Transcriptomic and Metabolomic Analyses Reveal the Importance of Lipid Metabolism and Photosynthesis Regulation in High Salinity Tolerance in Barley (Hordeum vulgare L.) Leaves Derived from Mutagenesis Combined with Microspore Culture.
Barley is the most salt-tolerant cereal crop. However, little attention has been paid to the salt-tolerant doubled haploids of barley derived from mutagenesis combined with isolated microspore culture. In the present study, barley doubled haploid (DH) line 20, which was produced by mutagenesis combined with isolated microspore culture, showed stably and heritably better salt tolerance than the wild type H30 in terms of fresh shoot weight, dry shoot weight, K+/Na+ ratio and photosynthetic characteristics. Transcriptome and metabolome analyses were performed to compare the changes in gene expression and metabolites between DH20 and H30. A total of 462 differentially expressed genes (DEGs) and 152 differentially accumulated metabolites (DAMs) were identified in DH20 compared to H30 under salt stress. Among the DAMs, fatty acids were the most accumulated in DH20 under salt stress. The integration of transcriptome and metabolome analyses revealed that nine key biomarkers, including two metabolites and seven genes, could distinguish DH20 and H30 when exposed to high salt. The pathways of linoleic acid metabolism, alpha-linolenic acid metabolism, glycerolipid metabolism, photosynthesis, and alanine, aspartate and glutamate metabolism were significantly enriched in DH20 with DEGs and DAMs in response to salt stress. These results suggest that DH20 may enhance resilience by promoting lipid metabolism, maintaining energy metabolism and decreasing amino acids metabolism. The study provided novel insights for the rapid generation of homozygous mutant plants by mutagenesis combined with microspore culture technology and also identified candidate genes and metabolites that may enable the mutant plants to cope with salt stress.


CellRank for directed single-cell fate mapping.
Computational trajectory inference enables the reconstruction of cell state dynamics from single-cell RNA sequencing experiments. However, trajectory inference requires that the direction of a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank ( https://cellrank.org ) for single-cell fate mapping in diverse scenarios, including regeneration, reprogramming and disease, for which direction is unknown. Our approach combines the robustness of trajectory inference with directional information from RNA velocity, taking into account the gradual and stochastic nature of cellular fate decisions, as well as uncertainty in velocity vectors. On pancreas development data, CellRank automatically detects initial, intermediate and terminal populations, predicts fate potentials and visualizes continuous gene expression trends along individual lineages. Applied to lineage-traced cellular reprogramming data, predicted fate probabilities correctly recover reprogramming outcomes. CellRank also predicts a new dedifferentiation trajectory during postinjury lung regeneration, including previously unknown intermediate cell states, which we confirm experimentally.


Can genetics guide exercise prescriptions in osteoarthritis?
Osteoarthritis (OA) is the most common form of arthritis and has a multifactorial etiology. Current management for OA focuses on minimizing pain and functional loss, typically involving pharmacological, physical, psychosocial, and mind-body interventions. However, there remain challenges in determining which patients will benefit most from which interventions. Although exercise-based interventions are recommended as first-line treatments and are known to be beneficial for managing both the disease and illness of OA, the optimal exercise "prescription" is unknown, due in part to our limited understanding of the precise mechanisms underlying its action. Here we present our perspective on the potential role of genetics in guiding exercise prescription for persons with OA. We describe key publications in the areas of exercise and OA, genetics and OA, and exercise and genetics, and point to a paucity of knowledge at the intersection of exercise, genetics, and OA. We suggest there is emerging evidence to support the use of genetics and epigenetics to explain the beneficial effects of exercise for OA. We identify missing links in the existing research relating to exercise, genetics, and OA, and highlight epigenetics as a promising mechanism through which environmental exposures such as exercise may impact OA outcomes. We anticipate future studies will improve our understanding of how genetic and epigenetic factors mediate exercise-based interventions to support implementation and ultimately improve OA patient care.


Stereotactic Atlas-Guided Laser Capture Microdissection of Brain Regions Affected by Traumatic Injury.
The ability to isolate specific brain regions of interest can be impeded in tissue disassociation techniques that do not preserve their spatial distribution. Such techniques also potentially skew gene expression analysis because the process itself can alter expression patterns in individual cells. Here we describe a laser capture microdissection (LCM) method to selectively collect specific brain regions affected by traumatic brain injury (TBI) by using a modified Nissl (cresyl violet) staining protocol and the guidance of a rat brain atlas. LCM provides access to brain regions in their native positions and the ability to use anatomical landmarks for identification of each specific region. To this end, LCM has been used previously to examine brain region specific gene expression in TBI. This protocol allows examination of TBI-induced alterations in gene and microRNA expression in distinct brain areas within the same animal. The principles of this protocol can be amended and applied to a wide range of studies examining genomic expression in other disease and/or animal models.


Diagnosis and management of obstructive sleep apnea. A multidisciplinary approach.
Snoring has been shown to be the primary sign of a potentially serious medical condition, ie, obstructive sleep apnea (OSA). Traditionally, the otolaryngologist has been the primary medical resource for patients with snoring problems. However, until recently, little was known about the now-acknowledged serious complications of this phenomenon. Of the primary treatments for this condition, those most commonly utilized to date involve surgical procedures routinely performed by the otolaryngologist, ie, tracheostomy and uvulopalatopharyngoplasty. Thus, the practicing otolaryngologist has been thrust into the forefront in the diagnosis and management of OSA. Hence, it behooves the modern practitioner to be cognizant of the multidisciplinary approach to this problem. Herein, we review snoring as a medical problem, sleep laboratory studies of patients with OSA, and the interaction of multidisciplinary team members in the optimal management of this ubiquitous problem.


SEABIRDS AS POSSIBLE RESERVOIRS OF ERYSIPELOTHRIX RHUSIOPATHIAE ON ISLANDS USED FOR CONSERVATION TRANSLOCATIONS IN NEW ZEALAND.
Erysipelothrix rhusiopathiae, the causative agent of the disease erysipelas, is a gram-positive bacillus, and an opportunistic pathogen in diverse species of animals. In New Zealand, E. rhusiopathiae has killed endangered birds on offshore islands, including Kākāpō (Strigops habroptilus), Takahē (Porphyrio hochstetteri), and Kiwi (Apteryx spp.). The source of infection is uncertain, and the prevalence of E. rhusiopathiae among wild birds is currently unknown. During October 2018 to December 2018, we surveyed dead and live seabirds that visit two of New Zealand's offshore islands used for Kākāpō conservation with the goal of determining the prevalence of E. rhusiopathiae. Bone marrow from dead birds was cultivated on selective agar, and organisms cultured were identified using matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry. The prevalence of E. rhusiopathiae was calculated in different species for each island. We surveyed live birds using PCR with Erysipelothrix spp.-specific primers on blood samples. The prevalence of E. rhusiopathiae in dead seabirds on Whenua Hou and Te Hauturu-o-Toi was 3.4% (3/86) and 11.4% (5/44), respectively. On Whenua Hou, E. rhusiopathiae was detected in Sooty Shearwaters (Puffinus griseus; 5.9%, 2/34) and Mottled Petrels (Pterodroma inexpectata; 2.7%, 1/36) while it was detected only in Cook's Petrels (Pterodroma cookie; 13.5%, 5/37) on Te Hauturu-o-Toi. Blood samples were collected from two seabird species; only one of 50 Mottled Petrels (2.0%) was positive for the presence of Erysipelothrix spp. Our findings confirm that burrowing seabirds are possible reservoirs of E. rhusiopathiae on both islands studied and may be the source of spillover to other species on the island. The differences in observed prevalence suggest the species composition of the reservoir of E. rhusiopathiae may vary geographically.


Velocity of shortening and myosin isozymes in two types of rabbit fast-twitch muscle fibers.
The fast-twitch tibialis anterior muscle of the rabbit was stimulated (10 Hz, 8 h/day for 7 wk) to cause complete transformation of the fibers from type IIb to type IIa. The velocity of unloaded shortening of permeabilized single fiber segments dissected from control and chronically stimulated tibialis anterior muscles was measured by the slack test at 20 degrees C. The myosin isozymes in these segments were separated on pyrophosphate-containing polyacrylamide gels. Peptide mapping of the myosin chain was performed on the myosin bands cut from the gels. The velocity of unloaded shortening of the IIb fibers was significantly higher (2.50 +/- 0.09 fiber length/s; n = 6) than that of the IIa fibers (1.33 +/- 0.08 fiber lengths/s; n = 6). The two groups of fibers differed with respect to their alkali light chain complement, as assessed by nondenaturing gel analyses, and with respect to their myosin heavy chain complement, as demonstrated by peptide mapping. Thus two groups of fast-twitch muscle fibers that contain distinguishable myosin isozyme contents differ in their velocities of unloaded shortening by a factor of two.


Finding the Right Balance: An Evidence-Informed Guidance Document to Support the Re-Opening of Canadian Nursing Homes to Family Caregivers and Visitors during the Coronavirus Disease 2019 Pandemic.
During the first few months of the coronavirus disease 2019 (COVID-19) pandemic, Canadian nursing homes implemented strict no-visitor policies to reduce the risk of introducing COVID-19 in these settings. There are now growing concerns that the risks associated with restricted access to family caregivers and visitors have started to outweigh the potential benefits associated with preventing COVID-19 infections. Many residents have sustained severe and potentially irreversible physical, functional, cognitive, and mental health declines. As Canada emerges from its first wave of the pandemic, nursing homes across the country have cautiously started to reopen these settings, yet there is broad criticism that emerging visitor policies are overly restrictive, inequitable, and potentially harmful. We reviewed the nursing home visitor policies for Canada's 10 provinces and 3 territories as well as international policies and reports on the topic to develop 10 provi-informed, data-driven, and expert-reviewed guidance for the re-opening of Canadian nursing homes to family caregivers and visitors.


VEGF Potentiates GD3-Mediated Immunosuppression by Human Ovarian Cancer Cells.
Natural killer T (NKT) cells are important mediators of antitumor immune responses. We have previously shown that ovarian cancers shed the ganglioside GD3, which inhibits NKT-cell activation. Ovarian cancers also secrete high levels of VEGF. In this study, we sought to test the hypothesis that VEGF production by ovarian cancers suppresses NKT-cell-mediated antitumor responses. To investigate the effects of VEGF on CD1d-mediated NKT-cell activation, a conditioned media model was established, wherein the supernatants from ovarian cancer cell lines (OV-CAR-3 and SK-OV-3) were used to treat CD1d-expressing antigen-presenting cells (APC) and cocultured with NKT hybridomas. Ovarian cancer-associated VEGF was inhibited by treatment with bevacizumab and genistein; conditioned medium was collected, and CD1d-mediated NKT-cell responses were assayed by ELISA. Ovarian cancer tissue and ascites contain lymphocytic infiltrates, suggesting that immune cells traffic to tumors, but are then inhibited by immunosuppressive molecules within the tumor microenvironment. OV-CAR-3 and SK-OV-3 cell lines produce high levels of VEGF and GD3. Pretreatment of APCs with ascites or conditioned medium from OV-CAR-3 and SK-OV-3 blocked CD1d-mediated NKT-cell activation. Inhibition of VEGF resulted in a concomitant reduction in GD3 levels and restoration of NKT-cell responses. We found that VEGF inhibition restores NKT-cell function in an in vitro ovarian cancer model. These studies suggest that the combination of immune modulation with antiangiogenic treatment has therapeutic potential in ovarian cancer. Clin Cancer Res; 22(16); 4249-58. ©2016 AACR.


Orexin, stress, and anxiety/panic states.
A panic response is an adaptive response to deal with an imminent threat and consists of an integrated pattern of behavioral (aggression, fleeing, or freezing) and increased cardiorespiratory and endocrine responses that are highly conserved across vertebrate species. In the 1920s and 1940s, Philip Bard and Walter Hess, respectively, determined that the posterior regions of the hypothalamus are critical for a "fight-or-flight" reaction to deal with an imminent threat. Since the 1940s it was determined that the posterior hypothalamic panic area was located dorsal (perifornical hypothalamus: PeF) and dorsomedial (dorsomedial hypothalamus: DMH) to the fornix. This area is also critical for regulating circadian rhythms and in 1998, a novel wake-promoting neuropeptide called orexin (ORX)/hypocretin was discovered and determined to be almost exclusively synthesized in the DMH/PeF perifornical hypothalamus and adjacent lateral hypothalamus. The most proximally emergent role of ORX is in regulation of wakefulness through interactions with efferent systems that mediate arousal and energy homeostasis. A hypoactive ORX system is also linked to narcolepsy. However, ORX role in more complex emotional responses is emerging in more recent studies where ORX is linked to depression and anxiety states. Here, we review data that demonstrates ORX ability to mobilize a coordinated adaptive panic/defense response (anxiety, cardiorespiratory, and endocrine components), and summarize the evidence that supports a hyperactive ORX system being linked to pathological panic and anxiety states.


Effects of the Exchange Coupling on Dynamic Properties in a Series of CoGdCo Complexes.
Reaction of 2-hydroxy3-methoxybenzaldehyde ( o-vanillin) with 1,1,1-tris(aminomethyl)ethane, Me-C(CH2NH2)3, or with N, N', N''-trimethylphosphorothioic trihydrazide, P(S)[NMe-NH2]3, yields two tripodal LH3 and L1H3 ligands which are able to give cationic heterotrinuclear [LCoGdCoL]+ or [L1CoGdCoL1]+ complexes. The CoII ions are coordinated to these deprotonated ligands in the inner N3O3 site, while the GdIII ion is linked to three deprotonated phenoxo oxygen atoms of two anionic [LCo]- or [L1Co]- units. Air oxidation of these trinuclear complexes does not yield complexes associating CoIII and GdIII ions. With the first ligand, the structurally characterized resulting complex is the neutral mononuclear LCoIII compound, while in the second case, oxidation of the CoII ions turned out to be impossible. The [L1CoLnCoL1]+ complexes behave as single-molecule magnets with effective energy barriers for the reversal of magnetization varying from Ueff = 51.3 K, τo = 2 × 10-6 s for the yttrium complex to Ueff = 29.5, 29.4, 27.4 K and τo = 1.3 × 10-7, 1.47 × 10-7, 1.50 × 10-7 s for the gadolinium ones, depending on the used counteranions. The energy decrease is compensated by the suppression of quantum tunneling of magnetization in absence of applied field, thanks to the introduction of a ferromagnetic Co-Gd interaction. Current work also shows that uncritical use of conventional spin Hamiltonians, based on quenched orbital momenta, can be misleading and that ab initio calculations are indispensable for establishing the picture of real magnetic interaction. Ab initio calculations show that the CoII sites in the investigated compounds possess large unquenched orbital moments due to the first-order spin-orbit coupling resulting in strongly axial magnetic anisotropy. Although the CoII ions are not axial enough for showing slow relaxation of magnetization by themselves, blocking barriers of exchange type are obtained thanks to the exchange interaction with GdIII ions.


A Personal Model of Trumpery: Linguistic Deception Detection in a Real-World High-Stakes Setting.
Language use differs between truthful and deceptive statements, but not all differences are consistent across people and contexts, complicating the identification of deceit in individuals. By relying on fact-checked tweets, we showed in three studies (Study 1: 469 tweets; Study 2: 484 tweets; Study 3: 24 models) how well personalized linguistic deception detection performs by developing the first deception model tailored to an individual: the 45th U.S. president. First, we found substantial linguistic differences between factually correct and factually incorrect tweets. We developed a quantitative model and achieved 73% overall accuracy. Second, we tested out-of-sample prediction and achieved 74% overall accuracy. Third, we compared our personalized model with linguistic models previously reported in the literature. Our model outperformed existing models by 5 percentage points, demonstrating the added value of personalized linguistic analysis in real-world settings. Our results indicate that factually incorrect tweets by the U.S. president are not random mistakes of the sender.


Multiple left atrial myxoma: case report.
Primary cardiac tumors are infrequent, with an incidence between 0.001% and 0.2%, mostly comprising benign histological characteristics in 75% of these cases. Myxomas account for approximately 50% of these neoplasms. As regards location, 75-80% of myxomas are in the left atrium, 18% in the right atrium, and more rarely in the ventricles. We report a case of a patient in functional class (FC) IV New York Heart Association (NYHA) and postoperative histological diagnosis of multilobular myxoma originating in the posterior left atrial wall. Clinical evaluation 3 months after surgery suggested NYHA functional class I and echocardiographic absence of intracardiac masses.


Steroidal antiandrogens and 5alpha-reductase inhibitors.
The purpose of this work is to synthesize a pregnane derivative with a high antiandrogenic effect or a high inhibitory activity for the enzyme 5 alpha-reductase type 2. Benign prostatic hyperplasia and prostate cancer are androgen dependent diseases which afflict a large percentage of the male population. Dihydrotestosterone 3, a 5 alpha-reductase metabolite of testosterone 2 has been implicated as a causative factor in the progression of these diseases, largely through the clinical evaluation of males who are genetically deficient of steroid 5 alpha-reductase enzyme. As a result of this study, the inhibition of this enzyme has become a pharmacological strategy for the design and synthesis of new drugs. The advent of finasteride 22 "figure 5" a 5 alpha-reductase inhibitor, has greatly alleviated the symptoms associated with benign prostatic hyperplasia. On the other hand, the discovery of cyproterone acetate 4 "figure 2" alone or in combination with the antiandrogens flutamide 14 "figure 3" or bicalutamide 21 has greatly reduced the misery of prostate cancer. Prostate cancer kills about 40,000 men in the USA and approximately 400,000 prostatectomies are performed each year. In our laboratory we have recently synthesized ten new progesterone derivatives 17 alpha-acyloyloxy-6-halo (chloro, bromo) 16 beta-methyl-4, 6-pregnadiene-3, 20-diones (54a-54e and 55a-55e), "figure 10". These steroids were evaluated as antiandrogens and exhibited a much higher activity than the commercially available cyproterone acetate 4. The same compounds were also evaluated as 5 alpha-reductase inhibitors and showed a slightly higher inhibitory activity than that of finasteride 22, the drug of choice today for the treatment of benign prostatic hyperplasia In another study we synthesized several new 4-halo (bromo and chloro) 17 alpha-benzoyloxy and also 4-halo-17 alpha-acetoxy progesterone derivatives (58-63) "figure 13". These compounds were prepared from the commercially available 17 alpha-acetoxy progesterone 56. The pharmacological evaluation of these steroids "figure 14" indicated that the 17 alpha-benzoyloxy derivatives (4-chloro and bromo) 62 and 63 were very potent antiandrogens. On the other hand, the 4-halo (bromo and chloro) 17 alpha-acetoxy (58, 59) and the 17 alpha-benzoyloxy-4-chloro analog 63 showed a very high inhibitory activity for the enzyme 5 alpha-reductase type 2 "figure 15".


Dietary plant sterols and cholesterol metabolism.
Plant sterols, naturally occurring in foods of plant origin, reduce cholesterol absorption. Experimental studies show plant sterols to be an important part of the serum-cholesterol lowering effect of certain diets and dietary components. Epidemiological data show that individuals with higher intakes of plant sterols from their habitual diets have lower serum-cholesterol levels. To date, the role of naturally occurring plant sterols for lowering serum cholesterol has probably been underestimated. The consumption of dietary plant sterols should be a part of dietary advice to patients with hypercholesterolemia and the general public for the prevention and management of coronary heart disease.


Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience.
The effects of convalescent plasma (CP) infusion, one of the treatment options for severe Middle East respiratory syndrome coronavirus (MERS-CoV) infections, have not yet been evaluated. Serological responses of CP-infused MERS patients during the 2015 Korean MERS outbreak at a tertiary care centre were evaluated. Serological activity was evaluated with anti-MERS-CoV enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)G, ELISA IgA, immunofluorescence assay IgM and plaque reduction neutralization test (PRNT). Donor plasma and one or two recipient's serum samples per week of illness including one taken the day after each CP infusion were evaluated. For sensitivity and specificity analysis of ELISA IgG in predicting neutralization activity, a data set of 138 previously evaluated MERS-CoV-infected patients was used. Three of thirteen MERS patients with respiratory failure received four CP infusions from convalesced MERS-CoV-infected patients, and only two of them showed neutralizing activity. Donor plasma with a PRNT titre 1:80 demonstrated meaningful serological response after CP infusion, while that with a PRNT titre 1:40 did not. ELISA IgG predicted neutralization activity of a PRNT titre ≥1:80 with more than 95% specificity at a cutoff optical density (OD) ratio of 1.6, and with 100% specificity at an OD ratio of 1.9. For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used. ELISA IgG could substitute for the neutralization test in resource-limited situations.


Lipoatrophy among patients on antiretroviral therapy in Lagos, Nigeria: Prevalence, pattern and association with cardiovascular risk factors.
Antiretroviral therapy (ART) is linked with morphologic abnormalities such as lipoatrophy (LA), which may accompany metabolic alterations (dysglycemias, dyslipidemia and insulin resistance) that increase cardiovascular disease risk. LA and its association with metabolic alterations have been infrequently studied amongst Nigerians on ART. To determine the prevalence, pattern and association of LA with metabolic abnormalities and hypertension among patients on ART attending an ambulatory human immunodeficiency virus clinic in Lagos, Nigeria. A cross-sectional study was carried out among patients on ART using a structured interviewer administered questionnaire. Data obtained included patients and physician's assessment of body fat changes, drug history, blood pressure, body composition assessment using bioelectrical impedance analysis and biochemical evaluation (glucose, lipids). LA was defined clinically. Data were analyzed using IBM SPSS statistical software version 21. A total of 48 (33.1%) of the 145 patients had LA. The face was the most frequently affected body region. Patients with LA with lower body circumferences, skin-fold thickness and body fat (P < 0.05). The frequencies of lipid abnormalities were: Reduced high density lipoprotein-cholesterol (47.1%), elevated total cholesterol (35.6%), reduced low density lipoprotein-cholesterol (19.2%), elevated triglycerides (14.4%). Fasting plasma glucose (FPG)≥6.1 mmol/l and hypertension were present among 9.6% and 40.7% respectively. LA was not significantly associated with the presence of glucose intolerance, dyslipidemia or hypertension (P > 0.05). Lipoatrophy, though commonly encountered in patients on ART in Nigeria was not associated with the presence of dyslipidemia, abnormal FPG or hypertension. Regular monitoring by the physician and increased patients awareness are necessary to reduce its prevalence and impact.


Top No-Nonsense Tips: The Dos and Don'ts of Managing Flexor Tendon Injuries.
Flexor tendon injury surgical repairs can be challenging for surgeons, where the timing of surgery and precision of repair matter the most. The latest evidence and basic science discoveries in flexor tendon management are provided. It is important to review how wide-awake local anesthesia no tourniquet surgery has been a paradigm shift in surgical management and pearls learned from incorporating this into practice.


The α7-nicotinic receptor is upregulated in immune cells from HIV-seropositive women: consequences to the cholinergic anti-inflammatory response.
Antiretroviral therapy partially restores the immune system and markedly increases life expectancy of HIV-infected patients. However, antiretroviral therapy does not restore full health. These patients suffer from poorly understood chronic inflammation that causes a number of AIDS and non-AIDS complications. Here we show that chronic inflammation in HIV+ patients may be due to the disruption of the cholinergic anti-inflammatory pathway by HIV envelope protein gp120IIIB. Our results demonstrate that HIV gp120IIIB induces α7 nicotinic acetylcholine receptor (α7) upregulation and a paradoxical proinflammatory phenotype in macrophages, as activation of the upregulated α7 is no longer capable of inhibiting the release of proinflammatory cytokines. Our results demonstrate that disruption of the cholinergic-mediated anti-inflammatory response can result from an HIV protein. Collectively, these findings suggest that HIV tampering with a natural strategy to control inflammation could contribute to a crucial, unresolved problem of HIV infection: chronic inflammation.


Decay-accelerating factor protects human tumor cells from complement-mediated cytotoxicity in vitro.
The disialoganglioside GD2 is expressed on a wide spectrum of human tumor types, including neuroblastomas and melanomas. Upon binding of 3F8, a murine monoclonal antibody (MAb) specific for GD2, neuroblastomas and some melanomas are sensitive to killing by human complement, whereas some melanomas are not. To investigate the mechanism underlying these differences in complement mediated cytotoxicity, complement-insensitive melanoma cell lines were compared with respect to expression of the decay-accelerating factor (DAF), a membrane regulatory protein that protects blood cells from autologous complement attack. While DAF was undetectable among neuroblastomas, it was present in complement-insensitive melanomas. When the function of DAF was blocked by anti-DAF MAb, C3 uptake and complement-mediated lysis of the insensitive melanoma lines were markedly enhanced. F(ab')2 fragments were as effective in enhancing lysis as intact anti-DAF MAb. The DAF-negative and DAF-positive melanoma cell lines were comparably resistant to passive lysis by cobra venom factor-treated serum. The data suggest that in some tumors, DAF activity accounts for their resistance to complement-mediated killing. The ability to render these cells complement-sensitive by blocking DAF function may have implications for immunotherapy.


Purification and properties of arylsulphatase A from chicken brain.
1. Chicken brain arylsulphatase A was purified 2000-fold, with overall recovery 14%, by using ammonium sulphate fractionation, ethanol precipitation, Sephadex G-200 gel filtration and DEAE-Sephadex column chromatography. 2. The purified preparation was free from beta-glucuronidase, beta-galactosidase, acid phosphatase, inorganic pyrophosphatase and adenosine 3'-phosphate 5'-sulphatophosphate sulphohydrolase activities. 3. Polyacrylamide-gel electrophoresis indicated that the purified preparation was not homogeneous. 4. Chicken brain arylsulphatase was markedly inhibited by carbonyl reagents in the presence of traces of Cu(2+) in the system. Other metal ions such as Fe(2+) and Zn(2+), were inactive. 5. Ascorbic acid alone had no effect on enzyme activity but enhances the inhibition by Cu(2+). 6. Chicken brain arylsulphatase A resembled arylsulphatase A of other animal species in its kinetic properties such as K(m) value, anomalous time-activity relationship and the inhibitory effect of phosphate, sulphite and sulphate ions. However, its electrophoretic mobility, behaviour under zinc acetate fractionation and stimulation by Ag(+) were similar to arylsulphatase B of other animal species. Thus, this enzyme did not correspond to either arylsulphatase A or arylsulphatase B but properties of both. 7. The purified enzyme preparation can degrade cerebroside 3-sulphate.


Kctd15 inhibits neural crest formation by attenuating Wnt/beta-catenin signaling output.
Neural crest (NC) precursors are stem cells that are capable of forming many cell types after migration to different locations in the embryo. NC and placodes form at the neural plate border (NPB). The Wnt pathway is essential for specifying NC versus placodal identity in this cell population. Here we describe the BTB domain-containing protein Potassium channel tetramerization domain containing 15 (Kctd15) as a factor expressed in the NPB that efficiently inhibits NC induction in zebrafish and frog embryos. Whereas overexpression of Kctd15 inhibited NC formation, knockdown of Kctd15 led to expansion of the NC domain. Likewise, NC induction by Wnt3a plus Chordin in Xenopus animal explants was suppressed by Kctd15, but constitutively active beta-catenin reversed Kctd15-mediated suppression of NC induction. Suppression of NC induction by inhibition of Wnt8.1 was rescued by reduction of Kctd15 expression, linking Kctd15 action to the Wnt pathway. We propose that Kctd15 inhibits NC formation by attenuating the output of the canonical Wnt pathway, thereby restricting expansion of the NC domain beyond its normal range.


Image compression via improved quadtree decomposition algorithms.
Quadtree decomposition is a simple technique used to obtain an image representation at different resolution levels. This representation can be useful for a variety of image processing and image compression algorithms. This paper presents a simple way to get better compression performances (in MSE sense) via quadtree decomposition, by using near to optimal choice of the threshold for quadtree decomposition; and bit allocation procedure based on the equations derived from rate-distortion theory. The rate-distortion performance of the improved algorithm is calculated for some Gaussian field, and it is examined vie simulation over benchmark gray-level images. In both these cases, significant improvement in the compression performances is shown.


Population Growth, Climate Change and Water Scarcity in the Southwestern United States.
PROBLEM STATEMENT: In a simple economic model, water scarcity arises as a result of an imbalance between the supply of and demand for water sources. Distribution in this setting is the source of numerous conflicts globally. APPROACH: Already, the Southwestern United States (US) suffers from annual drought and long-standing feud over natural water resources. RESULTS: Population growth in the Southwestern United States along with the continued effects of climate change (natural and anthropogenic) predicts a perpetual decline in natural water sources, such as smaller snowpacks, in the coming years. As the increasing number of communities across multiple US states that subsist off of natural water supplies face water shortages with increasing severity, further water conflict will emerge. Such conflicts become especially protracted when the diversion of water from a source of benefit to one community negatively impacts nearby communities of humans and economically vital ecosystems (e.g., marshlands or tributaries). CONCLUSION/RECOMMENDATIONS: The ensuing politics and health effects of these diversions can be complicated and future water policies both domestically and internationally are lacking. To draw attention to and stimulate discussion around the lacking policy discussion domestically, herein we document existing and emerging consequences of watery scarcity in the Southwestern United States and briefly outline past and potential future policy responses.


Public access defibrillation--designing a universal report form and database for a national programme.
We describe the design of a universal report form for use by lay-responders using an automated external defibrillator (AED) as part of a national programme for public access defibrillation (PAD). The form was designed initially because the Department of Health in England required detailed audit data about the national programme for public access defibrillation they initiated. At that time (1999) there was very little reported experience of public access defibrillation and none from the UK. The form evolved pragmatically as experience showed the wide range of situations under which lay-persons might use an AED, and also the information likely to be available that could be collected reliably. This report may help others who wish to audit schemes for PAD and facilitate the evolution of an internationally acceptable template for data collection.


Spatial-Temporal Cluster Analysis of Childhood Cancer in California.
The observance of nonrandom space-time groupings of childhood cancer has been a concern of health professionals and the general public for decades. Many childhood cancers are suspected to have initiated in utero; therefore, we examined the spatial-temporal randomness of the birthplace of children who later developed cancer. We performed a space-time cluster analysis using birth addresses of 5,896 cases and 23,369 population-based, age-, sex-, and race/ethnicity-matched controls in California from 1997 to 2007, evaluating 20 types of childhood cancer and three a priori designated subgroups of childhood acute lymphoblastic leukemia (ALL). We analyzed data using a newly designed semiparametric analysis program, ClustR, and a common algorithm, SaTScan. We observed evidence for nonrandom space-time clustering for ALL diagnosed at 2-6 years of age in the South San Francisco Bay Area (ClustR P = 0.04, SaTScan P = 0.07), and malignant gonadal germ cell tumors in a region of Los Angeles (ClustR P = 0.03, SaTScan P = 0.06). ClustR did not identify evidence of clustering for other childhood cancers, although SaTScan suggested some clustering for Hodgkin lymphoma (P = 0.09), astrocytoma (P = 0.06), and retinoblastoma (P = 0.06). Our study provides evidence that childhood ALL diagnosed at 2-6 years and malignant gonadal germ cell tumors sporadically occurs in nonrandom space-time clusters. Further research is warranted to identify epidemiologic features that may inform the underlying etiology.


Randomized Controlled Trial of a Healthy Lifestyle Intervention Among Smokers With Psychotic Disorders.
People with severe mental disorders typically experience a range of health problems; consequently, interventions addressing multiple health behaviors may provide an efficient way to tackle this major public health issue. This two-arm randomized controlled trial among people with psychotic disorders examined the efficacy of nicotine replacement therapy (NRT) plus either a face-to-face or predominantly telephone delivered intervention for smoking cessation and cardiovascular disease (CVD) risk reduction. Following baseline assessment and completion of a common, individually delivered 90-minute face-to-face intervention, participants (n = 235) were randomized to receive NRT plus: (1) a "Healthy Lifestyles" intervention for smoking cessation and CVD risk behaviors or (2) a predominantly telephone-based intervention (designed to control for NRT provision, session frequency, and other monitoring activities). Research assistants blind to treatment allocation performed assessments at 15 weeks (mid-intervention) and 12 months after baseline. There were no significant differences between intervention conditions in CVD risk or smoking outcomes at 15 weeks or 12 months, with improvements in both conditions (eg, 12 months: 6.4% confirmed point prevalence abstinence rate; 17% experiencing a 50% or greater smoking reduction; mean reduction of 8.6 cigarettes per day; mean improvement in functioning of 9.8 points). The health disparity experienced by people with psychotic disorders is high. Face-to-face Healthy Lifestyle interventions appear to be feasible and somewhat effective. However, given the accessibility of telephone delivered interventions, potentially combined with lower cost, further studies are needed to evaluate telephone delivered smoking cessation and lifestyle interventions for people with psychotic disorders.


Metastatic Cutaneous Paraganglioma: A Case Report and Review of the Literature.
Paragangliomas are rare neoplasms that arise from chromaffin cells of the sympathetic and parasympathetic nervous system. These tumors are often cured by surgical resection but the risk for metastatic disease exists, particularly for extra-adrenal paragangliomas. The behavior of these tumors is unpredictable, and clinical and histopathological features associated with malignancy have not been determined. The most common sites of metastases include local and distant lymph nodes, bone, liver, and lung. Cutaneous metastases are exceedingly rare with only 2 reported cases, both of which presented on the scalp. Here we describe a 78-year-old woman with cutaneous metastatic paraganglioma presenting as a forehead nodule, which developed 15 years after her initial diagnosis of paraganglioma.


Characterization of a transition in the transport dynamics of a diffusive sandpile by means of recurrence quantification analysis.
Recurrence quantification analysis (RQA) is used to characterize a dynamical transition that takes place in the diffusive sandpile. The transition happens when a combination of the drive strength, diffusivity, and overturning size exceeds a critical value. Above the transition, the self-similar transport dynamics associated to the classical (nondiffusive) sandpile is replaced by new transport dynamics dominated by near system-size, quasiperiodic avalanche events. The deterministic content of transport dynamics, as quantified by RQA, turns out to be quite different in both phases. The time series analyzed with RQA in this work correspond to local sand fluxes at different radial locations across the diffusive sandpile.


ELPHA: Dynamically deformable liver phantom for real-time motion-adaptive radiotherapy treatments.
Real-time motion-adaptive radiotherapy of intrahepatic tumors needs to account for motion and deformations of the liver and the target location within. Phantoms representative of anatomical deformations are required to investigate and improve dynamic treatments. A deformable phantom capable of testing motion detection and motion mitigation techniques is presented here. The dynamically dEformable Liver PHAntom (ELPHA) was designed to fulfill three main constraints: First, a reproducibly deformable anatomy is required. Second, the phantom should provide multimodality imaging contrast for motion detection. Third, a time-resolved dosimetry system to measure temporal effects should be provided. An artificial liver with vasculature was casted from soft silicone mixtures. The silicones allow for deformation and radiographic image contrast, while added cellulose provides ultrasonic contrast. An actuator was used for compressing the liver in the inferior direction according to a prescribed respiratory motion trace. Electromagnetic (EM) transponders integrated in ELPHA help provide ground truth motion traces. They were used to quantify the motion reproducibility of the phantom and to validate motion detection based on ultrasound imaging. A two-dimensional ultrasound probe was used to follow the position of the vessels with a template-matching algorithm. This detected vessel motion was compared to the EM transponder signal by calculating the root-mean-square error (RMSE). ELPHA was then used to investigate the dose deposition of dynamic treatment deliveries. Two dosimetry systems, radio-chromic film and plastic scintillation dosimeters (PSD), were integrated in ELPHA. The PSD allow for time-resolved measurement of the delivered dose, which was compared to a time-resolved dose of the treatment planning system. Film and PSD were used to investigate dose delivery to the deforming phantom without motion compensation and with treatment-couch tracking for motion compensation. ELPHA showed densities of 66 and 45 HU in the liver and the surrounding tissues. A high motion reproducibility with a submillimeter RMSE (<0.32 mm) was measured. The motion of the vasculature detected with ultrasound agreed well with the EM transponder position (RMSE < 1 mm). A time-resolved dosimetry system with a 1 Hz time resolution was achieved with the PSD. The agreement of the planned and measured dose to the PSD decreased with increasing motion amplitude: A dosimetric RMSE of 1.2, 2.1, and 2.7 cGy/s was measured for motion amplitudes of 8, 16, and 24 mm, respectively. With couch tracking as motion compensation, these values decreased to 1.1, 1.4, and 1.4 cGy/s. This is closer to the static situation with 0.7 cGy/s. Film measurements showed that couch tracking was able to compensate for motion with a mean target dose within 5% of the static situation (-5% to +1%), which was higher than in the uncompensated cases (-41% to -1%). ELPHA is a deformable liver phantom with high motion reproducibility. It was demonstrated to be suitable for the verification of motion detection and motion mitigation modalities. Based on the multimodality image contrast, a high accuracy of ultrasound based motion detection was shown. With the time-resolved dosimetry system, ELPHA is suitable for performance assessment of real-time motion-adaptive radiotherapy, as was shown exemplary with couch tracking.


The natural course of giant paraesophageal hernia and long-term outcomes following conservative management.
Accurate information on the natural course of giant paraesophageal hernia is scarce, challenging therapeutic decisions whether or not to operate. We aimed to investigate the long-term outcomes, including hernia-related deaths and complications (e.g. volvulus, gastrointestinal bleeding, strangulation) of patients with giant paraesophageal hernia that were conservatively managed, and to determine factors associated with clinical outcome. We retrospectively analysed charts of patients diagnosed with giant paraesophageal hernia between January 1990 and August 2019, collected from a university hospital in The Netherlands. Included patients were subdivided into three groups based on primary therapeutic decision at diagnosis. Radiological, clinical and surgical characteristics, along with long-term outcomes at most recent follow-up, were collected. We included 293 patients (91 men, mean age 70.3 ± 12.4 years) with a mean duration of follow-up of 64.0 ± 58.8 months. Of the 186 patients that were conservatively treated, a total hernia-related mortality of 1.6% was observed. Hernia-related complications, varying from uncomplicated volvulus to strangulation, occurred in 8.1% of patients. Only 1.1% of patients included in this study required emergency surgery. Logistic regression analysis revealed the presence of symptoms (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.8-20.6), in particular obstructive symptoms (vomiting, OR 15.7, 95% CI 4.6-53.6; epigastric pain, OR 4.4, 95% CI 1.2-15.8 and chest pain, OR 6.1, 95% CI 1.8-20.6) to be associated with the occurrence of hernia-related complications. Hernia-related death and morbidity is low in conservatively managed patients. The presence of obstructive symptoms was found to be associated with the occurrence of complications during follow-up. Conservative therapy is an appropriate therapeutic strategy for asymptomatic patients.


Excess Pyrophosphate Restrains Pavement Cell Morphogenesis and Alters Organ Flatness in Arabidopsis thaliana.
In Arabidopsis thaliana, the vacuolar proton-pumping pyrophosphatase (H+-PPase) is highly expressed in young tissues, which consume large amounts of energy in the form of nucleoside triphosphates and produce pyrophosphate (PPi) as a byproduct. We reported that excess PPi in the H+-PPase loss-of-function fugu5 mutant severely compromised gluconeogenesis from seed storage lipids, arrested cell division in cotyledonary palisade tissue, and triggered compensated cell enlargement; this phenotype was recovered upon sucrose supply. Thus, we provided evidence that the hydrolysis of inhibitory PPi, rather than vacuolar acidification, is the major contribution of H+-PPase during seedling establishment. Here, examination of the epidermis revealed that fugu5 pavement cells exhibited defective puzzle-cell formation. Importantly, removal of PPi from fugu5 background by the yeast cytosolic PPase IPP1, in fugu5-1 AVP1pro::IPP1 transgenic lines, restored the phenotypic aberrations of fugu5 pavement cells. Surprisingly, pavement cells in mutants with defects in gluconeogenesis (pck1-2) or the glyoxylate cycle (icl-2; mls-2) showed no phenotypic alteration, indicating that reduced sucrose production from seed storage lipids is not the cause of fugu5 epidermal phenotype. fugu5 had oblong cotyledons similar to those of angustifolia-1 (an-1), whose leaf pavement cells display an abnormal arrangement of cortical microtubules (MTs). To gain insight into the genetic interaction between ANGUSTIFOLIA and H+-PPase in pavement cell differentiation, an-1 fugu5-1 was analyzed. Surprisingly, epidermis developmental defects were synergistically enhanced in the double mutant. In fact, an-1 fugu5-1 pavement cells showed a striking three-dimensional growth phenotype on both abaxial and adaxial sides of cotyledons, which was recovered by hydrolysis of PPi in an-1 fugu5-1 AVP1pro::IPP1. Live imaging revealed that cortical MTs exhibited a reduced velocity, were slightly fragmented and sparse in the above lines compared to the WT. Consistently, addition of PPi in vitro led to a dose-dependent delay of tubulin polymerization, thus supporting a link between PPi and MT dynamics. Moreover, mathematical simulation of three-dimensional growth based on cotyledon proximo-distal and medio-lateral phenotypic quantification implicated restricted cotyledon expansion along the medio-lateral axis in the crinkled surface of an-1 fugu5-1. Together, our data suggest that PPi homeostasis is a prerequisite for proper pavement cell morphogenesis, epidermal growth and development, and organ flattening.


Above-belowground interactions govern the course and impact of biological invasions.
Introduction of exotic organisms that subsequently become invasive is considered a serious threat to global biodiversity, and both scientists and nature-conservationists attempt to find explanations and means to meet this challenge. This requires a thorough analysis of the invasion phenomenon in an evolutionary and ecological context; in the case of invasive plants, we must have a major focus on above-belowground interactions. Thus, we discuss different theories that have been proposed to explain the course of invasions through interactions between plants and soil organisms. Further, a thorough analysis of invasion must include a temporal context. Invasions will typically include an initial acute phase, where the invader expands its territory and a later chronic phase where equilibrium is re-established. Many studies fail to make this distinction, which is unfortunate as it makes it impossible to thoroughly understand the invasion of focus. Thus, we claim that invasions fall into two broad categories. Some invasions irreversibly change pools and pathways of matter and energy in the invaded system; even if the abundance of the invader is reduced or it is completely removed, the system will not return to its former state. We use earthworm invasion in North America as a particular conspicuous example of invasive species that irreversibly change ecosystems. However, invasions may also be reversible, where the exotic organism dominates the system for a period, but in the longer term it either disappears, declines or its negative impact decreases. If the fundamental ecosystem structure and flows of energy and matter have not been changed, the system will return to a state not principally different from the original.


Toward stable genetic engineering of human O-glycosylation in plants.
Glycosylation is the most abundant and complex posttranslational modification to be considered for recombinant production of therapeutic proteins. Mucin-type (N-acetylgalactosamine [GalNAc]-type) O-glycosylation is found in eumetazoan cells but absent in plants and yeast, making these cell types an obvious choice for de novo engineering of this O-glycosylation pathway. We previously showed that transient implementation of O-glycosylation capacity in plants requires introduction of the synthesis of the donor substrate UDP-GalNAc and one or more polypeptide GalNAc-transferases for incorporating GalNAc residues into proteins. Here, we have stably engineered O-glycosylation capacity in two plant cell systems, soil-grown Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana tabacum) Bright Yellow-2 suspension culture cells. Efficient GalNAc O-glycosylation of two stably coexpressed substrate O-glycoproteins was obtained, but a high degree of proline hydroxylation and hydroxyproline-linked arabinosides, on a mucin (MUC1)-derived substrate, was also observed. Addition of the prolyl 4-hydroxylase inhibitor 2,2-dipyridyl, however, effectively suppressed proline hydroxylation and arabinosylation of MUC1 in Bright Yellow-2 cells. In summary, stably engineered mammalian type O-glycosylation was established in transgenic plants, demonstrating that plants may serve as host cells for the production of recombinant O-glycoproteins. However, the present stable implementation further strengthens the notion that elimination of endogenous posttranslational modifications may be needed for the production of protein therapeutics.


Bone marrow failure following severe injury in humans.
Hematopoietic failure has been observed in experimental animals following shock and injury. In humans, bone marrow dysfunction has been observed in the red cell component and characterized by a persistent anemia, low reticulocyte counts, and the need for repeated transfusions despite adequate iron stores. While a quantitative defect in white blood cell count has not been noted, an alteration in white blood cell function manifesting as an increased susceptibility to infection is well established. Since the etiology of this anemia remains unknown and the bone marrow has been rarely studied following injury, we measured various parameters of hematopoiesis directly using bone marrow from trauma patients and tested the hypothesis that trauma results in profound bone marrow dysfunction, which could explain both the persistent anemia and the alteration in white blood cell function. Bone marrow aspirates and peripheral blood were obtained between day 1 and 7 following injury from 45 multiple trauma patients. Normal volunteers served as controls. Peripheral blood was assayed for hemoglobin concentration, reticulocyte count, erythropoietin levels, white blood cell count, and differential. Peripheral blood and bone marrow were cultured for hematopoietic progenitors (CFU-GM, BFU-E, and CFU-E colonies). Bone marrow CFU-GM, BFU-E, and CFU-E colony formation was significantly reduced while peripheral blood CFU-GM, BFU-E, and CFU-E was increased in the trauma patients compared with normal volunteers. Bone marrow stroma failed to grow to confluence by day 14 in >90% of trauma patients. In contrast, bone marrow stroma from volunteers always reached confluence between days 10 and 14 in culture. The mean hemoglobin concentration and reticulocyte counts of the trauma patients were 8.6 +/- 1.0 g/dL and 2.75 +/- 0.7% respectively, while their plasma erythropoietin levels were 2 to 10 times greater than control values. Release of immature white blood cells into the circulation may also contribute to a failure to clear infection and an increased propensity to organ failure. Concomitantly, profound changes occur within the bone marrow, which include the increased release of erythroid and myeloid progenitors into the circulation, a decrease in progenitor cell growth within the bone marrow, and an impaired growth of the bone marrow stroma. Erythropoietin levels are preserved following trauma, implying that the persistent anemia of injury is related to the failure of the bone marrow to respond to erythropoietin.


Peripheral resolution and contrast sensitivity: effects of monochromatic and chromatic aberrations.
Correction and manipulation of peripheral refractive errors are indispensable for people with central vision loss and in optical interventions for myopia control. This study investigates further enhancements of peripheral vision by compensating for monochromatic higher-order aberrations (with an adaptive optics system) and chromatic aberrations (with a narrowband green filter, 550 nm) in the 20° nasal visual field. Both high-contrast detection cutoff and contrast sensitivity improved with optical correction. This improvement was most evident for gratings oriented perpendicular to the meridian due to asymmetric optical errors. When the natural monochromatic higher-order aberrations are large, resolution of 10% contrast oblique gratings can also be improved with correction of these errors. Though peripheral vision is mainly limited by refractive errors and neural factors, higher-order aberration correction beyond conventional refractive errors can still improve peripheral vision under certain circumstances.


Improvement of plasma adiponectin, leptin and C-reactive protein concentrations by orlistat: a systematic review and meta-analysis.
To conduct a systematic review and meta-analysis of relevant randomized clinical trials (RCTs) to ascertain the effect size of orlistat in modulating plasma levels of adipokines, ghrelin and C-reactive protein (CRP). Medline, SCOPUS, Web of Science and Google Scholar databases were searched. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using I(2) index. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of duration of treatment, percentage change in body mass index (BMI) and baseline BMI values as potential confounders of the estimated effect size. Meta-analysis suggested a significant increase in plasma levels of adiponectin [weighted mean difference (WMD): 19.18%, 95% confidence interval (CI): 5.80, 32.57, p = 0.005] and significant reductions in plasma levels of leptin (WMD: -13.24%, 95% CI: -20.69, -5.78, p = 0.001) and CRP (WMD: -11.52%, 95% CI: -16.55, -6.49, p < 0.001) following treatment with orlistat. In meta-regression, changes in plasma concentrations of adiponectin, leptin and CRP were associated with duration of treatment, but not with either change in BMI or baseline BMI values. Orlistat is effective in increasing plasma concentrations of adiponectin and decreasing those of leptin and CRP.


The impact of twisting on the intersystem crossing in acenes: an experimental and computational study.
Due to their unique excited state dynamics, acenes play a dominant role in optoelectronic and light-harvesting applications. Their optical and electronic properties are typically tailored by side-group engineering, which often result in distortion of the acene core from planarity. However, the effect of such distortion on their excited state dynamics is not clear. In this work, we investigate the effect of twisting on the photophysics of acenes, which are helically locked to a defined twist angle by tethers of different lengths. Ultrafast transient absorption and time resolved fluorescence show a clear dependence of the rate of intersystem crossing with twisting. This trend is explained using quantum chemical calculations, showing an increase of spin-orbit coupling (SOC). At much earlier times, structural reorganization in S1, including coherent vibrational wave packet motions, is reflected in transient spectral changes. As predicted by theory, decreasing the length of diagonal tether induces enhanced activity and frequency blue-shifting of a normal vibration consisting of anthracene twisting against restraint of the tethering chain. Overall, these results serve as design principles for tuning photophysical properties of acenes via controlled twisting of their aromatic core.


Immobilization/stabilization of acid urease on Eupergit® supports.
The adsorption capacity and immobilization rate of two Eupergit® supports for acid urease was studied by varying the ionic strength and enzyme preparation concentration in the immobilizing solution at pH 7. Eupergit® C250 L yielded a series of derivatives with enzyme loadings (Y(P/B)) ranging from 48 to 171 mg of bovine serum albumin equivalent (BSAE) per gram of dry support (ds). Use of drastic postimmobilization conditions at pH 9 for 3-9 days yielded a slight decrease (8-14%) in the initial activity of immobilized enzymes and a limited increase in the stabilization factor (1.1-1.5), as assessed by accelerated aging tests at 65 °C. Further storage tests at 4 °C in the wet state showed that the activity of several derivatives either stabilized or not was practically constant for as long as 547 days. Both free enzyme and immobilized acid urease derivatives exhibited a kinetic pattern of the Michaelis-Menten type. Using the Eadie-Hofstee diagram, the specific ammonia formation rate constant for free (k(cat)) or immobilized (k'(cat)) enzyme resulted to be little affected by immobilization (k(cat) ≈ k'(cat) ≈ 18.86 ± 0.34 IU/mg BSAE), whereas the apparent Michaelis constant for immobilized enzymes exhibited a statistically significant increase at P < 0.05 from the intrinsic value (2.55 ± 0.14 mM) for free enzyme to 5.38 ± 0.87 mM as Y(P/B) increased to 171 mg BSAE/g ds. By estimating the observable Thiele modulus (Φ(obs) ), the activity of the biocatalyst with the greatest enzyme loading at the lowest urea concentrations tested (0.833 mM) was reduced by a factor of about 2 due to internal diffusional limitations. By operating in the pseudofirst-order regime with immobilized derivatives at Y(P/B) about 126 mg BSAE/g ds, their activity after grinding was no more limited by intraparticle diffusion and approached the value for free enzyme.


Upgrading Vienna's wastewater treatment plant - linking point source emissions to Environmental Quality Standards.
The new water quality protection approach of the EU combines the control of emissions with instream Environmental Quality Standards (=EQS). Since 1 April 2006 and actually relevant in the version of 2010 in Austria, priority substances from list A of the EUROPEAN DIERECTIVE 76/464 and further EQS of relevant chemical substances (list B), identified by a national risk assessment, have to be reached to achieve a good ecological state in the surface water (Edict for Water Quality Standards, 2006; changes to the Edict for Water Quality Standards 2010). The practical assessment of these substances after point source emissions is prescribed in the Edict, but rarely carried out. In this paper, two substances, namely: (1) ammonium (list B); and (2) nonylphenol, an endocrine disrupting compound (list A) are presented to discuss: (i) the improvement of treatment efficiency due to the upgrade of a large Waste Water Treatment Plant (=WWTP); (ii) the relevance of mixing processes and modelling as a method to control EQS after point source emissions; and (iii) the improvement of water quality in the ambient surface waters. It is shown that the improved treatment in the case of nonylphenol leads to emission values which fall below the EQS, making an assessment unnecessary. In the case of ammonium emission, values are significantly reduced and violation of EQS is avoided, while mixing modelling is shown to be a suitable instrument to address the resulting instream concentrations at different border conditions.


Renal effects of dopamine during prolonged hemorrhagic hypotension in the dog.
Dopamine has been reported to increase renal blood flow during hemorrhagic shock. Since this effect would be of considerable benefit in shock, the effect of dopamine on hemorrhagic hypotension to 70 mm Hg for five hours was studied. Plasma renin activity and outer cortical blood flow were significantly greater in the group of dogs receiving dopamine. Total renal blood flow, sodium excretion, and potassium excretion were similar in both groups; however, the ratio of urine sodium to potassium concentration followed closely the plasma renin activity. We conclude that dopamine infusion alone is of limited value in improving renal hemodynamics and function during hemorrhagic hypotension to 70 mm Hg. In addition, increased plasma renin activity produced by dopamine infusion during hemorrhage would tend to offset the expected increases in renal blood flow and sodium excretion.


Medical Students' Attitudes Toward AI in Medicine and their Expectations for Medical Education.
Artificial intelligence (AI) is used in a variety of contexts in medicine. This involves the use of algorithms and software that analyze digital information to make diagnoses and suggest adapted therapies. It is unclear, however, what medical students know about AI in medicine, how they evaluate its application, and what they expect from their medical training accordingly. In the study presented here, we aimed at providing answers to these questions. In this survey study, we asked medical students about their assessment of AI in medicine and recorded their ideas and suggestions for considering this topic in medical education. Fifty-eight medical students completed the survey. Almost all participants were aware of the use of AI in medicine and had an adequate understanding of it. They perceived AI in medicine to be reliable, trustworthy, and technically competent, but did not have much faith in it. They considered AI in medicine to be rather intelligent but not anthropomorphic. Participants were interested in the opportunities of AI in the medical context and wanted to learn more about it. They indicated that basic AI knowledge should be taught in medical studies, in particular, knowledge about modes of operation, ethics, areas of application, reliability, and possible risks. We discuss the implications of these findings for the curricular development in medical education. Medical students need to be equipped with the knowledge and skills to use AI effectively and ethically in their future practice. This includes understanding the limitations and potential biases of AI algorithms by teaching the sensible use of human oversight and continuous monitoring to catch errors in AI algorithms and ensure that final decisions are made by human clinicians.


A role for DNA mismatch repair in sensing and responding to fluoropyrimidine damage.
The phenomenon of damage tolerance, whereby cells incur DNA lesions that are nonlethal, largely ignored, but highly mutagenic, appears to play a key role in carcinogenesis. Typically, these lesions are generated by alkylation of DNA or incorporation of base analogues. This tolerance is usually a result of the loss of specific DNA repair processes, most often DNA mismatch repair (MMR). The availability of genetically matched MMR-deficient and -corrected cell systems allows dissection of the consequences of this unrepaired damage in carcinogenesis as well as the elucidation of cell cycle checkpoint responses and cell death consequences. Recent data indicate that MMR plays an important role in detecting damage caused by fluorinated pyrimidines (FPs) and represents a repair system that is probably not the primary system for detecting damage caused by these agents, but may be an important system for correcting key mutagenic lesions that could initiate carcinogenesis. In fact, clinical studies have shown that there is no benefit of FP-based adjuvant chemotherapy in colon cancer patients exhibiting microsatellite instability, a hallmark of MMR deficiency. MMR-mediated damage tolerance and futile cycle repair processes are discussed, as well as possible strategies using FPs to exploit these systems for improved anticancer therapy.


Continuous recollection versus unitized familiarity in associative recognition.
Recollection has long been thought to play a key role in associative recognition tasks. Evidence that associative recollection might be a threshold process has come from analyses of the associative recognition receiver operating characteristic (ROC). Specifically, the ROC is not as curvilinear as a signal detection theory requires. In addition, the Z-ROC is usually curvilinear, as a threshold recollection model requires, not linear, as a signal detection model requires. In Experiment 1, word pairs were strengthened at study, which yielded a curvilinear ROC and a linear Z-ROC (in accordance with signal detection theory). This result suggests that associative recognition performance was based on a continuous variable, one that likely consists of either unitized familiarity or continuous recollection. The remember-know procedure and an unexpected cued recall test suggested that the more curvilinear ROC in the strong condition was mainly due to increased recollection. In Experiment 2, word pairs were presented for an old-new recognition decision before being presented for an associative recognition decision. When pairs consisting of items not recognized as having been seen on the list were removed from the analysis, the ROC again became curvilinear, the Z-ROC again became linear, and most associative recognition decisions were associated with remember judgments. These findings suggest that the curvilinear Z-ROC often observed on associative recognition tests results from noise, as a mixture signal detection model assumes, and that recollection is a continuous process that yields a curvilinear ROC that is well characterized by signal detection theory.


Discharge properties of MST neurons that project to the frontal pursuit area in macaque monkeys.
We have used antidromic activation to determine the functional discharge properties of neurons that project to the frontal pursuit area (FPA) from the medial-superior temporal visual area (MST). In awake rhesus monkeys, MST neurons were considered to be activated antidromically if they emitted action potentials at fixed, short latencies after stimulation in the FPA and if the activation passed the collision test. Antidromically activated neurons (n = 37) and a sample of the overall population of MST neurons (n = 110) then were studied during pursuit eye movements across a dark background and during laminar motion of a large random-dot texture and optic flow expansion and contraction during fixation. Antidromically activated neurons showed direction tuning during pursuit (25/37), during laminar image motion (21/37), or both (16/37). Of 27 neurons tested with optic flow stimuli, 14 showed tuning for optic flow expansion (n = 10) or contraction (n = 4). There were no statistically significant differences in the response properties of the antidromically activated and control samples. Preferred directions for pursuit and laminar image motion did not show any statistically significant biases, and the preferred directions for eye versus image motion in each sample tended to be equally divided between aligned and opposed. There were small differences between the control and antidromically activated populations in preferred speeds for laminar motion and optic flow; these might have reached statistical significance with larger samples of antidromically activated neurons. We conclude that the population of MST neurons projecting to the FPA is highly diverse and quite similar to the general population of neurons in MST.


Capillary high-performance liquid chromatography/mass spectrometric analysis of proteins from affinity-purified plasma membrane.
Proteomics analysis of plasma membranes is a potentially powerful strategy for the discovery of proteins involved in membrane remodeling under diverse cellular environments and identification of disease-specific membrane markers. A key factor for successful analysis is the preparation of plasma membrane fractions with low contamination from subcellular organelles. Here we report the characterization of plasma membrane prepared by an affinity-purification method, which involves biotinylation of cell-surface proteins and subsequent affinity enrichment with strepavidin beads. Western blotting analysis showed this method was able to achieve a 1600-fold relative enrichment of plasma membrane versus mitochondria and a 400-fold relative enrichment versus endoplasmic reticulum, two major contaminants in plasma membrane fractions prepared by conventional ultracentrifugation methods. Capillary-HPLC/MS analysis of 30 microg of affinity-purified plasma membrane proteins led to the identification of 918 unique proteins, which include 16.4% integral plasma membrane proteins and 45.5% cytosol proteins (including 8.6% membrane-associated proteins). Notable among the identified membrane proteins include 30 members of ras superfamily, receptors (e.g., EGF receptor, integrins), and signaling molecules. The low number of endoplasmic reticulum and mitochondria proteins (approximately 3.3% of the total) suggests the plasma membrane preparation has minimum contamination from these organelles. Given the importance of integral membrane proteins for drug design and membrane-associated proteins in the regulation cellular behaviors, the described approach will help expedite the characterization of plasma membrane subproteomes, identify signaling molecules, and discover therapeutic membrane-protein targets in diseases.


The physical characteristics underpinning performance of wheelchair fencing athletes: A Delphi study of Paralympic coaches.
Wheelchair fencing (WF) is a Paralympic sport which is practised by athletes with physical disabilities and is classified into three categories according to the degree of activity limitation the impairment causes in the sport. All Paralympic sports are requested to develop their own evidence-based classification system to enhance the confidence in the classification process; however, this is yet to be achieved in WF. Research within WF is scarce; therefore, the aim of this study was to reach expert consensus on the physical characteristics that underpin performance of athletes competing in the sport as this is known as one of the initial steps required to achieve an evidence-based classification system. Sixteen Paralympic WF coaches were invited to take part in a three-round Delphi study, with experts drawing consensus on qualities of speed, strength, power, flexibility and motor control of the trunk and fencing arm being associated with increased athletic success. The required qualities of the non-fencing arm led to diverging opinions across the expert panel. This study provides clear guidance of the physical qualities to be developed to maximize athletic performance while also providing the initial framework to guide future WF classification research.


Supernumerary teats in Ghanaian livestock: II. Cattle.
In 988 heads of cattle of all age groups and both sexes of various breeds and crosses at location near Legon/Accra the occurrence of supernumerary teats was studied. They were found to be more frequent in Sokoto Gudale and mixed Zebus (21 and 27%) than in the West African Shorthorn and N'Dama (8 and 6%). Crosses of these breeds with Friesian also had a higher prevalence than those with Jersey. There were significantly more caudal supernumerary teats (16%) than intercalary (2%) and ramal (1.5%). Bulls had fewer supernumerary teats than female cattle.


Dissociation of motor activity circadian rhythm in rats after exposure to LD cycles of 4-h period.
For > 30 days Wistar rats were subjected to six dark pulses per day (T4 cycles; 3 h light, 1 h dark) to study the possibility of dissociating their motor activity rhythm into distinct circadian components. Rats of both sexes were used, one-half of which were pinealectomized to examine the effect of the pineal gland on the entrainment process. Results show that when rats were maintained under T4 a 4-h rhythm in their motor activity was present. Rats showed anticipatory activity to dark phases, suggesting that the motor activity components are actually entrained to the external light/dark (LD) cycles. When rats were left under constant darkness after T4, some motor activity components coming from the dark phases free ran for several days with different circadian periods. This suggests that the motor activity pattern is generated by several circadian oscillators. Moreover, the free-running components of motor activity after T4 were more evident when T4 was applied after exposure to constant light than after exposure to constant darkness. These results support the hypothesis that the circadian system of the rat is formed by several circadian oscillators, whose degree of coupling depends on light conditions. In constant light, bright light may inhibit internal coupling within the system, making it subsequently more susceptible to the T4 cycles. No differences were observed between pinealectomized and sham-operated animals, although females were more sensitive to T4 cycles than males.


Color Stroop and negative priming in schizophrenia: an fMRI study.
Disturbances in selective attention represent a core characteristic of schizophrenia, whose neural underpinnings have yet to be fully elucidated. Consequently, we recorded brain activation using functional magnetic resonance imaging (fMRI) while 15 patients with schizophrenia and 15 age-matched controls performed a well-established measure of selective attention-the color Stroop negative priming task. We focused on two aspects of performance: overriding pre-potent responses (Stroop effect) and inhibition of prior negatively primed trials (negative priming effect). Behaviorally, controls demonstrated both significant Stroop and negative priming effects, while schizophrenic subjects only showed the Stroop effect. For the Stroop effect, fMRI indicated significantly greater activation in frontal regions-medial frontal gyrus/anterior cingulate gyrus and middle frontal gyrus for controls-but greater activation in medial parietal regions (posterior cingulate gyrus/precuneus) for patients. Negative priming elicited significant activation in right dorsolateral prefrontal cortex for both groups, but also in left dorsolateral prefrontal cortex for patients. These different patterns of fMRI activation may reflect faulty interaction in schizophrenia within networks of brain regions that are vital to selective attention.


Physical map of Caulobacter crescentus bacteriophage phi Cd1 DNA.
A restriction map of the Caulobacter crescentus bacteriophage phi Cd1 genome was constructed by using the restriction endonucleases HindIII and HpaI. A total of 12 fragments, ranging in molecular weight from 7.7 X 10(6) to 0.25 X 10(6), were produced by HindIII, and 7 fragments, ranging in molecular weight from 9.0 X 10(6) to 0.24 X 10(6), were generated by HpaI. The molecular weight of the genome was estimated to be approximately 28.8 X 10(6) on the basis of the relative electrophoretic mobilities of the restriction fragments. The relative order of the cleavage fragments was determined by specific cleavage of isolated restriction fragments, terminal labeling of both the whole genome and isolated fragments, and hybridization of isolated fragments to restriction fragments generated by other restriction enzymes. The genome of phi Cd1 was found to be terminally repetitive, and analysis of previously determined in vivo and in vitro RNA transcripts showed that the restriction map could be oriented such that transcription began on the left and proceeded to the right end of the genome.


Foraging behavior of two egg parasitoids exploiting chemical cues from the stink bug Piezodorus guildinii (Hemiptera: Pentatomidae).
Several parasitoids attacking the same host may lead to competition. Adult parasitoids' abilities to find, parasitize and defend hosts determine resource's retention potential. In soybean, two egg parasitoid species, Telenomus podisi and Trissolcus urichi (Hymenoptera: Platygastridae), compete on the egg masses of Piezodorus guildinii (Hemiptera: Pentatomidae) one of the major pest of this crop. We evaluated parasitoid's abilities to exploit hosts' footprints; and parasitoid's behavior when competing for the same host. Both arena residence time and retention time were similar for T. podisi and T. urichi on male or female host footprints. In its turn, T. urichi reentered the area contaminated with P. guildinii more times and staid longer in it than T. podisi. Furthermore, when competing for the same egg mass, each parasitoid species won (was in possession of the host by the end of the experiment) half of the replicates, and the number of times each wasp species contacted host in the first place was similar, without affecting replicate outcome (who ultimately won). Both species started agonistic and non-agonistic encounters. This study provides information about the potential interspecific competition between these parasitoids, which contributes to evaluate the compatibility of multiple natural enemies' biological control programs for stink bugs.


Targeting PIM kinase as a therapeutic strategy in human hepatoblastoma.
Increasing incidence coupled with poor prognosis and treatments that are virtually unchanged over the past 20 years have made the need for the development of novel therapeutics for hepatoblastoma imperative. PIM kinases have been implicated as drivers of tumorigenesis in multiple cancers, including hepatocellular carcinoma. We hypothesized that PIM kinases, specifically PIM3, would play a role in hepatoblastoma tumorigenesis and that PIM kinase inhibition would affect hepatoblastoma in vitro and in vivo. Parameters including cell survival, proliferation, motility, and apoptosis were assessed in human hepatoblastoma cells following PIM3 knockdown with siRNA or treatment with the PIM inhibitor AZD1208. An in vivo model of human hepatoblastoma was utilized to study the effects of PIM inhibition alone and in combination with cisplatin. PIM kinases were found to be present in the human hepatoblastoma cell line, HuH6, and in a human hepatoblastoma patient-derived xenograft, COA67. PIM3 knockdown or inhibition with AZD1208 decreased cell survival, attachment independent growth, and motility. Additionally, inhibition of tumor growth was observed in a hepatoblastoma xenograft model in mice treated with AZD1208. Combination therapy with AZD1208 and cisplatin resulted in a significant increase in animal survival when compared to either treatment alone. The current studies showed that PIM kinase inhibition decreased human hepatoblastoma tumorigenicity both in vitro and in vivo, implying that PIM inhibitors may be useful as a novel therapeutic for children with hepatoblastoma.


Impedance nanopore biosensor: influence of pore dimensions on biosensing performance.
Knowledge about electrochemical and electrical properties of nanopore structures and the influence of pore dimensions on these properties is important for the development of nanopore biosensing devices. The aim of this study was to explore the influence of nanopore dimensions (diameter and length) on biosensing performance using non-faradic electrochemical impedance spectroscopy (EIS). Nanoporous alumina membranes (NPAMs) prepared by self-ordered electrochemical anodization of aluminium were used as model nanopore sensing platforms. NPAMs with different pore diameters (25-65 nm) and lengths (4-18 μm) were prepared and the internal pore surface chemistry was modified by covalently attaching streptavidin and biotin. The performance of this antibody nanopore biosensing platform was evaluated using various concentrations of biotin as a model analyte. EIS measurements of pore resistivity and conductivity were carried out for pores with different diameters and lengths. The results showed that smaller pore dimensions of 25 nm and pore lengths up to 10 μm provide better biosensing performance.


A validation study of public health knowledge, skills, social responsibility and applied learning.
To design and validate a questionnaire to measure medical students' Public Health (PH) knowledge, skills, social responsibility and applied learning as indicated in the four domains recommended by the Association of Schools & Programmes of Public Health (ASPPH). A cross-sectional study was conducted to develop an evaluation tool for PH undergraduate education through item generation, reduction, refinement and validation. The 74 preliminary items derived from the existing literature were reduced to 55 items based on expert panel review which included those with expertise in PH, psychometrics and medical education, as well as medical students. Psychometric properties of the preliminary questionnaire were assessed as follows: frequency of endorsement for item variance; principal component analysis (PCA) with varimax rotation for item reduction and factor estimation; Cronbach's Alpha, item-total correlation and test-retest validity for internal consistency and reliability. PCA yielded five factors: PH Learning Experience (6 items); PH Risk Assessment and Communication (5 items); Future Use of Evidence in Practice (6 items); Recognition of PH as a Scientific Discipline (4 items); and PH Skills Development (3 items), explaining 72.05% variance. Internal consistency and reliability tests were satisfactory (Cronbach's Alpha ranged from 0.87 to 0.90; item-total correlation > 0.59). Lower paired test-retest correlations reflected instability in a social science environment. An evaluation tool for community-centred PH education has been developed and validated. The tool measures PH knowledge, skills, social responsibilities and applied learning as recommended by the internationally recognised Association of Schools & Programmes of Public Health (ASPPH).


Ultraviolet B suppresses immunity by inhibiting effector and memory T cells.
Contact hypersensitivity is a T-cell-mediated response to a hapten. Exposing C57BL/6 mice to UV B radiation systemically suppresses both primary and secondary contact hypersensitivity responses. The effects of UVB on in vivo T-cell responses during UVB-induced immunosuppression are unknown. We show here that UVB exposure, before contact sensitization, inhibits the expansion of effector CD4+ and CD8+ T cells in skin-draining lymph nodes and reduces the number of CD4+ and IFN-gamma+ CD8+ T cells infiltrating challenged ear skin. In the absence of UVB, at 10 weeks after initial hapten exposure, the ear skin of sensitized mice was infiltrated by dermal effector memory CD8+ T cells at the site of challenge. However, if mice were previously exposed to UVB, this cell population was absent, suggesting an impaired development of peripheral memory T cells. This finding occurred in the absence of UVB-induced regulatory CD4+ T cells and did not involve prostaglandin E2, suggesting that the importance of these two factors in mediating or initiating UVB-induced immunosuppression is dependent on UVB dose. Together these data indicate that in vivo T-cell responses are prone to immunoregulation by UVB, including a novel effect on both the activated T-cell pool size and the development of memory T cells in peripheral compartments.


Exenatide BID Observational Study (ExOS): results for primary and secondary endpoints of a prospective research study to evaluate the clinical effectiveness of exenatide BID use in patients with type 2 diabetes in a real-world setting.
The Exenatide BID Observational Study (ExOS) was designed to evaluate the clinical effectiveness of exenatide BID use in patients with type 2 diabetes (T2D) in a real-world clinical practice setting in the United States. Patients were enrolled from 74 practice sites from 9/2007 through 1/2009 and followed for 12 months. The primary effectiveness endpoint was achieving or maintaining hemoglobin A1C of ≤7.0%, or an absolute drop of 0.5% from baseline. Secondary measures included absolute and percentage change from baseline for a variety of clinical measures (lipid markers, weight, BMI, etc.), and quality of life (QOL) was assessed using the Impact of Weight on Quality of Life (IWQOL)-Lite. A total of 452 patients were included in the primary study population. At baseline, patients (60% female) had mean (SD) age of 55 (11), T2D duration of 9 (8) years, HbA1c of 8.0 (1.7) %, and body mass index (BMI) of 38.2 (7.4) kg/m(2). Family history of T2D was reported in 73.9% of patients. Hypertension was reported in 61.5% of patients, and 47.1% had hyperlipidemia. The HbA1c goal was achieved in 76.3% of the 118 patients with A1C measurements available at 12 months (P < 0.0001). Patients with available clinical measurements achieved significant improvements in HbA1c, weight, BMI, and QOL measurements at 12 months. A mean improvement of 4.56 was seen in the total IWQOL-Lite score at 12 months (P = 0.001). The single-arm design of this study is a limitation; however, the overall objective of the study was to observe patients on exenatide BID therapy over time, comparing their status at endpoint to baseline, rather than to make comparisons among different drug therapies. The Exenatide BID Observational Study supports the clinical effectiveness of exenatide BID observed in previous clinical trials and retrospective database studies.


Seasonal influenza vaccination of healthy working-age adults: a review of economic evaluations.
The recent impact of influenza on the working-age population of the US has led to changes in the recommendations for vaccination against seasonal influenza; however, the implications of vaccinating such a population have been debated. A review of cost-effectiveness analyses of vaccinating the working-age population of the US against seasonal influenza was conducted using articles published between January 1990 and January 2010. Studies considered for inclusion were identified using MEDLINE, EMBASE and Econlit. Reviewers worked in pairs, and each team member independently extracted relevant data using a standard abstraction form. The source and appropriateness of parameters (epidemiological data, probabilities and costs), the designs employed and the sufficiency of sensitivity analysis were considered during review. Key inputs extracted from the selected studies included influenza or influenza-like illness attack rates, outpatient visits averted, total vaccination days and lost workdays. Seven studies were identified as appropriate for this review. All studies were conducted in the US and from the societal perspective; three were randomized controlled trials and the remaining four were economic simulation models comparing vaccination and influenza antiviral drugs or no intervention; analyses focused on healthy working-age adults aged 18-49 years. Results ranged from net savings of $US68.96 to net costs of $US85.92 per person vaccinated (four studies) and net costs of $US104-1005 per episode of influenza averted (one study). Only two studies reported cost-effectiveness ratios; these ranged from $US26,565 to $US50,512 per quality-adjusted life-year gained. Nearly all of the studies conducted sensitivity analysis; results were most sensitive to variation in wage rates, levels of worker productivity, the costs and effectiveness of vaccination, and the rate of influenza illness. Review of the included studies suggests that seasonal influenza vaccination of healthy, working-age adults is generally not cost saving, requiring an investment to generate health benefits. The decision to vaccinate such a group will depend upon the societal and payer valuation of those benefits.


Benzo{a}pyrene-induced DNA damage in Mytilus galloprovincialis: measurement of bulky DNA adducts and DNA oxidative damage in terms of 8-oxo-7,8-dihydro-2´-deoxyguanosine formation.
Bulky DNA adducts and 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodGuo) were measured in gill DNA of benzo[a]pyrene (B[a]P)-exposed mussels (50 mg kg(-1) dw day(-1)), respectively by the (32)P-post-labelling technique and high performance liquid chromatography coupled to electrochemical detection assay. A time-course study was performed for both biomarkers and their potential use for marine biomonitoring discussed for the sentinel species studied. In gills, B[a]P-related DNA adducts were positively correlated with B[a.


Control of crystal polymorph in microfluidics using molluscan 28 kDa Ca²(+)-binding protein.
Biominerals produced by biological systems in physiologically relevant environments possess extraordinary properties that are often difficult to replicate under laboratory conditions. Understanding the mechanism that underlies the process of biomineralisation can lead to novel strategies in the development of advanced materials. Using microfluidics, we have demonstrated for the first time, that an extrapallial (EP) 28 kDa protein, located in the extrapallial compartment between mantle and shell of Mytilus edulis, can influence, at both micro- and nanoscopic levels, the morphology, structure and polymorph that is laid down in the shell ultrastructure. Crucially, this influence is predominantly dependent on the existence of an EP protein concentration gradient and its consecutive interaction with Ca²(+) ions. Novel lemon-shaped hollow vaterite structures with a clearly defined nanogranular assembly occur only where particular EP protein and Ca²(+) gradients co-exist. Computational fluid dynamics enabled the progress of the reaction to be mapped and the influence of concentration gradients across the device to be calculated. Importantly, these findings could not have been observed using conventional bulk mixing methods. Our findings not only provide direct experimental evidence of the potential influence of EP proteins in crystal formation, but also offer a new biomimetic strategy to develop functional biomaterials for applications such as encapsulation and drug delivery.


Expandable silicone implants for scleral buckling. IV. Experiments with an explant for macular breaks.
A new expandable silicone rubber explant used to indent the sclera at the macula was tested experimentally in rabbits. The device consists of a Dacron-reinforced silicone rubber strip that has an expandable portion (or balloon) at its midpoint connected to a silicone filling tube. The explant was expanded with 0.03 to 0.06 ml of an antibiotic solution. Smooth, round buckles that exerted even indentation were produced. A decrease in height of 20% to 50% was observed ophthalmoscopically during six months of follow-up. The degree of buckling can be easily controlled during operation and may be modified postoperatively.


Structural basis of conformational variance in phosphorylated and non-phosphorylated states of PKCβII.
PKCβII activation is achieved by primary phosphorylation at three phosphorylation sites, followed by the addition of secondary messengers for full activation. Phosphorylation is essential for enzyme maturation, and the associated conformational changes are known to modulate the enzyme activation. To probe into the structural basis of conformational changes on phosphorylation of PKCβII, a comprehensive study of the changes in its complexes with ATP and ruboxistaurin was performed. ATP is a phosphorylating agent in its phosphorylation reaction, and ruboxistaurin is its specific inhibitor. This study provides insight into the differences in the important structural features in phosphorylated and non-phosphorylated states of PKCβII. Less conformational changes when PKCβII is bound to inhibitor in comparison to when it is bound to its phosphorylating agent in both states were observed. The interactions of ruboxistaurin significant in restricting PKCβII to attain the conformational state competent for full activation are reported.


Pigmentary characteristics, sun sensitivity and non-Hodgkin lymphoma.
We report on pigmentary characteristics, sun sensitivity and some other possible risk factors for non-Hodgkin lymphoma (NHL) in people 20-74 years of age. A statewide case-control study was conducted in New South Wales, Australia, with population-based sampling of cases (n = 704) and controls (n = 694). Risk of NHL was increased in subjects with hazel eyes (OR = 1.48; 95% CI = 1.07-2.04), very fair skin (OR = 1.44; 95% CI = 1.01-2.07) and poor ability to tan (OR = 1.70; 95% CI = 1.06-2.71). Risk with mild facial freckling as a child (OR = 0.77; 95% CI = 0.59-0.99) was reduced relative to that with no or moderate to severe freckling. Smokers were not at increased risk of NHL. A past history of treatment for skin cancer was associated with a slight nonsignificant increase in risk. Previous radiotherapy and chemotherapy were associated with 1.5- to 2-fold increases in risk but with wide confidence intervals. These results provide weak support for the possibility that sun sensitivity or perhaps sun exposure increases risk of NHL.


Contribution of prepregnancy body mass index and gestational weight gain to adverse neonatal outcomes: population attributable fractions for Canada.
Low or high prepregnancy body mass index (BMI) and inadequate or excess gestational weight gain (GWG) are associated with adverse neonatal outcomes. This study estimates the contribution of these risk factors to preterm births (PTBs), small-for-gestational age (SGA) and large-for-gestational age (LGA) births in Canada compared to the contribution of prenatal smoking, a recognized perinatal risk factor. We analyzed data from the Canadian Maternity Experiences Survey. A sample of 5,930 women who had a singleton live birth in 2005-2006 was weighted to a nationally representative population of 71,200 women. From adjusted odds ratios, we calculated population attributable fractions to estimate the contribution of BMI, GWG and prenatal smoking to PTB, SGA and LGA infants overall and across four obstetric groups. Overall, 6% of women were underweight (<18.5 kg/m(2)) and 34.4% were overweight or obese (≥25.0 kg/m(2)). More than half (59.4%) gained above the recommended weight for their BMI, 18.6% gained less than the recommended weight and 10.4% smoked prenatally. Excess GWG contributed more to adverse outcomes than BMI, contributing to 18.2% of PTB and 15.9% of LGA. Although the distribution of BMI and GWG was similar across obstetric groups, their impact was greater among primigravid women and multigravid women without a previous PTB or pregnancy loss. The contributions of BMI and GWG to PTB and SGA exceeded that of prenatal smoking. Maternal weight, and GWG in particular, contributes significantly to the occurrence of adverse neonatal outcomes in Canada. Indeed, this contribution exceeds that of prenatal smoking for PTB and SGA, highlighting its public health importance.