Frequency of the Types of Alopecia at Twenty-Two Specialist Hair Clinics: A Multicenter Study.
The frequency of different types of alopecia is not clearly reported in recent studies. To analyze the frequency of the types of alopecia in patients consulting at specialist hair clinics (SHC) and to assess for global variations. Multicenter retrospective study including data from patients evaluated at referral SHC in Europe, America, Africa and Australia. A total of 2,835 patients (72.7% females and 27.3% males) with 3,133 diagnoses of alopecia were included (73% were non-cicatricial and 27% were cicatricial alopecias). In all, 57 different types of alopecia were characterized. The most frequent type was androgenetic alopecia (AGA) (37.7%), followed by alopecia areata (AA) (18.2%), telogen effluvium (TE) (11.3%), frontal fibrosing alopecia (FFA) (10.8%), lichen planopilaris (LPP) (7.6%), folliculitis decalvans (FD) (2.8%), discoid lupus (1.9%) and fibrosing alopecia in a pattern distribution (FAPD) (1.8%). There was a male predominance in patients with acne keloidalis nuchae, dissecting cellulitis and FD, and female predominance in traction alopecia, central centrifugal cicatricial alopecia, FFA, TE, FAPD and LPP. AGA followed by AA and TE were the most frequent cause of non-cicatricial alopecia, while FFA was the most frequent cause of cicatricial alopecia in all studied geographical areas.


Salt increases monocyte CCR2 expression and inflammatory responses in humans.
Inflammation may play a role in the link between high salt intake and its deleterious consequences. However, it is unknown whether salt can induce proinflammatory priming of monocytes and macrophages in humans. We investigated the effects of salt on monocytes and macrophages in vitro and in vivo by performing a randomized crossover trial in which 11 healthy human subjects adhered to a 2-week low-salt and high-salt diet. We demonstrate that salt increases monocyte expression of CCR2, a chemokine receptor that mediates monocyte infiltration in inflammatory diseases. In line with this, we show a salt-induced increase of plasma MCP-1, transendothelial migration of monocytes, and skin macrophage density after high-salt diet. Macrophages demonstrate signs of an increased proinflammatory phenotype after salt exposure, as represented by boosted LPS-induced cytokine secretion of IL-6, TNF, and IL-10 in vitro, and by increased HLA-DR expression and decreased CD206 expression on skin macrophages after high-salt diet. Taken together, our data open up the possibility for inflammatory monocyte and macrophage responses as potential contributors to the deleterious effects of high salt intake.


A scoping review of trials of interventions led or delivered by cancer nurses.
Advances in research and technology coupled with an increased cancer incidence and prevalence have resulted in significant expansion of cancer nurse role, in order to meet the growing demands and expectations of people affected by cancer (PABC). Cancer nurses are also tasked with delivering an increasing number of complex interventions as a result of ongoing clinical trials in cancer research. However much of this innovation is undocumented, and we have little insight about the nature of novel interventions currently being designed or delivered by cancer nurses. To identify and synthesise the available evidence from clinical trials on interventions delivered or facilitated by cancer nurses. A systematic review of randomised controlled trials (RCT), quasi-RCTs and controlled before and after studies (CBA) of cancer nursing interventions aimed at improving the experience and outcomes of PABC. Ten electronic databases (CENTRAL, MEDLINE, AMED, CINAHL, EMBASE, Epistemonikos, CDSR, DARE, HTA, WHO ICTRP) were searched between 01 January 2000 and 31 May 2016. No language restrictions were applied. Bibliographies of selected studies and relevant Cochrane reviews were also hand-searched. Interventions delivered by cancer nurses were classified according to the OMAHA System. Heat maps were used to highlight the volume of evidence available for different cancer groups, intervention types and stage of cancer care continuum. The search identified 22,450 records; we screened 16,169 abstracts and considered 925 full papers, of which 214 studies (247,550 participants) were included in the evidence synthesis. The majority of studies were conducted in Europe (n = 79) and USA (n = 74). Interventions were delivered across the cancer continuum from prevention and risk reduction to survivorship, with the majority of interventions delivered during the treatment phase (n = 137). Most studies (131/214) had a teaching, guidance or counselling component. Cancer nurse interventions were targeted at primarily breast, prostate or multiple cancers. No studies were conducted in brain, sarcoma or other rare cancer types. The majority of the studies (n = 153) were nurse-led and delivered by specialist cancer nurses (n = 74) or advanced cancer nurses (n = 29), although the quality of reporting was poor. To the best of our knowledge, this is the first review to synthesise evidence from intervention studies across the entire cancer spectrum. As such, this work provides new insights into the nature of the contribution that cancer nurses have made to evidence-based innovations, as well as highlighting areas in which cancer nursing trials can be developed in the future.


Enhanced growth of tellurium nanowires under conditions of macromolecular crowding.
An unprecedented rate enhancement was observed in the wet-chemical synthesis of tellurium nanowires under crowded conditions of inert macromolecules. The synthesis was carried out at 105 °C using solutions of sodium tellurite (Na2TeO3) as a precursor, hydrazine (N2H4) as a reducing agent, and polyvinylpyrrolidone (PVP) as both a stabilizing and crowding agent. The PVP concentration was systematically varied between the dilute and crowding regimes up to 166 g l-1. The growth of the nanowires was monitored by measuring their size-dependent optical properties in the UV-Vis spectrum characterizing the size and morphology evolution of the nanowires and a coexisting phase of amorphous tellurium nanoparticles. The observed growth characteristics were interpreted in terms of non-specific structural organization of the crowded media due to the entropic-driven effects of space compartmentalization.


Providing an Outdoor Exercise Area Affects Tie-Stall Cow Reactivity and Human-Cow Relations.
Confinement and restriction of movement are a reality for most dairy cows. Providing outdoor access is one method to increase movement opportunities. However, leading cows to an outdoor exercise area increases their exposure to manipulations different from those of an indoor housing system. These situations have the potential to induce fear reactions, which can lead to injuries for the cow and danger or economic losses for the farmer. Our aim was to evaluate the development of the human-cow relationship and general reactivity of cows after a 12-week period of outdoor access provision in winter, summer and fall. A total of 16 cows in the winter, 16 in the summer, and 15 in the fall were enrolled in the study and either allocated to the treatment (Out) or stayed in the tiestall (NonOut). A human reactivity test and suddenness test were performed before and after the 12-week treatment period. In winter and to a lesser extent in fall, Out cows had a better human reaction score compared to NonOut cows, suggesting that cows with outdoor access during the winter associated human approaches with positive events. Conversely, no difference in the human reaction score was found between treatments during the summer. For summer and fall, Out cows did, however, show a decrease in their reaction score to the suddenness test compared to NonOut cows. The results of the human reactivity test in the summer suggested that cows with outdoor access did not associate the manipulation with a positive event. Interestingly, this result is not due to the cows being more frightened, since the suddenness test suggested that the Out cows were less fearful than NonOut cows. The way in which cows were led to the outdoor area could explain the differences in cow responses. Here, summer cows faced greater movement restrictions during trips to the outdoor area than in the winter, which may have been negatively perceived by the cows. We conclude that, besides the provision of outdoor access, the manner in which cows are handled during these events may have significant impacts on their reactions and could facilitate future handling.


MiR-351 transiently increases during muscle regeneration and promotes progenitor cell proliferation and survival upon differentiation.
MicroRNAs (miRNAs) regulate many biological processes including muscle development. However, little is known regarding miRNA regulation of muscle regeneration. Murine tibialis anterior muscle was evaluated after cardiotoxin-induced injury and used for global miRNA expression analysis. From day 1 through day 21 following injury, 298 miRNAs were significantly changed at least at one time point, including 86 miRNAs that were altered >10-fold compared with uninjured skeletal muscle. Temporal miRNA expression patterns included inflammation-related miRNAs (miR-223 and -147) that increased immediately after injury; this pattern contrasted to that of mature muscle-specific miRNAs (miR-1, -133a, and -499) that abruptly decreased following injury followed by upregulation in later regenerative events. Another cluster of miRNAs were transiently increased in the early days of muscle regeneration including miR-351, a miRNA that was also transiently expressed during myogenic progenitor cell (MPC) differentiation in vitro. Based on computational predictions, further studies demonstrated that E2f3 was a target of miR-351 in myoblasts. Moreover, knockdown of miR-351 expression inhibited MPC proliferation and promoted apoptosis during MPC differentiation, whereas miR-351 overexpression protected MPC from apoptosis during differentiation. Collectively, these observations suggest that miR-351 is involved in both the maintenance of MPC proliferation and the transition into differentiated myotubes. Thus, a novel, time-dependent sequence of molecular events during muscle regeneration has been identified; miR-351 inhibits E2f3 expression, a key regulator of cell cycle progression and proliferation, and promotes MPC proliferation and protects early differentiating MPC from apoptosis, important events in the hostile tissue environment after acute muscle injury.


The clinical safety and efficacy of conventional transcatheter arterial chemoembolization and drug-eluting beads-transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: A meta-analysis.
Transcatheter arterial chemoembolization (TACE) plays an important role in the treatment of unresectable liver cancer. We conducted this meta-analysis to compare the clinical safety and efficacy of conventional TACE (C-TACE) and drug-eluting beads (DEB)-TACE. A search for those procedures was performed using the PubMed, EMBASE, and Cochrane Library databases. A meta-analysis of patients who underwent C-TACE or DEB-TACE was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Of 334 studies, 30 were analyzed. The complete response rate, disease control rate, objective response rate, 3-year survival rate, and non-response rate were significantly higher in patients who underwent DEB-TACE than those in patients who underwent C-TACE. The 1-year survival rate, 2-year survival rate, 30-day mortality rate, complete response rate, disease control rate, complete necrosis rate, non-response rate, objective response rate, progressive disease rate, and recurrence did not differ significantly between patients who underwent C-TACE and patients who underwent DEB-TACE. Patients who undergo DEB-TACE might have a higher complete response rate, disease control rate, and 3-year survival rate than patients who undergo C-TACE. Safety did not differ significantly between C-TACE and DEB-TACE.


Larrad biliopancreatic diversion in Sprague-Dawley rats. Analysis of weight loss related to food intake.
Existing medical therapeutic strategies to achieve and maintain clinically significant weight loss in morbid obesity remain limited and the biliopancreatic diversion (BPD) is still the most effective among the bariatric surgical procedures. Our objective was to evaluate the weight and food intake after this procedure in a rat model. Rats randomly underwent one of the following protocols (1) BPD (n = 12) versus sham (n = 12) with a follow-up period of 30 days and (2) BPD (n = 4) versus pair-fed (PF; n = 4) with a follow-up period of 50 days. Under intraperitoneal anesthesia with ketamine-xilacine, a subcardinal corpo-antral gastrectomy was made, preserving the gastric fundus that was anastomosed to a jejunal limb after dissecting the proximal jejunum 5 cm below the ligament of Treitz to form the alimentary limb. The biliopancreatic limb was terminolaterally anastomosed to the distal ileum 5 cm above the ileocecal valve to form the common limb. Sham animals underwent only abdominal incision. Weight and food intake were measured every day. In protocol 1, after postoperative day 30, BPD rats exhibited a mean weight reduction of 17.9% while shams increased 12.4%. There was no difference in food intake adjusted per 100 g of body weight. In protocol 2, after postoperative day 50, BPD rats had a mean weight reduction of 22.6% and, despite increasing their caloric intake from a mean of 42.6 after 6 days to 65.8 kcal/day after 50 days, they kept a similar mean weight of 344.0 and 340.2 g, respectively; on the contrary, PF rats exhibited a 30.8% body weight gain. After the BPD, body weight is maintained independently of changes in food and energy intake.


Dosage rescue by UBC4 restores cell wall integrity in Saccharomyces cerevisiae lacking the myosin type II gene MYO1.
Myosin II is important for normal cytokinesis and cell wall maintenance in yeast cells. Myosin II-deficient (myo1) strains of the budding yeast Saccharomyces cerevisiae are hypersensitive to nikkomycin Z (NZ), a competitive inhibitor of chitin synthase III (Chs3p), a phenotype that is consistent with compromised cell wall integrity in this mutant. To explain this observation, we hypothesized that the absence of myosin type II will alter the normal levels of proteins that regulate cell wall integrity and that this deficiency can be overcome by the overexpression of their corresponding genes. We further hypothesized that such genes would restore normal (wild-type) NZ resistance. A haploid myo1 strain was transformed with a yeast pRS316-GAL1-cDNA expression library and the cells were positively selected with an inhibitory dose of NZ. We found that high expression of the ubiquitin-conjugating protein cDNA, UBC4, restores NZ resistance to myo1 cells. Downregulation of the cell wall stress pathway and changes in cell wall properties in these cells suggested that changes in cell wall architecture were induced by overexpression of UBC4. UBC4-dependent resistance to NZ in myo1 cells was not prevented by the proteasome inhibitor clasto-lactacystin-beta-lactone and required the expression of the vacuolar protein sorting gene VPS4, suggesting that rescue of cell wall integrity involves sorting of ubiquitinated proteins to the PVC/LE-vacuole pathway. These results point to Ubc4p as an important enzyme in the process of cell wall remodelling in myo1 cells.


Anti-OX40 prevents effector T-cell accumulation and CD8+ T-cell mediated skin allograft rejection.
OX40 is a member of the tumor necrosis factor receptor superfamily and is a potent T-cell costimulatory molecule. Although the impact of blockade of the OX40-OX40L pathway has been documented in models of autoimmune disease, the effect on allograft rejection is less well defined. The expression of OX40 and impact of OX40 blockade on BM3 T cells (H2Kb-reactive, T-cell receptor-transgenic) after stimulation with alloantigen were assessed in vitro by the incorporation of 3H-thymidine and flow cytometry. In vivo, naïve BM3 or polyclonal CD8+ T cells were transferred into syngeneic recombinase-activating gene(-/-) mice, which received an H2b+ skin allograft with and without anti-OX40. Skin allograft survival was monitored, and the proliferation, number, and phenotype of BM3 T cells were determined using flow cytometry. In vitro allogeneic stimulation of CD8+ T cells resulted in OX40 expression, the blockade of which was found to partially inhibit 3H-thymidine incorporation as a result of increased cell death among activated T cells. Similarly, in vivo, anti-OX40 prevented skin allograft rejection mediated by CD8+ T cells. However, after cessation of anti-OX40 therapy, skin allografts were eventually rejected indicating that tolerance had not been induced. Correlating with the in vitro data, analysis of lymph nodes draining skin allografts revealed that OX40 blockade had no effect on the activation and proliferation of BM3 T cells but rather resulted in diminished effector T-cell accumulation. Taken together, these data demonstrate that anti-OX40 attenuates CD8+ T-cell responses to alloantigen by reducing the pool of effector T cells, suggesting that this may be a worthwhile adjunct to preexisting costimulatory molecule-blocking regimens.


Design of novel small molecule base-pair recognizers of toxic CUG RNA transcripts characteristics of DM1.
Myotonic Dystrophy type 1 (DM1) is an incurable neuromuscular disorder caused by toxic DMPK transcripts that carry CUG repeat expansions in the 3' untranslated region (3'UTR). The intrinsic complexity and lack of crystallographic data makes noncoding RNA regions challenging targets to study in the field of drug discovery. In DM1, toxic transcripts tend to stall in the nuclei forming complex inclusion bodies called foci and sequester many essential alternative splicing factors such as Muscleblind-like 1 (MBNL1). Most DM1 phenotypic features stem from the reduced availability of free MBNL1 and therefore many therapeutic efforts are focused on recovering its normal activity. For that purpose, herein we present pyrido[2,3-d]pyrimidin-7-(8H)-ones, a privileged scaffold showing remarkable biological activity against many targets involved in human disorders including cancer and viral diseases. Their combination with a flexible linker meets the requirements to stabilise DM1 toxic transcripts, and therefore, enabling the release of MBNL1. Therefore, a set of novel pyrido[2,3-d]pyrimidin-7-(8H)-ones derivatives (1a-e) were obtained using click chemistry. 1a exerted over 20% MBNL1 recovery on DM1 toxic RNA activity in primary cell biology studies using patient-derived myoblasts. 1a promising anti DM1 activity may lead to subsequent generations of ligands, highlighting a new affordable treatment against DM1.


Regulation of cholesterol homeostasis by the liver X receptors in the central nervous system.
The nuclear oxysterol receptors liver X receptor-alpha [LXRalpha (NR1H3)] and LXRbeta (NR1H2) coordinately regulate genes involved in cholesterol homeostasis. Although both LXR subtypes are expressed in the brain, their roles in this tissue remain largely unexplored. In this report, we show that LXR agonists have marked effects on gene expression in murine brain tissue both in vitro and in vivo. In primary astrocyte cultures, LXR agonists regulated several established LXR target genes, including ATP binding cassette transporter A1, and enhanced cholesterol efflux. In contrast, little or no effect on gene expression or cholesterol efflux was detected in primary neuronal cultures. Treatment of mice with a selective LXR agonist resulted in the induction of several LXR target genes related to cholesterol homeostasis in the cerebellum and hippocampus. These data provide the first evidence that the LXRs regulate cholesterol homeostasis in the central nervous system. Because dysregulation of cholesterol balance is implicated in central nervous system diseases such as Alzheimer's and Niemann-Pick disease, pharmacological manipulation of the LXRs may prove beneficial in the treatment of these disorders.


Management of Paratrichodorus allius Damage to Onion in the Columbia Basin of Oregon.
Production of storage and dehydration (dehy) onions is increasing rapidly in the northcentral Oregon region of the Columbia Basin. Roughly circular patches of stunted onions have been observed in many fields and are often numerous and (or) extensive in area. Onions in these patches often exhibit symptoms typical of stubby-root nematodes, and Paratrichodorus allius has been collected from several damaged areas. This study examined the relationship of P. allius densities to onion yield reduction and benefit from oxamyl application. Transect samples and onions harvested across areas with varying P. allius densities revealed that the total number of onions was not affected by P. allius but that onions were in smaller, less valuable size classes. Yield of the largest size class of storage onions (colossals) declined substantially (57-61%) even at low (5-16/250 g soil) nematode densities. Treatment with oxamyl at 1.1 kg a.i./ha mitigated most of the damage, and the value of both storage and dehy onions was increased by more than $1,200/ha. Early applications were superior to later applications, whereas treatment at both times was no better than the early treatment alone. Damage at low (<10/250 g soil) nematode densities, low treatment cost ($86-172/ha), and high crop values suggest an economic benefit from treatment at population densities of four or more P. allius/250 g soil. However, stunted patches of onions may occur for reasons other than nematodes, and the presence of P. allius should be confirmed before treating fields. This is the first report of stubby-root nematode damage to dehy onions and to storage onions in the Columbia Basin.


Resuscitation During Critical Care Transportation in Afghanistan.
These data describe the critical care procedures performed on, and the resuscitation markers of, critically wounded personnel in Afghanistan following point of injury (POI) transports and intratheater transports. Providing this information may help inform discussion on the design of critical care transportation platforms for future conflicts. The Department of Defense Trauma Registry (DoDTR) was queried for descriptive data on combat casualties with Injury Severity Score (ISS) greater than 15 who were transported in Operation Enduring Freedom (OEF) from 1 January 2010 to 31 December 2010. Both POI transportation events and interfacility transportation events were reviewed. Base deficit (BD) was evaluated as a maker of resuscitation, and international normalized ratio (INR) was evaluated as a measure of coagulopathy. There were 1198 transportation events that occurred during the study period--634 (53%) transports from the POI and 564 (47%) intratheater transports. Critical care interventions were performed during 147 (12.3%) transportation events, including intubation, cricothyrotomy, double-lumen endotracheal tube placement, needle or tube thoracostomy, central venous access placement, and cardiopulmonary resuscitation. The mean BD on arrival in the emergency department was -5.4 mEq/L for POI transports and 0.68 mEq/L intratheater transports (ρ<.001). The mean INR on arrival in the emergency department was 1.48 for POI transports and 1.21 for intratheater transports (ρ<.001). Critical care interventions were needed frequently during evacuation of severely injured personnel. Furthermore, many troops arrived acidotic and coagulopathic following initial transport from POI. Together, these data suggest that a platform capable of damage control resuscitation and critical care interventions may be warranted on longer transports of more critically injured patients.


Public service media, universality and personalisation through algorithms: mapping strategies and exploring dilemmas.
This contribution compares personalisation strategies of public service media (PSM) and how these are reconciled with PSM's core values, especially universality. To this end, it combines mapping of a sample of PSM with in-depth analysis of Flemish VRT and Norwegian NRK. The theoretical framework discusses universality in relationship to PSM's historical remit and to contemporary personalisation through digital options like algorithms. Subsequently, strategies of the sampled PSM are analysed, using data from documents, an online survey and interviews. Results suggest that most PSM, including VRT and NRK, engage in implicit and explicit digital personalisation, yet vary in type of engagement and in views on how personalisation strengthens or threatens universality. It is argued that histories and the understanding of technology within specific institutions affect their personalisation approach. We argue that policies focus on news and information but that negotiating universality and personalisation, while dealing with issues like filter bubbles and privacy, extends to the entire range of PSM programmes and goals.


Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most potent and perilous diseases known, with a median survival rate of 3-5 months due to the combination of only advanced stage diagnosis and ineffective therapeutic options. Metformin (1,1-Dimethylbiguanide hydrochloride), the leading drug used for type 2 diabetes mellitus, emerges as a potential therapy for PDAC and other human cancers. Metformin exerts its anticancer action via a variety of adenosine monophosphate (AMP)-activated protein kinase (AMPK)- dependent and/or AMPK-independent mechanisms. We present data here showing that metformin downregulated pancreatic transcription factor pancreatic duodenal homeobox-1 (PDX-1), suggesting a potential novel mechanism by which metformin exerts its anticancer action. Metformin inhibited PDX-1 expression at both protein and mRNA levels and PDX-1 transactivity as well in PDAC cells. Extracellular signal-regulated kinase (ERK) was identified as a PDX-1-interacting protein by antibody array screening in GFP-PDX-1 stable HEK293 cells. Co-transfection of ERK1 with PDX-1 resulted in an enhanced PDX-1 expression in HEK293 cells in a dose-dependent manner. Immunoprecipitation/Western blotting analysis confirmed the ERK-PDX-1 interaction in PANC-1 cells stimulated by epidermal growth factor (EGF). EGF induced an enhanced PDX-1 expression in PANC-1 cells and this stimulation was inhibited by MEK inhibitor PD0325901. Metformin inhibited EGF-stimulated PDX-1 expression with an accompanied inhibition of ERK kinase activation in PANC- 1 cells. Taken together, our studies show that PDX-1 is a potential novel target for metformin in PDAC cells and that metformin may exert its anticancer action in PDAC by down-regulating PDX-1 via a mechanism involving inhibition of ERK signaling.


Evidence that bottlenose dolphins can communicate with vocal signals to solve a cooperative task.
Cooperation experiments have long been used to explore the cognition underlying animals' coordination towards a shared goal. While the ability to understand the need for a partner in a cooperative task has been demonstrated in a number of species, there has been far less focus on cooperation experiments that address the role of communication. In humans, cooperative efforts can be enhanced by physical synchrony, and coordination problems can be solved using spoken language. Indeed, human children adapt to complex coordination problems by communicating with vocal signals. Here, we investigate whether bottlenose dolphins can use vocal signals to coordinate their behaviour in a cooperative button-pressing task. The two dolphin dyads used in this study were significantly more likely to cooperate successfully when they used whistles prior to pressing their buttons, with whistling leading to shorter button press intervals and more successful trials. Whistle timing was important as the dolphins were significantly more likely to succeed if they pushed their buttons together after the last whistle, rather than pushing independently of whistle production. Bottlenose dolphins are well known for cooperating extensively in the wild, and while it remains to be seen how wild dolphins use communication to coordinate cooperation, our results reveal that at least some dolphins are capable of using vocal signals to facilitate the successful execution of coordinated, cooperative actions.


[Effect of green tea (matcha) on gastrointestinal tract absorption of polychlorinated biphenyls, polychlorinated dibenzofurans and polychlorinated dibenzo-p-dioxins in rats].
This paper presents the liver distribution and fecal excretion of polychlorinated biphenyls (PCB), polychlorinated dibenzofurans (PCDF) congeners and polychlorinated dibenzo-p-dioxins (PCDD) congeners, in male rats fed with powdered green tea (matcha). The rats were given a treatment diet containing 10% matcha for the first five days. Then, the animals were administered 4 g of 10% matcha diet containing 0.5 ml of the casual rice-bran oil of Yusho that had occurred in the Southwest part of Japan in 1968 and kept on the same diet for another five days. The fecal excretion of PCB, PCDF and PCDD in the group fed with 10% matcha were 4.4, 2.4-9.1 and 2.5-4.7 times higher (p < 0.01), respectively, than that in the control group. The liver distribution of PCB, PCDF and PCDD in the same groups were 79%, 20-75% and 26-67% of the control group, respectively. These findings suggest that administration of matcha is useful as a treatment of Yusho patients exposed to PCB, PCDF and PCDD.


QRS pattern and improvement in right and left ventricular function after cardiac resynchronization therapy: a radionuclide study.
Predicting response to cardiac resynchronization therapy (CRT) remains a challenge. We evaluated the role of baseline QRS pattern to predict response in terms of improvement in biventricular ejection fraction (EF). Consecutive patients (pts) undergoing CRT implantation underwent radionuclide angiography at baseline and at mid-term follow-up. The relationship between baseline QRS pattern and mechanical dyssynchrony using phase analysis was evaluated. Changes in left and right ventricular EF (LVEF and RVEF) were analyzed with regard to baseline QRS pattern. We enrolled 56 pts, 32 with left bundle branch block (LBBB), 4 with right bundle branch block (RBBB) and 20 with non-specific intraventricular conduction disturbance (IVCD). A total of 48 pts completed follow-up. LBBB pts had significantly greater improvement in LVEF compared to RBBB or non-specific IVCD pts (+9.6 ± 10.9% vs. +2.6 ± 7.6%, p = 0.003). Response (defined as ≥ 5% increase in LVEF) was observed in 68% of LBBB vs. 24% of non-specific IVCD pts (p = 0.006). None of the RBBB pts were responders. RVEF was significantly improved in LBBB (+5.0 ± 9.0%, p = 0.007), but not in non-specific IVCD and RBBB pts (+0.4 ± 5.8%, p = 0.76). At multivariate analysis, LBBB was the only predictor of LVEF response (OR, 7.45; 95% CI 1.80-30.94; p = 0.006), but not QRS duration or extent of mechanical dyssynchrony. Presence of a LBBB is a marker of a positive response to CRT in terms of biventricular improvement. Pts with non-LBBB pattern show significantly less benefit from CRT than those with LBBB.


Robust anatomical correspondence detection by hierarchical sparse graph matching.
Robust anatomical correspondence detection is a key step in many medical image applications such as image registration and motion correction. In the computer vision field, graph matching techniques have emerged as a powerful approach for correspondence detection. By considering potential correspondences as graph nodes, graph edges can be used to measure the pairwise agreement between possible correspondences. In this paper, we present a novel, hierarchical graph matching method with sparsity constraint to further augment the power of conventional graph matching methods in establishing anatomical correspondences, especially for the cases of large inter-subject variations in medical applications. Specifically, we first propose to measure the pairwise agreement between potential correspondences along a sequence of intensity profiles which reduces the ambiguity in correspondence matching. We next introduce the concept of sparsity on the fuzziness of correspondences to suppress the distraction from misleading matches, which is very important for achieving the accurate, one-to-one correspondences. Finally, we integrate our graph matching method into a hierarchical correspondence matching framework, where we use multiple models to deal with the large inter-subject anatomical variations and gradually refine the correspondence matching results between the tentatively deformed model images and the underlying subject image. Evaluations on both synthetic data and public hand X-ray images indicate that the proposed hierarchical sparse graph matching method yields the best correspondence matching performance in terms of both accuracy and robustness when compared with several conventional graph matching methods.


Patterns of care and dropout rates from outpatient mental healthcare in low-, middle- and high-income countries from the World Health Organization's World Mental Health Survey Initiative.
There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries. Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan-Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function. Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care. Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.


Multicentre study of hepatitis B virus genotypes in France: correlation with liver fibrosis and hepatitis B e antigen status.
The clinical significance of hepatitis B virus (HBV) genotypes is still under debate. The aims of this study were to assess the distribution of HBV genotypes in France and to identify the associations between HBV genotypes and patient demographics, severity of liver disease and HBeAg status in patients referred to tertiary care centres. This was a French, multicentre, retrospective study on 262 patients with chronic HBV infection. HBV genotypes were determined using INNO-LiPA. Liver fibrosis damage was evaluated by histological analysis of biopsy samples. Patients were mainly male (74%), of Caucasian (65%), Asian (17%) or African (18%) ethnicity and 36% were HBeAg positive. All A-G genotypes were found, the most frequent being genotypes D (27%) and A (24%), followed by E (13%) and C (12%), and B (7%). Mixed genotypes were detected in 16% of the cases. Genotype A was associated with sexual contact (P < 0.001) and genotype D with transfusion (P < 0.001) and HBe antibody positivity (P = 0.03).The distribution of HBV genotypes differed with regard to the ethnicity, and may reflect migration patterns. Genotypes A and D were the most frequent in France. Genotype A was associated with HBeAg positivity and genotype D with HBe antibody positivity. In our European patients, we find no clear association between a given HBV genotype and liver disease severity.


How leaders self-regulate their task performance: evidence that power promotes diligence, depletion, and disdain.
When leaders perform solitary tasks, do they self-regulate to maximize their effort, or do they reduce effort and conserve their resources? Our model suggests that power motivates self-regulation toward effective performance-unless the task is perceived as unworthy of leaders. Our 1st studies showed that power improves self-regulation and performance, even when resources for self-regulation are low (ego depletion). Additional studies showed that leaders sometimes disdain tasks they deem unworthy, by withholding effort (and therefore performing poorly). Ironically, during ego depletion, leaders skip the appraisal and, therefore, work hard regardless of task suitability, so that depleted leaders sometimes outperform nondepleted ones. Our final studies replicated these patterns with different tasks and even with simple manipulation of framing and perception of the same task (Experiment 5). Experiment 4 also showed that the continued high exertion of leaders when depleted takes a heavy toll, resulting in larger impairments later. The judicious expenditure of self-control resources among powerful people may help them prioritize their efforts to pursue their goals effectively.


Glucose and glutamine gavage increase portal vein nitric oxide metabolite levels via adenosine A2b activation.
Postprandial intestinal hyperemia is a complex vascular response during nutrient absorption. Many mediators have been studied including enteric reflexes, GI hormones, and absorption-stimulated metabolic mediators such as pH and adenosine. We have shown that nitric oxide (NO) mediates premucosal arteriolar dilation during glucose absorption and that glucose-induced portal vein NO metabolite production requires adenosine A2b receptor activation. We hypothesize that Na+-linked absorption of l-glutamine or l-glycine might also stimulate NO release in the enteroportal circulation via adenosine A2b receptors. Male Sprague-Dawley rats (190-220 g) were anesthetized with urethane/alpha-chloralose and cannulated for hemodynamic monitoring and blood sampling. A right paramedian abdominal incision was made for access to both the stomach (gavage) and the portal vein (blood sampling). Animals received intragastric nutrient gavage (saline, d-glucose, l-glutamine, racemic glycine, or oleic acid) with and without adenosine A2b receptor blockade. NO metabolites (NOx) were measured by a fluorescent modified-Greiss assay at baseline and 30 min after nutrient gavage. Glucose and glutamine gavage increased portal NOx levels compared to baseline, while glycine and oleic acid gavage did not. Adenosine A2b antagonism returned NOx levels to baseline in both glucose and glutamine gavage animals, but did not alter portal NOx levels in glycine- or oleic acid-treated animals. These data suggest that nutrient-induced adenosine is involved in a signaling process from the intestinal epithelium to nitric oxide-producing cells elsewhere in the vasculature. Adenosine A2b receptors are required for NO production during Na+-linked glucose or glutamine absorption.


Continuity and cascade in offspring of bipolar parents: a longitudinal study of externalizing, internalizing, and thought problems.
There is growing evidence that many offspring of bipolar parents will develop moderate to severe forms of psychopathology during childhood and adolescence. The purpose of this study was to apply growth curve models to evaluate developmental progression with regard to continuity and cascades representative within the context of a family risk study of bipolar disorder (BD). Repeated assessments of externalizing, internalizing, and thought problems, spanning more than a decade, were examined in a total of 94 offspring of parents with BD (O-BD), major depressive disorder (O-UNI), or no significant psychiatric or medical problems (O-WELL). Continuity was defined by the growth curve of the O-WELL group who exhibited low levels of problems from early childhood through late adolescence. Discontinuity, as evidenced by greater complexity of growth curves relative to the O-WELL group, was exhibited in the at- risk offspring groups for internalizing problems. Different patterns of developmental cascades were supported for the at-risk group with O-UNI showing a robust cascade from self-regulatory deficits (externalizing problems) to internalizing problems. There was also support for a cascade from self-regulatory deficits to thought problems across the entire group (with some support that this pattern was accounted for primarily by O-BD). This study not only serves to advance our understanding of the risks associated with a family history of BD, but also provides a novel approach to examining developmental cascades.


A manual collection of Syt, Esyt, Rph3a, Rph3al, Doc2, and Dblc2 genes from 46 metazoan genomes--an open access resource for neuroscience and evolutionary biology.
Synaptotagmin proteins were first identified in nervous tissue, residing in synaptic vesicles. Synaptotagmins were subsequently found to form a large family, some members of which play important roles in calcium triggered exocytic events. These members have been investigated intensively, but other family members are not well understood, making it difficult to grasp the meaning of family membership in functional terms. Further difficulty arises as families are defined quite legitimately in different ways: by common descent or by common possession of distinguishing features. One definition does not necessarily imply the other. The evolutionary range of genome sequences now available, can shed more light on synaptotagmin gene phylogeny and clarify family relationships. The aim of compiling this open access collection of synaptotagmin and synaptotagmin-like sequences, is that its use may lead to greater understanding of the biological function of these proteins in an evolutionary context. 46 metazoan genomes were examined and their complement of Syt, Esyt, Rph3a, Rph3al, Doc2 and Dblc2 genes identified. All of the sequences were compared, named, then examined in detail. Esyt genes were formerly named Fam62. The species in this collection are Trichoplax, Nematostella, Capitella, Helobdella, Lottia, Ciona, Strongylocentrotus, Branchiostoma, Ixodes, Daphnia, Acyrthosiphon, Tribolium, Nasonia, Apis, Anopheles, Drosophila, Caenorhabditis, Takifugu, Tetraodon, Gasterosteus, Oryzias, Danio, Xenopus, Anolis, Gallus, Taeniopygia,Ornithorhynchus, Monodelphis, Mus and Homo. All of the data described in this paper is available as additional files. Only a subset of synaptotagmin proteins appear able to function as calcium triggers. Syt1, Syt7 and Syt9 are ancient conserved synaptotagmins of this type. Some animals carry extensive repertoires of synaptotagmin genes. Other animals of no less complexity, carry only a small repertoire. Current understanding does not explain why this is so. The biological roles of many synaptotagmins remain to be understood. This collection of genes offers prospects for fruitful speculation about the functional roles of the synaptotagmin repertoires of different animals and includes a great range of biological complexity. With reference to this gene collection, functional relationships among Syt, Esyt, Rph3a, Rph3al, Doc2 and Dblc2 genes, which encode similar proteins, can better be assessed in future.


Development of the Behavioral Inflexibility Scale for Children with Autism Spectrum Disorder and Other Developmental Disabilities.
Behavior inflexibility (BI) refers to rigid patterns of behavior that contrast with the need to be adaptable to changing environmental demands. We developed a parent-reported outcome measure of BI for children with autism spectrum disorder (ASD) and other developmental disabilities with a multi-step iterative process. A pool of 62 candidate items was generated through expert panel feedback, review of existing scales and focus groups. A consensus process was used to generate the final 38 items. Parents of 943 children (age range, 3-18 years; average, 11.4 years; 79% boys) with ASD completed an online survey. One hundred thirty-three parents rated their child twice within 3 weeks (average = 16.5 days). A series of factor analyses suggested that the 38 items measured a single construct. Scores had a weak correlation with level of functioning (-0.12) and did not differ based on sex. Scores had a negligible correlation with age (-0.07), although measurement invariance was not supported. The mean total score for the Behavioral Inflexibility Scale (BIS) was normally distributed. Internal consistency was α = 0.97 and temporal stability was r = 0.92. Correlations with parent ratings on the subscales of the Repetitive Behavior Scale-Revised varied from 0.48 to 0.89. The correlation with parent ratings on the Social Communication Questionnaire total score was 0.52. Our data show that BI in children with ASD ranges significantly from mild to severe and that the 38-item BIS is valid and reliable. Autism Res 2020, 13: 489-499. © 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: We developed a parent-completed rating scale of behavior inflexibility (BI) for children with developmental disabilities using a multistep process. The Behavioral Inflexibility Scale (BIS) contains 38 questions rated on a 6-point scale. Parents of 943 children with autism spectrum disorder (ASD) completed an online survey. We examined associations between the BIS and other scales and demographic variables. The BIS is valid and reliable. BI in children with ASD ranges from mild to severe.


Complete Genome Sequence of Salmonella enterica subsp. enterica Serovar Paratyphi B Sequence Type 28 Harboring mcr-1.
In 2015, plasmid-mediated colistin resistance was reported to be caused by a mobilized phosphoethanolamine transferase gene (mcr-1) in Enterobacteriaceae Here, we announce the complete genome sequence of the earliest d-tartrate-fermenting Salmonella enterica subsp. enterica serovar Paratyphi B isolate harboring mcr-1 from the collection of the German National Reference Laboratory for Salmonella.


Iridium complexes of new NCP pincer ligands: catalytic alkane dehydrogenation and alkene isomerization.
Iridium complexes of novel NCP pincer ligands containing pyridine and phosphinite arms have been synthesized. One Ir complex shows good catalytic activity for alkane dehydrogenation, and all complexes are highly active for olefin isomerization. A combination of the Ir complex and a (PNN)Fe pincer complex catalyzes the formation of linear alkylboronates selectively from internal olefins via sequential olefin isomerization-hydroboration.


Axial CT recognition of anteroposterior displacement of fourth ventricle.
The recognition of anterior or posterior displacement of the fourth ventricle on axial computed tomography (CT) has proven to be difficult because the apparent position of this structure is variable and dependent on scanning angle. In most cases direct visualization of a lesion and its relationship to normal anatomic structures allows for the correct assessment. However, in some instances it would be advantageous for lesion localization to be able to identify relatively subtle displacements of the fourth ventricle. This is possible on CT by determining the position of this structure relative to Twining's line (the line between the tuberculum sellae and torcula). The position of the fourth ventricle, tuberculum sellae, and torcula relative to an arbitrary fixed point can be established in virtually all cases, and thus the position of the fourth ventricle relative to Twining's line can be determined. In a control group of 100 patients with normal CT examinations, the ratio of the distance from the tuberculum sellae to the center of the fourth ventricle and the distance from the tuberculum sellae to torcula (Twining's line) was between 0.47 and 0.53. In 66% of the cases the ratio was 0.49-0.51. THere were 54 posterior fossa masses evaluated by this technique. Determination of fourth ventricular position by this method proved to be of particular value in recognizing brainstem glioma, and in determining the site of origin of laterally placed posterior fossa masses.


Improving outcomes for primary school children at risk of cerebral visual impairment (the CVI project): protocol of a feasibility study for a cluster-randomised controlled trial and health economic evaluation.
Cerebral visual impairment (CVI) refers to a spectrum of brain-related vision problems. CVI is associated with poor educational and mental health outcomes. An intervention has been developed to help children with CVI, involving input from clinicians, teachers and parents. The effectiveness of this intervention needs to be evaluated. This study aims to guide any refinements to the intervention or the design of a future cluster-randomised trial that may be needed. This study will include all methods anticipated for a future cluster-randomised controlled trial. Eight primary schools will be recruited and randomised to receive the intervention or carry on with usual practice. The intervention will comprise an information pack for schools and access to a local paediatric ophthalmology clinic (who are prepared to assess them for CVI), for up to 5% of participating children. Outcome assessments will be carried out at baseline (before randomisation) and after 4-5 months of intervention period. Assessments will include children's self-reported quality of life, their learning ability and behaviour as reported by teachers, and family functioning reported by parents. Cost data will include service use, family expenditure on additional support (eg, private appointments and administration) and school spending and resource used in helping children with special educational needs or disability. A process evaluation (PE) will collect additional data relating to the implementation of the intervention and the trial processes, in the school and clinic settings. The protocol for the PE will be reported separately. Ethical permission was obtained from the University of Bristol Faculty of Health Sciences Ethical Committee. The results will inform the design of a future trial to assess the effectiveness and cost-effectiveness of the intervention and will be shared with participants, CVI-support groups and peer-viewed journals. ISRCTN13762177; Pre-results.


Normal-mode approach to wave propagation in the turbulent atmosphere.
Recent studies have used the superposition principle (extended Huygens-Fresnel principle) to characterize completely the statistics of a field that has propagated through a thick slab of turbulent air in terms of the statistics for spherical-wave sources. In this paper, we consider the normal-mode decomposition associated with this linear system propagation model. In particular, we use the statistics of the atmospheric impulse response (Green's function) to show that the atmospheric mode decomposition exhibits far-field and near-field regimes very similar to those of free-space propagation. The significance of these results for optical communication through the atmosphere is briefly discussed.


Chronic primary insomnia: efficacy of homeopathic simillimum.
Chronic primary insomnia is defined as difficulty in initiating or maintaining sleep or of non-restorative sleep that lasts for at least 1 month and causes significant distress or impairment in social, occupational or other important areas of functioning. The homeopathic simillimum is that remedy which most closely corresponds to the totality of symptoms; remedy selection is based on a full evaluation of the patient's physical, emotional and mental characteristics. The purpose of this randomised, double-blind, placebo-controlled study was to evaluate the efficacy of homeopathic simillimum in the treatment of chronic primary insomnia. 30 participants were selected in accordance with DSM-IV TR (2000)(1) criterion 307.42 Primary Insomnia and then randomly divided between treatment and placebo groups. The measurement tools used were a Sleep Diary (SD) and the Sleep Impairment Index (SII).(2) After an initial consultation, 2 follow-up consultations at 2-week intervals took place. Homeopathic medication was prescribed at the first and second consultations. The SII was completed at each consultation and participants were instructed at the first consultation to start the SD. SD data revealed that verum treatment resulted in a significant increase in duration of sleep throughout the study, compared to the placebo treatment which resulted in no significant increase in duration of sleep. A significant improvement in SII summary scores and number of improved individual questions were found in the verum group, responses to all 11 questions having improved significantly upon completion of the study. An initial improvement occurred in the placebo group, but was not sustained. Comparison of results between the groups revealed a statistically significant difference. The homeopathic simillimum treatment of primary insomnia was effective, compared to placebo. Homeopathy is a viable treatment modality for this condition and further research is justified.


Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.
New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.


Suppression of adult neurogenesis increases the acute effects of kainic acid.
Adult neurogenesis, the generation of new neurons in the adult brain, occurs in the hippocampal dentate gyrus (DG) and the olfactory bulb (OB) of all mammals, but the functions of these new neurons are not entirely clear. Originally, adult-born neurons were considered to have excitatory effects on the DG network, but recent studies suggest a net inhibitory effect. Therefore, we hypothesized that selective removal of newborn neurons would lead to increased susceptibility to the effects of a convulsant. This hypothesis was tested by evaluating the response to the chemoconvulsant kainic acid (KA) in mice with reduced adult neurogenesis, produced either by focal X-irradiation of the DG, or by pharmacogenetic deletion of dividing radial glial precursors. In the first 4 hrs after KA administration, when mice have the most robust seizures, mice with reduced adult neurogenesis had more severe convulsive seizures, exhibited either as a decreased latency to the first convulsive seizure, greater number of convulsive seizures, or longer convulsive seizures. Nonconvulsive seizures did not appear to change or they decreased. Four-21 hrs after KA injection, mice with reduced adult neurogenesis showed more interictal spikes (IIS) and delayed seizures than controls. Effects were greater when the anticonvulsant ethosuximide was injected 30 min prior to KA administration; ethosuximide allows forebrain seizure activity to be more easily examined in mice by suppressing seizures dominated by the brainstem. These data support the hypothesis that reduction of adult-born neurons increases the susceptibility of the brain to effects of KA.


Metal vs. ligand protonation and the alleged proton-shuttling role of the azadithiolate ligand in catalytic H2 formation with FeFe hydrogenase model complexes.
Electron and proton transfer reactions of diiron complexes [Fe2adt(CO)6] (1) and [Fe2adt(CO)4(PMe3)2] (4), with the biomimetic azadithiolate (adt) bridging ligand, have been investigated by real-time IR- and UV-vis-spectroscopic observation to elucidate the role of the adt-N as a potential proton shuttle in catalytic H2 formation. Protonation of the one-electron reduced complex, 1- , occurs on the adt-N yielding 1H and the same species is obtained by one-electron reduction of 1H+ . The preference for ligand vs. metal protonation in the Fe2(i,0) state is presumably kinetic but no evidence for tautomerization of 1H to the hydride 1Hy was observed. This shows that the adt ligand does not work as a proton relay in the formation of hydride intermediates in the reduced catalyst. A hydride intermediate 1HHy+ is formed only by protonation of 1H with stronger acid. Adt protonation results in reduction of the catalyst at much less negative potential, but subsequent protonation of the metal centers is not slowed down, as would be expected according to the decrease in basicity. Thus, the adtH+ complex retains a high turnover frequency at the lowered overpotential. Instead of proton shuttling, we propose that this gain in catalytic performance compared to the propyldithiolate analogue might be rationalized in terms of lower reorganization energy for hydride formation with bulk acid upon adt protonation.


Quetiapine-induced hypertriglyceridaemia causing acute pancreatitis.
Second-generation antipsychotics have well-known metabolic side effects such as hyperlipidaemia and hyperglycaemia. A middle-aged man presented with epigastric and flank pain associated with nausea, and was noted to have elevated triglycerides (3590 mg/dL or 40.53 mmol/L), lipase and glucose. Haematological parameters revealed neutropenia with pancytopaenia. The patient was started on conservative management for acute pancreatitis, and on intravenous insulin and oral gemfibrozil for lowering of his triglycerides. He gradually improved and was transitioned to oral atorvastatin and fenofibrate. His triglycerides, glucose and leucocyte counts normalised at discharge and he was transitioned to ziprasidone. The combination of hypertriglyceridaemia, worsening hyperglycaemia and neutropenia made us suspect quetiapine as the causative agent. Medications cause only 0.1-7% of acute pancreatitis cases, with quetiapine implicated in only five-reported cases. Hypertriglyceridaemia (>600 mg/dL or 6.77 mmol/L) is frequently reported with quetiapine use, but severe hypertriglyceridaemia (>1000 mg/dL or 11.29 mmol/L) has been reported in <10 patients.


"Pure" human hematopoietic progenitors: permissive action of basic fibroblast growth factor.
Methodology has been developed that enables virtually complete purification and abundant recovery of early hematopoietic progenitors from normal human adult peripheral blood. A fraction of the pure progenitors is multipotent (generates mixed colonies) and exhibits self-renewal capacity (gives rise to blast cell colonies). This methodology provides a fundamental tool for basic and clinical studies on hematopoiesis. Optimal in vitro cloning of virtually pure progenitors requires not only the stimulatory effect of interleukin-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin, but also the permissive action of basic fibroblast growth factor. These findings suggest a regulatory role for this growth factor in early hematopoiesis.


Deep Brain Stimulation as Clinical Innovation: An Ethical and Organizational Framework to Sustain Deliberations About Psychiatric Deep Brain Stimulation.
Deep brain stimulation (DBS) for psychiatric disorders needs to be investigated in proper research trials. However, there are rare circumstances in which DBS could be offered to psychiatric patients as a form of surgical innovation, therefore potentially blurring the lines between these research trials and health care. In this article, we discuss the conditions under which surgical innovation may be accepted as a practice falling at the frontiers of standard clinical care and research per se. However, recognizing this distinction does not settle all ethical issues. Our article offers ethical guideposts to allow clinicians, surgical teams, institutions, and institutional review boards to deliberate about some of the fundamental issues that should be considered before surgical innovation with psychiatric DBS is undertaken. We provide key guiding questions to sustain this deliberation. Then we review the normative and empirical literature that exists to guide reflection about the ethics of surgical innovation and psychiatric DBS with respect to general ethical questions pertinent to psychiatric DBS, multidisciplinary team perspectives in psychiatric DBS, mechanisms for oversight in psychiatric DBS, and capacity and consent in psychiatric DBS. The considerations presented here are to recognize the very specific nature of surgical innovation and to ensure that surgical innovation in the context of psychiatric DBS remains a limited, special category of activity that does not replace appropriate surgical research or become the standard of care based on limited evidence. DBS, deep brain stimulationIRB, institutional review boardOCD, obsessive-compulsive disorder.


Single-molecule FRET reveals the pre-initiation and initiation conformations of influenza virus promoter RNA.
Influenza viruses have a segmented viral RNA (vRNA) genome, which is replicated by the viral RNA-dependent RNA polymerase (RNAP). Replication initiates on the vRNA 3' terminus, producing a complementary RNA (cRNA) intermediate, which serves as a template for the synthesis of new vRNA. RNAP structures show the 3' terminus of the vRNA template in a pre-initiation state, bound on the surface of the RNAP rather than in the active site; no information is available on 3' cRNA binding. Here, we have used single-molecule Förster resonance energy transfer (smFRET) to probe the viral RNA conformations that occur during RNAP binding and initial replication. We show that even in the absence of nucleotides, the RNAP-bound 3' termini of both vRNA and cRNA exist in two conformations, corresponding to the pre-initiation state and an initiation conformation in which the 3' terminus of the viral RNA is in the RNAP active site. Nucleotide addition stabilises the 3' vRNA in the active site and results in unwinding of the duplexed region of the promoter. Our data provide insights into the dynamic motions of RNA that occur during initial influenza replication and has implications for our understanding of the replication mechanisms of similar pathogenic viruses.


Who is violent?: factors associated with aggressive behaviors in Latin America and Spain.
The main purpose of this paper was to evaluate the strength of the association between: 1) aggressive behaviors and 2) attitudes and self-efficacy for alternatives to violence, in different cities of the Region of the Americas and Spain. Results were based on a cross-sectional house-hold survey of a sample of the population aged 18 to 70 years. The survey was conducted in eight metropolitan areas of Latin America and Spain: Rio de Janeiro, Brazil; Salvador, Bahia, Brazil; Santiago, Chile; Cali, Colombia; San José, Costa Rica; San Salvador, El Salvador; Caracas, Venezuela; and Madrid, Spain. Each sample of approximately 1,200 respondents per city was stratified by clusters and was proportional in terms of socioeconomic position and population density. In all cities and for all targets of aggression studied, people who reported using aggression were less likely to feel confident that they could solve conflicts without violence, and they were more likely to hold attitudes supporting violence. Young persons were also more likely to commit aggression against all the targets. In addition, aggression toward nonfamily members was found most frequently among young men who reported binge drinking, who either carried a firearm or would have liked to carry one, or who perceived the police as inefficient. Additional studies need to be done in each country to describe more specific attitudes associated with aggression within each subculture. Future prevention programs should focus on modifying attitudes that support violence, increasing self-efficacy in solving problems without using violence, supporting the development of a police system that people can trust, regulating firearms and access to alcohol, and raising people's education levels.


A computational statistics approach for estimating the spatial range of morphogen gradients.
A crucial issue in studies of morphogen gradients relates to their range: the distance over which they can act as direct regulators of cell signaling, gene expression and cell differentiation. To address this, we present a straightforward statistical framework that can be used in multiple developmental systems. We illustrate the developed approach by providing a point estimate and confidence interval for the spatial range of the graded distribution of nuclear Dorsal, a transcription factor that controls the dorsoventral pattern of the Drosophila embryo.


Longitudinal analyses of immune responses to Plasmodium falciparum derived peptides corresponding to novel blood stage antigens in coastal Kenya.
We have recently described 95 predicted alpha-helical coiled-coil peptides derived from putative Plasmodium falciparum erythrocytic stage proteins. Seventy peptides recognized with the highest level of prevalence by sera from three endemic areas were selected for further studies. In this study, we sequentially examined antibody responses to these synthetic peptides in two cohorts of children at risk of clinical malaria in Kilifi district in coastal Kenya, in order to characterize the level of peptide recognition by age, and the role of anti-peptide antibodies in protection from clinical malaria. Antibody levels from 268 children in the first cohort (Chonyi) were assayed against 70 peptides. Thirty-nine peptides were selected for further study in a second cohort (Junju). The rationale for the second cohort was to confirm those peptides identified as protective in the first cohort. The Junju cohort comprised of children aged 1-6 years old (inclusive). Children were actively followed up to identify episodes of febrile malaria in both cohorts. Of the 70 peptides examined, 32 showed significantly (p<0.05) increased antibody recognition in older children and 40 showed significantly increased antibody recognition in parasitaemic children. Ten peptides were associated with a significantly reduced odds ratio (OR) for an episode of clinical malaria in the first cohort of children and two of these peptides (LR146 and AS202.11) were associated with a significantly reduced OR in both cohorts. LR146 is derived from hypothetical protein PFB0145c in PlasmoDB. Previous work has identified this protein as a target of antibodies effective in antibody dependent cellular inhibition (ADCI). The current study substantiates further the potential of protein PFB0145c and also identifies protein PF11_0424 as another likely target of protective antibodies against P. falciparum malaria.


Induction of squamous cell carcinomas in the salivary glands of rats by potassium iodide.
In a 2-year carcinogenicity study of potassium iodide (KI) in F344/DuCrj rats, squamous cell carcinomas (SCCs) were observed in the salivary glands of 4/40 males and 3/40 females receiving 1000 ppm KI in the drinking water. Ductular proliferation with lobular atrophy was observed at high incidence in the submandibular glands of the high-dose animals, and squamous metaplasia was frequently evident within the proliferative ductules and the larger interlobular ducts. A transition from metaplasia to SCC was apparent. The results suggest that squamous metaplasia in proliferative ductules, occurring secondarily to lobular impairment induced by KI, may develop into SCCs via a non-genotoxic, proliferation-dependent mechanism.


Xenbase, the Xenopus model organism database; new virtualized system, data types and genomes.
Xenbase (http://www.xenbase.org), the Xenopus frog model organism database, integrates a wide variety of data from this biomedical model genus. Two closely related species are represented: the allotetraploid Xenopus laevis that is widely used for microinjection and tissue explant-based protocols, and the diploid Xenopus tropicalis which is used for genetics and gene targeting. The two species are extremely similar and protocols, reagents and results from each species are often interchangeable. Xenbase imports, indexes, curates and manages data from both species; all of which are mapped via unique IDs and can be queried in either a species-specific or species agnostic manner. All our services have now migrated to a private cloud to achieve better performance and reliability. We have added new content, including providing full support for morpholino reagents, used to inhibit mRNA translation or splicing and binding to regulatory microRNAs. New genomes assembled by the JGI for both species and are displayed in Gbrowse and are also available for searches using BLAST. Researchers can easily navigate from genome content to gene page reports, literature, experimental reagents and many other features using hyperlinks. Xenbase has also greatly expanded image content for figures published in papers describing Xenopus research via PubMedCentral.


Fouling resilient perforated feed spacers for membrane filtration.
The improvement of feed spacers with optimal geometry remains a key challenge for spiral-wound membrane systems in water treatment due to their impact on the hydrodynamic performance and fouling development. In this work, novel spacer designs are proposed by intrinsically modifying cylindrical filaments through perforations. Three symmetric perforated spacers (1-Hole, 2-Hole, and 3-Hole) were in-house 3D-printed and experimentally evaluated in terms of permeate flux, feed channel pressure drop and membrane fouling. Spacer performance is characterized and compared with standard no perforated (0-Hole) design under constant feed pressure and constant feed flow rate. Perforations in the spacer filaments resulted in significantly lowering the net pressure drop across the spacer filled channel. The 3-Hole spacer was found to have the lowest pressure drop (50%-61%) compared to 0-Hole spacer for various average flow velocities. Regarding permeate flux production, the 0-Hole spacer produced 5.7 L m-2.h-1 and 6.6 L m-2.h-1 steady state flux for constant pressure and constant feed flow rate, respectively. The 1-Hole spacer was found to be the most efficient among the perforated spacers with 75% and 23% increase in permeate production at constant pressure and constant feed flow, respectively. Furthermore, membrane surface of 1-Hole spacer was found to be cleanest in terms of fouling, contributing to maintain higher permeate flux production. Hydrodynamic understanding of these perforated spacers is also quantified by performing Direct Numerical Simulation (DNS). The performance enhancement of these perforated spacers is attributed to the formation of micro-jets in the spacer cell that aided in producing enough unsteadiness/turbulence to clean the membrane surface and mitigate fouling phenomena. In the case of 1-Hole spacer, the unsteadiness intensity at the outlet of micro-jets and the shear stress fluctuations created inside the cells are higher than those observed with other perforated spacers, resulting in the cleanest membrane surface.


Risk assessment in travel medicine: how to obtain, interpret, and use risk data for informing pre-travel advice.
It has been recommended that numerical risk data should be provided during the pre-travel consultation in order for travelers to make informed decisions regarding uptake of preventive interventions. In this article, we review the definitions of the various risk measures, particularly as they relate to travel health, and discuss the study designs and methodological details required to obtain each measure. Risk measures can be broadly divided into absolute risk measures (including incidence rate, attack rate, and incidence density) and risk factor measures (including relative risk, risk ratio, and odds ratio). Although there are limitations inherent to each measure, absolute risk measures estimate the baseline risk for an "average" traveler, and risk factor measures help determine whether the risks for an individual traveler are likely to be higher or lower than this average, which is determined by specific traveler and itinerary characteristics. Incremental risk considerations add additional complexity, and risk communication plus risk perception/risk tolerance have additional impact on the individual traveler's interpretation of risk measures. Travel health practitioners should be aware of the complexities, limitations, and difficulties in understanding numerical risk data, as these factors are important in travelers' acceptance or rejection of interventions offered.


Can We Accomplish Better Oncological Results with Robot-Assisted Radical Prostatectomy?
Surgical removal with radical prostatectomy has been a cornerstone for the treatment of prostate cancer and is associated with level 1 evidence for survival advantage compared with watchful waiting. Since the first structured robotic program was launched in 2000, robot-assisted radical prostatectomy (RARP) has had a rapid diffusion and surpassed its open radical prostatectomy (ORP) and laparoscopic radical prostatectomy (LRP) counterparts in the United States and is progressively expanding in other countries. Interestingly, this common acceptance of RARP was initially driven in the paucity of robust clinical evidence. There is still lack of level 1 evidence with prospective randomized trials on the oncologic outcomes of RARP. In that scenario, the clinician has to rely on retrospective data and systemic and meta-analyses. In comparison with ORP and LRP, RARP has proven to reach at least equivalent oncological outcomes. Lower rate of positive surgical margins may probably be achieved with RARP in pT2 patients. Although urologists were initially reluctant to embrace RARP in high-risk patients and lymph node yield was low, contemporary series have revealed that RARP and extended lymphadenectomy may be safely performed with obtaining similar (or better) nodal yields compared with ORP. Surgeon experience is universally of utmost importance in obtaining good outcomes. We will need to wait for long-term results of contemporary series to comprehend the impact of RARP on cancer-specific survival and overall survival. Using novel imaging before surgery and frozen section analysis during surgery may allow for superior oncological outcomes.


A case of gynecomastia due to entecavir.
Hepatitis B is an important health problem all over the world as well as in our country. Entecavir is a nucleoside analog used in the treatment of chronic hepatitis B. We present a case of a 55-year-old male patient who developed unilateral gynecomastia while under treatment with entecavir. Physical examination was unremarkable except for minimal hepatomegaly. Laboratory examination revealed: HbsAg: positive, HBeAg: negative, anti-HBe: positive, HBV DNA: 800,000 copies/ml, total anti-HDV: negative, and alanine aminotransferase: 105 U/L (normal range: 0-41). The treatment was started with pegylated interferon. During the follow-up, transaminases did not regress and HBV DNA was found to still be highly positive at the sixth month evaluation. Pegylated interferon treatment was stopped and entecavir was started at a dose of 0.5 mg/day. Six months after the initiation of entecavir treatment, the patient presented with a painful swelling in the right breast. On physical examination, there was painful gynecomastia on the right side, which was confirmed with mammography and ultrasound of the breast tissue. The patient was not taking any drug that may have caused gynecomastia. Hormonal status of the patient was normal. Laboratory values were normal. We considered that this unilateral gynecomastia might be an adverse effect of entecavir. Since the patient had a rapid viral and biochemical response to entecavir, the drug was continued under close follow-up and there was no further progression of the gynecomastia.


Simultaneous Assessment of Acidogenesis-Mitigation and Specific Bacterial Growth-Inhibition by Dentifrices.
Dentifrices can augment oral hygiene by inactivating bacteria and at sub-lethal concentrations may affect bacterial metabolism, potentially inhibiting acidogenesis, the main cause of caries. Reported herein is the development of a rapid method to simultaneously measure group-specific bactericidal and acidogenesis-mitigation effects of dentifrices on oral bacteria. Saliva was incubated aerobically and anaerobically in Tryptone Soya Broth, Wilkins-Chalgren Broth with mucin, or artificial saliva and was exposed to dentifrices containing triclosan/copolymer (TD); sodium fluoride (FD); stannous fluoride and zinc lactate (SFD1); or stannous fluoride, zinc lactate and stannous chloride (SFD2). Minimum inhibitory concentrations (MIC) were determined turbidometrically whilst group-specific minimum bactericidal concentrations (MBC) were assessed using growth media and conditions selective for total aerobes, total anaerobes, streptococci and Gram-negative anaerobes. Minimum acid neutralization concentration (MNC) was defined as the lowest concentration of dentifrice at which acidification was inhibited. Differences between MIC and MNC were calculated and normalized with respect to MIC to derive the combined inhibitory and neutralizing capacity (CINC), a cumulative measure of acidogenesis-mitigation and growth inhibition. The overall rank order for growth inhibition potency (MIC) under aerobic and anaerobic conditions was: TD> SFD2> SFD1> FD. Acidogenesis-mitigation (MNC) was ordered; TD> FD> SFD2> SFD1. CINC was ordered TD> FD> SFD2> SFD1 aerobically and TD> FD> SFD1> SFD2 anaerobically. With respect to group-specific bactericidal activity, TD generally exhibited the greatest potency, particularly against total aerobes, total anaerobes and streptococci. This approach enables the rapid simultaneous evaluation of acidity mitigation, growth inhibition and specific antimicrobial activity by dentifrices.


Identification of Trypanosomatids by detecting Single Nucleotide Fingerprints using DNA analysis by dynamic chemistry with MALDI-ToF.
Protozoan parasites of the Trypanosomatidae family can cause devastating diseases in humans and animals, such as Human African Trypanosomiasis or Sleeping Sickness, Chagas disease and Leishmaniasis. Currently, there are molecular assays for detecting parasitic infections and their post-treatment monitoring based on nucleic acid amplification, but there are still certain limitations which limit the development of assays that can detect and discriminate between parasite infections with a single test. Here, we present the development of a novel molecular assay for the rapid identification of Trypanosomatids, integrating DNA analysis by dynamic chemistry in conjunction with Matrix-Assisted Laser Desorption Ionization - Time-of-Flight Mass Spectrometry (MALDI-ToF). Differentiation of Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp. is now possible using a single reaction tube, and enables rapid identification of Trypanosomatids. The test is based on a singleplex PCR, using a specific primer pair that amplifies a 155 base pair segment of the 28S ribosomal RNA gene, within a conserved homology region of Trypanosomatidae species. Amplified fragments are analysed by dynamic chemistry using two abasic PNA probes and the four reactive nucleobases - containing an aldehyde functional group - with MALDI-ToF to identify unique molecular patterns created by each specie due to their single base differences (Single Nucleotide Fingerprint 'SNF') in this highly homologous region. This novel assay offers the possibility to expand routine diagnostic testing for Trypanosomatids, and monitoring of therapeutic responses to these infectious diseases.


Angiogenesis in cancer: Anti-VEGF escape mechanisms.
It is now widely accepted that tumor-angiogenesis plays a crucial role in tumor growth, tumor propagation and metastasis formation. Among several angiogenic activators, the vascular endothelial growth factor (VEGF) and its receptors represent one of the major inducers of tumor angiogenesis. Thus, this system has become the focus of therapeutic interventions, which led to the approval of the anti-VEGF blocking antibody bevacizumab and the VEGFR-2 pathway inhibitors pazopanib, sorafenib and sunitinib. However, not every cancer patient benefits from such treatment or finally becomes resistant to anti-VEGF approaches; others are suffering from adverse effects. Thus, there is an urgent need for a better understanding of VEGF-independent mechanisms leading to angiogenesis in cancer. This review focuses on anti-VEGF escape mechanisms of tumor cells and its microenvironment.


Perivascular macrophages in the neonatal macaque brain undergo massive necroptosis after simian immunodeficiency virus infection.
We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid cell populations. The number of CD206+ brain perivascular macrophages (PVMs) was significantly greater in uninfected infants than in uninfected adults and was markedly lower in SIV-infected infants while microglia numbers were unchanged across groups. CD206+ PVMs, which proliferate after infection in SIV-infected adults, did not undergo proliferation in infants. While virtually all CD206+ cells in adults are also CD163+, infants have a distinct CD206 single-positive population in addition to the double-positive population commonly seen in adults. Notably, we found that more than 60% of these unique CD206+CD163- PVMs in SIV-infected infants were positive for cleaved caspase-3, an indicator of apoptosis, and that nearly 100% of this subset were concomitantly positive for the necroptosis marker receptor-interacting protein kinase-3 (RIP3). These findings show that distinct subpopulations of PVMs found in infants undergo programmed cell death instead of proliferation following SIV infection, which may lead to the absence of PVM-dependent SIVE and the limited size of the virus reservoir in the infant brain.


Relapsing acute disseminated encephalomyelitis associated with chronic Epstein-Barr virus infection: MRI findings.
A 25-year-old women had a fever, left cervical lymphadenopathy, neurological symptoms and signs, CSF pleocytosis and persistent high serum antibodies to the Epstein-Barr virus (EBV); she had a recurrence 1 year later. She was thought to have relapsing acute disseminated encephalomyelitis associated with chronic EBV infection. MRI revealed abnormalities, mainly in the right basal ganglia and left midbrain. At the time of the recurrence, further abnormalities appeared in the opposite basal ganglia and right cerebral white matter.


Chimaeras reveal the role of the catalytic core in the activation of the plasma membrane Ca2+ pump.
Isoform 2b of the plasma membrane calcium pump differs from the ubiquitous isoform 4b in the following: (a) higher basal activity in the absence of calmodulin; (b) higher affinity for calmodulin; and (c) higher affinity for Ca(2+) in the presence of calmodulin [Elwess, Filoteo, Enyedi and Penniston (1997) J. Biol. Chem. 272, 17981-17986]. To investigate which parts of the molecule determine these kinetic differences, we made four chimaeric constructs in which portions of isoform 2b were grafted into isoform 4b: chimaera I contains only the C-terminal regulatory region of isoform 2b; chimaera II contains the N-terminal moiety of isoform 2b, including both cytoplasmic loops; chimaera III contains the sequence of isoform 2b starting from the N-terminus to after the end of the first (small) cytoplasmic loop; and chimaera IV contains only the second (large) cytoplasmic loop. Surprisingly, chimaera I showed low basal activity in the absence of calmodulin and low affinity for calmodulin, unlike isoform 2b. In contrast, the chimaera containing both loops showed high basal activity, and Ca(2+) activation curves (both in the absence and in the presence of calmodulin) similar to those of isoform 2b. The rates of activation by calmodulin and of inactivation by calmodulin removal were measured, and the apparent K(d) for calmodulin was calculated from the ratio between these rate constants. The order of affinity was: 2b=II>4b=IV>III=I. From these results it is clear that the construct that most closely resembles isoform 2b is chimaera II. This shows that, in order to obtain an enzyme with properties similar to those of isoform 2b, both cytoplasmic loops are needed.


Interleukin-8, interleukin-1β and tumour necrosis factor-α in sequential units of packed red blood cells collected from retired racing Greyhounds.
We hypothesised that concentrations of interleukin-8 (IL-8), interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) would increase during storage in the third sequential unit (U3) of canine packed red blood cells (PRBC) collected from terminal donors in haemorrhagic shock. We further hypothesised that leucoreduction would prevent cytokine accumulation in U3 and that cytokine concentrations in U3 would be higher than in the first units (U1) collected from the same dogs. U1 and U3 were each collected from 12 anaesthetised healthy Greyhounds. Removal of leucocytes from half of each PRBC unit produced one leucoreduced (LR) and one non-leucoreduced (NLR) unit. Canine IL-8, IL-1β and TNF-α concentrations were measured in samples collected from the units during storage on days 0, 10, 20, 30 and 37. The IL-8 concentration in U3 NLR units was significantly higher on days 10, 20, 30 and 37 than on day 0 and was significantly higher than in the LR units at all time points. The IL-1β concentration in U3 did not change over time, or between LR and NLR units. TNF-α was not detected in any unit. There were no significant differences in IL-8 or IL-1β concentrations between U3 and U1 at any time point; however, some NLR U3 units had markedly elevated IL-8 concentrations at day 37 (2060-20,682 pg/mL) compared with NLR U1 units (3369-5280 pg/mL). NLR U3 units collected from dogs in haemorrhagic shock showed a significant increase in IL-8 concentrations during storage. Leucoreduction was effective at preventing the accumulation of IL-8. There was no difference detected between U3 and U1.


Towards Providing Solutions to the Air Quality Crisis in the Mexico City Metropolitan Area: Carbon Sequestration by Succulent Species in Green Roofs.
In the first months of 2016, the Mexico City Metropolitan Area experienced the worst air pollution crisis in the last decade, prompting drastic short-term solutions by the Mexico City Government and neighboring States. In order to help further the search for long-term sustainable solutions, we felt obliged to immediately release the results of our research regarding the monitoring of carbon sequestration by green roofs. Large-scale naturation, such as the implementation of green roofs, provides a way to partially mitigate the increased carbon dioxide output in urban areas. Here, we quantified the carbon sequestration capabilities of two ornamental succulent plant species, Sedum dendroideum and Sedum rubrotinctum, which require low maintenance, and little or no irrigation. To obtain a detailed picture of these plants' carbon sequestration capabilities, we measured carbon uptake on the Sedum plants by quantifying carbon dioxide exchange and fixation as organic acids, during the day and across the year, on a green roof located in Southern Mexico City. The species displayed their typical CAM photosynthetic metabolism. Moreover, our quantification allowed us to conservatively estimate that a newly planted green roof of Sedum sequesters approximately 180,000,000 ppm of carbon dioxide per year in a green roof of 100 square meters in the short term. The patterns of CAM and carbon dioxide sequestration were highly robust to the fluctuations of temperature and precipitation between seasons, and therefore we speculate that carbon sequestration would be comparable in any given year of a newly planted green roof. Older green roof would require regular trimming to mantain their carbon sink properties, but their carbon sequestration capabilities remain to be quantified. Nevertheless, we propose that Sedum green roofs can be part of the long-term solutions to mitigate the air pollution crisis in the Mexico City Metropolitan area, and other "megacities" with marked seasonal drought.


Time-division-multiplexing using pulse position locking for 100 Gb/s applications.
Recently, there is a great interest in pushing communication technologies to 100 Gb/s. However, there are still many challenges to perform high speed (> 40 Gb/s) clock and data recovery, and data time-division-multiplexing (TDM). Here, we propose and numerically analyze an asynchronous optical packet retimer using parabolic or sinusoidal phase modulation and linear dispersion. This scheme is named pulse position locking (PPL). Numerical simulation shows that this scheme can effectively resynchronize input signals with arbitrary delays to the local clock, and reduce input jitter. The scheme can also be applied to TDM 10 Gb/s and 40 Gb/s signals to over 100 Gb/s.


First Report of Powdery Mildew on Spanish Needles (Bidens bipinnata) Caused by Podosphaera xanthii in Korea.
Spanish needles (Bidens bipinnata L.) is an annual herb that belongs to a genus of flowering plants in family Asteraceae native to United States, and tropical regions around world. The plant produces important flavonoid compounds quercitin and hyperoside that function as anti-allergens, anti-inflammatories, anti-microbials, and anti-cancer agents. Between July and October 2011 and 2012, white superficial mycelia were observed initially on leaf and stem portions, but later progressed to the flower head. Surveys showed that the disease was widespread in Gwangju and most areas of South Korea. Abundant, necrotic, dark brown spots showing chasmothecia were frequently observed in October and were abundant on the adaxial surface of leaves. Chasmothecia were blackish brown to yellow without typical appendages. They ranged from 51.2 to 71.1 (mean 66.8) μm in diameter. Conidia were formed singly and the primary conidia were ellipsoid, rounded at the apex, truncated base, and ranged from 25.4 to 33.2 (mean 27.3) μm long × 10.2 to 12.2 (mean 11.3) μm wide. Conidiophores were erect, 60.1 to 101.3 (mean 98.3) μm long × 6.2 to 9.2 (mean 7.3) μm wide. From extracted genomic DNA, the internal transcribed spacer (ITS) region inclusive of 5.8S and 28S rDNA was amplified with ITS1F (5'-TCCGTAGGTGAACCTGCGG-3') and LR5F (5'-GCTATCCTGAGGGAAAC-3'), and LROR (5'-ACCCGCTGAACTTAAGC-3') and LR5F primer sets, respectively. rDNA ITS (GenBank Accession No. JX512555) and 28S (JX512556) homologies of the fungus (EML-BBPW1) represented 99.6% (532/534) and 100% (661/661) identity values with Podosphaera xanthii (syn. P. fusca) AB040349 and P. xanthii (syn. P. fusca) AB462798, respectively. The rDNA sequence analysis revealed that the causal fungus matched P. xanthii (syn. P. fusca), forming a xanthii/fusca group (3,4). A pathogenicity test was performed on three plants in a greenhouse. The treated leaves were sealed in vinyl pack in humid condition for 2 days. Seven days after inoculation, similar symptoms were observed on the inoculated Spanish needles plant leaves. No symptoms were observed on control plants treated with distilled water. Koch's postulates were fulfilled by re-observing the fungal pathogen on the inoculated leaves. Podosphaera (syn. Sphaerotheca) xanthii (or fusca) has been known as an ubiquitous species with a broad host range. So far, five records regarding P. xanthii (=P. fusca) have been found in plants of genus Bidens. P. xanthii has been reported to occur on B. cernua in Belarus and Switzerland. In addition, the powdery mildew species was reported to occur on B. frondosa and B. tripartita in Korea, Russia, and Switzerland (2). To our knowledge, this is the first report of powdery mildew caused by P. xanthii on Spanish needles (B. bipinnata) in Korea. References: (1) U. Braun et al. Schlechtendalia 10:91, 2003. (2) D. F. Farr and A. Y. Rossman. Fungal Databases, Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ , 2012. (3) H. B. Lee. J. Microbiol. 51:1075, 2012. (4) S. Takamatsu, et al. Persoonia 24:38, 2010.


Functional activity and functional gene diversity of a Cu-contaminated soil remediated by aided phytostabilization using compost, dolomitic limestone and a mixed tree stand.
Trace elements (TEs) availability, biochemical activity and functional gene diversity was studied in a Cu-contaminated soil, revegetated for six years with a mixed stand of willow, black poplar, and false indigo-bush, and amended or not with compost plus dolomitic limestone (OMDL). The OMDL amendment significantly reduced Cu and As availability and soil toxicity, and increased the biochemical activity and microbial functional diversity assessed with the GEOCHIP technique, as compared to the unamended soil (Unt). The OMDL soil showed significantly higher abundance of 25 functional genes involved in decomposition organic compounds, and 11, 3 and 11 functional genes involved in the N, P and S biogeochemical cycles. Functional gene abundance was positively correlated with nutrient contents but negatively correlated with Cu availability and soil toxicity. The abundance of microbial functional genes encoding for resistance to various TEs also increased, possibly due to the microbial proliferation and lower Cu exposure in the presence of high total soil Cu concentration. Genes encoding for antibiotic resistance due to the co-occurrence of TEs and antibiotic resistant genes on genetic mobile elements. Overall, phytomanagement confirmed its potential to restore the biological fertility and diversity of a severely Cu-contaminated soil, but the increase of TEs and antibiotic resistant gene abundances deserve attention in future studies.


Risk factors for coronary heart disease and acute-phase proteins. A population-based study.
Circulating levels of C-reactive protein and serum amyloid A protein increase markedly, and albumin levels fall, during the acute-phase response to tissue injury, infection and inflammation. Some acute-phase proteins have been associated with increased risks of coronary heart disease in long-term prospective studies. The aim of the present study was to determine whether circulating concentrations of C-reactive protein, albumin and serum amyloid A protein are correlated with one another, standard vascular risk factors, markers of persistent infection, or indicators of socio-economic status. We report a cross-sectional study of 704 individuals without a history of coronary heart disease from five general practices in Bedfordshire, U.K. Plasma levels of C-reactive protein and serum amyloid A protein were strongly associated with each other (2 P<0.00001) and inversely related to levels of serum albumin (2 P<0.00001). There were highly significant associations of plasma C-reactive protein concentrations with cigarette smoking and obesity (2 P<0.00001 for each). Serum albumin levels were strongly associated with blood pressure (2 P<0.0001) and plasma lipids (2 P<0.001), and concentrations of serum amyloid A protein were strongly correlated with obesity (2 P<0.0001). Previously reported long-term prospective studies have found an increased risk of coronary heart disease of about 50% in people with raised baseline levels of plasma C-reactive protein or low albumin. The strong cross-sectional associations we have found between levels of these proteins with each other and with concentrations of serum amyloid A protein suggest that some underlying process related to inflammation is likely to be of relevance to the causation of disease. Further studies are needed to determine if the strong associations of plasma levels of C-reactive protein with cigarette smoking and obesity indicate that this particular protein can mediate some of the effects of those risk factors on coronary heart disease.