Controls on coral-ground development along the northern Mesoamerican Reef tract.
Coral-grounds are reef communities that colonize rocky substratum but do not form framework or three-dimensional reef structures. To investigate why, we used video transects and underwater photography to determine the composition, structure and status of a coral-ground community located on the edge of a rocky terrace in front of a tourist park, Xcaret, in the northern Mesoamerican Reef tract, Mexico. The community has a relatively low coral, gorgonian and sponge cover (<10%) and high algal cover (>40%). We recorded 23 species of Scleractinia, 14 species of Gorgonacea and 30 species of Porifera. The coral community is diverse but lacks large coral colonies, being dominated instead by small, sediment-tolerant, and brooding species. In these small colonies, the abundance of potentially lethal interactions and partial mortality is high but decreases when colonies are larger than 40 cm. Such characteristics are consistent with an environment control whereby storm waves periodically remove larger colonies and elevate sediment flux. The community only survives these storm conditions due to its slope-break location, which ensures lack of burial and continued local recruitment. A comparison with similar coral-ground communities in adjacent areas suggests that the narrow width of the rock terrace hinders sediment stabilization, thereby ensuring that communities cannot escape bottom effects and develop into three-dimensional reef structures on geological time scales.


Exogenous nitric oxide upregulates p21(waf1/cip1) in pulmonary microvascular smooth muscle cells.
The histopathology of chronic pulmonary hypertension includes microvascular proliferation and neointimal formation. Nitric oxide (NO) has been implicated in the regulation of these mechanisms, but how NO controls microvascular proliferation and its effect on pulmonary microvascular cells is still unclear. In this study, we characterized the in vitro effects of NO on rat pulmonary microvascular smooth muscle cell (PMVSMC) proliferation and investigated the contribution of the p42/44 mitogen-activated protein kinase (MAPK) pathway and p21(waf1/cip1) induction to this response. NO donors inhibited PMVSMC proliferation in a dose-dependent manner. In the presence of hypoxia, the degree of inhibition was significantly enhanced. This inhibition was reversible and independent of apoptosis. The soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) had no impact on proliferation rates, suggesting a cyclic guanosine monophosphate-independent process. Administration of MEK1/2 inhibitors failed to abrogate the antimitotic effect of NO. There was a two- fold induction of the cyclin-dependent kinase inhibitor p21 in PMVSMC treated with NO donors. Under hypoxic conditions, NO caused a three-fold increase in p21 levels. These results demonstrate that NO inhibits PMVSMC proliferation and that this inhibition is not the result of p42/44 MAPK activation. The ability of NO to induce p21 upregulation may be a mechanism by which it exerts antiproliferative effects in PMVSMC.


Analgesic studies of codeine and oxycodone in patients with cancer. I. Comparisons of oral with intramuscular codeine and of oral with intramuscular oxycodone.
The relative analgesic potency of oral and intramuscular codeine was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral codeine was 6/10 as potent as the intramuscular form. This is a high oral/parenteral analgesic relative potency ratio compared with morphine, metopon and oxymorphone and correlates well with the results of recent studies which have determined the oral vs. intramuscular bioavailability of codeine in man. Oral and intramuscular oxycodone were also compared in a similar patient group. Like codeine, oxycodone retained at least 1/2 of its analgesic activity when administered orally. We hypothesize that the high oral/parenteral relative potency ratios of codeine and oxycodone relative to morphine and its congeners are not due to more efficient absorption after oral administration, but rather that methylation at position 3 in codeine and oxycodone protects these drugs from rapid first-pass metabolism.


The Safety and Efficacy of Second-Generation Basal Insulin Analogues in Adults with Type 2 Diabetes at Risk of Hypoglycemia and Use in Other Special Populations: A Narrative Review.
Hypoglycemia is a major barrier impeding glycemic control in persons with type 2 diabetes mellitus and creates a substantial burden on the healthcare system. Certain populations that require special attention, such as older adults and individuals with renal impairment, a longer duration of diabetes or those who have experienced prior hypoglycemia, may be at a higher risk of hypoglycemia, particularly with insulin treatment. Second-generation basal insulin analogues (insulin glargine 300 U/mL and degludec) have demonstrated reductions in hypoglycemia compared with insulin glargine 100 U/mL although evidence of this benefit across specific populations is less clear. In this review we summarize the literature with respect to the efficacy and safety data for second-generation basal insulin analogues in adults with type 2 diabetes mellitus who are at risk of hypoglycemia or who require special attention. Randomized controlled trials, meta-analyses and real-world evidence demonstrate that the use of second-generation basal insulin analogues is associated with less hypoglycemia compared with insulin glargine 100 U/mL without compromising glycated hemoglobin control. A reduced risk of hypoglycemia with second-generation basal insulin analogues was evident in older adults and in individuals with obesity, renal impairment, a history of cardiovascular disease or a long duration of insulin use. Further studies are needed in other populations, including those with more severe renal impairment or hepatic dysfunction, the hospitalized population and those with cognitive impairment. Overall, less hypoglycemia associated with second-generation basal insulin analogues may help reduce barriers for insulin use, improve adherence and offset the costs of hypoglycemia-related healthcare resource utilization.


Poly(ADP-ribose) synthetase activation mediates increased permeability induced by peroxynitrite in Caco-2BBe cells.
Peroxynitrite induces cytotoxicity by generating DNA single-strand breaks and activating poly(ADP-ribose) synthetase (PARS), a nuclear enzyme that consumes oxidized nicotinamide adenine dinucleotide (NAD+) and depletes cellular adenosine triphosphate (ATP). The aim of this study was to examine this mechanism of injury in an intestinal epithelial cell model after exposure to exogenous peroxynitrite (ONOO-) and nitric oxide (NO). Caco-2BBe cell monolayers exposed to donors of peroxynitrite (3-morpholino-sydnonimine [SIN-1], 3 mmol/L) or NO (S-nitroso-N-acetyl penicillamine [SNAP]; 3 mmol/L) were analyzed for DNA strand breaks, [NAD+], [ATP], and transepithelial flux of fluorescein sulfonic acid. SIN-1 but not SNAP induced DNA single-strand breakage. Both SIN-1 and SNAP reduced [ATP], but only SIN-1 reduced [NAD+]. Inhibition of PARS activity by the PARS inhibitors 5-iodo-6-amino 1,2-benzopyrone or 3-aminobenzamide prevented the SIN-1-induced reduction in [NAD+] and [ATP] but had no effect on the SNAP-induced reduction in [ATP]. PARS inhibition reduced SIN-1-but not SNAP-induced hyperpermeability. Peroxynitrite but not NO increases transepithelial permeability by inducing DNA strand breaks that activate the PARS pathway and cause the depletion of intracellular energy stores. Inhibition of PARS activity may represent a novel strategy in ameliorating peroxynitrite-mediated epithelial injury during intestinal inflammation.


Inhabiting the body: Exploring the link between embodiment and identity in community adolescents.
The intricate relationship between the body and identity has been highlighted in previous studies. However, a holistic approach to the body that focuses on embodiment is lacking in research examining body - identity linkages. The current study (N = 917 adolescents; 58% female; Mage = 16.17, range = 14-19 years) examined the psychometric properties of a Dutch translation of the Experience of Embodiment Scale (EES) and explored the link between embodiment and personal identity. First, confirmatory factor analysis revealed a second-order factor structure for the EES and adequate reliability coefficients were obtained. Metric invariance across gender was demonstrated for the first- and second-order factors. Second, path analysis demonstrated that experiencing embodiment was positively associated with adaptive identity work. Third, five identity statuses emerged using cluster analysis. Adolescents in statuses reflecting less adaptive identity functioning displayed lower levels of embodiment. The EES shows promising indications of reliability and factor structure for assessing adolescents' Experience of Embodiment, and the present study demonstrates that embodiment is meaningfully related to identity functioning. These findings support the call for the adoption of a positive psychology framework within this research field, with attention given to more broadly defined body-related concepts such as embodiment.


Nursing care of older people: a personal construct theory perspective.
This paper outlines the use of the repertory grid technique, with nurses caring for elderly residents, and residents of a nursing home. The method focuses on the individuality of each person's attempt at making sense of her/his caring world. Previous papers have focused on a discussion of the repertory grid technique as a research method and tool for psychiatric nurses, an overview of studies using this technique with nurses and social workers, and applications of personal construct theory (from which the technique is derived) to nursing research. A paper by Rawlinson described content analysis of the role constructs elicited from the nurses. In this study, content analysis of caring constructs elicited by nurses and residents was also undertaken, and the results are presented. Additionally, principal component analysis of the repertory grids was carried out, and three examples are presented. This combined analysis provides an in-depth insight into nurses' perceptions of caring for others; perceptions which guide their caring behaviours. This information can be used by individual nurses to review their caring practice.


Isosorbide dinitrate-hydralazine combination therapy in African Americans with heart failure.
Despite significant improvement in therapy and management, heart failure remains a worrisome disease state that is especially problematic in special populations. African Americans suffer a disproportionately higher prevalence of heart failure when compared to other populations. It has been recently demonstrated that vasodilator therapy using the combination of isosorbide dinitrate (ISDN) and hydralazine (HYD) as an adjunct to background evidence-based therapy appears to display the strongest signal of benefit in reducing mortality and morbidity in the African American population. Through review of the retrospective and more recent prospective data, we will focus on the benefit of ISDN-HYD as adjunctive therapy for use in African Americans with systolic heart failure on concomitant appropriate evidence based therapy. This review also closely examines some of the potential contributions to endothelial dysfunction in African Americans, and the relationship of vascular homeostasis and nitric oxide. The role of oxidative stress in left ventricular dysfunction will also be explored as a reduction of oxidative stress offers particular promise in the management of heart failure. Although neurohormonal blockade has been responsible for notable event reductions in patients with systolic heart failure, the addition of ISDN-HYD, vasodilator therapy that enhances nitric oxide and reduces oxidative stress, further improves quality of life and survival in African American patients with heart failure. These findings strongly imply that nitric oxide enhancement and/or oxidative stress reduction may be important new therapeutic directions in the management of heart failure.


Effects of selective serotonin reuptake inhibitors on objective and subjective sleep quality.
The purpose of this paper is to review the effects of selective serotonin (5-HT) reuptake inhibitors on objective and subjective sleep and awakening quality measures. Polysomnography (PSG) demonstrated in both healthy volunteers and depressed patients a decrease in sleep efficiency and total sleep time, a lengthening of sleep latency and a deterioration in sleep continuity, including an increase in the number of awakenings and wake time during the total sleep period. Sleep architecture mostly showed an increase in S1 and S2 and a decrease in S3, S4 and REM sleep as well as a lengthening of REM latency. Objective awakening quality, if measured at all by psychometry, generally showed no decrements. Concerning subjective sleep and awakening quality, normals demonstrated either no changes or a tendency towards a deterioration, while in patients some improvement was observed. Reasons for this discrepancy will be discussed. Novel 5-HT reuptake inhibitors with additional modes of action such as 5-HT2 antagonism (e.g. trazodone, nefazodone) are more likely to improve objective and subjective sleep quality, although some shortcomings may be inherent in regard to comorbidity (e.g. sleep-related breathing disorders). Thus, PSG seems to be a necessity for diagnosis and treatment of complex sleep disorders.


[Multiple carcinomas of large bowel].
Thirty-eight patients with multiple carcinomas of large bowel were encountered during 32 years period in our hospital. The incidence of synchronous carcinomas (SC) was 1.5% (22/1430) and metachronous carcinomas (MC) 1.1% (16/1430). Thirty-one patients were found to have two primary carcinomas and seven patients have three primary malignancies. Among the 38 patients, six also had cancers in ether organs. The authors discussed the diagnosis, tumor distribution, the cancer association with familial colonic polyposis, and hereditary colon cancer. The 5 years survival rate with SC treated by surgery was 35.7% (5/14), and was 93% (15/16) with MC. It is the authors' opinion that surgical resection should always be attempted in patients with SC and MC.


Hormonal regulation of oestrogen formation by Leydig cells in vitro: immunocytochemical approach.
The ability of the testis to convert androgens into oestrogens is related to the presence of a microsomal enzyme, aromatase, in testicular cells. The aim of this study was to show whether the supplementation of culture media with LH or an aromatase inhibitor could affect the process of aromatisation in Leydig cells of the bank vole in vitro. This was investigated by means of immunocytochemistry and radioimmunological assays. In control cultures of Leydig cells, both steroid hormones secretion as well as immunoreactivities for aromatase and oestrogen receptor were weaker than in those treated with LH. On the contrary, the addition of aromatase inhibitor into the culture medium resulted in a decreased intensity of immunocytochemical stainings in comparison with the control. Concomitantly, the androgen level was slightly higher, whereas that of oestrogen significantly lower than in the control cultures. Additionally, to check whether steroid hormones are able to regulate aromatase or oestrogen receptor immunoexpressions, some of the Leydig cell cultures were enriched with testosterone or oestradiol, respectively. Strong immunoreactivities for both aromatase and oestrogen receptor were observed. This suggests that Leydig cells in vitro are able to regulate directly the secretion of oestrogens by active aromatase. Finally, it is concluded that oestrogen formation in bank vole Leydig cells in vitro can be influenced by various factors. It should be stressed, however, that the effect of hormone stimulation or aromatase inhibitor action appeared to be dependent on the length of light cycles that bank voles were exposed prior to the isolation of Leydig cells.


Aminoacylation of anticodon loop substituted yeast tyrosine transfer RNA.
A procedure for replacing residues 33-35 in the anticodon loop of yeast tRNATyr with any desired oligonucleotide has been developed. The three residues were removed by partial ribonuclease A digestion. An oligonucleotide was inserted into the gap in four steps by using RNA ligase, polynucleotide kinase, and pseT 1 polynucleotide kinase. The rate of aminoacylation of anticodon loop substituted tRNATyr by yeast tyrosyl-tRNA synthetase was found to depend upon the sequence of the oligonucleotide inserted. This suggests that the nucleotides in the anticodon loop of yeast tRNATyr are required for optimal aminoacylation. In addition, tRNATyr modified to have a phenylalanine anticodon was shown to be misacylated by yeast phenylalanyl-tRNA synthetase at a rate at least 10 times faster than unmodified tRNATyr. Thus, the anticodon is used by phenylalanyl-tRNA synthetase to distinguish between tRNAs.


Amitraz Marker Residues in Honey from Honeybee Colonies Treated with Apiwarol.
Amitraz is a formamide exhibiting both acaricidal and insecticidal activity and is frequently used by beekeepers to protect honeybee colonies against Varroa destructor mites. The aim of this apiary trial was to evaluate the impact of honeybee colony fumigation with amitraz on the level of contamination of honey stored in combs. Experimental colonies were fumigated four times every four days with one tablet of Apiwarol per treatment. Honey was sampled from combs of brood chambers and combs of supers one day after each amitraz application and from harvested honey. Amitraz marker residues (as a total of amitraz and metabolites containing parts of molecules with properties specific to the 2,4-DMA group, expressed as amitraz) were evaluated in honey. All analysed samples were contaminated with amitraz metabolites. 2,4-DMA and DMPF were the most frequently determined compounds. The average concentration of amitraz marker residue in honey from groups where a smouldering tablet was located directly in beehives was significantly higher than that of residue in honey from groups with indirect smoke generation. No significant effect on the honey contamination deriving from the place where it was exposed to smoke (combs of brood chambers and supers) was noted. Amitraz marker residues exceeded the MRL in 10% of honey samples from combs. Fumigation of beehives with amitraz results in contamination of honey stored in combs.


Tolerability of acute migraine medications: influence of methods of assessment and relationship with headache attributes.
Tolerability is an important attribute of patient satisfaction with, and consequence adherence to, migraine acute treatment. Nevertheless, the determinants of tolerability are poorly explored. Accordingly, our objectives were: (i) in subjects receiving triptans, to contrast two methods of assessing adverse events (AEs); and (ii) to explore the relationship between migraine features and treatment attributes with tolerability. We surveyed 365 migraineurs who had been using the same triptan for at least 3 months. After prospectively treating an attack, headache characteristics and treatment response were assessed using headache calendars. Subjects also completed a standardized questionnaire, first asking about any AE and then prompting patients with a list of possible AEs. We contrasted both sets of answers and conducted logistic regression to assess if headache attributes or response to therapy influenced tolerability. Using the unprompted method, AEs occurred in 11.5-36.4% of patients, depending on the triptan used. Using the prompted method, they ranged from 26.9 to 64.3%. Chest and neck tightness were spontaneously reported by 3.5% of the sample, vs. 7.4% when prompted (P < 0.05). Chest pain was not spontaneously reported and was elicited in nine patients (2.5%, P = 0.002). Feeling groggy occurred in 5.7 and 17.5% (P < 0.001). AEs were not a function of headache severity, disability, efficacy of the drug, time to meaningful relief with the drug or recurrence of pain. The report of AEs varies dramatically with the methods of assessment. However, tolerability is not influenced by the severity of the attacks or by medication efficacy.


Alcohol and psoriasis: sobering thoughts.
The association between psoriasis and alcohol consumption is complex. Epidemiological evidence suggests that patients with moderate to severe psoriasis have an increased incidence of alcohol-related diseases and mortality. This appears to be unique to psoriasis compared with other autoimmune diseases. Excessive alcohol consumption may contribute to systemic inflammation and the comorbidities associated with psoriasis, including cardiovascular disease and depression. Screening for hazardous alcohol consumption and appropriate interventions may be useful in patients with moderate to severe psoriasis.


Coupled cryoconite ecosystem structure-function relationships are revealed by comparing bacterial communities in alpine and Arctic glaciers.
Cryoconite holes are known as foci of microbial diversity and activity on polar glacier surfaces, but are virtually unexplored microbial habitats in alpine regions. In addition, whether cryoconite community structure reflects ecosystem functionality is poorly understood. Terminal restriction fragment length polymorphism and Fourier transform infrared metabolite fingerprinting of cryoconite from glaciers in Austria, Greenland and Svalbard demonstrated cryoconite bacterial communities are closely correlated with cognate metabolite fingerprints. The influence of bacterial-associated fatty acids and polysaccharides was inferred, underlining the importance of bacterial community structure in the properties of cryoconite. Thus, combined application of T-RFLP and FT-IR metabolite fingerprinting promises high throughput, and hence, rapid assessment of community structure-function relationships. Pyrosequencing revealed Proteobacteria were particularly abundant, with Cyanobacteria likely acting as ecosystem engineers in both alpine and Arctic cryoconite communities. However, despite these generalities, significant differences in bacterial community structures, compositions and metabolomes are found between alpine and Arctic cryoconite habitats, reflecting the impact of local and regional conditions on the challenges of thriving in glacial ecosystems.


Canalicular obstruction associated with dupilumab.
Dupilumab is a novel treatment for severe atopic dermatitis and is associated with a range of ocular complications such as blepharoconjunctivitis, keratitis, cicatricial ectropion and punctal stenosis. We report 4 patients with canalicular obstruction in association with dupilumab therapy, and we describe their treatment and outcomes in each case. Canalicular obstruction was diagnosed by an oculoplastic consultant between 3 years and 3 months and 4 years and 9 months after the commencement of dupilumab therapy. Case 1 underwent nasolacrimal intubation, case 2 was treated conservatively, and case 4 underwent endonasal dacryocystorhinostomy and these patients' symptoms resolved. Unfortunately, in case 3 despite endonasal dacryocystorhinostomy with stenting they remained symptomatic. This case series adds to the growing number of ocular complications associated with dupilumab therapy, and there is yet an optimal treatment strategy to mitigate these complications. It is possible that simple conservative measures such as discontinuation of dupilumab and topical treatments with steroids can eventually lead to some form of recovery and recanalisation of the canalicular system. Early referral to an ophthalmologist prior to the development of canalicular obstruction to control the inflammatory ocular surface could reduce the risks of cicatricial sequelae from dupilumab, and temporary stenting of the canalicular system could be attempted as a method to keep the canalicular system patent, whilst the patient remained on treatment.


[Influenza C: the immunological aspects of the problem].
The use of the complex of methods for the characterization of cell-mediated and humoral immunity to influenza C virus has made it possible to establish that with the increase of the age of children and, simultaneously, with the increase of the number of persons found to be seropositive to influenza C the asymptomatic forms of this infection occur more frequently. Practically all examined adults selected by random choice have proved to be immune to this infective agent. The results of this investigation indicate that influenza C virus constantly circulates among the population.


Transfiguring Light and Symphonic Blooming: A Wabi Sabi Story of Humanbecoming and Human Caring.
Transfiguring Light and Symphonic Blooming is word-art to describe the flowering of the humanbecoming and human caring schools of thought over time. A Wabi Sabi story journey was created to turn the tide in a world where the building of a unique body of knowledge for nursing has fallen into disfavor with nursing itself. Using nature-aligned paintings and a Japanese story-art aesthetic with poetry, the beauty of falling away to unitary essentials and holding the value of "both-and" in unitary consciousness was illuminated. Co-creating art-knowledge may transfigure nursing theory development and its acceptance with cosmic tree-rooted arches.


Benzyl Butyl Phthalate Induced Early lncRNA H19 Regulation in C3H10T1/2 Stem Cell Line.
Exposure to endocrine-disrupting chemicals used in plastic manufacturing may contribute to the current obesity and diabetes epidemic. Our previous study demonstrated that benzyl butyl phthalate (BBP) induced adipogenesis in the C3H10T1/2 stem cell line. Here we investigated if BBP deregulated long noncoding RNA H19 and its downstream pathway and whether BBP plays a role in the insulin signaling pathway during adipocyte diiferentiation. Cells treated with an 8 day BBP regimen showed that H19 expression was decreased at day 2 with 50 μM BBP exposure (p < 0.05). However, no significant changes were observed from day 4 to day 8. Expression of miRNA-103/107, H19 regulated miRNAs, was upregulated at day 2 (p < 0.05) but not from day 4 to day 8. Similarly, expression of the let-7 family members (a, b, c, d, f, and g) was also significantly increased at day 2 (p < 0.05 or p < 0.01), except for let-7e. Both let-7 and miRNA-103/107 are targets of H19 and play roles in insulin signaling. Insulin receptor substrate (IRS)-1, one of the key insulin signal transduction regulators, was significantly downregulated from day 2 to day 8 (p < 0.05). Gene expression of insulin receptor (IR) and IRS-2 were not altered by BBP exposure. The ratio of IRS1/IRS2 was significantly decreased from day 2 to day 8. On day 4, phospho-Akt protein expression was significantly decreased (p < 0.05). In conclusion, BBP exposure may lead to metabolic dysregulation by altering vital epigenetic regulators such as lncRNA H19 and its target microRNAs at an earlier stage, which further regulates insulin signaling.


The precursors effects on biomimetic hydroxyapatite ceramic powders.
In this study, effects of the starting material on chemical, physical, and biological properties of biomimetic hydroxyapatite ceramic powders (BHA) were investigated. Characterization and chemical analysis of BHA powders were performed by using XRD, FT-IR, and ICP-AES. Microstructural features such as size and morphology of the resulting BHA powders were characterized by using BET, nano particle sizer, pycnometer, and SEM. Additionally, biological properties of the BHA ceramic powders were also investigated by using water-soluble tetrazolium salts test (WST-1). According to the chemical analysis of BHA ceramic powders, chemical structures of ceramics which are prepared under different conditions and by using different starting materials show differences. Ceramic powders which are produced at 80°C are mainly composed of hydroxyapatite, dental hydroxyapatite (contain Na and Mg elements in addition to Ca), and calcium phosphate sulfide. However, these structures are altered at high temperatures such as 900°C depending on the features of starting materials and form various calcium phosphate ceramics and/or their mixtures such as Na-Mg-hydroxyapatite, hydroxyapatite, Mg-Whitlockit, and chloroapatite. In vitro cytotoxicity studies showed that amorphous ceramics produced at 80°C and ceramics containing chloroapatite structure as main or secondary phases were found to be extremely cytotoxic. Furthermore, cell culture studies showed that highly crystalline pure hydroxyapatite structures were extremely cytotoxic due to their high crystallinity values. Consequently, the current study indicates that the selection of starting materials which can be used in the production of calcium phosphate ceramics is very important. It is possible to produce calcium phosphate ceramics which have sufficient biocompatibility at physiological pH values and by using appropriate starting materials.


Menarche delay and menstrual irregularities persist in adolescents with type 1 diabetes.
Menarche delay has been reported in adolescent females with type 1 diabetes (T1DM), perhaps due to poor glycemic control. We sought to compare age at menarche between adolescent females with T1DM and national data, and to identify factors associated with delayed menarche and menstrual irregularity in T1DM. This was a cross-sectional study and females ages 12- 24 years (n = 228) with at least one menstrual period were recruited during their outpatient diabetes clinic appointment. The National Health and Nutrition Examination Survey (NHANES) 2001-2006 data (n = 3690) for females 12-24 years were used as a control group. Age at menarche was later in adolescent females with T1DM diagnosed prior to menarche (12.81 +/- 0.09 years) (mean+/- SE) (n = 185) than for adolescent females diagnosed after menarche (12.17 0.19 years, p = 0.0015) (n = 43). Average age of menarche in NHANES was 12.27 +/- 0.038 years, which was significantly earlier than adolescent females with T1DM prior to menarche (p < 0.0001) and similar to adolescent females diagnosed after menarche (p = 0.77). Older age at menarche was negatively correlated with BMI z-score (r = -0.23 p = 0.0029) but not hemoglobin A1c (A1c) at menarche (r = 0.01, p = 0.91). Among 181 adolescent females who were at least 2 years post menarche, 63 (35%) reported usually or always irregular cycles. Adolescent females with T1DM had a later onset of menarche than both adolescent females who developed T1DM after menarche and NHANES data. Menarche age was negatively associated with BMI z-score, but not A1c. Despite improved treatment in recent decades, menarche delay and high prevalence of menstrual irregularity is still observed among adolescent females with T1DM.


Gasdermin D-Mediated Pyroptosis in Diabetic Cardiomyopathy: Molecular Mechanisms and Pharmacological Implications.
Diabetic cardiomyopathy (DCM) is a pathophysiological condition triggered by diabetes mellitus (DM), which can lead to heart failure (HF). One of the most important cellular processes associated with DCM is the death of cardiomyocytes. Gasdermin D (GSDMD) plays a key role in mediating pyroptosis, a type of programmed cell death closely associated with inflammasome activation. Recent studies have revealed that pyroptosis is induced during hyperglycemia, which is crucial to the development of DCM. Although the effects of pyroptosis on DCM have been discussed, the relationship between DCM and GSDMD is not fully clarified. Recent studies gave us the impetus for clarifying the meaning of GSDMD in DCM. The purpose of this review is to summarize new and emerging insights, mainly discussing the structures of GSDMD and the mechanism of pore formation, activation pathways, molecular mechanisms of GSDMD-mediated pyroptosis, and the therapeutic potential of GSDMD in DCM. The implications of this review will pave the way for a new therapeutic target in DCM.


[Treatment of dysplasia of the gastric mucosal epithelium].
Examined were 53 patients with dysplasia of the gastric mucosal epithelium revealed at endoscopic and histologic study. In detection of moderately pronounced dysplasia, the conservative treatment of the underlying disease with endoscopic and histologic control every 6 mos is indicated; in severe dysplasia--conservative treatment with dynamic control every 3 mos; in absence of positive dynamics of the dysplastic process within a year, or in suspected malignant transformation--the operative intervention, the volume of which is determined by spreading of the foci of dysplasia. The patients operated on for severe dysplasia of the gastric mucosal epithelium should be under continuous supervision.


Detection of fintech P2P lending issues in Indonesia.
Financial technology (fintech) is a growing industry in Indonesia, supported by advances in the technological infrastructure. At the end of 2019, the Financial Services Authority (OJK), the financial authority in Indonesia, recorded 164 registered and licensed fintech (P2P lending) companies. However, since early 2018, the Investment Alert Task Force (SWI) and the Ministry of Communication and Information Technology have blocked 1,350 illegal fintech platforms. Illegal fintech lending practices have mechanisms beyond the responsibility and authority of the OJK, including the risk of collection and distribution of personal data. The essence of this study is to discuss the landscape of fintech P2P lending in Indonesia from Indonesian Online News data, explore cases of fintech p2p lending in Indonesia, and understand the rules and policies. Qualitative research with a case study approach and Focus Group Discussion techniques were used to obtain data from 4 stakeholders in the Fintech P2P Lending Industry in Indonesia. VOS Viewer software is used to build keywords from Indonesian Online News collections, NVIVO 12 qualitative software is used to assist data analysis. The research found the keyword clusters most frequently discussed in the Indonesian Online News collection and five case themes such as public awareness about P2P lending (user understanding), data leakage, and restriction of data access, including personal data protection, personal data fraud, illegal fintech lending, and Product marketing ethics.


[Remote results of using prostaglandins E1 and immunotherapy in combined modality treatment of various-aetiology trophic ulcers].
The purpose of this study was to assess short- and long-term efficacy of combined-modality therapy (comprising PGE1-group preparations and immunocorrection) used to treat indolent trophic ulcers in patients presenting with chronic venous insufficiency (CVI) and cutaneous angiitis. Examined herein were both immediate and remote therapeutic outcomes obtained in patients suffering from indolent trophic ulcers secondary to CVI (post-thrombophlebic disease [PTPD] and varicose disease [VD]), as well as ulcers resulting from vasculitis or vasculopathy. The conventional therapy was supplemented with infusion of PGE1-group preparations and immunocorrection. Also investigated were the indices of microcirculation and the immune status, the percentage of the trophic ulcers having healed, the trophic-ulcer recurrence rate in the remote period, feasibility offurther performing a radical surgical intervention, the patients' quality of life after the treatment, and the need for repeat therapeutic courses according to the regimen proposed. The use of PGE1-group preparations in a combination with immunocorrection confirmed high efficacy of the treatment for various-aetiology trophic ulcers (with the preserved arterial blood flow). The trophic ulcers were observed to epithelialize rapidly following the initiation of treatment, thus making it possible to appropriately prepare the patient suffering from varicose disease for further surgical management. The remote-period evidence clearly showed that the use of the proposed therapeutic regimen had eventually led to a considerable improvement in the patients' quality of life, dramatically decreasing the recurrence rate of trophic ulcers in patients with PTPD and vasculopathies, and thus may safely be recommended both for prevention of ulcer relapses and as part of maintaining therapeutic courses. The detected deviations in the immune status of the patients afflicted with vasculitis and those suffering from CVI confirmed the need for immunocorrection.


Two-photon mapping of neural circuits.
For the study of neural circuits, it would be ideal to be able to discern in a living preparation the interconnections among neurons. Working toward that aim, we have developed a method, using two-photon uncaging of glutamate in brain slices, by which we can detect neurons that are presynaptic to any particular cell. The method, described here, has single-cell resolution and can be applied systematically and quickly to test entire populations of neurons, making it possible to perform online functional analysis of connectivity.


Role of the autonomic nervous system in the thermogenic response to food in lean individuals.
The aim of this study was to determine the role of the autonomic nervous system (ANS) in obligatory and facultative components of the thermogenic response to food (TRF). Nineteen lean, healthy subjects participated in this study, which comprised two protocols, each exploring one component of the ANS. In the first experimental group, propranolol (prime: 80 micrograms/kg; continuous: 1 microgram.kg-1.min-1) was infused intravenously to inhibit sympathetic nervous activity (SNA), whereas in the second group atropine (prime: 5 micrograms/kg; continuous: 5 micrograms.kg-1.min-1) was used to inhibit parasympathetic nervous activity (PNA). The TRF was measured on four occasions: 1) after oral ingestion of a breakfast, during 0.9% NaCl perfusion, 2) after oral ingestion of the same breakfast, during the perfusion of one of the drugs, 3) after intragastric injection of a pureed form of the same meal as in part 1, during 0.9% NaCl perfusion, and 4) after intragastric feeding, during the administration of one of the drugs. Energy expenditure was measured by indirect calorimetry for 30 min before and 6 h after ingestion of the meal. Facultative TRF was defined as the difference between oral and intragastric TRF. Intragastric feeding significantly reduced TRF in both studies: 6.6 +/- 1.0 vs. 8.7 +/- 0.8% of the ingested energy in the SNA study and 5.5 +/- 1.6 vs. 7.4 +/- 3.1% in the PNA study. During propranolol infusion, TRF was significantly lower than it was during saline infusion after oral feeding (6.9 +/- 1.0% vs. 8.7 +/- 0.8% of ingested energy) but not after intragastric feeding. During atropine administration, TRF was reduced after both oral and intragastric feeding, although statistical significance was not reached in the latter. Atropine administration decreased gastric emptying (measured with an isotopic method) 2 h postingestion by 50%. These results show that the SNA is necessary for the facultative component of TRF to occur in humans. The role of the PNA appears to be related to its action on gastric emptying.


Seeing Is Believing: Ultrasound in Pediatric Procedural Performance.
Point-of-care ultrasound is currently widely used across the landscape of pediatric care. Ultrasound machines are now smaller, are easier to use, and have much improved image quality. They have become common in emergency departments, ICUs, inpatient wards, and outpatient clinics. Recent growth of supportive evidence makes a strong case for using point-of-care ultrasound for pediatric interventions such as vascular access (in particular, central-line placement), lumbar puncture, fluid drainage (paracentesis, thoracentesis, pericardiocentesis), suprapubic aspiration, and soft tissue incision and drainage. Our review of this evidence reveals that point-of-care ultrasound has become a powerful tool for improving procedural success and patient safety. Pediatric patients and clinicians performing procedures stand to benefit greatly from point-of-care ultrasound, because seeing is believing.


Microbial source tracking markers for detection of fecal contamination in environmental waters: relationships between pathogens and human health outcomes.
Microbial source tracking (MST) describes a suite of methods and an investigative strategy for determination of fecal pollution sources in environmental waters that rely on the association of certain fecal microorganisms with a particular host. MST is used to assess recreational water quality and associated human health risk, and total maximum daily load allocations. Many methods rely on signature molecules (markers) such as DNA sequences of host-associated microorganisms. Human sewage pollution is among the greatest concerns for human health due to (1) the known risk of exposure to human waste and (2) the public and regulatory will to reduce sewage pollution; however, methods to identify animal sources are receiving increasing attention as our understanding of zoonotic disease potential improves. Here, we review the performance of MST methods in initial reports and field studies, with particular emphasis on quantitative PCR (qPCR). Relationships among human-associated MST markers, fecal indicator bacteria, pathogens, and human health outcomes are presented along with recommendations for future research. An integrated understanding of the advantages and drawbacks of the many MST methods targeting human sources advanced over the past several decades will benefit managers, regulators, researchers, and other users of this rapidly growing area of environmental microbiology.


Association between infantile colic and carbohydrate malabsorption from fruit juices in infancy.
To determine whether infantile colic (IC) is associated with malabsorption of carbohydrates present in fruit juices. In this double-blind study, parents of 30 healthy infants (5.1 +/- 0.7 months, 7.4 +/- 1.0 kg, 64 +/- 4 cm) were administered a questionnaire to quantitatively assess IC. Thereafter, they were divided into 2 groups, 16 infants with and 14 without IC. Within each treatment group infants were fed 120 mL (16.3 +/- 2.0 mL/kg) of either white grape (sorbitol-free; 1:1 fructose-to-glucose ratio) or apple (sorbitol 0.5 g/dL; 2.6:1 fructose-to-glucose ratio) juice. Physical activity (PA), energy expenditure (EE), crying, and sleeping times were measured for 0.5 and 3.0 hours before and after juice feeding, respectively, using the Enhanced Metabolic Testing Activity Chamber. Carbohydrate malabsorption was determined by breath hydrogen (BH(2)) gas analysis after juice feedings. Statistical differences between groups were determined by 2-way analysis of variance with the Tukey procedure. Infants with IC fed apple juice exhibited carbohydrate malabsorption as shown by increased BH(2) excretion, whereas those without IC absorbed carbohydrates normally when fed this juice. Infants fed apple juice with carbohydrate malabsorption cried more and consequently slept less during the last 1.5 hours of the study. This was associated with increased PA and EE as compared with infants without IC fed apple juice. In contrast, infants fed white grape juice, regardless of IC, showed no increase in BH(2) excretion, PA, and EE. Furthermore, crying and sleeping times were unchanged in infants fed white grape juice regardless of the presence or absence of IC. IC was associated with carbohydrate malabsorption from fruit juices containing sorbitol and a high fructose-to-glucose ratio.


[Yield of blood cultures in relation to the cultured blood volume in Bactec 6A bottles].
Concentration of microorganisms in blood is low in bacteremia from extravascular sources. The best yield from blood cultures is achieved by culturing a minimum of 10-20 ml, although in some processing blood culture systems such as Bactec NR-860, smaller volume is used. The objectives of the present study were to establish the frequency in which inadequate small blood volumes are employed for culturing and to analyze the relation between the cultured blood volume in Bactec 6A bottles and the yield achieved. We weighed 2000 Bactec 6A bottles pertaining to consecutive blood cultures obtained from untreated patients with clinical suspicion of Infection. The cultured blood volume was estimated subtracting the mean empty bottle weight. Microorganisms were recovered from 251 bottles (12.5%). One hundred and thirty one (6.8%) isolates were considered as clinically significant and 115 (5.7%) as contaminant. The inoculated blood volume in both significant (5.532 +/- 1.587 ml) and non-significant (5.471 +/- 1.563 ml) recoveries was superior than that of bottles without microbiologic growth (5.209 +/- 1.575 ml, p = 0.016 and p = 0.06, respectively). A linear positive trend was found between the cultivated blood volume and the rate of recoveries (p = 0.008). Within the range of 1 up to 10 ml, the rate of recoveries increased 2.28% for each additional ml of cultivated blood (r = 0.953, p < 0.0001). Out of the 2,000 weighed bottles 127 (6.3%) contained less than 3 ml of blood and 576 (29%) between 3 and 5 ml. We have proved that the rate of recoveries from Bactec 6A bottles increased with the volume of cultured blood. In untreated patients, this increase is maintained up to volumes of 7 to 10 ml.


Chytrid fungi and global amphibian declines.
Discovering that chytrid fungi cause chytridiomycosis in amphibians represented a paradigm shift in our understanding of how emerging infectious diseases contribute to global patterns of biodiversity loss. In this Review we describe how the use of multidisciplinary biological approaches has been essential to pinpointing the origins of amphibian-parasitizing chytrid fungi, including Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans, as well as to timing their emergence, tracking their cycles of expansion and identifying the core mechanisms that underpin their pathogenicity. We discuss the development of the experimental methods and bioinformatics toolkits that have provided a fuller understanding of batrachochytrid biology and informed policy and control measures.


Efficacy and Toxicity of Panitumumab After Progression on Cetuximab and Predictive Value of MiR-31-5p in Metastatic Wild-type KRAS Colorectal Cancer Patients.
In metastatic colorectal cancer (mCRC), panitumumab is generally considered to be ineffective after the progression on cetuximab therapy. However, few studies have demonstrated that a small subset of mCRC patients may benefit from panitumumab in this setting. In our study, wild-type KRAS mCRC patients, enrolled into the nationwide Czech registry CORECT between January 2007 and December 2012, were screened for panitumumab therapy after progression on cetuximab. We identified 26 mCRC in the registry with well documented progression on cetuximab in combination with irinotecan-based chemotherapy (FOLFIRI or irinotecan alone) who received panitumumab monotherapy. Partial response (PR) was achieved in 3 (11.5%) patients and stable disease (SD) in 7 (26.9%) patients after 8 weeks of therapy. Thirteen (50.0%) patients had evidence of progressive disease (PD) and in 3 (11.5%) cases response was not available. Furthermore, we confirmed that higher expression levels of newly described biomarker, miR-31-5p, in tumor are significantly associated with shorter progression-free survival (PFS) in patients treated with cetuximab (p=0.038); however, we did not observe association between miR-31-5p and response to panitumumab in mCRC patients after progression on cetuximab. It remains possible that a subset of mCRC patients may benefit from panitumumab after progression on cetuximab.


Sensorimotor gating and habituation in antipsychotic-naive, first-episode schizophrenia patients before and after 6 months' treatment with quetiapine.
Impaired prepulse inhibition of the startle reflex (PPI) in schizophrenia has been replicated in many studies. However, previous results may have been influenced by course of illness, and antipsychotic medication. Studies on antipsychotic-naive, first-episode schizophrenia patients are lacking, since these patients are so difficult to recruit. Furthermore, longitudinal studies are few, and their results are inconsistent: some results indicating a reduction of PPI deficits by treatment with atypical antipsychotics, while others do not. This study reports on PPI, habituation and sensitization of the human startle reflex in a large group of antipsychotic-naive, first-episode schizophrenia patients, and the effect of subsequent treatment with quetiapine. Thirty-four antipsychotic-naive, first-episode schizophrenia patients (24 males, 10 females), and age- and gender-matched healthy controls were tested in a psychophysiological test battery at baseline and again after 6 months. During this period, the patients were treated with quetiapine, while the controls received no treatment. Sixteen patients completed the study. At baseline, male patients showed significantly lower PPI than controls. Treatment with quetiapine for 6 months increased male PPI to a level where it was no longer statistically different from the controls. The much smaller group of females did not show PPI deficits at baseline. In addition, compared to controls, patients appeared highly aroused and showed a strong yet non-significant trend for reduced sensitization at baseline, but not at follow-up. Patients and controls showed similar levels of habituation, both at baseline, and at follow-up. These findings indicate that PPI deficits are already present from the earliest stage of clinical onset of schizophrenia, before the patients have received any antipsychotic treatment. In addition, following 6 months' treatment with quetiapine these PPI deficits were normalized. Furthermore, the results suggest that schizophrenia patients in the antipsychotic-naive state show reduced levels of sensitization, yet normal levels of habituation.


Inhibition of binding of [3H]batrachotoxinin A 20-alpha-benzoate to sodium channels by local anesthetics.
The effects of several local anesthetics on the binding of ligands to receptors associated with voltage-sensitive sodium channels in rat brain synaptosomes have been examined. In the presence of 0.3 microM scorpion toxin, the 13 local anesthetics tested inhibited the specific binding of [3H]batrachotoxinin A 20 alpha-benzoate [( 3H]BTX-B), a ligand which binds to a receptor site responsible for the activation of sodium channel ion flux, in a dose-dependent fashion, with KD values ranging from 1.2 microM for tetracaine to 1.58 mM for benzocaine. A plot of log KD from these binding experiments against log K0.5 for inhibition of sodium currents by local anesthetics from electrophysiological experiments yielded a regression line with a slope of 0.84 and a correlation coefficient, r, of 0.86, demonstrating that the inhibition of [3H]BTX-B binding by local anesthetics occurs within a concentration range of physiological relevance. Tetracaine had little effect on basal 125I-labeled scorpion toxin binding to synaptosomes in the absence of batrachotoxin. However, in the presence of batrachotoxin, tetracaine inhibited the batrachotoxin-dependent increase in scorpion toxin binding (KD = 2.0 microM) in a dose-dependent manner, suggesting that inhibition of [3H]BTX-B binding by local anesthetics does not occur through binding at the scorpion toxin binding site. The inhibition of [3H]BTX-B binding by lidocaine was reversible within 30 min when samples were diluted from 10(-3)M to 10(-4) M lidocaine. Scatchard analysis of [3H]BTX-B binding to synaptosomes showed that bupivacaine and tetracaine reduced receptor affinity without decreasing maximal binding capacity. This reduction in receptor affinity in the presence of local anesthetics appears to be due, at least in part, to an increased rate of ligand dissociation from the receptor-ligand complex, suggesting an indirect allosteric mechanism for the inhibition of [3H]BTX-B binding by local anesthetics. Analysis of the effects of local anesthetics in terms of an allosteric model of drug action showed that they bind to inactive states of sodium channels with at least a 10-fold higher affinity than active states. A 7-fold difference in KD for inhibition of [3H]BTX-B binding between the local anesthetic stereoisomers RAC 109 I and RAC 109 II was observed. Similarly, the dissociation rate constant for the [3H]BTX-B/receptor complex was increased 9.3-fold in the presence of RAC 109 II and 4.3-fold in the presence of a comparable concentration of RAC 109 I.(ABSTRACT TRUNCATED AT 250 WORDS)


Using Transcranial Direct Current Stimulation to Augment the Effect of Motor Imagery-Assisted Brain-Computer Interface Training in Chronic Stroke Patients-Cortical Reorganization Considerations.
Introduction: Transcranial direct current stimulation (tDCS) has been shown to modulate cortical plasticity, enhance motor learning and post-stroke upper extremity motor recovery. It has also been demonstrated to facilitate activation of brain-computer interface (BCI) in stroke patients. We had previously demonstrated that BCI-assisted motor imagery (MI-BCI) can improve upper extremity impairment in chronic stroke participants. This study was carried out to investigate the effects of priming with tDCS prior to MI-BCI training in chronic stroke patients with moderate to severe upper extremity paresis and to investigate the cortical activity changes associated with training. Methods: This is a double-blinded randomized clinical trial. Participants were randomized to receive 10 sessions of 20-min 1 mA tDCS or sham-tDCS before MI-BCI, with the anode applied to the ipsilesional, and the cathode to the contralesional primary motor cortex (M1). Upper extremity sub-scale of the Fugl-Meyer Assessment (UE-FM) and corticospinal excitability measured by transcranial magnetic stimulation (TMS) were assessed before, after and 4 weeks after intervention. Results: Ten participants received real tDCS and nine received sham tDCS. UE-FM improved significantly in both groups after intervention. Of those with unrecordable motor evoked potential (MEP-) to the ipsilesional M1, significant improvement in UE-FM was found in the real-tDCS group, but not in the sham group. Resting motor threshold (RMT) of ipsilesional M1 decreased significantly after intervention in the real-tDCS group. Short intra-cortical inhibition (SICI) in the contralesional M1 was reduced significantly following intervention in the sham group. Correlation was found between baseline UE-FM score and changes in the contralesional SICI for all, as well as between changes in UE-FM and changes in contralesional RMT in the MEP- group. Conclusion: MI-BCI improved the motor function of the stroke-affected arm in chronic stroke patients with moderate to severe impairment. tDCS did not confer overall additional benefit although there was a trend toward greater benefit. Cortical activity changes in the contralesional M1 associated with functional improvement suggests a possible role for the contralesional M1 in stroke recovery in more severely affected patients. This has important implications in designing neuromodulatory interventions for future studies and tailoring treatment. Clinical Trial Registration: The study was registered at https://clinicaltrials.gov (NCT01897025).


Chronological set of E. coli O157:H7 bovine strains establishes a role for repeat sequences and mobile genetic elements in genome diversification.
Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a significant foodborne pathogen that resides asymptomatically within cattle and other ruminants. The EHEC genome harbors an extensive collection of mobile genetic elements (MGE), including multiple prophage, prophage-like elements, plasmids, and insertion sequence (IS) elements. A chronological collection of EHEC strains (FRIK804, FRIK1275, and FRIK1625) isolated from a Wisconsin dairy farm (farm X) comprised a closely related clade genetically differentiated by structural alterations to the chromosome. Comparison of the FRIK804 genome with a reference EHEC strain Sakai found a unique prophage like element (PLE, indel 1) and an inversion (1.15 Mb) situated symmetrically with respect to the terminus region. Detailed analysis determined the inversion was due to homologous recombination between repeat sequences in prophage. The three farm X strains were distinguished by the presence or absence of indel 3 (61 kbp) and indel 4 (48 kbp); FRIK804 contained both of these regions, FRIK1275 lacked indel 4, and indels 3 and 4 were both absent in FRIK1625. Indel 3 was the stx2 prophage and indel 4 involved a deletion between two adjacent prophage with shared repeat sequences. Both FRIK804 and FRIK1275 produced functional phage while FRIK1625 did not, which is consistent with indel 3. Due to their involvement in recombination events, direct and inverted repeat sequences were identified, and their locations mapped to the chromosome. FRIK804 had a greater number and overall length of repeat sequences than E. coli K12 strain MG1655. Repeat sequences were most commonly associated with MGE. This research demonstrated that three EHEC strains from a Wisconsin dairy farm were closely related and distinguished by variability within prophage regions and other MGE. Chromosome alterations were associated with recombination events between repeat sequences. An inventory of direct and inverted repeat sequences found a greater abundance and total length of repeat sequences in the EHEC strains compared to E. coli strain MG1655. The locations of the repeat sequences were biased towards MGE. The findings from this study expand our understanding of the precise molecular events and elements that contributed to genetic diversification of wild-type EHEC in the bovine and farm environments.


Association between Anterior Cingulate Neurochemical Concentration and Individual Differences in Hypnotizability.
Hypnosis is the oldest form of Western psychotherapy and a powerful evidence-based treatment for numerous disorders. Hypnotizability is variable between individuals; however, it is a stable trait throughout adulthood, suggesting that neurophysiological factors may underlie hypnotic responsiveness. One brain region of particular interest in functional neuroimaging studies of hypnotizability is the anterior cingulate cortex (ACC). Here, we examined the relationships between the neurochemicals, GABA, and glutamate, in the ACC and hypnotizability in healthy individuals. Participants underwent a magnetic resonance imaging (MRI) session, whereby T1-weighted anatomical and MEGA-PRESS spectroscopy scans were acquired. Voxel placement over the ACC was guided by a quantitative meta-analysis of functional neuroimaging studies of hypnosis. Hypnotizability was assessed using the Hypnotic Induction Profile (HIP), and self-report questionnaires to assess absorption (TAS), dissociation (DES), and negative affect were completed. ACC GABA concentration was positively associated with HIP scores such that the higher the GABA concentration, the more hypnotizable an individual. An exploratory analysis of questionnaire subscales revealed a negative relationship between glutamate and the absorption and imaginative involvement subscale of the DES. These results provide a putative neurobiological basis for individual differences in hypnotizability and can inform our understanding of treatment response to this growing psychotherapeutic tool.


Oxygen limitation and thermal tolerance in two terrestrial arthropod species.
Recent studies of marine invertebrates and fish have suggested that lower and upper critical temperatures (CT(min) and CT(max)) are coupled by a common mechanism: oxygen and capacity limitation of thermal tolerance (OCLT). Using thermolimit respirometry, we tested the predictions of this theory for terrestrial arthropods by measuring maxima and minima for both critical temperatures and metabolic rate in two arthropods, the isopod Porcellio scaber and the beetle Tenebrio molitor, at 40%, 21%, 10% and 2.5% ambient O(2). Critical temperatures were identified as particular points on both activity and traces in four ways. In the first two instances, we identified the inflection points in regressions of absolute difference sum (ADS) residuals calculated for activity (aADS) and (VI), respectively. In the third, we visually identified the lowest point before the post-mortal peak in CO(2) release (PMV). Finally, we pinpointed the sudden drop in at death, where fell outside the 95% confidence intervals of the 5 min period immediately preceding the drop-off (CI). Minimum and maximum metabolic rates were determined using CO(2) traces, and the temperatures corresponding to these identified as T(MetMin) and T(MetMax). For both species, ambient oxygen concentration did not influence CT(min), minimum metabolic rate, or T(MetMin). By contrast, severe hypoxia (2.5% O(2)) caused a 6.9 degrees C decline in activity-based CT(max) for T. molitor and a 10.6 degrees C decline for P. scaber, relative to normoxia (21% O(2)). The magnitude of this decrease differed between methods used to estimated critical thermal limits, highlighting the need for a standard method to determine these endpoints during thermolimit respirometry. Maximum metabolic rate also declined with decreasing ambient oxygen in both species. The combination of increasing metabolic rate and oxygen limitation affected upper thermal limits in these arthropods only in severe hypoxia (2.5% O(2)). In both species, CT(min) and CT(max) responded differently to oxygen limitation, suggesting that this is not a common mechanism coupling upper and lower limits in terrestrial arthropods.


Treatment of basilar invagination by atlantoaxial joint distraction and direct lateral mass fixation.
The author discusses the successful preliminary experience of treating selected cases of basilar invagination by performing atlantoaxial joint distraction, reduction of the basilar invagination, and direct lateral mass atlantoaxial plate/screw fixation. Twenty-two patients with basilar invagination-in which the odontoid process invaginated into the foramen magnum and the tip of the odontoid process was above the Chamberlain, McRae foramen magnum, and Wackenheim clival lines-were selected to undergo surgery. In all patients fixed atlantoaxial dislocations were documented. The 16 male and six female patients ranged in age from 8 to 50 years. A history of trauma prior to the onset of symptoms was documented in 17 patients. Following surgery, the author observed minimal-to-significant reduction of basilar invagination and alteration in other craniospinal parameters resulting in restoration of alignment of the tip of the odontoid process and the clivus and the entire craniovertebral junction in all patients. In addition to neurological and radiological improvement, preoperative symptoms of torticollis resolved significantly in all patients. The minimum follow-up period was 12 months and the mean was 28 months. Joint distraction and firm lateral mass fixation in selected cases of basilar invagination is a reasonable surgical treatment for reducing the basilar invagination, restoring craniospinal alignment, and establishing fixation of the atlantoaxial joint.


The use of immunoglobulin therapy for patients undergoing solid organ transplantation: an evidence-based practice guideline.
This guideline for the use of immunoglobulin (IG) for sensitized patients undergoing solid organ transplantation (SOT) is an initiative of the Canadian Blood Services and the National Advisory Committee on Blood and Blood Products of Canada to (1) provide guidance for Canadian practitioners involved in the care of patients undergoing SOT and transfusion medicine specialists on the use of IG and (2) standardize care, limit adverse events, and optimize patient care. A systematic expert and bibliography literature search up to July 2008 was conducted, with 791 literature citations and 45 reports reviewed. To validate the recommendations, the guideline was sent to physicians involved in SOT in Canada and a patient representative. The recommendations identify (1) sensitized patients undergoing SOT that would have a better survival and decreased morbidity by receiving IG preoperatively, postoperatively, and for the treatment of organ rejection; (2) patients who may not have any benefit from receiving IG; and (3) potential adversities to IG.


Relative validity effects with either one or two more valid cues in Pavlovian and instrumental conditioning.
Two experiments investigated the relative validity effect with either 1 or 2 continuously reinforced cues in Wistar rats using appetitive Pavlovian and instrumental preparations. Discrimination training involved 3 compound cues containing a common element (1AX: 1BX: 2CX). In the first true-discrimination group (TD-1), CX was followed by food, but AX and BX were not. In the second true-discrimination group (TD-2), AX and BX but not CX were followed by food. In the third, pseudodiscrimination group (PD), food followed 50% of each compound. Compared with the PD group, there were lower levels of responding to X in Groups TD-1 and TD-2, which did not differ. That is, both TD treatments showed equivalent relative validity effects. There was evidence for a relative validity effect on the context. The Rescorla-Wagner model incorrectly predicts a smaller relative validity effect after the TD-2 than the TD-1 treatment. Comparator theory predicts these results.


Pseudostratified epithelia - cell biology, diversity and roles in organ formation at a glance.
Pseudostratified epithelia (PSE) are widespread and diverse tissue arrangements, and many PSE are organ precursors in a variety of organisms. While cells in PSE, like other epithelial cells, feature apico-basal polarity, they generally are more elongated and their nuclei are more densely packed within the tissue. In addition, nuclei in PSE undergo interkinetic nuclear migration (IKNM, also referred to as INM), whereby all mitotic events occur at the apical surface of the elongated epithelium. Previous reviews have focused on the links between IKNM and the cell cycle, as well as the relationship between IKNM and neurogenesis, which will not be elaborated on here. Instead, in this Cell Science at a Glance article and the accompanying poster, I will discuss the cell biology of PSEs, highlighting how differences in PSE architecture could influence cellular behaviour, especially IKNM. Furthermore, I will summarize what we know about the links between apical mitosis in PSE and tissue integrity and maturation.


Reversible cerebral vasoconstriction syndrome associated with autonomic dysreflexia.
A 32-year-old man with a residual spastic quadriparesis from a traumatic C5-C6 fracture experienced a severe thunderclap headache. The medical history revealed an episode of autonomic dysreflexia (AD) due to neurogenic bladder/urinary tract infection (UTI). Blood pressure monitoring at admission revealed hypertension; blood pressure reaching 160/100 mmHg (average blood pressure in these patients and also in this patient being 90/60 mmHg). CT scan of the head, cerebrospinal fluid examination, CT angiography and MR angiography of the brain vessels were normal. Another UTI and a subsequent spell of AD were diagnosed. The patient continued to experience recurrent thunderclap headaches. Selective catheter cerebral angiography revealed multiple calibre changes in the intracranial blood vessels. A diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) due to AD was considered. A magnetic resonance imaging (MRI) of the brain after 2 weeks revealed ischaemic changes in the left hemisphere. Follow-up brain MRI after 3 weeks showed reduction in size of the ischaemic changes, and catheter angiography after 6 weeks demonstrated improvement/normalization. A diagnosis of RCVS could be established. Repeated MRI/CT of the brain after 6 months demonstrated a large infarction in the left hemisphere. RCVS has been reported to occur in various clinical settings. It can occur in the setting of AD in patients with traumatic cervical cord injury. Prompt recognition of RCVS may be of vital importance to avoid further morbidity in patients with spinal cord injury.


I-Ag7 is subject to post-translational chaperoning by CLIP.
Several MHC class II alleles linked with autoimmune diseases form unusually low-stability complexes with class II-associated invariant chain peptides (CLIP), leading us to hypothesize that this is an important feature contributing to autoimmune pathogenesis. We recently demonstrated a novel post-endoplasmic reticulum (ER) chaperoning role of the CLIP peptides for the murine class II allele I-E(d). In the current study, we tested the generality of this CLIP chaperone function using a series of invariant chain (Ii) mutants designed to have varying CLIP affinity for I-A(g7). In cells expressing these Ii CLIP mutants, I-A(g7) abundance, turnover and antigen presentation are all subject to regulation by CLIP affinity, similar to I-E(d). However, I-A(g7) undergoes much greater quantitative changes than observed for I-E(d). In addition, we find that Ii with a CLIP region optimized for I-A(g7) binding may be preferentially assembled with I-A(g7) even in the presence of higher levels of wild-type Ii. This finding indicates that, although other regions of Ii interact with class II, CLIP binding to the groove is likely to be a dominant event in assembly of nascent class II molecules with Ii in the ER.


Thoracic rat spinal cord contusion injury induces remote spinal gliogenesis but not neurogenesis or gliogenesis in the brain.
After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis) in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC) or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn) of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU) to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord) and unaltered in neurogenic regions (dentate gyrus and SVZ) of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement.


The clinical course of Behçet's disease in pregnancy: a retrospective analysis and review of the literature.
Although Behçet's disease is mainly diagnosed during the reproductive periods of life, we know little about the influence of pregnancy on the clinical course of Behçet's disease. Therefore, we analyzed the relationship between Behçet's disease and pregnancy retrospectively, in order to detect any possible interaction between the two multisystemic processes, particularly in regard to the influence of pregnancy on the clinical course of Behçet's disease. We studied 44 pregnancies in 28 women with Behçet's disease. The diagnoses were made according to the criteria of the International Study Group for Behçet's disease. The patients were observed during pregnancy and puerperium periods at monthly intervals. The existence and incidence of symptoms were recorded during these periods. There was remission of Behçet's disease during 23 (52.3%) pregnancies, although the disease had been in a stage of exacerbation before pregnancy. The disease became exacerbated during 12 (27.3%) pregnancies, although it had been in a stage of remission before pregnancy. There were no changes in the clinical course of Behçet's disease in 9 (20.4%) pregnancies. The most frequent manifestations of the clinical exacerbation were increases in the intensity and severity of outbreaks of oral ulcers during pregnancy. Outbreaks of genital ulcers, eye inflammations, and arthritis were other signs of exacerbation. Other than spontaneous abortion in three patients, we did not observe maternal or fetal complications. Although Behçet's disease tends toward remission during pregnancy, the influence of pregnancy on its clinical course is quite variable between patients and even during different pregnancies in the same patient. On the basis of our and previous results, we speculate that pregnancy in general does not seem to markedly affect the natural course of Behçet's disease.


[Various indicators of the B-system of immunity in endemic goiter].
Blood serum immunoglobulins (Ig) and the circulating antibodies against thyroglobulin, which are known to characterize the state of the immunity B-system, were investigated in 167 patients with endemic goiter and in 80 healthy persons. A significant elevation in the IgM, IgG, and antithyroglobulin antibody levels was observed in patients with hyperthyroid goiter. An increase in the antibody titre to thyroglobulin and in the IgG level was found in euthyroid goiter cases. The extent of functional activity of the thyroid gland and the presence of ophthalmopathy influenced the incidence and the level of the serum Ig elevation and of the antithyroglobulin antibodies increase.


Mangifera indica L. extract (Vimang) and its main polyphenol mangiferin prevent mitochondrial oxidative stress in atherosclerosis-prone hypercholesterolemic mouse.
Atherosclerosis is linked to a number of oxidative events ranging from low-density lipoprotein (LDL) oxidation to the increased production of intracellular reactive oxygen species (ROS). We have recently demonstrated that liver mitochondria isolated from the atherosclerosis-prone hypercholesterolemic LDL receptor knockout (LDLr(-/-)) mice have lower content of NADP(H)-linked substrates than the controls and, as consequence, higher sensitivity to oxidative stress and mitochondrial membrane permeability transition (MPT). In the present work, we show that oral supplementation with the antioxidants Mangifera indica L. extract (Vimang) or its main polyphenol mangiferin shifted the sensitivity of LDLr(-/-) liver mitochondria to MPT to control levels. These in vivo treatments with Vimang and mangiferin also significantly reduced ROS generation by both isolated LDLr(-/-) liver mitochondria and spleen lymphocytes. In addition, these antioxidant treatments prevented mitochondrial NAD(P)H-linked substrates depletion and NADPH spontaneous oxidation. In summary, Vimang and mangiferin spared the endogenous reducing equivalents (NADPH) in LDLr(-/-) mice mitochondria correcting their lower antioxidant capacity and restoring the organelle redox homeostasis. The effective bioavailability of these compounds makes them suitable antioxidants with potential use in atherosclerosis susceptible conditions.


Yersinia enterocolitica CsrA regulates expression of the Ysa and Ysc type 3 secretion system in unique ways.
This study investigated how carbon storage regulator A (CsrA) affects expression of the Ysa and Ysc type 3 secretion (T3S) system genetic regulatory cascades that control Ysps (Yersinia secreted proteins) and Yops (Yersinia outer proteins) export, respectively. Given that most often CsrA acts as a mediator of mRNA stability, an activity that can be monitored using lacZ transcriptional fusions, we employed a collection of reporter strains to assess Ysa and Ysc gene expression. To this end, bacteria were cultivated to induce either the Ysa or the Ysc T3S system. Comparison of csrA mutants to the wild-type strain revealed that, in response to the respective inducing conditions, genes spanning the Ysa and Ysc gene cascades displayed increased expressions. Then, the possibility that CsrA affects secretion of Ysps and Yops was tested and the profiles of secreted proteins by wild-type and csrA mutant strains were compared by proteomic analysis. Ysps were over-secreted and Yops were under-secreted, for the csrA mutant. These results support the hypothesis that CsrA affects both the Ysa and Ysc T3S systems in Yersinia enterocolitica. They further support the conclusion that CsrA plays an important role in controlling adaptation of this pathogenic bacterium during its lifecycle shift between a terrestrial and parasitic existence.


Expression of bacterial genes in plant cells.
Chimeric bacterial genes conferring resistance to aminoglycoside antibiotics have been inserted into the Agrobacterium tumefaciens tumor-inducing (Ti) plasmid and introduced into plant cells by in vitro transformation techniques. The chimeric genes contain the nopaline synthase 5' and 3' regulatory regions joined to the genes for neomycin phosphotransferase type I or type II. The chimeric genes were cloned into an intermediate vector, pMON120, and inserted into pTiB6S3 by recombination and then introduced into petunia and tobacco cells by cocultivating A. tumefaciens cells with protoplast-derived cells. Southern hybridization was used to confirm the presence of the chimeric genes in the transformed plant tissues. Expression of the chimeric genes was determined by the ability of the transformed cells to proliferate on medium containing normally inhibitory levels of kanamycin (50 micrograms/ml) or other aminoglycoside antibiotics. Plant cells transformed by wild-type pTiB6S3 or derivatives carrying the bacterial neomycin phosphotransferase genes with their own promoters failed to grow under these conditions. The significance of these results for plant genetic engineering is discussed.


Genome-Wide Analysis of CCA1-Like Proteins in Soybean and Functional Characterization of GmMYB138a.
Plant CIRCADIAN CLOCK ASSOCIATED1 (CCA1)-like proteins are a class of single-repeat MYELOBLASTOSIS ONCOGENE (MYB) transcription factors generally featured by a highly conserved motif SHAQK(Y/F)F, which play important roles in multiple biological processes. Soybean is an important grain legume for seed protein and edible vegetable oil. However, essential understandings regarding CCA1-like proteins are very limited in soybean. In this study, 54 CCA1-like proteins were identified by data mining of soybean genome. Phylogenetic analysis indicated that soybean CCA1-like subfamily showed evolutionary conservation and diversification. These CCA1-like genes displayed tissue-specific expression patterns, and analysis of genomic organization and evolution revealed 23 duplicated gene pairs. Among them, GmMYB138a was chosen for further investigation. Our protein-protein interaction studies revealed that GmMYB138a, but not its alternatively spliced isoform, interacts with a 14-3-3 protein (GmSGF14l). Although GmMYB138a was predominately localized in nucleus, the resulting complex of GmMYB138a and GmSGF14l was almost evenly distributed in nucleus and cytoplasm, supporting that 14-3-3s interact with their clients to alter their subcellular localization. Additionally, qPCR analysis suggested that GmMYB138a and GmSGF14l synergistically or antagonistically respond to drought, cold and salt stresses. Our findings will contribute to future research in regard to functions of soybean CCA1-like subfamily, especially regulatory mechanisms of GmMYB138a in response to abiotic stresses.


17β-estradiol attenuates exercise-induced neutrophil infiltration in men.
17β-estradiol (E2) attenuates exercise-induced muscle damage and inflammation in some models. Eighteen men completed 150 eccentric contractions after random assignment to placebo (Control group) or E2 supplementation (Experimental group). Muscle biopsies and blood samples were collected at baseline, following 8-day supplementation and 3 h and 48 h after exercise. Blood samples were analyzed for sex hormone concentration, creatine kinase (CK) activity and total antioxidant capacity. The mRNA content of genes involved in lipid and cholesterol homeostasis [forkhead box O1 (FOXO1), caveolin 1, and sterol regulatory element binding protein-2 (SREBP2)] and antioxidant defense (SOD1 and -2) were measured by RT-PCR. Immunohistochemistry was used to quantify muscle neutrophil (myeloperoxidase) and macrophage (CD68) content. Serum E2 concentration increased 2.5-fold with supplementation (P < 0.001), attenuating neutrophil infiltration at 3 h (P < 0.05) and 48 h (P < 0.001), and the induction of SOD1 at 48 h (P = 0.02). Macrophage density at 48 h (P < 0.05) and SOD2 mRNA at 3 h (P = 0.01) increased but were not affected by E2. Serum CK activity was higher at 48 h for both groups (P < 0.05). FOXO1, caveolin 1 and SREBP2 expression were 2.8-fold (P < 0.05), 1.4-fold (P < 0.05), and 1.5-fold (P < 0.001) and higher at 3 h after exercise with no effect of E2. This suggests that E2 attenuates neutrophil infiltration; however, the mechanism does not appear to be lesser oxidative stress or membrane damage and may indicate lesser neutrophil/endothelial interaction.


Harnessing Knowledge for Improving Access to Fruits and Vegetables at Farmers Markets: Interactive Data Visualization to Inform Food Security Programs and Policy.
High consumption of fruits and vegetables leads to decreased risk of various chronic diseases, including obesity and cardiovascular disease. Community-level barriers to access fruits and vegetables include the high cost, limited availability, and transportation. Farmers markets are a priority strategy for improving community access to fresh fruits and vegetables. The U.S. Department of Agriculture (USDA) National Farmers Market Directory is a voluntary self-reported data source on farmers markets. The objective of this investigation of the USDA farmers markets data directory was to determine how farmers markets in the United States are grouped according to (1) availability of fruits and vegetables and (2) the payment accepted. We designed and implemented interactive data visualizations in visual analytics software to understand access to fruits and vegetables at farmers markets from 8,497 entries in the USDA Farmers Market Directory. Among the 665 new or updated entries in year 2018, a subset of 641 (96%) farmers markets with availability of fresh fruits and vegetables had 16 subgroups. Additionally, a subgroup of 102 (16%) farmer markets accepted all four federal nutrition assistance benefits (SFMNP, SNAP, WIC CVVs, and WIC FMNP). The interactive data visualizations including geographic maps connected to social media resources can be useful in advocacy efforts and can inform policy improvements designed to improve physical, social, and economic access to fruits and vegetables at farmers markets.


Continuous electricity generation from domestic wastewater and organic substrates in a flat plate microbial fuel cell.
A microbial fuel cell (MFC) is a device that converts organic matter to electricity using microorganisms as the biocatalyst. Most MFCs contain two electrodes separated into one or two chambers that are operated as a completely mixed reactor. In this study, a flat plate MFC (FPMFC) was designed to operate as a plug flow reactor (no mixing) using a combined electrode/proton exchange membrane (PEM) system. The reactor consisted of a single channel formed between two nonconductive plates that were separated into two halves by the electrode/PEM assembly. Each electrode was placed on an opposite side of the PEM, with the anode facing the chamber containing the liquid phase and the cathode facing a chamber containing only air. Electricity generation using the FPMFC was examined by continuously feeding a solution containing wastewater, or a specific substrate, into the anode chamber. The system was initially acclimated for 1 month using domestic wastewater orwastewater enriched with a specific substrate such as acetate. Average power density using only domestic wastewater was 72+/-1 mW/m2 at a liquid flow rate of 0.39 mL/min [42% COD (chemical oxygen demand) removal, 1.1 h HRT (hydraulic retention time)]. At a longer HRT = 4.0 h, there was 79% COD removal and an average power density of 43+/-1 mW/m2. Power output was found to be a function of wastewater strength according to a Monod-type relationship, with a half-saturation constant of Ks = 461 or 719 mg COD/L. Power generation was sustained at high rates with several organic substrates (all at approximately 1000 mg COD/L), including glucose (212+/-2 mW/ m2), acetate (286+/-3 mW/m2), butyrate (220+/-1 mW/ m2), dextran (150+/-1 mW/m2), and starch (242+/-3 mW/ m2). These results demonstrate the versatility of power generation in a MFC with a variety of organic substrates and show that power can be generated at a high rate in a continuous flow reactor system.


Using Transition State Modeling To Predict Mutagenicity for Michael Acceptors.
The Ames mutagenicity assay is a long established in vitro test to measure the mutagenicity potential of a new chemical used in regulatory testing globally. One of the key computational approaches to modeling of the Ames assay relies on the formation of chemical categories based on the different electrophilic compounds that are able to react directly with DNA and form a covalent bond. Such approaches sometimes predict false positives, as not all Michael acceptors are found to be Ames-positive. The formation of such covalent bonds can be explored computationally using density functional theory transition state modeling. We have applied this approach to mutagenicity, allowing us to calculate the activation energy required for α,β-unsaturated carbonyls to react with a model system for the guanine nucleobase of DNA. These calculations have allowed us to identify that chemical compounds with activation energies greater than or equal to 25.7 kcal/mol are not able to bind directly to DNA. This allows us to reduce the false positive rate for computationally predicted mutagenicity assays. This methodology can be used to investigate other covalent-bond-forming reactions that can lead to toxicological outcomes and learn more about experimental results.


Evaluation of p27 Expression in Salivary Gland Neoplasms; A Step Forward in Unveiling the Role of p27.
Salivary gland neoplasms are not uncommon lesions that are seen in the head and neck region. The role of cell cycle regulators as well as that of oncogenes remains unexplored in the pathogenesis of these neoplasms. Present study was conducted to evaluate the expression of p27 in the three common salivary gland neoplasms. A total of 34 cases (19 pleomorphic adenoma, 8 mucoepidermoid carcinoma and 7 adenoid cystic carcinoma) were included. The sections were subjected to p27 staining and rated for the expression. Of the total 52.6% of pleomorphic adenoma cases, 25% of mucoepidermoid carcinoma cases and only 14.2% of adenoid cystic carcinoma cases showed strong expression suggesting variable p27 expression in both malignant neoplasms. Normal salivary gland tissue was stained as a positive control for the evaluation. The results of the study suggest an important role for p27 in pathogenesis of mucoepidermoid carcinoma as well as adenoid cystic carcinoma while its role in pathogenesis of pleomorphic adenoma remains questionable keeping in view the strong expression of p27 in the same.


[Qulerulousness--a disappearing psychopathologic behavioral disorder?].
Compulsive Querulousness (CQ) is a term for behaviour characterised by an exaggerated feeling of righteousness and is not a specific ingredient of any particular psychiatric illness. CQ was well represented in psychiatric literature until the year 1960 both in textbooks and in single-case studies, but has disappeared from clinical psychiatric interest in the last 30 years. In the first part of our study we present the syndrome in its various facets (epidemiology, aetiology, categorisation, symptoms, therapy). In an epidemiological study we extracted in chronological order all patients with compulsively querulous behaviour hospitalised in our clinic during the years 1922-1951 and 1964-1993. We found the compulsively querulous behaviour has been more rarely diagnosed in the last 30 years. Possible reasons for this are the CQ was used in more negative terms in former times than today and, consequently, there is a tendency today to avoid the term CQ even in cases of clearly querulous behaviour. In the second part we present, in a cross-sectional study, biographical and personality characteristics of all "legal compulsively querulous persons" hospitalised during 60 years--a characteristic subsection of persons with compulsively querulous behaviour. We found, among other facts, a predominance of male gender, of medium or higher education and professional status, a trigger experience of injustice, and discuss their relevance in the formation of compulsive querulous development.


Iatrogenic pronator syndrome: case report.
A case of congenital radio-ulnar synostosis with functional disability due to fixation of the forearm in maximal pronation was operated on with a rotational osteotomy in the proximal third of the forearm. Within four days postoperatively a total paralysis of the median nerve gradually developed. The median nerve was therefore explored and found to be strongly compressed by the stretched pronator teres and the superficialis bridge which were sectioned. Full motor and sensory recovery gradually occurred.


Complete mitochondrial genome of the natural pentaploid loach, Misgurnus anguillicaudatus (Teleostei: Cypriniformes: Cobitididae).
The complete mitochondrial genome of the natural pentaploid loach Misgurnus anguillicaudatus is a circular molecule of 16,643 bp in size, containing 13 protein-coding genes, 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and two main noncoding regions (the control region and the origin of the light strand replication). Most of the genes are encoded on the heavy strand, except for ND6 and eight tRNAs. The control region is 918 bp in length and located between the tRNA(Pro) and tRNA(Phe) genes, some typical conserved elements (TAS, CSB1-3 and CSB D-F) were found in this region. All these features reflect a typical vertebrate mitochondrial gene arrangement of the pentaploid M. anguillicaudatus.


Information about first-trimester screening and self-reported distress among pregnant women and partners - comparing two methods of information giving in Sweden.
Balanced information before prenatal diagnosis (PND) aims to help expectant parents to make an informed choice. However, it is important that the information does not increase the expectant parents' psychological distress. The aim was to examine psychological distress among expectant parents, before and after receiving information about PND, to evaluate the possible differences between two different procedures of information giving, and to evaluate the association between satisfaction with the information and psychological distress. A longitudinal design, based on questionnaire data from 380 expectant parents from four counties in Sweden. The measurement points; T1, before the information about PND was given and T2, 2 weeks after the prenatal screening or 15 weeks of gestation. The Hospital Anxiety and Depression Scale (HADS) and the Swedish version of the Cambridge Worrying Scale (CWS) measured psychological distress. The Satisfaction with Genetic Counseling Scale (SCS) measured satisfaction with information about PND. The rate of psychological distress was stable among the pregnant women, but decreased among their partners, after the information was received. General anxiety and the social-medical dimension of pregnancy-related worry decreased among the participants who received information, using the more distinct two-stage process (group A), but was unchanged in group B (less distinct two-stage process). Health-related worry decreased in both groups, whereas relational worry and level of depressive symptoms were unchanged in both groups. Information about PND does not increase the psychological distress among expectant parents. A more distinct two-stage process of information giving might even decrease their anxiety.


Standardized nomenclature for peripheral percutaneous cannulation of the pulmonary artery in extracorporeal membrane oxygenation: Current uptake and recommendations for improvement.
The rising application of extracorporeal membrane oxygenation (ECMO) has emphasized the need for consistent and standardized terminology, especially concerning peripheral percutaneous cannulation of the pulmonary artery (PPC-PA). The Extracorporeal Life Support Organization (ELSO) Nomenclature Task Force produced the ELSO Maastricht Treaty for extracorporeal life support (ECLS) Nomenclature to address this challenge. However, adherence to nomenclature recommendations has been poor in publications describing PPC-PA. We aim to describe common nomenclature errors and provide a user-guide for abbreviations that can be used by authors, reviewers, and journal staff to ensure properadherence to standardized nomenclature in publications describing PPC-PA.


The influence of early menopause on cardiovascular risk in women with rheumatoid arthritis.
Early menopause is associated with an increased risk for developing rheumatoid arthritis (RA). The risk for cardiovascular disease (CVD) in women increases following menopause. Because RA is associated with an increased risk of CVD, this study was undertaken to determine whether early menopause affects the risk of developing CVD in women with RA. A population-based inception cohort of 600 women with RA who fulfilled 1987 American College of Rheumatology criteria for RA between 1955 and 2007 and were age ≥ 45 years at diagnosis was assembled and followed. Age at menopause and duration of hormone replacement therapy, along with occurrence of CVD, was ascertained by review of medical records. Cox proportional hazard models compared women who underwent early menopause (natural or artificial menopause at age ≤ 45 yrs) to those within the cohort who did not undergo early menopause. Of 600 women, 79 experienced early menopause. Women who underwent early menopause were at significantly higher risk for developing CVD when compared to women who did not (HR 1.56; 95% CI 1.08-2.26). The risk of CVD in women with RA was higher in those who experienced early menopause, and like other known risk factors should increase clinician concern for development of CVD in these patients.


Expression of ZO-1 and occludin in normal human placenta and in hydatidiform moles.
Zonula occludens-1 (ZO-1) and occludin are key molecules in cell-cell contacts. They are tight junction constituents and therefore play a pivotal role in tissue differentiation and organogenesis. In the present report we have investigated the expression of ZO-1 and occludin in normal human placentae and in hydatidiform moles using immunohistochemical and Western blot analyses. In normal placentae, ZO-1 and occludin were mainly localized in the apical part of the syncytium, in cell-cell contacts between syncytium and villous cytotrophoblastic cells as well as between the latter. Extravillous cytotrophoblast of cell islands and cell columns was positive for ZO-1 and occludin in the cell layers proximally located to the villous stroma whereas the cytotrophoblastic cells, distally located from the villous stroma, were totally negative. Furthermore, fetal vessels showed a positive staining pattern for ZO-1 throughout gestation, whereas a positive reaction for occludin was produced mainly at term. A striking result was the altered expression of ZO-1 and occludin in partial and complete moles. In 11 moles, these two molecules were not expressed at all, while in the other nine, their expression was only cytoplasmic in syncytium and villous cytotrophoblastic cells. These findings suggest that ZO-1 and occludin participate in normal placental development, maintaining the organization and functions of different tissue components. The down-regulation and/or dysregulation of these two molecules may be related to phenotypic changes associated with epithelial cell transformation of the chorionic villi in partial and complete moles.


Integrative control of coronary resistance vessel tone by endothelin and angiotensin II is altered in swine with a recent myocardial infarction.
Several studies have indicated an interaction between the renin-angiotensin (ANG II) system and endothelin (ET) in the regulation of vascular tone. Previously, we have shown that both ET and ANG II exert a vasoconstrictor influence on the coronary resistance vessels of awake normal swine. Here, we investigated whether the interaction between ANG II and ET exists in the control of coronary resistance vessel tone at rest and during exercise using single and combined blockade of angiotensin type 1 (AT(1)) and ET(A)/ET(B) receptors. Since both circulating ANG II and ET levels are increased after myocardial infarction (MI), we investigated if the interaction between these systems is altered after MI. In awake healthy swine, coronary vasodilation in response to ET(A)/ET(B) receptor blockade in the presence of AT(1) blockade was similar to vasodilation produced by ET(A)/ET(B) blockade under control conditions. In awake swine with a 2- to 3-wk-old MI, coronary vasodilator responses to individual AT(1) and ET(A)/ET(B) receptor blockade were virtually abolished, despite similar coronary arteriolar AT(1) and ET(A) receptor expression compared with normal swine. Unexpectedly, in the presence of AT(1) blockade (which had no effect on circulating ET levels), ET(A)/ET(B) receptor blockade elicited a coronary vasodilator response. These findings suggest that in normal healthy swine the two vasoconstrictor systems contribute to coronary resistance vessel control in a linear additive manner, i.e., with negligible cross-talk. In contrast, in the remodeled myocardium, cross-talk between ANG II and ET emerges, resulting in nonlinear redundant control of coronary resistance vessel tone.