Xpo7 is a broad-spectrum exportin and a nuclear import receptor.
Exportins bind cargo molecules in a RanGTP-dependent manner inside nuclei and transport them through nuclear pores to the cytoplasm. CRM1/Xpo1 is the best-characterized exportin because specific inhibitors such as leptomycin B allow straightforward cargo validations in vivo. The analysis of other exportins lagged far behind, foremost because no such inhibitors had been available for them. In this study, we explored the cargo spectrum of exportin 7/Xpo7 in depth and identified not only ∼200 potential export cargoes but also, surprisingly, ∼30 nuclear import substrates. Moreover, we developed anti-Xpo7 nanobodies that acutely block Xpo7 function when transfected into cultured cells. The inhibition is pathway specific, mislocalizes export cargoes of Xpo7 to the nucleus and import substrates to the cytoplasm, and allowed validation of numerous tested cargo candidates. This establishes Xpo7 as a broad-spectrum bidirectional transporter and paves the way for a much deeper analysis of exportin and importin function in the future.


[Radioprotective effect of Corynebacterium michiganense polysaccharide].
Antiradiation activity of polysaccharide isolated from phytopathogenic coryneform bacteria Corynebacterium michiganense has been established. It is shown that the introduction of polysaccharide immediately or 2 h after irradiation with the lethal dose promotes maximum survivability of experimental animals (30 and 20%, respectively).


A single amino acid change in the E2 glycoprotein of Sindbis virus confers neurovirulence by altering an early step of virus replication.
Amino acid changes in the envelope glycoproteins of Sindbis virus have been linked to neurovirulence; however, the molecular mechanisms by which these amino acid changes alter neurovirulence are not known. Recombinant-virus studies have mapped an important determinant of neurovirulence in adult mice to a single amino acid change, glutamine to histidine, at position 55 of the E2 glycoprotein (P. C. Tucker, E. G. Strauss, R. J. Kuhn, J. H. Strauss, and D. E. Griffin, J. Virol. 67:4605-4610, 1993). To investigate how histidine confers neurovirulence, we examined the various stages of the virus life cycle in neural (N18) and nonneural (BHK) cells. In BHK cells, recombinant viruses 633 (E255Q) and TE (E255H) replicated similarly. In contrast, in N18 neuroblastoma cells, TE established infection more efficiently, replicated faster, and achieved higher rates of virus release than did 633. Viral structural protein synthesis was similar in 633- and TE-infected BHK cells, while in N18 cells, structural protein synthesis was detected only in TE-infected cells at 6 h and remained higher for at least 16 h postinfection. Viral RNA synthesis was initiated more rapidly and was up to fivefold greater in TE- versus 633-infected N18 cells. Taken together with other data demonstrating minimal effects on virus binding and entry (P. C. Tucker, S. H. Lee, N. Bui, D. Martinie, and D. E. Griffin, J. Virol. 71:6106-6112, 1997), these data suggest that E2 position 55 plays an important role at early stages of infection of neural cells, thereby facilitating neurovirulence.


Alzheimer's Disease: A Systems View Provides a Unifying Explanation of Its Development.
Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting 50 million people globally. It is characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles, consisting of amyloid-β and hyperphosphorylated tau proteins, respectively. Despite global research efforts, there is currently no cure available, due in part to an incomplete understanding of the disease pathogenesis. Numerous possible mechanisms, or hypotheses, explaining the origins of sporadic or late-onset AD have been proposed, including the amyloid-β, inflammatory, vascular, and infectious hypotheses. However, despite ample evidence, the failure of multiple trial drugs at the clinical stage illuminates the possible pitfalls of these hypotheses. Systems biology is a strategy which aims to elucidate the interactions between parts of a whole. Using this approach, the current paper shows how the four previously mentioned hypotheses of AD pathogenesis can be intricately connected. This approach allows for seemingly contradictory evidence to be unified in a system-focused explanation of sporadic AD development. Within this view, it is seen that infectious agents, such as P. gingivalis, may play a central role. The data presented here shows that when present, P. gingivalis or its virulence factors, such as gingipains, may induce or exacerbate pathologies underlying sporadic AD. This evidence supports the view that infectious agents, and specifically P. gingivalis, may be suitable treatment targets in AD.


Regulation of smooth muscle proliferation by heparin in vitro and in vivo.
Smooth muscle cell proliferation is central to the development of atherosclerotic plaques, intimal thickening, and recurrent stenosis in arteries following surgical reconstruction. The factors that might limit this process remain poorly defined. Studies reported recently from several laboratories suggest that heparin administered in pharmacological doses can suppress proliferation of smooth muscle cells. Furthermore, heparin-like molecules are synthesized by vascular wall cells, inhibit smooth muscle growth in vitro, and might act to regulate smooth muscle growth within the arterial wall.


KANSL1 variation is not a major contributing factor in self-limited focal epilepsy syndromes of childhood.
KANSL1 haploinsufficiency causes Koolen-de Vries syndrome (KdVS), characterized by dysmorphic features and intellectual disability; amiable personality, congenital malformations and seizures also commonly occur. The epilepsy phenotypic spectrum in KdVS is broad, but most individuals have focal seizures with some having a phenotype resembling the self-limited focal epilepsies of childhood (SFEC). We hypothesized that variants in KANSL1 contribute to pathogenesis of SFEC. We screened KANSL1 for single nucleotide variants in 90 patients with SFEC. We then screened a cohort of 208 patients with two specific SFEC syndromes, childhood epilepsy with centrotemporal spikes (CECTS) and atypical childhood epilepsy with centrotemporal spikes (ACECTS) for KANSL1 variants. The second cohort was also used to evaluate minor allelic variants that appeared overrepresented in the initial cohort. One variant, p.Lys104Thr, was predicted damaging and appeared overrepresented in our 90-patient cohort compared to Genome Aggregation Database (gnomAD) allele frequency (0.217 to 0.116, with no homozygotes in gnomAD). However, there was no difference in p.Lys104Thr allele frequency in the follow-up CECTS/ACECTS cohort and controls. Four rare KANSL1 variants of uncertain significance were identified in the CECTS/ACECTS cohort. Our data do not support a major role for KANSL1 variants in pathogenesis of SFEC.


Optogenetic Control of Microbial Consortia Populations for Chemical Production.
Microbial co-culture fermentations can improve chemical production from complex biosynthetic pathways over monocultures by distributing enzymes across multiple strains, thereby reducing metabolic burden, overcoming endogenous regulatory mechanisms, or exploiting natural traits of different microbial species. However, stabilizing and optimizing microbial subpopulations for maximal chemical production remains a major obstacle in the field. In this study, we demonstrate that optogenetics is an effective strategy to dynamically control populations in microbial co-cultures. Using a new optogenetic circuit we call OptoTA, we regulate an endogenous toxin-antitoxin system, enabling tunability of Escherichia coli growth using only blue light. With this system we can control the population composition of co-cultures of E. coli and Saccharomyces cerevisiae. When introducing in each strain different metabolic modules of biosynthetic pathways for isobutyl acetate or naringenin, we found that the productivity of co-cultures increases by adjusting the population ratios with specific light duty cycles. This study shows the feasibility of using optogenetics to control microbial consortia populations and the advantages of using light to control their chemical production.


Competence of urban rats as reservoir hosts for Lyme disease spirochetes.
To determine whether urban rats serve efficiently as reservoir hosts for the agent of Lyme disease, we recorded the frequency of infection in nymphal Ixodes ricinus (L.) ticks that had fed as larvae on experimentally infected Norway rats, Rattus norvegicus (Berkenhout), or on black rats, R. rattus (L.), and evaluated the nidicolous venue of transmission. Subadult vector ticks attached readily to Norway rats as well as black rats and virtually all became infected in the course of feeding. Larval ticks detached when these nocturnally active hosts were at rest. Rats appeared to be competent reservoir hosts of Lyme disease spirochetes in a transmission cycle in urban sites.


The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation.
This study characterized the kynurenine pathway (KP) in human obesity by evaluating circulating levels of kynurenines and the expression of KP enzymes in adipose tissue. Tryptophan and KP metabolite levels were measured in serum of individuals from the D.E.S.I.R. cohort (case-cohort study: 212 diabetic, 836 randomly sampled) and in women with obesity, diabetic or normoglycemic, from the ABOS cohort (n = 100). KP enzyme gene expressions were analyzed in omental and subcutaneous adipose tissue of women from the ABOS cohort, in human primary adipocytes and in monocyte-derived macrophages. In the D.E.S.I.R. cohort, kynurenine levels were positively associated with body mass index (BMI) (P = 4.68 × 10(-19) ) and with a higher HOMA2-IR insulin resistance index (P = 6.23 × 10(-4) ). The levels of kynurenine, kynurenic acid, and quinolinic acid were associated with higher BMI (P < 0.05). The expression of several KP enzyme genes (indoleamine 2,3-dioxygenase 1 [IDO1], kynureninase [KYNU], kynurenine 3-monooxygenase [KMO], and kynurenine aminotransferase III [CCBL2]) was increased in the omental adipose tissue of women with obesity compared to lean (P < 0.05), and their expression was induced by proinflammatory cytokines in human primary adipocytes (P < 0.05), except for KMO that is not expressed in these cells. The expressions of IDO1, KYNU, KMO, and CCBL2 were higher in proinflammatory than in anti-inflammatory macrophages (P < 0.05). In the context of obesity, the presence of macrophages in adipose tissue may contribute to diverting KP toward KMO activation.


Does Calculated Free Testosterone Overcome Total Testosterone in Protecting From Sexual Symptom Impairment? Findings of a Cross-Sectional Study.
Although erectile dysfunction (ED) has been associated with low circulating total testosterone (TT) levels, the utility of free testosterone (FT) over TT is debatable. To assess the relative impact of low TT and low calculated FT (cFT) on androgen-related sexual symptoms in men with ED. Data from 485 men were analyzed. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF) and the Beck Inventory for Depression (BDI). Descriptive statistics tested differences between patients with normal TT levels (>3 ng/mL) and normal cFT levels (>65 pg/mL; group 1) and men with normal TT and low cFT (group 2), low TT and normal cFT (group 3), and low TT and low cFT (group 4). Linear regression models tested the association between clinical predictors and sexual function impairment. We assessed the impact of different hormonal categories on androgen-related symptoms and the clinical utility of measuring cFT in men with ED. Groups 1, 2, 3, and 4 were composed of 338 (69.6%), 44 (9.1%), 34 (7.0%), and 69 (14.3%) patients, respectively. Compared with group 1, patients in group 2 were older (P < .001), had a higher body mass index (P < .01), and had a larger proportion with CCI scores of at least 1 (P = .006). Likewise, group 2 presented lower scores for the IIEF erectile function (P = .07), sexual desire (P = .04), and orgasmic function (P = .007) domains and lower BDI scores (P = .02) than group 1. Similar findings were found for group 4 vs 1. Conversely, patients in group 3 had similar scores on the questionnaires to those in group 1. Low cFT and normal or low TT achieved independent predictor status for pathologic IIEF domains and BDI scores after accounting for age, CCI, and body mass index. Conversely, low TT and normal cFT status was not associated with pathologic scores on the questionnaires. The inclusion of cFT in the first-line assessment of hypogonadal symptoms in men with ED has major clinical utility. This is the first study evaluating the concomitant impact of TT and cFT on men with ED using well-validated instruments to assess patients' sexuality and depressive symptoms. Limitations are the retrospective nature of the study and lack of physical function data and bone ultrasound measurements. Although normal cFT was not associated with signs and symptoms suggestive of testosterone deficiency, even when concomitant with low TT or low cFT irrespective of TT values, it was indicative of poorer clinical profiles and impaired sexual and depressive parameters compared with normal TT and normal cFT in a cohort of patients with ED. Boeri L, Capogrosso P, Ventimiglia E, et al. Does Calculated Free Testosterone Overcome Total Testosterone in Protecting From Sexual Symptom Impairment? Findings of a Cross-Sectional Study. J Sex Med 2017;14:1549-1557.


Environmental and Pathogenic Carbapenem Resistant Bacteria Isolated from a Wastewater Treatment Plant Harbour Distinct Antibiotic Resistance Mechanisms.
Wastewater treatment plants are important reservoirs and sources for the dissemination of antibiotic resistance into the environment. Here, two different groups of carbapenem resistant bacteria-the potentially environmental and the potentially pathogenic-were isolated from both the wastewater influent and discharged effluent of a full-scale wastewater treatment plant and characterized by whole genome sequencing and antibiotic susceptibility testing. Among the potentially environmental isolates, there was no detection of any acquired antibiotic resistance genes, which supports the idea that their resistance mechanisms are mainly intrinsic. On the contrary, the potentially pathogenic isolates presented a broad diversity of acquired antibiotic resistance genes towards different antibiotic classes, especially β-lactams, aminoglycosides, and fluoroquinolones. All these bacteria showed multiple β-lactamase-encoding genes, some with carbapenemase activity, such as the blaKPC-type genes found in the Enterobacteriaceae isolates. The antibiotic susceptibility testing assays performed on these isolates also revealed that all had a multi-resistance phenotype, which indicates that the acquired resistance is their major antibiotic resistance mechanism. In conclusion, the two bacterial groups have distinct resistance mechanisms, which suggest that the antibiotic resistance in the environment can be a more complex problematic than that generally assumed.


Safety and efficacy of paramedic treatment of regular supraventricular tachycardia: a randomised controlled trial.
Supraventricular tachycardias (SVTs) are a common cause of acute hospital presentations. Adenosine is an effective treatment. To date, no studies have directly compared paramedic-with hospital-delivered treatment of acute SVT with adenosine. Randomised controlled trial comparing the treatment of SVT and discharge by paramedics with conventional emergency department (ED)-based care. Patients were excluded if they had structural heart disease or contraindication to adenosine. Discharge time, follow-up management, costs and patient satisfaction were compared. Eighty-six patients were enrolled: 44 were randomised to paramedic-delivered adenosine (PARA) and 42 to conventional care (ED). Of the 37 patients in the PARA group given adenosine, the tachycardia was successfully terminated in 81%. There was a 98% correlation between the paramedics' ECG diagnosis and that of two electrophysiologists. No patients had any documented adverse events in either group. The discharge time was lower in the PARA group than in the ED group (125 min (range 55-9513) vs 222 min (range 72-26 153); p=0.01), and this treatment strategy was more cost-effective (£282 vs £423; p=0.01). The majority of patients preferred this management approach. Being treated and discharged by paramedics did not result in the patients being less likely to receive ongoing management of their arrhythmia and cardiology follow-up. Patients with SVT can effectively and safely be treated with adenosine delivered by trained paramedics. Implementation of paramedic-delivered acute SVT care has the potential to reduce healthcare costs without compromising patient care. NCT02216240.


Dizziness in a community hospital: central neurological causes, clinical predictors, and diagnostic yield and cost of neuroimaging studies.
Objectives: Neuroimaging is contributing to the rising costs of dizziness evaluation. This study examined the rate of central neurological causes of dizziness, relevant clinical predictors, and the costs and diagnostic yields of neuroimaging in dizziness assessment. Methods: We retrospectively reviewed the records of 521 adult patients who visited the hospital during a 12-month period with dizziness as the chief complaint. Clinical findings were analyzed using Fisher's exact test to determine how they correlated with central neurological causes of dizziness identified by neuroimaging. Costs and diagnostic yields of neuroimaging were calculated. Results: Of the 521 patients, 1.5% had dizziness produced by central neurological causes. Gait abnormalities, limb ataxia, diabetes mellitus, and the existence of multiple neurological findings predicted central causes. Cases were associated with gait abnormalities, limb ataxia, diabetes mellitus, and the existence of multiple neurological findings . Brain computed tomography (CT) and magnetic resonance imaging (MRI) were performed in 42% and 9.5% of the examined cases, respectively, with diagnostic yields of 3.6% and 12%, respectively. Nine cases of dizziness were diagnosed from 269 brain scans, costing $607 914. Conclusion: Clinical evaluation can predict the presence of central neurological causes of dizziness, whereas neuroimaging is a costly and low-yield approach. Guidelines are needed for physicians, regarding the appropriateness of ordering neuroimaging studies. Abbreviations: OR: odds ratio; CI: confidence interval; ED: emergency department; CT: computed tomography; MRI: magnetic resonance imaging; HINTS: Head impulse, Nystagmus, Test of skew.


Targeted knockout of a chemokine-like gene increases anxiety and fear responses.
Emotional responses, such as fear and anxiety, are fundamentally important behavioral phenomena with strong fitness components in most animal species. Anxiety-related disorders continue to represent a major unmet medical need in our society, mostly because we still do not fully understand the mechanisms of these diseases. Animal models may speed up discovery of these mechanisms. The zebrafish is a highly promising model organism in this field. Here, we report the identification of a chemokine-like gene family, samdori (sam), and present functional characterization of one of its members, sam2 We show exclusive mRNA expression of sam2 in the CNS, predominantly in the dorsal habenula, telencephalon, and hypothalamus. We found knockout (KO) zebrafish to exhibit altered anxiety-related responses in the tank, scototaxis and shoaling assays, and increased crh mRNA expression in their hypothalamus compared with wild-type fish. To investigate generalizability of our findings to mammals, we developed a Sam2 KO mouse and compared it to wild-type littermates. Consistent with zebrafish findings, homozygous KO mice exhibited signs of elevated anxiety. We also found bath application of purified SAM2 protein to increase inhibitory postsynaptic transmission onto CRH neurons of the paraventricular nucleus. Finally, we identified a human homolog of SAM2, and were able to refine a candidate gene region encompassing SAM2, among 21 annotated genes, which is associated with intellectual disability and autism spectrum disorder in the 12q14.1 deletion syndrome. Taken together, these results suggest a crucial and evolutionarily conserved role of sam2 in regulating mechanisms associated with anxiety.


Depressive residual symptoms are associated with illness course characteristics in a sample of outpatients with bipolar disorder.
Rates of 50-70% of residual symptoms referring to subsyndromal manifestations between episodes that do not meet the required criteria for episode definition were reported in bipolar disorder (BD). However, the specific role of these symptoms on the course of BD patients is poorly understood; thus, we aimed to investigate factors associated with depressive residual symptoms. Overall, 255 currently euthymic BD outpatients on maintenance treatment, including 95 (37.2%) males and 160 (62.8%) females, were consecutively recruited at the Section of Psychiatry, Department of Neuroscience, University of Genoa (Italy) and underwent detailed structured interviews, comprehensive clinical interviews, and clinical record reviews for assessment/collection of relevant information concerning the course of illness and clinical status including cross-referral of all available information. After categorizing subjects according to the presence/absence of residual symptoms, groups were compared along clinical variables and variables associated with residual symptoms were analyzed using multivariate analyses. Subjects with residual symptoms were less likely to report substance abuse (χ2(2) = 11.937, p ≤ 0.005) and lifetime psychotic symptoms (χ2(2) = 10.577, p = 0.005), and more likely to report higher illness episodes, longer duration of illness (t253 = 67.282, p ≤ 0.001; t253 = 10.755, p ≤ 0.001), and longer duration of current illness episode (t253 = 7.707, p ≤ 0.001) than those without residual symptoms. After multivariate analyses, a significant positive contribution to residual symptoms was given only by duration of current illness episode (β = 0.003; p ≤ 0.05), and lifetime psychotic symptoms (β = 1.094; p ≤ 0.005). Clinicians have to pay attention to minimize residual symptoms that may significantly impact on the course of BD and achievement of full remission between episodes.


When wax wanes: competitors for beeswax stabilize rather than jeopardize the honeyguide-human mutualism.
Many mutualisms are exploited by third-party species, which benefit without providing anything in return. Exploitation can either destabilize or promote mutualisms, via mechanisms that are highly dependent on the ecological context. Here we study a remarkable bird-human mutualism, in which wax-eating greater honeyguides (Indicator indicator) guide humans (Homo sapiens) to wild bees' nests, in an exchange of knowledge about the location of nests for access to the wax combs inside. We test whether the depletion of wax by mammalian and avian exploiter species either threatens or stabilizes the mutualism. Using camera traps, we monitored feeding visits to wax comb made available following honey harvests. We found that greater honeyguides face competition for wax from conspecifics and nine exploiter species, five of which were not previously known to consume wax. Our results support the hypothesis that heterospecific exploiters stabilize the mutualism, because wax depletion by these competitors probably limits feeding opportunities for conspecific exploiters, favouring the early-arriving individual that guided humans to the bees' nest. These findings highlight the importance of the ecological context of species interactions and provide further evidence for how mutualisms can persist because of, and not in spite of, exploitation by third-party species.


The mystic experience: a psychiatric reflection.
This paper reviews the phenomenology of the mystical experience and its varied contexts epilepsy, toxicity, organic brain syndromes, the major psychoses and hysterical dissociative states as well as in apparently normal persons. The impact of the experience on the personality is noted and its significance briefly reviewed. The author notes that two fallacies await the unwary psychiatrist: the fallacy of reductionism which defines the mystical experience in pathological terms only; and the fallacy of speculation without adequate philosophical or theological tools.


Interactions between diphtheria toxin entry and anion transport in vero cells. III. Effect on toxin binding and anion transport of tumor-promoting phorbol esters, vanadate, fluoride, and salicylate.
When Vero cells were incubated with TPA (12-O-tetradecanoylphorbol 13-acetate) and related tumor promoters, their ability to bind diphtheria toxin in a functional way was rapidly reduced to less than 1% of the normal value. Upon further incubation with TPA, the cells recovered their ability to bind the toxin, apparently because they became resistant to TPA. Treatment with Na3VO4 reduced the ability of the cells to bind diphtheria toxin to approximately the same extent as treatment with TPA, but the reduction required longer time to develop and it persisted upon prolonged incubation with Na3VO4. ATP depletion of the cells prevented the reduction in binding capability. Such treatment also prevented the reduction in toxin binding induced by treatment with salicylate or fluoride. Treatment with TPA, fluoride, vanadate, and salicylate altered the ability of the cells to carry out anion transport and interfered with their ability to regulate the transport. The results indicate that the binding sites for diphtheria toxin on Vero cells are modulated by TPA, Na3VO4, salicylate, and fluoride by a process which requires ATP. The possibility is discussed that the modulation consists in phosphorylation of the toxin binding sites, which may be identical with, or closely linked to, the anion antiporter in the cells.


Molecular Characterization of Human Lymph Node Stromal Cells During the Earliest Phases of Rheumatoid Arthritis.
Rheumatoid arthritis (RA) is a progressive, destructive autoimmune arthritis. Break of tolerance and formation of autoantibodies occur years before arthritis. Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSCs) play a crucial role in shaping the immune response and maintaining peripheral tolerance. Here we performed the first epigenomic characterization of LNSCs during health and early RA, by analyzing their transcriptome and DNA methylome in LNSCs isolated from lymph node needle biopsies obtained from healthy controls (HC), autoantibody positive RA-risk individuals and patients with established RA. Of interest, LNSCs from RA-risk individuals and RA patients revealed a common significantly differential expressed gene signature compared with HC LNSCs. Pathway analysis of this common signature showed, among others, significant enrichment of pathways affecting the extracellular matrix (ECM), cholesterol biosynthesis and immune system. In a gel contraction assay LNSCs from RA-risk individuals and RA patients showed impaired collagen contraction compared to healthy LNSCs. In RA LNSCs a significant enrichment was observed for genes involved in cytokine signaling, hemostasis and packaging of telomere ends. In contrast, in RA-risk LNSCs pathways in cancer (cell cycle related genes) were differentially expressed compared with HC, which could be validated in vitro using a proliferation assay, which indicated a slower proliferation rate. DNA methylation analyses revealed common and specific differentially methylated CpG sites (DMS) in LNSC from RA patients and RA-risk individuals compared with HC. Intriguingly, shared DMS were all associated with antigen processing and presentation. This data point toward alterations in cytoskeleton and antigen-processing and presentation in LNSC from RA-risk individuals and RA patients. Further studies are required to investigate the consequence of this LNSC abnormality on LNSC-mediated immunomodulation.


First Report of Okra enation leaf curl virus and Associated Cotton leaf curl Multan betasatellite and Cotton leaf curl Multan alphasatellite Infecting Cotton in Pakistan: A New Member of the Cotton Leaf Curl Disease Complex.
Cotton (Gossypium hirsutum L.) is an important and widely cultivated crop in Pakistan, upon which many rely for economic security. Cotton leaf curl disease (CLCuD) is caused by a complex comprising of more than eight species in the genus Begomovirus (family Geminiviridae) with associated betasatellite and alphasatellites. During 2011, characteristic symptoms of leaf curl disease were widespread (>40%), and the whitefly Bemisia tabaci (Genn.) vector of the leaf curl complex was abundant in commercial cotton fields in Burewala, Pakistan. Symptoms included vein thickening, upward or downward leaf curling, and foliar enations. To test for the presence of a begomovirus(es), total DNA was extracted from 100 mg of symptomatic leaf tissues from five different plants (isolates CLCuDBur1 to 5) using the CTAB method (1). Total DNA extracts were used for rolling circle amplification (RCA) using TempliPhi DNA Amplification Kit (GE Healthcare). Of the five field isolates, the RCA product for only one, CLCuDBur3, digested with HindIII, produced an apparently full-length ~2.7 kb fragment, suggesting that CLCuD-Bur3 represented a distinct isolate. The 2.7-kb fragment was cloned into the plasmid vector pGEM-3Zf+ (Promega, Madison, WI). To test for the presence of associated alphasatellites and betasatellites, the PCR primers, AlphaF/R and BetaF/R (2), were used to amplify the putative 1.4-kbp molecules. The resultant 1.4-kb PCR products were ligated into the pGEMT-Easy vector and cloned. Cloned inserts for each were subjected to DNA sequencing, bidirectionally. The cloned monopartite, helper begomovirus genome (HF567945), one betasatellite (HF567946), and one alphasatellite (HF567947) sequences were determined and found to be 2,742, 1,358, and 1,376 bases long, respectively. Pairwise sequence comparisons were carried out for each using the 10 most closely related species or strains (identified in GenBank using BLASTn) using MEGA5 software. The CLCuDBur3 genome sequence shared its highest identity (99.6%) with Okra enation leaf curl virus (OELCuV) (KC019308), so CLCuDBur3 is a variant of OELCuV, a begomovirus reported previously from Abelmoschus esculentus (L.) (okra) plants in India. The betasatellite and alphasatellite shared their highest nt identity at 96 and 98.7% with Cotton leaf curl Multan betasatellite (CLCuMB) (AM774311) and Cotton leaf curl Multan alphasatellite (CLCuMA), respectively (misnamed as CLCuBuA in GenBank) (FN658728). Additionally, the HindIII-digested RCA products were analyzed by Southern blot hybridization using a DIG-labeled DNA probe specific for the intergenic region of either Cotton leaf curl Burewala virus (CLCuBuV) or OELCuV. The OELCuV, but not the CLCuBuV, probe hybridized with HindIII digested RCA products (CLCuDBur3 genome), confirming the presence of OELCuV and the absence of CLCuBuV, the latter being the most prevalent begomovirus species infecting cotton in Pakistan. This is the first report of OELCuV infecting cotton plants in Pakistan, underscoring the discovery of yet another begomovirus member of the CLCuD complex. Further, the possible co-infection of cotton by OELCuV and other recognized species of the CLCuD complex could facilitate further diversification (potentially, through recombination) and lead to the emergence of new variants with the potential to cause damage to the cotton crop in Pakistan. References: (1) J. J. Doyle and J. L. Doyle. Focus. 12:13, 1990. (2) M. Zia-Ur-Rehman et al. Plant Dis. 97:1122, 2013.


An evaluation of left ventricular function after surgery for pure mitral regurgitation using dobutamine-stress echocardiography--should the mitral complex be preserved?
To evaluate the importance of preserving the mitral complex, clinical outcomes and postoperative left ventricular (LV) functions of 175 patients with pure mitral regurgitation (MR) were analyzed. They were divided into three groups; patients who had conventional mitral valve replacement (cMVR; n = 47), posterior mitral leaflet preserved MVR (pMVR; n = 66) or mitral valvuloplasty (MVP; n = 62). There was no operative death or hospital death in this study. The actuarial survival rate was 85.2% in cMVR, 78.5% in pMVR, and 84.7% in MVP at 10 years after operation. The actuarial freedom from reoperation 10 years postoperatively was 100% in cMVR, 97.9% in pMVR, 85.8% in MVP. The actuarial freedom from thromboembolism (TE) at 10 years was 92.2% in cMVR, 87.1% in pMVR, 93.5% in MVP. Freedom from all types of events including non-cardiac death was 78.3% in cMVR, 64.8% in pMVR, 65.3% in MVP at 10 years, respectively. Pre- and postoperative LV function was evaluated using echocardiography. Patients with MVP had better LV performance than those with MVR. However, there was no significant difference between the cMVR and pMVR groups. For further estimation of postoperative LV function, dobutamine-stress echocardiography (DSE) was performed. The results of DSE revealed that the LV contractility in MVP was obviously better than those in MVR groups especially in systole. The change in ejection fraction (EF) from baseline to peak dobutamine stress in the pMVR group was significantly greater than in cMVR. This study supports the concept that the preservation of continuity between the mitral annulus and papillary muscle plays an important role in clinical outcome and postoperative LV function. In conclusion, MVP should be a first choice as an operative method for pure MR when technically feasible. When it is impossible to perform MVP, pMVR, not cMVR, should be the next choice. This study suggests that preservation of papillary muscle-mitral annular continuity during mitral valve surgery for pure MR is beneficial to LV systolic function.


Selective visuo-haptic processing of shape and texture.
Previous functional neuroimaging studies have described shape-selectivity for haptic stimuli in many cerebral cortical regions, of which some are also visually shape-selective. However, the literature is equivocal on the existence of haptic or visuo-haptic texture-selectivity. We report here on a human functional magnetic resonance imaging (fMRI) study in which shape and texture perception were contrasted using haptic stimuli presented to the right hand, and visual stimuli presented centrally. Bilateral selectivity for shape, with overlap between modalities, was found in a dorsal set of parietal areas: the postcentral sulcus and anterior, posterior and ventral parts of the intraparietal sulcus (IPS); as well as ventrally in the lateral occipital complex. The magnitude of visually- and haptically-evoked activity was significantly correlated across subjects in the left posterior IPS and right lateral occipital complex, suggesting that these areas specifically house representations of object shape. Haptic shape-selectivity was also found in the left postcentral gyrus, the left lingual gyrus, and a number of frontal cortical sites. Haptic texture-selectivity was found in ventral somatosensory areas: the parietal operculum and posterior insula bilaterally, as well as in the right medial occipital cortex, overlapping with a medial occipital cortical region, which was texture-selective for visual stimuli. The present report corroborates and elaborates previous suggestions of specialized visuo-haptic processing of texture and shape.


Classical and distonic radical cations: a valence bond approach.
The conventional radical cations arising from the ionization of CH(3)CH(2)X (X=F, OH, NH(2), Cl, SH, PH(2)), and their distonic isomers, CH(2)CH(2)XH(.+), were studied by means of standard Møller-Plesset and G2 methods, and by an ab initio valence bond method. Among the conventional structures, two distinct states are considered. In the so-called c' states, the unpaired electron is in an orbital that lies in the plane of the heavy atoms, while the c'' states have their unpaired electron in an orbital lying out of the plane. It is shown that c' states are, as a rule, more stable than the c'' states, by up to approximately 20 kJ mol(-1) depending on the nature of X, owing to a stabilizing interplay of resonating structures. While the geometries of the c'' states are rather similar to those of the neutral molecules, some of the c' states display very different geometries, characterized by elongated C--C bonds, particularly when X=F or, to a lesser extent, when X=OH or Cl. These peculiar geometric features are rationalized by the valence bond analysis, which reveals that the C--C bond in these species is better viewed as a two-center, one-electron bond. The distonic radical cations are generally more stable than the conventional ones (by 20-100 kJ mol(-1)), except for the less electronegative X groups of the series, namely X=SH and PH(2). In these two cases, together with X=NH(2), the radical cation displays a classical distonic structure, as regards the geometry and electronic state. On the other hand, considerable C--X elongation is found for X=F or Cl. In these last cases, the valence bond analysis shows that the radical cation is better viewed as an ion-molecule complex between an ionized ethylene and a neutral HX molecule. The electronic structure of the distonic radical cation with X=OH lies between the two previous limiting descriptions.


Fixed-dose-rate gemcitabine in combination with oxaliplatin in patients with metastatic pancreatic cancer refractory to standard-dose-rate gemcitabine: a single-institute study.
There is a paucity of data exploring treatment options for refractory pancreatic cancer. Oxaliplatin has interesting activity in second-line therapy. Fixed-dose-rate gemcitabine (GFDR, 10 mg/m(2)/min) has shown promising results in patients with advanced pancreatic cancer over standard-dose-rate (30 min) gemcitabine (GSDR). We conducted a retrospective analysis of the experience of our cancer center with GFDR and oxaliplatin (GEMOX) in patients who failed GSDR. GEMOX consisted of gemcitabine 1,000 mg/m(2) over 100 min on day 1 and oxaliplatin 100 mg/m(2) over 2 h on day 2 every 2 weeks. Eligible patients were required to have measurable metastatic adenocarcinoma of the pancreas and to have failed prior GSDR. Seventeen patients (median age 62 years) who were treated at the Ohio State University with GEMOX following GSDR failure between November 2003 and January 2008 were included in this study. Twenty-four percent of all patients had a partial response, 29% had stable disease and 47% had progressive disease. The median progression-free survival was 2.6 months and the median overall survival was 6.4 months. There were no unexpected toxicities. GEMOX shows interesting activity and acceptable tolerability in patients with metastatic pancreatic cancer who failed prior GSDR. Our results are consistent with previously published results.


Multiclass Classification by Adaptive Network of Dendritic Neurons with Binary Synapses Using Structural Plasticity.
The development of power-efficient neuromorphic devices presents the challenge of designing spike pattern classification algorithms which can be implemented on low-precision hardware and can also achieve state-of-the-art performance. In our pursuit of meeting this challenge, we present a pattern classification model which uses a sparse connection matrix and exploits the mechanism of nonlinear dendritic processing to achieve high classification accuracy. A rate-based structural learning rule for multiclass classification is proposed which modifies a connectivity matrix of binary synaptic connections by choosing the best "k" out of "d" inputs to make connections on every dendritic branch (k < < d). Because learning only modifies connectivity, the model is well suited for implementation in neuromorphic systems using address-event representation (AER). We develop an ensemble method which combines several dendritic classifiers to achieve enhanced generalization over individual classifiers. We have two major findings: (1) Our results demonstrate that an ensemble created with classifiers comprising moderate number of dendrites performs better than both ensembles of perceptrons and of complex dendritic trees. (2) In order to determine the moderate number of dendrites required for a specific classification problem, a two-step solution is proposed. First, an adaptive approach is proposed which scales the relative size of the dendritic trees of neurons for each class. It works by progressively adding dendrites with fixed number of synapses to the network, thereby allocating synaptic resources as per the complexity of the given problem. As a second step, theoretical capacity calculations are used to convert each neuronal dendritic tree to its optimal topology where dendrites of each class are assigned different number of synapses. The performance of the model is evaluated on classification of handwritten digits from the benchmark MNIST dataset and compared with other spike classifiers. We show that our system can achieve classification accuracy within 1 - 2% of other reported spike-based classifiers while using much less synaptic resources (only 7%) compared to that used by other methods. Further, an ensemble classifier created with adaptively learned sizes can attain accuracy of 96.4% which is at par with the best reported performance of spike-based classifiers. Moreover, the proposed method achieves this by using about 20% of the synapses used by other spike algorithms. We also present results of applying our algorithm to classify the MNIST-DVS dataset collected from a real spike-based image sensor and show results comparable to the best reported ones (88.1% accuracy). For VLSI implementations, we show that the reduced synaptic memory can save upto 4X area compared to conventional crossbar topologies. Finally, we also present a biologically realistic spike-based version for calculating the correlations required by the structural learning rule and demonstrate the correspondence between the rate-based and spike-based methods of learning.


[The evolution of methods of active irrigation of paranasal sinuses in rhinosinusitis. Part 2].
Inflammation of the paranasal sinuses significantly reduces the quality of life of people and causes marked economic damage to society. The striking clinical picture of sinusitis has always forced doctors to study the disease, as evidenced by the first records of the anatomy and diseases of the paranasal sinuses by doctors in ancient Egypt more than 3.000 years BC. Sinusitis has been treated in different ways in different historical periods. Effective medication treatment appeared relatively recently and began to steadily replace the older instrumental methods, to which many people had a preconceived notion of invasiveness. However, many studies are showing the positive effect of active drainage methods and, moreover, there is data showing that the discomfort during such procedures is slightly higher than during dental treatment under local anesthesia. This article presents a review of the available scientific literature on the use of different treatments for bacterial rhinosinusitis at different historical stages, ranging from the first publications on puncture techniques to balloon dilatation and the modern approach to conservative treatment.


[Surgery for congestive heart failure--the role of computed tomography in the pre- and postoperative diagnostic evaluation].
The treatment of advanced, drug resistant congestive heart failure gains in importance in the field of cardiac surgery. Cardiac imaging for preoperative assessment and follow-up focuses on the determination of ventricular volumes and function as well as on the detection of postoperative complications. Computed tomography (CT) is highly accurate irrespective of the individual patient's anatomic situation, has a low examiner dependence and short examination time, does not require an arterial vascular access and can be performed in patients with metal implants. CT is the modality of choice in the follow-up of heart transplants to detect extracardiac and cardiac complications including coronary calcifications as an early sign of transplant vasculopathy. In addition, CT visualizes the elements of mechanical assist devices and can identify their possible local cardiac and mediastinal complications. CT can detect fibrolipomatous involution of the mobilized muscle flap in dynamic cardiomyoplasty and can depict fibrous reactions along the epicardial mesh implant in passive cardiac containment. Further indications include assessment of typical local postoperative complications, such as intrathoracic infection and mediastinal bleeding, intracardiac thrombus formation or pericardial effusion. CT is routinely used for evaluating bypass patency but is limited in assessing associated valve defects since it does not visualize flow.


Novel soy germ pasta improves endothelial function, blood pressure, and oxidative stress in patients with type 2 diabetes.
To compare the effects of a novel soy germ-enriched pasta, containing isoflavone aglycons, with conventional pasta on endothelial function and cardiovascular risk markers in patients with type 2 diabetes (T2D). This randomized controlled double-blind crossover study compared one serving/day of soy germ pasta and conventional pasta for 8 weeks for effects on brachial artery flow-mediated vasodilation, blood pressure, plasma lipids, oxidized LDL cholesterol, 8-iso-PGF2α, total antioxidant capacity (TAC), glutathione (GSH), and homocysteine. Isoflavone-enriched pasta significantly improved arterial stiffness (P = 0.005) and reduced systolic (P = 0.026) and diastolic (P = 0.017) blood pressures. Plasma TAC increased (P = 0.0002), oxidized LDL cholesterol decreased (P = 0.009), 8-iso-PGF2α decreased (P = 0.001), GSH levels increased (P = 0.0003), and homocysteine decreased (P = 0.009) consistent with a reduction in oxidative stress. No significant changes were observed with conventional pasta. Pasta enriched with biologically active isoflavone aglycons improved endothelial function and had beneficial effects on cardiovascular risk markers in patients with T2D.


Quality of life and mortality after surgical treatment for vertebral osteomyelitis (VO): a prospective study.
Vertebral osteomyelitis (VO) has a high mortality and leads to chronic pain and functional disability. Surgical treatment is often necessary. To date, little is known about the consequences of surgery on patient outcome. The aim of this study was to determine the quality of life (QoL) and mortality rates of surgically treated VO patients for a period of 2 years. Patients with VO undergoing surgical treatment in a tertiary referral hospital from 2008 to 2015 were included prospectively. Data were collected before (T0) as well as 1 year (T1) and 2 years (T2) post-surgery. Within the European Spine Tango registry, prospective patient and QoL data were collected using validated outcome scores: Oswestry Disability Index, Short Form 36/EuroQol, Visual Analog Scale, and Core Outcome Measures Index. From 195 patients surgically treated for VO, QoL data were available from 136 patients at T0, 100 patients at T1, and 82 patients at T2, respectively. The 1- and 2-year mortality rates were 20% and 23%. Mainly all QoL outcome scores showed significant improvement at T1 and did not change significantly from T1 to T2. Surgical treatment of VO patients leads to significantly improved QoL. Nevertheless, QoL levels were below those of the general population. Our results underscore that spine disability questionnaires measuring QoL are mandatory to demonstrate comprehensively the severity of this entity. Our study confirms a high mortality and points out the role of VO as a potentially life-threatening condition.


Plasma β-amyloid and MRI markers of cerebral small vessel disease: Three-City Dijon study.
We investigated the relation of circulating plasma β-amyloid (Aβ) with MRI markers of small vessel disease (SVD) in dementia-free community persons. Participants were 1,690 individuals aged 65 to 80 years from the Three-City Dijon Study. Plasma Aβ measurement and MRI examination were performed at baseline and after a 4-year follow-up. MRI markers of SVD included white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces. We examined the relation of plasma Aβ levels with MRI markers of SVD at baseline and with progression of WMH over follow-up (n = 1,057). We also assessed whether these relations were modified by vascular risk factors, notably blood pressure. Low plasma Aβ1-40 levels were associated with increased progression of WMH, and low Aβ1-42 with higher odds of extensive WMH progression over the follow-up (odds ratio = 1.66, 95% confidence interval = 1.16-2.38). Consistently low Aβ1-40 and Aβ1-42 levels on both measurements were associated with accelerated progression of WMH. These associations were modified by blood pressure levels but not the APOE ε4 genotype. Progression of WMH volume in dementia-free older persons is associated with levels of circulating plasma Aβ. These results reinforce the notion of an interrelation of vascular and neurodegenerative mechanisms in cerebral aging.


Prevalence of chronic complications in korean patients with type 2 diabetes mellitus based on the korean national diabetes program.
The Korean National Diabetes Program (KNDP) cohort study is performing an ongoing large-scale prospective multicenter investigation to discover the pathogenesis of type 2 diabetes in Korean patients. This study was performed to examine the prevalence of chronic complications in patients with type 2 diabetes among those registered in the KNDP cohort within the past 4 years. This study was performed between June 2006 and September 2009 at 13 university hospitals and included 4,265 KNDP cohort participants. Among the participants, the crude prevalence of microvascular and macrovascular diseases of those checked for diabetes-related complications was determined, and the adjusted standard prevalence and standardization of the general population prevalence ratio (SPR) was estimated based on the 2005 Korean National Health and Nutrition Examination Survey (KNHANES) population demographics. Among the KNDP registrants, 43.2% had hypertension, 34.8% had dyslipidemia, 10.8% had macrovascular disease, and 16.7% had microvascular disease. The SPR of the KNDP registrants was significantly higher than that of the KNHANES subjects after adjusting for demographics in the KNHANES 2005 population. However, with the exception of cardiovascular disease in females, the standardized prevalence for the most complicated items in the survey was significantly higher than that in the KNHANES subjects. The prevalence of macrovascular disease and peripheral vascular disease were significantly higher in Korean patients with type 2 diabetes than in the normal population. However, no significant difference was noted in the prevalence of cardiovascular disease in females.


HRT decreases DNA and lipid oxidation in postmenopausal women.
Postmenopausal women have increased oxidative stress and decreased antioxidant status. Estrogen has great antioxidant capacity both in vitro and in vivo. Few authors have studied the effect that hormone replacement therapy (HRT) has on the oxidant and antioxidant status and none have studied the effect on DNA oxidation as a possible explanation for the aging process itself. The aim of this study was to evaluate both oxidation and antioxidation markers in postmenopausal woman and to determine the effects that HRT has on them. Sixty-two postmenopausal women with similar biophysical characteristics were divided into three groups: (1) 18 not taking any HRT, (2) 20 receiving estrogen-only replacement therapy (ERT, conjugated equine estrogen), and (3) 22 receiving combined estrogen/progestin HRT (conjugated equine estrogen + medroxyprogesterone acetate). Specific molecular oxidative damage was detected by measuring 8- hydroxy-2-deoxy guanosine (8-OH-2dG) (DNA damage), standardized thiobarbituric acid reactive substances (TBARS) (lipid damage) and protein carbonyl (proteins). Antioxidant enzyme activity was detected by measuring catalase activity, and total antioxidant status was measured using 1,1,difenil-2-picril hydrazil. Both ELISA and photometric methods were used. 8-OH-2dG levels were significantly lower in women who received combined HRT compared to women who did not receive HRT (ANOVA, p < 0.05). Lipid oxidation was significantly lower in women on ERT compared to women taking no HRT (ANOVA, p < 0.05). Pearson correlation showed that lipid oxidation decreased as the estradiol concentration increased within the study range (r = -0.362, p < 0.05). No statistical difference was noted for protein oxidation and catalase activity among the groups. No statistical difference was found for total antioxidant status between the groups (ANOVA). HRT decreases oxidative damage to both DNA and lipids in postmenopausal women. Lipid oxidation status may be inversely related to estrogen levels in postmenopausal women.


Mental health consequences of child sexual abuse.
Survivors of child sexual abuse (CSA) can experience a variety of long-term mental health effects on their life trajectory, which brings them to the attention of mental health services. It is vital that the mental health nurse remains aware of the mental health consequences of CSA and receptive towards patients' efforts to disclose a history of CSA. Moreover, fundamentally, the mental health nurse should endeavour to consider his/her own personal feelings on this emotive subject. This article explores the mental health effects of CSA on pre-adolescent children, adolescents, and the long-term effects of CSA into adulthood.


Distribution, phylogenetic diversity and physiological characteristics of epsilon-Proteobacteria in a deep-sea hydrothermal field.
Epsilon-Proteobacteria is increasingly recognized as an ecologically significant group of bacteria, particularly in deep-sea hydrothermal environments. In this study, we studied the spatial distribution, diversity and physiological characteristics of the epsilon-Proteobacteria in various microbial habitats in the vicinity of a deep-sea hydrothermal vent occurring in the Iheya North field in the Mid-Okinawa Trough, by using culture-dependent and -independent approaches. The habitats studied were inside and outside hydrothermal plume, and annelid polychaete tubes. In addition, we deployed colonization devices near the vent emission. The polychaete tubes harboured physiologically and phylogenetically diverse microbial community. The in situ samplers were predominantly colonized by epsilon-Proteobacteria. Energy metabolism of epsilon-Proteobacteria isolates was highly versatile. Tree topology generated from the metabolic traits was significantly different (P = 0.000) from that of 16S rRNA tree, indicating current 16S rRNA gene-based analyses do not provide sufficient information to infer the physiological characteristics of epsilon-Proteobacteria. Nevertheless, culturability of epsilon-Proteobacteria in various microbial habitats differed among the phylogenetic subgroups. Members of Sulfurimonas were characterized by the robust culturability, and the other phylogenetic subgroups appeared to lose culturability in seawater, probably because of the sensitivity to oxygen. These results provide new insight into the ecophysiological characteristics of the deep-sea hydrothermal vent epsilon-Proteobacteria, which has never been assessed by comparative analysis of the 16S rRNA genes.


Long-Term Radiographic and Patient-Reported Outcomes in Patients with Rheumatoid Arthritis Treated with Tofacitinib: ORAL Start and ORAL Scan Post-hoc Analyses.
Here we examine the relationship between achieving different levels of disease activity with tofacitinib (an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis), long-term structural progression, and patient-reported physical function. This was a post hoc analysis of two 24-month, phase III randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder (IR) patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily as either monotherapy or with background MTX. The modified total Sharp score (mTSS) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were analyzed at month 24 according to disease activity at month 6 defined by the Clinical Disease Activity Index (CDAI) or the Disease Activity Score in 28 joints, C-reactive protein (DAS28CRP). Mean changes from baseline in mTSS at month 24 were less in patients with CDAI remission at month 6 than in those with CDAI moderate/high disease activity (MDA/HDA) at month 6. A DAS28CRP of < 1.9 most closely approximated CDAI remission (≤ 2.8). Tofacitinib appeared to inhibit joint damage in the presence of persistent inflammation compared with MTX. More patients receiving tofacitinib or MTX with CDAI remission or low disease activity (LDA) at month 6 reported normative HAQ-DI scores (< 0.5) at month 24 than did those with CDAI MDA/HDA. Regardless of treatment, in both MTX-naïve and MTX-IR patients, remission or LDA at month 6 was associated with successful long-term outcomes: inhibition of structural progression and normative HAQ-DI scores. Long-term outcomes were similar when patients achieved CDAI remission or a DAS28CRP of < 1.9, confirming that this is an appropriate cut-off for remission with DAS28CRP. Tofacitinib potentially inhibits joint damage even with persistent inflammation. Pfizer Inc. Clinicaltrials.gov identifiers: NCT01039688 and NCT00847613.


A recombination repair gene of Schizosaccharomyces pombe, rhp57, is a functional homolog of the Saccharomyces cerevisiae RAD57 gene and is phylogenetically related to the human XRCC3 gene.
To identify Schizosaccharomyces pombe genes involved in recombination repair, we identified seven mutants that were hypersensitive to both methyl methanesulfonate (MMS) and gamma-rays and that contained mutations that caused synthetic lethality when combined with a rad2 mutation. One of the mutants was used to clone the corresponding gene from a genomic library by complementation of the MMS-sensitive phenotype. The gene obtained encodes a protein of 354 amino acids whose sequence is 32% identical to that of the Rad57 protein of Saccharomyces cerevisiae. An rhp57 (RAD57 homolog of S. pombe) deletion strain was more sensitive to MMS, UV, and gamma-rays than the wild-type strain and showed a reduction in the frequency of mitotic homologous recombination. The MMS sensitivity was more severe at lower temperature and was suppressed by the presence of a multicopy plasmid bearing the rhp51 gene. An rhp51 rhp57 double mutant was as sensitive to UV and gamma-rays as an rhp51 single mutant, indicating that rhp51 function is epistatic to that of rhp57. These characteristics of the rhp57 mutants are very similar to those of S. cerevisiae rad57 mutants. Phylogenetic analysis suggests that Rhp57 and Rad57 are evolutionarily closest to human Xrcc3 of the RecA/Rad51 family of proteins.


Prothymosin-α and parathymosin expression predicts poor prognosis in squamous and adenosquamous carcinomas of the gallbladder.
The present study aimed to investigate the expression patterns of prothymosin-α (PTMA) and parathymosin (PTMS) in patients with squamous cell carcinoma (SCC), adenosquamous cell carcinoma (ASC) and adenocarcinoma (AC) of the gallbladder, and to assess their association with the clinicopathological characteristics and prognosis of the patients. A retrospective analysis of data pertaining to patients with SCC/ASC (n=46) and AC (n=80) of the gallbladder, who were treated with surgical resection, was conducted. Kaplan-Meier survival analysis was also performed to assess the correlation of the expression pattern with survival. The results revealed a higher percentage of patients with a large tumor diameter (>3 cm) in the SCC/ASC group as compared with those in the AC group (P<0.05). No significant differences were observed between patients with SCC/ASC and those with AC with respect to the patient sex, presence of gallstones, TNM stage, lymph node metastasis, invasive growth into anatomically contiguous structures, surgical methods used, survival rate, and the expression levels of PTMA and PTMA (P>0.05). However, positive expression of PTMA and PTMA was associated with tumor size, TNM stage, lymph node metastasis, locally invasive growth, and treatment with radical resection in patients with SCC/ASC and AC (P<0.05). In addition, positive expression of PTMA and PTMA was observed in a significantly lower number of patients with advanced AC as compared with those in early AC (P<0.05), while these expression levels were also associated with shorter survival in the SCC/ASC group and AC group (P<0.05). Cox multivariate analysis also demonstrated a negative correlation between PTMA and PTMA levels, and the postoperative survival rate in the two groups. In conclusion, the present study indicated that the expression levels of PTMA and PTMA were closely associated with the tumorigenesis and progression of SCC, ASC and AC of the gallbladder. Positive expression of PTMA and PTMA may serve as a valuable prognostic factor in these patients.


Host-odour recognition in two tick species is coded in a blend of vertebrate volatiles.
The questing behaviour of ixodid ticks serves for identification and localisation of approaching hosts and is evoked by carbon dioxide, vibrations, visual and odour stimuli. In an olfactometer, we examined the specificity of the questing response of larvae of Boophilus microplus, a one-host tick which develops mainly on cattle, and Ixodes ricinus, a three-host tick with a broader host spectrum. While all mammalian odours tested were equally stimulatory for I. ricinus, B. microplus was clearly more activated by bovine odours. A phenolic fraction of bovine odour stimulated B. microplus only. Attractive components of the host odours were identified by exposing the ticks to single chemicals and mixtures. Single chemicals stimulated questing responses only at levels higher than the levels detected in the bovine odour. However, an artificial odour blend of 37 pure chemicals, diluted to concentrations at which the individual components were inactive, proved to be as effective as natural host odour for both tick species. Further fractionation of the blend revealed that the combinatory effect was achieved by only 7 compounds in both species. Although B. microplus responded to the same synergistic mixture of volatiles as I. ricinus, it showed significant higher sensitivity to the cattle-associated compounds 1-octen-3-ol and 2-nitrophenol and this might contribute to its host-specificity.


Prescribing for personality disorder: qualitative study of interviews with general and forensic consultant psychiatrists.
Aims and method To explore experiences of psychiatrists considering medication for patients with personality disorder by analysis of transcribed, semi-structured interviews with consultants. Results Themes show important relational processes in which not prescribing is expected to be experienced as uncaring rejection, and psychiatrists felt helpless and inadequate as doctors when unable to relieve symptoms by prescribing. Discontinuity in doctor-patient relationships compounds these problems. Clinical implications Problems arise from: (a) the psychopathology creating powerful relational effects in consultation; (b) the lack of effective treatments, both actual and secondary to under-resourcing and neglect of non-pharmaceutical interventions; and (c) the professionally constructed role of psychiatrists prioritising healing and cure through provision of technological interventions for specific diagnoses. There is a need for more treatments and services for patients with personality disorder; more support and training for psychiatrists in the relational complexities of prescribing; and a rethink of the trend for psychiatrists to be seen primarily as prescribers.


Effects of varying statistical uncertainty using a Monte Carlo based treatment planning system for VMAT.
To determine the severity of the effects on VMAT dose calculations caused by varying statistical uncertainties (SU) per control point in a Monte Carlo based treatment planning system (TPS) and to assess the impact of the uncertainty during dose volume histogram (DVH) evaluation. For this study, 13 archived patient plans were selected for recalculation. Treatment sites included prostate, lung, and head and neck. These plans were each recalculated five times with varying uncertainty levels using Elekta's Monaco Version 5.11.00 Monte Carlo Gold Standard XVMC dose calculation algorithm. The statistical uncertainty per control point ranged from 2 to 10% at intervals of 2%, while the grid spacing was set at 3 mm for all calculations. Indices defined by the RTOG describing conformity, coverage, and homogeneity were recorded for each recalculation. For all indices tested, one-way ANOVA tests failed to reject the null hypothesis that there is no significant difference between SU levels (p>0.05). Using the Bland-Altman analysis method, it was determined that we can expect the indices (with the exception of CIRTOG) to be within 1% of the lowest uncertainty calculation when calculating at 4% SU per control point. Beyond that, we can expect the indices to be within 3% of the lowest uncertainty calculation. Increasing the SU per control point exponentially decreased the amount of time required for dose calculations, while creating minimal observable differences in DVHs and isodose lines.


The value of pre-operative high resolution CT scans in cholesteatoma surgery.
Cholesteatoma is traditionally diagnosed by otoscopic examination and treated by explorative surgery. The need for imaging in an uncomplicated case is contentious. This study assesses the usefulness of a pre-operative high-resolution CT scan in depicting the status of the middle ear structures in the presence of cholesteatoma. The surgical findings of 36 ears with cholesteatoma operated on by the first author were retrospectively compared with the CT findings reported on by the second author. The following were analysed: diagnostic features of cholesteatoma on CT, status of the middle ear structures (ossicles, facial nerve canal, semicircular canals and tegmen tympani), and presence of any anatomical variations and disease complications. All cases had at least 1, and 30 cases (83.3%) had all, of the following radiological features: (a) a non-dependent tissue mass, (b) a location typical for cholesteatoma and (c) bony erosion. The radiosurgical agreement was excellent for the malleus (kappa statistics, k=0.83), stapes (0.94) and semicircular canals (0.8), good for the incus (0.62) and tegmen (0.65), but poor for the facial nerve canal (0.3). Potential surgical hazards detected by the scans included: low lying dura, high jugular bulb, anterior lying sigmoid sinus, facial nerve dehiscence and other situations brought about by the destructive nature of the lesion. There is good to excellent radiosurgical correlation in cholesteatoma for most middle ear structures except for the integrity of the facial canal. The scan alerts the surgeon to potential surgical dangers and complications of disease. High-resolution CT scan is an important investigative tool prior to cholesteatoma surgery.


Dose-Related Severity Sequence, and Risk-Based Integration, of Chemically Induced Health Effects.
Risk assessment of chemical hazards is typically based on single critical health effects. This work aims to expand the current approach by characterizing the dose-related sequence of the development of multiple (lower- to higher-order) toxicological health effects caused by a chemical. To this end a "reference point profile" is defined as the relation between benchmark doses for considered health effects, and a standardized severity score determined for these effects. For a given dose of a chemical or mixture the probability for exceeding the reference point profile, thereby provoking lower- to higher-order effects, can be assessed. The overall impact at the same dose can also be derived by integrating contributions across all health effects following severity-weighting. In its generalized form the new impact metric relates to the probability of response for the most severe health effects. Reference points (points of departure) corresponding to defined levels of response can also be estimated. The proposed concept, which is evaluated for dioxin-like chemicals, provides an alternative for characterizing the low-dose region below the reference point for a severe effect like cancer. The shape and variability of the reference point profile add new dimensions to risk assessment, which for example extends the characterization of chemical potency, and the concept of acceptable effect sizes for individual health effects. Based on the present data the method shows high stability at low doses/responses, and is also robust to differences in severity categorization of effects. In conclusion, the novel method proposed enables risk-based integration of multiple dose-related health effects. It provides a first step towards a more comprehensive characterization of chemical toxicity, and suggests a potential for improved low-dose risk assessment.


Stories of management in the future by young adults and young nurses.
Abstract Aim: The aim of this study was to describe the phenomenon of management by way of the ideas by secondary school students and young nurses. Background: Young adults are changing workplaces more than ever before, yet their work expectations and perspectives of management differ to those of previous generations. Methods: The data was collected from upper secondary school students and professionally educated nurses (n = 68), some of whom were immigrants (n = 41). Framed essays were used as a research method and emergent data was analysed using content analysis. Results: According to the results, good management involves systematic management, equality, appreciation of know-how, and the promotion of wellbeing at work. Conclusion: New perspectives on management were drawn from the study, in particular the multiple dimensions of equality in workplace organization and the manager's role in an employee's professional development process. Implication for nursing management: The interactive skills of the manager are emphasized in promoting wellbeing at work. This is especially so in multi-cultural teams, where the manager is expected to be adept at understanding intercultural communication and the values of young employees.


The 3C protease of enterovirus A71 counteracts the activity of host zinc-finger antiviral protein (ZAP).
Enterovirus A71 (EV-A71) is a positive-strand RNA virus that causes hand-foot-mouth disease and neurological complications in children and infants. Although the underlying mechanisms remain to be further defined, impaired immunity is thought to play an important role. The host zinc-finger antiviral protein (ZAP), an IFN-stimulated gene product, has been reported to specifically inhibit the replication of certain viruses. However, whether ZAP restricts the infection of enteroviruses remains unknown. Here, we report that EV-A71 infection upregulates ZAP mRNA in RD and HeLa cells. Moreover, ZAP overexpression rendered 293 T cells resistant to EV-A71 infection, whereas siRNA-mediated depletion of endogenous ZAP enhanced EV-A71 infection. The EV-A71 infection stimulated site-specific proteolysis of two ZAP isoforms, leading to the accumulation of a 40 kDa N-terminal ZAP fragment in virus-infected cells. We further revealed that the 3C protease (3Cpro) of EV-A71 mediates ZAP cleavage, which requires protease activity. Furthermore, ZAP variants with single amino acid substitutions at Gln-369 were resistant to 3Cpro cleavage, implying that Gln-369 is the sole cleavage site in ZAP. Moreover, although ZAP overexpression inhibited EV-A71 replication, the cleaved fragments did not show this effect. Our results indicate that an equilibrium between ZAP and enterovirus 3Cpro controls viral infection. The findings in this study suggest that viral 3Cpro mediated ZAP cleavage may represent a mechanism to escape host antiviral responses.


Calcium phosphate composite layers for surface-mediated gene transfer.
In this review, the surface-mediated gene transfer system using calcium phosphate composite layers is described. Calcium phosphate ceramics are osteoconductive bioceramics used typically in orthopedic and dental applications. Additionally, calcium phosphate particles precipitated by a liquid-phase process have long been used as a safe and biocompatible transfection reagent in molecular biology. Recently, calcium phosphate composite layers immobilizing DNA were fabricated on the surfaces of base materials through a biomimetic process using supersaturated solutions. These composite layers possess useful characteristics of both osteoconductive bioceramics and transfection reagents; they thus provide a biocompatible surface to support cell adhesion and growth, and can stimulate the cell effectively via surface-mediated gene transfer. By modifying the fabrication conditions, physicochemical and biological properties of the composite layers can be varied. With such an approach, these composite layers can be designed to have improved affinity for cells and to exhibit increased gene transfer efficiency over that of conventional lipid transfection reagents. The composite layers with the increased gene transfer efficiency induced specific cell differentiation and tissue regeneration in vivo. These composite layers, given their good biocompatibility and the potential to control cell behavior on their surfaces, have great potential in tissue engineering applications.


Low cost, p-ZnO/n-Si, rectifying, nano heterojunction diode: Fabrication and electrical characterization.
A low cost, highly rectifying, nano heterojunction (p-ZnO/n-Si) diode was fabricated using solution-processed, p-type, ZnO nanoparticles and an n-type Si substrate. p-type ZnO nanoparticles were synthesized using a chemical synthesis route and characterized by XRD and a Hall effect measurement system. The device was fabricated by forming thin film of synthesized p-ZnO nanoparticles on an n-Si substrate using a dip coating technique. The device was then characterized by current-voltage (I-V) and capacitance-voltage (C-V) measurements. The effect of UV illumination on the I-V characteristics was also explored and indicated the formation of a highly rectifying, nano heterojunction with a rectification ratio of 101 at 3 V, which increased nearly 2.5 times (232 at 3 V) under UV illumination. However, the cut-in voltage decreases from 1.5 V to 0.9 V under UV illumination. The fabricated device could be used in switches, rectifiers, clipper and clamper circuits, BJTs, MOSFETs and other electronic circuitry.


Expression of coordinately regulated defence response genes and analysis of their role in disease resistance in Medicago truncatula.
Microarray technology was used to identify the genes associated with disease defence responses in the model legume Medicago truncatula. Transcript profiles from M. truncatula cv. Jemalong genotype A17 leaves inoculated with Colletotrichum trifolii and Erysiphe pisi and roots infected with Phytophthora medicaginis were compared to identify the genes expressed in response to all three pathogens and genes unique to an interaction. The A17 genotype is resistant to C. trifolii and E. pisi, exhibiting a hypersensitive response after inoculation, and is moderately susceptible to P. medicaginis. Among the most strongly up-regulated genes in all three interactions were those encoding a hevein-like protein, thaumatin-like protein (TLP) and members of the pathogenesis response (PR)10 family. Transcripts of genes for enzymes in the phenylpropanoid pathway leading to the production of isoflavonoid phytoalexins increased dramatically in response to inoculation with the foliar pathogens. In P. medicaginis-inoculated roots, transcripts of genes in the phenylpropanoid pathway peaked at 5 days post-inoculation, when symptoms became visible. Transcript accumulation of three PR10 family members, a TLP and chalcone synthase (CHS) was assessed in M. truncatula genotype R108 plants. The R108 plants are resistant to C. trifolii and moderately susceptible to E. pisi and P. medicaginis. Transcript accumulation paralleled the stages of pathogen development. To evaluate the role of a TLP, a PR10 family member and CHS in disease resistance, transgenic R108 plants containing interfering RNA (RNAi) constructs were produced. Reduced expression of PR10 and TLP had no effect on the disease phenotype, whereas reduced expression of CHS resulted in increased susceptibility to necrotrophic pathogens.


The implications of respondent concurrency on sex partner risk in a national, web-based study of men who have sex with men in the United States.
Men who have sex with men (MSM) represent the largest HIV risk group in the United States. Sexual concurrency catalyzes HIV transmission in populations by increasing the indirect exposure of one's sex partners to one another. Although individual-level (egocentric) designs have demonstrated a high prevalence of concurrency among MSM respondents, methods are lacking for understanding the exposure implications for partners (dyads) reported in such studies. A new technique for manipulating egocentrically collected partnership timing data to measure the degree to which respondents' patterns of concurrency and serial monogamy resulted in the indirect exposure of respondents' partners to other partners was developed. Two outcomes were constructed for each partner: any concurrent or serially monogamous exposure to another partner (any exposure) and any concurrent exposure to another partner, irrespective of serial monogamy (any concurrent exposure). Reports of unprotected anal intercourse (UAI) were incorporated to construct the outcomes of 'any UAI exposure' and 'any concurrent UAI exposure.' This method was applied to an online study of MSM aged ≥18 years, with comparisons made by partner's race-ethnicity, age, type, and meeting location. Among 4060 repeat partners of 2449 MSM, 73% had any exposure in the previous 6 months; 58% had any concurrent exposure. Among UAI partners, 37% had concurrent UAI exposure. Black UAI partners were more likely than whites to have any concurrent UAI exposure [unadjusted odds ratio (95% confidence interval) = 1.34 (1.05 to 1.70)], as were casual UAI partners relative to main partners [unadjusted odds ratio (95% confidence interval) = 4.37 (3.58 to 5.35)]. In adjusted models, black UAI partners were significantly more likely to have any UAI exposure, but not concurrent UAI exposure. Casual UAI partners remained more exposed by both outcomes. Sex partners of MSM, particularly casual and black non-Hispanic partners, face a high degree of exposure to other partners.


The cellular contributions of blastema and stump to 180 degrees supernumerary limbs in the axolotl.
By inverting triploid blastemas onto diploid stumps (and vice versa) the cellular contributions to supernumerary limbs so generated have been assessed. The four classes of 180 degrees supernumerary limbs each had a different mixture of stump and blastemal cells. The mesoderm of normal supernumeraries was composed entirely or almost entirely of stump cells and were always of stump handedness. The mesoderm of symmetrical supernumeraries was of variable composition, it could be mostly stump, mostly blastema or half and half. In part normal/part symmetrical supernumeraries the normal part was usually of stump origin and the aberrant symmetrical part of blastemal origin. In part normal/part inverted supernumeraries the normal part came from the stump and the inverted part from the inverted blastema. The handedness of each part of these supernumeraries corresponded with its cellular origin. The epidermis of the supernumeraries was not of the same relative composition as the mesoderm, it tended to have a larger stump component. The black/white marker was also used and this too tended not to conform to the mesodermal contribution patterns. These results are discussed in terms of rules for generating supernumeraries and it is concluded that with the exception of symmetrical supernumeraries the cellular contributions of stump and blastema determine their structure.


Prospective large-scale field study generates predictive model identifying major contributors to colony losses.
Over the last decade, unusually high losses of colonies have been reported by beekeepers across the USA. Multiple factors such as Varroa destructor, bee viruses, Nosema ceranae, weather, beekeeping practices, nutrition, and pesticides have been shown to contribute to colony losses. Here we describe a large-scale controlled trial, in which different bee pathogens, bee population, and weather conditions across winter were monitored at three locations across the USA. In order to minimize influence of various known contributing factors and their interaction, the hives in the study were not treated with antibiotics or miticides. Additionally, the hives were kept at one location and were not exposed to potential stress factors associated with migration. Our results show that a linear association between load of viruses (DWV or IAPV) in Varroa and bees is present at high Varroa infestation levels (>3 mites per 100 bees). The collection of comprehensive data allowed us to draw a predictive model of colony losses and to show that Varroa destructor, along with bee viruses, mainly DWV replication, contributes to approximately 70% of colony losses. This correlation further supports the claim that insufficient control of the virus-vectoring Varroa mite would result in increased hive loss. The predictive model also indicates that a single factor may not be sufficient to trigger colony losses, whereas a combination of stressors appears to impact hive health.


How and why children instigate talk in pediatric allergy consultations: A conversation analytic account.
Involving children in their healthcare encounter is a national and international priority. While existing research has examined the ways in which children are recruited to participate in the consultation, no work has examined whether and how children instigate talk, and the extent to which their contributions are successful. This paper presents a conversation analysis of a selection of 10 out of 30 video recordings in which children aged 4-10 years instigate talk during consultations they attend with their parents/carers at a UK pediatric clinic. The analysis reveals for the first time that children do successfully instigate talk without being asked or selected in 22 episodes during their consultation with the doctor. Children most frequently address their parent/carer (16/22). They capitalize on specific contexts within the consultation to instigate talk, for example: history-taking questions about what they ate or how they reacted (10/22); or discussions surrounding the child's feelings or sensations following the skin-prick testing (7/22) - aspects of experience to which they have access. Children's non-solicited talk necessarily occurs when they are not currently active participators and children engage in extra interactional work including various verbal strategies (summons and prosodic variations) and non-verbal resources (tapping and gaze) to break into the interaction. The benefits of their contributions include the opportunity to affirm the child's role as a legitimate contributor, and the potential for additional medically-relevant information to arise which could enrich the clinical process. Our analysis shows that the previously overlooked phenomenon of children instigating talk, although not common, can play a crucial role in the consultation. We suggest that strategies to increase such involvement have the potential to augment the healthcare process. Our findings offer a critical baseline for the introduction of new consultations models, such as digital appointments, which may exclude some children completely.


Emergence of colistin resistance in Enterobacteriaceae after the introduction of selective digestive tract decontamination in an intensive care unit.
Selective decontamination of the digestive tract (SDD) selectively eradicates aerobic Gram-negative bacteria (AGNB) by the enteral administration of oral nonabsorbable antimicrobial agents, i.e., colistin and tobramycin. We retrospectively investigated the impact of SDD, applied for 5 years as part of an infection control program for the control of an outbreak with extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae in an intensive care unit (ICU), on resistance among AGNB. Colistin MICs were determined on stored ESBL-producing K. pneumoniae isolates using the Etest. The occurrence of both tobramycin resistance among pathogens intrinsically resistant to colistin (CIR) and bacteremia caused by ESBL-producing K. pneumoniae and CIR were investigated. Of the 134 retested ESBL-producing K. pneumoniae isolates, 28 were isolated before SDD was started, and all had MICs of <1.5 mg/liter. For the remaining 106 isolated after starting SDD, MICs ranged between 0.5 and 24 mg/liter. Tobramycin-resistant CIR isolates were found sporadically before the introduction of SDD, but their prevalence increased immediately afterward. Segmented regression analysis showed a highly significant relationship between SDD and resistance to tobramycin. Five patients were identified with bacteremia caused by ESBL-producing K. pneumoniae before SDD and 9 patients thereafter. No bacteremia caused by CIR was found before SDD, but its occurrence increased to 26 after the introduction of SDD. In conclusion, colistin resistance among ESBL-producing K. pneumoniae isolates emerged rapidly after SDD. In addition, both the occurrence and the proportion of tobramycin resistance among CIR increased under the use of SDD. SDD should not be applied in outbreak settings when resistant bacteria are prevalent.


Thalamocortical network interruption: A fresh view for migraine symptoms
Migraine is a multifaceted brain disorder where multisensory disturbances are associated with headache. Yet sensory symptoms are conventionally justified by dysfunctions confined to the cerebral cortex, a perspective through the complex interplay of thalamocortical network would provide the entire picture, more pertinent to the central sensory processing. It is important to consider thalamus as a hub that integrates multiple domains via extensive connections among anatomically and functionally separate cortical areas. Accordingly, cortical spreading depression (CSD), implicated in migraine pathophysiology can be seen as a tool to disconnect thalamocortical network by functionally eliminating cerebral cortex. Hence, including thalamic reticular nucleus and higher order thalamic nuclei, which conveys the information transthalamically among visual, somatosensory, language and motor cortical areas, would greatly improve our current understanding of migraine.


Spatiotemporal changes of carbon storage in forest carbon pools of Western Turkey: 1972-2016.
This study analyzes the impacts of spatiotemporal changes on C dynamics based on the various C pools and forest structure in western Turkey. The forest C dynamics were projected by forest inventory data between 1972 and 2016, and the spatial distribution of C storage was mapped by GIS. Total C storage increased from 1135.22 Gg in 1972 to 1816.60 Gg in 2016 with a net accumulation of 681.38 Gg. While the largest contribution to C pool was from soil organic carbon with 58.6% and 49.3% of the total C storage in 1972 and 1994, it was from living biomass with 54.0% and 57.7% in 2004 and 2016, respectively. The mean annual C sequestration was 1.57 Mg ha-1 year-1, including 1.49 Mg ha-1 year-1 in biomass and 0.08 Mg ha-1 year-1 in soil over four decades. The mixed cover type was the most significant contributor to biomass, soil, and total C storages. However, the hardwood cover type was the most significant contributor to C densities due to the higher growing stock. The mature development stages (35.6 Gg year-1), the fully covered areas (13.2 Gg year-1), and the older forests have played an essential role in C sequestration. The spatial distribution of C dynamics was heterogenic due to forest cover type, forest structure, and species composition. Monitoring spatiotemporal changes in forest ecosystems in terms of forest cover type, development stage, coverages, and age class distribution can provide opportunities in developing effective forest management policies based on the ecological sustainability of C pools and mitigating climate change effects.


Development of lymphoma in the thymus of AKR mice treated with the lymphomagenic virus SL 3-3.
A chronological study of the individual thymic lobes of young AKR mice after neonatal inoculation of the oncogenic AKR retrovirus SL 3-3 was performed. 100% of mice treated in this manner develop lymphoma between 60 and 100 days of age. A search for early lymphoma cells in individual thymi was carried out by inoculating the thymocytes subcutaneously in syngeneic and intrathymically in syngeneic and semisyngeneic recipients. Tumor progression was observed in animals between 48 and 60 days of age. These animals have: (a) normal weight lobes, in which no lymphoma cells could be detected, (b) thymus-dependent lymphoma cells, in one or both normal weight lobes; (c) thymus-independent lymphoma cells, found in lobes of normal weight as well as in thymi enlarged by lymphoma cells. Thymocyte characteristics of virus-treated animals of 21 to 63 days of age were compared with those of age-matched controls. Beginning at 28 days a concordant, progressive with time, increase of thymocyte surface staining for the viral envelope glycoprotein gp70 was seen in all lobes from virus-treated animals. Evaluation of cell surface markers by two-color fluorescence with antibodies to CD4 and CD8 showed that after 50 days of age, thymic lobes with and without lymphomas had nonspecific, but marked, alterations of the typical thymocyte surface marker pattern. No characteristic CD4, CD8 surface phenotype was found in primary lymphomas. Using probes for the T-cell receptor J beta 2 gene segments and the Akv ecotropic virus gp70 envelope genes, oligoclonality in J beta 2 rearrangements and clonality using the Akv env genes was demonstrated in thymi with the thymus-dependent phenotype. In lymphomas T-cell receptor beta gene probes showed either oligoclonality or clonality. Clonal virus integrations were found in these lymphomas. These experiments suggest the following series of events in virus-accelerated AKR lymphomagenesis. First, lymphoma cells arise which are initially thymus-dependent and can appear in one or simultaneously in both thymic lobes. These progress to become thymus-independent, fully autonomous, tumor cells. Thymocytes close to or at the time of the initial transformation event show a marked disorder of differentiation defined by the alterations in the CD4, CD8 surface phenotype distribution.


Quality audit of the guidelines for the use of RhD immunoglobulin in obstetrics: Are we getting it right?
Administration of RhD immunoglobulin (Ig) is important for RhD negative women throughout pregnancy and postnatally to prevent alloimmunisation and haemolytic disease of the fetus and newborn in subsequent pregnancies. The aim of this audit was to understand compliance with the Australian guidelines on RhD Ig prophylaxis in pregnancy. This was a retrospective audit of RhD negative pregnant women in Victoria, Northern Territory, Australian Capital Territory and Tasmania at maternity services of level 2 or higher care, between July 2017 and June 2018. Medical records were reviewed to identify how many RhD negative women received care compliant with the guidelines covering antibody testing, consent, administration of RhD Ig, and feto-maternal haemorrhage (FMH) quantification. Analysis included 939 RhD negative women from 43 health services. Compliance with postnatal RhD Ig was high (98%); however, other practice was poor. Documented consent was obtained and recorded for 585 women (62%). Only 76% of eligible women received RhD Ig at the appropriate dose and time (28 and 34 weeks gestation). Similarly, management of potentially sensitising events was suboptimal with 78% receiving RhD Ig when recommended by guidelines. The results of our audit indicate a need for practice improvement across all aspects of care for women who need to receive RhD Ig. A major focus should be not just educating clinical staff, but also educating women to understand the importance of RhD Ig and the potential impact on subsequent pregnancies in order to improve guideline adherence and reduce risk.


Necrotizing enterocolitis in the neonate.
Necrotizing enterocolitis has become the most common condition requiring emergency surgical treatment in the newborn infant, far surpassing all major congenital anomalies in number of presentations and in deaths after surgical treatment. No single cause for the disease is known. Necrotizing enterocolitis is characterized by ischemic necrosis of the intestine, with minimal inflammation. In 25 of 50 per cent of patients, surgical resection of gangrenous bowel is necessary. Operation is reserved for infants with intestinal perforation or grangrene. Recent refinements of indications for operation often permit surgical intervention to coincide with the advent of intestinal gangrene. At operation, expeditious resection of frankly necrotic bowel and exteriorization of the marginally viable ends is all that should be attempted. Special problems postoperatively consist of management of sepsis, maintenance of nutrition and vigilant observation for early and late complications, particularly the development of ischemic intestinal stricture.


[Community analysis serving as a foundation for community-based health promotion programming--results of a citizen survey in Karlshuld, Germany].
Analysing a community's needs and requirements is useful for planning a community-based health promotion programme. The literature recommends the analysis of existing population-based data, the discussion with a community's key persons, and standardised surveys among the community members. With regagrd to the latter method, German-language literature is scarce. A community analysis in the Bavarian rural community Karlshuld (5 000 inhabitants) was intended to provide a starting point for tailored health promotion activities in the community. As a part of the community analysis, a survey among the Karlshuld citizens was intended to inform about (1) health-related knowledge and behaviour of the community members, (2) their utilization and acceptance of existing health-related offers and activities, (3) their possibilities for active participation, their state of empowerment and (4) community-related aspects influencing quality of life. A standardised telephone survey was performed with a random sample of Karlshuld community members aged 15 years and older. The questions covered health-related living conditions and activities in Karlshuld, quality of life and participation of community members. In addition, data were collected on knowledge, attitude and behaviour with regard to the issues nutrition, physical activity and tobacco consumption. The sample comprised 314 community members (f=68.8%; age 43.9+/-13.8 years). Shortcomings in knowledge on healthy nutrition were evident, especially among male participants. Whereas the general attitude towards a healthy diet was favourable in the majority of respondents, only 45.9%/58.6% stated that they daily consumed vegetables/fruit. One third of the 27.4% smokers among the respondents had intended but failed to quit smoking in the previous year; 80% stated they were willing to quit. The participants named infrastructure, nature and health-related activities as positive aspects in Karlshuld. Only 50% knew where to get information on health-related issues. 42.9% of respondents felt they could influence decisions on health-related issues in the community. There was no correlation between school education and knowledge or participation. The survey among Karlshuld community members identified potential approaches to improving the community environment and to tailor health education activities to the special needs of Karlshuld. A follow-up survey in 2008/2009 will be carried out in order to evaluate whether or not the Karlshuld health promotion programme was successful in building on Karlshuld's strengths and influencing its weaknesses.


Effect of oxygen on breathing irregularities during haemodialysis in patients with chronic uraemia.
Hypoxaemia and breathing irregularities have been shown to occur during haemodialysis in patients with chronic renal failure. This study examined the role of hypoxia in the genesis of the irregular breathing during haemodialysis. The ventilatory patterns using respiratory inductance plethysmography and arterial blood gases were studied in seven males with chronic renal failure on long-term haemodialysis. The study was carried out before and during dialysis on one day without (D1) and another day with intranasal oxygen at 4 L x min(-1) (D2). On D1, mean (SD) arterial oxygen tension (Pa,O2) fell 1.9 (0.9) kPa (p<0.001) and mean minute ventilation (V'E) fell 1.9 (1.1) L x min(-1) (p<0.01) during dialysis. The arterial carbon dioxide tension (Pa,CO2) did not show a significant decrease (4.7 (0.2) kPa before and 4.6 (0.2) kPa during dialysis). Cumulative number of apnoeas was 64 and the coefficients of variation (COV) of respiratory frequency (fR) and tidal volume (VT) were 29.6 (11.9) and 38.2 (11.9)%, respectively. On D2, mean Pa,O2 remained stable (20.4 (4.1) kPa before, 21.3 (4.1) kPa during dialysis). There was no significant change in mean V'E (6.4 (0.9) L x min(-1) before, 5.5 (0.5) L x min(-1) during dialysis). Pa,CO2 decrease was not significant but the fall was greater (4.8 (0.1) kPa before, 45 (0.5) kPa during dialysis). Cumulative number of apnoeas was 94 and the COVs offR and VT were 35.8 (5.1) and 40.5 (11.3)%, respectively. Oxygen administration did not significantly affect the haemodialysis-induced changes in ventilation and breathing pattern, despite a significant protective effect from the fall in arterial oxygen tension. It was concluded that the fall in arterial oxygen tension is not the main determinant of breathing irregularities during haemodialysis.