CD200Fc reduces TLR4-mediated inflammatory responses in LPS-induced rat primary microglial cells via inhibition of the NF-κB pathway.
Based on recent information, CD200Fc, a CD200R1 agonist, could attenuate the inflammatory response of microglial cells in autoimmune diseases and neuro-degeneration. However, the exact molecular mechanisms responsible for the anti-inflammatory activity of CD200Fc in microglial cells have not been elucidated. In the present study, we investigated the anti-inflammatory effects and the molecular mechanisms of CD200Fc in lipopolysaccharide (LPS)-stimulated rat primary microglial cells. The cell viability was measured by MTT assay. The LPS-induced cytokines release (IL-1β, IL-6, TNF-α, iNOS, MCP-1, and COX-2) was monitored by ELISA or real-time PCR, while NF-κB-related signals (MyD88, p-TAK1, TRIF, p-TBK1, p-IRF3, p-IκB, and NF-κB-P65) were assessed by real-time PCR, western blot and/or Immunofluorescent staining. CD200Fc and/or LPS exerted no significant cytotoxicity on microglial cells. LPS reduced the CD200R1 expression in microglial cells, and this effect was attenuated by CD200Fc. In addition, CD200Fc inhibited LPS-induced expression of TLR4 and its adapter molecules (MyD88 and p-TAK1, TRIF, p-TBK1, and p-IRF3), and abolished its interactions with MyD88, TAK1, and TRIF in microglial cells. CD200Fc also attenuated LPS-induced protein expression of p-IκB and NF-κB-P65 translocation to nucleus in microglial cells. Moreover, CD200Fc suppressed the LPS-induced release of inflammatory mediators in microglial cells, including IL-1β, IL-6, TNF-α, iNOS, MCP-1, and COX-2. These results indicated that CD200Fc displayed an anti-inflammatory effect in LPS-induced microglial cells by blocking TLR4-mediated NF-κB activation.


COVID-19 behavior determinants dataset.
The COVID-19 Behavior Determinants Database (http://covid19-database.com) is a research project that examined the sociodemographic and psychological determinants of COVID-19 related attitudes and behaviors. It is a comprehensive web-based survey that was administered to adults ages 18 or older (total n=8070) from the United States of America (n = 5326), including the four most populous states, specifically New York, California, Florida, and Texas, and Canada (n = 2744), including all provinces, except Quebec. The survey was collected at three timepoints, May 2020 (n=1019), July 2020 (n=4027), and March 2021 (n=3024). Participants provided detailed sociodemographic information and completed a battery of psychological assessments. Participants also provided information about prior testing for COVID-19 and perceived seriousness of COVID-19 and the need for current physical (social) distancing restrictions. The database is helpful to researchers and public health policy decision-makers who are interested in investigating and identifying the determinants of COVID-19 related attitudes and behaviors in North America.


Analyses of specific and total antibody responses of rabbits to four kinds of immunogens.
As a basic study to investigate suitable conditions to immunize rabbits with drug-immunogens, two highly sensitive and accurate enzyme immunoassays (EIAs) for specific antibody to viomycin (VM) and blasticidin S (BLS) were developed using the corresponding standard antibody, the solid-phase antigens, and enzyme-labeled goat anti-rabbit immunoglobulin G (IgG) antibody as immunological reagents. The accuracy of the assay results with these newly developed EIAs was demonstrated. The new EIAs as well as two previously developed EIAs, EIA for antibody specific to neocarzinostatin (NCS) and a sandwich EIA for rabbit IgG, were applied for analyses of the changes in contents of total and specific antibodies in rabbit antisera samples collected during immunizations with four antigens. Total IgG levels increased from 7.0-9.9 mg/ml to 30-50 mg/ml in all rabbits immunized under the same immunizing schedule, despite the use of four kinds of antigens. The highest level of specific antibodies, anti-BLS, anti-VM and anti-NCS, was 0.5 mg/ml in each case.


Low cost, microprocessor-based system for flow evaluation in a hydraulic model using the dilution method.
An Automatic Dye Dilution Processor (ADP) based on a microprocessor is applied to a hydraulic model to process on-line dilution curves, using saline or thermodilution methods. A low cost, F8 microcomputer with minimum parts configuration was used in an Automatic Dilution Processor (ADP) system. Software allows an operator to select methods, amount of indicator to be injected, cell calibration constant, and temperature step. Care has been taken in the curve data processing, to avoid errors when recirculation occurs. The system is used, together with an open hydraulic model, for flow measurement demonstration, and the estimation of cell calibration constant.


Motor lumbosacral radiculopathy in HIV-infected patients.
This study is a review of the clinical findings and treatment outcome of 11 HIV-infected patients with motor lumbosacral radiculopathy. To describe the clinical, laboratory, electrophysiological features and treatment outcome in HIV-infected motor lumbosacral radiculopathy which is a rare manifestation of HIV. A retrospective review of HIV-infected patients with motor lumbosacral radiculopathy was performed at Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa between 2010 and 2015. Eleven black African patients met the inclusion criteria. There were six women. The median age was 29 years, the interquartile range (IQR) was 23-41 years, the median duration of symptom progression was 6.5 months (IQR 3-7.5 months). The median CD4 count was 327 cells/µL (IQR 146-457). The cerebrospinal fluid (CSF) median polymorphocyte count was 0 cells/µL (IQR 0 cells/µL - 2 cells/µL), lymphocyte count was 16 cells/µL (IQR 1 cells/µL - 18 cells/µL), glucose level was 3.1 mmol/L (IQR 2.8 mmol/L - 3.4 mmol/L) and protein level was 1.02 g/dL (IQR 0.98 g/dL - 3.4 g/dL). All patients were treated with corticosteroid therapy. Ninety-one per cent recovered fully within 6 months of treatment, the median time for recovery was 3.4 months (IQR 1.8-5.6 months). There were no relapses during the 18-month follow-up. HIV-infected patients with motor lumbosacral radiculopathy responded to corticosteroids, with no relapses during the 18-month follow-up period.


Extrahepatic biliary cystadenocarcinoma arising from the left hepatic duct.
A 54-year-old man, who had no clinical symptoms, underwent a routine health checkup at our hospital. Abdominal ultrasonography disclosed a well demarcated tumor containing a solid portion occupying the dilated left hepatic duct and a cystic portion expanding into the parenchyma of the left hepatic lobe, with mild dilatation of the intrahepatic bile ducts. These findings were later confirmed by computed tomography (CT) and magnetic resonance imaging. Endoscopic retrograde cholangiography revealed a complete defect at the level of the left hepatic duct, while drip infusion cholangiographic-CT (DIC-CT) disclosed a defect of the left hepatic duct only, with the distal portions of the left intrahepatic ducts being visualized on the image. Hepatic angiography revealed light stains in the solid portion in the parenchymal phase. At left lobectomy, a multiloculated polyp-like tumor was found arising from the left hepatic duct and expanding into the parenchyma of the left hepatic lobe. Microscopically, all the lining cells in the cysts and the tumor cells in the solid portion showed the features of papillary adenocarcinoma. In this patient with extrahepatic biliary cystadenocarcinoma, DIC-CT was useful in identifying the site of origin of the tumor, and hepatic angiography was also useful in differentiating this rare malignant tumor from benign cystadenoma.


ICP-MS determination of trace elements in aerosols using a dynamic reaction cell: first results in PM10 comparing road and aerial traffic in Nice area (France).
An analytical methodology was developed for the determination of 21 trace elements in suspended particulate matter (PM) using a microwave digestion procedure associated with an inductively coupled plasma mass spectrometry (ICP-MS). The dynamic reaction cell (DRC) of the instrument was carefully optimized to eliminate polyatomic species causing spectral interferences for three specified elements (Cr, Fe, Mn). With this method, the detection limits based on the analysis of seven quartz fibre filters (QFF) considering a one-week sample (250 m3) varied between 0.2 and 650 pg m(-3) for trace elements and between 2.1 and 5.6 ng m(-3) for major elements (Fe, Ti, Zn). The recovery of the analytes was tested with NIST SRM 1648 urban dust within 10% of the certified values only for 3-4 mg of material. The first results were discussed for a field campaign which was carried out simultaneously in the heaviest traffic road tunnel of the centre of Nice and near the landing-taking-off runways in the international airport of Nice Côte d'Azur. The behaviour of some combustion tracers was especially studied.


Mock circulatory loop generated database for dynamic characterization of pressure-based cardiac output monitoring systems.
Pulse contour cardiac output monitoring systems allow real-time and continuous estimation of hemodynamic variables such as cardiac output (CO) and stroke volume variation (SVV) by analysis of arterial blood pressure waveforms. However, evaluating the performance of CO monitoring systems to measure the small variations in these variables sometimes used to guide fluid therapy is a challenge due to limitations in clinical reference methods. We developed a non-clinical database as a tool for assessing the dynamic attributes of pressure-based CO monitoring systems, including CO response time and CO and SVV resolutions. We developed a mock circulation loop (MCL) that can simulate rapid changes in different parameters, such as CO and SVV. The MCL was configured to simulate three different states (normovolemic, cardiogenic shock, and hyperdynamic) representing a range of flow and pressure conditions. For each state, we simulated stepwise changes in the MCL flow and collected datasets for characterizing pressure-based CO systems. Nine datasets were generated that contain hours of peripheral pressure, central flow and pressure waveforms. The MCL-generated database is provided open access as a tool for evaluating dynamic characteristics of pressure-based CO algorithms and systems in detecting variations in CO and SVV indices. In an example application of the database, a CO response time of 10 s, CO and SVV resolutions with lower and upper limits of (-9.1%, 8.4%) and (-5.0%, 3.8%), respectively, were determined for a pressure-based CO benchtop system. This tool will support a more comprehensive assessment of pressure-based CO monitoring systems and algorithms.


Meningo-orbital band detachment: A key step for the extradural exposure of the cavernous sinus and anterior clinoid process.
The meningo-orbital band (MOB) is the most superficial dural band that tethers the fronto-temporal dura to the periorbita. It is usually encountered when performing a pterional or fronto-temporo-sphenoidal approach, and it disrupts surgical access to deeper regions. Our objective was to perform a detailed anatomy study and a stepwise method to successfully detach the MOB using cadaveric specimens. We used six formalin-fixed, silicone-injected cadaveric heads. On each side, we performed a pterional approach plus mini-peeling of the anterior third of the middle fossa and/or extradural anterior clinoidectomy. We also applied this technique in three clinical cases to prove its safety and efficacy. The detachment of the MOB consists in four steps, 1) detachment of the temporal and frontal dura, 2) cutting of the MOB, 3) exposure and drilling of the anterior clinoid process, and 4) pealing of the lateral wall of the cavernous sinus. Using clinical cases, we explain how to adapt the technique depending on the localization of the lesion. The detachment of the MOB is the key to safely expose the cavernous sinus and the anterior clinoid process. The authors proposed a step-by-step method for the safe and effective detachment of the MOB. It is recommended, particularly to less experienced neurosurgeons that are starting with skull base surgery, and also to experts that want to expand their knowledge.


Race, sex, and socioeconomic disparities affect the clinical stage of patients presenting for treatment of superficial venous disease.
Superficial venous disease has a U.S. prevalence of nearly 30%, with advanced disease contributing to a significant healthcare burden. Although the risk factors for venous disease are well known, the correlation between race, sex, socioeconomic status, and disease severity on presentation is not well established. The area deprivation index (ADI) is a validated metric with respect to regional geography, social determinants of health, and degree of socioeconomic disadvantage. In the present study, we aimed to identify the disparities and the effect that the ADI, in addition to race and sex, has among patients associated with an advanced venous disease presentation. A retrospective review between 2012 and 2022 was performed at four tertiary U.S. institutions to identify patients who underwent endovenous closure of their saphenous veins. Patient demographics, state ADI, comorbidities, CEAP (clinical, etiologic, anatomic, pathophysiologic) classification, and periprocedural outcomes were included. Pearson's correlation was performed between the CEAP classification and ADI. Poisson regression analysis was performed to identify factors predicting for an increasing CEAP classification at presentation. Variables with P < .05 were deemed significant. A total of 2346 patients underwent endovenous saphenous vein closure during the study period, of whom 7 were excluded because of a lack of follow-up data. The mean age was 60.4 ± 14.9 years, 65.9% were women, and 55.4% were White. Of the 2339 patients, 73.3% presented with an advanced CEAP class (≥3). The mean state ADI for the entire cohort was 4.9 ± 3.1. The percent change in the CEAP classification is an increase of 2% and 1% for every level increase in the state ADI for unadjusted (incidence rate ratio [IRR] = 1.02; P < .001) and adjusted (IRR = 1.01; P < .001) models, respectively. Black race has a 12% increased risk of a higher CEAP class on presentation compared with White race (IRR = 1.12; P = .005). Female sex had a 16% lower risk of a higher CEAP presentation compared with male sex (IRR = 0.84; P < .01). Low socioeconomic status, Black race, and male sex are predictive of an advanced CEAP classification on initial presentation. These findings highlight the opportunity for improved mechanisms for identification of venous disease and at-risk patients before advanced disease progression in known disadvantaged patient populations.


The continuing challenge of hepatic cancer in Asia.
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The number of new cases is estimated to be 564,000 per year. About 80% of all cases are found in Asia. The goal of HCC management is "cancer control"--a reduction in its incidence and mortality as well as an improvement in the quality of life of patients with HCC and their family. Overall, 80% of HCC can be attributed to chronic hepatitis B and C infection. Prevention of infection with hepatitis B and C virus is the key strategy to reduce the incidence of HCC in Asia. Liver resection and liver transplantation remain the options that give the best chance of a cure. In the past two decades, operative mortality and surgical outcome of liver resection and liver transplantation for HCC have improved. Progress also has been made in multi-modality therapy which can increase the chance of survival and improve the quality of life for patients with advanced HCC. Many challenges are still present in Asia, such as the high prevalence of chronic hepatitis, the low resection rate of HCC, the high postoperative recurrence and the severe shortage of cadaveric organ donor. This article aims to discuss the development and challenges in the prevention and management of HCC in Asia.


Evaluation of the prognostic value of lncRNA UCA1 combined with extravascular lung water index and lung ultrasound score in patients with acute lung injury.
Acute lung injury (ALI) is a common and rapidly developing critical inflammatory lung disease in clinic. This study investigated the predictive value of lncRNA UCA1, extravascular lung water index (EVLWI), and lung ultrasound score (LUS) in predicting the overall outcome of patients with ALI. Patients with ALI were recruited for detecting the content of UCA1, EVLWI, and LUS. All patients were cataloged into the survival group and death group according to the prognosis. The discrepancy of UCA1, EVLWI, and LUS was compared in the two groups. The prognostic significance of UCA1, EVLWI, LUS, and their combination was estimated by logistic regression and the receiver operating characteristic (ROC) curve. The levels of UCA1, LUS, and EVLWI were elevated in the death group compared with the survival group. The content of UCA1 was positively correlated with LUS scores and EVLWI scores. UCA1, LUS, and EVLWI were independent indicators of predicting the prognosis of patients with ALI. The ROC curve reflected that UCA1, LUS, and EVLWI could forecast the endpoint events of patients with ALI whereas their combined approach had the highest accuracy. Highly expressed UCA1 is a biomarker in forecasting the outcome of patients with ALI. It had high accuracy in predicting the endpoint of patients with ALI when combined with LUS and EVLWI.


Changes in the status of nucleolus during long-term culturing of human HeLa cells.
Changes in the immunocytochemical status of the nucleoli during long-term (6-8 months) in vitro culturing of HeLa (carcinoma of the cervix uteri) cells were described using new A3 monoclonal antibodies selectively reacting with human cell nucleoli. The appearance of cells with abnormal location of A3 antigen was paralleled by a significant increase of culture sensitivity to some external factors (protein synthesis inhibition and oxidative stress). The data indicate that location of one of the nucleolar antigens is an indicator of the qualitative status of HeLa cells in the culture.


The Relationships Among Autism Spectrum Disorder Traits, Loneliness, and Social Networking Service Use in College Students.
This study aimed to explore the relationships among autism spectrum disorder (ASD) traits, loneliness, and social networking services (SNS) use. We created a questionnaire to evaluate manners during LINE use, which included five factors: "low literacy," "inactive use," "low responsiveness," "lack of consideration," and "low group activity." Structural equation modeling revealed that difficulties in attention switching and low communication skills were associated with low literacy, low social skills were associated with inactive use, and low literacy and inactive use were associated with loneliness. We suggested that SNS use plays a role in maintaining and enhancing friendships, whereas college students with higher ASD traits tend to use inappropriate manners for SNS, which is associated with loneliness.


A novel measure of socioeconomic status using individual housing data to assess the association of SES with rheumatoid arthritis and its mortality: a population-based case-control study.
To assess whether HOUSES (HOUsing-based index of socioeconomic status (SES)) is associated with risk of and mortality after rheumatoid arthritis (RA). We conducted a population-based case-control study which enrolled population-based RA cases and their controls without RA. The study was performed in Olmsted County, Minnesota. Study participants were all residents of Olmsted County, Minnesota, with RA identified using the 1987 American College of Rheumatology criteria for RA from 1 January 1988, to 31 December 2007, using the auspices of the Rochester Epidemiology Project. For each patient with RA, one control was randomly selected from Olmsted County residents of similar age and gender without RA. The disease status was RA cases and their matched controls in relation to HOUSES as an exposure. As a secondary aim, post-RA mortality among only RA cases was an outcome event. The associations of SES measured by HOUSES with the study outcomes were assessed using logistic regression and Cox models. HOUSES, as a composite index, was formulated based on a summed z-score for housing value, square footage and number of bedrooms and bathrooms. Of the eligible 604 participants, 418 (69%) were female; the mean age was 56±15.6 years. Lower SES, as measured by HOUSES, was associated with the risk of developing RA (0.5±3.8 for controls vs -0.2±3.1 for RA cases, p=0.003), adjusting for age, gender, calendar year of RA index date, smoking status and BMI. The lowest quartile of HOUSES was significantly associated with increased post-RA mortality compared to higher quartiles of HOUSES (HR 1.74; 95% CI 1.10 to 2.74; p=0.017) in multivariate analysis. Lower SES, as measured by HOUSES, is associated with increased risk of RA and mortality after RA. HOUSES may be a useful tool for health disparities research concerning rheumatological outcomes when conventional SES measures are unavailable.


Regulatory and evolutionary roles of pseudo γ-butyrolactone receptors in antibiotic biosynthesis and resistance.
Bacteria modulate their physiological behavior by responding to various signal molecules. The signals are received by cognate receptors, which usually mediate transcriptional regulation. Streptomyces employ γ-butyrolactones (GBLs) and cognate GBL receptors (GblRs) to regulate secondary metabolism and morphological development. However, there are additional transcriptional regulators called pseudo GblR regulators, which cannot bind GBLs and are not directly associated with GBL synthase. The pseudo GblR regulators may act as transcriptional repressors and respond to antibiotic signals. They play regulatory roles in coordination of antibiotic biosynthesis by connecting the hormone feed-forward loops and the antibiotic feedback loops. As the TetR family members, they might also have evolutionary roles between the transcriptional regulators of quorum sensing and antibiotic resistance. Understanding the regulatory and evolutionary roles of the pseudo GblR family would be helpful for fine-tuning regulation of antibiotic biosynthesis and resistance.


Bumetanide inhibition of NaCl transport by Necturus gallbladder.
Salt transport by the Necturus gallbladder epithelium is the result of the coupled entry of NaCl into the cells across the apical membrane and the active transport of Na out of the cells across the basolateral membrane. The NaCl entry step was studied by measuring the rate of cell volume increase accompanying ouabain inhibition of the Na--K-ATPase in the basolateral membrane. When bumetanide, a diuretic analog of furosemide, was added to the mucosal bathing solution it reversibly blocked the entry of NaCl into the cells and abolished fluid transport. A dose-response relationship showed half-maximal inhibition of NaCl entry at a bumetanide concentration of 10(-9) M; complete inhibition of coupled NaCl movement occurred with as little as 10(-7) M bumetanide. Partial substitution of Na or Cl in the mucosal solution failed to demonstrate competition between bumetanide and either of the ions. The drug was also effective in blocking NaCl entry in the absence of ouabain; addition of the diuretic to the mucosal bathing solution resulted in prompt cell shrinkage and a decrease in intracellular NaCl. Cell volume decrease followed bumetanide addition to the mucosal bath because NaCl entry was blocked but active Na transport continued for several minutes until the intracellular Na transport pool was depleted.


Microbiome alterations from volatile organic compounds (VOC) exposures among workers in salons primarily serving women of color.
Salon workers, especially those serving an ethnically and racially diverse clientele (i.e., Black/Latina), may experience disparately high levels of workplace exposures to respiratory irritants, including volatile organic compounds (VOCs). Salon workers are also reported to have a greater risk of developing respiratory conditions compared to the general population. Emerging evidence suggests that occupational chemical exposures may alter the human microbiome and that these alterations may be an important mechanism by which workplace VOC exposures adversely impact respiratory health. This preliminary research investigated the potential effects of 28 VOC urinary biomarkers on the 16S rRNA nasal microbiome in 40 workers from salons primarily serving women of color (Black and Dominican salons) compared to office workers. Our exploratory analysis revealed significant differences in microbial composition by worker group; namely dissimilar levels of Staphylococcus species (S. epidermidis and S. aureus, specifically) in salon workers compared to office workers, and higher alpha diversity levels in workers in Dominican salons compared to workers in Black salons. Within-sample alpha diversity levels tended to be decreased with higher VOC urinary biomarker concentrations, significantly for carbon disulfide, acrolein, acrylonitrile, crotonaldehyde, and vinyl chloride biomarkers. Our research highlights that occupational exposures, particularly to chemicals like VOCs, can impact the respiratory microbiome in the vulnerable salon worker group. Further understanding of the potential effects of chemical mixtures on microbial composition may provide key insights to respiratory health and other adverse health outcomes, as well as direct prevention efforts in this largely historically understudied occupational population.


Using Single-Molecule FRET to Evaluate DNA Nanodevices at Work.
The observation of DNA nanodevices at a single molecule (i.e., device) level and in real time provides rich information that is typically masked in ensemble measurements. Single-molecule fluorescence resonance energy transfer (smFRET) offers a means to directly follow dynamic conformational or compositional changes that DNA nanodevices undergo while operating, thereby retrieving insights critical for refining them toward optimal function. To be successful, smFRET measurements require careful execution and meticulous data analysis for robust statistics. Here we outline the elemental steps for smFRET experiments on DNA nanodevices, starting from microscope slide preparation for single-molecule observation to data acquisition and analysis.


Real-world utilization patterns of intravenous immunoglobulin in adults with generalized myasthenia gravis in the United States.
To evaluate real-world utilization patterns of intravenous immunoglobulin (IVIg) among patients with generalized myasthenia gravis (gMG) over 3 years post-IVIg initiation. Patients with gMG who initiated IVIg treatment were identified from a United States claims database (Symphony Health's Integrated Dataverse [IDV]®, January 1, 2014 - December 31, 2019). The frequency of subsequent IVIg treatment and associated cost during the year post-IVIg initiation were analyzed. Usage patterns of IVIg and concomitant gMG treatments during the year preceding and 3 years post-IVIg initiation were compared. Among 1225 patients with gMG who initiated IVIg treatment, 706 patients (57.6%) received 1 to 5 IVIg treatment courses (intermittent IVIg users), and 519 patients (42.4%) received ≥6 IVIg treatment courses (chronic IVIg users) within the subsequent year. Mean annual medical cost per patient was nearly 2.5-fold higher for chronic vs. intermittent IVIg users ($161,478 vs. $64,888, p < 0.001). The proportion of patients using corticosteroids and nonsteroidal immunosuppressive treatments (NSISTs) was not reduced over the 3-year follow-up period following IVIg initiation, even for patients who continued annual chronic IVIg for 3 consecutive years post-initiation. Nearly half of patients with gMG received chronic and multiple IVIg treatment courses within the first year once initiating IVIg treatment, indicating higher usage than expected. For all IVIg initiators, the proportion of patients using corticosteroids and NSISTs did not decrease over 3 years despite IVIg initiation.


Correlated ATP-induced changes in membrane area and membrane conductance in single rat adipocytes.
In the past few years it has been shown that, like many other non-neuroendocrine cells, adipocytes possess a mechanism for triggered exocytosis. Endocytosis and exocytosis affect the plasma membrane surface area, which can be directly monitored with electrophysiological patch-clamp techniques by measuring membrane capacitance, a parameter linearly related to the plasma membrane area. In this study we used the whole-cell mode of the patch-clamp technique to measure changes in membrane capacitance to monitor the effect of extracellular adenosine triphosphate (ATP) on the dynamics of membrane area changes in single adipocytes. Experimental evidence shows that extracellular application of ATP (100 microM) increases membrane capacitance for 30 +/- 2%. In controls a significantly smaller increase of 3 +/- 2% was measured, which is due to a slow exocytic-endocytic membrane cycling rate of 0.3%/min. We found that ATP induces a transient increase in membrane current, temporally associated with the peak rate in membrane capacitance increase. These results show directly the presence of ATP-induced increase in membrane area correlated to the increase in membrane current in single adipocytes.


Genomic changes in spermatozoa of the aging male.
Modern society is witnessing a widespread tendency to postpone parenthood due to a number of socioeconomic factors. This ever-increasing trend relates to both women and men and raises many concerns about the risks and consequences lying beneath the natural process of aging. The negative influence of the advanced maternal age has been thoroughly demonstrated, while the paternal age has attracted comparatively less attention. A problematic issue of defining whether advanced paternal age can be considered an independent risk factor, not only for a man's fertility but also for the offspring's health, is represented by the difficulty, linked to reproductive studies, in characterizing the impact of maternal and paternal age, separately. Researchers are now trying to overcome this obstacle by directly analyzing the male germ cell, and emerging data prove this sperm-specific approach to be a valid tool for providing novel insights on the effects of aging on the spermatozoa and, thus, on the reproductive outcome of an aging male. The purpose of this chapter is to summarize most of what is known about the relationship between male aging and changes in the spermatozoa, giving special focus on the events occurring with age at the genomic level.


Posttraumatic stress, alcohol use, and alcohol use reasons in firefighters: The role of sleep disturbance.
Firefighters are at elevated risk for posttraumatic stress and alcohol use, with research indicating that individuals with posttraumatic stress are likely to use alcohol as a coping strategy. A behavioral mechanism of clinical relevance to these associations is sleep disturbance. Thus, it was hypothesized that higher posttraumatic stress and sleep disturbance would be associated with higher alcohol use and alcohol use coping reasons; and sleep disturbance would moderate the association between posttraumatic stress and alcohol use and alcohol use coping reasons. Participants included 639 urban career firefighters (93.6% male; 77.9% White; Mage = 38.5). Covariates included fire department years and occupational stress. Structural equation models were tested. Posttraumatic stress severity was significantly, positively associated with alcohol use severity and alcohol use coping reasons. Similarly, sleep disturbance severity was significantly, positively associated with alcohol use severity and alcohol use coping reasons. After accounting for covariates and main effects, the interaction of PTSD severity and sleep disturbance was significantly associated with alcohol use severity, with the model accounting for 23.6% of variance, and alcohol use coping reasons, with the model accounting for 37.6% of variance. As predicted, the interaction of posttraumatic stress severity and sleep disturbance was not significantly associated with alcohol use enhancement, conformity, or social reasons. These findings indicate that posttraumatic stress severity is related to heightened alcohol use severity and alcohol use coping reasons, and this association is markedly stronger when firefighters' levels of sleep disturbance are heightened. Clinical and research implications are to be discussed.


Reliability and validity of the Malay version of the International Prostate Symptom Score in the Malaysian population.
We validated the Malay version of the International Prostate Symptom Score in patients with and without urinary symptoms in the Malaysian population. Validity and reliability were studied in patients with and without lower urinary tract symptoms. Reliability was evaluated using the test-retest method and internal consistency was assessed by Cronbach's alpha. Sensitivity to change was expressed as the effect size in the pre-intervention versus post-intervention score in additional patients with lower urinary tract symptoms who underwent transurethral prostate resection. Internal consistency was excellent. A high degree of internal consistency was observed for each of the 7 items and for the total score (Cronbach's alpha 0.53 and greater, and 0.68, respectively). The test-retest correlation coefficients of the 7 items were highly significant. The intraclass correlation coefficient was high at 0.51 and greater. There was a high degree of sensitivity and specificity to the effects of treatment. Significant change from baseline to posttreatment scores was observed in all 8 items in the treated but not in the control group. The Malay International Prostate Symptom Score is a suitable, reliable, valid instrument that is sensitive to clinical change in the Malaysian population.


Alternatives to Transfusion.
We discuss two main categories of blood substitutes: perfluorocarbons and hemoglobin-based oxygen carriers. We provide a review of the notable products developed in both categories and include their attributes as well as their setbacks. We contribute a case report tothe growing literature of the successful use of Sanguinate. We find that artificial oxygen carriers are an attractive field of research because of the practical limitations and the multitude of potential complications that surround human blood transfusions.


Globular adiponectin inhibits GnRH secretion from GT1-7 hypothalamic GnRH neurons by induction of hyperpolarization of membrane potential.
Reproduction is accurately regulated by metabolic states in mammals. Adiponectin regulates luteinizing hormone (LH) secretion in the pituitary and energy homeostasis in the hypothalamus. We further investigated the gonadotropin-releasing hormone (GnRH) secretion regulation by adiponectin and its related molecular and electrophysiological mechanisms. The results showed that adiponectin receptors (AdipR1 and 2) were expressed in GT1-7 cells derived from hypothalamus neurons. GnRH secretion was inhibited via activation of AMP-activated protein kinase (AMPK). Moreover, we revealed that hyperpolarization of plasma membrane potentials and reduction of calcium influx was also caused by adiponectin.


Isolation of Microvesicles from Plasma Samples Avoiding Lipoprotein Contamination.
Dengue is an infectious disease caused by Dengue Virus, mainly transmitted by Aedes aegypti mosquitoes. Severe dengue is a potentially fatal syndrome in consequence of overwhelmed inflammation, in which thrombocytopenia and increased vascular permeability are frequently observed. Several experimental evidences point to the participation of both microvesicles (MVs) and circulating lipoproteins in inflammatory amplification in dengue pathogenesis. On this regard, many protocols for isolating plasma MVs have shown lipoproteins as the main contaminant. This is a limitation to studies aiming at the functional characterization of MVs, since both MVs and lipoproteins can modulate inflammatory responses. Here, we describe a biphasic density-based gradient ultracentrifugation as a tool for concomitant isolation of MVs and lipoproteins without cross-contamination. Flow cytometry for MVs quantification and western blot for detection of apoB100 may be used to confirm the isolation and purity of the MVs.


Exploring Factors Associated With Long-Term Opioid Therapy in Cancer Survivors: An Integrative Review.
The prevalence of chronic pain in cancer survivors is double that of the general U.S. Opioids have been the foundation of cancer pain management for decades; however, there is a paucity of literature on long-term opioid therapy (LTOT) in cancer survivors. An understanding of factors related to LTOT use in cancer survivors is needed to address chronic pain and balance opioid harms in the expanding population of cancer survivors. To analyze the research of LTOT utilization and factors associated with persistent opioid use in cancer survivors. A five-stage integrative review process was adapted from Whittemore and Knafl. Data sources searched included Web of Science, PubMed, Embase, Cochrane, and Google Scholar. Quantitative research studies from 2010 to present related to cancer survivors managed on LTOT were included. Editorials, reviews, or abstracts were excluded. After reviewing 315 articles, 21 articles were included. We found that there were several definitions of LTOT in the reviewed studies, but the duration of opioid use (i.e., more than three months after completion of curative treatment) was the most common. The reviewed literature describes a relationship between LTOT and important biopsychosocial factors (cancer type, socioeconomic factors, and comorbidities). The studies in this review shed light on the factors associated with LTOT in cancer survivors. LTOT was common in certain populations of cancer survivors and those with a collection of patient-specific characteristics. This review suggests that there is a critical need for specialized research on chronic cancer pain and opioid safety in cancer survivors.


Physical parameters of chlorphenamine maleate suppositories and its release as a function of particle size, concentration and nature of the base.
Suppositories of chlorphenamine maleate were formulated. The influence of particle size and percentage concentration of chlorphenamine maleate on the physical standards of its suppositories as well as the release of the drug from oily base (cacao butter), water-soluble base (carbowax) and emulsifying base (Witepsol) has been investigated.


Protective Role of Aerobic Exercise Against Cisplatin-Induced Nephrotoxicity in Rats.
Cisplatin (CP) is a chemotherapy drug and nephrotoxicity is considered as its major side effect. Aerobic exercise is well known as an approach to reduce the side effects of many drugs. This study was designed to determine the protective role of aerobic exercise against CP-induced nephrotoxicity. Thirty male Wistar rats were randomly divided into four groups. Group I had aerobic exercise on a treadmill one hour per day and five days per week for eight weeks. Then, the exercise protocol was continued for another week, but during this week, the animals also received CP (2.5 mg/kg/day; ip). Group II underwent the same protocol as group I without exercise in the last week during the CP therapy. Groups III and IV were assigned as positive and negative control groups, and were treated with CP and saline without exercise, respectively. Finally, the animals were sacrificed for the biochemical measurement and tissue histopathology investigation. CP alone without exercise increased serum levels of blood urea nitrogen (BUN), creatinine (Cr), and malondialdehyde (MDA); and kidney nitrite level, while treadmill exercise in group I significantly ameliorated these parameters (P < 0.05). Kidney and serum levels of MDA and nitrite did not alter significantly. Also, the severity of kidney tissue damage decreased significantly in groups I and II (P < 0.05). Aerobic exercise may reduce CP-induced nephrotoxicity with a favorable effect on renal function by increasing activation of antioxidant system.


Orifice Areas of Balloon-Expandable Transcatheter Heart Valves: A Three-Dimensional Transesophageal Echocardiographic Study.
Accurate expected effective orifice area (EOA) values for balloon-expandable (BE) transcatheter heart valves (THV) are crucial for preventing patient-prosthesis mismatch (PPM) and assessment of THV function. Currently published reference EOAs, however, are based on transthoracic echocardiography (TTE), which may be subject to left ventricular outflow tract diameter underestimation and/or suboptimal THV Doppler interrogation. The objective of this study was to establish reference EOA values for BE THVs on the basis of Doppler and three-dimensional (3D) transesophageal echocardiography (TEE). Two hundred twelve intraprocedural transesophageal echocardiographic examinations performed during BE THV implantation with optimal postimplantation Doppler and 3D imaging were retrospectively reviewed. Continuity equation-derived EOAs were compared with geometric orifice areas by 3D planimetry (GOA3D). Performance indices (i.e., EOA normalized to valve size) and PPM rates were determined. TTE-based EOAs obtained within 30 days were also calculated in a subset of 170 patients. The average EOA for all BE THV valves (77% SAPIEN 3) was 2.3 ± 0.5 cm2, while the average EOA was 1.6 ± 0.2 cm2 for 20-mm, 2.0 ± 0.2 cm2, for 23-mm, 2.5 ± 0.3 cm2 for 26-mm, and 3.0 ± 0.3 cm2 for 29-mm THV size (P < .001). Bland-Altman analysis demonstrated very good agreement between EOA and GOA3D (bias -0.04 ± 0.15 cm2). There were strong correlations between annular area and TEE-based EOA (R = 0.84) and GOA3D (R = 0.87). The mean performance index was 47 ± 5% and was similar for all THV sizes (P = .21). EOAs based on TTE were smaller compared with those based on TEE, while the correlation with annular area (R = 0.67) and agreement with GOA3D (bias -0.26 ± 0.43 cm2) was not as strong. The overall PPM rate was 2% in the TEE cohort and 12% in the TTE cohort. EOAs for BE THVs based on intraprocedural Doppler and 3D TEE suggest that previously published TTE-based reference values for EOA are underestimated, while PPM rates may be overestimated. Our findings have important clinical implications for preimplantation decision-making and for the evaluation of THV hemodynamics and function during follow-up.


Intercalative and nonintercalative binding of large cationic porphyrin ligands to polynucleotides.
The interactions of two positional isomers and one analogue of meso-tetra (4-N-methylpyridyl) porphine, with the synthetic polynucleotides poly[d(A-T)] . poly[d(A-T)] and poly[d(G-C)] . poly[d(G-C)] have been investigated by circular dichroism. All four porphyrins were found to bind to the polynucleotides as shown by the induction of circular dichroism in their Soret bands. Furthermore, the sign of the induced ellipticity reflects selective occupation of binding sites by the porphyrin ligands. The conformational lability of poly[d(A-T)] X poly[d(A-T)] was found to be appreciable as micromolar amounts of meso-substituted 4-N-methylpyridyl, 3-N-methylpyridyl, and p-N-trimethylanilinium porphines induced a CD spectrum similar but not identical to that of DNA in the Z-form, i.e. a negative band at 280 nm and a positive band at 259 nm. The effect of porphyrin binding to poly[d(G-C)] X poly[d(G-C)] was less pronounced and dissimilar to that seen in the AT polymer.


Muscle inflammation induces a protein kinase Cepsilon-dependent chronic-latent muscle pain.
Skeletal muscle injuries can induce chronic pain, but the underlying mechanism is unknown. One possible cause has been suggested to be an increased sensitivity to inflammatory mediators. We demonstrate that self-limited inflammatory hyperalgesia induced by intramuscular carrageenan (lasting approximately 5 days) results in a state of chronic-latent hyperalgesia, revealed by injection of prostaglandin E(2) (PGE(2)) 10 days after carrageenan at the same site. In carrageenan-pretreated muscle, PGE(2) produced hyperalgesia that was unattenuated even 14 days after injection, markedly longer than the 4-hour hyperalgesia induced by PGE(2) in naive rats. This chronic-latent hyperalgesia was reversed as well as prevented by spinal intrathecal injection of oligodeoxynucleotide antisense to protein kinase Cepsilon, a second messenger implicated in long-lasting plasticity in cutaneous nociceptors. We describe a novel experimental model for chronic muscle pain, produced by mild acute muscle inflammation, that has clinical significance since it has the potential to reveal cellular processes by which acute inflammation or muscle trauma underlies chronic muscle pain.


Development of a routine method for the simultaneous confirmation and determination of clenbuterol in urine by minimal labeling isotope pattern deconvolution and GC-EI-MS.
A novel and fast routine method for the simultaneous determination and confirmation of clenbuterol in bovine and human urine samples by gas chromatography electron ionization mass spectrometry (GC-EI-MS) has been developed. The method employs isotope dilution mass spectrometry (IDMS) and is based on a combination of minimal labeling (a single (13)C label in the molecule) and isotope pattern deconvolution (IPD). This new methodology does not require the construction of a methodological calibration graph, and was compared with the classical IDMS procedure employed in clenbuterol analysis based on the use of a deuterated compound as internal standard (d(9)-clenbuterol) and a calibration curve. The sample preparation consists of simple extraction with dichloromethane, which was dried and derivatized with chloro(chloromethyl)dimethylsilane, generating a cyclic dimethylsilamorpholine (DMS) derivative suitable for GC(EI)MS detection and identification. This compound produces five intense ions in the electron ionization source, which allow the presence of clenbuterol to be confirmed in just one analysis, as demanded by European Union directives. The accuracy of the method was studied by performing recovery experiments at different concentration levels (from 0.3 to 5 ng g(-1)) in 5 mL bovine urine samples using two labeled compounds: an in-house-synthesized (13)C(1)-clenbuterol and a commercially available d(9)-clenbuterol. The detection limit of the method in human urine was 0.050 ng g(-1) with a sample volume of 10 mL, and is thus suitable for antidoping control purposes. Finally, the (13)C(1)-clenbuterol standard was employed for the determination of clenbuterol in two reference materials, BCR-503 and BCR-504 (lyophilized bovine urine). The concentrations obtained were in agreement with the certified values, with a reproducibility of below 1% RSD.


Image compression for medical imaging systems.
The physical size of typical digital images, in terms of the number of bytes of data one image contains, is large; e.g., a 1024 X 1024 image with 8 bits of data per pixel contains a megabyte of data. To transmit many such images over a network, sometimes over low-capacity phone lines to remote sites, or to store large numbers of images over a long period of time as part of the medical records for patients, the need for image compression arises to alleviate these large demands for image data storage and transmission capacity. This paper discusses image compression in terms of the information theory upon which it is based. The two basic categories of algorithms for implementing image compression are presented along with considerations for image quality and accuracy, which are of primary importance to the medical imaging community.


Effects of intracellular calcium chelation on voltage-dependent and calcium-dependent currents in cat neocortical neurons.
Large neurons from layer V in a slice preparation of cat sensorimotor cortex were impaled with microelectrodes containing KCl plus different concentrations of the Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA) or two of its derivatives. Impalement with electrodes containing high BAPTA (200 mM) quickly abolished Ca(2+)-dependent afterhyperpolarizations. Spike parameters were normal, but the usual time- and voltage-dependent rectification of subthreshold membrane potential was absent. Normally, this rectification results from activation of two voltage-gated currents, the persistent sodium current (INaP) and the hyperpolarizing inward rectifier current (Ih). Both of these currents were absent during voltage clamp with high BAPTA microelectrodes. Impalement with electrodes containing low BAPTA (2 mM) or derivatives caused a different effect. Injection of a 1-s current pulse evoked phasic firing instead of the tonic firing seen normally. Both the amplitude and the duration of the Ca(2+)-dependent afterhypolarization that followed repetitive firing were much greater than normal. The effectiveness of BAPTA derivatives in altering afterhyperpolarizations and firing properties were similar to their effectiveness in chelating Ca2+. It is assumed that the BAPTA effects result from reduction of intracellular Ca2+ concentration. Results with high BAPTA suggest that (i) both INaP and Ih require a minimal intracellular calcium concentration for normal expression, and that (ii) these voltage-gated currents may be modulated by changes in intracellular calcium concentration. Results with low BAPTA suggest that a small reduction of intracellular calcium concentration preferentially enhances a slow, Ca(2+)-dependent K+ current which then dominates the firing properties of the cell. The transformed firing properties resemble those of hippocampal pyramidal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)


Frequent and histological type-specific inactivation of 14-3-3sigma in human lung cancers.
One isoform of the 14-3-3 family, 14-3-3sigma, plays a crucial role in the G2 checkpoint by sequestering Cdc2-cyclinB1 in the cytoplasm, and the expression of 14-3-3sigma is frequently lost in breast cancers. This loss of expression is thought to cause a G2 checkpoint defect, resulting in chromosomal aberrations. Since lung cancers frequently carry numerous chromosomal aberrations, we examined the DNA methylation status and expression level of the 14-3-3sigma gene in 37 lung cancer cell lines and 30 primary lung tumor specimens. We found that small cell lung cancer (SCLC) cell lines frequently showed DNA hypermethylation (9 of 13 lines, 69%), and subsequent silencing of the 14-3-3sigma gene. Among non-small cell lung cancers (NSCLC), large cell lung cancer cell lines showed frequent hypermethylation and silencing of 14-3-3sigma (4 or 7 lines, 57%). In contrast, in other NSCLC cell lines, hypermethylation occurred very rarely (1 of 17 lines, 6%). All eight primary SCLC specimens examined also showed a loss or significant reduction in 14-3-3sigma expression in vivo, while a loss or reduction of 14-3-3sigma expression was very rare in primary NSCLC specimens (1 of 22 tissues, 5%). This is the first description that indicates lung cancers frequently show significant inactivation of the 14-3-3sigma gene mainly due to DNA hypermethylation in SCLC, but rarely in NSCLC, suggesting involvement of the 14-3-3sigma gene in lung tumorigenesis in a histological type-specific manner.


The management of otitis externa: a randomised controlled trial of a glycerol and icthammol ribbon gauze versus topical antibiotic and steroid drops.
We compared the use of glycerol and icthammol (G&I) ribbon gauze versus topical antibiotic and steroid drops in the management of otitis externa. Patients presenting with acute otitis externa were systematically recruited from attendance in the ENT emergency clinic. Exclusion criteria were age <18 years, diabetic patients, and those who had been previously treated for otitis externa by the department within the last month. A total of 43 patients were recruited with 48 infected ears, the mean patient age was 47 years, (range 18-80 years). Patients were randomised to either insertion of a G&I ribbon gauze or topical ear drops by means of a ballot with no stratification. All patients were reviewed 5 days later. Patients were asked to comment on their pain using the ten point visual analogue pain score. Oedema of the canal wall, presence of debris and visibility of the tympanic membrane were graded on microscopy. Patient satisfaction and return to work were assessed. There was a statistically significant decrease in the pain score between each visit for the entire group of patients and decrease in canal wall swelling (P < 0.001). There was no significant difference between drops and ribbon gauze in terms of pain relief, canal wall oedema, or aural discharge. Following microbiological analysis, 27.8% of bacteria were resistant to neomycin. The cost of treatment with G&I is less than a third of that for topical antibiotic-steroid drops and requires less patient compliance. Patient concerns with the ribbon gauze included its cosmetic appearance and loss of hearing and with drops included frequency of application. We recommend the use of G&I ribbon gauze as first-line treatment, particularly for those who have had allergies to carriers of drops, those that are poorly compliant or with poor manual dexterity, for example patients with rheumatic hands.


Laboratory growth rates of six species of freshwater Gymnamoebia.
Laboratory growth rates of six species of Gymnamoebia, isolated from English chalk streams and cultured on bacteria, have been determined at four different temperatures. Generation times ranged from 4.46 to 33.3 h. A linear relationship between log10 specific growth rate and the reciprocal of the absolute temperature was demonstrated for four species. A significant regression of log10 generation time on log10 cell volume was obtained for data on amoebae in combination with data on ciliates taken from the literature. This regression may be used to predict the growth rates of other species of amoebae and ciliates of known cell volume.


What is the frequency of floor of the mouth lesions? A descritive study of 4,016 cases.
The aim of this study was to investigate the frequency of oral lesions in the floor of the mouth from representative oral pathology centres in Latin America. This study was conducted on biopsies obtained from January of 1978 to December of 2018 at nine Latin America oral and maxillofacial pathology centres. Gender, age and histopathological diagnosis were evaluated. Data were analysed using descriptive methods. Chi-square test was used for pairwise comparisons. From 114,893 samples, 4,016 lesions (3.49%) occurred in the floor of the mouth. Brazil showed 3,777 cases (94%), Mexico 182 cases (4.5%) and Argentina 57 cases (1.4%). Benign lesions represented 65.1% (2,617 cases), followed by 34.9% (1,404 cases) of malignant disorders. Lesions of epithelial origin were more frequent (1,964 cases; 48.9%), followed by salivary glands (1,245 cases; 31%) and soft tissue lesions (475 cases; 11.7%). The most common histological subtypes were oral squamous cell carcinoma (1,347 cases; 33.5%), ranula (724 cases; 18%), oral leukoplakia (476 cases; 11.8%) and inflammatory fibrous hyperplasia (239 cases; 5.9%). The lesion affected males in 2,129 cases and females in 1,897 cases. In the current study, lesions in the floor of the mouth represented 3.49% of biopsies submitted to oral pathology services and oral squamous cell carcinoma, ranula and leukoplakia were the most common lesions.


Cutaneous surgery under local anesthesia in very elderly patients 90 years of age and older is as safe as in elderly patients ranging in age from 75 to 80 years old.
The number of very elderly patients who require surgery for cutaneous tumors is increasing. However, there is limited information on the safety of cutaneous surgery in such patients. To evaluate the safety of cutaneous surgery in patients 90 years of age and older, we retrospectively reviewed the elderly patients who underwent surgery for cutaneous tumors under local anesthesia. Consecutive patients 90 years of age and older and 75-80 years old were included in the elderly group and the control group. The elderly and control groups included 104 and 106 patients, respectively. The mean age of the patients was 93.4 years (range, 90-101 years) in the elderly group and 77.4 years (range, 75-80 years) in the control group. The preoperative performance status was significantly worse in the elderly group than in the control group (P < 0.001). The surgical time was not significantly different between the two groups (P = 0.09). The occurrences of intraoperative and postoperative complications were not significantly different between the two groups (P = 0.19 and P = 0.07, respectively). The result of the present study indicates that cutaneous surgery for very elderly patients 90 years of age and older is as safe as for patients ranging in age from 75-80 years old.


The amylase creatinine clearance ratio in acute pancreatitis.
One hundred and twenty-two patients have been studied in order to evaluate the usefulness of the amylase creatinine clearance ratio (ACCR) as a simple diagnostic test for acute pancreatitis. Sixteen out of 17 patients with acute pancreatitis had significant elevations in ACCR; in only 10 of these 17 cases was the serum amylase greater than 1200iu/l. The mean ACCR was within the normal range in control patients, in patients with chronic gastro-intestinal disease and in patients with acute abdominal conditions excluding pancreatitis; however, the mean serum amylase was significantly greater in patients with acute abdominal conditions than in the control group (P less than 0-05). The ACCR remained significantly elevated in patients with acute pancreatitis for longer than either serum or urine amylase values. The findings of the study suggest that the amylase creatinine clearance ratio is a simple yet reliable diagnostic test which could be used when screening patients suspected of having acute pancreatitis.


The use of external fixation in complex trauma of upper limb.
From 1997 to 2003 (7 years follow-up) we treated 33 complex traumas of the upper limbs with the use of external fixation: forearm or humeral complete amputation, complex crash, sometimes with hand crash associated. Often a revascularisation was necessary like as a secondary skin coverage for soft tissue loss or following ischaemic necrosis. Three patients were reluctant to agree to a secondary amputation for large soft tissue necrosis and infection. A high percentage of cases need a successive operation because of bone non-union. Revision of our casistic helps us answer the following: how complex and long is the prognosis of this kind of patient, which are the most important choices we have to make, how important is the length of time taken to make a decision and what are the weak spots in the treatment of these traumas.


Heart-rate correlates of childhood activities: play, exploration, problem-solving and day-dreaming.
Heart-rate was monitored while children were engaged in different activities. The first study examined the hypothesis that the behavioural distinction between exploration and play would be supported by the psychophysiological measure. Two-year-olds showed suppression of heart rate variability (HRV) during exploration, and even more during solution of a puzzle, suggesting that the task demands these two activities were greater than those during play. The second study demonstrated a relationship between HRV during daydreaming and during problem solving in 9-year-old children which was similar to that obtained between play and problem solving in younger children. The correlative use of HRV thus strengthened functional interpretations of behaviour.


Structurally diverse coumarin-homoisoflavonoid derivatives with hepatoprotective activities from the fruits of Cucumis bisexualis.
Cucumis bisexualis is a favorite wild fruit with high nutritional and medicinal values because of its bioactive constituents. Four previously undescribed coumarin-homoisoflavonoid derivatives (1-4), together with seven known coumarin and homoisoflavonoid derivatives (5-11) were isolated from the fruits of C. bisexualis for the first time. All the compounds were elucidated by their extensive and comprehensive spectroscopic data and references. Compounds (1-11) were evaluated for their hepatoprotective activities in HepG2 cells by the acetaminophen (APAP)-induced damage model at 10.0 μM with bicyclol as the positive control. Among them, compounds 1, 3, 5, and 6 showed moderately hepatoprotective activities to improve the HepG2 cell survival rates from 51.68 ± 2.49% (APAP, 10 mM) to 71.55 ± 4.08%, 65.95 ± 4.39%, 60.77 ± 3.44%, 62.94 ± 2.30%, respectively.


Chlorinated emodin as a natural antibacterial agent against drug-resistant bacteria through dual influence on bacterial cell membranes and DNA.
The rise in infections caused by drug-resistant pathogens and a lack of effective medicines requires the discovery of new antibacterial agents. Naturally chlorinated emodin 1,3,8-trihydroxy-4-chloro-6-methyl-anthraquinone (CE) from fungi and lichens was found to markedly inhibit the growth of Gram-positive bacteria, especially common drug-resistant bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). CE was confirmed to cause significant potassium leakage, cell membrane depolarization and damage to the selective permeability of cell membranes in bacterial cells, resulting in bacterial cell death. In addition, CE was shown to have a strong electrostatic interaction with bacterial DNA and induce DNA condensation. Thus, CE is a promising natural antibacterial pharmacophore against Gram-positive bacteria, especially common drug-resistant MRSA and VRE isolates, with a dual antibacterial mechanism that damages bacterial cell membranes and DNA.


Chlamydia trachomatis inhibits apoptosis in infected cells by targeting the pro-apoptotic proteins Bax and Bak.
Apoptosis acts in defense against microbial infection, and many infectious agents have developed strategies to inhibit host cell apoptosis. The human pathogen Chlamydia trachomatis (Ctr) is an obligate intracellular bacterium that strongly inhibits mitochondrial apoptosis of its human host cell but there is no agreement how the bacteria achieve this. We here provide a molecular analysis of chlamydial apoptosis-inhibition in infected human cells and demonstrate that the block of apoptosis occurs during the activation of the effectors of mitochondrial apoptosis, Bak and Bax. We use small-molecule Bcl-2-family inhibitors and gene targeting to show that previous models cannot explain the anti-apoptotic effect of chlamydial infection. Although the anti-apoptotic Bcl-2-family protein Mcl-1 was strongly upregulated upon infection, Mcl-1-deficient cells and cells where Mcl-1 was pharmacologically inactivated were still protected. Ctr-infection could inhibit both Bax- and Bak-induced apoptosis. Apoptotic Bax-oligomerization and association with the outer mitochondrial membrane was reduced upon chlamydial infection. Infection further inhibited apoptosis induced conformational changes of Bak, as evidenced by changes to protease sensitivity, oligomerization and release from the mitochondrial porin VDAC2. Mitochondria isolated from Ctr-infected cells were protected against the pro-apoptotic Bcl-2-family proteins Bim and tBid but this protection was lost upon protease digestion. However, the protective effect of Ctr-infection was reduced in cells lacking the Bax/Bak-regulator VDAC2. We further found that OmpA, a porin of the outer membrane of Ctr, associated upon experimental expression with mitochondria and inhibited apoptosis, phenocopying the effect of the infection. These results identify a novel way of apoptosis inhibition, involving only the most downstream modulator of mitochondrial apoptosis and suggest that Chlamydia has a protein dedicated to the inhibition of apoptosis to secure its survival in human cells.


Effects of alfalfa particle size and starch content in diets on feeding behaviour, intake, rumen parameters, animal performance and meat quality of growing lambs.
Thirty-two crossbred Merino branco male lambs were randomly allocated to eight diets, combining two forms of alfalfa presentation (chopped or ground), with four barley grain levels (0%, 11.2%, 21.3% and 33% dry matter (DM)), balanced by low starch agro-industrial by-products (LSBP). The diets were supplemented with 6% soybean oil and included 40% of alfalfa in DM. The lambs were individually housed and the trial lasted six weeks. Intake of DM, average daily weight gain (ADG) and carcass weight were higher with ground alfalfa (P < 0.01). Replacing barley grain by LSBP reduced linearly DM intake and ADG (P < 0.001) but increased meat tenderness (P = 0.046). Regardless of the treatments, meat showed a healthy biohydrogenation fatty acid (FA) profile, with high proportions of t11-18:1, c9,t11-18:2 and a t10-18:1/t11-18:1 ratio clearly below 1. The reduction of barley in diet had a moderate positive impact on meat FA composition, decreasing t10-18:1, which was enhanced by the increase of forage particle size.


Food foreign body injuries.
The purpose of this study is to acquire a better understanding of Food Foreign Bodies (FFB) injuries in children characterizing the risk of complications and prolonged hospitalization due to food items according to patients' characteristics, circumstances of the accident, Foreign Body (FB) features and FB location, as emerging from the SUSY Safe Web-Registry. The present study uses data provided by the SUSY Safe Project, a DG SANCO co-funded project started in February 2005, which was aimed at establishing an international registry of cases of Foreign Bodies (FB) injuries in children aged 0-14 years. The analysis was carried out on injuries due to a food item. FB location was reported according to ICD9-CM code: ears (ICD931), nose (ICD932), pharynx and larynx (ICD933) trachea, bronchi and lungs (ICD934), mouth, esophagus and stomach (ICD935). Age and gender injury distributions were assessed. Data regarding adult supervision and activity before injury were also evaluated. FBs which most frequently cause complications were identified. The association between children age, adult presence, object characteristics and hospitalization/complications was computed using unweighted odds ratios and the related 95% confidence intervals. 16,878 FB injuries occurred in children aged 0-14 years have been recorded in the SUSY Safe databases. FB type was specified in 10,564 cases; among them 2744 (26%) were due to a food item. FB site was recorded in 1344 cases: FB was located in the ears in 99 patients, while 1140 occurred in the upper and lower respiratory tract; finally, 105 food items were removed from mouth, esophagus and stomach. Complications occurred in 176 cases and the most documented was pulmonary or bronchial infections (23%) followed emphysema or atelectasis and by and asthma (7%). Bones were the commonest retrieved FFB encountered in this study, while nuts seem to be the FFB most frequently associated to complications. On the basis of this study we make the strong recommendation that parents should be adequately educated and provide age-appropriate food to their children and be present in order to supervise them during eating especially during a critical period ranging from 2 to 3 years of age.


Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells.
Cytotoxic T-Lymphocytes (CTLs) kill pathogen-infected or transformed cells following interaction of their T-cell receptors (TCRs) with foreign (e.g. virus-derived) peptides bound to MHC-I molecules on the target cell. TCR binding triggers CTLs to secrete perforin, which forms pores in the target cell membrane, promoting target death. Here, we show that by conjugating drug-loaded lipid nanoparticles to the surface of CTLs, their lytic machinery can be co-opted to lyse the cell-bound drug carrier, providing triggered release of drug cargo upon target cell recognition. Protein encapsulated in T-cell-bound nanoparticles was released following culture of CTLs with target cells in an antigen dose- and perforin-dependent manner and coincided with target cell lysis. Using this approach, we demonstrate the capacity of HIV-specific CTLs to deliver an immunotherapeutic agent to an anatomical site of viral replication. This strategy provides a novel means to couple drug delivery to the action of therapeutic cells in vivo.


Multiple mRNA species with distinct 3' termini are transcribed from the beta 2-microglobulin gene.
beta 2-Microglobulin is the small, relatively invariant subunit of a family of cell-surface glycoproteins encoded within the major histocompatibility complex (MHC). Proteins associated with beta 2-microglobulin in the mouse include the classical transplantation antigens (H-2K, D and L), the thymus leukaemia antigen (TL) and certain haematopoietic cell differentiation antigens (Qa-1 and Qa-2). The genes encoding these proteins are members of a large, multigene family. In contrast, beta 2-microglobulin is encoded by a single copy gene on mouse chromosome 2 (refs 5, 6). We have shown that this gene consists of four coding blocks separated by three intervening sequences. We now demonstrate that the single beta 2-microglobulin gene is transcribed into at least two different size classes of mRNA that differ in the lengths of their 3' untranslated regions. We further show that three polyadenylation signals and a poly (A) tail are encoded at the 3' end of the gene.


Thiopurine S-methyltransferase polymorphisms: efficient screening method for patients considering taking thiopurine drugs.
More than 11% of the Caucasian population are heterozygous or homozygous carriers of thiopurine S-methyltransferase (TPMT) mutants and are at risk for toxic side effects when treated with thiopurine drugs. Therefore, screening for TPMT polymorphisms in a patient prior to prescribing these agents is recommended. The goal of this study was to determine a cut-off concentration of the TPMT activity assay beyond which genotyping of the TPMT gene should be performed. The TPMT activity of 240 unrelated Caucasian subjects was measured using high-performance liquid chromatography. Genotyping for the most frequent allelic variants, TPMT*2, *3A, *3B, *3C and *7 was performed by LightCycler technology and sequencing. The inter-individual TPMT activity showed a range from 23 nmol MTG/g*Hb*h(-1) to 97 nmol MTG/g*Hb*h(-1) with a median of 56 nmol MTG/g*Hb*h(-1). Using a cut-off concentration of 45.5 nmol MTG/g*Hb*h(-1), a test sensitivity of 100% and a specificity of 89% were reached for heterozygous carriers of a TPMT mutation. We identified 1 carrier of TPMT*2, 14 carriers of TPMT*3A and 3 carriers of TPMT*3C, resulting in a TPMT heterozygosity prevalence of 7.5%. This study defines the cut-off value for the TPMT phenotyping assay at 45.5 nmol/g*Hb*h(-1), beyond which additional genotyping elucidates the individual risk for drug therapy. Using this cut-off concentration, the number of genotyping assays could be reduced by about 60%.


Measurement of HPRT mutant frequencies in T-lymphocytes from healthy human populations.
Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning technique in healthy human populations. A statistical analysis was performed of assays from 232 individuals (77 males and 155 females) ranging in age from 19 to 80 years. Data from 4 donor groups were compiled: (a) 132 participants in a study of identical and fraternal twins; (b) 17 health care workers studied as part of an assessment of the risks of handling chemotherapeutic drugs; (c) 62 women with benign breast masses; and (d) 21 normal laboratory and office personnel. The relationship between age and mutant frequency (MF) was expressed by the equation: ln MF = 1.46 + 0.018 age (P < 0.001). Thus, MF increased by about 2% per year. Increases in cloning efficiency (CE) reduced the MF, as shown in the equation: ln MF = 2.91 - 1.32 CE (P < 0.001). CE was significantly related to age (CE = 0.47 - 0.002 age, P = 0.038), and the interdependent relationship between MF, age and CE expressed by the equation: ln MF = 1.99 - 1.13 CE + 0.016 age was significant at the P < 0.001 level. There was no statistically significant effect of donor gender or smoking history on MF in our population, but CE was significantly lower in males (P < 0.001). These findings confirm the importance of age and CE as factors which influence the thioguanine-resistant MF in circulating T-lymphocytes from normal adults.


Soluble CD40 ligand as a predictor of coronary artery disease and long-term clinical outcomes in stable patients undergoing coronary angiography.
In patients with acute coronary syndrome (ACS), elevated levels of soluble CD40 ligand (sCD40L) are associated with increased risk of cardiovascular events. We evaluated sCD40L levels and future cardiovascular events in patients not experiencing ACS. Serum sCD40L levels were measured in 909 patients undergoing angiography. A three-way matching scheme (age, gender and catheterization time period) identified 303 patients with coronary artery disease (CAD) who experienced a cardiac event within 1 year (CAD/event), 303 patients with CAD free of events (CAD/no event) and 303 patients without CAD and free of events (no CAD). Average age was 64 +/- 11 years; 74% were males. Median (+/- SE) sCD40L levels were higher for no CAD patients (335 +/- 60 pg/ml) compared to CAD (248 +/- 65 pg/ml, p = 0.01) and to CAD/event (233 +/- 63 pg/ml, p < 0.001). There was no significant difference in median sCD40L levels between CAD/no event and CAD/event patients. Higher sCD40L quartiles were associated with a significant decrease in the risk of CAD/event versus no CAD (quartile 4 versus quartile 1: odds ratio = 0.59, p = 0.03). There was a nonsignificant trend towards a decreased risk of CAD as compared to no CAD, and for CAD/event versus CAD. In non-ACS patients, higher sCD40L levels were associated with a decreased risk of CAD. This novel interaction of sCD40L raises interesting questions for CAD pathogenesis.


A selective inhibitor of N8-acetylspermidine deacetylation in mice and HeLa cells without effects on histone deacetylation.
The inhibitory effects of 7-[N-(3-aminopropyl)amino]heptan-2-one (APAH) on N8-acetylspermidine deacetylation were studied. In in vitro studies, APAH produced inhibition (apparent Ki of 0.18 microM) of N8-acetylspermidine deacetylation by the 100,000g supernatant fraction of rat liver. This apparent Ki was 60-fold less than the apparent Km (11 microM) for deacetylation of the substrate, N8-acetylspermidine, suggesting that APAH could be a potent, effective inhibitor in vivo. APAH was administered to mice by intraperitoneal injection at a dose of 200 mg/kg, and polyamine and acetylpolyamine levels in liver and spleen were measured. In tissues of control mice, N8-acetylspermidine was not detectable but increased to detectable levels 30-360 min after APAH treatment. These data are consistent with inhibition of the deacetylase by APAH. Increases in putrescine and N1-acetylspermidine levels occurred in liver after APAH treatment with increases in N1-acetylspermidine levels observed in spleen. In HeLa cells, a significant increase in N8-acetylspermidine was observed following 24 h exposure to 10 microM APAH while no change occurred in the acetylation level of HeLa cell histones. In contrast, 24 h exposure to 10 mM sodium butyrate produced no change in N8-acetylspermidine levels and an increase in the acetylation level of histones H4 and H2B. These results suggest that APAH has a relatively selective inhibitory effect on N8-acetylspermidine but not histone deacetylation. This is the first report of significant levels of N8-acetylspermidine in animal tissues and of the effects of in vivo inhibition of N8-acetylspermidine deacetylase.


Changes in blood values of sheep suffering from acute and chronic helminthiasis.
Systematic blood changes in two groups of sheep, one suffering from acute and the other from chronic helminthiasis were studied. In the group with acute infection, there was a rapid increase in helminth egg output coupled with rapid decline in the values of packed cell volume (PCV), haemoglobin (Hb) and red blood cells (RBC). Fluctuations were observed in the value of white blood cells (WBC). In the group with chronic infection, a slow and unsteady increase in helminth egg output was accompanied by a slow and steady fall in the values of PCV, Hb and RBC. As with acute infection, the value of WBC was unsteady.


COVID-19 vaccination for patients with epilepsy: A Chinese expert consensus.
Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.


Viral antibodies in maternal and cord sera.
Viral antibodies were determined in paired maternal and cord blood sera of 258 consecutive deliveries. Antibodies to Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex type 1 (HSV-1), adenovirus (ADV), and varicella zoster (VZV) were tested by indirect immunofluorescence and to rubella (RUB) by hemagglutination inhibition. Analysis of the overall pattern of differences between maternal and cord blood showed a highly significant difference for all six viruses. Analysis regarding individual viruses showed significantly higher titers to CMV and RUB in cord blood, a higher titer to VZV in maternal blood, and similar levels of antibodies to EBV, HSV-1, and ADV in maternal and cord blood. Infants with one or more risk indicators (weight less than 3 kg, Apgar score less than or equal to 7, clinical jaundice, meconium-stained amniotic fluid, respiratory distress syndrome) were defined as "at risk." Infants free of such indicators were defined as "normal." Significantly lower antibody levels to all six viruses were found in both maternal and cord blood of the "at risk" as compared to the "normal" group, while the ratios between the maternal and cord blood levels remained similar. Birth defects were found to have no effect on antibody titers. These results indicate an efficient and selective transfer through the placenta of certain viral antibodies and the possible association of lower antibody production with the presence of risk indicators in the infants.


Estrogen and antiestrogen action: studies in reproductive target tissues and tumors.
Studies are reported using unlabelled and radiolabelled antiestrogens which are aimed at elucidating the nature of interaction of antiestrogens with uterine and mammary tissue. Antiestrogens and long-acting estrogens move estrogen receptor sites to the nucleus and maintain elevated nuclear receptor levels for a prolonged period. The antagonistic action of antiestrogens in the uterus, however, appears to derive from their ability to effect a marked perturbation in the subcellular distribution of receptor whereby very little (ca. 10%) is cytoplasmic and further estrogen receptor accumulation is blocked. In DMBA-induced rat mammary tumors, the nonphototoxic antiestrogen, U-23, 469, effectively antagonizes the development and growth of tumors and elicits regression of 90% of established tumors with a time course similar to that seen after ovariectomy. Again, during antiestrogen treatment, the levels of cytoplasmic estrogen receptor are depressed with over 90% of total receptor being found in the nucleus. Two radiolabelled antiestrogens of high specific activity and purity have been prepared by us and their interaction with nuclear and cytoplasmic estrogen receptors is reported. Both 3H-CI-628 and 3H-U-23, 469 are metabolized in vivo to more polar forms which are found associated with the nuclear estrogen receptor, and which may be the true agents active in vivo.


Chlorophyll a Dimers Bound in the Water-Soluble Protein BoWSCP Photosensitize the Reduction of Cytochrome c.
When bound to water-soluble proteins of the WSCP family, chlorophyll molecules form dimers structurally similar to the "special pair" of chlorophylls (bacteriochlorophylls) in photosynthetic reaction centers. Being exposed to red light (λ ≥ 650 nm) in oxygen-free solutions, chlorophyll a dimers harbored by BoWSCP holoproteins (from Brassica oleracea var. botrytis) have sensitized the reduction of cytochrome c. According to absorption and circular dichroism spectroscopy data, the photochemical process did not significantly impair the structure of chlorophyll a molecules as well as their dimers harbored by BoWSCP protein. Adding tris(hydroxymethyl)aminomethane as an electron donor for chlorophyll recovery stimulated the photoreduction of cytochrome c.


The Central Role of the Ubiquitin-Proteasome System in EBV-Mediated Oncogenesis.
Deregulation of the ubiquitin-proteasome system (UPS) plays a critical role in the development of numerous human cancers. Epstein-Barr virus (EBV), the first known human tumor virus, has evolved distinct molecular mechanisms to manipulate the ubiquitin-proteasome system, facilitate its successful infection, and drive opportunistic cancers. The interactions of EBV antigens with the ubiquitin-proteasome system can lead to oncogenesis through the targeting of cellular factors involved in proliferation. Recent studies highlight the central role of the ubiquitin-proteasome system in EBV infection. This review will summarize the versatile strategies in EBV-mediated oncogenesis that contribute to the development of specific therapeutic approaches to treat EBV-associated malignancies.


Specialist palliative care out of hours telephone advice in Ireland: a national survey.
In 2015 the All-Ireland Institute of Hospice and Palliative Care identified access to specialist palliative care (SPC) advice out of hours (OOH) as their number one research priority. Receiving appropriate advice in response to palliative care needs OOH can address a patient/family's concerns and prevent unnecessary hospital attendances.The aim of this study was to describe the current model of SPC OOH advice in the units that run this service, and gain a greater understanding of the nature of calls received by these services. A national online survey was sent to staff providing OOH advice to patients with SPC needs and a second survey was sent to the managers of the organisations within Ireland. Surveys were emailed with a link to managers of both inpatient and community services who provide SPC. 78 clinical staff who provide OOH telephone advice responded to the survey and there were 23 responses to the managers' survey. The most common type of call received was in relation to symptom management (97%); however, 73% of staff indicated that they had no specific training in giving OOH advice over the phone and furthermore 44% of respondents felt ill equipped and uncomfortable giving OOH advice for a number of reasons. This survey has highlighted the need for support and training to the staff providing OOH SPC advice and that a set of standards to guide practice would be useful to this cohort of staff.


Success rate and factors predictive of redo endothermal ablation of small saphenous veins.
Endothermal ablation, such as endovenous laser ablation (EVLA) and radiofrequency ablation (RFA), has been increasingly used for treatment of small saphenous vein (SSV) insufficiency. Prior studies have shown recurrence rates of 0% to 10% in incompetent SSVs (ISSVs). The objective of the present study was to determine the efficacy of redo venous ablation for symptomatic recanalized SSVs and to predict the factors related to recanalization. A retrospective analysis of 2566 procedures in 1752 patients with chronic venous insufficiency due to ISSVs from 2012 to 2018 was performed, using individual medical record review for data extraction. All 2566 procedures were performed using endothermal ablation for patients in whom initial conservative management had failed. Postoperative duplex ultrasound scans were performed within 3 to 7 days after treatment. We defined successful obliteration as a lack of color flow using postoperative duplex ultrasound. We defined recanalization as the presence of reflux on duplex ultrasound in the target vessel during follow-up. We conducted follow-up examinations every 3 months during the first year and every 6 months subsequently. Of the 2566 procedures, redo ablation was performed in 91 ISSVs for 86 patients, including 58 women and 28 men. Of the 91 procedures, 54 were performed on the left lower extremity and 37 on the right lower extremity. The mean body mass index was 32.2 ± 7.66 kg/m2. The mean age was 62.4 ± 15.10 years. The CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) class was C1, C2, C3, C4, C5, and C6 for 0, 0, 29, 43, 1, and 18 patients, respectively. The mean maximum diameter of the targeted veins for the redo procedures was 4.51 ± 1.33 mm. Of the 91 procedures, 40 were performed using EVLA and 51 were performed using RFA. The initial technical success was 98.9%. The redo procedures showed an early closure of 96.7%. At a mean follow-up duration of 24.9 ± 14.9 months, the closure rate was 96.5%. No correlation was found between successful obliteration with the redo procedure and age, gender, CEAP class, laterality, EVLA vs RFA, body mass index, or vein diameter. The rates of successful closure for ISSVs with initial and redo procedures were comparable. These data have validated the potential usefulness of performing redo SSV ablation.


Increasing audiovisual speech integration in autism through enhanced attention to mouth.
Autistic children (AC) show less audiovisual speech integration in the McGurk task, which correlates with their reduced mouth-looking time. The present study examined whether AC's less audiovisual speech integration in the McGurk task could be increased by increasing their mouth-looking time. We recruited 4- to 8-year-old AC and nonautistic children (NAC). In two experiments, we manipulated children's mouth-looking time, measured their audiovisual speech integration by employing the McGurk effect paradigm, and tracked their eye movements. In Experiment 1, we blurred the eyes in McGurk stimuli and compared children's performances in blurred-eyes and clear-eyes conditions. In Experiment 2, we cued children's attention to either the mouth or eyes of McGurk stimuli or asked them to view the McGurk stimuli freely. We found that both blurring the speaker's eyes and cuing to the speaker's mouth increased mouth-looking time and increased audiovisual speech integration in the McGurk task in AC. In addition, we found that blurring the speaker's eyes and cuing to the speaker's mouth also increased mouth-looking time in NAC, but neither blurring the speaker's eyes nor cuing to the speaker's mouth increased their audiovisual speech integration in the McGurk task. Our findings suggest that audiovisual speech integration in the McGurk task in AC could be increased by increasing their attention to the mouth. Our findings contribute to a deeper understanding of relations between face attention and audiovisual speech integration, and provide insights for the development of professional supports to increase audiovisual speech integration in AC. HIGHLIGHTS: The present study examined whether audiovisual speech integration in the McGurk task in AC could be increased by increasing their attention to the speaker's mouth. Blurring the speaker's eyes increased mouth-looking time and audiovisual speech integration in the McGurk task in AC. Cuing to the speaker's mouth also increased mouth-looking time and audiovisual speech integration in the McGurk task in AC. Audiovisual speech integration in the McGurk task in AC could be increased by increasing their attention to the speaker's mouth.


Application of exosomes in the diagnosis and treatment of pancreatic diseases.
Pancreatic diseases, a serious threat to human health, have garnered considerable research interest, as they are associated with a high mortality rate. However, owing to the uncertain etiology and complex pathophysiology, the treatment of pancreatic diseases is a challenge for clinicians and researchers. Exosomes, carriers of intercellular communication signals, play an important role in the diagnosis and treatment of pancreatic diseases. Exosomes are involved in multiple stages of pancreatic disease development, including apoptosis, immune regulation, angiogenesis, cell migration, and cell proliferation. Thus, extensive alterations in the quantity and variety of exosomes may be indicative of abnormal biological behaviors of pancreatic cells. This phenomenon could be exploited for the development of exosomes as a new biomarker or target of new treatment strategies. Several studies have demonstrated the diagnostic and therapeutic effects of exosomes in cancer and inflammatory pancreatic diseases. Herein, we introduce the roles of exosomes in the diagnosis and treatment of pancreatic diseases and discuss directions for future research and perspectives of their applications.


A new tubal classification system for fertility prognosis after laparoscopic salpingostomy for tubal pregnancy.
To assess the objectivity and accuracy of a new system that predicts the pregnancy outcomes in patients with tubal pregnancy after laparoscopic salpingostomy. 480 tubal pregnancy patients were retrospectively stratified as mild, moderate, or severe group according to the new tubal classification system in which pelvic adhesions, tubal morphology, structure, and patency were included. The follow-up was performed for 24 months to determine spontaneous pregnancy outcomes. The tubal classification was significantly associated with intrauterine pregnancy rates (mild 70.9% vs. moderate 66.0% vs. severe 41.8%, P=0.001) and recurrent ectopic pregnancy rates (mild 2.8% vs. moderate 4.2% vs. severe 10.9%, P=0.047). The 24-month cumulative rate of intrauterine pregnancy was 73.5% in the mild group, 68.5% in the moderate group, and 45.8% in the severe group (P=0.002). The 24-month cumulative repeat ectopic pregnancy rate was 6.6% in the mild group, 9.1% in the moderate group, and 15% in the severe group (P=0.154). In Cox multivariate regression analysis, a lack of a history of infertility [hazard ratio (HR)=0.633, P=0.001] and tubal scoring (mild HR=2.408, P=0.008; moderate HR=2.147, P=0.010) were significantly associated with a higher rate of spontaneous intrauterine pregnancy. Having a history of infertility (HR=0.351, P=0.037) and no prior abdominopelvic surgery (HR=2.907, P=0.014) were significantly associated with a lower ectopic pregnancy rate. The new tubal classification system significantly correlated with spontaneous pregnancy outcomes in patients with tubal pregnancy following laparoscopic salpingostomy.


Generalizing from experiments: is predation strong or weak in the New England rocky intertidal?
Petraitis (1990) recently critized previous generalizations regarding the effects of predation in the New England rocky intertidal region (e.g., Menge 1976; Lubchenco and Menge 1978). Contrary to Lubchenco's and my conclusions, Petraitis concluded that (1) barnacles and not mussels are the favored prey of dogwhelks and (2) barnacles and not dogwhelks control mussel abundances in the mid and low rocky intertidal region. I provide evidence that these criticisms are unwarranted. First, Lubchenco and I never claimed that diet composition reflected prey preference. Moreover, predators can influence prey abundance without preferring the prey. Hence, claims regarding preferences have no bearing on our conclusions. Second, Petraitis' experiments do not invalidate Lubchenco's and my experimental results. Reanalyses of our experimental data support the earlier conclusion that at wave-sheltered sites, whelks reduce the abundance of mussels independently of barnacle abundances. Further, at all but one of Lubchenco's and my study sites, predator densities were higher than at Petraitis' site. Thus, the absence of a predator effect in Petraitis's study was most likely due to low predator density rather than a lack of generality of our earlier results. This reevaluation therefore suggests that within a broader conceptual framework, Petraitis' apparently divergent results are actually consistent with ours.


Sediment Profile and Fluxes of Mercury and Methyl Mercury in Weihe Watershed in Henan, China.
Sediment core samples were collected from the Weihe River in February and August 2013. Cores were sectioned and analyzed for total Hg (THg) and methyl mercury (MeHg). THg in sediment cores ranged from 156 to 282 ng g(-1) in February, and from 172 to 300 ng g(-1) in August. MeHg concentrations ranged from 0.80 to 3.11 ng g(-1) in both seasons. Results showed that the diffusive fluxes were up to two orders of magnitude lower than the in situ benthic fluxes. Fluxes of MeHg measured in in situ experiments in August were positively correlated with [Formula: see text] (r = 0.930). THg and MeHg release were not strongly correlated with TOC in February. Patterns of MeHg flux differed greatly depending on oxidation-reduction potential (Eh) (r > 0.70) conditions in the two seasons.


Occurrence and distribution of microplastics in long-term biosolid-applied rehabilitation land: An overlooked pathway for microplastic entry into terrestrial ecosystems in Australia.
Wastewater treatment plants (WWTPs) efficiently eliminate over 98% of microplastics (MPs) from wastewater discharge, subsequently accumulating them in sludge. This sludge is frequently employed as fertilizer in agricultural practices or land rehabilitation. While there is significant research on biosolid application in agriculture, the discussion regarding its application in rehabilitating industrial zones and MPs contamination is limited. The current study investigates the abundance, distribution, and composition of MPs in rehabilitation land with long-term biosolid-application in Australia. Three minesite fields (designated 1-3), each with distinct biosolid application histories since 2011, 2012, and 2017, and a control field without any biosolid application history, were chosen for this study. The abundances of MPs in biosolid-applied fields 1-3 (6.04 ± 1.92 x 102 MP kg-1; 4.94 ± 0.73 x 102 MP kg-1; 2.48 ± 0.70 x 102 MP kg-1) were considerably higher compared to non-biosolid-applied field (0.70 ± 0.63 x 102 MP kg -1). This indicates that the application of biosolids significantly contributes to the presence of MPs in the soil. Moreover, the results suggest that with each successive application, the abundance of MPs increases. The abundance and size of MPs in both biosolid and non-biosolid soils decreased as the soil depth increased. Microbeads were dominant in soils where biosolids were applied (up to 61.9%), while fibres were dominant in non-biosolid soils (accounting for 85.7%). The distribution of plastic polymer types varied among fields and soil depths. Most MPs were microbeads of polyamide (PA), fragments of polyethylene (PE), foam of polystyrene (PS), and fibres of rayon. This research presents evidence that the extended utilization of biosolids results in elevated MP pollution in minesite rehabilitation land, highlighting a frequently overlooked origin of MP contamination in terrestrial settings. Additional evaluations needed to understand ecological risks of MPs in soil ecosystems affected by biosolid application.


A comparative study of vitreous-body and zonular glycoconjugates that bind to the lectin from Ulex europaeus.
Eyes from adult rodents, rabbits and humans were fixed in formalin, embedded in paraffin and incubated with a horseradish peroxidase-conjugated lectin from Ulex europaeus to localize vitreous-body and zonular glycoconjugates. Rodent eyes had reaction product for peroxidase activity in fibrous structures in the posterior chamber, vitreous base and vitreous cortex. The zonules and the internal limiting membrane region of the retina also were stained. Rabbit eyes had more stained fibrous material in the vitreous base than rodent eyes and the attachment region of the zonules on the lens capsule, the anterior hyaloid membrane and tracts in the vitreous cortex were more heavily stained in rabbits. There was heavy staining of the thick vitreous base in the human eyes as well as staining of zonules, anterior hyaloid membrane and vitreous cortex. The localization of this lectin may be specific for fucose in glycoproteins or other glycoconjugates, although this was not demonstrated here. However, the location of lectin binding sites correlates well with known sites of uptake of tritiated fucose and tritiated glucosamine in rabbit eyes. Eyes from the larger species studied had more lectin-binding glycoconjugates in fibrous structures in the vitreous body than those from smaller species. The amount of glycoconjugate identified in some of the lectin-binding sites may be related to some extent to the degree of stress incident upon those sites.


[Effectiveness of local delivery of ofloxacin using controlled-release strips (PT-01) in periodontal patients. Part 1. PT-01 application among treatment plans for periodontal disease].
Three different sites which have more than 5 mm pocket were randomly selected in each periodontal patient and were divided into three groups: PT-01 treated site, placebo treated site and control site. After application of either PT-01 or placebo twice for two weeks, subgingval scaling and root planing were performed. Then PT-01 and the placebo were applied weekly to the periodontal pocket for four weeks and clinical and microbiological evaluations were made. The results obtained were as follows: 1. On clinical evaluation, significant improvement was found in the PT-01 treated site in comparison with the placebo treated and/or control site. 2. On microbiological evaluation, slight improvement was found in the PT-01 treated site, whereas there was no significant difference among the three sites.