Changes in ploidy affect vascular allometry and hydraulic function in Mangifera indica trees.
The enucleated vascular elements of the xylem and the phloem offer an excellent system to test the effect of ploidy on plant function because variation in vascular geometry has a direct influence on transport efficiency. However, evaluations of conduit sizes in polyploid plants have remained elusive, most remarkably in woody species. We used a combination of molecular, physiological and microscopy techniques to model the hydraulic resistance between source and sinks in tetraploid and diploid mango trees. Tetraploids exhibited larger chloroplasts, mesophyll cells and stomatal guard cells, resulting in higher leaf elastic modulus and lower dehydration rates, despite the high water potentials of both ploidies in the field. Both the xylem and the phloem displayed a scaling of conduits with ploidy, revealing attenuated hydraulic resistance in tetraploids. Conspicuous wall hygroscopic moieties in the cells involved in transpiration and transport indicate a role in volumetric adjustments as a result of turgor change in both ploidies. In autotetraploids, the enlargement of organelles, cells and tissues, which are critical for water and photoassimilate transport at long distances, point to major physiological novelties associated with whole-genome duplication.


Application of CE-ICP-MS and CE-ESI-MS in metalloproteomics: challenges, developments, and limitations.
Application of capillary electrophoresis (CE) as a high-resolution separation technique in metalloproteomics research is critically reviewed. The focus is on the requirements and challenges involved in coupling CE to sensitive element and molecule-specific detection techniques such as inductively coupled plasma mass spectrometry (ICP-MS) or electrospray ionisation mass spectrometry (ESI-MS). The complementary application of both detection techniques to the structural and functional characterisation of metal-binding proteins and their structural metal-binding moieties is emphasised. Beneficial aspects and limitations of mass spectrometry hyphenated to CE are discussed, on the basis of the literature published in this field over the last decade. Recent metalloproteomics applications of CE are reviewed to demonstrate its potential and limitations in modern biochemical speciation analysis and to indicate future directions of this technique.


The inexpensive additive N-methylmorpholine effectively decreases the equivalents of nucleophiles in the catalytic highly enantioselective arylation of aryl aldehydes.
Highly enantioselective arylation of aryl aldehydes catalyzed by (S)-H8 -BINOL-Ti(Oi-Pr)2 complex in the presence of N-methylmorpholine (NMM) as an effective and inexpensive additive is described for the first time. We found high enantioselectivity and yield but successfully reduced the equivalents of nucleophiles triarylaluminums by 50% compared with our previous report. The practicability of the process was thereby greatly increased.


Amine oxidases in apoptosis and cancer.
Amine oxidases, the major enzymes of biogenic amines metabolism, are considered to be biological regulators, especially for cell growth and differentiation. A primary involvement of amine oxidases in cancer growth inhibition and progression, especially by means of aldehydes, H(2)O(2) and other reactive oxygen species, the amine oxidase-mediated products of biogenic amines oxidation, has been demonstrated. Amine oxidases are involved in cancer growth inhibition because of the higher content in tumour cells of biogenic amines in comparison to normal cells. The cytotoxic effect can be explained by a damage to cell membranes and/or nuclei or, indirectly, through modulation of membrane permeability transition and therefore apoptosis. The oxidation products of biogenic amines appears to be also carcinogenic, while acrolein, produced from the oxidation of spermine and spermidine, should be a key compound both carcinogenic and cytotoxic. The cancer inhibition/promotion effect of amine oxidases could be explained by taking into consideration the full pattern of the enzyme content of the cell. The balance of amine oxidases and antioxidant enzymes appear to be a crucial point for cancer inhibition or progression. A long lasting imbalance of these enzymes appears to be carcinogenic, while, for a short time, amine oxidases are cytotoxic for cancer cells.


First Report of Phoma herbarum Causing Leaf Spot on Rhapis humilis in China.
Rhapis humilis Blume is an ornamental plant for landscaping that is widely distributed in China. In February 2020, a leaf spot disease was observed on R. humilis in a nursery shed in Zhanjiang (21.17 N, 110.18 E), Guangdong, China. The disease incidence was more than 90%. The early symptom was small water-soaked lesions, which then turned into black necrotic spots. Eventually, the individual lesions coalesced into larger ones, leading to the death of diseased leaves. Ten diseased leaves were collected from the nursery. The diseased tissues were cut into 2 × 2 mm pieces, surface disinfected with 75% ethanol for 30 s and 2% sodium hypochlorite for 60 s, and then rinsed three times with sterile water before pathogen isolation. The tissues were plated on potato dextrose agar (PDA) medium and incubated at 28°C in the dark for 4 days. Pure cultures were produced by transferring hyphal tips to new PDA plates. Three isolates (RHPH-1, RHPH-2, and RHPH-3) were obtained. The colonies of the isolates were approximately 5 cm in diameter after 7 days. They were initially whitish and later became grayish white. The NaOH testing on MEA cultures was negative. No sporulation was detected after 30 days. The fertile structures of the specimens collected in the nursery were examined. Pycnidia were globose, measured 68 to 265 × 72 to 360 µm (n = 20), and mostly embedded. Conidia were aseptate, hyaline, and ellipsoid, measuring 3.6 to 6.5 × 2.2 to 2.7 µm (n = 30). Based on the morphological characteristics, the fungus was identified as in genus Phoma (Boerema et al. 2004). For molecular identification, the colony PCR method with MightyAmp DNA Polymerase (Takara-Bio, Dalian, China) (Lu et al. 2012) was used to amplify the internal transcribed spacer (ITS), partial RNA polymerase II largest subunit (RPB2), and beta-tubulin (β-tub) loci of three isolates using primer pairs ITS4/ITS5, RPB2-6F/RPB2-7R, and BT2a/BT2b, respectively (Chen et al, 2015; White et al, 1990). The sequences were deposited in GenBank (ITS, MZ419364-MZ419366; RPB2, MZ562293-MZ562295; and β-tub, MZ562296-MZ562298). Based on BLAST analysis, the sequences of the ITS, RPB2, and β-tub all showed 100% similarity to Phoma herbarum Westend. (CBS 377.92, accession nos. KT389536 for ITS; KT389663 for RPB2; and KT389837 for β-tub). Pathogenicity testing was performed in a greenhouse with 80% relative humidity at 25 to 30°C. Ten healthy plants of R. humilis were grown in pots, with one plant in each pot. The leaves were pinpricked with sterile needles before inoculation. They were inoculated with mycelial plugs of the isolates or sterile agar plugs (as control), with four plugs for each leaf. Five plants were used in each treatment. Disease symptoms similar to those in the nursery were observed on the inoculated plants 2 weeks after inoculation, whereas the control plants remained healthy. The fungus was reisolated from the symptomatic leaves and confirmed as P. herbarum by morphology and ITS analysis. P. herbarum was reported to cause leaf spot on Atractylodes lancea, Camellia sinensis, Elaeis guineensis, Lilium brownii, and Vetiveria zizanioides in China; Bituminaria bituminosa, Glycine max, Medicago sativa, and Pisum sativum in Australia; and Salvia nemorosa in Italy (Li et al. 2011; Li et al. 2012; Thangaraj et al. 2018). To our knowledge, the present study was the first to report P. herbarum causing leaf spot on R. humilis in China. P. herbarum seriously affects the supply of seedlings in R. humilis, and its epidemiology on R. humilis should be further studied.


Comparative study of the forelimbs of the semifossorial prairie dog, Cynomys gunnisoni, and the scansorial fox squirrel, Sciurus niger.
A comparative study of the forelimbs of the semifossorial prairie dog, Cynomys gunnisoni , and the scansorial tree squirrel, Sciurus niger, was focused on the musculoskeletal design for digging in the former and climbing in the latter. Based on lever arm mechanics, it was expected that the forelimb of the prairie dog would show features appropriate to the production of relatively large forces and that of the fox squirrel to relatively great velocity. Force and lever arm measurements were made of select forelimb muscles at the shoulder, elbow, and wrist joints for a series of angles in both species. Contraction time and fatigue indexes were determined for the same forelimb muscles. Contrary to expectation, in the few cases in which significant (P less than .05) differences were found, the forces, lever arms, and torques (force times its lever arm) were greater in the smaller fox squirrel. The observed variation in the torques produced fits the demands on the forelimb during climbing and digging as estimated from films. Several forelimb muscles of the fox squirrel show significantly higher mean contraction times than do the homologous muscles of the prairie dog. There were no significant differences between the two species in the fatigability of the selected forelimb muscles, although the mean fatigue index was always higher (less fatigable muscle) in the prairie dog. Similarities in the forelimbs of these two sciurids suggest that only minor modifications may have been required of the ancestral forelimb in order for descendent forms to operate successfully as climbers and diggers .


Role of Subtalar Arthroscopy in Operative Treatment of Sanders Type 2 Calcaneal Fractures Using a Sinus Tarsi Approach.
This study was conducted to evaluate the usefulness of subtalar arthroscopy in the operative treatment of Sanders type 2 calcaneus fractures using a sinus tarsi approach. Forty-six Sanders type 2 calcaneal fractures were consecutively treated using a sinus tarsi approach. Intraoperative fluoroscopy was used to evaluate fracture reduction in the first 23 patients (fluoroscopy group), and intraoperative fluoroscopy and subtalar arthroscopy were used in the latter 23 patients (arthroscopy group). Clinical evaluations were performed using a visual analog scale, the Ankle-Hindfoot Scale developed by the American Orthopaedic Foot & Ankle Society, and Short Form Health Survey. Radiographic evaluations were performed using calcaneal and lateral radiographs and computed tomography (CT) scans. Böhler's angles and calcaneal widths were compared between the groups. Reduction of the posterior facet was graded according to articular step, defect, and angulation of the posterior facet on CT. At the last follow-up, clinical results as well as Böhler's angles and calcaneal widths were not different between the groups. On immediately postoperative CT, reduction of the posterior facet showed a higher-than-good grade in 17 feet (73.9%) in the fluoroscopy group and a higher-than-good grade in 22 feet (95.7%) in the arthroscopy group, and these values were significantly different between the groups ( P = .04). A combined approach using fluoroscopy and subtalar arthroscopy showed better reduction of the posterior facet on CT than using fluoroscopy alone. Therefore, subtalar arthroscopy could be a useful method for detecting joint incongruence when using the sinus tarsi approach for Sanders type 2 calcaneal fractures. Level III, comparative series.


[Long-acting beta-2-agonists in the treatment of asthma].
The long-acting beta-2-agonist bronchodilators salmeterol and formoterol are relatively new drugs that may significantly improve the treatment of chronic bronchial asthma. Their physical and chemical properties partly explain the long duration of their bronchodilating action and their high affinity for beta-2-receptors. Numerous clinical studies have demonstrated their ability to alleviate the symptoms of asthma. In vitro studies have also revealed interesting effects of these two drugs in some aspects of the bronchial inflammatory process. However, they should not be considered equivalent to antiinflammatory medication from a clinical point of view. National and international consensus conferences insist on the fact that salmeterol or formoterol should always be prescribed in conjunction with inhaled corticosteroids.


Induction of immunological tolerance in bone marrow-derived lymphocytes of the IgE antibody class.
Administration of the 2,4-dinitrophenyl (Dnp) determinant conjugated to the "nonimmunogenic" copolymer of D-glutamic acid and D-lysine (D-GL) induces Dnp-specific immunological tolerance which is essentially restricted to bone marrow-derived (B) lymphocytes. Previous studies have demonstrated tolerance induction by Dnp-D-GL in predominantly B lymphocytes of the IgG class. The present studies establish and analyze conditions for tolerance induction in Dnp-specific B lymphocytes of the IgE antibody class by taking advantage of: (i) the relatively easy capacity to induce tolerance with Dnp-D-GL in an animal or cell population previously primed to the Dnp determinant; (ii) previously established parameters for the successful adoptive transfer of Dnp-specific IgE antibody responses; and (iii) the capacity to induce, and maintain a state of Dnp-specific tolerance with Dnp-D-GL in adoptive transfer responses. Using these approaches, we have successfully rendered Dnp-specific B cells of the IgE class profoundly and apparently irreversibly tolerant after exposure of such cells to Dnp-D-GL. These observations represent a starting point of wide potential for solving many therapeutic problems concerned with clinical allergies.


DSM-III-R: too much too soon?
Some of the more important changes carried out in the recently published revision of the DSM-III classification (DSM-III-R) are described, and an assessment is made on whether a revision of this nature was necessary and whether it achieved its aims. Since a large number of disorders have been modified in one way or another and since empirical evidence for many of the changes is lacking, the author concludes that DSM-III-R, rather than illuminating the field, is likely to cause confusion and frustration in the minds of clinicians, researchers and administrators, and that in fact DSM-III-R is a new classification, a DSM-IV in disguise.


Role of neuroinflammation in neurodegeneration: new insights.
Previously, the contribution of peripheral infection to cognitive decline was largely overlooked however, the past 15 years have established a key role for infectious pathogens in the progression of age-related neurodegeneration. It is now accepted that the immune privilege of the brain is not absolute, and that cells of the central nervous system are sensitive to both the inflammatory events occurring in the periphery and to the infiltration of peripheral immune cells. This is particularly relevant for the progression of Alzheimer's disease, in which it has been demonstrated that patients are more vulnerable to infection-related cognitive changes. This can occur from typical infectious challenges such as respiratory tract infections, although a number of specific viral, bacterial, and fungal pathogens have also been associated with the development of the disease. To date, it is not clear whether these microorganisms are directly related to Alzheimer's disease progression or if they are opportune pathogens that easily colonize those with dementia and exacerbate the ongoing inflammation observed in these individuals. This review will discuss the impact of each of these challenges, and examine the changes known to occur with age in the peripheral immune system, which may contribute to the age-related vulnerability to infection-induced cognitive decline.


3D Printing of Thermoflexible Therapeutic Splints: Treating Bruxism More Comfortably.
Three-dimensional (3D) printing has helped drive rapid and abundant growth in the field of digital dentistry and has been largely spurred on by the development of material innovation. Thermoflexible occlusal splints represent a recent innovation in this area, as they feature a remarkably elastic behavior. Now, practitioners can provide patients with a comfortable, soft, class II medical device generated through a simple digital workflow. This article presents a case report that demonstrates the management of temporomandibular joint disorders by means of a flexible 3D-printed splint. Providing the patient relative comfort while wearing the splint to prevent the negative effects of bruxism helped enhance patient acceptance and compliance. The simple, non-invasive splint fabrication described in this report can be performed by any clinicians willing to incorporate occlusal devices into their digital workflow.


LRRFIP1 expression triggers platelet agglutination by enhancing αIIbβ3 expression.
Platelets primarily participate in hemostasis and antimicrobial host defense. The present study aimed to investigate the effects of leucine-rich repeat flightless-interacting protein-1 (LRRFIP1) on platelet agglutination. The bacterial strain of LRRFIP1 was used to synthesize the recombinant protein and a mouse model of LRRFIP1 gene knockout was established. Platelets were isolated from the mice and divided into the different trial groups according to their treatment with collagen, thrombin receptor SFLLRN, anti-wild-type (w)LRRFIP1monoclonal antibodies and the model of LRRFIP1 gene knockout. The platelets were prepared and platelet agglutination was examined using platelet aggregation apparatus. The active αIIbβ3 integrin was examined by flow cytometry. The results revealed that the combined wLRRFIP1 protein was successfully expressed. wLRRFIP1 treatment significantly triggered platelet agglutination of collagen, thrombin and monoclonal antibody treated platelets. wLRRFIP1 knockout significantly decreased αIIbβ3 levels compared with the wild-type. Platelet agglutination was also significantly inhibited in the LRRFIP1-/-mouse model compared with the wild-type. LRRFIP1 knockout significantly decreased the αIIbβ3 levels in platelets undergoing convulxin treatment. In conclusion, LRRFIP1 treatment triggered platelet agglutination and LRRFIP1 gene knockout inhibited platelet agglutination. In addition, LRRFIP1 gene knockout significantly decreased the levels of αIIbβ3. This suggests that LRRFIP1 my be applied to patients in a clinical setting to trigger platelet agglutination in inflammatory diseases and atherothrombotic diseases.


Principles of care for women experiencing intimate partner violence: Views of expert Japanese health professionals and advocates.
In Japan, interventions for Intimate Partner Violence (IPV) in the health care setting are rare, partly due to Japanese cultural norms that marginalize women's IPV experiences. A thematic analysis of narratives of eight Japanese health professionals who are experts in IPV care identified shared core values and practices that have guided their development of culturally relevant IPV interventions: supporting women's autonomy to define what is at stake for her, appreciating unique trajectories and timing for recovery, and practicing shared decision-making. These shared practices may be essential for training health professionals to respond to IPV in Japan and elsewhere.


Phase 2 trial of imatinib mesylate in myelofibrosis with myeloid metaplasia.
In a phase 2 study, 23 patients with myelofibrosis with myeloid metaplasia were treated with imatinib mesylate at a constant dose of 400 mg/d. Treatment was held in 16 patients (70%), after 1 to 12 weeks, because of side effects (neutropenia, 6 patients; musculoskeletal pain, 5 patients; thrombocytosis, 4 patients; edema, 3 patients; diarrhea and hyperbilirubinemia, 1 patient). Including patients in whom retreatment at a reduced dose was possible, 11 patients (48%) were able to continue treatment beyond 3 months. None of the patients experienced a response in anemia, and only 2 had partial responses in splenomegaly. A greater than 50% increase in platelet count was documented in 11 (48%) patients, but not in those with baseline platelet counts of less than 100 x 10(9)/L. In vitro, imatinib mesylate caused variable degrees of growth suppression of myeloid and erythroid progenitors that unfortunately did not translate into clinical benefit.


Phenolic content and antioxidant and antimicrobial properties of fruits of Capsicum baccatum L. var. pendulum at different maturity stages.
The phenolic content, antioxidant potential, and antimicrobial activity of extracts of different parts of the fruit from Capsicum baccatum L. var. pendulum were investigated. The analysis of phenolic content was performed by the Folin-Ciocalteu method and reversed-phase high-performance liquid chromatography. The in vitro antioxidant activity was assessed by the total reactive antioxidant potential and total antioxidant reactivity index. The antioxidant activity was positively correlated with the amount of phenolics found in each sample. The ex vivo antioxidant potential was assessed using the rat liver slice model. The antimicrobial activity was screened using Gram-positive and Gram-negative bacteria and fungi. All the extracts revealed antioxidant activity and a weak antimicrobial activity.


Histamine H2-receptors on guinea-pig ileum myenteric plexus neurons mediate the release of contractile agents.
Dimaprit, a highly selective H2-agonist, caused a multiphasic contraction of guinea-pig ileal segments and ileal myenteric plexus-longitudinal muscle preparations. The initial phase was characterized by a twitch which reached a maximum in 15 to 30 sec and was followed by a partial relaxation. The later phase was variable and consisted of a series of twitch responses or of a slowly developing contracture which sometimes was accompanied by oscillatory changes in tension. dose-response curves were generated for the initial response; for isolated ileal segments the EC50 was 5.1 +/- 1.8 micrometers (mean +/- S.D., N = 7) and the Hill coefficient was 1.1 +/- 0.2 and for longitudinal muscle strips the EC50 was 5.8 +/- 1.2 micrometer and the Hill coefficient was 1.2 +/- 0.1 (N = 7). Both the initial and secondary components of the contractile responses to dimaprit were prevented by 0.2 micron tetrodotoxin or 10 microns mefenamic acid and by the production of tachphylaxis to either substance P or serotonin. Scopolamine, 0.001 to 0.1 micron, insurmountably antagonized only the initial component of the response. Mepyramine (1.0 micrometer), hexamethonium (100 microns), bromolysergic acid (0.25 microns) and p-(imidazol-1-yl)phenyl (10 microns) were without effect on the response to dimaprit. The histamine H2-receptor antagonist, tiotidine, produced parallel dextral shifts in the dose-response curve for dimaprit. The apparent pA2 value for tiotidine was 7.65. The results suggest that dimaprit acts on H2-receptors located on myenteric plexus neurons to cause the release of contractile substances. The mediators of the contractile response are tentatively identified as acetylcholine, substance P, serotonin and a product(s) of the arachadonic acid cascade.


Permeation and deposition of fibrinogen and low-density lipoprotein in the aorta and cerebral artery of rabbits--immuno-electron microscopic study.
The localization of fibrinogen and low-density lipoprotein (LDL) in the arterial wall has been studied to determine whether they mediate the effects of hypertension and/or hypercholesteraemia on atherogenesis. In untreated control rabbits, fibrinogen was localized in the caveolae and vesicles of the endothelial cells and in the subendothelial spaces of the aorta. No fibrinogen was found in the subendothelial spaces of the cerebral artery. Hypertension or hypercholesteraemia was accompanied by enhanced insudation of fibrinogen into the subendothelial spaces of the aorta and cerebral artery, and fibrinogen deposition was most prominent in the hypercholesteraemic rabbits with induced renovascular hypertension. The insudation of fibrinogen appeared to occur by way of vesicular transport, and to some extent by junctional transport. In the untreated control rabbits, LDL was localized only in the caveolae and vesicles of endothelial cells in both aorta and cerebral artery. LDL was deposited in the subendothelial space of the aorta of hypercholesteraemic rabbits with or without hypertension, and in the cerebral artery of hypercholesteraemic rabbits with hypertension. These findings suggest that fibrinogen insudates into the intima of the aorta and cerebral artery both during hypertension and hypercholesteraemia, and that LDL insudation into the intima of the aorta in hypercholesteraemia is accentuated by hypertension. LDL insudated into the intima of the cerebral artery in the presence of hypercholesteraemia linked to hypertension. Thus, hypertension plays a significant role in the pathogenesis of cerebral atherosclerosis.


Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma.
The conversion rate of tegafur (a component of S-1) to fluorouracil (FU) differs in Asians and whites because of polymorphic differences in the CYP2A6 gene. S-1 with cisplatin is considered highly active in Japanese gastric cancer patients. Therefore, we initiated a phase I pharmacokinetic study of this combination in our gastric cancer patients. Patients received cisplatin intravenously on day 1 and S-1 orally, twice daily, on days 1 to 21 every 28 days. At level 1, the S-1 dose was 25 mg/m2/dose (50 mg/m2/d), but it was increased by 5 mg/m2/dose for the next level. Cisplatin was administered at 75 mg/m2 (for levels 1 and 2) but was then reduced to 60 mg/m2 (level 1A). At every level, a cohort of three patients, which could be expanded to six patients, was studied. Maximum-tolerated dose (MTD) was determined based on the dose-limiting toxicity (DLT) in the first cycle. Patients with histologic proof of gastric adenocarcinoma and near-normal organ function were studied. Sixteen patients were enrolled. No DLTs occurred at level 1. However, DLTs occurred at levels 2 and 1A. The area under the curve for FU correlated significantly with DLT (P = .006) and grade 3 to 4 diarrhea (P = .004). Six partial responses were confirmed, including three at the MTD. At the established MTD of S-1 plus cisplatin, the S-1 dose (50 mg/m2/d for 21 days) is lower in our study than in the Japanese study (80 mg/m2/d for 21 days). A multi-institutional phase II study of this active combination is currently accruing patients.


Building communities of trust: Challenges for disability.
This article asks questions about power and partnership in disability research in Africa. Research has been located too much in one type of organisation or another and not sufficiently in the interaction between a range of legitimate stakeholders. Across Africa and Europe, and government and civil society dialogues, the African development research agenda must be owned by Africans. Fully inclusive national and international research partnerships are crucial, but they must be driven from Africa. European constructions of and interventions concerning people with disability have often been inhumane, seeking to eliminate them from society. African cultures have also stigmatised people with disability. I call for a new African-driven research agenda that promotes the human rights of people with disability, and has people with disability not only participating in this research, but directing it. The Southern African Federation of the Disabled (SAFOD) Research Programme (SRP) is breaking new ground in this regard by allowing 'the researched' to become 'the researcher'.


Clozapine-induced bicytopenia: An unusual side effect.
Agranulocytosis is a rare documented side effect of clozapine which can be associated with grave consequences. When it is associated with other blood dyscrasia, prognosis worsens further. In literature, there are very few cases of pancytopenia and bicytopenia caused by clozapine. We present a case of bicytopenia (reduced white and red blood cells' counts) caused by clozapine within a month of therapy and complicated by a Klebsiella pneumoniae infection. Patient improved in 3 weeks after stopping clozapine along with medical management in the Intensive Care Unit. Such side effects, though rare, can be life threatening and warrants intermittent complete blood monitoring besides regular assessment of granulocytes and neutrophils when any patient is prescribed clozapine.


IL-13Ralpha2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice.
Development of persistent Th2 responses in asthma and chronic helminth infections are a major health concern. IL-10 has been identified as a critical regulator of Th2 immunity, but mechanisms for controlling Th2 effector function remain unclear. IL-10 also has paradoxical effects on Th2-associated pathology, with IL-10 deficiency resulting in increased Th2-driven inflammation but also reduced airway hyperreactivity (AHR), mucus hypersecretion, and fibrosis. We demonstrate that increased IL-13 receptor alpha 2 (IL-13Ralpha2) expression is responsible for the reduced AHR, mucus production, and fibrosis in BALB/c IL-10(-/-) mice. Using models of allergic asthma and chronic helminth infection, we demonstrate that IL-10 and IL-13Ralpha2 coordinately suppress Th2-mediated inflammation and pathology, respectively. Although IL-10 was identified as the dominant antiinflammatory mediator, studies with double IL-10/IL-13Ralpha2-deficient mice illustrate an indispensable role for IL-13Ralpha2 in the suppression of AHR, mucus production, and fibrosis. Thus, IL-10 and IL-13Ralpha2 are both required to control chronic Th2-driven pathological responses.


Cerebral arterial gas embolism, ingestion of hydrogen peroxide and flight.
We read with interest the recent report by Smedley et al. on an interesting case of cerebral arterial gas embolism (CAGE) after pre-flight ingestion of hydrogen peroxide (H₂O₂). The authors discuss the safety of aero-medical transfer following H₂O₂ ingestion. We agree with the possible problems but the concern on the other side of the coin needs to be mentioned; can transfer be delayed is the big question? Indeed, as reported by others, ingestion of even a small amount of concentrated H₂O₂ can result in CAGE. Hence, whether aero-medical transfer proceeds or not, severe, life-threatening embolism can occur. Since it was reported that "complete neurologic recovery occurred quickly with hyperbaric therapy", this supports the contention that the fastest transfer of the patient for hyperbaric treatment should be the primary focus.


Moving to Another World: Understanding the Impact of Clinical Trial Closure on Research Participants Living With HIV in Uganda.
Despite an increasing need for clinical trials involving people living with HIV (PLWH), little is known about how PLWH experience trial closure, particularly in low-income countries, where the majority of trials take place. We sought to explore the impact of trial closure on PLWH in Uganda. This was an interpretive, grounded theory study using in-depth interviews, conducted between October 2014 and August 2015. Adult participants (N = 23) from 3 trials were included. The findings indicated that trial closure was represented as "moving to another world" and was an emotional transition, linked to a loss of quality care in the research environment, the need to find alternative health facilities, fear of experiencing unwanted side effects, a desire to receive trial feedback, and difficulties linking to posttrial care. We concluded that PLWH leaving trials in a resource-limited setting required holistic care to facilitate their transition back to "usual care."


Towards a scientific community consensus on designating Vulnerable Marine Ecosystems from imagery.
Management of deep-sea fisheries in areas beyond national jurisdiction by Regional Fisheries Management Organizations/Arrangements (RFMO/As) requires identification of areas with Vulnerable Marine Ecosystems (VMEs). Currently, fisheries data, including trawl and longline bycatch data, are used by many RFMO/As to inform the identification of VMEs. However, the collection of such data creates impacts and there is a need to collect non-invasive data for VME identification and monitoring purposes. Imagery data from scientific surveys satisfies this requirement, but there currently is no established framework for identifying VMEs from images. Thus, the goal of this study was to bring together a large international team to determine current VME assessment protocols and establish preliminary global consensus guidelines for identifying VMEs from images. An initial assessment showed a lack of consistency among RFMO/A regions regarding what is considered a VME indicator taxon, and hence variability in how VMEs might be defined. In certain cases, experts agreed that a VME could be identified from a single image, most often in areas of scleractinian reefs, dense octocoral gardens, multiple VME species' co-occurrence, and chemosynthetic ecosystems. A decision flow chart is presented that gives practical interpretation of the FAO criteria for single images. To further evaluate steps of the flow chart related to density, data were compiled to assess whether scientists perceived similar density thresholds across regions. The range of observed densities and the density values considered to be VMEs varied considerably by taxon, but in many cases, there was a statistical difference in what experts considered to be a VME compared to images not considered a VME. Further work is required to develop an areal extent index, to include a measure of confidence, and to increase our understanding of what levels of density and diversity correspond to key ecosystem functions for VME indicator taxa. Based on our results, the following recommendations are made: 1. There is a need to establish a global consensus on which taxa are VME indicators. 2. RFMO/As should consider adopting guidelines that use imagery surveys as an alternative (or complement) to using bycatch and trawl surveys for designating VMEs. 3. Imagery surveys should also be included in Impact Assessments. And 4. All industries that impact the seafloor, not just fisheries, should use imagery surveys to detect and identify VMEs.


o-Orsellinaldehyde from the submerged culture of the edible mushroom Grifola frondosa exhibits selective cytotoxic effect against Hep 3B cells through apoptosis.
The tumoricidal activity of a bioactive metabolite produced by submerged culture in a 2.1-L airlift fermentor of Grifola frondosa NTUS was investigated. After 14 days of cultivation, ethyl acetate extracts from the supernatant of culture broth (EES) were analyzed by cell viability assay. The IC50 of EES for cytotoxicity against human carcinoma cells (Hep 3B, Hep G2, HeLa, CL1-1) and normal human lung fibroblast MRC-5 was 78.4, 52.7, 77.6, 71.0, and 233.3 microg/mL, respectively. EES was further fractionated and a main cytotoxic compound, HE-5-5, was obtained. The IC50 of HE-5-5 based on the cell viability of Hep 3B and MRC-5 cells was 3.6 and 33.1 microg/mL, respectively. Thus, HE-5-5 showed a selective cytotoxic effect against Hep 3B cells and MRC-5. According to the UV, MS, and NMR data, HE-5-5 was identified as o-orsellinaldehyde. A DNA fragmentation assay together with the presence of a significant sub-G1 peak by flow cytometry suggested that o-orsellinaldehyde might mediate its cytotoxicity through apoptosis.


Long-term observation of cardiac arrhythmias during and after cardiac surgery. II. Congenital heart disease.
Twelve arrhythmias that occurred in conjunction with surgery for congenital heart disease were studied in a group of 38 randomly selected patients. Halothane was used for anaesthesia and procaine-magnesium-aspartate solution for cardiac arrest. Registration and analysis of rhythm disturbances were carried out at 10 different time points, spaced narrowly in the intra- and early postoperative phases, then more widely up to the 96th hour of observation. Arrhythmic incidence per case and occurrence per case and phase are given, thereby also allowing an account of transient arrhythmias. The peak occurrence of intra-operative rhythm disturbances was found at about the time of aortic cross-clamping and release (ischaemia and halothane effect). A decline in arrhythmic incidence in the 1st-6th post-bypass hours was followed by a 2nd peak in the 6th-23rd postoperative hours (electrolyte and acid-base disturbances and/or a digitalis effect). All 12 arrhythmia types of the cardiopulmonary bypass group, as well as the separately considered ventricular arrhythmias of the first "arrhythmia peak", did not reveal any significant relation to: patients' age, total anaesthesia time, total surgery time and total bypass time. It is recognized that any comparative evaluation of operative arrhythmias, and especially a study of the causes and development of "surgically induced" A-V block, is problematic.


Long-Term Effect of a Leonardite Iron Humate Improving Fe Nutrition As Revealed in Silico, in Vivo, and in Field Experiments.
Novel, cheap and ecofriendly fertilizers that solve the usual iron deficiency problem in calcareous soil are needed. The aim of this work is to study the long-term effect of an iron leonardite fertilizer on citrus nutrition taking into account a properly characterization, kinetic response with a ligand competition experiment, efficiency assessment using Saccharomyces cerevisiae strain and finally, in field conditions with citrus as test plants. Its efficiency was compared with the synthetic iron chelate FeEDDHA. Leonardite iron humate (LIH) is mainly humic acid with a high-condensed structure where iron is present as ferrihydrite and Fe3+ polynuclear compounds stabilized by organic matter. Iron and humic acids form aggregates that decrease the iron release from these kinds of fertilizers. Furthermore, LIH repressed almost 50% of the expression of FET3, FTR1, SIT1, and TIS11 genes in Saccharomyces cerevisiae cells, indicating increasing iron provided in cells and improved iron nutrition in citrus.


How decision analysis can further nanoinformatics.
The increase in nanomaterial research has resulted in increased nanomaterial data. The next challenge is to meaningfully integrate and interpret these data for better and more efficient decisions. Due to the complex nature of nanomaterials, rapid changes in technology, and disunified testing and data publishing strategies, information regarding material properties is often illusive, uncertain, and/or of varying quality, which limits the ability of researchers and regulatory agencies to process and use the data. The vision of nanoinformatics is to address this problem by identifying the information necessary to support specific decisions (a top-down approach) and collecting and visualizing these relevant data (a bottom-up approach). Current nanoinformatics efforts, however, have yet to efficiently focus data acquisition efforts on the research most relevant for bridging specific nanomaterial data gaps. Collecting unnecessary data and visualizing irrelevant information are expensive activities that overwhelm decision makers. We propose that the decision analytic techniques of multicriteria decision analysis (MCDA), value of information (VOI), weight of evidence (WOE), and portfolio decision analysis (PDA) can bridge the gap from current data collection and visualization efforts to present information relevant to specific decision needs. Decision analytic and Bayesian models could be a natural extension of mechanistic and statistical models for nanoinformatics practitioners to master in solving complex nanotechnology challenges.


Meat quality responses to feeding distiller's grains to finishing Holstein steers.
Strip loins from two experiments were used to evaluate effects of feeding dry (DDG) or wet (WDG) distiller's grains on beef color, tenderness, and sensory traits of Holstein steers. In Exp. 1, conducted at the University of Illinois at Champaign-Urbana, dietary treatments consisted of a control whole corn-corn silage diet with soybean meal (SBM) or diets formulated with 12.5% DDG plus urea, 25% DDG, 25% WDG, 50% DDG, or 50% WDG (DM basis). In Exp. 2, conducted at Iowa State University, dietary treatments consisted of cracked corn-corn silage-hay diets with either SBM or urea (Urea) as the control diets, or diets formulated with 10, 20, or 40% DDG or WDG (DM basis). Within each study, strip loins from each of four steers (representing 45.7 and 66.6% of steers in Exp. 1 and 2, respectively) in four replicate pens per treatment were aged for 13 d at 4 degrees C for subsequent color, tenderness, and palatability evaluation. Color of steaks was measured objectively using a HunterLab Miniscan XE spectrophotometer and was subjectively evaluated by a trained panel. Tenderness was measured using the Warner-Bratzler shear force (WBSF) instrument on steaks cooked to 70 degrees C. For sensory evaluation, 95 consumers were recruited to evaluate tenderness, juiciness, and flavor of cooked steaks. In Exp. 1, steaks from steers fed 25% WDG had higher (P < 0.05) a* values after 138 h of simulated retail display than all other treatments, except for those from steers fed 12.5% DDG. In Exp. 2, a greater (P < 0.05) percentage of steaks from steers fed 40% DDG or 40% WDG were considered moderately undesirable during retail display (steaks that received a consumer acceptability score of 3 or less). There were no (P = 0.20 in Exp. 1, and P = 0.33 in Exp. 2) differences among treatments in Exp. 1 and Exp. 2 for WBSF (1.47 +/- 0.66 kg and 1.58 +/- 0.72 kg, respectively) or taste panel tenderness (5.7 +/- 0.30 and 6.2 +/- 0.22, respectively), beef flavor (6.0 +/- 0.23 and 6.2 +/- 0.22, respectively), and juiciness (5.6 +/- 0.31 and 5.8 +/- 0.23). Feeding distiller's grains at up to 50% of the dietary DM did not affect tenderness or sensory traits, and seems to be a viable feed alternative without negatively impacting sensory attributes.


Divergent Pathways to Assimilation? Local Marriage Markets and Intermarriage among U.S. Hispanics.
The growing diversity of the U.S. population raises questions about integration among America's fastest growing minority population-Hispanics. The canonical view is that intermarriage with the native-born white population represents a singular pathway to assimilation, one that varies over geographic space in response to uneven local marital opportunities. Using data on past-year marriage from the 2009-2014 American Community Survey, we demonstrate high rates of intermarriage among Hispanics. Our analyses identify whether Hispanics marry co-ethnics, non-co-ethnic Hispanics, non-Hispanic whites, non-Hispanic blacks, or other minorities. We highlight variation by race, nativity, and socioeconomic status, but also reveal that Hispanics living in new immigrant destinations are more likely to intermarry than those living in traditional Hispanic gateways. Indeed, the higher out-marriage in new destinations disappears when the demographic context of reception is taken into account. Our analysis underscores that patterns of marital assimilation among Hispanics are neither monolithic nor expressed uniformly across geographic space.


[Relationship between geratic frailty and cognitive dysfunction in the eldly].
To analyze the current situation and correlation between frailty and cognitive dysfunction in the old patients of orthopedic emergency. Enrolling 248 elderly people( ≥65 years old) in orthopedic emergency department of Beijing Jishuitan Hospital from September to December 2018, the cognitive function of the subjects was assessed by Mini-mental State Examination( MMSE). The frailty situation was assessed by FRAIL Scale. In addition, ADL, exercise tolerance assessment, gripping power and geriatric nutritional risk index( GNRI) were also tested in this study. In this research, 58( 23. 4%) were the elderly with normal cognitive function, 69( 27. 8%) were MCI, and 86( 34. 7%) were dementia and 35( 14. 1%) were severe dementia. The prevalence of seniors over 76 years old was significantly higher than that of the younger age group( χ~2= 39. 300, P < 0. 001), the prevalence of seniors below primary school was significantly higher than that of junior middle school and above( χ~2= 117. 082, P<0. 001), and the prevalence of dementia in patients with chronic obstructive pulmonary disease( COPD) was higher( χ~2= 11. 685, P = 0. 009). The study subjects were strong elderly, accounting for 69( 27. 8%), 114( 46. 0%) and 65( 26. 2%)were in prefrailty and frailty. The prevalence of prefrailty in 75-85 years old people was significantly higher than that in other groups, and the prevalence of prefrailty and frailty in85 years old people was both higher( χ~2= 45. 247, P<0. 001). In addition, education level( χ~2= 13. 909, P = 0. 008), hypertension( χ~2= 6. 892, P = 0. 032), COPD( χ~2= 8. 411, P =0. 015), cerebral infarction( χ~2= 7. 477, P = 0. 024) and GNRI( χ~2= 22. 942, P = 0. 001)were all the influencing factors of frailty. There were also significant differences in ADL, exercise tolerance and gripping power among the above factors. There were significant differences in cognitive function among subjects with different levels of frailty( χ~2=61. 259, P = 0. 000), ADL( χ~2= 54. 652, P<0. 001), exercise tolerance( χ~2= 77. 001, P =0. 000) and grip strength( χ~2= 54. 778, P < 0. 001). After adjusting for demographic characteristics and chronic diseases such as age, sex, education, BMI, coronary heart disease, hypertension and et al. Logistic regression analysis showed that the OR values of prefrailty, frailty, ADL and exercise tolerance affect cognition are 1. 918( 95% CI 0. 990-3. 716), 2. 732( 95%CI 1. 063-7. 023), 3. 217( 95% CI 1. 421-7. 285), 6. 440( 95% CI1. 803-22. 997). Prefrailty and frailty are closely related to cognitive dysfunction in the elderly.


The Sun is less active than other solar-like stars.
The magnetic activity of the Sun and other stars causes their brightness to vary. We investigated how typical the Sun's variability is compared with other solar-like stars, i.e., those with near-solar effective temperatures and rotation periods. By combining 4 years of photometric observations from the Kepler space telescope with astrometric data from the Gaia spacecraft, we were able to measure photometric variabilities of 369 solar-like stars. Most of those with well-determined rotation periods showed higher variability than the Sun and are therefore considerably more active. These stars appear nearly identical to the Sun except for their higher variability. Therefore, we speculate that the Sun could potentially also go through epochs of such high variability.


Malate accumulation in different organs of Mesembryanthemum crystallinum L. following age-dependent or salinity-triggered CAM metabolism.
Different organs of Mesembryanthemum crystallinum exhibit differing levels of CAM (Crassulacean acid metabolism), identifiable by quantification of nocturnal malate accumulation. Shoots and also basal parts of young leaves were observed to accumulate high concentrations of malate. It was typically found in mature leaves and especially prominent in plants subjected to salt stress. Small amount of nocturnal malate accumulation was found in roots of M. crystallinum plants following age-dependent or salinity-triggered CAM. This is an indication that malate can be also stored in non-photosynthetic tissue. Measurements of catalase activity did not produce evidence of the correlation between activity of this enzyme and the level of malate accumulation in different organs of M. crystallinum although catalase activity also appeared to be dependent on the photoperiod. In all material collected at dusk catalase activity was greater than it was observed in the organs harvested at dawn.


Construction of chromosomally located T7 expression system for production of heterologous secreted proteins in Bacillus subtilis.
Bacillus subtilis is most commonly employed for secretion of recombinant proteins. To circumvent the problems caused by using plasmids, the T7 expression system known for its high efficiency was rebuilt in B. subtilis. Accordingly, a markerless and replicon-free method was developed for genomic insertion of DNAs. By the act of homologous recombination via the guide DNA, a suicidal vector carrying the gene of interest was integrated into genomic loci of bacteria. Removal of the inserted selection marker and replicon flanked by FRT sites was mediated by the FLP recombinase. By using the mentioned system, B. subtilis strain PT5 was constructed to harbor a genomic copy of the spac promoter-regulated T7 gene 1 located at wprA (encoding the cell wall-associated protease). Similarly, the T7 promoter-driven nattokinase or endoglucanase E1 of Thermomonospora fusca genes were also integrated into mpr (encoding an extracellular protease) of strain PT5. Consequently, the integrant PT5/Mmp-T7N or PT5/MT1-E1 resulted in a "clean" producer strain deprived of six proteases. After 24 h, the strain receiving induction was able to secret nattokinase and endoglucanase E1 with the volumetric activity reaching 10860 CU/mL and 8.4 U/mL, respectively. This result clearly indicates the great promise of the proposed approach for high secretion of recombinant proteins in B. subtilis.


Early Paleocene landbird supports rapid phylogenetic and morphological diversification of crown birds after the K-Pg mass extinction.
Evidence is accumulating for a rapid diversification of birds following the K-Pg extinction. Recent molecular divergence dating studies suggest that birds radiated explosively during the first few million years of the Paleocene; however, fossils from this interval remain poorly represented, hindering our understanding of morphological and ecological specialization in early neoavian birds. Here we report a small fossil bird from the Nacimiento Formation of New Mexico, constrained to 62.221-62.517 Ma. This partial skeleton represents the oldest arboreal crown group bird known. Phylogenetic analyses recovered Tsidiiyazhi abini gen. et sp. nov. as a member of the Sandcoleidae, an extinct basal clade of stem mousebirds (Coliiformes). The discovery of Tsidiiyazhi pushes the minimum divergence ages of as many as nine additional major neoavian lineages into the earliest Paleocene, compressing the duration of the proposed explosive post-K-Pg radiation of modern birds into a very narrow temporal window parallel to that suggested for placental mammals. Simultaneously, Tsidiiyazhi provides evidence for the rapid morphological (and likely ecological) diversification of crown birds. Features of the foot indicate semizygodactyly (the ability to facultatively reverse the fourth pedal digit), and the arcuate arrangement of the pedal trochleae bears a striking resemblance to the conformation in owls (Strigiformes). Inclusion of fossil taxa and branch length estimates impacts ancestral state reconstructions, revealing support for the independent evolution of semizygodactyly in Coliiformes, Leptosomiformes, and Strigiformes, none of which is closely related to extant clades exhibiting full zygodactyly.


Cardiac rupture complicating acute myocardial infarction in presence of normal electrocardiogram.
Cardiac rupture following acute myocardial infarction occurs most frequently in patients with electrocardiographic evidence of transmural infarction. Unusual presentations of cardiac rupture need immediate recognition to enable successful surgical treatment. An unusual case is presented of cardiac rupture complicating acute myocardial infarction despite a normal electrocardiogram prior to the rupture.


The Acute Impact of Different Types of Aerobic Exercise on Arterial Wave Reflections and Inflammation.
Whilst physical activity is linked to cardiovascular health, it has lately been recognized that different types of exercise exert diverse effects on the cardiovascular system. Therefore, we investigated the acute effects of continuous moderate-intensity aerobic exercise (CAE) and high-intensity interval aerobic exercise (hIAE) on arterial function and inflammation. Twenty healthy men (mean age 22.6 ± 3.3 years) were recruited in this crossover study. Each of the 20 volunteers participated in two separate sessions (hIAE and CAE). The augmentation index (AIx) of aortic pressure waveforms and serum levels of interleukin-17 (IL-17) were measured before and after each exercise session. There were no significant differences in baseline hemodynamic and inflammatory measurements before CAE and hIAE. Compared to baseline, AIx was significantly improved after CAE (p = 0.04), while there was no significant change after hIAE (p = 0.65). Serum levels of IL-17 were significantly elevated after CAE (p = 0.042), while hIAE had no significant effect on IL-17 levels (p = 0.47). Interestingly, there was an inverse association between the elevation of IL-17 levels and the AIx improvement after CAE (p = 0.05). These findings provide additional evidence concerning the cardiovascular effects of different types of exercise training through modification of peripheral hemodynamics and the inflammatory process.


Barcoding bias in high-throughput multiplex sequencing of miRNA.
Second-generation sequencing is gradually becoming the method of choice for miRNA detection and expression profiling. Given the relatively small number of miRNAs and improvements in DNA sequencing technology, studying miRNA expression profiles of multiple samples in a single flow cell lane becomes feasible. Multiplexing strategies require marking each miRNA library with a DNA barcode. Here we report that barcodes introduced through adapter ligation confer significant bias on miRNA expression profiles. This bias is much higher than the expected Poisson noise and masks significant expression differences between miRNA libraries. This bias can be eliminated by adding barcodes during PCR amplification of libraries. The accuracy of miRNA expression measurement in multiplexed experiments becomes a function of sample number.


Label-free photoacoustic microscopy of peripheral nerves.
Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies.


The marginalization of hormesis.
Despite the substantial development and publication of highly reproducible toxicological data, the concept of hormetic dose-response relationships was never integrated into the mainstream of toxicological thought. Review of the historical foundations of the interpretation of the bioassay and assessment of competitive theories of dose-response relationships lead to the conclusion that multiple factors contributed to the marginalization of hormesis during the middle and subsequent decades of the 20th Century. These factors include the following: (a) the close association of hormesis with homeopathy, which led to the hostility of modern medicine toward homeopathy, thereby creating a guilt-by-association framework, and the carryover influence of that hostility toward hormesis in the judgements of medically based pharmacologists/toxicologists; (b) the emphasis of high-dose effects linked with a lack of appreciation of the significance of the implications of low-dose stimulatory effects; (c) the lack of an evolution-based mechanism(s) to account for hormetic effects; and (d) lack of appropriate scientific advocates to counter aggressive and intellectually powerful critics of the hormetic perspective.


Health information given by Swiss travel agencies.
Many of the 1 million Swiss traveling to tropical or subtropical countries book their trip through travel agencies every year. These agencies are thus an important source of information about malaria and other important health risks and little is known about the appropriate health information provided by these. A study was conducted to assess health-related information in members of the Swiss Federation of Travel Agencies in the metropolitan area of Zurich, Switzerland. A covert investigator (F.M.S.) visited these agencies and requested information on a package holiday for 2 or 3 weeks to Kenya. Following an in-person interview, the investigator recorded any health-related information provided on a pretested form. If none was mentioned, the agent was prompted using a standardized procedure. A total of 88 agencies were visited. Spontaneous health advice was given in 44% of all visits. After prompting, 99% of all travel agents mentioned preventive measures against malaria, but only 69% indicated the need for vaccinations against other diseases. Spontaneous advice on malaria risk and vaccinations was better than advice given upon prompting. One fifth of all travel agents neither mentioned malaria prevention measures spontaneously nor recommended seeing a health specialist. Overall, travel medicine knowledge of travel agents in the Zurich area needs improvement as many tended to draw attention to health risks only when prompted. Attitude, personal knowledge, and experience of individual travel agents were key to the health information given. Up-to-date and readily available information on health risks should be provided to travel agencies and structured training given in collaboration with health professionals.


Quantitative assessment method for computer-generated holograms free from the effect of viewpoint.
A quantitative assessment method for computer-generated holograms is presented. Our scheme is based on a simple evaluation quantity reflecting the optical radiating power from the holograms; this assures the overall validity of our method as a three-dimensional (3D) display assessment technique. Moreover, the effect of location from which the 3D view is observed is ruled out from the result. This contributes to both economy of computation and conciseness of the result.


Modular Knowledge-Based Decision Support System Dedicated to a Cooperative Decision to Prevent Cardiovascular Diseases.
Despite the success of artificial intelligence solutions in the recent years, physicians are still reticent to use integrated functionalities to support their decision. Methods used to create these functionalities can be divided into two groups, each being associated to different questions. Data-based methods are seen as black boxes for which it is impossible to understand how the decision is taken; knowledge-based methods need to rely on formalized knowledge sources on the basis of evidence, which can be discussed and criticized by physicians for their use in real life. This paper presents a new modular decision support system for the prevention of cardiovascular diseases, based on knowledge and on cooperative decision between the patient and the physician. The decision support system is based on two layers: (i) the first layer is a knowledge-based module which generates automatically patient profile, and prevention strategies associated to the profile; (ii) the second layer is a dynamic collaborative graphic user interface which displayed information about the risks of treatment adherence failure, personalized motivation and follow-up strategies. In the future, we aim at assessing the platform in real life.


Increased incidence and reduced mortality after first attack of acute pancreatitis over an 18-year period.
To determine time trends in the incidence and etiology of acute pancreatitis and identify predictors for in-hospital mortality. Retrospective study of 1722 patients with acute pancreatitis admitted to Akershus University Hospital between January 2000 and December 2017. Data were obtained from electronic patient files and computed tomography scans. We estimated a logistic regression model to assess differences in associations between patient characteristics and in-hospital mortality in two time periods, 2000-2009 (first period) and 2010-2018 (second period). First attack of acute pancreatitis (FAAP) was identified in 1579 patients (91.7%). The incidence of FAAP increased from 20.1/100,000 during the first period to 27.7/100,000 in the second period (p = .011). Etiology showed no differences between the two time periods. Gallstone was the most frequent etiology (47.2%). In total, 187 patients (11.8%) had necrotizing pancreatitis; more in the second period compared to the first (14.2 vs. 7.7%; p < .001). The overall mortality rate was 3.9%. Mortality rates decreased for both inflammatory and necrotizing pancreatitis during the study period. Age and comorbidity according to Charlson Comorbidity Index (CCI) were predictors of in-hospital mortality (OR 1.07, 95% CI 0.07; 0.40 and 13.58, 95% CI 3.88; 47.52), as were alcohol and organ failure (OR 7.20, 95% CI 2.02; 25.67 and OR 34.15, 95% CI 8.94; 130.53, respectively). The incidence of FAAP is increasing in southeast Norway. The etiology has remained unchanged over an 18-year period, with gallstones being the most frequent cause. The outcomes for both inflammatory and necrotic pancreatitis are improving.


[Suspicion of Haemophilus influenzae endocarditis of the bicuspid aortic valve in a 7-month-old infant].
The authors report a case of probable Haemophilus influenzae endocarditis in a 7 month-old infant with a bicuspid aortic valve. Precocity of the occurrence of endocarditis in such asymptomatic cardiac abnormality, scarcity of the suspected germ, and the observed mode of evolution are underlined. This case raises the problem of an endocardial involvement in an infant properly treated by adapted intravenous antibiotherapy. It can be concluded that regular clinical and echocardiographic examination is necessary for every case of severe Haemophilus influenzae infection.


Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative.
Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ2 = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI.


[Silent myocardial ischemia before and after revascularization].
In 82 patients with unstable ischemic heart disease (IHD) before and after revascularisation (percutaneous transluminal coronary angioplasty-PTCA-in 11 patients and coronary artery bypass graft-CABG-in 71 patients) silent ischemia incidence was observed. In these patients before and after operation election fraction (EF) and wall motion score index (IK) were compared echocardiographically as well as physical ability according to Bruce protocol in treadmill exercise test. Data (EF and IK and exercise test) before and after operation didn't change significantly. Silent ischemia was directed before operation in 17 patients (21.8%) and in 15 patients (19.4%) one month after those procedures.


Distributions of the Wigner reaction matrix for microwave networks with symplectic symmetry in the presence of absorption.
We report on experimental studies of the distribution of the reflection coefficients, and the imaginary and real parts of Wigner's reaction (K) matrix employing open microwave networks with symplectic symmetry and varying size of absorption. The results are compared to analytical predictions derived for the single-channel scattering case within the framework of random-matrix theory (RMT). Furthermore, we performed Monte Carlo simulations based on the Heidelberg approach for the scattering (S) and K matrix of open quantum-chaotic systems and the two-point correlation function of the S-matrix elements. The analytical results and the Monte Carlo simulations depend on the size of absorption. To verify them, we performed experiments with microwave networks for various absorption strengths. We show that deviations from RMT predictions observed in the spectral properties of the corresponding closed quantum graph and attributed to the presence of nonuniversal short periodic orbits does not have any visible effects on the distributions of the reflection coefficients and the K and S matrices associated with the corresponding open quantum graph.


Commentary: the importance of Medicaid expansion for criminal justice populations in the south.
Though the full implications of a Trump presidency for ongoing health care and criminal justice reform efforts remain uncertain, whatever policy changes are made will be particularly salient for the South, which experiences the highest incarceration rates, highest uninsured rates, and worst health outcomes in the United States. The passage of the Affordable Care Act (ACA) in 2010 was a watershed event and many states have taken advantage of opportunities created by the ACA to expand healthcare coverage to their poorest residents, and to develop partnerships between health and justice systems. Yet to date, only four have taken advantage of the benefits of healthcare reform. Expanding Medicaid would provide Southern states with the opportunity to significantly impact health outcomes for criminal justice-involved individuals. In the context of an uncertain policy landscape, we suggest the use of three strategies, focusing on advancing incremental change while safeguarding existing gains, rebranding Medicaid as a local or statewide initiative, and linking Medicaid expansion to criminal justice reform, in order to implement Medicaid expansion across the South.


[Risk factors and possibilities of prevention of bowel cancer].
The incidence of bowel cancer has doubled over the past 50 years. Although the treatment outcome has improved, 40% of those affected with the disease still die from it. Treatment in the terminal phase of the disease is expensive and requires plenty of resources without resulting in patient recovery. Bowel cancer could theoretically be reduced by changing the living habits. Focusing of endoscopy resources to screening of symptomless patients would be a more realistic means. Because bowel cancer develops through an endoscopically detectable and slow-growing precancerous adenoma, it is possible to reduce massive disease burden through screening.


Case Report: SMARCA4 (BRG1)-deficient undifferentiated carcinoma of gallbladder with genetic analysis.
SMARCA4 (BRG1)-deficient undifferentiated carcinoma is a rare and highly aggressive malignancy. It has been reported to occur in a multiple range of organs. However, to the best of our knowledge, SMARCA4 (BRG1)-deficient undifferentiated carcinoma of gallbladder has not yet been reported. Here, we describe a case of SMARCA4 (BRG1)-deficient undifferentiated carcinoma of gallbladder. Through comprehensive genetic analysis, we hypothesized that in addition to SMARCA4 (BRG1) deficiency, other genetic changes might also be involved in the tumorigenesis of undifferentiated gallbladder cancer in this patient, particularly somatic mutations in the CTNNB1, KRAS, PIK3CA, TP53, CREBBP, and FANCI genes. To the best of our knowledge, this is the first report of SMARCA4 (BRG1)-deficient undifferentiated carcinoma of gallbladder with genetic analysis.


Surgical Reconstruction Technique of Two Patients With Tarsal Type Preaxial Polydactyly: Two True Prehalluces.
Polydactyly of the foot occurs in 1.7 cases per 1000 live births, comprising 45% of congenital abnormalities of the foot. Most reported cases of polydactyly of the foot are postaxial, and 15% are preaxial; of those, tarsal type preaxial polydactyly (a true prehallux) occurs in only 3% of cases. Because of this rarity, there is minimal literature available to guide management or surgical reconstruction. Two newborns presented with similar tarsal type preaxial polydactylies in the context of multiple congenital anomalies at a single institution. Patient 1 presented at birth with an accessory digit arising medially from the right foot at the medial malleolus. Two weeks later, genetically unrelated, patient 2 presented at birth with an accessory digit arising medially from the right foot at the talus. Both patients underwent resection of the extra digit and reconstruction including transfer of the accessory anterior tibial tendon arising from the preaxial extra digit to the remaining first ray. Two years after surgery, both patients are walking well with preserved dorsiflexion strength. Given the rarity of true prehallux cases, reported surgical treatment and outcomes are lacking. This case demonstrates the management of 2 patients to better guide future patient care. Although nonsurgical treatment with shoewear modification is an option, surgical reconstruction facilitated wearing typical shoes while preserving ambulatory ability. Both patients in this series had an accessory anterior tibial tendon. Surgical transfer of the tendon prevented loss of dorsiflexion strength and foot drop postoperatively.


HAI-2 stabilizes, inhibits and regulates SEA-cleavage-dependent secretory transport of matriptase.
It has recently been shown that hepatocyte growth factor activator inhibitor-2 (HAI-2) is able to suppress carcinogenesis induced by overexpression of matriptase, as well as cause regression of individual established tumors in a mouse model system. However, the role of HAI-2 is poorly understood. In this study, we describe 3 mutations in the binding loop of the HAI-2 Kunitz domain 1 (K42N, C47F and R48L) that cause a delay in the SEA domain cleavage of matriptase, leading to accumulation of non-SEA domain cleaved matriptase in the endoplasmic reticulum (ER). We suggest that, like other known SEA domains, the matriptase SEA domain auto-cleaves and reflects that correct oligomerization, maturation, and/or folding has been obtained. Our results suggest that the HAI-2 Kunitz domain 1 mutants influence the flux of matriptase to the plasma membrane by affecting the oligomerization, maturation and/or folding of matriptase, and as a result the SEA domain cleavage of matriptase. Two of the HAI-2 Kunitz domain 1 mutants investigated (C47F, R48L and C47F/R48L) also displayed a reduced ability to proteolytically silence matriptase. Hence, HAI-2 separately stabilizes matriptase, regulates the secretory transport, possibly via maturation/oligomerization and inhibits the proteolytic activity of matriptase in the ER, and possible throughout the secretory pathway.


Protein biomarkers of nephrotoxicity; a review and findings with cyclosporin A, a signal transduction kinase inhibitor and N-phenylanthranilic acid.
Biomarkers of nephrotoxicity range from plasma and urine biochemistry, enzymic assays for brush border and lysosomal markers plus new protein markers by immunoassay. Because of the complexity of the nephron and regional sensitivity to xenobiotics, it is important to co-localise sites of marker release with pathological lesions. Han Wistar rats were treated p.o.for up to 14 days with compounds causing selective nephrotoxicity. Compounds used were cyclosporin A ,a signal transduction inhibitor and N-phenylanthranylic acid (NPAA). Plasma and urine was collected for biochemistry and urinalysis (including proteomics and metabonomics) and at termination kidneys were fixed for standard H&E pathology and immunohistochemistry examinations for D28 k calbindin, calmodulin, phospho-erk, Cox 1, Cox 2 and other markers. Cyclosporin A treatment caused injury to the thick ascending limb (TAL) of the nephron and was associated with a down-regulation of calbindin protein expression in cortical distal tubules (mean score 75% reduction) and TALs (21% reduction). Inhibition of signal transduction used p-erk as a downstream marker of activity. P-erk was highly expressed in the collecting ducts and inhibition of signalling caused a 39% reduction in IHC score. There was no evidence of direct renal injury by there was a hypercalcaemia (9% increase) and hyperphosphataemia (24% increase) at 24 hrs post-dose and metastatic calcification by 7 days. NPAA treatment caused renal papillary necrosis in some treated rats (sometimes unilateral) with some secondary dilation of distal tubules. Unlike NSAID treatment, there was no evidence of Cox 1 or 2 dysregulation on IHC and the Cox1 positive interstitial cells did not loose integrity before the onset of necrosis. There were a number of urinary proteomic and metabonomic alterations which are being characterised. The 3 model nephrotoxicants studied demonstrated the linkage of protein expression on IHC to nephron segment-specific sites as important for urinary biomarker validation and linkage to mechanisms.


Synthesis and characterization of uranyl compounds with iminodiacetate and oxydiacetate displaying variable denticity.
Eight uranyl compounds containing the dicarboxylate ligands iminodiacetate (IDA) or oxydiacetate (ODA) have been characterized in the solid state. The published polymeric structures for [UO(2)(C(4)H(6)NO(4))(2)] and [UO(2)(C(4)H(4)O(5))](n) have been confirmed, while Ba[UO(2)(C(4)H(5)NO(4))(2)] x 3H(2)O, [(CH(3))(2)NH(CH(2))(2)NH(CH(3))(2)][UO(2)(C(4)H(4)O(5))(2)] [orthorhombic space group Pnma, a = 10.996(5) A, b = 21.42(1) A, c = 8.700(3) A, Z = 4], and [C(2)H(5)NH(2)(CH(2))(2)NH(2)C(2)H(5)][UO(2)(C(4)H(4)O(5))(2)] [monoclinic space group P2(1)/n, a = 6.857(3) A, b = 9.209(5) A, c = 16.410(7) A, beta = 91.69(3), Z = 2] contain monomeric anions. The distance from the uranium atom to the central heteroatom (O or N) in the ligand varies. Crystallographic study shows that U-heteroatom (O/N) distances fall into two groups, one 2.6-2.7 A in length and one 3.1-3.2 A, the latter implying no bonding interaction. By contrast, EXAFS analysis of bulk samples suggests that either a long U-heteroatom (O/N) distance (2.9 A) or a range of distances may be present. Three possible structural types, two symmetric and one asymmetric, are identified on the basis of these results and on solid-state (13)C NMR spectroscopy. The two ligands in the complex can be 1,4,7-tridentate, giving five-membered rings, or 1,7-bidentate, to form an eight-membered ring. (C(4)H(12)N(2))[(UO(2))(2)(C(4)H(5)NO(4))(2)(OH)(2)] x 8H(2)O [monoclinic space group P2(1)/a, a = 7.955(9) A, b = 24.050(8) A, c = 8.223(6) A, beta = 112.24(6), Z = 2], (C(2)H(10)N(2))[(UO(2))(2)(C(4)H(5)NO(4))(2)(OH)(2)] x 4H(2)O, and (C(6)H(13)N(4))(2)[(UO(2))(2)(C(4)H(4)O(5))(2)(OH)(2)] x 2H(2)O [monoclinic space group C2/m, a = 19.024(9) A, b = 7.462(4) A, c = 2.467(6) A, beta = 107.75(4), Z = 4] have a dimeric structure with two capping tridentate ligands and two mu(2)-hydroxo bridges, giving edge-sharing pentagonal bipyramids.


Economic implications of tobacco industry in India: An overview.
Tobacco usage has become engraved in the cultural practices of our country since time immemorial. With increased demand comes increased production, employment, and growth of the tobacco industry but for a deadly cost of human lives which fall prey to its use in either forms. In this article, we describe the economic burden faced by the country due to the emerging tobacco epidemic. The need of the hour is to understand the impact faced due to the tobacco industry in the country and to bring in appropriate efforts to reduce loss of economy and human lives.


Multiple origins of viral capsid proteins from cellular ancestors.
Viruses are the most abundant biological entities on earth and show remarkable diversity of genome sequences, replication and expression strategies, and virion structures. Evolutionary genomics of viruses revealed many unexpected connections but the general scenario(s) for the evolution of the virosphere remains a matter of intense debate among proponents of the cellular regression, escaped genes, and primordial virus world hypotheses. A comprehensive sequence and structure analysis of major virion proteins indicates that they evolved on about 20 independent occasions, and in some of these cases likely ancestors are identifiable among the proteins of cellular organisms. Virus genomes typically consist of distinct structural and replication modules that recombine frequently and can have different evolutionary trajectories. The present analysis suggests that, although the replication modules of at least some classes of viruses might descend from primordial selfish genetic elements, bona fide viruses evolved on multiple, independent occasions throughout the course of evolution by the recruitment of diverse host proteins that became major virion components.


The advantages of "Dance-group" for psychotic patients.
Psychosocial rehabilitation and in particular group dances allow the recovery of lost or compromised ability of patients with mental illness, and they facilitate their reintegration into the social context. The dance group has enabled users of the Day Centre of the Unit of Mental Health Torre del Greco ASL NA 3 south to achieve the objectives of rehabilitation such as: taking care of themselves, of their bodies and their interests, improving self-esteem , the management of pathological emotions, socialization and integration, overcoming the psychotic closing and relational isolation. In particular, patients with schizophrenia, psychotic and mood disorders had a concrete benefit from such rehabilitation activities, facilitating interpersonal relationships, therapy compliance and significantly improved mood, quality of life, providing them with the rhythm and the security in their relationship with each other. The dance group and for some individuals, also psychotherapy and drug therapy, have facilitated social inclusion, improved the quality of life and cured their diseases. The work is carrying out in a group with patients, practitioners, family members, volunteers, social community workers, following the operating departmental protocols. Using the chorus group "Sing that you go" as an operational tool for psychosocial rehabilitation and therapeutic element we promote the psychological well-being and the enhancement of mood.


[Application of nucleolar organizer region staining technique to air-dried blood smears].
Silver staining of nucleolar organizer regions (NOR) was applied to air-dried peripheral and bone marrow smears of normal subjects and leukemic patients. Specimens were fixed in buffered acetone formalin. Even in smears kept for 2 years at room temperature, the stainability of Ag-NOR was well preserved. By dipping Giemsa-stained smears in 5% trichloracetic acid and then placing them in methanol for 5 minutes, the stain was leached out. After the dye had been removed, the smears were clearly stained by a Ag-NOR staining technique. The mean number of Ag-NOR per nucleus of mature granulocytes and mononuclear cells in normal peripheral bloods was 0.59 and 1.43 respectively. The mean number of Ag-NOR per nucleus of peripheral and bone marrow leukemic cells from patients with acute leukemia and chronic myelocytic leukemia in blastic crisis was 2.32 and 2.66 respectively. On the other hand, the mean number of Ag-NOR per nucleus of peripheral leukemic cells from patients with chronic lymphocytic leukemia was 1.48. These results suggest that acute leukemia cells possess a more active proliferating potential. The Ag-NOR staining technique is very simple and might be useful for investigation of hematologic cells.


[A Case of Trousseau Syndrome Associated with Advanced Rectal Cancer].
We report a case of Trousseau syndrome associated with advanced rectalcancer. A 67-year-old man visited our hospital for right hemiparesis and gait disturbance. Head magnetic resonance imaging showed multiple cerebral infarctions. Abdominal computed tomography showed wallthickening of the rectum and colonoscopy showed type 2 circumferentialrectalcancer. Therefore, he was diagnosed with Trousseau syndrome. After anticoagulation therapy with heparin, an operation was performed. Thereafter, chemotherapy was continued and he has experienced no recurrence of cerebralinfarction.


Tinosporae radix: A Review of Traditional Use, Botany, Phytochemistry, Bioactivity, and Quality Marker.
Tinosporae radix is the root tuber of Tinospora capillipes Gagnep of the Menispermaceae family. It has the effects of clearing away heat and toxins, benefiting the throat, relieving pain, and treating sore throat, carbuncle and boils, and other diseases in clinical practice. The related references about T. radix in this review were collected by online databases, including PubMed, Elsevier, Web of Science, Willy, SciFinder, SpringLink, Google Scholar, Baidu Scholar, ACS publications, Scopus, and CNKI. The other information about T. radix was acquired from ancient books and classical works. T. radix is an important medicinal plant with a variety of traditional uses according to the theory of Chinese medicine. Previous studies revealed that T. radix contained a variety of chemical components, including diterpenoids, alkaloids, steroids, cinnamic acid derivatives, and other compounds. Many pharmacological researches have exhibited that T. radix possesses various biological activities, including anti-cancer, hypoglycemic, anti-inflammatory, anti-bacterial, anti-ulcer, and anti-oxidant activities. Furthermore, the quality markers of T. radix were summarized and analyzed in this paper. The traditional use, botany, phytochemistry, bioactivity, and quality markers of T. radix were reviewed in this paper. It will not only provide an important clue for further studying T. radix, but also supply an important theoretical basis and a valuable reference for in-depth research and exploitations of this plant in the future.


Acknowledgments - OOTR Annual Conference 2012 Proceedings.
It gives me great pleasure to announce the successful conclusion of the OOTR 8th Annual Conference, which was held on 20 and 21 April 2012 at the Westin Miyako Hotel, Kyoto, Japan. Since its last conference in Hong Kong in 2011, the Organisation for Oncology and Translational Research has continued to conduct a wide range of detailed clinical trials alongside hi-tech translational research, pushing on further than ever before in finding an optimal treatment strategy and a range of individualized treatment modalities for cancer patients. A great deal of valuable feedback from seasoned oncology professionals as well as newcomers to the field has been gratefully received and acted on by OOTR, helping us to continue our progress into cancer therapeutic research. Ever since the founding meeting in Hong Kong in 2004, OOTR has continued to learn and grow with the passing of each annual conference. Every conference has had a fundamental bearing on how we define treatment and guidelines regarding the latest scientific findings and methodologies toward improving cancer treatment and prevention. Based upon valuable lessons learned from the previous conferences, the OOTR 8th Annual Conference this time focused on cancer stem cells and cancer stroma. There were lectures on angiogenesis, predictive biomarkers for cancer therapy, prevention of oncological diseases, and hormone dependency and therapy. We held in-depth sessions in which we discussed the promotion of more appropriate therapeutic research and the advancement of more individualized treatments. The OOTR 8th Annual Conference proved to be an excellent opportunity for oncology professionals to participate in discussions, share experiences, meet like-minded professionals, and evaluate state-of-the-art hi-tech technologies. I extend my most heartfelt thanks to the contributing lecturers who traveled from all parts of the world to present their wonderful lectures at the seven key sessions: Session 1 - Hormone dependency and independence Session 2 - Prevention of oncological diseases Session 3 - Cancer stem cell and innovative therapeutics Session 4 - Advances in endothelial biology and cancer biology Session 5 - Antiangiogenesis update Session 6 - Predictive biomarkers and novel therapeutics Session 7 - Prevention of oncological diseases I would also like to express my gratitude to the three guest editors of the OOTR proceedings: Dr Shigehira Saji of the Target Therapy Oncology Department, Graduate School of Medicine, Kyoto University; Dr Kiyotsugu Yoshikawa of the Innovation Center, Laboratory for Malignancy Control Research, Graduate School of Medicine, Kyoto University, and Dr Katsumasa Kuroi, Deputy-Director, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital. Their selfless assistance is much appreciated. I would like to thank the sponsors of the OOTR 8th Annual Conference for providing us with the means to make the conference a success: the Kyoto Prefecture, the Osaka Community Foundation, the Novartis Foundation (Japan), plus the many other pharmaceutical companies, charitable foundations and private businesses who have offered us their generous support.


Penicillin allergy-getting the label right.
Penicillini allergy is a potentially serious adverse reaction that impacts on antibacterial treatment options. Although it is commonly reported and recorded in medical records, only a minority of patients with a label of penicillin allergy actually have the condition confirmed. The term 'allergy' may be incorrectly applied to adverse reactions that do not have an immunological basis and inappropriate labelling of penicillin allergy can lead to the unnecessary avoidance of penicillins and other beta-lactam antibacterials. Here, we discuss key features that help to distinguish patients at low or high risk of having a true penicillin allergy, summarise what is known about the risk of allergic reactions to other beta-lactam antibacterials in patients with penicillin allergy and discuss the steps to consider when assessing a label of penicillin allergy.


Tuning the energy transfer in Ruddlesden-Popper perovskites phases through isopropylammonium addition - towards efficient blue emitters.
Here we demonstrate blue LEDs with a peak wavelength of 481 nm, with outstanding colour purity of up to 88% (CIE coordinates (0.1092, 0.1738)), an external quantum yield of 5.2% and a luminance of 8260 cd m-2. These devices are based on quasi-2D PEA2(Cs0.75MA0.25)Pb2Br7, which is cast from solutions containing isopropylammonium (iPAm). iPAm as additive assist in supressing the formation of bulk-like phases, as pointed out by both photophysical and structural characterization. Additionally, the study of the excitation dynamics demonstrates a hindering of the energy transfer to domains of lower energy that generally undermines the performance and emission characteristics of blue-emitting LEDs based on quasi-2D perovskites. The achieved narrow distribution of quantum well sizes and the hindered energy transfer result in a thin film photoluminescence quantum yield exceeding 60%. Our work demonstrates the great potential to tailor the composition and the structure of thin films based on Ruddlesden-Popper phases to boost performance of optoelectronic devices - specifically blue perovskite LEDs.


Mode of delivery and antenatal steroids and their association with survival and severe intraventricular hemorrhage in very low birth weight infants.
To determine whether CS delivery and receipt of antenatal steroids (ANS) in vertex-presenting singletons with a gestational age (GA) between 24 and 30 weeks is associated with improved survival and improved severe intraventricular hemorrhage (sIVH)-free survival. Multicenter cohort, retrospective analysis of prospectively collected data. Vertex-presenting singletons newborns with GA 24 to 30 weeks, birth weight between 500 and 1500 g, without major congenital malformations, born between 2001 and 2011 at Neocosur centers were included. Four thousand three hundred and eighty-six infants fulfilled inclusion criteria: 45.8% were delivered vaginally and 54.2% by cesarean section (CS). Newborns delivered vaginally received less ANS, had lower GA, Apgar scores and a lower incidence of survival and sIVH-free survival (P<0.001). Newborns with better survival were those with ANS, independent of mode of delivery. At 24 to 25 weeks GA, increased survival and sIVH-free survival were associated with ANS and CS delivery, compared with those who received ANS and delivered vaginally. Among vertex-presenting singletons with GA 24 to 30 weeks, better survival and IVH-free survival were associated with ANS, independent of mode of delivery. In infants at 24 to 25 weeks gestation the combination of ANS/CS was associated with improvement in both outcomes.


Synergistic effect of oligochitosan and silicon on inhibition of Monilinia fructicola infections.
Oligochitosan has broad-spectrum antimicrobial activity and shows an obvious inhibitory effect on phytopathogens. In addition, as an exogenous elicitor, it can induce various defence responses, including affecting the activities of several defence-related enzymes and substances in some plants. Owing to this dual function of oligochitosan, it can be used to control postharvest diseases of fruits. Silicon, like oligochitosan, also has a dual function. In this study the synergistic effect of oligochitosan and silicon on the decay control of apple fruit was investigated. In vitro, both oligochitosan and silicon significantly inhibited spore germination, germ tube elongation and mycelial growth of Monilinia fructicola, with higher concentrations having a greater effect. The synergistic effect of oligochitosan and silicon at half-maximal inhibitory concentration on disease control at 25 degrees C was much better than the effect of oligochitosan or silicon alone, not only in vitro but also in vivo. The results showed that a combination of oligochitosan and silicon had a synergistic effect on the control of disease caused by M. fructicola in apple fruit at 25 degrees C.


Detection of DT-diaphorase Enzyme with a ParaCEST MRI Contrast Agent.
A responsive magnetic resonance (MRI) contrast agent has been developed that can detect the enzyme activity of DT-diaphorase. The agent produced different chemical exchange saturation transfer (CEST) MRI signals before and after incubation with the enzyme, NADH, and GSH at different pH values whereas it showed good stability in a reducing environment without enzyme.


Polymers on nanoparticles: structure & dynamics.
Grafting polymers to nanoparticle surfaces influences properties from the conformation of the polymer chains to the dispersion and assembly of nanoparticles within a polymeric material. Recently, a small body of work has begun to address the question of how grafting polymers to a nanoparticle surface impacts chain dynamics, and the resulting physical properties of a material. This Review discusses recent work that characterizes the structure and dynamics of polymers that are grafted to nanoparticles and opportunities for future research. Starting from the case of a single polymer chain attached to a nanoparticle core, this Review follows the structure of the chains as grafting density increases, and how this structure slows relaxation of polymer chains and affects macroscopic material properties.


Successfully managing multigenerational workforces.
Never before have members of so many diverse generations worked in organizations at the same time. Successfully working with and managing this multigenerational workforce requires that managers know the values and strengths of each generation and understand how each generation can best contribute to the needs of the organization. This article looks at each generation--how and why certain values were developed, the differences and similarities between the generations, and how members of each generation can work most effectively with members of other generations.


Randomized Controlled Trial Testing Mobile-Based Attention-Bias Modification for Posttraumatic Stress Using Personalized Word Stimuli.
Although behavioral therapies are effective for posttraumatic stress disorder (PTSD), access for patients is limited. Attention-bias modification (ABM), a cognitive-training intervention designed to reduce attention bias for threat, can be broadly disseminated using technology. We remotely tested an ABM mobile app for PTSD. Participants (N = 689) were randomly assigned to personalized ABM, nonpersonalized ABM, or placebo training. ABM was a modified dot-probe paradigm delivered daily for 12 sessions. Personalized ABM included words selected using a recommender algorithm. Placebo included only neutral words. Primary outcomes (PTSD and anxiety) and secondary outcomes (depression and PTSD clusters) were collected at baseline, after training, and at 5-week-follow-up. Mechanisms assessed during treatment were attention bias and self-reported threat sensitivity. No group differences emerged on outcomes or attention bias. Nonpersonalized ABM showed greater declines in self-reported threat sensitivity than placebo (p = .044). This study constitutes the largest mobile-based trial of ABM to date. Findings do not support the effectiveness of mobile ABM for PTSD.


Therapeutic Strategy for Heart Failure with Reduced Ejection Fraction and Cardiac Amyloidosis.
We sometimes encounter patients with systolic heart failure and cardiac amyloidosis. Neurohormonal blockers are guideline-directed medical therapy for those with systolic heart failure. However, its implication among the above cohort remains controversial. Of 3 patients with systolic heart failure and cardiac amyloidosis who we encountered, cardiac reverse remodeling was achieved in 2 patients who received neurohormonal blockers, whereas cardiac function remained unchanged in a patient not receiving neurohormonal blockers. Neurohormonal blockers might be keys to achieve cardiac reverse remodeling and favorable clinical outcomes even in patients with systolic heart failure and cardiac amyloidosis, although further larger-scale studies are required to validate our hypothesis.


Nanohybrid Electro-Coatings Toward Therapeutic Implants with Controlled Drug Delivery Potential for Bone Regeneration.
Coatings of metallic implants facilitate a new bioactive interface that favors osteogenic responses and bone formation. Providing a therapeutic capacity to the coatings, involving with a sustainable and controllable delivery of drug molecules, significantly improves the bone regenerative potential. Here we design a novel nanocomposite coating, made of mesoporous silica-shelled hydroxyapatite (MS-HA) nanoparticles and chitosan (Chi), incorporating osteogenic drug dexamethasone phosphate (Dex(P)) within the MS-HA, by the process of an electrophoretic deposition (EPD). MS-HA, produced by a sol–gel reaction of silica onto an HA nanorod, exhibited mono-dispersed core–shell nanoparticles with a size of ∼40 nm and a shell thickness of ∼25 nm. The highly mesoporous structure enabled an effective loading of Dex(P) onto the nanocarriers, showing a loading capacity as high as 15% by weight. The Dex(P) loaded MS-HA were homogenized with Chi in acidic ethanol/water to allow for the EPD process. Nanocomposite coatings were produced well, forming thicknesses a few micrometers largely tunable with EPD parameters and exhibiting MS-HA nanoparticles evenly distributed within Chi matrix. While Dex(P) release from the bare MS-HA nanocarrier was very abrupt, showing a complete release within 24 h, the Dex(P) release from the nanocomposite coatings profiled a highly sustainable pattern over a month. Rat mesenchymal stem cells cultured on the Dex(P)-releasing coatings were substantially stimulated to an osteoblastic lineage, presenting enhanced alkaline phosphate activity and higher levels of osteogenic genes, with respect to coatings free of Dex(P). An indirect culture test also confirmed the long-term release effects of Dex(P) from the coatings over 4 weeks. The currently-developed nanocomposite EPD coatings, with a capacity to load osteogenic drug at large quantity and to deliver for a long-term period, are considered as a promising therapeutic coating platform for metallic bone implants.