Analysis and functional annotation of expressed sequence tags from the fall armyworm Spodoptera frugiperda.
Little is known about the genome sequences of lepidopteran insects, although this group of insects has been studied extensively in the fields of endocrinology, development, immunity, and pathogen-host interactions. In addition, cell lines derived from Spodoptera frugiperda and other lepidopteran insects are routinely used for baculovirus foreign gene expression. This study reports the results of an expressed sequence tag (EST) sequencing project in cells from the lepidopteran insect S. frugiperda, the fall armyworm. We have constructed an EST database using two cDNA libraries from the S. frugiperda-derived cell line, SF-21. The database consists of 2,367 ESTs which were assembled into 244 contigs and 951 singlets for a total of 1,195 unique sequences. S. frugiperda is an agriculturally important pest insect and genomic information will be instrumental for establishing initial transcriptional profiling and gene function studies, and for obtaining information about genes manipulated during infections by insect pathogens such as baculoviruses.


Development of a functional point-of-need diagnostic for myeloperoxidase detection to identify neutrophilic bronchitis.
With over 4.8 million Canadians suffering from chronic airway diseases, respiratory exacerbations are currently the leading cause of hospitalization in Canada. In cases of bacterial infection, neutrophil cell density increases from ∼10 million cells per gram to over 15 million cells per gram. As sputum is a direct discharge from the primarily affected areas of respiratory diseases, quantification of granulocytes (including neutrophils) can be used to effectively determine a course of patient treatment. Unfortunately this quantification is currently limited to labour-intensive and time-consuming cell counts. In the present study, we describe a simple one-step lateral flow test (LFT) that can semi-quantitatively determine myeloperoxidase (MPO), a biomarker found in neutrophils, in minimally-processed sputum samples. This point-of-need (PON) diagnostic device provides positive results observable to the naked eye after 15 minutes. 37 human sputum samples were quantified for MPO using the developed LFT and compared to neutrophil levels quantified through traditional cell counting. A trend between sputum MPO concentration and total neutrophils was observed, suggesting that the LFT has the potential to replace cell counting for neutrophil approximation to aid in directing therapies quickly at the point of need.


The SCL/TAL-1 gene is expressed in progenitors of both the hematopoietic and vascular systems during embryogenesis.
Activation of the SCL (or TAL-1) gene as a result of chromosomal translocation or deletion is a frequent molecular lesion in acute T-cell leukemia. By virtue of its membership in the basic helix-loop-helix family of transcription factors, the SCL gene is a candidate to regulate events in hematopoietic differentiation. We have used polyclonal antibody raised against a bacterial expressed malE-SCL fusion protein to characterize SCL protein expression in postimplantation embryos and in neonatal and adult mice. SCL protein was detected at day 7.5 post coitum at both embryonic and extraembryonic sites, approximately 24 hours before the formation of recognizable hematopoietic elements. Expression then localized to blood islands of the yolk sac followed by localization to fetal liver and spleen, paralleling the hematopoietic activity of these tissues during development. SCL protein was detected in erythroblasts in fetal and adult spleen, myeloid cells and megakaryocytes in spleen and bone marrow, mast cells in skin, and in rare cells in fetal and adult thymus. In addition, SCL protein was noted in endothelial progenitors in blood islands and in endothelial cells and angioblasts in a number of organs at times coincident with their vascularization. SCL expression was also observed in other nonhematopoietic cell types in the developing skeletal and nervous systems. These results show that SCL expression is one of the earliest markers of mammalian hematopoietic development and are compatible with a role for this transcription factor in terminal differentiation of the erythroid and megakaryocytic lineages. SCL expression by cells in the thymus suggests that the gene may be active at some stage of T-cell differentiation and may be relevant to its involvement by chromosomal rearrangements in T-lymphoid leukemias. Finally, expression of the gene in developing brain, cartilage, and vascular endothelium indicates SCL may have actions in neural development, osteogenesis, and vasculogenesis, as well as in hematopoietic differentiation.


Effectiveness of suicide prevention gatekeeper training: 12-month follow-up of SafeTALK training to community members.
Long-term assessments of gatekeeper training (GKT) with multiple follow-ups are rare. Therefore, the aim of the current analysis is to examine 12-month follow-up outcomes of SafeTALK training in addition to the earlier analysis of pre-, post-, and 6-month follow-up. Two hundred and sixty two community volunteers participated in half-day (4-h) gatekeeper training sessions. Before, after, and 6- and 12-month follow-up surveys were used to assess participants' knowledge, efficacy, and reluctance to intervene. Linear mixed effects regression was used in statistical analysis. Fifty six participants (21.4%) completed the 12-month follow-up, representing an attrition rate of 78.6% from pre-test. Linear mixed model analysis revealed a significant, consistent effect for time for knowledge, efficacy, and reluctance. Post-hoc testing revealed significant differences between scores at pre-test and 12-month follow-up for GK knowledge and efficacy; however, no significant difference was seen between these time points for reluctance to intervene. No significant change was measured between the 6 and 12 months for any outcomes. GK knowledge and efficacy remained significantly above pre-test scores. The evaluation of the GKT demonstrated the long-term effectiveness of community-based suicide prevention training programs to improve and maintain GK knowledge and efficacy.


Renal localization of the membrane attack complex in systemic lupus erythematosus nephritis.
The membrane attack complex (MAC) of the complement system was localized in both glomeruli and peritubular regions of 22 kidneys manifesting systemic lupus erythematosus (SLE) nephritis. A similar distribution was observed for immune complex markers (IgG, Clq, and C3) and MAC in glomeruli, although the deposits of MAC were more discrete and showed lesser immunofluorescence staining intensity compared with immunoglobulins and complement components. In contrast, peritubular immune complexes were present in only 7 out of 22 kidneys, involved comparatively small clusters of tubules, exhibited weaker immunofluorescence staining than MAC, and failed to correlate with interstitial foci of inflammation. Granular or irregular, linear aggregates of the MAC were observed at the periphery of larger groups of tubules contiguous to areas of interstitial inflammation. Comparable amounts of IgG, Clq, C3, and MAC were present in blood vessel walls in areas of fibrinoid necrosis. These data suggest that the MAC is a direct mediator of tissue injury occurring in renal glomeruli, tubules, and blood vessels. The discordance between immune complexes and MAC localized in the peritubular region, but not in glomeruli or blood vessels, raises the possibility that both immune complexes and nonimmune agents, such as bacterial antigens, may activate the classical or alternative complement pathways and thereby play a role in the pathogenesis of tubulointerstitial lesions of SLE nephritis.


Elevated plasma homocysteine in association with decreased vitamin B(12), folate, serotonin, lipids and lipoproteins in depressed patients.
Increased plasma homocysteine, decreased vitamin B(12) and folic acid levels have been implicated in depressive mood. Plasma homocystine, vitamin B(12), folic acid tryptophan, lipids and lipoproteins were determined in depressed patients and controls. Sixty subjects consisting of 30 depressed patients and 30 apparently healthy volunteers, who served as controls, were selected for this study. Anthropometric indices and biochemical parameters were determined using standard procedures. The results showed a significantly higher plasma homocysteine level amongst depressed patients when compared with the corresponding controls (p < 0.001), the percentage increase was 116%, while the plasma vitamin B(12) (p < 0.01), total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol levels (p < 0.001) were markedly lower when amongst depressed patients when compared with the corresponding controls; the percentage differences were 21%, 42% and 42% respectively. Plasma triglyceride, folic acid and tryptophan levels amongst depressed patients were not significantly different from the controls. The male subjects had significantly higher plasma tHcy levels than the female counterparts ( p < 0.001). This study showed a significant increase in plasma tHcy coexisting with a decrease in plasma vitamin B(12) TC, LDLC and HDLC, in depressed patients. Increased plasma homocysteine could be a sensitive indicator of plasma B vitamin deficiency.


Cultural influences on the prevalence of common mental disorder, general practitioners' assessments and help-seeking among Punjabi and English people visiting their general practitioner.
Culture influences symptom presentation and help-seeking and may influence the general practitioner's assessment. We recruited Punjabi and English GP attenders to a two-phase survey in London (UK) using the Amritsar Depression Inventory and the General Health Questionnaire as screening instruments. The Clinical Interview Schedule was the criterion measure. General practitioners completed Likert assessments. The second phase was completed by 209 Punjabi and 180 English subjects. The prevalence of common mental disorders was not influenced by culture. Punjabi cases more often had 'poor concentration and memory' and 'depressive ideas' but were not more likely to have somatic symptoms. General practitioners were more likely to assess Punjabis with common mental disorder as having 'physical and somatic' symptoms or 'sub-clinical disorders'. Punjabi cases with depressive ideas were less likely to be detected compared with English ones. In comparison to English men, English women were under-detected by Asian general practitioners. Help-seeking English subjects were more likely to be correctly identified as cases. The prevalence of common mental disorders and somatic symptoms does not differ across cultures. Among English subjects, general practitioners were more likely to identify correctly pure psychiatric illness and mixed pathology; but Punjabi subjects with common mental disorders were more often assessed as having 'sub-clinical disorders' and 'physical and somatic' disorders. English women were less well detected than English men. English help-seeking cases were more likely to be detected.


Prenatal stress alters noradrenergic modulation of LTP in hippocampal slices.
Long-term effects of stress during pregnancy on brain and behavior have been analyzed extensively in recent years. These effects include changes in emotional behavior, a reduction in learning capacity, and ability to generate long-term potentiation (LTP) in the offspring. In earlier studies, we and others have described a difference in ability to express LTP in dorsal and ventral sectors of the hippocampus (DH and VH, respectively) and its modification by prior stress. We now found that norepinephrine (NE) facilitated conversion of short-term potentiation to LTP in the normal DH but not in VH. Prenatal stress (PS) switched the locus of the facilitating action of NE from the DH to the VH. The effects of NE are likely to be mediated by activation of calcium stores. PS also facilitated (S)-3,5-dihydroxyphenylglycine hydrate (DHPG)-induced LTD in the VH, assumed to be mediated by release of calcium from stores. These observations have important implications for the role of the hippocampus in cognitive and emotional memories.


Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.
Mentha spicata Labiatae, known as spearmint and Mentha piperita Labiatae, known as peppermint can be used for various kinds of illnesses in herbal medicine and flavoring in industry. M. spicata Labiatae grows on the Anamas plateau of Yenithornarbademli town of Isparta, located in southwest part of Turkey. In this town, clinicians thought that consumption of tea steeped with M. spicata or M. piperita caused a diminished libido. Because antiandrogenic effects of spearmint and peppermint were found previously in rats, it was decided to observe the effect of this herbal tea on the androgen levels in hirsute women.Twenty-one female hirsute patients, 12 with polycystic ovary syndrome and 9 with idiopathic hirsutism were included to the study. They were took a cup of herbal tea which was steeped with M. spicata for 5 days twice a day in the follicular phase of their menstrual cycles. After treatment with spearmint teas, there was a significant decrease in free testosterone and increase in luteinizing hormone, follicle-stimulating hormone and estradiol. There were no significant decreases in total testosterone or dehydroepiandrostenedione sulphate levels. Spearmint can be an alternative to antiandrogenic treatment for mild hirsutism. Further studies are needed to test the reliability of these results and the availability of spearmint as a drug for hirsutism.


Networks of face-to-face social contacts in Niakhar, Senegal.
We present the first analysis of face-to-face contact network data from Niakhar, Senegal. Participants in a cluster-randomized influenza vaccine trial were interviewed about their contact patterns when they reported symptoms during their weekly household surveillance visit. We employ a negative binomial model to estimate effects of covariates on contact degree. We estimate the mean contact degree for asymptomatic Niakhar residents to be 16.5 (95% C.I. 14.3, 18.7) in the morning and 14.8 in the afternoon (95% C.I. 12.7, 16.9). We estimate that symptomatic people make 10% fewer contacts than asymptomatic people (95% C.I. 5%, 16%; p = 0.006), and those aged 0-5 make 33% fewer contacts than adults (95% C.I. 29%, 37%; p < 0.001). By explicitly modelling the partial rounding pattern observed in our data, we make inference for both the underlying (true) distribution of contacts as well as for the reported distribution. We created an estimator for homophily by compound (household) membership and estimate that 48% of contacts by symptomatic people are made to their own compound members in the morning (95% CI, 45%, 52%) and 60% in the afternoon/evening (95% CI, 56%, 64%). We did not find a significant effect of symptom status on compound homophily. We compare our findings to those from other countries and make design recommendations for future surveys.


Assessment of chronic neuropsychological effects of mercury vapour poisoning in chloral-alkali plant workers.
A prospective case study was conducted in the Department of Occupational Medicine, Tuzla. The purpose of this study was to indicate negative effects from occupational exposure to mercury on behavioural and mental health, memory and psychomotor function that was tested in 46 chloral-alkali plant workers (mean age was 38. 8+/- 5. 7 years; mean age of occupational history 16. 5+/- 6. 0 years). Data on toxicological monitoring on atomic absorption spectrometer, and data on mental health were collected, psychiatric and other subjective symptoms, and behavioural, psychomotor and memory function tested. The data were compared to control group, 32 healthy non exposed workers. The study was designed to assess blood and urine mercury levels and length of occupational exposure and investigate its relationships to effects on the mental health. The mean air mercury levels were 0.23 mg/m3, the mean blood mercury concentrations was 3. 6 mg/ dl and the mean urine mercury concentrations were 151.7 +/- 180.4 mg/l. In 25 (53%) workers exposed to mercury vapour was identified Depression-Hypochondrias Syndrome (p trend < 0. 001) with higher scores for scales: Hysteria (p trend <0. 001), Schizoid and Psychoastenia (MMPI). All psychological parameters were in highly significantly correlations with mercury levels and length of occupational exposure. Pathological parameters were possible general identified if the concentration of blood mercury levels are >2. 9 mg/ dl, or urine mercury levels > 87 mg/l workers exposed to mercury vapour knew that toxic effects in body resulted in loosing some of intellectual abilities, and that people who handle chemicals had an increased health risk (ESW questionnaire). The occupational mercury exposed workers had introvert behaviour (EPQ). Aggressiveness was found in 71.7% workers. The cognitive disturbances: short-term memory loss, difficult to concentrate on tasks which require attention and thinking, were significantly differed compared to those of controls (p trend < 0. 001). In 24 (52%) exposed to mercury workers we have determined ego strength loss and regressive defensive mechanisms (LB). Handwriting disturbances-micrography we have identified in 27 (58.7%) workers.


Survival of a specialist natural enemy experiencing resource competition with an omnivorous predator when sharing the invasive prey Tuta absoluta.
Can specialist natural enemies persist in ecosystems when competing with omnivorous natural enemies for their shared prey? The consequences of omnivory have been studied theoretically, but empirical studies are still lacking. Omnivory is nevertheless common in nature and omnivorous predators coexist with specialists in many ecosystems, even when they are intraguild predators. This type of association is also common in agroecosystems in which biological control strategies are used. Our study provides an example of the outcome of such an association in the context of biological control of the invasive pest Tuta absoluta (Lepidoptera) in a tomato agroecosystem. The two natural enemies involved, that is, a specialist (Stenomesius japonicus (Hymenoptera) parasitoid) and an omnivore (Macrolophus pygmaeus (Hemiptera) predator), were able to coexist for 3 months in our experimental cages in the absence of metacommunity mechanisms (i.e., emigration and recolonization), contrary to theoretical expectations. However, they negatively affected each other's population dynamics. We found that spatial resource segregation was not a mechanism that promoted their coexistence. Regarding pest control, the specialist and omnivorous natural enemies were found to exhibit complementary functional traits, leading to the best control when together. Mechanisms that may have promoted the coexistence of the two species as well as consequences with regard to the inoculative biological control program are discussed.


Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice.
1. To determine whether nitric oxide (NO) was involved in tolerance and sensitization to the effects of phencyclidine (PCP), we examined NO synthase activity and the number of NADPH-diaphorase (NADPH-d)-positive cells in discrete brain regions of saline-, acute PCP- and repeated PCP-treated mice. We also investigated the effects of a NO synthase inhibitor, NG-nitro-L- arginine methyl ester (L-NAME), on the behavioural changes induced by repeated PCP treatment in mice. 2. Acute PCP (1, 3, and 10 mg kg-1, s.c.) treatment induced dose-dependent hyperlocomotion, motor incoordination and stereotyped behaviours, consisting of sniffing, head movement and ataxia in mice. 3. In mice treated repeatedly with PCP (1, 3, and 10 mg kg-1 day-1), s.c., once a day for 14 days), the sniffing, head movement, ataxia and motor incoordination induced by PCP were attenuated (indicating the development of tolerance to these behaviours), whereas the hyperlocomotion induced by PCP was potentiated (indicating the development of sensitization to hyperlocomotion). The development of tolerance and sensitization to PCP-induced behaviours in the repeated PCP-treated mice was more marked at the dose of 10 mg kg-1 day-1) than at other doses. 4. NO synthase activity in the cerebral cortex and cerebellum, but not in the striatum and hippocampus, was significantly decreased by acute PCP (10 mg kg-1) treatment in comparison with saline treatment, and such changes in activity in the cerebral cortex and cerebellum were reversed by repeated PCP treatment (10 mg kg-1 day-1). 5. The number of neurones containing NADPH-d reactivity in the cerebral cortex, nucleus accumbens, and striatum of acute and repeated PCP-treated mice showed no change in comparison with saline-treated mice. 6. Tolerance to PCP (10 mg kg-1 day-1)-induced ataxia and motor incoordination was significantly attenuated by combined treatment with L-NAME (50 mg kg-1 day-1 i.p.). 7. Sensitization to PCP-induced hyperlocomotion was further enhanced by combined treatment with L-NAME (50 mg kg-1 day-1). However, NG-nitro-D-arginine methyl ester (D-NAME, 50 mg kg-1 day-1, i.p.), a less active enantiomer of L-NAME, had no effect, suggesting a stereospecific mechanism. 8. The PCP-induced behaviours in animals that had exhibited tolerance and sensitization to PCP (10 mg kg-1 day-1) were not influenced by acute L-NAME (5 and 50 mg kg-1, i.p.) or D-NAME (50 mg kg-1, i.p.) treatment. 9. These results suggest that NO may play an important role in the development, but not in the maintenance, of tolerance and sensitization to the effect of PCP in mice.


Transport of benzylpenicillin by the rat choroid plexus in vitro.
To characterize the transport system by which benzylpenicillin, an organic anion, is accumulated by the isolated rat choroid plexus, kinetic analysis of benzylpenicillin transport was performed. Accumulation of benzylpenicillin was against an electrochemical potential gradient via a saturable process (Km = 58 microM and Vmax = 84 nmol/ml of tissue per min) that was inhibited by sulfhydryl reagents (p-hydroxymercuribenzoate and N-ethylmaleimide), metabolic inhibitors (KCN and 2,4-dinitrophenol) and anion exchange inhibitors (4-acetamide-4'-isothiocyanatostilbene-2,2'-disulfonic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid), but is major transport system did not require the inward Na+ gradient. Organic anions, such as 5-hydroxyindoleacetic acid, homovanillic acid, p-aminohippuric acid and probenecid inhibited the accumulation of benzylpenicillin, whereas dipeptides did not affect it. Kinetic analysis of the accumulation of benzylpenicillin suggests that both phenoxymethylpenicillin and cefpiramide are also transported via the benzylpenicillin transport system. Other penicillin and cephalosporin derivatives inhibited the accumulation of benzylpenicillin with different affinities. Penicillin derivatives without dissociating groups in the side chain had the higher affinity for the benzylpenicillin transport system than other beta-lactam antibiotics did. Among penicillin derivatives examined, a good correlation (r = 0.92) was observed between the lipophilicity and the affinity for the benzylpenicillin transport system, whereas no correlation was observed among the cephalosporin derivatives. These findings suggest that the major transport system of benzylpenicillin in the rat choroid plexus is via a carrier-mediated active anion transport process which is distinct from that of dipeptides, and does not require the inward Na+ gradient.(ABSTRACT TRUNCATED AT 250 WORDS)


Nanotopography-based engineering of retroviral DNA integration patterns.
Controlling the interactions between cells and viruses is critical for treating infected patients, preventing viral infections, and improving virus-based therapeutics. Chemical methods using small molecules and biological methods using proteins and nucleic acids are employed for achieving this control, albeit with limitations. We found, for the first time, that retroviral DNA integration patterns in the human genome, the result of complicated interactions between cells and viruses, can be engineered by adapting cells to the defined nanotopography of silica bead monolayers. Compared with cells on a flat glass surface, cells on beads with the highest curvature harbored retroviral DNAs at genomic sites near transcriptional start sites and CpG islands during infections at more than 50% higher frequencies. Furthermore, cells on the same type of bead layers contained retroviral DNAs in the genomic regions near cis-regulatory elements at frequencies that were 2.6-fold higher than that of cells on flat glass surfaces. Systems-level genetic network analysis showed that for cells on nanobeads with the highest curvature, the genes that would be affected by cis-regulatory elements near the retroviral integration sites perform biological functions related to chromatin structure and antiviral activities. Our unexpected observations suggest that novel engineering approaches based on materials with specific nanotopography can improve control over viral events.


A content analysis of mass media sources in relation to the MMR vaccine scare.
In light of the mass media coverage that the MMR (measles, mumps and rubella) vaccine received as a result of questions raised about its safety, a content analysis of mass media articles about the MMR vaccine was undertaken. The analysis examined 227 articles published in five different information sources in a 2 month period. The analysis looked at 94 content-based variables and the key attributes of these articles including word count and date of publication. Descriptive and analytical statistics relating to both article content and format were produced. The analysis showed that the content and format of articles between different information sources varied widely. These differences can be attributed to the information source in which they are published, but the variability in the content of these information sources provides a challenge to parents who were shown to be using the mass media as an information source.


The role of kinesiotaping combined with botulinum toxin to reduce plantar flexors spasticity after stroke.
To evaluate the effect of kinesiotaping as an adjuvant therapy to botulinum toxin A (BTX-A) injection in lower extremity spasticity. This is a single-center, randomized, and double-blind study. Twenty hemiplegic patients with spastic equinus foot were enrolled into the study and randomized into 2 groups. The first group (n=10) received BTX-A injection and kinesiotaping, and the second group (n=10) received BTX-A injection and sham-taping. Clinical assessment was done before injection and at 2 weeks and 1, 3, and 6 months. Outcome measures were modified Ashworth scale (MAS), passive ankle dorsiflexion, gait velocity, and step length. Improvement was recorded in both kinesiotaping and sham groups for all outcome variables. No significant difference was found between groups other than passive range of motion (ROM), which was found to have increased more in the kinesiotaping group at 2 weeks. There is no clear benefit in adjuvant kinesiotaping application with botulinum toxin for correction of spastic equinus in stroke.


The American Society of Breast Surgeons and Quality Payment Programs: Ranking, Defining, and Benchmarking More Than 1 Million Patient Quality Measure Encounters.
To identify and remediate gaps in the quality of surgical care, the American Society of Breast Surgeons (ASBrS) developed surgeon-specific quality measures (QMs), built a patient registry, and nominated itself to become a Center for Medicare and Medicaid Services (CMS) Qualified Clinical Data Registry (QCDR), thereby linking surgical performance to potential reimbursement and public reporting. This report provides a summary of the program development. Using a modified Delphi process, more than 100 measures of care quality were ranked. In compliance with CMS rules, selected QMs were specified with inclusion, exclusion, and exception criteria, then incorporated into an electronic patient registry. After surgeons entered QM data into the registry, the ASBrS provided real-time peer performance comparisons. After ranking, 9 of 144 measures of quality were chosen, submitted, and subsequently accepted by CMS as a QCDR in 2014. The measures selected were diagnosis of cancer by needle biopsy, surgical-site infection, mastectomy reoperation rate, and appropriateness of specimen imaging, intraoperative specimen orientation, sentinel node use, hereditary assessment, antibiotic choice, and antibiotic duration. More than 1 million patient-measure encounters were captured from 2010 to 2015. Benchmarking functionality with peer performance comparison was successful. In 2016, the ASBrS provided public transparency on its website for the 2015 performance reported by our surgeon participants. In an effort to improve quality of care and to participate in CMS quality payment programs, the ASBrS defined QMs, tracked compliance, provided benchmarking, and reported breast-specific QMs to the public.


Topcoat-Assisted Perpendicular and Straightly Parallel Coexisting Orientations of Block Copolymer Films.
Highly ordered perpendicular orientation and straightly parallel orientation coexisting polystyrene-block-polydimethylsiloxane (PS-b-PDMS) cylindrical microdomains with 10 nm width can be realized by using polyvinyl acetate as a partially dewetted topcoat and solvent annealing with acetone vapor. During solvent annealing, the swelled topcoat begins to dewet and the dewetting rim sweeps the surface of the block copolymer films to align the cylindrical microdomains with the direction of dewetting propagation. However, the wetted region of the topcoat/PS-b-PDMS film forms with a perpendicular orientation due to reduced surface tension and sufficient concentration gradient in the solvent evaporation step. The orientational changes (perpendicular/straightly parallel orientation) in the dewetted/wetted area are also investigated according to the vapor pressure of solvent annealing. The degree of directionality of the swept PS-b-PDMS films according to the distance from the dewetting front, which is equivalent with time after sweeping, is examined. To control the direction of dewetting and complex structures within a specific area, an imprinting process is introduced to form topographical line-space patterns in the topcoat and perpendicular/parallel orientation of BCP patterns in the line-space patterns, respectively.


Association of BRM promoter polymorphisms and esophageal adenocarcinoma outcome.
Brahma (BRM) is a critical catalytic subunit of the SWI/SNF chromatin remodeling complex; expression of BRM is commonly lost in various cancer types. BRM promoter polymorphisms (BRM-741; BRM-1321) are associated with loss of BRM expression, and with cancer risk/survival. We evaluated these two polymorphisms in the overall survival (OS) of esophageal adenocarcinoma (EAC) patients. Of 270 patients, 37% were stage IV. Minor allele frequencies were 47-49%; 15% were double-homozygotes. When compared to the wild-type genotype, the homozygous variant of BRM-741 carried an adjusted OS hazard ratio (aHR) of 1.64 (95% CI:1.1-2.4); for BRM-1321, the aHR was 2.09 (95% CI:1.4-3.0). Compared to the double wild-type, carrying homozygous variants of both promoter polymorphisms (double-homozygote) yielded an aHR of 2.21 (95% CI:1.4-3.6). Directions/magnitudes of associations were similar in subsets by age, gender, smoking status, use of platinum agents, and disease stage, and for progression-free survival. In a cohort of EAC patients of all stages (84% male; median age of 64 years), two BRM polymorphisms were genotyped. Cox proportional hazards models, adjusted for known prognostic variables, estimated the association of polymorphisms with OS. BRM polymorphisms were associated with OS in EAC in this study. Validation studies are warranted.


Image analysis of the tapetal-like reflex in carriers of X-linked retinitis pigmentosa.
To increase understanding of the tapetal-like reflex (TLR), a unique retinal feature in carriers of X-linked retinitis pigmentosa (XLRP). Color fundus photographs of XLRP carriers were digitized at high resolution. A mathematical model of the imaging system was used to restore the digital retinal images. TLR was separated from the retinal background with an automated segmentation method. Mathematical morphology was used to estimate directional properties. Images from serial photos were registered and compared to study temporal progression. Quantitative analysis of well-focused funduscopic images show point-like unit reflexes forming the TLR. The average unit reflex is circularly symmetric with a diameter of approximately 8.5 microns and has a maximum reflectance 40% higher than that of the neighboring nonreflex retina. Two or more unit reflexes form small elongate patches that can cluster together into larger patches. Both smaller and larger patches have a strong preferential direction toward the fovea. Comparison of images taken 23 years apart in one patient and 3 years apart in another patient show no detectable changes in the size and location of the reflexes. The pattern of reflexes at high and low resolution suggests that the TLR represents an X-inactivation mosaic. Based on the size of the unit reflexes, the authors speculate that the cone photoreceptors participate in the TLR. The stability of the reflex over more than two decades questions the longstanding assumption that the TLR is a stage of the retinal degeneration.


[Psychotherapy with physically challenged children and young people: implications of a change of paradigm].
In the light of newer scientific developments the biopsychosocial approach in psychotherapy appears to be in need of a revision. In neurosciences a paradigm change from a linear to a dynamic outlook on development as a self-organizing process guided by interactions with the environment took place under the heading of Neural Plasticity during the last ten years. This implies that the conditions of development for challenged children are not comparable with those of healthy children as the case-examples of children with Spina Bifida indicate. On this background, a pilot project was launched with the goal of determining which forms of psychotherapy are helpful for challenged children. A practically oriented, eclectic approach was developed applying empiric-regulative cycles which promotes the dynamics of self-organizing psychic and physical processes as shown in a presented example of a child experiencing post-lesional plasticity. Thus, psychotherapy is understood as a co-constructive process of reciprocal shaping of relationship; it fosters beneficial organization processes of psychic and physical impact.


Management of Unruptured Intracranial Aneurysms and Cerebrovascular Malformations.
Unruptured intracranial aneurysms and vascular malformations are detected more frequently because of the increased use and availability of brain imaging. Management of these entities requires knowledge of which patients are at high risk for hemorrhage and what treatment options are available. This article summarizes the epidemiology, natural history, and management strategies for unruptured intracranial aneurysms, arteriovenous malformations, cavernous malformations, developmental venous anomalies, and capillary telangiectasias. Pooled cohort studies and meta-analyses have improved the ability to predict hemorrhage for each vascular abnormality. Scores and tools have been developed to aid the practitioner in predicting hemorrhage risk for unruptured intracranial aneurysms. Advances in endovascular techniques for unruptured intracranial aneurysms have improved the ability to treat difficult wide-necked aneurysms. Unruptured intracranial aneurysms are a common incidental finding. The PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, site of aneurysm) score and Unruptured Intracranial Aneurysm Treatment Score may be useful tools for predicting natural history and treatment recommendations. The overall risk of hemorrhage for both arteriovenous malformations and cavernous malformations is about 2% to 4% per year. With both of these entities, prior hemorrhage predicts future hemorrhage. In addition, other select patient and radiologic factors influence risk of hemorrhage. The risk of future hemorrhage should be compared to the risk of treatment. Developmental venous anomalies and capillary telangiectasias are largely benign entities and rarely symptomatic.


Social-ecological timelines to explore human adaptation to coastal change.
Through the construction of a socio-ecological timeline for the Porsanger fjord ecosystem, this article illustrates the different ways in which environmental and social-ecological changes have influenced the adaptations of rural households in coastal Sami communities in Finnmark, north Norway. The main finding is that, although environmental change in the form of seal invasions and dwindling fish stocks directly impacted the fisheries, the introduction of a new vessel quota system decisively changed adaptive capacity and coastal Sami household adaptation strategies. These changes represented a tipping point for the social-ecological system in the period between 1986 and 1990. It is thus important to discuss the ways in which governance systems may facilitate actions to adapt to climate and biodiversity change and foster sustainable rural livelihood systems in coastal Norway. Based on traditional and local ecological knowledge on the state of the ecosystem prior to the tipping point, two relevant actions to increase the resilience of the system were identified: ensuring the possibility of re-entry into fisheries as part of rural livelihood combinations, and ecological restoration of kelp beds. Flexible diversification of livelihoods allows exploitation of a range of adjacent species without large investments in a fossile fuel-driven fisheries economy. Investing in regrowth of macroalgae to foster cod nursery areas and increase carbon sequestration can be a relevant alternative for communities that are interested in contributing to climate change mitigation on a larger scale.


Isoxanthohumol--Biologically active hop flavonoid.
Isoxanthohumol (IXN), apart from xanthohumol (XN) and 8-prenylnaringenin (8PN), is one of the most important prenylflavonoids found in hops. Another natural source of this compound is a shrub Sophora flavescens, used in traditional Chinese medicine. Main dietary source of IXN is beer, and the compound is produced from XN during wort boiling. In the human body, the compound is O-demethylated to 8PN, the strongest known phytoestrogen. This process takes place in the liver and in the intestine, where it is mediated by local microflora. It has been reported in some studies that even though beer contains small amounts of hops and its preparations, these compounds may affect the functioning of the human body. IXN exhibits an antiproliferative activity against human cell lines typical for breast cancer (MCF-7), ovarian cancer (A-2780), prostate cancer (DU145 and PC-3), and colon cancer (HT-29 and SW620) cells. It strongly inhibits the activation of the following carcinogens: 2-amino-3-methylimidazol-[4,5-f]quinoline and aflatoxin B1 (AFB1) via human cytochrome P450 (CYP1A2). It also inhibits the production of prostate specific antigen (PSA). IXN significantly reduces the expression of transforming growth factor-β (TGF-β) in the case of invasive breast cancer MDA-MB-231. It interferes with JAK/STAT signaling pathway and inhibits the expression of pro1inflammatory genes in the monoblastic leukemia cell line (MonoMac6). It activates apoptosis in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMCs). In addition, IXN shows an antiviral activity towards herpes viruses (HSV1 and HSV2) and bovine viral diarrhea virus (BVDV).


Non-Abelian gauge fields in photonic cavities and photonic superfluids.
We show that the TE-TM modes splitting and the structure anisotropy of a semiconductor microcavity combine into a non-Abelian gauge field for exciton-polaritons or cavity photons. The field texture can be tuned simply by rotating the sample and ranges continuously from a Rashba to a monopolar field. In the noninteracting regime, the latter leads to remarkable focusing and conical diffraction effects. In the interacting regime, the spin-orbit coupling induces a breakdown of superfluidity. The spatially homogeneous flows become unstable and dynamically evolve into spin textured states, such as stripes or domain walls.


Impulse-coded and analog signaling in single mechanoreceptor neurons.
Although most sensory neurons convey temporally coded impulses to the central nervous system, certain nonspiking receptors use only graded afferent signals. Each of three large nerve fibers from the lobster oval organ, a mechanoreceptor subserving ventilation, carry both impulses and graded potentials. Thus, both impulse frequency and receptor potential amplitude are available for information transfer.


MAP-IT: A Practical Tool for Planning Complex Behavior Modification Interventions.
Health research often aims to prevent noncommunicable diseases and to improve individual and public health by discovering intervention strategies that are effective in changing behavior and/or environments that are detrimental to one's health. Ideally, findings from original research support practitioners in planning and implementing effective interventions. Unfortunately, interventions often fail to overcome the translational block between science and practice. They often ignore theoretical knowledge, overlook empirical evidence, and underrate the impact of the environment. Accordingly, sustainable changes in individual behavior and/or the environment are difficult to achieve. Developing theory-driven and evidence-based interventions in the real world is a complex task. Existing implementation frameworks and theories often do not meet the needs of health practitioners. The purpose of this article is to synthesize existing frameworks and to provide a tool, the Matrix Assisting Practitioner's Intervention Planning Tool (MAP-IT), that links research to practice and helps practitioners to design multicomponent interventions. In this article, we use physical activity of older adults as an example to explain the rationale of MAP-IT. In MAP-IT, individual as well as environmental mechanisms are listed and behavior change techniques are linked to these mechanisms and to intervention components. MAP-IT is theory-driven and evidence-based. It is time-saving and helpful for practitioners when planning complex interventions.


Molecular forms of lactoferrin in stool and urine from infants fed human milk.
The molecular forms of lactoferrin (LF) were examined in stools and urine collected at 2.5 or 5 wk of age from very low birth wt infants fed either a cow's milk formula or a fortified human milk preparation. LF was not found by Western blotting in excreta from infants fed cow's milk. In contrast, intact and fragmented forms of LF were detected in stools and concentrated urine of each infant who received human milk. Only intact LF was detected in the fortified human milk preparation, whereas many types of LF fragments were present in the stools and urine. The approximate molecular wt of the most prominent fragments were 44, 38, 34, and 32 kD. However, the stools also displayed lower molecular wt fragments that were not found in urines of those infants. The LF fragments in those excreta were similar in size to those produced in vitro by limited digestion of apo-LF with trypsin. Furthermore, fragments produced by in vitro proteolysis were immunoreactive in an ELISA for LF. Thus, the fragments of LF in stools of very low birth wt infants fed human milk appeared to be produced by in vivo proteolysis, and the close resemblance between the LF fragments in the stools and urine suggests that the urinary LF fragments originated in the gastrointestinal tract. It remains unclear, however, whether the whole LF molecules that were fragmented were derived solely from ingested LF in human milk or in part from LF produced by the infant in response to human milk feedings.


Effects of formoterol, salmeterol or oxitropium bromide on airway responses to salbutamol in COPD.
We examined whether a pretreatment with formoterol, oxitropium bromide, or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease (COPD). Sixteen outpatients with partially reversible, stable COPD received 24 microg formoterol, 50 microg salmeterol, 200 microg oxitropium bromide, or placebo on four non-consecutive days. Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve to inhaled salbutamol was then constructed using doses of 100, 100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg. Dose increments were given at 20 min intervals with measurements being made 15 min after each dose. Formoterol, salmeterol, or oxitropium bromide elicited a significant increase in forced expiratory volume in one second (FEV1) compared with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol 0.27; oxitropium bromide 0.23). Dose-dependent increases in FEV1 were seen (mean values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and 800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41, 1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; oxitropium bromide: 1.27, 1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy with formoterol, salmeterol, or oxitropium bromide compared with placebo. This study clearly shows that a pretreatment with a conventional dose of formoterol, salmeterol, or oxitropium bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease.


Up-regulation of heparanase in the ethmoid sinus mucosa of patients with chronic sinusitis.
Heparanase (HPA) is known to be involved in tissue remodeling of various organs with inflammatory diseases. The aim of this study was to investigate the level of expression and the pattern of distribution of HPA in normal human sinus mucosa, inflammatory sinus mucosa, and nasal polyps to evaluate the possible effect of HPA on the tissue remodeling of chronic inflammatory sinus mucosa and nasal polyps. Normal sinus mucosa was obtained from the ethmoid sinus during endoscopic reduction in 25 patients with blowout fractures. Inflammatory sinus mucosa and nasal polyps were obtained from 25 patients undergoing endoscopic sinus surgery for chronic sinusitis with nasal polyps. The levels of expression and the pattern of distribution of HPA were evaluated in normal human sinus mucosa, inflammatory sinus mucosa, and nasal polyps, using reverse transcriptase-polymerase chain reaction, immunohistochemical analysis, and Western blot analysis. HPA mRNA and protein were detected in inflammatory sinus mucosa and nasal polyps but not in normal sinus mucosa. HPA was mainly localized in the vascular endothelium, epithelium, submucosal glands, and inflammatory cells of inflammatory sinus mucosa. In nasal polyps, inflammatory cells and vascular endothelium showed immunopositivity in the entire portion, whereas glands and epithelial cells did not show positivity. Our results indicate that HPA is not constitutively expressed in normal sinus mucosa and is upregulated in chronic inflammatory sinus mucosa and nasal polyps, suggesting that HPA may play an important role in the tissue remodeling in chronic sinusitis.


Analogs of the Scorpion Venom Peptide Stigmurin: Structural Assessment, Toxicity, and Increased Antimicrobial Activity.
Scorpion venom is a rich source of biologically active components and various peptides with high-potential therapeutic use that have been characterized for their antimicrobial and antiproliferative activities. Stigmurin is a peptide identified from the Tityus stigmurus venom gland with high antibacterial and antiproliferative activities and low toxicity. Amino acid substitutions in peptides without a disulfide bridge sequence have been made with the aim of reducing their toxicity and increasing their biological activities. The purpose of this study was to evaluate the structural conformation and structural stability, as well as antimicrobial, antiproliferative, and hemolytic activities of two peptide analogs to Stigmurin, denominated StigA6 and StigA16. In silico analysis revealed the α-helix structure for both analog peptides, which was confirmed by circular dichroism. Data showed that the net charge and hydrophobic moment of the analog peptides were higher than those for Stigmurin, which can explain the increase in antimicrobial activity presented by them. Both analog peptides exhibited activity on cancerous cells similar to the native peptide; however, they were less toxic when tested on the normal cell line. These results reveal a potential biotechnological application of the analog peptides StigA6 and StigA16 as prototypes to new therapeutic agents.


Information processing and signal integration in bacterial quorum sensing.
Bacteria communicate using secreted chemical signaling molecules called autoinducers in a process known as quorum sensing. The quorum-sensing network of the marine bacterium Vibrio harveyi uses three autoinducers, each known to encode distinct ecological information. Yet how cells integrate and interpret the information contained within these three autoinducer signals remains a mystery. Here, we develop a new framework for analyzing signal integration on the basis of information theory and use it to analyze quorum sensing in V. harveyi. We quantify how much the cells can learn about individual autoinducers and explain the experimentally observed input-output relation of the V. harveyi quorum-sensing circuit. Our results suggest that the need to limit interference between input signals places strong constraints on the architecture of bacterial signal-integration networks, and that bacteria probably have evolved active strategies for minimizing this interference. Here, we analyze two such strategies: manipulation of autoinducer production and feedback on receptor number ratios.


Comparative analysis of Panicum streak virus and Maize streak virus diversity, recombination patterns and phylogeography.
Panicum streak virus (PanSV; Family Geminiviridae; Genus Mastrevirus) is a close relative of Maize streak virus (MSV), the most serious viral threat to maize production in Africa. PanSV and MSV have the same leafhopper vector species, largely overlapping natural host ranges and similar geographical distributions across Africa and its associated Indian Ocean Islands. Unlike MSV, however, PanSV has no known economic relevance. Here we report on 16 new PanSV full genome sequences sampled throughout Africa and use these together with others in public databases to reveal that PanSV and MSV populations in general share very similar patterns of genetic exchange and geographically structured diversity. A potentially important difference between the species, however, is that the movement of MSV strains throughout Africa is apparently less constrained than that of PanSV strains. Interestingly the MSV-A strain which causes maize streak disease is apparently the most mobile of all the PanSV and MSV strains investigated. We therefore hypothesize that the generally increased mobility of MSV relative to other closely related species such as PanSV, may have been an important evolutionary step in the eventual emergence of MSV-A as a serious agricultural pathogen.The GenBank accession numbers for the sequences reported in this paper are GQ415386-GQ415401.


The expert witness in psychology and psychiatry.
The involvement of psychologists and psychiatrists within the legal arena continues to grow rapidly but remains highly controversial. Extensive research on clinical judgement provides a scientific basis for clarifying the growing disputes about the values of such professional activities. Studies show that professionals often fail to reach reliable or valid conclusions and that the accuracy of their judgements does not necessarily surpass that of laypersons, thus raising substantial doubt that psychologists or psychiatrists meet legal standards for expertise. Factors that underlie the research findings and implications for courtroom testimony are discussed.


Neuronal morphology and efferent projections of the dorsal nucleus of the lateral lemniscus in the rat.
The dorsal nucleus of the lateral lemniscus (DLL) is the main source of inhibitory influence in the auditory brainstem of mammals. The cytoarchitecture and connectional properties of DLL were established in the cat in contrast to the rat. The goal of the present study was to establish to what extent the anatomical properties of the rat DLL compare to those of the cat, thus providing a basis of interpretation for future functional studies in the rat, an animal model used more and more in the auditory system. DLL of the rat contains four well-differentiated neuronal types, as seen in Nissl-stained material. Type I neurons are large and multipolar with abundant cytoplasm and darkly stained Nissl substance. Type II neurons are large, bipolar and darkly stained in Nissl material. Type III neurons are medium in size and their soma is round or ovoid. Type IV neurons are small and round with scant cytoplasm; they seem to be also the least common neuronal type of the DLL. After Phaseolus vulgaris-leucoagglutinin or biocytin injections in the DLL, fibers and terminals labeled by orthograde transport were observed in the corresponding region of the contralateral DLL and in the inferior colliculus, bilaterally. A few labeled fibers and terminal fields were seen in the deep layers of the superior colliculus bilaterally, as well as in the medial division of the medial geniculate body and, even more rostrally, in the posterior nucleus of the thalamus. Descending projections from DLL terminated in the periolivary regions of the ipsilateral superior olivary complex. Retrograde tracing based on injections of horseradish peroxidase in the various targets of the DLL confirmed the connections established with orthograde labeling.


Training to acquire psychomotor skills for endoscopic endonasal surgery using a personal webcam trainer.
Existing training methods for neuroendoscopic surgery have mainly emphasized the acquisition of anatomical knowledge and procedures for operating an endoscope and instruments. For laparoscopic surgery, various training systems have been developed to teach handling of an endoscope as well as the manipulation of instruments for speedy and precise endoscopic performance using both hands. In endoscopic endonasal surgery (EES), especially using a binostril approach to the skull base and intradural lesions, the learning of more meticulous manipulation of instruments is mandatory, and it may be necessary to develop another type of training method for acquiring psychomotor skills for EES. Authors of the present study developed an inexpensive, portable personal trainer using a webcam and objectively evaluated its utility. Twenty-five neurosurgeons volunteered for this study and were divided into 2 groups, a novice group (19 neurosurgeons) and an experienced group (6 neurosurgeons). Before and after the exercises of set tasks with a webcam box trainer, the basic endoscopic skills of each participant were objectively assessed using the virtual reality simulator (LapSim) while executing 2 virtual tasks: grasping and instrument navigation. Scores for the following 11 performance variables were recorded: instrument time, instrument misses, instrument path length, and instrument angular path (all of which were measured in both hands), as well as tissue damage, max damage, and finally overall score. Instrument time was indicated as movement speed; instrument path length and instrument angular path as movement efficiency; and instrument misses, tissue damage, and max damage as movement precision. In the novice group, movement speed and efficiency were significantly improved after the training. In the experienced group, significant improvement was not shown in the majority of virtual tasks. Before the training, significantly greater movement speed and efficiency were demonstrated in the experienced group, but no difference in movement precision was shown between the 2 groups. After the training, no significant differences were shown between the 2 groups in the majority of the virtual tasks. Analysis revealed that the webcam trainer improved the basic skills of the novices, increasing movement speed and efficiency without sacrificing movement precision. Novices using this unique webcam trainer showed improvement in psychomotor skills for EES. The authors believe that training in terms of basic endoscopic skills is meaningful and that the webcam training system can play a role in daily off-the-job training for EES.


Drought advances spring growth phenology of the Mediterranean shrub Erica multiflora.
Current climate projections predict drier and warmer conditions in the Mediterranean basin over the next century. While advanced spring growth due to warming has been described in the literature, few data are available on the effects of drought on phenology. Hence, the phenology and growth of two Mediterranean shrubs, Erica multiflora and Globularia alypum, was studied in a rainfall exclusion field experiment to simulate spring drought in a natural shrubland. We estimated the onset of growth in spring by monitoring the appearance of new stems, and the end of growth in summer by following the elongation of stems. Drought treatment caused earlier onset of the spring growing season in E. multiflora, whereas no advance was observed in G. alypum. However, growth cessation was not affected in E. multiflora. Drought reduced the growth of both shrubs, as reflected in less stem elongation. The results show that a drier climate might affect not only growth but also spring phenology of some Mediterranean species. We suggest that a reduction in the cooling effect of transpiration may have analogous effects to warming and might advance the start of growth in E. multiflora, a species whose phenology has been described as warming-sensitive. The lengthening of the growing season resulting from advanced growth did not imply higher productivity, as growth was restricted by drought.


Molecular characteristics and physical state of human papillomavirus DNA change with progressing malignancy: studies in a patient with epidermodysplasia verruciformis.
In order to establish the role of human papillomavirus (HPV) in carcinogenesis of epidermodysplasia verruciformis (EV), the presence, the molecular characteristics and the physical state of HPV DNA in a benign lesion, a primary carcinoma and a metastatic carcinoma developing in the same EV patient were studied and compared. Of the 2 HPV DNAs isolated from benign macular lesions, only one (a subtype of HPV 5) was detected in both primary and metastatic tumors. Only one normal species of viral DNA molecule was detected in the benign lesion, whereas most, if not all, viral DNA molecules present in the carcinoma (both primary and metastatic) were aberrant ones. The major viral DNA molecule in the primary carcinoma was a large HPV DNA with duplicated 40% subgenomic segments, and was present as free episomes. The major viral DNA molecule in the metastatic carcinoma was the 40% subgenomic segment itself, lacking the remaining 60% segment of the viral genome, and was integrated within cellular DNA. Thus, HPV DNA was present in tumors at any stage of malignancy, and its molecular characteristics and physical state changed not only with the development but also with the enhancement of malignancy, consistently conserving its defined 40% subgenomic segment as the predominant viral sequences. Our results suggest that HPV 5 may be actually involved in carcinogenesis in EV patients.


Two-color in vivo imaging of photoreceptor apoptosis and development in Drosophila.
We report a new two-color fluorescent imaging system to visualize the mosaic adult photoreceptor neurons (PRs) in real-time. Using this method, we examined a collection of 434 mutants and identified genes required for PR survival, planar cell polarity (PCP), patterning and differentiation. We could track the progression of PR degeneration in living flies. By introducing the expression of p35, a caspase inhibitor, we found mutations that specifically activate caspase-dependent death. Moreover, we showed that grh is required in R3 for correct PCP establishment. The "Tomato/GFP-FLP/FRT" method allows high-throughput, rapid and precise identification of survival and developmental pathways in living adult PRs at single-cell resolution.


Expression and prognostic significance of 14-3-3sigma and ERM family protein expression in periampullary neoplasms.
Aberrant gene expression in pancreatic ductal adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5' region of 14-3-3sigma (stratifin) is hypomethylated in pancreatic adenocarcinomas and is associated with gene overexpression. In multiple experimental systems, ezrin (ERM, Radixin, Moesin) has been identified as being important in the metastatic behavior of pancreatic and other cancers. We investigated the prognostic significance of aberrant expression of 14-3-3sigma and the ERM proteins (Ezrin, radixin, Moesin) in a series of invasive periampullary adenocarcinomas including 300 infiltrating pancreatic adenocarcinomas, 54 ampullary adenocarcinomas, and 33 noninvasive intraductal papillary mucinous neoplasms from patients who underwent pancreaticoduodenal resection at The Johns Hopkins Hospital, Baltimore, MD, between 1991 and 2003. Two-hundred fourty-four (82%) primary infiltrating adenocarcinomas of the pancreas demonstrated positive expression of the 14-3-3sigma, 45 (15%) showed weak immunolabelling, and 9 (3%) were negative. 201 (68%) showed positive immunolabeling of the ERM proteins, 75 (25%) demonstrated weak expression and 20 (7%) no expression. A similar proportion of ampullary cancers showed 14-3-3sigma and ERM protein expression. Expression of 14-3-3sigma and ERM protein was more likely in poorly differentiated cancers (p = 0.00005), and their expression was associated with poor survival in univariate analysis (p = 0.09). By multivariate analysis, patients whose cancers expressed 14-3-3sigma, but not ERM tended to have a poorer prognosis (Hazard ratio, 1.4; 0.9-2.2, p = 0.14). Aberrant expression of 14-3-3sigma may contribute to the outcome of patients with pancreatic ductal adenocarcinoma.


Natural selection of altruism in inelastic viscous homogeneous populations.
Biological explanations are given of three main uninterpreted theoretical results on the selection of altruism in inelastic viscous homogeneous populations, namely that non-overlapping generations hinder the evolution of altruism, fecundity effects are more conducive to altruism than survival effects, and one demographic regime (so-called death-birth) permits altruism whereas another (so-called birth-death) does not. The central idea is 'circles of compensation', which measure how far the effects of density dependence extend from a focal individual. Relatednesses can then be calculated that compensate for density dependence. There is very generally a 'balancing circle of compensation', at which the viscosity of the population slows up selection of altruism, but does not affect its direction, and this holds for altruism towards any individual, not just immediate neighbours. These explanations are possible because of recent advances in the theory of inclusive fitness on graphs. The assumption of node bitransitivity in that recent theory is relaxed to node transitivity and symmetry of the dispersal matrix, and new formulae show how to calculate relatedness from dispersal and vice versa.


Immunogenicity of a Bivalent Adjuvanted Glycoconjugate Vaccine against Salmonella Typhimurium and Salmonella Enteritidis.
Salmonella enterica serovars Typhimurium and Enteritidis are the predominant causes of invasive non-typhoidal Salmonella (iNTS) disease. Considering the co-endemicity of S. Typhimurium and S. Enteritidis, a bivalent vaccine formulation against both pathogens is necessary for protection against iNTS disease, thus investigation of glycoconjugate combination is required. In the present work, we investigated the immune responses induced by S. Typhimurium and S. Enteritidis monovalent and bivalent glycoconjugate vaccines adjuvanted with aluminum hydroxide (alum) only or in combination with cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG). Humoral and cellular, systemic and local, immune responses were characterized in two different mouse strains. All conjugate vaccines elicited high levels of serum IgG against the respective O-antigens (OAg) with bactericidal activity. The bivalent conjugate vaccine induced systemic production of antibodies against both S. Typhimurium and S. Enteritidis OAg. The presence of alum or alum + CpG adjuvants in vaccine formulations significantly increased the serum antigen-specific antibody production. The alum + CpG bivalent vaccine formulation triggered the highest systemic anti-OAg antibodies and also a significant increase of anti-OAg IgG in intestinal washes and fecal samples, with a positive correlation with serum levels. These data demonstrate the ability of monovalent and bivalent conjugate vaccines against S. Typhimurium and S. Enteritidis to induce systemic and local immune responses in different mouse strains, and highlight the suitability of a bivalent glycoconjugate formulation, especially when adjuvanted with alum + CpG, as a promising candidate vaccine against iNTS disease.


Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods.
Most patients with type 2 diabetes mellitus develop cardiovascular disease (CVD), with substantial loss of life expectancy. Nonfatal CVD contributes greatly to excess healthcare costs and decreased quality of life in patients with diabetes. The current epidemic of obesity has raised expectations that CVD associated with type 2 diabetes will become an even greater public health challenge. Despite the importance of this health problem, there is a lack of definitive data on the effects of the intensive control of glycemia and other CVD risk factors on CVD event rates in patients with type 2 diabetes. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is a randomized, multicenter, double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type 2 diabetes who are at high risk for CVD events because of existing CVD or additional risk factors. ACCORD is testing the effects of 3 medical treatment strategies to reduce CVD morbidity and mortality. All participants are in the glycemia trial, which is testing the hypothesis that a therapeutic strategy that targets a glycosylated hemoglobin (HbA1c) level of <6.0% will reduce the rate of CVD events more than a strategy that targets an HbA1c level of 7.0%-7.9%. The lipid trial includes 5,518 of the participants, who receive either fenofibrate or placebo in a double-masked fashion to test the hypothesis of whether, in the context of good glycemic control, a therapeutic strategy that uses a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels together with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) to lower low-density lipoprotein cholesterol will reduce the rate of CVD events compared with a strategy that uses a statin plus a placebo. The blood pressure trial includes the remaining 4,733 participants and tests the hypothesis that a therapeutic strategy that targets a systolic blood pressure of <120 mm Hg in the context of good glycemic control will reduce the rate of CVD events compared with a strategy that targets a systolic blood pressure of <140 mm Hg. The primary outcome measure for all 3 research questions is the first occurrence of a major CVD event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Upon the expected completion of participant follow-up in 2009, the ACCORD trial should document for the first time the benefits and risks of intensive glucose control, intensive blood pressure control, and the combination of fibrate and statin drugs in managing blood lipids in high-risk patients with type 2 diabetes.


A multicentered, randomized, controlled trial comparing radioguided seed localization to standard wire localization for nonpalpable, invasive and in situ breast carcinomas.
Studies suggest radioguided seed localization (RSL) yields fewer positive margins than wire-guided localization (WL). The goal of this study is to determine whether RSL is superior to WL. Women with confirmed invasive or ductal carcinoma in situ (DCIS) undergoing localization and breast conserving surgery were enrolled. Outcomes measured include positive margin and reoperation rates, specimen weight, operative and localization times, and surgeon and radiologist ranking of procedural difficulty. Randomization was centralized, concealed, and stratified by surgeon with 153 patients in the WL group and 152 in RSL group. Localizations were performed using either ultrasound (70%) or mammographic guidance (30%). Pathology was either DCIS (18%) or invasive carcinoma (82%). Procedures were performed at 3 sites, by 7 surgeons. Only difference found for patient and tumor characteristics was more multifocal disease in RSL group. Using intention-to-treat analysis, there were no differences in positive margins rates for RSL (10.5%) and WL (11.8%), (P=.99) or for positive or close margins (<1 mm) (RSL 19% and WL 22%; P=.61). Mean operative time (minutes) was shorter for RSL (RSL 19.4 vs WL 22.2; P<.001). Specimen volume, weight, reoperation and localization times were similar. Surgeons ranked the seed technique as easier (P=.008), while radiologists ranked them similarly. Patient's pain rankings during wire localization were higher (P=.038). In contrast to other trials positive margin and reoperation rates were similar for RSL and WL. However, for RSL operative times were shorter, and the technique was preferred by surgeons, making it an acceptable method for localization.


Cervical cancers diagnosed after negative results on cervical cytology: perspective in the 1980s.
To assess the magnitude of the problem of interval cancers of the cervix (those that are diagnosed within a short time after negative screening test results) in the 1980s, to compare the nature of interval cancers in younger women with that in older women, and, by reviewing negative cervical smears, to determine the proportion of interval cancers that might represent the development of malignancy anew compared with the proportion that might be associated with difficulties in sampling or errors in reporting. An audit of the interval cases of cervical cancer that had been diagnosed within 36 months of a smear having been reported as negative by the Victorian Cytology Gynaecological Service among women registered with cervical cancer during 1982-6. The Victorian Cytology Gynaecological Service, a free public sector cytology laboratory in Victoria, Australia. 138 Women, all of whom had had cervical cancer diagnosed during the 36 months after having had a negative cervical smear. Subjects were divided into two age groups: younger women, aged less than 35; older women, aged 35-69. Negative slides were reviewed for evidence of optimal sampling and for the presence of cellular abnormalities that had been missed at the time of the original reporting. The number of interval cases of cancer of the cervix registered during 1982-6. The proportion of interval cases occurring in younger women and the proportion occurring in older women. Division of women into three risk categories based on clinical history and screening history that broadly corresponded to the probability that a diagnosis of cervical cancer might be expected during the 36 months after the issuing of a negative smear report. 138 Of 1044 (13.2%) women who had been registered with cervical cancer during 1982-6 had had one or more negative smears during the 36 months preceding the diagnosis of cancer. Interval cancers comprised a larger proportion of registrations of cervical cancer in women aged less than 35 years than in women aged 35-69 (21.1% v 11.0%, p less than 0.01). Women with interval cancer who had had at least three negative smears during the 10 years before the diagnosis of cancer were commoner in the younger age group than in the older age group (7.0% v 2.5%, p less than 0.01). When, however, the number of observed cases of squamous cell carcinoma was related to the number of expected cases in the absence of screening, no significant difference was found between the two age groups (6.8% v 4.8%, p greater than 0.10). The rate of diagnosis of interval cancer per 100,000 negative tests was lower among younger women than among older women (10/100,000 v 16/100,000). Review of the negative slides showed that 11.9% were again considered to be negative with an optimal sample having been obtained as evidenced by the presence of endocervical cells or metaplastic cells, or both. Interval cancers might comprise a larger proportion of all registered cases of cervical cancer among younger women owing to the larger proportion of such cancers being prevented in this age group. Among women with interval cancer review of the negative slides showed that most were accounted for by suboptimal sampling or by errors of reporting.


Association of Alanine Aminotransferase and Periodontitis: A Cross-Sectional Analysis-NHANES 2009-2012.
Objective. Alanine Aminotransferase is an enzyme associated with not only liver diseases, liver conditions, and metabolic syndrome, but also inflammation. Periodontitis is associated with increased cytokines and other markers of inflammation. The purpose of this study is to determine if an independent association between Alanine Aminotransferase and periodontitis exists. Methods. Data from the 2009-2010 and 2011-2012 National Health and Nutrition Surveys (NHANES) were combined. Data concerning periodontitis and Alanine Aminotransferase were extracted and analyzed with Rao Scott Chi-square and logistic regressions. Serum Alanine Aminotransferase was dichotomized at 40 units/liter, and periodontitis was dichotomized to the presence or absence of periodontitis. Results. In bivariate Chi-square analyses, periodontitis and Alanine Aminotransferase were associated (p = 0.0360) and remained significant in unadjusted logistic regression (OR = 1.30 [95% CI: 1.02, 1.65]). However, when other known risk factors of periodontitis were included in the analyses, the relationship attenuated and failed to reach significance (adjusted OR = 1.17 [95% CI: 0.85, 1.60]). Conclusion. Our study adds to the literature a positive but attenuated association of serum Alanine Aminotransferase with periodontitis which failed to reach significance when other known, strong risk factors of periodontitis were included in the analysis.


Assessment of musculoskeletal toxicity 5 years after therapy with levofloxacin.
Safety concerns for fluoroquinolones exist from animal studies demonstrating cartilage injury in weight-bearing joints, dependent on dose and duration of therapy. For children treated with levofloxacin or comparator in randomized, prospective, comparative studies for acute otitis media and community-acquired pneumonia, this 5-year follow-up safety study was designed to assess the presence/absence of cartilage injury. Children enrolled in treatment studies were also enrolled in a 1-year follow-up safety study, which; focused on musculoskeletal adverse events (MSAE). Those with persisting MSAEs, protocol-defined musculoskeletal disorders, or of concern to the Data Safety and Monitoring Committee were requested to enroll in four additional years of follow-up, the subject of this report. Of the 2233 subjects participating in the 12-month follow-up study, 124 of 1340 (9%) of the levofloxacin subjects, and 83 of 893 (9%) of the comparator subjects were continued for 5-year posttreatment assessment. From children identified with an MSAE during years 2 through 5 posttreatment, the number that were "possibly related" to drug therapy was equal for both arms: 1 of 1340 for levofloxacin and 1 of 893 for comparator. Of all cases of MSAE assessed by the Data Safety and Monitoring Committee at 5 years' posttreatment, no case was assessed as "likely related" to study drug. With no clinically detectable difference between levofloxacin- and comparator-treated children in MSAEs presenting between 1 and 5 years in these safety studies, risks of cartilage injury with levofloxacin appear to be uncommon, are clinically undetectable during 5 years, or are reversible.


Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis.
There have been many studies of the effects of non-alcoholic fatty liver disease (NAFLD) and the risk of cardiovascular disease (CVD), but these have produced conflicting results. We performed a meta-analysis of these studies to quantify the magnitude of the association between NAFLD (and NAFLD severity) and risk of CVD events. We searched PubMed, Google scholar, and Web of Science databases using terms "NAFLD", "cardiovascular events", "cardiovascular mortality", "prognosis" and their combinations to identify observational studies published through January 2016. We included only observational studies conducted in adults >18years and in which NAFLD was diagnosed on imaging or histology. Data from selected studies were extracted and meta-analysis was then performed using random effects modelling. A total of 16 unique, observational prospective and retrospective studies with 34,043 adult individuals (36.3% with NAFLD) and approximately 2,600 CVD outcomes (>70% CVD deaths) over a median period of 6.9years were included in the final analysis. Patients with NAFLD had a higher risk of fatal and/or non-fatal CVD events than those without NAFLD (random effect odds ratio [OR] 1.64, 95% CI 1.26-2.13). Patients with more 'severe' NAFLD were also more likely to develop fatal and non-fatal CVD events (OR 2.58; 1.78-3.75). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias. NAFLD is associated with an increased risk of fatal and non-fatal CVD events. However, the observational design of the studies included does not allow to draw definitive causal inferences. The data on whether NAFLD by itself is associated with increased cardiovascular events and death remains an issue of debate. The findings of this updated and large meta-analysis of observational studies indicate that NAFLD is significantly associated with an increased risk of fatal and non-fatal cardiovascular events. However, the observational design of the studies included does not allow us to prove that NAFLD causes cardiovascular disease. Clinicians who manage patients with NAFLD should not focus only on liver disease but should also consider the increased risk of cardiovascular disease and undertake early, aggressive risk factor modification.


Data and models determine treatment proposals--an illustration from meta-analysis.
A relevant problem in meta-analysis concerns the possible heterogeneity between trial results. If a test of heterogeneity is not significant the trials are often considered to be "homogeneous" and the individual trial results are replaced by an overall mean effect size and its confidence interval ("equal effects model"). If the trials are heterogeneous the individual trial effect sizes are conserved ("fixed effects model"). In a more flexible approach ("random effects model"), each trial makes use of knowledge from the other trials so individual effect sizes are "shrunken" towards an overall mean effect size. The more flexible tool may be useful for doctors involved in a trial when the outcome of their individual trial differs markedly from the overall mean effect size. Where a particular trial result is opposite in direction to the overall mean result, a conflict may arise: should a new patient be treated with the new method or not? The more flexible position and a graphical comparison of the three approaches are likely to be helpful in guiding the decision. Applying different models to the same data may lead to apparently paradoxical results: an individual trial result may be interpreted to be beneficial or harmful depending on the choice of model.


Application of the correlation coefficient method for determination of the focal plane to digital particle holography.
The correlation coefficient (CC) method, which was proposed by our research group, is applied to digital particle holography to locate the focal plane of particles. It uses the fact that the CC is maximum at the focal plane. The factors influencing this method are discussed with a numerical simulation of holograms. For real holograms, the Wiener filter was proposed to process both recorded holograms and reconstructed images. The application results using the dot array target showed that the Wiener filter is a very effective tool for processing holography-related images. The effects of the dot size and the object distance on the errors in the determination of the focal plane by the CC method were investigated by using the calibration target.


Paired suicide in a young refugee couple on the Thai-Myanmar border.
A young refugee woman attended antenatal clinic on the Thai-Myanmar border at 9 weeks' gestation. As part of an ongoing study of perinatal mental health, she underwent a structured psychiatric interview during which she described occasional depressed mood, anhedonia and passive suicidal ideation. Her husband was a young refugee known to use alcohol and drugs. 2 days later, the couple committed suicide together by herbicide ingestion. Refugee populations are at risk of developing mental disorders as a result of their marginalised status, socioeconomic disadvantage and exposures to trauma. Pregnancy may have exacerbated feelings of hopelessness in this couple. The prevalence of mental disorders such as depression is increased in the perinatal period and suicide is the second leading cause of death in young women globally. Prevention programmes and early recognition of mental disorders may improve detection and lead to better support for vulnerable individuals.


Incidence of sternal wound infection after reexploration in the intensive care unit and the use of local gentamycin.
Reoperation for bleeding is a known emergency complication after cardiac operations. When performed in the intensive care unit (ICU), sterility issues arise. Our aim was to examine the incidence of sternal wound infection (SWI) after reexploration in the ICU for bleeding with routine use of local gentamycin. From January 2003 until December 2009, 4,863 patients underwent cardiac operations through a median sternotomy at our institution. We conducted a retrospective database review identifying all patients who required reoperations. The occurrence of SWI in this group was compared with the general cardiac surgical population. Reoperations for bleeding during this period were conducted routinely in the ICU with prophylactic application of a gentamycin sponge between the sternal halves before closure in all cases. Reexploration for bleeding was necessary in 302 patients (6.2%), and SWI occurred in 11, for a rate of 3.6%. SWI occurred in 174 of the 4,561 non-reexplored patients, for a similar rate of 3.8% (p>0.9). These values are similar to our overall rate of SWI of 3.8% (n=185) in the total cohort of 4,863 patients. The incidence of SWI was not increased in our study group after emergency reoperation for bleeding in the ICU after the local use of gentamycin. Our data suggest that reexploration in an ICU setting for bleeding does not pose a sterility challenge and that life-threatening delays due to transfer to the operating theater may be avoided.


Spontaneous Transport of Single-Stranded DNA through Graphene-MoS2 Heterostructure Nanopores.
The effective transport of a single-stranded DNA (ssDNA) molecule through a solid-state nanopore is essential to the future success of high-throughput and low-cost DNA sequencing. Compatible with current electric sensing technologies, here, we propose and demonstrate by molecular dynamics simulations the ssDNA transport through a quasi-two-dimensional nanopore in a heterostructure stacked together with different 2D materials, such as graphene and molybdenum disulfide (MoS2). Due to different chemical potentials, U, of DNA bases on different 2D materials, it is energetically favorable for a ssDNA molecule to move from the low- U MoS2 surface to the high- U graphene surface through a nanopore. With the proper attraction between the negatively charged phosphate group in each nucleotide and the positively charged Mo atoms exposed on the pore surface, the ssDNA molecule can be temporarily seized and released thereafter through a thermal activation, that is, a slow and possible nucleotide-by-nucleotide transport. A theoretical formulation is then developed for the free energy of the ssDNA transiting a heterostructure nanopore to properly characterize the non-equilibrium stick-slip-like motion of a ssDNA molecule.


The amino-terminal transforming region of simian virus 40 large T and small t antigens functions as a J domain.
Simian virus 40 (SV40) encodes two proteins, large T antigen and small t antigen that contribute to virus-induced tumorigenesis. Both proteins act by targeting key cellular regulatory proteins and altering their function. Known targets of the 708-amino-acid large T antigen include the three members of the retinoblastoma protein family (pRb, p107, and p130), members of the CBP family of transcriptional adapter proteins (cap-binding protein [CBP], p300, and p400), and the tumor suppressor p53. Small t antigen alters the activity of phosphatase pp2A and transactivates the cyclin A promoter. The first 82 amino acids of large T antigen and small t antigen are identical, and genetic experiments suggest that an additional target(s) important for transformation interacts with these sequences. This region contains a motif similar to the J domain, a conserved sequence found in the DnaJ family of molecular chaperones. We show here that mutations within the J domain abrogate the ability of large T antigen to transform mammalian cells. To examine whether a purified 136-amino-acid fragment from the T antigen amino terminus acts as a DnaJ-like chaperone, we investigated whether this fragment stimulates the ATPase activity of two hsc70s and discovered that ATP hydrolysis is stimulated four- to ninefold. In addition, ATPase-defective mutants of full-length T antigen, as well as wild-type small t antigen, stimulated the ATPase activity of hsc70. T antigen derivatives were also able to release an unfolded polypeptide substrate from an hsc70, an activity common to DnaJ chaperones. Because the J domain of T antigen plays essential roles in viral DNA replication, transcriptional control, virion assembly, and tumorigenesis, we conclude that this region may chaperone the rearrangement of multiprotein complexes.


Abnormal Anatomical Variations of Extra-Hepatic Biliary Tract, and Their Relation to Biliary Tract Injuries and Stones Formation.
To determine the most common abnormal anatomical variations of extra-hepatic biliary tract (EHBT), and their relation to biliary tract injuries and stones formation. This is a retrospective review of 120 patients, who underwent endoscopic retrograde cholangiopancreaticography (ERCP) and/or magnetic resonance cholangiopancreaticography (MRCP), between July 2011 and June 2013. The patients' ERCP and MRCP images were reviewed and evaluated for the anatomy of EHBT; the medical records were reviewed for demographic data, biliary tracts injuries and stones formation. Out of 120 patients, 50 were males (41.7%) and 70 were females (58.3%). The mean age was 54 years old (range 20 - 88). Abnormal anatomy was reported in 30% (n = 36). Short cystic duct (CD) was found in 20% (n = 24), left CD insertion in 5% (n = 6), CD inserted into the right hepatic duct (RHD) in 1.7% (n = 2), duct of Luschka in 3.33% (n = 4) and accessory hepatic duct in also 3.33% (n = 4). Biliary tract injuries were reported in 15% (n = 18) and stones in 71.7% (n = 86). Biliary tract injuries were higher in abnormal anatomy (P = 0.04), but there was no relation between abnormal anatomy and stones formation. Abnormal anatomy of EHBT was found to be 30%. The most common abnormality is short CD followed by left CD insertion. Surgeons should be aware of these common abnormalities in our patients, hence avoiding injuries to the biliary tract during surgery. The abnormal anatomy was associated with high incidence of biliary tract injury but has no relation to biliary stone formation.


Increased nerve growth factor level in the distal stump of transected sciatic nerve in relation to aging and its application for neural grafting.
The nerve growth factor (NGF) level in the distal stump of mouse sciatic nerve transected 24 h before increased significantly compared with that in the nontransected contralateral side. This level was higher in aged (24-month-old) mice than in aging (12-month-old) or in young (1-month-old) mice. Adrenal medullary tissue mixed with the pretransected (24 h before) distal stump of the sciatic nerve of aged mice was cografted into the ipsilateral striatum of aged mice with a unilateral 6-hydroxydopamine lesion of dopaminergic system. Two and 4 weeks after transplantation, cografted mice showed partial functional compensation in amphetamine-induced motor asymmetry while mice with adrenal grafts alone did not show the functional recovery. The immunocytochemical staining of tyrosine hydroxylase revealed large numbers of chromaffin cells surviving in cografted animals. It is concluded that NGF level in the distal stump of pretransected peripheral nerve is increased even in aged animals and cografting of this nerve stump with adrenal medulla can be effectively utilized in aged animals with nigrostriatal insufficiency.


Tissue and host species-specific transcriptional changes in models of experimental visceral leishmaniasis.
Background: Human visceral leishmaniasis, caused by infection with Leishmania donovani or L. infantum, is a potentially fatal disease affecting 50,000-90,000 people yearly in 75 disease endemic countries, with more than 20,000 deaths reported. Experimental models of infection play a major role in understanding parasite biology, host-pathogen interaction, disease pathogenesis, and parasite transmission. In addition, they have an essential role in the identification and pre-clinical evaluation of new drugs and vaccines. However, our understanding of these models remains fragmentary. Although the immune response to Leishmania donovani infection in mice has been extensively characterized, transcriptomic analysis capturing the tissue-specific evolution of disease has yet to be reported. Methods: We provide an analysis of the transcriptome of spleen, liver and peripheral blood of BALB/c mice infected with L. donovani. Where possible, we compare our data in murine experimental visceral leishmaniasis with transcriptomic data in the public domain obtained from the study of L. donovani-infected hamsters and patients with human visceral leishmaniasis. Digitised whole slide images showing the histopathology in spleen and liver are made available via a dedicated website, www.leishpathnet.org. Results: Our analysis confirms marked tissue-specific alterations in the transcriptome of infected mice over time and identifies previously unrecognized parallels and differences between murine, hamster and human responses to infection. We show commonality of interferon-regulated genes whilst confirming a greater activation of type 2 immune pathways in infected hamsters compared to mice. Cytokine genes and genes encoding immune checkpoints were markedly tissue specific and dynamic in their expression, and pathways focused on non-immune cells reflected tissue specific immunopathology. Our data also addresses the value of measuring peripheral blood transcriptomics as a potential window into underlying systemic disease. Conclusions: Our transcriptomic data, coupled with histopathologic analysis of the tissue response, provide an additional resource to underpin future mechanistic studies and to guide clinical research.


Evaluation of Iron Overload Between Age Groups Using Magnetic Resonance Imaging and Its Correlation with Iron Profile in Transfusion-dependent Thalassemia.
routine blood transfusion in transfusion-dependent-thalassemia (TDT) causes iron accumulation in various organ. Serum markers of iron overload, serum ferritin and transferrin saturation, are sensitive but not specific. MRI T2-star (T2*) is valuable for detecting iron level in organs. This study aimed to explore the degree of iron overload in various organs, iron deposition difference between children and adults, also its correlation with serum marker of iron overload. this was a cross-sectional study of TDT patients who had been evaluated by MRI T2* examination in Cipto Mangunkusumo Hospital from 2014 to 2018. a total of 546 subjects was included in this study. The number of subjects between children and adults was almost equal. Most of subjects had normal cardiac iron deposition. The difference of cardiac iron overload between children and adults was significant (p=0.009). Liver evaluation showed that most of subjects had moderate to severe iron overload. This difference between children and adults was significant (p=0.017). Pancreas evaluation showed that either children or adults mostly had mild pancreatic iron overload. Analysis of T2* showed that pancreatic iron deposition progressed with increasing age. Serum ferritin had weak correlation with heart T2* MRI, moderate correlation with pancreas and liver T2* MRI. Relationship between transferrin saturation and T2* MRI was extremely weak. cardiac and hepatic iron deposition between children and adults differ significantly. Liver has the greatest iron overload, followed by pancreas and heart. Iron deposition in liver and pancreas has been started from earlier age. Pancreatic iron deposition rises with increasing age. Serum ferritin and transferrin saturation should not be used solely to predict iron overload in various organs. We suggest that MRI evaluation must be conducted at least once to assess iron deposition in organs.


Impact of oral antibiotics on health-related quality of life after mandibular third molar surgery: An observational study.
To compare the impact of antibiotics on health-related quality of life (QoL) outcomes following third molar surgery. The study population consisted of 135 subjects that required surgical extraction of mandibular third molar under local anesthesia and met the inclusion criteria. The subjects were randomized into three study groups of 45 subjects each: Group A - extended amoxicillin/clavulanic acid (GlaxoSmithKline Beecham England), 1 gram pre-operatively and then 625 mg BD for 5 days Group B - prophylactic amoxicillin/clavulanic acid (GlaxoSmithKline Beecham England) 1 gram pre-operatively only, and Group C - prophylactic levofloxacin 1 gram pre-operatively only. Patients were assessed pre- and post-operatively on days 1, 3, 5, 7, and 14 using the United Kingdom oral health-related QoL (OHRQoL) questionnaire. This study showed that surgical removal of impacted teeth exerted a negative influence on patient's QoL across various physical, social, and psychological aspects of life. Comparing the three groups, Group A showed a slightly better QoL score; although, there was no statistically significant difference among them. Studies have shown better clinical recovery following administration of antibiotics after third molar surgery. There was a significant deterioration in OHRQoL in the immediate postoperative period, particularly postoperative days 1 and 3 following third molar surgery. QoL was also observed to be slightly better in Group A than Groups B and C, although this was not statistically significant.