Increased nitrotyrosine in exhaled breath condensate of patients with asthma.
The reaction of nitric oxide (NO) and superoxide anions (O(2)(-)) in the airway results in the formation of peroxynitrite, a highly reactive oxidant species. Peroxynitrite reacts with tyrosine residues in proteins to form the stable product nitrotyrosine. We investigated whether nitrotyrosine in exhaled breath condensates may be increased in patients with asthma. Four groups of nonsmoking subjects were studied. We measured exhaled NO, nitrotyrosine, and leukotrienes concentrations in breath condensate in healthy nonatopic subjects (n = 15) and in patients with mild asthma (steroid naive, n = 15), moderate asthma (inhaled steroid treatment, n = 12), and severe asthma (oral steroid treatment, n = 12). Exhaled NO was increased significantly in patients with mild (19.2 +/- 2.7 ppb, p < 0.01) and moderate asthma (14.0 +/- 1.53 ppb, p < 0.05), as compared with normal control (6.58 +/- 0.61 ppb). The levels of LTC(4)/D(4)/E(4) and LTB(4) were increased significantly in patients with moderate and severe asthma treated with steroids. Nitrotyrosine concentrations were detectable (6.3 +/- 0.8 ng/ml) in breath condensate of normal subjects, and were increased significantly in patients with mild asthma (15.3 +/- 2.0 ng/ml, p < 0.01). However, the levels of nitrotyrosine in exhaled condensate were lower in patients with moderate (5.0 +/- 0.6 ng/ml) and severe asthma (3.3 +/- 0.6 ng/ml, p < 0.05). There was a significant correlation between nitrotyrosine in breath condensate and exhaled NO in patients with mild asthma (r = 0.65, p < 0.05). We conclude that nitrotyrosine formation in exhaled breath condensates may be a marker of oxidative stress in airways of asthma.


Agelastatin E, agelastatin F, and benzosceptrin C from the marine sponge Agelas dendromorpha.
The study of the n-butanol extract of the New Caledonian sponge Agelas dendromorpha led to the isolation and identification of three new pyrrole-2-aminoimidazole (P-2-AI) alkaloids, named agelastatins E (3) and F (4) and benzosceptrin C (5), together with 10 known metabolites, agelastatin A (1), agelastatin D (2), sceptrin (6), manzacidin A, tauroacidin A, taurodispacamide A, nortopsentin D, thymine, longamide, and 4,5-dibromopyrrole-2-carboxamide. Their structures were assigned by spectroscopic data interpretation. All the compounds were tested for cytotoxic activity.


Sociomedical and behavioural aspects of dental care for the elderly: statement of the problem.
In providing dental care for the elderly, dynamic changes in disease states and population groups must be recognized. These are creating a need for the dental profession to address itself to the increasing complexity of dental treatment required for ageing populations. The existence of different populations of elderly has implications for geriatric dentistry. There are similarities between the problems in countries with ageing populations, isolated from society, and the problems in countries without such populations, but with the problem of accessing other isolated populations.


YM155 sensitizes triple-negative breast cancer to membrane-bound TRAIL through p38 MAPK- and CHOP-mediated DR5 upregulation.
Because available treatments have limited efficacy in triple-negative breast cancer (TNBC), the identification of new therapeutic strategies to improve patients' outcome is urgently needed. In our study, we investigated the effects of the administration of the small molecule selective survivin suppressant YM155, alone or in association with CD34+ cells transduced with a replication-deficient adenovirus encoding the human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene (CD34-TRAIL+ cells), in three TNBC cell models. YM155 exposure significantly impaired TNBC cell growth and selectively modulated survivin expression at both mRNA and protein level. In addition, co-culturing YM155-treated TNBC cells with CD34-TRAIL+ cells resulted in markedly increased cytotoxic effect and apoptotic response in comparison with single treatments. Such a chemosensitizing effect was observed only in TNBC cells inherently expressing DR5 and relied on the ability of YM155 to upregulate DR5 expression through a p38 MAPK- and CHOP-dependent mechanism. YM155/CD34-TRAIL+ combination also showed a significant inhibitory effect on the growth of DR5-expressing TNBC cells following xenotransplantation into NOD/SCID mice, in the absence of toxicity. Overall, our data (i) provide, for the first time, evidence that YM155 sensitizes TNBC cells to CD34-TRAIL+ cells-induced apoptosis by a mechanism involving the downregulation of survivin and the simultaneous p38 MAPK- and CHOP-mediated upregulation of DR5, and (ii) suggest the combination of YM155 with TRAIL-armed CD34+ progenitor cells as a promising therapeutic option for patients with TNBC expressing DR5.


Hepatic long-chain acyl-CoA synthetase 5 mediates fatty acid channeling between anabolic and catabolic pathways.
Long-chain acyl-CoA synthetases (ACSLs) and fatty acid transport proteins (FATPs) activate fatty acids (FAs) to acyl-CoAs prior to their downstream metabolism. Of numerous ACSL and FATP isoforms, ACSL5 is expressed predominantly in tissues with high rates of triacylglycerol (TAG) synthesis, suggesting it may have an anabolic role in lipid metabolism. To characterize the role of ACSL5 in hepatic energy metabolism, we used small interference RNA (siRNA) to knock down ACSL5 in rat primary hepatocytes. Compared with cells transfected with control siRNA, suppression of ACSL5 expression significantly decreased FA-induced lipid droplet formation. These findings were further extended with metabolic labeling studies showing that ACSL5 knockdown resulted in decreased [1-(14)C]oleic acid or acetic acid incorporation into intracellular TAG, phospholipids, and cholesterol esters without altering FA uptake or lipogenic gene expression. ACSL5 knockdown also decreased hepatic TAG secretion proportionate to the observed decrease in neutral lipid synthesis. ACSL5 knockdown did not alter lipid turnover or mediate the effects of insulin on lipid metabolism. Hepatocytes treated with ACSL5 siRNA had increased rates of FA oxidation without changing PPAR-α activity and target gene expression. These results suggest that ACSL5 activates and channels FAs toward anabolic pathways and, therefore, is an important branch point in hepatic FA metabolism.


Using the test of variables of attention to determine the effectiveness of modafinil in children with attention-deficit hyperactivity disorder (ADHD): a prospective methylphenidate-controlled trial.
The efficacy of modafinil in comparison with methylphenidate in treatment of pediatric attention-deficit hyperactivity disorder (ADHD) has not been thoroughly investigated. This study compared the effect of modafinil versus methylphenidate on continuous attention task in children with ADHD, using the Test of Variables of Attention. Twenty-eight participants completed a baseline test followed by administration of a single dose of either methylphenidate or modafinil, after which the test was repeated. The test was performed a third time, after each subject received a dose of the medication not previously administered. Comparison of scores showed mean baseline, postmethylphenidate, and postmodafinil scores of -2.04, 0.017, and 0.09, respectively. No difference was found between improvements observed with either medication (P < .05). Adverse events for both agents were mild and self-limited, including abdominal pain, diarrhea, and hyposomnia. The authors conclude that modafinil is as effective as methylphenidate; however, a larger scale long-term study is required to confirm these results.


Personality profile and allodynic migraine.
Migraine is known to be associated to particular psychological features. Cutaneous allodynia is a painful sensation or discomfort induced by a non-noxious stimulus, and is a frequent complaint during migraine attacks. The aim of this study was to compare the personality profile of allodynic and non-allodynic migraineurs to identify possible relationships between psychological aspects and the presence of allodynia. The Symptom Check List 90-R (SCL90R), a 90-item self-report psychological symptom inventory, was used to investigate the psychological profile of our patients. The presence of allodynia was assessed by a set of semi-structured questions that investigated if the patient experienced abnormal scalp sensitiveness and/or discomfort during headache episodes. Twenty-five nonallodynic patients and 38 allodynic migraineurs were studied. No significant difference was found between the two groups in any area of the personality profile. The psychological profile seems not to affect the presence/absence of cutaneous allodynia in migraine patients. This reinforces the hypothesis that allodynia is a "somatic" symptom, not modified by psychological aspects.


Circadian phase-dependent effect of nitric oxide on L-type voltage-gated calcium channels in avian cone photoreceptors.
Nitric oxide (NO) plays an important role in phase-shifting of circadian neuronal activities in the suprachiasmatic nucleus and circadian behavior activity rhythms. In the retina, NO production is increased in a light-dependent manner. While endogenous circadian oscillators in retinal photoreceptors regulate their physiological states, it is not clear whether NO also participates in the circadian regulation of photoreceptors. In this study, we demonstrate that NO is involved in the circadian phase-dependent regulation of L-type voltage-gated calcium channels (L-VGCCs). In chick cone photoreceptors, the L-VGCCα1 subunit expression and the maximal L-VGCC currents are higher at night, and both Ras-mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (Erk) and Ras-phosphatidylinositol 3 kinase (PI3K)-protein kinase B (Akt) are part of the circadian output pathways regulating L-VGCCs. The NO-cGMP-protein kinase G (PKG) pathway decreases L-VGCCα1 subunit expression and L-VGCC currents at night, but not during the day, and exogenous NO donor or cGMP decreases the phosphorylation of Erk and Akt at night. The protein expression of neural NO synthase (nNOS) is also under circadian control, with both nNOS and NO production being higher during the day. Taken together, NO/cGMP/PKG signaling is involved as part of the circadian output pathway to regulate L-VGCCs in cone photoreceptors. In cone photoreceptors, the protein expression of neural nitric oxide synthase (nNOS) and NO production are under circadian control. NO-cGMP-protein kinase G (PKG) signaling serves in the circadian output pathway to regulate the circadian rhythms of L-type voltage-gated calcium channels (L-VGCCs) in part through regulating the phosphorylation states of extracellular-signal-regulated kinase (Erk) and protein kinase B (Akt).


Dietary advanced glycated end-products and medicines influence the expression of SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes patients.
Quantitative polymerase chain reaction was employed to quantify expression of two genes coding for advanced glycation end-product receptors [RAGE ( AGER) and AGER1 ( DDOST)] and of the gene coding the deacetylase SIRT1 ( SIRT1) in peripheral blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35; 28.5 (24-39) years old; median (interquartile interval)] or with at least one microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy controls were also included. In a subgroup of 48 patients, daily advanced glycation end-products intake before blood collection was assessed. Lower expression of DDOST was found in patients than in controls after adjustment for sex, age, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were observed in Group A. Stratifying by complications, AGER and DDOST expressions were higher in those without retinopathy and without diabetic kidney disease, respectively, compared to patients with these complications. Patients using statins or angiotensin receptor blockers presented higher expression of DDOST. Expression of SIRT1 was higher in patients consuming ≥12,872 KU daily of advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently expressed in peripheral blood mononuclear cells from type 1 diabetes patients with and without microvascular complications, they are also influenced by dietary advanced glycation end-products and by statins and angiotensin receptor blockers.


Divergent nod-containing Bradyrhizobium sp. DOA9 with a megaplasmid and its host range.
Bradyrhizobium sp. DOA9, a non-photosynthetic bacterial strain originally isolated from the root nodules of the legume Aeschynomene americana, is a divergent nod-containing strain. It exhibits a broad host range, being able to colonize and efficiently nodulate the roots of most plants from the Dalbergioid, Millettioid, and Robinioid tribes (7 species of Papilionoideae). In all cases, nodulation was determinate. The morphology and size of DOA9 bacteroids isolated from the nodules of various species of Papilionoideae were indistinguishable from the free-living form. However, they were spherical in Arachis hypogaea nodules. GusA-tagged DOA9 also colonized rice roots as endophytes. Since broad-host-range legume symbionts often carry multiple replicons in their genome, we analyzed the replicons for symbiosis genes by electrophoresis. DOA9 carried two replicons, a chromosome (cDOA9) and single megaplasmid (pDOA9) larger than 352 kb. The genes for nodulation (nodA, B, C) and nitrogen fixation (nifH) were localized on the megaplasmid. Southern blot hybridization revealed two copies of nodA on the megaplasmid, single copies of nodB and C on the megaplasmid, and one copy each of nifH on the chromosome and megaplasmid. These results suggested that Bradyrhizobium sp. DOA9 may have the unusual combination of a broad host range, bacteroid differentiation, and symbiosis-mediating replicons.


First measurement of transferred polarization in the exclusive ep-->e'K+Lambda--> reaction.
The first measurements of the transferred polarization for the exclusive e-->p-->e(')K+Lambda--> reaction have been performed at Jefferson Laboratory using the CLAS spectrometer. A 2.567 GeV beam was used to measure the hyperon polarization over Q2 from 0.3 to 1.5 (GeV/c)(2), W from 1.6 to 2.15 GeV, and over the full K+ center-of-mass angular range. Comparison with predictions of hadrodynamic models indicates strong sensitivity to the underlying resonance contributions. A nonrelativistic quark-model interpretation of our data suggests that the ssmacr; quark pair is produced with spins predominantly antialigned. Implications for the validity of the most widely used quark-pair creation operator are discussed.


Peripheral Insulin Extraction in Non-Diabetic Subjects and Type 2 Diabetes Mellitus Patients.
Insulin has to be transported across the capillary endothelium to stimulate muscle glucose uptake. We investigated insulin uptake from the peripheral circulation in non-diabetic (ND) individuals and in type 2 diabetes (T2D) patients. Single-center cross-sectional study involving 40 ND (age 65±11 years) and 30 T2D patients (age 67±8 years). Thirty-six participants were studied in the fasted state (22 ND subjects and 14 T2D patients termed NDF and T2DF) and 34 participants 1-h following a glucose challenge (18 ND subjects and 16 T2D patients indicated as NDG and T2DG). Main outcome measure was fractional extraction (FE) of insulin (FEins) and glucose using the forearm balance method. In NDF, FEins was 18 (10-26) % at lower insulin levels (63 51-80] pmol/l), while in NDG at higher insulin levels (776 [543-1176] pmol/l), FEins was 9 (4-16) % (p = 0.01 vs. NDF). In NDF only, a negative correlation was observed between FEins and arterial plasma insulin load (rho = - 0.575;p = 0.006) and fasting plasma glucose levels (rho = - 0.551;p = 0.01). In T2DF FEins was 6 (1-19) % and not different from FEins in T2DG (10 2-14) %), and was not associated to fasting glucose. FEins tended to be higher in NDF compared to T2DF (p = 0.07). We propose that in ND individuals, besides passive diffusion, an active high-affinity pathway with limited capacity around lower physiologic insulin levels exists for insulin transendothelial transport, contributing to glycemic control. In T2D patients, this mechanism of peripheral insulin uptake is diminished or even absent. Modulation of insulin extraction from the circulation may be a novel target to improve glucose metabolism in T2D.


Posttranslational processing of the xylanase Xys1L from Streptomyces halstedii JM8 is carried out by secreted serine proteases.
The xylanase Xys1L from Streptomyces halstedii JM8 is known to be processed extracellularly, to produce a protein of 33.7 kDa, Xys1S, that retains catalytic activity but not its cellulose-binding capacity. This paper demonstrates that at least five serine proteases isolated from Streptomyces spp. have the ability to process the xylanase Xys1L. The genes of two of these extracellular serine proteases, denominated SpB and SpC, were cloned from Streptomyces lividans 66 (a strain commonly used as a host for protein secretion), sequenced, and overexpressed in S. lividans; both purified proteases were able to process Xys1L in vitro. Three other previously reported purified Streptomyces serine proteases, SAM-P20, SAM-P26 and SAM-P45, also processed Xys1L in vitro. The involvement of serine proteases in xylanase processing-degradation in vivo was demonstrated by co-expression of the xylanase gene (xysA) and the gene encoding the serine protease inhibitor (SLPI) from S. lividans. Co-expression prevented processing and degradation of Xys1L and resulted in a threefold increase in the xylanase activity present in the culture supernatant. SpB and SpC also have the capacity to process other secreted proteins such as p40, a cellulose-binding protein from S. halstedii JM8, but do not have any clear effect on other secreted proteins such as amylase (Amy) from Streptomyces griseus and xylanase Xyl30 from Streptomyces avermitilis.


A Novel Imaging Technique for The On-site Assessment of Renal Biopsy Specimens.
When performing renal biopsy, it is necessary to identify the cortex, where glomeruli are exclusively distributed, to ensure the quality of the specimen for histological diagnosis. However, conventional methods using a stereomicroscope or magnifying lens often fail to clarify the quality of the specimen. We have established a fluorescent-based imaging technique for the on-site assessment of renal biopsy specimens. The fluorescent images can be easily obtained by adding an optical filter to the microscope and with a short incubation of an activatable fluorescent probe. This novel imaging technique can be applied to renal biopsy specimens for distinguishing the renal cortex.


I'm Not Feeling It: Momentary Experiential Avoidance and Social Anxiety Among Individuals With Social Anxiety Disorder.
Previous studies have found that social anxiety and experiential avoidance (EA) are significantly associated, but the directionality of this relationship has not been firmly established. The present study examined momentary EA and social anxiety using repeated measurements during an opposite-sex interaction. Participants were 164 individuals (50% female): 42 were diagnosed with social anxiety disorder (SAD) and the remaining 122 were non-socially-anxious individuals (NSAs). Participants formed 42 experimental dyads including 1 individual with SAD and 1 NSA individual, and 40 control dyads including 2 NSA individuals. Lower-level mediational modeling indicated that for individuals with SAD, a reciprocal relationship was observed in which changes in both EA and social anxiety mediated changes in each other. However, changes in EA explained approximately 89% of changes in social anxiety whereas changes in social anxiety explained approximately 52% of changes in EA throughout the interaction. For NSA individuals, only social anxiety predicted EA. These findings point to a deleterious cycle driven mostly by EA among individuals with SAD, but not NSA individuals. Findings are discussed within the context of previous empirical findings as well as acceptance and commitment therapy (ACT) and cognitive-behavioral models of psychopathology.


Psychopathology and its effect on treatment compliance in pediatric obesity patients.
Obesity is a common health problem in children and adolescents and has life-threatening physical complications as well as psychological consequences, including negative self-image, low self-esteem and social difficulties. Psychiatric disorders, especially depression and anxiety disorders, are present at higher rates in obese patients. The aim of this study was to investigate the presence and type of psychopathology in a group of obese children and to determine the effect of comorbid psychiatric disorders on treatment compliance. Fifty-four obese patients were evaluated by clinical interviews as well as Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version (KIDI-SADS-PL) for psychiatric diagnosis. Fifty percent of the sample was found to have psychopathology and treatment compliance was found to be poor in the group with comorbid psychiatric disorders. This shows that child and adolescent psychiatrists should be included as team members while treating pediatric obese patients.


Rural Cancer Disparities: Understanding Implications for Breast and Cervical Cancer Diagnoses.
Rural populations experience several disparities, influenced by structural-, community-, and individual-level barriers, across the breast and cervical cancer continuum. This study seeks to identify structural-, community-, and individual-level barriers that affect rural populations across the cancer continuum, understand the role of nurses serving rural populations in breast and cervical cancer screening and diagnostics, and provide recommendations for working with rural patients. This is a secondary analysis of qualitative interviews conducted with public health nurses serving rural populations. Emergent themes indicate that rural populations experience barriers that affect disparities across the breast and cervical cancer continuum, including a changing healthcare landscape, access to cancer-focused care, access to insurance, collective poverty, and demographic factors. Nurses working with rural communities can address these disparities as they fulfill multiple roles and responsibilities.


Does the A3333G mutation in the CACNL1A3 gene, detected in malignant hyperthermia, also occur in central core disease?
Malignant hyperthermia (MH) and central core disease (CCD) are two conditions associated with susceptibility to volatile anesthetics and depolarizing muscle relaxants. The gene RYR1, encoding the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum, is responsible for about 50% of the cases of MH and some cases of CCD. However, genetic heterogeneity occurs in MH and a mutation in a second gene (CACLN1A3), encoding the alpha1-subunit of the dihydropyridine (DHP) channel, has recently been found in a large MH French family. The presence of this mutation in patients with CCD has not yet been reported. In this study, we analyzed the A3333G mutation in 5 unrelated patients affected by CCD and 31 MH-susceptible relatives (from 19 MH families) and did not find this mutation in any of them. Nevertheless, the report of data on newly described mutations in different populations is important to estimate the contributions of each gene mutation to the phenotype of MH and CCD.


Radiation and immunotherapy combinations in non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is a common and lethal malignancy. The recent development of immune checkpoint inhibitors has afforded a durable, dramatic treatment response for a subset of patients, but strategies to expand these benefits to a broader swath of patients are needed. Preliminary evidence suggests radiotherapy may modulate a patient's immune system, particularly when delivered in high doses over few fractions with conformal techniques, as with stereotactic ablative radiotherapy (SABR). Radiotherapy for advanced stage NSCLC has traditionally been administered with palliative intent. However, an emergence of data from retrospective studies and, more recently, prospective trials has indicated the potential of using stereotactic ablative radiotherapy (SABR), in combination with systemic immunotherapy agents have synergistic effect and may enhance survival. We review current evidence for synergy between radiation and immunotherapy in metastatic, locally advanced, and localized NSCLC and discuss ongoing studies.


An esophagogastroduodenal anastomosis model for esophageal adenocarcinogenesis in rats and enhancement by iron overload.
The aim of this study is to establish a good animal model for esophageal adenocarcinoma (EAC) and to test the hypothesis that iron over-nutrition enhances EAC formation. With rats, esophagogastroduodenal anastomosis (EGDA) was accomplished by anastomosing the duodenum to the gastroesophageal junction. Iron supplementation was given by i.p. injection of iron dextran (4 mg Fe/kg/week). This model mimics the development of human EAC by introducing mixed reflux of gastric and duodenal contents. At 40 weeks after surgery, the body weight, food intake, hemoglobin, total serum iron, transferrin saturation, serum albumin, and plasma levels of alpha-tocopherol, gamma-tocopherol and retinol of the EGDA rats were not significantly different from those of the non-operated controls. The animals generally had only mild esophagitis, except that the area surrounding the anastomosis opening had more severe esophagitis. Columnar-lined esophagus (CLE), CLE with dysplasia, and EAC were diagnosed in 53.5, 34.9 and 25.6%, respectively, of the 43 rats. Intraperitoneal iron supplementation significantly enhanced esophageal lesions with CLE, CLE with dysplasia, and EAC to 78.0, 53. 7 and 53.7%, respectively, of the 41 rats. All the tumors were well-differentiated mucinous adenocarcinomas at the squamocolumnar junction area, where most iron deposition was observed. EGDA avoids nutritional problems seen in other animal models for EAC. We believe that direct anastomosis of squamous epithelium to columnar epithelium and mixed reflux of gastric and duodenal contents lead to the formation of CLE and EAC. With this model, we demonstrated that iron supplementation significantly enhanced EAC formation, suggesting that iron over-nutrition could also be a risk factor for human EAC.


Social support networks and medical service use among HIV-positive injection drug users: implications to intervention.
The study used network analysis to identify forms and sources of social support associated with a medical services use among a medically underserved population living with HIV/AIDS. Participants were African American former or current injection drug users (n=295; 34% female, 45% current drug users and 17% AIDS diagnosed). Outcomes were access to the same medical provider, use of outpatient services and emergency room (ER) use with or without subsequent hospitalization. Controlling for AIDS diagnosis, insurance, current drug use and gender, access to the same medical care provider was associated with more females in one's support network and more network sources of emotional support, financial support and instrumental assistance. Adjusting for confounders, outpatient service use was associated with more female support network members and more sources of emotional support. Controlling for participants' drug use and insurance, sub-optimal emergency department use was associated with greater number of active drug users in one's support network. Contrary to other study findings, having a supportive sex partner was associated with lower access to medical care, and kin support was not associated with medical service use. Results indicate that specific sources and forms of social support had differential influences on the sample's utilization of medical services. The findings suggest that promoting HIV-positive African American injection drug users' support network functioning may help improve HIV medical services utilization among this medically underserved population.


Scale-down simulators for metabolic analysis of large-scale bioprocesses.
Analytical approaches for a comprehensive understanding of the metabolic networks in microbial cultures are mostly based on small-scale cultures which are in a steady state or undergo dynamic changes. For drawing conclusions to industrial-scale bioprocesses, however, it is important to understand that cells in large-scale bioreactors are exposed steadily to fast changes, because of an inhomogeneous environment. Analytical approaches that aim for large-scale bioprocess understanding need to apply specific laboratory simulators. Recent developments in cell cultivation techniques and computational tools provide improved possibilities to evaluate how a process will behave in the final scale. These simulators will pave the way for screening robust strains and process conditions.


Aspirin and indomethacin enhance platelet aggregation in mouse mesenteric arterioles.
The cyclooxygenase inhibitors aspirin and indomethacin enhanced platelet aggregation in mesenteric vessels, suggesting that the normal mesentery produces an antiaggregatory prostaglandin. Testing of mesentery incubate in mouse platelet-rich plasma disclosed an antiaggregatory material with the properties of prostacyclin. Chromatography showed that mesentery made several radiolabeled products from [3H]arachidonic acid, including one that cochromatographed with 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), the stable hydrolysis product of prostacyclin. Gas chromatography-mass spectrometric analysis of mesentery incubate showed the presence of 6-keto-PGF1 alpha, synthesized from the mesentery's endogenous arachidonic acid. The enhancement of platelet aggregation in mesenteric vessels contrasts with earlier data showing that in similarly injured mouse cerebral vessels aggregation was retarded by both aspirin and indomethacin. This divergent effect of cyclooxygenase inhibitors in different vascular beds may depend on the relative importance of prostacyclin in the different beds or on the capacity of cyclooxygenase inhibitors to influence this prostacyclin production in different beds. Caution is urged before acceptance of a central role for PGI2, however, because of the capability of microvasculatures and adjacent tissue to synthesize a number of other products whose interaction with platelets and with aspirin and indomethacin remains to be elucidated.


Pharmacologic elevation of high-density lipoproteins: recent insights on mechanism of action and atherosclerosis protection.
Despite the best efforts in reduction of low-density lipoprotein cholesterol, most cardiovascular events are not being prevented. Because high-density lipoprotein (HDL) promotes reverse cholesterol transport and other antiatherogenic effects, interventions aimed at raising HDL cholesterol or mimicking its beneficial effects may greatly improve treatment and prevention of cardiovascular disease. This article reviews the antiatherogenic effects of HDL, recent insights into the mechanisms of action of currently available, and emerging HDL-based therapies. New insights into the basic science of HDL function and metabolism (such as the discovery of beta-chain ATP synthase as a hepatic catabolic HDL receptor) are further characterizing the importance of HDL in atheroprotection and identifying novel targets of drug development. Nicotinic acid, fibrates, statins, and thiazolidinediones not only increase HDL cholesterol but also alter HDL subpopulation size and composition. Furthermore, these drugs promote direct antiatherogenic effects of HDL (antioxidation, anti-inflammation, antithrombotic effects, endothelial stabilization). Emerging HDL-raising therapies (such as cholesteryl ester transfer protein inhibitors and 1,2-dimyristoyl-sn-glycero-phosphocholine) and novel interventions that mimic HDL's beneficial effects (such as apolipoprotein AImilano and apolipoprotein AI mimetic peptides) are proving beneficial in animal and human studies. An understanding of the atheroprotective mechanisms of HDL is essential for the rational use of currently available drugs and directed development of new drugs. Increasing total HDL cholesterol may not be as important as increasing the functional properties of HDL. Cardiovascular disease treatment and prevention can be improved by combining current low-density lipoprotein-based strategies with effective HDL-based interventions.


Elastic and pH-Responsive Hybrid Interfaces Created with Engineered Resilin and Nanocellulose.
We investigated how a genetically engineered resilin fusion protein modifies cellulose surfaces. We characterized the pH-responsive behavior of a resilin-like polypeptide (RLP) having terminal cellulose binding modules (CBM) and showed its binding to cellulose nanofibrils (CNF). Characterization of the resilin fusion protein at different pHs revealed substantial conformational changes of the protein, which were observed as swelling and contraction of the protein layer bound to the nanocellulose surface. In addition, we showed that employment of the modified resilin in cellulose hydrogel and nanopaper increased their modulus of stiffness through a cross-linking effect.


Convergent adaptation in the dominant global hospital clone ST239 of methicillin-resistant Staphylococcus aureus.
Infections caused by highly successful clones of hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) are a major public health burden. The globally dominant sequence type 239 (ST239) HA-MRSA clone has persisted in the health care setting for decades, but the basis of its success has not been identified. Taking a collection of 123 ST239 isolates spanning 32 years, we have used population-based functional genomics to investigate the evolution of this highly persistent and successful clone. Phylogenetic reconstruction and population modeling uncovered a previously unrecognized distinct clade of ST239 that was introduced into Australia from Asia and has perpetuated the epidemic in this region. Functional analysis demonstrated attenuated virulence and enhanced resistance to last-line antimicrobials, the result of two different phenomena, adaptive evolution within the original Australian ST239 clade and the introduction of a new clade displaying shifts in both phenotypes. The genetic diversity between the clades allowed us to employ genome-wide association testing and identify mutations in other essential regulatory systems, including walKR, that significantly associate with and may explain these key phenotypes. The phenotypic convergence of two independently evolving ST239 clades highlights the very strong selective pressures acting on HA-MRSA, showing that hospital environments have favored the accumulation of mutations in essential MRSA genes that increase resistance to antimicrobials, attenuate virulence, and promote persistence in the health care environment. Combinations of comparative genomics and careful phenotypic measurements of longitudinal collections of clinical isolates are giving us the knowledge to intelligently address the impact of current and future antibiotic usage policies and practices on hospital pathogens globally. Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for innumerable drug-resistant health care-associated infections globally. This study, the first to investigate the evolutionary response of hospital-associated MRSA (HA-MRSA) over many decades, demonstrates how MRSA can persist in a region through the reintroduction of a previously unrecognized distinct clade. This study also demonstrates the crucial adaptive responses of HA-MRSA to the highly selective environment of the health care system, the evolution of MRSA isolates to even higher levels of antibiotic resistance at the cost of attenuated virulence. However, in vivo persistence is maintained, resulting in a clone of HA-MRSA able to resist almost all antimicrobial agents and still cause invasive disease in the heavily compromised hosts found in modern health care settings.


Microbiome Characterization of Infected Diabetic Foot Ulcers in Association With Clinical Outcomes: Traditional Cultures Versus Molecular Sequencing Methods.
Infected diabetic foot ulcers (IDFU) are a major complication of diabetes mellitus. These potentially limb-threatening ulcers are challenging to treat due to impaired wound healing characterizing diabetic patients and the complex microbial environment of these ulcers. To analyze the microbiome of IDFU in association with clinical outcomes. Wound biopsies from IDFU were obtained from hospitalized patients and were analyzed using traditional microbiology cultures, 16S rRNA sequencing and metagenomic sequencing. Patients' characteristics, culture-based results and sequencing data were analyzed in association with clinical outcomes. A total of 31 patients were enrolled. Gram-negative bacteria dominated the IDFU samples (79%, 59% and 54% of metagenomics, 16S rRNA and cultures results, respectively, p<0.001). 16S rRNA and metagenomic sequencing detected significantly more anaerobic bacteria, as compared to conventional cultures (59% and 76%, respectively vs. 26% in cultures, p=0.001). Culture-based results showed that Staphylococcus aureus was more prevalent among patients who were treated conservatively (p=0.048). In metagenomic analysis, the Bacteroides genus was more prevalent among patients who underwent amputation (p<0.001). Analysis of metagenomic-based functional data showed that antibiotic resistance genes and genes related to biofilm production and to bacterial virulent factors were more prevalent in IDFU that resulted in amputation (p<0.001). Sequencing tools uncover the complex biodiversity of IDFU and emphasize the high prevalence of anaerobes and Gram-negative bacteria in these ulcers. Furthermore, sequencing results highlight possible associations among certain genera, species, and bacterial functional genes to clinical outcomes.


Consciousness influences the enhancement of visual statistical learning in Zipfian distributions.
It has been reported that visual statistical learning (VSL) is facilitated in skewed distributions. However, it remains unclear whether enhancement of VSL in Zipfian distributions is due to consciousness of the regularities presented at high frequency. This study addressed this issue. We measured participants' subjective confidence in regularities and awareness of regularities during familiarization by combining a previously reported procedure for VSL with a postdecision wagering task and posttest questionnaire. The results demonstrated that Zipfian distribution enhanced not only VSL but also metacognitive sensitivity, particularly for high-frequency regularities, as the effects of consciousness on VSL were limited to high-frequency regularities. Moreover, the results indicated that awareness during familiarization mediated VSL enhancement in the Zipfian distribution. These results suggest that VSL for events with high-frequency regularities plays an important role in the cognition of events with low-frequency regularities via awareness. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Reduction of N-hydroxy-sulfonamides, including N-hydroxy-valdecoxib, by the molybdenum-containing enzyme mARC.
Purification of the mitochondrial enzyme responsible for reduction of N-hydroxylated amidine prodrugs led to the identification of two newly discovered mammalian molybdenum-containing proteins, the mitochondrial amidoxime reducing components mARC-1 and mARC-2 (Gruenewald et al., 2008). These 35-kDa proteins represent a novel group of molybdenum proteins in eukaryotes as they form a molybdenum cofactor-dependent enzyme system consisting of three separate proteins (Havemeyer et al., 2006). Each mARC protein reduces N-hydroxylated compounds after reconstitution with the electron transport proteins cytochrome b(5) and b(5) reductase. In continuation of our drug metabolism investigations (Havemeyer et al., 2006; Gruenewald et al., 2008), we present data from reconstituted enzyme systems with recombinant human and native porcine enzymes showing the reduction of N-hydroxy-sulfonamides (sulfohydroxamic acids) to sulfonamides: the N-hydroxy-sulfonamide N-hydroxy-valdecoxib (N-hydroxy-4-[5-methyl-3-phenyl-4-isoxazolyl]-benzenesulfonamide) represents a novel cyclooxygenase (COX)-2 inhibitor and is therefore a drug candidate in the treatment of diseases associated with rheumatic inflammation, pain, and fever. It was synthesized as an analog of the known COX-2 inhibitor valdecoxib (4-[5-methyl-3-phenyl-4-isoxazolyl]-benzenesulfonamide) (Talley et al., 2000). N-Hydroxy-valdecoxib had low in vitro COX-2 activity but showed significant analgesic activity in vivo and a prolonged therapeutic effect compared with valdecoxib (Erdélyi et al., 2008). In this report, we demonstrate that N-hydroxy-valdecoxib is enzymatically reduced to its pharmacologically active metabolite valdecoxib. Thus, N-hydroxy-valdecoxib acts as prodrug that is activated by the molybdenum-containing enzyme mARC.


Overexpression of GATA-3 in T cells accelerates dextran sulfate sodium-induced colitis.
Ulcerative colitis (UC) is an inflammatory bowel disease, and its pathogenesis includes genetic, environmental, and immunological factors, such as T helper cells and their secreted cytokines. T helper cells are classified as Th1, Th2, and Th17 cells. However, it is unclear which T helper cells are important in UC. Dextran sulfate sodium (DSS)-induced colitis is a commonly used model of UC. In this study, we induced DSS colitis in Th1 dominant (T-bet transgenic (Tg)) mice, Th2 dominant (GATA-3 Tg) mice, and Th17 dominant (RORγt Tg) mice to elucidate the roles of T helper cell in DSS colitis. The results showed that GATA-3 Tg mice developed the most severe DSS colitis compared with the other groups. GATA-3 Tg mice showed a significant decreased in weight from day 1 to day 7, and an increased high score for the disease activity index compared with the other groups. Furthermore, GATA-3 Tg mice developed many ulcers in the colon, and many neutrophils and macrophages were detected on day 4 after DSS treatment. Measurement of GATA-3-induced cytokines demonstrated that IL-13 was highly expressed in the colon from DSS-induced GATA-3 Tg mice. In conclusion, GATA-3 overexpression in T-cells and IL-13 might play important roles in the development of DSS colitis.


Review of Singapore's air quality and greenhouse gas emissions: current situation and opportunities.
Singapore has many environmental accomplishments to its credit. Accessible data on air quality indicates that all criteria pollutants satisfy both U.S. Environmental Protection Agency (EPA) and World Health Organization (WHO) air quality standards and guidelines, respectively. The exception is PM2.5 (particles with an aerodynamic diameter < or = 2.5 microm), which is not currently considered a criteria pollutant in Singapore but may potentially be the major local air pollution problem and cause for health concern. Levels of other airborne pollutants as well as their physical and chemical processes associated with local formation, transformation, dispersion, and deposition are not known. According to available emission inventories, Singapore contribution to the total atmospheric pollution and carbon budget at the regional and global scales is small. Emissions per unit gross domestic product (GDP) are low compared with other countries, although Singapore's per-capita GDP and per-capita emissions are among the highest in the world. Some information is available on health effects, but the impacts on the ecosystem and the complex interactions of air pollution and climate change at a regional level are also unknown. This article reviews existing available information on atmospheric pollution and greenhouse gas emissions and proposes a multipollutant approach to greenhouse gas mitigation and local air quality. Singapore, by reducing its per-capita emissions, increasing the availability of information (e.g., through regularly publishing hourly and/or daily PM2.5 concentrations) and developing a research agenda in this area, would likely be seen to be a model of a high-density, livable, and sustainable city in Southeast Asia and other tropical regions worldwide.


Open intramedullary nailing and bone-grafting for non-union of tibial diaphyseal fracture.
Twenty consecutive patients who had non-union of twenty-two fractures (two of the patients had a segmental fracture) of the tibia underwent open reduction, débridement, and intramedullary nailing that was supplemented by bone-grafting with either autogenous cancellous iliac bone or cortical reamings of bone from the intramedullary canal. Eighteen patients had significant deformity associated with the tibial fracture. All but three patients had postoperative splinting for two to four weeks, followed by walking without a brace; the three patients who did not have postoperative splinting were more than sixty-five years old. All of the fractures went on to union. Two patients had a minor complication that did not affect the final result. Incorporation of callus across the site of non-union occurred at a rapid rate. Anatomical alignment of the tibial shaft was obtained in nineteen of the twenty patients.


An undescribed coexistence of benign metastasizing leiomyoma in the lung with serous borderline tumor of the ovary.
Pulmonary benign metastasizing leiomyoma (BML) is a rare disease occurring predominantly in women of reproductive age and usually develops several years after the resection of a uterine leiomyoma. Serous borderline tumor (SBT) occurs most frequently in the ovary originated from sex hormone dependence. This report describes such a co-existing case. A 46-year-old woman developed a uterine leiomyoma co-existing SBT of the right ovary ten years ago and then underwent abdominal total hysterectomy and right side oophorectomy. In 2008, she developed a co-existing pulmonary BML and SBT of the left ovary. Left side oophorectomy was performed and no further therapeutic actions were taken. The patient is currently alive and well. To the authors' knowledge, this is the first case of a coexisting BML and SBT. Herein, they describe the clinicopathological features of BML and the possible existence of a close causative association between BML and SBT.


Surgical optimization and characterization of a minimally invasive aortic banding procedure to induce cardiac hypertrophy in mice.
Left ventricular pressure overload in response to aortic banding is an invaluable model for studying progression of cardiac hypertrophy and transition to heart failure. Traditional aortic banding has recently been superceded by minimally invasive transverse aortic banding (MTAB), which does not require ventilation so is less technically challenging. Although the MTAB approach is superior, few laboratories have documented success, and minimal information on the model is available. The aim of this study was to optimize conditions for MTAB and to characterize the development and progression of cardiac hypertrophy. Isofluorane proved the most suitable anaesthetic for MTAB surgery in mice, and 1 week after surgery the MTAB animals showed significant increases in systolic blood pressure (MTAB 110 ± 6 mmHg versus sham 78 ± 3 mmHg, n = 7, P < 0.0001) and heart weight to body weight ratio (MTAB 6.2 ± 0.2 versus sham 5.1 ± 0.1, n = 12, P < 0.001), together with systolic (e.g. fractional shortening, MTAB 31.7 ± 1% versus sham 36.6 ± 1.4%, P = 0.01) and diastolic dysfunction (e.g. left ventricular end-diastolic pressure, MTAB 12.7 ± 1.0 mmHg versus sham 6.7 ± 0.8 mmHg, P < 0.001). Leucocyte infiltration to the heart was evident after 1 week in MTAB hearts, signifying an inflammatory response. More pronounced remodelling was observed 4 weeks postsurgery (heart weight to body weight ratio, MTAB 9.1 ± 0.6 versus sham 4.6 ± 0.04, n = 10, P < 0.0001) and fractional shortening was further decreased (MTAB 24.3 ± 2.5% versus sham 43.6 ± 1.7%, n = 10, P = 0.003), together with a significant increase in cardiac fibrosis and further cardiac inflammation. Our findings demonstrate that MTAB is a relevant experimental model for studying development and progression of cardiac hypertrophy, which will be highly valuable for future studies examining potential novel therapeutic interventions in this setting.


Space-time clustering at birth and at diagnosis of type 1 diabetes mellitus in relation to early clinical manifestation.
To investigate whether space-time clustering at diagnosis of type 1 diabetes mellitus (DM1) is related to clinical manifestations and to see whether there is a time-space clustering at birth of children who later develop DM1. Using the method by Knox, clustering was analysed in all 1,144 children diagnosed between 1977 and 1994 in south-east Sweden. The strongest significance was obtained for the cut-off value of 5 km and 7 months (p<0.01). Using this cut-off, children with a short duration of symptoms before diagnosis had the same degree of clustering as children with a longer duration. Children diagnosed during autumn and winter tended to have a higher degree of clustering than children diagnosed during spring and summer. We found no significant clustering regarding birthplace and birth month. This study is consistent with the existence of space-time clustering at diagnosis. The most plausible explanation is that infections elicit several cases of DM1 in children in whom the disease process has already begun.


Tanycytes As Regulators of Seasonal Cycles in Neuroendocrine Function.
Annual cycles of physiology and behavior are highly prevalent in organisms inhabiting temperate and polar regions. Examples in mammals include changes in appetite and body fat composition, hibernation and torpor, growth of antlers, pelage and horns, and seasonal reproduction. The timing of these seasonal cycles reflects an interaction of changing environmental signals, such as daylength, and intrinsic rhythmic processes: circannual clocks. As neuroendocrine signals underlie these rhythmic processes, the focus of most mechanistic studies has been on neuronal systems in the hypothalamus. Recent studies also implicate the pituitary stalk (pars tuberalis) and hypothalamic tanycytes as key pathways in seasonal timing. The pars tuberalis expresses a high density of melatonin receptors, so is highly responsive to changes in the nocturnal secretion of melatonin from the pineal gland as photoperiod changes across the year. The pars tuberalis in turn regulates tanycyte function in the adjacent hypothalamus via paracrine signals. Tanycytes are radial glial cells that persist into adulthood and function as a stem cell niche. Their cell soma are embedded in the ependymal lining of the third ventricle, and they also send elaborate projections through the arcuate nucleus, many of which terminate on capillaries in the median eminence. This anatomy underlies their function as sensors of nutrients in the circulation, and as regulators of transport of hormones and metabolites into the hypothalamus. In situ hybridization studies reveal robust seasonal changes in gene expression in tanycytes, for example, those controlling transport and metabolism of thyroid hormone and retinoic acid. These hormonal signals play a key role in the initial development of the brain, and experimental manipulation of thyroid hormone availability in the adult hypothalamus can accelerate or block seasonal cyclicity in sheep and Siberian hamsters. We hypothesize that seasonal rhythms depends upon reuse of developmental mechanisms in the adult hypothalamus and that tanycytes are key orchestrators of these processes.


Effector gene reshuffling involves dispensable mini-chromosomes in the wheat blast fungus.
Newly emerged wheat blast disease is a serious threat to global wheat production. Wheat blast is caused by a distinct, exceptionally diverse lineage of the fungus causing rice blast disease. Through sequencing a recent field isolate, we report a reference genome that includes seven core chromosomes and mini-chromosome sequences that harbor effector genes normally found on ends of core chromosomes in other strains. No mini-chromosomes were observed in an early field strain, and at least two from another isolate each contain different effector genes and core chromosome end sequences. The mini-chromosome is enriched in transposons occurring most frequently at core chromosome ends. Additionally, transposons in mini-chromosomes lack the characteristic signature for inactivation by repeat-induced point (RIP) mutation genome defenses. Our results, collectively, indicate that dispensable mini-chromosomes and core chromosomes undergo divergent evolutionary trajectories, and mini-chromosomes and core chromosome ends are coupled as a mobile, fast-evolving effector compartment in the wheat pathogen genome.


[Derivatives of pro-opiomelanocortin (ACTH and beta-endorphin) in chronic alcoholics].
The plasmatic concentration of beta-endorphins and ACTH were measured in 31 alcoholic patients and in a control group (N = 16), to test the possible relation between chronic alcohol intake and propiomelanocortin production. There were found a decrease of beta-endorphins plasmatic levels in chronic alcoholic group, apart of clinical manifestations or abstinence period (one month maximum). This decrease can be cause by the chronic alcohol intake, and can be mediated by the tetrahydroisoquinolines (TIQs) or otherwise be the cause and not the consequence of alcoholism. The global plasmatic levels of ACTH were decreased but it was significant in the subgroup of alcoholics with liver disfunction, mental illness and those who carry on drinking.


Relation of melatonin to sleep architecture in children with autism.
Children with autism often suffer from sleep disturbances, and compared to age-matched controls, have decreased melatonin levels, as indicated by urine levels of the primary melatonin metabolite, 6-sulfatoxymelatonin (6-SM). We therefore investigated the relationship between 6-SM levels and sleep architecture in children with autism spectrum disorders (ASD). Twenty-three children, aged 4-10 years, completed two nights of polysomnography and one overnight urine collection for measurement of urinary 6-SM excretion rate. Parents completed the Children's Sleep Habits Questionnaire. We found that higher urinary 6-SM excretion rates were associated with increased N3 sleep, decreased N2 sleep, and decreased daytime sleepiness. The results warrant further examination to examine the effects of supplemental melatonin on sleep architecture and daytime sleepiness.


Estradiol receptor-binding protein in head and neck neoplastic and normal tissue.
Estradiol (E2) receptor-binding protein was measured in 42 neoplasms and normal tissues from the head and neck region. Tissues with high E2 receptor protein content included normal skin and normal mucosa of the nose and the floor of the mouth and of the parotid and submandibular salivary glands. Two of four papillary carcinomas of the thyroid, three of five pleomorphic adenomas of the parotid, four of six squamous cell carcinomas of the oral cavity, one of angiofibroma of the nose, and an eye (sclera) melanoma also had a high content of E2-binding protein. The demonstration of estrogen receptors in these neoplasms may indicate that these tumors also, as many breast lesions, may be hormone-dependent. If this is correct, an appropriate hormonal treatment may influence their biological evolution.


Analysis of difference spectra of protonated DNA: determination of degree of protonation of nitrogen bases and the fractions of disordered nucleotide pairs.
The titration curves of nitrogen bases and fractions of disordered nucleotide pairs are obtained during DNA protonation. It is shown that purine bases are the first sites of the DNA double helix protonation. The cytosine protonation is due to proton-induced conformational transition within GC pairs with the sequence proton transfer from (N-7) of guanine to (N-3) of cytosine. Within DNA with unwound regions the bases are protonated in the following order: cytosine, adenine, guanine. It is shown that GC pairs are the primary centres in which the unwinding of protonated DNAs occurs.


Diversity and potential application of endophytic bacteria in ginger.
Here, 248 endophytic bacterial strains were isolated to assess the distribution and population diversity of endophytic bacteria in ginger plants. A total of 10.4 x 10(4) to 20.2 x 10(4) CFU/g fresh weight endophytic bacteria of different growth stages were isolated. Maximum bacterium numbers were obtained at the seedling stage. A total of 107 functional strains were screened, including 17 antibacterial strains and 90 indole acetic acid-producing strains. Based on 16S rDNA sequence restriction fragment length polymorphism and 16S rDNA sequences, these 107 strains were mapped and grouped into 16 genera. Bacillus and Pseudomonas were the dominant genera; however, the bacteria belonged to a tremendous range of genera, with the highest species richness being observed at the seedling stage. Sixteen strains exhibited antimicrobial activity against Pythium myriotylum Drechsler, while 7 strains exhibited antimicrobial activity against Phyllosticta zingiberi Hori. Bacillus was the dominant antibacterial strain. Pseudomonas fluorescens, B. megaterium, and Enterobacter ludwigii produced remarkably high levels of IAA. Only a few endophytic bacterial strains were inhibited in fresh ginger juice. Most of these strains were present during seedling stage, including Roseateles depolymerans, Chryseobacterium taiwanense, E. ludwigii, Agrobacterium larrymoorei, P. fluorescens, and Bacillus amyloliquefaciens. This study indicates that the community of endophytic bacteria in ginger changes with the synthesis of antibacterial substances.


Progress in Australian dendroclimatology: Identifying growth limiting factors in four climate zones.
Dendroclimatology can be used to better understand past climate in regions such as Australia where instrumental and historical climate records are sparse and rarely extend beyond 100years. Here we review 36 Australian dendroclimatic studies which cover the four major climate zones of Australia; temperate, arid, subtropical and tropical. We show that all of these zones contain tree and shrub species which have the potential to provide high quality records of past climate. Despite this potential only four dendroclimatic reconstructions have been published for Australia, one from each of the climate zones: A 3592year temperature record for the SE-temperate zone, a 350year rainfall record for the Western arid zone, a 140year rainfall record for the northern tropics and a 146year rainfall record for SE-subtropics. We report on the spatial distribution of tree-ring studies, the environmental variables identified as limiting tree growth in each study, and identify the key challenges in using tree-ring records for climate reconstruction in Australia. We show that many Australian species have yet to be tested for dendroclimatological potential, and that the application of newer techniques including isotopic analysis, carbon dating, wood density measurements, and anatomical analysis, combined with traditional ring-width measurements should enable more species in each of the climate zones to be used, and long-term climate records to be developed across the entire continent.


Fatal Multiorgan Failure Syndrome in a Strongyloides-HTLV-1 Coinfected Patient, after Treatment with Ivermectin.
Because of its characteristic features of autoinfection, the parasitic nematode Strongyloides stercoralis can infect patients for years. An acceleration of its autoinfective cycle can be triggered by human T-lymphotropic virus-1 (HTLV-1) infection, mainly by the deviation of the protective Th2- to Th1-type immune response and can lead to severe disease by dissemination of Strongyloides stercoralis larvae carrying intestinal bacteria to multiple organs. Meningitis caused by enteric Gram-negative bacteria is a potentially fatal complication of disseminated strongyloidiasis. Herein, we present the case of a Strongyloides-HTLV-1 coinfected patient, admitted for E. coli meningitis. One day after initiation of ivermectin, the patient developed significant S. stercoralis dissemination, complicated by multiorgan failure syndrome, and died from neurological failure. While the initial clinical scenario of our case has already been well described in the literature, its course after antihelminthic treatment initiation remains unclear and needs to be discussed.


Fracture of the greater tubercle of the humerus in a filly.
A fracture of the caudal portion of the greater tubercle of the humerus was diagnosed in a 16-month-old Thoroughbred filly. Initially the fracture caused severe lameness. Radiography of the affected shoulder revealed the fracture fragment to be extra-articular, with a surrounding bony callus and no evidence of joint disease. After 5 weeks rest in a stall and 11 months at pasture, the filly was trained and raced without lameness.


Evaluation of the cocaine-like discriminative stimulus effects and reinforcing effects of modafinil.
Modafinil [(diphenyl-methyl)sulphinyl-2-acetamide] is a novel psychostimulant drug which is effective in the treatment of narcolepsy and idiopathic hypersomnia. It also has neuroprotective effects in animal models of striatal neuropathology. Although the cellular mechanisms of action of modafinil are poorly understood, it has been shown to have a profile of pharmacological effects that differs considerably from that of amphetamine-like stimulants. There is some evidence that modafinil has central alpha 1-adrenergic agonist effects. In the present study modafinil was evaluated for cocaine-like discriminative stimulus effects in rats and for reinforcing effects in rhesus monkeys maintained on intravenous cocaine self-administration. Modafinil, l-ephedrine and d-amphetamine all produced dose dependent increases in cocaine-lever responding, with maximal levels of 67%, 82% and 100%, respectively. Modafinil produced full substitution in four out of the six rats tested while the highest levels of substitution were associated with substantial response rate decreasing effects. Little evidence was obtained that the discriminative stimulus effects of modafinil were produced by alpha 1-adrenergic activation, based upon results of tests performed in combination with prazosin. In the self-administration procedure, modafinil and l-ephedrine functioned as reinforcers in rhesus monkeys. The reinforcing and discriminative stimulus effects of modafinil-required very high doses: modafinil was over 200 times less potent than d-amphetamine and was also less potent than l-ephedrine. These results show that modafinil has some cocaine-like discriminative stimulus effects and, like other abused stimulants, can serve as a reinforcer at high doses.


Blood Flow Restricted Exercise Compared to High Load Resistance Exercise During Unloading.
Bed rest studies have shown that high load (HL) resistance training can mitigate the loss of muscle size and strength during musculoskeletal unloading; however, not all individuals are able to perform HL resistance exercise. Blood flow restricted (BFR) resistance exercise may be a novel way to prevent maladaptation to unloading without requiring HL exercise equipment. This study evaluated the muscular training adaptations to HL and BFR resistance training during unilateral lower limb suspension (ULLS), a human limb unloading model. ULLS allows for evaluation of exercise training in both weight-bearing and nonweight-bearing legs within the same individual. There were 13 participants who completed 25 d of ULLS and were counterbalanced to: 1) HL, N = 6; or 2) BFR, N = 7, training groups. During ULLS, HL and BFR performed unilateral leg press and heel raise exercise (3 d/wk). In weight-bearing legs, both HL and BFR increased knee extensor muscle cross-sectional area (CSA) and strength. In nonweight-bearing legs, knee extensor CSA and strength increased only in HL and decreased with BFR. HL and BFR resistance exercise were both effective exercise programs for the weight-bearing leg. However, BFR exercise was not as effective as HL resistance exercise in the nonweight-bearing leg. These data show that exercise that improved muscle CSA and strength in ambulatory weight-bearing conditions was not sufficient to maintain muscle function during unloading. For the preservation of muscle CSA and strength, BFR exercise should be considered an adjunct but not a primary exercise countermeasure for future space missions. Hackney KJ, Downs ME, Ploutz-Snyder L. Blood flow restricted exercise compared to high load resistance exercise during unloading. Aerosp Med Hum Perform. 2016; 87(8):688-696.


Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage.
In this randomized multicenter study of 136 patients, 6 courses of CHOP (cyclo-phosphamide/doxorubicin/vincristine/prednisone) followed by rituximab (CHOP-R) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting (R-HDS) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma (FL) after the introduction of monoclonal antibodies. The analysis was intention to treat with event-free survival (EFS) as the primary endpoint. Complete remission (CR) was 62% with CHOP-R and 85% with R-HDS (P < .001). At a median follow-up (MFU) of 51 months, the 4-year EFS was 28% and 61%, respectively (P < .001), with no difference in overall survival (OS). Molecular remission (MR) was achieved in 44% of CHOP-R and 80% of R-HDS patients (P < .001), and was the strongest independent outcome predictor. Patients relapsing after CHOP-R underwent salvage R-HDS in 71% of cases. Salvage R-HDS had an 85% CR rate and a 68% 3-year EFS (MFU, 30 months). We conclude that (1) achieving MR is critical for effective disease control, regardless of which treatment is used; (2) R-HDS ensures superior disease control and molecular outcome than CHOP-R, but no OS improvement; and (3) CHOP-R failures have a good outcome after salvage R-HDS, suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS-like treatments. This trial was registered at www.clinicaltrials.gov as no. NCT00435955.


Searching for the proverbial needle in a haystack: advances in mosquito-borne arbovirus surveillance.
Surveillance is critical for the prevention and control of mosquito-borne arboviruses. Detection of elevated or emergent virus activity serves as a warning system to implement appropriate actions to reduce outbreaks. Traditionally, surveillance of arboviruses has relied on the detection of specific antibodies in sentinel animals and/or detection of viruses in pools of mosquitoes collected using a variety of sampling methods. These methods, although immensely useful, have limitations, including the need for a cold chain for sample transport, cross-reactivity between related viruses in serological assays, the requirement for specialized equipment or infrastructure, and overall expense. Advances have recently been made on developing new strategies for arbovirus surveillance. These strategies include sugar-based surveillance, whereby mosquitoes are collected in purpose-built traps and allowed to expectorate on nucleic acid preservation cards which are submitted for virus detection. New diagnostic approaches, such as next-generation sequencing, have the potential to expand the genetic information obtained from samples and aid in virus discovery. Here, we review the advancement of arbovirus surveillance systems over the past decade. Some of the novel approaches presented here have already been validated and are currently being integrated into surveillance programs. Other strategies are still at the experimental stage, and their feasibility in the field is yet to be evaluated.


Stem cells and cell therapy approaches in lung biology and diseases.
Cell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases, including emphysema, pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune responses in mouse lung disease models. Based on these studies and on safety and initial efficacy data from trials of adult stem cells in other diseases, groundbreaking clinical trials of cell-based therapy have been initiated for pulmonary hypertension and for chronic obstructive pulmonary disease. In parallel, the identity and role of endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular reference to animal models.


Comparative Genomics and Transcriptomics Analyses Reveal Divergent Plant Biomass-Degrading Strategies in Fungi.
Plant biomass is one of the most abundant renewable carbon sources, which holds great potential for replacing current fossil-based production of fuels and chemicals. In nature, fungi can efficiently degrade plant polysaccharides by secreting a broad range of carbohydrate-active enzymes (CAZymes), such as cellulases, hemicellulases, and pectinases. Due to the crucial role of plant biomass-degrading (PBD) CAZymes in fungal growth and related biotechnology applications, investigation of their genomic diversity and transcriptional dynamics has attracted increasing attention. In this project, we systematically compared the genome content of PBD CAZymes in six taxonomically distant species, Aspergillus niger, Aspergillus nidulans, Penicillium subrubescens, Trichoderma reesei, Phanerochaete chrysosporium, and Dichomitus squalens, as well as their transcriptome profiles during growth on nine monosaccharides. Considerable genomic variation and remarkable transcriptomic diversity of CAZymes were identified, implying the preferred carbon source of these fungi and their different methods of transcription regulation. In addition, the specific carbon utilization ability inferred from genomics and transcriptomics was compared with fungal growth profiles on corresponding sugars, to improve our understanding of the conversion process. This study enhances our understanding of genomic and transcriptomic diversity of fungal plant polysaccharide-degrading enzymes and provides new insights into designing enzyme mixtures and metabolic engineering of fungi for related industrial applications.


[Radioepidemiological studies in the nuclear industry of China].
The results of retrospective-cohort radioepidemiological studies on workers of mines and plants governed by China National Nuclear Corporation was reported. The total number was 40,122 persons and 575,411 person-years. The accumulated personal dose in workers of reactor, nuclear fuel reprocessing plants and research units was 57 mSv on the average. For fuel element fabrication and diffusion plants, it was about 5 mSv. Mortality of cancers, especially the non-cancerous diseases was not higher but lower than the controlled group and national values, showing the so-called health worker effect. 31,786 off springs of workers in the nuclear plants were examined. There were no significant difference in the incidence of hereditary-congenital diseases among exposed and controlled groups. The results mentioned above provide the direct medical evidences of the safety of nuclear industry in China. Owing to the high concentration of radon in the uranium prospective and mining tunnels in early years, the average cumulative exposure to radon progeny was about 80 WLM for miners who had the history of working underground. The relative risk of lung cancer was about 2. The excess relative risk per WLM was similar to the value reported abroad.


Lifestyle, Glycosylated Hemoglobin A1c, and Survival Among Patients With Stable Ischemic Heart Disease and Diabetes.
The importance of glycosylated hemoglobin A1c (A1c) control as part of comprehensive risk factor management in patients with stable ischemic heart disease (SIHD) and diabetes mellitus (DM) is controversial. The purpose of this study was to determine whether a greater number of controlled risk factors at 1 year, including A1c, affects survival in patients with DM and SIHD. Of 690 patients with DM followed in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 592 (86%) had complete ascertainment of 7 pre-specified risk factors at baseline and after 1 year: systolic blood pressure, low-density lipoprotein cholesterol, nonsmoking, physical activity, diet adherence, body mass index, and A1c. The primary outcome measure was mortality beyond 1 year after randomization. During a mean follow-up of 7.0 ± 4.2 years beyond 1 year after randomization, 186 subjects died (31.4% overall, 4.5%/year). The greater the number of risk factors controlled at 1 year, the higher the probability of survival (unadjusted log rank p = 0.002). Compared with 0 to 1 controlled risk factors, attaining 3 to 7 goals predicted progressively lower mortality (hazard ratio for control of 6 or 7 risk factors was 0.13; 95% confidence interval: 0.05 to 0.40). Importantly, only 10.3% of subjects achieved control of 6 or 7 risk factors. In multivariate analysis, the strongest predictors of improved survival were no smoking, regular physical activity, dietary adherence, and A1c <7%. In this high-risk subset of SIHD patients with DM, the number of controlled risk factors, particularly lifestyle behaviors and A1c, were associated with improved survival. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).


Drosophila C-terminal binding protein, dCtBP is required for sensory organ prepattern and sharpens proneural transcriptional activity of the GATA factor Pnr.
The peripheral nervous system is required for animals to detect and to relay environmental stimuli to central nervous system for the information processing. In Drosophila, the precise spatial and temporal expression of two proneural genes achaete (ac) and scute (sc), is necessary for development of the sensory organs. Here we present an evidence that the transcription co-repressor, dCtBP acts as a negative regulator of sensory organ prepattern. Loss of dCtBP function mutant exhibits ectopic sensory organs, while overexpression of dCtBP results in a dramatic loss of sensory organs. These phenotypes are correlated with mis-emerging of sensory organ precursors and perturbated expression of proneural transcription activator Ac. Mammalian CtBP-1 was identified via interaction with the consensus motif PXDLSX(K/R) of adenovirus E1A oncoprotein. We demonstrated that dCtBP binds directly to PLDLS motif of Drosophila Friend of GATA-1 protein, U-shaped and sharpens the adult sensory organ development. Moreover, we found that dCtBP mediates multivalent interaction with the GATA transcriptional activator Pannier and acts as a direct co-repressor of the Pannier-mediated activation of proneural genes. We demonstrated that Pannier genetically interacts with dCtBP-interacting protein HDAC1, suggesting that the dCtBP-dependent regulation of Pannier activity could utilize a repressive mechanism involving alteration of local chromatine structure.


25th anniversary article: a decade of organic/polymeric photovoltaic research.
Organic photovoltaic (OPV) technology has been developed and improved from a fancy concept with less than 1% power conversion efficiency (PCE) to over 10% PCE, particularly through the efforts in the last decade. The significant progress is the result of multidisciplinary research ranging from chemistry, material science, physics, and engineering. These efforts include the design and synthesis of novel compounds, understanding and controlling the film morphology, elucidating the device mechanisms, developing new device architectures, and improving large-scale manufacture. All of these achievements catalyzed the rapid growth of the OPV technology. This review article takes a retrospective look at the research and development of OPV, and focuses on recent advances of solution-processed materials and devices during the last decade, particular the polymer version of the materials and devices. The work in this field is exciting and OPV technology is a promising candidate for future thin film solar cells.


Miniaturized approach for excipient selection during the development of oral solid dosage form.
The present study introduces a miniaturized high-throughput platform to understand the influence of excipients on the performance of oral solid dosage forms during early drug development. Wet massing of binary mixtures of the model drug (sodium naproxen) and representative excipients was followed by sieving, drying, and compaction of the agglomerated material. The mini-compacts were subjected to stability studies at 25°C/5% relative humidity (RH), 25°C/60% RH and 40°C/75% RH for 3 months. The physical stability of the drug was affected by the storage condition and by the characteristics of the excipients, whereas all the samples were chemically stable. Force-distance curves obtained during the compression of agglomerated material were used for the comparison of compressibility of different drug-excipient mixtures. The agglomerated drug-excipient mixtures were also subjected to studies of the dissolution trend under sequential pH conditions to simulate pH environment of gastrointestinal tract. Major factors affecting the dissolution behavior were the diffusion layer pH of the binary mixtures and the ability of the excipients to alter the diffusion layer thickness. The proposed approach can be used for excipient selection and for early-stage performance testing of active pharmaceutical ingredient intended for oral solid dosage form.


Which daily experiences can foster well-being at work? A diary study on the interplay between flow experiences, affective commitment, and self-control demands.
Previous research has provided strong evidence for affective commitment as a direct predictor of employees' psychological well-being and as a resource that buffers the adverse effects of self-control demands as a stressor. However, the mechanisms that underlie the beneficial effects of affective commitment have not been examined yet. Drawing on the self-determination theory, we propose day-specific flow experiences as the mechanism that underlies the beneficial effects of affective commitment, because flow experiences as peaks of intrinsic motivation constitute manifestations of autonomous regulation. In a diary study covering 10 working days with N = 90 employees, we examine day-specific flow experiences as a mediator of the beneficial effects of interindividual affective commitment and a buffering moderator of the adverse day-specific effects of self-control demands on indicators of well-being (ego depletion, need for recovery, work engagement, and subjective vitality). Our results provide strong support for our predictions that day-specific flow experiences a) mediate the beneficial effects of affective commitment on employees' day-specific well-being and b) moderate (buffer) the adverse day-specific effects of self-control demands on well-being. That is, on days with high levels of flow experiences, employees were better able to cope with self-control demands whereas self-control demands translated into impaired well-being when employees experienced lower levels of day-specific flow experiences. We then discuss our findings and suggest practical implications. (PsycINFO Database Record


On the possibility of AgZSM-5 zeolite being a partial oxidation catalyst for methane.
A silver-ion-exchanged HZSM-5 zeolite sample (Ag(H)ZSM-5) evacuated at 573 K exhibited prominent catalytic behavior in the partial oxidation of CH(4) at temperatures above 573 K, exceeding the performance of Ag/SiO(2)Al(2)O(3) and Ag/SiO(2) catalysts. From the infrared (IR) and X-ray absorption fine structure (XAFS) spectra, as well as the dioxygen adsorption measurement, it was concluded that the simultaneous existence of Ag(+) ions and small clusters of Ag particles leads to the partial oxidation of methane. Taking the magnitude of the formation enthalpy (per oxygen atom) of Ag(2)O (DeltaH=26 kJ/mol) into consideration, we propose the interpretation that the dioxygen activated on small Ag metal clusters formed in ZSM-5 elaborates a surface oxide layer on small Ag clusters and the thus-formed species is simultaneously and easily decomposed at 573 K or above, and the oxygen activated in this way on the Ag metal spills over and can react with methane that has been activated by the Ag(+) ions exchanged in ZSM-5, resulting in the high catalytic activity of the Ag(H)ZSM-5 sample in the partial oxidation of methane. This interpretation is also well evidenced by XAFS and IR data. It is anticipated that this material has the potential to be a promising catalyst in the conversion of natural gas into higher value-added chemicals and fuels.


Mapping the regulatory landscape of AI in healthcare in Africa.
Introduction: Artificial intelligence (AI)-enhanced technology has seen unprecedented expansion in the recent past. This growth brings with it huge opportunities for the positive transformation of the economy, business, healthcare, and society. However, a critical question is whether, and to what extent, regulatory measures and mechanisms have been implemented to safeguard its design, development, and deployment. This paper offers a scoping exercise that maps the regulatory landscape of AI in healthcare (including health research) in certain African countries. Methods: This research is conducted across 12 African countries: Botswana, Cameroon, The Gambia, Ghana, Kenya, Malawi, Nigeria, Rwanda, South Africa, Tanzania, Uganda, and Zimbabwe. As limited specific AI legislation is found in these African countries, and because AI is informed by ancillary regulatory frameworks, we include data protection, digital health, consumer protection, and intellectual property in our research. A scoping review method was applied with a manual search of digital libraries with search terms customised for each repository consisting of core search terms for the various topics, including, among others, "law," "regulation," "artificial intelligence," "data protection," "intellectual property," and "digital health". Results and discussion: Analysis of the data demonstrated that while in the African countries under investigation there is no sui generis AI regulation, recent developments were found in areas that inform AI adoption, including in digital health, data protection, consumer protection, and intellectual property. Our findings highlight the fragmentation of the African AI regulatory landscape and illustrate the importance of continued AI regulatory development to ensure that Africa is well positioned for future AI adoption in health.


Computational study of precision nitrogen doping on graphene nanoribbon edges.
Nitrogen doping in graphene is important for applications spanning from electronics to metal-free electrocatalysts. Despite much experimental study, limited theoretic work has been done in understanding the mechanism of the doping process, especially from a precision perspective. Herein, we present a computational study on precision nitrogen doping on edges of graphene nanoribbons (GNRs) by combining molecular dynamics (MD) simulation at a time scale of 40 ns and density function theory (DFT) calculation. In the MD study both ammonia and acetonitrile were used as nitrogen sources. MD results revealed that the ammonia produces almost all amine-type dopants, while the acetonitrile produces a considerable amount of pyrrolic and pyridinic nitrogen dopants which are beneficial to electronics and electrocatalysts. Results also show that the concentration of pyrrolic and pyridinic dopants can be precisely controlled by the edge geometries of the GNRs. Furthermore, DFT calculation illustrated the reaction mechanism in these different types of the GNRs when using acetonitrile as the nitrogen source. The calculated energies in different reaction stages indicate the stability of dopants on various GNRs, agreeing well with the MD results. The disclosed mechanism of controllable nitrogen doping on the edges of the GNRs would provide guidance to experimental realization, paving new routes to widespread applications.


The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay.
The nonsense-mediated decay (NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3' untranslated regions (UTRs). The umbravirus Pea enation mosaic virus 2 (PEMV2) is a nonsegmented, positive-sense RNA virus with an unusually long 3' UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2 long-distance movement protein p26 was previously shown to both stabilize viral RNAs and bind them for transport through the plant's vascular system. The current study demonstrated that p26 protects both viral and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of long-distance movement. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, p26 protected a subset of cellular NMD target transcripts, particularly those containing long, structured, GC-rich 3' UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the host transcriptome are common during plant RNA virus infections, and these results suggest that, in at least some instances, virus-mediated NMD inhibition may be a major contributing factor.IMPORTANCE Nonsense-mediated decay (NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3' untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in host cells. A protein required for long-distance movement of Pea enation mosaic virus 2 (PEMV2) is shown to also protect both viral and host mRNAs from NMD. RNA-seq analyses of the Nicotiana benthamiana transcriptome revealed that PEMV2 infection significantly impairs the host NMD pathway. RNA viruses routinely induce large-scale changes in host gene expression, and, like PEMV2, may use NMD inhibition to alter the host transcriptome in an effort to increase virus amplification.


Association between dry eye symptoms and suicidal ideation in a Korean adult population.
This study assessed the association of dry eyes with depression and suicidal ideation in a Korean adult population. Data from 16408 participants (6972 men and 9436 women) aged ≥ 19 years included in the fifth Korea National Health and Nutrition Examination Survey, conducted from 2010-2012, were analyzed. For dry eyes, surveys of previous diagnosis of dry eye disease (DED) by an ophthalmologist and experience of subjective dry eye symptoms were separately used. Diagnosis of depression and suicidal ideation were obtained via responses to an interviewer-assisted questionnaire, and questions were asked in a closed-ended response format. Logistic regression was used to examine the associations between dry eyes, depression, and suicidal ideation. DED diagnosis exhibited an odds ratio (OR) of 1.32 (95% confidence interval [CI] 1.11-1.57) for depression and 1.24 (95% CI 1.05-1.48) for suicidal ideation compared to those without DED, after adjusting for sex, age, education, occupation, household income, body mass index, smoking behavior, alcohol consumption, physical activity, hypertension, diabetes, dyslipidemia, thyroid diseases, major cardiovascular disease, and cancer. Similarly, the adjusted OR (95% CI) of dry eye symptoms was 1.50 (95% CI 1.30-1.73) for depression and 1.47 (95% CI 1.27-1.70) for suicidal ideation. Our findings suggest that dry eyes (either DED diagnosis or dry eye symptoms) may be associated with the prevalence of depression and suicidal ideation in the Korean adult population.


Rare Earth Elements Alter Redox Balance in Methylomicrobium alcaliphilum 20ZR.
Background: Rare Earth Elements (REEs) control methanol utilization in both methane- and methanol-utilizing microbes. It has been established that the addition of REEs leads to the transcriptional repression of MxaFI-MeDH [a two-subunit methanol dehydrogenase (MeDH), calcium-dependent] and the activation of XoxF-MeDH (a one-subunit MeDH, lanthanum-dependent). Both enzymes are pyrroquinoline quinone-dependent alcohol dehydrogenases and show significant homology; however, they display different kinetic properties and substrate specificities. This study investigates the impact of the MxaFI to XoxF switch on the behavior of metabolic networks at a global scale. Results: In this study we investigated the steady-state growth of Methylomicrobium alcaliphilum 20ZR in media containing calcium (Ca) or lanthanum (La, a REE element). We found that cells supplemented with La show a higher growth rate compared to Ca-cultures; however, the efficiency of carbon conversion, estimated as biomass yield, is higher in cells grown with Ca. Three complementary global-omics approaches-RNA-seq transcriptomics, proteomics, and metabolomics-were applied to investigate the mechanisms of improved growth vs. carbon conversion. Cells grown with La showed the transcriptional activation of the xoxF gene, a homolog of the formaldehyde-activating enzyme (fae2), a putative transporter, genes for hemin-transport proteins, and nitrate reductase. In contrast, genes for mxaFI and associated cytochrome (mxaG) expression were downregulated. Proteomic profiling suggested additional adjustments of the metabolic network at the protein level, including carbon assimilation pathways, electron transport systems, and the tricarboxylic acid (TCA) cycle. Discord between gene expression and protein abundance changes points toward the possibility of post-transcriptional control of the related systems including key enzymes of the TCA cycle and a set of electron-transport carriers. Metabolomic data followed proteomics and showed the reduction of the ribulose-monophosphate (RuMP) pathway intermediates and the increase of the TCA cycle metabolites. Conclusion: Cells exposed to REEs display higher rates of growth but have lower carbon conversion efficiency compared to cells supplemented with Ca. The most plausible explanation for these physiological changes is an increased conversion of methanol into formate by XoxF-MeDH, which further stimulates methane oxidation but limits both the supply of reducing power and flux of formaldehyde into the RuMP pathway.


The nine-banded armadillo (Dasypus novemcinctus) is naturally infected with Sarcocystis neurona.
Sarcocysts were dissected from the tongue of a nine-banded armadillo (Dasypus novemcinctus). DNA was extracted and characterised by PCR amplification followed by restriction fragment length polymorphism analysis and nucleotide sequencing. A total of 1879 nucleotides were compared; the sarcocyst DNA sequence was identical to that reported for Sarcocystis neurona. DNA was extracted from the sarcocysts of five more nine-banded armadillos. A 254-nucleotide sequence was determined for each and found to be identical to S. neurona. Western blot techniques for detection of anti-S. neurona antibody were developed for use with armadillo plasma and samples from 19 wild-caught and 17 captive-raised armadillos were examined. Whereas all of the 19 wild-caught armadillos had antibodies to S. neurona, only one of 17 captive-raised armadillos did. These results suggest that the nine-banded armadillo are naturally infected with S. neurona.


Direct medical costs of type 2 diabetes and its complications in Switzerland.
This paper analyses the direct medical costs of type 2 diabetes and its complications in Switzerland. Individual healthcare resource consumption related to type 2 diabetes and its complications was determined retrospectively in 1479 non-incident and non-dying patients over 12 months (1998-1999). Literature-derived attributable risks were used to correct for non-diabetes related macrovascular disease. A total of 111 primary care physicians from 19 cantons throughout Switzerland participated. Their diabetic patients on average had 10.3 consultations per year related to this disease (95% CI: 10.0-10.7). Patients spent on average 2.7 days (95% CI: 2.2-3.3) per year in hospital due to diabetes and diabetes-related complications. Mean annual type 2 diabetes-related direct medical costs per patient amounted to CHF 3,508 / Euro 2,323 (95% CI: CHF 3,140-3,876 / Euro 2,080-2,567). They were particularly high in patients with insulin treatment or with complications. After application of attributable risks and a correction for the use of adjuvant materials, costs were CHF 3,324 / Euro 2,201. Assuming 250,000 patients with type 2 diabetes in Switzerland leads to an estimate of CHF 0.88 billion spent for this disease and its complications in 1998. This represents a share of about 2.2% of the country's total healthcare expenditures. These findings demonstrate the high economic importance of type 2 diabetes and its complications in Switzerland.


Diet quality among older adults: What the Index Associated with the Digital Food Guide and the Brazilian Healthy Eating Index-Revised Reveal.
The aim of the present study was to compare the Diet Quality Index-Digital Food Guide (DQI-DFG) to a more widely used measure in the literature: the Brazilian Healthy Eating Index-Revised (BHEI-R). A cross-sectional population-based study was conducted with 822 older adults (≥ 60 years) from the city of Campinas/SP, Brazil. The BHEI-R resulted in a higher overall score compared to DQI-DFG (62.9 vs. 47.7). For the BHEI-R, mean scores increased with age and were worse among smokers and individuals with a higher level of schooling. Regarding the DQI-DFG scores, no significant associations with age, schooling or smoking were detected; however, scores were higher in higher income segments. The components with the worst scores were whole grains, sodium and milk (BHEI-R); fruits, whole grains, roots/tubers, milk, refined cereals and red meat/processed (DQI-DFG). Divergences were found in the global scores and components of the indicators, reflecting important methodological differences. Studies of this nature constitute an opportunity to increase awareness regarding indicators of particular aspects of diet.


The rate and route of fluid resorption from the subretinal space of the rabbit.
Small nonrhegmatogenous detachments were formed in living rabbit eyes by injecting a few microliters of fluid into the subretinal space. The change in volume of these detachments was followed by sequential photogrammetric measurements. Detachments of 1 to 3 mm diameter filled with a balanced salt and glucose solution (Ames' solution) resorbed at a constant rate over approximately 80 min of observation and appeared to be totally resorbed within 2 to 6 hr. The rate at which fluid resorbed per unit area of pigment epithelium was consistent with the rate of resorption in other transporting epithelia as well as with clinical observations in humans. Detachments filled with isotonic sucrose resorbed much more slowly than those filled with saline solutions, suggesting that fluid resorption requires the passage of ions through cell membranes. Hypoxia markedly and reversibly reduced the rate of resorption, suggesting that active transport is involved in the removal of the saline solutions from the subretinal space Anatomical and physiological evidence indicate that the site of active transport is the pigment epithelium. Active resorption of subretinal fluid is probably a factor in the maintenance of normal retinal adhesion.


Oncology nursing: our past is the prologue ... can we author the future?
The development of the standards of care, roles in oncology nursing, and role competencies was an opportunity for Canadian nurses to revisit their professional roots, review and validate their present roles, and revise or reaffirm their future roles. The standards of care for individuals with cancer and their families affirmed the centrality of the individual and family in any nursing interaction and gave voice to the stated needs of Canadians at risk for, or living with cancer. For the first time in Canada, a specialty nursing organization has taken the lead to clearly define contemporary nursing roles and competencies. This new vision has captured the interest of oncology nurses. CANO, the nursing profession, other health care professionals, and health care decision-makers must now also consider how this enlightened view of oncology nursing can be operationalized. The presenters have had the opportunity to "hear" the stories of Canadian oncology nurses and their experiences in striving for excellence in their practice. These stories highlight the evidence supporting the standards of oncology nursing. In addition, the challenges and facilitators for achieving excellence in oncology nursing practice are identified. Through these stories, the future for the development of oncology practice and operationalization of the new standards of care emerges.