[Incidence of left renal vein anomalies in routine abdominal CT scans].
To study the appearance and incidence of left renal vein anomalies in abdominal CT examinations. One thousand and three abdominal CT examinations were reviewed retrospectively for the presence of left renal vein anomalies. Nineteen CT scans were excluded from the study because of technical or patient-dependent factors. The course of the left renal vein was assessed on the CT slices to detect any anomalies. Left renal vein anomaly was detected in 32 (3.2%) of 984 cases. Twenty-three (2.3%) of them were a retroaortic and 9 (0.9%) of them were a circumaortic left renal vein. It is important to detect left renal vein anomalies before retroperitoneal surgery or interventional procedures. These anomalies can be identified in routine abdominal CT examinations with a careful inspection.


Benign-to-malignant B16 melanoma progression induced in two stages in vitro by exposure to hypoxia.
Benign tumors apparently become malignant by generating a succession of variants with ever-greater growth potential and autonomy. Such stepwise progression has not been achieved in vitro under conditions likely to occur in developing tumors. Tumors initiated by clone G3.5 of the mouse B16 melanoma regularly generate stable variants that are more malignant. We investigated the possibility that hypoxia might promote stepwise progression along a benign-to-malignant pathway in monolayer cultures of G3.5 cells. Confluent monolayers of metastatic clone G3.5 and the nonmetastatic clone G3.15 were subjected to severe hypoxia (< 50 ppm O2) for up to 72 hours, or to moderate hypoxia (300-1200 ppm O2) for up to 12 days, and were then maintained subconfluent or at confluence for several weeks to permit emergence of progression variants. The relative malignancy of variants was assayed in vivo after subcutaneous injection into mice, by measuring tumor growth rate and counting lung metastases, and after intravenous injection, by counting lung colonies. In vitro assessment of the variants involved growth as monolayers with or without serum, growth in soft agar, and measurement of invasiveness. G3.5 cells were converted to a more malignant variant (G3.5*) by 12-48 hours of severe hypoxia, or longer periods of moderate hypoxia, when followed by maintenance at confluence for 3-5 weeks. Conversions occurred in discrete foci of morphologically-discernible cells (optimum focus formation about one in 1-2 x 10(5) cells) that rapidly expanded to dominate the cultures. The G3.5* phenotype was comparable to the conversion phenotype generated in tumors and included acquisition of growth autonomy in serum-free medium. G3.15 cells were converted to a G3.5-like phenotype by one round of exposure to hypoxia and confluence, and then to the G3.5* phenotype during a second round, at a low frequency (one focus in 5 x 10(6) cells). This behavior was consistent with a failure of all but the largest G3.15 tumors to generate G3.5* conversion cells. Progression from a relatively benign phenotype, G3.15, to a highly malignant phenotype, G3.5*, can be produced in monolayer culture in two stable stages by sequential rounds of exposure to hypoxia and confluence. The resulting conversions corresponded to phenotypes generated within tumors. Both conversions resulted in populations with enhanced growth capabilities, which could establish dominance within tumors. The stepwise conversion of B16 melanoma clones provides a unique model for the in vitro investigation of mechanisms underlying acquisition of malignancy during tumor development.


[Purification of soil from oil pollutants with the use of denitrifying hydrocarbon-oxidizing microorganisms].
The efficiency of an oil-oxidizing microbial community in the bioremediation of oil-polluted soil was studied under laboratory conditions. A specific feature of the community was its ability to oxidize oil hydrocarbons under both aerobic and anoxic conditions. The degree of oil-hydrocarbon degradation in various bioremediation modes increased as follows: self-remediation (40%) < nitrate application (42%) < introduction of the denitrifying oil-oxidizing community (50%) < introduction of the denitrifying oil-oxidizing community plus nitrate application (60%). The intensification of bioremediation is related to the increase in the population of the hydrocarbon-oxidizing microorganisms, first of all, denitrifying ones, resulting from the introduction of the community.


An examination of the influences on New South Wales general practitioners regarding the provision of opioid substitution therapy.
Few general practitioners (GP) prescribe opioid substitution therapy. Our aim was to analyse their previously identified motivating factors by describing their frequency and demographic associations. An anonymous, cross-sectional questionnaire-based survey on opioid prescribing in pain and dependency was distributed across five New South Wales Divisions of GPs. Questions elicited opinions on 11 barriers and five facilitators previously described in qualitative literature. Data were analysed against demographic variables, including opioid substitution therapy prescriber (OSTP) status and postgraduate training status. 'Profiles' of non-OSTPs were then constructed using latent class analysis. Of the 1735 surveys posted, there were 404 responses (23.3%), with 16% respondents being OSTPs. Frequently reported barriers included: 'negative experiences with the opioid dependent' (72%), 'heavy workload' (60%) and 'lack of specialist support' (58%), with most barriers less frequent among OSTPs. Facilitating factors included: 'more accessible specialist support' (75%), 'more accessible training' (67%) and 'better evidence of safety and efficacy' (64%), with the latter two significantly less frequently among OSTPs. Latent class analysis of the non-OSTPs revealed three distinct clusters. The smallest ('class 3') had the least barriers and resembled OSTPs demographically. The pattern of motivating factors towards the psychological, social and behavioural challenges of the management of dependency has a predominantly negative bias. However, this lessens with postgraduate training and OSTP experience. Structural and logistical options are identified to promote OSTP recruitment and retention. GPs resembling class 3 may be more amenable to becoming OSTPs and may be worth targeting for recruitment.


Sciatic nerve endometriosis treated with a gonadotropin releasing hormone agonist. A case report.
Sciatic nerve endometriosis was previously treated primarily with surgery. Most commonly hysterectomy and bilateral salpingo-oophorectomy have been used; however, two reports also describe successful conservative surgery with resection of the endometriosis from the sciatic nerve. Only one case of sciatic nerve endometriosis has been reported to have responded to medical management. This report details the rapid and complete resolution of sciatica secondary to endometriosis after medical treatment with the gonadotropin releasing hormone analog leuprolide acetate for depot suspension.


Evaluation of candidate barcoding markers in Orinus (Poaceae).
Orinus is an alpine endemic genus of Poaceae. Because of the imperfect specimens, high level of intraspecific morphological variability, and homoplasies of morphological characters, it is relatively difficult to delimitate species of Orinus by using morphology alone. To this end, the DNA barcoding has shown great potential in identifying species. The present study is the first attempt to test the feasibility of four proposed DNA barcoding markers (matK, rbcL, trnH-psbA, and ITS) in identifying four currently revised species of Orinus from the Qinghai-Tibetan Plateau (QTP). Among all the single-barcode candidates, the differentiation power was the highest for the nuclear internal transcribed spacer (ITS), while the chloroplast barcodes matK (M), rbcL (R), and trnH-psbA (H) could not identify the species. Meanwhile, the differentiation efficiency of the nuclear ITS (I) was also higher than any two- or three-locus combination of chloroplast barcodes, or even a combination of ITS and any chloroplast barcode except H + I and R + I. All the combinations of chloroplast barcodes plus the nuclear ITS, H + I, and R + I differentiated the highest portion of species. The highest differentiation rate for the barcodes or barcode combinations examined here was 100% (H + I and R + I). In summary, this case study showed that the nuclear ITS region represents a more promising barcode than any maternally inherited chloroplast region or combination of chloroplast regions in differentiating Orinus species from the QTP. Moreover, combining the ITS region with chloroplast regions may improve the barcoding success rate.


High molecular weight adiponectin dominates in cord blood of newborns but is unaffected by pre-eclamptic pregnancies.
This study is the first to report high molecular weight (HMW) adiponectin in newborns from normal and pre-eclamptic pregnancies (PE). Adiponectin is adversely related to Metabolic Syndrome-linked diseases such as obesity, dyslipidaemia, insulin resistance and hypertension. It is abundant in human plasma where it circulates as several characteristic multimeric forms of which the HMW form is the most active. As children from PE-pregnancies have a greater susceptibility to hypertensive disorders later in life, we hypothesized that adiponectin measured in cord blood could be a putative risk marker. Cross-sectional, hospital-based study of newborns from mothers with pre-eclampsia (30 cases and 62 controls). Venous cord blood samples were collected immediately after birth and were analysed for total adiponectin and HMW adiponectin. Total adiponectin and HMW adiponectin were measured by commercially available enzyme-linked immunosorbent assay (ELISA) kits. The PE newborns showed a significantly lower gestational age (GA), total adiponectin and HMW adiponectin levels than the controls. No differences in adiponectin levels were found between case and control groups when correcting for GA. In combined groups, log (total adipo) = 0.40 + 0.027*GA; r = 0.43, P < 0.001. Furthermore, the HMW form is the dominant form of adiponectin: HMW adipo = -5.06 + 0.81*total adipo; r = 0.90, P < 0.001. Adiponectin in cord blood from PE pregnancies may not be a tentative risk marker for Metabolic Syndrome-linked diseases. HMW adiponectin is the dominant form of adiponectin in cord blood. Its role during pregnancy and postnatal life should be further explored.


Complete assignments of NMR data of salens and their cobalt (III) complexes.
Salens, derived from 1,2-ethylenediamine and salicylaldehydes, have been widely used as ligands for metal complexes which have been showing enormous potential in chemical properties of asymmetric catalysts as well as biological properties such as anticancer agents. Almost all of the salen-metal complexes with their corresponding metal (II)-complexes show the evidences of chelation of two oxygens in salens. However, several metal (II) complexes, especially cobalt (II) complexes, could not show NMR spectra due to their paramagnetism. Recently, it has been reported that one of the cobalt (III) complexes was used for NMR spectroscopy to evaluate its stereoselectivity as a catalyst. Even though many salen ligands are known, their NMR data are not assigned completely. It was possible that modification in northern part of salen with 2-hydroxyphenyl group afforded another oxygen chelation site in salen ligand. Here we report that synthesis and full NMR assignment of new salen ligands, which form meso 1,2-bis(2-hydroxyphenyl)ethylenediamine) and their cobalt (III) complexes. The assignments of (1)H and (13)C NMR data obtained in this experiment can help us to predict the NMR data of other salen ligands.


Resveratrol derivatives as a pharmacological tool.
Prodrugs of resveratrol are under development. Among the long-term goals, still largely elusive, are (1) modulating physical properties (e.g., water-soluble derivatives bearing polyethylene glycol chains), (2) changing distribution in the body (e.g., galactosyl derivatives restricted to the intestinal lumen), (3) increasing absorption from the gastrointestinal tract (e.g., derivatives imitating the natural substrates of endogenous transporters), and (4) hindering phase II metabolism (e.g., temporarily blocking the hydroxyls), all contributing to (5) increasing bioavailability. The chemical bonds that have been tested for functionalization include carboxyester, acetal, and carbamate groups. A second approach, which can be combined with the first, seeks to reinforce or modify the biochemical activities of resveratrol by concentrating the compound at specific subcellular sites. An example is provided by mitochondria-targeted derivatives. These proved to be pro-oxidant and cytotoxic in vitro, selectively killing fast-growing and tumor cells when supplied in the low micromolar range. This suggests the possibility of anticancer applications.


[influence and improvement of metal artifacts in dental structures by CT for radiation treatment planning: reconstruction of transverse images using oblique images by gantry tilt scanning].
Intensity-modulated radiation therapy (IMRT) radiation treatment planning (RTP) requires accuracy. Metal artifacts are one of the factors that influence RTP. The metal artifacts from dental structures are problems at the level of the oropharynx, since these artifacts impair visualization of tumors or lymph nodes and change CT (computed tomography) values. We simulated RTP at the level of the oropharynx using CT images with and without artifacts from dental structures. Gantry tilt scanning was performed to avoid artifacts from dental structures and transverse images reconstructed from oblique images by gantry tilt scanning using a technique of multiplanar reconstruction (MPR) . The reconstructed transverse images were used for the RTP. The reconstructed transverse images were useful to obtain accurate target volumes and the RTP of two opposed equally weighted beams by correct CT values. As dose distribution was changed slightly by the metal artifacts, the use of CT images without artifact is recommended in RTP.


The relationship between the plasma concentration of blonanserin, and its plasma anti-serotonin 5-HT(2A) activity/anti-dopamine D₂ activity ratio and drug-induced extrapyramidal symptoms.
Blonanserin is a second-generation antipsychotic that was developed in Japan. We investigated the relationships between plasma concentration, the plasma anti-5-HT(2A) activity/anti-D₂ activity (S/D) ratio and extrapyramidal symptoms (EPS) in blonanserin dosing. The subjects were 29 outpatients with schizophrenia. We assessed EPS using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The plasma concentrations were measured by high performance liquid chromatography, and the plasma anti-D₂ and anti-5-HT(2A) activities were measured by [³H]-spiperone and [³H]-ketanserin radioreceptor assays. The results revealed that there were significant correlations between both the plasma concentration and the DIEPSS total score (P<0.05). A negative correlative tendency was found between the S/D ratio and the DIEPSS total score. Furthermore, the plasma concentrations were divided into a low plasma concentration group and a high plasma concentration group, and the S/D ratios were divided into a low S/D ratio group and a high S/D ratio group. We then compared each group based on the DIEPSS total scores. The score in the high plasma concentration-low S/D ratio group was significantly higher than in the high plasma concentration-high S/D ratio, low plasma concentration-high S/D ratio and low plasma concentration-low S/D ratio groups (P<0.05 for all). These findings indicate that the incidence of EPS during treatment with blonanserin is mainly determined by plasma concentration, but the incidence of EPS may be inhibited when anti-5HT(2A) activity is predominant over anti-D₂ activity.


Minocycline ameliorates D-galactose-induced memory deficits and loss of Arc/Arg3.1 expression.
Dysfunction of learning and memory is widely found in many neurological diseases. Understanding how to preserve the normal function of learning and memory will be extremely beneficial for the treatment of these diseases. However, the possible protective effect of minocycline in memory impairment is unknown. We used the well-established D-galactose rat amnesia model and two behavioral tasks, the Morris water maze and the step-down task, for memory evaluation. Western blot and PCR were used to examine the protein and mRNA levels of Arc/Arg3.1. We report that minocycline supplementation ameliorates both the spatial and fear memory deficits caused by D-galactose. We also found that Arc/Arg3.1, c-fos, and brain-derived neurotrophic factor levels are decreased in the D-galactose animal model, and that minocycline reverses the protein and mRNA levels of Arc in the hippocampus, suggesting the potential role of Arc/Arg3.1 in minocycline's neuroprotective mechanism. Our study strongly suggests that minocycline can be used as a novel treatment for memory impairment in neurological diseases.


Process of repair in the neuroepithelium of developing rat brain during neurogenesis: chronological and quantitative observation of DNA-replicating cells.
The neuroepithelium (NE) of the cerebrum of the developing brain has been reported to 'regenerate' within a certain period after being injured. To clarify the process of repair of the NE during neurogenesis, we chronologically examined the number of cells in the neocortex, and the rate of DNA-replicating cells and the mitotic figure ratio in the NE of rats after injury. The injury was induced by transplacental administration of ethylnitrosourea (ENU), which is cytotoxic immediately after administration, to the pregnant rats on embryonic day 16. The number of living and pyknotic cells in a 220-micron width of the neocortex was evaluated in each of three groups, such as NE, subventricular zone (SVZ) + intermediate zone (IMZ) + subplate (SP), and cortical plate (CP). The 5-bromo-2-deoxyuridine (BrdU)-labeling index and the mitotic index were examined 4, 8, 16, 24, 36, and 48 h after ENU administration. Up to 16 h after ENU administration, the number of living cells per 220 microns width in the NE and SVZ + IMZ + SP decreased, but increased in CP. From 16 to 24 h, the living cell number per 220 microns width in the NE and CP was unchanged, but increased in the SVZ + IMZ + SP. From 24 to 36 h, the living cell number per 220 microns width increased in all the groups, NE, SVZ + IMZ + SP and CP. From 36 to 48 h, the living cell number per 220 microns width in the NE was unchanged, but increased in the SVZ + IMZ + SP and CP. The BrdU-labeling index reached its nadir at 8 h, but markedly increased by 16 h, and then decreased to the control level by 36 h. No mitotic figures were observed at 16 h after administration, but a significant increase in mitotic index was noted at 24 h, and after which it decreased to almost the control value by 36 h. These findings indicate: (i) that temporary arrest of neuroepithelial cell cycle occurs in the G1-phase from 4 to 8 h after ENU administration, (ii) that the cell synchronizes in the S-phase at 16 h, (iii) that a proportion of neuroepithelial cells of rat fetal neocortex at the neurogenesis stage return to neuroepithelial cell proliferation stage, to repair the NE, and (iv) that regulation of the cell kinetics of neuroepithelial cells depends on the number of cells in a certain width of NE during regeneration.


Antibody produced against isolated Rh(D) polypeptide reacts with other Rh-related antigens.
Rh(D) antigen-containing polypeptide was prepared by immune precipitation of intact cDE/cDE erythrocytes by using a high-titer preparation of polyclonal anti-D. when isolated Rh(D) polypeptide was administered to rabbits, antibody was produced that was unresponsive toward Rh-positive and -negative cells but reacted strongly with the immunogen in enzyme-linked immunosorbent assay-type immunobinding and Western blot immunostaining assays. Rabbit antibody also immunostains isolated Rh(c) polypeptide as well as the Rh antigen-containing components of sodium dodecyl sulfate-polyacrylamide gel electrophoresis-separated membrane proteins from Rh(D)-positive (cDE/cDE,CDe/CDe), Rh(D)-negative (cde/cde,Cde/Cde), and -D-/-D- cells. It does not react with any membrane protein from Rh-null regulator type cells, thus indicating a specificity for Rh-related proteins. We have also been able to demonstrate that polyclonal and monoclonal anti-D preparations that do not immunostain isolated Rh(D) polypeptide will react with it in our immunobinding assay.


Cyclin A expression in human hematological malignancies: a new marker of cell proliferation.
Several in vitro studies have shown that the cyclin A gene is expressed and plays an important role in both the S and G2-M phases of the cell cycle. We analyzed cells from the blood and bone marrow of patients with various, mostly neoplastic, hematological disorders to determine whether (a) the cyclin A protein level correlated with that of cyclin A RNA and (b) cell distribution among the different phases of the cell cycle correlated with cyclin A RNA expression. Thirty-eight patients were studied by means of dot blot and Western blot techniques for cyclin A RNA and protein accumulation, and 21 were also studied for cell cycle distribution by using flow cytometric analysis. Semiquantitative studies were based on densitometric computerized evaluation of dot and Western blots. There was a very strong positive correlation between cyclin A RNA and protein expression (r = 0.99; P < 0.00005), indicating that cyclin A accumulation is regulated in these cells at a transcriptional level. There was also a highly significant positive correlation between cyclin A RNA expression and the cumulative percentage of cells in S plus G2-M phase (r = 0.98; P < 0.00005). Therefore, this in vivo study shows that the expression of cyclin A RNA and protein in human hematological malignancies correlates with the percentage of cells in S plus G2-M phase and identifies cyclin A as a new potential cell proliferation index in oncology.


Population health and status of epidemiology: WHO European Region I.
This article of the International Epidemiological Association commissioned paper series stocktakes the population health and status of epidemiology in 21 of the 53 countries of the WHO European Region. By United Nations geographical classification, these countries belong to Eastern Europe, Western Asia and South-Central Asia. Published data were used to describe population health indicators and risk factors. Epidemiological training and research was assessed based on author knowledge, information searches and E-mail survey of experts. Bibliometric analyses determined epidemiological publication outputs. Between-country differences in life expectancy, amount and profile of disease burden and prevalence of risk factors are marked. Epidemiological training is affected by ongoing structural reforms of educational systems. Training is advanced in Israel and several Eastern European countries. Epidemiological research is mainly university-based in most countries, but predominantly conducted by governmental research institutes in several countries of the former Soviet Union. Funding is generally external and limited, partially due to competition from and prioritization of biomedical research. Multiple relevant professional societies exist, especially in Poland, the Czech Republic and Hungary. Few of the region's 39 epidemiological academic journals have international currency. The number of epidemiological publications per population is highest for Israel and lowest for South-Central Asian countries. Epidemiological capacity will continue to be heterogeneous across the region and depend more on countries' individual historical, social, political and economic conditions and contexts than their epidemiologists' successive efforts. National and international research funding, and within- and between-country collaborations should be enhanced, especially for South-Central Asian countries.


[Erythrocyte immunologic function effects of Patrinia scabra extracts by macroporous adsorptive resins on mice burdened transplanted tumor].
To research the erythrocyte immunoregulation effects of Patrinia scabra extracts by macroporous adsorptive resins on mice burdened transplanted tumor. Extracts of Patrinia scabra Bunge were separated by macroporous adsorptive resins, ingredients were analysised. Mice burdened transplanted tumor were given extracted drugs. Life prolongation rate was observed, erythrocyte immunologic function and the CD35, CD44s contents of red blood cell were evaluated. Polysaccharide and saponin accounted for 8.4% and 48.4%. Extracts could porolong life expectancy of mice, improve erythrocyte immunolgic function and increase the CD35 and CD44s contents of red blood cell. Extracts of Patrinia scabra Bunge by macroporous adsorptive resins have erythrocyte immunoregulation effects on mice burdened transplanted tumor.


A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome.
Otofaciocervical syndrome (OFCS) is an autosomal recessively inherited disorder characterized by facial dysmorphism, external ear anomalies with preauricular pits and hearing impairment, branchial cysts or fistulas, anomalies of the vertebrae and the shoulder girdle, and mild intellectual disability. In a large consanguineous family with OFCS from Turkey, we performed whole-exome sequencing (WES) of a single pooled DNA sample of four affected individuals. Filtering for variants with a percentage of alternate reads ≥ 90 % and a coverage of at least five reads identified only a single novel homozygous variant, c.497G>T, located in PAX1 that co-segregated with the disease in the family. PAX1 encodes a transcription factor with a critical role in pattern formation during embryogenesis in vertebrates. The mutation is predicted to substitute the glycine at position 166 to valine (p.G166V) within the highly conserved paired-box domain of the PAX1 protein. We performed a dual luciferase reporter assay to examine the transactivation of a regulatory sequence in the Nkx3-2 promoter region, which is a direct target of mouse Pax1 transcriptional regulation. We observed a significantly reduced transactivation in HEK293T cells overexpressing Pax1(G157V) in comparison to Pax1(WT) expressing cells, indicating a reduced DNA-binding affinity of the mutant protein. Taken together, our results show that the strategy of pooling DNA is a powerful, cost-effective application for WES in consanguineous families and establish PAX1 as a new disease-causing gene for OFCS and as part of the EYA-DACH-SIX-PAX network, important in early embryogenesis.


Phylogenetic relationships of Steinernema Travassos, 1927 (Nematoda: Cephalobina: Steinernematidae) based on nuclear, mitochondrial and morphological data.
Entomopathogenic nematodes of the genus Steinernema are lethal parasites of insects that are used as biological control agents of several lepidopteran, dipteran and coleopteran pests. Phylogenetic relationships among 25 Steinernema species were estimated using nucleotide sequences from three genes and 22 morphological characters. Parsimony analysis of 28S (LSU) sequences yielded a well-resolved phylogenetic hypothesis with reliable bootstrap support for 13 clades. Parsimony analysis of mitochondrial DNA sequences (12S rDNA and cox 1 genes) yielded phylogenetic trees with a lower consistency index than for LSU sequences, and with fewer reliably supported clades. Combined phylogenetic analysis of the 3-gene dataset by parsimony and Bayesian methods yielded well-resolved and highly similar trees. Bayesian posterior probabilities were high for most clades; bootstrap (parsimony) support was reliable for approximately half of the internal nodes. Parsimony analysis of the morphological dataset yielded a poorly resolved tree, whereas total evidence analysis (molecular plus morphological data) yielded a phylogenetic hypothesis consistent with, but less resolved than trees inferred from combined molecular data. Parsimony mapping of morphological characters on the 3-gene trees showed that most structural features of steinernematids are highly homoplastic. The distribution of nematode foraging strategies on these trees predicts that S. hermaphroditum, S. diaprepesi and S. longicaudum (US isolate) have cruise forager behaviours.


Effects of September 11 on patients with obsessive compulsive disorder.
Effects of the September 11, 2001 terrorist attacks in the USA were investigated in 25 patients with obsessive compulsive disorder and 27 normal controls 4-6 months after the attacks. Participants completed a 15-item questionnaire to retrospectively assess changes in mood, cognition, behavior and somatic complaints since September 11, 2001. Overall, both patients with obsessive compulsive disorder and normal controls reported minor changes in mood, behavior and somatic complaints. However, normal controls reported severe to extreme initial impact, slightly more cognitive symptoms (uncertainty about the future, intrusive recollections and greater desire to be with loved ones) and a slightly greater degree of overall impact on emotion and behavior at 1, 2 and 3 months after September 11 than did patients with obsessive compulsive disorder. Results support previous research that has found a relatively minor lasting impact of September 11 on both clinical and normal populations. Differences in cognition and coping mechanisms between normal controls and patients with obsessive compulsive disorder are proposed.


Prevalence of dermatomycosis in a Brazilian tertiary care hospital.
A total of 233 specimens obtained from suspected cases of dermatomycosis from 189 patients were examined for causative fungi from December 2009 to May 2010 in a tertiary care hospital in the city of Belo Horizonte, state of Minas Gerais, southeastern Brazil. Yeast and fungal isolates obtained from specimens were regarded as conclusive diagnosis of mycoses in 82 cases (35.19 %), with the exception of two patients with pityriasis versicolor (2.4 %), in which the diagnosis was made only by direct examination plus clinical diagnostics of individuals. Forty-four subjects (23.28 %) were infected in more than one anatomical site. There was a higher occurrence on female patients (146, 77.2 %) than male (43, 22.8 %). Most of the infected patients were aged between 41 and 70 years (68.29 %). There were no statistically significant differences between occurrence of fungal infection and gender, presence of secondary disease and contact with animals. The largest number of examined material occurred in samples from toenails, which resulted in 50 % of positive cultures. Candida species were the most frequent group causing dermatomycosis in many anatomical sites, mainly in toenails and fingernails. Candida parapsilosis was the most representative (40.24 %) among all agents causing dermatomycosis of toenails and fingernails, followed by Candida tropicalis (20.73 %) and Trichophyton rubrum (10.98 %). Among the dermatophytes, Trichophyton genus represented over 80 % of the isolates, with T. rubrum representing 64.29 %, T. interdigitale (T. mentagrophytes) (21.43 %) and Microsporum gypseum (14.29 %).


[Risk assessment of chronic HPV HR infection in babies who contacted the virus in the perinatal period].
One of the potential ways of HPV transmission to fetuses and newborns is a direct perinatal infection, manifested as juvenile laryngeal papillomatosis (JLP). This applies to children after traditional birth, born to mothers in whom the DNA sequences of the HPV HR in the paraepidermal epithelium of cervix were found during pregnancy and delivery Risk assessment of the development of chronic HPV HR infection in babies who had contact with the virus in the perinatal period. During the pre- and perinatal period, research was carried out among 185 pregnant women and a group of 105 newborns (5 pairs of twins), hospitalized in the Delivery Room of the Gynecology and Obstetrics Clinic of the Poznań Medical University between 2005-2007. Cellular material from the uterine cervical canal using a brush-type Cervex Brush was collected from each woman participating in the study and oral swabs using swab sticks were taken from the newborns. The second phase of testing was conducted following the postpartum, 3 to 6 months after the delivery Uterine cervix swabs were re-collected from 28 HPV HR positive women and swab from the mouth and nasopharynx were taken from their children (29 samples--1 pair of twins). The study was conducted with the use of PCR, trade named AMPLICOR Human Papilloma Virus (HPV) Test by Roche. DNA HPV HR was found in 55 cases of the cellular material derived from 185 swabs taken from the cervical canal, representing 29.7% of researched women. The chronic HPV HR viral infection was detected in 25 cases out of the 28 HPV HR positive women, representing 89.2% of the study group. Of the 105 infants from whom oral swabs were taken in the perinatal period, presence of DNA HPV HR was found in 2 infants (2%) after traditional birth. Whereas the repeated test, within 3-6 months after delivery revealed the presence of DNA HPV HR viruses in swab oral in 1 infant, who had been DNA HPV HR positive. Perinatal transmission of Human Papillomavirus of the high-risk oncogenic type is rare and concerns below 2% of babies of HPV HR positive mothers. Prolonged infection by the Human Papillomavirus is an extremely rare complication of pregnancy and delivery and concerns below 1% of children of HPV HR positive mothers. Perinatal transmission of the oncogenic type infection of the virus in humans is primarily of the ascending type or occurs during the perinatal period if the delivery was a traditional one.


The cellular immune response in the tracheal mucosa to Mycoplasma gallisepticum in vaccinated and unvaccinated chickens in the acute and chronic stages of disease.
Mycoplasma gallisepticum causes a lymphoproliferative response in the tracheal mucosa of infected birds. The studies reported here aimed to determine, using immunohistochemical and immunofluorescent staining, which lymphocyte subsets were infiltrating the mucosa during the acute and chronic phases of disease and to determine whether these subsets differed in birds that had been vaccinated with strain ts-11. In vaccinates there was no detectable infiltration of T or B lymphocytes between 1 and 6 weeks after infection with a virulent strain. Unvaccinated birds had an initial influx of CD8+TCR- lymphocytes at 1 week, with the numbers decreasing over the next 5 weeks. CD8+TCR+ cells increased over the 6 weeks. The proportion of CD4+TCRalphabeta2+ cells also increased, whilst there was an increase in CD4+TCRalphabeta1+ cells at 3 weeks and then a decrease by 6 weeks. B lymphocytes were not detected until 3 weeks after infection, and their appearance coincided with a decrease in the concentration of mycoplasma DNA detectable in the trachea. The formation of clusters of CD8+TCR- lymphocytes was a prominent feature of the early response, while at 3 and 6 weeks after infection clusters of B cells became prominent, although in some cases they surrounded a cluster of CD8+ cells. These observations suggest a primary role for local antibody mediated responses in controlling M. gallisepticum infection, but also show that there are probably significant natural killer and cytotoxic T cell responses to infection, although the efficacy of these in controlling infection was not able to be determined.


[Clinico-histologic spectrum of lichen sclerosus et atrophicus].
Report on several clinical and histological variants of lichen sclerosus et atrophicus by means of two cases.


Relationship between pulmonary hemodynamics and arterial pH and carbon dioxide tension in critically ill patients.
To ascertain the clinical significance of derangements in arterial pH and arterial carbon dioxide tension (PaCO2) in modifying pulmonary arterial pressures and pulmonary vascular resistance in critically ill patients, the relationship between these two sets of variables was evaluated in 75 patients. No significant differences in pulmonary hemodynamic values were found among patients with acidemia, a normal pH, or alkalemia, even at extreme pH values; and there was no consistent relationship between PaCO2 and each of the pulmonary hemodynamic measurements. In patients who initially had a normal pH but subsequently developed acidemia or alkalemia, there was also no significant correlation between changes in pH and pulmonary hemodynamic values. We conclude that abnormalities of pulmonary hemodynamic values in seriously ill patients are usually due to factors other than acid-base derangements. Of practical importance is the observation that the predictability of the pulmonary arterial wedge pressure from the pulmonary arterial diastolic pressure is not invalidated by acid-base disturbances.


Pneumococcal polysaccharide vaccine: a systematic review of clinical effectiveness in adults.
Pneumococcal polysaccharide vaccine is recommended in western countries for individuals at high risk of pneumococcal illness. We undertook a systematic review of randomised controlled trials of pneumococcal vaccine in adults, to determine the effects on clinical outcomes. In industrialised populations, no benefit was detected for outcomes other than pneumococcal bacteraemia, and this did not reach statistical significance. In non-industrial populations, clear benefit was demonstrated for mortality and all-cause pneumonia. Benefit from pneumococcal vaccination depends on the baseline risk of infection and characteristics of a given population. Evidence from randomised trials for widespread adult vaccination in industrial countries is lacking.


Metabolite profiling in human urine by LC-MS/MS: method optimization and application for glucuronides from dextromethorphan metabolism.
Analysis of human urine for specific compounds or metabolites is an established method for biomonitoring occupational or environmental exposures. Modern liquid chromatography-tandem mass spectrometry is not limited to single compounds but can simultaneously analyze whole classes of urine constituents with both high sensitivity and specificity. Individual differences in the composition of urine are very large in humans, which raises a number of problems that are not encountered in animal experimentation. In this report, we investigated whether analysis of glucuronides as a class could reflect differences between human individuals regarding the polymorphic activity of the cytochrome P450 enzyme CYP2D6. From a group of 152 students that had been classified for CYP2D6 activity, urine of 12 "poor metabolizers" and 35 "extensive metabolizers" was collected 90 min after ingestion of 10mg of the antitussive drug dextromethorphan (DEX) and analyzed for glucuronides. Methods development included the following aspects: adjustment of urine samples to equal creatinine concentration to avoid differences between samples in retention times and ion suppression; on-line enrichment of low-level analytes by column switching; precursor ion scan vs. theoretical multiple reaction monitoring; use of quality control samples to check for reproducibility in large sample series; peak extraction and handling of null entries to build the data matrix; logarithmic data transformation and different scaling procedures; principal component analysis (PCA) vs. discriminant analysis. Our results show that an optimized procedure not only identified the known DEX metabolites as predictors of CYP2D6-specific metabolic pathways but also indicated the presence of additional, so far unknown path-specific glucuronide metabolites. We conclude that metabolite profiling of urine and other biofluids by modern mass spectrometric methodology may help characterize individual differences and become useful in drug development and personalized pharmacotherapy.


Inhibition studies of porphobilinogen synthase from Escherichia coli differentiating between the two recognition sites.
Porphobilinogen synthase condenses two molecules of 5-aminolevulinate in an asymmetric way. This unusual transformation requires a selective recognition and differentiation between the substrates ending up in the A site or in the P site of porphobilinogen synthase. Studies of inhibitors based on the key intermediate first postulated by Jordan allowed differentiation of the two recognition sites. The P site, whose structure is known from X-ray crystallographic studies, tolerates ester functions well. The A site interacts very strongly with nitro groups, but is not very tolerant to ester functions. This differentiation is a central factor in the asymmetric handling of the two identical substrates. Finally, it could be shown that the keto group of the substrate bound at the A site is not only essential for the recognition, but that an increase in electrophilicity of the carbon atom also increases the inhibition potency considerably. This has important consequences for the recognition process at the A site, whose exact structure is not yet known.


Rearrangement of trnQ-trnM in the mitochondrial genome of Allantus luctifer (Smith) (Hymenoptera: Tenthredinidae).
The complete mitochondrial genome of the Allantus luctifer (Smith) (Hymenoptera: Tenthredinidae: Allantinae) is reported in this study (GenBank accession No. KJ713152). This is the first mitochondrial genome from the subfamily Allantinae and the first completely sequenced mitochondrial genome from the Tenthredinoidea. The length of this mitochondrial genome is 15,418 bp with an A+T content of 81.13%, including 13 protein-coding, 2 rRNA and 22 tRNA gene, and an A+T-rich region (Table 1). Gene arrangement is identical to the other two mitochondrial genomes of tenthredinoid species in nearly all region as in the pupative ancestral arrangement of insects. The ancestral pattern of "A+T-rich region-trnI(+)-trnQ(-)-trnM(+)" was rearranged to "trnM(-)-trnQ(+)-A+T-rich region-trnI(+)", which is novel to the Hymenoptera. All protein-coding genes start with ATN start codon. Eleven protein-coding genes stop with termination codon TAA, whereas one protein-coding gene uses incomplete stop codon TA and one uses T. The A+T-region is 463 bp long with an A+T content of 86.6%.


Sirtuin mechanism and inhibition: explored with N(ε)-acetyl-lysine analogs.
Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of intracellular protein deacetylases that can catalyze the β-nicotinamide adenine dinucleotide (β-NAD(+))-dependent deacetylation of N(ε)-acetyl-lysine on protein substrates, with the formation of lysine N(ε)-deacetylated protein species and small molecule products, i.e. nicotinamide and 2'-O-acetyl-ADP-ribose (2'-O-AADPR). These enzymes are evolutionarily conserved among all the three kingdoms of life, with the yeast Sir2 being the founding family member. In humans, seven sirtuins, i.e. SIRT1-7, have been identified. The past a few years have witnessed a tremendous interest in investigating the unique mechanism for the sirtuin-catalyzed deacetylation reaction. We have also seen a lot of research employing different strategies to identify different types of the inhibitors for this enzymatic deacetylation reaction. These inhibitors hold great potential toward a fuller exploration of sirtuin biology and pharmacology as well as toward developing novel therapeutics for metabolic and age-related diseases and cancer. Here we would like to review the significant contributions that the judicious use of a variety of N(ε)-acetyl-lysine analogs has been able to make toward our enhanced mechanistic understanding and capability of pharmacological exploitation of the sirtuin-catalyzed deacetylation reaction.


Medical management of calcium oxalate urolithiasis.
Dietary modifications and medical therapy can reduce the risk of urinary stone formation. Using the described stepwise approach, the medical management of stone disease should become a less daunting task for physicians. Unfortunately, the optimal medical and dietary management of urolithiasis remains uncertain and recurrent stone disease remains a significant cause of morbidity. Approaches to diagnosis and medical management have improved considerably in the last decade and it is hoped that well-designed studies in the near future will help further optimize management.


Surgical adhesive may cause false positives in integrated positron emission tomography and computed tomography after lung cancer resection.
Surgical adhesives are frequently used after pulmonary resection to prevent or reduce pulmonary air leakages, since leakages may cause complications delaying the removal of chest drainage tubes and prolonging in-hospital stay. In this paper, we present 2 patients who underwent curative-intent pulmonary resection for non-small-cell lung carcinoma, in which the biological adhesive BioGlue(®) was used. Follow-up fluoro-2-deoxy-D-glucose positron emission tomography/computed tomographic (FDG-PET/CT) imaging revealed hypermetabolic pulmonary nodular lesions. Subsequent surgical exploration showed that the lesions were foreign body reactions to the bioadhesive. To our knowledge, this is the first study to examine false-positive follow-up FDG-PET/CT scans caused by the use of BioGlue(®) in pulmonary resection procedures.


[Vascular space-occupying lesions of the carotid artery--detection with color-coded Doppler sonography. Comparison with duplex sonography and angiography].
Nine patients with a cervical tumour, diagnosed by duplex Doppler sonography were additionally evaluated by colour-coded Doppler sonography (CCDS). The duplex Doppler diagnosis of three internal carotid artery aneurysm was confirmed by CCDS in only one patient. In the remaining two cases CCDS identified a marked coiling of the internal carotid artery. Three low echogenic lesions, interpreted as cervical lymphomas by conventional Doppler sonography were identified as two internal carotid aneurysm with partial thrombosis and a carotid body tumour in the third patient by CCDS. Duplex-Doppler sonography and CCDS agreed in the diagnosis of two AV-malformations and one carotid body tumour. Angiography confirmed the CCDS-diagnosis in 7 patients. In the two patients with coiling of the ICA angiographic evaluation was not performed. Thus, CCDS was superior to duplex Doppler sonography in the evaluation of vascular lesions of the extracranial section of the carotid artery and provided additional diagnostic information.


[Investigations on peptide synthesis with polymeric supports: synthesis and characterization of the deamido-calcitonin-M-(19-32)-tetradecapeptide by use of the soluble support polyethyleneglycol and coupling of the products to the insoluble polystyryl-benzhydrylamine resin (author's transl)].
The synthesis of the deamido-calcitonin-M-(19-32)-tetradecapeptide Boc-Phe-His-Thr(Bzl)-Phe-Pro-Gln-Thr(Bzl)-Ala-Ile-Gly-Val-Gly-Ala-Pro-OH (I) by the use of the soluble polymeric support polyethyleneglycol is described. For product characterization the following compounds were prepared:H-Phe-His-Thr(Bzl)-Phe-Pro-Gln-Thr(Bzl)-Ala-Ile-Gly-Val-Gly-Ala-Pro-OH and H-Phe-His-Thr-Phe-Pro-Gln-Thr-Ala-Ile-Gly-Ala-Pro-OH. The analyses of these products by ion exchange chromatography indicates that the correct tetradecapeptide sequence was synthesized to more than 90%. Despite high yields in the coupling reactions, crude I was inhomogenous due to partial cleavage to O-benzyl ether bonds. In order to use I for the total synthesis of calcitonin M, it was coupled to the insoluble polystyryl-benzhydrylamine resin. 0.08 mmol of peptide was coupled per g of resin. Treatment of this peptide resin with hydrogen fluoride yielded H-Phe-His-Thr-Phe-Gln-Thr-Ala-Ile-Gly-Val-Gly-Ala-Pro-NH2.


Contagious bovine pleuropneumonia: a rationale for the development of a mucosal sub-unit vaccine.
Contagious bovine pleuropneumonia (CBPP) remains a major cattle disease in Africa with serious socio-economic consequences. Its eradication requires the development of improved vaccines. Knowledge on this disease and its causing agent, Mycoplasma mycoides subsp. mycoides biotype Small Colony (MmmSC), has been progressing significantly in the last years, opening new areas for vaccine design. Advances were achieved in the understanding of the protective immune responses to MmmSC infection and immunopathological mechanisms allowing the pathogen to escape the host immune response. Based on sequencing and genomic studies, some virulence factors and metabolic pathways were unraveled leading to the identification of potential MmmSC vaccine candidates. Based on these findings, this review presents a scientific strategy to design multi-component sub-unit vaccines for mucosal delivery as the most promising approach for efficient long-term protective vaccines to prevent CBPP.


Fingertip skin wrinkling - the effect of varying tonicity.
Fingertip skin wrinkling after prolonged immersion in water is a well-recognized phenomenon, whereas a denervated digit does not exhibit normal skin wrinkling while a finger with a regenerated or repaired nerve shows at least partial reappearance of wrinkling. This is the basis for the bedside immersion-wrinkling test of autonomic digital nerve function. The exact mechanism of fingertip skin wrinkling is still subject to controversy. The purpose of this study was to investigate the relationship between the tonicity of a solution and the time elapsed to skin wrinkling. Fourteen healthy volunteers (28 hands) were recruited for investigation. We submerged all 28 hands in solutions of varying tonicity while maintaining all other parameters constant. We found that increased tonicity significantly slowed the time to wrinkling (TTW). Hypotonic solutions such as water should be used when performing clinical bedside testing for autonomic digital nerve function.


Intraocular pressure spikes after a sequential laser peripheral iridotomy for angle closure.
To determine the incidence of intraocular pressure (IOP) spikes within the first 30 minutes after sequential argon-Nd:YAG laser peripheral iridotomy (LPI) in patients with angle closure and to explore risk factors for their occurrence. A total of 428 consecutive eyes of 298 patients who had undergone LPI at the Singapore National Eye Centre between June 2011 and August 2011 were reviewed retrospectively. There were 238 primary angle closure suspect eyes, 85 primary angle closure eyes, 92 primary angle closure glaucoma eyes, and 13 acute primary angle closure (APAC) eyes. The pre-LPI IOP and post-LPI IOP, gonioscopic findings, medications, laser parameters, and the need for acute IOP-lowering treatment were recorded. The proportion of patients with a post-LPI IOP elevation ≥8 mm Hg was 10.7% (n=46) and those with a significant IOP spike of ≥30 mm Hg was 31 (7.2%). There were no significant differences between those with or without a post-LPI IOP elevation ≥8 mm Hg and those with or without a post-LPI IOP of ≥30 mm Hg, in terms of age, gender, race, total laser energy used, and seniority of the physician performing the procedure. Patients who experienced IOP spike ≥8 mm Hg were on fewer pre-LPI medications (P=0.009). On logistic regression, patients with APAC had a significantly higher probability of an IOP spike (P=0.003). The incidence of postsequential LPI IOP elevation ≥8 mm Hg was 10.7%. The primary diagnosis of APAC was a risk factor, and using preprocedure ocular hypotensives can potentially reduce their occurrence.


Distribution of cerebellar mossy fibers arising from neurons of the raccoon main cuneate nucleus.
The present study demonstrates that fibers originating in the raccoon main cuneate nucleus are not segregated in specific cortical regions of target cerebellar folia as reported in studies of the cat cuneocerebellar tract. This observation supports the hypothesis that exteroceptive and proprioceptive divisions of the raccoon cuneocerebellar tract do not exist as distinct structural entities. The findings of this study do not preclude the possibility that projections from the external and main cuneate nuclei are segregated within the cerebellar cortex on the basis of functional modality rather than nucleus of origin.


Integrating active tuberculosis case finding in antenatal services in Zambia.
Three out-patient antenatal care (ANC) clinics in Lusaka, Zambia. To estimate tuberculosis (TB) prevalence in human immunodeficiency virus (HIV) infected and symptomatic, non-HIV-infected pregnant women and explore the feasibility of routine TB screening in ANC settings. Peer educators administered TB symptom questionnaires to pregnant women attending their first ANC clinic visit. Presumptive TB patients were defined as all HIV-infected women and symptomatic non-HIV-infected women. Sputum samples were tested using smear microscopy and culture to estimate TB prevalence. All 5033 (100%) women invited to participate in the study agreed, and 17% reported one or more TB symptoms. Among 1152 presumed TB patients, 17 (1.5%) had previously undiagnosed culture-confirmed TB; 2 (12%) were smear-positive. Stratified by HIV status, TB prevalence was 10/664 (1.5%, 95%CI 0. 7-2.8) among HIV-infected women and 7/488 (1.4%, 95%CI 0.6-2.9) among symptomatic non-HIV-infected women. In HIV-infected women, the only symptom significantly associated with TB was productive cough; symptom screening was only 50% sensitive. There is a sizable burden of TB in pregnant women in Zambia, which may lead to adverse maternal and infant outcomes. TB screening in ANC settings in Zambia is acceptable and feasible. More sensitive diagnostics are needed.


Horseradish peroxidase mutants that autocatalytically modify their prosthetic heme group: insights into mammalian peroxidase heme-protein covalent bonds.
The mammalian peroxidases, including myeloperoxidase and lactoperoxidase, bind their prosthetic heme covalently through ester bonds to two of the heme methyl groups. These bonds are autocatalytically formed. No other peroxidase is known to form such bonds. To determine whether features other than an appropriately placed carboxylic acid residue are important for covalent heme binding, we have introduced aspartate and/or glutamic acid residues into horseradish peroxidase, a plant enzyme that exhibits essentially no sequence identity with the mammalian peroxidases. Based on superposition of the horseradish peroxidase and myeloperoxidase structures, the mutated residues were Leu(37), Phe(41), Gly(69), and Ser(73). The F41E mutant was isolated with no covalently bound heme, but the heme was completely covalently bound upon incubation with H(2)O(2). As predicted, the modified heme released from the protein was 3-hydroxymethylheme. The S73E mutant did not covalently bind its heme but oxidized it to the 8-hydroxymethyl derivative. The hydroxyl group in this modified heme derived from the medium. The other mutations gave unstable proteins. The rate of compound I formation for the F41E mutant was 100 times faster after covalent bond formation, but the reduction of compound I to compound II was similar with and without the covalent bond. The results clearly establish that an appropriately situated carboxylic acid group is sufficient for covalent heme attachment, strengthen the proposed mechanism, and suggest that covalent heme attachment in the mammalian peroxidases relates to peroxidase biology or stability rather than to intrinsic catalytic properties.


Characterization of adult stem/progenitor cell populations from bone marrow in a three-dimensional collagen gel culture system.
Stem cell transplantation therapy using mesenchymal stem cells (MSCs) is considered a useful strategy. Although MSCs are commonly isolated by exploiting their plastic adherence, several studies have suggested that there are other populations of stem and/or osteoprogenitor cells that are removed from primary culture during media replacement. Therefore, we developed a three-dimensional (3D) culture system in which adherent and nonadherent stem cells are selected and expanded. Here, we described the characterization of 3D culture-derived cell populations in vitro and the capacity of these cells to differentiate into bone and/or cartilage tissue when placed inside of demineralized bone matrix (DBM) cylinders, implanted subcutaneously into the backs of rat for 2, 4, and 8 weeks. Our results demonstrates that 3D culture cells were a heterogeneous population of uncommitted cells that express pluripotent-, hematopoietic-, mesenchymal-, and endothelial-specific markers in vitro and can undergo osteogenic differentiation in vivo.


Enamel incremental lines as recorders for disease in infancy and their relation to the diagnosis of SIDS.
The sudden infant death syndrome (SIDS) is a major diagnosis of post-neonatal mortality in the industrialised countries. The cause of death is, however, still elusive. The development of complementary diagnostic methods widening the possibility to analyse the postmortem findings is therefore important. The aim of this study was to histologically examine the enamel of teeth from children dying suddenly and unexpectedly in order to disclose if the presence of enamel disturbances corresponded to neo- or postnatal disorders. During enamel formation ameloblasts are susceptible to local and systemic disturbances which may be reflected in the fully formed enamel as hypoplasia, hypocalcification or accentuated incremental lines. Nineteen consecutive cases of deaths in infants between 1-19 months of age were investigated at the Department of Forensic Pathology, Stockholm, Sweden. The analyses of anamnestic and postmortem data and the analyses of incremental lines were done independently without knowledge of the conclusion of the other part. The results show a good agreement between enamel changes on one hand and the antemortem history and the autopsy findings on the other. This type of investigation may be a valuable complement to the ordinary postmortem investigations of a child who has suddenly and unexpectedly died.


The binding pattern of peanut lectin associated with sclerotome migration and the formation of the vertebral axis in the chick embryo.
Lectins have been used extensively to detect changes in carbohydrate moieties on the surfaces of embryonic cells during early development. Peanut agglutinin (PNA) in particular has been used to investigate changes related to cell differentiation. PNA has also been used to differentiate between the rostral and caudal sclerotome halves which have been shown to be functionally different, with neural crest cells and neurites traversing only the rostral half during their migration. In this study, we have sectioned and stained chick embryos between 3 and 8 days of age with PNA to examine the distribution of PNA binding sites associated with the vertebral column during this period and also to determine the fates of the rostral and caudal sclerotome halves. Ultrastructural localisation of PNA-gold conjugate showed that binding sites for this lectin were present intracellularly and extracellularly both on cell surfaces and in the matrix. At the light microscope level, a clear banding pattern emerged after staining with PNA which consisted of alternating light and dark staining along the entire length of the vertebral axis of the embryo. In the younger embryos, a simple banding pattern emerged where the rostral sclerotome half of each segment stained only lightly while the caudal half stained darkly. This banding pattern was present throughout the 6 day period of development and could be traced continuously but grew more complex as the sclerotome cells migrated to surround the notochord and neural tube and as the dorsal root ganglia developed. The rostral sclerotome half was found to contribute to the caudal part of one vertebral body and its neural arch, while the caudal sclerotome half was found to contribute to the intervertebral disc, the rostral half of the next caudal vertebra, and part of its neural arch.


Psychometric properties of the HI-FI problem checklist in a sample of adults with neurological and neuropsychiatric disorders: factors contributing to life satisfaction after long-term disability.
Purpose To assess psychometric properties of the problem checklist (PCL) in a sample of individuals with neurological and neuropsychiatric disorders many years after trauma; to identify factors that impact life satisfaction and promote functional competence after long-term disability. Method Cross-sectional, interview- and assessment-based study. Participants were community-dwelling adults with disabilities resulting from neurological and neuropsychiatric disorders (N = 53), who participated in a pre-vocational readiness and social skills training program. The Problem Checklist from the New York University Head Injury Family Interview (PCL), a battery of self-rated and clinician-rated measures of social/emotional status, and neuropsychological tests were main outcome measures. Results PCL is a valid and reliable instrument with acceptable psychometric properties (reliability coefficients for two scales and the total score are above (0.795). Use of maladaptive coping strategies in our sample was reflected in inverse relationship between depression and denial of disability, and in the tendency to overrate self-reported symptoms by participants with acquired trauma. Considerably lower self-ratings of symptoms across all PCL scales were seen in those of our participants who live with parents. Conclusions The study offers initial support for the use of PCL as a measure of long-term functional outcome in individuals with neurological and neuropsychiatric diagnoses. The goal of rehabilitation in patients with long-term disabilities is increase in life satisfaction. Implications for Rehabilitation An important goal of rehabilitation and training programs for individuals with long-term disabilities due to dysfunction of the central nervous system is to improve their quality of life. The HI-FI Problem Checklist (PCL) is a brief and efficient instrument for assessing functional outcomes after long-term disability. This study demonstrated acceptable psychometric properties of the PCL in a sample of 53 individuals participating in a pre-vocational training program and provided initial support for its utility for patients with various diagnoses.


Endovascular treatment of two concomitant causes of pulsatile tinnitus: sigmoid sinus stenosis and ipsilateral jugular bulb diverticulum. Case report and literature review.
We describe a rare case of highly invalidating pulsatile tinnitus associated with both stenosis of the sigmoid sinus and ipsilateral jugular bulb diverticulum. Both conditions were successfully treated by positioning a stent across the sigmoid sinus and jugular bulb. To our knowledge, the present clinical case represents the first report of such an approach. The therapeutic decision-making is discussed in relation to the etiopathologic hypothesis put forward.


Solution structure of micelle-bound H5 peptide (427-452): a primary structure corresponding to the pore forming region of the voltage dependent potassium channel.
A 26-mer peptide with the sequence of the pore forming region (residues 427-452) of the Shaker K(+) channel (H5 region) was chemically synthesized. Analyses by CD and two-dimensional 1H NMR spectroscopy were used to investigate the structure of the peptide bound to SDS micelles in solution, which are commonly used in biophysical studies. The tertiary structure of the peptide as a monomer was composed of an alpha-helix (431-438), a turn (439-442), and random coils (427-430, 443-452), and was very similar to that of the pore forming region of the native K(+) channel from Streptomyces lividans determined by X-ray analysis. This result suggests that even an isolated peptide forms a native-like conformation for residues from 431 to 442, depending on its intrinsic amino acid sequence and the surrounding environment.


Health Expenditure Growth under Single-Payer Systems: Comparing South Korea and Taiwan.
Achieving universal health coverage has been an important goal for many countries worldwide. However, the rapid growth of health expenditures has challenged all nations, both those with and without such universal coverage. Single-payer systems are considered more efficient for administrative affairs and may be more effective for containing costs than multipayer systems. However, South Korea, which has a typical single-payer scheme, has almost the highest growth rate in health expenditures among industrialized countries. The aim of the present study is to explicate this situation by comparing South Korea with Taiwan. This study analyzed statistical reports published by government departments in South Korea and Taiwan from 2001 to 2015, including population and economic statistics, health statistics, health expenditures, and social health insurance reports. Between 2001 and 2015, the per capita national health expenditure (NHE) in South Korea grew 292%, whereas the corresponding growth of per capita NHE in Taiwan was only 83%. We find that the national health insurance (NHI) global budget cap in Taiwan may have restricted the growth of health expenditures. Less comprehensive benefit coverage for essential diagnosis/treatment services under the South Korean NHI program may have contributed to the growth of out-of-pocket payments. The expansion of insurance coverage for vulnerable individuals may also contribute to higher growth in NHE in South Korea. Explicit regulation of health care resource distribution may also lead to more limited provisioning and utilization of health services in Taiwan. Under analogous single-payer systems, South Korea had a much higher growth in health spending than Taiwan. The annual budget cap for total reimbursement, more comprehensive coverage for essential diagnosis and treatment services, and the regulation of health care resource distribution are important factors associated with the growth of health expenditures.


Spectroscopy approach to methanol detection in waste fat methyl esters.
Second-generation biodiesel manufactured from waste cooking oils (WCO) and inedible animal fats (AF) are one of the alternatives to the first generation (1G) vegetable oil-based biodiesel. In this study, a quality control method is proposed to evaluate methanol content in waste fat methyl esters and is based on near infrared spectroscopy (NIR) combined with multivariate analysis. More specifically, calibration models are constructed using partial least squares regression (PLS) for the prediction of methanol content in rapeseed oil methyl ester (ROME), waste cooking oil methyl ester (WCOME), chicken fat methyl ester (CFME) and pork fat methyl ester (PFME) by Vis-NIR spectrometer. The calibration models are based on the absorbance spectra and computed data from five wavelength regions of 400-2170 nm, 780-2170 nm, 1400-2170 nm, 1400-1600 nm and 1970-2170 nm. For the cases with the highest prediction ability obtained in this study, the coefficient of determination of the model's goodness-of-fit for methanol concentrations range 0-5% (v/v) was R2 > 0.990, and for concentrations 0-1% (v/v) was R2 > 0.994, indicating the spectroscopic approach effectiveness in methanol content detection relevant to the biofuel quality assessment. A pseudo-univariate limits of detection (LODpu) and quantification (LOQpu) as well as ratio of performance to deviation (RPD) were used to confirm the validity and to evaluate the practical applicability of developed models. In addition, the obtained results indicate the possibility of developing a transmission sensor for online monitoring of the production process and the quality of biofuel.


Serpinopathies and the conformational dementias.
The serpin superfamily of serine proteinase inhibitors has a central role in controlling proteinases in many biological pathways in a wide range of species. The inhibitory function of the serpins involves a marked conformational transition, but this inherent molecular flexibility also renders the serpins susceptible to point mutations that result in aberrant intermolecular linkage and polymer formation. The effects of such protein aggregation are cumulative, with a progressive loss of cellular function that results in diseases as diverse as cirrhosis and emphysema. The recent recognition that mutations in a serpin can also result in late-onset dementia provides insights into changes that underlie other conformational diseases, such as the amyloidoses, the prion encephalopathies and Huntington and Alzheimer diseases.


Philosophy and stimulus design for neuroethology of complex-sound processing.
In research on the neural mechanisms for the processing of biologically important sounds such as species-specific sounds and sounds produced by prey and predators, it is necessary to study responses of central auditory neurons to biologically important sounds, information-bearing elements (IBEs) in them, and tone bursts. The tone bursts or constant-frequency (CF) components can be an IBE in many species of animals. Information-bearing parameters characterizing these sounds must be systematically varied, and tuning of neurons to individual parameters must be studied. The measurement of a tuning curve must be performed not only for excitatory responses, but also for inhibitory and facilitative responses, if any. The selectivity of a neuron to a particular type of sound must be tested for whether it is level-tolerant. Responses to complex sounds can probably be explained on the basis of those to IBEs and tone bursts, so that the use of the tone bursts, even though they are not IBEs, is as essential as that of the biologically important sounds.


Analysis of Indium Tin Oxide Film Using Argon Fluroide (ArF) Laser-Excited Atomic Fluorescence of Ablated Plumes.
A two-pulse laser-excited atomic fluorescence (LEAF) technique at 193 nm wavelength was applied to the analysis of indium tin oxide (ITO) layer on polyethylene terephthalate (PET) film. Fluorescence emissions from analytes were induced from plumes generated by first laser pulse. Using this approach, non-selective LEAF can be accomplished for simultaneous multi-element analysis and it overcomes the handicap of strict requirement for laser excitation wavelength. In this study, experimental conditions including laser fluences, times for gating and time delay between pulses were optimized to reveal high sensitivity with minimal sample destruction and penetration. With weak laser fluences of 100 and 125 mJ/cm2 for 355 and 193 nm pulses, detection limits were estimated to be 0.10% and 0.43% for Sn and In, respectively. In addition, the relation between fluorescence emissions and number of laser shots was investigated; reproducible results were obtained for Sn and In. It shows the feasibility of depth profiling by this technique. Morphologies of samples were characterized at various laser fluences and number of shots to examine the accurate penetration. Images of craters were also investigated using scanning electron microscopy (SEM). The results demonstrate the imperceptible destructiveness of film after laser shot. With such weak laser fluences and minimal destructiveness, this LEAF technique is suitable for thin-film analysis.


Emergency department organisation for disasters: a review of emergency department disaster plans in public hospitals of Singapore.
Disaster management plans of emergency departments (EDs) in four major public hospitals were reviewed. A comparison was made between these plans, and they were analyzed to gain an understanding of the differing objectives and doctrines behind the practices. These were summarized into five major management concepts, which are considered to be critical to the success of a disaster plan: 1) staff mobilization systems (cascading vs batch mobilization); 2) staff deployment systems; 3) team organization (surgeons vs residents); 4) area management (the role of the area manager); 5) casualty volume management (accommodation vs expansion vs extension concepts). The concepts derived should serve as a useful guide to the development of an ED disaster plan and potentially influence how new ED facilities could be planned.


Structure and dynamics of Trichoderma harzianum Cel7B suggest molecular architecture adaptations required for a wide spectrum of activities on plant cell wall polysaccharides.
Cellulases from glycoside hydrolase family 7 (GH7) play crucial roles in plant lignocellulose deconstruction by fungi, but structural information available for GH7 fungal endoglucanases is limited when compared to the number of known sequences in the family. Here, we report the X-ray structure of the glycosylated catalytic domain (CD) of Trichoderma harzianum endoglucanase, ThCel7B, solved and refined at 2.9 Å resolution. Additionally, our extensive molecular dynamics simulations of this enzyme in complex with a variety of oligosaccharides provide a better understanding of its promiscuous hydrolytic activities on plant cell wall polysaccharides. The simulations demonstrate the importance of the hydrogen bond between substrate O2 hydroxyl in the subsite -1 and a side chain of catalytic Glu196 which renders ThCel7B capable to catalytically cleave cello and xylooligosaccharides, but not mannooligosaccharides. Moreover, detailed structural analyses and MD simulations revealed an additional binding pocket, suitable for accommodation of oligosaccharide decorations and/or substrates with mixed glycoside bonds that abuts onto the binding cleft close to subsite +2.


In vitro attachment of trypanosomes to plastic.
Description of an in vitro system for the study of the attachment of trypanosomes to polystyrene flasks by means of hemidesmosomes. This type of attachment, whose significance is so far unknown, reproduces a natural stage in the life cycle of medically important trypanosomatid flagellates in their vector.


Effect of infectious bursal disease virus infection on the phagocytosis of Staphylococcus aureus by mononuclear phagocytic cells of susceptible and resistant strains of chickens.
Studies were conducted to determine why chickens infected with infectious bursal disease (IBD) are more susceptible to Staphylococcus aureus. We evaluated the effect of IBD virus on functions of the peripheral mononuclear phagocytes and looked for humoral abnormalities in the serum. An in vitro opsonophagocytic assay using (H3) thymidine-labeled opsonized Staphylococcus aureus was used to measure phagocytosis. Infection of IBD-sensitive (SCWL 420) chickens with IBD virus did not cause any cellular defects, as shown by phagocytic inability, or any humoral abnormalities, as shown by the lack of opsonics. However, IBD virus did cause some humoral defects 2 weeks postinfection in resistant (Hardy Red) chickens. Therefore, the basic mechanisms governing increased susceptibility of IBD-infected chickens to S. aureus is still unknown.


Halonitromethanes formation in wastewater treatment plant effluents.
Halonitromethanes (HNMs) constitute one class of emerging disinfection by-products with high potential health risks. This study investigated the formation and occurrence of HNMs under different disinfection scenarios and the presence of their precursors in municipal wastewater treatment plant (WWTPs) effluents. Formation potential tests performed on WWTP effluents revealed that HNM formation occurred in the order of ozonation-chlorination >> ozonation-chloramination > chlorination > chloramination. Ozonation alone did not produce any HNM. Municipal WWTP effluents contained some reactive HNM precursors, possibly the by-products of biological treatment processes and/or some moiety of industry or household origin. No effects of nitrate on the formation of HNMs were observed in this study, and nitrification in WWTPs appears to remove appreciable portion of HNM precursors, especially those reactive to chlorine. UV disinfection using low pressure lamps in municipal WWTPs had negligible impact on HNM formation potential. HNM concentrations in the effluents of selected WWTPs were either non-detectable or less than minimum reporting level, except for one WWTP that gave trichloronitromethane concentrations in the range of 0.9-1.5 microg L(-1). No HNMs were observed in the effluents disinfected with UV radiation. Therefore, it appears the typical wastewater disinfection processes involving chlorination or UV treatment in WWTPs do not produce significant amounts of HNMs.


Effect of chronic treatment of norethisterone (a progestogen-only contraceptive) on preputial gland activity of the female rat.
Long-term treatment of norethisterone (a progestogen-only contraceptive) at a daily dosage of 0.5 mg/rat for consecutive 75 days inhibited the preputial gland activity of the female albino rat. It was evident from the decreased mitotic rate as well as from the decline in the per cent of matured acini. It is suggested that chronic treatment of norethisterone perhaps also involves this gland in contraception in the rat.


Watchmaker's pin-vise for manual tattooing of vitiligo.
Tattooing is a commonly used procedure for camouflage of depigmented lesions, especially in vitiligo. To find a cheap and effective instrument for manual tattooing. A watchmaker's pin-vise has been described for use as an instrument along with sewing needles for tattooing in vitiligo. A watchmaker's pin-vise is a cheap and effective for manual tattooing of vitiligo. A watchmaker's pin-vise loaded with sewing needles is an effective, cheap, and sterilizable instrument for tattooing. Sewing needles can be used as disposable needles.


Risks associated with dietary sodium reduction in the spontaneous hypertensive rat model of hypertension.
Sodium balance is maintained by a complex set up of hemodynamic, hormonal and neural mechanisms that affect intake, reabsorption and excretion. The focus of the following research was on the cardiovascular and neuroeffector effects of dietary Na reduction primarily in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) raised from 4 to 15 weeks on a control Na diet (CNa: 12 mmol per 100 g food) or various low Na diets (LNa: 0.5 to 3 mmol per 100 g food). With regards to hemodynamics and volume regulation, the lowest Na diet reduced blood pressure 15% and raised resting heart rate (20%) in SHRs but not WKYs. Blood volume, hematocrit, plasma electrolytes, extracellular volume, and cardiac output were not different between diets or strains. However, both LNa strains were abnormally sensitive to blood loss and showed attenuated pressor responses to both acute and chronic stress situations. Cardiac function was not altered by LNa treatment in either rat strain although structural compensations occurred. LNa treatment significantly attenuated the pressor reduction in mesenteric blood flow during stress which was primarily due to reduction in noradrenergic transmitter release and not due to altered receptor sensitivity, density, or Na/K ATPase activity. Compensatory sympathetic activity was increased as was sodium conservation through humoral mechanisms which maintained homeostasis. However, further neurohumoral compensation was markedly reduced. The data suggests that the hygienic sodium intake in humans should be experimentally defined before generalized measures are taken to reduced dietary sodium use throughout society.


Synthesis, characterization, and conformational analysis of DNA adducts from methylated anilines present in tobacco smoke.
The ability of a series of aromatic amines present in tobacco smoke (2-, 3-, and 4-methylaniline, 2,3- and 2,4-dimethylaniline) to bind to DNA has been investigated by reacting N-(acyloxy)arylamines with dG, dG nucleotides, and DNA. The predominant products from reactions with dG and the nucleotides were characterized as N-(deoxyguanosin-8-yl)arylamines by spectroscopic and HPLC methods. HPLC and spectroscopic analyses of the modified DNA indicated the same adducts. Analyses of the 1H and 13C NMR spectra suggested that the adducts containing a methyl substituent ortho to the arylamine nitrogen had a higher percentage of syn conformers. This observation was supported by theoretical simulation studies that indicated substantial percentages of low energy syn conformers, increasing with the substitution pattern in the order para < meta < ortho < ortho,para < ortho,meta. The results demonstrate that, although single-ring arylamines are considered weak carcinogens, their electrophilic N-acetoxy derivatives, which are plausible metabolic intermediates, react with DNA to yield covalent adducts structurally identical to those derived from carcinogenic polyarylamines, such as 2-aminofluorene and 4-aminobiphenyl. Furthermore, the conformational perturbation induced in DNA by the formation of the monoarylamine-DNA adducts, especially those with an ortho substituent, may contribute to the biological activities of these compounds.


The devil in the details of life-history evolution: instability and reversal of genetic correlations during selection on Drosophila development.
The evolutionary relationships between three major components of Darwinian fitness, development rate, growth rate and preadult survival, were estimated using a comparison of 55 distinct populations of Drosophila melanogaster variously selected for age-specific fertility, environmental-stress tolerance and accelerated development. Development rate displayed a strong net negative evolutionary correlation with weight at eclosion across all selection treatments, consistent with the existence of a size-versus-time tradeoff between these characters. However, within the data set, the magnitude of the evolutionary correlation depended upon the particular selection treatments contrasted. A previously proposed tradeoff between preadult viability and growth rate was apparent only under weak selection for juvenile fitness components. Direct selection for rapid development led to sharp reductions in both growth rates and viability. These data add to the mounting results from experimental evolution that illustrate the sensitivity of evolutionary correlations to (i) genotype-by-environment (G x E) interaction, (ii) complex functional-trait interactions, and (iii) character definition. Instability, disappearance and reversal of patterns of genetic covariation often occur over short evolutionary time frames and as the direct product of selection, rather than some stochastic process. We suggest that the functional architecture of fitness is a rapidly evolving matrix with reticulate properties, a matrix that we understand only poorly.


Quantitative trait loci map for growth and morphometric traits using a channel catfish x blue catfish interspecific hybrid system.
Head length, head depth, head width, body depth, body width, caudal depth, and caudal width and total length and BW were measured for 71 backcross full sibs between the interspecific backcross F1 (female channel catfish [Ictalurus punctatus] × male blue catfish [Ictalurus furcatus]) female × blue catfish male. Body measurements were corrected for both size and the relationship between relative body shape and size, which is critical but usually ignored in fish research. Amplified fragment length polymorphism analysis was used for construction of a QTL map with 44 linkage groups. Eleven of 44 linkage groups had at least 1 significant QTL (P ≤ 0.05) and 11 of 44 at P = 0.10. Linkage group 19 was unique as it had multiple QTL for every trait measured, except for caudal width for which no QTL was identified on any linkage group. Approximately half of the markers measured were associated with positive effects (increase in size) on the traits and half had negative effects (decrease in size). Linkage groups 5, 9, 18, 20, 39, and 40 were significant for multiple traits and always had a trait negative effect. Total length is represented on the map by the most linkage groups and the most markers. The linkage relationships found among BW, total length, and the 7 morphometric traits indicated that multiple trait marker-assisted selection to simultaneously increase BW body depth, body width, and caudal depth while decreasing the head traits with the goal to increase body weight and carcass yield would be very difficult. Multiple genetic enhancement approaches would likely be needed to simultaneously improve BW and body conformation.


Synergistic bacterial gangrene and allied lesions: a unified etiological theory.
Synergistic bacterial gangrene is a distressing and destructive mixed infection where early recognition is essential. It is suggested that synergistic bacterial gangrene with its allied states may be manifestations of the same process with a wide spectrum. Prompt and appropriate bactericidal therapy may arrest spread before tissue destruction makes radical and immediate surgical intervention, with its attendant high mortality, inevitable.


Escherichia coli thymine auxotrophs suppressible by carbon dioxide.
Two independently-isolated thymine-requiring mutant strains of Escherichia coli were found to possess an unusual phenotype: in the presence of CO2, growth was independent of thymine. The two strains showed different profiles of temperature sensitivity. Glycine, serine and methionine were unable to relieve the thymine-dependence. Both strains were susceptible to trimethoprim under conditions where they were thymine-independent. The results are consistent with the occurrence of partial defects in thymidylate synthase.


Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice.
Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice.


Efficacy and safety of topiramate in combination with metformin in the treatment of obese subjects with type 2 diabetes: a randomized, double-blind, placebo-controlled study.
To investigate the efficacy and safety of topiramate in obese subjects with type 2 diabetes treated with metformin. This was a multicenter, double-blind, placebo-controlled trial. All subjects received a non-pharmacological program of diet, exercise and behavioral modification throughout the study; the assigned diet was 600 kcal/day less than the subject's individually calculated energy expenditure. After a 6-week single-blind placebo run-in, subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Following an 8-week titration period, subjects remained on their assigned dose for 52 weeks. However, the sponsor ended the study early in order to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. A total of 646 obese men and women (age: 18-75 years, body mass index: 27-50 kg/m(2)) with an established history of type 2 diabetes mellitus controlled by metformin monotherapy were randomized. Efficacy was assessed in a pre-determined modified intent-to-treat (MITT) population of 307 subjects whose randomization date would have allowed them to complete 24 weeks on study medication before the announcement of study termination. Joint primary efficacy parameters were mean percent change in weight and change in glycosylated hemoglobin (HbA(1c)) from baseline to week 24. Subjects in the placebo, topiramate 96 mg/day and topiramate 192 mg/day groups lost 1.7%, 4.5% (P<0.001) and 6.5% (P<0.001), respectively, of their baseline body weight and had absolute decreases in HbA(1c) of 0.1%, 0.4% (P<0.001) and 0.6% (P<0.001) (MITT, last observation carried forward). Topiramate-treated subjects also experienced statistically significant decreases in systolic blood pressure. Most common adverse events were paresthesia and events related to the central nervous system. Topiramate was effective for weight reduction and improvement in glycemic control in obese subjects with type 2 diabetes treated with metformin monotherapy. Further study in obese diabetics is warranted.


Detecting stable individual differences in the functional organization of the human basal ganglia.
Moving from group level to individual level functional parcellation maps is a critical step for developing a rich understanding of the links between individual variation in functional network architecture and cognitive and clinical phenotypes. Still, the identification of functional units in the brain based on intrinsic functional connectivity and its dynamic variations between and within subjects remains challenging. Recently, the bootstrap analysis of stable clusters (BASC) framework was developed to quantify the stability of functional brain networks both across and within subjects. This multi-level approach utilizes bootstrap resampling for both individual and group-level clustering to delineate functional units based on their consistency across and within subjects, while providing a measure of their stability. Here, we optimized the BASC framework for functional parcellation of the basal ganglia by investigating a variety of clustering algorithms and similarity measures. Reproducibility and test-retest reliability were computed to validate this analytic framework as a tool to describe inter-individual differences in the stability of functional networks. The functional parcellation revealed by stable clusters replicated previous divisions found in the basal ganglia based on intrinsic functional connectivity. While we found moderate to high reproducibility, test-retest reliability was high at the boundaries of the functional units as well as within their cores. This is interesting because the boundaries between functional networks have been shown to explain most individual phenotypic variability. The current study provides evidence for the consistency of the parcellation of the basal ganglia, and provides the first group level parcellation built from individual-level cluster solutions. These novel results demonstrate the utility of BASC for quantifying inter-individual differences in the functional organization of brain regions, and encourage usage in future studies.


Tumour oxygenation, radiosensitivity, and necrosis before and/or after nicotinamide, carbogen and perflubron emulsion administration.
Hypoxia is one of the factors involved in tumour resistance to radiotherapy. One way to improve tumour oxygenation is to use oxygen carriers such as perflubron emulsion plus carbogen or vasoactive drugs such as nicotinamide. The perflubron emulsion and carbogen act mainly on hypoxia caused by limited diffusion of oxygen; nicotinamide acts mainly on acute hypoxia. The aim was to correlate radiosensitivity and pO2 measurements (computerized pO2 histograph) after nicotinamide, perflubron emulsion and carbogen administration, and to determine the role of necrosis in this correlation. Two human tumour xenografts (HRT18, Na11 +) and one rodent tumour (EMT6) were used. Clonogenic assays and pO2 measurements were performed under similar conditions. The radiosensitization and oxygenation levels increased with all treatments. The maximal effects were found with the combination of nicotinamide (1 g/kg), perflubron emulsion and carbogen. A correlation between the radiosensitization and the pO2 measurements was found for the three cell lines with a cut-off point of 10 mmHg. The presence of necrosis could explain the low pO2 (< 2 mmHg) found even when complete radiosensitization was observed.


Accommodating Indigenous Nurse-Initiated and Managed Antiretroviral Therapy (NIMART) Reporting in a Developing Country Context.
Financial reporting represents a critical tool in eliminating HIV across Papua New Guinea (PNG). Using the tenets of the theory of indigenous alternative reporting, this paper considers how the PNG Nursing Council may accommodate nurse-initiated and managed antiretroviral therapy (NIMART) reporting. Textual analysis of indigenous reporting expectations placed on the PNG Nursing Council are examined in a NIMART context to examine levels of reporting compliance exercised by council administrators from year-end reports (1980 to 2016) to accommodate NIMART reporting. The study revealed that the 2014 annual report of the PNG Nursing Council generated a 40% NIMART compliance rate, offering encouraging signs of financial reporting that could make room for NIMART reporting. The study suggested that local mechanisms could be used to meet local indigenous reporting expectations in order to adopt NIMART reporting. The study also has far-reaching implications for other developing country nursing councils wanting to develop NIMART reporting.


[Overprescribing of antibiotics outside the hospital].
Overprescription of antibiotics is evident in the community as well as in hospital, in veterinary practice or in agriculture. This leads to bacterial multiresistance and treatment failures. The limitation of this overprescription will not be obtained unless diagnostic, therapeutic and preventive guidelines are followed particularly in the management of the upper respiratory tract infections.


Congenital muscular dystrophy. A histochemical study with morphometric analysis on biopsied muscles.
Muscle biopsies from 10 Japanese patients (9 females and 1 male) with congenital muscular dystrophy (CMD) were studied. Their clinical features varied remarkably in severity; one patient died at 6 years of age. Family history was negative in all but one patient who had an affected sibling. Muscle biopsy findings varied from mild myopathic to advanced dystrophic changes. Hypertrophic fibers associated with occasional fiber splitting were assumed to reflect a chronic dystrophic process. Histochemical examination revealed type 1 fiber predominance in 5 patients, and type 2 fiber predominance in one. Eight patients had a slight to moderate increase in the number of undifferentiated type 2C fibers suggesting a regenerating process after fiber necrosis. Type 2B fibers were fairly well preserved in 8 patients. The overall findings differed from those of the Fukuyama type congenital muscular dystrophy (FCMD) and Duchenne muscular dystrophy (DMD) in which more active fiber necrosis and regeneration are seen. We conclude that the present CMD patients suffered from a chronic dystrophic process similar to that in limb-girdle muscular dystrophy.


Is perioperative examination of frozen sections necessary in nephron-sparing surgery?
To evaluate the role of perioperative freezing in the management of surgical procedures in patients with malignant renal masses. The study group consisted of 17 patients diagnosed with renal masses who underwent nephron-sparing surgery. The group included 5 females and 12 males aged from 44 to 68 years (mean = 54.6). The mean mass size was 5.5 cm. Mass locations were as follows: 9 were in the lower pole, 4 were in the mid-pole, and 6 were in the upper pole. Perioperative freezing was not carried out. The patients were followed-up in a period ranging from 3 months to 7 years. Tumor pathology was reported as renal cell carcinoma in all cases, and surgical margins were negative in all of them. One patient died after 1 year because of tumor metastasis. In another patient, the tumor reoccurred in the same kidney and a radical nephrectomy was performed. Other patients were followed without recurrence. Imaging of the renal vascular system and freezing during surgery is not necessary for nephron-sparing surgery for renal cell carcinoma; however, we should be careful in terms of capsule invasion because of tumor recurrence.


Functional studies of left upper quadrant mass aid management of idiopathic thrombocytopenic purpura.
ITP (idiopathic thrombocytopenic purpura) causes rapid sequestration and destruction of thrombocytes by the spleen, liver, bone marrow, and reticuloendothelial elements of other organs. The usefulness of multiple radionuclide functional imaging procedures in the management of a 34-year-old woman with chronic ITP, two splenectomies (removal of the initial spleen and then a hypertrophied accessory spleen), and the failure of chemotherapy to control her thrombocytopenia, are discussed. A combination of In-111 oxine autologous platelet imaging, liver/spleen imaging, disofenin (liver/gallbladder) imaging, and glucoheptonate renal imaging demonstrated that her platelets were being sequestered by a markedly enlarged left hepatic lobe extending to the left lateral wall, with a small amount in the kidneys and lungs, and that there was no second accessory spleen.