Anti-Arthritic and Antiinflammatory Effects of the Traditional Uighur Formula Kursi Caper In Vivo.
Kursi Caper (KC) is a Uighur medicine based on caper which is widely used to treat arthritis and rheumatism, and preliminary studies in our laboratory showed that this traditional formula may possess potent antiinflammatory effects. This study confirms the antiinflammatory effect of KC in the adjuvant induced arthritis (AIA) model, the carrageenan and cotton-pellet induced granuloma rat models, and further investigates in vivo the mechanism of action by measuring relevant indicators of anti-arthritic activity. KC showed significant and dose-dependent anti-arthritic and antiinflammatory effects, demonstrated by reduced paw edema and arthritic scores in all animal models. Histopathological examination showed that KC reduced levels of synovial inflammatory factors in AIA rats. The overproduction of TNF-α and IL-1β was attenuated, and CAT, MDA and SOD levels were restored to normal in KC-treated rats. KC also significantly reduced LPS-induced proliferation of B lymphocytes and ConA induced proliferation of T lymphocytes in a dose-dependent manner. Flow cytometry showed that the high dose KC-treated group had a significantly decreased frequency of Th17 cells. This study indicates that KC can significantly attenuate arthritis and inflammation in rats by decreasing the levels of inflammatory cytokines, regulating oxidative stress, reducing lymphocyte proliferation and decreasing Th17. This supports the traditional use of KC as a potential modern therapeutic agent for the treatment of arthritis and related conditions.


Use of RNA fingerprinting to identify fungal genes specifically expressed during ectomycorrhizal interaction.
The ecosystem soil is characterized by interactions between microorganisms and plants including mycorrhiza--mutualistic interactions between fungi and plant roots. Species of the basidiomycete genus Tricholoma form ectomycorrhiza with tree roots which is characterized by morphological and metabolic changes of both partners, yet molecular mechanisms of the interaction are poorly understood. We performed differential display with arbitrarily primed RT-PCR using ectomycorrhiza between the basidiomycete Tricholoma vaccinum and its compatible host spruce (Picea abies) to isolate mycorrhiza-specific fungal gene fragments. 76 differentially expressed PCR fragments were verified and checked for plant or fungal origin and expression pattern. Of 20 fungal fragments with mycorrhiza-specific expression, sequence analyses were performed to identify homologs with known function of the encoded protein. Among the genes identified were orthologs to an aldehyde dehydrogenase, an alcohol dehydrogenase and a protein of the MATE transporter family, all with possible function in plant pathogen response. A phospholipase B, a beta-glucosidase and a binding protein of basic amino acids might play a role in nutrient exchange and growth in planta. A protein similar to inactive E2 compounds of ubiquitin-conjugating enzymes like CROC-1 and MMS2, a Ras protein and an APS kinase were placed in signal transduction and two retrotransposons of the Ty3-gypsy and the Ty1-copia family are expressed most likely due to stress.


Identification of cadmium-regulated genes by cDNA-AFLP in the heavy metal accumulator Brassica juncea L.
In this study, cDNA-amplified fragment length polymorphism (cDNA-AFLP) analysis was employed to identify genes that exhibited a modulated expression following cadmium (Cd) treatment in Brassica juncea grown in hydroponic culture. Plants were treated for 6 h, 24 h, and 6 weeks with 10 microM Cd(NO3)2 and untreated 6-week-old plants were used as controls. Cd content was measured at these four time points. Long exposure to Cd affected root morphology: roots appeared thinner and sent out side roots. Seventy-three transcript-derived fragments were identified as Cd responsive. Fifty-two of them showed significant homology to genes with known or putative function, 10 transcript-derived fragments were homologous to uncharacterized genes, while 11 transcript-derived fragments did not show significant matches. The expression pattern of several of these genes was confirmed by northern blot analysis. Fifty-two genes of known or putative function were transcriptional factors, expression regulators, and stress responding and transport facilitation genes, as well as genes involved in cellular metabolism and organization and the photosynthetic process, suggesting that a multitude of processes are implicated in Cd stress response. The transcription of drought- and abscisic acid-responsive genes observed in this study also suggested that Cd imposes water stress and that abscisic acid may be involved in the Cd plant response.


Valdecoxib does not interfere with the CYP2D6 substrate metoprolol.
We reported recently that celecoxib inhibits the metabolism of the cytochrome P450 (CYP)2D6 substrate metoprolol in volunteers. Valdecoxib, the active metabolite of parecoxib, has also been claimed to interfere with the metabolism of CYP2D6 substrates. However, little support for this contention is available despite the intensive use of parecoxib in the perioperative setting. Therefore, the objective of this study was to examine the effect of valdecoxib on the pharmacokinetics of the clinically relevant CYP2D6 substrate metoprolol. An open, randomized, 3-period crossover study was performed in 15 healthy male volunteers. Metoprolol (50 mg) was given in all 3 periods without, or following a 7-day pre-treatment with valdecoxib (20 mg, o.d.) or rofecoxib (25 mg, o.d.), to achieve steady state conditions of COX-2 inhibitors in Periods 2 and 3. In a small group of extensive metabolizers (EM/EM), short-term application of twice the dose was investigated. No effect of valdecoxib (20 mg/d) or rofecoxib (25 mg/d) were detected on the area under the plasma concentration-time curve of metoprolol (323 +/- 333 to 324 +/- 296 or 309 +/- 256 microg x h/l) or at a higher dose. No significant changes of pharmacokinetic or pharmacodynamic parameters of metoprolol were apparent. We conclude that, at therapeutic doses, valdecoxib and rofecoxib do not influence the CYP2D6 substrate metoprolol.


Variations in bone density across the body of the immature human mandible.
During growth the mandible accommodates increases in biomechanical loading resulting from changes in the function of structures of the oral cavity. Biomechanical loads are thought to play an intricate and vital role in the modelling and remodelling of bone, with site-specific effects on bone mineral density. It is anticipated that the effects of this loading on bone mineral density are intensified during the functional transition from prenatal to postnatal stages. The aim of this study was thus to evaluate changes in bone mineral density across the body of the immature human mandible during the early stages of dental development. The study sample included 45 human mandibles, subdivided into three age groups: prenatal (30 gestational weeks to birth; n = 15); early postnatal (birth to 12 months; n = 18); and late postnatal (1-5 years; n = 12). Mandibles were scanned using X-ray micro-computed tomography. Eight landmarks were selected along the buccal/labial and lingual surfaces of each dental crypt for evaluation of the bone mineral density. Bone mineral density values were calculated using a reference standard and analysed using multivariate statistics. The bone mineral density of the lingual surface was found to be significantly higher (P ≤ 0.000) than that of the buccal/labial surface. Furthermore, bone mineral density in the alveolar region of the buccal/labial surface of the deciduous central incisor (P ≤ 0.001), the deciduous first molar (P ≤ 0.013) and lingual alveolar area of the deciduous second molar (P ≤ 0.032) were significantly greater in the early postnatal period than in the prenatal period. While changes in bone mineral density across the lingual surface were consistent with the progression of development and the biomechanical demand of the tongue as previously demonstrated, changes observed across the buccal/labial surface of the mandible appeared to accompany the advancing dental development. Thus, changes in bone mineral density across the mandible appear to be reflective of the stage of dental development and the level of biomechanical loading.


Understanding P450-mediated Bio-transformations into Epoxide and Phenolic Metabolites.
Adverse drug reactions are commonly the result of cytochrome P450 enzymes (CYPs) converting the drugs into reactive metabolites. Thus, information about the CYP bioactivation of drugs would not only provide insight into metabolic stability, but also into the potential toxicity. For example, oxidation of phenyl rings may lead to either toxic epoxides or safer phenols. Herein, we demonstrate that the potential to form reactive metabolites is encoded primarily in the properties of the molecule to be oxidized. While the enzyme positions the molecule inside the binding pocket (selects the site of metabolism), the subsequent reaction is only dependent on the substrate itself. To test this hypothesis, we used this observation as a predictor of drug inherent toxicity. This approach was used to successfully identify the formation of reactive metabolites in over 100 drug molecules. These results provide a new perspective on the impact of functional groups on aromatic oxidation of drugs and their effects on toxicity.


Supercooling of Water to -92{degrees}C Under Pressure.
The temperature at which "clean" supercooled water freezes has been determined as a function of pressure up to 3 kilobars, using a differential thermal analysis technique on subdivided water samples. The supercooling limit of such samples, -38 degrees C at normal pressure, is lowered by initial increase of pressure, reaching a minimum value of -92 degrees C at 2.00 kilobars.


Effects of low-dose acetazolamide on exercise performance in simulated altitude.
Preventive effects of acetazolamide (ACZ) on acute mountain sickness (AMS) are well established but effects on exercise performance at high altitude or in hypoxia have been less considered and are still inconsistent. We hypothesized that low-dose ACZ would not impair exercise performance at simulated high altitude. Thus, the aim of this study was to evaluate the interaction between low-dose ACZ and exercise performance in normobaric hypoxia. Sixteen subjects (8 males and 8 females) were randomly assigned either to receive low-dose ACZ (3×125 mg in 36 hours) or placebo. Incremental cycle spiro-ergometry was performed before and after drug treatment in normobaric hypoxia (inspired fraction of oxygen, FiO2 = 13.5%; equivalent to about 4000 m). Whereas maximal power output and submaximal exercise responses did not change differently from pre- to post-treatment between ACZ and placebo, absolute and relative VO2max values and maximal oxygen pulse were slightly decreased in hypoxia after ACZ pre-treatment. ANOVA results suggest that aerobic capacity in males might be more affected by ACZ pre-treatment than in females. In conclusion, the presented findings may be of practical importance, possibly more meaningful for female mountaineers, because low-dose ACZ (125 mg bd) was shown to prevent AMS development with similar effectiveness as higher doses. This means that low-dose ACZ would prevent both, AMS development and a pronounced reduction in exercise performance.


[A case report: sepsis associated with hypoglycemia].
A 78-year-old woman was admitted to our hospital because of disturbance of consciousness. She had been diagnosed as uterus carcinoma and had undergone radiotherapy one year before admission. On admission, her body temperature was 35.5 degrees C and systolic blood pressure was 50 mmHg. Ascites and semicomatose consciousness were detected. Laboratory evaluation demonstrated the following values: leukocyte count 38800/microliters, blood sugar 3 mg/l and arterial blood pH 6.9. Therapy with catecholamine and antibiotics was started, but she expired 10 hours after admission. Bacteroides ovatus was detected from her blood. Autopsy findings disclosed abscess and perforation of the uterus, and liver cirrhosis. Hypoglycemia has rarely been described as a clinical manifestation of sepsis and this case is, to our knowledge, is the first report of sepsis complicated with hypoglycemia in Japan.


Risk Factor, Job Stress and Quality of Life in Workers With Lower Extremity Pain Who Use Video Display Terminals.
To investigate the general characteristics of video display terminal (VDT) workers with lower extremity pain, to identify the risk factors of work-related lower extremity pain, and to examine the relationship between work stress and health-related quality of life. A questionnaire about the general characteristics of the survey group and the musculoskeletal symptom was used. A questionnaire about job stress used the Korean Occupational Stress Scale and medical outcome study 36-item Short Form Health Survey (SF-36) to assess health-related quality of life. There were 1,711 subjects in the lower extremity group and 2,208 subjects in the control group. Age, sex, hobbies, and feeling of loading affected lower extremity pain as determined in a crossover analysis of all variables with and without lower extremity pain. There were no statistically significant difference between the two groups in terms of job stress and SF-36 values of the pain and control groups. Job stress in VDT workers was higher than average, and the quality of life decreased as the stress increased. Factors such as younger age, women, hobbies other than exercise, and feeling of loading influenced lower extremity pain of workers. Further long-term follow-up and supplementary studies are needed to identify risk factors for future lower extremity pain, taking into account ergonomic factors such as worker's posture.


Complete mitochondrial genome of the larch hawk moth, Sphinx morio (Lepidoptera: Sphingidae).
The larch hawk moth, Sphinx morio, belongs to the lepidopteran family Sphingidae that has long been studied as a family of model insects in a diverse field. In this study, we describe the complete mitochondrial genome (mitogenome) sequences of the species in terms of general genomic features and characteristic short repetitive sequences found in the A + T-rich region. The 15,299-bp-long genome consisted of a typical set of genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes) and one major non-coding A + T-rich region, with the typical arrangement found in Lepidoptera. The 316-bp-long A + T-rich region located between srRNA and tRNA(Met) harbored the conserved sequence blocks that are typically found in lepidopteran insects. Additionally, the A + T-rich region of S. morio contained three characteristic repeat sequences that are rarely found in Lepidoptera: two identical 12-bp repeat, three identical 5-bp-long tandem repeat, and six nearly identical 5-6 bp long repeat sequences.


University and community hospital medical student emergency medicine clerkship experiences.
To determine whether there is a significant difference between educational opportunities for fourth-year medical students rotating at a university hospital (UH) compared with several community hospitals (CHs) during a mandatory emergency medicine (EM) clerkship. A self-reported clinical tool was completed in real time by each student rotating for 2 weeks at the UH and 2 weeks at 1 of 4 CHs (3 affiliated and 1 unaffiliated). Students are required to document the number of patients seen and the number of procedures performed on each of 20 six-hour shifts. They rated the EM attending clinical teaching by site using a 5-point scale at the end of the clerkship. Most (95%) of the 87 students in the 7 clerkship blocks of the 1996-97 academic year rotated at the UH and a CH. Most (71%) students rated both the UH and the CH for the quality of teaching by attendings. There was a significant difference in the mean number of patients evaluated/shift (2.2 +/- 0.10 vs 2.8 +/- 0.10, UH vs CH; p < 0.001) and the mean number of procedures performed/shift (0.36 +/- 0.04 vs 0.56 +/- 0.05, UH vs CH; p < 0.001). Attending clinical teaching scores were significantly higher (p = 0.03) at the CHs. The educational opportunities for students in an EM clerkship to evaluate patients and perform procedures were significantly greater at the community hospitals. Inclusion of community hospital settings in a medical student EM clerkship may optimize the clinical experience.


The HMG domain protein SSRP1/PREIIBF is involved in activation of the human embryonic beta-like globin gene.
The human embryonic beta-like globin (epsilon-globin) gene is expressed in primitive erythroid cells of the yolk sac during the first few weeks of development. We have previously shown that developmental stage-specific expression of the epsilon-globin gene is mediated by multiple positive and negative regulatory elements upstream of the start of transcription. Of particular interest is one positive regulatory element, PRE II, that works together with other elements (PRE I and PRE V) to confer developmental stage- and/or tissue-specific expression on a minimal promoter. An approximately 85- to 90-kDa PRE II binding factor (PREIIBF) was identified in the nuclei of erythroid cells and shown to bind specifically to a novel 19-bp region within PRE II; binding of this protein to PRE II resulted in bending of the target DNA and was required for promoter activation. In this report, we present the cDNA expression cloning of PREIIBF. The cDNA encodes a previously identified member of the HMG domain family of DNA binding proteins termed SSRP1. By a number of biochemical and immunological criteria, recombinant SSRP1 appears to be identical to the PREII binding factor from erythroid nuclei. A hallmark of HMG domain proteins is their ability to bend their target DNAs; therefore, as we speculated previously, DNA bending by SSRP1/PREIIBF may contribute to the mechanism by which PRE II synergizes with other regulatory elements located upstream and downstream. In contrast with reports from other investigators, we demonstrate that SSRP1 binds DNA with clear sequence specificity. Moreover, we show that SSRP1/PREIIBF lacks a classical activation domain but that binding by this protein to PRE II is required for activation of a minimal promoter in stable erythroid cell lines. These studies provide the first evidence that SSRP1 plays a role in transcriptional regulation. SSRP1/PREIIBF may serve an architectural function by helping to coordinate the assembly of a multiprotein complex required for stage-specific regulation of the human epsilon-globin gene.


Clinical and Epidemiological Findings from Enhanced Monkeypox Surveillance in Tshuapa Province, Democratic Republic of the Congo During 2011-2015.
Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa. Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011-2015, we evaluated differences in incidence, exposures, and clinical presentation of polymerase chain reaction-confirmed cases by sex and age. We report 1057 confirmed cases. The average annual incidence was 14.1 per 100 000 (95% confidence interval, 13.3-15.0). The incidence was higher in male patients (incidence rate ratio comparing males to females, 1.21; 95% confidence interval, 1.07-1.37), except among those 20-29 years old (0.70; .51-.95). Females aged 20-29 years also reported a high frequency of exposures (26.2%) to people with monkeypox-like symptoms.The highest incidence was among 10-19-year-old males, the cohort reporting the highest proportion of animal exposures (37.5%). The incidence was lower among those presumed to have received smallpox vaccination than among those presumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score. Monkeypox incidence was twice that reported during 1980-1985, an increase possibly linked to declining immunity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow sociocultural norms.


Water for preventing urinary calculi.
Urinary calculi is a common condition characterized of high incidence and high recurrence rate. For a long time, increased water intake has been the main preventive measure for the disease and its recurrence. To access the effectiveness of increased water intake for the primary and secondary prevention of urinary calculi. Relevant RCTs were identified by electronic and documental searches of MEDLINE, EMBASE, the Chinese Biomedical Disk and the Cochrane Central Register of Controlled Trials. No language restriction was applied. Date of last search: May 2004. Randomised controlled trials (RCTs) and quasi-RCTs of increased water intake for the prevention of urinary calculi and its recurrence. Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or weight mean difference (WMD) for continuous data with 95% confidence intervals (CI). No trials of increased water intake for the primary prevention of urinary calculi met the inclusion criteria. One trial with 199 patients provided results of increased water intake for the recurrence of urinary calculi. The recurrence rate was lower in the increased water intake group than that of the no intervention group (12% versus 27%, P = 0.008, RR = 0.45, 95% CI 0.24 to 0.84). The average interval for recurrences was 3.23 +/-1.1 years in increased water intake group and 2.09 +/- 1.37 years in the no intervention group (P = 0.016, WMD = 1.14, 95% CI 0.33 to 1.95). The evidence from only one trial indicates that increased water intake reduces the risk of recurrence of urinary calculi and prolongs the average interval for recurrences. However further research is required. Due to the lack of appropriate RCTs, no conclusions can be drawn on increased water intake for the primary and secondary prevention of urinary calculi.


Childhood leukemia presenting as a diaphyseal radiolucency.
A 41-month-old black child with a symtomatic diaphyseal destructive lesion of the femur, and a corresponding area of increased uptake on a technetium99m bone scan, had an upper respiratory tract infection. An open biopsy was performed because of an initial clinical diagnosis of osteomyelitis, histiocytosis X or a round cell sarcoma. The biopsy showed numerous blast cells compatible with acute lymphocytic leukemia. Acute leukemia should be included in the differential diagnosis of symptomatic diaphyseal destructive lesions in children. A peripheral blood smear should be carefully interpreted prior to any other invasive diagnostic tests.


A dimensional model of psychopathology.
The question of whether mental disorders are discrete clinical conditions or arbitrary distinctions along dimensions of functioning is a longstanding issue, but the importance of this question is escalating with the growing recognition of the frustrations and limitations engendered by the categorical model. Researchers are now focusing their attention on developing alternative dimensional models of classification. Concerns have been raised with regard to these dimensional models. Addressed in this brief commentary are two of these concerns: clinical utility and credibility.


Characterization of a Kunitz-type protease inhibitor (MjKuPI) reveals the involvement of MjKuPI positive hemocytes in the immune responses of kuruma shrimp Marsupenaeus japonicus.
Serine proteases and their inhibitors play vital roles in biological processes. Serine protease inhibitors, including Kunitz-type protease inhibitors play important roles not only in physiological process (i.e. blood clotting and fibrinolysis) but also in immune responses. In this study, we characterized a Kunitz-type protease inhibitor, designated MjKuPI, from kuruma shrimp Marsupenaeus japonicus. An expression profile showed that MjKuPI was mainly expressed in hemocytes. Immunostaining revealed that some hemocytes expressed MjKuPI (MjKuPI(+) hemocytes) and others did not (MjKuPI(-) hemocytes). Injection of shrimp with Vibrio penaeicida and white spot syndrome virus (WSSV) upregulated the mRNA level of MjKuPI, and a flow cytometry analysis revealed that the proportion of MjKuPI(+) hemocytes increased significantly 24 h after injection. Together, these results suggest that MjKuPI and MjKuPI(+) hemocytes have a role in the innate immune system of kuruma shrimp.


Risperidone in cocaine-dependent patients with comorbid psychiatric disorders.
: A high percentage of individuals with cocaine dependence have a comorbid psychiatric illness, which complicates treatment of the substance abuse. This report will describe clinical experience using risperidone in cocaine-dependent patients with psychiatric disorders. : Sixteen male patients with cocaine dependence and comorbid psychiatric disorder (DSM-III-R) diagnoses, who were admitted to a voluntary, post-detoxification, intermediate-care inpatient substance abuse program, were started on risperidone (mean starting dose 2.3 mg/day) in an open-label, naturalistic trial. Patients were assessed weekly using the Clinical Global Impressions scale to assess overall functioning, a Likert scale for craving, the Abnormal Involuntary Movement Scale, interviews with substance abuse counselors and patients, and laboratory tests. All patients had at least one other substance use diagnosis besides cocaine dependence, and 13 patients were taking another psychiatric medication. : Of the 16 patients, 13 (81%) were rated improved or much improved on the CGI scale, and all patients reported mild or no craving at the last assessment (after a mean of 32.6 days of risperidone treatment). No patient developed extrapyramidal symptoms or hypomania. Compared to a 32% historical completion rate for patients receiving treatment as usual, fourteen (88%) of these patients completed the program, and 9 moved on to the next level of care. : The results of this naturalistic trial suggest that risperidone is safe and well tolerated in patients with cocaine dependence and comorbid psychiatric illness. In the short term, risperidone may also be effective in reducing cocaine craving and use and may increase the likelihood of completing substance abuse treatment.


Academic industry relationships in biotechnology: a primer on policy and practice.
Academic industry relationships (AIRs) in biotechnology are part of the modern life science economy. They cannot and should not be prevented. But their benefits should not be exaggerated, nor their risks minimized or ignored. It is essential that these relationships be understood, monitored, and managed in a manner that protects the investments and the integrity of involved individuals, institutions, and science in general. Failure to do so could result in loss of public confidence and support for research enterprise--a priceless resource whose integrity and independence are critical to the future of the scientific endeavor.


Effects of Davallia formosana Hayata Water and Alcohol Extracts on Osteoblastic MC3T3-E1 Cells.
The Taiwanese native fern Davallia formosana Hayata (DFH) is used to treat bone diseases in classical Chinese medicine. We analyzed MC3T3E1 osteoblasts treated with different concentrations of water and ethanol extracts (10, 25, and 50 [both], and 100 μg/mL [DFE only]) using cell viability, expression of osteoblast differentiation markers [bone morphogenetic protein 2 (BMP-2), collagen 1 (CoL-1), alkaline phosphatase (ALP), and Runt-related transcription factor 2 (Runx 2)], and mineralization. These were significantly increased by DFW or DFE after 24-h incubation compared with the untreated controls. Compared with other treatments, DFW 50 and DFE 100 μg/mL significantly increased MC3T3E1 cell survival. DFW 25 and 50 μg/mL increased bone BMP-2, CoL-1, ALP, and Runx2 protein expression, ALP activity, and mineralization more than DFE did. Repeated chromatographic separation of DFW yielded compound (-)-epicatechin-3-O-d-allipyranoside (ECAP), which was characterized using 1 H and 13 C nuclear magnetic resonance spectroscopy. (-)-Epicatechin-3-O-d-allipyranoside (0.01 μg/mL) significantly increased cell survival (118.9%) and mineralization (218.7%) compared with that of the control treatment. We inferred that ECAP could mediate the main activity of DFW in bone formation, likely through BMP-2-induced Runx2 transcription, which increased bone cell differentiation factors ALP and CoL-1 and promoted mineralization. (-)-Epicatechin-3-O-d-allipyranoside could be an anti-osteoporotic agent. Copyright © 2017 John Wiley & Sons, Ltd.


A case of probable non-familial early onset Alzheimer dementia in a Hispanic male.
Early onset Alzheimer's type dementia (EOAD) is usually familial and associated with mutations in the Presenilin-1 (PSEN1), Presenilin-2 (PSEN2) or amyloid precursor protein (APP) genes. It is rarely reported in patients of Hispanic descent. A 49-year-old Hispanic male developed significant cognitive impairment over a 4-year period. PET scan showed diminished metabolic activity in the posterior parietal/temporal lobes. Genetic testing revealed the presence of a PSEN1 gene mutation. Disparities in health care may account for an under-recognition of EOAD in the Hispanic population. Clinicians should test for EOAD in all patients with appropriate symptomatology, regardless of ethnicity. Early recognition and enrollment in clinical trials is vital to enhancing our understanding of the natural history and treatment of this condition.


How predictive of dementia are peripheral inflammatory markers in the elderly?
Dementia is a huge public health concern today owing to the exponentially increasing number of older adults it affects each year, and there has been a large number of investigators looking at potential biomarkers of dementia. Peripheral inflammatory markers have emerged as one potential class of markers that may be useful in predicting those individuals at a greater risk of developing dementia, or in expounding the underlying mechanisms or pathways of this complex disease. Although some evidence has been promising, indicating that peripheral inflammatory markers are indeed crucial in brain changes that occur in both normal aging and in dementia, results have been mixed on their usefulness for predicting dementia or cognitive decline in older adults. Here, the authors present a review of existing studies investigating inflammatory markers as potential biomarkers of dementia, highlighting some strengths and limitations of the current research and discuss the future directions for this field.


Transcriptional profiling reveals gland-specific differential expression in the three major salivary glands of the adult mouse.
RNA-Seq was used to better understand the molecular nature of the biological differences among the three major exocrine salivary glands in mammals. Transcriptional profiling found that the adult murine parotid, submandibular, and sublingual salivary glands express greater than 14,300 protein-coding genes, and nearly 2,000 of these genes were differentially expressed. Principle component analysis of the differentially expressed genes revealed three distinct clusters according to gland type. The three salivary gland transcriptomes were dominated by a relatively few number of highly expressed genes (6.3%) that accounted for more than 90% of transcriptional output. Of the 912 transcription factors expressed in the major salivary glands, greater than 90% of them were detected in all three glands, while expression for ~2% of them was enriched in an individual gland. Expression of these unique transcription factors correlated with sublingual and parotid specific subsets of both highly expressed and differentially expressed genes. Gene ontology analyses revealed that the highly expressed genes common to all glands were associated with global functions, while many of the genes expressed in a single gland play a major role in the function of that gland. In summary, transcriptional profiling of the three murine major salivary glands identified a limited number of highly expressed genes, differentially expressed genes, and unique transcription factors that represent the transcriptional signatures underlying gland-specific biological properties.


Kinetics of the nucleoside triphosphate hydrolase of Toxoplasma gondii in mice with acute and chronic toxoplasmosis.
The kinetics of the nucleoside triphosphate hydrolase (NTPase) of Toxoplasma gondii was examined using an avidin-biotin sandwich-ELISA (ABS-ELISA) based on an anti-NTPase monoclonal antibody, 6C6. The RH and ME49 strains of the parasite were used to produce acute and chronic infections in mice, respectively. In the acute model, detectable serum concentrations of NTPase were observed from day 1 post-infection and gradually increased until the death of the mice. They were associated with parasitaemia (as estimated by bioassay). No anti-T. gondii antibody could be detected at any time. In the chronic model, in which 20 T. gondii ME49 cysts were given to each mouse per os, the NTPase concentration generally increased from day 3, peaked between days 7 and 14 and then declined. However, one of the four mice used still had a high serum concentration of NTPase on day 35. Again, detectable NTPase concentrations occurred when the mice had parasitaemias. Antibody to T. gondii was detected from day 7 (IgM) or 10 (IgG) and brain cysts were observed from day 14. Since detectable serum concentrations of NTPase appear to be associated with parasitaemia in both acute and chronic toxoplasmosis, the ABS-ELISA of the enzyme may make a useful diagnostic tool.


Complete Genome Sequence of Variant Porcine Epidemic Diarrhea Virus Strain CH/HNZZ47/2016 Isolated from Suckling Piglets in China.
Porcine epidemic diarrhea virus (PEDV) could cause an acute and highly contagious enteric disease in swine. Here, we report the complete genome sequence of PEDV strain CH/HNZZ47/2016 isolated from suckling piglets with mild diarrhea in Henan Province, China. It will help understand the molecular and evolutionary characteristics of PEDV in China.


The immunocytochemical demonstration of human placental lactogenic hormone (hPL): a parameter for the functional capacity of the trophoblast.
Forty-two placentae from pregnancies of 36 to 42 weeks' gestation were examined: the maternal serum human placental lactogen (hPL) values of the mothers during the last week of gestation ranged between 3 and 12 micrograms/ml. hPL was demonstrated by the indirect immunofluorescence technique and was present in all placentae. A significant regional difference in hPL concentration was not found, but within individual sections focal differences in intensity were apparent. Of intensity group I (weakly positive) 92 per cent correlated with maternal serum hPL values of 3 to 6 micrograms/ml; 78 per cent of group II/III (very strongly positive) with values above 6 micrograms/ml. In the four-field Chi-square test the probability of error was at 5%. In 32 cases trophoblast islands (Islands of Ortmann) were present, of which 20 were hPL positive. Their degree of intensity corresponded to group I of the syncytiotrophoblast. Of the placentae showing hPL-positive Islands of Ortmann, 95 per cent correlated with maternal serum hPL values below 6 micrograms/ml whilst 70 per cent of the hPL-negative trophoblast islands correlated with serum values above 8 micrograms/ml. It is suggested that maternal serum hPL values are determined by the rate of synthesis of hPL by the placenta and not by the rate of secretion. The focal differences in intensity indicates that the serum level does not only depend on the absolute surface area of the trophoblast, but that there also exist qualitative and functional differences between different areas of the syncytiotrophoblast. Heterotopic hPL synthesis in the Islands of Ortmann is considered to be independent of hPL synthesis by the syncytiotrophoblast.


Medicinal applications of delta-9-tetrahydrocannabinol and marijuana.
The use of crude marijuana for herbal medicinal applications is now being widely discussed in both the medical and lay literature. Ballot initiatives in California and Arizona have recently made crude marijuana accessible to patients under certain circumstances. As medicinal applications of pure forms of delta-9-tetrahydrocannabinol (THC) and crude marijuana are being considered, the most promising uses of any form of THC are to counteract the nausea associated with cancer chemotherapy and to stimulate appetite. We evaluated the relevant research published between 1975 and 1996 on the medical applications, physical complications, and legal precedents for the use of pure THC or crude marijuana. Our review focused on the medical use of THC derivatives for nausea associated with cancer chemotherapy, glaucoma, stimulation of appetite, and spinal cord spasticity. Despite the toxicity of THC delivered in any form, evidence supports the selective use of pure THC preparations to treat nausea associated with cancer chemotherapy and to stimulate appetite. The evidence does not support the reclassification of crude marijuana as a prescribable medicine.


First molecular genetic evidence for automictic parthenogenesis in cockroaches.
Parthenogenesis is an asexual mode of reproduction that plays an important role in the evolution of sex, sociality, and reproduction strategies in insects. Some species of cockroach exhibit thelytoky, a type of parthenogenesis in which female offspring are produced without fertilization. However, the cytological and genetic mechanisms of parthenogenesis in cockroaches are not well understood. Here we provide the first molecular genetic evidence that cockroaches can reproduce through automixis. Using the American cockroach Periplaneta americana, we performed microsatellite analysis to investigate the genetic relationship between parthenogenetically produced nymphs and the parent virgin females, and found that all parthenogenetic offspring were homozygous for autosomal microsatellite markers, whereas the female parents were heterozygous. In addition, flow cytometry analysis revealed that the parthenogenetic offspring were diploid. Taken together, our results demonstrate that P. americana exhibits automixis-type thelytoky, in which diploidy is restored by gamete duplication or terminal fusion. These findings highlight the unique reproduction strategies of cockroaches, which are more varied than was previously recognized.


Production of chronic congestive heart failure by rapid ventricular pacing in the rabbit.
The aim was to produce a model of low output congestive heart failure by rapid pacing in rabbits. To perform rapid pacing in rabbits, a custom made pacemaker was developed which is light (about 80 g) and can pace at up to 400 beats.min-1 for more than two weeks. A thoracotomy was done and two electrodes were sutured onto the left ventricle. A central venous pressure line was chronically implanted. With the use of this pacemaker, rabbits were paced at 350-400 beats.min-1 for several weeks. Central venous pressure increased from 1.4(SEM 0.2) to 6.4(0.5) mm Hg (p < 0.01, n = 14). After pacing for 16.1(1.6) d, haemodynamic studies were performed under anaesthesia with thiamylal sodium. Left ventricular end diastolic pressure was higher in the paced rabbits (n = 10) than in the control rabbits which underwent sham operation but were not paced (n = 6), at -0.6(0.6) v 19.3(2.0) mm Hg (p < 0.01). Cardiac output [673(56) v 536(45) ml.min-1, p < 0.10] and +dP/dt [1433(97) v 722(51) mm Hg.s-1, p < 0.01] were lower in the paced rabbits (n = 7-8) than in the control rabbits (n = 6). The paced rabbits had more ascites [1.9(1.0) v 45.9(18.9) ml, p < 0.05] and pleural effusion [0.4(0.3) v 12.9(6.7) ml, p < 0.10] than control rabbits. Plasma noradrenaline was higher in the paced rabbits (n = 11) than in the control rabbits (n = 7), at 1.59(0.43) v 0.60(0.05) ng.ml-1 (p < 0.05). The ratio of wet heart weight or lung weight to body weight was higher (p < 0.01) in the paced rabbits than in the control rabbits. Chronic biventricular congestive heart failure can be produced in rabbits by rapid pacing.


Interleukin-1.
For the past 30 years, considerable experimentation on the mechanisms of host responses to infection has centered on soluble products derived from phagocytic cells. The biologic activities of some of these products include fever mediated by endogenous pyrogen (EP) and induction of acute-phase responses by leukocytic endogenous mediator (LEM), EP and LEM have been characterized and purified and appear to be closely related, if not identical, molecules. Lymphocyte-activating factor (LAF), a recently described polypeptide that acts on lymphocytes, shares many of the physical properties of EP and LEM; when incubated with lymphocytes, purified EP/LEM is indistinguishable from LAF. The term interleukin-1 (IL-1) is now used to describe LAF, EP, and LEM as a single molecule or as a family of closely related molecules, although at present there is no known sequence analysis of EP, LEM, or LAF. In this review, experimental and clinical data are presented that link mediation of host responses to infection and inflammation to the production and activity of IL-1. Cell sources and inducers of IL-1 are discussed, as are its chemical nature and mechanisms of action. In addition, the importance of IL-1 and its effects on host defense mechanisms are presented. For example, how IL-1-mediated responses, such as elevated temperature, lymphocyte activation, and systemic metabolic changes, alter the host as well as the invading microbe are considered. The conclusions of this review are (1) that IL-1 is a key mediator of host responses to microbial invasion, (2) that IL-1 represents a true hormone produced during infection and inflammation, and (3) that its biologic activities account for several aspects of the acute-phase reaction.


The Relationship Between Plasma Eosinophil Count and Coronary Artery Ectasia.
The pathophysiology of coronary artery ectasia (CAE) has not been clearly identified, although multiple abnormalities including arteritis, endothelial dysfunction, and atherothrombosis have been reported. It is known that eosinophils play an important role in inflammation and thrombosis. Also vascular anomalies such as aneurysm have been noted in patients with hypereosinophilic syndromes. We aimed to compare the numbers of eosinophil counts of the patients CAE versus controls. This study included 50 CAE patients (20 male, mean age 60.26 ± 10.6 years) and 30 control person (10 male, mean age 57.86 ± 11.6 years). These participants were performed concurrent routine biochemical tests and neutrophil, lymphocyte, eosinophil count and mean platelet volume (MPV) on whole blood count. These parameters were compared between groups. Baseline characteristics of the study groups were comparable. CAE patients had a higher MPV value, eosinophil, neutrophil lymphocyte ratio (NLR) than controls (8.5 ± 1 vs 76.2 ± 1.6 fl and 0.198 ± 0.14 vs 0.093 ± 0.058 and 3.0 ± 2.5vs 1.14 ± 0.9; P < 0.001, 0.002 and 0.028 respectively). As a result, our study revealed a relationship between eosinophil count, NLR and MPV in patients with CAE.


Enrichment of self-domestication and neural crest function loci in the heritability of neurodevelopmental disorders.
Self-domestication could contribute to shaping the biology of human brain and consequently the predisposition to neurodevelopmental disorders. Leveraging genome-wide data from the Psychiatric Genomics Consortium, we tested the enrichment of self-domestication and neural crest function loci with respect to the heritability of autism spectrum disorder, schizophrenia (SCZ in East Asian and European ancestries, EAS and EUR, respectively), attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and Tourette's syndrome (TS). Considering only self-domestication and neural-crest-function annotations in the linkage disequilibrium score regression (LDSC) model, our partitioned heritability analysis revealed statistically significant enrichments across all disorders investigated. The estimates of the heritability enrichments for self-domestication loci were similar across neurodevelopmental disorders, ranging from 0.902 (EAS SCZ, p = 4.55 × 10-20) to 1.577 (TS, p = 5.85 × 10-5). Conversely, a wider spectrum of heritability enrichment estimates was present for neural crest function with the highest enrichment observed for TS (enrichment = 3.453, p = 2.88 × 10-3) and the lowest for EAS SCZ (enrichment = 1.971, p = 3.81 × 10-3). Although these estimates appear to be strong, the enrichments for self-domestication and neural crest function were null once we included additional annotations related to different genomic features. This indicates that the effect of self-domestication on the polygenic architecture of neurodevelopmental disorders is not independent of other functions of human genome.


FOXP3: not just for regulatory T cells anymore.
The forkhead family transcription factor FOXP3 has been shown to be critical for the development and function of CD4+ CD25+ regulatory T cells. Recently, FOXP3 expression has been shown to be induced upon activation of human CD4+ T cells. A new report in this issue of the European Journal of Immunology shows that expression of FOXP3 in activated T cell leads to hyporesponsiveness, but not necessarily to acquisition of suppressor function. This finding suggests a new role for FOXP3 in human CD4+ T cells: down-modulating responses to TCR-mediated stimulation.


Influence of socioeconomic status and BMI on the quality of life after mastectomy in Bangladeshi breast cancer patients in a public hospital.
Quality of life after diagnosis and during treatment phases of breast cancer varies across individual to individual, country to country and from ethnicity to ethnicity. So factors affecting it are of growing research interest. The aim of the study was to investigate the influence of socioeconomic status and body mass index on the quality of life of breast cancer patients during the phases of treatment-before and after mastectomy. Two hundred and fifty-one women with breast cancer undergoing surgery were interviewed prior to and after mastectomy in National Institute of Cancer Research and Hospital, Dhaka from January 2012 to March 2013 using European Organization for Research and Treatment of Cancer Core Questionnaire (and QLQ-Br23). Socioeconomic factors like educational status, family income, occupation and body mass index were taken as investigating factors against global health status and breast cancer-related factors. Significant reduction of the scores found that means deterioration of function in the following domains of the quality of life were found such as physical well-being (P = 0.019), emotional well-being (P = 0.035), cognitive status (P = 0.05) and the breast-specific subscales like BRBI (body image), BRBS (breast symptoms), BRAS (arm symptoms); (P = 0.013, 0.103, 0.015) was observed after surgery in lower income group. Worker group expressed also similar effect on the global health status/quality-of-life scales (P = 0.05, 0.043, 0.021) and breast subscales (P = 0.002, 0.027, 0.05), patients with lower body mass index also have a lower score also. Educational status does not affect the two groups. Younger age group patients expressed much distress. Improvement of family income, nutritional status and improvement of working environment might have an impact on the improvement of the quality of life of breast cancer patients during the phases of treatment.


Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles.
Glycoscience, despite its myriad of challenges, promises to unravel the causes of, potential new detection methods for, and novel therapeutic strategies against, many disease states. In the last two decades, glyco-gold nanoparticles have emerged as one of several potential new tools for glycoscientists. Glyco-gold nanoparticles consist of the unique structural combination of a gold nanoparticle core and an outer-shell comprising multivalent presentation of carbohydrates. The combination of the distinctive physicochemical properties of the gold core and the biological function/activity of the carbohydrates makes glyco-gold nanoparticles a valuable tool in glycoscience. In this review we present recent advances made in the use of one type of click chemistry, namely the azide-alkyne Huisgen cycloaddition, for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles.


Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose.
Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight. For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based on CYP3A5 genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing. Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set. This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients.


The role of endothelial cells in the vasculopathy of systemic sclerosis: A systematic review.
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by fibroproliferative vasculopathy, immunological abnormalities and progressive fibrosis of multiple organs including the skin. In this study, all English speaking articles concerning the role of endothelial cells (ECs) in SSc vasculopathy and representing biomarkers are systematically reviewed and categorized according to endothelial cell (EC) (dys)function in SSc. A sensitive search on behalf of the EULAR study group on microcirculation in Rheumatic Diseases was developed in Pubmed, The Cochrane Library and Web of Science to identify articles on SSc vasculopathy and the role of ECs using the following Mesh terms: (systemic sclerosis OR scleroderma) AND pathogenesis AND (endothelial cells OR marker). All selected papers were read and discussed by two independent reviewers. The selection process was based on title, abstract and full text level. Additionally, both reviewers further searched the reference lists of the articles selected for reading on full text level for supplementary papers. These additional articles went through the same selection process. In total 193 resulting articles were selected and the identified biomarkers were categorized according to description of EC (dys)function in SSc. The most representing and reliable biomarkers described by the selected articles were adhesion molecules for EC activation, anti-endothelial cell antibodies for EC apoptosis, vascular endothelial growth factor (VEGF), its receptor VEGFR-2 and endostatin for disturbed angiogenesis, endothelial progenitors cells for defective vasculogenesis, endothelin-1 for disturbed vascular tone control, Von Willebrand factor for coagulopathy and interleukin (IL)-33 for EC-immune system communication. Emerging, relatively new discovered biomarkers described in the selected articles, are VEGF165b, IL-17A and the adipocytokines. Finally, myofibroblasts involved in tissue fibrosis in SSc can derive from ECs or epithelial cells through a process known as endothelial-to-mesenchymal transition. This systematic review emphasizes the growing evidence that SSc is primarily a vascular disease where EC dysfunction is present and prominent in different aspects of cell survival (activation and apoptosis), angiogenesis and vasculogenesis and where disturbed interactions between ECs and various other cells contribute to SSc vasculopathy.


Treatment of trichomoniasis in the female. A comparison of metronidazole and nimorazole.
The effectiveness of metronidazole (Flagyl) and nimorazole (Naxogin) has been compared by using these drugs in the recommended dosage in alternate patients in a series of 218 consecutive cases of vaginal trichomoniasis. Follow-up tests in 100 patients treated with metronidazole and 97 treated with nimorazole indicated cure-rates of 95 and 82 per cent. respectively. Male consorts were examined and given treatment on epidemiological grounds in about 70 per cent. of both treatment groups. Both drugs were free from significant side-effects. The causes of treatment failure in trichomoniasis are discussed and the desirability of relating dosage to the patient's body-weight is suggested. This factor may be especially important in deciding the dosage given on epidemiological grounds to the male consorts. It may also be an important advantage in the current trend of treating trichomoniasis in both sexes with larger doses over a much shorter time.


[Pannus development in adjuvant arthritis of the rat - an autoradiographic study (author's transl)].
After the injection of complete adjuvant, rats develop arthritis with increased proliferation of synovial tissue cells at the attachment of the synovial membrane to cartilage and bone. From this synovial tissue a connective tissue pannus develops which covers the cartilage surface as a monocellular or multicellular layer of proliferating cells. Areas with cartilage destruction are usually characterized by a great number of proliferating connective tissue cells. Cartilage destruction is not restricted to the superficial pannus, since granulation tissue of the subchondral bone may also participate in cartilage resorption. The quantitative determination of 3H-thymidine labelled chondrocytes excludes participation of these cells in pannus formation.


KATP channels and basal coronary vascular tone.
After reviewing recent experimental work from various laboratories we have come to the following conclusions. (1) An increase in transmural pressure causes depolarisation of coronary arterioles, which increases smooth muscle tone. Under these conditions the opening of KATP channels can induce a much larger change in membrane potential than in relaxed arteries. Furthermore, the rate of ATP hydrolysis by contractile proteins, and thus the submembrane nucleotide concentrations, might also be changed in the presence of myogenic tone. Therefore care should be taken when extrapolating patch clamp results from isolated coronary smooth muscle cells to the function of KATP channels in vivo. (2) The opening of KATP channels is increased in situations related to energy imbalance, such as hypoxia, adenosine release, intracellular acidification, and lactate accumulation. However, there is increasing evidence that KATP channels also contribute to the setting of the membrane potentials of coronary smooth muscle cells under normoxic conditions. Thus the modulation of KATP channels by intracellular metabolites and by vasoactive autacoids may play an important role in the regulation of coronary blood flow even in the presence of normal intracellular ATP concentrations. (3) The smooth muscle cells of coronary terminal arterioles form an electrical syncytium. The opening of a new KATP channels in smooth muscle cells of a terminal arterioles might induce a spatially homogeneous hyperpolarisation of the entire arteriole. The resulting homogeneous decrease in the tone of the coronary smooth muscle cells of the arteriole may induce a considerable change in vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)


Dietitians' attitudes regarding elderly nutritional factors.
The elderly are becoming a significant segment of the public receiving medical nutritional care in the community. Since dietitians are the professionals responsible for their nutritional care, the aim of this study was to assess dietitians' attitudes and correlates regarding elderly nutritional factors. Questionnaires were distributed at a dietitians' conference to 114 dietitians working in the second largest HMO in Israel. Ninety-five questionnaires were returned. The questionnaire assessed different aspects of elderly nutrition, such as factors affecting elderly nutrition, medical conditions influenced by nutrition, and the dietitian's role in modifying elderly nutritional habits. Participants reported that between 25% and 50% of their patients were elderly. They believed that dietitians are the only health care professionals who should be giving nutritional advice to the elderly. The more experienced dietitians were willing to share nutritional treatment plans with the patients' physicians. The participants in this study believed that nutritional advice may influence the elderly to change their nutritional habits. They recognized the impact that nutrition can have on different health conditions and identified a variety of factors affecting elderly nutrition, especially functional and medical conditions. Overall, dietitians working in the community viewed themselves as the main professionals responsible for counseling the elderly on nutritional issues. Although dietitians perceived their knowledge and skills in this area as very good, the researchers identified a need for further education, especially regarding the possible influence of socio-demographic characteristics on dietary intake and the value of educating the elderly to read and understand nutrition labels.


Benefits of Less Restrictive Regulation of Advance Practice Registered Nurses in Florida.
Advanced Practice Registered Nurses (APRNs) provide access to cost-effective, high quality care. APRNs are underutilized in states that restrict their practice. Removing restrictions could expand access to quality health care, cost-effectively relieve the physician shortage, and contribute economically. This study forecasts the health system and economic impacts of reducing practice restrictions for Florida APRNs. The analysis utilized a number of data sources and IMPLAN software and estimated changes in APRN supply given less restrictive practice laws, and consequential health system and economic benefits. Between 2013 and 2025 APRN full time equivalents could increase an additional 11% with less restrictive practice regulations. This could eliminate or reduce the shortage of different types of physicians. Health care cost-savings could be $50 to $493 per resident. There would be a number of general economic benefits. A number of health system and economic benefits would ensue from less restrictive APRN regulation.


Sulfonamide hypersensitivity.
Sulfonamide antibiotics can result in a wide variety of hypersensitivity reactions. No validated diagnostic tests are available for sulfonamide reactions; therefore, clinicians must rely on the combination of a careful patient history, review of medical records, and a sound knowledge base regarding the common clinical manifestations of sulfonamide hypersensitivity reactions. Although HIV-infected individuals have a high risk for hypersensitivity reactions to sulfamethoxazole, readministering the drug can usually be performed safely by using a desensitization protocol. Sulfonamide-containing medications that are not antibiotics also have the capacity for causing hypersensitivity reactions. Whether the sulfa moiety confers a risk of cross-reaction is controversial. The preponderance of available evidence suggests that sulfonamide antibiotics probably do not cross-react with sulfonamide nonantibiotics.


Naringin from Coffee Inhibits Foodborne Aspergillus fumigatus via the NDK Pathway: Evidence from an In Silico Study.
In the tropics, coffee has been one of the most extensively cultivated economic crops, especially Arabica coffee (Coffea arabica L.). The coffee pulp, which includes phytochemicals with a proven antifungal action, is one of the most insufficiently utilized and neglected byproducts of coffee refining. In the current experiment, we carried out in silico screening of the isolated Arabica coffee phytochemicals for antifungal activity against Aspergillus fumigatus: a foodborne fungus of great public health importance. As determined by the molecular docking interactions of the library compounds indicated, the best interactions were found to occur between the nucleoside-diphosphate kinase protein 6XP7 and the test molecules Naringin (-6.771 kcal/mol), followed by Epigallocatechin gallate (-5.687 kcal/mol). Therefore, Naringin was opted for further validation with molecular dynamic simulations. The ligand-protein complex RMSD indicated a fairly stable Naringin-NDK ligand-protein complex throughout the simulation period (2-16 Å). In ADME and gastrointestinal absorbability testing, Naringin was observed to be orally bioavailable, with very low intestinal absorption and a bioavailability score of 0.17. This was further supported by the boiled egg analysis data, which clearly indicated that the GI absorption of the Naringin molecule was obscure. We found that naringin could be harmful only when swallowed at a median lethal dose between 2000 and 5000 mg/kg. In accordance with these findings, the toxicity prediction reports suggested that Naringin, found especially in citrus fruits and tomatoes, is safe for human consumption after further investigation. Overall, Naringin may be an ideal candidate for developing anti-A. fumigatus treatments and food packaging materials. Thus, this study addresses the simultaneous problems of discarded coffee waste management and antifungal resistance to available medications.


Chlorpromazine metabolism VII: new quantitative fluorometric determination of chloropromazine and its sulfoxide.
A new, sensitive assay is described for chlorpromazine and/or its sulfoxide. The method is based on reacting the tertiary amine base with 9-bromomethylacridine to form a quaternary compound which, on photolysis, yields highly fluorescent products that are determinable fluorometrically. The procedural steps were standardized, and an optimum assay procedure was developed. The method shows a less than 3% coefficient of variation when applied directly to chlorpromazine samples and is capable of determining 15-20 ng of the drug. The method is readily adaptable to clinical and bioavailability studies.


Lethal bacterial trap: Cationic surface for endodontic sealing.
Insoluble antibacterial cationic nanoparticles have been previously shown to have potent and long-lasting antibacterial properties. Our tested hypothesis was that root canal pathogens will be attracted to and eliminated when exposed to epoxy resin-based surfaces incorporating cationic nanoparticles. In our research, an epoxy resin-based surface incorporating quaternary ammonium polyethyleneimine (QPEI) nanoparticles was evaluated. Surface characterization was performed using atomic force microscopy and X-ray photoelectron spectra. The surface anti-Enterococcus faecalis effect was evaluated in an anti-gravitational model. Cell membrane potential, viability, biofilm thickness, and biomass were tested using flow cytometry and confocal laser scanning microscopy. Additionally, the antibiofilm activity of the bacterial supernatant was assessed. The surface characterization showed QPEI nanoparticle embedment on the modified sealer. The epoxy resin-based surface incorporating the QPEI nanoparticles actively attracted bacteria, causing membrane destabilization, and bacterial death. The supernatant of bacteria pre-exposed to QPEI showed an antibacterial effect. In conclusion, the tested epoxy resin-based surface incorporating QPEI nanoparticles traps and kills bacteria. The nanoparticles attracted bacteria, reducing their viability, and promoting cell death.


Autoimmune premature ovarian failure.
Premature ovarian failure (POF), also termed as primary ovarian insufficiency (POI), is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS) in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.


[Extra-osseous maxillary cysts--nasolabial cyst].
The maxillary cysts are classified on the basis of the recommendations by the World Health Organisation (1971), based on pathogenic criteria, in developmental and inflammatory, odontogenic and nonodontogenic cysts. Only two maxillary cysts lie primarily extraosseous: a non-odontogenic cyst, the nasolabial cyst, and an odontogenic cyst, the gingival cyst. The nasolabial cyst is a rare, developmental, non-odontogenic maxillary cyst, which offers the peculiarity of its constant extraosseous localization. On the basis of our cases from 1966 to 1988 the clinical patterns, histopathology, differential diagnosis, therapy, prognosis and histopathogenesis of the nasolabial cyst are presented.


A study on pesticide runoff from paddy fields to a river in rural region--2: development and application of a mathematical model.
A mathematical model was developed to predict the runoff of pesticides from paddy fields to a river in a rural region. The model comprises three submodels: (1) submodel for river flow, (2) submodel for pesticide behavior in paddy fields, (3) submodel for pesticide behavior in a river. The tank model was applied to predict the river flow and the paddy water. In order to reproduce the actual behavior of pesticides in paddy fields, the kinetics of the transport and reaction mechanisms of pesticides applied to paddy fields were considered in the model. The model was applied to the Kozakura River Basin where the detailed field survey was conducted. The model reflected well the runoff characteristics of pesticides obtained from the detailed field survey.


Toward a systems- and control-oriented agent framework.
This paper develops a systems- and control-oriented intelligent agent framework called the hybrid intelligent control agent (HICA), as well as its composition into specific kinds of multiagent systems. HICA is essentially developed around a hybrid control system core so that knowledge-based planning and coordination can be integrated with verified hybrid control primitives to achieve the coordinated control of multiple multimode dynamical systems. The scheme is applied to the control of teams of unmanned air and ground vehicles engaged in a pursuit-evasion war game. Results are demonstrated in simulation.


Branched Chondroitin Sulfate Oligosaccharides Derived from the Sea Cucumber Acaudina molpadioides Stimulate Neurite Outgrowth.
Fucosylated chondroitin sulfate (FCS) from the sea cucumber Acaudina molpadioides (FCSAm) is the first one that was reported to be branched by disaccharide GalNAc-(α1,2)-Fuc3S4S (15%) and sulfated Fuc (85%). Here, four size-homogenous fractions, and seven oligosaccharides, were separated from its β-eliminative depolymerized products. Detailed NMR spectroscopic and MS analyses revealed the oligomers as hexa-, hepta-, octa-, and nonasaccharide, which further confirmed the precise structure of native FCSAm: it was composed of the CS-E-like backbone with a full content of sulfation at O-4 and O-6 of GalNAc in the disaccharide repeating unit, and the branches consisting of sulfated fucose (Fuc4S and Fuc2S4S) and heterodisaccharide [GalNAc-(α1,2)-Fuc3S4S]. Pharmacologically, FCSAm and its depolymerized derivatives, including fractions and oligosaccharides, showed potent neurite outgrowth-promoting activity in a chain length-dependent manner. A comparison of analyses among oligosaccharides revealed that the sulfate pattern of the Fuc branches, instead of the heterodisaccharide, could affect the promotion intensity. Fuc2S4S and the saccharide length endowed the neurite outgrowth stimulation activity most.


Diagnosing autoimmune encephalitis based on clinical features and autoantibody findings.
Autoimmune encephalitides have been accepted as a reproducible and treatable new group of diseases. At present, there is concern that such diagnoses might be made too liberally. Areas covered: This article suggests how to make valid diagnoses. They should consist of three elements: the clinical syndrome, the associated antibody and the presumed cause or predisposition. Recently, an international consortium published formal clinical criteria for autoimmune encephalitides to enable diagnoses even if antibody testing is not (immediately) available and to prevent overinterpretation of questionable antibody results. Antibody testing has greatly benefitted from the introduction of cell-based assays for the demonstration of antibodies against surface antigens. Paraneoplastic or post-infectious situations, side effects of tumor therapies or genetic predispositions help to explain why a patient develops autoimmune encephalitis. Expert opinion: With the application of this three-fold diagnostic system, clinicians can counsel patients regarding therapy and prognosis, while researchers can form meaningful patient cohorts. An operationalization of criteria would be advantageous.


Interferon production by a human lymphoblastoid cell line (DG-75) free of the Epstein-Barr genome.
A new lymphoblastoid cell line, DG-75, was investigated for its ability to produce interferon. DG-75 cells, previously shown to be free of Epstein-Barr virus genome and receptors, could be grown in submerged culture and could produce interferon in titers comparable to interferon produced by Namalva cells. The interferon produced was similar in size to the Namalva interferon as determined by gel filtration in Ultrogel AcA54. The DG-75 cells present a new source of large quantities of interferon which may be safer for human use than the Namalva interferon.


Emerging Experiences with Virtual Clinical Ethics Consultation: Case Studies from the United States and Malaysia.
AbstractThe COVID-19 pandemic has inspired numerous opportunities for telehealth implementation to meet diverse healthcare needs, including the use of virtual communication platforms to facilitate the growth of and access to clinical ethics consultation (CEC) services across the globe. Here we discuss the conceptualization and implementation of two different virtual CEC services that arose during the COVID-19 pandemic: the Clinical Ethics Malaysia COVID-19 Consultation Service and the Johns Hopkins Hospital Ethics Committee and Consultation Service. A common strength experienced by both platforms during virtual delivery included improved ability for local practitioners to address consultation needs for patient populations otherwise unable to access CEC services in their respective locations. Additionally, virtual platforms allowed for enhanced collaboration and sharing of expertise among ethics consultants. Both contexts encountered numerous challenges related to patient care delivery during the pandemic. The use of virtual technologies resulted in decreased personalization of patient-provider communication. We discuss these challenges with respect to contextual differences specific to each service and setting, including differences in CEC needs, sociocultural norms, resource availability, populations served, consultation service visibility, healthcare infrastructure, and funding disparities. Through lessons learned from a health system in the United States and a national service in Malaysia, we provide key recommendations for health practitioners and clinical ethics consultants to leverage virtual communication platforms to mitigate existing inequities in patient care delivery and increase capacity for CEC globally.


Characteristics associated with pain in long-term care residents with dementia.
This article describes the prevalence, assessment, and treatment of pain, as well as characteristics associated with pain, in 331 residents with dementia in 45 assisted living facilities and nursing homes. Overall, 21% of residents had pain, and pain was more commonly reported in for-profit facilities, and for those receiving professional assessment and treatment.


Myenteric neurons and intestinal mucosa of diabetic rats after ascorbic acid supplementation.
To investigate the effect of ascorbic acid (AA) dietary supplementation on myenteric neurons and epithelial cell proliferation of the jejunum of adult rats with chronic diabetes mellitus. Thirty rats at 90 d of age were divided into three groups: Non-diabetic, diabetic and diabetic treated with AA (DA) (1 g/L). After 120 d of treatment with AA the animals were killed. The myenteric neurons were stained for myosin-V and analyzed quantitatively in an area of 11.2 mm(2)/animal. We further measured the cellular area of 500 neurons per group. We also determined the metaphasic index (MI) of the jejunum mucosa layer of about 2500 cells in the intestinal crypts, as well as the dimensions of 30 villi and 30 crypts/animal. The data area was analyzed using the Olympus BX40 microscope. There was an increase of 14% in the neuronal density (792.6 +/- 46.52 vs 680.6 +/- 30.27) and 4.4% in the cellular area (303.4 +/- 5.19 vs 291.1 +/- 6.0) respectively of the diabetic group treated with AA when compared to control diabetic animals. There were no significant differences in MI parameters, villi height or crypt depths among the groups. Supplementation with AA in the diabetic animal promoted moderate neuroprotection. There was no observation of alteration of the cellular proliferation of the jejunum mucosa layer of rats with chronic diabetes mellitus with or without supplementation with AA.


A novel backscatter focus diagnostic for the TRIDENT 200 TW laser.
Here we present the first direct focal spot images and analysis of an ultrahigh intensity short-pulse laser focus (>5x10(19) W/cm(2)) on target. Such a focal spot characterization is typically done previous to the shot with a low-power alignment beam using equivalent plane imaging techniques. The resulting intensity of the shot is then inferred from these results. We report on the development of a backscatter focus diagnostic, which enables imaging of the on-target full-power focal spot.


Influence of needle insertion speed on backflow for convection-enhanced delivery.
Fluid flow back along the outer surface of a needle (backflow) can be a significant problem during the direct infusion of drugs into brain tissues for procedures such as convection-enhanced delivery (CED). This study evaluates the effects of needle insertion speed (0.2 and 1.8 mm/s) as well as needle diameter and flow rate on the extent of backflow and local damage to surrounding tissues. Infusion experiments were conducted on a transparent tissue phantom, 0.6% (w/v) agarose hydrogel, to visualize backflow. Needle insertion experiments were also performed to evaluate local damage at the needle tip and to back out the prestress in the surrounding media for speed conditions where localized damage was not excessive. Prestress values were then used in an analytical model of backflow. At the higher insertion speed (1.8 mm/s), local insertion damage was found to be reduced and backflow was decreased. The compressive prestress at the needle-tissue interface was estimated to be approximately constant (0.812 kPa), and backflow distances were similar regardless of needle gauge (22, 26, and 32 gauge). The analytical model underestimated backflow distances at low infusion flow rates and overestimated backflow at higher flow rates. At the lower insertion speed (0.2 mm/s), significant backflow was measured. This corresponded to an observed accumulation of material at the needle tip which produced a gap between the needle and the surrounding media. Local tissue damage was also evaluated in excised rat brain tissues, and insertion tests show similar rate-dependent accumulation of tissue at the needle tip at the lower insertion speed. These results indicate that local tissue damage and backflow may be avoided by using an appropriate insertion speed.


30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor mutations.
Aldosterone and the mineralocorticoid receptor (MR) are key elements for maintaining fluid and electrolyte homeostasis as well as regulation of blood pressure. Loss-of-function mutations of the MR are responsible for renal pseudohypoaldosteronism type 1 (PHA1), a rare disease of mineralocorticoid resistance presenting in the newborn with weight loss, failure to thrive, vomiting and dehydration, associated with hyperkalemia and metabolic acidosis, despite extremely elevated levels of plasma renin and aldosterone. In contrast, a MR gain-of-function mutation has been associated with a familial form of inherited mineralocorticoid hypertension exacerbated by pregnancy. In addition to rare variants, frequent functional single nucleotide polymorphisms of the MR are associated with salt sensitivity, blood pressure, stress response and depression in the general population. This review will summarize our knowledge on MR mutations in PHA1, reporting our experience on the genetic diagnosis in a large number of patients performed in the last 10 years at a national reference center for the disease. We will also discuss the influence of rare MR variants on blood pressure and salt sensitivity as well as on stress and cognitive functions in the general population.


Depressive symptoms in children and adolescents: changing aetiological influences with development.
Evidence suggests that depressive symptoms become increasingly heritable as children grow into adolescence. However, the literature is not entirely consistent in this respect and existing longitudinal twin studies have examined changes within adolescence only. Parent and self-report questionnaire data were used to examine the genetic and environmental influences on depressive symptoms in a UK sample of 670 twin pairs aged 5-17. Age effects were examined cross-sectionally and longitudinally using data collected over a 3-year period. Cross-sectional analyses showed that shared environmental effects had significant influence in younger children but not in adolescence, when depression scores were significantly more heritable. The results of these cross-sectional analyses were supported when two waves of parent-report data collected over three years were analysed. Significant new genetic influences emerged in adolescence but no new shared environmental influences. Some sex differences were found, with girls showing greater genetic influence than boys, but only from parent-report data. These findings support and extend earlier work which has shown increasing genetic influence on depressive symptoms as children grow into adolescence.


The molybdate-responsive Escherichia coli ModE transcriptional regulator coordinates periplasmic nitrate reductase (napFDAGHBC) operon expression with nitrate and molybdate availability.
Expression of the Escherichia coli napFDAGHBC operon (also known as aeg46.5), which encodes the periplasmic molybdoenzyme for nitrate reduction, is increased in response to anaerobiosis and further stimulated by the addition of nitrate or to a lesser extent by nitrite to the cell culture medium. These changes are mediated by the transcription factors Fnr and NarP, respectively. Utilizing a napF-lacZ operon fusion, we demonstrate that napF gene expression is impaired in strain defective for the molybdate-responsive ModE transcription factor. This control abrogates nitrate- or nitrite-dependent induction during anaerobiosis. Gel shift and DNase I footprinting analyses establish that ModE binds to the napF promoter with an apparent K(d) of about 35 nM at a position centered at -133.5 relative to the start of napF transcription. Although the ModE binding site sequence is similar to other E. coli ModE binding sites, the location is atypical, because it is not centered near the start of transcription. Introduction of point mutations in the ModE recognition site severely reduced or abolished ModE binding in vitro and conferred a modE phenotype (i.e., loss of molybdate-responsive gene expression) in vivo. In contrast, deletion of the upstream ModE region site rendered napF expression independent of modE. These findings indicate the involvement of an additional transcription factor to help coordinate nitrate- and molybdate-dependent napF expression by the Fnr, NarP, NarL, and ModE proteins. The upstream ModE regulatory site functions to override nitrate control of napF gene expression when the essential enzyme component, molybdate, is limiting in the cell environment.


Tunable Mechanical, Antibacterial, and Cytocompatible Hydrogels Based on a Functionalized Dual Network of Metal Coordination Bonds and Covalent Crosslinking.
Tissue engineering has become a rapidly developing field of research because of the increased demand from regenerative medicine, and hydrogels are a promising tissue engineering scaffold because of their three-dimensional structures. In this study, we constructed novel hydrogels of gelatin methacrylate (GelMA) hydrogels modified with histidine and Zn2+ (GelMA-His-Zn(II)), which possessed fascinating antibacterial properties and tunable mechanical properties because of the formation of a functionalized dual network of covalent crosslinking and metal coordination bonds. The introduction of metal coordination bonds not only improves the strength of the GelMA hydrogels with covalent crosslinking but also makes their mechanical properties tunable via adjustments to the concentration of Zn2+. The synergistic effect of Zn2+ and the imidazole groups gives the GelMA-His-Zn(II) hydrogels fascinating antibacterial properties (up to 100% inhibition). Counting the colony forming units and compression tests confirmed the fascinating antibacterial abilities and tunable mechanical properties, respectively, of the GelMA-His-Zn(II) hydrogels. In addition, Cell Counting Kit-8 assays, cytoskeletal staining assays, and live/dead assays confirmed the excellent cytocompatibility of the GelMA-His-Zn(II) hydrogels. Therefore, the GelMA-His-Zn(II) hydrogels are promising for applications in tissue engineering.


Direct Operando Visualization of Metal Support Interactions Induced by Hydrogen Spillover During CO2 Hydrogenation.
The understanding of catalyst active sites is a fundamental challenge for the future rational design of optimized and bespoke catalysts. For instance, the partial reduction of Ce4+ surface sites to Ce3+ and the formation of oxygen vacancies are critical for CO2 hydrogenation, CO oxidation, and the water gas shift reaction. Furthermore, metal nanoparticles, the reducible support, and metal support interactions are prone to evolve under reaction conditions; therefore a catalyst structure must be characterized under operando conditions to identify active states and deduce structure-activity relationships. In the present work, temperature-induced morphological and chemical changes in Ni nanoparticle-decorated mesoporous CeO2 by means of in situ quantitative multimode electron tomography and in situ heating electron energy loss spectroscopy, respectively, are investigated. Moreover, operando electron energy loss spectroscopy is employed using a windowed gas cell and reveals the role of Ni-induced hydrogen spillover on active Ce3+ site formation and enhancement of the overall catalytic performance.


Evaluation of osteogenic/chondrogenic cellular proliferation and differentiation in the xenogeneic periosteal graft.
To determine whether grafted young periosteum can induce new bone formation in elderly patients, this preliminary study evaluated cell proliferation and differentiation in xenogeneic periosteal grafts in old rats radiographically, histologically, and immunohistochemically. Periosteum harvested from the tibia of young Japanese white rabbits were grafted into old Sprague-Dawley rats with or without administration of 1.0 mg per kilogram per day immunosuppressant FK506. Autogenous old periosteal tissue grafts were also evaluated as a control. Grafted tissue was extirpated after 7, 14, 21, and 45 days. In the xenogeneic group, proliferative cell nuclear antigen-positive cells were observed 7 days after surgery, which differentiated into chondroblasts with bone morphogenetic protein-2 expression and finally formed cartilage by 14 days. Endochondral ossification was observed at 21 days, and bone replacement was completed by 45 days. No osteogenic cell activity was observed in the two other groups. Xenogeneic young periosteum thus maintained its osteogenic/chondrogenic potentiality in older rats.


On the pyrolysis mechanism of 2-pyranones and 2-pyranthiones: thermally induced ground electronic state chemistry of pyran-2-thione.
[reaction: see text] This work reports studies of thermochemistry of pyran-2-thione (PT), a sulfur derivative of alpha-pyrone (AP). Moderate heating of PT results in scrambling of sulfur and oxygen atoms in the molecule and formation of isomeric thiapyran-2-one (TP). The products of pyrolysis of PT were studied experimentally by a combined use low temperature matrix isolation and Fourier transform infrared spectroscopy. The infrared spectrum of the TP monomer isolated in solid argon at 10 K was completely assigned based on comparison with theoretical calculations undertaken at the DFT(B3LYP)/6-311++G(d,p) level. The upper limit of thermal stability of PT was investigated using the differential scanning calorimetry technique. It was found that pyrolysis of PT is already initiated at temperatures below 130 degrees C. The mechanism of the observed pyrolytical conversion has been studied theoretically at the MP2/6-311++G(d,p) level, in the ground electronic state. The primary step of the pyrolytical reaction in PT is the alpha-cleavage of the C-O single bond. It proceeds via an open-ring thioketene-aldehyde structure, TK1. According to the calculations, the ring-opening reaction from PT to TK1 requires an activation energy less than 80 kJ mol(-1), at 130 degrees C, being the rate-determining step. Further steps of the pyrolytical reaction involve internal rotations around single bonds and [1,5] sigmatropic shift of the aldehydic hydrogen. Pyrolytical ring-opening reactions were studied theoretically also for AP and TP and compared to the pyrolysis of PT. It is suggested that the relative ease of the pyrolytical transformation in PT can be explained in terms of existence of the additional minimum TK1 in the reaction path. No counterparts for this structure could be theoretically located for AP and TP.


Cephalosporin-induced neurotoxicity: clinical manifestations, potential pathogenic mechanisms, and the role of electroencephalographic monitoring.
To review the clinical manifestations of cephalosporin-induced neurotoxicity, underlying potential mechanisms, role of electroencephalographic (EEG) monitoring, and management of neurotoxicity. A PubMed search (1970-May 2008) was conducted using search terms such as cephalosporins, neurotoxicity, seizures, and status epilepticus. The search was not limited to the English language and yielded approximately 187 articles. Several case reports and case series were included to outline the salient clinical features of cephalosporin neurotoxicity. Laboratory studies investigating the potential mechanisms were also included. Reports outlining the EEG features of cephalosporin neurotoxicity were included and the role of continuous EEG monitoring was extracted. Finally, management strategies of such neurotoxicity are discussed. Cephalosporin-induced neurotoxicity may manifest in a variety of clinical presentations, ranging from simple encephalopathy or mental status changes to myoclonus, asterixis, seizures, nonconvulsive status epilepticus, as well as coma. Patients who are elderly, those with renal insufficiency, and those with prior neurologic disease may be particularly prone to the neurotoxic effects. The main mechanism of neurotoxicity appears to involve gamma-aminobutyric acid A receptor inhibition, although other mechanisms may be possible. Cephalosporin neurotoxicity may be associated with a variety of EEG manifestations. Treatment mainly involves withdrawal of the offending drug, in addition to hemodialysis in patients with renal failure, and use of benzodiazepines or other anticonvulsants in patients who develop frank status epilepticus. Neurotoxicity can be prevented in high-risk cases with dosage adjustments and monitoring of serum concentrations. Knowledge and awareness of the neurotoxic clinical manifestations, EEG findings, and underlying mechanisms are essential for clinicians in identifying and treating this potentially lethal but reversible complication of cephalosporin therapy. Further studies are needed to determine the most appropriate treatment paradigms for patients who develop status epilepticus as a result of cephalosporins.


Faith and reason and physician-assisted suicide.
Aquinas's conception of the relationship of faith and reason calls into question the arguments and some of the conclusions advanced in contributions to the debate on physician-assisted suicide by David Thomasma and H. Tristram Engelhardt. An understanding of the nature of theology as based on revelation calls into question Thomasma's theological argument in favor of physician-assisted suicide based on the example of Christ and the martyrs. On the other hand, unaided reason calls into question his assumptions about the nature of death as in some cases a good for the human person. Finally, if Aquinas is right about the relationship of faith and reason, Engelhardt's sharp contrast between "Christian" and "secular" approaches to physician-assisted suicide needs reconsideration, although his conclusions about physician-assisted suicide would find support.


[Fundamental study on ataxic mice (wriggle mouse Sagami)].
Wriggle mouse Sagami (WMS), a newly discovered BALB/C mouse strain, is characterized by its locomotor instability, abnormal gait pattern and neck wriggling. Although the growth of WMS mice is delayed, compared with normal BALB/C mice, the brain size corresponds to the relatively smaller body weight. In gross or histological examinations no local atrophy appears in the cerebrum, cerebellum, brain stem or spinal cord. The c-GMP level in the WMS cerebellum is decreased, but the c-AMP level is normal. The ataxic gait is not improved significantly by the administration of thyrotropin releasing hormone (TRH). These results indicate that the mechanism inducing ataxia and abnormal gait pattern in WMS may be different from those in other genetically-determined ataxic mice, e. g., Rolling mouse Nagaya (RMN), PCD, Staggerer and Reeler.


Polyethylene Ear Reconstruction: A State-of-the-Art Surgical Journey.
The use of a porous high-density polyethylene implant for ear reconstruction is gradually gaining acceptance because it allows for a pleasing ear reconstruction in young children before they enter school. In response to this growing interest, the authors decided to write an article clarifying in detail all the steps of this challenging procedure. In this article, the authors also answer all the common questions that surgeons have when they come to observe the operation, or when they go back to their respective practices and start performing this procedure. The authors describe in detail the operative steps that allow for a successful ear reconstruction using porous high-density polyethylene. The key parts of this operation are to meticulously harvest a well-vascularized superficial temporoparietal fascia flap and to use appropriate color-matched skin grafts. This method allows for a pleasing ear reconstruction with excellent definition, projection, symmetry, and long-term viability. The use of porous high-density polyethylene with a thin superficial temporoparietal fascia flap coverage is the authors' preferred method of ear reconstruction because it can be performed at an earlier age, in a single stage, as an outpatient procedure, and with minimal discomfort and psychological trauma for the patients and parents.


Cancer mortality in Europe, 1970-2009: an age, period, and cohort analysis.
The aim of this study was to interpret long-term trends in cancer mortality. We analyzed age, period of death, and cohort of birth effects for 18 major cancer sites and all neoplasms combined in the European Union and 16 European countries over the period 1970-2009 using data from the WHO mortality database. We used a log-linear Poisson model with a likelihood penalizing function to solve the identifiability problem. The present comprehensive analysis confirms the appreciable declines of cancer mortality since the late 1980s in most European countries. For several major sites, the declines were appreciably greater for cohort effects than for period ones. This reflects - besides the inherent characteristics of the model used - a major impact of tobacco smoking on total cancer mortality, particularly in men, as the role of tobacco in mortality of subsequent generations is largely - although not totally - a cohort effect. For neoplasms largely affected by improvements in management and therapy (e.g. testis, Hodgkin lymphoma, leukemia, but also breast and colorectal cancer), a favorable period effect is evident. However, there is also a cohort effect as the advancements have been generally greater in younger generations. For several cancer sites, there were considerable differences in cohort and period effects across Europe, and particularly high age-specific estimates were observed in eastern countries.


Rolling and slipping motion of Euler's disk.
We present an experimental study of the motion of a circular disk spun onto a table. With the help of a high speed video system, the temporal evolution of (i) the inclination angle alpha, (ii) the angular velocity omega, and (iii) the precession rate Omega are studied. The influence of the mass of the disk as well as the friction between the disk and the supporting surface are considered. Both inclination angle and angular velocity are observed to decrease according to a power law. We also show that the precession rate diverges as the motion stops. Measurements are performed very near the collapse as well as on long range times. Times to collapse have been also measured. Results are compared with previous theoretical and experimental works. The major source of energy dissipation is found to be the slipping of the disk on the plane.


Inner mitochondrial membranes bound to concanavalin A-sepharose display succinate dehydrogenase, ATPase, and cytochrome oxidase activity.
A fraction (15-20% of the total protein) of a preparation of bovine submitochondrial particles (SMPs) binds to concanavalin A-sepharose. The bound membranes displayed succinate dehydrogenase, cytochrome oxidase, and ATPase activity, which, as in SMPs, were inhibited by malonate, cyanide, and oligomycin, respectively. These results indicate that the bound membranes are inner mitochondrial membranes and that they contain a glycoprotein which was recognized by concanavalin A. It was possible to repeatedly perform the three enzyme assays, one after the other, in the same gel with the bound membranes. Long-term stability tests (22 days) showed that cytochrome oxidase was much more stable in the membranes bound to the gel than in SMPs, while the ATPase activity decayed at a similar rate in the two conditions. Thus, inner mitochondrial membranes bound to ConA-Sepharose appear to be a potentially interesting model for the study of immobilized multienzymatic complexes.


The Cytochrome P450 Gene CsCYP85A1 Is a Putative Candidate for Super Compact-1 (Scp-1) Plant Architecture Mutation in Cucumber (Cucumis sativus L.).
The dwarf or compact plant architecture is an important trait in plant breeding. A number of genes controlling plant height have been cloned and functionally characterized which often involve in biosynthesis or signaling of plant hormones such as brassinosteroids (BRs). No genes for plant height or vine length have been cloned in cucurbit crops (family Cucurbitaceae). From an EMS-induced mutagenesis population, we identified a super compact (SCP) mutant C257 which was extremely dwarf due to practically no internode elongation. Under dark growing condition, C257 did not undergo skotomorphogenesis and its mutant phenotype could be rescued with exogenous application of brassinolide (BL), suggesting SCP might be a BR-deficient mutant. Segregation analysis revealed a single recessive gene scp-1 that was responsible for the SCP mutation. Map-based cloning combined with a modified MutMap identified CsCYP85A1, a member of the plant cytochrome P450 monooxygenase gene family, as the most possible candidate gene for scp-1, which encodes a BR-C6-oxidase in the BR biosynthesis pathway. We show that a SNP within the second exon of scp-1 candidate gene caused the SCP phenotype. Three copies of the CsCYP85A gene are present in the cucumber genome, but only the scp-1/CsCYP85A1 gene seemed active. The expression of CsCYP85A1 was higher in flowers than in the leaves and stem; its expression in the wild type (WT) was feedback regulated by BL application. Its expression was reduced in C257 as compared with the WT. This was the first report of map-based cloning of a plant height gene in cucurbit crops. The research highlighted the combined use of linkage mapping, an improved MutMap method and allelic diversity analysis in natural populations in quick cloning of simply inherited genes in cucumber. The roles of CsCYP85A1 in regulation of internode elongation in cucumber was discussed.