CBD-oil as a potential solution in case of severe tamoxifen-related side effects.
Tamoxifen may lead to bothersome side effects contributing to non-compliance and decreased quality of life. Patients searching for relief are increasingly turning to cannabinoids such as CBD-oil. However, CBD-oil might affect tamoxifen pharmacokinetics (PK) through CYP2D6 inhibition. The aims of this open-label, single-arm study were (1) to determine the PK profile of tamoxifen when using CBD-oil, and (2) to subsequently investigate whether CBD-oil has a beneficial influence on side effects. Study patients had to have steady-state endoxifen concentrations ≥16 nM (conservative threshold). PK sampling and side effect assessment was done at initiation of CBD-oil and 28 days thereafter. Bio-equivalence could be concluded if the 90% confidence interval (CI) for the difference in endoxifen AUC fell within the [-20%; +25%] interval. The effect of CBD-oil on side effects was evaluated using the FACT-ES questionnaire. Endoxifen AUC decreased after CBD-oil by 12.6% (n = 15, 90% CI -18.7%, -6.1%) but remained within bio-equivalence boundaries. The endocrine sub-scale of the FACT-ES improved clinically relevant with 6.7 points (n = 26, p < 0.001) and health-related quality of life improved with 4.7 points after using CBD (95% CI + 1.8, +7.6). We conclude that CBD-oil, if of good quality and with a dosage below 50 mg, does not have to be discouraged in patients using it for tamoxifen-related side effects. Clinical trial registration: International Clinical Trial Registry Platform (NL8786; https://www.who.int/clinical-trials-registry-platform ).


Relation of dance skills to body cathexis and locus of control orientation.
33 subjects provided measures on extent of dance training, dance performance, locus of control orientation, and three measures of body cathexis. Pearson product-moment correlations yielded significant, though modest, positive relations between three measures of body cathexis and performance, and between time dancing and the Levenson Internal scale; and a negative relation between body cathexis and the Levenson Chance scale.


Concordance between premortem and postmortem diagnosis in the autopsy: results of a 10-year study in a tertiary care center.
We describe the concordance between clinical diagnoses and autopsy findings in a tertiary care center. Clinical autopsy is a useful tool for the evaluation of accuracy of the clinical diagnoses. However, autopsy rates have declined around the world recently. We randomly evaluated 500 of 2,211 autopsies performed in the department of pathology of a tertiary care hospital during a 10-year period. We computed the sensitivity, specificity, predictive values, and concordance scores between premortem and postmortem diagnoses. The autopsy diagnoses were used as the "gold standard." Four-hundred twenty-two (84.4%) of the autopsies met inclusion criteria. Diseases of the respiratory tract were diagnosed in 44.1% (186) of all autopsy reports reviewed. The higher sensitivity for diagnosis was observed in congenital anomalies (87.5%), while the higher specificity was observed in diagnosis of complications of pregnancy, childbirth, and the puerperium (98.98%). The higher concordance between premortem and postmortem diagnosis was observed with the diagnoses of neoplasms (kappa = 0.76), and for the group of complications of pregnancy, childbirth, and the puerperium (kappa = 0.76). A clinical diagnosis successfully addressed the cause of death in 40% of the cases Low values for concordance between autopsy reports and clinical diagnoses were present in most of the autopsies reports reviewed. We encourage physicians to continue considering the autopsy as an important tool that extends our understanding of diseases.


Phase II study with a combination of epirubicin, cisplatin, UFT, and leucovorin in advanced hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the outcome of systemic chemotherapy has been disappointing in advanced HCC. This study was conducted to test the efficacy and toxicity of the combined regimen of epirubicin, cisplatin, and UFT moderated by leucovorin in advanced or recurrent HCC. All 53 patients received epirubicin (50 mg/m2 i.v.) on day 1 and cisplatin (60 mg/m2 i.v.) after epirubicin administration. Oral UFT 400-600 mg/day, determined by body surface area, and leucovorin 75 mg/day were administered for 21 consecutive days, followed by a 7-day drug free interval. Nine had a partial response, representing 16.9% of response rate (95% confidence interval rate; 7.0-26.8%) with median response duration of 17.1 weeks (95% CI; 5.0-29.3 weeks, range; 7.1-51.7 weeks). Fifteen patients had stable disease and the disease progressed in 26 patients. The median overall survival for the patients was 24.6 weeks (95% CI; 17.3-31.9 weeks, range; 3.0-131.3 weeks). The main toxicities were hematologic toxicities including neutropenia, which reached grade 3/4 in 17 patients (38.5%), and grade 3 or 4 thrombocytopenia in five patients (9.4%). The combination of epirubicin, cisplatin, and UFT moderated by leucovorin showed modest anti-tumor activity with relatively tolerable toxicities. However, a randomized phase III trial based on this regimen is warranted to clarify its survival benefit in patients with advanced HCC.


Underage E-Cigarette Purchasing and Vaping Progression Among Young Adults.
Despite laws prohibiting sale of e-cigarettes to individuals aged less than 21 years, many underage young adults purchase e-cigarettes from retail stores, which may increase likelihood of continued use due to a greater access to vaping products and exposure to point-of-sale marketing. Data are from a prospective cohort of young adults aged 18-20 years in Los Angeles who had ever used e-cigarettes at baseline (N = 1,029). We evaluated the association of underage e-cigarette purchasing behavior (owned and purchased vs. owned but never purchased vs. never owned an e-cigarette) with subsequent vaping frequency, intensity, and dependence symptoms one year later, adjusting for vaping behaviors prior to baseline; additional models evaluated whether associations differed by purchase location or product type. At baseline, 332 (32%) had purchased e-cigarettes while underage, 227 (22%) owned but never purchased e-cigarettes themselves, and 470 (46%) never owned an e-cigarette. Compared to never owning e-cigarettes, those who had purchased their own e-cigarettes vaped more days in the past month (rate ratio [RR] = 2.97; 95% confidence interval [CI]: 2.15-4.09), had more vaping episodes per day (RR: 2.58; 95% CI: 2.12-3.14), vaped more puffs per vaping episode (RR: 1.90; 95% CI: 1.61-2.23), and had greater odds of dependence (odds ratio: 3.68; 95% CI: 2.51-5.40); elevated estimates were also observed for those who owned but never purchased e-cigarettes (vs. never owned). Vaping dependence was greatest among participants who purchased JUULs or other pod-mods. Participants who purchased e-cigarettes underage subsequently vaped more intensely and had greater vaping dependence. Regulations that reduce underage retail access to e-cigarettes may help prevent vaping progression among those most at risk of dependence.


Doppler and B-mode ultrasound for avascular nephrotomy.
Doppler sonography for intraoperative localization of the intrarenal arteries combined with B-scan sonography for intraoperative visualization of stones allows complete stone removal via small radial nephrotomies for which clamping of the renal artery is no longer necessary. Since September 1980 we used this technique on 35 patients with staghorn or recurrent calculi. The main advantages of this technique are exact and quick stone localization, minimal loss of renal function owing to preservation of the intrarenal vascular system, and no need for renal ischemia and cooling.


Liposome-mediated gene transfer in rat lung transplantation: A comparison between the in vivo and ex vivo approaches.
We compared the efficacy of in vivo and ex vivo liposome transfection in rat lung transplantation. (1) Chloramphenicol acetyltransferase group: Fischer rats underwent isogeneic transplantation (n = 4 per group). Recipients were put to death on postoperative day 2 for chloramphenicol acetyltransferase activity. Ex vivo setting: Grafts received cDNA complexed or not with liposomes and were transplanted after 1.5 or 10 hours at 10 degreesC. In vivo setting: Donors were intravenously injected with cDNA complexed or not with liposomes. Lungs were harvested after 1.5 or 10 hours, preserved at 10 degreesC, and transplanted. (2) Transforming growth factor-beta1 group: Brown-Norway rats served as donors and Fischer rats as recipients. All grafts were preserved for 3 hours at 10 degreesC. On postoperative day 5, arterial oxygenation and histologic rejection scores were assessed. Ex vivo setting: Grafts received transforming growth factor-beta1 sense (n = 8) or antisense (n = 7) complexed with liposomes or cDNA alone (n = 5). In vivo setting: Donors were intravenously injected with liposome:transforming growth factor-beta1 sense cDNA (n = 7). Exposure time was 3 hours. (1) Chloramphenicol acetyltransferase-transfection was superior in the ex vivo group but was not statistically different for longer exposure times. (2) Transforming growth factor-beta1-arterial oxygenation was superior in the ex vivo liposome:sense group. cDNA alone was inefficient. Rejection scores were not statistically different between ex vivo and in vivo liposome:sense groups but were better when the ex vivo liposome:sense group was compared with the cDNA alone or the antisense groups. (1) With current liposome technology, the ex vivo route is superior to the in vivo approach; (2) cDNA alone does not provide transgene expression at levels to produce a functional effect.


The landscape of chimeric RNAs in bladder urothelial carcinoma.
Gene fusions and products have been identified as oncogenic drivers in many cancers, making them attractive diagnostic markers and therapeutic targets. However, the landscape of fusion transcripts in bladder cancer has not been fully characterized. To identify fusion transcripts with potential therapeutic or diagnostic values, TCGA bladder urothelial carcinoma RNA-sequencing dataset was used. In order to avoid false positives, we applied multiple criteria including filtering out fusions detected in normal samples from GTEx dataset. We validated a subset of candidate fusions with a collection of bladder cancer and adjacent normal samples. We identified 19,547 high confidence fusion genes from 414 bladder cancer samples. After filtering off M/M fusions, fusions in GTEx normal samples, and occurrence frequency <5, we obtained a list of 271 gene fusions, 13 of which were novel and specific to cancer samples. Six of those fusions were validated using cell lines and clinical samples. We discovered that two chimeric RNAs, BCL2L2-PABPN1 and CHFR-GOLGA3, were detected to be expressed significantly higher in bladder cancer samples compared to adjacent normal samples. Impressively, the wild-type of the parental genes were not differentially expressed. Mechanistically, we demonstrated that these two fusions are generated by cis-splicing between adjacent genes. These two fusions were detected mainly in the fraction of cell nucleus, suggesting a potential long noncoding RNA role. Our findings provide a panoramic view of the landscape of chimeric RNAs in bladder cancer. Some frequent chimeric RNAs are generated by intergenic splicing, and represent a new repertoire for potential biomarkers.


Picrorhiza kurroa Prevents Memory Deficits by Inhibiting NLRP3 Inflammasome Activation and BACE1 Expression in 5xFAD Mice.
One of the most significant pathologies of Alzheimer's disease (AD), an irreversible and progressive neurodegenerative disease that causes cognitive impairment, is the neuroinflammation facilitating the accumulation of amyloid-β (Aβ) peptide. Hence, the inhibition of abnormal neuroinflammatory response is considered a promising therapeutic approach for AD. Picrorhiza kurroa Bentham, Scrophulariae (PK) is a medicinal herb that has been traditionally used for the treatment of various diseases, including inflammation. This study aims to report the significance of PK treatment in markedly improving spatial learning memory and dramatically decreasing Aβ levels in Tg6799 mice, also known 5xFAD mice, which have five familial AD (FAD) mutations. Remarkably, these effects correlated with reversal of disease-related microglial neuroinflammation, as evidenced by shifting microglia phenotypes from the inflammatory form to the anti-inflammatory form and inhibiting the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 inflammasome activity. Moreover, PK administration induced silent information regulator type1/peroxisome proliferator-activated receptor-γ signaling, resulting in a decrease of β-secretase 1 (BACE1) expression, which involved in Aβ production. Overall, this study suggests that PK exhibits a neuroprotective effect by inducing alternative activation of microglia and downregulating the BACE1 expression, thereby ameliorating the disease pathophysiology and reversing the cognitive decline related to Aβ deposition in AD mice.


A co-production approach guided by the behaviour change wheel to develop an intervention for reducing sedentary behaviour after stroke.
Stroke survivors are highly sedentary; thus, breaking up long uninterrupted bouts of sedentary behaviour could have substantial health benefit. However, there are no intervention strategies specifically aimed at reducing sedentary behaviour tailored for stroke survivors. The purpose of this study was to use co-production approaches to develop an intervention to reduce sedentary behaviour after stroke. A series of five co-production workshops with stroke survivors, their caregivers, stroke service staff, exercise professionals, and researchers were conducted in parallel in two-stroke services (England and Scotland). Workshop format was informed by the behaviour change wheel (BCW) framework for developing interventions and incorporated systematic review and empirical evidence. Taking an iterative approach, data from activities and audio recordings were analysed following each workshop and findings used to inform subsequent workshops, to inform both the activities of the next workshop and ongoing intervention development. Co-production workshop participants (n = 43) included 17 staff, 14 stroke survivors, six caregivers and six researchers. The target behaviour for stroke survivors is to increase standing and moving, and the target behaviour for caregivers and staff is to support and encourage stroke survivors to increase standing and moving. The developed intervention is primarily based on co-produced solutions to barriers to achieving the target behaviour. The developed intervention includes 34 behaviour change techniques. The intervention is to be delivered through stroke services, commencing in the inpatient setting and following through discharge into the community. Participants reported that taking part in intervention development was a positive experience. To our knowledge, this is the first study that has combined the use of co-production and the BCW to develop an intervention for use in stroke care. In-depth reporting of how a co-production approach was combined with the BCW framework, including the design of bespoke materials for workshop activities, should prove useful to other researchers and practitioners involved in intervention development in stroke.


Ethylene signaling in salt stress- and salicylic acid-induced programmed cell death in tomato suspension cells.
Salt stress- and salicylic acid (SA)-induced cell death can be activated by various signaling pathways including ethylene (ET) signaling in intact tomato plants. In tomato suspension cultures, a treatment with 250 mM NaCl increased the production of reactive oxygen species (ROS), nitric oxide (NO), and ET. The 10(-3) M SA-induced cell death was also accompanied by ROS and NO production, but ET emanation, the most characteristic difference between the two cell death programs, did not change. ET synthesis was enhanced by addition of ET precursor 1-aminocyclopropane-1-carboxylic acid, which, after 2 h, increased the ROS production in the case of both stressors and accelerated cell death under salt stress. However, it did not change the viability and NO levels in SA-treated samples. The effect of ET induced by salt stress could be blocked with silver thiosulfate (STS), an inhibitor of ET action. STS reduced the death of cells which is in accordance with the decrease in ROS production of cells exposed to high salinity. Unexpectedly, application of STS together with SA resulted in increasing ROS and reduced NO accumulation which led to a faster cell death. NaCl- and SA-induced cell death was blocked by Ca(2+) chelator EGTA and calmodulin inhibitor W-7, or with the inhibitors of ROS. The inhibitor of MAPKs, PD98059, and the cysteine protease inhibitor E-64 reduced cell death in both cases. These results show that NaCl induces cell death mainly by ET-induced ROS production, but ROS generated by SA was not controlled by ET in tomato cell suspension.


Toxic effects of acetochlor, methamidophos and their combination on nifH gene in soil.
Toxic effects of two agrochemicals on nifH gene in agricultural black soil were investigated using denaturing gradient gel electrophoresis (DGGE) and sequencing approaches in a microcosm experiment. Changes of soil nifH gene diversity and composition were examined following the application of acetochlor, methamidophos and their combination. Acetochlor reduced the nifH gene diversity (both in gene richness and diversity index values) and caused changes in the nifH gene composition. The effects of acetochlor on nifH gene were strengthened as the concentration of acetochlor increased. Cluster analysis of DGGE banding patterns showed that nifH gene composition which had been affected by low concentration of acetochlor (50 mg/kg) recovered firstly. Methamidophos reduced nifH gene richness that except at 4 weeks. The medium concentration of methamidophos (150 mg/kg) caused the most apparent changes in nifH gene diversity at the first week while the high concentration of methamidophos (250 mg/kg) produced prominent effects on nifH gene diversity in the following weeks. Cluster analysis showed that minimal changes of nifH gene composition were found at 1 week and maximal changes at 4 weeks. Toxic effects of acetochlor and methamidophos combination on nifH gene were also apparent. Different nifH genes (bands) responded differently to the impact of agrochemicals: four individual bands were eliminated by the application of the agrochemicals, five bands became predominant by the stimulation of the agrochemicals, and four bands showed strong resistance to the influence of the agrochemicals. Fifteen prominent bands were partially sequenced, yielding 15 different nifH sequences, which were used for phylogenetic reconstructions. All sequences were affiliated with the alpha- and beta-proteobacteria, showing higher similarity to eight different diazotrophic genera.


Estimation of the uptake and gut retention of microplastics in juvenile marine fish: Mummichogs (Fundulus heteroclitus) and red seabreams (Pagrus major).
We investigated the impact of microplastics (MPs) on marine fish by estimating the uptake and retention by mummichogs (Fundulus heteroclitus) and red seabreams (Pagrus major) of MPs similar in size (≥0.25 mm) and composition (polyethylene) to MPs detected in fish intestines. Results revealed a correlation between MP concentrations in aquarium water and the content of MPs in the gastrointestinal tracts of exposed fish. More than 95% were excreted from both species within 25 h; this retention time is similar to the processing time of food items. The rate of excretion showed little dependence on MP size, but there was some dependence on fish species and MP shape. These results suggest that MPs similar to those we studied have little direct adverse impact on these two marine fish species.


Seizures and X-linked intellectual disability.
Intellectual disability occurs as an isolated X-linked trait and as a component of recognizable X-linked syndromes in the company of somatic, metabolic, neuromuscular, or behavioral abnormalities. Seizures accompany intellectual disability in almost half of these X-linked disorders. The spectrum of seizures found in the X-linked intellectual disability syndromes is broad, varying in time of onset, type of seizure, and response to anticonvulsant therapy. The majority of the genes associated with XLID and seizures have now been identified.


[Diabetes prevalence estimated using a standard algorithm based on electronic health data in various areas of Italy].
the goal of this study was to estimate the prevalence of diabetes through record linkage of various data sources in four Italian areas. Aulss 12 Veneziana, Aulss 4 Alto vicentino, Torino, ASL10 of Firenze. all 2002 to 2004 residents in the four areas (n = 2,123,913 on 30th June 2003). crude prevalence by age and gender and standardized prevalence by gender. we used three different data sources. The first was the set of files of all persons discharged from hospitals with a primary or secondary diagnosis of diabetes (ICD-9-CM code 250*) in the year of interest or in the four previous years. The second data source was the set of files of all prescriptions of antidiabetic drugs (ATC code: A10A* and A10B*) prescribed in the year of interest; we considered as persons with diabetes only those who had at least two prescriptions of antidiabetic drugs at two different times. The third source was the set of files of all subjects who obtained exemption from payment of drugs or laboratory testing due to a diagnosis of diabetes mellitus in the year of interest or in the 3 previous years. All data sources were matched by a deterministic linkage procedure. We defined as "prevalent case" those persons who were present in at least one of the three data sources. We compared the estimated prevalence in the four different areas. in 2003, the prevalence of diabetes in the four areas ranged from 3.93% to 5.55% among men, and from 3.55% to 4.52% among women. After adjustment for age, differences among men were reduced and were no longer present among women. Prevalence is higher among the elderly and among men. using routinely collected data we were able to identify large cohorts of persons with known diabetes and to estimate the prevalence of the disease, which was shown to be highly homogeneous among participating centres, and similar to that reported in other studies conducted in Italy with more costly and time consuming methods.


Rapid and quantitative detection of Shiga toxin1 and Shiga toxin2 based on multiple targets UPT-LF assay.
Shiga toxin-producing Escherichia coli (STEC) infection causes a series of diseases that are highly pathogenic and deadly in humans and animals, seriously endangering public health. Of the pathogenic factors within STEC, the two groups of Shiga toxin (Stx) consisting Stx1 and Stx2 plays a prominent role in the pathogenesis of STEC infection. In this study, we developed single-target up-converting phosphor technology-based lateral flow assay (Stx-UPT-LFA) for the rapid detection of Stx1 and Stx2, respectively, and also developed a dual-target Stx1/2-UPT-LFA based on single-target strips to detect of Stx1 and Stx2 at the meantime within 20 min. We choose the purified Stx1 and Stx2 standard samples, and the optimum monoclonal antibody (namely 8E7-E6, 2F6-F8 for Stx1 and S1D8, S2C4 for Stx2) were selected for use in Stx-UPT-LFA in double-antibody-sandwich mode. The sensitivities of single-target Stx-UPT-LFA for both Stx1 and Stx2 were 1 ng mL-1 with accurate quantitation ranges of 1-1000 ng mL-1 and 1-800 ng mL-1 respectively. No false-negative result was found in the Stx2-UPT-LFA even with a high-test concentration up to 1000 ng mL-1. Meanwhile, both targets detection sensitivities for dual-target Stx1/2-UPT-LFA were 5 ng mL-1, and accurate quantitation ranges were 5-1000 ng mL-1 and 5-800 ng mL-1 for standard Stx1 and Stx2 solutions without cross-interference between two targets. Both techniques showed good linearities, with a linear fitting coefficient of determination(r) of 0.9058-0.9918. Therefore, the UPT-LFA could realize simultaneous detection for multiple targets on a single strip and thus to quickly determine the type of infectious Stxs. In addition, the single-target Stx1-UPT-LFA and Stx2-UPT-LFA showed excellent specificity to six toxins, even at high concentrations of 1000 ng mL-1. In conclusion, the developed Stx-UPT-LFA allows the rapid, quantitative, reliable and simultaneous detection of Stx1 and Stx2 within 20 min, providing an alternative method for clinical diagnosis of STEC infection.


Prevalence and trend of atrial fibrillation and its associated risk factors among the population from nationwide health check-up centers in China, 2012-2017.
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, which poses huge disease burdens in China. A study was conducted to systematically analyze the recent prevalence trend of AF and age-related disparities in AF risk among the nationwide healthy check-up population. We conducted a nationwide cross-sectional study involving 3,049,178 individuals ≥35 years from health check-up centers to explore the prevalence and trend of AF by age, sex, and region from 2012 to 2017. Additionally, we analyzed risk factors associated with AF among the overall population and different age groups via the Boruta algorithm, the LASSO regression, and the Logistic regression. The age-, sex-. and regional-standardized prevalence of AF kept stable between 0.4%-0.45% among national physical examination individuals from 2012 to 2017. However, the prevalence of AF showed an undesirable upward trend in the 35-44-year age group (annual percentage changes (APC): 15.16 [95%CI: 6.42,24.62]). With increasing age, the risk of AF associated with the overweight or obesity gradually exceeds that associated with diabetes and hypertension. In addition to traditional leading risk factors such as age≥65 and coronary heart disease, elevated uric acid and impaired renal function were tightly correlated with AF in the population. The significant rise in the prevalence of AF in the 35-44 age group reminds us that in addition to the elderly (the high-risk group), younger people seem to be in more urgent need of attention. Age-related disparities in AF risk also exist. This updated information may provide references for the national prevention and control of AF.


IgM secretion and absorption in the materno-fetal interface of a viviparous teleost, Neoditrema ransonneti (Perciformes; Embiotocidae).
We investigated maternal IgM secretion in the ovary and the absorption of IgM by fetuses in a viviparous fish, Neoditrema ransonneti (Embiotocidae). Serum IgM, whose molecular weight was approx. 820k, was purified by two steps of gel filtration chromatography. Immunohistochemistry and Western blotting revealed that IgM was secreted from the epithelia of the ovigerous lamellae of pregnant females into ovarian cavity fluid. The IgM-secreting activity of ovigerous folds showed notable changes according to the reproductive stage. In fetuses, IgM was absorbed as macromolecules by enterocytes of the hypertrophied hindgut. IgM in the fetal blood was also demonstrated, although its concentration remained low during gestation. These findings suggest that IgM was transported from the maternal tissues to embryos via a unique pathway in N. ransonneti.


The distribution of fetal hemoglobin and the types of gamma chain in red cell fractions separated by gradient centrifugation from blood of patients with sickle cell anemia and other hemoglobinopathies.
Isopycnic separations of red cells from cord bloods, and from patients with sickle cell anemia, different forms of HPFH, S-beta O-thalassemia, and a beta +-thalassemia homozygosity were made in order to evaluate the distribution of Hb F and the relative levels of G gamma and A gamma chains over the cell fractions. As expected, the cord blood data showed decreased levels of both Hb-F and G gamma chains in the top cell fractions since the beta leads to gamma and high G gamma: A gamma low G gamma: A gamma switches are operative around the time of birth. Complete cell fractionations were made on the blood of three SS patients with low G gamma values (40%) and three SS patients with high G gamma values (60%). The proportion of G gamma chain was constant in all cell fractions, while the Hb-F level was higher in cells with higher densities. The difference in the quantities of the three types of gamma chain in the fetal hemoglobins of two SS patients with an A gamma T heterozygosity, one having a low G gamma value and the other a high G gamma level, can be explained by assuming an alteration in a regulatory mechanism. Considerable variation both in the level of Hb F and in the percentage of G gamma chain was observed in two G gamma A gamma-HPFH heterozygotes with a relatively low G gamma percentage of 30%; an inverse relationship was present between the two parameters. Such a phenomenon was not evident for the G gamma A gamma-HPFH homozygote, and also did not exist in two additional G gamma A gamma-HPFH heterozygotes with an associated alpha-thalassemia-2 heterozygosity who had a similar amount of Hb F but with higher G gamma values of about 50%. The difference in G gamma values between these two categories of G gamma A gamma-HPFH could be due to a higher affinity of the G gamma chains over A gamma chains for a slightly decreased amount of alpha chains as in an alpha-thalassemia-2 heterozygosity. 2 heterozygosity. Although an increased synthesis of Hb-F with G gamma chains was again observed after in vitro incubation of reticulocytes with [35S]methionine none of the isolated cell fractions contained a Hb F with the alpha 2 G gamma 2 composition.


Comprehensive Treatment Uncertainty Analysis and PTV Margin Estimation for Fiducial Tracking in Robotic Liver Stereotactic Body Radiation Therapy.
This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy (SBRT) cases, and evaluate the required planning target volume (PTV) margins. A total of 11 liver tumor patients with a total of 57 fractions, who underwent SBRT with synchronous fiducial tracking, were enrolled for the present study. The correlation/prediction model error, geometric error, and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties. The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment. The correlation model error-related uncertainty was 4.3±1.8, 1.4±0.5 and 1.8±0.7 mm in the superior-inferior (SI), left-right, and anterior-posterior directions, respectively. These were the primary contributors among all uncertainty sources. The geometric error significantly increased for treatments without rotation correction. The fraction-level composite uncertainties had a long tail distribution. Furthermore, the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions, and only 75% of uncertainties in the SI direction. In order to cover 90% of uncertainties in the SI direction, an 8-mm margin would be needed. For scenarios without rotation correction, additional safety margins should be added, especially in the superior-inferior and anterior-posterior directions. The present study revealed that the correlation model error contributes to most of the uncertainties in the results. Most patients/fractions can be covered by a 5-mm margin. Patients with large treatment uncertainties might need a patient-specific margin.


Unusual stress fracture in an adolescent baseball pitcher affecting the trochlear groove of the olecranon.
Stress fractures of the proximal ulna are known to occur in throwing athletes. Most cases extend to involve the olecranon, and cases limited to the trochlear groove are rare. In this report we present a 17-year-old elite baseball pitcher with a stress fracture of the trochlear groove of the proximal ulna. Diagnosis was made by demonstration of characteristic signal changes on MRI of the elbow. The fracture occurred at the cortical notch, also known as the pseudodefect of the trochlear groove. This case suggests that the cortical notch serves as an area of weakness predisposing pitchers to development of a stress fracture.


Cervical vertebrae measurements in syringomyelia.
Lateral X-rays of the cervical spine taken under standard conditions in 69 cases of syringomyelia have been measured to assess the relative sizes of the canals and bodies. One hundred and five cases without cervical spine abnormality provided controls. The expected expansion has been observed in males from C5 to C7 and in females from C3 to C7. The oddity that the expansive process seemed to come higher in females than in males has been noted by other workers. In both sexes it has been found that diminution of vertebral body size is a more consistent finding than enlargement of the canals and correlation coefficients have confirmed that enlargement of the canal appears to take place at least in part at the expense of the body. Possible factors in the enlargement are discussed. Oblique measurements taken in 57 syrinx cases and 89 controls showed the expected change caused by the view of the lower cervical vertebrae being closer to AP and pictures of the upper vertebrae being progressively closer to lateral views. There was a tendency for the bigger oblique diameters to occur in these cases with the biggest sagittal diameters and an insignificant tendency for the biggest canals to have a diminished difference between the two oblique measurements. There was no evidence that oblique measurements could be used to detect slight degrees of enlargement in cases of syringomyelia.


Cumulation of mycotoxins in maize cobs infected withFusarium gramihearum.
Maize cobs withFusarium ear rot were collected at 1986 season and five infected byFusarium graminearum were analyzed for presence of triohothecenes and zearalenone. Collected material was subsampled forFusarium damaged kernels and corresponding axial stems and healthy looking kernels. All investigated cobs contained deoxynivalenol (DON) (range 18.0-131.5 mg/kg) and zearalenone (ZEA) (range 0.38-2.17 mg/kg), in four cobs 15-acetyl-deoxynivalenol (15-AcDON) (range 5.2-6.2 mg/kg) was present and two cobs besides three all metabolites contained 3-acetyl-deoxynivalenol (3-AcD0N) (range 0.5-0.8 mg/kg).The average of individual toxins amount in axial stems: in mg/kg was equal to: DON - 110.36, ZEA - 4.57, 15-AcD0N - 16.66, and 3-AcD0N - 1.32.Fusarium damaged kernels contained in average the following amount (mg/kg) of: DON 77.00, ZEA 0.98, 15-AcD0N 3.78 and 3-AcD0N 0.06. Healthy looking kernels contained DON 1.96 mg/kg and ZEA 0.07 mg/kg only. Cooccurrence of 3-AcDON and 15-AcDON in two samples was an interesting finding. The amount of DON in total cob was highly correlated (r = 0.94) with percentage ofFusarium damaged kernels in given ear.


Hepatocyte growth factor suppresses ischemic cerebral edema in rats with microsphere embolism.
The present study was aimed at determining whether human recombinant hepatocyte growth factor (HGF) ameliorates cerebral edema induced by microsphere embolism (ME). Rats were injected with 700 microspheres (48 microm in diameter). Continuous administration of HGF at 13 microg/3 days/animal into the right ventricle was started from 10 min after embolism to the end of the experiment by using an osmotic pump. On day 3 after the ME, the rats were anesthetized, and their brains were perfused with an isotonic mannitol solution to eliminate constituents in the vascular and extracellular spaces. Thereafter, tissue water and cation contents were determined. A significant increase in tissue water content of the right hemisphere by ME was seen. This ME-induced increase in water content was associated with increases in tissue sodium and calcium ion contents and decreases in tissue potassium and magnesium ion contents of the right hemisphere. The treatment of the animal with HGF suppressed the increases in water and sodium and calcium ion contents, but not the decreases in potassium and magnesium ion contents. These results suggest that HGF suppresses the formation of ischemic cerebral edema provoked intracellularly in rats with ME.


Issues for mature women with epilepsy.
Specific concerns regarding mature women with epilepsy (WWE), specifically epilepsy-associated issues during perimenopause, menopause, and postmenopause, have been emerging in the epilepsy community. This chapter presents evidence that for WWE, seizure frequency may increase during perimenopause and decrease at postmenopause, especially if a catamenial epilepsy pattern was present during the reproductive years. This finding implies that, as in other age groups, a subset of mature WWE are particularly susceptible to endogenous reproductive hormonal changes. An adverse effect on seizure frequency with the use of hormone replacement therapy (HRT) during postmenopause for WWE was reported in surveys, and a dose-related association between standard HRT and increased seizures was later borne out in a double-blind, placebo-controlled, randomized clinical trial. Management of symptomatic postmenopausal WWE using estrogenic and progestogenic compounds that are less likely to promote seizures is discussed. WWE are at risk for premature ovarian failure and for menopause at a younger age than the general population. This appears to be related to epilepsy severity in terms of seizure frequency and is likely a consequence of adverse effects of seizures and interictal activity on the hypothalamo-pituitary-gonadal axis. The decline in antiepileptic drug (AED) clearance, as well as alterations in gastric functioning and decreasing albumin levels, with maturity can affect AED use in the aging population; therefore, mature individuals with epilepsy need to be monitored carefully for toxicity and for increasing AED levels that could eventually cause toxicity. Information about gender differences for AED use in the mature population is scant.


Hydrocephalus in primary intradural spinal cord tumors: a systematic review of the literature in the pediatric population.
Hydrocephalus in children with primary intradural spinal cord tumors is exceedingly rare. Herewith, we performed a systematic literature review to address epidemiology, suggested pathophysiological mechanisms, prognostic factors, and treatment of such cases. We performed a systematic review with the best available evidence on cases of pediatric primary intradural tumors of the spinal cord presented with hydrocephalus. The patients were subjected to quantitative analysis on a basis of epidemiological features (age, sex, tumor type and location, clinical presentation, survival, dissemination). The possible pathophysiological theories are discussed in detail. Forty-four studies with a total of 121 patients were included in the study. Astrocytomas were the most frequent tumor (64.5%) type, while most tumors were located in cervical (31.4%) or cervicothoracic region (25.6%). About half of the cases concerned children under 6 years of age. The block of subarachnoid CSF (cerebrospinal fluid) pathways from disseminated tumor cells and the neoplastic inflammation caused by tumor elements advocated to be the major pathogenetic mechanisms. Surgical excision of the tumor and hydrocephalus treatment is usually performed. Primary intradural spinal cord tumors should be considered in children with communicative hydrocephalus of unknown etiology. Onset of hydrocephalus after tumor removal is related to higher mortality.


Military neurosurgery in operation: experience in the French role-3 medical treatment facility of Kabul.
In 2009, during the war in Afghanistan, the increasing number of head injuries led to the deployment of a military neurosurgeon at the Kabul International Airport (KaIA) medical treatment facility, in March 2010. The main goal of this study was to depict the neurosurgical activity in this centre and to analyse its different aspects. A retrospective study of all the neurosurgical patients treated in KaIA from March 2010 to June 2013. Three hundred and seventy-three interventions performed by the neurosurgeon deployed were reported for 373 surgeries, in 335 patients, representing 10.6 % of the overall surgical activity of the centre. Among the 69 interventions performed on soldiers, 57 surgeries were undertaken in emergency (82.6 %), while 12 were elective procedures (17.4 %). On the other hand, 289 surgeries were performed in civilian Afghans, with 126 emergency procedures in (43.6 %), against 163 elective interventions (56.4 %). Among the 44.5 % (n = 149) of the traumatic casualties, cerebral lesions represented 28.7 % (n = 96) and spinal lesions 12.4 % (n = 42). Ninety patients had multiple injuries. Additionally, patients without trauma accounted for 55.5 % (n = 186) of the overall population. Thus, 49 % (n = 164) were operated on for non-traumatic lesion of the spine. These were mostly civilian Afghans treated under medical aid to the population (90.2 %, n = 148/164). The military neurosurgeon had two roles in KaIA: both to support the armed forces and to manage medical aid to the civilian population. This study gives food for thought on the neurosurgical needs in modern warfare, and on the skills required for the military neurosurgeon.


Topographic localization of neuromedin U-like structures in the rat brain: an immunohistochemical study.
The distribution of neuromedin Us, uterus-stimulating and hypertensive peptides newly identified in porcine spinal cord, was examined in the rat brain by the indirect immunofluorescent method. Neuromedin U-like immunoreactive structures were found to be unevenly distributed in the neuronal system. Neuromedin U-like immunoreactive neurons were present in the cranial motor nuclei, reticular nuclei, nucleus vestibularis lateralis, trigeminal sensory nuclei, colliculus superior and inferior, lemniscus lateralis, nucleus pontis, nucleus ruber, zona incerta, substantia innominata, horizontal limb of the diagonal band and cerebral cortex. The immunoreactive fibres were found in the above areas, particularly near the labelled cells, forming a fibre plexus with various intensities of immunoreactivity. In addition, dense plexuses were also seen in the nucleus reticularis thalami, nucleus ventralis posteromedialis, nucleus ventralis posterolateralis, nucleus tegmentalis dorsalis and ventralis, vertical limb of the diagonal band, nucleus olivaris superior, and nucleus pontis. In the first six structures, no labelled neurons were present and in the remaining structures, a few scattered neurons were noted. This indicates that these fibres are probably of extrinsic origin.


Long-term outcome following extracorporeal membrane oxygenation for congenital diaphragmatic hernia: the UK experience.
We evaluated the long-term outcome of neonates receiving extracorporeal membrane oxygenation (ECMO) for congenital diaphragmatic hernia (CDH). Study design A retrospective review of all 73 neonates with CDH supported with ECMO in the United Kingdom between 1991 and 2000, with follow-up to January 2003. Information was from hospital charts and from communication with family doctors and pediatricians. Median follow-up period for survivors was 67 months. 46 infants (63%) were weaned from ECMO, 42 (58%) survived to hospital discharge, and 27 (37%) survived to age 1 year or more. A higher birth weight, higher 5-minute Apgar score, and postnatal diagnosis were "pre-ECMO" predictors of long-term survival. Comorbidity was common in long-term survivors: 13 (48%) had respiratory symptoms, 16(59%) had gastrointestinal problems, and 6 (19%) had severe neurodevelopmental problems. Only 7 children were free of significant neurodevelopmental deficit and required no further medical or surgical intervention. Using the current referral criteria, ECMO can be used to support the sickest neonates with CDH. However, there is significant mortality in the first year of life, and long-term physical and neurodevelopmental morbidity remains in the majority of survivors.


Preliminary study on chromosomal aberrations in eggs of mice fertilized in vitro after X-irradiation.
The X-ray induction of chromosomal aberrations in the eggs of mice fertilized in vitro was studied by using a fertilization technique developed by Yamada et al. (1982a,b). Mature sperm, eggs just before insemination and zygotes at the early pronuclear stage were irradiated with 40 R of X-rays. In a control and two groups of irradiated sperm or unfertilized eggs, most of the 1-cell eggs progressed to the metaphase stage (92.2-94.4%) at 15-17 h after insemination. In the group irradiated at the early pronuclear stage, 38.2% of the 1-cell eggs were still at the pronuclear stage; furthermore, a delay of chromatin condensation in one of the pronuclei was often observed. The frequency of chromosomal aberrations in the irradiated zygotes (20.6%) was much higher than that in the irradiated sperm (2.9%) or in unfertilized eggs (11.0%).


Propionic and methylmalonic acids inhibit the in vitro phosphorylation of a 85 kDa cytoskeletal protein from cerebral cortex of rats.
In this study we examine the action of methylmalonic (MMA) and propionic (PA) acids, metabolites which accumulate in methylmalonic and propionic acidemias respectively, on the endogenous phosphorylating system associated with the cytoskeletal fraction of cerebral cortex of young rats. Chronic treatment with PA and treatment of tissue slices with MMA or PA are effective in decreasing the in vitro phosphorylation into a 85 kDa cytoskeletal associated protein. We tested the effect of the acids on the endogenous kinase activities by using specific kinase activators and inhibitors. Results demonstrated that the acids interfere with the endogenous cAMP-dependent and Ca2+/calmodulin-dependent kinase activities. Furthermore, in vitro dephosphorylation of the 85 kDa protein was totally inhibited in brain slices treated with the acids. Considering the importance of protein phosphorylation to cellular function, we speculate that alteration in the phosphorylating level of cytoskeletal associated phosphoproteins induced by MMA and PA treatments may somehow be involved in steps leading to brain damage.


A GATA4/WT1 cooperation regulates transcription of genes required for mammalian sex determination and differentiation.
In mammals, sex determination is genetically controlled. The SRY gene, located on Y chromosome, functions as the dominant genetic switch for testis development. The SRY gene is specifically expressed in a subpopulation of somatic cells (pre-Sertoli cells) of the developing urogenital ridge for a brief period during gonadal differentiation. Despite this tight spatiotemporal expression pattern, the molecular mechanisms that regulate SRY transcription remain poorly understood. Sry expression has been shown to be markedly reduced in transgenic mice harboring a mutant GATA4 protein (a member of the GATA family of transcription factors) disrupted in its ability to interact with its transcriptional partner FOG2, suggesting that GATA4 is involved in SRY gene transcription. Although our results show that GATA4 directly targets the pig SRY promoter, we did not observe similar action on the mouse and human SRY promoters. In the mouse, Wilms' tumor 1 (WT1) is an important regulator of both Sry and Müllerian inhibiting substance (Amh/Mis) expression and in humans, WT1 mutations are associated with abnormalities of sex differentiation. GATA4 transcriptionally cooperated with WT1 on the mouse, pig, and human SRY promoters. Maximal GATA4/WT1 synergism was dependent on WT1 but not GATA4 binding to their consensus regulatory elements in the SRY promoter and required both the zinc finger and C-terminal regions of the GATA4 protein. Although both isoforms of WT1 synergized with GATA4, synergism was stronger with the +KTS rather than the -KTS isoform. WT1/GATA4 synergism was also observed on the AMH promoter. In contrast to SRY, WT1/GATA4 action on the mouse Amh promoter was specific for the -KTS isoform and required both WT1 and GATA4 binding. Our data therefore provide new insights into the molecular mechanisms that contribute to the tissue-specific expression of the SRY and AMH genes in both normal development and certain syndromes of abnormal sex differentiation.


Using fetal nuchal translucency to screen for major congenital cardiac defects at 10-14 weeks of gestation: population based cohort study.
To examine the utility of measuring fetal nuchal translucency thickness in screening for major defects of the heart and great arteries at 10-14 weeks of gestation. Population based cohort study. 29 154 singleton pregnancies with chromosomally normal fetuses at 10-14 weeks of gestation. Fetal medicine centre in London. Prevalence of major defects of the heart and great arteries. Of 50 cases with major defects of the heart and great arteries (prevalence 1.7 per 1000 pregnancies) 28 (56%, 95% confidence interval 42% to 70%) were in the subgroup of 1822 pregnancies with fetal nuchal translucency thicknesses above the 95th centile of the normal range. The positive and negative predictive values for this cut off point of nuchal translucency thickness were 1.5% and 99.9% respectively. Measurement of fetal nuchal translucency thickness-traditionally used to identify fetuses at high risk of aneuploidy-at 10-14 weeks of gestation can identify a large proportion of fetuses with major defects of the heart and great arteries.


Smoking cessation in patients with COPD in daily general practice (SMOCC): six months' results.
Chronic Obstructive Pulmonary Disease (COPD) forms an increasing health problem. Despite smoking cessation improving the prognosis of the disease, many patients persist smoking. The present study presents the results of a smoking cessation counseling protocol in general practice (Smoking Cessation in patients with COPD in general practice (SMOCC)). A randomized controlled trial of patients with COPD compared smoking cessation counseling according to an intensified minimal intervention strategy with usual care. In total 43 general practices with 392 patients participated in Nijmegen, The Netherlands, in 2001-2002. Significantly more smokers in the experimental group made a quit attempt (44.9% versus 36.5%) and actually quit smoking than in the control group (16.0% versus 8.8%). The motivation to stop smoking at baseline was not associated with smoking cessation. The SMOCC strategy doubled the self-reported quit rates and was complied well by the general practitioners. Implementation in general practice is recommended.


Structure-based functional annotation of putative conserved proteins having lyase activity from Haemophilus influenzae.
Haemophilus influenzae is a small pleomorphic Gram-negative bacteria which causes several chronic diseases, including bacteremia, meningitis, cellulitis, epiglottitis, septic arthritis, pneumonia, and empyema. Here we extensively analyzed the sequenced genome of H. influenzae strain Rd KW20 using protein family databases, protein structure prediction, pathways and genome context methods to assign a precise function to proteins whose functions are unknown. These proteins are termed as hypothetical proteins (HPs), for which no experimental information is available. Function prediction of these proteins would surely be supportive to precisely understand the biochemical pathways and mechanism of pathogenesis of Haemophilus influenzae. During the extensive analysis of H. influenzae genome, we found the presence of eight HPs showing lyase activity. Subsequently, we modeled and analyzed three-dimensional structure of all these HPs to determine their functions more precisely. We found these HPs possess cystathionine-β-synthase, cyclase, carboxymuconolactone decarboxylase, pseudouridine synthase A and C, D-tagatose-1,6-bisphosphate aldolase and aminodeoxychorismate lyase-like features, indicating their corresponding functions in the H. influenzae. Lyases are actively involved in the regulation of biosynthesis of various hormones, metabolic pathways, signal transduction, and DNA repair. Lyases are also considered as a key player for various biological processes. These enzymes are critically essential for the survival and pathogenesis of H. influenzae and, therefore, these enzymes may be considered as a potential target for structure-based rational drug design. Our structure-function relationship analysis will be useful to search and design potential lead molecules based on the structure of these lyases, for drug design and discovery.


Rapid and transient induction of c-fos, c-myc and c-Ha-ras in rat liver following glycine administration.
Administration of glycine (2.5 mmoles/100 g., i.p.) results in an increased expression of several cell cycle dependent genes such as c-fos, c-myc and c-Ha-ras in the rat liver. The increased expression could be noticed as early as 20-40 minutes and declined by 2 hours following glycine administration. The rapid rise and decline in the mRNA levels of c-fos, c-myc and c-Ha-ras in response to glycine is of significance because in response to a wide variety of growth stimuli, these proto-oncogenes exhibit a temporal sequence in their expression; for example, the expression of c-fos precedes that of c-myc, which in turn precedes the increased expression of c-Ha-ras. The experimental model using a simple amino acid such as glycine will be useful in exploring some of the mechanisms of regulation of expression of these proto-oncogenes.


Are subarctic Indians undergoing the epidemiologic transition?
The applicability of A. R. Omran's 'epidemiologic transition' theory to subarctic Indians in Canada is examined in a historical review of health and demographic data. The major trends since the time of European contact include the rise-and-fall of infectious diseases, the emergence of chronic, degenerative diseases, and the preeminence of the social pathologies in the post-World War II era. The divergences of the Amerindian experience from the 3 models in the epidemiologic transition theory and their implications for health care delivery are discussed.


Is polycystic ovarian syndrome a risk factor for urolithiasis?
Urinary stone disease is a complex multifactorial disorder influenced by both intrinsic and environmental factors. It is generally known that age and sex are risk factors for urinary stone disease. Also men have higher mean urinary oxalate concentrations than women. In addition, in animal and human studies, testosterone has been shown to increase the formation of urinary stones. This suggests that sex hormones are considered to be involved in the pathogenesis of stone disease. Polycystic ovary syndrome (PCOS) is one of the most frequent endocrine disorders of women in the reproductive age, affecting 5-10 % of women in this life span. It is characterized with chronic anovulation\oligo-ovulation, clinical or biochemical evidence of hyperandrogenism and polycystic ovaries on ultrasound examination. Hyperandrogenism, the main feature of PCOS, may trigger the urinary stone formation besides hirsutism, alopecia and acne. Therefore, we hypothesize that PCOS accompanied by hyperandrogenism may be a risk factor in the formation of urinary stone disease.


An historical perspective from the Green Revolution to the gene revolution.
Since the 1960s conventional crop breeding has increased food production commesurate with the growing population. For agricultural development to continue, the exploitation of greater genetic diversity and modern biotechnology are becoming increasingly important. This article reviews the milestones achieved by the Green Revolution and many of the recent breakthroughs of modern biotechnology.


Fossil and biogenic CO₂ from waste incineration based on a yearlong radiocarbon study.
We describe the first long-term implementation of the radiocarbon (¹⁴C) method to study the share of biogenic (%Bio C) and fossil (%Fos C) carbon in combustion CO₂. At five Swiss incinerators, a total of 24 three-week measurement campaigns were performed over 1 year. Temporally averaged bag samples were analyzed for ¹⁴CO₂ by accelerator mass spectrometry. Significant differences between the plants in the share of fossil CO₂ were observed, with annual mean values from 43.4 ± 3.9% to 54.5 ± 3.1%. Variations can be explained by the waste composition of the respective plant. Based on our dataset, an average value of 48 ± 4%Fos C was determined for waste incineration in Switzerland. No clear annual trend in %Fos C was observed for four of the monitored incinerators, while one incinerator showed considerable variations, which are likely due to the separation and temporary storage of bulky goods.


Galectin-3 expression in papillary thyroid carcinoma: relation to histomorphologic growth pattern, lymph node metastasis, extrathyroid invasion, and tumor size.
Galectin-3 has been recently recognized as a promising presurgical marker of thyroid malignancy. Galectin-3 expression was examined immunohistochemically in 202 specimens of papillary thyroid carcinoma (PTC) in relation to histomorphologic subtypes and clinicopathologic data. RESULTS.: The sensitivity of galectin-3 immunostaining versus conventional histology was 98% (100 of 102) for classical PTC, 85.2% (46 of 54) for follicular variant, and 50% (23 of 46) for follicular/solid variant of PTC. All cases (n = 36) involving lymph node metastases and 42 of 45 cases with extrathyroid invasion expressed galectin-3. However, among the galectin-3-positive cases (n = 169), 133 were without lymph node metastases, and 127 were without extrathyroid invasion. Galectin-3 expression was not related to the size of intrathyroid PTC. Galectin-3 immunohistochemical expression itself is not an indicator of local metastatic spread or extrathyroid invasion of PTC, thus being irrelevant clinically from this aspect. Galectin-3 is an excellent marker for classical PTC but must be used with caution in diagnosing unconventional variants of PTC because of the possibility of false-negative results.


Angiotensin II receptor blocker inhibits tumour necrosis factor-alpha-induced cell damage in human renal proximal tubular epithelial cells.
We investigated the effect of angiotensin II (AII) type 1 (AT1) and angiotensin II type 2 (AT2) receptor blockers on tumour necrosis factor alpha (TNF-alpha)-induced cell damage in human renal proximal tubular epithelial cells (RPTEC). The lactate dehydrogenase (LDH) and N-acetyl-beta-glucosaminidase (NAG) release into the medium after TNF-alpha treatment in RPTEC were determined using modified commercial procedures. In addition, the levels of caspase 3/7 activity in RPTEC were measured after TNF-alpha treatment with AlphaTau1 or AT2 receptor blockers. Finally we investigated the change of p22phox protein levels after TNF-alpha with AlphaTau1 or AT2 receptor blockers in RPTEC. Tumour necrosis factor alpha (10(-8) mol/L) significantly increased LDH and NAG release into the medium from RPTEC. AlphaTau1 receptor blockers, olmesartan and valsartan (10(-9)-10(-6) mol/L) showed a significant reduction on TNF-alpha-induced LDH and NAG release in RPTEC. AT2 receptor blocker, PD123319 (10(-7)-10(-5) mol/L) also decreased TNF-alpha-induced LDH and NAG release in RPTEC. Blockade of both AlphaTau1 and AT2 receptor indicated additional reduction on TNF-alpha-induced LDH and NAG release. TNF-alpha (10(-8) mol/L) treatment showed small but significant increases of caspase 3/7 activity in RPTEC, and AT1 and AT2 receptor blockers (10(-8) mol/L) comparably decreased TNF-alpha-induced caspase 3/7 activity. Significant increases of p22phox protein levels were observed in TNF-alpha-treated group in RPTEC. However, only AlphaTau1 (10(-8) mol/L) but not AT2 (10(-5) mol/L) receptor blocker significantly decreased TNF-alpha-induced p22phox protein levels. The present study demonstrates that TNF-alpha induces renal tubular cell damage in RPTEC and AT1/AT2 receptor blockers showed cytoprotective effects probably via at least partly different mechanism.


Herpes simplex virus type 1 (HSV-1) UL56 gene is involved in viral intraperitoneal pathogenicity to immunocompetent mice.
A comparison of the pathogenicity in mice of the recombinant herpes simplex virus type 1 (HSV-1) strain HSV-1-M-LacZ, in which the UL56 gene has been deleted, was made with its parental strain F, following infection in different mouse strains. The polymerase chain reaction (PCR) technique was used to study the migration of virus DNA in the mouse model. Tissues from adult mice infected intraperitoneally (IP) with one of three HSV-1 strains (F, HFEM or HSV-1-LacZ) were examined for the presence of viral DNA. DNA of the pathogenic strain F was detected in the adrenal glands, spinal cord, brain, liver and pancreas. DNA of HSV-1-M-LacZ was detected in the same tissues. However, DNA of the apathogenic strain HFEM was detected transiently (on days 2 and 3 p.i., but not days 1, 5 or 7), only in the adrenal glands and no viral DNA was detected in any of the other tissues. HSV-1 pathogenic strains injected intraperitoneally into newborn mice (7 days old) killed most of the mice. In the surviving mice viral DNA of the three virus strains was found in peritoneal exudate cells (PEC), adrenal glands, spinal cord, liver and spleen. It was found that HSV-1-M-LacZ, which lacks the UL56 gene, resembled in pathogenicity to the newborn mice the pathogenic HSV-1 strains F and KOS. The PCR technique was used to trace viral DNA in tissues of the mice which survived HSV-1 infection at 7 weeks of age. Only HSV-1 (KOS) DNA was detected in the pancreas. The brains of these mice did not contain viral DNA. It is suggested that HSV-1 DNA may reside in surviving HSV-1- infected newborn mice in a "latent" state in nonneural tissues.


Stability of SARS-CoV-2 and other airborne viruses under different stress conditions.
Viral stability under stress conditions may directly affect viral dissemination, seasonality, and pathogenesis. We exposed airborne viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mumps virus, coxsackievirus B5, human rhinovirus A16, and respiratory syncytial virus, to different temperatures, UV light exposure time, pH values, and osmotic pressures and measured the remaining viral infectivity. Reduced thermal stability was observed for coxsackievirus B5 at 45 °C, while SARS-CoV-2 demonstrated residual infectivity at 55 °C. UV light exposure was an efficient means of viral inactivation but was less efficient for non-enveloped viruses. Rhinovirus A16 and respiratory syncytial virus demonstrated extreme sensitivity to acid conditions, while SARS-CoV-2, rhinovirus A16, and respiratory syncytial virus were unstable in an alkaline environment. The information obtained in this study will be useful for the development of viral inactivation methods and may be correlated with epidemiological and seasonal viral characteristics.


Guidelines for the management of hospital-acquired pneumonia in the UK: report of the working party on hospital-acquired pneumonia of the British Society for Antimicrobial Chemotherapy.
These evidence-based guidelines have been produced after a systematic literature review of a range of issues involving prevention, diagnosis and treatment of hospital-acquired pneumonia (HAP). Prevention is structured into sections addressing general issues, equipment, patient procedures and the environment, whereas in treatment, the structure addresses the use of antimicrobials in prevention and treatment, adjunctive therapies and the application of clinical protocols. The sections dealing with diagnosis are presented against the clinical, radiological and microbiological diagnosis of HAP. Recommendations are also made upon the role of invasive sampling and quantitative microbiology of respiratory secretions in directing antibiotic therapy in HAP/ventilator-associated pneumonia.


[Management of glycemia: an audit in 66 ICUs].
The interest of tight glucose control in ICU is still debated. In France, no data are available regarding this therapy and the implementation of its guidelines. Sub-study of a one-day audit performed between January and May 2009. During a one-day audit performed in 66 ICUs, trained residents collected data regarding the presence of a formal glucose control protocol and its practical application. A formalized glucose control protocol was found in 88% of patients. During the day before the audit, 3645 glycemia measurements were performed accounting for six measurements [4-9] per patient with a median higher value of 1.6 [1.4-2.1]. Hypoglycemia (<0.8 g/L) and hyperglycemia (>1.4 g/L in non-diabetic and >1.8 g/L in diabetic patients) were found in 81 (15%) and 326 (58%) patients respectively. Two episodes (0.36%) of severe hypoglycemia (<0.4 g/L) were reported. Factors associated with glucose control protocol application were: a high SOFA score, cardioversion, mechanical ventilation, intracranial pressure monitoring, steroid use and nurse to patient ratio less than 1/2.5. Hepatic failure was the only factor associated with hypoglycemia. Glucose control protocols are available in more than 80% ICUs but their implementation is still imperfect. However, the median glycemia meets international current recommendations. Severe hypoglycemia is a very rare event in ICU.


Targeting the JAK/STAT Pathway in T Cell Lymphoproliferative Disorders.
T cell lymphoproliferative disorders represent a diverse group of hematologic malignancies with poor prognosis underscoring the need for novel therapeutic approaches. Disruption of the JAK/STAT signaling pathway has been described in this group of blood cancers and may represent an approach for targeted therapy. Here, we summarize the current data describing the disruptions of JAK/STAT signaling in T cell malignancies and focus on the existing evidence for exploitation of this pathway with targeted therapies. To date, preclinical studies have demonstrated the efficacy of JAK/STAT inhibition in the treatment of several T cell lymphoproliferative disorders. More recently, several early clinical trials have demonstrated promising results utilizing this approach as well. The benefit of the combination of JAK/STAT-targeted therapies along with immunotherapy and other molecularly targeted therapies is also discussed. There is substantial evidence that targeting the JAK/STAT pathway in T cell lymphoproliferative disorders could be of clinical benefit. There are several early clinical trials showing promise and many ongoing trials investigating the optimal utility of agents that inhibit this signaling pathway. In addition, targeting this pathway may provide a platform for further rational combination therapies.


Inhibition of zinc absorption by iron depends on their ratio.
Previous studies upon zinc-iron interactions gave conflicting results that could come from differences in protocol design or in trace element status of subjects. The present work assessed the influence of zinc : iron ratio and iron deficiency upon zinc absorption. The digestive absorption of zinc sulphate (100 micromol Zn/l) in presence of iron gluconate was studied in perfused jejunal loops (n = 6/group) of normal rats (range 0-1000 micromol Fe/l) and iron deficient rats (200-750 micromol Fe/l). In normal rats no significant iron inhibition on zinc absorption occurred at Fe:Zn ratio below 2:1. At higher ratios zinc uptake and net absorption decreased significantly (p<0.05). Between 2:1 and 5:1 a dose dependent inhibition of zinc absorption occurred and reached a plateau beyond this ratio. In iron deficient animals no changes in zinc uptake, mucosal retention and absorption compared to normal animals occurred at ratio 2:1. At higher ratios differences were observed at every zinc absorption step except for mucosal retention at 7.5:1 ratio. Iron-zinc interactions depend on their ratio and on previous trace elements status of subjects. Due to the wide and unknown variations that were likely to occur between the subjects of previous human and experimental studies, these results could explain some of the discrepancies between their results.


A novel C-terminal truncating NR5A1 mutation in dizygotic twins.
Nuclear receptor subfamily 5, group A, member 1 (NR5A1) is a nuclear receptor involved in gonadal and adrenal development. We identified a novel C-terminally truncating NR5A1 mutation, p.Leu423Trpfs*7, in dizygotic twins with 46,XY disorders of sex development. Our results highlight the functional importance of C-terminal region of NR5A1 and indicate that NR5A1 mutations can be associated with intrafamilial phenotypic variations, progressive testicular dysfunction, hypogonadotropic hypogonadism, and borderline adrenal dysfunction.


A sandcastle worm-inspired strategy to functionalize wet hydrogels.
Hydrogels have been extensively used in many fields. Current synthesis of functional hydrogels requires incorporation of functional molecules either before or during gelation via the pre-organized reactive site along the polymer chains within hydrogels, which is tedious for polymer synthesis and not flexible for different types of hydrogels. Inspired by sandcastle worm, we develop a simple one-step strategy to functionalize wet hydrogels using molecules bearing an adhesive dibutylamine-DOPA-lysine-DOPA tripeptide. This tripeptide can be easily modified with various functional groups to initiate diverse types of polymerizations and provide functional polymers with a terminal adhesive tripeptide. Such functional molecules enable direct modification of wet hydrogels to acquire biological functions such as antimicrobial, cell adhesion and wound repair. The strategy has a tunable functionalization degree and a stable attachment of functional molecules, which provides a tool for direct and convenient modification of wet hydrogels to provide them with diverse functions and applications.


A NaYbF4: Tm3+ nanoprobe for CT and NIR-to-NIR fluorescent bimodal imaging.
Early diagnosis that combines the high-resolutional CT and sensitive NIR-fluorescence bioimaging could provide more accurate information for cancerous tissues, which, however, remain a big challenge. Here we report a simple bimodal imaging platform based on PEGylated NaYbF(4): Tm(3+) nanoparticles (NPs) of less than 20 nm in diameter for both CT and NIR-fluorescence bioimaging. The as-designed nanoprobes showed excellent in vitro and in vivo performances in the dual-bioimaging, very low cytotoxicity and no detectable tissue damage in one month. Remarkably, the Yb(3+) in the lattice of NaYbF(4): Tm(3+) NPs functions not only as a promising CT contrast medium due to its high X-ray absorption coefficiency, but also an excellent sensitizer contributing to the strong NIR-fluorescent emissions for its large NIR absorption cross-section. In addition, these NPs could be easily excreted mainly via feces without detectable remnant in the animal bodies.


Mapping knowledge structure and research trends of knee osteoarthritis with meniscus in two decades: A bibliometric analysis.
Knee osteoarthritis (KOA) is a chronic degenerative disease that is closely related to the meniscus. Currently, no bibliometric studies have jointly analyzed KOA and the meniscus. This study aimed to provide a comprehensive analysis of the knowledge structure of KOA and the meniscus across two decades and to identify the emerging research trends from a bibliometric perspective. All articles reporting KOA and the meniscus from 2001 to 2021 were obtained from the Web of Science Core Collection. R software, CiteSpace, VOS Viewer, and Microsoft Excel were used to analyze the publications including the authors, cited authors, journals, cited journals, country of research, institutions, and research focus. These data were used to generate visual knowledge maps of the outputs. A total of 3,218 articles were retrieved. Guermazi was identified as the author who had contributed the most to the field and Osteoarthritis and Cartilage was identified as the most productive research journal. The United States is the global leader in the field and the center for international cooperation with less international collaboration occurring in Eastern Asia. Boston University was the most prolific institution. According to the data, "articular-cartilage," "meniscectomy," "follow-up," "anterior cruciate ligament," and "cartilage" were identified as research hotspots in the field. "Consequences," "prognostic-factors," and "receptor" were predicted as future hot topics of research. This study is the first comprehensive bibliometric study to jointly analyze KOA and the meniscus. Our data enable a better understanding of research trends and identify research hotspots and gaps in knowledge across the field. Our findings provide practical information for researchers to better understand the key research areas and identify the research frontiers and future hot topics.


Effects of bereavement on indicators of mental health in elderly widows and widowers.
The effects of bereavement on self-report measures of psychological distress were evaluated in widows and widowers at approximately 2 months after the death of a spouse. These data represent the first time of measurement in an ongoing longitudinal study of conjugal bereavement in elders. Responses of 95 male and 104 female elderly bereaved on measures of grief, depression, global severity of psychological distress, and general mental health functioning were compared with those of 79 male and female elderly individuals who were not currently suffering from the loss of a spouse. In general, means for the bereaved group were not in ranges consistent with the presence of serious psychopathology. Women in both groups reported greater distress than men, and significant sex-by-bereavement-status interactions on mental health measures were not observed.


Surface sorption and nanoparticle production as a silver detoxification mechanism of the freshwater alga Parachlorella kessleri.
SEM, EDS, TEM, FTIR and UV-vis analysis were used to investigate the biosorption, bioaccumulation and bioreduction of silver by the freshwater green alga Parachlorella kessleri. The dead algal biomass showed high potential for silver removal; 75% of silver was removed within 2min. Surface sorption was the main mechanism; bioreduction contributed to the biosorption only to a small extent. In the presence of living P. kessleri cells a 68% decrease of silver concentration was observed within 24h, but subsequently the majority of silver was released back into the solution within the next 14days. According to UV-vis spectrometry, silver nanoparticles were formed in that time. The nanoparticles produced by the alga exhibited a lower toxicity against algal cells than silver ions at the same silver concentrations. The study demonstrated that living algal cells used a combination of two main mechanisms (sorption and reduction) for silver detoxification in their environment.


Characterization of a cAMP responsive transcription factor, Cmr (Rv1675c), in TB complex mycobacteria reveals overlap with the DosR (DevR) dormancy regulon.
Mycobacterium tuberculosis (Mtb) Cmr (Rv1675c) is a CRP/FNR family transcription factor known to be responsive to cAMP levels and during macrophage infections. However, Cmr's DNA binding properties, cellular targets and overall role in tuberculosis (TB) complex bacteria have not been characterized. In this study, we used experimental and computational approaches to characterize Cmr's DNA binding properties and identify a putative regulon. Cmr binds a 16-bp palindromic site that includes four highly conserved nucleotides that are required for DNA binding. A total of 368 binding sites, distributed in clusters among ~200 binding regions throughout the Mycobacterium bovis BCG genome, were identified using ChIP-seq. One of the most enriched Cmr binding sites was located upstream of the cmr promoter, and we demonstrated that expression of cmr is autoregulated. cAMP affected Cmr binding at a subset of DNA loci in vivo and in vitro, including multiple sites adjacent to members of the DosR (DevR) dormancy regulon. Our findings of cooperative binding of Cmr to these DNA regions and the regulation by Cmr of the DosR-regulated virulence gene Rv2623 demonstrate the complexity of Cmr-mediated gene regulation and suggest a role for Cmr in the biology of persistent TB infection.


Global epidemiology of human herpesvirus 8 in men who have sex with men: A systematic review and meta-analysis.
Men who have sex with men (MSM) were highly vulnerable to HIV/AIDS and Human herpes virus 8 (HHV8), while the epidemiologic features of HHV8 among MSM remain obscure. We therefore performed a systematic review and meta-analysis to assess the burden of HHV8 in MSM. Electronic databases were searched for publications on HHV8 epidemiologic characteristics among MSM. Random-effect meta-analysis was applied to combine the HHV8 seroprevalence in MSM and odds ratios (ORs) for associated risk factors. Meta-regression and stratified analyses were performed to detect the potential sources of heterogeneity. The pooled HHV8 seroprevalence in MSM was 33.0% (95%CI 29.2%-37.1%). Significant factors associated with HHV8 included HIV (OR 3.70, 95%CI 2.93-4.67), STDs (OR 2.32, 95%CI 1.82-2.97), and high risk sexual behaviors (OR 1.50, 95%CI 1.17-1.92). Race (OR 1.44, 95%CI 0.94-2.12) and multiple sexual partners (OR 1.61, 95%CI 0.95-2.72) were also associated with HHV8 (P < 0.10). We found no significant association between IDU and HHV8 (OR 1.44, 95%CI 0.06-32.47). HHV8 is highly prevalent among MSM and the high risk behaviors may facilitate the transmission of this virus. This situation could be of significant public health importance, especially in the context of HIV coinfection.


Direct measurement of high molecular weight forms of renin in plasma.
Gel filtration of normal mouse serum revealed the presence of high molecular-weight forms of renin, in addition to the well-recognized 40 000 dalton form. The distribution of renin was measured by using both the antibody trapping method, which measures renin's enzymatic reactivity, and by a direct radio-immunoassay, which detects the renin molecule by its antigenic properties. A well characterized and distinct peak corresponding to a molecular weight of 200 000 or greater was always present. A less distinct peak was seen between 70 000 and 140 000 daltons. The well separated and symmetrical peak at 40 000-45 000 daltons was secreted from both kidneys and submaxillary glands and disappeared almost completely after combined nephrectomy and sialoadenectomy in contrast to the forms of higher molecular weight. The higher the molecular weight the lower was the specific enzymatic reactivity found to be. The 200 000-dalton peak was mainly detectable by the direct assay, although it was demonstrated to contain enzymatic reactivity to a small extent. The 40 000-dalton peak had a specific enzymatic reactivity and molecular weight identical to that of pure submaxillary renin.


Suppressive effect of captopril on platelet aggregation in essential hypertension.
Effects of captopril on platelet aggregation were studied in 12 essential hypertensive subjects. At the same time, the effects of captopril and angiotensin II on platelet aggregation in vitro were examined in 20 volunteers. A 50-mg oral dose of captopril was administered daily to hypertensive subjects for 2 weeks; the dose was then increased to 100 mg daily for the next 2 weeks. Values of platelet aggregation induced by ADP, epinephrine, collagen, and arachidonic acid before captopril treatment were 71.9 +/- 4.5, 77.3 +/- 4.2, 72.4 +/- 4.1, and 70.8 +/- 4.3% (mean +/- SE), respectively. Two weeks after daily administration of 50 mg captopril, these values were 56.7 +/- 4.5, 50.8 +/- 7.6, 64.0 +/- 4.6, and 60.9 +/- 3.9%, respectively, with significant reduction of platelet aggregation (p less than 0.001, p less than 0.01, p less than 0.01, and p less than 0.005, respectively). Daily administration of 100 mg captopril also had a significant suppressive effect on platelet aggregation. Changes of platelet count and serum lipids were not significant. In vitro, captopril and angiotensin II added to platelet-rich plasma had no effect on platelet aggregation. These results show that the suppressive effect of captopril on platelet aggregation is a secondary action in vivo.


[Antibacterial activity of cefmenoxime against clinical isolates. Comparative study].
Antibacterial activity of cefmenoxime (CMX) against clinically isolated organisms was examined in comparison with that of 4 other antibiotics and concluded as follows: Antibacterial activity of CMX was markedly stronger than those of cefazolin (CEZ), cefmetazole, latamoxef and ampicillin against E. coli, K. pneumoniae, S. marcescens, H. influenzae, P. mirabilis and indole positive Proteus. But the MIC level of CMX against S. aureus was higher than that of CEZ.


Exercise intensity domains determined by heart rate at the ventilatory thresholds in patients with cardiovascular disease: new insights and comparisons to cardiovascular rehabilitation prescription recommendations.
To compare the elicited exercise responses at ventilatory thresholds (VTs: VT1 and VT2) identified by cardiopulmonary exercise testing (CPET) in patients with cardiovascular disease (CVD) with the guideline-directed exercise intensity domains; to propose equations to predict heart rate (HR) at VTs; and to compare the accuracy of prescription methods. A cross-sectional study was performed with 972 maximal treadmill CPET on patients with CVD. First, VTs were identified and compared with guideline-directed exercise intensity domains. Second, multivariate linear regression analyses were performed to generate prediction equations for HR at VTs. Finally, the accuracy of prescription methods was assessed by the mean absolute percentage error (MAPE). Significant dispersions of individual responses were found for VTs, with the same relative intensity of exercise corresponding to different guideline-directed exercise intensity domains. A mathematical error inherent to methods based on percentages of peak effort was identified, which may help to explain the dispersions. Tailored multivariable equations yielded r2 of 0.726 for VT1 and 0.901 for VT2. MAPE for the novel VT1 equation was 6.0%, lower than that for guideline-based prescription methods (9.5 to 23.8%). MAPE for the novel VT2 equation was 4.3%, lower than guideline-based methods (5.8%-19.3%). The guideline-based exercise intensity domains for cardiovascular rehabilitation revealed inconsistencies and heterogeneity, which limits the currently used methods. New multivariable equations for patients with CVD were developed and demonstrated better accuracy, indicating that this methodology may be a valid alternative when CPET is unavailable.


Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers.
A fraction of COVID-19 convalescent individuals mount a potent antibody response to SARS-CoV-2 with cross-reactivity to SARS-CoV-1. To uncover their humoral response in detail, we performed single B cell analysis from 10 SARS-CoV-2 elite neutralizers. We isolated and analyzed 126 monoclonal antibodies, many of which were sarbecovirus cross-reactive, with some displaying merbecovirus- and embecovirus-reactivity. Several isolated broadly neutralizing antibodies were effective against B.1.1.7, B.1.351, B.1.429, B.1.617, and B.1.617.2 variants and 19 prominent potential escape sites. Furthermore, assembly of 716,806 SARS-CoV-2 sequences predicted emerging escape variants, which were also effectively neutralized. One of these broadly neutralizing potent antibodies, R40-1G8, is a IGHV3-53 RBD-class-1 antibody. Remarkably, cryo-EM analysis revealed that R40-1G8 has a flexible binding mode, targeting both "up" and "down" conformations of the RBD. Given the threat of emerging SARS-CoV-2 variants, we demonstrate that elite neutralizers are a valuable source for isolating ultrapotent antibody candidates to prevent and treat SARS-CoV-2 infection.


Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus.
Lorazepam was compared with diazepam for the treatment of acute convulsions and status epilepticus in 102 children in a prospective, open, 'odd and even dates' trial. Convulsions were controlled in 76 per cent of patients treated with a single dose of lorazepam and 51 per cent of patients treated with a single dose of diazepam. Significantly fewer patients treated with lorazepam required additional anticonvulsants to terminate the seizure. Respiratory depression occurred in 3 per cent of lorazepam-treated patients and 15 per cent of diazepam-treated patients. No patient who received lorazepam required admission to the intensive care unit for either respiratory depression or persisting status epilepticus. Rectally administered lorazepam appeared to be particularly valuable (100 per cent efficacy) when venous access was not possible.


The vOTU domain of highly-pathogenic porcine reproductive and respiratory syndrome virus displays a differential substrate preference.
Arterivirus genus member Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically devastating disease, recently exacerbated by the emergence of highly pathogenic strains (HP-PRRSV). Within the nonstructural protein 2 of PRRSV is a deubiquitinating enzyme domain belonging to the viral ovarian tumor (vOTU) protease superfamily. vOTUs, which can greatly vary in their preference for their host ubiquitin (Ub) and Ub-like substrates such as interferon stimulated gene 15 (ISG15), have been implicated as a potential virulence factor. Since various strains of PRRSV have large variations in virulence, the specificity of vOTUs from two PRRSV strains of varying virulence were determined. While both vOTUs showed de-ubiquitinating activity and markedly low deISGylating activity, HP-PRRSV demonstrated a strong preference for lysine 63-linked poly-Ubiquitin, tied to innate immune response regulation. This represents the first report of biochemical activity unique to HP-PRRSV that has implications for a potential increase in immunosuppression and virulence.


Correction: Structural Perturbations to Population Skeletons: Transient Dynamics, Coexistence of Attractors and the Rarity of Chaos.
[This corrects the article DOI: 10.1371/journal.pone.0024200.].


Concomitant formation of two different solvates of a hexa-host from a binary mixture of solvents.
Crystallization of hexakis(4-cyanophenyloxy)benzene from a mixture of two different solvents produces two different solvates concomitantly, which were characterized by X-ray diffraction, thermal analysis and NMR spectroscopy.


Thymol inhibits Candida albicans biofilm formation and mature biofilm.
Candida albicans has a high propensity to develop biofilms that are resistant to traditional antifungal agents. Thymol is credited with a series of pharmacological properties including antimicrobial and antifungal effects. As C. albicans biofilms are known to be important factors underlying its virulence and pathogenicity, the aim of this study was to investigate whether thymol can interfere with biofilm formation as well as acting on mature biofilms. Tests of C. albicans strains ATCC 3153A and ATCC MYA 2876 showed that thymol interferes with the starting phases of biofilm production as well as with mature C. albicans biofilms. The metabolic activity of sessile cells was reduced by >90% at twice the minimum inhibitory concentration of planktonic cells. As biofilm is a multifactorial phenomenon, the multiple mechanisms of thymol (terpenes) could act on different steps in the evolution of mature biofilm.


Experiences with the dual digestion of municipal sewage sludge.
The dual digestion process was investigated using sludge samples collected at the WWTP of Tomaszow Mazowiecki (Poland). Mixed sludge was treated in a laboratory setup under batch and semi-continuous conditions. Dual digestion with a 1d SRT aerobic thermophilic pretreatment followed by an anaerobic step with 20 d of SRT turned out to be optimal, since a 44-46% VS reduction and a biogas yield of 480 dm(3)/kg VS fed were achieved. In the course of the process, the concentration of nitrogen in supernatant increased over 5 times and its major portion was converted into ammonia. Phosphorus also entered the supernatant, reaching over 200 g/m(3). The dual digestion noticeably deteriorated the sludge dewaterability. Following completion of the process, capillary suction time measurements averaged 64 s for the raw sludge, 400 s for aerobically pretreated sludge and 310-360 for the anaerobically digested sludge. Aerobic pretreatment consistently reduced Enterobacteriaceae content to below detectable limits.


Candidate genes involved in the biosynthesis of lignan in Schisandra chinensis fruit based on transcriptome and metabolomes analysis.
Schisandra chinensis Turcz. (Baill.) is a plant species with fruits that have been well known in Far Eastern medicine for a long time. It has traditionally been used as a stimulating and fortifying agent in cases of physical exhaustion and to inhibit fatigue. The major bioactive compounds found in S. chinensis are lignans with a dibenzocyclooctadiene skeleton, but little is known about their biosynthesis in plants. S. chinensis is the ideal medicinal plant for studying the biosynthesis of lignans, especially the dibenzocyclooctadiene skeleton. Genomic information for this important herbal plant is unavailable. To better understand the lignan biosynthesis pathway, we generated transcriptome sequences from the fruit during ripening and performed de novo sequence assembly, yielding 136 843 unique transcripts with N50 of 1778 bp. Putative functions could be assigned to 41 824 transcripts (51.57%) based on BLAST searches against annotation databases including GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes). Furthermore, 22 candidate cytochrome P450 genes and 15 candidate dirigent proteins genes that were most likely involved in the lignan biosynthesis pathway were discovered based on transcriptome sequencing of S. chinensis. The genomic data obtained from S. chinensis, especially the identification of putative genes involved in the lignan biosynthesis pathway, will facilitate our understanding of lignan biosynthesis at the molecular level. The lignan metabolite profiles were analyzed by metabolomes, the accumulation patterns of 30 metabolites involved in the lignan pathway were studied. Co-expression network of lignan contents and transcriptional changes showed 355 strong correlations (correlation coefficient, R2 > 0.9) between 21 compounds and 153 transcripts. Furthermore, the comprehensive analysis and characterization of the genes involved in lignan pathways and the metabolite profiles of lignans are expected to provide better insight regarding the diversity of the chemical composition, synthetic characteristics, and regulatory mechanisms of this medical herb.


The mesocolon: a prospective observational study.
The aim of this study was to characterize formally the mesocolic anatomy during and following total mesocolic excision. Total mesocolic excision may improve survival in patients with colon cancer. Although this requires a detailed knowledge of normal and variant mesocolic anatomy, the latter is poorly characterized. No studies have prospectively characterized the anatomy of the entire mesocolon. Total mesocolic excision was performed in 109 patients undergoing total abdominal colectomy. The mesocolon was maintained intact thereby permitting a precise anatomical characterization from ileocaecal to mesorectal levels. Two- and three-dimensional schematic reconstructions were generated to illustrate in situ conformation. Several previously undocumented findings emerged, including: (i) the mesocolon was continuous from ileocaecal to rectosigmoid level; (ii) a mesenteric confluence occurred at the ileocaecal and rectosigmoid junction as well as at the hepatic and splenic flexures; (iii) each flexure (and ileocaecal junction) was a complex of peritoneal and omental attachments to the colon centred on a mesenteric confluence; (iv) the proximal rectum originated at the confluence of the mesorectum and mesosigmoid; and (v) a plane occupied by Toldt's fascia separated the entire apposed mesocolon from the retroperitoneum. When the mesocolon is fully mobilized during a total mesocolic excision of the colon, several anatomical findings that have not been previously documented emerge. These findings provide a rationalization of the surgical, embryological and anatomical approaches to the mesocolon. This has implications for all related sciences.


In Vitro Tumorigenic Assay: The Tumor Spheres Assay.
Cancer stem cells (CSCs) are a subpopulation of cells within cancer tissues that are thought to mediate tumor initiation. CSCs are furthermore considered the cause of tumor progression and recurrence after conventional therapies, based on their enhanced therapy resistance properties. A method commonly used to assess CSC potential in vitro is the so-called tumor spheres assay in which cells are plated under non-adherent culture conditions in serum-free medium supplemented with growth factors. Tumor spheres assays have been used in cancer research as an intermediate in vitro cell culture model to be explored before performing more laborious in vivo tumor xenograft assays.


Evaluation of the Speed-oligo® Mycobacteria assay for identification of Mycobacterium spp. from fresh liquid and solid cultures of human clinical samples.
We evaluated the ability of a novel DNA strip assay (Speed-oligo® Mycobacteria) to differentiate mycobacterial species. It is based on polymerase chain reaction targeting 16S rRNA and 16S-23S rRNA regions and double-reverse hybridization on a dipstick using probes bound to colloidal gold and to the membrane. We blindly tested its capacity to identify 182 acid-fast bacilli grown on fresh liquid (BacT/Alert, MGIT) and solid (Lowenstein-Jensen) cultures (from Spanish mycobacteriology laboratories), previously identified by means of Genotype(®) Mycob.CM/AS or Gen-Probe(®) AccuprobeMTC, and 11 collection strains of mycobacteria-related organisms. Discrepancies were resolved by 16S rRNA sequencing. Results were interpreted by identification of 7 specific bands for the following: Mycobacterium sp., M. fortuitum, Mycobacterium avium-intracellulare complex, Mycobacterium tuberculosis complex, Mycobacterium kansasii, M. gordonae, and M. abscessus-chelonae complex. No cross-reactivity was observed with any mycobacteria-related organism. Concordant results were obtained for 177/182 bacilli (97.2%). There was only 1 major discrepancy, misidentification of Mycobacterium marinum as M. kansasii, verified by sequencing.


REIN: a tool to support scientific research
On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue its role in research, the following key messages were retained. The growing number of publications, dissertations, theses and teams involved shows that the REIN registry has attained its objective of being a shared research infrastructure, in the field of epidemiology as well as in public health, health economics or medical data processing. REIN is a valuable tool for the study of specific kidney diseases, particularly for epidemiological data pertaining to rare diseases that may lead to stage 5 of a chronic kidney disease. The linkage with the data from the National Healthcare Data System enables integrating and analysing the medical treatments received by patients, before the initiation of the replacement therapy and towards the end, as well as the details of the hospital stays.


Cluster roots--an underground adaptation for survival in extreme environments.
Cluster roots are a characteristic of members of the Proteaceae and of several other plant species that are adapted to habitats of extremely low soil fertility, usually without formation of mycorrhizal associations. Functionally linked with intense mobilization of nutrients (P, Fe, Zn, Mn) by root-induced chemical changes (pH, root exudates, redox potential) in the rhizosphere, cluster-rooted plant species can serve as model plants to study rhizosphere processes and regulatory aspects of plant adaptations for chemical mobilization of nutrients in the rhizosphere.


Gene dosage imbalances: action, reaction, and models.
Single-gene deletions, duplications, and misregulation, as well as aneuploidy, can lead to stoichiometric imbalances within macromolecular complexes and cellular networks, causing their malfunction. Such alterations can be responsible for inherited or somatic genetic disorders including Mendelian diseases, aneuploid syndromes, and cancer. We review the effects of gene dosage alterations at the transcriptomic and proteomic levels, and the various responses of the cell to counteract their effects. Furthermore, we explore several biochemical models and ideas that can provide the rationale for treatments modulating the effects of gene dosage imbalances.


Prevalence of ovarian cancer found at the time of infertility microsurgery.
We found the prevalence of ovarian cancer in infertile women less than 40 years at the time of planned microsurgery for infertility to be 1 in 95. This may represent a greater prevalence of ovarian cancer than that of all women less than 40 years. Importantly, laparoscopy did not find the ovarian cancer in these women. In conclusion, laparoscopists and microsurgeons need to be aware of the possibility of finding ovarian cancer in these young, infertile women, and this knowledge should be used to counsel and manage the patient appropriately.