Characterization of the analytical performance of δ15 N and δ18 O measurements by the silver nitrate method in the framework of nitrate source apportioning.
Nitrate pollution represents one of the most important issues for ground and surface water quality and source identification is essential for developing effective mitigation practices. Nitrate isotopic fingerprinting can be utilized to identify the sources of nitrate pollution in aquifers. However, it is crucial to assess the performances (precision and accuracy) of the analytical procedure applied to measure the δ15 N and δ18 O values of nitrates from field samples to correctly apply this tool. Nitrates were extracted from a large number of KNO3 samples using the AgNO3 method, and the δ15 N and δ18 O values of these nitrate extracts were measured by isotope ratio mass spectrometry. The availability of this dataset, comprising 693 unprocessed quality control (QC) KNO3 samples and 618 processed samples, allowed us to rigorously quantify the performance of the procedures employed. A salt doping experiment was also performed from which the effects of contaminants on the performance of the method could be ascertained. The overall instrumental reproducibility for the analysis of unprocessed QC samples was 0.5‰ and 2‰ for δ15 N and δ18 O values, respectively, and a strict dependence on signal amplitude was observed. No isotope fractionation was reported for reference samples that were processed according to the "identical treatment" principle (ITP) but normalized by unprocessed reference materials. A significant increase in the standard deviation (SD) was, however, observed compared with that for unprocessed samples. The SD of the processed QC samples allowed us to quantify the reproducibility of the entire procedure as 0.6‰ and 1.0‰ for δ15 N and δ18 O values, respectively. This was comparable with the system reproducibility when normalization using processed reference materials was applied according to the ITP. Normalization with processed standards is essential to achieve high-precision measurements of the δ15 N and δ18 O values of nitrates extracted from unknown samples. This procedure allowed good accuracy to be guaranteed, and precision levels comparable with the observed instrumental performance to be achieved. A salt doping experiment showed a significant influence of the SO4 2- content on the δ15 N values.


Acute toxicity, toxicokinetics, and tissue target of lead and uranium in the clam Corbicula fluminea and the worm Eisenia fetida: comparison with the fish Brachydanio rerio.
The general objective of our work was to propose new reference material for chemical toxicity testing and new sentinel organisms for environmental quality survey programs (freshwater or soils). We also wanted to provide basic toxicological data on the environmental effects of uranium. Thus, we conducted a comparative study to establish the acute toxicity and toxicokinetics of lead (Pb) and uranium (U) to the bivalve mollusc Corbicula fluminea and the terrestrial annelid Eisenia fetida andrei and to compare these findings with those of the well-known teleost fish Brachydanio rerio. We then measured the concentration of these metals in various tissues of the clam and the worm after two periods of exposure (4 and 11 days) to identify the affinities of these tissues for Pb and U. Our results have shown that Pb and U are very toxic to Eisenia and relatively nontoxic to Corbicula. By comparison, Pb was relatively nontoxic and U appeared to be very toxic to the fish. The toxicokinetic studies indicated that the three species are able to accumulate Pb and U, the rate and level of accumulation depending both on the species and the metal. We also found that fish and clams depurate the two metals. Data collected for the worm were conflicting: Pb was not depurated whereas tissue concentrations of U declined after the eighth day of exposure. Our study has also shown that the tissue distribution of Pb in the mollusc and in the earthworm differs significantly from that of U, both after 4 and 11 days exposure. In conclusion, these three species showed potential as bioindicators of environmental contamination by metals. Indeed, they could be used in conjunction to test different compartments of an ecosystem: worms for soils, fish for the water column, and clams for the water/sediment interface.


Intramuscular granular cell tumor: emphasizing the stripe sign.
We present a case of an intramuscular granular cell tumor in the thigh manifesting a 'stripe sign' on magnetic resonance imaging (MRI). This MR finding may correspond with the entrapped muscle fibers within the tumor, which demonstrated parallel arrangement on histopathologic examination. In addition, other disease entities characterized by the presence of this sign such as proliferative myositis, heterotopic ossification, and muscular sarcoidosis will be reviewed.


DNA synthesis in a cell-free system from Xenopus eggs: priming and elongation on single-stranded DNA in vitro.
We describe a eucaryotic in vitro system for DNA replication derived from Xenopus eggs. In this system, priming and elongation of DNA chains occurs with unusually high efficiency on single-stranded circular DNA templates. Up to 1.5 micrograms M13 DNA can be converted to a completely double-stranded form by 100 microliters egg extract in 1 hr at 22 degrees C, a rate of synthesis comparable with the fastest rates of chromosomal DNA synthesis in early embryogenesis. Initiation of DNA synthesis on double-stranded circular DNA templates was undetectable however. The enzymatic events responsible for complementary-strand synthesis in vitro resemble those presumed to act at the lagging strand of the eucaryotic replication fork in vivo in three ways. First, inhibitor studies indicate that DNA polymerase alpha is required. Second, priming of DNA synthesis by oligoribonucleotides is strongly supported by the complete dependence on ribonucleoside triphosphates in the assay, and the detection of an oligoribonucleotide terminus of 9 or possibly 10 nucleotides associated with nascent DNA chains. Third, the priming reaction is resistant to alpha-amanitin.


Reconstruction of the medial canthus.
The keystone for successful reconstruction of the medial canthal area is adequate positioning of the medial canthal complex to maintain proper intercanthal distance and apposition of the lids to the globe. This requires an understanding of the dynamics of the tripartite insertion of the MCT and its relationship to the medial orbital wall. We have previously described a technique for transnasal wiring based on anatomic studies that is anatomically and physiologically precise and that is applicable to a variety of clinical situations. Soft-tissue problems need to be dealt with on an individual basis with grafts, flaps, or a combination of these modalities.


Modulation of acyl-carnitines, the broad mechanism behind Wolbachia-mediated inhibition of medically important flaviviruses in Aedes aegypti.
Wolbachia-infected mosquitoes are refractory to flavivirus infections, but the role of lipids in Wolbachia-mediated virus blocking remains to be elucidated. Here, we use liquid chromatography mass spectrometry to provide a comprehensive picture of the lipidome of Aedes aegypti (Aag2) cells infected with Wolbachia only, either dengue or Zika virus only, and Wolbachia-infected Aag2 cells superinfected with either dengue or Zika virus. This approach identifies a class of lipids, acyl-carnitines, as being down-regulated during Wolbachia infection. Furthermore, treatment with an acyl-carnitine inhibitor assigns a crucial role for acyl-carnitines in the replication of dengue and Zika viruses. In contrast, depletion of acyl-carnitines increases Wolbachia density while addition of commercially available acyl-carnitines impairs Wolbachia production. Finally, we show an increase in flavivirus infection of Wolbachia-infected cells with the addition of acyl-carnitines. This study uncovers a previously unknown role for acyl-carnitines in this tripartite interaction that suggests an important and broad mechanism that underpins Wolbachia-mediated pathogen blocking.


Targeting Solute Carrier Transporters through Functional Mapping.
Solute carrier (SLC) transporters are emerging drug targets. Identifying the molecular determinants responsible for their specific and selective transport activities and describing key interactions with their ligands are crucial steps towards the design of potential new drugs. A general functional mapping across more than 400 human SLC transporters would pave the way to the rational and systematic design of molecules modulating cellular transport.


Cytoprotective effects of CSTMP, a novel stilbene derivative, against H2O2-induced oxidative stress in human endothelial cells.
A novel stilbene derivative, (E)-2-(2-chlorostyryl)-3,5,6-trimethylpyrazine (CSTMP), was designed and synthesized based on the pharmacophores of tetramethylpyrazine (TMP) and resveratrol (RES). In the present study, we investigated the protective effects of CSTMP on vascular endothelial cells under oxidative stress and elucidated its molecular mechanisms. The radical scavenging activity of CSTMP was assessed by the DPPH test. Human Umbilical Vein Endothelial Cells (HUVECs) were exposed to 150 μM hydrogen peroxide (H(2)O(2)) for 12 h, resulting in a decrease of cell viability assessed by the MTT assay and an increase of apoptotic cells assessed by the nuclear staining assay and flow cytometry. The activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and nitric oxide synthase (NOS) and the contents of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) in cells were determined by commercial kits. The expression levels of pro-apoptotic factor caspase-3 and anti-apoptotic signal ERK1/2 were detected by western blot. The results showed that CSTMP had a moderate anti-oxidative effect against the DPPH test, which was less than RES. Co-incubation with CSTMP increased the cell viability, markedly reduced the LDH leakage from the cells and decreased the lipid peroxidation. These effects of CSTMP were accompanied by increasing activity of the endogenous antioxidant enzyme SOD, the level of GSH, the production of NO and cNOS activity. Moreover, CSTMP showed stronger effects on the inhibition of apoptosis, caspase-3 expression, and the activation of phosphorylated ERK1/2 compared to RES. Furthermore, CSTMP could inhibit the expression of phospho-JNK and phospho-p38 induced by H(2)O(2). These results suggest that CSTMP prevents H(2)O(2)-induced cell injury through anti-oxidation and anti-apoptosis via the MAPK and caspase-3 pathways.


Severe hypothyroidism due to atrophic thyroiditis from second year of life influenced developmental outcome.
From the second year of life a girl showed an insidious development of clinical hypothyroidism due to a non-goitrous lymphocytic thyroiditis without traceable circulating levels of thyroid antibodies measured by routine immunoassays. The diagnostic delay of this rare variant of atrophic thyroiditis caused persistent neuropsychological deficits. Her difficulties with speed of processing and working memory in particular could suggest a frontal deficit, possibly in the dorsolateral prefrontal circuit. This contrasts with findings in congenital hypothyroidism, suggesting a relatively preserved frontal function, and could illustrate different neuropsychological deficits of hypothyroidism at different ages in early childhood.


Is early cord clamping, delayed cord clamping or cord milking best?
To compare the antioxidant status of three cord clamping procedures (early clamping, delayed clamping and milking) by analyzing the thiol-disulfide balance. This randomized controlled study enrolled 189 term infants who were divided into three groups according to the cord clamping procedure: early clamping, delayed clamping and milking. Blood samples were collected from the umbilical arteries immediately after clamping, and the thiol/disulfide homeostasis was analyzed. The native and total thiol levels were significantly (p < .05) lower in the early cord clamping group compared with the other two groups. The disulfide/total thiol ratio was significantly (p = .026) lower in the delayed cord clamping and milking groups compared with the early clamping groups. Early cord clamping causes the production of more disulfide bonds and lower thiol levels, indicating that oxidation reactions are increased in the early cord clamping procedure compared with the delayed cord clamping and milking procedures. The oxidant capacity is greater with early cord clamping than with delayed clamping or cord milking. Delayed cord clamping or milking are beneficial in neonatal care, and we suggest that they be performed routinely in all deliveries.


Method validation for detection of afidopyropen and M440I007 in tea.
Afidopyropen is a novel biorational insecticide for controlling piercing pests with great potential for application in tea gardens that can form the metabolite M440I007 when utilized for crops. However, because of a lack of analytical method for afidopyropen and M440I007 in tea, there is no means of monitoring the residues. Therefore, method development, validation and simultaneous determination of afidopyropen and M440I007 in fresh tea leaves, dried tea and tea infusion is of prime significance. A TPT cartridge-based method was developed for the solid phase extraction of afidopyropen and M440I007 from tea matrices. Extraction and clean-up conditions, including the composition, volume and temperature of elutions, were optimized to achieve the best results. Both targets were extracted using water and acetonitrile, with a water:acetonitrile (v/v) ratio of 4:10 for fresh leaves and 8:10 for dried tea, which were then cleaned and analyzed using ultraperformance liquid chromatography-tandem mass spectrometry. Both analytes demonstrated excellent linearity with a correlation coefficient above 0.998. The optimized analytical method offered limits of quantifications of 0.005, 0.005 and 0.002 mg kg-1 (converted to dried tea) in fresh tea shoots, dried tea and tea infusion for both targets, respectively. Average recoveries of afidopyropen and M440I007 ranged from 79.0% to 101.5%, with relative standard deviations ≤ 14.7%. The results showed that the method of determination for these insecticides in tea matrices was practical and efficient. © 2023 Society of Chemical Industry.


Psychometric properties of Malay neuropsychiatry unit cognitive assessment tool among Alzheimer's disease patients in comparison to Malay Montreal Cognitive Assessment.
This study aims to establish psychometric properties of the Malay Neuropsychiatry Unit Cognitive Assessment Tool (Malay NuCOG) in Alzheimer's disease. NuCOG was translated to Malay language and compared with Montreal Cognitive Assessment Tool on 80 individuals. The Malay NuCOG showed good internal consistency and reliability (Cronbach's alpha = 0.895). It demonstrated 100% sensitivity and 87.5% specificity at the cutoff score of 78.50/100. The Malay NuCOG is a valid and reliable cognitive instrument that is sensitive and specific for the detection of dementia and has clinical advantages in its ability to examine individual cognitive domains.


Intravenous morphine consumption in outpatients with cancer during their last week of life--an analysis based on patient-controlled analgesia data.
Studies on opioid use in terminally ill cancer patients have shown a prefinal dose increase in the majority of patients. Mostly oral opioids were used. Due to the pharmacokinetic properties of opioids, it is rather difficult to get a reliable estimate of the true opioid need from those results. Retrospectively, we analyzed opioid use during the last week of life of 30 consecutive outpatients with cancer on intravenous (i.v.) morphine patient-controlled analgesia (PCA). A dose increase (decrease) was defined as an increase (decrease) of the patient's individual daily dose by at least 30% with respect to their prior daily dose. We also analyzed circadian variations in morphine use. Thirty patients fulfilled the primary study inclusion criteria. Fulfilling the exclusion criteria, seven patients had to be excluded from analysis (n = 3, on PCA for less than 7 days; n = 4, PCA was finished before death). Twenty-three patients with a total of 161 treatment days were analyzed. The patients' median age was 57 years (range, 4 to 72). The median duration of intravenous morphine PCA was 19 days (range, 8 to 58). The median daily intravenous morphine dose during the last week of life was 96 to 115 mg, without significant change over time/from day to day (Friedman test). On 144/161 days (89.2%), morphine dose remained stable. On 9 treatment days (5.6%), the dose increased, and on 8 days (5.0%), it decreased. In three patients, only dose increases, and in four patients, only dose decreases were observed. In four patients, both dose increases and decreases were observed. Twelve patients showed no change in daily morphine dose. Opioid use lacked a diurnal pattern. During their end-of-life phase, cancer patients on i.v. morphine PCA showed a stable daily opioid need.


Dermatosurgery using subcutaneous infusion anesthesia with prilocaine and ropivacaine in children.
Pediatric surgical procedures under local anesthesia have been limited by the pain of injections and, because of low body weight, rapidly reached maximum doses. In subcutaneous infusion anesthesia (SIA) highly diluted local anesthetics are administered by flow- and volume-controlled infusion pumps. This article presents a retrospective review of the use of SIA in children undergoing excision of dermatologic problem lesions. A total of 354 surgical procedures, predominantly excisions of nevi in 271 children (3 months-16 years) were performed in 1999: 67 children were operated on under general anesthesia and 204 children with local anesthesia. For local anesthesia we used SIA with diluted prilocaine and ropivacaine (equivalent mixtures of 0.3%, 0.15%, 0.08%). The 67 children operated on under general anesthesia were younger (mean age 3.05 +/- 2.93 years, median age 2.00 years) than the 204 children who had surgery with SIA (mean age 9.00 +/- 4.2 years, median age 9.00 years). The sizes of excisions under general anesthesia were larger (maximum 1060 cm2, mean 76 +/- 225 cm2, median 7 cm2) than those under SIA (maximum 628 cm2, mean 22 +/- 100 cm2, median 3 cm2). No side effects of local anesthesia were observed in these pediatric procedures. The additional use of ropivacaine resulted in prolonged postoperative analgesia. SIA in children is a well-accepted, safe anesthesia that in some cases offers an alternative to general anesthesia.


The function of the frontal lobe in neonates for response to a prosodic voice.
We examined how neonates responded at the brain level to an element of acoustic stimulation using near-infrared spectroscopy (NIRS). Twenty full-term, healthy neonates were included in the study. The neonates were tested in their cribs while they slept in a silent room. First, two probe holders were placed on the left and right sides of the forehead over the eyebrows using double-sided adhesive tape. Then the neonates were exposed to the auditory stimuli from an external auditory speaker. The stimuli, readings of the first scene of "Little Red Riding Hood," were made with a digital voice. The stimuli consisted of two conditions: variably pitched speech (variable speech: VS) and monotonous flat-pitched speech (monotonous speech: MS). The analyses focused on changes in O(2)Hb because O(2)Hb is the most sensitive indicator of changes in cerebral blood flow in NIRS measurement. The O(2)Hb level promptly increased at the beginning of the VS condition, and then returned to baseline again, while O(2)Hb did not show any changes during the MS condition. Differences between baseline-stimulation relative values were used to perform a 2 (condition)x2 (recording site)x2 (gender) analysis of variance. The results show that VS (M=0.45, S.D.=1.33) produced a greater increase of oxygenated blood to the frontal area of the brain area than MS (M=-0.19, S.D.=1.28). Neonates' brain activation patterns suggest that they can discriminate differences in the prosodic patterns of utterances.


Effects of metal ions on disinfection byproduct formation during chlorination of natural organic matter and surrogates.
The effects of calcium, cupric, ferrous and ferric ions on the formation of trihalomethanes (THMs) and haloacetic acids (HAAs) were investigated using natural organic matter (NOM), small molecular weight NOM surrogates and natural water samples. The results showed that the effects were greatly dependent on the disinfection byproduct (DBP) precursor structure and molecular weight, and metal ions species. While using NOM as precursors, addition of 4.00 mM calcium ions increased the formation of THMs, dihaloacetic acids (DHAAs) and trihaloacetic acids (THAAs) by 24-47%, 51-61% and 15-25%, respectively. Addition of cupric ions at 0.02 mM increased the formation of THMs and DHAAs by 74-83% and 90-100%, respectively, but decreased the formation of THAAs by 26-27%. Similar effect was not observed when 0.04 mM ferrous or ferric ions were added. The effects of calcium and cupric ions on DBP formation were generally more evident for the NOM surrogates than that for NOM. The primary catalytic effect of calcium ions was due to complexation and less sensitive to molecular structure or weight, while that of cupric ions was attributed to redox reactions and greatly dependent on molecular structure. Both ferric and ferrous iron had substantial effects on the DBP formation of surrogates (citric acid and catechol in particular), which implied that the catalytic effects of ferric and ferrous iron mainly depended on molecular weight. The catalytic effect of cupric ions was also observed on natural water samples, while the effects of calcium, ferrous and ferric ions on natural water samples were not evident.


Percutaneous dilatational versus conventional surgical tracheostomy in intensive care patients.
Tracheostomy is usually performed in patients with difficult weaning from mechanical ventilation or some catastrophic neurologic insult. Conventional tracheostomy involves dissection of the pretracheal tissues and insertion of the tracheostomy tube into the trachea under direct vision. Percutaneous dilatational tracheostomy is increasingly popular and has gained widespread acceptance in many intensive care unit and trauma centers. Aim of the study was to compare percutaneous dilatational tracheostomy versus conventional tracheostomy in intensive care patients. 64 critically ill patients admitted to intensive care unit subjected to tracheostomy and randomly divided into two groups; percutaneous dilatational tracheostomy and conventional tracheostomy. Mean duration of the procedure was similar between the two procedures while the mean size of tracheostomy tube was smaller in percutaneous technique. In addition, the Lowest SpO(2) during procedure, PaCO(2) after operation and intra-operative bleeding for both groups were nearly similar without any statistically difference. Postoperative infection after 7 days seen to be statistically lowered and the length of scar tend to be smaller among PDT patients. PDT technique is effective and safe as CST with low incidence of post operative complication.


Clinical utility of intraoperative electrocorticography for epilepsy surgery: A systematic review and meta-analysis.
Despite the widespread use of intraoperative electrocorticography (iECoG) during resective epilepsy surgery, there are conflicting data on its overall efficacy and inability to predict benefit per pathology. Given the heterogeneity of iECoG use in resective epilepsy surgery, it is important to assess the utility of interictal-based iECoG. This individual patient data (IPD) meta-analysis seeks to identify the benefit of iECoG during resective epilepsy surgery in achieving seizure freedom for various pathologies. Embase, Scopus, and PubMed were searched from inception to January 31, 2021 using the following terms: "ecog", "electrocorticography", and "epilepsy". Articles were included if they reported seizure freedom at ≥12-month follow-up in cohorts with and without iECoG for epilepsy surgery. Non-English articles, noncomparative iECoG cohorts, and studies with <10% iECoG use were excluded. This meta-analysis followed the PRISMA 2020 guidelines. The primary outcome was seizure freedom at last follow-up and time to seizure recurrence, if applicable. Forest plots with random effects modeling assessed the relationship between iECoG use and seizure freedom. Cox regression of IPD was performed to identify predictors of longer duration of seizure freedom. Kaplan-Meier curves with log-rank test were created to visualize differences in time to seizure recurrence. Of 7504 articles identified, 18 were included for study-level analysis. iECoG was not associated with higher seizure freedom at the study level (relative risk = 1.09, 95% confidence interval [CI] = 0.96-1.23, p = .19, I2 = 64%), but on IPD (n = 7 studies, 231 patients) iECoG use was independently associated with more favorable seizure outcomes (hazard ratio = 0.47, 95% CI = .23-.95, p = .037). In Kaplan-Meier analysis of specific pathologies, iECoG use was significantly associated with longer seizure freedom only for focal cortical dysplasia (FCD; p < .001) etiology. Number needed to treat for iECoG was 8.8, and for iECoG in FCD it was 4.7. We show iECoG seizure freedom is not achieved uniformly across centers. iECoG is particularly beneficial for FCD etiology in improving seizure freedom.


Neuronal degeneration in the brain of the brindled mouse. II. Ultrastructure of neuronal inclusions in the cerebral cortex.
Two types of intra-cytoplasmic inclusions were observed in many cortical neurons of hemizygous brindled mutant mice (MObr/Y) which survived for more than 1 month. One type is an electron-lucent vacuole containing numerous vesicles and membrane fragments, some arranged concentrically, and the other consisted of electron-dense matrix with myelin figures. These inclusions were, as a rule, found near the axonal hillock where abnormally enlarged mitochondria were often present. In view of the presence of many features suggestive of autophagic vacuoles and absence of such inclusions in the oldest mice (91 days old), we hypothesize that these inclusions probably represent a focal repairing process of neurons from the sublethal injury.


Cerebral creatine deficiency disorders - A clinical, genetic and follow up study from India.
Cerebral creatine deficiency syndromes (CCDS) are a group of potentially treatable neurometabolic disorders. The clinical, genetic profile and follow up outcome of Indian CCDS patients is presented. This was a retrospective cohort of CCDS patients seen over six-years. Diagnosis was based either on low creatine peak on proton magnetic resonance spectroscopy (MRS) and/or genetic evaluation. Thirteen patients were eligible [8 creatine transporter deficiency (CTD), 4 guanidinoacetate methyltransferase (GAMT) deficiency and 1 could not be classified]. The mean (±SD) age at diagnosis was 7.2(±5.0) years. Clinical manifestations included intellectual disability (ID) with significant expressive speech delay in all. Most had significant behavior issues (8/13) and/or autism (8/13). All had history of convulsive seizures (11/13 had epilepsy; 2 patients only had febrile seizures) and 2/13 had movement disorder. Constipation was the commonest non-neurological manifestation (5/13 patients). Cranial MRI was normal in all CTD patients but showed globus pallidus hyperintensity in all four with GAMT deficiency. MRS performed in 11/13 patients, revealed abnormally low creatine peak. A causative genetic variant (novel mutation in nine) was identified in 12 patients. Three GAMT deficiency and one CTD patient reported neurodevelopmental improvement and good seizure control after creatine supplementation. Intellectual disability, disproportionate speech delay, autism, and epilepsy, were common in our CCDS patients. A normal structural neuroimaging with easily controlled febrile and/or afebrile seizures differentiated CTD from GAMT deficiency patients who had abnormal neuroimaging and often difficult to control epilepsy and movement disorder.


Adsorption of ionized and neutral pentachlorophenol to phosphatidylcholine membranes.
We have studied adsorption of pentachlorophenol (PCP) to phosphatidylcholine (PC) membranes by measuring the electrophoretic mobility of multilayered lipid vesicles in PCP solutions. PC vesicles become negatively charged due to the adsorption of ionized PCP, and we have found that their zeta potential depends upon the ionic strength and pH of the aqueous suspension. We have shown that the experimental results can be adequately accounted for in terms of a two-component Langmuir-Stern-Grahame adsorption model assuming that the 'PCP adsorption sites' are occupied either by the neutral (HA) or the ionized (A-) species. The characteristics of adsorption isotherms of the PCP - PC membrane are as follows: the association constants are KA = 55,000 dm3/mol, KHA = 279,000 dm3/mol; 4.3 PC molecules make up each PCP adsorption site at saturation; the linear partition coefficients are beta HA = (15.5 +/- 0.7) x 10(-5) m and beta A = (3.0 +/- 0.3) x 10(-5) m. The properties of PCP adsorption isotherms for PC membranes predict an increased pKa value of membrane-bound PCP, which has been observed in related studies.


Port site recurrences after laparoscopic cholecystectomy.
Port site metastasis is a well-documented event after laparoscopic procedures in cancer patients. We summarize current epidemiological knowledge about the risk of this complication after laparoscopic/conventional cholecystectomy in patients with unexpected gallbladder cancer as well as other intraabdominal malignancies. We found 174 cases of port site metastasis after laparoscopic cholecystectomy and 12 recurrences in the surgical scar after converted or open cholecystectomy. A review of all case reports and its comparison with four international surveys show a 14% incidence of port site metastases 7 months after laparoscopic cholecystectomy for cancer. Similar numbers are available for open cholecystectomy. Our data suggest that abdominal wall metastases of gallbladder cancer are not a specific complication of laparoscopy. The long-term prognosis of patients with unknown gallbladder cancer however seems to be worsened by laparoscopy. The registry of the German Society of Surgery, which prospectively compares follow-up and prognosis of all cases of cholecystectomy, laparoscopic as well as open, in patients with incidental gallbladder cancer will definitively clarify whether laparoscopy affects the prognosis of patients with unsuspected gallbladder cancer.


Use of Quantitative Structure-Activity Relationship (QSAR) and ADMET prediction studies as screening methods for design of benzyl urea derivatives for anti-cancer activity.
2D and 3D quantitative structure-activity relationship studies have been carried out for establishing a correlation between the structural properties of benzyl urea derivatives and their anti-tumour activities. From this correlation, the new chemical entities were designed, and their activity and absorption, distribution, metabolism, excretion, and toxicity properties were also predicted. Finally, the most promising compounds from these screening were synthesized and biologically evaluated for their anti-cancer properties. Compound 1-(2, 4-dimethylphenyl)-3, 3-dimethyl-1-(2-nitrobenzyl) urea (7d) showed significant anti-proliferative activity (at 100 µg/mL) in human cancer cell lines-T-cell leukemia (Jurkat J6), myelogenous leukemia (K562), and breast cancer (MCF-7) compared to reference standard 5-flurouracil.


Analgesia Use in Children with Acute Long Bone Fractures in the Pediatric Emergency Department.
Practice variation exists in pain management of children with long bone fractures (LBFs). The objectives of this study were to describe current pain management in children with LBFs and the factors associated with the undertreatment of pain. We retrospectively studied children (aged 0-18 years) with a diagnosis of LBF in a pediatric emergency department (PED) from November 2015 through August 2016. Demographic characteristics and quality measures were noted. We determined the impact of PED crowding using the National Emergency Department Overcrowding Scale. A total of 905 patients (63% male, 48% African American) were enrolled. Median age was 6 years (interquartile range [IQR] 7 years), 72% had upper extremity injuries, falls were the most common mechanism (74%), and the majority were discharged (77%). Median time to pain score was 6 min (IQR 14 min). Seventy-two percent received analgesia with a median time to order of 63 min and medication receipt of 87 min. Ibuprofen was the analgesia prescribed most commonly. There were no identified factors associated with oligoanalgesia. Nonuse of narcotics was associated with African-American race, public insurance, single fractures, and arrival via private vehicle. Ambulance arrivals, lower extremity fractures, and disaster mode were associated with receiving analgesia within 60 min. In our study, 28% of children with LBFs did not receive pain medications, especially during normal PED volumes. Additional studies are required to explore triage as a venue for analgesia delivery for LBFs.


Substance use, dependence and treatment seeking in the United States and Australia: a cross-national comparison.
To compare the prevalence of alcohol and drug use, dependence and treatment seeking in the United States of America and Australia. Two cross-sectional national surveys assessing substance use and DSM-IV substance dependence in the USA and Australia. Age-matched cohorts (18-54 years old) were selected from nationally representative Australian (National Survey of Mental Health and Well-being, 1997, n=7570) and American (National Comorbidity Survey, 1992, n=7423) household surveys. Both studies utilised a structured interview based on the Composite International Diagnostic Interview (CIDI). The 12-months prevalence of alcohol use was substantially higher in Australia (77.2%) than in the U.S. (46.3%) and the rates of alcohol dependence were also higher in Australia, although rates of alcohol dependence conditional on use were similar (6.8 and 6.5%, respectively). In contrast, although rates of use of drugs were similar in the two countries, rates of drug dependence and the probability of dependence conditional on use were higher in Australia than in the U.S. Importantly, the absence of significant interactions between correlates of alcohol and drug use disorders and country indicated that the influence of these factors was consistent across the two countries. Despite relatively similar cultural influences in Australia and the U.S. interesting cross-national differences emerged in the use of alcohol and drug dependence among those who used drugs and treatment seeking among people diagnosed with dependence. The cross-national generalizability of the associations between common correlates and rates of alcohol and drug use and dependence indicates that similar process of vulnerability to dependence may be operating in the two countries. Future research could usefully exploit these cross-national differences to help elucidate the cultural and structural factors influencing drug use, the development of dependence and treatment seeking.


Astrocytes protect against copper-catalysed loss of extracellular glutathione.
Glutathione (GSH) is one of the major antioxidants in the brain. GSH is secreted by astrocytes and this extracellular GSH is used by neurones to maintain and increase their intracellular GSH levels. For efficient GSH trafficking between astrocytes and neurones, GSH needs to be maintained in the reduced form. In model systems, GSH trafficking has been shown to be essential for neuroprotection against a variety of stress conditions. Previously we and others have shown that GSH and thiols are unstable in cell culture media and are easily oxidised. In the present study it is shown that nanomolar concentrations of copper (II) ions can cause decay of GSH in cell culture media. Increased free or redox active copper has been implicated in a variety of diseases and degradation of extracellular GSH is a possible mechanism by which it exerts its harmful effects. Rat astrocytes, a human astrocytoma cell line and astrocyte-conditioned media, in the absence of cells, are able to retard this copper-catalysed decay of GSH and maintain GSH in its reduced form. The protective effect of astrocytes appears to be a combination of copper removing and antioxidant mechanisms. The importance of these protective mechanisms is discussed with regards to neurodegenerative diseases.


Influence of whole body irradiation and local shielding on matrix-induced endochondral bone differentiation.
Subcutaneous implantation of demineralized bone matrix into allogeneic rats induces endochondral bone formation. We have investigated the effects of irradiation on the sequelae of the interaction of collagenous matrix and mesenchymal cells and on cartilage and bone differentiation. Rats were irradiated in a vertical direction with a midline dose of 850 rad. Radiation entered the rats ventrally while a small area of the upper thorax was locally shielded. After irradiation, bone matrix was implanted in shielded and nonshielded sites, and the implants were studied at various stages. On day 3, [3H]thymidine incorporation, an index of cell proliferation, was inhibited by 70% in the nonshielded sites compared to nonirradiated control rats. The degree of inhibition (35%) was less pronounced in shielded sites. Furthermore, there was recovery of cell proliferation in the shielded sites as opposed to the nonshielded contralateral site. A similar pattern was observed on day 7 as assessed by 35SO4 incorporation into proteoglycans during chondrogenesis. Bone formation and mineralization were quantified on day 11 by alkaline phosphatase activity and 45Ca incorporation. In nonshielded sites, there was a 73% inhibition of alkaline phosphatase activity. In conclusion, radiation impaired progenitor cell proliferation which resulted in decreased cartilage and bone differentiation. These findings imply that local mesenchymal cells proliferate and differentiate into bone in response to implanted collagenous matrix.


Kinetic of transgene expression after electrotransfer into skeletal muscle: importance of promoter origin/strength.
We determined over a 3-week period some of the factors that may influence the kinetic of gene expression following in vivo gene electrotransfer. Histochemical analysis of beta-galactosidase and biochemical analysis of luciferase expressions were used to determine reporter gene activity in the Tibialis anterior muscles of young Sprague-Dawley male rats. Transfection efficiency peaked 5 days after gene electrotransfer and then exponentially decreased to reach non-detectable levels at day 28. Reduction of muscle damage by decreasing the amount of DNA injected or the cumulated pulse duration did not improve the kinetic of gene expression. Electrotransfer of luciferase expression plasmids driven either by viral or mammalian promoters rather show that most of the decrease in transgene expression was related to promoter origin/strength. By regulating the amount of transgene expression, the promoter origin/strength could modulate the immune response triggered against the foreign protein and ultimately the kinetic of transgene expression.


[Improved survival and less hepatocellar carcinoma following the successful treatment of chornic hepatitis B].
Successful therapy of hepatitis B e antigen(HBeAg)-positive chronic hepatitis-B patients with interferon alpha leads to HBeAg-seroconversion. The long-term results show that HBeAg-seroconversion is more than a laboratory parameter. In the long run, therapy-induced HBeAg-seroconversion leads to improved survival and a reduced risk for the development of hepatocellular carcinoma. It is striking that cirrhosis was seen twice as often among the responders to interferon therapy as among the non-responders; this could well be an expression of the degree of inflammation in the liver, which is also higher in responders.


Comprehensive Assessment of Indocyanine Green Usage: One Tracer, Multiple Urological Applications.
The intraoperative use of fluorescent tracers and matching cameras can empower urologists' ability to recognize critical anatomical and functional features. Indocyanine green is the most extensively used near-infrared fluorescent tracer. It has been widely applied due to its ability to illuminate vascular and lymphatic anatomies. A plurality of fluorescence cameras are available allowing the connection of this technology with many surgical approaches, including robotic surgery. Although large comparative validation studies are lacking, numerous studies support the role of fluorescence guidance in urology.


Ligand docking simulations by generalized-ensemble algorithms.
In protein chemistry and structural biology, conventional simulations in physical statistical mechanical ensembles, such as the canonical ensemble with fixed temperature and isobaric-isothermal ensemble with fixed temperature and pressure, face a great difficulty. This is because there exist a huge number of local-minimum-energy states in the system and the conventional simulations tend to get trapped in these states, giving wrong results. Generalized-ensemble algorithms are based on artificial unphysical ensembles and overcome the above difficulty by performing random walks in potential energy, volume, and other physical quantities or their corresponding conjugate parameters such as temperature and pressure. The advantage of generalized-ensemble simulations lies in the fact that they not only avoid getting trapped in states of energy local minima but also allow the calculations of physical quantities as functions of temperature or other parameters from a single simulation run. In this chapter, we review the generalized-ensemble algorithms. Some of their specific examples such as replica-exchange molecular dynamics and replica-exchange umbrella sampling are described in detail. Examples of their applications to drug design are presented.


A high-throughput LC-MS/MS method for simultaneous determination of isoniazid, ethambutol and pyrazinamide in human plasma.
Tuberculosis (TB) remains a challenging global infectious disease, mainly affecting the lungs. First-line anti-TB drugs play a crucial role in slowing down the rapid spread of TB. In addition, the patient might benefit from therapeutic drug monitoring since it has become an accepted clinical tool for optimizing TB treatment. A simple and sensitive liquid chromatography/tandem mass spectrometry method was developed to monitor the plasma level of isoniazid, ethambutol and pyrazinamide in plasma samples. A one-step extraction procedure using an Ostro™ plate was applied, and extracts were analyzed by gradient elution followed by detection on a mass spectrometer by multiple reaction monitoring mode. The analytes were separated within 4.2 min and over the concentration range of 0.2-10 μg/ml for isoniazid and ethambutol and 1-65 μg/ml for pyrazinamide. The method was successfully validated according to the European Medicine Agency guideline for the selectivity, linearity and lower limit of detection, precision and accuracy, matrix effect, extraction recovery, carryover, dilution integrity and stability, and applied for quantification of analytes in clinical samples from TB patients. The presented method allows sensitive and reproducible determination of selected anti-TB drugs with advantages such as low sample volume requirement, short run time of analysis, one-step sample preparation procedure with capabilities for phospholipids removal, and a low quantification limit as well as a high degree of selectivity.


Toxicity mechanism of silver nanoparticles to Chlamydomonas reinhardtii: photosynthesis, oxidative stress, membrane permeability, and ultrastructure analysis.
Silver nanoparticles (Ag-NPs) are widely used in daily life and inevitably discharged into the aquatic environment, causing increasingly serious pollution. Research on the toxicity of Ag-NPs is still in infancy, little information is available on the relationships between oxidative stress and antioxidant, as well as damaging degrees of Ag-NPs to cellular structural components of Chlamydomonas reinhardtii (C. reinhardtiii). In the present study, we revealed the toxicity mechanism of C. reinhardtii under Ag-NPs stress using flow cytometry (FCM), metabolic methods, and transmission electron microscopy. The results showed that the chloroplasts were damaged and the synthesis of photosynthetic pigments was inhibited under Ag-NPs stress, which inhibited the growth of C. reinhardtii. Meanwhile, Ag-NPs also caused C. reinhardtii to produce excessive reactive oxygen species (ROS), increased malondialdehyde content and changed the permeability of cell membrane, resulting in the acceleration of internalization of Ag-NPs. The decrease of cell size and intracellular chlorophyll autofluorescence was observed with FCM. To deal with the induced excessive ROS that could lead to lethal and irreversible structure damage, C. reinhardtii activated antioxidant enzymes including superoxide dismutase and peroxidase. This study provides new information for better understanding the potential toxicity risks of Ag-NPs in the aquatic environment.


Giardia lamblia assemblages A and B isolated from symptomatic and asymptomatic persons in Hamadan, west of Iran.
Giardia is a very abundant organism bringing about diarrhoea in human beings. The focus of this analysis was the detection of Giardia lamblia assemblages in human stool specimens in Hamadan, west of Iran, as well as the association between obtained assemblages and clinical symptoms. Faecal samples of 4066 individuals admitted to the medical and health care facilities in Hamadan were inspected microscopically for the existence of Giardia cysts/trophozoites, and the clinical symptoms of the patients were recorded. The DNA of positive samples was isolated from and the nucleotide sequences of both glutamate dehydrogenase (gdh) (n = 15) and triose phosphate isomerase (tpi) (n = 8) genes were analyzed. In direct microscopy, a total of sixty-four samples (1.6%), were considered as positive for G. lamblia cysts or trophozoites. The sequence analysis showed that 18 out of 23 sequenced isolates (78.2%) were assemblage A and 5 (21.7%) were assemblage B. Clinical symptoms were observed in 44.4% and 40% of patients with assemblages A and B, respectively. Overall, the predominant assemblage A detected in the tested samples along with bioinformatics analysis suggest a potential zoonotic transmission in the region of the study. Although advanced analyses are necessary to understand the foundation and path of the infection, it seems that more sanitary regulations regarding contact with livestock and pet animals are essential.


Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice.
Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, hyperphosphorylation of tau, and neurodegeneration, which lead to cognitive disorders. Here, we investigated the neuroprotective effect of fisetin in the Aβ1-42 mouse model of AD. Single intracerebroventricular injections of Aβ1-42 (3 μl/5 min/mouse) markedly induced memory/synaptic deficits, neuroinflammation, and neurodegeneration. Intraperitoneal injections of fisetin at a dose of 20 mg/kg/day for 2 weeks starting 24 h after Aβ1-42 injection significantly decreased the Aβ1-42-induced accumulation of Aβ, BACE-1 expression, and hyperphosphorylation of tau protein at serine 413. Fisetin treatment also markedly reversed Aβ1-42-induced synaptic dysfunction by increasing the levels of both presynaptic (SYN and SNAP-25) and postsynaptic proteins (PSD-95, SNAP-23, p-GluR1 (Ser 845), p-CREB (Ser 133) and p-CAMKII (Thr 286) and ultimately improved mouse memory, as observed in the Morris water maze test. Fisetin significantly activated p-PI3K, p-Akt (Ser 473), and p-GSK3β (Ser 9) expression in Aβ1-42-treated mice. Moreover, fisetin prevented neuroinflammation by suppressing various activated neuroinflammatory mediators and gliosis; it also suppressed the apoptotic neurodegeneration triggered by Aβ1-42 injections in the mouse hippocampus. Fluorojade-B and immunohistochemical staining for caspase-3 revealed that fisetin prevented neurodegeneration in Aβ1-42-treated mice. Our results suggest that fisetin has a potent neuroprotective effect against Aβ1-42-induced neurotoxicity. These results demonstrate that polyphenolic flavonoids such as fisetin could be a beneficial, effective and safe neuroprotective agent for preventing neurological disorders such as AD.


Expression of T cell receptor genes in the thymus: localization of transcripts in situ and comparison of mature and immature subsets.
We have analyzed the expression of T cell receptor (TcR) genes in the thymus using in situ RNA hybridizations with probes to the constant regions of the TcR alpha, beta, gamma and delta chains. Localization of transcripts revealed low TcR alpha mRNA levels in the thymus cortex and very low levels in the subcapsular region. In contrast, TcR beta message was very abundant in the cortex. TcR gamma or delta mRNA+ thymocytes showed a scattered, predominantly cortical localization. In contrast to gamma, TcR delta transcripts were abundant in the subcapsular region. Control experiments with sorted TcR alpha/beta or gamma/delta cells revealed a detection efficiency of 75%-85% for the respective TcR mRNA and data on TcR gene expression in mature, CD3+ thymocytes were consistent with previous reports. The analysis of immature, CD3- thymocyte subsets, however, revealed a virtual absence of TcR alpha transcripts and an unexpectedly high proportion of cells (14%-29%) expressing the gene for the TcR delta chain. The data are discussed in view of current models of lineage relationships in the thymus.


Neuromuscular end-point predictive capability of published rocuronium pharmacokinetic/pharmacodynamic models: An observational trial.
Objective neuromuscular monitoring remains the single most reliable method to ensure optimal perioperative neuromuscular management. Nevertheless, the prediction of clinical neuromuscular endpoints by means of Pharmacokinetic (PK) and Pharmacodynamic (PD) modelling has the potential to complement monitoring and improve perioperative neuromuscular management.s STUDY OBJECTIVE: The present study aims to assess the performance of published Rocuronium PK/PD models in predicting intraoperative Train-of-four (TOF) ratios when benchmarked against electromyographic TOF measurements. Observational trial. Tertiary Belgian hospital, from August 2020 up to September 2021. Seventy-four patients undergoing general anaesthesia for elective surgery requiring the administration of rocuronium and subject to continuous EMG neuromuscular monitoring were included. PK/PD-simulated TOF ratios were plotted and synchronised with their measured electromyographic counterparts and their differences analysed by means of Predictive Error derivatives (Varvel criteria). Published rocuronium PK/PD models overestimated clinically registered TOF ratios. The models of Wierda, Szenohradszky, Cooper, Alvarez-Gomez and McCoy showed significant predictive consistency between themselves, displaying Median Absolute Performance Errors between 38% and 41%, and intra-individual differences (Wobble) between 14 and 15%. The Kleijn model outperformed the former with a lower Median Absolute Performance Error (16%, 95%CI [0.01; 57]) and Wobble (11%, 95%CI [0.01; 34]). All models displayed considerably wide 95% confidence intervals for all performance metrics, suggesting a significantly variable performance. Simulated TOF ratios based on published PK/PD models do not accurately predict real intraoperative TOF ratio dynamics. NCT04518761 (clinicaltrials.gov), registered on 19 August 2020.


Heroin-related attentional bias and monthly frequency of heroin use are positively associated in attenders of a harm reduction service.
The relationship between heroin-related attentional bias (AB) and a proxy for dependence severity (monthly frequency of heroin use-injecting or inhaling) was measured in individuals attending a heroin harm reduction service. A flicker change blindness paradigm was employed in which change detection latencies were measured to either a heroin-related or to a neutral change made to a stimulus array containing an equal number of heroin-related and neutral words. Individuals given the heroin-related change to detect showed a positive relationship between heroin-related AB and the proxy for dependence severity; those given the neutral change showed a negative relationship. Both findings complement each other--and are consistent with the sending of more attention to heroin-related stimuli than neutral, the more severe is the dependence.


Is Early Reperfusion a Good Thing? Optimal Timing of CABG Surgery Postacute Myocardial Infarction.
The optimal timing of coronary artery bypass grafting (CABG) following an acute myocardial infarction (AMI) is a topic of debate. The present study was designed to evaluate patients undergoing CABG both early (<5 days) and late (>5 days) after AMI in the era of percutaneous coronary intervention. The medical records at our institution from 2008 through 2012 were reviewed. A total of 128 patients underwent CABG after AMI during this time period and fulfilled criteria for the study. Death, stroke, renal failure, need for intraaortic balloon pump, postoperative ventilator days, and length of stay were examined. Patients undergoing early CABG had an increased need for an intraaortic balloon pump. There were no other correlations that we could discern between early and late CABG. Our data demonstrate no statistical difference in mortality or in the factors of morbidity studied between either early or late CABG after AMI.


Selectively eliminated blood monocytes and splenic suppressor macrophages in mice depleted of bone marrow by strontium 89.
The contribution of specific activity to the effects of the bone-seeking isotope, strontium 89 on radiosensitive components of mononuclear phagocyte populations was investigated in mice. CBA/J mice received a fixed dose of 2 microCi/g body weight of 89Sr with three different specific activities, 6 Ci, 100 microCi and 20 microCi per mg Sr. The estimated radioactivity located in the bone surface was 4,200, 3,000 and 2,400 cpm/mg bone when measured 2 days after the administration of 89Sr, and was lost with an estimated biological half-life of 27, 25, and 23 days, respectively. Bone marrow suppression was assessed by quantitation of the depletion of macrophage-colony forming cells (M-CFC) grown in vitro in the presence of macrophage growth factor. The decline in M-CFC closely paralleled the level of radioactivity in the bone. These effects were clearly reflected by the depletion of monocytes in the blood, which were reduced to 14%, 14%, and 21% of control levels corresponding to SA's of 6 Ci/mg, 100 microCi/mg and 20 microCi/mg when counted on day 10. By day 30 the respective monocyte levels were 15%, 31%, and 77%. Furthermore, the induction of prostaglandin E producing suppressor macrophages (M phi) by Corynebacterium parvum administration was found to vary inversely with the effects of radioactivity in the bone, with initial impairment followed by quantitative recovery. Resident-type M phi in peritoneal cavity, however, appear to be unaffected by 89Sr-treatment. These data suggest, as before, that the monocytes and suppressor M phi are dependent on radiosensitive marrow cells. The observations also lead to the conclusion that the specific activity of 89Sr preparations is an important determinant of the degree of suppression and of the rate of recovery of bone marrow from the effects of irradiation that follow the administration of this isotope.


Diffuse intimal thickening of coronary arteries in patients with coronary spastic angina.
The purpose of this study was to evaluate the extent of atherosclerotic changes in angiographically normal coronary arteries using intravascular ultrasound (IVUS) technique in patients with coronary spastic angina. Nitric oxide activity was shown to be decreased in coronary arteries of patients with coronary spastic angina (CSA). Decrease in nitric oxide causes arterial intimal hyperplasia or thickening. However, it remains unclear whether intimal thickening is diffusely present in coronary arteries of patients with CSA. The IVUS study was performed in 26 patients with CSA and with normal coronary angiograms and in 31 control subjects in whom age and gender was matched with those in patients with CSA. Compared with control subjects, patients with CSA had significantly larger percent intima + media area (%I + M area), intima + media area and maximal intima + media thickness in all of proximal, middle and distal segments (p<0.01, respectively). Lumen area was comparable between these groups. The presence of spasm was the most powerful independent predictor of increase in percent intima + media area, in multiple-regression analysis with the traditional risk factors as covariates. Intimal thickening existed entirely in a coronary artery in patients with CSA and with normal angiograms, independently of other traditional risk factors. The diffuse intimal thickening in the spasm coronary arteries is intimately related with coronary spasm.


Measurement of N tau-methylhistamine concentrations in urine as a parameter for histamine release by radiographic contrast media.
In a group of 750 patients who were admitted for excretory urography using iodamide, 14 distinct adverse reactions were observed. 2 of these patients exhibited a severe reaction, 4 a moderate reaction and 8 a mild reaction. In the urine portions collected 1 h after the administration of the contrast medium N tau-methylhistamine (an important histamine metabolite) was elevated both in patients showing severe adverse reactions and in those with moderate reactions. There was a rather good correlation between the increase of urinary N tau-methylhistamine concentrations and the severity of the reaction to iodamide.


Association between bone turnover markers and periodontitis: A population-based cross-sectional study.
To examine the associations between bone turnover markers and periodontitis in two cross-sectional population-based studies. We used data from two independent adult samples (N = 4993), collected within the Study of Health in Pomerania project, to analyse cross-sectional associations of N-procollagen type 1 amino-terminal propeptide (P1NP), C-terminal cross-linking telopeptide, osteocalcin, bone-specific alkaline phosphatase (BAP), fibroblast growth factor 23, wingless-type mouse mammary tumour virus integration site family member 5a (WNT5A), and sclerostin values with periodontitis. Confounder-adjusted gamma and fractional response regression models were applied. Positive associations were found for P1NP with mean pocket probing depth (PPD; eβ=1.008 ; 95% confidence interval [CI]: 1.001-1.015), mean clinical attachment loss (mean CAL; eβ=1.027 ; 95% CI: 1.011-1.044), and proportion of sites with bleeding on probing (%BOP; eβ=1.055 ; 95% CI: 1.005-1.109). Similar associations were seen for BAP with %BOP ( eβ=1.121 ; 95% CI: 1.042-1.205), proportion of sites with PPD ≥4 mm (%PPD4) ( eβ=1.080 ; 95% CI: 1.005-1.161), and sclerostin with %BOP ( eβ=1.308 ; 95% CI: 1.005-1.704). WNT5A was inversely associated with mean PPD ( eβ=0.956 ; 95% CI: 0.920-0.993) and %PPD4 ( eβ=0.794 ; 95% CI: 0.642-0.982). This study revealed scattered associations of P1NP, BAP, WNT5A, and sclerostin with periodontitis, but the results are contradictory in the overall context. Associations reported in previous studies could not be confirmed.


Stimulation of dopamine output from adrenal medullary cells by beta-endorphin and its C-terminal tetrapeptide (MPF).
The output of dopamine from cultures of rat adrenal medullary strips was increased by 71-120% when Lys-Lys-Gly-Glu (MPF), the C-terminal tetrapeptide sequence of human beta-endorphin, was added to the culture medium at 100 micrograms/ml concentration. Human beta-endorphin caused a 44% increase, but an N-terminal fragment of its molecule and somatotrophin caused no increase. Results with analogs of MPF show that small structural change of the C-terminal Glu residue causes complete loss of activity.


Familial multiple polyposis coli with multiple associated tumors.
A case is described of familial polyposis of the colon, which combines almost every recorded manifestation of the syndrome of associated tumors; namely, carcinomatous changes in the polyps, osteomas of facial and other bones, periampullary carcinoma, transitional-cell carcinoma of the bladder, adrenal adenoma, intra-abdominal fibrous tumors with bowel obstruction, and a remarkable tendency to contain and survive the malignancies.


Understanding the viral shedding time of Omicron variant BA.2 infection in Shanghai: A population-based observational study.
To explore the multifactorial causality of prolonged viral shedding time and identify different viral shedding trajectories in Omicron BA.2 variant infections. The Kaplan-Meier method was used to estimate the survivor function, and the Cox proportional hazards model was fitted to identify factors associated with viral shedding time. Group-based trajectory model (GBTM) was used to identify different viral shedding trajectories. Ordinal logistic regression was used to identify factors that significantly impacted the trajectory membership. The overall median viral shedding time was 12 days (interquartile range [IQR]: 8-15). Viral shedding time was longer for female cases, cases who were incompletely vaccinated, cases with comorbidities, cases with severe or critical infections and cases who had not taken Paxlovid within 5 days after diagnosis. Compared to the 3 to 17-year-old group, all older groups had significantly longer viral shedding times. The GBTMs based on the N gene and the ORF1ab gene were consistent. Three viral shedding trajectories were identified and age group, comorbidities, vaccination status, disease state, Paxlovid treatment were significantly associated with the trajectory membership. Increased age, comorbidities, incomplete vaccination, severe or critical infections, and delayed Paxlovid treatment were the risk factors for prolonged viral shedding time.


Similarity of aroma attributes in hot-air-dried shrimp (Penaeus vannamei) and its different parts using sensory analysis and GC-MS.
The objective of the study was to determine the similarities of aroma attributes in hot-air-dried whole shrimp (HDWS) and its different parts using sensory analysis and gas chromatography-mass spectrometry (GC-MS). In this study, eight samples of different parts of shrimp were compared with its whole. Characteristic volatile compounds based on odor activity value (OAV) were selected, and a cluster analysis (CA) method was used to determine the similarities of aroma profiles between the whole and parts. The potential correlations among sensory attributes and volatile compounds were analyzed by analysis of partial-least-squares regression (PLSR). A total of 78 volatile compounds were identified, and 25 volatile compounds with OAV greater than 1 were selected as the aroma-active compounds (AACs) contributing to samples' integral aroma profile. Sixteen AACs in HDWS were identified, and four of them made important contributions, namely, 3-ethyl-2,5-dimethylpyrazine, 2,5-dimethyl pyrazide, trimethylamine, and 3-(methylthio)propionaldehyde. Fourteen AACs were the common constituents of hot-air-dried epidermis (HDE) and the whole, and their contents were quite close. CA result showed that HDWS and HDE had the highest similarity and were the first classified in a cluster. AACs summations and sensory scores of hot-air-dried head, shell, and meat decreased to various degrees after removal of shrimp epidermis, the reduction of which was more than 95% in the shell. The PLSR results showed a good correlation between most variables of sensory attributes and volatile compounds. It was concluded that shrimp epidermis made an important contribution to the aroma profile of dried shrimp and was the main source site of shrimp aroma. These results have important theoretical value for reconstructing and producing characteristic flavor substances of shrimp.


Delivery of small interfering RNAs by nanovesicles for cancer therapy.
Small interfering ribonucleic acids (siRNAs) are originally recognized as an intermediate of the RNA interference (RNAi) pathway. They can inhibit or silence various cellular pathways by knocking down specific messenger RNA molecules. In cancer cells, siRNAs can suppress the expression of several multidrug-resistant genes, leading to the increased deposition of chemotherapeutic drugs at the tumor site. siRNA therapy can be used to selectively increase apoptosis of cancer cells or activate an immune response to the cancer. However, delivering siRNAs to the targeted location is the main limitation in achieving safe and effective delivery of siRNAs. This review highlights some representative examples of nonviral delivery systems, especially nanovesicles such as exosomes, liposomes, and niosomes. Nanovesicles can improve the delivery of siRNAs by increasing their intracellular delivery, and they have demonstrated excellent potential for cancer therapy. This review focuses on recent discoveries of siRNA targets for cancer therapy and the use of siRNAs to successfully silence these targets. In addition, this review summarizes the recent progress in designing nanovesicles (liposomes or niosomes) for siRNA delivery to cancer cells and the effects of a combination of anticancer drugs and siRNA therapy in cancer therapy.


A review of psychophysiological research with hyperkinetic children.
A number of studies have appeared which focus on the issue of whether hyperactive children are psychophysiologically different from normal children and what impact the stimulant drugs may have on psychophysiological characteristics of these children. The present paper reviews these studies under the type of measures that were employed. In general, the results suggest that hyperactive children are probably not under- or overaroused in their resting levels of autonomic functions, although some children may display resting cortical underarousal. However, the findings of studies on the impact of stimulation on autonomic or central functions intimate that some hyperactive children are probably underreactive to environmental stimulation, or are "underarousable." Indeed, where differences between hyperactive and normal children are found in such evoked-response studies, they are consistently in this direction of "underarousability." Results for the effects of stimulant drugs suggest that these drugs energize or increase the "arousal" of these children and enhance the impact of stimulation on the nervous system. The implications of these results for current theories of hyperactivity and for future research are discussed.


Portable real-time sonography--a valuable adjunct to computed tomography.
As fast high-resolution total body computed tomography (CT) scanners have proliferated in hospitals and radiologists' offices across the country, they have tended to eclipse the usefulness of sonography in abdominal and thoracic diagnosis. This paper discusses some of the limitations of CT techniques as applied to common abdominal and thoracic problems. Emphasized here are situations wherein a quick examination with a portable real-time ultrasound device while the patient is on the CT table can result in a definitive CT report.


Nuciferine attenuates atherosclerosis by regulating the proliferation and migration of VSMCs through the Calm4/MMP12/AKT pathway in ApoE(-/-) mice fed with High-Fat-Diet.
Atherosclerosis (AS) is the pathological basis of multiple cardiovascular diseases. The pathogenesis of AS is closely related to the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). Nuciferine, an aporphine alkaloid from lotus leaf, has various pharmacological activities. However, the effect and mechanism of nuciferine on regulating proliferation and migration of VSMCs against AS is still unclear. To elucidate the pharmacological effect and molecular mechanism of nuciferine on AS in ApoE(-/-) mice fed with High-Fat-Diet (HFD). HFD-fed ApoE(-/-) mice and 3% fetal bovine serum (FBS) induced mouse aortic vascular smooth muscle cells (MOVAS) were used to investigate the protective effect and mechanism of nuciferine on AS. Oil red O staining was used to detect the atherosclerotic lesions. Western blotting and immunofluorescence were used to determine calmodulin 4 (Calm4) expression and localization. CCK-8 assay, transwell and wound-healing assays were used to measure the migration and proliferation of MOVAS cells. Nuciferine at 40 mg/kg significantly ameliorated the aortic lesion and vascular plaque in AS model, which was equal to the effect of the positive control drug (atorvastatin). In addition, nuciferine attenuated the migration and proliferation of VSMCs in vivo and in vitro. Importantly, nuciferine down-regulated the increase of Calm4 induced by HFD-fed in ApoE(-/-) mice or 3% FBS induced MOVAS cells. However, the inhibitory effect of nuciferine on the migration and proliferation of MOVAS cells was blocked when Calm4 was overexpressed. Furthermore, we found that nuciferine suppressed MMP12 and PI3K/Akt signaling pathway via Calm4. Our results illustrated that Calm4 promoted the proliferation and motility of MOVAS by activating MMP12/Akt signaling pathway in AS. Nuciferine has a significant anti-atherogenic effect by regulating the proliferation and migration of VSMCs through the Calm4/MMP12/AKT signaling pathway. Thus, Calm4 could potentially be a new target for AS therapy, and nuciferine could be a potential drug against AS.


Effect of fentanyl on the minimum alveolar concentration of isoflurane in swine.
Fentanyl is used in anesthetic protocols for swine, but there are no reports on its potency in this species. This study measured the extent to which fentanyl reduces the minimum alveolar concentration of isoflurane (MACISO) in swine. Sixteen swine were randomly assigned to four groups. For each group, baseline MACISO was determined, and three groups received two of three fentanyl infusions as follows: 50 micrograms.kg-1.h-1 intravenously followed by 100 micrograms.kg-1.h-1, 50 micrograms.kg-1.h-1 followed by 200 micrograms.kg-1.h-1, or 100 micrograms.kg-1.h-1 followed by 200 micrograms.kg-1.h-1 (n = 8 for each dosage). A loading dose of fentanyl preceded each infusion. Each infusion was maintained for 60 min before initiating minimum alveolar concentration determination. The infusions were maintained throughout the period of minimum alveolar concentration determination. Plasma fentanyl samples were obtained after 30 min of each infusion, and plasma fentanyl and hemodynamic parameters were obtained immediately before stimulating swine for the final isoflurane concentration used in determining minimum alveolar concentration. A fourth group, control animals, received saline infusions. After each infusion, the MACISO was redetermined. Minimum alveolar concentration was determined using incremental changes in isoflurane concentrations until gross purposeful movement resulted when using a hemostat stimulus applied for 1 min to a rear dewclaw. MACISO for controls was 2.19 +/- 0.17% (mean +/- SEM) and changed minimally over time (-0.13 +/- 4.77%). MACISO decreased significantly (P < or = 0.01) 24.5 +/- 3.2%, 29.9 +/- 4.8%, and 45.9 +/- 5.5% with fentanyl dosages of 50, 100, and 200 micrograms.kg-1.h-1, respectively. Corresponding plasma fentanyl concentrations were 14 +/- 1 ng/ml, 26 +/- 3 ng/ml, and 59 +/- 5 ng/ml, respectively. A ceiling effect on reduction of MACISO was not observed. Changes over time or between groups were not observed for arterial blood gas tensions, blood pressure, heart and respiratory rate, or body temperature. These fentanyl dosages are larger than those commonly used in humans and other species. Anesthetic protocols using fentanyl for swine should be designed with the knowledge that a fentanyl infusion of 200 micrograms.kg-1.h-1 contributes approximately a 50% MACISO equivalent.


Muscarinic modulation of purine release from electrically stimulated rat cortical slices.
The release of 3H-labeled purines at rest and during electrical stimulation was investigated in slices of rat cortex prelabeled with [3H]adenine and perfused with Krebs solution. A linear relationship was found between radioactivity efflux and stimulation frequency from 2.5 to 20 Hz. At frequencies of less than 2.5 Hz, no increase in radioactivity efflux was detected. The amount of tritium released per pulse increased with stimulation frequency up to 10 Hz and declined at 20 Hz. The tritium efflux from the slices at rest and at a stimulation frequency of 10 Hz, analyzed by HPLC with ultraviolet absorbance detection at 254 nm, consisted mostly of adenosine, inosine, and hypoxanthine. The 3H-labeled purine release evoked by 10-Hz stimulation increased with current intensity from 15 to 100 mA/cm2. At 20 mA/cm2, addition of 0.5 microM tetrodotoxin to the superfusing Krebs solution brought about a 98% decrease of 3H-labeled purine release. At higher current strength, the percentage of tetrodotoxin-sensitive-evoked tritium efflux was smaller. At 30 mA/cm2, 86% of the evoked release was tetrodotoxin sensitive. Under these stimulation conditions, tritium efflux showed a 69% decrease when the slices were superfused with calcium-free Krebs solution containing 0.5 mM EGTA. The muscarinic agonist oxotremorine (30 microM) significantly enhanced the 10-Hz-stimulated 3H-labeled purine release. The effect of oxotremorine was partially prevented by tetrodotoxin, was antagonized by atropine (1.5 microM), and was mimicked by addition of physostigmine (3.8 microM) to the superfusion fluid. Atropine alone did not affect the evoked release, and none of the drugs modified the basal tritium efflux.(ABSTRACT TRUNCATED AT 250 WORDS)


Late radiation-related fibrosis: pathogenesis, manifestations, and current management.
Radiation-induced fibrosis (RIF) represents one of the most common long-term adverse effects of curative radiotherapy. Current cancer treatment approaches, involving more intensive radiotherapy regimens, used in combination with systemic agents, will likely be associated with a higher incidence and greater degree of damage to normal tissues, especially RIF. Traditionally, the development of fibrosis after radiation therapy has been considered static and irreversible. Contemporary understanding recognizes RIF as a continuum of responses mediated by molecular pathways that may be amenable to interventions. Preliminary evidence suggests that pharmacological or other interventions may be possible to reverse the manifestation of the injury and restore function to tissues. A variety of strategies have been tested for the management of RIF, although formal trials of these therapies that permit treatment comparisons are unavailable at this time. It is critical that we formally evaluate new management approaches for RIF with larger patient accrual. To this end, it is also important to develop a means of registering its occurrence for outcome analysis and to refer these patients to colleagues familiar with optimal management and enrollment in clinical trials.


Interspecific comparisons of relative assimilation efficiencies for zinc and cadmium in an ecological series of talitrid amphipods (Crustacea).
A dual-labelling radioisotope technique has enabled the relative assimilation efficiencies of an essential (Zn) and a non-essential trace metal (Cd) to be determined in an ecological series of talitrid amphipods from low-shore to fully terrestrial habitats. All species exhibited high assimilation efficiencies for zinc and cadmium (within the range 66.7-96.4%). Interspecific differences in assimilation rates showed no trend with increasing terrestriality of the habitat. Elevated dietary zinc concentrations failed to enhance zinc assimilation efficiency. Incorporation of antibiotics into the diet to eliminate gut microflora did not affect zinc assimilation efficiencies. The implications of having high trace-metal assimilation efficiencies are discussed in terms of land invasion by talitrids.


Efficacy of induction chemotherapy in lymph node-positive stage III nasopharyngeal carcinoma and identification of beneficiaries based on clinical features: A propensity score matching analysis.
To investigate the role of induction chemotherapy (IC) in lymph node-positive (LN-positive) stage III nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). In total, 627 patients with newly diagnosed LN-positive stage III NPC receiving CCRT or IC plus CCRT were included. The primary endpoint was progression-free survival (PFS). Propensity-score matching (PSM) was conducted to balance the intergroup covariates. Kaplan-Meier method with log-rank test was employed to compare survival curves. Subgroup analyses were conducted based on baseline characteristics. After 1:1 PSM, 414 patients were identified (207 patients per group). Compared with CCRT, IC plus CCRT provided better survival (5-year PFS 88.4% vs. 78.6%, P = 0.01; overall survival [OS] 94.8% vs. 85.3%, P = 0.003; and distant metastasis-free survival [DMFS] 93.1% vs. 85.6%, P = 0.03). The IC beneficial effects on PFS were mainly present in patients with grade 2-3 ENE, elevated serum lactate dehydrogenase (LDH > 170U/L), and N2 disease. Patients with grade 2 CNN had comparable PFS benefits to those with grade 0-1 CNN. For patients with grade 0-1 ENE combined with LDH ≤ 170U/L, survival between the two groups was similar with 5-year PFS 93.6% vs. 90.4% (P = 0.50), OS 94.2% vs. 93.0% (P = 0.72), and DMFS 98.6% vs. 97.7% (P = 0.98). Adding IC before CCRT improved survival in LN-positive stage III NPC patients. Additional IC did not provide better survival for patients with grade 0-1 ENE combined with LDH ≤ 170U/L and could be avoided in this population. CNN may not be a good risk factor for tailoring a personalized treatment plan.


Preliminary studies on the relationship among peel force, quantitative measures of skin damage and subjective discomfort.
The ability to anticipate skin damage and subject/patient discomfort due to the removal of adhesive materials without human testing is currently limited. While standardized laboratory methods have been developed, their ability to model and predict the interaction with relevant living substrate is imperfect. The aim of this study was to assess the adhesion of various materials as a function of time using the abdomen as the body site, and determine if a relationship existed with skin damage and subject discomfort. Strips of six different materials used in medical devices and known to have different adhesive properties in the laboratory setting were tested in this study. The strips were adhered to the abdomens of normal volunteer subjects for varying periods of time. Peel force was measured under conditions developed to lessen the influence of skin elasticity. Disturbance of the skin barrier was assessed by measuring transepidermal water loss; erythema by reflectance L*a*b* measurements; skin cells removal by quantitation of dyed cells adhering to the test strips; and discomfort using subject self-assessment. When measured at times from 30 min to 72 h after application, the peel force was highest for materials at 30 min. The peel force for one of the six materials, designated F, was clearly higher than the others at time points from 30 min to 48 h after application. Interestingly, this material caused less disruption to the skin barrier and was reported to cause less discomfort. In this system, there was not a correspondence between adhesion as measured by peel force and skin damage or self-report of discomfort. Further investigations will be required to establish the predictive value of other biophysical measurements and discomfort.


Identification and characterization of a novel sativene synthase from Fischerella thermalis.
Sesquiterpene synthases (TPS) determine the structural diversity of terpenoids, which are species specific. In this study, we report a TPS from Fischerella thermalis (named as FtTPS), recombinantly expressed as a soluble protein in Escherichia coli BL21(DE3) strain. The FtTPS protein could catalyze the conversion of farnesyl pyrophosphate (FPP) to sativene, a kind of tricyclic sesquiterpene. The optimal pH and temperature of FtTPS were 7.5 and 30 °C, respectively. The KM and Vmax values of FtTPS for FPP were 1.846 μM and 0.372 μM/min, respectively. By constructing an engineered E. coli strain carrying the FtTPS and the heterologous mevalonate (MVA) pathway genes, sativene could be detected and its yield reached 24 mg/L after 96 h cultivation. The highest yield of sativene was obtained when E.coli BL21 Star was used as the host with SBMSN medium. These results exhibited the biosynthesis of sativene for the first time.


Rapid Progression of Kaposi's sarcoma complicated with hemophagocytic syndrome in a severely immunosuppressed patient with HIV-infection: a case report.
AIDS-related KS generally involves cutaneous lesions, that slowly progress over months to years. Neither rapidly progressing of KS nor KS complicated with hemophagocytic syndrome (HPS) has rarely been reported. We report a rare case of rapid progression of Kaposi's sarcoma complicated with hemophagocytic syndrome in a severely immunosuppressed patient with HIV-infection. The symptoms of this patient were atypical, showing only persistent high fever and rapid progressed to hemophagocytic syndrome. This patient was successfully treated with antiretroviral therapy combined with liposomal doxorubicin. The condition of the KS patient could deteriorate rapidly over a period of days and even developeded into HPS, which was life-threatening. However, chemotherapy initiated in a timely manner might improve prognosis.


Diagnostic performance of 64-section CT using CT gastrography in preoperative T staging of gastric cancer according to 7th edition of AJCC cancer staging manual.
To evaluate the accuracy of 64-section multidetector CT with CT gastrography for determining the depth of mural invasion in patients with gastric cancer according to the 7th edition of the AJCC cancer staging manual. A total of 127 patients with gastric cancer and who had undergone both esophago-gastro-duodenoscopy and 64-section CT were included in this study. Two radiologists independently reviewed the preoperative CT images with respect to the detectability and T-staging of the gastric cancers. The sensitivity, specificity, accuracy and overall accuracy of each reviewer for the T staging of gastric cancer were calculated. Overall, gastric cancer was detected in 123 (96.9%) of the 127 cancers on the CT images. Reviewer 1 correctly staged 98 gastric cancers, and reviewer 2 correctly classified 105 gastric cancers. The overall diagnostic accuracy of the T staging was 77.2% (98/127) for reviewer 1 and 82.7% (105/127) for reviewer 2. 64-section CT using CT gastrography showed a reasonable diagnostic performance for determining the T staging in patients with gastric cancer according to the 7th edition of the AJCC cancer staging manual. 64-section CT is useful for determining the T staging of gastric cancer Virtual gastroscopy is helpful for detecting early gastric cancer New CT criteria may be applicable to the T staging The normal gastric wall frequently shows a multilayered pattern.


Magnetic anomalies and seafloor spreading rates in the northern South Atlantic.
A geomagnetic profile across the northern South Atlantic yields spreading rates for the last 70 m.y. which vary from 1.6 to 2.0 cm/year. There is evidence for three regional discontinuities in the spreading history of the South Atlantic.


Penicillin-induced epileptic foci in the motor cortex: vertical inhibition.
Neuronal mechanisms responsible for a vertical restriction of focal seizure activity in the motor cortex were analysed. For this purpose intracellular recording from neurones in superficial (50-300 microns below cortical surface), middle (300-800 microns) and deep cortical layers (800-1300 microns) was performed. As a model of foci of various vertical extensions the spread of seizure activity from superficial to deeper cortical laminae following epicortical penicillin application was used. The appearance of characteristic epileptiform potentials in the surface record with a focus restricted to upper cortical laminae was accompanied (i) in superficial neurones by the development of paroxysmal depolarization shifts (PDS), (ii) in middle neurones by depolarization often followed by hyperpolarization, and (iii) in deep neurones by a sequence of membrane potential changes. The latter consisted of an initial depolarization, an early hyperpolarization, an intermediate depolarization, a late hyperpolarization and a final depolarization. The hyperpolarizing components led to complete suppression of action potentials (vertical inhibition). The early hyperpolarization and the first part of the late hyperpolarization were reduced in amplitude when the intracellular chloride activity was elevated. The intermediate depolarization was replaced by PDS with the enlargement of the epileptic focus into the cortex. The actual effect of the vertical inhibition may in part be responsible for the variability in epileptic motor phenomena coinciding with epileptiform potentials in the surface EEG.


Clinical study of medial area infarction in the region of posterior inferior cerebellar artery.
Our objective is to study the neurological characteristics of medial area infarction in the caudal cerebellum. Medial area of the caudal cerebellum is supplied with 2 branches of the posterior inferior cerebellar artery (PICA). The medial hemispheric branch of the PICA distributes to the medial area of the caudal cerebellar hemisphere. The medial branch of the PICA (mPICA) distributes to the inferior vermis. We studied the neurological characteristics of 18 patients with medial area infarction of the caudal cerebellum. The infarction was located in the medial area of the cerebellar hemisphere and vermis (medial ch/vermis) in 11 patients and in the medial area of the cerebellar hemisphere (medial ch) in 7 patients. All the 18 patients showed acute vertigo and disturbance of standing and gait at onset. On admission, the lateropulsion and wide-based gait were present in 13 patients, respectively. Mild ataxia of the extremities was shown in 7 patients. Acute vertigo and unsteadiness were prominent at onset in the 18 patients, although their ataxia of the extremities was mild or none. This result was consistent with the characteristics of medial area infarction of the caudal cerebellum. Comparing the neurological symptoms between the medial ch/vermis group and medial ch group, both lateropulsion and wide-based gait were significantly infrequent in medial ch group. This result indicated that the vermis was spared because the mPICA was not involved in the medial ch group. It is necessary to make a careful diagnosis when we encounter patients who present acute vertigo because truncal and gait ataxia are unremarkable on admission in patients with the medial area infarction of the caudal cerebellum without vermis involvement.


Influence of pH on capillary filtration coefficient of rat mesenteries perfused with solutions containing albumin.
A preparation of rat mesentery was vascularly isolated from the intestine and perfused with a physiological salt solution containing either Ficoll 70 or bovine serum albumin, to act as colloidal agents. The capillary filtration coefficient (Kf; units, ml. min-1 100 g-1 mmHg-1) was measured by following the weight change after graded increases in venous pressure. At pH values greater than 7.05, Kf, during perfusion with 3 and 4% bovine serum albumin solutions, was 0.219 +/- 0.023 (mean +/- S.E. of mean), ninety-eight observations in thirteen experiments, which was significantly less than the value of 0.507 +/- 0.038 which was obtained during perfusion with albumin solutions at pH less than 7.05, seventy-six observations in eleven experiments, (P less than 0.05). The value of Kf obtained during perfusion with 4% Ficoll solutions was 0.267 +/- 0.018, 119 observations in sixteen experiments, and remained uninfluenced by pH over the same range that had been used with the albumin solutions; however, perfusion of the tissues with Ficoll solutions at pH greater than 7.05, after perfusion with albumin solution pH less than 7.05, did cause the Ficoll-derived value of Kf to rise to 0.502 +/- 0.055, seventy-two observations in eleven experiments. It was concluded that the changes in Kf were not due to pH alone, but were mediated by albumin at acidic pH.


Impact of non-small cell lung cancer histology on survival predicted from the graded prognostic assessment for patients with brain metastases.
The Graded Prognostic Assessment (GPA) provides prognostic classification for patients with brain metastases (BM), based on Radiation Therapy Oncology Group (RTOG) data. Recent evidence suggests differential response and outcomes to chemotherapy for different non-small cell lung cancer (NSCLC) histologies. Using a large BM patient database, we assessed the impact of histologic subtypes on survival stratified by the GPA. From an IRB-approved database, we analyzed 780 patients with NSCLC BM treated from 1982 to 2004. GPA classification variables included age, KPS, number of BM, and presence of extracranial disease. Histology was identified for each patient. Median survival time (MST) based on GPA class and histology were calculated using Kaplan-Meier analysis. The log rank test was used to determine statistical differences. MST, in months, by histology were: adenocarcinoma (AC) 6.2 (n=464), large cell (LC) 4.1 (n=98), squamous (SQ) 4.2 (n=108) (p=0.0549). For GPA 3.5-4.0, MSTs did not differ significantly by histology. Differences in MST by histology were noted for GPA 3.0 (p=0.04), GPA 1.5-2.5 (p=0.01), and GPA 0-1.0 (p=0.02). For all patients with brain metastases BM from NSCLC, MSTs by GPA score were: GPA 3.5-4.0, 12.6; GPA 3.0, 10.2; GPA 1.5-2.5, 5.8; and GPA 0-1.0, 2.7. Adenocarcinoma showed a statistically significant higher MST than other histologies of NSCLC for patients with GPA 0-3.0. Using histology as a prognostic factor for BM from NSCLC warrants further investigation. Our cohort of NSCLC BM patients validates the GPA, with MST comparable to that of published data.


Dihydropyridine calcium-channel blockers for antihypertensive treatment in older patients--evidence from the Systolic Hypertension in Europe Trial.
The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension. Randomised, placebo-controlled, double-blind outcome trial. Hypertension clinics or general practitioners' surgeries in 198 centres in 23 Western and Eastern European countries. Patients aged > or = 60 years with sitting systolic blood pressure (BP) 160-219 mmHg and sitting diastolic BP < 95 mmHg during run-in phase. Four thousand, six hundred and ninety-five patients were randomly assigned to active treatment (N = 2,398), i.e. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or to matching placebos (N = 2,297). In the intention-to-treat analysis, the between-group difference in blood pressure (BP) amounted to 10.1/4.5 mmHg (P < 0.001). Active treatment reduced the incidence of fatal and non-fatal stroke (primary endpoint) by 42% (P = 0.003). On active treatment all cardiac endpoints decreased by 26% (P = 0.03) and all cardiovascular endpoints by 31% (P < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, P = 0.07), but all-cause mortality was not influenced (-14%, P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age, and for total mortality it decreased with lower systolic BP at entry (P = 0.05). The benefits of active treatment were not independently related to sex or to the presence of cardiovascular complications at entry. The antihypertensive regimen was more effective in patients with diabetes than in those without diabetes at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. Active treatment reduced all strokes by 44% (P = 0.004), all cardiac endpoints by 26% (P = 0.05) and all cardiovascular endpoints by 32% (P < 0.001). Total mortality was reduced by 26% (P = 0.05), but a similar reduction in cardiovascular mortality did not reach statistical significance in this analysis. Compared with placebo, active treatment also reduced the incidence of dementia by 50%. Stepwise antihypertensive drug treatment, starting with the dihydropiridine calcium-channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension.


Size of Sentinel Node Metastasis Predicts Non-sentinel Node Involvement in Endometrial Cancer.
To analyze the relationship between the size of metastatic sentinel lymph nodes (SLNs) and the risk of non-sentinel lymph node (non-SLN) metastasis in endometrial cancer. From a total of 328 patients with endometrial cancer who underwent SLN mapping from January 2013 to April 2019, 142 patients also underwent systematic completion pelvic ± paraaortic node dissections, and they form the basis of this study. The SLNs were examined by immunohistochemistry (IHC) when the hematoxylin-eosin stain was negative. The median age was 60 years. The overall detection rate for SLNs was 87.5%, and bilateral SLNs were observed in 66.2%, with a median of 2 SLNs resected (range 1-8). Twenty-nine (20.4%) cases had positive SLNs, with a median of one positive SLN. Regarding the size of SLN metastasis, 5 (3.5%) cases had isolated tumor cells (ITCs), 13 (9.2%) had micrometastases, and 11 (7.7%) had macrometastases. Notably, 14/29 (48.3%) had node metastases that were detected after IHC. Eight (27.6%) patients had positive non-SLNs, with a median count of 7 positive nodes (range 2-23). Regarding the size of SLN metastasis, non-SLN involvement was not present in cases with ITC (0/5) but was present in 15.4% (2/13) of cases with micrometastases and 54.5% (6/11) of cases with macrometastases. The only risk factor for positive non-SLNs was the size of SLN metastasis. Our data suggest that size of SLN metastasis is associated with the risk of non-SLN metastasis. No patients with ITCs in SLNs had another metastatic lymph node in this study.


Honey bee microRNAs respond to infection by the microsporidian parasite Nosema ceranae.
In order to study the effects of Nosema ceranae infection on honey bee microRNA (miRNA) expression, we deep-sequenced honey bee miRNAs daily across a full 6-day parasite reproduction cycle. Seventeen miRNAs were differentially expressed in honey bees infected by N. ceranae that potentially target over 400 genes predicted to primarily involve ion binding, signaling, the nucleus, transmembrane transport, and DNA binding. Based on Enzyme Code analysis, nine biological pathways were identified by screening target genes against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, seven of which involved metabolism. Our results suggest that differentially expressed miRNAs regulate metabolism related genes of host honey bees in response to N. ceranae infection.


The Coupling Effect of O₂ and H₂S on the Corrosion of G20 Steel in a Simulating Environment of Flue Gas Injection in the Xinjiang Oil Field.
Flue gas injection for heavy oil recovery has received a great deal of attention, because it is more cost effective than lots of other injection methods. However, the corrosion could occur easily, because the flue gas usually contains corrosive gases such as CO₂, H₂S, and O₂. In this work, the corrosion behaviors of G20 steel in flue gas injection environment simulating Xinjiang oil field (China) were investigated using weight loss measurement and surface characterization techniques. The effect of environments including the O₂-containing environment, the H₂S-containing environment, and the O₂-H₂S-coexisting environment on the corrosion of G20 steel in gas phase and liquid phase was discussed. The results show that the corrosion rate of G20 steel in the O₂-H₂S-coexisting environment is much higher than the sum of corrosion rates of the O₂-containing environment and the H₂S-containing environment, regardless of the gas phase and the liquid phase. This indicates that there is a coupling effect between O₂ and H₂S, which can further accelerate the corrosion of steel in O₂-H₂S-coexisting environment. The results of surface characterization demonstrate that in a typical flue gas injection environment, the corrosion products are composed of FeCO₃, FeS, FeO(OH), and elemental sulfur. Elemental sulfur could obviously accelerate the corrosion of steel. Therefore, it can be considered that the coupling effect of O₂ and H₂S on corrosion of G20 steel in flue gas injection environment is caused by the formation of elemental sulfur in corrosion products.