Climate Change and Ecosystem Services Output Efficiency in Southern Loblolly Pine Forests.
Forests provide myriad ecosystem services that are vital to humanity. With climate change, we expect to see significant changes to forests that will alter the supply of these critical services and affect human well-being. To better understand the impacts of climate change on forest-based ecosystem services, we applied a data envelopment analysis method to assess plot-level efficiency in the provision of ecosystem services in Florida natural loblolly pine (Pinus taeda L.) forests. Using field data for n = 16 loblolly pine forest plots, including inputs such as site index, tree density, age, precipitation, and temperatures for each forest plot, we assessed the relative plot-level production of three ecosystem services: timber, carbon sequestered, and species richness. The results suggested that loblolly pine forests in Florida were largely inefficient in the provision of these ecosystem services under current climatic conditions. Climate change had a small negative impact on the loblolly pine forests efficiency in the provision of ecosystem services. In this context, we discussed the reduction of tree density that may not improve ecosystem services production.


pBINPLUS: an improved plant transformation vector based on pBIN19.
We describe the construction of a new plant transformation vector, pBINPLUS, based on the popular pBIN19 vector. Improvements over pBIN19 include location of the selectable marker gene at the left T-DNA border, a higher copy number in E. coli, and two rare restriction sites around the multiple cloning site for easier cloning and analysis of T-DNA insertions in plant genomes.


Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control 'NOHA first' study.
Factor V Leiden (FVL) and prothrombin G20210A (FIIG20210A) mutations are associated with a higher risk of miscarriage: we sought to understand whether this association differs by clinical time of unexplained miscarriage, and by ethnic origin, among women with no previous thrombotic episode, during the first intended pregnancy. We performed a case-control study nested in a cohort of 32 683 women. We analyzed 3496 pairs of women matched for classical confounding factors. The FVL and FIIG20210A mutations were associated with an increased risk of miscarriage in Caucasian women [odds ratio (OR) 3.19, 95% confidence interval (CI) 2.37-4.30, P < 0.001 and OR 2.36, 95% CI, 1.72-3.24, P < 0.001, respectively]. Among non-Caucasian women, the mutations were rare and the associations with risk of miscarriage less clear. FVL and FIIG20210A mutations were independent risk factors for miscarriages only for women with related clinical signs occurring from the 10th week of gestation on (OR 3.46, 95% CI 2.53-4.72, P < 0.001 and OR 2.60, 95% CI 1.86-3.64, P < 0.001, respectively). These results indicate that FVL and FIIG20210A mutations are associated with a significant risk of spontaneous abortion which clinical signs occur from the 10th week on of the first intended pregnancy.


Association between lncRNA CASC8 polymorphisms and the risk of cancer: a meta-analysis.
To explore the relationship between single-nucleotide polymorphisms (SNPs) in one of the long noncoding RNA (lncRNA), cancer susceptibility candidate 8 (CASC8) gene and the risk of cancer. A meta-analysis was conducted to summarize the relationship between common SNPs (rs10505477 and rs7837328) in the lncRNA CASC8 gene and the risk of cancer. The relevant references were retrieved from several authoritative databases. Rigorous inclusion and exclusion criteria were adopted to ensure the credibility of the results. The fixed effects or random effects model was used to calculate the OR and 95% CI. We tested for publication bias. Fifteen articles containing 20 datasets (24,504 cases and 22,969 controls) were finally included in the meta-analysis. Compared to the individuals carrying the rs10505477 TT genotype, those with the TC or CC genotype had a decreased risk of cancer (TC vs TT: OR 0.876, 95% CI 0.832-0.923, P<0.001; CC vs TT: OR 0.748, 95% CI 0.703-0.795, P<0.001). Allele C of rs10505477 might be a protective factor for decreasing susceptibility to cancer (OR 0.866, 95% CI 0.840-0.893, P<0.001). As for rs7837328, the GA and AA genotypes were associated with increased risks of cancer as compared to the GG genotype (ORs 1.209 and 1.336; 95% CIs 1.127-1.298 and 1.202-1.484, respectively); its A allele could significantly increase the risk of cancer compared with the G allele (OR 1.169, 95% CI 1.114-1.227, P<0.001). The rs10505477 and rs7837328 polymorphisms might be associated with risk of cancer.


Psychiatry and children in the child welfare system.
The child welfare system is, for better or worse, an unavoidable associate of the child and adolescent psychiatrist. Although the child psychiatrist rarely plays an integral role in decision making about the children who are involved with the system, the authors point out that a large percentage of children maintained in and involved with the system have psychiatric and developmental disorders. When these children's difficulties are either minimized or unrecognized by child welfare workers, the interventions and treatment that the children receive may be inappropriate. Worse still, when the children's difficulties are improperly addressed, the vicissitudes of the system may further harm them. The authors propose several ways in which the child and adolescent psychiatrist can have an important reparative role and voice in child welfare systems.


Perspectives Regarding Adherence to Prescribed Treatment in Highly Adherent HIV-Infected Gay Men.
Focus group methodology was used to describe the medication adherence experience of 24 HIV-infected gay men who reported being adherent to their medication regimens. A conceptualization of medication adherence as an evolving process consisted of challenges to adherence (learning the diagnosis, starting the medications, struggling with the medications, dealing with side effects, coping with stigma) as well as those factors supportive of adherence (believing in medications, finding motivating factors, using reminders, depending on others, owning the disease). Themes associated with challenges to adherence focused on diagnosis and the physical and emotional adjustments individuals made to incorporate antiretroviral medications into their daily lives and move toward medication adherence. The factors supportive of adherence were related to the ongoing behaviors identified with establishing and maintaining adherence behaviors. What can be taken from the study is that adherence is a complex and dynamic process rather than a static behavior.


Dietary prevention of post-angioplasty restenosis. From illusion and disillusion to pragmatism.
Prevention of restenosis and major cardiac events after percutaneous coronary intervention (PCI) is of enormous public health importance. Despite the considerable decrease in the restenosis rate in relation to the advent of the drug-eluting stents, it is likely that the complication will still occur in some patients and/or after a certain delay. Thus, dietary or systemic drug prevention will probably have a role in the drama in the future, although the way they can be used is not clear at present. This discussion focuses on the dietary approach of post-PCI restenosis because, among the many drugs that have been tested, none has been consistently shown to be helpful--with the exception of the potent antioxidant drug probucol--, whereas the results of several dietary trials have been encouraging. As discussed in the present issue of NMCD, vitamins of the B group were recently shown to decrease the risk of restenosis, supposedly through an effect on homocysteine metabolization. It seems, however, that homocysteine is a minor risk factor of post-PCI restenosis. On the other hand, 5-methyltetrahydrofolate (the active form of folic acid) was shown to improve endothelial function independently from homocysteine. Thus, folic acid could prevent restenosis not only by reducing homocysteine, but also by promoting nitric oxide formation. Because of their potential to prevent post-PCI restenosis and acute cardiac complications, n-3 fatty acids have been the most widely studied post-PCI medical intervention. Taken together, trial data suggest that if n-3 fatty acids can be useful in certain populations to prevent restenosis, their effects are probably weak. However, according to recent studies on endothelial nitric oxide synthase (eNOS) gene polymorphisms, it is likely that only certain patients could benefit from n-3 fatty acid supplementation. The same reasoning can probably apply to the folic acid and eNOS issue. In conclusion, although none has been concluding, the studies about n-3 fatty acids and folic acid after PCI suggest that certain nutrients (or more probably a combination of nutrients) may be useful for the prevention of post-PCI restenosis. Any future trial involving these nutrients should combine them and take into account some major genetic confounders. In the meantime, it is medically and ethically justified to supplement our CHD patients after PCI. They should receive n-3 fatty acids to prevent sudden cardiac death, and B group vitamins (at the dosages tested in the Swiss Heart Study) to decrease the risk of restenosis. This would be, at least, a low cost intervention, and there is no fear of adverse side effects, contrary to those one can expect from drug treatments.


Transcriptional activation by TGF beta 1 mediated by the dyad symmetry element (DSE) and the TPA responsive element (TRE).
Transforming growth factor beta 1 (TGF beta 1) is a multifunctional regulator of growth and differentiation. However, both cytoplasmatic and nuclear signal transduction mechanisms leading to the biological effects of TGF beta 1 are largely unknown. In this report we show, that TGF beta 1 induces the expression of the immediate early genes c-jun and jun B, that encode trans-acting factors regulating transcription of a variety of genes in response to growth factors and phorbol esters. The jun genes are induced by TGF beta 1 in a protein synthesis independent fashion both in quiescent mouse 3T3 fibroblasts, which are growth stimulated by TGF beta 1, as well as in mink lung CCL64 (ML-CCL64) epithelial cells, which are growth inhibited by TGF beta 1. The PDGF inducible JE gene was induced by TGF beta 1 in 3T3, but not in ML-CCL64 cells. Furthermore, we show that chimaeric reporter-CAT constructs containing the TPA responsive element (TRE) or the dyad symmetry element (DSE) are activated by TGF beta 1 in transient transfection assays in both growth inhibited and growth stimulated cells. These results show that the early genomic responses to TGF beta 1 resemble changes in gene expression induced by serum, growth factors and phorbol esters, suggesting common mechanisms of transcriptional activation.


Chemical constituents from the bioactive fraction of the seeds of Psoralea corylifolia and proliferation activities on osteoblastic-like UMR106 cells.
A new flavonol named 5,4'-dihydroxy-6,7-[(1''S,2''R)-1''-hydroxy-2''-(1-hydroxy-1-methylethyl)-furano]flavonol (1), together with eight known compounds (2-9), were isolated from the seeds of Psoralea corylifolia. Their chemical structures were elucidated on the basis of spectroscopic analyses. In addition, all compounds were firstly studied for their proliferation effects on osteoblastic-like UMR 106 cells. Results showed that compounds 1, 2, 5 and 8 possessed significant promoting effects on cell proliferation and increased osteoblastic cell numbers by 26.3%, 34.6%, 20.5% and 21.1% at concentrations of 10-8 M, 10-8 M, 10-10 M and 10-10 M, respectively. These data indicated that flavonoids may be the main constituents accounting for the bone protective effects of the seeds of P. corylifolia.


High prevalence of Human Herpes Virus 8 (HHV-8) in patients with Warthin's tumors of the salivary gland.
Warthin's tumor is a common benign neoplasm of the salivary gland. Human Herpes Virus 8 (HHV-8) is the etiologic agent for all forms of Kaposi's sarcoma (KS), and HHV-8 DNA is present in saliva, suggesting that non-sexual transmission is associated with latent infection of the salivary gland. To provide insights into the HHV-8 cell tropism, the presence of HHV-8 was investigated in a series of Warthin's tumors of the salivary gland and corresponding adjacent normal tissue. Forty-three patients with Warthin's tumors (cystadenolymphoma) were tested for the presence of HHV-8 DNA, and corresponding adjacent normal tissue samples were obtained from 15 patients. DNA was extracted from the paraffin-embedded tissues. A nested polymerase chain reaction (PCR) assay was applied, and the positive samples were confirmed by direct sequencing. HHV-8 DNA was detected in 19 out of 43 (44%) salivary gland tumor samples. Among the 15 cases with paired samples, 9 were HHV-8-positive for both samples, 4 were HHV-8-negative for both samples while in two cases HHV-8 was detected only in the tumor specimens. HHV-8 is frequently detected in adenoid salivary neoplasms, suggesting a significant role of the virus in the etiopathogenesis of the disease. Larger studies are required to investigate the role of HHV-8 in the development or progression of Warthin's tumors.


Treatment of advanced gastric carcinoma with 5-fluorouracil adriamycin, and mitomycin C (FAM).
Thirty-three evaluable patients with advanced gastric adenocarcinoma were treated with a combination of 5-fluorouracil, adriamycin, and mitomycin C (FAM). Two complete and five partial remissions (21% response rate) were observed. The overall median survival of all 33 patients was 5.9 months. Responding patients had significantly better survival than the non-responders (P less than 0.02). Analysis of the results according to sex, pretreatment performance status, and the histologic differentiation of the tumor failed to demonstrate that any of these factors influenced therapeutic results. The low response rate to FAM found in this study might be related to the fact that in the majority of the patients (85%) the primary gastric tumor had not been resected. The side-effects of this regimen were moderate. Taking into account the low response rate and the moderate myelotoxicity observed, a more intensive use of these three drugs in combination is suggested.


Ultraviolet light and ocular diseases.
The objective of this study is to review the association between ultraviolet (UV) light and ocular diseases. The data are sourced from the literature search of Medline up to Nov 2012, and the extracted data from original articles, review papers, and book chapters were reviewed. There is a strong evidence that ultraviolet radiation (UVR) exposure is associated with the formation of eyelid malignancies [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)], photokeratitis, climatic droplet keratopathy (CDK), pterygium, and cortical cataract. However, the evidence of the association between UV exposure and development of pinguecula, nuclear and posterior subcapsular cataract, ocular surface squamous neoplasia (OSSN), and ocular melanoma remained limited. There is insufficient evidence to determine whether age-related macular degeneration (AMD) is related to UV exposure. It is now suggested that AMD is probably related to visible radiation especially blue light, rather than UV exposure. From the results, it was concluded that eyelid malignancies (BCC and SCC), photokeratitis, CDK, pterygium, and cortical cataract are strongly associated with UVR exposure. Evidence of the association between UV exposure and development of pinguecula, nuclear and posterior subcapsular cataract, OSSN, and ocular melanoma remained limited. There is insufficient evidence to determine whether AMD is related to UV exposure. Simple behaviural changes, appropriate clothing, wearing hats, and UV blocking spectacles, sunglasses or contact lens are effective measures for UV protection.


Antenatal care in Mozambique: Number of visits and gestational age at the beginning of antenatal care.
1)to assess the gestational age at the beginning of antenatal care and its covariates; 2)to assess the number of antenatal visits and its covariates; and 3)to identify the reasons for the late initiation of antenatal care and for attending less than four visits among postpartum women living in Nampula, Mozambique. cross-sectional study conducted with 393 mothers who answered a structured instrument in face-to-face interviews. Logistic regression was used to analyze the covariates of having initiated antenatal care up to the 16thgestational week, having attended four or more antenatal visits, and reporting both situations simultaneously. all postpartum women underwent antenatal care, but only 39.9% started it until the 16thgestational week, 49.1% attended four or more visits, and 34.1% reported both events. Having concluded high school (ORadj=1.99; 95%CI=1.19-3.31) or college (ORadj=3.87; 95%CI=1.47-10.18) were aspects associated with reporting both situations. The reasons for the late initiation of antenatal care and attending less than four visits were as follows: not finding it important to attend several visits, not having easy access to the health facility, not being aware about pregnancy, and not having a companion for the visits. the gestational age at the beginning of antenatal care and the number of antenatal visits are lower than the current recommendations in the country.


Treatment of renal cell carcinoma: Current status and future directions.
Answer questions and earn CME/CNE Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents-including molecules against vascular endothelial growth factor, platelet-derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine-protein kinase receptors; and an immune-checkpoint inhibitor-have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017;67:507-524. © 2017 American Cancer Society.


A Prospective Validation of the Updated Movement Disorders Society Research Criteria for Prodromal Parkinson's Disease.
The objective of this study was to validate the recently updated research criteria for prodromal Parkinson's disease (pPD) proposed by the International Parkinson's Disease and Movement Disorders Society. A total of 16 of 21 markers of pPD were ascertained in the Hellenic Longitudinal Investigation of Aging and Diet cohort composed of community-dwelling individuals aged ≥65 years. The probability of pPD was calculated for 961 individuals without Parkinson's disease (PD) or dementia with Lewy bodies at baseline who were followed-up for a median of 3 years. The ability of the criteria to predict conversion to PD/dementia with Lewy bodies was assessed by estimating their sensitivity and specificity, plotting receiver operating characteristics curves, and using logistic regression. These analyses were repeated using the original criteria. No incident PD/dementia with Lewy bodies case had probable pPD at baseline (ie, ≥80% pPD probability). At cut-offs of 10%, 30%, and 50% probability of pPD, the sensitivity and specificity of the criteria ranged from 4.5% to 27.3%, and 85.7% to 98.3% respectively. The area under the receiver operating characteristics curve was 0.691 (95% confidence intervals, 0.605-0.777). In logistic regression models, the criteria-derived posttest odds of pPD were a significant predictor of conversion at follow-up. The updated criteria performed similarly to the original but showed a slight increase in sensitivity. The new criteria demonstrated suboptimal sensitivity in our random sample of community-dwelling individuals. The absence of specialized assessments with high likelihood ratios in our cohort could be hindering the demonstration of higher sensitivities. Such assessments should be a part of future validation attempts. © 2020 International Parkinson and Movement Disorder Society.


Use of beta-adrenoceptor blockers in patients with congestive heart failure.
The beneficial effect of chronic beta-blockade in patients with congestive heart failure has been repeatedly shown since its introduction into treatment for this condition in 1975. Still this kind of therapy remains controversial, it is sometimes regarded as a therapeutic paradox, and its use is mainly limited to specialist centers. Various favorable effects of beta-blockers in patients with heart failure due to idiopathic dilated cardiomyopathy and ischemic heart disease have been demonstrated, the principal among them being reduction in energy requirements and ischemia, antiarrhythmogenic effect, improvement of diastolic function, protection of myocytes against catecholamine overload, centrally mediated increase in vagal tone, upregulation of beta-adrenergic receptors, and possible blockade of autoantibodies against beta 1-receptors. Although most of the studies used metoprolol, these effects may be relevant to certain other beta-blockers. Despite very solid pathophysiological and pharmacological rationales for the use of beta-blockade, a major obstacle for a general acceptance of this therapeutic concept is the striking contrast between hemodynamic changes during the acute effect and long-term treatment. When titrated carefully from very low doses and used with a true commitment to long-term treatment, beta-blockers have been shown to prevent further deterioration of heart failure and to improve hemodynamics, exercise tolerance, quality of life, and prognosis.


Disfacilitation and long-lasting inhibition of neostriatal neurons in the rat.
Excitatory postsynaptic potentials evoked in rat neostriatal spiny projections neurons were followed by a long (100-300 ms) period of membrane hyperpolarization, followed in turn by a late depolarization. Concomitant with these changes in membrane potential were inhibition and subsequent excitation of spontaneous firing and excitatory activity evoked from substantia nigra and cerebral peduncle, but not from cortical stimulating sites. Thalamic-evoked excitatory activity was sometimes sensitive and sometimes insensitive to this inhibition, which has previously been believed to result from intrinsic inhibitory synaptic activity among neostriatal neurons. In intracellular recordings from neostriatal neurons in urethane anesthetized rats this long-lasting inhibitory response (1) exhibited alterations with intracellularly applied steady currents comparable to those of the EPSP, (2) failed to respond to intracellular injection of chloride ions, (3) was associated with either a decrease or no detectable change in the input conductance of the neurons, and (4) was abolished after lesions that interrupted polysynaptic pathways to neostriatum through intracortical and intrathalamic synaptic circuits. These findings indicate that the long lasting inhibitory portion of the responses of neostriatal neurons arises from a phasic inhibition of tonically active corticostriatal and thalamostriatal neurons and a concurrent decrease in the excitability of polysynaptic pathways converging on neostriatal neurons.


Prevention of catheter-related infections by silver coated central venous catheters in oncological patients.
Catheter-related infection (CRI) is a serious complication of central venous catheterization. We have investigated the efficacy of a silver-coated polyurethane catheter (Pellethane, Fresenius AG, Germany) in preventing CRI in oncological patients receiving chemotherapy in a phase II study. From November 1992 through April 1994, 266 patients were assigned to receive single lumen catheters, either standard uncoated catheters (UC, n = 113) or silver-coated ones (SC, n = 120). Catheters were inserted into the internal jugular vein after institutional approval and informed consent. Duration of catheterization (UC vs. SC = 13.3 vs. 12.7 days) and leukopenia (< 1.0 x 10(9) WBC/l; 4.3 vs. 3.6 days) were similar in both groups demonstrating a comparable risk for infections. Skin reactions at the catheter entry site were recorded daily. CRI and colonization rates were studied by semiquantitatively culturing intradermal and intravascular segments. CRI were confirmed by blood cultures obtained via catheter and from peripheral veins in cases of suspected sepsis or at the end of catheterization. No adverse effects from the silver-coated catheter could be observed. The bacteriological results showed that SC were colonized (> 15 CFU) in 45.1% and UC in 44.2%. CRI developed in 21.2% of the UC patients but only in 10.2% of the SC patients (p = 0.011). We conclude that this new silver-coated central venous catheter is biocompatible and effective in reducing the incidence of catheter-related infections in oncological patients.


Assimilation of the seabird and ship drift data in the north-eastern sea of Japan into an operational ocean nowcast/forecast system.
At the present time, ocean current is being operationally monitored mainly by combined use of numerical ocean nowcast/forecast models and satellite remote sensing data. Improvement in the accuracy of the ocean current nowcast/forecast requires additional measurements with higher spatial and temporal resolution as expected from the current observation network. Here we show feasibility of assimilating high-resolution seabird and ship drift data into an operational ocean forecast system. Data assimilation of geostrophic current contained in the observed drift leads to refinement in the gyre mode events of the Tsugaru warm current in the north-eastern sea of Japan represented by the model. Fitting the observed drift to the model depends on ability of the drift representing geostrophic current compared to that representing directly wind driven components. A preferable horizontal scale of 50 km indicated for the seabird drift data assimilation implies their capability of capturing eddies with smaller horizontal scale than the minimum scale of 100 km resolved by the satellite altimetry. The present study actually demonstrates that transdisciplinary approaches combining bio-/ship- logging and numerical modeling could be effective for enhancement in monitoring the ocean current.


Spatial scale, time and process in mega-events: The complexity of host community perspectives on neighbourhood change.
A focus on the 'mega' aspect of hallmark events can divert attention from the micro - those local communities who are most impacted by the event. Similarly, attention to the 'event' aspect underplays the long process of bidding and preparation before any putative legacy of urban transformation for local people. This paper uses qualitative data to unpack the complex and multi-layered views of local residents, living in a deprived neighbourhood beside the Glasgow 2014 Commonwealth Games site in Scotland. They reflect on five years of intensive urban regeneration, evaluate the experience of 'lockdown' at Games time, and consider their hopes and fears for the future of the community. Interviewing a mixture of lifelong, established, new and returning residents, we found considerable common ground across the different groups in terms of hopes for a new, mixed community in the area. However, findings also highlight concerns around urban governance practices and the limitations of a market-led approach to regeneration.


Down-regulation of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase by polyunsaturated fatty acids in hepatocytes is not mediated by PPARalpha.
alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) is a key enzyme in NAD biosynthesis from tryptophan. Dietary polyunsaturated fatty acids (PUFA) have been shown to suppress hepatic ACMSD activity and its mRNA level in rat. However the mechanism of the suppressive action has not been clarified yet. Although the phenomena that fatty acids suppress the expression of ACMSD in rat liver have been established in vivo experiment, it is still obscure whether the effect of fatty acids on the expression of the enzyme is caused by its direct or indirect action, because there have been very few investigations performed in vitro. In this study, to examine whether down-regulation of ACMSD mRNA by PUFA involves peroxisome proliferator-activated receptor (PPAR) alpha mediated mechanism or not, we investigated the effect of PUFA on the ACMSD expression by using primary cultured rat hepatocytes. For this purpose we investigated the effect of PUFA (linoleic acid and eicosapentanoic acid) on the ACMSD mRNA level in primary-cultured rat hepatocytes and compared its effect with that of WY-14,643 (a PPARalpha agonist). After the incubation of hepatocytes with fatty acids, WY-14,643 and/or MK886 (a PPARalpha antagonist), mRNA levels of ACMSD and a peroxisome marker enzyme acyl-CoA oxidase (ACO) were determined by competitive reverse transcription-polymerase chain reaction (RT-PCR) method. ACMSD mRNA level in primary hepatocytes were decreased by the incubation with high concentrations of linoleic acid, eicosapentaenoic acid (EPA) and WY-14,643. The appearance of ACO mRNA by WY-14,643 was remarkably increased, and those by linoleic acid and EPA were increased less than that by WY-14,643. Moreover, the suppression of ACMSD mRNA and the augmentation of ACO mRNA by WY-14,643 were inhibited by MK886, but the suppression by PUFA was not substantially affected by MK886. The present study suggesting that the mechanism of decrease in ACMSD mRNA level by PUFA was different from that by WY-14,643, and that there would be any pathway other than PPARalpha mediated one for PUFA to regulate ACMSD expression.


Multidrug-resistant Salmonella strains from food animals as a potential source for human infection in Iran.
This study aimed to determine the frequency and characterization of Salmonella isolates from food-producing animals and human diarrheal samples in Shiraz, Iran. Overall, 105 Salmonella isolates were obtained from chicken meat (70/100, 70.0%), beef (19/100, 19.0%), lamb (11/100, 11.0%), and human stool (5/295, 1.7%). S. Infantis (40.9%), S. Enteritidis (29.5%), and S. Paratyphi B (8.6%) were the most prevalent serotypes. Totally 59.1% of the isolates were multidrug-resistant. High resistance to nalidixic acid (67.6%), tetracycline (62.9%), and trimethoprim-sulfamethoxazole (42.3%) were observed. Mutations in the gyrA and parC genes were detected in nalidixic acid-resistant isolates from chicken meat and human stool. No qnrA, qnrB or qnrS genes were detected. The blaTEM and blaCMY-2 genes were detected in β-lactam-resistant isolates from beef and lamb. Despite the high genetic diversity of PFGE patterns, some isolates from different sources and times showed identical PFGE patterns suggesting specific Salmonella species circulate between various sources over time.


Children patients with COVID-19: How can parental and peer support lessen the psychological burden of isolation.
To assess the effect of parental and peer support on children's self-esteem during the isolation period in COVID-19-infected children is the main objective of this study. This is a descriptive cross-sectional study. One hundred ninety children with a confirmed diagnosis of COVID-19 were included. A survey questionnaire to assess family and children's demographic characteristics was used for this study. A 13-item scale to assess parental support during the isolation period and a 10-item scale to assess peers' support during the isolation period were evaluated. Along with it, a 10-item scale to assess self-esteem during the isolation period was also measured. Home isolation was associated with higher parental and peer support scores than hospital isolation. The mean age of study participants was 13.23 ± 4.05 years; 52.6% were isolated at home versus 47.4% in hospital isolation. Phone calling and WhatsApp/messenger chat were methods of communication for 44.2% and 33.2% of patients, respectively. 6.3% of them had no method of communication. Child self-esteem was significantly affected by both parental and peer support during isolation. The increase in pronounced negative psychological effects such as disorientation, anger, low self-esteem and post-traumatic distress may be caused by a lack of parental care. Patients or the general public were not involved in the design, analysis or interpretation of the data in this study. The study's aim and objectives were developed based on children's self-esteem, which was limited by questionnaire data information, so the researchers completed demographic and disease-related questionnaires by interviewing them.


Lodenafil.
Lodenafil is a class of drugs called an inhibitor of PDE5 which also include a wide range of other erectile medicines, such as sildenafil, tadalafil and vardenafil. It is part of a new generation of PDE5 inhibitors that includes udenafil and avanafil. Lodenafil is a prodrug manufactured in the form of lodenafil carbonate, the carbonate dimer that divides in the body into two active drug lodenafil molecules. The oral bioavailability of this formulation is higher than that of the parent drug. This article discusses, by a critical comprehensive review of the literature on lodenafil in terms of its description, names, formulae, elemental composition, appearance, and therapeutic uses. The article also discusses the methods for preparation of lodenafil, its physical-chemical properties, analytical methods for its determination, pharmacological-toxicological properties, and dosing information.


Treating dyslipidaemia in the setting of diabetes mellitus and cardiovascular disease: a less commonly perceived therapeutic perspective in clinical practice.
Diabetes mellitus and cardiovascular disease are being managed more belligerently in recent times, with multifactorial cardiovascular risk reduction being the focus of therapeutic interventions. We review some of the caveats to be exercised in the treatment of these patients that are pertinent to clinicians in daily clinical practice.


Breast Reconstruction after Surgical Treatment of Ductal Carcinoma In Situ.
The role of plastic surgeon in breast reconstruction is mandatory in those cases of ductal carcinoma in situ (DCIS) requiring a wide surgical excision. The reconstructive treatment must be tailored on each patient with the aim to obtain a good cosmetic result in terms of form and symmetry, avoiding surgical complications.


A comparison of urinary complications following total laparoscopic radical hysterectomy and laparoscopic pelvic lymphadenectomy to open abdominal surgery.
The objective of this study was to compare total laparoscopic radical hysterectomy (TLRH) and laparoscopic pelvic lymphadenectomy (LPS) to total abdominal radical hysterectomy (TARH) and pelvic lymphadenectomy (LPT) in terms of urinary tract lesions and postoperative urinary retention. Starting in 2004, we treated all early stage cervical cancer patients with TLRH and LPS. The control group for this analysis was a historical cohort of patients treated with TARH+LPT. Within the TLRH+LPS group, we assessed whether the width of parametrial tissue removed was a risk factor for urinary tract injuries or postoperative urinary retention. Fifty women were included in the TLRH+LPS group and forty-eight were included in the TARH+LPT group. There were no conversions from laparoscopy to laparotomy. There was no statistically significant difference in intraoperative urinary complications between the groups. Four (8%) intraoperative urinary tract injuries in the LPS (3 cystotomies and 1 ureteral lesions all repaired laparoscopically) and 2 (4.2%) in the LPT group (2 cystotomies) occurred (p=0.68). Similarly, there was no statistically significant difference in postoperative urinary complications between groups. Urinary postoperative complications were: 1 (2%) ureterovaginal and 1 vesicovaginal fistulas, 1 delayed ureteric fistula in LPS group vs. 0 in LPT group (p=0.24). Urinary retention was complained by 7 (14%) and 7 (14.6%) patients in LPS and LPT groups respectively (p=1.00). The average width of parametrial tissue removed in the LPS group was 32.2+14.0 mm in patients with vs. 39.5+13.6 mm in patients without urinary complications (p=0.11). A laparoscopic approach is comparable to the laparotomy in terms of urinary lesions and postoperative retention. The width of parametrium removed does not affect the risk of urinary lesions or postoperative retention.


Laboratory study of the particle-size distribution of Decabromodiphenyl ether (BDE-209) in ambient air.
Laboratory measurements for particle-size distribution of Decabromodiphenyl ether (BDE-209) were performed in a 0.5 m(3) sealed room at 25 °C. BDE-209 was manually bounded to ambient particles. An electrostatic field-sampler was employed to collect particles. The number of collected particles (n(i,j), i and j was the class of particle diameter and applied voltage on electrostatic field-sampler sampler, respectively) and the corresponding mass of BDE-209 in collected particles (m(∑i,j)) were determined in a series of 6 experiments. The particle-size distribution coefficient (ki) was calculated through equations related to n(i,j) and m(∑i,j), and the particle-size distribution of BDE-209 was determined by ki·n(i,j). Results revealed that BDE-209 distributed in particles of all size and were not affiliated with fine particles as in field measurements. The particle size-fraction should be taken into account when discussing the particle-size distribution of BDE-209 in ambient air due to the normalized coefficients (normalized to k1) and were approximately in the same order of magnitude for each diameter class. The method described in the present study was deemed feasible in determining the particle-size distribution of BDE-209 from vaporization sources and helpful to understanding the instinct rule of particle-size distribution of BDE-209, and potentially feasible for other SVOCs.


Sensitivity of the Alternaria infectoria species-group 1 to cycloheximide.
A possibility of using cycloheximide tolerance and/or sensitivity as an additional diagnostic tool for distinguishing morphologically related species within common small-spored Alternaria has been tested during this study. A total of 33 strains from four Alternaria species-groups, namely Alternaria alternata, Alternaria arborescens, Alternaria infectoria and Alternaria tenuissima were tested for their growth response to 100 microg m(-1) cycloheximide in potato carrot agar. All A. infectoria strains were completely inhibited, showing no growth at all even after prolonged incubation. In contrast, all other strains representing the remnant three species exhibited a high resistance to this antibiotic. Cycloheximide sensitivity represents a further important physiological character for distinguishing A. infectoria from the three similar species. The relevance of these findings corresponds with the potential ability of the Alternaria species produce mycotoxins. Cycloheximide may be in future used in the design of selective media for the isolation of some potentially toxigenic food-borne Alternaria species such as A. alternata, A. tenuissima and/or A. arborescens, for example in screening cereals for toxigenic Alternaria spp. and for their direct separation from nontoxigenic representatives of A. infectoria species-group.


Dog Welfare, Well-Being and Behavior: Considerations for Selection, Evaluation and Suitability for Animal-Assisted Therapy.
Health care and human service providers may include dogs in formal intervention settings to positively impact human physical, cognitive and psychosocial domains. Dogs working within this context are asked to cope with a multitude of variables including settings, populations, activities, and schedules. In this article, the authors highlight how both the preparation and operation of dogs within animal-assisted therapy (AAT) differs from less structured animal-assisted activities (AAA) and more exclusive assistance animal work; the authors highlight the gaps in our knowledge in this regard, and propose an ethically sound framework for pragmatic solutions. This framework also emphasizes the need for good dog welfare to safeguard all participants. If dogs are not properly matched to a job or handler, they may be subjected to unnecessary stress, anxiety, and miscommunication that can lead to disinterest in the work, overt problematic behavioral or health outcomes, or general unsuitability. Such issues can have catastrophic outcomes for the AAT. The authors propose standards for best practices for selection, humane-based preparation and training, and ongoing evaluation to ensure the health, welfare and well-being of dogs working in AAT, which will have concomitant benefits for clients and the professionalism of the field.


Conditioning hyperpolarization-induced delays in the potassium channels of myelinated nerve.
Hyperpolarizing conditioning pulses delay the onset of potassium channel current in voltage-clamped myelinated nerve fibers. Both the development of and recovery from this conditioning are approximately exponential functions of time: the time constants are functions of the conditioning voltage. The delay is larger and develops faster for more hyperpolarized conditioning pulses. The magnitude of the delay (but not the rate of development or recovery) depends upon the test potential-small test depolarizations produce larger delays than large depolarizations. The currents with and without the conditioning pulse cannot be made to superimpose by a simple time translation.


Mediators involved in the rat uterus contraction in calcium-free solution.
1. The effect of (Na+ + K+)-ATPase inhibitor ouabain (10(-5)-3 x 10(-4) M), and the (Ca2+ + Mg2+)-ATPase inhibitors vanadate (6 x 10(-6)-6 x 10(-4) M), oxytocin (2 x 10(-9)-4 x 10(-8) M, and prostaglandin F2 alpha (PGF2 alpha, 10(-7)-6 x 10(-6) M) were assayed on rat uterus incubated in Ca-free medium. 2. Vanadate, oxytocin and PGF2 alpha, but not ouabain, induced contractions in a dose-dependent way (ED50: 7.5 +/- 0.03 x 10(-5) M; 6.5 +/- 0.064 x 10(-9) M and 3.8 +/- 0.085 x 10(-7) M). 3. Vanadate (3 x 10(-4) M) and oxytocin (OT, 10 mU/ml = 2 x 10(-8) M)-induced tonic contraction were not modified by nifedipine (10(-10)-10(-6) M), monensin (10(-5)-3 x 10(-4) M) or amiloride (10(-5)-10(-3) M). 4. The intracellular calcium release inhibitors TMB-8 (10(-6)-10(-4) M) and dantrolene (3 x 10(-6)-10(-4) M), and the prostaglandin release inhibitor indomethacin (3 x 10(-8)-6 x 10(-5) M) relaxed the vanadate and OT-induced tonic contractions. 5. The calmodulin inhibitors trifluoperazine (3 x 10(-5)-3 x 10(-4) M), bepridil (10(-8)-3 x 10(-4) M), calmidazolium (10(-7)-10(-4) M) and W-7 (10(-7)-10(-5) M) also relaxed the vanadate and OT-induced tonic contractions. 6. Our results suggest that oxytocin and vanadate-induced contractions on rat uterus in Ca-free medium could be produced by release of prostaglandins and intracellular calcium, and mediated by calmodulin.


Biomechanical modelling of the facet joints: a review of methods and validation processes in finite element analysis.
There is an increased interest in studying the biomechanics of the facet joints. For in silico studies, it is therefore important to understand the level of reliability of models for outputs of interest related to the facet joints. In this work, a systematic review of finite element models of multi-level spinal section with facet joints output of interest was performed. The review focused on the methodology used to model the facet joints and its associated validation. From the 110 papers analysed, 18 presented some validation of the facet joints outputs. Validation was done by comparing outputs to literature data, either computational or experimental values; with the major drawback that, when comparing to computational values, the baseline data was rarely validated. Analysis of the modelling methodology showed that there seems to be a compromise made between accuracy of the geometry and nonlinearity of the cartilage behaviour in compression. Most models either used a soft contact representation of the cartilage layer at the joint or included a cartilage layer which was linear elastic. Most concerning, soft contact models usually did not contain much information on the pressure-overclosure law. This review shows that to increase the reliability of in silico model of the spine for facet joints outputs, more needs to be done regarding the description of the methods used to model the facet joints, and the validation for specific outputs of interest needs to be more thorough, with recommendation to systematically share input and output data of validation studies.


129Xe MRI as a measure of clinical disease severity for pediatric asthma.
Measurement of regional lung ventilation with hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI) in pediatric asthma is poised to advance our understanding of disease mechanisms and pathophysiology in a disorder with diverse clinical phenotypes. 129Xe MRI has not been investigated in a pediatric asthma cohort. We hypothesized that 129Xe MRI is feasible and can demonstrate ventilation defects that relate to and predict clinical severity in a pediatric asthma cohort. Thirty-seven children (13 with severe asthma, 8 with mild/moderate asthma, 16 age-matched healthy controls) aged 6 to 17 years old were imaged with 129Xe MRI. Ventilation defect percentage (VDP) and image reader score were calculated and compared with clinical measures at baseline and at follow-up. Children with asthma had higher VDP (P = .002) and number of defects per image slice (defects/slice) (P = .0001) than children without asthma. Children with clinically severe asthma had significantly higher VDP and number of defects/slice than healthy controls. Children with asthma who had a higher number of defects/slice had a higher rate of health care utilization (r = 0.48; P = .03) and oral corticosteroid use (r = 0.43; P = .05) at baseline. Receiver-operating characteristic analysis demonstrated that the VDP and number of defects/slice were predictive of increased health care utilization, asthma, and severe asthma. VDP correlated with FEV1 (r = -0.35; P = .04) and FEV1/forced vital capacity ratio (r = -0.41; P = .01). 129Xe MRI correlates with asthma severity, health care utilization, and oral corticosteroid use. Because delineation of clinical severity is often difficult in children, 129Xe MRI may be an important biomarker for severity, with potential to identify children at higher risk for exacerbations and improve outcomes.


A common set of immediate-early response genes in liver regeneration and hyperplasia.
Partial hepatectomy (PH) and some tumor-promoting agents stimulate hepatocyte cell proliferation, but each treatment acts through distinct transcription factors. We compared mouse immediate-early gene expression changes after PH with those induced by 1,4-bis[2-(3,5-dichoropyridyloxy)]benzene (TCPOBOP), a tumor-promoting liver mitogen. PH activates nuclear factor kappa B (NF-kappa B) and Stat3, whereas TCPOBOP is a ligand for the nuclear receptor, constitutive androstane receptor (CAR). RNA from 1 and 3 hours after each treatment was hybridized to a 9,000 complementary DNA (cDNA) microarray. Of about 6,000 messenger RNAs that had detectable expression, 127 showed reproducible up-regulation or down-regulation at a significant level. The TCPOBOP response was more discrete than the PH response; they amounted to 1% and 1.9% of positive hybridizations, respectively. Twenty-three genes were regulated only by TCPOBOP, 57 only by PH, and 59 by both treatments. More detailed analysis defined 16 clusters with common patterns of expression. These patterns and quantification of hybridization levels on the array were confirmed by Northern blots. TCPOBOP selectively activated expression of a number of detoxification enzymes. In conclusion, the genes that were regulated by both treatments suggest down-regulation of apoptosis, altered signal transduction, and early biogenesis of critical cell components.


Alternation of ten-eleven translocation 1, 2, and 3 expression in eutopic endometrium of women with endometriosis-associated infertility.
Little is known about the differences in ten-eleven translocation 1, 2, and 3 (TET1-3) expression in the endometrial phases in eutopic endometrium from infertile women with endometriosis (IWE) and fertile women without endometriosis (FW). Using RT-qPCR and western blot analysis, we assessed the TET expression in the mid-follicular and mid-luteal phases in eutopic endometrium from IWE (n = 38) and FW (n = 18). Both IWE and FW underwent laparoscopic and histological examinations for endometriosis. In the mid-luteal eutopic endometrium in IWE, compared to that of FW, we found significantly reduced levels of TET1 transcripts and proteins (p = .001 and p = .003, respectively) at the severity stage of I/II (p = .029 and p = .003, respectively) and transcripts only at the severity stage of III/IV (p = .003). In the mid-follicular eutopic endometrium of IWE, compared to that of FW, there was a statistically significant reduction in TET2 transcript levels at the severity stage of III/IV (p = .037). Compared to the mid-follicular endometrium, we found a statistically significant increase in TET3 transcript levels during the mid-luteal phase in the eutopic endometrium of all IWE (p = .034) and in the severity stage of III/IV (p = .025). We observed a change in the expression levels of TET1-3 in the eutopic endometrium of IWE.


Francisella noatunensis subsp. noatunensis triggers calcium metabolism gene modulation in Eleginops maclovinus.
Francisella noatunensis subsp. noatunensis is the responsible agent of Francisellosis, a bacterial disease that affects an important amount of aquatic farmed species. Eleginops maclovinus is a fish that cohabits with salmonids cages in Chile and can also act as a vector of this bacterial disease. In the present study, we evaluated calcium metabolism in the liver of E. maclovinus injected intraperitoneally with different doses of F. noatunensis subsp. noatunensis (low 1.5 × 101, medium 1.5 × 105 and high doses 1.5 × 1010 cells/μL). Fish were sampled at 1, 3, 7, 14, 21 and 28 days post injection (dpi). No mortalities nor clinical signs were observed. Plasma calcium levels were higher in the high doses group of F. noatunensis subsp. noatunensis at day 7 and 14 compared to the control group (fish injected with bacterial medium alone). Hypercalcemic factors increased at day 14 and 21 for the medium and low dose (parathyroid hormone-related protein precursor), while vitamin D3 receptor increased its expression at times 1, 3 and 7 for the low dose. On the other hand, hypocalcemic factors such as calcitonin receptor and stanniocalcin increased its expression at time 7 and 14, respectively. Calmodulin involved in calcium storage decreased its expression during all experimental days in fish subjected to high bacterial dose. Proteins involved in calcium transport, such as L-type voltage-gated calcium channel and trpv5 increased their transcription at day 1 and 14, compared to calcium sensing-receptor and plasma membrane Ca2 +- ATPase that showed peak expression at times 14 and 28. The results suggest a clear alteration of calcium metabolism, mainly in high bacterial doses. This study provides new knowledge about the calcium metabolism in fish infected with bacteria.


The protective role of Wnt3a in peroxynitrite-induced damage of cochlear hair cells in vitro.
To investigate the effect of peroxynitrite on the cultured cochlear hair cells of C57BL/6 P3 mice in vitro as well as the role of Wnt3a, as an activator of the canonical Wnt signaling pathway, underlying the action of such an oxidative stress. The in vitro primary cultured cochlear hair cells were subjected to l00 μM peroxynitrite and l00 μM peroxynitrite +25 ng/mL Wnt3a for 24 h, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy. The number of surviving hair cells was significantly reduced in the 100 μM peroxynitrite group, while it was significantly higher in the Wnt3a + peroxynitrite treated group compared with the peroxynitrite treated group. The transmission electron microscopy showed that exposure to peroxynitrite induced a dramatic decrease in the number of mitochondria and severely disrupted mitochondrial ultrastructure, while Wnt3a clearly diminished the disruption of mitochondrial structure and preserved a higher number of mitochondria. These results indicated that peroxynitrite could cause oxidative damage to the cochlear hair cells, and low concentrations of Wnt3a has a protective effect against oxidative damage. Level 2.


Effect of asthma, COPD, and ACO on COVID-19: A systematic review and meta-analysis.
The prevalence of asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) in patients with COVID-19 varies, as well as their risks of mortality. The present study aimed to assess the prevalence of asthma, COPD, and ACO as comorbidities, and to determine their risks of mortality in patients with COVID-19 using a systematic review and meta-analysis. We systematically reviewed clinical studies that reported the comorbidities of asthma, COPD, and ACO in patients with COVID-19. We searched various databases including PubMed (from inception to 27 September 2021) for eligible studies written in English. A meta-analysis was performed using the random-effect model for measuring the prevalence of asthma, COPD, and ACO as comorbidities, and the mortality risk of asthma, COPD, and ACO in patients with COVID-19 was estimated. A stratified analysis was conducted according to country. One hundred one studies were eligible, and 1,229,434 patients with COVID-19 were identified. Among them, the estimated prevalence of asthma, COPD, and ACO using a meta-analysis was 10.04% (95% confidence interval [CI], 8.79-11.30), 8.18% (95% CI, 7.01-9.35), and 3.70% (95% CI, 2.40-5.00), respectively. The odds ratio for mortality of pre-existing asthma in COVID-19 patients was 0.89 (95% CI, 0.55-1.4; p = 0.630), while that in pre-existing COPD in COVID-19 patients was 3.79 (95% CI, 2.74-5.24; p<0.001). France showed the highest prevalence of asthma followed by the UK, while that of COPD was highest in the Netherlands followed by India. Pre-existing asthma and COPD are associated with the incidence of COVID-19. Having COPD significantly increases the risk of mortality in patients with COVID-19. These differences appear to be influenced by the difference of locations of disease pathophysiology and by the daily diagnosis and treatment policy of each country.


Increased Use of Anti-Tumor Necrosis Factor Following the Implementation of the ECCO-ESPGHAN Guidelines and its Impact on the Outcome of Pediatric Crohn's Disease: A Retrospective Single-Center Study.
The first ECCO-ESPGHAN guidelines for the medical management of pediatric Crohn disease (CD) were published in 2014. Whether their implementation, and the consequent increased use of an upfront anti-tumor necrosis factor therapy, have changed the course of the disease has not been investigated yet. We aimed at comparing the evolution of pediatric CD patients diagnosed and treated before and after 2014. Single-center retrospective study including all children diagnosed with CD from January 2010 to December 2018. Patients diagnosed between 2010 and 2014 (group 1) were compared to those diagnosed after 2014 (group 2). For each patient, at baseline and every 6-month, number of relapses, the occurrence of complication, therapy received and biological parameters were noted, as well as any endoscopic or radiologic evaluation. One hundred and fifty-four patients were included in the analysis, 78 (51%) diagnosed after 2014. The cumulative probability of a relapse-free and surgery-free course was significantly higher for patients treated according to the guidelines (log rank hazard ratio [HR] = 1,818, P = 0.003 and HR = 3,15, 95% confidence interval, P = 0.04, respectively). Mucosal healing rate was significantly higher among patients of group 2 at 1 and 2 years (P = 0.04 and P = 0.05, respectively), while no significant difference was observed for transmural healing rates, as well as for the risk of complications. The implementation of the 2014 CD guidelines appears to have a significant impact on disease outcomes, with a significantly lower risk for relapse and surgery, while no effect could be observed on the risk of developing complications.


Determining the activity of the transporter associated with antigen processing in the compartments of the secretory pathway.
Peptide-receptive MHC class I molecules and the TAP (transporter associated with antigen processing) peptide transporter are known to leave the ER and cycle through the cis side of the Golgi apparatus. The amount, and the extent of the activity, of TAP in post-ER compartments is likely to vary between different cell types. Here we describe a convenient microscopic assay to determine it.


Remifentanil and glucose suppress inflammation in a rat model of surgical stress.
Postoperative stress produces an inflammatory response. Recent studies have shown that narcotic analgesics suppress the immune system. Nutritional management during perioperative care has also been reported to affect inflammation. We therefore examined whether remifentanil or glucose administration could ameliorate postsurgical inflammatory responses using a rat model of surgical stress. We divided male Wistar rats randomly into five groups: (1) control, (2) sevoflurane+lactated Ringer's solution, (3) sevoflurane+lactated Ringer's solution with 1% glucose, (4) sevoflurane+remifentanil+lactated Ringer's solution, and (5) sevoflurane+remifentanil+ lactated Ringer's solution with 1% glucose. In all groups, serum samples were obtained at various time points after surgery, and secreted cytokine concentrations were determined. In addition, we assessed the activation of protein kinase B (Akt) and forkhead/winged helix box class O (FOXO3), which play a role in gluconeogenesis/stress responses. Surgical stress increased the serum concentrations of tumor necrosis factor-α and interleukin-6. Groups receiving remifentanil with anesthesia showed an attenuated inflammatory response. The inflammatory response was also reduced by administering 1% glucose. Furthermore, 1% glucose induced Akt and FOXO3 phosphorylation in the quadriceps femoris muscle 12 h after surgery. Anesthesia based on remifentanil and perioperative administration of lactated Ringer's solution containing 1% glucose may be able to control inflammatory responses caused by surgical stress.


To evaluate the prevalence and clinical outcomes using a one-step method versus a two-step method to screen gestational diabetes mellitus.
The goal of this study is to compare the prevalence and clinical outcomes of a one-step with a two-step screening method, both of which are commonly used for the diagnosis of gestational diabetes mellitus (GDM). Women who presented for GDM screening and who consented to participate in this study were randomized into two groups. The women in Group 1 (n = 386) were screened using a one-step method (2-h, 75 g oral glucose tolerance test (OGTT)) and in Group 2 (n = 400) by a two-step method (the 50 g glucose challenge test (GCT) followed by the 100 g OGTT). The pregnancies were then classified into three subgroups as follows: women who had negative 2-h 75 g OGTT results according to IADPSG criteria (IADPSG-negative), women with negative 50 g GCT results (GCT-negative) and women with positive 50 g GCT results but negative 3-h 100 g OGTT results according to C&C criteria (C&C-negative). The prevalence of GDM using the one-step and two-step methods was 14.5% and 6%, respectively. In adjusted multivariable regression models, women in the GCT-negative and the C&C-negative groups had greater risk of polyhydramnios than women in the IADPSG-negative group [adjusted prevalence risk ratios (aPR), 1.40; 95% confidence intervals (CI), 1.03-1.91; aPR, 2.76; 95% CI, 1.27-6.02, respectively]. Women in the C&C-negative group had greater risk of pre-eclampsia than women in the IADPSG-negative group (aPR, 3.30; 95% CI, 1.57-6.91). Women who were defined as having normal glucose tolerance by IADPSG had better perinatal outcomes than women who were defined as having normal glucose tolerance by GCT and women who were GCT-positive with a negative OGTT.


Axillary sampling and radiotherapy does not compromise the patient with early breast cancer: Trafford database experience.
Local recurrence has been studied in a selected group of 379 patients, 39% of whom underwent simple mastectomy and 61% lumpectomy. The axilla was sampled in 52%, cleared in 8% and untreated in 40%. Axillary recurrence occurred in 16% of patients with a median follow-up of 54 months. Ninety-one per cent of these patients with lymph node recurrence had no surgery or sampling to the axilla, and a third received radiotherapy. Local recurrence was satisfactorily controlled by various modalities of treatment in all but 29 patients. Death related to distant metastasis in all but six of these 29 patients. Analysis suggests that patients with locally uncontrolled disease had aggressive tumours at diagnosis which were larger than average, most often grade 3 histologically and more frequently required mastectomy. Our results support previous studies indicating that survival would not be influenced by more radical surgery but that sampling followed by radiotherapy would have prevented the majority of our lymph node recurrences.


Silent cerebral events as a result of left atrial catheter ablation do not cause neuropsychological sequelae--a MRI-controlled multicenter study.
Recently, diffusion-weighted magnetic resonance imaging (DW-MRI) revealed silent cerebral events (SCEs) as an acute complication of pulmonary vein isolation (PVI). We investigated whether SCEs following PVI are associated with neuropsychological deficits observed during patients' follow-up examinations. After PVI, 52 patients were eligible for follow-up. PVI was performed using a variety of ablation technologies (duty-cycled phased radiofrequency (RF) multipolar ablation with the Pulmonary Vein Ablation Catheter® (PVAC) in 24 patients, cooled-tip RF ablation in 23 patients, and cryoballoon ablation in five patients). Fluid-attenuated inversion recovery (FLAIR)- and DW-MRI studies were performed 1 day before PVI and 1 day and 1 month afterward to detect pre-existing cerebral lesions or post-ablation SCEs. At the same times, eight neuropsychological tests were administered. We evaluated changes in patients' neuropsychological capabilities and compared changes in patients with SCEs to those without SCEs. FLAIR-MRI revealed pre-existing cerebral lesions in 42 patients (81 %), and DW-MRI demonstrated new SCEs in 25 patients (48 %) (17 treated with phased RF (PVAC) (71 %), six treated with irrigated RF (26 %), and two treated with cryoablation (40 %)). Neuropsychological test results showed no significant impairment (in median z scores) 1 day and 1 month after the ablation procedure. There was no difference in neuropsychological capabilities between patients with SCEs and those without SCEs except in one subtest (part of the verbal working memory test). The incidence of pre-existing cerebral lesions and post-ablation SCEs was high. The frequency of SCEs depends on the ablation technology used. Neither PVI nor post-ablation SCEs have any effect on neuropsychological capabilities.


Basic study of less invasive high-intensity focused ultrasound (HIFU) in fetal therapy for twin reversed arterial perfusion (TRAP) sequence.
The objective of the present study was to develop a high-intensity focused ultrasound (HIFU) transducer more suitable for clinical use in fetal therapy for twin reversed arterial perfusion (TRAP) sequence. We created a cooling and degassed water-circulating-type HIFU treatment device. HIFU was applied to renal branch vessels in three rabbits. Sequential HIFU irradiation contains a trigger wave, heating wave, and rest time. The duration of HIFU application was 10 s/course. Targeting could be achieved by setting the imaging probe in the center and placing the HIFU beam and imaging ultrasonic wave on the same axis. We confirmed under sequential HIFU irradiation with a total intensity of 1.94 kW/cm(2) (spatial average temporal average intensity) that the vein and artery were occluded in all three rabbits. Simultaneous occluding of the veins and arteries was confirmed with trigger waves and a resting phase using the HIFU transducer treatment device created for this study. Clinical application appears possible and may represent a promising option for fetal therapy involving TRAP sequence.


Identification of presomitic mesoderm (PSM)-specific Mesp1 enhancer and generation of a PSM-specific Mesp1/Mesp2-null mouse using BAC-based rescue technology.
Bacterial artificial chromosome (BAC) modification technology is a powerful method for the identification of enhancer sequences and genetic modifications. Using this method, we have analyzed the Mesp1 and/or Mesp2 enhancers and identified P1-PSME, a PSM-specific enhancer of Mesp1, which contains a T-box binding site similar to the previously identified P2-PSME. Hence, Mesp1 and Mesp2 use different enhancers for their PSM-specific expression. In addition, we find that these two genes also use distinct enhancers for their early mesodermal expression. Based on these results, we generated a PSM-specific Mesp1/Mesp2-null mouse by introducing a BAC clone, from which only early mesodermal Mesp1 expression is possible, into the Mesp1/Mesp2 double knockout (dKO) genetic background. This successfully rescued gastrulation defects due to the lack of the early mesoderm in the dKO mouse and we thereby obtained a PSM-specific Mesp1/Mesp2-null mouse showing a lack of segmented somites.


Monoclonal antibodies directed against human Rh antigens in tests with the red cells of nonhuman primates.
Monoclonal antibodies against Rh related antigens on human red cells often crossreact with the red cells of the highest subhuman primate species. Depending on specificity of antibody, the species tested, and technique used, these reactions can be either species-specific or type specific. In tests with chimpanzee red cells, some of the latter type reactions have specificities related to the R antigen of the R-C-E-F blood group system of chimpanzee; specificities of some others seem to be unrelated to any known chimpanzee blood groups. Monoclonal anti-D reagents that give uniformly positive reactions with human D-positive (common and rare types) red cells, display wide individual differences in tests with chimpanzee blood. This indicates that there are minute structural variations of antibody molecules from one monoclonal anti-D antibodies apparently have no bearing on recognition of the D combining site on the human red cells, but come into play when in contact with chimpanzee rbcs. Some of the monoclonal antibodies directed against Rh and LW molecules are distinguished by unusually strong reactions with the red cells of the Old World monkeys (macaques and baboons), which is in contrast with negative or weak reactions of the same antibodies with the red cells of anthropoid apes and human bloods. One may recall, that polyclonal anti-Rh sera do not react with the blood of rhesus monkeys, the phenomenon that was the source of controversy surrounding the discovery of the rhesus factor of the human blood.


Pain management in palliative cancer patients: a prospective observational study on the use of high dosages of transdermal buprenorphine.
Despite guidelines and recommendations, a large proportion of patients with cancer still have inadequate pain control. Transdermal opioid administration can overcome problems such as swallowing and compliance, because only one application every three days is needed. Transdermal buprenorphine was documented to provide effective pain relief in cancer and non-cancer patients. A ceiling effect was described in animals at supratherapeutic dose levels. This prospective observational pilot study was designed to explore the need for doses of transdermal buprenorphine beyond the recommended maximum dose of 140 microg/h, in a cohort of palliative patients with cancer pain. 36 consecutive palliative patients with uncontrolled cancer pain were prescribed transdermal buprenorphine after having received adequate information on the disease, its evolution, the pain and the drug. They gave written informed consent for participation in this observational study. Pain intensity and use of breakthrough medication were registered by the patient and the health care provider. Pain was judged to be satisfactory controlled, by the patient and the health care providers, in 21 of 28 evaluable patients at a dose lower than or equal to 140 microg/h. The success rate was higher in the hospitalized patient group. The observation of adequate pain control in two patients treated with doses up to 210 microg/h supports the hypothesis that buprenorphine dose titration above 140 microg/h can be clinically effective and well tolerated. This also refutes the assumption of a clinically relevant ceiling effect. Transdermal buprenorphine control cancer pain in the majority of palliative patients.


Fate and contaminant transport model-driven probabilistic human health risk assessment of DNAPL-contaminated site.
In this study, fate and contaminant transport model-driven human health risk indexes were calculated due to the presence of dense non-aqueous phase liquids (DNAPLs) in the subsurface environment of air force base area in Florida, USA. Source concentration data of DNAPLs was used for the calculation of transport model-driven health risk indexes for the children and adult sub-population via direct oral ingestion and skin dermal contact exposure scenario using 10,000 Monte Carlo type simulations. The highest variation in the probability distribution of transformed DNAPL compound (cis-dichloroethene (cis-DCE) > vinyl chloride (VC)) was observed as compared to parent DNAPL (tetrachloroethene (PCE)) based on the 50-year simulation timespan. Transformed DNAPL compounds (VC, cis-DCE) posed the highest risk to human health for a longer duration (up to 15 years) in comparison to parent DNAPL (PCE), as non-carcinogenic hazard quotient varied from 400 to 1100. Carcinogenic health risks were observed as 3-order of magnitude higher than safe limit (HQSafe < 10-6) from 2nd to 5th year timespan and fall in the high-risk zone, indicating the need for a remediation plan for a contaminated site. Variance attribution analysis revealed that concentration, body weight, and exposure duration (contribution percentage - 70 to 95%) were the most important parameters, highlighting the impact of dispersivity and exposure model in the estimation of risk indexes. This approach can help decision-makers when a contaminated site with partial data on hydrogeological properties and with higher uncertainty in model parameters is to be assessed for the formulation of remediation measures.


Persistent effects of chronic Δ9-THC exposure on motor impulsivity in rats.
In humans, long-term marijuana use is associated with impaired impulse control and attentional capacity, though it has been difficult to distinguish pre-existing cognitive deficits from possible consequences of prolonged marijuana exposure. To evaluate the effects of long-term exposure to Δ9-Tetrahydrocannabinol (Δ9-THC), the primary psychoactive constituent in marijuana, on indices of impulse control and attentional capacity using the rat 5-Choice Serial Reaction Time Task (5-CSRTT). Ten 14-day cycles of Δ9-THC dosing and 5-CSRTT testing were employed, each comprised of 5-day Δ9-THC dosing (0.3 or 3 mg/kg b.i.d.) and 5-CSRTT testing during the 9 days of drug abstinence. Subsequent 5-CSRTT testing continued during 5 weeks of protracted abstinence. Dose-dependent increases in motor impulsivity (premature responses) and behavioral disinhibition (perseverative responses) emerged following 5 cycles of Δ9-THC exposure that persisted for the remaining dosing and testing cycles. Δ9-THC-related disruptions in motor impulsivity and behavioral inhibition were most pronounced during cognitively challenging 5-CSRTT sessions incorporating varying novel inter-trial intervals (ITIs), and these disruptions persisted for at least 5 weeks of Δ9-THC abstinence. Δ9-THC-related impairments in attentional capacity (response accuracy) were also evident during variable ITI challenge tests, though these attentional disruptions abated within 3 weeks of Δ9-THC abstinence. These observations demonstrate that long-term intermittent exposure to clinically meaningful Δ9-THC doses induces persistent impairments in impulse control and attentional function. If present in humans, these disruptions may impact academic and professional performance.


The significance of hypotension developing during treadmill exercise testing.
The significance of hypotension developing during treadmill exercise testing was evaluated and correlated with the findings at cardiac catheterization in two groups of patients. Twenty-five patients (Group I) had a fall in systolic pressure during exercise and were compared to 50 consecutive unselected patients (Group II) with a normal blood pressure response. Clinical characteristics were similar in both groups. Females comprised 48 per cent of the patients in Group I and only 30 per cent in Group II. The incidence of significant coronary artery disease was not different when the two groups were compared as a whole, 56 per cent in Group I and 36 per cent in Group II (P = NS). When males and females were considered separately, it was noted that the incidence of coronary artery disease was higher in hypotensive males (77 per cent) when compared to control males (40 per cent) (p less than 0.01). Females in both groups had a lower but comparable incidence of coronary artery disease (25 per cent and 27 per cent, respectively). Resting hemodynamics and angiographic characteristics, such as contraction abnormalities, and the number and distribution of diseased coronary vessels, were similar in both groups of patients. These findings suggest that hypotension in females does not necessarily connote coronary artery disease. Males with hypotension have a higher incidence of coronary artery disease, but the extent and distribution of their disease is no different from that of patients with a normal blood pressure response to exercise.


A likely protective effect of dimethyl itaconate on cerebral ischemia/reperfusion injury.
As a membrane-permeable derivative of itaconate, dimethyl itaconate (DMI) was recently showed to limit inflammatory response of activated macrophages, and to decrease the generation of reactive oxygen species and reduce cardiac ischemia/reperfusion injury. However, the effect of DMI in the context of cerebral ischemia/reperfusion injury remains unclear. Here, we treated the transient middle cerebral artery occlusion (tMCAO) mice with DMI or saline at the beginning of occlusion, and allowed them to recover for 3 days. We found that DMI obviously decreased the neurologic deficit score. Further, DMI significantly inhibited the toxic conversion of the peri-infarct microglia, and decreased the protein level of interleukin 1β. The present findings suggest that DMI might be recognized as a promising candidate for the treatment of ischemic stroke.


The central actions of nicotine on blood pressure and heart rate after administration via the left vertebral artery of anaesthetized cats. Distribution of nicotine into the brain after central application.
After injection into the vertebral artery of anaesthetized cats, low does of nicotine (10(-9)--10(-8) mol = 0.5--5 micrograms . kg-1) induce potent cardiovascular effects. The hypotensive action is always accompanied by a severe bradycardia. Dose-response curves for these pharmacological actions have been established. It is concluced that nicotinic receptors in the medulla oblongata and pons are involved. Administration of 10(-8) mol = 5 micrograms (radioactive) nicotine/kg into the left vertebral artery gives rise to a specific distribution pattern. Nicotine mainly accumulates into the ponto-medullary area, whereas higher brain regions (hypothalamus) contain only insignificant amounts. The experimental results suggest that the nicotine-like effect of endogenous acetylcholine might play an important physiological part in the central regulation of blood pressure and cardiac frequency.


Characterization of the endogenous protein kinase activity of the hepatitis B virus.
During the assembly of the nucleocapsid of the hepatitis B virus a protein kinase, probably of cellular origin, is encapsidated. This enzyme phosphorylates serine residue(s) localized within the lumen of the particle. By using purified, liver-derived core particles, we characterized the protein kinase activity in the presence of different ions and inhibitors. Controls were performed with cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) and recombinant core particles. We showed that the endogenous protein kinase of the core particles was not inhibited by H89, a specific inhibitor of PKA. Staurosporine, a selective inhibitor of PKC inhibited the endogenous kinase activity only within the first minutes of the reaction. In contrast, quercetine, a selective inhibitor of the protein kinase M (PKM) did not inhibit during the first minutes but inhibited efficiently during later phases of incubation. PKM represents an enzymatically active proteolytic fragment of PKC. These results suggest that PKC is encapsidated into human core particles and is converted to PKM during the in vitro reaction. This conclusion implies the association of a protease activity localized with the HBV nucleocapsid inside liver-derived core particles.


Boric Acid Inhibits RANKL-Stimulated Osteoclastogenesis In Vitro and Attenuates LPS-Induced Bone Loss In Vivo.
Boron and boric acid (BA) can promote osteogenic differentiation and reduce bone resorption, which controls bone growth and maintenance of bone tissue. It has been reported that BA activates PERK-eIF2α signaling to induce cytoplasmic stress granules and cell senescence in human prostate DU-145 cells. However, whether BA can affect osteoclasts formation and LPS-induced inflammatory bone loss, and the role of the PERK-eIF2α pathway in the process, remains unknown. In vitro, RAW264.7 cells were pre-treated with boric acid (BA, 1, 10, 100 μmol/L) for 4 h, and then incubated with receptor activator of nuclear factor-kappaB ligand (RANKL, 50 ng/mL) in the presence or absence of BA for 5 days. CCK-8 and tartrate-resistant acid phosphatase (TRAP) were used to examine cell viability, osteoclastogenesis, and bone resorption; quantitative real-time PCR was performed to examine mRNA levels of c-Fos, nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), TRAP, and cathepsin K; western blotting was used to examine protein expressions of glucose-regulated protein 78 (GRP78), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α), and phosphorylated eIF2α (p-eIF2α). In vivo, lipopolysaccharide (LPS)-induced bone loss model in mice was established, and micro-computed tomography (micro-CT) scanning, bone biochemical analysis, and osteoclastogenic cytokines were detected to evaluate the effect of BA on LPS-induced bone loss. In our vitro results showed that BA treatment for 5 days inhibited osteoclasts formation as well as osteoclastic bone resorption in a dose-dependent manner. The expression of osteoclasts marker genes c-Fos, NFATc1, TRAP, and cathepsin K were attenuated by BA. Immunoblotting analysis demonstrated that BA attenuated RANKL-induced PERK-eIF2α pathway activation. The in vivo data indicated that BA significantly prevented lipopolysaccharide (LPS)-induced bone loss. Our findings strongly suggest that BA may be a promising agent for the treatment of bone destructive diseases caused by excessive osteoclastogenesis.


Patient compliance and the "usefulness product" of timolol.
The practical value of any therapy depends upon a combination of effectiveness of the agent (or procedure) and the extent to which the patient complies in its proper administration. Thus, it might be said that the multiple of effectiveness times compliance equals the "usefulness product." Among the various glaucoma therapies, this product seems to range from about 30%--90%. Timolol's effectiveness in lowering intraocular pressure combined with its low incidence of side effects yields a high usefulness product, and this may decrease the incidence of surgery required for the treatment of the open-angle glaucomas.


Decalintetracids A and B, two pairs of unusual 3-decalinoyltetramic acid derivatives with phytotoxicity from Fusarium equiseti D39.
The filamentous fungi Fusarium sp. are well-known for their ability to produce abundant specialised metabolites with attractive chemical structures and bioactivities. In this study, chemical analyses of the endophyte F. equiseti D39 led to the isolation and identification of two pairs of undescribed 3-decalinoyltetramic acids (3DTAs) E/Z diastereomers, decalintetracids A and B. Their structures were elucidated by comprehensive spectroscopic analysis and quantum-chemical calculations. Although 3DTAs were commonly reported from fungi, decalintetracid A possessed an unprecedented tricyclo [7.2.1.02,7] dodecane skeleton, which added the diversity of these fungal metabolites. In addition, decalintetracid B was featured by a unique 6/6/5 ring system core. A plausible biosynthetic pathway for decalintetracids A and B was proposed. Both compounds exhibited phytotoxicity toward Amaranthus retroflexus L. and Amaranthus hybrid, indicating their potential as natural herbicides.


Comparison of continuous intradermal with simple interrupted suture pattern: an experimental study in dogs.
The aim of the study was to compare incisional wound healing in intradermal and simple interrupted suture patterns. Ten dogs were included. Surgically created skin incisions were apposed with (a) continuous intradermal pattern, (b) simple interrupted pattern, [both with 3/0 poliglecaprone 25], and (c) continuous intradermal pattern with 4/0 poliglecaprone 25. Cosmetic, clinical and histologic scores were evaluated. Simple interrupted sutures required significantly less time than intradermal sutures to complete. Cosmetic evaluation scoring was not statistically significant among the techniques. Irrespectively of the technique, the cosmetic, clinical and histologic appearance of the incisions improved over time. The cosmetic and histologic differences between the techniques were large during the first month, but decreased latter, whereas clinical differences persisted. The clinical appearance of the intradermal pattern was initially very good, worsened during the second postoperative month, and improved afterwards. Intradermal pattern with 4/0 poliglecaprone 25 was superior in terms of cosmetic, clinical and histologic appearance compared to simple interrupted pattern and to intradermal pattern with 3/0 poliglecaprone 25 for skin closure in dogs.


In Silico Simulations Reveal Molecular Mechanism of Uranyl Ion Toxicity towards DNA-Binding Domain of PARP-1 Protein.
The molecular toxicity of the uranyl ion (UO22+) in living cells is primarily determined by its high affinity to both native and potential metal-binding sites that commonly occur in the structure of biomolecules. Recent advances in computational and experimental research have shed light on the structural properties and functional impacts of uranyl binding to proteins, organic ligands, nucleic acids, and their complexes. In the present work, we report the results of the computational investigation of the uranyl-mediated loss of DNA-binding activity of PARP-1, a eukaryotic enzyme that participates in DNA repair, cell differentiation, and the induction of inflammation. The latest experimental studies have shown that the uranyl ion directly interacts with its DNA-binding subdomains, zinc fingers Zn1 and Zn2, and alters their tertiary structure. Here, we propose an atomistic mechanism underlying this process and compute the free energy change along the suggested pathway. Our Quantum Mechanics/Molecular Mechanics (QM/MM) simulations of the Zn2-UO22+ complex indicate that the uranyl ion replaces zinc in its native binding site. However, the resulting state is destroyed due to the spontaneous internal hydrolysis of the U-Cys162 coordination bond. Despite the enthalpy of hydrolysis being +2.8 kcal/mol, the overall reaction free energy change is -0.6 kcal/mol, which is attributed to the loss of domain's native tertiary structure originally maintained by a zinc ion. The subsequent reorganization of the binding site includes the association of the uranyl ion with the Glu190/Asp191 acidic cluster and significant perturbations in the domain's tertiary structure driven by a further decrease in the free energy by 6.8 kcal/mol. The disruption of the DNA-binding interface revealed in our study is consistent with previous experimental findings and explains the loss of PARP-like zinc fingers' affinity for nucleic acids.


Assessment of clinically significant urolithiasis positivity rate using CT KUB for suspected renal colic.
Unenhanced low-dose computed tomography of the kidneys, ureter and bladder (CT KUB) is the gold standard diagnostic imaging modality in the assessment of suspected renal colic. As the radiation dose is not negligible, it is important to monitor the diagnostic yield of CT KUBs. The aim of this study is to evaluate the diagnostic yield of CT KUB studies performed for suspected renal colic in patients presenting to the emergency department. A retrospective review was performed of 500 patients who underwent CT KUB for suspected renal colic over a seven month period from June 2019 to January 2020. Clinical information and imaging was reviewed for each patient. Statistical analysis was performed using GraphPad Prism 8 (GraphPad Software, San Diego, CA, USA). Forty-nine percent of patients in the series were female (248/500) and the mean age was 45. The positivity rate for obstructing ureteral calculus was 34% (169/500). Concerningly, there was a significantly lower positivity rate in females compared to males (19% versus 48%; p < 0.0001) which raises the issue of unnecessary radiation exposure to this cohort. In the 200 female patients who were negative for obstructing urolithiasis, the mean age was 43. Females also had a significantly higher rate of negative CT KUB (62% versus 37%; p < 0.0001) where no underlying alternative pathology was diagnosed. Women are less likely than men to have obstructing urolithiasis on CT KUB for suspected renal colic. This difference is not accounted for by a higher rate of alternative diagnoses among female patients. The findings of this study should prompt clinicians to exercise caution when considering this imaging modality in this patient cohort.


End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide-alkyne cycloaddition.
Functionalizable monotelechelic polymers are useful materials for chemical biology and materials science. We report here the synthesis of a capping agent that can be used to terminate polymers prepared by ring-opening metathesis polymerization of norbornenes bearing an activated ester. The terminating agent is a cis-butene derivative bearing a Teoc (2-trimethylsilylethyl carbamate) protected primary amine. Post-polymerization modification of the polymer was accomplished by amidation with an azido-amine linker followed by Cu(I)-catalyzed azide-alkyne cycloaddition with propargyl sugars. Subsequent Teoc deprotection and conjugation with pyrenyl isothiocyanates afforded well-defined end-labeled glycopolymers.


Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia.
Several G-protein-coupled receptors (GPCRs) have been shown to be important signaling mediators between neurons and glia. In our previous screening for identification of nerve injury-associated GPCRs, G-protein-coupled receptor 84 (GPR84) mRNA showed the highest up-regulation by microglia after nerve injury. GPR84 is a pro-inflammatory receptor of macrophages in a neuropathic pain mouse model, yet its function in resident microglia in the central nervous system is poorly understood. We used endogenous, natural, and surrogate agonists for GPR84 (capric acid, embelin, and 6-OAU, respectively) and examined their effect on mouse primary cultured microglia in vitro. 6-n-Octylaminouracil (6-OAU), embelin, and capric acid rapidly induced membrane ruffling and motility in cultured microglia obtained from C57BL/6 mice, although these agonists failed to promote microglial pro-inflammatory cytokine expression. Concomitantly, 6-OAU suppressed forskolin-induced increase of cAMP in cultured microglia. Pertussis toxin, an inhibitor of Gi-coupled signaling, completely suppressed 6-OAU-induced microglial membrane ruffling and motility. In contrast, no 6-OAU-induced microglial membrane ruffling and motility was observed in microglia from DBA/2 mice, a mouse strain that does not express functional GPR84 protein due to endogenous nonsense mutation of the GPR84 gene. GPR84 mediated signaling causes microglial motility and membrane ruffling but does not promote pro-inflammatory responses. As GPR84 is a known receptor for medium-chain fatty acids, those released from damaged brain cells may be involved in the enhancement of microglial motility through GPR84 after neuronal injury.


The gel phase of dipalmitoyl phosphatidylcholine. An infrared characterization of the acyl chain packing.
It is shown, by infrared spectroscopy, that the packing in the gel phase of fully-hydrated dipalmitoyl phosphatidylcholine is not uniform over a large temperature range. With decreasing temperature, starting at that of the pretransition, there is a gradual change in the molecular packing of the acyl chains, from near hexagonal to orthorhombic of monoclinic.


Long-term outcome and quality of life of adult patients on home parenteral nutrition.
The outcome and prognosis of home parenteral nutrition (HPN) patients may depend on their age and underlying disease and on HPN techniques. Results in the literature are confounded by mixing child and adult populations, short- and long-term HPN treatments and malignant and non-malignant cases. Only four papers have reported the probability of survival and only one of these used multivariate analysis. The quality of life of HPN patients, focusing on community and social rehabilitation, has been reported. The aspects of treatment differ depending upon the circumstances under which HPN is started (acute vs chronic) and the nature of the disease, facts which have to be taken into account in patient management. Prognosis of the underlying disease obviously has a major influence on how rehabilitation is viewed. Patients should be informed of the objectives of HPN by the nutrition team and family circumstances taken into account, before time-consuming and expensive HPN treatment is started.


Strain variability in biofilm formation: A food safety and quality perspective.
The inherent differences in microbial behavior among identically treated strains of the same microbial species, referred to as "strain variability", are regarded as an important source of variability in microbiological studies. Biofilms are defined as the structured multicellular communities with complex architecture that enable microorganisms to grow adhered to abiotic or living surfaces and constitute a fundamental aspect of microbial ecology. The research studies assessing the strain variability in biofilm formation are relatively few compared to the ones evaluating other aspects of microbial behavior such as virulence, growth and stress resistance. Among the available research data on intra-species variability in biofilm formation, compiled and discussed in the present review, most of them refer to foodborne pathogens as compared to spoilage microorganisms. Molecular and physiological aspects of biofilm formation potentially related to strain-specific responses, as well as information on the characterization and quantitative description of this type of biological variability are presented and discussed. Despite the considerable amount of available information on the strain variability in biofilm formation, there are certain data gaps and still-existing challenges that future research should cover and address. Current and future advances in systems biology and omics technologies are expected to aid significantly in the explanation of phenotypic strain variability, including biofilm formation variability, allowing for its integration in microbiological risk assessment.


Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent.
The dipeptide carnosine (beta-alanyl-L-histidine) was readily glycosylated non-enzymatically upon incubation with the sugars glucose, galactose, deoxyribose and the triose dihydroxyacetone. Carnosine inhibited glycation of actyl-Lys-His-amide by dihydroxyacetone and it protected alpha-crystallin, superoxide dismutase and catalise against glycation and cross-linking mediated by ribose, deoxyribose, dihydroxyacetone, dihydroxyacetone phosphate and fructose. Unlike certain glycated amino acids, glycated carnosine was non-mutagenic. The potential biological and therapeutic significance of these observations are discussed.


Movement disorders in cerebrovascular disease.
Movement disorders can occur as primary (idiopathic) or genetic disease, as a manifestation of an underlying neurodegenerative disorder, or secondary to a wide range of neurological or systemic diseases. Cerebrovascular diseases represent up to 22% of secondary movement disorders, and involuntary movements develop after 1-4% of strokes. Post-stroke movement disorders can manifest in parkinsonism or a wide range of hyperkinetic movement disorders including chorea, ballism, athetosis, dystonia, tremor, myoclonus, stereotypies, and akathisia. Some of these disorders occur immediately after acute stroke, whereas others can develop later, and yet others represent delayed-onset progressive movement disorders. These movement disorders have been encountered in patients with ischaemic and haemorrhagic strokes, subarachnoid haemorrhage, cerebrovascular malformations, and dural arteriovenous fistula affecting the basal ganglia, their connections, or both.


[Evaluation of vascular access for hemodialysis using combined measurement of recirculation in normal and inverted needle placement and determination of blood flow through the access].
The article describes novel method of vascular access quality assessment by means of combined measurement of recirculation with normal and inverse needles placement and calculation of vascular access blood flow from the recirculation data. Blood flow values seen in a large group of patients ranged from as low as 200 ml/min up to as high as 2 l/min. Females and diabetics exhibited lower values as compared to males and non-diabetics. The method enables to detect a number of anomalous sates which cannot be detected by conventional means based on monitoring of pressures or recirculation measurement at normal needles placement only (stenosis between both needles, uintentionally erroneous placement of needles in accesses with a loop). Assessment of access blood flow is suitable also for evaluation of interventions on the access, such as percutaneous transluminal angioplasty or surgical narrowing of anastomosis in case of too high blood flow.


Induction of DNA crosslinks in vitro upon reduction of the nitroimidazole-aziridines RSU-1069 and RSU-1131.
The interaction of the nitroimidazole-aziridines RSU-1069 and RSU-1131, as parent or radiation-reduced species, with plasmid DNA in aqueous solution at pH 7 results in strand breakage. The yields of DNA single strand breaks (ssb), "alkali-labile" damage and DNA crosslinks induced by these alkylating agents have been assessed. It is shown that DNA crosslinks are induced only by the reduced nitro-compounds. RSU-1069, as parent or reduced compound, is more efficient at producing these effects than the equivalent form of RSU-1131. Further, RSU-1069 is about 2 X more susceptible to nucleophilic attack by inorganic phosphate and deoxynucleotides than RSU-1131. RSU-1069 also shows greater selectivity for reaction with the nucleotide base moiety than does the less-reactive monomethyl analogue, RSU-1131. The yields of ssb and "alkali-labile" damaged sites induced by the two agents reflect their respective chemical reactivities and appear largely to determine their aerobic cytotoxicities. In contrast, the yield of DNA crosslinks induced by the reduced compounds appears to correspond rather better with the observed hypoxic cytotoxicities. From these findings it is suggested that the induction of DNA crosslinks by these agents may play a major role in their effectiveness as hypoxia-selective cytotoxins.