 was only 13.1%. Ten years have now passed our previous study, and we hypothesized that the rate of appropriate pharmacologic treatment for the prevention of secondary fractures has improved. We studied 730 osteoporosis patients (102 men and 628 women; average age of 78 years, range 33-102 years) who underwent surgical treatment for fragility fractures, during 3-year period from 2010 to 2012. The 730 cases consisted of 489 hip fractures and 241 distal radius fractures. All patients were admitted and underwent surgical intervention in hospitals. Variables were examined to ascertain whether pharmaceutical treatment was performed after discharge. Based on these data, we compared results for patients in the present study with those from our previous study. The rate of treatment with anti-osteoporosis medication in the present (16.2%) was slightly but significantly improved from that in our previous study (13.1%). The rate of pharmaceutical treatment following hip fractures increased significantly, while that following distal radius fractures showed no significant change. Regarding the categories of anti-osteoporotic drugs prescribed to the patients, the rate of treatment with bisphosphonate as a higher evidenced drug for the prevention of fractures in the present study was significantly higher than that in our previous study. We demonstrated that the rate of pharmacologic treatment by orthopaedic surgeons and the rate of more effective anti-osteoporotic drugs prescribed to the patients following surgical intervention for the first fragility fracture in the present study were improved in comparison with those of 10 years ago.


What the Rheumatologist Is Looking for and What the Radiologist Should Know in Imaging for Rheumatoid Arthritis.
This article outlines what the rheumatologist is looking for and wants to know in the clinical diagnosis and imaging of rheumatoid arthritis, and what the radiologist should know to facilitate this.


Variations in brain gray matter associated with chronic pain.
Variations in brain gray matter volume and density have been reported in association with a variety of disorders characterized by chronic pain, including chronic low back pain, fibromyalgia, and irritable bowel syndrome. Correlation analyses have demonstrated relationships between morphometric and clinical variables. However, conclusions regarding the nature of these relationships are problematic given that currently available data are derived exclusively from cross-sectional studies. Further efforts to determine the relationship between chronic pain and variations in brain morphometry will depend in part on longitudinal studies of patients at various stages of illness, as well as those at risk of the development of chronic pain. Interpretation of findings from morphometric studies also must take into account genetic and experiential factors that recently have been demonstrated to influence brain morphometry and the risk of developing chronic pain.


Group G streptococcal endocarditis: two case reports, a review of the literature and recommendations for treatment.
Two cases of endocarditis caused by a group G streptococcus are reported and the literature on group G streptococcal endocarditis is reviewed. The onset of illness is usually acute and the portal of entry for the organism through the skin. The left side of the heart is mainly involved and in about 50% cases the endocarditis arises on a normal valve. Most patients develop complications, both embolic and cardiac, and the mortality is high (36%). We suggest that patients with proven group G streptococcal endocarditis should be treated with large doses of benzyl penicillin and with an aminoglycoside for not less than 4 weeks. Patients with complications should be referred to a cardiothoracic centre. We should be glad to know details of complications, treatment and outcome in other cases of group G streptococcal endocarditis.


Free Thyroxine Determination in the Emergency Department Is a Predictor of Acute Pancreatitis Evolution.
The aim of this study was to determine the prevalence and type of thyroid hormone levels alterations in patients with acute pancreatitis (AP) and analyze if variations are useful AP progression predictors. Three groups of patients were analyzed: AP patients (n = 90), abdominal pain patients (n = 30), and healthy control subjects (n = 40). Usual blood parameters for AP diagnosis and prognosis, thyroid-stimulating hormone (or thyrotropin), FT4 (free thyroxine), FT3 (free triiodothyronine), and TT3 (total triiodothyronine) levels were analyzed. Thyroid hormone level alterations were detected only within the AP group (41% of total cases), being the reduction in T3 levels the most frequently detected deviation (15.6% of FT3 and 8.3% of TT3 cases). Alterations were not influenced by age or sex. Free thyroxine average values were also significantly higher in the AP group, compared with the healthy control group (P = 0.0005), resulting as independent predictors of both severity and mortality. Mortality in this group was 50%, with deceased patients showing FT4 levels above the reference limit. Our results show that FT4 level determination during the initial clinical evaluation of patients admitted to the emergency service with AP can be included as a severity indicator to help determine the differential care of these cases.


Stomatin-like protein-2 attenuates macrophage pyroptosis and H9c2 cells apoptosis by protecting mitochondrial function.
Myocytes undergoing hypoxia condition can recruit macrophages and cause pro-inflammation initiation around the injury area. Mitochondrial dysfunction is related to macrophage pyroptosis. Stomatin-like protein-2 (SLP-2) can regulate mitochondrial biogenesis and function. Whether SLP-2 could affect macrophage pyroptosis remains unclear. In this study, bone marrow derived macrophages (BMDMs) were extracted from WT and SLP-2 knocked out mice, then stimulated by LPS/Nigericin. Western blot showed that SLP-2-/- promoted the expression of NLRP3, GSDMD-N, caspase-11 in macrophages, which means the deficiency of SLP-2 augments macrophage pyroptosis. Higher fluorescence intensity of dihydroethidium and TUNEL represented the increased ROS releasing and macrophage programmed death in SLP-2 deficiency groups. The immunofluorescence intensity of MtioTracker Red decreased and that of mitochondrial ROS (mtROS) increased in SLP-2 deletion groups with LPS/Nigericin stimulation, representing the increased mitochondrial damage. The expression level of HIF-1α increased in SLP-2 deletion macrophages with LPS and Nigericin stimulation. The level of Parkin and the ratio of LC3II/I decreased in SLP-2 deficiency macrophages after stimulated by LPS/Nigericin, compared with untreated macrophages. H9c2 cells were cultured in hypoxia condition before being cocultured with macrophage supernatant. The cocultured H9c2 cells were injured due to the serious pyroptosis of SLP-2 deficiency macrophages. According to these results, we suggest that SLP-2 can reduce macrophage pyroptosis and relieve hypoxia H9c2 cells injury through protecting mitochondrial function.


Cold acclimation and cryoprotectants in a freeze-tolerant Antarctic nematode, Panagrolaimus davidi.
Panagrolaimus davidi is a freeze-tolerant Antarctic nematode which survives extensive intracellular freezing. This paper describes the development of culture techniques which provide clean samples, with a high degree of freeze tolerance and in sufficient quantities for the analysis of potential cryoprotectants. Cultures grown at 20 degrees C survived a short-term freezing stress but survival declined with the time spent frozen. Acclimation of cultures at 5 degrees C enhanced the long-term survival of freezing. Starvation, however, reduced the nematode's ability to survive short-term freezing. The principal cryoprotectants detected by gas chromatography were trehalose and glycerol. The levels of trehalose, but not those of glycerol, increased significantly after acclimation. Trehalose may stabilise membranes and protect them against the dehydrating effects of the osmotic stresses resulting from freeze concentration effects but other factors, such as recrystallisation inhibition, may be involved in long-term survival.


The functional significance of the browser-grazer dichotomy in African ruminants.
The allometric relationships for the fermentation rate of dry matter, the total energy concentration of volatile fatty acids (VFAs), the energy supplied from VFA production and the mass of the digesta contents within the rumen or caecum and proximal colon (hindgut) were used to test whether the digestive strategies of grazing and browsing African ruminants differ. The wet and dry mass of the contents of the rumen and hindgut were allometrically related to body mass (BM). These relationships did not differ between browsing and grazing ruminants. The fermentation rates in the rumen were strongly allometric and the intercepts of the relationships did not differ between browsers and grazers. The fermentation rates in the hindgut were not allometrically related to BM and did not differ between ruminants with different feeding habits. Likewise, the total energy concentration of the VFAs in the rumen and hindgut showed no allometric scaling and did not differ between browsing and grazing ruminants. The energy supplied by VFA production in both the rumen and hindgut of African ruminants scaled at around 0.8 with BM. Only in the case of the energy supplied by VFAs in the rumen were there significantly different intercepts for browsing and grazing ruminants. The energy supplied by VFA production in the rumen was inadequate to meet the energy requirements for maintenance of browsers and small grazers. The retention time of digesta in the alimentary tract was positively related to BM although there was no difference in the allometric relationships for grazers and browsers. The results of these analyses suggest that, after controlling for the effects of body mass, there is little difference in digestive strategy between African ruminants with different morphological adaptations of the gut.


Trisomy 4 in a case of acute myelogenous leukemia accompanied by subcutaneous soft tissue tumors. Report of a case and review of the literature.
We report a patient with acute myelogenous leukemia [AML, French-American-British classification (FAB) M2] with trisomy 4, who developed subcutaneous soft tissue tumors at the time leukemia was diagnosed. A review of the literature on AML with trisomy 4 suggests a relation between trisomy 4 and tumor formation of leukemic cells.


Isolation and characterization of the yeast ARGRII gene involved in regulating both anabolism and catabolism of arginine.
ARGRII is one of the three regulatory genes controlling arginine metabolism in yeast. From a pool of hybrid plasmids carrying Sau3A fragments representing the entire yeast genome, a DNA fragment containing the regulatory gene ARGRII was cloned by complementation of an argRII- mutation, which prevents growth on ornithine as sole nitrogen source. Cells containing the cloned DNA regained the ability to repress the synthesis of anabolic enzymes and to induce the synthesis of the catabolic ones, when arginine is present. The 6.2 kb cloned DNA fragment encodes five transcripts (2.8 kb, 1.3 kb, 0.75 kb, 0.45 kb, 0.45 kb), which were located by S1 endonuclease mapping. By marker rescue the argRII- mutations were mapped in the DNA region coding for the 2.8 kb transcript, showing its importance in the control mechanism. Subcloning experiments confirm this result. However, at present the role of the 0.75 kb and 1.3 kb transcripts in the ARGR+ phenotype is unclear.


The Use of Magnetic Resonance Spectroscopy in the Evaluation of Pediatric Patients With Seizures.
The objective was to determine if it is useful to routinely add magnetic resonance spectroscopy (MRS) to magnetic resonance imaging (MRI) in the evaluation of seizure in the pediatric patient. Specifically, how often does MRS contribute information to conventional MRI? A retrospective search, over a period of 3 years, of patients <18 years of age who underwent both MRI and MRS as part of the evaluation of seizures yielded a total of 233 cases in 216 patients. The medical records were reviewed to determine how many patients carried a diagnosis relevant to seizures. The MRIs and MRSs were reviewed by two neuroradiologists and an MR physicist/spectroscopist who determined by consensus in how many cases MRS contributed information regarding management, diagnosis, or prognosis, in addition to the findings on MRI alone. In 100 of 233 cases (43%), MRS contributed information additional to MRI. In 40 cases, MRS contributed information relevant to patient management by prompting an evaluation for an underlying inborn error of metabolism. MRS contributed information relevant to diagnosis in 24 of 100 cases (e.g., neoplasm versus dysplasia). MRS contributed information relevant to prognosis in 36 cases (e.g., hypoxic-ischemic injury). MRS added more information in cases where the patients had a diagnosis relevant to seizure before imaging. Interestingly, in 25 cases where the MRI was normal, MRS was found to be abnormal, which prompted evaluation for an inborn error of metabolism. These results suggest that MRS is a useful evaluation tool in addition to MRI for children undergoing imaging for the evaluation of seizures.


Uptake of thyroid hormones (L-T3 and L-T4) by isolated rat adipocytes.
3,5,3'-triiodo-L-thyronine is taken up by isolated rat adipocytes under physiological conditions by a saturable sigmoidal process, while L-thyroxine uptake follows Michaelian kinetics. Comparative studies performed with intact adipocytes and derived liposomes suggest that thyroid hormones are taken up into cells via carrier-mediated transport.


Analysis of Molecular Recognition Features (MoRFs) in membrane proteins.
Molecular Recognition Features (MoRFs) are defined as short, intrinsically disordered regions in proteins that undergo disorder-to-order transition upon binding to their partners. As their name suggests, they are implicated in molecular recognition, which serves as the initial step for protein-protein interactions. Membrane proteins constitute approximately 30% of fully sequenced proteomes and are responsible for a wide variety of cellular functions. The aim of the current study was to identify and analyze MoRFs in membrane proteins. Two datasets of MoRFs, transmembrane and peripheral membrane protein MoRFs, were constructed from the Protein Data Bank, and sequence, structural and functional analysis was performed. Characterization of our datasets revealed their unique compositional biases and membrane protein MoRFs were categorized depending on their secondary structure after the interaction with their partners. Moreover, the position of transmembrane protein MoRFs in relation with the protein's topology was determined. Further studies were focused on functional analyses of MoRF-containing proteins and MoRFs' partners, associating them with protein binding, regulation and cell signaling, indicating half of them as putative hubs in protein-protein interaction networks. In conclusion, we provide insights into the disorder-based protein-protein interactions involving membrane proteins.


Characterization of macrophage subsets regulating murine natural killer cell activity.
We examined the relationship of I-A expression by normal murine macrophages to their immunoregulatory role on natural killer cell activity. Macrophages were isolated on the basis of plastic adherence; characterized on the basis of conventional markers such as phagocytic ability, cytoplasmic non-specific esterase activity, surface MAC-1 and F4/80 antigen expression; and then used for functional studies relative to their expression of surface I-A. Two functional macrophage subsets were identified: NK-stimulatory and NK-suppressive subsets. The former function was associated with splenic macrophages, which were predominantly I-A+ as identified with a radioautographic immunolabeling technique; the latter function with peritoneal macrophages which were predominantly I-A-. Loss of macrophage I-A expression in vitro was delayed in the presence of indomethacin and enhanced in the presence of PGE2, indicating that PGE2 down-regulates I-A expression on macrophages. The NK stimulatory function of I-A+ macrophages was attributable to a soluble mediator, identified as IFN-gamma, since the stimulatory ability was abrogated with an anti-IFN-gamma antibody. I-A expression appears to be important for the stimulatory function, since some interference with this function was noted in the presence of anti-I-A antibody. The NK-suppressor function of I-A- macrophages was attributable to the soluble mediator PGE2, since this function was abrogated with indomethacin or anti-PGE2 antibody. These results are relevant to the understanding of normal in vivo immunoregulation by macrophages.


Molecular cloning, characterization and expression analysis of multiple leptin genes in Jian carp (Cyprinus carpio var. Jian).
Three leptin genes (jlLEP-A1, jlLEP-A2 and jlLEP-B) were cloned and characterized in Jian carp (Cyprinus carpio var. Jian), with a highly conserved organization encoded by two exons and one intron. jlLEP-A1 and jlLEP-A2 contained 93 and 102bp introns, respectively, encoding a 171-amino acid protein. jlLEP-B contained a 687bp intron encoding a 168-aa protein. jlLEP-A1 and jlLEP-A2 shared 82.5% identity, but only 29.2% and 28.6% with jlLEP-B, respectively. jlLEP-A1, jlLEP-A2, and jlLEP-B were expressed in a wide range of tissues, but the expression pattern differed between juveniles and adults (and females and males). In juveniles, the expression of jlLEP-A1 and jlLEP-B was higher than jlLEP-A2, and was the highest in the liver and gonad. In females, jlLEP-A1 and jlLEP-A2 expression was the highest in the hypothalamus and liver, whereas jlLEP-B mRNA was detected at low levels in all tissues. In males, jlLEP-A1 mRNA was expressed primarily in the hypothalamus, with only very low levels in the peripheral tissues. jlLEP-A2 and jlLEP-B mRNA were primarily expressed in the muscle, hypothalamus, and liver. The expression of jlLEP-A1 and jlLEP-B mRNA was high in the ovary and testis, respectively. Our results suggest that leptins play an important physiological role in reproduction.


BCL2 and BCL3 are recurrent translocation partners of the IGH locus.
Chromosomal translocations affecting the immunoglobulin heavy chain (IGH) locus in chromosomal band 14q32 are the most frequent cytogenetic changes in B-cell lymphomas. We studied the presence of IGH translocations in a consecutively ascertained series of 94 classical Hodgkin lymphomas (cHL) by combined immunofluorescence for CD30 and interphase cytogenetics (FICTION technique). The Hodgkin and Reed-Sternberg cells of a total of 11 of 87 evaluable cases (13%) showed signal patterns indicative of IGH translocations. To identify the translocation partners, these cases were further studied with probes for the MYC, BCL2, BCL6, BCL3, REL/BCL11A, JAK2/PDCD1LG2 (alias PDL2) C14orf43, and C2TA loci. The IGH translocation partner could be identified in four cHL and involved BCL2 and BCL3 in two cases each. Immunohistochemistry in cases with suitable material revealed that tumor cells of the two cHL with IGH/BCL2 fusion and the cHL with IGH/BCL3 fusion expressed the BCL2 and BCL3 protein, respectively. These data indicate that BCL2 or BCL3 are recurrent translocation partners of the IGH locus in cHL; however, most of the translocation partners of IGH translocations in cHL remain to be identified.


[A 3-dimensional finite element analysis of displacement of maxillary first molar on mesial movement in lingual orthodontics].
To analyze the displacement of maxillary first molar on mesial movement by lingual technique with the finite element method,and compare with that by labial technique. The finite element model was built using the advanced 3-dimensional laser scanning, comprising a maxillary first molar, periodontal ligament, alveolar bone, and a lingual or buccal tube. Different kinds of loads were applied at a point of the lingual or buccal tube separately. By finite element method,the displacement of maxillary first molar was calculated and analyzed. When the mesial force was applied to the maxillary first molar,the tooth was tipped mesially, rotated distally and lingually by lingual technique. By the labial technique,the tooth was tipped mesially, rotated distally and buccally. The degree of tipping and rotation by labial technique was bigger than that by lingual technique. By labial technique, Mt/F=8.1:1,Mr/F=8:1. By lingual technique, Mt/F=6.9:1,Mr/F=7.1:1. When the tooth moved bodily,the displacement of lingual technique was larger than that by labial technique. When the maxillary first molar moved bodily toward mesial direction, lingual orthodontics is more efficient than labial orthodontics.


Association between the rs1036819 polymorphism of the ZFAT gene and pelvic organ prolapse: a case-control study.
The identification of risk factors for pelvic organ prolapse (POP) would contribute to planning prevention strategies. This study tests the hypothesis that the rs1036819 polymorphism in the ZFAT gene is associated with POP and investigates other risk factors for prolapse development. A case-control study was carried out including 826 postmenopausal women divided into POP cases (stages III and IV) and controls (stages 0 and I), assessed by anamnesis, examination, and peripheral blood samples. DNA was extracted from blood and genotyped by real-time RT-PCR. We used logistic regression models for the association analyses of variables, with p < 0.05 for significance. Five hundred and sixty-eight women were evaluated (315 POP and 253 controls). The minor allele C was found in 19.3% of our sample and the genotype frequencies of AA, AC, and CC were similar in both groups. Age (OR 1.09, 95% CI 1.06-1.13), number of pregnancies (OR 1.23, 95% CI 1.08-1.41), history of one vaginal delivery (OR 3.39, 95% CI 1.38-8.33) or two or more (OR 2.51, 95% CI 1.04-6.07), weight of the largest newborn (OR 1.0001, 95% CI 1-1.001), and family history of POP (OR 2.27, 95% CI 1.24-4.13) were independent risk factors for POP, whereas one cesarean section (OR 0.48, 95% CI 0.27-0.88) or two or more (OR 0.14, 95% CI 0.05-0.38) were protective. No association was detected between the rs1036819 polymorphism of the ZFAT gene and advanced POP. Age, number of pregnancies, at least one vaginal delivery, weight of the newborn, and POP family history were independent risk factors for POP.


Pharmacokinetics of a new angiotensin I converting enzyme inhibitor (delapril) in patients with deteriorated kidney function and in normal control subjects.
Pharmacokinetic properties of a new angiotensin-converting enzyme inhibitor, delapril (CV-3317), which converts to two active metabolites (M-1 and M-2) and one inactive metabolite (M-3) after oral administration, were investigated in six subjects with normal, 10 subjects with slight (SRF), and six subjects with markedly (MRF) deteriorated kidney function. The elimination half-life of M-1 was prolonged significantly in subjects with MRF and that of M-3 was also prolonged in subjects with SRF or MRF. The peak plasma drug concentration, time to reach peak concentration (tmax), and AUC were significantly larger in subjects with SRF and MRF than in normal subjects, except for Tmax in subjects with SRF. In M-2 and unchanged delapril, no difference was observed. The 24-hour cumulative urinary excretion of those metabolites was significantly lower in subjects with MRF than in normal subjects. Plasma angiotensin-converting enzyme activity, suppressed at 4 hours in all subjects, remained significantly low in patients with MRF at 24 hours. Blood pressure was reduced more in subjects with chronic renal failure. It was concluded that delapril is excreted mainly through the kidney and its pharmacodynamics and biologic effects are affected by the renal dysfunction.


Discovery and mechanism study of a novel chromium-accumulating plant, Lonicera japonica Thunb.
Finding chromium-accumulating plants is of great interest for phytoremediation of soil contaminated by chromium (Cr). Inspired by Traditional Chinese Medicine, we examined the Cr-resistance and Cr-accumulation of Lonicera japonica Thunb. After a two-phase study using both soil and water culture, we found that L. japonica could be a novel Cr-accumulating plant, which contains an average Cr(III) content of 1297.14 mg.kg-1 in its leaves. The Cr enrichment factor and the Cr transport coefficient of Lonicera japonica was 5.19 and 1.79, respectively. Lonicera japonica is the fifth Cr-accumulating plant discovered worldwide, and the first Cr-accumulating woody plant ever discovered. The results support the conclusions drawn from studies of Cr-accumulating Leersia hexandra that oxalic acid production can increase Cr tolerance whereas citric acid or malic acid has no effect, suggesting that oxalic acid might be a common reason for Cr tolerance in all Cr-accumulating plants. Moreover, this study revealed that the production of anthocyanin and carotene can also increase Cr(III) tolerance, suggesting that anthocyanin and carotene might also account for Cr tolerance in Cr-accumulating plants. We believe that the discovery of Lonicera japonica as a Cr-accumulating plant will offer great opportunities in phytoremediation, and the success should be a strong sign that Traditional Chinese Medicine harbors more secrets to be uncovered with modern science.


Recovery of Visual Field After Awake Stimulation Mapping of the Optic Pathway in Glioma Patients.
Brain mapping during awake craniotomy for gliomas can help preserve neurological functions, including maintenance of central and peripheral vision. However, the consecutive changes in the visual field remain unknown. We retrospectively assessed 14 patients who underwent awake craniotomy for gliomas infiltrating into the optic radiation. Cortico-subcortical direct electrical stimulation (DES) was intraoperatively applied until transient visual symptoms were elicited and recorded. The visual fields were examined consecutively in the preoperative period and postoperative subacute and chronic periods. To evaluate the anatomo-functional validity of the recordings, all DES-elicited points were overlaid onto a three-dimensional template that included the optic radiation, using voxel-based morphometry (VBM) mapping. All patients experienced visual symptoms that were classified as phosphenes, blurred vision, or hallucinations during DES, and surgical resection was limited to within the functional boundaries. In VBM, almost all the subcortical positive mapping points overlapped with the surface of the optic radiation, and the distribution of sites that induced visual phenomena in the upper or lower visual fields could be differentiated in the anatomical space. We observed no postoperative visual deficit in four patients (29%), time-dependent improvements in five out of eight patients that presented transient quadrantanopia or partial visual defect (36% out of 57%), and permanent hemianopsia (14%) in two patients with occipital lesions. Intraoperative DES that identifies and preserves optic radiation in awake craniotomy for gliomas is a reliable and effective technique to reduce risk of permanent deficits, but has a low success rate in patients with occipital involvement.


Generation of human embryonic stem cells from abnormal blastocyst diagnosed with adrenoleukodystrophy.
Human embryonic stem cell (hESC) line chHES-480 was derived from abnormal blastocyst diagnosed with adrenoleukodystrophy (ALD) after preimplantation genetic diagnosis (PGD) treatment. DNA sequencing analysis confirmed that chHES-480 cell line carried a hemizygous missense mutation c.1825G>A(p.Glu609Lys) of ABCD1 gene. Characteristic tests proved that the chHES-480 cell line presented typical markers of pluripotency and had the capability to form the three germ layers both in vitro and in vivo.


N6-methyladenosine-related lncRNAs in combination with computational histopathology and radiomics predict the prognosis of bladder cancer.
Identification of m6A- related lncRNAs associated with BC diagnosis and prognosis. From the TCGA database, we obtained transcriptome data and corresponding clinical information (including histopathological and CT imaging data) for 408 patients. And bioinformatics, computational histopathology, and radiomics were used to identify and analyze diagnostic and prognostic biomarkers of m6A-related lncRNAs in BC. 3 significantly high-expressed m6A-related lncRNAs were significantly associated with the prognosis of BC. The BC samples were divided into two subgroups based on the expression of the 3 lncRNAs. The overall survival of patients in cluster 2 was significantly lower than that in cluster 1. The immune landscape results showed that the expression of PD-L1, T cells follicular helper, NK cells resting, and mast cells activated in cluster 2 were significantly higher, and naive B cells, plasma cells, T cells regulatory (Tregs), and mast cells resting were significantly lower. Computational histopathology results showed a significantly higher percentage of tumor-infiltrating lymphocytes (TILs) in cluster 2. The radiomics results show that the 3 eigenvalues of diagnostics image-original minimum, diagnostics image-original maximum, and original GLCM inverse variance are significantly higher in cluster 2. High expression of 2 bridge genes in the PPI network of 30 key immune genes predicts poorer disease-free survival, while immunohistochemistry showed that their expression levels were significantly higher in high-grade BC than in low-grade BC and normal tissue. Based on the results of immune landscape, computational histopathology, and radiomics, these 3 m6A-related lncRNAs may be diagnostic and prognostic biomarkers for BC.


Warthin-starry silver method showing particulate matter in macrophage.
To verify whether Warthin-Starry (WS) silver method could detect the air particulate matter (PM)/dust particles (Ps) located within the macrophages in situ. There were 26 autopsy cases that resulted from cerebral hemorrhage (group A), silicosis (group B), and fetal death during pregnancy (group C). Samples were collected separately and serial sections were prepared from the lungs and lymph nodes and stained with hematoxylin and eosin (HE), WS silver, immunohistochemistry of CD68. Furthermore, ultrathin sections were taken from the WS positive serial sections of groups A and B. Ps were observed under a transmission electron microscope (TEM) and the elements of Ps were measured by X-ray spectrum analysis (X-RSA). In both groups A and B, WS staining was positive for the larger and fine Ps, the so called "dust cells", but HE staining was almost negative for fine Ps. In group C, no larger or fine Ps were found. Immunohistochemical staining of CD68 certified that the "dust cells" containing Ps were macrophages. The results of TEM and X-RSA proved that the structure and elements of Ps belonged to PM indeed. WS staining is a better than HE staining in showing the location of PM within macrophages.


Gendered beliefs about mathematics ability transmit across generations through children's peers.
In many societies, beliefs about differential intellectual ability by gender persist across generations. These societal beliefs can contribute to individual belief formation and thus lead to persistent gender inequality across multiple dimensions. We show evidence of intergenerational transmission of gender norms through peers and how this affects gender gaps in learning. We use nationally representative data from China and the random assignment of children to middle-school classrooms to estimate the effect of being assigned a peer group with a high proportion of parents who believe that boys are innately better than girls at learning mathematics. We find this increases a child's likelihood of holding the belief, with greater effects from peers of the same gender. It also affects the child's demonstrated mathematics ability, generating gains for boys and losses for girls. Our findings highlight how the informational environment in which children grow up can shape their beliefs and academic ability.


Macrophages in heterotopic ossification: from mechanisms to therapy.
Heterotopic ossification (HO) is the formation of extraskeletal bone in non-osseous tissues. It is caused by an injury that stimulates abnormal tissue healing and regeneration, and inflammation is involved in this process. It is worth noting that macrophages are crucial mediators of inflammation. In this regard, abundant macrophages are recruited to the HO site and contribute to HO progression. Macrophages can acquire different functional phenotypes and promote mesenchymal stem cell (MSC) osteogenic differentiation, chondrogenic differentiation, and angiogenesis by expressing cytokines and other factors such as the transforming growth factor-β1 (TGF-β1), bone morphogenetic protein (BMP), activin A (Act A), oncostatin M (OSM), substance P (SP), neurotrophin-3 (NT-3), and vascular endothelial growth factor (VEGF). In addition, macrophages significantly contribute to the hypoxic microenvironment, which primarily drives HO progression. Thus, these have led to an interest in the role of macrophages in HO by exploring whether HO is a "butterfly effect" event. Heterogeneous macrophages are regarded as the "butterflies" that drive a sequence of events and ultimately promote HO. In this review, we discuss how the recruitment of macrophages contributes to HO progression. In particular, we review the molecular mechanisms through which macrophages participate in MSC osteogenic differentiation, angiogenesis, and the hypoxic microenvironment. Understanding the diverse role of macrophages may unveil potential targets for the prevention and treatment of HO.


Therapeutic mammaplasty--analysis of 50 consecutive cases.
This is a descriptive analysis of 50 consecutive cases of therapeutic mammaplasty, the use of reduction mammaplasty and radiotherapy to treat breast tumours. Breast cancers may lie within the normal excision site of a recognised mammaplasty method (scenario A) or outside of the expected excision sites (scenario B), then requiring a modified mammaplasty. A third group are central tumours requiring removal of the nipple. This series includes 13 scenario A, 27 scenario B and 10 central tumours. Wise pattern skin incision was used in 29 (58%) and vertical in 14 (28%). Seven different pedicles were employed but inferior (11), superior (9) and superio-medial (19) comprised the majority (78%). In the 27 scenario B cases an extension of the nipple aereolar pedicle was used to fill the tumour defect in 19 (70%) and a secondary pedicle in 8 (30%). There were no incomplete excisions of invasive tumour but incomplete excision of DCIS requiring mastectomy occurred in 4 (8%) patients. There are no deaths or recurrences to date (mean follow-up 13 months, range 3-32). Complications have occurred in 8 (16%) with a return to theatre for one complication (2%) and the four patients (8%) requiring mastectomy. No patient has had a delay in adjuvant treatment. Cosmetic outcome was deemed good/excellent in 63%, satisfactory in 33%, poor in 4%. Follow-up is restricted to 3-32 months.


Release of mediators from purified rat mast cells during phagocytosis.
Purified mature rat peritoneal mast cells, on exposure to zymosan or latex beads, phagocytize these particles, although less efficiently than macrophages. During phagocytosis, histamine, beta-glucuronidase, and eosinophil chemotactic factor are released from mast cells in a time-, temperature- and dose-dependent fashion. Complement components, cytochalasin B (5 microgram/ml), and indomethacin (10-6M), enhanced mediator release, whereas compound BW 755C (20 microgram/ml), a cyclooxygenase and lipoxygenase inhibitor of arachidonate metabolism, totally abolished this process. Phagocytosis of mast cell thus activates intracellular mechanisms that closely resemble those observed with other phagocytic cells. These observations add a new perspective to the role of mast cells in inflammatory events.


Swim training reduces metformin levels in fructose-induced insulin resistant rats.
Regular exercise training and metformin medication are widely considered to increase insulin sensitivity and protect against type 2 diabetes, however, evaluating the effect of exercise training on the disposition and pharmacokinetics of metformin is unclear. We investigated the effect of a 4-wk swim training program (45 min/day, 5 days/wk) on the pharmacokinetics for the use of metformin in fructose-induced insulin resistant rats. Fructose-induced insulin resistant rats were assigned into two groups (n=6/group): swim training with metformin (SM), and non-swim training with metformin (CM). Blood samples were collected from 12 h-fasted rats at baseline and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, and 12 h after an oral glucose tolerance test (OGTT) with administration of a single dose of metformin (450 mg/kg). Our study revealed that both glucose and insulin levels in the SM group were significantly lower than those in the CM group at 15 min following OGTT. The maximum concentration (C(max)) and area under the serum concentration-time curve (AUC) for the SM group were significantly lower than CM group. The apparent distribution volume (Vd) and the time-averaged total body clearance (CL) for the SM group were significantly higher than those for the CM group. There were no significant differences in the time to maximum concentration (T(max)) or the time to half-life concentration (t(1/2)) between the two groups. Our data demonstrate that swim training reduces metformin serum levels.


Physiological and Environmental Regulation of Seed Germination: From Signaling Events to Molecular Responses.
A timely and efficient seed germination is critical for plantlets' establishment and robustness as well as plant development and plant performance in both natural ecosystems and agrosystems [...].


Penetrating head wound: a remarkable case.
The modern management of penetrating head injuries is generally considered a neurosurgical specialty that relies heavily on the use of sequential imaging techniques, an ever-changing armamentarium of sophisticated antibiotics and specific neurosurgical operative skills. Unfortunately these optimal therapeutic components are frequently not available to patients injured in underdeveloped countries. An unusual case of a young patient suffering a penetrating brain wound and undergoing delayed treatment in an African mission hospital is reviewed. A functional but neurologically impaired outcome resulted from limited surgical debridement and short-term broad-spectrum antibiotic administration. The multiple exigencies of surgical practice in an underdeveloped African nation do not preclude successful management of penetrating head trauma.


Content of polychlorinated dibenzo-p-dioxins, dibenzofurans and dioxin-like polychlorinated biphenyls in fish from Latvian lakes.
Seventeen polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/PCDFs) of the highest priority as well as twelve dioxin-like polychlorinated biphenyls (dl-PCBs) were analyzed in the muscle tissues of the following freshwater fish species sampled from eleven Latvian freshwater lakes: perch (Perca flavescens), carp (Cyprinus carpio), eel (Anguilla rostrata), bream (Abramis brama), chub (Leuciscus cephalus), pike (Esox lucius), sheatfish (Silurus glanis) and roach (Rutilus). To analyze the selected persistent organic pollutants in fish matrices, an optimization of EPA-1613 and EPA-1668A clean-up procedures was carried out, followed by validation of the analytical procedure according to Commission Regulation (EC) No 1883/2006. The adopted analytical procedure was in compliance with requirements of the more recent Commission Regulation (EU) No 252/2012. Modifications of carbon column chromatography clean-up and separation steps were used for treatment of the fish samples. Other clean-up procedure stages were performed according to the methods EPA-1613 and EPA-1668A and involved gel permeation chromatography (GPC), as well as manual acidic silica and Florisil column chromatography for purification and fractionation of the samples. An isotope dilution method was used for the qualitative and quantitative determination of individual congeners. Analytes of interest were separated and detected using gas chromatography - high resolution mass spectrometry. The concentration of PCDD/PCDFs and dl-PCBs in freshwater fish and eel samples ranged from 0.05 to 8.0 pg WHO(1998)-PCDD/PCDF-PCB-TEQ g(-1) fresh weight. These levels are below the EU maximum permissible limits although calculation of the content of these compounds relative to the weight of fat shows contamination levels similar to those found in Baltic herring and sprats, that are known to be highly contaminated. A difference in congener pattern between the Baltic Sea fish and freshwater fish was detected with lower contribution of 2,3,4,7,8-PeCDF to the contamination of inland water fish.


Simultaneous and trace level quantification of two potential genotoxic impurities in valsartan drug substance using UPLC-MS/MS.
A sensitive and selective Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for the identification and quantification of two potential genotoxic impurities (PGIs) - viz. methyl N-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-N-nitroso-L-valinate (PGI-1) and N-nitroso Valsartan (PGI-2) - in the angiotensin II receptor blocker valsartan. Among these impurities, PGI-1 is a distinctive compound which has never been reported. For this, chromatographic separation was performed using a Waters XBridge BEH C18 column (150 mm × 4.6 mm, 2.5 µm), with ammonium acetate aqueous solution (0.01 mol/L) as mobile phase A and acetonitrile as mobile phase B, in a gradient elution mode at a 0.5 mL/min flow rate. Mass spectrometric conditions were optimized using electrospray ionization (ESI) in positive mode. Following the International Conference of Harmonization (ICH) guidelines, this methodology is capable of quantifying 2 PGIs at 0.016 ppm in samples at 50 mg/mL concentration. This validated approach presented good linearity over the concentration range of 0.016-0.06 ppm for 2 PGIs. The correlation coefficient of each impurity was observed greater than 0.999. The accuracy of this method was in the range of 83-113% for the aforementioned PGIs. In addition, expert knowledge rules (Derek-based) and statistical (Q) SAR evaluation system (Sarah-based) were used to evaluate and classify the genotoxicity of both valsartan-related PGIs as well as to define their standard limits. The predicted results were positive and classified into the third category, and the total nitrosamine limit was set to 0.03 ppm. As such, this approach represents a good quality control system for the simultaneous and precise quantitation of PGIs in valsartan.


Long-term changes in major ion chemistry-similarities and differences between inflow rivers and the lake in Taihu watershed, China.
The major ion chemistry in the Taihu watershed has dramatically changed due to human disturbances; however, little is known about the similarities and differences in the responses of the inflow rivers and Taihu lake to the disturbances. Using historical (1950s-1970s) and recent (2018-2021) water chemistry data of inflow rivers and the lake, as well as socioeconomic and land use data, we explored the drivers for the major ion chemistry change and different responses of the inflow rivers and the receiving lake. The results indicated that, compared with 1950s-1970s, all the major ions and TDS in rivers and Taihu lake significantly increased (by 91% for Mg2+ and by 395% for Cl- in rivers; by 68% for HCO3- and 134% for Na+ in the lake); however, their increases in major ion composition presented a clear difference, i.e., although current dominant cation remained Ca in inflow rivers, the second dominant cation has shifted from Mg2+ (1950s-1970s) to Na+ (2018-2021) for rivers, while for the lake, the second dominant cation has become frequently Na+ (2018-2021), followed by Ca2+, indicating a clear salinization tendency. Furthermore, the change of some indicative ratio indices of inflow rivers and the lake in the past decades presented an apparent difference, i.e., the river systems had a higher increase rate in Ca2+/Mg2+ and SO42-/Cl- than the lake, while the lake had a higher increase in (Ca2+ + Mg2+)/HCO3-, TH/TA, and Cl-/Na+ than the river systems. Analyses indicated that increased human disturbances were the major driver for the similar increase in the TDS and major ions for both river systems and the lake, while the different algal biomass in the rivers and lake, the land use change, and declined hydrological connectivity in this watershed played important roles in the different alterations of the water chemistry indices. Comparison of major ion correlation change between the running and stagnant waters indicated a clear "lacunification" trend of inflow rivers in terms of water chemistry characteristics in this dense river-network region. Our work revealed the cause and effect of the fundamental water chemistry change in a rapid development region and will provide scientific basis for the integrated management and recovery in the watershed.


[Roaming through methodology. X. The testing of diagnostic procedures].
In this era of evidence-based medicine, diagnostic tests cannot escape close scrutiny of their effectiveness. Sensitivity and specificity have up till now played a central role in the evaluation of diagnostic tests. These terms are not without their shortcomings when it comes to the characterisation of a test's true worth for patients. Randomised clinical trials are increasingly used for evaluation of medical tests and outlining of strategy. The indirect relationship between test results and health outcome creates additional challenges for designers of such trials.


Cortical complexity in bipolar disorder applying a spherical harmonics approach.
Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms.


Treatment-induced changes of lymphocyte subsets in patients with adenoid cystic carcinoma of the head and neck.
Adenoid cystic carcinoma (ACC) of the head and neck is a rare and highly malignant tumor, characterized by perineural growth and early distant metastases. The composition of immune cells in the peripheral blood and the tumor microenvironment is critical to tumor growth and control. However, little is known about the frequency and function of the relevant immune cell subsets in this entity. In ACC patients (n = 11) and matched healthy donors (n = 11), the frequency of peripheral blood T and B cells was measured by flow cytometry at different treatment stages of disease (24 samples). Cells were further characterized by their expression of CCR7, PD-1, CD39 and CD73. Tumor-infiltrating lymphocytes (TIL) were analyzed by immunohistochemistry for ten patients and for three patients by flow cytometry. CD4+ T cells had significantly lower frequency after radiotherapy (RT). All other cell frequencies, including Treg, were stable through course of the disease. In B cells, CD73 was reduced after RT. CCR7 expression on T and B cells in patients with relapse/metastases (R/M) differed significantly from patients with active disease. PD-1 remained stable. Treg were more present in TIL compared to peripheral blood. Composition of lymphocyte subgroups behaves similar to squamous cell carcinoma in the head and neck, except for Treg, which remained stable. Nevertheless, the CD4+/Treg ratio was lower after RT, which could stand for an immunosuppressive effect in these patients. Therefore, it could be beneficial treating ACC with combined RT and immunomodulatory drugs.


The temporal lobe epilepsy syndrome elucidated through Søren Kierkegaard's authorship and life.
In 1975 American scientists postulated the existence of the temporal lobe epilepsy syndrome. The authors of this paper demonstrate that the Danish philosopher Søren Kierkegaard in "The Book on Adler" 140 years ago has given an eminent phenomenological description of this syndrome. The authors at the same time state the hypothesis that Søren Kierkegaaard's description of Magister Adler actually might be a disguised self portrait.


DNA-membrane complex formation during electroporation is DNA size-dependent.
Size of DNA molecules governs their interaction with the cell membrane during electroporation and their subsequent transport inside the cell. In order to investigate the effect of DNA size on DNA-membrane interaction during electroporation, cells are electro-pulsed with DNA molecules; 15 bp, 25 bp, 50 bp, 100 bp and 1000 bp (bp = base pairs). Within the experimental parameter space, DNA-membrane complexes or DNA aggregates are observed at the cell membrane for DNA molecules containing 25 or more base pairs. No aggregates are observed for DNA molecules containing 15 bp. For all DNA sizes, direct access to the cytoplasm is observed, however the amount translocated decays with the size. The observed dependency of DNA aggregate formation on the size of the DNA molecules is consistent with the Onsager's theory of condensation of anisotropic rod-like molecules.


Prevalence, awareness and control of hypertension in estate workers in Malaysia.
Hypertension continues to be a major causative factor contributing to cardiovascular, cerebrovascular and renal morbidity and mortality. The objective of this study was to assess the prevalence, awareness and control of hypertension in the estate population in Johor, Malaysia. A mercury sphygmomanometer was used to record systolic and diastolic blood pressures. Cross sectional population survey was carried out in the study. The overall prevalence of hypertension in 903 subjects studied was 26.91% (243). A higher prevalence 27.65 % (133) was found in males against 26.07% (110) in females. Awareness of the disease was present in only 39% (96) of which 86.45% (83) received treatment. Among those who received treatment, control of hypertension was present in 15.66% (13). The prevalence of hypertension among the estate population is lower than that of the general population of Malaysia, which can be attributed to their regular physical activity but the awareness, treatment, control and follow-up of patients is disappointingly low.