An integrated approach for prospectively investigating a mode-of-action for rodent liver effects.
Registration of new plant protection products (e.g., herbicide, insecticide, or fungicide) requires comprehensive mammalian toxicity evaluation including carcinogenicity studies in two species. The outcome of the carcinogenicity testing has a significant bearing on the overall human health risk assessment of the substance and, consequently, approved uses for different crops across geographies. In order to understand the relevance of a specific tumor finding to human health, a systematic, transparent, and hypothesis-driven mode of action (MoA) investigation is, appropriately, an expectation by the regulatory agencies. Here, we describe a novel approach of prospectively generating the MoA data by implementing additional end points to the standard guideline toxicity studies with sulfoxaflor, a molecule in development. This proactive MoA approach results in a more robust integration of molecular with apical end points while minimizing animal use. Sulfoxaflor, a molecule targeting sap-feeding insects, induced liver effects (increased liver weight due to hepatocellular hypertrophy) in an initial palatability probe study for selecting doses for subsequent repeat-dose dietary studies. This finding triggered the inclusion of dose-response investigations of the potential key events for rodent liver carcinogenesis, concurrent with the hazard assessment studies. As predicted, sulfoxaflor induced liver tumors in rats and mice in the bioassays. The MoA data available by the time of the carcinogenicity finding supported the conclusion that the carcinogenic potential of sulfoxaflor was due to CAR/PXR nuclear receptor activation with subsequent hepatocellular proliferation. This MoA was not considered to be relevant to humans as sulfoxaflor is unlikely to induce hepatocellular proliferation in humans and therefore would not be a human liver carcinogen.


Surgical accuracy in 3D planned bimaxillary osteotomies: intraoral scans and plaster casts as digital dentition models.
The aim of this study was to assess whether the use of intraoral scans (IOS) is an eligible alternative to conventional plaster casts in terms of surgical accuracy of three-dimensionally planned bimaxillary osteotomies. This retrospective cohort study included patients who underwent bimaxillary surgery between 2016 and 2020 in the Department of Oral and Maxillofacial Surgery at Radboud University Medical Center, Nijmegen. Three-dimensional virtual planning was performed with the use of plaster casts in one group and IOS in the other group. Cone beam computed tomography scans were acquired preoperatively and at 1 week following surgery. By using voxel-based matching, the maxillary movements were quantified in six degrees of freedom. The primary outcome variable, surgical accuracy, was defined as the difference between the planned maxillary movements and those achieved. Of 152 patients, 113 were documented with plaster casts and 39 with IOS. The surgical accuracy was comparable in terms of maxillary vertical, sagittal, and transverse translations, as well as roll and yaw. Maxillary pitch (difference 0.55 ± 0.26°; P = 0.001) was in favour of the IOS group. This study demonstrated that IOS can be used as an alternative to conventional plaster casts in the three-dimensional planning of bimaxillary osteotomies.


Nomenclature for factors of the HLA system, 1984.
This article presents the decisions of the nomenclature committee on leukocyte antigens, which met in Vienna on 16-17 May 1984.


Prognostic relevance of pretreatment proliferative rapidity of marrow blast cells in childhood acute lymphoblastic leukaemia.
Cell proliferation rate is a well-established prognostic factor in cancer, but it has not been considered to identify the risk group of childhood acute lymphoblastic leukaemia (ALL) at presentation. We carried out a study to demonstrate the prognostic importance of the rapidity of cell proliferation in patients with ALL. To measure the rapidity of cell proliferation we used the parameter relative to the area of silver-stained nucleolar organiser regions (AgNORs) as evaluated by morphometric analysis on smeared marrow blast cells. The mean AgNOR area of leukaemic marrow cells was measured in 119 children. By using a cut-off value of 3 microns2, we identified a group of 91 children with low proliferating blast activity (mean AgNOR value 2.11 microns2) and a group of 28 children with high proliferating activity (mean AgNOR value 3.29 microns2). The group of patients with a mean AgNOR value > 3 microns2 was characterised by a higher number of deaths, more frequent relapse and shorter time interval to relapse than the group of patients with mean AgNOR value < 3 microns2 (P < 0.01). Multivariate analysis performed to include T-cell immunophenotype, FAB morphology, leucocyte count and presence of mediastinal mass showed that the mean AgNOR value was the only independent predictor of unfavourable event-free survival probability (P > 0.01). Our results indicate that the rapidity of marrow blast cell proliferation is an important prognostic parameter in childhood ALL and should be routinely introduced in the group risk definition.


Occurrence and regional distribution of calcareous concretions in the rat pineal gland.
Serial sections of 90 Sprague-Dawley rat brains with the pineal in situ were scanned to determine the occurrence and regional distribution of calcareous concretions within the pineal gland and its surrounding leptomeningeal tissue. In 90% of the cases examined concretions were found in varying number and appearance, predominantly lying in the dorsal region of the pineal gland and in the distal portion of the pineal stalk. Discussing the hypothesis advanced by Lukaszyk and Reiter (1975) that the origin of pineal concretions may be related to a neurosecretory process involving a pineal carrier protein, called neuroepiphysin, it is thought that, in view of the intra- and extra-pineal occurrence of concretions, processes other than secretion should be considered. Since in the pineal organ lymphatics are lacking it may well be that, due to a reduced drainage of tissue fluid, the coagulation of intercellular organic debris mingled with minerals increases with age.


D-penicillamine-induced angiopathy in rats. Changes in aortic collagen, glycosaminoglycans, DNA and RNA in rats treated with D-penicillamine.
Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) in doses of 100, 250 or 500 mg/kg per day for 10, 32, 42 or 70 days. In addition animals were examined 28 days after withdrawal from 42 day's treatment with D-pen at 100 or 500 mg/kg per day. Pair-fed rats served as controls. The changes in aortic collagen, glycosaminoglycans (GAGs), DNA and RNA were studied. D-Pen had a dose- and time-related solubilizing effect on aortic collagen, which regained normal resistance to extraction within 28 days after cessation of the treatment. In contrast, D-pen caused a progressive accumulation of hydroxyproline (Hyp) in the aortic wall during and after treatment, probably mediated by an increased number of matrix synthesizing cells, as judged by augmentation of the DNA content in the presence of unaltered Hyp/DNA and RNA/DNA ratios. The relative amount of type III collagen was increased after 500 mg/kg per day D-pen for 10 and 42 days. High doses of D-pen increased the percentage of water in the aortic wall and reduced the ratio of Hyp to total tissue protein, suggesting an increased content of water-binding substances. This was confirmed by GAG accumulation. Hyaluronic acid (HA) and chondroitin 4,6-sulphate (CHS) were predominant after 32 and 42 days, whereas CHS, heparan sulphate (HS) and dermatan sulphate (DS) prevailed after 70 days of treatment. These observations suggest that processes of repair and regeneration are elicited secondary to the inhibitory effect of D-pen on aortic collagen and elastin crosslinking. Hypertrophy of the vessel wall may imply an increased rigidity, resulting in further increase of the susceptibility to haemodynamic injury.


The pharmacology of cycloplegics.
A brief review of the pharmacological action of cycloplegic drugs is followed by a specification of the doses and actions of five commonly used cycloplegics. Some criterion for selecting a cycloplegic are presented.


An open-label, single-dose, parallel-group study of the effects of chronic hepatic impairment on the safety and pharmacokinetics of desvenlafaxine.
Many antidepressants are extensively metabolized in the liver, requiring dose adjustments in individuals with hepatic impairment. Clinical studies indicate that the serotonin-norepinephrine reuptake inhibitor desvenlafaxine is metabolized primarily via glucuronidation, and ∼45% is eliminated unchanged in urine. The objectives of this study were to assess the pharmacokinetic profile, safety, and tolerability of desvenlafaxine in adults with chronic Child-Pugh class A, B, and C hepatic impairment. Subjects (aged 18-65 years) with mild (Child-Pugh class A, n = 8), moderate (Child-Pugh class B, n = 8), and severe (Child-Pugh class C, n = 8) hepatic impairment and 12 healthy matched subjects received a single 100-mg oral dose of desvenlafaxine. Disposition of (R)-, (S)-, and (R+S)-enantiomers of desvenlafaxine were examined in plasma and urine. Geometric least squares (GLS) mean ratios and 90% CIs for AUC, AUC0-τ, Cmax, and Cl/F were calculated; comparisons were made by using a 1-factor ANOVA. Safety was evaluated according to adverse events, physical examination, vital signs, and laboratory assessments. Healthy participants had a mean age of 51 years (range, 36-62 years) and weight of 79.1 kg (range, 52.5-105.0 kg); hepatically impaired participants had a mean age of 52 years (range, 31-65 years) and weight of 80.9 kg (range, 50.2-119.5 kg). In both groups, 67% of participants were male. No statistically significant differences (≥50%) in the disposition of desvenlafaxine were detected between hepatically impaired patients and healthy subjects based on GLS mean ratios for Cmax, AUC0-τ, AUC, or Cl/F (P > 0.05 for each comparison). Median Tmax was similar for all groups (range, 6-9 hours). A nonsignificant increase was observed for desvenlafaxine exposure in patients with moderate or severe hepatic impairment (GLS mean ratios [90% CIs] for AUC, 31% [93.2-184], 35% [96.5-190], respectively). The most common adverse events were nausea (n = 2, healthy subjects; n = 3, hepatically impaired subjects) and vomiting (n = 1, healthy subjects; n = 2, hepatically impaired subjects). A single 100-mg dose of desvenlafaxine was well tolerated in healthy subjects and hepatically impaired patients. A mild increase in exposure was observed for moderate and severe hepatically impaired subjects (Child-Pugh class B and C).


Hypolipidemic effect of SIPI-7623, a derivative of an extract from oriental wormwood, through farnesoid X receptor antagonism.
Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.


First Successful Kidney Transplantation After Hematopoeitic Stem Cell Transplantation in Malaysia.
Promising outcomes of kidney transplantation following hematopoeitic stem cell transplantation has been reported. Data from some centers have demonstrated stable graft function without long term immunosuppression. We present our experience with the first successful case in Malaysia. This is a 21-year-old man who had acute myeloid leukemia, received stem cell transplant from his younger brother 8 years prior, underwent kidney transplantation from the same donor, and had an excellent 1-year graft function post-transplant. As the post-transplant genetic analysis revealed full chimerism, his immunosuppression regimen can be tapered to minimal doses safely. The concept of immunotolerance is now widely studied and could potentially be the curative strategy for patients who develop end stage kidney disease after hematopoeitic stem cell transplantation.


The role of the magnocellular and parvocellular systems in the redundant target effect.
The redundant target effect (RTE) consists in the speeding of reaction time with single versus multiple targets and can be explained either by a neural coactivation or by a race model. To try to understand the role of the magnocellular and parvocellular systems in the determination of the RTE we carried out three experiments using onset or feature singletons. The former are likely to be mainly processed by the magnocellular system while the latter are mainly processed by the parvocellular system. In experiment 1 we found an RTE both when the target (red disk) was presented in isolation and when it was surrounded by equiluminant green distractors. Thus, the RTE occurred both with onset and feature singletons. However, with the former, the RTE could be accounted for by neural coactivation while with the latter it could be accounted for by a probabilistic explanation. In experiment 2 we tried to ascertain the role of distractors in yielding a probabilistic RTE: we used either targets in isolation or surrounded by distractors of lower luminance and found an RTE that could be explained by neural coactivation for both kinds of targets. This ruled out an effect of distractors per se in determining a probabilistic RTE. Finally, in experiment 3 we used targets of lower luminance than either the background or the distractors. We found that the RTE could be accounted for by neural coactivation with targets alone while it was probabilistic with distractors. Overall, these results show that stimuli presumably processed by the magnocellular system yield redundancy gains that result from a neural coactivation mechanism. In contrast, stimuli presumably processed by the parvocellular system are compatible with a probabilistic redundancy gain.


Value of internal thoracic artery grafting to the left anterior descending coronary artery at coronary reoperation.
The study sought to determine if left internal thoracic artery (LITA) grafting of the left anterior descending (LAD) at reoperative coronary artery bypass grafting (CABG) improves patient outcomes. LITA grafting to the LAD is the gold standard for primary CABG, but its value for reoperative CABG is unknown. From January 1985 to January 2007, reoperative CABG was performed in 3,473 patients who did not receive a LITA during their primary CABG and whose anterior myocardium (LAD) was at risk at reoperation: 2,389 had LITA grafting and 1,084 saphenous vein (SV) grafting to the LAD. Propensity matching (908 matched pairs) was used for balanced comparison of outcomes. Follow-up was continued to 20 years post-operatively, with a mean follow-up of 11 ± 8.2 years. Unadjusted hospital mortality was 2.2% and 6.5% in the LITA and SV groups, respectively (p < 0.001), but 3.1% and 5.6% in propensity-matched groups (p = 0.008). Unadjusted survival at 1, 5, 10, 15, and 20 years was 94%, 82%, 64%, 46%, and 32% for the LITA group, but 88%, 73%, 50%, 32%, and 18% for the SV group (p <.0001), respectively. For propensity-matched groups, both early (p = 0.01) and late survival was greater (p = 0.005) in the LITA group. At 20 years, LITA grafting of the LAD at reoperation resulted in an absolute mortality risk reduction of 6.0% and a hazard ratio of 0.85, with number needed to treat of 16 patients. LITA-to-LAD grafting at reoperation is safe and confers a risk-adjusted survival advantage. When appropriate, a LITA should be used to revascularize the LAD at coronary reoperations.


Evaluation of the use of methylprednisolone and dexamethasone in asthma critically ill patients with COVID-19: a multicenter cohort study.
Previous studies have shown mortality benefits with corticosteroids in Coronavirus disease-19 (COVID-19). However, there is inconsistency regarding the use of methylprednisolone over dexamethasone in COVID-19, and this has not been extensively evaluated in patients with a history of asthma. This study aims to investigate and compare the effectiveness and safety of methylprednisolone and dexamethasone in critically ill patients with asthma and COVID-19. The primary endpoint was the in-hospital mortality. Other endpoints include 30-day mortality, respiratory failure requiring mechanical ventilation (MV), acute kidney injury (AKI), acute liver injury, length of stay (LOS), ventilator-free days (VFDs), and hospital-acquired infections. Propensity score (PS) matching, and regression analyses were used. A total of one hundred-five patients were included. Thirty patients received methylprednisolone, whereas seventy-five patients received dexamethasone. After PS matching (1:1 ratio), patients who received methylprednisolone had higher but insignificant in-hospital mortality in both crude and logistic regression analysis, [(35.0% vs. 18.2%, P = 0.22) and (OR 2.31; CI: 0.56 - 9.59; P = 0.25), respectively]. There were no statistically significant differences in the 30-day mortality, respiratory failure requiring MV, AKI, acute liver injury, ICU LOS, hospital LOS, and hospital-acquired infections. Methylprednisolone in COVID-19 patients with asthma may lead to increased in-hospital mortality and shorter VFDs compared to dexamethasone; however, it failed to reach statistical significance. Therefore, it is necessary to interpret these data cautiously, and further large-scale randomized clinical trials are needed to establish more conclusive evidence and support these conclusions.


[Amplification of Extrachromosomal Oncogene and Tumorigenesis and Development].
Extrachromosomal DNA (ecDNA) is a small segment of circular DNA located outside the chromosome, which has the function of self-replication. Recently, amplification of oncogenes on ecDNA has been proved to be a common phenomenon in tumor cells, and has some characteristics worth studying, such as correlation with patients' poor prognosis. Multiple chromosomal events are involved in the formation of ecDNA, and its amplification can directly increase the number of DNA copies of extra-chromosomal oncogenes and accelerate the generation and development of tumors. Moreover, the segregation pattern of unequal transmission of parental ecDNA cells to offspring not only increases tumor heterogeneity, but also enhances tumor adaptation to environment and response to therapy. This article reviews the current status and potential significance of ecDNA in tumor cells. .


Induction of 6-thioguanine- and ouabain-resistant mutations in synchronized Syrian hamster cell cultures during different periods of the S phase.
Cells of a transformed Syrian hamster line, BP6T, were synchronized by a period of growth in low serum with a subsequent blockage of the cells at the G1/S boundary by hydroxyurea. This method provided cells with nearly 100% synchrony, although approximately 20% of the cells were non-cycling. The cells were then treated with 10(-5) M 5-bromodeoxyuridine for 1 of 5 1-h periods during the S phase and subsequently irradiated with near-ultraviolet light for 5 min. The BrdU plus irradiation treatment induced 6-thioguanine- and ouabain-resistant mutants while BrdU alone or irradiation alone was not mutagenic. 6-Thioguanine-resistant mutants were induced only during early S phase by BrdU plus irradiation treatment. Ouabain-resistant mutants, however, were induced in a biphasic pattern, during early S phase and also during late S phase. The induction of ouabain-resistant mutants at two distinct periods of S phase suggests the presence of two loci for the gene(s) of Na+/K+ ATPase.


Electrophysiological and immunocytochemical characterization of DRG neurons on an organosilane surface in serum-free medium.
We are attempting to recreate a stretch reflex circuit on a patterned Bio-MEMS (bio-microelectromechanical systems) chip with deflecting micro-cantilevers. The first steps to recreate this system is to be able to grow individual components of the circuit (sensory neuron, motoneuron, skeletal muscle, and muscle spindle) on a patternable, synthetic substrate coating the MEMS device. Sensory neurons represent the afferent portion of the stretch reflex arc and also play a significant role in transmitting the signal from the muscle spindle to the spinal cord motoneurons. We have utilized a synthetic silane substrate N-1[3-(trimethoxysilyl) propyl) diethylenetriamine (DETA) on which to grow and pattern the cells. DETA forms a self-assembled monolayer on a variety of silicon substrates, including glass, and can be patterned using photolithography. In this paper, we have evaluated the growth of sensory neurons on this synthetic silane substrate. We have investigated the immunocytochemical and electrophysiological properties of the sensory neurons on DETA and compared the resultant properties with a biological control substrate (ornithine/laminin). Immunocytochemical studies revealed the survival and growth of all three subtypes of sensory neurons: trkA, trkB, and trkC on both surfaces. Furthermore, whole-cell patch clamp recordings were used to study the electrophysiological properties of the sensory neurons on the two surfaces. There were no significant differences in the electrical properties of the neurons grown on either surface. This is the first study analyzing the immunocytochemical and electrophysiological properties of sensory neurons grown long-term in a completely defined environment and on a nonbiological substrate.


Insight into a bad omen for white men: coronary artery disease--the Bogalusa Heart Study.
Clinical experience of diagnostic and interventional procedures, including cardiac surgery, indicates a greater prevalence of coronary heart disease in white men than in other race-gender groups. Studies of children and young adults in the Bogalusa Heart Study have provided evidence that might account for this race-gender contrast. A variety of anthropometric and metabolic parameters influencing serum lipid and lipoprotein levels places white boys and young white men selectively at high risk for the development of atherosclerotic coronary artery disease. Obesity and greater central body fat, subtle aberrations in carbohydrate-lipid metabolic relations and variability in sex hormone profiles appear to underlie a trend to adverse lipoprotein changes in white men. A lower high-density lipoprotein cholesterol level and apolipoprotein A-l at puberty and a dramatic increase of low-density lipoprotein cholesterol are seen in young white men; such adverse changes identify them to be at greater risk. It is noteworthy that children whose fathers had myocardial infarction tend to be white. These children also have relatively high ratios of apolipoprotein B/apolipoprotein A-l and apolipoprotein B/low-density lipoprotein cholesterol. Studies of risk factors in children emphasize their importance in the early natural history of coronary artery disease. These findings show the need for beginning prevention of adult heart disease in childhood.


Retinoic Acid-Mediated Differentiation of Mouse Embryonic Stem Cells to Neuronal Cells.
The capability of pluripotent embryonic stem cells (ESCs) to proliferate and differentiate into specific lineages makes them an important avenue of research in the field of cell therapy as well as a useful model to study patterns of differentiation and gene expression, recapitulating many events that occur during the very early stages of development of the mammalian embryo. With striking similarities that exist between inherently programmed embryonic development of the nervous system in vivo and the differentiation of ESCs in vitro, they have already been used to treat locomotive and cognitive deficits caused by brain injury in rodents. A suitable differentiation model thus empowers us with all these opportunities. In this chapter, we describe a neural differentiation model from mouse embryonic stem cells using retinoic acid as the inducer. This method is among the most commonly used one to acquire a homogeneous population of neuronal progenitor cells or mature neurons as desired. The method is scalable, efficient, and results in production of ~70% neural progenitor cells within 4-6 days.


Health consequences and daily life modifications in children and adolescents with epilepsy during the COVID-19 pandemic - a systematic review: Running Title: Covid-19 Pandemic in Children/Adolescents with Epilepsy.
To describe the impact of the COVID-19 pandemic on the health care and daily life of children and adolescents with epilepsy. This systematic review followed the preferred reporting items guidelines and was registered on the PROSPERO platform (CRD42021255931). The PECO (Patient, Exposure, Comparison, Outcome) framework criteria were as follows: people with epilepsy (0-18 years old); exposed to the COVID-19 pandemic; and outcomes, including epilepsy type, time of clinical diagnosis, seizure exacerbation, treatment and medications, need for emergency because of seizures, sleep, behavior, comorbidities and/or concerns, social and/or economic impact, insurance status, electronic device use, telemedicine, and distance learning. Literature searches for cross-sectional and longitudinal studies were conducted on Embase and PubMed. The methodological quality of identified studies was assessed using the Newcastle‒Ottawa Scale (NOS). Data were extracted from 23 eligible out of 597 identified articles and included 31,673 patients. The mean NOS scores for cross-sectional study design was 3.84/10, and for longitudinal, it was 3.5/8 stars. Seizure exacerbations were reported in three studies, difficulties with access to anti-seizure medications in two, changes in dosage in five, and visit postponed or cancelation in five studies. Problems with sleep were highlighted in three, issues related to distance learning in two, an increased time spent on electronic devices in three, and increased behavioral problems in eight studies. Telemedicine, when available, was described as useful and supporting patient's needs. The pandemic affected the health care and lifestyle of young individuals with epilepsy. The main problems described revolved around seizure control, accessing anti-seizure medication, sleep and behavioral complains.


Correction of vascular hypercontractility in spontaneously hypertensive rats using shRNAs-induced delta protein kinase C gene silencing.
Potassium conductance in vascular smooth muscle (VSM) is known to be altered in arterial hypertension. High level of protein kinase C (PKC) activity is a common feature for hypertension of different genesis. The main goal of this study was to investigate the efficacy of the RNA interference (RNAi) technique targeting PKC delta-isoform gene as a possible pharmacological tool to restore vasodilator potential in spontaneously hypertensive rats (SHR). Experimental design of the study comprised RNAi and patch-clamp techniques, RT-PCR analysis and standard acetylcholine test. Total outward currents and acetylcholine-induced endothelium-dependent relaxant responses were blunted in SHR. BKCa alpha subunit mRNA expression in SHR was unchanged whereas KV and KATP mRNA expression appeared significantly increased. PKC inhibitor, chelerythrine (100 nM), restored potassium channels activity in SHR. PKC-delta-isoform protein expression and PKC-delta-isoform mRNA expression are 2.5-4 fold increased in VSM from SHR. PKC gene silencing with the short hairpin RNAs (shRNAs)-plasmid delivery system administered intravenously led to an increment in maximal amplitude of acetylcholine-relaxation, restored outward K(+) currents and PKC-delta-isoform mRNA and protein expression. Arterial blood pressure in SHR was normalized following shRNAs administration. We conclude that BKCa channels are likely to be the most PKC-dependent member of K(+) channels family responsible for vascular hypercontractility in SHR while Kv and KATP channels may constitute a reserve mechanism for the maintenance of vasodilator potential under BKCa channelopathy. It is likely that RNAi technique is a good therapeutic approach to inactivate PKC gene and to normalize vascular functions and high arterial blood pressure in SHR.


Subjective dimensions of patient competence: relationships with selected healthcare usage behaviors and general features of self-rated competence.
To introduce the concept of patient competence and provide additional information on the concurrent validity of a new self-rating measure of patient competence in the context of cancer employing healthcare usage behaviors and more general self-rated features of patient competence as criteria. Based on a multi-center sample of n=536 patients with cancer, bivariate correlations and multiple regressions were computed. The competence subscale of striving for autonomous decisions emerged as significant, albeit weak predictor of having used professional psycho-social support (r=.31, beta=.28) and employing other complementary medicines (r=.28; B=.65) in relation to one's cancer. Problem-focused and emotion-focused competencies relate differently to different general features of self-rated competence like feeling informed and assertive or adapting well. Additional support for the concurrent validity of the new self-rating measure of patient competence in the context of cancer has been found. Viewed in perspective, this measure may therefore provide a methodological basis to examine determinants and health effects of patient competence empirically. Nevertheless, further research on the conceptualization and measurement of patient competence appears necessary. Having available measures of patients' specific competencies in the context of cancer will help identify their strength and weaknesses in dealing with life-threatening disease and enhance their coping resources.


Resistin is expressed in different rat tissues and is regulated in a tissue- and gender-specific manner.
Resistin is a polypeptide hormone first reported from human and rodent adipocytes. In order to better define the potential biological role of resistin we undertook a detailed analysis of its expression in different rat tissues. We demonstrate by real-time reverse transcription polymerase chain reaction, Southern blotting and immunohistochemistry that resistin is expressed not only in brown and white adipose tissue, but also in the stomach, small and large intestines, adrenal gland, and skeletal muscle. Food deprivation led to a decrease in resistin mRNA expression only in adipose tissue, not in any of the other tissues studied. Furthermore, resistin mRNA expression is higher in males than in females in adipose tissue, not in any of the other tissues. Thus, our data suggest that resistin is not exclusively localized in adipocytes, and indicate that its expression is regulated in a tissue- and sex-specific manner.


New radiographic monitoring indices for total trapeziometacarpal prostheses.
The objective of this study is to propose and evaluate a method of monitoring implants via the calculation of a trapezial and metacarpal index from radiological measurements and to describe an initial patient analysis. This retrospective study describes the trapezial index which reflects the trapezial bone stock not occupied by the trapezial cup, while the metacarpal index reflects the rate of metacarpal occupation by the prosthetic stem. Those indexes were used on a series of 20 patients with a Maïa™ prosthesis with a minimum follow-up of seven years. The indexes were measured immediately postoperatively and at the various annual check-ups. Four observers measured each index on two occasions, to obtain an inter- and intra-observer correlation coefficient. The average intra-observer correlation coefficient for the trapezium index was 0.94, for the metacarpal index 0.98. The inter-observer correlation coefficient was 0.93 for the trapezium index, 0.94 for the metacarpal index on average. The post-hoc calculated power was 0.98 as the number of subjects required was not usable. The mean immediate postoperative trapezial index was 45.74%, compared with a value at longest follow-up of 41.74%, reflecting a highly significant loss of height of 8,74%. The mean immediate postoperative metacarpal index was 77.69% compared with a mean value at longest follow-up of 78.99% indicating a non-significant increase in the index of 1,67%. Proposed indexes had excellent inter- and intra-observer correlation, the metacarpal one is stable over time whereas the trapezial one reveals changes in some patients, requiring further investigations. These simple and reproducible indexes allow precise monitoring of trapeziometacarpal prostheses and identify radiographic changes that should lead to additional examinations to improve survival of implants. III, retrospective single cohort study.


Laser-assisted microdissection of membrane-mounted tissue sections.
Biological tissues (in particular those affected by disease) are inherently complex mixtures of different cell types and matrices. This heterogeneity can complicate the interpretation of molecular biological studies performed on whole-tissue extracts if the precise cellular origin of the molecules being tested is not known. Laser-assisted microdissection (LAM) has emerged as a leading histological technique for obtaining samples enriched for specific target cell populations or tissue components for subsequent molecular (especially polymerase chain reaction-based) analysis. This method allows the identification and study of target-specific molecular alterations in heterogeneous specimens, and enables more accurate detection and quantification of target molecules. In this chapter, we focus on tissue microdissection performed with an ultraviolet laser system and describe protocols for the basic procedure and for handling of the samples.


Comparison of maternal separation and early handling in terms of their neurobehavioral effects in aged rats.
In the rat, relative to pup nonhandling (NH), early handling (EH) leads to old-adult offspring with a hyporesponsive HPA axis, superior spatial cognition, and greater hippocampal (HIPP) neuronal density. The present study compared the effects of EH and repeated maternal separation (MS), in the form of 6-hr separation on each of 4 days beginning at day 12, on spatial cognition, corticosterone (CORT) levels, and HIPP characteristics, in aged rats. Male Wistar rat pups were exposed to EH, MS, NH or our normal in-house husbandry (CON) and tested at 18-20 months. Relative to NH and CON, EH demonstrated superior spatial cognition, reduced CORT stress response, reduced CA-field volume and no change in HIPP neuronal number. MS demonstrated a trend to superior spatial cognition, an unaffected CORT stress response, reduced CA-field volume and no change in HIPP neuronal number. These findings are important in terms of the life-span mechanisms via which postnatal manipulations induce neurobehavioral effects, and the mechanisms via which CORT and HIPP structure relate to HIPP function.


The effect of food provisioning on persistent organic pollutant bioamplification in Chinook salmon larvae.
Fall spawning pacific salmon provision large amounts of yolk to their eggs to allow survival of larvae during under the ice winter conditions. This yolk provisioning leads to maternal offloading of persistent organic pollutants (POPs) to eggs and larvae. Previous research has shown that Chinook salmon larvae exhibit limited capacity to eliminate POPs during the cold water period resulting in bioamplification of POP residues. This study compared POPs bioamplification in Chinook salmon larvae under a high food provisioning treatment and a non-fed treatment to test whether or not food availability attenuates POPs bioamplification via growth dilution. Results demonstrate that larvae in the food provisioning treatment did not gain weight until after day 129. Between hatching and day 129, fed and non-fed treatments exhibited similar decreases in whole body lipid content, negligible POPs elimination and POPs bioamplification factors approaching 1.6. By day 184 of the study, POPs bioamplification factors in the non-fed treatment were as high as 5.3 across chemicals but ranged from non-detectable to approaching 1 in the fed group. This study demonstrates that POPs bioamplification occurs in Chinook salmon larvae even under ideal rearing conditions but peaks after day 129, following which growth dilution can attenuate bioamplification relative to starved individuals.


Bio/phyremediation potential of Leptospirillum ferrooxidans and Ricinus communis on metal contaminated mine sludge.
The heavy metal pollution is a serious environmental pollution around the globe and threatens the ecosystem. The physicochemical traits (pH, Electrical conductivity, hardness, NPK, Al, Fe, Cd, Cr, Pb, Mg, and Mn) of soil sample collected from the polluted site were analyzed and found that the most of the metal contents were beyond the acceptable limits of national standards. The metals such as Mn (1859.37 ± 11.25 mg kg-1), Cd (24.86 ± 1.85 mg kg-1), Zn (795.64 ± 9.24 mg kg-1), Pb (318.62 ± 5.85 mg kg-1), Cr (186.84 ± 6.84 mg kg-1), and Al (105.84 ± 5.42 mg kg-1) were crossing the permissible limits. The pre-isolated L. ferrooxidans showed considerable metal tolerance to metals such as Al, Cd, Cr, Pb, Mg, and Mn at up to the concentration of 750 μg mL-1 and also have remediation potential on polluted soil in a short duration of treatment. The greenhouse study demonstrated that the bio/phytoremediation potential of metal tolerant L. ferrooxidans and R. communis under various remediation (A, B, and C) groups. Surprisingly, remediation group C demonstrated greater phytoextraction potential than the other remediation groups (A and B). These results strongly suggest that coexistence of L. ferrooxidans and R. communis had a significant positive effect on phytoextraction on metal-contaminated soil.


Does the patient's position influence the detection of detrusor overactivity?
The demonstration of preoperative detrusor overactivity (DO) with associated overactive bladder symptoms (OAB) is known to have an adverse effect on surgery performed for stress incontinence or for prostatic obstruction. The purpose of this review is to examine the best position, when filling the bladder during urodynamics, to demonstrate detrusor overactivity and reproduce the OAB symptoms, when the demonstration of DO might be important. MEDLINE and PUBMED literature searches were performed, spanning the period from 1956 to August 2005 using the keywords "detrusor overactivity" or "detrusor instability" combined with "posture or position or standing or sitting" and "urodynamics." Other studies were identified by reviewing secondary references in the original citations. Sixteen studies looked at the effect of position on the detection rate of DO. There is good consistency between the studies analyzed. All but two [Ramsden et al., Br J Urol 49:633-9, 1977; Choe et al., J Urol 161:1541-4, 1999] showed a clear effect, with an increase in DO when the patient is filled in the vertical position or is asked to sit or stand, with a full bladder, after being filled supine. Performing the urodynamics (UDS) in the supine position would have missed a large proportion of DO diagnoses ranging from 33% to 100%. This review confirms that the patient's position is a significant variable during urodynamics and that supine cystometry will fail to detect a significant percentage of patients with DO. We suggest that all patients should be filled sitting or standing, unless physically disabled. It seems desirable for the International Continence Society (ICS) to extend its "Good urodynamic practice guideline" [Schafer et al., Neurourol Urodyn 21:261-74, 2002] to cover this important issue.


Microwave-assisted ultraviolet digestion of petroleum coke for the simultaneous determination of nickel, vanadium and sulfur by ICP-OES.
A method for the simultaneous determination of Ni, V and S in petroleum coke by inductively coupled plasma optical emission spectrometry (ICP-OES) after microwave-assisted ultraviolet digestion (MW-UV) in closed vessels was proposed. Digestion was performed using electrodeless discharge lamps positioned inside quartz vessels and turned on by microwave radiation. The following parameters were evaluated: HNO3 concentration (15 mL of 1, 4, 7, 10 or 14.4 mol L(-1)), volume of H2O2 (30%, 1 or 3 mL), sample mass (100, 250 or 500 mg) and heating time (40 or 60 min) with or without the use of UV lamps. Digestion efficiency was evaluated by the determination of the residual carbon content (RCC) in digests. Using UV lamps lower RCC was obtained and the combination of 4 mol L(-1) HNO3 with 3 mL of H2O2 and 60 min of heating allowed a suitable digestion of up to 500 mg of petroleum coke (RCC< 21%). The agreement with the reference values for Ni, V and S (obtained by digestion of petroleum coke by microwave-induced combustion) and with a certified reference material of petroleum coke was between 96 and 101%. The proposed method was considered as advantageous when compared to American Society for Testing and Materials method because it allowed the simultaneous determination of Ni, V and S with lower limit of detection (0.22, 0.12 and 8.7 µg g(-1) for Ni, V and S, respectively) avoiding the use of concentrated nitric acid and providing digests suitable for routine analysis by ICP-OES.


Novel database and cut-off value for bacterial amoA gene revealed a spatial variability pattern of the ammonia-oxidizing bacteria community from river to sea.
Ammonia-oxidizing bacteria (AOB) catalyze the first step of nitrification, oxidizing ammonia to nitrite, and are characterized by amoA gene encoding ammonia monooxygenase. To analyze the AOB community effectively, an integral taxonomy database containing 14,058 amoA sequences and the optimal cut-off value at 95 % for OTU clustering were determined. This method was evaluated to be efficient by the analysis of environmental samples from the river, estuary, and sea. Using this method, a significant spatial variance of the AOB community was found. The diversity of AOB was highest in the estuary and lowest in the ocean. Nitrosomonas were the predominant AOB in the sediments of the freshwater river and estuary. Nearly all the AOB-amoA sequences belonged to uncultured bacterium in the sediments of deep sea. In general, an integral AOB taxonomic database and a suitable cut-off value were constructed for the comprehensive exploration of the diversity of AOB from river to sea.


A comparative study of the disease burden attributable to asbestos in Brazil, China, Kazakhstan, and Russia between 1990 and 2019.
Brazil, China, Kazakhstan, and Russia are the main asbestos-producing countries, and all forms of asbestos are carcinogenic to humans. The objective of this study was to estimate the disease burden attributable to asbestos between 1990 and 2019 in major producing countries, including Brazil, China, Kazakhstan, and Russia. Age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life year (DALY) rates (ASDR) of disease burden attributable to asbestos by country, age, and sex were extracted from the Global Burden of Disease 2019. Percentage change and estimated annual percentage change (EAPC) were used to assess the trends of ASDR and ASMR of disease burden attributable to asbestos between 1990 and 2019. Asbestos-related diseases were highly heterogeneous across Global, Brazil, China, Kazakhstan, and Russia. There was a downward trend in ASMR and ASDR of diseases burden related to asbestos globally. The age-specific mortality rate of disease attributable to asbestos increased in men and women, although it decreased in women aged 85-89, the highest age-specific mortality rate were observed in age 95 + group in men [162.14 (95% UI: 103.76-215.45)] and women [30.58 (95% UI: 14.83-44.33)] per 100 000 population, respectively. Tracheal, bronchus, and lung (TBL) cancer was the leading cause of death and DALYS attributable to asbestos between 1990 and 2019 globally and in Brazil, China, Kazakhstan, and Russia. China had the highest percentage change (73.31%) and EAPC [3.41 (95% CI: 2.75-4.08)] in ASMR related to exposure to asbestos in men, with the highest percentage change (73.31%) and EAPC [3.41 (95% CI: 2.75-4.08)] in ASDR in men. The ASMR and ASDR of disease burden attributable to asbestos decreased between 1990 and 2019 globally. TBL cancer was the leading cause of death and DALYs attributable to asbestos between 1990 and 2019. There has been an increasing trend in mortality and DALYs globally, especially in older men. The burden of disease attributable to asbestos is increasing in China, especially in men.


Temperature Monitoring and Thermal Support in Exotic Animal Critical Care.
Body temperature measurement is one of the most important parameters to assess the health of a patient. In small exotic mammals, rectal temperature is obtained via a similar process as in dogs or cats, with a few specific differences. In reptiles and birds, measurement of body temperature can provide important information, albeit its accuracy may be limited. In most animals, temperature should be taken at the beginning of the examination to not artificially elevate the temperature during the physical exam. Heat support is typically indicated any time a patient's temperature is below the accepted core temperature range and cooling may be indicated whenever a patient's temperature exceeds a critical point.


Quinolone antibacterial agents for the treatment of genitourinary tract infections.
The fluoroquinolones have expanded the therapeutic options available for the treatment of genitourinary tract infections. Their ease of oral administration, favourable pharmacokinetics, low incidence of adverse reactions, and broad spectrum of in vitro activity against aerobic and facultative organisms make them especially suitable for treating bacteriuria, particularly when pathogens are resistant to other available oral agents. Their efficacy has also been established in the treatment of prostatis, gonorrhea and chancroid. They have lower in vitro activity against chlamydia, ureaplasma and anaerobes, and their role in the treatment of non-gonococcal urethritis, vaginitis and acute pelvic inflammatory disease is less well established.


alpha-Aspartate 261 is a key residue in noncatalytic sites of Escherichia coli F1-ATPase.
X-ray structure analysis of the noncatalytic sites of F1-ATPase revealed that residue alpha-Asp261 lies close to the Mg of bound Mg-5'-adenylyl-beta,gamma-imidodiphosphate. Here, the mutation alpha D261N was generated in Escherichia coli and combined with the alpha R365W mutation, allowing nucleotide binding at F1 noncatalytic sites to be specifically monitored by tryptophan fluorescence spectroscopy. Purified alpha D261N/alpha R365W F1-ATPase showed catalytic activity similar to wild-type. An important feature was that, without any resort to nucleotide-depletion procedures, the noncatalytic sites in purified native enzyme were already empty. Binding studies with MgATP, MgADP, and the corresponding free nucleotides led to the following conclusions. Residue alpha-Asp261 interacts with the Mg of Mg-nucleotide in noncatalytic sites and provides a large component of the binding energy (approximately 3 kcal/mol). It is the primary determinant of the preference of noncatalytic sites for Mg-nucleotide. The natural ligands at these sites in wild-type enzyme are the Mg-nucleotides and free nucleotides bind poorly. Under conditions where noncatalytic sites were empty, alpha D261N/alpha R365W F1 showed significant hydrolysis of MgATP. This established unequivocally that occupancy of noncatalytic sites by nucleotide is not required for catalysis.


Schistosomicidal Effects of the Essential Oils of Citrus limonia and Citrus reticulata Against Schistosoma mansoni.
We report the in vitro schistosomicidal effects of the essential oil obtained from Citrus limonia leaves (CL-EO) and C. reticulata fruit peels (CR-EO), cultivated in Brazil, against Schistosoma mansoni worms. Limonene (29.9%), β-pinene (12.0%), sabinene (9.0%), citronellal (9.0%), and citronellol (5.8%) are the major constituents of CL-EO; limonene (26.5%), γ-terpinene (17.2%), linalool (11.1%), octanal (8.0%), myrcene (6.2%), and capraldehyde (3.9%) predominate in CR-EO. CL-EO displayed moderate lethal concentration 50% (LC50 ) of 81.7 and 38.9 μg/ml against male and female worms at 24 and 72 h, respectively. At concentrations of 25 and 100 μg/ml, CL-EO separated between 50 and 75% of the coupled worm pairs during the evaluated period. CR-EO presented moderate LC50 of 81.7 μg/ml against male and female worms at 24 and 72 h. However, this oil separated coupled worm pairs more effectively than CL-EO and displayed lower cytotoxicity to GM07492-A cells (IC50 = 987.7 ± 88.9 μg/ml) as compared to CL-EO (IC50 = 187.8 ± 2.9 μg/ml). The enantiomers (+)-(R)-limonene and (-)-(S)-limonene did not affect S. mansoni adult worm pairs significantly. Taken together, these data indicate that CL-EO and CR-EO exhibit moderate in vitro schistosomicidal activity against adult S. mansoni worms.


Occurrence and source identification of perfluoroalkyl acids (PFAAs) in the Metedeconk River Watershed, New Jersey.
The Brick Township Municipal Utilities Authority (BTMUA), which relies on the Metedeconk River as its primary source of water supply, initiated a perfluoroalkyl acid (PFAA) source trackdown study in collaboration with the New Jersey Department of Environmental Protection (NJDEP) after discovering that the concentration of one PFAA, perfluorooctanoic acid (PFOA), was elevated at their raw surface water intake. Water samples were collected over eight sampling events between September 2011 and July 2014. Samples included surface water, groundwater, stormwater, sanitary sewer water, and commercial/industrial process water. Each sample was analyzed for ten PFAAs. Results from a set of samples collected from the 80 km2 South Branch Metedeconk River watershed directed the focus of this study to a 7.5-km2 area of interest. Within this area, a high concentration of PFAA contamination was documented in a localized zone. Subsequent groundwater sampling led to the identification of a plume of groundwater contamination emanating from an industrial/business park. The suspected source of PFAA detected in the river and drinking water intake was identified to a small industrial facility that used materials containing PFOA. Groundwater PFOA concentrations as high as 70,000 ng/L were found in samples taken within 200 m of the parcel and surface water concentrations as high as 130 ng/L were observed in the river. While various PFAAs were detected in the samples, particularly in groundwater samples, PFOA was identified as the primary contaminant of concern with respect to the river and the BTMUA water supply.


Why listening to traumatic disclosures sometimes fails and how it can succeed.
Traumatic events often launch searches for meaning, which can be advanced through emotional disclosure. Listeners contribute to reparative disclosures by attending to and accepting their content, imagery, feelings, and meanings. However, engaging in such highly attuned "authentic listening" can disrupt listeners' own fundamental beliefs. As a result, listeners can experience secondary traumatization-the intrusive images, negative emotions, and meaning searches that resemble post-traumatic stress. Listeners sometimes avoid these psychic costs by responding defensively to speakers' stories, altering their meaning, or commandeering their expression. However, listening defensively might be reduced, and authentic listening sustained by bolstering listeners' psychosocial resources. Providing listeners with their own disclosure opportunities might be a particularly potent way to do so.


FSP1 confers ferroptosis resistance in KEAP1 mutant non-small cell lung carcinoma in NRF2-dependent and -independent manner.
Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as a novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted a thorough investigation of the genomic and transcriptomic data derived from hundreds of human cancer cell lines and primary tissue samples, with a particular focus on non-small cell lung carcinoma (NSCLC). It was observed that mutations in Kelch-like ECH-associated protein 1 (KEAP1) and subsequent nuclear factor erythroid 2-related factor 2 (NRF2, also known as NFE2L2) activation are strongly associated with ferroptosis resistance in NSCLC. Additionally, AIFM2 gene, which encodes ferroptosis suppressor protein 1 (FSP1), was identified as the gene most significantly correlated with ferroptosis resistance, followed by multiple NRF2 targets. We found that inhibition of NRF2 alone was not sufficient to reduce FSP1 protein levels and promote ferroptosis, whereas FSP1 inhibition effectively sensitized KEAP1-mutant NSCLC cells to ferroptosis. Furthermore, we found that combined inhibition of FSP1 and NRF2 induced ferroptosis more intensely. Our findings imply that FSP1 is a crucial suppressor of ferroptosis whose expression is partially dependent on NRF2 and that synergistically targeting both FSP1 and NRF2 may be a promising strategy for overcoming ferroptosis resistance in cancer.


Proteolysis in samples of quarter milk with varying somatic cell counts. 1. Comparison of some indicators of endogenous proteolysis in milk.
Eighty-six samples of quarter milk from 31 cows, the mean SCC of which exceeded 400,000 cells/ml, were analyzed for SCC, chloride content, pH, clotting time, total N, soluble N, casein N, proteose-peptone content, plasmin activity, and amount of free NH2 groups, parameters that are related to the udder health condition and to the deterioration of the protein quality. Analysis of the milk from each quarter separately improved the correlations considerably compared with analyses of samples from all 4 quarters mixed together. Measurement of free NH2 groups, using the 2, 4, 6-trinitrobenzene sulfonic acid, was not appropriate for estimating the extent of protein deterioration in milk samples with different SCC. Unlike SCC, the proteolysis index, plasmin activity, and the proteose-peptone content were highly correlated themselves and with most of the parameters related to proteolysis in milk. Proteolysis occurred in milk samples with SCC as low as 250,000 cells/ml. The quality of milk protein decreased unavoidably during lactation, regardless of SCC.


Description and genome analysis of Luteimonas viscosa sp. nov., a novel bacterium isolated from soil of a sunflower field.
Strain XBU10T was isolated from a soil sample of a sunflower plot in Inner Mongolia, China. The isolate was a Gram-stain-negative, aerobic, non-motile, rod-shaped bacterium, and its colonies were bright yellow in colour. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain XBU10T belonged to the genus Luteimonas of the family Lysobacteraceae and was most closely related to Luteimonas panaciterrae Gsoil 068T (97.8%), Luteimonas marina FR1330T (97.6%), Luteimonas aquatica RIB1-20T (97.4%) and Luteimonas huabeiensis HB2T (97.2%). Growth occurred at 4-40 °C (optimum, 28-30 °C), with 0-5.0% (w/v) NaCl (optimum, 0.5%) and at pH 6.0-10.0 (optimum, pH 7.0 - 8.0). The chemotaxonomic characteristics of strain XBU10T, which had Q-8 as its predominant quinone and iso-C17:1 ω9c, iso-C15:0, iso-C17:0 and iso-C16:0 as its major fatty acids, were consistent with classification in the genus Luteimonas. The polar lipid profile of strain XBU10T comprised phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid, two unidentified aminophospholipids and three unidentified polar lipids. The genome of strain XBU10T was 4.17 Mbp with a G + C content of 69.9%. Its genome sequence showed genes encoding alkaline phosphatase and catalase. Protein-coding genes related to carbohydrate-active enzymes were also observed. Average nucleotide identity (ANI) values between XBU10T and other species of the genus Luteimonas were found to be low (ANIm < 88.0%, ANIb < 85.0% and OrthoANIu < 85.0%). Furthermore, digital DNA-DNA hybridization (dDDH) and average amino acid identity (AAI) values between strain XBU10T and the closely related species ranged from 20.3 to 28.9% and from 64.2 to 82.3%, respectively. Based on the results of our phylogenetic, phenotypic, genotypic and chemotaxonomic analyses, it is concluded that strain XBU10T represents a novel species within the genus Luteimonas, for which the name Luteimonas viscosa sp. nov. is proposed. The type strain is XBU10T (= CGMCC 1.12158T = KCTC 23878T).


Histogram analysis parameters identify multiple associations between DWI and DCE MRI in head and neck squamous cell carcinoma.
Nowadays, multiparametric investigations of head and neck squamous cell carcinoma (HNSCC) are established. These approaches can better characterize tumor biology and behavior. Diffusion weighted imaging (DWI) can by means of apparent diffusion coefficient (ADC) quantitatively characterize different tissue compartments. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) reflects perfusion and vascularization of tissues. Recently, a novel approach of data acquisition, namely histogram analysis of different images is a novel diagnostic approach, which can provide more information of tissue heterogeneity. The purpose of this study was to analyze possible associations between DWI, and DCE parameters derived from histogram analysis in patients with HNSCC. Overall, 34 patients, 9 women and 25 men, mean age, 56.7±10.2years, with different HNSCC were involved in the study. DWI was obtained by using of an axial echo planar imaging sequence with b-values of 0 and 800s/mm2. Dynamic T1w DCE sequence after intravenous application of contrast medium was performed for estimation of the following perfusion parameters: volume transfer constant (Ktrans), volume of the extravascular extracellular leakage space (Ve), and diffusion of contrast medium from the extravascular extracellular leakage space back to the plasma (Kep). Both ADC and perfusion parameters maps were processed offline in DICOM format with custom-made Matlab-based application. Thereafter, polygonal ROIs were manually drawn on the transferred maps on each slice. For every parameter, mean, maximal, minimal, and median values, as well percentiles 10th, 25th, 75th, 90th, kurtosis, skewness, and entropy were estimated. Сorrelation analysis identified multiple statistically significant correlations between the investigated parameters. Ve related parameters correlated well with different ADC values. Especially, percentiles 10 and 75, mode, and median values showed stronger correlations in comparison to other parameters. Thereby, the calculated correlation coefficients ranged from 0.62 to 0.69. Furthermore, Ktrans related parameters showed multiple slightly to moderate significant correlations with different ADC values. Strongest correlations were identified between ADC P75 and Ktrans min (p=0.58, P=0.0007), and ADC P75 and Ktrans P10 (p=0.56, P=0.001). Only four Kep related parameters correlated statistically significant with ADC fractions. Strongest correlation was found between Kep max and ADC mode (p=-0.47, P=0.008). Multiple statistically significant correlations between, DWI and DCE MRI parameters derived from histogram analysis were identified in HNSCC.


Upper tibial hyperextension fractures in infants: another occult toddler's fracture.
We describe the radiographic findings associated with occult upper tibial fractures in infants and young children and offer an explanation for the underlying mechanism from which they result. These fractures tend to be subtle, just as the classic spiral tibial fracture originally described by Dunbar et al. (1964, J Can Assoc Radiol 15: 136-144). The fracture we describe results from a hyperextension injury to the knee, and the knowledge of the mechanism of injury, the subtle radiographic findings, and the findings on physical examination allow one to diagnose this fracture with confidence. Otherwise, it easily can go undetected.


Detection of nitric oxide production in mice by spin-trapping electron paramagnetic resonance spectroscopy.
We describe here a spin-trapping method combined with X-band electron paramagnetic resonance (EPR) spectroscopy for ex vivo measurement of nitric oxide (.NO) levels in the urine of both normal and lipopolysaccharide (LPS)-induced shock mice. Normal or LPS-treated mice were injected subcutaneously with a metal-chelator complex, N-methyl-D-glucamine dithiocarbamate-ferrous iron, [(MGD)2/Fe], which binds to .NO and forms a water-soluble [(MGD)2/Fe-NO] complex. At 2 h after injection of the [(MGD)2/Fe] complex, a three-line EPR signal characteristic of the [(MGD)2/Fe-NO] complex was detected in the urine of either normal or LPS-treated mice. It is estimated that the concentrations of the [(MGD)2/Fe-NO] complex in normal and LPS-treated mouse urine were 1.3 and 35 microM, respectively. This 25-fold increase in .NO levels in the LPS-treated mouse urine provides the direct evidence that LPS challenge induces the overproduction of .NO in mice. Administration of N-monomethyl-L-arginine (NMMA; 50 mg/kg) inhibited the ex vivo signal intensities of the [(MGD)2/Fe-NO] complex in the urine of either normal or LPS-treated mouse urine. Furthermore, after injection of 15N-arginine (10 mg per mouse), a composite EPR spectrum, consisting of a three-line spectrum of the [(MGD)2/Fe-14NO] complex and a two-line spectrum of the [(MGD)2/Fe-15NO] complex, was detected in the urine. These isotopic tracer experiments further confirm that the detected .NO levels in the mouse urine are produced via the arginine-nitric oxide pathway. This ex vivo spin-trapping method should readily be adapted to experiments on larger animals and provide a noninvasive way of measuring both constitutive and inducible .NO synthase activities in living animals under physiological as well as pathophysiological conditions where .NO is overproduced.


Anesthesia and the renal sympathetic nervous system in perioperative AKI.
Approximately 7% of patients undergoing non-cardiac surgery with general anesthesia develop postoperative acute kidney injury (AKI). It is well-known that general anesthesia may have an impact on renal function and water balance regulation, but the mechanisms and potential differences between anesthetics are not yet completely clear. Recently published large animal studies have demonstrated that volatile (gas) anesthesia stimulates the renal sympathetic nervous system more than intravenous propofol anesthesia, resulting in decreased water and sodium excretion and reduced renal perfusion and oxygenation. Whether this is the case also in humans remains to be clarified. Increased renal sympathetic nerve activity may impair renal excretory function and oxygenation and induce structural injury in ischemic AKI models and could therefore be a contributing factor to AKI in the perioperative setting. This review summarizes anesthetic agents' effects on the renal sympathetic nervous system that may be important in the pathogenesis of perioperative AKI.


United Nations Declaration of Commitment on HIV/AIDS.
The United Nations General Assembly Declaration of Commitment on HIV/AIDS calls for a fundamental shift in the response to HIV/AIDS.


Cyclosporine increases calcium in kidney medulla.
Treatment of rats with 20, 50 or 100 mg/kg of cyclosporine p.o. markedly increased 45Ca accumulation in kidney slices especially in medulla. The effect was related to dose and duration of treatment, and was also observed in slices of kidney medulla from cyclosporine-treated mice. Total calcium was elevated in kidney medulla of cyclosporine-treated rats so that the effect is not merely an increased exchange but a build-up of calcium in the tissue. No histopathologic evidence of cyclosporine-related cell necrosis was present in mouse kidney, showing that calcium accumulation is not dystrophic in character. Accumulation of 45Ca in slices of rat heart, liver, or brain was not affected by cyclosporine pretreatment of the animals. It is suggested that cyclosporine-induced changes in calcium metabolism in kidney medulla may influence kidney function.


The early oxidative biodegradation steps of residual kraft lignin models with laccase.
A number of model compounds resembling the fundamental bonding patterns of residual kraft lignin, including a series of stilbenes, were incubated with laccase from Trametes versicolor in the presence and absence of delignification 'mediators' ABTS and HBT. The condensed kraft lignin model compounds seem to undergo initial degradation by laccase mainly via benzylic oxidation, demethylation and hydroxylation reactions. Phenolic 5-5', diphenylmethane and alpha-5 lignin models were found to be degraded mainly via side-chain oxidation reactions. Among the models studied, a phenolic stilbene was found to be the most reactive, yielding several products showing side-chain oxidation/transposition, demethoxylation and hydroxylation reactions. Non-phenolic 5-5', diphenylmethane and stilbene model compounds were found unreactive even in the presence of the laccase-mediator system.


A substitution of arginine to lysine at the COOH-terminus of MIP caused a different binocular phenotype in a congenital cataract family.
To detect the cataractogenetic mutation for a six-generation family of Chinese origin with autosomal dominant binocular polymorphic cataracts. A genome wide scan was performed using 382 fluorescent-labeled microsatellite markers. Multiple polymerase chain reaction (PCR) was performed according to the protocols previously described. Two-point linkage analysis was performed with the FASTLINK version of the MLINK in Linkage Program Package. The candidate gene was screened by direct sequencing. The disease locus was mapped to a 61 cM region on chromosome 12 defined by D12S310 and D12S351 near the major intrinsic protein gene (MIP). The maximum two-point lod score of 5.44 was obtained at marker D12S83 at theta=0.00. Direct sequencing of the encoding region of the candidate gene revealed a novel missense mutation G>A in exon 4 at nucleotide 702, which caused the replacement of arginine to lysine at codon 233 (p.R233K). The change located in the alpha-helix domain of the COOH-terminus of MIP was determined to be associated with the binocular polymorphic cataract in this study. It suggests that arginine in this domain plays a crucial role in the function of the carboxyl-end of this protein and provides a helpful clue to further studies on completely understanding the physiological significance of MIP and its role in the formation of cataract.


Quantitative perceived depth from sequential monocular decamouflage.
We present a novel binocular stimulus without conventional disparity cues whose presence and depth are revealed by sequential monocular stimulation (delay > or = 80 ms). Vertical white lines were occluded as they passed behind an otherwise camouflaged black rectangular target. The location (and instant) of the occlusion event, decamouflaging the target's edges, differed in the two eyes. Probe settings to match the depth of the black rectangular target showed a monotonic increase with simulated depth. Control tests discounted the possibility of subjects integrating retinal disparities over an extended temporal window or using temporal disparity. Sequential monocular decamouflage was found to be as precise and accurate as conventional simultaneous stereopsis with equivalent depths and exposure durations.


Reinnervation, myelination and organization of iris tissue implanted into the rat midbrain--an ultrastructural study.
The ultrastructure of autologous irides implanted into the midbrain of mature Sprague-Dawley rats was studied over a time period of 4-14 days. Most features of the normal iris still persisted throughout this time, including typical iris blood vessels and amelanotic melanocytes. At 5-4 days after implantation, the normal innervation of the implanted iris had degenerated, except for the presence of intact Schwann cells and some myelin debris. Reinnervation, beginning about the seventh day, proceeded rapidly. By the fourteenth day, extensive reinnervation of the implant was evidenced by the presence of numerous small (0.1-0.6 micrometer) and large (2-4 micrometer) non-myelinated axons ensheathed in Schwann cell cytoplasm. Axonal varicosities, filled either with dense core or clear core vesicles, formed junctions with axons. These junctions were characterized by an accentuation of areas of the axonal membrane and pre- or post-junctional thickenings; however, we did not observe typical synaptic complexes. Some large axons within the myelinated iris developed thick myelin sheaths of the peripheral nervous system (PNS) type; we believe this is the first reported instance in which myelination of central axons by Schwann cells within the brain parenchyma has been produced by the implantation of PNS elements.


"A picture is worth a thousand words": smoking in multi-unit housing in Israel.
A brief commentary on the need for policy change by the Israeli government to address the problem of tobacco smoke incursion in multi-unit housing. The commentary also includes a call for enhanced products, programs, and services to help smokers in Israel quit.


Cardiac and hemodynamic profile of the new cardiotonic agent, DPI 201-106, in the conscious dog.
The cardiac and hemodynamic effects of increasing doses (0.1-3 mg/kg i.v.) of the novel cardiotonic agent, DPI 201-106 (DPI), were investigated over a 60 min period in conscious dogs chronically instrumented for the measurement of arterial pressure, heart rate, left ventricular pressure (LVP), LV (+) dP/dtmax and cardiac output. LV (+) dP/dtmax, cardiac output and stroke volume were significantly increased by DPI whereas the total peripheral resistance was significantly decreased. These effects were dose-dependent in intensity and in duration. The mean arterial pressure and heart rate remained unaffected, except by the 3 mg/kg dose, which increased them slightly. Autonomic blockade with hexamethonium, atropine and propranolol did not alter the positive inotropic properties of DPI but unmasked its intrinsic bradycardic effect. At equipotent positive inotropic doses, DPI (0.3 mg/kg), milrinone (40 micrograms/kg) and dobutamine (5 micrograms/kg per min) induced similar increases in cardiac output and similar decreases in total peripheral resistance, but only dobutamine and milrinone accelerated the heart rate, whereas ouabain (17.5 micrograms/kg) induced a strong rise in the total peripheral resistance and markedly lowered the heart rate and cardiac output. After coadministration of DPI and ouabain, LV (+) dP/dtmax was further increased whereas the ouabain-induced bradycardia, the rise in the total peripheral resistance and the decrease in cardiac output were reinforced, halved and unaltered, respectively. We conclude that (a) DPI exhibits potent and direct positive inotropic properties, associated with a peripheral vasodilating action, and almost no positive chronotropic effects, and (b) coadministration of DPI and ouabain results in synergistic positive inotropic effects.


Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor.
There is a clinical need for new oral anticoagulants to prevent and treat thromboembolic diseases. Given its integral role in the coagulation cascade, factor Xa is a particularly promising target for new anticoagulation therapies. The aim of this study was to investigate the safety, pharmacodynamics, and pharmacokinetics of BAY 59--7939, an oral, direct factor Xa inhibitor. This single-center, randomized, single-blinded, placebo-controlled, dose-escalation study included 108 healthy white male subjects aged 19 to 45 years. Subjects received single oral doses of either BAY 59--7939 (1.25--80 mg) or placebo; in addition, 1 group received 2 doses of BAY 59--7939 (5--mg tablet and oral solution) or placebo in a crossover design. Oral BAY 59--7939 in single doses up to 80 mg was safe and well tolerated and was not associated with an increased risk of bleeding compared with placebo. Pharmacodynamic effects (inhibition of factor Xa activity, prothrombin time, activated partial thromboplastin time, and Hep Test) and plasma concentration profiles were dose-dependent. Maximum inhibition of factor Xa activity was achieved 1 to 4 hours after administration of BAY 59--7939 and ranged from 20% to 61% for the 5- to 80-mg doses. BAY 59--7939 selectively inhibited factor Xa activity; thrombin (factor IIa) and antithrombin were unaffected. Inhibition of factor Xa activity and prolongation of prothrombin time correlated well with BAY 59--7939 plasma concentrations (r=0.949 and 0.935, respectively). BAY 59--7939 was well tolerated with predictable pharmacodynamics and pharmacokinetics across a wide range of doses in healthy male subjects. BAY 59--7939 was shown to be an effective and specific factor Xa inhibitor.


Gene targeting in polymerase theta-deficient Arabidopsis thaliana.
Agrobacterium tumefaciens-mediated transformation has been for decades the preferred tool to generate transgenic plants. During this process, a T-DNA carrying transgenes is transferred from the bacterium to plant cells, where it randomly integrates into the genome via polymerase theta (Polθ)-mediated end joining (TMEJ). Targeting of the T-DNA to a specific genomic locus via homologous recombination (HR) is also possible, but such gene targeting (GT) events occur at low frequency and are almost invariably accompanied by random integration events. An additional complexity is that the product of recombination between T-DNA and target locus may not only map to the target locus (true GT), but also to random positions in the genome (ectopic GT). In this study, we have investigated how TMEJ functionality affects the biology of GT in plants, by using Arabidopsis thaliana mutated for the TEBICHI gene, which encodes for Polθ. Whereas in TMEJ-proficient plants we predominantly found GT events accompanied by random T-DNA integrations, GT events obtained in the teb mutant background lacked additional T-DNA copies, corroborating the essential role of Polθ in T-DNA integration. Polθ deficiency also prevented ectopic GT events, suggesting that the sequence of events leading up to this outcome requires TMEJ. Our findings provide insights that can be used for the development of strategies to obtain high-quality GT events in crop plants.


Stimulus control over induction produced by upcoming food-pellet reinforcement.
Research has demonstrated that rats increase their rate of lever pressing for sucrose reinforcement when food-pellet reinforcement will soon be available within the session. Recent results suggest that this increase occurs because stimuli in the session come to signal different levels of overall reinforcement. The present experiment tested this idea by having rats respond in two types of session. In one, they pressed lever A for 1% sucrose reinforcers in the first half of the session and lever B for food-pellet reinforcers in the second half (the opposing lever was retracted in the respective half). In the other, they pressed lever B for 1% sucrose reinforcers in the first half and lever A for 1% sucrose reinforcers in the second. Thus, the presence of lever A in the first half of the session was predictive of upcoming food-pellet reinforcement, but only lever B was ever used to obtain food pellets. Subjects responded at a higher rate on lever B in the first half of the session than on lever A, despite food-pellet reinforcement being unavailable in such sessions. Furthermore, they responded at a higher rate on lever B during probe sessions in which both levers were available. These results demonstrate that stimulus control over induction occurs when a stimulus becomes differentially associated with a heightened level of reinforcement. However, questions remain as to whether this association is Pavlovian or whether stimuli with "predictive value" may ever lead to induction.


Learning effect on perinatal post-mortem magnetic resonance imaging reporting: single reporter diagnostic accuracy of 200 cases.
The objective of the study is to compare diagnostic accuracy of perinatal post-mortem magnetic resonance (PMMR) imaging against conventional autopsy, when reported by a single-blinded observer for all organ systems following a period of initial experience. We compared pre-autopsy PMMR with conventional autopsy for the detection of (1) major pathological abnormalities related to the cause of death and (2) all diagnostic findings in five different body organ systems. PMMR was reported blinded to autopsy findings. In 201 cases, 123/146 (84.2%) of major abnormalities were identified by PMMR. Overall diagnostic accuracy of PMMR was 89.6% [95% confidence interval (CI): 84.3, 93.2%] across all cases, with high concordance 91.8% (95% CI: 89.9, 93.4%) across most organ systems. Our study showed higher concordance than single reporter statistics previously reported in neurological [92.2% vs 73.8%; diff 18.4% (95% CI: 11.0, 25.4%) p < 0.01] and thoracic systems [93.7% vs 81.2%; diff 12.5% (95% CI: 6.3, 18.4%) p < 0.01] and slightly better overall [91.8% vs 87.1%; diff 4.7% (95% CI: 2.1, 7.3%) p < 0.01]. The PMMR examinations can be reliably reported by a single radiologist, following a period of experience and training with this specific modality, with high-diagnostic accuracy for all organ systems. © 2017 John Wiley & Sons, Ltd.


Two small open reading frames are co-transcribed with the pea chloroplast genes for the polypeptides of cytochrome b-559.
The genes encoding the 9 kDa and 4 kDa polypeptides of cytochrome b-559 have been located in pea chloroplast DNA by coupled transcription-translation of cloned restriction fragments of chloroplast DNA in a cell-free extract of Escherichia coli and by nucleotide sequence analysis. The genes (psbE and psbF) are located approximately 1.0 kbp downstream of the gene for cytochrome f and are transcribed in the opposite direction, similar to the arrangement in the chloroplast genomes of other higher plants. Nucleotide sequence analysis of this region revealed four open reading frames encoding hydrophobic proteins of 83 (psbE), 39 (psbF), 38 and 40 amino acid residues, which are co-transcribed as a single major RNA of 1.1 kb. The 5' and 3' ends of this RNA have been located by primer extension and S1 nuclease mapping. The 5' end of the RNA is located 140 bp upstream of the initiating ATG codon of psbE and is preceded by typical chloroplast promoter sequences. The 3' end of the RNA is located approximately 515 bp downstream of the TAA stop codon of psbF close to a stable stem-loop structure.


Immobilization of Candida antarctic lipase B on MWNTs modified by ionic liquids with different functional groups.
Multiwalled carbon nanotubes (MWNTs) were modified by imidazole-based ionic liquids with different kinds of functional groups such as alkyl, carboxyl, amino and hydroxyl. The supports were used to immobilize Candida antarctic lipase B (CALB) and the influence of different functional groups of ionic liquids on enzymatic properties was investigated by the hydrolysis reaction of triacetin. The results revealed that the functionalization process did not destroy the structural integrity of MWNTs, and the enzymatic properities of CALB which immobilized on the MWNTs modified by ionic liquids with different kinds of functional groups were all improved. The hydroxyl functionalized ionic liquids which exhibited the best enzymatic properities was selected to investigate the effects of different carbon chain length on the enzymatic properties of immobilized CALB. Among them, CALB which immobilized on MWNTs modified by hydroxyl functionalized ionic liquid with suitable chain length (MWNTs-IL(8C)-OH-CALB) had the highest specific activity, with a specific activity of 18.11 times that of MWNTs-CALB. Furthermore, it also presented best thermal stability and reusability. The residual activity of MWNTs-IL(8C)-OH-CALB held over 64.01% of the initial activity after being incubated for 20min at 70°C, and the residual activity was 85.56% after 4 cycles of use.


HLY78 protects blood-brain barrier integrity through Wnt/β-catenin signaling pathway following subarachnoid hemorrhage in rats.
Wnt/β-catenin signaling plays an essential role in blood-brain barrier (BBB) formation and maintenance under pathophysiological conditions. HLY78, a lycorine derivative, has been identified as a novel activator of Wnt/β-catenin signaling in vitro. However, the effects of HLY78 on the BBB function in subarachnoid hemorrhage (SAH) are not yet validated. The present study was designed to investigate the impacts of HLY78 on the BBB in an endovascular perforation induced SAH model of Sprague-Dawley rats. Western blot, immunofluorescence staining, neurological function, brain water content, and Evans blue assay were performed after SAH induction. The results revealed that the expression of phosphorylated low-density lipoprotein receptor-related protein 6 (p-LRP6) was significantly increased after SAH and further augmented by HLY78. Administration of HLY78 significantly improved neurobehavioral functions and attenuated BBB leakage following SAH. Moreover, HLY78 markedly increased the β-catenin expression followed with the up-regulation of Occludin, ZO-1, and Claudin-5 after SAH, which was reversed by LRP6 siRNA. In conclusion, HLY78 could preserve BBB integrity, possibly through the Wnt/β-catenin signaling pathway. HLY78 might be a potential treatment option to protect BBB integrity following SAH.


Succession of oral bacterial colonizers on dental implant materials: An in vitro biofilm model.
Oral bacterial adhesion on dental implant materials has been extensively studied using in vitro systems but has yielded results restricted to in vitro growth patterns due to limitations in species selection, sustained fastidious anaerobe growth, and mixed culture longevity. The aim of this study was to develop an oral bacterial biofilm model consisting of colonizers representative of the oral microbiome exhibiting temporal shifts characteristic of plaque development and maturation in vivo. Streptococcus oralis, Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Veillonella parvula, Fusobacterium nucleatum, and Porphyromonas gingivalis were grown in monoculture prior to combination in mixed culture. Commercially pure titanium (cpTi) and yttria-stabilized zirconia (ZrO2) disks with polished, acid-etched, or sandblasted surfaces were prepared to evaluate oral bacterial adhesion. After 6 h, 1, 3, 7, 14 and 21 days, genomic DNA from planktonic and adherent bacteria was isolated. Quantitative polymerase chain reaction (qPCR) was used to enumerate the amount and proportion of each species. Early-colonizing S. oralis and A. actinomycetemcomitans, dominated after 6 h prior to secondary colonization by F. nucleatum and V. parvula in planktonic (1 day) and sessile (3 days) form. A. naeslundii maintained relatively low but stable bacterial counts throughout testing. After 14 days, late-colonizing P. gingivalis became established in mixed culture and persisted, becoming the dominant species after 21 days. The composition of adherent bacteria across all substrates was statistically similar at all timepoints with notable exceptions including lower S. oralis bacterial counts on polished cpTi (3 days). Within the present model's limitations, multispecies oral bacterial attachment is similar on surface-treated cpTi and ZrO2.


Heat tolerance of two Cladonia species and Campylopus praemorsus in a hot steam vent area of Hawaii.
Temperatures were measured in soil, Cladonia skottsbergii, Cl. oceanica, and Campylopus praemorsus growing in the almost barren geothermal area at Puhimau, Hawaii. The measurements were made in the early morning in winter when insolation and air temperatures were minimal and the geothermal effects were predominant. Measurements were made on healthy, dew moistened plants. Close to steam vents Campylopus praemorsus forms thick cushions on hot soil and temperatures up to 29.8°C are recorded in the active parts of the moss. Cladonia oceanica grows exclusively on moss in this area, but not as close to steam vents as the moss itself. Maximum temperatures were 27.2°C in stunted and 23°C in ramified growth forms. In this area Cl. skottsbergii normally colonizes tree stumps of Metrosideros only where the steam is already cool. Maximum temperatures were 23°C in normal thalli, through higher temperatures were measured in partly damaged or killed thalli overhanging the stump where they are immersed in hot steam. With respect to heat tolerance only Campylopus can be considered as adapted to the hot environment. Therefore it is able to colonize the hot dry soil while deriving its moisture from adjacent steam vents. The lichens, particularly Cl. skottsbergii, are not adapted and are as sensitive to heat as most other lichens. Therefore they can only survive where there is at most a small geothermal impact yet they are obviously dependent on moisture from the steam vents.


Pathological findings after preoperative irradiation for carcinoma of the urinary bladder.
Pathological descriptions of specimens obtained in 17 patients with urinary bladder carcinoma both at biopsy before preoperative irradiation and after surgery are presented. No positive lymph nodes were found in 16 patients who had lymphadenectomy at the time of surgery. No tumor was found postoperatively in 58.8% of patients and 82.3% had a reduction in tumor stage.


Automatic morphometry of synaptic boutons of cultured cells using granulometric analysis of digital images.
Numbers, linear density, and surface area of synaptic boutons can be important parameters in studies on synaptic plasticity in cultured neurons. We present a method for automatic identification and morphometry of boutons based on filtering of digital images using granulometric analysis. Cultures of cortical neurons (DIV8 and DIV21) were fixed and marked with fluorescently labeled antibodies for synapsin I (a marker for synaptic boutons) and MAP-2 (a marker for dendrites). Images were acquired on a confocal microscope and automatically processed. Granulometry, a morphological operator sensitive to the geometry and size of objects, was used to construct a filter passing fuzzy fluorescent grains of a certain size. Next, the filter was overlaid with the original image (masking) and the positive pixels were identified by an integral intensity threshold (thresholding). Disjoint grains, representing individual boutons, were reconstructed from the connected pixels above the threshold, numbered and their area was measured. In total, 1498 boutons with a mean diameter of 1.63 +/- 0.49 microm (S.D.) were measured. Comparisons with manual counts showed that the proposed method was capable of identifying boutons in a systematic manner at the light microscopic level and was a viable alternative to manual bouton counting.


Perceived HIV Stigma and Associated Factors Among Adult ART Patients in Wolaita Zone, Southern Ethiopia.
This study aimed to assess perceived HIV stigma and associated factors among adult ART patients in Wolaita Zone, Southern Ethiopia. A facility-based cross-sectional study was conducted among 638 participants selected using a multistage sampling technique from July 10 to September 2020. A 12-item short version of the HIV stigma scale was used to measure HIV-related stigma. Data were collected by the interview method using a pre-tested questionnaire. Binary and multivariable logistic regression analyses were performed to identify the factors associated with the outcome variable. The strength and direction of the association were measured using the adjusted odds ratio (AOR) with a 95% confidence interval (CI). Statistical significance was declared at P-value <0.05. In this study, 57.8% (95% CI = 54.1%-61.9%) of people under HIV care perceived high stigma and 450 (70.5%) disclosed their HIV status. Widowed marital status (AOR = 2.984; 95% CI = 1.728-5.155), primary education (AOR = 3.36; 95% CI = 2.072-5.42), undisclosed HIV status (AOR = 1.657; 95% CI = 1.121-2.451), poor social support (AOR: 2.05; 95% CI = 1.195-3.433), and being member of an HIV support group (AOR: 0.396; 95% CI = 0.249-0.630) were significantly associated with perceived stigma. The perceived stigma is high among adult ART patients in the study setting. Widowed marital status, primary education, undisclosed HIV status, membership to the social support network NEP+ and poor social support were predictors of perceived HIV stigma. Thus, ART patients should be given more psychosocial support to minimize their perceived public HIV-related stigma.


Suicidal behavior among people with epilepsy in Northwest Ethiopia: A comparative cross-sectional study.
Premature mortality is common in people with epilepsy, but the causes vary where suicide is considered as one of the commonest. The objective of this study was to compare suicidal behavior between people with epilepsy and the general population and identify associated factors in Northwest Ethiopia. We have conducted a comparative cross-sectional study in Northwest Ethiopia. We have selected people with epilepsy from outpatient departments and the comparisons from the general population. Suicidal behavior was assessed by the revised version of Suicidal Behaviors Questionnaire (SBQ-R). Logistic regression was implemented to look for associations between factors and the dependent variable. The prevalence of suicidal behavior in people with epilepsy was 18.2%, significantly higher than the community sample, which was 9.8% (p-value = .001). This difference persists in the multivariable logistic regression model by which the odds of suicidal behavior in people with epilepsy was two times more as compared to the community sample. Other variables positively associated with suicidal behavior for the overall sample were depressive symptoms, no formal education, divorced/widowed marital status, and higher perceived criticism. Better social support was protective factor for suicidal behavior. The proportion of suicidal behavior is twofold higher in people with epilepsy than the general population. Routine screening for suicide risk should be an integral part of epilepsy treatment.


The Slovak Drug Information (Druginfo) Centre during the period 1997-2004.
The aim of the presented study was to evaluate the profile of users, the number and character of questions which were received during the period May 1997-December 2004. The drug information centre (Druginfo) has been established in Slovak Republic at the Department of Pharmacology in May 1997. Since 2002 Druginfo is a member of International Register of Drug Information Services of the Society of Hospital Pharmacists of Australia. Druginfo provides voluntarily free of charge drug information for healthcare professionals. Druginfo receives questions addressed via phone, fax and e-mail. The questions were replied by consulting pharmacologists on duty. The data for this study were obtained from records which include list the received questions and the basic information about the questioners. The Druginfo received 495 questions during the period May 1997-December 2004. Questions were mostly from hospital physicians, followed by outpatient physicians and employees of the Faculty of Medicine. The most frequent specializations of the asking physicians were internal medicine, gynaecology-obstetrics, clinical pharmacology and general medicine. The most common topic was basic information about drugs, followed by questions concerning the use of drugs in pregnancy and lactation. According to the ATC classification the questions were most often related to antiinfective drugs, cardiovascular drugs and psychiatric drugs. The existence of Druginfo in Slovak Republic represents a possibility of an open access to independent drug information. (Fig. 3, Ref. 11.)


Spinous process morphology: the effect of ageing through adulthood on spinous process size and relationship to sagittal alignment.
Blinded radiographic analysis of CT scans reformatted for precise lumbar spinous process (LSP) measurement. To investigate the effect of ageing on LSP morphology and influence of LSP morphology on lumbar spine sagittal alignment. There is little data reporting the influence of ageing on spinous process size. There is data describing the increase in size of other body parts with age, such as the femur, ears, vertebral body, and nose. Several old cadaveric and radiographic studies have reported the formation of osseous spurs within the supraspinous and interspinous ligaments. 200 abdominal CT scans taken for trauma and vascular investigation were reformatted to allow precise bony measurement of the lumbar spine. Two observers were blinded from the age and demographics of the patients. Sagittal and coronal plane projections were used to measure the height and width of the spinous processes (L1-L5), respectively. The relationship between spinous process size, age, and supine lordosis was investigated. LSP height increases by 0.03-0.07 mm/year (p < 10(-3) to 10(-8)) and width by 0.05-0.06 mm/year (p < 10(-11) to 10(-15)). Lumbar lordosis decreases with increasing LSP height (p < 0.0004) but is not related to increasing LSP width (p = 0.195). Supine lordosis increases by 0.1°/year (p = 0.004). This study demonstrates that the dimensions of the LSP change with age. Increases in LSP height and even more impressive increases in LSP width occur with advancing age. There is an inverse relationship between lumbar lordosis and LSP height.


Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans.
The vanilloid receptor TRPV1 has been identified as a molecular target for the treatment of pain associated with inflammatory diseases and cancer. Hence, TRPV1 antagonists have been considered for therapeutic evaluation in such diseases. During Phase I clinical trials with AMG 517, a highly selective TRPV1 antagonist, we found that TRPV1 blockade elicited marked, but reversible, and generally plasma concentration-dependent hyperthermia. Similar to what was observed in rats, dogs, and monkeys, hyperthermia was attenuated after repeated dosing of AMG 517 (at the highest dose tested) in humans during a second Phase I trial. However, AMG 517 administered after molar extraction (a surgical cause of acute pain) elicited long-lasting hyperthermia with maximal body temperature surpassing 40 degrees C, suggesting that TRPV1 blockade elicits undesirable hyperthermia in susceptible individuals. Mechanisms of AMG 517-induced hyperthermia were then studied in rats. AMG 517 caused hyperthermia by inducing tail skin vasoconstriction and increasing thermogenesis, which suggests that TRPV1 regulates vasomotor tone and metabolic heat production. In conclusion, these results demonstrate that: (a) TRPV1-selective antagonists like AMG 517 cannot be developed for systemic use as stand alone agents for treatment of pain and other diseases, (b) individual susceptibility influences magnitude of hyperthermia observed after TRPV1 blockade, and (c) TRPV1 plays a pivotal role as a molecular regulator for body temperature in humans.


Simple technique for removing broken pedicular screw with plain and serviceable screwdriver.
Removing the broken pedicular screw after spinal hardware failure is usually problematic. A specially designed simple screwdriver and easy removal technique of broken pedicular screw with this screwdriver are described in this article.


Candida amidevorans sp. nov., a new ascomycetous anamorph yeast from soil.
A strain of an undescribed Candida species was isolated from soil. A description of the new species Candida amidevorans is given and its distinction from the most closely resembling species of the genus is discussed.


[Disseminated cysticercosis affecting the brain, the eye and the skin on a Senegalese patient].
Cysticercosis is a neglected tropical disease set as health priority by WHO. Most of the reported cases included isolated types of cysticercosis affecting the skin, the eyes or the brain . Disseminated types, however, are rare. We here report a case of disseminated cysticercosis affecting the brain, the eyes and the skin in a Senegalese female patient aged 66 years admitted with headaches and chronic seizures. Clinical examination showed cerebellar syndrome associated with generalized and painless nodular subcutaneous lesions. Diagnosis was confirmed based on histopathological examination of skin biopsy which showed cysticerci. Patient's outcome was good under albendazole therapy.


Identification of Isonitrile-Containing Natural Products in Complex Biological Matrices through Ligation with Chlorooximes.
Isonitrile-containing natural products have garnered attention for their manifold bioactivities but are difficult to detect and isolate due to the chemical lability of the isonitrile functional group. Here, we used the isonitrile-chlorooxime ligation (INC) in a reactivity-based screening (RBS) protocol for the detection and isolation of alkaloid and terpene isonitriles in the cyanobacterium Fischerella ambigua and a marine sponge of the order Bubarida, respectively. A trifunctional probe bearing a chlorooxime moiety, a UV active aromatic moiety, and a bromine label facilitated the chemoselective reaction with isonitriles, UV-Vis spectroscopic detection, and mass spectrometric analysis. The INC-based RBS allowed for the detection, isolation, and structural elucidation of isonitriles in microgram quantities.