Primary pancreatic glomus tumor invading into the superior mesenteric vein: a case report.
Glomus tumors are subcutaneous tumors arising from glomus bodies, thermoregulatory components of the skin. These tumors could occur in visceral organs where glomus bodies are not normally present. Herein, we report a case of primary pancreatic glomus tumor with aggressive direct invasion into the superior mesenteric vein (SMV). To the best of our knowledge, this is the second case report of a glomus tumor arising in the pancreas. A 46-year-old woman was referred to our hospital due to vomiting with epigastric and back pain. Dynamic-CT revealed a well-circumscribed hypervascular mass, measuring 37 mm in its maximal diameter involving the pancreatic head. Both CT and endoscopic ultrasonography (EUS) revealed direct invasion into the SMV and radiologically suspected tumor thrombus. Biopsy sample obtained by EUS-guided fine needle aspiration revealed proliferation of small cells, round-to-oval tumor cells with round nuclei and scant cytoplasm. A histological diagnosis of pancreatic neuroendocrine tumor, G1 was initially considered. Therefore, subtotal stomach-preserving pancreatoduodenectomy using Child-II reconstruction was subsequently performed. Her SMV was resected and reconstructed due to extensive tumor involvement. Subsequent histopathological analysis revealed solid tumor cells proliferation that comprised oval-shaped nuclei and scant cytoplasm around disorganized or slit-shaped vessels in hematoxylin-eosin-stained slides. Immunohistochemical analysis then demonstrated positive immunoreactivity for smooth muscle actin, vimentin, and CD34, but negative for chromogranin A, synaptophysin, CD56, and signal transducer and activator of transcription 6. Based on these histological findings of resected specimens, the lesion was subsequently diagnosed as a primary pancreatic glomus tumor harboring direct invasion into the SMV. Her postoperative course was uneventful and annual surveys for the following 4 years post-op detected no clinical signs of recurrence. We report a very rare case of glomus tumor of the pancreas accompanied by venous invasion. Curative surgical resection is the best treatment option for pancreatic glomus tumors. Although pancreatic glomus tumor is rare, it should be taken into consideration in the differential diagnosis of a pancreatic solid tumor with hypervascularity.


Agonist-independent activation of acetylcholine receptor channels by protein kinase A phosphorylation.
Protein phosphorylation is a ubiquitous and one of the most effective means of regulating protein activity. Receptor phosphorylation is a key event in signal transduction. The question, therefore, that arises is whether this modulatory mechanism might produce functional changes in a membrane receptor in the absence of its naturally occurring ligand. To examine this issue, single-channel properties of purified acetylcholine receptors (AChRs) from Torpedo californica reconstituted in lipid bilayers were studied in the absence of ACh in both unphosphorylated preparations and after in vitro phosphorylation by a purified catalytic subunit of cyclic AMP-dependent protein kinase (protein kinase A). Notably, the spontaneous open-channel probability of phosphorylated AChRs is significantly higher than that of unphosphorylated AChRs. Channel activation by protein kinase A is correlated with AChR phosphorylation and is abolished by alpha-bungarotoxin. Analysis of probability distributions of the open dwell times indicates that, similar to unphosphorylated AChR has two distinct open states, short- and long-lived. The frequency of occurrence of the long openings over the short and the magnitude of both time constants increase after phosphorylation, as they do with agonist concentration. Thus, phosphorylation of AChR gamma and delta subunits activates AChR channel opening in the absence of ligand binding. This result is compatible with the notion that protein phosphorylation may effectively act as an intracellular ligand with the phosphorylation sites envisioned as cytoplasmic ligand binding sites.


Reactivity and activation of dioxygen-derived species in aprotic media (a model matrix for biomembranes).
In aprotic media the electrochemical reduction of dioxygen yields superoxide ion (O2-), which is an effective Brønsted base, nucleophile, one-electron reductant, and one-electron oxidant of reduced transition metal ions. With electrophilic substrates (organic halides and carbonyl carbons) O2- displaces a leaving group to form a peroxy radical (ROO.) in the primary process. Superoxide ion oxidizes the activated hydrogen atoms of ascorbic acid, catechols, hydrophenazines and hydroflavins. Combination of O2- with 1,2-diphenylhydrazine yields the anion radical of azobenzene, which reacts with O2 to give azobenzene and O2- (an example of O2--induced autoxidation). With phenylhydrazine, O2- produces phenyl radicals. The in situ formation of HO2. (O2- plus a proton source) results in H-atom abstraction from allylic and other groups with weak heteroatom--H bonds (binding energy (b.e.) less than 335 kJ). This is a competitive process with the facile second-order disproportionation of HO2. to H2O2 and O2 (kbi approximately equal to 10(4) mol-1 s-1 in Me2SO). Addition of [FeII(MeCN)4] (ClO4)2 to solutions of hydrogen peroxide in dry acetonitrile catalyses a rapid disproportionation of H2O2 via the initial formation of an adduct [FeII(H2O2)2+----Fe(O)(H2O)2+], which oxidizes a second H2O2 to oxygen. In the presence of organic substrates such as 1,4-cyclohexadiene, 1,2-diphenylhydrazine, catechols and thiols the FeII-H2O2/MeCN system yields dehydrogenated products; with alcohols, aldehydes, methylstyrene, thioethers, sulphoxides, and phosphines, the FeII(H2O2)2+ adduct promotes their monoxygenation. The product from the FeO2+-H2O2 reaction, [FeII(H2O2)22+], exhibits chemistry that is closely similar to that for singlet oxygen (1O2), which has been confirmed by the stoichiometric dioxygenation of diphenylisobenzofuran, 9,10-diphenylanthracene, rubrene and electron-rich unsaturated carbon-carbon bonds (Ph2C = CPh2, PhC = CPh and cis-PhCH = CHPh). In dry ligand-free acetonitrile (MeCN), anhydrous ferric chloride (FeIIICl3) activates hydrogen peroxide for the efficient epoxidation of alkenes. The FeIIICl3 further catalyses the dimerization of the resulting epoxides to dioxanes. These observations indicate that strong Lewis acids that are coordinatively unsaturated, [FeII(MeCN)4]2+ and [FeIIICl3], activate H2O2 to form an effective oxygenation and dehydrogenation agent.(ABSTRACT TRUNCATED AT 400 WORDS)


[Pulmonary lymphangioleiomyomatosis. Morphologic and immunohistochemical findings].
Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease affecting only women which is characterised by cystic parenchymal changes and smooth muscle proliferation and has to be considered in the differential diagnosis of interstitial lung disease. The LAM cell is classified as a so-called perivascular epithelioid cell (PEC) showing immunohistochemical co-expression of smooth muscle and melanocytic markers (melanomyopericyte). A total of 18 cases of LAM and 56 cases of various other pulmonary diseases were analysed by immunohistochemistry. For the diagnosis of LAM in transbronchial or open lung biopsies, immunohistochemistry using the antibody HMB 45 is decisive because it shows a highly specific and sensitive, but often only faint reaction for pulmonary LAM. The immunohistochemical detection of nuclear localised microphthalmia transcription factor (MiTF) in LAM as an additional melanocytic marker further emphasises the melanocytic (as well as smooth muscle) line of differentiation within the cells of LAM. Using the concept of a melanomyopericyte, pulmonary LAM could be classified as a hamartomatous interstitial lung disease showing perivascular smooth muscle and partial melanocytic differentiation.


The influence of HES on the filtration properties of capillary membrane plasmaseparation.
Plasmaseparation is a treatment under discussion for critically ill patients, especially in sepsis and multiorgan failure. These patients receive a variety of different fluid substitutes, including hydroxyethylstarch (HES). HES is known to influence rheological properties, but nothing is known about the possible interactions between HES and the plamaseparation procedure. We used an in vitro plasmaseparation circuit with heparinized porcine blood. Before priming the system, 2 liters of blood were supplemented by adding 100 ml of either NaCl 0.9% or HES (n=6 in each group). We monitored the transmembrane (TMP) and the filtration pressure (PF) and measured free plasma hemoglobin (free Hb) and platelet counts before and after the two hours plasmaseparation procedure. The final transmembrane pressure was significantly higher with HES substitution. In the HES group we found negative filtration pressures from the very beginning with a significant further decrease toward the end of the experiments. A significant increase in free Hb and decrease in platelet counts were noted only in the HES group. Volume substitution with HES leads to impaired filtration properties and deteriorated hemocompatibility in in vitro plasmaseparation. Further studies have yet to evaluate whether or not the effects described also occur under clinical conditions.


Symptom clusters in incident dialysis patients: associations with clinical variables and quality of life.
To date, the pathophysiology underlying symptoms in renal patients is still unclear. Symptom management research suggests that identification of related clusters of symptoms could provide insight into underlying determinants associated with multiple symptom experience. Theoretically, symptoms within a cluster could have a synergistic relationship. We aimed to identify symptom clusters in incident dialysis patients, and investigated associations between symptom clusters, clinical variables, functional status as measured by the Karnofsky Index and quality of life. 1553 haemodialysis (HD) and peritoneal dialysis (PD) patients completed the Kidney Disease Quality of Life Short Form symptom/problem list at 3 months after the start of dialysis. Principal component analysis using varimax rotation was used to identify symptom clusters. Patients were bothered by an average of 2.8 (+/-2.4) symptoms of 'moderate bother' or more. Three clusters were identified, explaining 49% of the total variance. All clusters showed strong negative associations with the SF-36 quality of life dimensions (-0.142 to -0.593) and with functional status (-0.130 to -0.332) in HD and PD patients. In contrast, only the clinical variables serum albumin (-0.084 to -0.232) and haemoglobin (-0.068 to -0.126) were associated with all clusters in HD patients, and Kt/V(urea) (-0.089 to -0.125) in PD patients. Symptom clustering does not explain the lack of meaningful associations between symptoms and clinical variables. Strong associations of symptom clusters with quality of life dimensions suggest that psychological factors could better explain symptom burden. Patients' perceptions of symptoms should be routinely assessed as part of clinical care to improve self-management strategies.


Therapeutic Use of the Elkins Hypnotizability Scale: A Feasibility Study.
Hypnotizability assessment can inform hypnotic interventions, and studies on brief hypnotic inductions suggest that it may also confer therapeutic benefits. However, hypnotizability is rarely assessed in clinical practice due to limitations of current measures. The Elkins Hypnotizability Scale (EHS) improved upon such limitations and has been shown to be a very reliable and valid hypnotizability measure. This is the first study to examine the feasibility of the EHS as a therapeutic measure. Fifty-five participants were administered the EHS and randomized to two weeks of self-hypnosis with or without a recording. Results indicated that relaxation increased immediately after EHS administration, and relaxation and psychological distress improved after two weeks of self-hypnosis with the EHS induction. These results suggest that the EHS may be considered as a therapeutic measure and an avenue to introduce self-hypnosis in clinical practice with or without audio recordings.


Ferroptosis mechanism and Alzheimer's disease.
Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms. This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms. Ferroptosis is a classic regulatory mode of cell death. Extensive studies of regulatory cell death in Alzheimer's disease have yielded increasing evidence that ferroptosis is closely related to the occurrence, development, and prognosis of Alzheimer's disease. This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferroptosis in Alzheimer's disease. Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer's disease.


Predicting Accommodative Response Using Paraxial Schematic Eye Models.
Previous ultrasound biomicroscopy (UBM) studies showed that accommodative optical response (AOR) can be predicted from accommodative biometric changes in a young and a pre-presbyopic population from linear relationships between accommodative optical and biometric changes, with a standard deviation of less than 0.55D. Here, paraxial schematic eyes (SE) were constructed from measured accommodative ocular biometry parameters to see if predictions are improved. Measured ocular biometry (OCT, A-scan, and UBM) parameters from 24 young and 24 pre-presbyopic subjects were used to construct paraxial SEs for each individual subject (individual SEs) for three different lens equivalent refractive index methods. Refraction and AOR calculated from the individual SEs were compared with Grand Seiko (GS) autorefractor measured refraction and AOR. Refraction and AOR were also calculated from individual SEs constructed using the average population accommodative change in UBM measured parameters (average SEs). Schematic eye calculated and GS measured AOR were linearly related (young subjects: slope = 0.77, r = 0.86; pre-presbyopic subjects: slope = 0.64, r = 0.55). The mean difference in AOR (GS - individual SEs) for the young subjects was -0.27D and for the pre-presbyopic subjects was 0.33D. For individual SEs, the mean ± SD of the absolute differences in AOR between the GS and SEs was 0.50 ± 0.39D for the young subjects and 0.50 ± 0.37D for the pre-presbyopic subjects. For average SEs, the mean ± SD of the absolute differences in AOR between the GS and the SEs was 0.77 ± 0.88D for the young subjects and 0.51 ± 0.49D for the pre-presbyopic subjects. Individual paraxial SEs predict AOR, on average, with a standard deviation of 0.50D in young and pre-presbyopic subject populations. Although this prediction is only marginally better than from individual linear regressions, it does consider all the ocular biometric parameters.


The biologic activities of peptidoglycan in experimental Haemophilus influenzae meningitis.
While gram-positive bacterial cell walls are known to incite inflammation, the contribution of gram-negative peptidoglycan to disease has not been characterized. The ability of cell wall, purified peptidoglycan, and soluble peptidoglycan subcomponents from Haemophilus influenzae to provoke inflammation was determined in a rabbit model of meningitis. Haemophilus peptidoglycan, with or without associated proteins, produced brain edema at > or = 0.1 micrograms/mL of cerebrospinal fluid (CSF); leukocytosis and protein accumulation in CSF occurred only at > or = 10.0 micrograms/mL of CSF. Solubilized peptidoglycan was 10-fold more active than intact cell wall. The bioactivity of peptidoglycan from ampicillin-resistant H. influenzae was at least twofold greater than that of ampicillin-sensitive strains. Consistent with these pathologic effects of purified peptidoglycan, ampicillin-induced bacterial lysates in which endotoxin was neutralized induced brain edema and protein influx but little leukocytosis. Thus, peptidoglycan seems to contribute to the pathology of gram-negative meningitis, particularly brain edema.


Failure of flunarizine to improve cerebral blood flow or neurologic recovery in a canine model of complete cerebral ischemia.
Ten minutes of cerebral ischemia was produced in 12 dogs by temporary ligation of the venae cavae and aorta. After reperfusion the dogs received the calcium entry blocker, flunarizine, 6 micrograms/kg infused over a ten minute period. Cerebral blood flow (CBF) and metabolism (CMRO2) were measured pre-ischemia and for 2 h post-ischemia in 6 dogs. At the end of the study brain biopsies were analyzed for cerebral metabolites. Neurologic recovery was evaluated for up to 48 h post-ischemia in an additional 6 dogs. The results of each study were compared to those previously obtained in untreated animals. The cerebral blood flows (when expressed as a percent of the pre-ischemic control value) of the flunarizine-treated and untreated groups were similar throughout the post-ischemic period. Following an initial hyperemia, the CBF fell to significantly less than the pre-ischemic control values, and remained approximately 26% of control during the final 90 min in both groups. The CMRO2 was also the same for both groups. Cerebral metabolites were similar although abnormal in both groups. Flunarizine produced pulmonary edema in 5 of 6 dogs studied for neurologic recovery. Four of these dogs died within 12 h and another dog demonstrated severe neurologic damage. None of the untreated dogs developed pulmonary edema, but 6 of 7 dogs evidenced severe neurologic damage or were dead at 48 h. Thus, flunarizine failed to improve either cerebral blood flow or neurologic outcome when given after complete cerebral ischemia in the dog. A cardiodepressive effect of flunarizine might have contributed to the poor neurologic outcome.(ABSTRACT TRUNCATED AT 250 WORDS)


Gender-Related Differences in BMP Expression and Adult Hippocampal Neurogenesis within Joint-Hippocampal Axis in a Rat Model of Rheumatoid Arthritis.
BMPs regulate synovial quiescence and adult neurogenesis in the hippocampus in non-stress conditions. However, changes in BMP expression that are induced by inflammation during rheumatoid arthritis (RA) have not yet been reported. Here, we show that signalling with synovial BMPs (BMP-4 and -7) mediates the effect of systemic inflammation on adult neurogenesis in the hippocampus during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Moreover, we show gender differences in BMP expressions and their antagonists (Noggin and Gremlin) during PIA and their correlations with the clinical course and IL-17A and TNF-α levels in serum. Our results indicate gender differences in the clinical course, where male rats showed earlier onset and earlier recovery but a worse clinical course in the first two phases of the disease (onset and peak), which correlates with the initial increase of serum IL-17A level. The clinical course of the female rats worsened in remission. Their prolonged symptoms could be a reflection of an increased TNF-α level in serum during remission. Synovial inflammation was greater in females in PIA-remission with greater synovial BMP and antagonist expressions. More significant correlations between serum cytokines (IL-17A and TNF-α), and synovial BMPs and their antagonists were found in females than in males. On the other hand, males showed an increase in hippocampal BMP-4 expression during the acute phase, but both genders showed a decrease in antagonist expressions during PIA in general. Both genders showed a decrease in the number of Ki-67+ and SOX-2+ and DCX+ cells and in the ratio of DCX+ to Ki67+ cells in the dentate gyrus during PIA. However, in PIA remission, females showed a faster increase in the number of Ki67+, SOX-2+, and DCX+ cells and a faster increase in the DCX/Ki67 ratio than males. Both genders showed an increase of hippocampal BMP-7 expression during remission, although males constantly showed greater BMP-7 expression at all time points. Our data show that gender differences exist in the BMP expressions in the periphery-hippocampus axis and in the IL-17A and TNF-α levels in serum, which could imply differences in the mechanisms for the onset and progression of the disease, the clinical course severity, and adult neurogenesis with subsequent neurological complications between genders.


The Influence of Plants from the Alliaceae Family on Morphological Parameters of the Intestine in Atherogenic Rats.
Bulbs from the Alliaceae family have been well-known and valued spices for thousands of years, not only for their unique flavor and aroma features, but also for their high nutritional and health-promoting values. Long-term or excessive consumption of these vegetables, especially raw garlic, can have side effects in the body (including in the digestive tract), causing a number of pathological changes in the intestinal wall; these changes lead, in turn, to its damage, dysfunction, and disorder development. Therefore, the aim of this study was to investigate the effect of the addition of freeze-dried vegetables from the Alliaceae family, i.e., garlic (Allium sativum L.), white onion, and red onion (Allium cepa L.) on the morphometric parameters (intestinal villi length, crypt depth, thickness of tunica mucosa, and the thickness of tunica muscle) of the jejunum of rats fed a semi-synthetic atherogenic diet (1% dietary cholesterol). In freeze-dried vegetables administered to rats, the contents of selected bioactive ingredients and their antioxidant potentials were determined. The effect of the onion vegetable supplements on growth parameters, serum lipid profile, plasma antioxidant potential, and the intestinal morphological parameters of rats loaded with cholesterol was determined. In an animal experiment, 30 male Wistar rats were divided into 5 diet groups, diet consumption and FER were studied. Supplementation of the atherogenic diet with vegetables improved the blood plasma lipid profiles and atherogenic indices, in a manner that was dependent on the type of supplementation used, with the best hypolipidemic and anti-atherosclerotic effects found in garlic use. The atherogenic diet, as well as the supplementation of this diet with the tested vegetables from the Alliaceae family, influenced the histological changes in the epithelium of the jejunum of rats. The damage to the intestinal mucosa was the greatest in animals fed an atherogenic diet supplemented with garlic. Bearing in mind that the desired beneficial therapeutic or prophylactic effects of onion vegetables (in particular garlic) in the course of various metabolic ailments (including atherosclerosis) are achieved during long-term supplementation, it is important to remember their possible cytotoxic effects (e.g., on the digestive tract) in order to achieve real benefits related to the supplementation with vegetables from the Alliaceae family.


Phenotypic Characterization of Polycystic Ovary Syndrome in Adolescents Based on Menstrual Irregularity.
Polycystic ovary syndrome (PCOS) in adolescents is associated with adverse metabolic outcomes. The association of menstrual irregularity with metabolic risk among adolescents with PCOS was assessed. A retrospective medical record review of 366 adolescents with PCOS aged 13-18 years was conducted, from which 265 girls newly diagnosed with PCOS were included and divided into those presenting with primary amenorrhea (PA), secondary amenorrhea (SA) and oligomenorrhea (OM). Androgen concentrations and markers of metabolic risk were compared among the groups. Most subjects presented with OM (PA = 17, SA = 30 and OM = 218). Subjects with PA were younger than those with OM but not different from those with SA. Mean BMI was not different between groups. Total testosterone and insulin levels were higher in PA than SA and OM (p < 0.01 and 0.02, respectively). Fasting glucose was higher in PA than OM (p = 0.048) but not different from SA. Triglyceride levels were higher in PA than SA and OM (p < 0.001 each). More subjects with PA and SA had metabolic syndrome (52%) than those with OM (29.1%) (p = 0.027). The differences in triglycerides and glucose persisted despite BMI adjustment in multivariate regression models. Adolescents with PCOS presenting with PA are at risk of metabolic disease beyond expected based on BMI.


Evaluation of the reactive oxygen metabolite levels in plasma, gingival crevicular fluid, and saliva in generalized chronic periodontitis patients before and after nonsurgical periodontal therapy: A case-control and interventional study.
Reactive oxygen metabolites (ROMs) produced in periodontitis could contribute to excessive tissue damage. Thus, treatment of chronic periodontitis may decrease the ROM levels. The aim of this study is to evaluate the ROM levels in plasma, saliva, and gingival crevicular fluid (GCF) in generalized chronic periodontitis (GCP) patients before and after nonsurgical periodontal treatment. Two groups were included in this study. Group I consisted of 30 healthy controls (C) and Group II consisted of 30 subjects with GCP. Plaque index (PI), papillary bleeding index, Probing Depth (PD), and clinical attachment level were recorded. GCF, saliva, and plasma samples were collected from both groups. ROM levels were assessed. A baseline comparison was made between the two groups. Nonsurgical periodontal treatment was carried out for Group II subjects. Two months posttreatment, the clinical parameters and ROM levels in GCF, saliva, and plasma were reassessed in Group II, and the data were compared with their baseline values. Statistical analysis was done using SPSS 20 software and results were derived. Two months posttreatment, Group II exhibited significant reduction in ROM levels in plasma, saliva, and GCF with significant decrease in PI, bleeding on probing, probing depth, and attachment loss. Thus, significant oxidative stress may occur in chronic periodontitis and nonsurgical periodontal therapy may be regarded as an effective treatment modality to treat the diseased periodontium, thereby preventing possible systemic diseases in future.


Prior approval in the pediatric emergency room.
Managed-care plans for low-income Americans are widely promoted to improve the quality and control the cost of medical care by reducing unnecessary specialty and emergency room (ER) care through the use of primary care physicians as case managers/gatekeepers. The purpose of this study was to evaluate one element of managed care, gatekeeping prior approval, for children who use the pediatric ER of one urban public hospital. Over a 6-month period, 518 children and adolescents insured under managed-care plans that required authorization from the primary care physician to receive treatment presented to the ER. Of the 385 records reviewed for this study, the majority (87%) received their primary care at community health centers or the hospital's own outpatient clinics. Most ER visits (72%) were made when primary care sites were closed. According to nursing triage assessment, 57% presented with urgent or emergent conditions, and 26% had a history of chronic illness. Nine percent required hospitalization. Although an elaborate system for gatekeeping was established, only 13 (3%) patients' requests for ER care were denied. Of these, 3 were seen in the ER without authorization, 6 received the recommended follow-up, and 4 were not seen in follow-up. Twenty-nine participating primary care physicians (74%) and 19 ER staff (63%) responded to a survey of their experience with and attitudes toward prior approval. For a variety of reasons, the majority of primary care physicians and ER staff found the gatekeeping policies for after-hours visits burdensome and inappropriate.(ABSTRACT TRUNCATED AT 250 WORDS)


[Urticating hairs of "brown-tail" moth (Euproctis chrysorrhoea L.) (Lepidoptera): preliminary studies in urban and laboratory].
Urticating hairs of the brown-tail moth (Euproctis chrysorrhoea L.) are detectable in the air using apparatus designed for the collection of airborne microorganisms and pollen research studies. The hairs are produced by caterpillars and are distributed by air currents or via moths. They were collected in Bordeaux. In the laboratory a nycthemeral cycle of hair emission is observed and is correlated with the biological activities of these species.


Protoporphyrin IX Content Correlates with Activity of Photobleaching Herbicides.
Several laboratories have demonstrated recently that photobleaching herbicides such as acifluorfen and oxadiazon cause accumulation of protoporphyrin IX (PPIX), a photodynamic pigment capable of herbicidal activity. We investigated, in acifluorfen-treated tissues, the in vivo stability of PPIX, the kinetics of accumulation, and the correlation between concentration of PPIX and herbicidal damage. During a 20 hour dark period, PPIX levels rose from barely detectable concentrations to 1 to 2 nanomoles per 50 cucumber (Cucumis sativus L.) cotyledon discs treated with 10 micromolar acifluorfen. When placed in 500 micromoles per square meter per second PAR, PPIX levels decayed logarithmically, with an initial half-life of about 2.5 hours. PPIX levels at each time after exposure to light correlated positively with the cellular damage that occurred during the following 1 hour in both green and yellow (tentoxin-treated) cucumber cotyledon tissues. PPIX levels in discs incubated for 20 hours in darkness correlated positively with the acifluorfen concentration in which they were incubated. In cucumber, the level of herbicidal damage caused by several p-nitrodiphenyl other herbicides, a p-chlorodiphenylether herbicide, and oxadiazon correlated positively with the amount of PPIX induced to accumulate by each of the herbicide treatments. Similar results were obtained with acifluorfen-treated pigweed and velvetleaf primary leaf tissues. In cucumber, PPIX levels increased within 15 and 30 minutes after exposure of discs to 10 micromolar acifluorfen in the dark and light, respectively. These data strengthen the view that PPIX is responsible for all or a major part of the photobleaching activity of acifluorfen and related herbicides.


[Economic evaluation of drugs. Effectiveness in diabetes therapy].
The article explains the systematic manner of applying important basic principles to economic aspects within the health system and also makes transparent the basic principles of cost minimization. In health economics the concern is not cost minimization but optimization of the relationship between cost and medical effectiveness. It is important to realize that health economic evaluation has to take into account not only pure acquisition costs of a drug but also the costs connected with its being prescribed.


Sex-dependent differences in stress-induced depression in Wistar rats are accompanied predominantly by changes in phosphatidylcholines and sphingomyelins.
With a high annual and lifetime prevalence, depression is becoming the leading contributor to the global disease burden. During the COVID-19 crisis, the depression and mood disorders accelerated significantly. Despite the growing evidence, the precise underlying mechanisms of depression disorders (DD) remain unknown. When studying DD in humans, there are many uncontrollable factors such as medication history, age of the patient or living conditions. In this regard, animal models provide an essential step for examining neural circuitry or molecular and cellular pathways in a controlled environment. As far as we know, women have a consistently higher prevalence of DD than men. Thus, the aim of our study was to evaluate sex-related changes in blood metabolites in a model of stress-induced depression in Wistar rats. Pregnant females were stressed using restriction of mobility in the final week of the pregnancy three times a day for 45 minutes each, three following days. After the birth, the progeny aged 60 days was stressed repeatedly. The perturbation in overall energy metabolism as well as in lipid metabolism was found. While in males, phosphatidylcholines (the most phosphatidylcholine with acyl-alkyl residue sum C40:4 - PC ae C40:4), sphingomyelins, and acylcarnitines were changed, in females, lipid metabolism perturbation was seen with the most critical alteration in hydroxysphingomyelin with acyl residue sum C16:1 (SM OH C16:1). Our results confirm that the animal model may be used further in the research of depression. Our results may provide an essential insight into the sex-dependent pathogenesis of depression and contribute to the search for effective treatment and prevention of depression with respect to sex.


Subretinal surgery for choroidal neovascularization in patients with high myopia.
To analyze the visual outcome in patients undergoing surgical removal of subfoveal choroidal neovascularization (CNV) in eyes with high myopia. We retrospectively reviewed the medical records of 48 consecutive patients with high myopia (> or =6 diopters [D]) who underwent vitrectomy with surgical removal of subfoveal CNV. The patient population consisted of 2 groups. Group 1 included 23 patients with findings only of myopic degeneration, and group 2 included 25 patients with presumed ocular histoplasmosis syndrome and myopia of 6 D or more. In group 1, the visual acuity improved by 2 or more Snellen lines in 9 eyes (39%), decreased in 8 eyes (35%), and remained unchanged in 6 (26%), with a mean follow-up of 24 months (range, 8-60 months). The preoperative visual acuity was 20/40 or better in only 1 eye (4%), but 8 (35%) achieved a final visual acuity of 20/40 or better. In group 2, the visual acuity improved in 16 eyes (64%), was stable in 4 (16%), and deteriorated in 5 (20%), with a mean follow-up of 18 months (range, 6-44 months). Only 3 eyes (12%) had a preoperative visual acuity of 20/40 or better, but 11 (44%) achieved a final visual acuity of 20/40 or better. Recurrence occurred in 13 (57%) of the 23 eyes in group 1 and in 9 (36%) of the 25 eyes in group 2. Univariate analysis demonstrated a significant relation between younger patient age (group 1) and absence of postoperative CNV recurrence (group 2) and an improvement of visual acuity (P<.01). Surgical removal of CNV may provide visual benefit in selected cases of subfoveal CNV associated with high myopia. The determination of whether surgical intervention is appropriate in these cases requires a prospective, randomized, clinical trial.


Metal-Ion-Responsive Bionanocomposite for Selective and Reversible Enzyme Inhibition.
A bionanocomposite with artificial binding pockets for a DNA repair enzyme has been developed by in situ assembly of an affinity protein with a surrounding contact surface of polydopamine on the surface of silica coated magnetic nanoparticles via molecular imprinting reactions. The obtained nanoparticles exhibited antibody-like binding behavior toward the target enzyme with highly specific and efficient inhibition effect. Moreover, the binding and inhibition could be flexibly tuned by the addition of metal ions such as Mn2+ and Mg2+, which provided a convenient tool to regulate enzyme activity with artificially engineered nanoinhibitors.


Relationship Between Cognitive Functions and Multilevel Language Processing: Data From Chinese Speakers With Aphasia and Implications.
This study aims to investigate the relationship between nonverbal cognitive functions and language processing of people with aphasia (PWA) by taking a data-driven approach, as well as multiple cognitive components and multilevel linguistic perspectives. It is hypothesized that language performance is differentially associated with cognitive processing of PWA, with executive functions (EFs) playing a stronger role in language tasks with increasing linguistic complexity. A language battery assessing word comprehension/production, sentence comprehension, and discourse production, together with a series of nonlinguistic cognitive tasks targeting simple/complex attention, short-term/working memory, or EFs, was administered to 53 Cantonese-speaking PWA. Cognitive factors extracted from principal component analysis applied to the cognitive battery served as predictors in four multiple regression analyses to predict PWA's performance at various linguistic levels. Two cognitive factors, representing (a) simple attention and memory and (b) EF, were extracted. The former predicted performance in word processing tasks, whereas EF significantly predicted performance in all language tasks with increasing contribution as a function of linguistic complexity. The results based on Chinese PWA provide comprehensive evidence for the view that language performance is the end product of interaction between linguistic and nonlinguistic functions and have clear implications for clinical management of PWA.


Alterations in tumor development in vivo mediated by expression of wild type or mutant p53 proteins.
To study the mechanism of p53 involvement in malignant transformation, we compared the tumor development patterns induced by a parental p53 nonproducer pre-B cell line with those by cell lines generated from this parental cell line following transfection of either wild type or mutant p53. It was found that whereas mutant p53 facilitated tumor development, expression of wild type p53 restrained tumor development. Cell lines expressing the wild type p53 induced the development of faster regressing tumors than the parental cell line. The parental p53 nonproducer and the wild type p53 producer regressor tumors underwent in vivo cell differentiation, manifested as IgG production. Mutant p53, producer cell lines, on the other hand, failed to show any immunoglobulin synthesis and gave rise to highly proliferative lethal tumors. Our results support the conclusion that these pre-B cells develop regressor tumors because they have undergone differentiation. Whereas the wild type p53 facilitates this differentiation, mutant p53 cells block it. We suggest that, in addition to inactivating the growth-suppressive activity of wild type p53, the expression of mutant p53 facilitates malignant transformation.


Intra- and post-dialytic platelet activation and PDGF-AB release: cellulose diacetate vs polysulfone membranes.
During haemodialysis the blood-membrane contact causes a release of platelet granule content, which contains platelet-derived growth factor AB (PDGF-AB). In view of the potential role of this in altering biocompatibility during haemodialysis, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during haemodialysis sessions performed with cellulose diacetate (CDA) and polysulfone (PS) membranes respectively. PDGF-AB, platelet factor 4 (PF4), beta thromboglobulin (betaTG), and mean platelet volume (MPV) levels were determined in 30 patients, each of whom underwent six dialysis sessions: three with a CDA and three with a PS membrane. Blood samples were taken at times 0, 15, 30, 120, 180, and 240 min during dialysis and at 1, 4, and 20 h after the end of the session. Statistical analysis was performed using a one-way ANOVA and Student's t test. PDGF-AB at 15 min was increased to +41+/-9% with CDA vs +20+/-5% with PS (P<0.001) from the T0 values, and at 120 min it was +19+/-8% with CDA vs -25+/-9% with PS (P<0.001) from T0 levels. At 240 min it was +95+/-14% with CDA vs +49+/-15% with PS (P<0.001) from the T0 values, returning to basal only 20 h after the end of the session. betaTG at 15 min was +60+/-8% for CDA vs +24+/-7.5% for PS (P<0.001) from the T0 values. PF4 showed a similar trend to betaTG. MPV at 30 min from the start of dialysis was 7.4+/-0.3 fl with CDA and 8+/-0.3 fl with PS (P<0.001), and at 240 min MPV was 7.9+/-0.3 fl with CDA and 8.4+/-0.3 fl with PS (P<0.001). Platelet activation and platelet release reactions are lower with PS than with CDA membranes. PDGF-AB, released during and after dialysis, represents a clear biocompatibility marker. Its slow return to basal values and its action on vascular cells make it a potential risk factor for atherosclerosis in uraemic patients.


Prognostic Value of Ankle-Brachial Index in Prediction of Cardiovascular Events in an Asian Population with Multiple Atherosclerotic Risk Factors.
We aimed to evaluate the incremental prognostic value after incorporation of the ankle-brachial index (ABI) into the 10-year pool cohort equation (PCE) risk model in patients with multiple risk factors (MRFs). A total of 4332 MRFs patients were divided into 2 groups as ABI ≤.9 or >.9. The primary outcome was hard cardiovascular events (hCVE: including cardiovascular death, myocardial infarction, or ischemic stroke) over a median follow-up of 36 months. The Cox proportional hazards survival model, C-statistic, and net reclassification indices (NRI) were used. The occurrence of the primary outcome in the ABI ≤.9 group (3.7%) was significantly greater than in the ABI > .9 group (1.3%), P < .001. ABI is an independent predictor of hCVE in addition to the variables in the standard risk model (age, gender, and smoking status). ABI modestly improved the C-index when added to the PCE risk model (PCE .70 vs ABI+PCE .74). The addition of ABI to the PCE risk model did not significantly improve the classification of patients (NRI -.029; 95% CI: -.215 to .130). Despite ABI being one of the independent predictors of hCVE, integration of ABI into the PCE model did not improve the efficacy of risk reclassification in patients with MRFs.


High-risk Allele for Herpes Labialis Severity at the IFNL3/4 Locus is Associated With Vestibular Neuritis.
Objective: Vestibular neuritis (VN) is a peripheral vestibular disorder leading to a sudden loss of unilateral vestibular function. Although the underlying etiological mechanisms for disease development are not yet known, there is evidence that a latent infection with herpes simplex virus type 1 (HSV-1) might be involved. The polymorphism rs12979860 has been associated with the severity of recurrent herpes labialis and hepatitis C virus (HCV) clearance and treatment outcome and is located within the first intron of the IFNL4 gene on chromosome 19.q13.2. This case control study was conducted to evaluate the association of rs12979860 with VN occurrence. Methods: DNA was extracted from EDTA blood of 151 VN patients and 1,775 healthy controls. Genotyping of rs12979860 was performed using iPLEX and MassARRAY Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) mass spectrometry. For association analyses, an additive, dominant and recessive logistic regression model was calculated, using age and sex as covariates. Results: A significant association of rs12979860 with VN was obtained for the additive [OR = 1.51 (1.18-1.92); p = 9.23 × 10-4] and dominant models [OR = 2.15 (1.48-3.13); p = 5.86 × 10-5], with the T allele being more frequent in the VN group. Conclusion: By detecting a significant association of the rs12979860-T risk allele for herpes labialis severity with susceptibility to VN, this study gives further indirect evidence for an involvement of HSV-1 in VN pathology, thereby strengthening the virus hypothesis.


Assessment of alternative tissue approximation techniques for laparoscopy.
To investigate the feasibility and results of applying alternative techniques of tissue approximation for experimental urothelial re-anastomosis in an open and laparoscopic setting. The study was carried out in two phases; in phase 1, an open porcine ureteric re-anastomosis was performed using gelatin/resorcin/ formaldehyde (GRF) glue, fibrin glue or potassiumtitanyl-phosphate laser tissue-welding with a fluorescein-doped human albumin solder. The anastomoses were assessed both immediately, by leak pressure, and by the operating time, upper tract urodynamic studies and light and scanning electron microscopy, 6 weeks after surgery. In phase 2 the best technique from phase 1 was compared with sutured controls for porcine retroperitoneoscopic dismembered pyeloplasty, using the same assessment criteria. In phase 1, GRF glue produced adhesion which was insufficiently flexible to withstand rotation of the anastomosis and this technique was therefore abandoned. Fibrin-glued anastomoses withstood leak pressures equal to those from laser-welding (P = 0.91) and gave similar changes in maximum pressure with a Whitaker test at 6 weeks (P = 0.30), but were superior in requiring a shorter operating time (P = 0.02) and in their electron and light microscopic appearances. In phase 2, fibrin glue gave similar changes in maximum pressure with a Whitaker test to those from polyglactin 910 sutures (P = 0.51) but withstood higher leak pressures (P = 0.01), had a shorter operating time (P = 0.01) and had superior electron and light microscopic appearances. Fibrin glue produced effective experimental laparoscopic pelvi-ureteric anastomoses within less operating time than did sutured controls. Such anastomoses withstood supra-physiological pressures, with no evidence of functional obstruction and with a more favourable histological result after 6 weeks. Laparoscopic evaluation of this modality in a clinical setting is now justified.


A multi-electrode array and inversion technique for retrieving six conductivities from heart potential measurements.
A method for accurately finding cardiac bidomain conductivity parameters is a crucial part of efforts to study and understand the electrical functioning of the heart. The bidomain model considers current flowing along (longitudinal) and across (transverse) sheets of cardiac fibres, as well as between these sheets (normal), in both the extracellular and intracellular domains, which leads to six conductivity values. To match experimental studies, such a method must be able to determine these six conductivity values, not just the four where it is assumed that the transverse and normal conductivities are equal. This study presents a mathematical model, solution technique, multi-electrode array and two-pass inversion method, which can be used to retrieve all six conductivities from measurements of electrical potential made on the array. Simulated measurements of potential, to which noise is added, are used to demonstrate the ability of the method to retrieve the conductivity values. It is found that not only is it possible to accurately retrieve all six conductivity values, as well as a value for fibre rotation angle, but that the accuracy of such retrievals is comparable to the accuracy found in a previous study when only four conductivities (and fibre rotation) were retrieved.


Selective antitumor effect on L10 hepatocarcinoma cells of a potent immunoconjugate composed of the A chain of abrin and a monoclonal antibody to a hepatoma-associated antigen.
The toxic A chain of abrin was isolated by affinity chromatography and was demonstrated to be a potent inhibitor of protein synthesis in a cell-free rabbit reticulocyte system with a complete inhibitory dose at 1 X 10(-9) M. This A chain was coupled by a disulfide linkage to a purified monoclonal antibody directed against a tumor-associated antigen found on the line 10 hepatocarcinoma tumor in strain two guinea pigs. The immunoconjugate retained the functions of the individual components, i.e., antigen binding to the intact cell in vitro and inhibition of its protein synthesis. This conjugate was a selective antineoplastic agent with a cytocidal dose at 5 X 10(-9) M toward antigen-bearing cells in vitro. Several antigen-negative cells were much less susceptible to its cytotoxic effect. The cytotoxicity of the conjugate appeared to be by antibody-mediated delivery of toxic A chain into the target cell. When cells were pretreated with excess free antibody followed by a brief exposure to conjugate, there was a reversal of the cytotoxicity to antigen-positive cells but not to the antigen-negative cells. The therapeutic efficacy of the conjugate was assayed by injecting a single dose s.c. or i.v. into syngeneic guinea pigs bearing established line 10 tumors. These in vivo studies showed that (a) the conjugate was not toxic at a dosage of 60 to 1120 micrograms/guinea pig, (b) the conjugate decreased or abolished the growth of established solid tumors, (c) the conjugate delayed or inhibited tumor metastases to lymph nodes, and (d) 20 to 40% of the animals in selective groups had a long-term complete regression.


Intracranial lymphatic drainage discharges iron from the ventricles and reduce the occurrence of chronic hydrocephalus after intraventricular hemorrhage in rats.
Background: The discovery of intracranial lymphatic system provides a new theory about cerebrospinal fluid circulation. In order to investigate the role of lymphatic drainage in hydrocephalus after intraventricular hemorrhage (IVH), three parts of experiments were performed.Methods: IVH model was produced by 200ul autologous blood injection into lateral ventricle of SD male rats. Perls Prussian blue reaction was used to confirm the ability of iron drainage through deep cervical lymph nodes (DCLNs) in part I. The part II measured the volume of ventricles by MR scanner , and the part III compared the ferritin level of area surrounding ventricles by Western blotting after IVH.Results: The ability of iron drainage through DCLNs was confirmed. DCLNs-excised rats got a 19.6% higher incidence of hydrocephalus than DCLNs-preserved rats at day 28 after IVH. And DCLNs-excised group showed higher ferritin level than DCLNs-preserved group at day 3 after IVH.Conclusion: The whole experiments revealed the role of intracranial lymphatic system in discharging iron out of central nervous system at acute phase of IVH, and proved the function in alleviating and avoiding hydrocephalus at chronic phase after IVH.


[A surgically treated case of ventrally exophytic pontine glioma].
A surgically treated case of ventrally exophytic pontine glioma is reported. A 49-year-old woman, complaining of dysarthria, dysphagia and gait disturbance, was admitted to our department. Her past history included bronchial asthma. Plain skull x-p and tomography revealed destruction of the dorsum sellae and upper clivus. CT demonstrated an enhanced oval mass at the ventral side of the upper brainstem. The mass was severely compressing the brainstem dorsally. MRI revealed a low-intensity band between the tumor and the brainstem. Dynamic MRI demonstrated a pattern of rapid increasing and slow reduction. Cerebral angiogram demonstrated a paradoxical sign that pontine branches were located anterior to the basilar artery. The finding demonstrated that the tumor was an intraaxial mass. The first operation was performed by the orbitofrontomalar approach. On the trans-sylvian route, the tumor was removed partially with CUSA and neuronavigation system. Its histology was astrocytoma grade III. Radiation therapy was added. The patient's symptoms aggravated again. On the second operation, the transtemporal route with tentorial resection was chosen. Under a wide visual field, intracapsular subtotal resection of the tumor was performed. Interferon therapy was added. She was discharged to her home with no neurological deficits. Ventrally exophytic pontine glioma is very rare. Low-intensity band of MRI, a sign of extraaxial mass, was visualised in our case. On the other hand, cerebral angiogram demonstrated a paradoxical sign. This sign suggested that the tumor originated from the brainstem. With update skull base surgery and neuronavigation system, surgical therapy of ventrally exophytic pontine glioma is safe and effective.


Experts: cut costs of ED observation.
Keeping an observation unit operating with current reimbursement might depend on successful implementation of cost-reduction strategies. A "hybrid" model with scheduled-procedure patients in addition to observation patients allows you to staff with fewer nurses per patient. Observe patients with only one specific acute problem who are likely to be discharged within 18 hours. By offering stress testing in close proximity to the observation unit, length of stay is reduced, and the hospital can provide stress testing to inpatients on weekends.


Mitochondrial respiratory chain dysfunction in dorsal root ganglia of streptozotocin-induced diabetic rats and its correction by insulin treatment.
Impairments in mitochondrial physiology may play a role in diabetic sensory neuropathy. We tested the hypothesis that mitochondrial dysfunction in sensory neurons is due to abnormal mitochondrial respiratory function. Rates of oxygen consumption were measured in mitochondria from dorsal root ganglia (DRG) of 12- to- 22-week streptozotocin (STZ)-induced diabetic rats, diabetic rats treated with insulin, and age-matched controls. Activities and expression of components of mitochondrial complexes and reactive oxygen species (ROS) were analyzed. Rates of coupled respiration with pyruvate + malate (P + M) and with ascorbate + TMPD (Asc + TMPD) in DRG were unchanged after 12 weeks of diabetes. By 22 weeks of diabetes, respiration with P + M was significantly decreased by 31-44% and with Asc + TMPD by 29-39% compared with control. Attenuated mitochondrial respiratory activity of STZ-diabetic rats was significantly improved by insulin that did not correct other indices of diabetes. Activities of mitochondrial complexes I and IV and the Krebs cycle enzyme, citrate synthase, were decreased in mitochondria from DRG of 22-week STZ-diabetic rats compared with control. ROS levels in perikarya of DRG neurons were not altered by diabetes, but ROS generation from mitochondria treated with antimycin A was diminished compared with control. Reduced mitochondrial respiratory function was associated with downregulation of expression of mitochondrial proteins. Mitochondrial dysfunction in sensory neurons from type 1 diabetic rats is associated with impaired rates of respiratory activity and occurs without a significant rise in perikaryal ROS.


Antibacterial activity of traditional therapeutic coastal medicinal plants against some pathogens.
Antimicrobial activity of 10 traditional coastal medicinal plant species from South west coast of India were tested against 12 human bacterial pathogens and two cattle pathogens. Among the plant species tested, a butanolic extract of Bacopa monnieri showed maximum inhibitory activity against the human pathogen Escherichia coli, whereas the butanolic extract of Aristolochia indica. L showed maximum inhibitory activity against the cattle pathogen Listeria monocytogen. The mean zone of inhibition indicates that the growth of Salmonella enteritidis and Pseudomonas aeruginosa were highly inhibited by the coastal medicinal plant extract than the other bacterial species and also the antibacterial activity was found higher in the butanolic extract than water extract.


The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis.
The transcriptional programs that regulate blood vessel formation are largely unknown. In this paper, we examine the role of the zinc finger transcription factor LKLF in murine blood vessel morphogenesis and homeostasis. By in situ hybridization and immunohistochemistry, we show that LKLF is expressed as early as embryonic day 9.5 (E9.5) in vascular endothelial cells throughout the developing mouse embryo. To better understand the function of LKLF, we used homologous recombination in embryonic stem (ES) cells to generate LKLF-deficient (LKLF-/-) mice. Both angiogenesis and vasculogenesis were normal in the LKLF-/- mice. However, LKLF-/- embryos died between E12.5 and E14.5 from severe intra-embryonic and intra-amniotic hemorrhaging. This bleeding disorder was associated with specific defects in blood vessel morphology. Umbilical veins and arteries in the LKLF-/- embryos displayed an abnormally thin tunica media and aneurysmal dilatation before rupturing into the amniotic cavity. Similarly, vascular smooth muscle cells in the aortae from the LKLF-/- animals displayed a cuboidal morphology and failed to organize into a compact tunica media. Consistent with these findings, electron microscopic analyses demonstrated endothelial cell necrosis, significant reductions in the number of vessel-wall pericytes and differentiating smooth muscle cells, and decreased deposition of extracellular matrix in the LKLF-/- vessels. Despite these defects, in situ hybridization demonstrated normal expression of platelet-derived growth factor B, Tie1, Tie2, transforming growth factor beta, and heparin-binding epidermal growth factor in the vasculature of the LKLF-/- embryos. Therefore, LKLF defines a novel transcriptional pathway in which endothelial cells regulate the assembly of the vascular tunica media and concomitant vessel wall stabilization during mammalian embryogenesis.


Surpassing the current limitations of high purity H2 production in microbial electrolysis cell (MECs): Strategies for inhibiting growth of methanogens.
Microbial electrolysis cells (MECs) are perceived as a potential and promising innovative biotechnological tool that can convert carbon-rich waste biomass or wastewater into hydrogen (H2) or other value-added chemicals. Undesired methane (CH4) producing H2 sinks, including methanogens, is a serious challenge faced by MECs to achieve high-rate H2 production. Methanogens can consume H2 to produce CH4 in MECs, which has led to a drop of H2 production efficiency, H2 production rate (HPR) and also a low percentage of H2 in the produced biogas. Organized inference related to the interactions of microbes and potential processes has assisted in understanding approaches and concepts for inhibiting the growth of methanogens and profitable scale up design. Thus, here in we review the current developments and also the improvements constituted for the reduction of microbial H2 losses to methanogens. Firstly, the greatest challenge in achieving practical applications of MECs; undesirable microorganisms (methanogens) growth and various studied techniques for eliminating and reducing methanogens activities in MECs were discussed. Additionally, this extensive review also considers prospects for stimulating future research that could help to achieve more information and would provide the focus and path towards MECs as well as their possibilities for simultaneously generating H2 and waste remediation.


Increased carotid artery intima-media thickness and myeloperoxidase level in children with newly diagnosed juvenile idiopathic arthritis.
Juvenile idiopathic arthritis (JIA) is a frequent childhood rheumatic disease characterized by chronic inflammation. The latter has been related to impairment of arterial functional-structural properties, atherogenesis and later cardiovascular events. The objective of this study was to examine intima-media thickness (IMT) and the parameters of arterial stiffness in children with JIA at diagnosis and their correlation with JIA subtype and markers of inflammation and atherosclerosis. Thirty-nine newly diagnosed patients with JIA (26 girls; mean age, 13.2 ± 2.6 years) and 27 healthy controls (9 girls; mean age, 13.6 ± 3.4 years) were included in the study. Twelve patients had oligoarthritis, fifteen had extended oligoarthritis and twelve had rheumatoid factor-negative polyarthritis. IMT of the common carotid artery was determined by ultrasonography, carotid-femoral pulse wave velocity (cfPWV) and augmentation index adjusted to a heart rate of 75 beats/min (AIx@75) were determined by applanation tonometry. The serum levels of atherosclerosis-related biomarkers, such as asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and adiponectin, were measured by enzyme-linked immunosorbent assay. Mean IMT (0.46 ± 0.04 vs. 0.42 ± 0.04 mm; p = 0.0003) and MPO concentration (115.2 [95% confidence interval {95% CI}, 97.4-136.3] vs. 57.6 [95% CI, 47.1-70.3] ng/ml; p < 0.0001) were higher in the patients with JIA than in the control subjects. The cfPWV, AIx@75 and serum ADMA and adiponectin levels did not significantly differ between the groups and JIA subtypes. Serum adiponectin level correlated negatively with AIx@75 in patients with JIA (r = -0.38; p < 0.05). Patients with JIA have increased mean IMT and elevated MPO levels at early stages of the disease. AIx@75 was inversely independently associated with adiponectin level in the patients, suggesting that lower adiponectin levels might influence arterial subclinical stiffening in patients with newly diagnosed JIA.


Congenital hyperinsulinism: intraoperative biopsy interpretation can direct the extent of pancreatectomy.
Most cases of congenital hyperinsulinism (HI) manifest as either a diffuse or focal form. Diffuse HI is characterized by the presence of enlarged islet cell nuclei, defined as those occupying an area 3 times larger than the surrounding nuclei, throughout the pancreas, and usually requires near total pancreatectomy. Focal HI contains, within an otherwise normal pancreas with islet cell nuclei of normal size, a focus of adenomatous hyperplasia characterized by endocrine cell overgrowth occupying more than 40% of a given area. This form of HI is amenable to partial pancreatectomy. The current study assesses whether intraoperative frozen section evaluation can distinguish the 2 forms and guide the extent of pancreatectomy. By frozen section analysis, diffuse HI is diagnosed when enlarged islet cell nuclei are present in random intraoperative biopsies from the head, body, and tail of the pancreas. Focal HI is suggested when random biopsies contain no large islet cell nuclei, prompting a further search for a focal lesion. Fifty-two HI patients who underwent pancreatectomy from October 1, 1998 to September 30, 2002 were reviewed. On permanent sections, 18 were classified as diffuse HI, 30 had focal HI, and 4 could not be categorized as either. Among 18 diffuse HI patients, 17 were correctly diagnosed by frozen section; all underwent near total pancreatectomy. One case was interpreted as not belonging to typical diffuse or focal HI; however, the permanent sections showed diffuse HI. Twenty-six of 30 focal HI cases were correctly diagnosed by frozen section. The remaining 4 focal HI cases posed diagnostic difficulties on frozen sections because of one the following reasons: 1) presence of equivocally large islet cell nuclei or rare truly large islet cell nuclei in areas nonadjacent to the focal lesion, and 2) large and/or ill defined focus of adenomatous hyperplasia. Twenty-one of 30 focal HI patients eventually had 10% to 93% (mean, 41.8%) of their pancreas resected. In addition to cases typical for diffuse and focal HI, there were 4 other cases whose pancreata did not fit well with either category. These pancreata showed islet cell nuclear enlargement, as characteristically seen in diffuse HI, but only in confined areas of the pancreas. Examination of routinely processed tissue confirmed frozen section findings in all 4 cases. Intraoperative frozen section evaluation, therefore, can assume an essential role in identifying patients with focal HI to limit the extent of pancreatectomy. However, a small number of cases with unusual histology warrant caution when performing frozen section evaluation.


Expression of polysialic acid in primary laryngeal squamous cell carcinoma.
Expression of polySia is associated with metastatic dissemination and progression of various malignant diseases. In particular, it may contribute to tumorigenesis by a negative modulatory effect on cellular signaling cascades responsible for cellular migration, differentiation and proliferation. In this study, we investigated the expression of polySia in primary metastatic and non-metastatic laryngeal squamous cell carcinoma (LSCC) tumor tissues and its potential impact on the LSCC progression. The expression of polySia in metastatic and non-metastatic primary laryngeal squamous cell carcinoma (LSCC) tumor biopsy specimens was investigated by immunohistochemistry, while the expression of polysialyltransferase IV (ST8SiaIV)(), fibroblast growth factor receptor 1 (FGFR1), extracellular signal regulated kinases 1 and 2 (Erk 1/2) and c-Raf was tested in metastatic and non-metastatic primary tumor tissues (including the corresponding non-tumor control tissues) by Western blot analysis. The expression of polySia was detected in LSCC biopsies specimens with generally stronger immunoreactivity in non-metastatic tumor LSCC sections and in histologically undifferentiated tumors. Also, increased polySia expression was observed in adjacent histologically unaltered laryngeal tumor-associated tissue of the metastatic sections. In addition, we provide an evidence of increased polysialyltransferase IV (ST8SiaIV) expression, involved in polySia synthesis in both metastatic and non-metastatic primary tumors which is accompanied by decreased levels of FGFR1, Erk 1/2 and c-Raf. We present for the first time the evidence for the polySia expression in LSCC biopsies specimens which suggests its potential impact on initial steps of LSCC malignant transformation.


Selective right parietal lobe activation during mental rotation: a parametric PET study.
Regional cerebral blood flow (rCBF) was measured with PET in seven healthy subjects while they carried out a mental rotation task in which they decided whether alphanumeric characters presented in different orientations were in their canonical form or mirror-reversed. Consistent with previous findings, subjects took proportionally longer to respond as characters were rotated further from the upright, indicating that they were mentally rotating the characters to the upright position before making a decision. We used a parametric design in which we varied the mental rotation demands in an incremental fashion while keeping all other aspects of the task constant. In four different scanning conditions, 10, 40, 70 or 100% of the stimuli presented during the scan required mental rotation while the rest were upright. The statistical parametric mapping technique was used to identify areas where changes in rCBF were correlated with the rotational demands of the task. Significant activation was found in only one area located in the right posterior parietal lobe, centred on the intraparietal sulcus (Brodmann area 7). The experimental literature on monkeys and humans suggests that this area is involved in a variety of spatial transformations. Our results contribute evidence that such transformations are recruited during mental rotation and add to a body of evidence which suggests that the right posterior parietal lobe is important for carrying out visuospatial transformations.


Alteration of Bacterial Wilt Resistance in Tomato Plant by Microbiota Transplant.
Plant-associated microbiota plays an important role in plant disease resistance. Bacterial wilt resistance of tomato is a function of the quantitative trait of tomato plants; however, the mechanism underlying quantitative resistance is unexplored. In this study, we hypothesized that rhizosphere microbiota affects the resistance of tomato plants against soil-borne bacterial wilt caused by Ralstonia solanacearum. This hypothesis was tested using a tomato cultivar grown in a defined soil with various microbiota transplants. The bacterial wilt-resistant Hawaii 7996 tomato cultivar exhibited marked suppression and induction of disease severity after treatment with upland soil-derived and forest soil-derived microbiotas, respectively, whereas the transplants did not affect the disease severity in the susceptible tomato cultivar Moneymaker. The differential resistance of Hawaii 7996 to bacterial wilt was abolished by diluted or heat-killed microbiota transplantation. Microbial community analysis revealed the transplant-specific distinct community structure in the tomato rhizosphere and the significant enrichment of specific microbial operational taxonomic units (OTUs) in the rhizosphere of the upland soil microbiota-treated Hawaii 7996. These results suggest that the specific transplanted microbiota alters the bacterial wilt resistance in the resistant cultivar potentially through a priority effect.


The antibacterial effect of aquatic and methanolic extract of Myrtus communis on Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia.
Anaerobic Gram negative bacteria are the main cause of periodontal destruction. It has been shown that Myrtus communis have anti-bacterial activity on Gram positive and Gram negative bacteria. The aim of this study was to determine the antibacterial effect of aquatic and methanolic extract of Myrtus communis on some of the oral Gram-negative bacteria. The antibacterial effect of aquatic and methanolic extracts of Myrtus communis was determined using disk diffusion method at different concentrations from 10 to 500 mg/ml. The diameter of inhibition zones were determined. The MIC was defined using the standard broth macrodilution method. The results of the study were reported descriptively. The aquatic extract of Myrtus communis from 20 to 500 mg/ml had antibacterial effect on Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia. The methanolic extract from 10 to 500 mg/ml had antibacterial effect on A. actinomycetemcomitans, P. gingivalis and P. intermediate. The MIC was achieved at 10 mg/ml, 10 mg/ml and 10 mg/ml for aquatic and methanolic extracts of Myrtus communis on A. Actinomycetemcomitans, P. Gingivalis and P. Intermediate, respectively. Aquatic and methanolic extracts of Myrtus communis had antibacterial effect on P. gingivalis, A. actinomycetemcomitans and P. intermediate. Most concentrations of aqueous extract were effective on bacteria, so, providing an alcoholic extract, that is a time consuming and costly method, does not seem necessary.


Collagenase 3 is a target of Cbfa1, a transcription factor of the runt gene family involved in bone formation.
Collagenase 3 (MMP-13) is a recently identified member of the matrix metalloproteinase (MMP) gene family that is expressed at high levels in diverse human carcinomas and in articular cartilage from arthritic patients. In addition to its expression in pathological conditions, collagenase 3 has been detected in osteoblasts and hypertrophic chondrocytes during fetal ossification. In this work, we have evaluated the possibility that Cbfa1 (core binding factor 1), a transcription factor playing a major role in the expression of osteoblastic specific genes, is involved in the expression of collagenase 3 during bone formation. We have functionally characterized a Cbfa motif present in the promoter region of collagenase 3 gene and demonstrated, by cotransfection experiments and gel mobility shift assays, that this element is involved in the inducibility of the collagenase 3 promoter by Cbfa1 in osteoblastic and chondrocytic cells. Furthermore, overexpression of Cbfa1 in osteoblastic cells unable to produce collagenase 3 leads to the expression of this gene after stimulation with transforming growth factor beta. Finally, we show that mutant mice deficient in Cbfa1, lacking mature osteoblasts but containing hypertrophic chondrocytes which are also a major source of collagenase 3, do not express this protease during fetal development. These results provide in vivo evidence that collagenase 3 is a target of the transcriptional activator Cbfa1 in these cells. On the basis of these transcriptional regulation studies, together with the potent proteolytic activity of collagenase 3 on diverse collagenous and noncollagenous bone and cartilage components, we proposed that this enzyme may play a key role in the process of bone formation and remodeling.


Positron emission tomography in three children with pleomorphic xanthoastrocytoma.
The pleomorphic xanthoastrocytoma is generally considered a low-grade neoplasm with favorable prognosis. These tumors, however, can demonstrate primary anaplastic features, undergo malignant transformation, disseminate, or progress with poor outcome. Currently, there are no histologic or clinical features that reliably predict recurrent tumor or tumor progression. We report three children with confirmed pleomorphic xanthoastrocytoma who were studied with positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) coregistered with magnetic resonance imaging. One patient had decreased FDG metabolism and, despite a gross total resection and benign pathology, had early local recurrence. Subsequent to a second surgical resection and radiation therapy, he has remained stable for 8 years. One patient with significant FDG uptake had gross total resection of an anaplastic pleomorphic xanthoastrocytoma. Follow-up FDG studies showed no abnormal metabolic activity, and he has been stable without adjuvant treatment for 5 years. The last patient had intermediate FDG uptake and a moderate-grade pleomorphic xanthoastrocytoma by histopathology. She showed early tumor progression with spinal metastases. Following a near-total resection of the recurrent intracranial lesion and neuroaxis radiation, she has been stable for 4 years. Although there are still no reliable prognostic indicators for pleomorphic xanthoastrocytoma, PET with FDG correlates with histopathology, and increased uptake may be a marker for more malignant or aggressive tumors. The extent of surgical resection in regard to prognosis in our limited study is unclear but appears helpful in the anaplastic pleomorphic xanthoastrocytoma case. Adjuvant radiation therapy also may benefit certain patients. Further PET studies are warranted in this group of tumors.


Comparison of Acid Titration, Conductivity, Flame Photometry, ICP-MS, and Accelerated Lamellae Formation Techniques in Determining Glass Vial Quality.
Certain types of glass vials used as primary containers for liquid formulations of biopharmaceutical drug products have been observed with delamination that produced small glass like flakes termed lamellae under certain conditions during storage. The cause of this delamination is in part related to the glass surface defects, which renders the vials susceptible to flaking, and lamellae are formed during the high-temperature melting and annealing used for vial fabrication and shaping. The current European Pharmacopoeia method to assess glass vial quality utilizes acid titration of vial extract pools to determine hydrolytic resistance or alkalinity. Four alternative techniques with improved throughput, convenience, and/or comprehension were examined by subjecting seven lots of vials to analysis by all techniques. The first three new techniques of conductivity, flame photometry, and inductively coupled plasma mass spectrometry measured the same sample pools as acid titration. All three showed good correlation with alkalinity: conductivity (R(2) = 0.9951), flame photometry sodium (R(2) = 0.9895), and several elements by inductively coupled plasma mass spectrometry [(sodium (R(2) = 0.9869), boron (R(2) = 0.9796), silicon (R(2) = 0.9426), total (R(2) = 0.9639)]. The fourth technique processed the vials under conditions that promote delamination, termed accelerated lamellae formation, and then inspected those vials visually for lamellae. The visual inspection results without the lot with different processing condition correlated well with alkalinity (R(2) = 0.9474). Due to vial processing differences affecting alkalinity measurements and delamination propensity differently, the ratio of silicon and sodium measurements from inductively coupled plasma mass spectrometry was the most informative technique to assess overall vial quality and vial propensity for lamellae formation. The other techniques of conductivity, flame photometry, and accelerated lamellae formation condition may still be suitable for routine screening of vial lots produced under consistent processes. Recently, delamination that produced small glass like flakes termed lamellae has been observed in glass vials that are commonly used as primary containers for pharmaceutical drug products under certain conditions during storage. The main cause of these lamellae was the quality of the glass itself related to the manufacturing process. Current European Pharmacopoeia method to assess glass vial quality utilizes acid titration of vial extract pools to determine hydrolytic resistance or alkalinity. As alternative to the European Pharmacopoeia method, four other techniques were assessed. Three new techniques of conductivity, flame photometry, and inductively coupled plasma mass spectrometry measured the vial extract pool as acid titration to quantify quality, and they demonstrated good correlation with original alkalinity. The fourth technique processed the vials under conditions that promote delamination, termed accelerated lamellae formation, and the vials were then inspected visually for lamellae. The accelerated lamellae formation technique also showed good correlation with alkalinity. Of the new four techniques, inductively coupled plasma mass spectrometry was the most informative technique to assess overall vial quality even with differences in processing between vial lots. Other three techniques were still suitable for routine screening of vial lots produced under consistent processes.


Interstitial deletion of chromosome 2 (p23p25).
We report a patient with a de novo interstitial deletion of the short arm of chromosome 2 (p23p25). The patient had microcephaly with prominent forehead and occiput, narrow rectangular face, clinodactyly, failure to thrive, delayed psychomotor development, and seizures. Maternal serum alpha-fetoprotein was undetectable at 18 weeks of gestation. Heterozygosity at the red cell acid phosphatase locus (SRO-2p25) and normal levels of red cell malate dehydrogenase (SRO-2p23) are findings consistent with the presence of genetic material from bands 2p25 and 2p23.


Electrical dysfunctions in human-induced pluripotent stem cell-derived cardiomyocytes from a patient with an arrhythmogenic right ventricular cardiomyopathy.
Our aim is to investigate the arrhythmogenic mechanism in arrhythmogenic right ventricular cardiomyopathy (ARVC)-patients by using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Human-induced pluripotent stem cell-derived cardiomyocytes were generated from human skin fibroblasts of two healthy donors and an ARVC-patient with a desmoglein-2 (DSG2) mutation. Patch clamp, quantitative polymerase chain reaction, and calcium imaging techniques were employed for the study. The amplitude and maximal upstroke velocity (Vmax) of action potential (AP) in ARVC-cells were smaller than that in healthy donor cells, whereas the resting potential and AP duration (APD) was not changed. The reduced Vmax resulted from decreased peak sodium current. The reason for undetected changes in APD may be the counter-action of reduced transient outward, small conductance Ca2+-activated, adenosine triphosphate-sensitive, Na/Ca exchanger (INCX) currents, and enhanced rapidly delayed rectifier currents. Isoprenaline (Iso) reduced INCX and shortened APD in both donor and ARVC-hiPSC-CMs. However, the effects of Iso in ARVC-cells are significantly larger than that in donor cells. In addition, ARVC-hiPSC-CMs showed more frequently than donor cells arrhythmogenic events induced by adrenergic stimulation. Cardiomyocytes derived from the ARVC patient with a DSG2 mutation displayed multiple ion channel dysfunctions and abnormal cellular electrophysiology as well as enhanced sensitivity to adrenergic stimulation. These may underlie the arrhythmogenesis in ARVC patients.


Dental resins used in 3D printing technologies release ovo-toxic leachates.
We recently engineered the first female reproductive tract on a chip (EVATAR), to enable sex-based ex vivo research. To increase the scalability and accessibility of EVATAR, we turned to 3D printing (3DP) technologies, selecting two biocompatible 3DP resins, Dental SG (DSG) and Dental LT (DLT) to generate 3DP microphysiologic platforms. Due to the known sensitivity of reproductive cells to leachable compounds, we first screened for toxicity of these biomaterials using an in vitro mammalian oocyte maturation assay. Culture of mouse oocytes in 3DP plates using conventionally treated DSG resin resulted in rapid oocyte degeneration. Oxygen plasma treatment of the surface of printed DSG resin prevented this degeneration, and the majority of the resulting oocytes progressed through meiosis in vitro. However, 57.0% ± 37.2% of the cells cultured in the DSG resin plates exhibited abnormal chromosome morphology compared to 19.4% ± 17.3% of controls cultured in polystyrene. All tested DLT resin conditions, including plasma treatment, resulted in complete and rapid oocyte degeneration. To identify the ovo-toxic component of DLT, we analyzed DLT leachate using mass spectroscopy. We identified Tinuvin 292, a commercial light stabilizer, as a major component of the DLT leachate, which resulted in a dose-dependent disruption of meiotic progression and increase in chromosomal abnormalities with oocyte exposure, showing significant ovo-toxicity in mammals. Severe reproductive toxicity induced by in vitro exposure to these 3D-printed resins highlights potential risks of deploying insufficiently characterized materials for biomedical applications and underscores the need for more rigorous evaluation and designation of biocompatible materials.


Catalytic intermolecular haloamidation of simple alkenes with N-halophthalimide as both nitrogen and halogen source.
A simple, efficient, and highly atom economic haloamidation of simple alkenes has been developed, using AgBF4 or InBr3/AgBF4 (1:3) as catalyst and N-halophthalimide as both nitrogen and halogen source. A broad range of olefins can be applied to afford vicinal haloamines in good yields and with high regioselectivity and diastereoselectivity.


Twelve tips for institutional approach to outcome-based education in health professions programmes.
Outcome-based education (OBE) has brought along a significant development in health professions education in the past decade. The shift from a process-driven to product-driven model of education is valuable for ensuring graduate quality and facilitating global movement of healthcare workers. Such a model can align the expectations of key stakeholders in an era of rapid knowledge expansion and technological advancement. Nevertheless, the experienced benefits of OBE depend on the effectiveness of its implementation. This article therefore provides practical tips and strategies for implementing OBE in order to maximize its potential.


The common myelolymphoid progenitor: a key intermediate stage in hemopoiesis generating T and B cells.
We have previously shown that the common progenitors for myeloid, T, and B cell lineages are enriched in the earliest population of murine fetal liver. However, it remained unclear whether such multipotent progenitors represent the pluripotent progenitors capable of generating all hemopoietic cells or they also comprise progenitors restricted to myeloid, T, and B cell lineages. To address this issue, we have developed a new clonal assay covering myeloid, erythroid, T, and B cell lineages, and using this assay the developmental potential of individual cells in subpopulations of lineage marker-negative (Lin(-)) c-kit(+) murine fetal liver cells was investigated. We identified the progenitor generating myeloid, T, and B cells, but not erythroid cells in the Sca-1(high) subpopulation of Lin(-)c-kit(+) cells that can thus be designated as the common myelolymphoid progenitor (CMLP). Common myeloerythroid progenitors were also detected. These findings strongly suggest that the first branching point in fetal hemopoiesis is between the CMLP and common myeloerythroid progenitors. T and B cell progenitors may be derived from the CMLP through the previously identified myeloid/T and myeloid/B bipotent stages, respectively.


Androgen deprivation therapy and the risk of parkinsonism in men with prostate cancer.
Case reports and anecdotal experiences suggest that some men develop parkinsonism after initiating androgen deprivation therapy (ADT) for the treatment of prostate cancer, possibly due to neurophysiological effects of changes in testosterone and/or estrogen. We hypothesized that ADT would increase the risk of parkinsonism. Using linked administrative databases in Ontario, Canada, men age 40 or older with prostate cancer on continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 38,931) were matched 1:1 with men with prostate cancer who had never received ADT. Treated and untreated groups were range-matched on age at index date and year of diagnosis, and propensity-matched on comorbidities, medications, cardiovascular risk factors, and socio-economic variables. A competing risk analysis was conducted where the primary outcome was time to a new diagnosis of parkinsonism. The cohort was followed for a mean of 5.76 years. Based on the results from the multivariable cause-specific hazard regression model, the adjusted relative rate of experiencing parkinsonism among ADT users compared to non-users was 0.74 (95% confidence interval (CI) 0.67-0.83, p < 0.0001). The adjusted relative rate of experiencing the competing event of death among ADT users compared to non-users was 1.33 (95% CI 1.30-1.36, p < 0.0001). The 5-year incidence of parkinsonism was 1.03% in ADT users versus 1.56% in non-users. Contrary to our hypothesis, continuous ADT use for at least 6 months in men with prostate cancer was not associated with an increased risk of parkinsonism after accounting for the substantial competing risk of death.


How frequently are words used on naming tests used in spoken conversation?
Naming, or word-finding ability, is typically assessed using measures that require a patient to name a pictured object. Words used less frequently tend to be more difficult to find when speaking; thus word frequency can be used as a measure of item difficulty on such tests. However, frequency data for words on naming measures has either not been used in the creation of these tests or has been derived from data on how frequently words have been used in written materials. The present study determined how frequently words on the Boston Naming Test (BNT), the Neuropsychological Assessment Battery (NAB) naming subtest, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) naming subtest, and auditory naming measures developed by Hamberger and Seidel (2003, Journal of the International Neuropsychological Society, 9, 479) and Brandt et al. (2010, The Clinical Neuropsychologist, 24, 1326) are used in spoken language. Items on the auditory naming measures had the highest mean frequency, and the BNT items 30-60 had the lowest mean frequency. Furthermore, item frequency on the full BNT, NAB naming forms 1 and 2, and RBANS forms A correlated with item number, indicating items increase in difficulty on these tests, with trends in the same direction found for RBANS form B and Hamberger and Seidel's auditory naming measure. Finally, differences in mean word frequency between tests underscore how interpretation of change in naming ability based on different measures should be made with caution.


Selection of S18326 as a new potent and selective boronic acid direct thrombin inhibitor.
Using enzymatic microassays, the potency of a series of new boroarginine tripeptides was determined versus thrombin and a panel of serine-proteases implicated in the coagulation and fibrinolysis pathways. The inhibition of the serine-protease complement factor I was also studied. Factor I regulates the alternate pathway of the complement and its inhibition appears to be responsible for the toxic effects of the orally available thrombin inhibitor Ac-D-Phe-Pro-boroArg (DuP-714). The structure of the new boronic acid derivatives tested was modified from that of DuP-714 by replacing the proline in the P2 position by N-cycloalkyl-glycine residues of increasing size (S18989: cyclopropyl; S18563: cyclobutyl; S18326: cyclopentyl; S18229: cyclohexyl). All compounds were found to be slow-tight binding inhibitors of thrombin versus purified human fibrinogen. Replacement of proline by N-cycloalkyl-glycines did not decrease the anti-thrombin potency of the substances up to the cyclopentyl size and this result was confirmed by classical coagulation assays with human plasma in vitro. In contrast, the inhibitory activities of the four new boronic acids were found to be lower than those of DuP-714 versus plasmin, urokinase (u-PA), plasmatic kallikrein, activated protein C (aPC) and complement factor I. The cyclopentyl derivative S18326 is a slightly more active inhibitor of thrombin than DuP-714 (initial IC50 values 3.99 +/- 0.18 nM versus 4.73 +/- 0.27 nM, respectively). Moreover S18326 was identified as the most selective compound of the series with relative potencies being 2 to 29 fold higher than that of DuP-714 versus the panel of serine-proteases tested; the rank order of potency versus the other serine-proteases for S18326 was t-PA>kallikrein>aPC>factor I>plasmin>fXa>u-PA. These results indicate that the size of the thrombin hydrophobic pocket S2 is sufficient to accept larger residues than proline in the P2 position of Ac-D-Phe-X-boroArg derivatives while this is not the case for other important serine-proteases of the fibrinolysis, coagulation and complement pathways. The N-cyclopentyl glycine containing derivative S 18326, which is the most potent and the most selective anti-thrombin compound of the series, currently undergoes major preclinical testing.


Ontogeny of behaviour in intact and beak trimmed layer pullets, with special reference to preening.
1. The effects of commercial beak trimming on layer pullet behaviour were investigated, with special reference to preening. 2. One-d-old chicks, 96 in all, were housed in 12 litter floor pens, with 8 birds in each, to 20 weeks of age. Approximately one quarter of the beak was trimmed in all birds in half of the pens (BT) at 8 d of age using a hot blade debeaker. The birds in the other pens remained intact (NBT). 3. There was no significant effect of beak trimming on body weight at any age. At the end of the study, upper mandible lengths were shorter in BT birds. 4. Beak trimming had very little effect on behaviour. NBT birds showed more litter-directed behaviour than did BT birds, and BT birds spent more time in preening directed at the preen gland, and at the back while sitting. 5. Feather damage was minimal and there was no difference in mean feather damage scores between treatments at any age. 6. The young age and small amount of beak removed during beak trimming may be at least partly responsible for the lack of effects of beak treatment on behaviour and plumage condition.


SARS-CoV-2 antibody kinetics in blood donors with a previously positive SARS-CoV-2 antibody test within a seroprevalence survey.
The persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is a matter of importance regarding the coronavirus disease 19 (COVID-19) pandemic. To observe antibody dynamics, 105 blood donors, positive for SARS-CoV-2 antibodies by a lateral flow test within a seroprevalence study, were included in this study. Thirty-nine (37%) of 105 the donors were confirmed positive by a total Ig Wantai enzyme-linked immunosorbent assay (ELISA). Three (8%) in this group of 39 reported severe and 26/39 (67%) mild to moderate COVID-19 symptoms. By further ELISA-testing, 33/39 (85%) donors were initially positive for IgG antibodies, 31/39 (79%) for IgA, and 32/39 (82%) for IgM, while 27/39 (69%) were positive for all three isotypes. Persistence of IgG, IgA, and IgM was observed in 73%, 79%, and 32% of donors, respectively, after 6-9 months of observation. For IgM antibodies, the decline in the proportion of positive donors was statistically significant (p = 0.002) during 12 months observation, for IgG only the decline at 3 months was statistically significant (p = 0.042). Four donors exhibited notable increases in antibody levels. In conclusion, persistent SARS-CoV-2 IgA antibodies and IgG antibodies at 6-9 months are present in approximately three of four individuals with previous mild to moderate COVID-19.


Detection of biofilm-forming strains of Staphylococcus epidermidis and S. aureus.
The formation of biofilm represents an important virulence factor of certain strains of Staphylococcus epidermidis and S. aureus. The ability of bacteria to aggregate, forming biofilms, is strictly related to the capacity of producing an extracellular mucoid substance often referred to as slime, whose main component is of polysaccharidic nature and consists of glycosaminoglycans. In recent years, new molecular techniques based on PCR have come alongside more traditional methods for identification of virulent biofilm-forming strains. The detection of the genes governing the production of such extracellular polysaccharide and, in particular, the icaA, the icaC and the icaD genes, provides us with a rapid and accurate technique for strain characterization. However, well-established methods, such as the Congo red agar test are still needed in order to confirm the phenotypic expression in the case of possible phase-variant strains. In future, the complete knowledge of the genetic mechanisms of phenotype modulation, comprehending all regulatory genes, could permit the characterization of the isolates just by molecular means in a single step.


Environmental signaling: what embryos and evolution teach us about endocrine disrupting chemicals.
The term "endocrine disrupting chemicals" is commonly used to describe environmental agents that alter the endocrine system. Laboratories working in this emerging field-environmental endocrine research-have looked at chemicals that mimic or block endogenous vertebrate steroid hormones by interacting with the hormone's receptor. Environmental chemicals known to do this do so most often with receptors derived from the steroid/thyroid/retinoid gene family. They include ubiquitous and persistent organochlorines, as well as plasticizers, pharmaceuticals, and natural hormones. These chemicals function as estrogens, antiestrogens, and antiandrogens but have few, if any, structural similarities. Therefore, receptor-based or functional assays have the best chance of detecting putative biological activity of environmental chemicals. Three nuclear estrogen receptor forms-alpha, beta, and gamma-as well as multiple membrane forms and a possible mitochondrial form have been reported, suggesting a previously unknown diversity of signaling pathways available to estrogenic chemicals. Examples of environmental or ambient estrogenization occur in laboratory experiments, zoo animals, domestic animals, wildlife, and humans. Environmentally estrogenized phenotypes may differ depending upon the time of exposure-i.e., whether the exposure occurred at a developmental (organizational and irreversible) or postdevelopmental (activational and reversible) stage. The term "estrogen" must be defined in each case, since steroidal estrogens differ among themselves and from synthetic or plant-derived chemicals. An "estrogen-like function" seems to be an evolutionarily ancient signal that has been retained in a number of chemicals, some of which are vertebrate hormones. Signaling, required for symbiosis between plants and bacteria, may be viewed, therefore, as an early example of hormone cross-talk. Developmental feminization at the structural or functional level is an emerging theme in species exposed, during embryonic or fetal life, to estrogenic compounds. Human experience as well as studies in experimental animals with the potent estrogen diethylstilbestrol provide informative models. Advances in the molecular genetics of sex differentiation in vertebrates facilitate mechanistic understanding. Experiments addressing the concept of gene imprinting or induction of epigenetic memory by estrogen or other hormones suggest a link to persistent, heritable phenotypic changes seen after developmental estrogenization, independent of mutagenesis. Environmental endocrine science provides a new context in which to examine the informational content of ecosystem-wide communication networks. As common features come to light, this research may allow us to predict environmentally induced alterations in internal signaling systems of vertebrates and some invertebrates and eventually to explicate environmental contributions to human reproductive and developmental health.


Three-dimensional demarcation of perfusion zones corresponding to specific coronary arteries: application for automated interpretation of myocardial SPECT.
In this study, three-dimensional maps of specific coronary artery territories were derived and combined with normal distribution maps as a reference for automated characterization of defects, including location and size. One hundred sixty-eight 99mTc-sestamibi myocardial perfusion SPECT scans from normal patients and patients with single-vessel disease were selected according to angiographic data. Five separate groups were established for men and women: normal, proximal left anterior descending (PLAD), distal left anterior descending (DLAD), right coronary artery (RCA) and left circumflex (LCx). All myocardial perfusion studies were aligned and sized to the same three-dimensional orientation using a previously developed automated image registration technique. Mean and variation three-dimensional templates were constructed from stress images in each group. Normal templates were demarcated with hypoperfusion regions obtained from disease templates. The defects were detected in the individual patient's images by a region-growing algorithm which identified abnormal voxels by comparison to the corresponding voxels in the mean and variation templates. Defects were quantified with respect to volume, location relative to the expected hypoperfusion zones and severity index. Abnormal regions could be marked directly on tomographic slices and visualized in various orientations. Single defects greater than 2% of the myocardium positioned within demarcated perfusion territories were detected in 105/119 abnormal patients and in 3/49 normal patients. Maps of myocardial perfusion zones created from images of angiographically selected patients provide a reference for automated localization of myocardial perfusion defects. A template-based region-growing is a robust technique for volumetric quantification and localization of abnormal regions.