Aspartame and dental caries in the rat.
Aspartame (NutraSweet--The NutraSweet Co., Deerfield, IL) an artificial intense sweetener, was tested for its cariogenicity alone and in the presence of sucrose. Sprague-Dawley rat pups (Charles River Laboratories, Bloomington, MA) inoculated with Streptococcus mutans were fed basal diet 2000 with one of the following added: 50% sucrose; 30% sucrose; 30% sucrose + 0.15% aspartame; 0.30% aspartame; 0.15% aspartame and no addition. The animals were sacrificed after eight weeks. Caries was evaluated using Keyes' technique. It was found that the addition of 0.15% aspartame to 30% sucrose diet significantly reduced caries in comparison to rats fed only 30% sucrose diet. In animals fed aspartame only, there was no caries. The S. mutans counts were high in the animals receiving sucrose diets with and without aspartame. The animals receiving only aspartame had very low S. mutans counts.


Increased expression of TGF-beta 1 in brain tissue after ischemic stroke in humans.
Occlusion in cerebral vessels results in ischemic stroke and is followed by proliferation of microvessels, ie, angiogenesis. The process is particularly marked in the border zone of the infarct, known as the ischemic penumbra. This increase in vascularization is likely to be caused by the action of angiogenic factors, such as TGF-beta 1, which is a powerful regulator of angiogenesis. In this study we examined 10 brain samples from patients who suffered from ischemic stroke for the expression of mRNA encoding TGF-beta 1. The ischemic penumbra contained the highest levels of TGF-beta 1 mRNA, whereas the normal contralateral hemispheres had the least (P < .001, Mann-Whitney U test). Unlike those from normal brain, protein extracts from infarcted tissue contained active TGF-beta 1 as a 25-kD band in Western blot analysis. Extracts from the penumbra also contained a 12.5-kD isoform of TGF-beta 1. Both penumbra and infarct contained TGF-beta 1 immunoreactive products as assessed with immunohistochemistry, whereas very weak staining was observed in the contralateral hemisphere. These results suggest that TGF-beta 1 is important in the pathogenesis of the angiogenic response in ischemic brain tissue and its modulation may be used for therapeutic purposes.


Learning from small fry: the zebrafish as a genetic model organism for aquaculture fish species.
In recent years, the zebrafish has become one of the most prominent vertebrate model organisms used to study the genetics underlying development, normal body function, and disease. The growing interest in zebrafish research was paralleled by an increase in tools and methods available to study zebrafish. While zebrafish research initially centered on mutagenesis screens (forward genetics), recent years saw the establishment of reverse genetic methods (morpholino knock-down, TILLING). In addition, increasingly sophisticated protocols for generating transgenic zebrafish have been developed and microarrays are now available to characterize gene expression on a near genome-wide scale. The identification of loci underlying specific traits is aided by genetic, physical, and radiation hybrid maps of the zebrafish genome and the zebrafish genome project. As genomic resources for aquacultural species are increasingly being generated, a meaningful interaction between zebrafish and aquacultural research now appears to be possible and beneficial for both sides. In particular, research on nutrition and growth, stress, and disease resistance in the zebrafish can be expected to produce results applicable to aquacultural fish, for example, by improving husbandry and formulated feeds. Forward and reverse genetics approaches in the zebrafish, together with the known conservation of synteny between the species, offer the potential to identify and verify candidate genes for quantitative trait loci (QTLs) to be used in marker-assisted breeding. Moreover, some technologies from the zebrafish field such as TILLING may be directly transferable to aquacultural research and production.


Morphologic Analysis of M2 Macrophage in Glioblastoma: Involvement of Macrophage Extracellular Traps (METs).
Macrophages are classified into two phenotypes, M1 and M2, based on their roles. M2 macrophages suppress inflammation and increase in proportion to the malignancy of brain tumors. Recently, macrophage extracellular traps (METs), which change into a network, have been reported as a unique form of macrophage cell death. In this study, immunohistochemical analysis of macrophages in METs in human glioblastoma was performed. To distinguish between M1 and M2 macrophages, multiple immunostainings with Iba1 combined with CD163 or CD204 were performed. M2 macrophages were present in small amounts in normal and borderline areas but showed an increasing trend as they shifted to tumor areas, and most of them were the activated- or phagocytic-type. We also successfully detected METs coexisting with fibrin and lactoferrin near the border between the tumor and necrotic area. M2 macrophages not only suppressed inflammation but also were involved in the formation of METs. This study found that M2 macrophages play various roles in unstable situations.


Vaginal bleeding patterns in women receiving hormone replacement therapy. Impact of various progestogen regimens.
Postmenopausal bleeding is more prevalent than was previously thought, occurring in women regardless of whether or not they are on hormone replacement therapy. While estrogen-only regimens have been used for several beneficial effects, bleeding patterns associated with these regimens can be irregular and unpredictable, causing discomfort to the patient as well as increasing the risk of both endometrial hyperplasia and carcinoma. Studies in recent years have examined the effects of estrogen-only regimens as compared to different estrogen-plus-progestogen combination therapies to help regulate and minimize postmenopausal bleeding while providing endometrial protection.


A rice homolog of Cdk7/MO15 phosphorylates both cyclin-dependent protein kinases and the carboxy-terminal domain of RNA polymerase II.
The activation of cyclin-dependent protein kinases (CDKs) requires phosphorylation of a threonine residue within the T-loop by a CDK-activating kinase (CAK). The R2 protein of rice is very similar to CAKs of animals and fission yeast at the amino acid level but phosphorylation by R2 has not yet been demonstrated. When R2 was overexpressed in a CAK-deficient mutant of budding yeast, it suppressed the temperature sensitivity of the mutation. Immunoprecipitates of rice proteins with the anti-R2 antibody phosphorylated human CDK2, one of the rice CDKs (Cdc2Os1), and the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II of Arabidopsis. Mutational analysis indicated that R2 phosphorylated the threonine residue within the T-loop of CDK2 and Cdc2Os1. R2 was found mainly in two protein complexes which had molecular masses of 190 kDa and 70 kDa, respectively, whilst the CDK- and CTD-kinase activities associated with R2 were identified in a complex of 105 kDa. These results indicate that R2 is closely related to CAKs of animals and fission yeast in terms of its phosphorylation activity and, moreover, that this CAK of rice is distinct from a CAK of the dicotyledonous plant Arabidopsis.


Effect of prophylactic endoscopic clipping for prevention of delayed bleeding after endoscopic papillectomy for ampullary neoplasm: a multicenter randomized trial.
BACKGROUND : Endoscopic clip placement is technically challenging using a duodenoscope, limiting their application for treatment of bleeding after endoscopic papillectomy. This study evaluated the efficacy of newly designed clips to prevent bleeding after endoscopic papillectomy. METHODS : Patients (n = 80) with suspected benign adenomas on the major papilla who were scheduled for endoscopic papillectomy with or without clipping were randomized. A new duodenoscope-compatible clip capable of being rotated, reopened, and repeatedly repositioned was used. The primary end point was incidence of delayed bleeding. RESULTS : The clipping procedure was successful in all patients. The incidence of delayed bleeding was nonsignificantly higher in the no-clipping group than in the clipping group (31.6 % [95 % confidence interval (CI) 19.1-47.5] vs. 15.0 % [95 %CI 7.1-29.1]). The incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis did not differ significantly between the groups (clipping vs. no-clipping: 17.5 % [95 %CI 8.7-31.9] vs. 5.3 % [95 %CI 1.5-17.3]), and all cases were mild. CONCLUSIONS : Placement of the newly designed rotatable clip was technically feasible and tended to have a protective effect by preventing delayed bleeding after endoscopic papillectomy, although statistical significance was not reached.


Audit of near patient cholesterol testing in occupational health clinics.
An audit of near patient cholesterol testing was carried out in occupational health clinics. The aims were to examine the statistical agreement between Reflotron and laboratory measurements of blood cholesterol and to formulate a policy for the use of Reflotrons in cholesterol testing. Three hundred and fifty-two staff members attending occupational health clinics over a period of 10 months had blood taken for both Reflotron and laboratory measurements. The correlation between the two methods was 0.95. The Reflotron had a negative bias compared to the laboratory, with the mean difference between the two methods of measurement being -0.21 mmol/l (95 per cent confidence interval -0.18 to -0.25 mmol/l). Despite the high correlation coefficient and small mean difference, the scatter of Reflotron-laboratory differences was broad, with 95 per cent of the differences lying in the range of 0.95 mmol/l below to 0.52 mmol/l above the laboratory result. For Reflotron results of 5.50 mmol/l and greater, the sensitivity and specificity of the Reflotron in detecting subjects with laboratory cholesterol levels greater than 6.5 mmol/l were 100 per cent and 70 per cent respectively. The laboratory participated in two external quality assessment schemes for cholesterol testing during the course of the audit and all the results of these fell within the acceptable limits. The audit demonstrated that the Reflotron was too imprecise to be used to give accurate measurements of blood cholesterol. However, providing a suitable Reflotron result above which patients were sent for confirmatory laboratory testing was selected, it was an acceptable screening device in the detection of hypercholesterolaemia. Other Reflotron users should consider carrying out similar audits.


Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis.
The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.


Identifying young adult substance abusers: the Rutgers Collegiate Substance Abuse Screening Test.
Substance abuse is a serious problem in the young adult population, yet there exists a lack of reliable screening measures for use in identifying problem users in this age group. The Rutgers Collegiate Substance Abuse Screening Test (RCSAST) is a 25-item, true/false questionnaire that was created to provide a reliable means of identifying young adult substance abusers. Three groups completed the RCSAST: a clinical sample of 84 young adult, problem substance users; a group of 33 young adults who were referred to an assistance program but were judged not to have a substance use problem; and a control sample of 87 young adult, nonproblem substance users. The RCSAST correctly classified 94% of the clinical subjects as problem users, and 89% of the control subjects as nonproblem users. The difference between the average total scores for the two groups was highly significant. In addition, the RCSAST was able to distinguish between problem and nonproblem users within the sample of subjects who were referred for evaluation. The findings support the use of the RCSAST in identifying young adult substance abusers.


Mindfulness and eating behavior in adolescent girls at risk for type 2 diabetes.
The purpose of this investigation was to examine the relationship of dispositional mindfulness to binge eating and associated eating attitudes and behaviors among adolescent girls at risk for type 2 diabetes (T2D). Participants were 114 overweight or obese adolescents enrolled in a study of girls with a family history of T2D and mild depressive symptoms. Adolescent self-reports of mindfulness, eating in the absence of hunger, and depressive symptoms were collected. An interview was administered to determine presence of binge eating episodes and a behavioral task was used to assess the reinforcing value of food relative to other nonsnack food rewards. Body composition was assessed using dual-energy X-ray absorptiometry. In analyses accounting for race, percent body fat, lean mass, height, age, and depressive symptoms, dispositional mindfulness was associated with a lower odds of binge eating (p = .002). Controlling for the same potential confounds, mindfulness was also inversely associated with eating concern, eating in the absence of hunger in response to fatigue/boredom, and higher food reinforcement relative to physical activity (all p < .05). In girls with a family history of T2D, independent of body composition and depressive symptoms, intraindividual differences in mindfulness are related to binge eating and associated attitudes and behaviors that may confer risk for obesity and metabolic problems. Further research is needed to determine the extent to which mindfulness plays a role in the etiology and/or maintenance of disinhibited eating in adolescents at risk for T2D.


High Plasticity of the Amicetin Biosynthetic Pathway in Streptomyces sp. SHP 22-7 Led to the Discovery of Streptcytosine P and Cytosaminomycins F and G and Facilitated the Production of 12F-Plicacetin.
A chemical reinvestigation of the Indonesian strain Streptomyces sp. SHP 22-7 led to the isolation of three new pyrimidine nucleosides, along with six known analogues and zincphyrin. The structures of the new compounds (6, 7, 10) were elucidated by employing spectroscopic techniques (NMR, MS, CD, and IR) as well as enantioselective analyses of methyl branched side chain configurations. Application of the precursor-directed feeding approach led to the production and partial isolation of nine further pyrimidine analogues. The new compounds 6, 7, and 11 and three of the known compounds (2-4) were found to possess antimycobacterial and cytotoxic properties.


Word-level prosodic measures and the differential diagnosis of apraxia of speech.
Impaired production of prosody is considered a primary diagnostic criterion for apraxia of speech. In this study, we examined diagnostic relevance for five word-level prosody measures. Seven speakers with AOS, nine with aphasia and no AOS, and 19 age-matched neurotypical controls produced nine words consisting of three or four syllables. Lexical stress indices were computed based on relative values for duration, fundamental frequency, and intensity across pairs of unstressed-stressed syllables with varying intrinsic vowel duration contrast patterns. A simple average syllable duration measure was also obtained. AOS speakers differed from the other two groups on three metrics that were solely or primarily derived from duration measures. The degree of diagnostic overlap was smallest for the syllable duration metric, which also showed the strongest inter-observer reliability and most complete overlap between neurotypical speakers and speakers with aphasia and no AOS. Vowel intrinsic durational properties affected lexical stress metrics significantly, indicating a need to select word targets purposefully. Based on these results, it appears that the average syllable duration metric is a more stable and informative alternative for differential diagnostic purposes. The results will, however, need to be replicated in a larger sample.


Predictors of pathological complete response to neoadjuvant treatment and changes to post-neoadjuvant HER2 status in HER2-positive invasive breast cancer.
The response of human epidermal growth factor receptor2 (HER2)- positive breast cancer (BC) patients to anti-HER2 targeted therapy is significant. However, the response is not uniform and a proportion of HER2-positive patients do not respond. This study aims to identify predictors of response in the neoadjuvant treatment and to assess the discordance rate of HER2 status between pre- and post-treatment specimens in HER2-positive BC patients. The study group comprised 500 BC patients treated with neoadjuvant chemotherapy (NACT) and/or neoadjuvant anti-HER2 therapy and surgery who had tumours that were 3+ or 2+ with HER2 immunohistochemistry (IHC). HER2 IHC 2+ tumours were classified into five groups by fluorescence in situ hybridisation (FISH) according to the 2018 ASCO/CAP guidelines of which Groups 1, 2 and 3 were considered HER2 amplified. Pathological complete response (pCR) was more frequent in HER2 IHC 3+ tumours than in HER2 IHC 2+/HER2 amplified tumours, when either in receipt of NACT alone (38% versus 13%; p = 0.22) or neoadjuvant anti-HER2 therapy (52% versus 20%; p < 0.001). Multivariate logistic regression analysis showed that HER2 IHC 3+ and histological grade 3 were independent predictors of pCR following neoadjuvant anti-HER2 therapy. In the HER2 IHC 2+/HER2 amplified tumours or ASCO/CAP FISH Group 1 alone, ER-negativity was an independent predictor of pCR following NACT and/or neoadjuvant anti-HER2 therapy. In the current study, 22% of HER2-positive tumours became HER2-negative by IHC and FISH following neoadjuvant treatment, the majority (74%) HER2 IHC 2+/HER2 amplified tumours. Repeat HER2 testing after neoadjuvant treatment should therefore be considered.


Clinical features of AIDS in the Edinburgh City Hospital cohort.
In order to describe the clinical features of AIDS, particularly injection drug use (IDU) related AIDS in patients attending the Regional Infectious Diseases Unit in Edinburgh a prospective review of the 680 HIV-positive patients, 30% of whom were women and 68% were infected via IDU was undertaken. The commonest AIDS-related clinical problem in Edinburgh was Pneumocystis carinii pneumonia (PCP). Whilst gender differences were not apparent in terms of clinical problems, differences were observed in risk groups as previously reported; Kaposi's sarcoma (KS), cytomegalovirus (CMV) and toxoplasmosis were commoner in homo/ bisexuals whilst oesophageal candidiasis was commoner in drug users. Extrapulmonary tuberculosis was uncommon unlike cohorts from the USA or Italy. Each patient with AIDS can expect 1-2 AIDS-related clinical events per year of survival. Considerable differences in mortality rates by risk group but not by gender were observed and explanations for this difference need to be considered further. The mortality rates for drug users were however remarkably similar to published rates from Amsterdam and the Bronx, New York.


Acute lymphoblastic leukaemia incidence in the UK by immunophenotype.
The incidence of acute lymphoblastic leukaemia (ALL) is described for both children and adults for the three major immunophenotypes: null, CD10-positive (CD+) which includes both common and pre-B types, and T-cell (including pre-T variants). The data are derived from a population-based specialist registry of leukaemias and lymphomas covering approximately one-half of England and Wales. Null ALL predominates in those under 1 year old and CD10+ ALL in the 1-7 year olds. There is a male excess at all ages for T-cell disease, which is particularly prominent in adolescents and young adults. The effect of socioeconomic levels is seen most clearly for CD10+ ALL in the childhood peak, where B-cell precursor disease occurs more frequently in areas of higher socioeconomic status.


The effects of hydrodynamic stretch on the flame propagation enhancement of ethylene by addition of ozone.
The effect of O(3) on C(2)H(4)/synthetic-air flame propagation at sub-atmospheric pressure was investigated through detailed experiments and simulations. A Hencken burner provided an ideal platform to interrogate flame speed enhancement, producing a steady, laminar, nearly one-dimensional, minimally curved, weakly stretched, and nearly adiabatic flame that could be accurately compared with simulations. The experimental results showed enhancement of up to 7.5% in flame speed for 11 000 ppm of O(3) at stoichiometric conditions. Significantly, the axial stretch rate was also found to affect enhancement. Comparison of the flames for a given burner exit velocity resulted in the enhancement increasing almost 9% over the range of axial stretch rates that was investigated. Two-dimensional simulations agreed well with the experiments in terms of flame speed, as well as the trends of enhancement. Rate of production analysis showed that the primary pathway for O(3) consumption was through reaction with H, leading to early heat release and increased production of OH. Higher flame stretch rates resulted in increased flux through the H+O(3) reaction to provide increased enhancement, due to the thinning of the flame that accompanies higher stretch, and thus results in decreased distance for the H to diffuse before reacting with O(3).


Pawedness and motor asymmetries in toads.
Pawedness was investigated in three species of toads, Bufo bufo , Bufo viridis , and Bufo marinus. Samples from natural populations were collected in two successive years and tested during attempts to remove a strip of paper stuck onto the snout ( Bufo bufo and Bufo viridis ) or during attempts to remove an elastic balloon wrapped around the head ( Bufo bufo ). A preferential right forelimb use at the population level was observed in Bufo bufo in both tests, whereas no clear pawedness was observed in Bufo viridis. Bufo marinus also showed no laterality in the paper-strip test, but it appeared to be strongly lateralised in another test that investigated which side the toad rotated when turned on its back underwater. Preferentially turning to the toad's left side as part of a righting response, Bufo marinus released the left forelimb first, using the right forelimb to control the roll to the upright position, and push to the surface. These results suggest that preferential limb use has a long evolutionary history, which dates back to early tetrapods.


[A case of isolated tuberculosis of the appendix at the University Hospital Center in Brazzaville, Congo].
Since the outbreak of human immunodeficiency virus (HIV) infection, extrapulmonary tuberculosis has become increasingly frequent in developing countries. The purpose of this report is to describe a case of isolated tuberculosis of the appendix diagnosed following generalized peritonitis in a 53-year-old man. The appendix is the least frequent gastrointestinal location of isolated tuberculosis. Diagnosis was achieved by histopathological examination of the appendix immersed in formalin 10% after appendectomy. Paraffin-embedded histological sections stained with hematoxylin-eosin (HE) displayed caseofollicular lesions characteristic of infection by Koch bacillus. Outcome was favourable with a 9-month regimen of antituberculosis treatment according to the protocol of the World Health Organization (WHO).


Opinion: A role for placebo therapy in psychogenic movement disorders.
Psychogenic movement disorders (PMDs) mimic known movement disorders but are not attributed to an underlying neurological pathology and are generally thought to have a psychological origin. Owing to the lack of a clear pathology, patients often experience multiple referrals, frequent office visits, and numerous--often fruitless--technically sophisticated tests and interventions. No standard of care exists for PMDs, and affected patients can experience debilitating symptoms for a lifetime. Some physicians advocate the use of placebo treatment for patients with PMDs, and placebo therapy can have beneficial neurophysiological effects. Innovative research will be necessary to develop effective therapeutics for psychogenic disorders and to make recommendations for future clinician training and health care policy. This Perspectives article aims to trigger international dialogue focusing on the diagnosis and treatment of patients with PMDs, and to reframe and deepen discussion of placebo prescribing for PMDs and beyond.


When causality does not imply correlation: more spadework at the foundations of scientific psychology.
Experimental research in psychology is based on an open-loop causal model which assumes that sensory input causes behavioral output. This model was tested in a tracking experiment where participants were asked to control a cursor, keeping it aligned with a target by moving a mouse to compensate for disturbances of differing difficulty. Since cursor movements (inputs) are the only observable cause of mouse movements (outputs), the open-loop model predicts that there will be a correlation between input and output that increases as tracking performance improves. In fact, the correlation between sensory input and motor output is very low regardless of the quality of tracking performance; causality, in terms of the effect of input on output, does not seem to imply correlation in this situation. This surprising result can be explained by a closed-loop model which assumes that input is causing output while output is causing input.


Treatment outcomes for students with learning disabilities: how important are internal and external validity?
This study analyzed the magnitude of experimental intervention outcomes as a function of violations in internal and external validity for studies that included students with learning disabilities. The results indicated that treatment outcomes were significantly affected by the following violations: teacher effects, establishing criterion levels of instructional performance, reliance on experimental measures, using different measures between pretest and posttest, using a sample heterogenous in age, and using incorrect units of analysis. Furthermore, the underreporting of information related to ethnicity, locale of the study, psychometric data, and teacher applications positively inflated the magnitude of treatment outcomes. A weighted hierarchical regression analysis revealed that composite scores of the aforementioned high-risk variables accounted for 16% of the total variance in effect size. The implications for interpreting intervention research to practice are discussed.


Identification and immunocytochemical localization of proctolin in pericardial organs of the shore crab, Carcinus maenas.
The occurrence of proctolin (Arg-Tyr-Leu-Pro-Thr) in crab neurohemal pericardial organs (POs) has been demonstrated by isolation of the pentapeptide by HPLC and manual microsequencing according to the DABITC-PITC double coupling technique. From one pair of POs approximately 5.4 pmol were obtained (= 45 pmol/mg protein). Immunocytochemically, an extensive system of positive structures was found in both whole mount preparations and semithin sections, consisting of numerous varicose fibres of varying diameter and many knoblike neurosecretory terminals abutting upon the epineurium of the PO trunks. The relatively high concentration in the POs as well as the pattern of proctolin-positive fibres and terminals clearly suggest a neurohormonal role of the pentapeptide in decapod crustaceans.


Secular changes in cognitive predictors of dementia and mortality in 70-year-olds.
Successive elderly birth cohorts improved in cognitive performance during the 20th century. It is not clear whether this influences cognitive predictors of dementia and mortality. In 2 longitudinal population studies, representing 2 cohorts of 70-year-olds examined 30 years apart, we investigated the relation between baseline cognitive function and 5-year occurrence of dementia and mortality. Two representative cohorts of 70-year-olds initially free from dementia born in 1901-1902 (cohort 1901-1902: n = 381) and 1930 (cohort 1930: n = 551) from Gothenburg, Sweden, were examined in 1971-1972 and 2000-2001 and after 5 years for the outcome of dementia and death. Recent memory was evaluated during psychiatric examinations, and nonmemory domains using psychometric tests. At age 70, cohort 1930 performed better on psychometric tests, and had fewer recent memory problems compared to cohort 1901-1902. During 5-year follow-up, 5.0% in cohort 1901-1902 and 4.4% in cohort 1930 (p = 0.742) developed dementia, and 15.7% in cohort 1901-1902 and 4.4% in cohort 1930 died (p < 0.001). Recent memory was associated with incident dementia in both cohorts. Low scores in nonmemory tests were associated with incident dementia in cohort 1901-1902, but not in cohort 1930. Recent memory problems and lower scores in nonmemory tests were associated with 5-year mortality in cohort 1901-1902, but not in cohort 1930. Secular changes in cognitive performance may influence cognitive predictors of dementia and mortality, despite similar incidence of dementia. The findings should be taken cautiously due to differences between cohorts in refusal rates, quality of education, and dementia recognition in medical records.


Public participation in health planning agencies: promise and practice.
Federal legislation provided an opportunity for health planning to "catch up" with the expanding citizen participation movements of recent years. Although the literature on health planning is mounting, there as yet has been no comprehensive, systematic effort to inventory the status of participation on a national scale. This note reports on a national study of Health Systems Agencies designed to inventory the participation objectives and methods in use, identify major participants and obstacles, and analyze impacts and factors influencing practice in the field. Among the findings are that agencies have favored "safe" participation methods that satisfy minimum federal requirements and provide information and public relations without transfer of power to consumers; and have broadened the base of participation in planning without mobilizing consumers or reducing the dominance of providers, who remain the most active, organized, and influential participants.


Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma.
Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). In our previous study, transcatheter arterial infusion chemotherapy using SMANCS for HCC showed a response rate of 20%. In an effort to obtain a superior anti-tumor effect against HCC, we conducted a phase II study of transcatheter arterial embolization (TAE) using SMANCS and gelatin sponge in 50 chemotherapy-naive patients with HCC. Four milligrams SMANCS plus 4 ml lipiodol emulsion was injected into the hepatic artery, followed by an injection of gelatin sponge. The responses were evaluated by computed tomography (CT) 1 month after treatment and thereafter every 3-4 months. One patient (2%) showed complete response and 15 patients (30%) had partial response resulting in an overall response rate of 32% (16/50; 95% confidence interval 19-45%). In 33 patients (66%), the disease remained stable, and 1 patient (2%) showed progressive disease. In 35 patients (70%), the rate of necrotic area to whole tumor was more than 50% according to the evaluation method using lipiodol accumulation in CT. The 1-, 3- and 5-year survival rates were 90, 55 and 19%, respectively. Grade 3 hematological toxicity was observed as thrombocytopenia in 2 patients (4%). Grade 3 and 4 non-hematological toxicity (liver dysfunction) occurred in 17 (34%) and 7 patients (14%), respectively. TAE using SMANCS, which was well tolerated, may be an effective treatment for advanced HCC.


Control of coronary blood flow during exercise.
Under normal physiological conditions, coronary blood flow is closely matched with the rate of myocardial oxygen consumption. This matching of flow and metabolism is physiologically important due to the limited oxygen extraction reserve of the heart. Thus, when myocardial oxygen consumption is increased, as during exercise, coronary vasodilation and increased oxygen delivery are critical to preventing myocardial underperfusion and ischemia. Exercise coronary vasodilation is thought to be mediated primarily by the production of local metabolic vasodilators released from cardiomyocytes secondary to an increase in myocardial oxygen consumption. However, despite various investigations into this mechanism, the mediator(s) of metabolic coronary vasodilation remain unknown. As will be seen in this review, the adenosine, K(+)(ATP) channel and nitric oxide hypotheses have been found to be inadequate, either alone or in combination as multiple redundant compensatory mechanisms. Prostaglandins and potassium are also not important in steady-state coronary flow regulation. Other factors such as ATP and endothelium-derived hyperpolarizing factors have been proposed as potential local metabolic factors, but have not been examined during exercise coronary vasodilation. In contrast, norepinephrine released from sympathetic nerve endings mediates a feed-forward betaadrenoceptor coronary vasodilation that accounts for approximately 25% of coronary vasodilation observed during exercise. There is also a feed-forward alpha-adrenoceptor-mediated vasoconstriction that helps maintain blood flow to the vulnerable subendocardium when heart rate, myocardial contractility, and oxygen consumption are elevated during exercise. Control of coronary blood flow during pathophysiological conditions such as hypertension, diabetes mellitus, and heart failure is also addressed.


[Combination chemotherapy of S-1 +CPT-11 (q 4-5 w) for metastatic gastric cancer].
The effectiveness of systemic chemotherapy for metastatic gastric cancer has already been established. However, a standard chemotherapy still remains uncertain. New agents such as S-1, CPT-11 and taxanes are markedly improving the response rates for gastric cancer. Including these new drugs, several randomized phase III trials are ongoing in Japan. In the near future, the candidate for standard regimen to treat gastric cancer will be reported. In this article, we described the current state of S-1 +CPT-11 combination chemotherapy for gastric cancer. Among various CPT-11 based chemotherapy, S-1 +CPT-11 appears to be the most effective and less toxic treatment.


Effects of medium composition and carbon dioxide on circadian conidiation in neurospora.
Efforts to significantly perturb the timing mechanism, and thus the period, of the rhythm responsible for circadian conidiation in bd, a strain of Neurospora crassa, by altering the medium composition have been unsuccessful. Various salt solutions, sugars, and amino acids do, however, have pronounced effects on growth and conidiation, and thus on the expression and persistence of rhythmicity.Aeration stimulates conidiation in growth-tube cultures, thereby allowing experiments which demonstrate that nearly all strains and species of Neurospora are capable of circadian conidiation. These results extend to Neurospora the generalization that physiological and developmental regulation in all eukaryotic organisms has a circadian component. Aeration also increases the persistence of circadian conidiation suggesting that the damping of rhythmicity previously observed on certain media represents the cessation of conidiation, rather than the stopping of a timing mechanism.Aeration is apparently effective in that it maintains CO(2) levels in growth-tube cultures below a critical concentration. Carbon dioxide was shown to inhibit conidiation in both wildtype and bd strains, with the latter being about 200 times more resistant than the former.


Buddleja officinalis inhibits high glucose-induced matrix metalloproteinase activity in human umbilical vein endothelial cells.
The aim of the present investigation was to investigate whether an aqueous extract of Buddleja officinalis (ABO), a traditional Korean herbal medicine, suppresses the endothelial extracellular matrix degradation under high glucose condition. The incubation with high concentration of glucose (25 mM) increased significantly matrix metalloproteinase (MMP)-2/-9 expressions and activities in primary cultured human umbilical vein endothelial cells (HUVEC). Pretreatment with ABO decreased high glucose-induced increase of MMP-2/-9 activities in a dose-dependent manner. Real time qRT-PCR revealed that high glucose-induced MMP-2/-9 mRNA expression levels were attenuated by pretreatment with ABO. High glucose-induced MCP-1 and IL-8 mRNA expression levels also decreased by ABO. ABO decreased high glucose-induced hydrogen peroxide production, oxidative stress marker. These results provide new insights into the pathophysiological mechanisms for anti-inflammatory properties of ABO in vascular diseases associated with diabetes mellitus.


Distortion Correction for a Brewster Angle Microscope Using an Optical Grating.
A distortion-corrected Brewster angle microscope (DC-BAM) is designed, constructed, and tested based on the combination of an optical grating and a relay lens. Avoiding the drawbacks of most conventional BAM instruments, this configuration corrects the image propagation direction and consequently provides an image in focus over the entire field of view without any beam scanning or imaging reconstruction. This new BAM can be applied to both liquid and solid subphases with good spatial resolution in static and dynamic studies.


Liver gamma-glutamyltransferase activity in viral liver disease.
gamma-Glutamyltransferase (GGT) activity was determined in serum and liver tissue obtained by needle biopsy in 104 patients with viral hepatic disease. The liver GGT activity in these patients was significantly greater than that in the controls. The tissue GGT activity was also significantly greater in the patients with chronic persistent hepatitis than in the patients with acute viral hepatitis or posthepatitic cirrhosis. The serum and tissue GGTs in the patients with non-A, non-B chronic active hepatitis were significantly greater than those in the patients with B-related chronic active hepatitis. The increased serum GGT is due to the synthesis of the enzyme in liver tissue and its release in viral hepatic disease.


Circulating methylated RUNX3 and SFRP1 genes as a noninvasive panel for early detection of colorectal cancer.
This study was conducted to assess the methylation status of runt-related transcription factor 3 (RUNX3) and secreted frizzled-related protein 1 (SFRP1) genes in paired tissue and serum samples of colorectal cancer (CRC), adenomatous, and control subjects and elucidate the association between methylation status on RUNX3 and SFRP1 mRNA expression. Methylation status of RUNX3 and SFRP1 in paired tissue and serum samples and RUNX3 and SFRP1 mRNA expression in tissue from 85 patients with CRC, 40 with adenoma, and 40 healthy controls were determined using methylation-specific PCR and reverse transcription PCR. The frequency RUNX3 and SFRP1 genes methylation was significantly higher in both tissues and serum of CRC patients and was significantly associated with absence of its corresponding mRNA expression. The concordance between tissue and serum methylation status was 94.4% for RUNX3 and 94.3% for SFRP1. Tissue RUNX3 methylation status detected CRC with 63.53% sensitivity and 80.00% specificity, while serum RUNX3 methylation status detected CRC with 60.00% sensitivity and 82.50% specificity. Tissue SFRP1 methylation status showed a sensitivity of 82.35% and specificity of 65.00%, while serum SFRP1 methylation status showed a sensitivity of 77.65% and specificity of 70.00% in detection of CRC. RUNX3/SFRP1/carcinoembryonic antigen (CEA) panel identified CRC with sensitivity of 89.41% in tissue and 84.71% in serum. Our results verified the reliability of using serum RUNX3 and SFRP1 methylation status as a noninvasive biomarker for diagnosis of CRC and that combined detection of RUNX3/SFRP1/CEA panel might be a promising strategy for early detection of CRC.


Two highly specialized histone H1 proteins are the major chromosomal proteins of the sperm of the sea anemone Urticina (Tealia) crassicornis.
The sperm nuclear basic proteins (SNBPs) from a sea anemone (Urticina crassicornis) have been isolated and characterized for the first time. They consist of two sperm-specific members of the histone H1 family with Mr 22,700 and 24,600. They amount to about 60--70% of the total chromosomal sperm proteins. Their amino acid composition and the primary structure of their trypsin-resistant core indicate a strong relation to histone H5 from the nucleated erythrocytes of birds and amphibians as well as to other high sperm-specific H1-like (PL-I) proteins from phylogenetically distant groups. The major presence of histone H1-like protein in the sperm of an organism belonging to such a low phylogenetic group provides experimental support to the hypothesis that SNBPs may all have evolved from a primitive histone precursor.


Evaluating an Aboriginal tobacco social marketing project in Sydney, Australia.
A partnership between three Aboriginal Community Controlled Organisations and a mainstream health service was formed to develop, implement and evaluate a comprehensive and culturally appropriate social marketing project which aimed to encourage smokers to quit smoking. The project also supported quit attempts and promoted denormalisation of smoking. The project was evaluated through baseline (n = 427) and follow-up (n = 611) surveys carried out face-to-face with Aboriginal and/or Torres Strait Islander participants 18 years and older recruited through convenience sampling at community events and venues during 2010-2011 and 2015. The proportion of participants who had made one or more quit attempts increased significantly between baseline and follow-up surveys (54%, 101 out of 187; vs 64%, 189 out of 297; P < 0.05). Participants who had intended to quit within 6 months (AOR, 3.29; 95% CI 1.90-5.68; P < 0.01); and participants disagreeing with the statement "I don't mind if people smoke inside my home" (AOR, 1.74; 95% CI 1.06-2.84; P < 0.05) were significantly more likely to have made one or more quit attempts compared to the respective reference groups. Study findings demonstrate that the project was associated with increased quit attempts. Intention to quit and attitude were found to be the predictors of making a quit attempt. SO WHAT?: Many studies suggest the need to denormalise smoking; this study demonstrated both change in attitudes and an increase in quit attempts. It is recognised that many quit attempts may be needed for long-term smoking cessation.


Drug Interaction between Dexamethasone and Ketoprofen with Thiopental in Male Dogs: Effect on the Recovery from Anesthesia and Pharmacokinetics Parameters.
Drug-drug interactions (DDIs) are an important part of clinical veterinary pharmacology. Forty-two healthy mixed breed male dogs were randomly divided into three groups. The control group (C) received normal saline (1 mg/kg) 5 minutes before intravenous administration of thiopental (17 mg/kg), the T1 group received ketoprofen (2.2 mg/kg), and the T2 group received dexamethasone (0.2 mg/kg) 5 minutes before thiopental, respectively. Clinical parameters of anesthesia, heart rate, respiration rate, and electrocardiography were measured. Serum samples were also used to assay thiopental concentration using the high-performance liquid chromatography (HPLC) method, and then, thiopental pharmacokinetic parameters were calculated. Changes in the heart rate and respiration were significant intragroup differences 5 and 10 minutes after anesthesia, respectively. Recovery time parameters showed a significant increase between T1 and control groups (P < 0.05). Elimination rate and half-life of thiopental in the T1 group compared to the control and T2 groups showed a significant decrease and increase, respectively. In addition, the distribution of thiopental in T1 showed a significant increase compared to other groups. However, thiopental clearance in T1 and T2 groups had no significant difference with control (P > 0.05). It can be concluded that drug interaction between ketoprofen and thiopental causes to change in the pharmacokinetics parameters and recovery time from anesthesia in comparison with dexamethasone.


Insect cuticular hydrocarbon composition influences their interaction with spider capture threads.
Insects represent the main prey of spiders, and spiders and insects co-diversified in evolutionary history. One of the main features characterizing spiders is their web as a trap to capture prey. Phylogenetically, the cribellate thread is one of the earliest thread types that was specialized to capture prey. In contrast to other capture threads, it lacks adhesive glue and consists of nanofibres, which do not only adhere to insects via van der Waals forces but also interact with the insects' cuticular hydrocarbon (CHC) layer, thus enhancing adhesion. The CHC layer consists of multiple hydrocarbon types and is highly diverse between species. In this study, we show that CHC interaction with cribellate capture threads is affected by CHC composition of the insect. We studied the interaction in detail for four insect species with different CHC profiles and observed a differential migration of CHCs into the thread. The migration depends on the molecular structure of the hydrocarbon types as well as their viscosity, influenced by the ambient temperature during the interaction. As a consequence, adhesion forces to CHC layers differ depending on their chemical composition. Our results match predictions based on biophysical properties of hydrocarbons, and show that cribellate spiders can exert selection pressure on the CHC composition of their insect prey.


Resistance to the weevils Cylas puncticollis and Cylas brunneus conferred by sweetpotato root surface compounds.
Seven resistant varieties of sweetpotato were compared with three susceptible varieties in field trials and laboratory bioassays and showed that resistance was an active process rather than an escape mechanism, as field resistant varieties also had reduced root damage and oviposition compared with susceptible varieties in the laboratory. Liquid chromatography-mass spectrometry (LC-MS) of root surface and epidermal extracts showed significant variation in the concentration of hexadecyl, heptadecyl, octadecyl, and quinic acid esters of caffeic and coumaric acid, with higher concentrations correlated with resistance. All compounds were synthesized to enable their positive identification. Octadecyl coumarate and octadecyl caffeate applied to the surface of susceptible varieties in laboratory bioassays reduced feeding and oviposition, as observed on roots of resistant varieties, and therefore are implicated in weevil resistance. Segregating populations from breeding programs can use these compounds to identify trait loci for resistance and enable the development of resistant varieties.


Differential regulation of metabotropic glutamate receptor 5-mediated phosphoinositide hydrolysis and extracellular signal-regulated kinase responses by protein kinase C in cultured astrocytes.
The metabotropic glutamate receptor 5 (mGluR5) exhibits a rapid loss of receptor responsiveness to prolonged or repeated agonist exposure. This receptor desensitization has been seen in a variety of native and recombinant systems, and is thought to result from receptor-mediated, protein kinase C (PKC)-dependent phosphorylation of the receptor, uncoupling it from the G protein in a negative feedback regulation. We have investigated the rapid PKC-mediated desensitization of mGluR5 in cortical cultured astrocytes by measuring downstream signals from activation of mGluR5. These include activation of phosphoinositide (PI) hydrolysis, intracellular calcium transients, and extracellular signal-regulated kinase 2 (ERK2) phosphorylation. We present evidence that PKC plays an important role in rapid desensitization of PI hydrolysis and calcium signaling, but not in ERK2 phosphorylation. This differential regulation of mGluR5-mediated responses suggests divergent signaling and regulatory pathways which may be important mechanisms for dynamic integration of signal cascades.


Immunological and structural characterization of a high affinity anti-fluorescein single-chain antibody.
Single-chain antibody of the (NH2) VL-linker-VH (COOH) design, was constructed based on prototype high affinity anti-fluorescein monoclonal antibody (mAb) 4-4-20. Purified single-chain antibody (SCA) 4-4-20/212 was studied relative to Ig mAb 4-4-20 in terms of ligand binding, kinetics, idiotypy, metatypy, and stability in denaturing agents. Ligand-binding data correlated with metatypic relatedness of the liganded site. Anti-metatypic reagents reacted preferentially with the liganded conformer of the 4-4-20 antibody active site and were unreactive with free ligand and the non-liganded (idiotypic) state. All results were consistent with the conclusion that SCA 4-4-20/212, with a 14-amino acid linker folded into a native conformational state that closely simulated the prototypical mAb. Furthermore, GndHCl unfolding and refolding studies demonstrated H and L chain variable domain intrinsic stability between SCA 4-4-20/212 and a 50 kDa antigen-binding fragment were nearly identical. This suggested CH1 and CL domain interactions may be more prevalent in V region molecular dynamics than structure.


Survey of multicopy single-stranded DNAs and reverse transcriptase genes among natural isolates of Myxococcus xanthus.
Twenty different isolates of the soil bacterium Myxococcus xanthus were examined for the presence of multicopy single-stranded DNA (msDNA)-producing retroelements, or retrons. Each strain was analyzed by ethidium bromide staining for msDNA, 32P labeling of the msDNA molecule by the reverse transcriptase (RT) extension method, and DNA hybridization experiments with probes derived from two retrons, Mx162 and Mx65, previously cloned from M. xanthus DZF1. These analyses revealed that all M. xanthus strains contain an msDNA very similar to Mx162 msDNA, and 13 strains also contain a second smaller msDNA very similar to Mx65 msDNA. In addition, the strains contained retron-encoded genes msr and msd, which code for msDNA, and a gene for RT responsible for the synthesis of msDNA. These genes show greater than 80% nucleotide sequence similarity to retrons Mx162 or Mx65. The near-ubiquitous occurrence of msDNA retrons among M. xanthus strains and their homogeneous nature are in marked contrast to the highly diverse but rarely occurring msDNA-producing elements of Escherichia coli. The possible origin and evolution of RT and retron elements is discussed in view of these findings.


A nanowire-based shift register for display scan drivers.
The development of display scan drivers is an essential step in the effort to develop transparent and flexible display devices based on nanowire transistors. Here we report a transparent nanowire-based shift register that functions as the standard logic circuit of a display scan driver. To form the shift register circuits using only n-type nanowire transistors, a novel circuit structure was introduced to avoid the output voltage drop typical of purely n-type circuits. A circuit simulation based on the measured nanowire transistor characteristics was developed in the planning phase to verify the circuit operation of the shift register. The shift register successfully produced an output of 0-3 V without an output voltage drop while applying an input of 3 V peak to peak. In addition, the shift register was designed to have multiple channels with a randomly oriented nanowire placement method to enhance the operation yield.


The pathogenesis and pathophysiology of gestational diabetes mellitus: Deductions from a three-part longitudinal metabolomics study in China.
Gestational diabetes mellitus (GDM) is a form of diabetes that is first recognised during pregnancy, with no evidence of pre-existing type 1 or type 2 diabetes. The prevalence of GDM has been rising steadily over the past few decades, coinciding with the ongoing epidemic of obesity and type 2 diabetes. Although GDM normally disappears after delivery, women who have been previously diagnosed with GDM are at a greater risk of developing gestational diabetes in subsequent pregnancies, and type 2 diabetes later in life. Infants born to mothers with GDM also have a higher risk of developing type 2 diabetes in their teens or early adulthood. There are many possible causes of insulin resistance, and multiple metabolic aberrants are known to be involved in the development of different forms of diabetes. Increasing evidence suggests that different forms of diabetes share common pathogenesis and pathophysiological dysregulation resulting from a progressive β-cell demise or dysfunction. The outcome manifests clinically as hyperglycaemia. The development of GDM may represent a very early stage of the progression to type 2 diabetes that is being manifested under the stresses of pregnancy. However, the exact mechanisms of GDM development are not clearly understood. Based on the results of a three-part longitudinal metabolomics study of Chinese pregnant women, in combination with the current literature, a new model of GDM development is proposed to outline the biomolecular mechanisms underpinning GDM. A possible cause of GDM is obesity, which is an important clinical risk factor for the development of diabetes. Women who develop GDM generally have higher body mass indices when compared with healthy pregnant women, and obesity can induce low-grade inflammation. Chronic low-grade inflammation induces the synthesis of xanthurenic acid, which is known to be associated with the development of type 2 diabetes, pre-diabetes and GDM. Hyperglycaemia accelerates purine nucleotide synthesis, which in turn stimulates nucleotide breakdown and increases the concentration of nucleotide degradation products, including superoxide molecules and uric acid. Reactive oxygen species and excessive intracellular uric acid may also have direct effects on the development of the disease or further deterioration of the condition.


Review of Nephelium lappaceum and Nephelium ramboutan-ake: A High Potential Supplement.
Nephelium lappaceum (N. lappaceum) and Nephelium ramboutan-ake (N. ramboutan-ake) are tropical fruits that gain popularity worldwide due to their tastiness. Currently, their potential to be used as pharmaceutical agents is underestimated. Chronic diseases such as cancer, diabetes and aging have high incidence rates in the modern world. Furthermore, pharmaceutical agents targeting pathogenic microorganisms have been hampered by the growing of antimicrobial resistance threats. The idea of food therapy leads to extensive nutraceuticals research on the potential of exotic fruits such as N. lappaceum and N. ramboutan-ake to act as supplements. Phytochemicals such as phenolic compounds that present in the fruit act as potent antioxidants that contribute to the protective effects against diseases induced by oxidative stress. Fruit residuals such as the peel and seeds hold greater nutraceutical potential than the edible part. This review highlights the antioxidant and biological activities (anti-neoplastic, anti-microbial, hypoglycemic actions and anti-aging), and chemical contents of different parts of N. lappaceum and N. ramboutan-ake. These fruits contain a diverse and important chemical profile that can alleviate or cure diseases.


Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia in Patients With Congenital Heart Disease.
Atrioventricular (AV) nodal reentrant tachycardia represents the most common regular supraventricular arrhythmia in humans, and catheter ablation of the so called slow AV nodal pathway has been effectively performed for decades. In patients with congenital heart disease, a combination of different factors makes catheter ablation of AV nodal reentrant tachycardia substrate particularly challenging, including abnormal venous access to intracardiac structures, abnormal intracardiac anatomy, potentially deviant and often unpredictable sites of the specific conduction system, loss of traditional anatomic landmarks, and congenital cardiac surgery that may complicate the access to the AV nodal area. Published experiences have confirmed the efficacy and the relative safety of such procedures when performed by experts, but the risk of complications, in particular AV block, remains non-negligible. A thorough knowledge and understanding of anatomic and electrical specificities according to underlying phenotype are essential in addressing these complex cases. Considering the major consequences associated with AV block in patients with complex congenital heart disease, particularly those without low risk access for transvenous ventricular pacing (eg, single ventricle physiology or Eisenmenger syndrome), the individual risk-benefit ratio should be carefully evaluated. The decision to defer ablation may be the wisest approach in selected patients with either infrequent or hemodynamically tolerated arrhythmias, or when the location of the AV conduction pathways remains uncertain. This narrative review aims to synthetize existing literature on catheter ablation of AV nodal reentrant tachycardia in congenital heart disease, to present main features of common associated pathologies, and to discuss approaches to mapping and safely ablating the slow AV nodal pathway in challenging cases.


Selected features of nonendocrine pancreatic cancer.
We survey some interesting features of gene expression in nonendocrine pancreatic cancer, the response to some less widely known agents as they impact on pancreatic cell proliferation and programmed death, and several developing approaches to therapy. The proliferative and cellular suicide responses of Panc-1 cells to the free radical spin trap, NTBN, and to the 5-lipoxygenease inhibitor, MK 886, the latter assessed with CLONTECH Atlas Human cDNA Array 1, are reviewed. Difficulties in identifying those factors whose suppression or augmentation could result in inhibition of malignantly transformed cell properties are considered.


The incidence of Chiari malformation in nonsyndromic, single suture craniosynostosis.
This study was designed to determine the incidence of Chiari malformation (CM) in nonsyndromic single suture craniosynostosis (N-SSSC). A retrospective analysis of brain magnetic resonance imaging (MRI) studies of children undergoing craniofacial surgery during 1 January, 2004-31 March, 2009 in Cleft Palate and Craniofacial Centre, Department of Plastic Surgery, Helsinki University Hospital, Helsinki, Finland, was conducted. One hundred twenty-four N-SSSC patients were imaged using brain MRI. Of these 124 patients, seven patients were diagnosed with N-SSSC with an associated CM; the incidence CM in association with N-SSSC was thus 5.6%. The average age at the time of MRI was 37.7 months. All were males, except one. Only two types of synostosis were identified in this patient cohort: synostosis involving the sagittal suture in five cases and right coronal synostosis in two cases. The CM malformations were relatively large. The tonsillar herniation varied from 6 to 12 mm (median 9 mm). All these patients were asymptomatic of their CMs. None had operation designed directly to correct the CM. As a conclusion, we state that the association of CM and N-SSSC is a relatively common finding, with an incidence of 5.6% in preoperative brain MRI. The significance of finding CM in preoperative brain MRI should be assessed individually in asymptomatic patients.


Genome annotation with long RNA reads reveals new patterns of gene expression and improves single-cell analyses in an ant brain.
Functional genomic analyses rely on high-quality genome assemblies and annotations. Highly contiguous genome assemblies have become available for a variety of species, but accurate and complete annotation of gene models, inclusive of alternative splice isoforms and transcription start and termination sites, remains difficult with traditional approaches. Here, we utilized full-length isoform sequencing (Iso-Seq), a long-read RNA sequencing technology, to obtain a comprehensive annotation of the transcriptome of the ant Harpegnathos saltator. The improved genome annotations include additional splice isoforms and extended 3' untranslated regions for more than 4000 genes. Reanalysis of RNA-seq experiments using these annotations revealed several genes with caste-specific differential expression and tissue- or caste-specific splicing patterns that were missed in previous analyses. The extended 3' untranslated regions afforded great improvements in the analysis of existing single-cell RNA-seq data, resulting in the recovery of the transcriptomes of 18% more cells. The deeper single-cell transcriptomes obtained with these new annotations allowed us to identify additional markers for several cell types in the ant brain, as well as genes differentially expressed across castes in specific cell types. Our results demonstrate that Iso-Seq is an efficient and effective approach to improve genome annotations and maximize the amount of information that can be obtained from existing and future genomic datasets in Harpegnathos and other organisms.


Pacing after shocks stronger than the upper limit of vulnerability: impact on fibrillation induction.
After upper-limit-of-vulnerability (ULV) shocks of the same strength and coupling interval (CI) during the T wave, (1) the epicardial activation pattern (EAP) for the first postshock cycle is indistinguishable between shocks that do (VF) and do not (NoVF) induce ventricular fibrillation (VF) and (2) >/=3 cycles in rapid succession always occur during VF but not during NoVF episodes. To study the role of these rapid cycles, rapid pacing was performed after a shock stronger than the ULV that by itself did not induce rapid cycles and VF. A 504-electrode sock was sutured to the heart in 6 pigs to map EAPs. The S2 shock strength and S1-S2 CI at the ULV were determined by T-wave scanning with an up/down protocol. Ten shocks 50 to 100 V above the ULV (aULV) were delivered at the same S1-S2 CI to confirm that VF was not induced. Then, the postshock interval after aULV shocks was scanned with an S3 pacing stimulus from the LV apex until the shortest S2-S3 CI that captured was reached. This was repeated for S4, S5, etc, until VF was induced. To induce VF, 3 pacing stimuli (S3-S5) with progressively shorter CIs were required; S3 or S3, S4 never induced VF. After cycle S5, which induced VF, 2 EAP types occurred: focal (74%) and reentrant (26%). At least 3 cycles with short CIs are necessary for VF induction after aULV shocks. Cycles S3-S4 may create the substrate for cycle S5 to initiate VF.


Analysis of the Interprofessional Clinical Learning Environment for Quality Improvement and Patient Safety From Perspectives of Interprofessional Teams.
In 2018 the Clinical Learning Environment Review (CLER) Program reported that quality improvement and patient safety (QIPS) programs in graduate medical education (GME) were largely unsuccessful in their efforts to transfer QI knowledge and substantive interprofessional QIPS experiences to residents, and CLER 2.0 called for improvement. However, little is known about how to improve the interprofessional clinical learning environment (IP-CLE) for QIPS in GME. To determine the current state of the IP-CLE for QIPS at our institution with a focus on factors affecting the IP-CLE and resident integration into interprofessional QIPS teams. We interviewed an interprofessional group of residents, faculty, and staff of key units engaged in IP QIPS activities. We performed thematic analysis through general inductive approach using template analysis methods on transcripts. Twenty individuals from 6 units participated. Participants defined learning on interprofessional QIPS teams as learning from and about each other's roles through collaboration for improvement, which occurs naturally when patients are the focus, or experiential teamwork within QIPS projects. Resident integration into these teams had various benefits (learning about other professions, effective project dissemination), barriers (difficult rotations or program structure, inappropriate assumptions), and facilitators (institutional support structures, promotion of QIPS culture, patient adverse events). There were various benefits (strengthened relationships, lowered bar for further collaboration), barriers (limited time, poor communication), and facilitators (structured meetings, educational culture) to a positive IP-CLE for QIPS. Cultural factors prominently affected the IP-CLE and patient unforeseen events were valuable triggers for IP QIPS learning opportunities.


[Progress in TcpC research].
TcpC is a homolog of the Toll/interleukin-1 receptor (TIR) domain and is secreted by uropathogenic E. coli strain CFT073. TcpC can bind to MyD88, hereby exerting inhibitory effects on macrophages. TcpC represents an important virulence factor that promotes bacterial survival and pathogenicity. TcpC plays a critical role in urinary tract infection, particularly in the pathogenesis of pyelonephritis. In this review,the progress and prospects in TcpC research are discussed.


Ulcer piercing: cleansing of complicated diabetic neuropathic foot ulcers by positive pressure irrigation.
To demonstrate the efficacy of the ulcer piercing procedure, which allows constant cleansing of the ulcer and facilitates a positive pressure irrigation of any pierced hidden tracts, in order to reduce the negative impact of stasis on wound healing. We designed a surgical procedure of ulcer piercing and drainage with a silastic tube, which allows positive pressure irrigation of any pierced tracts. This procedure was performed in a continuous series of 25 selected diabetic patients affected by a Wagner stage 3 ulcer of the toe (n=16), metatarsal midfoot (n=5) and plantar Charcot foot (n=4), and with adequate foot arterial blood supply. Within 6 months of the ulcer piercing procedure, 23/25 of ulcers had completely healed. In two further cases, the ulcer piercing ring was still in place after 3 and 5 months, progressively healing with no active signs of infection. Taking into consideration the advantages and the lack of side effects afforded by this procedure, ulcer piercing represents a small but effective step towards an easier and safer approach to treating complicated diabetic neuropathic foot ulcers with adequate arterial blood supply. There were no external sources of funding for this study. The author has no conflicts of interest to declare with regard to the manuscript or its content.


Mycobacterium xenopi and Mycobacterium kansasii in a hospital water supply.
A steady rise in the number of isolations of Mycobacterium xenopi from patients in a general hospital led to an examination of water taps. Most patients had been accommodated in a group of wards which had a common water supply. This organism was recovered from 35 of 69 outlets, mostly from hot and mixer taps in those wards. Mycobacterium kansasii was also isolated from 14, mostly cold and mixer taps. Ten strains of Myco. xenopi were recovered from 131 taps sampled at 10 other locations. We conclude that colonization of water supplies by mycobacteria is a likely source of contamination of clinical specimens.


Functional magnetic resonance imaging correlates of emotional word encoding and recognition in depression and anxiety disorders.
Major depressive disorder (MDD), panic disorder, and social anxiety disorder are among the most prevalent and frequently co-occurring psychiatric disorders in adults and may be characterized by a common deficiency in processing of emotional information. We used functional magnetic resonance imaging during the performance of an emotional word encoding and recognition paradigm in patients with MDD (n = 51), comorbid MDD and anxiety (n = 59), panic disorder and/or social anxiety disorder without comorbid MDD (n = 56), and control subjects (n = 49). In addition, we studied effects of illness severity, regional brain volume, and antidepressant use. Patients with MDD, prevalent anxiety disorders, or both showed a common hyporesponse in the right hippocampus during positive (>neutral) word encoding compared with control subjects. During negative encoding, increased insular activation was observed in both depressed groups (MDD and MDD + anxiety), whereas increased amygdala and anterior cingulate cortex activation during positive word encoding were observed as depressive state-dependent effects in MDD only. During recognition, anxiety patients showed increased inferior frontal gyrus activation. Overall, effects were unaffected by medication use and regional brain volume. Hippocampal blunting during positive word encoding is a generic effect in depression and anxiety disorders, which may constitute a common vulnerability factor. Increased insular and amygdalar involvement during negative word encoding may underlie heightened experience of, and an inability to disengage from, negative emotions in depressive disorders. Our results emphasize a common neurobiological deficiency in both MDD and anxiety disorders, which may mark a general insensitiveness to positive information.


ICP27 phosphorylation site mutants are defective in herpes simplex virus 1 replication and gene expression.
Herpes simplex virus 1 (HSV-1) protein ICP27 is a multifunctional regulatory protein that is posttranslationally modified by phosphorylation during viral infection. ICP27 has been shown to be phosphorylated on three serine residues, specifically serine residues 16 and 18, which are within casein kinase 2 (CK2) sites, and serine residue 114, which is within a protein kinase A (PKA) site. Phosphorylation is an important regulatory mechanism that is reversible and controls many signaling pathways, protein-protein interactions, and protein subcellular localization. To determine the role of phosphorylation in modulating the activities of ICP27, we constructed phosphorylation site mutations at each of the three serine residues. Single, double, and triple viral mutants were created in which alanine or glutamic acid was substituted for serines 16, 18, and 114. ICP27 phosphorylation site mutants were defective in viral replication and viral gene expression. Notably, ICP4-containing replication compartment formation was severely compromised, with the appearance of small ring-like structures that persisted even at late times after infection. Neither the colocalization of ICP27 with RNA polymerase II nor the formation of Hsc70 nuclear foci was observed during infection with the phosphorylation site mutants, both of which occur during wild-type HSV-1 infection. These data indicate that several key events in which ICP27 plays a role are curtailed during infection with ICP27 phosphorylation site mutants.


Selection of patients for carotid thromboendarterectomy: the role of magnetic resonance angiography.
It has been shown in clinical trials that patients with high grade symptomatic carotid stenosis benefit from carotid thromboendarterectomy. Because of the invasiveness and the costs of intra-arterial digital subtraction angiography, the current standard of reference for the grading of carotid stenosis, magnetic resonance angiography, has become a technique of utmost interest for evaluation of the carotid arteries. The time-of-flight and the newly developed contrast-enhanced magnetic resonance angiography techniques are discussed. At present, we recommend computer enhanced magnetic resonance angiography for screening procedures and for the post-operative follow-up. For pre-operative evaluation we still recommend intra-arterial digital subtraction angiography.


Tetrahydropyrimidines, ZL-5015 Alleviated Lipopolysaccharide (LPS)-Induced Acute Pneumonia in Rats by Activating the NRF-2/HO-1 Pathway.
BACKGROUND Acute pneumonia is a severe inflammatory disease of the respiratory system. Drugs used to treat acute pneumonia often have strong side effects. Recent studies have shown that tetrahydropyrimidines, ZL-5015 has anti-inflammatory and antitumor effects. However, whether ZL-5015 can relieve symptoms of acute pneumonia is unclear. MATERIAL AND METHODS In this study, we used lipo-polysaccharide (LPS) to stimulate SD rats to simulate conditions of acute pneumonia. Diverse doses of ZL-5015 were used for treatment of these rats. After the rates were sacrificed, serum, lung tissue, and bronchoalveolar lavage fluid were collected for the next study. Hematoxylin-eosin (H&E) staining then was used to detect pathologic changes in lung tissues. Enzyme-linked immunosorbent assay was performed to assess levels of inflammatory factors in serum. Commercial kits were used to assess levels of reactive oxygen species (ROS) in bronchoalveolar lavage fluid. RESULTS Treatment of ZL-5015 relieved stenosis of the alveolar space and pulmonary edema. Furthermore, levels of inflammatory factors (TNF-alpha, IL-1ß and IL-18) in the lung tissues and serum were downregulated after treatment with ZL-5015. Production of ROS also was suppressed after application of ZL-5015. Moreover, inhibition of expression of NRF-2 and HO-1 was relieved after treatment with ZL-5015. The therapeutic effect of ZL-5015 showed a dose-response relationship. CONCLUSIONS ZL-5015 alleviated LPS-induced inflammatory injury and oxidative damage by activating the NRF-2/HO-1 pathway.


Fasting or caloric restriction for healthy aging.
Aging is associated with a host of biological changes that contribute to a progressive decline in cognitive and physical function, ultimately leading to a loss of independence, and increased risk of mortality. To date, prolonged caloric restriction (i.e., a reduction in caloric intake without malnutrition) is the only non-genetic intervention that has consistently been found to extend both mean and maximal life span across a variety of species. Most individuals have difficulty sustaining prolonged caloric restriction, which has led to a search for alternative approaches that can produce similar to benefits as caloric restriction. A growing body of evidence indicates that fasting periods and intermittent fasting regimens in particular can trigger similar biological pathways as caloric restriction. For this reason, there is increasing scientific interest in further exploring the biological and metabolic effects of intermittent fasting periods, as well as whether long-term compliance may be improved by this type of dietary approach. This special will highlight the latest scientific findings related to the effects of both caloric restriction and intermittent fasting across various species including yeast, fruit flies, worms, rodents, primates, and humans. A specific emphasis is placed on translational research with findings from basic bench to bedside reviewed and practical clinical implications discussed.


Mutagenicity of cigarette smoke condensate in Neurospora crassa.
The mutagenicity of cigarette smoke condensate (CSC) was investigated in Neurospora crassa in the presence and absence of S9 mix prepared from Aroclor-1254-induced rat liver. CSC from the University of Kentucky Reference Cigarette 1R1 was assayed in a forward-mutation test at the adenine-3 (ad-3) region in resting conidia of 2-component heterokaryons. In the absence of S9 mix, CSC exhibited direct-acting mutagenicity. CSC was also mutagenic in the presence of S9 mix, but higher doses were required than in the absence of S9 mix. The dose range, survival curves, and mutation-induction curves were not significantly different when CSC was used in the presence of unheated or heat-inactivated S9. There was a positive association between killing and mutagenicity, and CSC killed conidia of N. crassa by a cytoplasmic, rather than by a nuclear, mechanism. The mutagenic potency of CSC was similar in a repair-sufficient and a nucleotide excision repair-deficient heterokaryon of N. crassa. CSC did not exhibit a photodynamic effect for killing, and CSC caused more killing at high pH than at low pH. In addition, CSC caused more killing at 37 degrees C than at 25 degrees C and also caused more killing in higher concentrations (20%) of solvent (DMSO) than in low concentrations (1%). This is the first report of the presence of potent direct-acting mutagens in CSC.


Effects of a single post-partum injection of a high dose of vitamin D on glucose tolerance and insulin resistance in mothers with first-time gestational diabetes mellitus.
This study was performed to determine the effect of a single, large, intramuscular injection of vitamin D post-partum on glucose tolerance and insulin resistance in women with gestational diabetes. Forty-five participants in a randomized controlled trial on gestational diabetes mellitus were divided into an intervention group and a control group. Only subjects in the intervention group received one intramuscular injection of 300,000 IU of vitamin D3. HbA(1c), serum 25-hydroxyvitamin D3, fasting insulin and blood glucose, C-peptide, homeostasis model assessment insulin resistance index (HOMA-IR), β-cell function, insulin sensitivity and the Quantitative Insulin Sensitivity Check Index (QUICKI) were measured at baseline and after 3 months of intervention. Approximately 80% of the mothers had a degree of vitamin D deficiency. Post-intervention, this was found in 4.2 and 71.4% in the intervention and control groups, respectively. The medians of HOMA-IR indices before and after intervention were 0.6 and 0.5 (P = 0.7), respectively, in subjects in the intervention group, and 0.5 and 0.9 (P = 0.01) in subjects in the control group. The mean of the QUICKI fell only in the control group (P = 0.008). In the control group, β-cell function increased by ~8% (P = 0.01) and insulin sensitivity decreased after 3 months (P = 0.002). Post-intervention, the median C-peptide decreased in the intervention group and increased in the control group, but the change was significant only in the control group (P = 0.03). A single injection of 300,000 IU of vitamin D3 achieves a 3-month serum 25-hydroxyvitamin D range of 50-80 nmol/l and is an efficient, effective and safe procedure for improving the vitamin status and indices of insulin resistance in mothers with gestational diabetes after delivery.


Preparation and antibacterial properties of gelatin grafted with an epoxy silicone quaternary ammonium salt.
Gelatin (GE) was modified with epoxy silicone quaternary ammonium salt (EPSiQA) under alkaline conditions (pH 10-11). Silyl and quaternary ammonium groups were linked to gelatin skeleton simultaneously. It was illustrated by XRD and DSC that the short-range order of GE is destroyed and the glass transition temperature (Tg) of GE drops 10 °C after modification. The measured contact angles and surface free energy calculated by Owens-Wendt equation showed that the surface energy of modified gelatin EPSiQA-GE is mainly contributed by the dispersive component of non-polarity silicone groups, the hydrophobility of EPSiQA-GE increases with the increase of grafted silicone units in gelatin. The results of minimum inhibitory concentration indicated that EPSiQA-GE has bactericidal property against Gram-positive bacteria, Gram-negative bacteria and has no antibacterial effect on mold.


Experimental chemotherapy of rabies. Preliminary results.
The effect of 17 immunosuppressive, cytostatic or antiviral agents on the course of illness in weanling conventional mice infected intracerebrally (i.c.) or intramuscularly (i. m.) with lethal or sublethal doses of rabies virus strains isolated from fox and small wild rodents was studied. Potentiation or suppression of virulence by the same compound with some virus strains depended on the route of infection. The best protective effect on i.c. and i. m. infections was achieved with iododeoxyuridine (IUdR) and Actinomycin D on i.c. and with 6-azacytidine and Imuran on i.m. infections, respectively.


Porous 2D coordination polymeric formate built up by Mn(II) linking of Fe3O units: influence of guest molecules on magnetic properties.
A first representative of coordination polymers, built from polynuclear carboxylate bridged by mononuclear carboxylate, has been synthesised and structurally characterized. The compound [{Fe(3)O(HCOO)(6)}{Mn(HCOO)(3)(H(2)O)(3)}].3.5HCOOH crystallised in the hexagonal system (space group P6(3)), a = b = 12.369(5) A, c = 12.992(5) A, alpha = beta = 90 degrees , gamma = 120 degrees , V = 1721.4(12) A(3). The crystal structure is built from 2D layers, which are formed by the linking of trinuclear {Fe(3)O(HCOO)(6)}(+) units by mononuclear {Mn(HCOO)(3)(H(2)O)(3)}(-) bridges. These 2D honeycomb layers are connected by molecules of formic acid through a hydrogen bond network. The compound has the voids at the centre of the hexagons. These voids are filled by captured solvent molecules. Solvate molecules are also located between the 2D layers, linking them through a system of H-bonds. All these solvates can be easily removed and/or exchanged, which results in the formation of [{Fe(3)O(HCOO)(6)}{Mn(HCOO)(3)(H(2)O)(3)}].0.5HCOOH.H(2)O and [{Fe(3)O(HCOO)(6)}{Mn(HCOO)(3)(H(2)O)(3)}]. Magnetic properties of the compounds can be considered as the superposition of magnetism of Fe(3)O trinuclear units, for which magnetism is governed by the superexchange interaction between Fe(3+) spins (with one Fe-Fe superexchange parameter J) and the magnetism of spins of Mn(2+) ions, the interactions between these units can be taken into account by molecular field, zJ'. The destruction of the hydrogen bond network caused by evacuation of solvent molecules significantly modifies the overall magnetism. It was found that zJ' depends on the presence of solvent molecules in the structure.


Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer.
Androgen-deprivation therapy (ADT) is a common treatment for men with prostate cancer. Although ADT is effective at suppressing prostate-specific antigen (PSA), stabilizing disease, alleviating symptoms in advanced disease, and potentially prolonging survival, it is not without serious side effects. However, to the authors' knowledge, there is lack of a systematic review of its major adverse effects to date. The authors of this report systematically reviewed and quantitatively assessed the literature on skeletal and cardiac side effects associated with ADT in men with prostate cancer. The PubMed database was searched for relevant published articles from 1966 to May 2008, and 683 articles were reviewed systematically from an original 20 different Medical Subject Heading search combinations. The focus of the review was on bone-related and cardiovascular-related outcomes. When appropriate, results were pooled from articles on specific adverse outcomes, summary risk estimates were calculated, and tests of heterogeneity were performed. Fourteen articles were identified that met inclusion criteria from the original 683 studies. Men who underwent ADT for prostate cancer had a significantly increased risk of overall fracture of 23% (summary relative risk, 1.23; 95% confidence interval [95% CI], 1.10-1.38) compared with men who had prostate cancer but who did not undergo ADT. Furthermore, men who underwent ADT had a 17% increase in cardiovascular-related mortality compared with men who did not undergo with ADT (summary hazards ratio, 1.17; 95% CI, 1.07-1.29). Significant elevations in the risk of diabetes also were observed from 2 large studies. ADT was associated with an increased risk of skeletal fracture, incident diabetes, and cardiovascular-related mortality, although the absolute risk of these events was low. Preventive measures against these adverse effects and careful assessment of patient's baseline health status should be considered.


K-Nutrition, Growth Bud Formation, and Amine and Hydroxycinnamic Acid Amide Contents in Leaf Explants of Nicotiana tabacum Variety Xanthi n.c. Cultivated in Vitro.
The effects of K-nutrition on growth (increase of fresh weight), bud formation (time of emergence, number of buds), and amine and hydroxycinnamic acid amide contents in foliar explants of Nicotiana tabacum cv Xanthi n.c. cultivated in vitro were examined. In K-deficient medium and in high K medium growth and bud formation were markedly inhibited. Marked changes of amine content (a diamine, putrescine; a phenolic amine, phenethylamine) were observed after a few days of culture. No apparent relationship was found between these amines and growth or bud differentiation. In contrast, changes in hydroxycinnamic acid levels were shown to correlate well with growth and bud formation. The greatest stimulation of budding and growth was correlated with the greatest accumulation of these amides. The highest contents of hydroxycinnamic acid amides were found during the first 15 days in culture when intensive cell division took place. Then they declined sharply after 26 days in culture as the rate of cell division decreased and differentiation occurred.


Analysis of Trace Quaternary Ammonium Compounds (QACs) in Vegetables Using Ultrasonic-Assisted Extraction and Gas Chromatography-Mass Spectrometry.
A reliable, sensitive, and cost-effective method was developed for determining three quaternary ammonium compounds (QACs) including dodecyltrimethylammonium chloride, cetyltrimethylammonium chloride, and didodecyldimethylammonium chloride in various vegetables using ultrasonic-assisted extraction and gas chromatography-mass spectrometry. The variety and acidity of extraction solvents, extraction times, and cleanup efficiency of sorbents were estimated to obtain an optimized procedure for extraction of the QACs in nine vegetable matrices. Excellent linearities (R(2) > 0.992) were obtained for the analytes in the nine matrices. The limits of detection and quantitation were 0.7-6.0 and 2.3-20.0 μg/kg (dry weight, dw) in various matrices, respectively. The recoveries in the nine matrices ranged from 70.5% to 108.0% with relative standard deviations below 18.0%. The developed method was applied to determine the QACs in 27 vegetable samples collected from Guangzhou in southern China, showing very high detection frequency with a concentration of 23-180 μg/kg (dw).


Effects of Japanese herbal medicine, Kampo, on human UGT1A1 activity.
Kampo is a traditional Japanese herbal medicine and widely used in clinical practice in Japan. Little is known about interactions between Kampo and other medicines. Kampo contains many aglycones, which can be conjugated by UDP-glucuronosyltransferase (UGT). Therefore, in the present study, the effects of Kampo on human UGT1A1 activity were investigated in vitro. Substrates of human UGT1A1, beta-estradiol or 7-ethyl-10-hydroxycamptothecin (SN-38), were incubated with human liver microsomes in the presence of 51 Kampos, 14 medicinal herbs and their components. Beta-estradiol 3-glucuronidation was strongly inhibited by some Kampos such as Bofu-tsusho-san, Mashinin-gan and Otsuji-to. Medicinal herbs such as Daio (Rhei Rhizoma), Kanzo (Glycyrrhizae Radix), Keihi (Cinnamomi Cortex) and Ogon (Scutellariae Radix) exhibited potent inhibition on that activity. On beta-estradiol 3-glucuronidation, the major component of Keihi (cinnamaldehyde) and Ogon (wogonin) exhibited mixed-type inhibition of K(i) with values of 0.7 microM and 2.8 microM, respectively. On SN-38 glucuronidation, the inhibitory potencies of Kampos, medicinal herbs and their components tended to be similar to those on beta-estradiol 3-glucuronidation. In the present study, Kampo was clarified to inhibit beta-estradiol and SN-38 glucuronidation mainly catalyzed by UGT1A1.


A longitudinal view of resident education in pediatric emergency interhospital transport.
: The focus was to examine the educational structure and curricular planning involved in current pediatric emergency interhospital transport teams that use resident physicians as members of the team and to compare these current results with the findings from 2 previous, similar surveys complete during the past 2 decades. : A 33-item questionnaire, assessing curricular components of the transport experience, was sent to a chief resident at all the officially listed nonmilitary pediatric residency program in contiguous United States. Comparisons were done for each similar item on all 3 questionnaires. : After 3 rounds of mailing and telephone follow-up to nonresponders, the overall response rates for the 2006 and 1998 surveys were 81% (n = 156) and 89% (n = 173), respectively. A similar survey on a smaller sample, published in 1990, used for comparison, had a response rate of 99% (n = 75). When asked about training provided to residents before going on transport, respondents varied in the specific experiences and skills required of the residents. In addition, programs reported variation in team backup during the pediatric emergency transport. The most common method of evaluation for the resident on completion of the transport was "no specific method" as reported by 62% of respondents in 2006 compared with 50% in 1998 and 55% in 1990 (P = not significant). The percentage of programs providing informal verbal feedback was reduced significantly in 2006 as compared with that in 1998 (P = 0.011). : The educational structure for residents serving in pediatric emergency interhospital transport teams remains variable, and the full educational value of pediatric transports continues to be somewhat unrealized particularly in the area of posttransport performance feedback and evaluation. Having medical command available has consistently been a strong point of the residents' experience on the transport team.


[Osteoscintigraphy and dynamic studies of the kidneys using 99mTc-pyrophosphate in tumors of the retroperitoneal space in children].
Osteoscintigraphy and dynamic scintigraphy of the kidneys with 99mTc-pyrophosphate were used for investigation of 24 pediatric patients with tumorous involvement of the retroperitoneal space. Bone metastases were detected by osteoscintigraphy in 8 patients, pathological changes of the kidneys and urinary tract in 9 patients. Dynamic investigation of the kidneys with 99mTc-pyrophosphate performed in the first 20 min. after the drug injection showed disorders of renal evacuatory function of a varied degree of expression in all 24 patients. Dynamic investigation of the kidneys with 99mTc-pyrophosphate was not accompanied by an increase in radiation exposures therefore it was recommended at the first stage of radionuclide investigation of children with tumorous involvement of the retroperitoneal space followed by osteoscintigraphy.


Valproic acid toxicity: overview and management.
Acute valproic acid intoxication is an increasing problem, accounting for more than 5000 calls to the American Association of Poison Control Centers in 2000. The purpose of this paper is to review the pharmacology and toxicology of valproic acid toxicity. Unlike earlier antiepileptic agents, valproic acid appears to function neither through sodium channel inhibition nor through direct gamma-aminobutyric acid agonism, but through an indirect increase in regional brain gamma-aminobutyric acid levels. Manifestations of acute valproic acid toxicity are myriad, and reflect both exaggerated therapeutic effect and impaired intermediary metabolism. Central nervous system depression is the most common finding noted in overdose, and may progress to coma and respiratory depression. Cerebral edema has also been observed. Although hepatotoxicity is rare in the acute overdose setting, pancreatitis and hyperammonemia have been reported. Metabolic and hematologic derangements have also been described. Management of acute valproic acid ingestion requires supportive care and close attention to the airway. The use of controversial adjunctive therapies, including extracorporeal drug elimination and L-carnitine supplementation, will be discussed.


The pharmacokinetics of cefuroxime axetil in the sick elderly patient.
The pharmacokinetics of cefuroxime axetil (RS3 formulation) were studied in 20 elderly patients following admission for lower respiratory or urinary tract infection. The mean age was 83.9 years. A 12-hourly dose of 250 mg was given for five days. The mean time to attain maximum serum concentration was 3.2 h with a mean peak concentration of 8.5 mg/l. The mean serum elimination half-life was 3.5 h and the AUC0-infinity 60.4 mg/h.l. There was no accumulation of the drug in the patients studied after five days treatment. The data suggest that the standard dosage regimen is adequate in the sick elderly patient.


Strategies for acquiring the phospholipid metabolite inositol in pathogenic bacteria, fungi and protozoa: making it and taking it.
myo-Inositol (inositol) is an essential nutrient that is used for building phosphatidylinositol and its derivatives in eukaryotes and even in some eubacteria such as the mycobacteria. As a consequence, fungal, protozoan and mycobacterial pathogens must be able to acquire inositol in order to proliferate and cause infection in their hosts. There are two primary mechanisms for acquiring inositol. One is to synthesize inositol from glucose 6-phosphate using two sequentially acting enzymes: inositol-3-phosphate synthase (Ino1p) converts glucose 6-phosphate to inositol 3-phosphate, and then inositol monophosphatase (IMPase) dephosphorylates inositol 3-phosphate to generate inositol. The other mechanism is to import inositol from the environment via inositol transporters. Inositol is readily abundant in the bloodstream of mammalian hosts, providing a source from which many pathogens could potentially import inositol. However, despite this abundance of inositol in the host, some pathogens such as the bacterium Mycobacterium tuberculosis and the protist parasite Trypanosoma brucei must be able to make inositol de novo in order to cause disease (M. tuberculosis) or even grow (T. brucei). Other pathogens such as the fungus Candida albicans are equally adept at causing disease by importing inositol or by making it de novo. The role of inositol acquisition in the biology and pathogenesis of the parasite Leishmania and the fungus Cryptococcus are being explored as well. The specific strategies used by these pathogens to acquire inositol while in the host are discussed in relation to each pathogen's unique metabolic requirements.


A highly expressed 81 kDa protein in immortalized mouse fibroblast: its proliferative function and identity with ezrin.
An 81 kDa protein was found to be highly expressed in spontaneously immortalized CD1-ICR mouse fibroblasts, RS-4, as compared to normal fibroblasts. RS-4 cells have a reduced serum requirement and exhibit multilayered growth in vitro but are not tumorigenic. The protein was purified from RS-4 cell extracts and used to obtain a polyclonal antibody that specifically immunoprecipitated an 81 kDa protein from cell lysates. Immunocloning of its cDNA and sequence analysis revealed its identity with ezrin, an F-actin binding protein that is a component of the cortical cytoskeleton. Microinjection of the purified IgG fraction of the anti-p81 antiserum into the cytoplasm of RS-4 cells blocked their entry into S phase suggesting that the protein has a proliferative function. Immunostaining of normal mouse tissues showed that the expression of p81/ezrin was highest in proliferating cell populations. Unlike RS-4, NIH3T3 cells exhibit contact inhibition and express levels of p81/ezrin similar to those of normal fibroblasts. When NIH3T3 cells were transfected with p81/ezrin cDNA they lost contact inhibition and thus resembled RS-4 cells. The study demonstrates a proliferative function of p81/ezrin and suggests its involvement in pathways that negatively regulate contact inhibition.


Nasopharyngeal angiofibroma in an adult with Proteus syndrome. First reported case.
Proteus Syndrome (PS) is a rare hamartoneoplastic disorder consisting of a disproportionate and asymmetric overgrowth of body parts, leading to severe body and face disfigurement. Individuals with PS frequently need to undergo a number of surgical procedures including Otolaryngology interventions. Their peculiar anatomy turns even the most straightforward intervention to a challenging one. A 31-year-old adult male with PS presented with recurrent epistaxis and nasal obstruction. A nasal mass was found during the physical examination, which was surgically removed under general anesthesia. Histology revealed juvenile angiofibroma. This is the first reported case of a patient with PS presenting with juvenile nasopharyngeal angiofibroma. Although vascular malformations may appear in these patients, juvenile nasopharyngeal angiofibroma should be taken under consideration when PS patients present with recurrent epistaxis. HIPPOKRATIA 2017, 21(3): 147-149.