[Ability of self care of chronically diabetic patients].
A descriptive study was performed in a population of 181 chronic diabetic patients or both sexes from the medical office No. 2, Chillán with the aim of determining their self-care capacities and factors related to this capacity. A self-care capacity scale based on a study about requirements and self-care capabilities developed by Joan E. Backacneider, was made up. This scale was applied with the purpose of measuring physical, medical, emotional, and motivational capabilities, as well as health orientation for the diabetic patient. Results obtained suggest that only 18.3% of these patients have a high self-care capacity, while 81.7% does not have this kind of capacity. Also it is concluded that factors associated with this self-care capability in these patients are self-confidence, schooling level, occupational status, and social and economic situation.


Quantitative measurement of pseudoexfoliation in the anterior segment of the eye performed in visible light.
Pseudoexfoliation syndrome (PEX) is a systemic disease involving the accumulation of pathological material deposits in the tissues of the anterior segment of the eye. The problem of modern ophthalmology is a quantitative assessment of the severity of PEX in the diagnosis and evaluation of the treatment progress in patients. For the purposes of this study, 52 images of the anterior segment of the eye with the resolution of M × N = 1280 × 960 pixels were obtained in jpg format using the slit lamp CSO 450-SL. The patients were aged 50-80 and were recruited from Poland. All patients who participated in the study provided written informed consent after explanation of the nature and possible consequences of the study. The image analysis method proposed by the authors contains the calculation of the direction field, setting a straight perpendicular line passing through each pixel of the edge of the pupil, the calculation of the intersection of straight lines in order to determine the central point of the pupil position, the detection of the contour of PEX and the outer border of the iris with the use of the polar coordinate system. All analyzed parameters were set automatically with one exception parameter chosen manually depending on the slit lamp type. A fully automatic measurement of PEX was carried out with the proposed method. Quantitative results enable to perform reproducible tests independently of the research centre. Owing to the image analysis method proposed by the authors, it is possible to obtain results in no more than 1 second on the Intel Core 2 Quad CPU 2.50 GHz with a measurement error below 3%. Other known methods of image analysis and processing that are compared in this paper give results with a greater error (4-35%) which depends on the degree of magnification (×6, ×16, ×20) and are not fully automatic. The methods of image analysis and processing enable a quantitative, repeatable and automatic measurement of the severity and progress of PEX syndrome. They support medical diagnosis and automatic archiving of results.


Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era.
Covering: 2000 to 2018 The antimicrobial activity of many of their natural products has brought prominence to the Streptomycetaceae, a family of Gram-positive bacteria that inhabit both soil and aquatic sediments. In the natural environment, antimicrobial compounds are likely to limit the growth of competitors, thereby offering a selective advantage to the producer, in particular when nutrients become limited and the developmental programme leading to spores commences. The study of the control of this secondary metabolism continues to offer insights into its integration with a complex lifecycle that takes multiple cues from the environment and primary metabolism. Such information can then be harnessed to devise laboratory screening conditions to discover compounds with new or improved clinical value. Here we provide an update of the review we published in NPR in 2011. Besides providing the essential background, we focus on recent developments in our understanding of the underlying regulatory networks, ecological triggers of natural product biosynthesis, contributions from comparative genomics and approaches to awaken the biosynthesis of otherwise silent or cryptic natural products. In addition, we highlight recent discoveries on the control of antibiotic production in other Actinobacteria, which have gained considerable attention since the start of the genomics revolution. New technologies that have the potential to produce a step change in our understanding of the regulation of secondary metabolism are also described.


Where there is no brain imaging: Safety and diagnostic value of lumbar puncture in patients with neurological disorders in a rural hospital of Central Africa.
Analysis of cerebrospinal fluid (CSF) obtained by lumbar puncture (LP) is an essential step for the diagnostic approach of neurological disorders, in particular neuro-infections. In low-resource settings, it is even often the only available diagnostic method. Despite its key contribution, little is known on the risks and benefits of LP in the large tropical areas where hospital-based neuroimaging is not available. The objectives of this study were to assess the safety and diagnostic yield of LP in a rural hospital of central Africa and to identify predictors of CSF pleocytosis (white blood cell count >5/μL) as surrogate marker of neuro-infections. From 2012 to 2015, 351 patients admitted for neurological disorders in the rural hospital of Mosango, Kwilu province, Democratic Republic of Congo, were evaluated using a systematic clinical and laboratory workup and a standard operating procedure for LP. An LP was successfully performed in 307 patients (87.5%). Serious post-LP adverse events (headache, backache or transient confusion) were observed in 23 (7.5%) of them but were self-limiting, and no death or long-term sequelae were attributable to LP. CSF pleocytosis was present in 54 participants (17.6%), almost always associated with neuro-infections. Presenting features strongly and independently associated with CSF pleocytosis were fever, altered consciousness, HIV infection and positive screening serology for human African trypanosomiasis. In conclusion, the established procedure for LP was safe in this hospital setting with no neuroimaging and CSF analysis brought a substantial diagnostic contribution. A set of presenting features may help accurately selecting the patients for whom LP would be most beneficial.


Non-canonical inhibition of DNA damage-dependent ubiquitination by OTUB1.
DNA double-strand breaks (DSBs) pose a potent threat to genome integrity. These lesions also contribute to the efficacy of radiotherapy and many cancer chemotherapeutics. DSBs elicit a signalling cascade that modifies the chromatin surrounding the break, first by ATM-dependent phosphorylation and then by RNF8-, RNF168- and BRCA1-dependent regulatory ubiquitination. Here we report that OTUB1, a deubiquitinating enzyme, is an inhibitor of DSB-induced chromatin ubiquitination. Surprisingly, we found that OTUB1 suppresses RNF168-dependent poly-ubiquitination independently of its catalytic activity. OTUB1 does so by binding to and inhibiting UBC13 (also known as UBE2N), the cognate E2 enzyme for RNF168. This unusual mode of regulation is unlikely to be limited to UBC13 because analysis of OTUB1-associated proteins revealed that OTUB1 binds to E2s of the UBE2D and UBE2E subfamilies. Finally, OTUB1 depletion mitigates the DSB repair defect associated with defective ATM signalling, indicating that pharmacological targeting of the OTUB1-UBC13 interaction might enhance the DNA damage response.


Effect of nanosilver surfaces on peptide reactivity towards reactive oxygen species.
The interaction of a terminal tryptophan residue within collagen mimetic peptides when tethered to nanometric silver surfaces was studied using a combination of steady state spectroscopy, ultrafast spectroscopy, and molecular dynamics experiments. Our findings indicate that the effective interaction between the tryptophan and the metal surface occurs in short-time scales (ps) and it is responsible for improving the colloidal stability of the nanoparticles exposed to free radicals. The extent and efficiency of the interaction depends on factors beyond the peptide length that include conformation and distance from the terminal tryptophan to the metal surface.


PEPFAR's evolving HIV prevention approaches for key populations--people who inject drugs, men who have sex with men, and sex workers: progress, challenges, and opportunities.
In most countries, the burden of HIV among people who inject drugs, men who have sex with men, and sex workers is disproportionately high compared with that in the general population. Meanwhile, coverage rates of effective interventions among those key populations (KPs) are extremely low, despite a strong evidence base about the effectiveness of currently available interventions. In its first decade, President's Emergency Plan for AIDS Relief (PEPFAR) is making progress in responding to HIV/AIDS, its risk factors, and the needs of KPs. Recent surveillance, surveys, and size estimation activities are helping PEPFAR country programs better estimate the HIV disease burden, understand risk behavior trends, and determine coverage and resources required for appropriate scale-up of services for KPs. To expand country planning of programs to further reduce HIV burden and increase coverage among KPs, PEPFAR has developed a strategy consisting of technical documents on the prevention of HIV among people who inject drugs (July 2010) and prevention of HIV among men who have sex with men (May 2011), linked with regional meetings and assistance visits to guide the adoption and scale-up of comprehensive packages of evidence-based prevention services for KPs. The implementation and scaling up of available and targeted interventions adapted for KPs are important steps in gaining better control over the spread and impact of HIV/AIDS among these populations.


Knowledge of blood-borne infectious diseases and the practice of universal precautions amongst health-care workers in a tertiary hospital in Malaysia.
This study aimed to assess the knowledge of blood-borne diseases transmitted through needle stick injuries amongst health-care workers in a tertiary teaching hospital. We also aimed to assess the practices of universal precautions amongst these workers and its correlation with the facts. We carried out a cross-sectional study from January to July 2008 involving various levels of health-care workers in Serdang Hospital, Selangor, Malaysia. A self-administered questionnaire assessing knowledge of blood-borne diseases and universal precautions, and actual practice of universal precautions was used. Two hundred fifteen respondents participated in this study; 63.3% were staff nurses. The mean knowledge score was 31.84 (SD 4.30) and the mean universal practice score was 9.0 (SD 2.1). There was a small, positive correlation between knowledge and actual practice of universal precautions (r = 0.300, n = 206, p < 0.001) amongst the cohort studied. Factors such as age and years of experience did not contribute towards acquisition of knowledge about blood-borne illnesses or the practice of universal precautions.


HIF-1α is involved in blood-brain barrier dysfunction and paracellular migration of bacteria in pneumococcal meningitis.
Bacterial meningitis is a deadly disease most commonly caused by Streptococcus pneumoniae, leading to severe neurological sequelae including cerebral edema, seizures, stroke, and mortality when untreated. Meningitis is initiated by the transfer of S. pneumoniae from blood to the brain across the blood-cerebrospinal fluid barrier or the blood-brain barrier (BBB). The underlying mechanisms are still poorly understood. Current treatment strategies include adjuvant dexamethasone for inflammation and cerebral edema, followed by antibiotics. The success of dexamethasone is however inconclusive, necessitating new therapies for controlling edema, the primary reason for neurological complications. Since we have previously shown a general activation of hypoxia inducible factor (HIF-1α) in bacterial infections, we hypothesized that HIF-1α, via induction of vascular endothelial growth factor (VEGF) is involved in transmigration of pathogens across the BBB. In human, murine meningitis brain samples, HIF-1α activation was observed by immunohistochemistry. S. pneumoniae infection in brain endothelial cells (EC) resulted in in vitro upregulation of HIF-1α/VEGF (Western blotting/qRT-PCR) associated with increased paracellular permeability (fluorometry, impedance measurements). This was supported by bacterial localization at cell-cell junctions in vitro and in vivo in brain ECs from mouse and humans (confocal, super-resolution, electron microscopy, live-cell imaging). Hematogenously infected mice showed increased permeability, S. pneumoniae deposition in the brain, along with upregulation of genes in the HIF-1α/VEGF pathway (RNA sequencing of brain microvessels). Inhibition of HIF-1α with echinomycin, siRNA in bEnd5 cells or using primary brain ECs from HIF-1α knock-out mice revealed reduced endothelial permeability and transmigration of S. pneumoniae. Therapeutic rescue using the HIF-1α inhibitor echinomycin resulted in increased survival and improvement of BBB function in S. pneumoniae-infected mice. We thus demonstrate paracellular migration of bacteria across BBB and a critical role for HIF-1α/VEGF therein and hence propose targeting this pathway to prevent BBB dysfunction and ensuing brain damage in infections.


Harnessing expression data to identify novel candidate genes in polycystic ovary syndrome.
Novel pathways in polycystic ovary syndrome (PCOS) are being identified in gene expression studies in PCOS tissues; such pathways may contain key genes in disease etiology. Previous expression studies identified both dickkopf homolog 1 (DKK1) and DnaJ (Hsp40) homolog, subfamily B, member 1 (DNAJB1) as differentially expressed in PCOS tissue, implicating them as candidates for PCOS susceptibility. To test this, we genotyped a discovery cohort of 335 PCOS cases and 198 healthy controls for three DKK1 single nucleotide polymorphisms (SNPs) and four DNAJB1 SNPs and a replication cohort of 396 PCOS cases and 306 healthy controls for 1 DKK1 SNP and 1 DNAJB1 SNP. SNPs and haplotypes were determined and tested for association with PCOS and component phenotypes. We found that no single nucleotide polymorphisms were associated with PCOS risk; however, the major allele of rs1569198 from DKK1 was associated with increased total testosterone (discovery cohort P = 0.0035) and dehydroepiandrosterone sulfate (replication cohort P = 0.05). Minor allele carriers at rs3962158 from DNAJB1 had increased fasting insulin (discovery cohort P = 0.003), increased HOMA-IR (discovery cohort P = 0.006; replication cohort P = 0.036), and increased HOMA-%B (discovery cohort P = 0.004). Carriers of haplotype 2 at DNAJB1 also had increased fasting insulin, HOMA-IR, and HOMA-%B. These findings suggest that genetic variation in DKK1 and DNAJB1 may have a role in the hyperandrogenic and metabolic dysfunction of PCOS, respectively. Our results also demonstrate the utility of gene expression data as a source of novel candidate genes in PCOS, a complex and still incompletely defined disease, for which alternative methods of gene identification are needed.


Hydrogen-rich saline protects against renal ischemia/reperfusion injury in rats.
Recently it has been demonstrated that hydrogen, as a novel antioxidant, can selectively reduce hydroxyl radicals (·OH) and peroxynitrite anion (ONOO-) in vitro and exert therapeutic antioxidant activity in many diseases. This study was designed to investigate the effect of hydrogen-rich saline on renal ischemia/reperfusion (I/R) injury in rats. A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. Physiologic saline, hydrogen-rich saline, or nitrogen-rich saline (8 mL/kg) were administered intraperitoneally at 5 min before reperfusion, respectively. After I/R injury, serum blood urea nitrogen (BUN), creatinine (Cr), tissue malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OhdG), TNF-α, IL-1β, IL-6 levels, and myeloperoxidase (MPO) activity were all increased significantly, while tissue superoxide dismutase (SOD) and catalase (CAT) activities were all decreased significantly. Hydrogen-rich saline reversed these changes and relieved morphological renal injury and I/R-induced apoptosis, while no significant changes were observed in the nitrogen-rich saline-treated group compared with physiologic saline-treated group. Hydrogen-rich saline is able to attenuate the renal I/R injury, which is possibly by reduction of oxidative stress and inflammation.


Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan.
Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis are for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic included blood levels of reactive oxidants and anti-oxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress.


Problem gambling and internalising symptoms: a longitudinal analysis of common and specific social environmental protective factors.
Comorbidity between problem gambling and internalising disorders (anxiety and depression) has long been recognised. However, it is not clear how these relationships develop, and what factors can foster resilience to both conditions. The current study draws on longitudinal cohort data to investigate: 1) the cross-sectional and longitudinal relationships between problem gambling and internalising symptoms; 2) whether there are common and/or specific social environmental factors protective against both internalising symptoms and problem gambling in young adulthood; and 3) interactive protective factors (i.e., those that moderate the relationship between problem gambling and internalising symptoms). A sample of 2248 young adults (55% female) completed a survey in 2010 (T1) and 2012 (T2) which assessed problem gambling (measured via two items based on established measures), internalising symptoms, and social environmental protective factors. A positive cross-sectional relationship between problem gambling and internalising symptoms was found; however, there was no statistically significant longitudinal relationship between the two conditions. Protective factors for internalising symptoms were observed within the domains of the community, family and peer group; however, there were no statistically significant protective factors identified for problem gambling. These findings demonstrate that the social environmental protective factors for adult internalising symptoms assessed in the present study are poor longitudinal predictors of young adult problem gambling. Given the lack of common protective factors, it may be necessary to focus on separate factors to protect against each condition, if we are to address the comorbidity between problem gambling and internalising symptoms.


Calcium intake and risk of fracture: systematic review.
To examine the evidence underpinning recommendations to increase calcium intake through dietary sources or calcium supplements to prevent fractures. Systematic review of randomised controlled trials and observational studies of calcium intake with fracture as an endpoint. Results from trials were pooled with random effects meta-analyses. Ovid Medline, Embase, PubMed, and references from relevant systematic reviews. Initial searches undertaken in July 2013 and updated in September 2014. Randomised controlled trials or cohort studies of dietary calcium, milk or dairy intake, or calcium supplements (with or without vitamin D) with fracture as an outcome and participants aged >50. There were only two eligible randomised controlled trials of dietary sources of calcium (n=262), but 50 reports from 44 cohort studies of relations between dietary calcium (n=37), milk (n=14), or dairy intake (n=8) and fracture outcomes. For dietary calcium, most studies reported no association between calcium intake and fracture (14/22 for total, 17/21 for hip, 7/8 for vertebral, and 5/7 for forearm fracture). For milk (25/28) and dairy intake (11/13), most studies also reported no associations. In 26 randomised controlled trials, calcium supplements reduced the risk of total fracture (20 studies, n=58,573; relative risk 0.89, 95% confidence interval 0.81 to 0.96) and vertebral fracture (12 studies, n=48,967. 0.86, 0.74 to 1.00) but not hip (13 studies, n=56,648; 0.95, 0.76 to 1.18) or forearm fracture (eight studies, n=51,775; 0.96, 0.85 to 1.09). Funnel plot inspection and Egger's regression suggested bias toward calcium supplements in the published data. In randomised controlled trials at lowest risk of bias (four studies, n=44,505), there was no effect on risk of fracture at any site. Results were similar for trials of calcium monotherapy and co-administered calcium and vitamin D. Only one trial in frail elderly women in residential care with low dietary calcium intake and vitamin D concentrations showed significant reductions in risk of fracture. Dietary calcium intake is not associated with risk of fracture, and there is no clinical trial evidence that increasing calcium intake from dietary sources prevents fractures. Evidence that calcium supplements prevent fractures is weak and inconsistent.


The significance and scope of evolutionary developmental biology: a vision for the 21st century.
Evolutionary developmental biology (evo-devo) has undergone dramatic transformations since its emergence as a distinct discipline. This paper aims to highlight the scope, power, and future promise of evo-devo to transform and unify diverse aspects of biology. We articulate key questions at the core of eleven biological disciplines-from Evolution, Development, Paleontology, and Neurobiology to Cellular and Molecular Biology, Quantitative Genetics, Human Diseases, Ecology, Agriculture and Science Education, and lastly, Evolutionary Developmental Biology itself-and discuss why evo-devo is uniquely situated to substantially improve our ability to find meaningful answers to these fundamental questions. We posit that the tools, concepts, and ways of thinking developed by evo-devo have profound potential to advance, integrate, and unify biological sciences as well as inform policy decisions and illuminate science education. We look to the next generation of evolutionary developmental biologists to help shape this process as we confront the scientific challenges of the 21st century.


The Dual-Purpose Hen as a Chance: Avoiding Injurious Pecking in Modern Laying Hen Husbandry.
Dual-purpose strains, with hens housed for egg laying and roosters kept for meat production are one alternative to the killing of male day-old chickens. However, dual-purpose hens seem to have additional advantages compared to conventional layers, for instance, a lower tendency to develop behavioral disorders, such as feather pecking and cannibalism. In the present study, three batches of about 1850 conventional layers (Lohmann Brown plus, LB+) and 1850 dual-purpose hens (Lohmann Dual, LD) each, all of them with untrimmed beaks, were observed during production (20-71 (56) weeks of life) in a semi-commercial aviary system. The aim was to investigate whether the hybrid and batch affected the occurrence of injurious pecking, and to identify a detailed time course of the damage caused by this behavior. Therefore, the hens' plumage and skin condition were assessed as an indicator by means of a visual scoring method. The LB+ hens had higher production performances and higher mortality rates compared to the LD hens. Plumage loss in the LB+ flocks started at 23 to 25 weeks of age, and deteriorated continuously. The LD hens showed only moderate feather loss on the head/neck region, which started at 34 to 41 weeks and remained almost constant until the end of the observations. Compared to feather loss, injuries occurred in the LB+ hens with a delay of several weeks, with a maximum of 8% to 12% of hens affected. In contrast, skin injuries were observed only sporadically in single LD hens. In all batches, hybrid had an effect on the occurrence of feather loss (p < 0.05). Within the LB+ strain, the proportions of hens affected by plumage loss and injuries differed among batches (p < 0.05), whereas this was not the case in the LD flocks. Thus, severe feather pecking and cannibalism seemed to occur in the conventional layer hybrids but not in the dual-purpose hens, though both genetic strains were raised and managed under the same semi-commercial conditions. Therefore, keeping dual-purpose hens should also be considered as an alternative approach to avoid injurious pecking in laying hen husbandry.


Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis.
The TSC1-TSC2/Rheb/Raptor-mTOR/S6K1 cell growth cassette has recently been shown to regulate cell autonomous insulin and insulin-like growth factor I (IGF-I) sensitivity by transducing a negative feedback signal that targets insulin receptor substrates 1 and 2 (IRS1 and -2). Using two cell culture models of the familial hamartoma syndrome, tuberous sclerosis, we show here that Raptor-mTOR and S6K1 are required for phosphorylation of IRS1 at a subset of serine residues frequently associated with insulin resistance, including S307, S312, S527, S616, and S636 (of human IRS1). Using loss- and gain-of-function S6K1 constructs, we demonstrate a requirement for the catalytic activity of S6K1 in both direct and indirect regulation of IRS1 serine phosphorylation. S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T,P sites. IRS1 is preferentially depleted from the high-speed pellet fraction in TSC1/2-deficient mouse embryo fibroblasts or in HEK293/293T cells overexpressing Rheb. These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 cell autonomously promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and thus potentially in lesions associated with tuberous sclerosis.


Ring structures in microstructured polymer optical fibres.
Recent developments in polymer microstructured optical fibres allow for the realisation of microstructures in fibres that would be problematic to fabricate using glass-based capillary stacking. We present one class of such structures, where the holes lie on circular rings. A fibre of this type is fabricated and shown to be single moded for relatively long lengths of fibre, whereas shorter lengths are multimoded. An average index model for these fibres is developed. Comparison of its predictions to the calculated properties of the exact structure indicates that the ring structures emulate homogeneous rings of lower refractive index resulting in the ring structured fibres behaving approximately as cylindrically layered fibres.


Repetitive hyperbaric oxygen treatment increases insulin sensitivity in diabetes patients with acute intracerebral hemorrhage.
The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This study aims to investigate whether the peripheral insulin sensitivity of type 2 diabetes patients suffering from intracerebral hemorrhage can be increased after HBOT. Fifty-two type 2 diabetes participants were recruited after being diagnosed with intracerebral hemorrhage in our hospital. Insulin sensitivity was measured by the glucose infusion rate during a hyperinsulinemic euglycemic clamp (80 mU m-2 min-1) at baseline and 10 and 30 days after HBOT sessions. Serum insulin, fasting glucose, and hemoglobin A1C were measured in fasting serum at baseline and after HBOT sessions. In addition, early (∼10 days after onset) and late (1 month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. In response to HBOT, the glucose infusion rate was increased by 37.8%±5.76% at 1 month after onset compared with baseline. Reduced serum insulin, fasting glucose, and hemoglobin A1C were observed after HBOT. Both early and late outcomes of the HBOT group were improved compared with baseline (P<0.001). In the control group, there was significant difference only in the late outcome (P<0.05). In the assessment of efficacy, there were statistically significant differences between the groups when comparing changes in NIHSS scores at 10 days and 1 month after onset (P<0.05). Peripheral insulin sensitivity was increased following HBOT in type 2 diabetes patients with intracerebral hemorrhage. The HBOT used in this study may be effective for diabetes patients with acute stroke and is a safe and harmless adjunctive treatment.


Parameterized algorithmics for finding connected motifs in biological networks.
We study the NP-hard LIST-COLORED GRAPH MOTIF problem which, given an undirected list-colored graph G = (V, E) and a multiset M of colors, asks for maximum-cardinality sets S ⊆ V and M' ⊆ M such that G[S] is connected and contains exactly (with respect to multiplicity) the colors in M'. LIST-COLORED GRAPH MOTIF has applications in the analysis of biological networks. We study LIST-COLORED GRAPH MOTIF with respect to three different parameterizations. For the parameters motif size |M| and solution size |S|, we present fixed-parameter algorithms, whereas for the parameter |V| - |M|, we show W[1]-hardness for general instances and achieve fixed-parameter tractability for a special case of LIST-COLORED GRAPH MOTIF. We implemented the fixed-parameter algorithms for parameters |M| and |S|, developed further speed-up heuristics for these algorithms, and applied them in the context of querying protein-interaction networks, demonstrating their usefulness for realistic instances. Furthermore, we show that extending the request for motif connectedness to stronger demands, such as biconnectedness or bridge-connectedness leads to W[1]-hard problems when the parameter is the motif size |M|.


Aerobic exercise of low to moderate intensity corrects unequal changes in BK(Ca) subunit expression in the mesenteric arteries of spontaneously hypertensive rats.
Accumulating evidence indicates that hypertension is associated with "ion channel remodeling" of vascular smooth muscle cells (VSMCs). The objective of this study was to determine the effects of exercise intensity/volume on hypertension-associated changes in large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels in mesenteric arteries (MAs) from spontaneously hypertensive rats (SHR). Male SHRs were randomly assigned to three groups: a low-intensity aerobic exercise group (SHR-L: 14 m/min), a moderate-intensity aerobic exercise group (SHR-M: 20 m/min), and a sedentary group (SHR). Age-matched Wistar-Kyoto rats (WKYs) were used as normotensive controls. Exercise groups completed an 8-week exercise program. Elevation of the alpha and beta1 proteins was unequal in MA myocytes from SHRs, with the beta1 subunit increasing more than the alpha subunit. BK(Ca) contribution to vascular tone regulation was higher in the myocytes and arteries of SHRs compared to WKYs. SHR BK(Ca) channel subunit protein expression, beta1/alpha ratio, whole cell current density and single-channel open probability was also increased compared with WKYs. Aerobic exercise lowered systemic blood pressure and normalized hypertension-associated BK(Ca) alterations to normotensive control levels in the SHRs. These effects were more pronounced in the moderate-intensity group than in the low-intensity group. There is a dose-effect for aerobic exercise training in the range of low to moderate-intensity and accompanying volume for the correction of the pathological adaptation of BK(Ca) channels in myocytes of MAs from SHR.


Issues in developing a faculty evaluation system.
The increasing demands for accountability in higher education are resulting in calls for important personnel decisions--such as promotion, tenure, pay, and continuation--to be based directly on the outcomes of systematic faculty evaluations. This article provides a step-by-step procedure for developing a fair and meaningful faculty evaluation system on which such personnel decisions can be based. The procedure systematically involves faculty and administrators in the design and development of a faculty evaluation program that reflects the unique values, priorities, and heritage of an institution. The resultant faculty evaluation system integrates data from students, peers, and administrators to provide meaningful evaluative information for both faculty use in self-improvement efforts and administrative use in making personnel decisions that are based on a valid and reliable faculty performance record.


Early childhood education and life-cycle health.
This study forecasts the life-cycle treatment effects on health of a high-quality early childhood program. Our predictions combine microsimulation using nonexperimental data with experimental data from a midlife long-term follow-up. The follow-up incorporated a full epidemiological exam. The program mainly benefits males and significantly reduces the prevalence of heart disease, stroke, cancer, and mortality across the life-cycle. For men, we estimate an average reduction of 3.8 disability-adjusted life years (DALYs). The reduction in DALYs is relatively small for women. The gain in quality-adjusted life years is almost enough to offset all of the costs associated with program implementation for males and half of program costs for women.


How you count carbon matters: implications of differing cookstove carbon credit methodologies for climate and development cobenefits.
The opportunity to apply for carbon credits for cookstove projects creates a source of funding that can be leveraged to promote the "win-win" environmental and development benefits of improved cookstoves. Yet, as in most environment-development efforts, unacknowledged trade-offs exist under the all-encompassing "win-win" claims. This study therefore compares different scenarios for calculating cookstove carbon credits, including comparing different types of stoves using different fuels, different methodologies and theoretical scenarios to account for a range of climate-relevant emissions. The results of the study highlight the following: 1) impacts of different assumptions made within carbon credit methodologies, 2) discussion around potential trade-offs in such projects, and 3) considerations needed to truly promote sustainable development. The Gold Standard methodology was more comprehensive in its accounting and generally calculated more carbon credits per scenario than the Clean Development Mechanism methodology. Including black carbon in calculations would be more reflective of climate-relevant stove emissions and greatly increase the number of credits calculated. As health and other development benefits are not inherently included in carbon credit calculations, to achieve "win-win" outcomes, deliberate decisions about project design need to be made to ensure objectives are met and not simply assumed.


Toxin production and antimicrobial resistance of Escherichia coli river water isolates.
To establish the types of E. coli isolates that are found in river water around Nairobi and to assess the potential risk of use of this water to human health. Multiple stratified sampling was carried out. Surface sampling was used in the entire study. The study was carried out on river waters surrounding Nairobi, Kenya. Forty Escherichia coli strains isolated from river water. Serotyping, toxin gene tests and susceptibility to tetracyclines, ampicillin, chloramphenicol and kanamycin were analysed. None of the isolates could be specifically serotyped using the available antisera. Toxin gene production tests using the colony hybridisation technique revealed that nine (22.5%) of the strains were positive for heat stable (ST) toxin, seven (17.5%) to the heat labile (LT) toxin and two (5%) to both. Using the Agar Disk Diffusion technique, eighty per cent of the strains were susceptible to all four antibiotics, while twenty per cent of the strains showed multiple resistance. None of the strains was resistant to all four antibiotics while no strain showed resistance to kanamycin. None of the E. coli isolates was serotypable and it was therefore not possible to determine whether serologically identical strains of ETEC were haboured by man or animals. Toxin gene tests results showed that there is some risk of infection by diarrhoea causing ETEC to man and animals. Toxin gene tests results showed that there is some risk of infection by diarrhoea causing ETEC to man and animals if they consume this water untreated and there is evidence to show resistance of bacteria to antibiotics, hence appropriate health measures should be adhered to.


Albiglutide for the management of type 2 diabetes.
Albiglutide is a long acting GLP-1 receptor agonist (GLP-1 RA) administered by weekly injection and approved for use in type 2 diabetes. It has less gastrointestinal side effects than other GLP-1 RAs in current use but does not improve HbA1c or promote weight loss to the same extent as some competitor agents. Area covered: The current use of albiglutide is discussed. The review encompassed a search of PubMed and a thorough analysis of the European Union and US Food and Drug Administration approval documents. Expert opinion: Unlike competitor agents, the gastrointestinal side effects of albiglutide are not much greater than placebo. It has been studied and appears safe at all stages of renal failure. There exists concern about an imbalance of pancreatitis cases in the approval program as well as injection site reactions which led to discontinuance of therapy in up to 2% of participants. A large long-term study is now underway to determine if albiglutide, with its relatively favorable GI tolerance, has a place in the treatment of patients with increased risk of cardiovascular events. At present, albiglutide is a safe agent to introduce GLP-1 RA treatment into the regimen for type 2 diabetes patients and may be the GLP-1 agent of choice in patients with renal insufficiency.


Identifying and quantifying Phakopsora pachyrhizi spores in rain.
In summers of 2005 and 2006, rain was collected weekly at over 100 selected National Atmospheric Deposition Program/National Trends Network sites across the soybean-growing region of the central and eastern United States. Rain samples were screened for Phakopsora pachyrhizi (causal agent of soybean rust) DNA using a nested real-time polymerase chain reaction assay. Over this time frame, P. pachyrhizi spores were detected in every state in the study, but more frequently in states along the Gulf and Atlantic coasts and along the Ohio River Valley westward to Kansas. A bimodal temporal distribution of samples testing positive for P. pachyrhizi was found in both years. However, there was a greater than threefold increase in the number of samples testing positive for P. pachyrhizi in 2006 compared with 2005, with the most significant increase in August. There was also an increase in the average number of spores per sample in 2006 relative to 2005. Sequence analysis of a subset of positive samples was used to validate the assay results. From the sequence analysis, two reliable polymorphic regions were found, resulting in six distinct genotypes. One genotype was found in 56% of the samples tested, whereas the other genotypes were found less frequently.


Passively Q-switched erbium-doped fiber laser using evanescent field interaction with gold-nanosphere based saturable absorber.
We demonstrate an all-fiber passively Q-switched erbium-doped fiber laser (EDFL) using a gold-nanosphere (GNS) based saturable absorber (SA) with evanescent field interaction. Using the interaction of evanescent field for fabricating SAs, long nonlinear interaction length of evanescent wave and GNSs can be achieved. The GNSs are synthesized from mixing solution of chloroauricacid (HAuCl4) and sodium citrate by the heating effects of the microfiber's evanescent field radiation. The proposed passively Q-switched EDFL could give output pulses at 1562 nm with pulse width of 1.78 μs, a repetition rate of 58.1 kHz, a pulse energy of 133 nJ and a output power of 7.7 mW when pumped by a 980 nm laser diode of 237 mW.


Distinct short-range ovule signals attract or repel Arabidopsis thaliana pollen tubes in vitro.
Pollen tubes deliver sperm after navigating through flower tissues in response to attractive and repulsive cues. Genetic analyses in maize and Arabidopsis thaliana and cell ablation studies in Torenia fournieri have shown that the female gametophyte (the 7-celled haploid embryo sac within an ovule) and surrounding diploid tissues are essential for guiding pollen tubes to ovules. The variety and inaccessibility of these cells and tissues has made it challenging to characterize the sources of guidance signals and the dynamic responses they elicit in the pollen tubes. Here we developed an in vitro assay to study pollen tube guidance to excised A. thaliana ovules. Using this assay we discerned the temporal and spatial regulation and species-specificity of late stage guidance signals and characterized the dynamics of pollen tube responses. We established that unfertilized A. thaliana ovules emit diffusible, developmentally regulated, species-specific attractants, and demonstrated that ovules penetrated by pollen tubes rapidly release diffusible pollen tube repellents. These results demonstrate that in vitro pollen tube guidance to excised A. thaliana ovules efficiently recapitulates much of in vivo pollen tube behaviour during the final stages of pollen tube growth. This assay will aid in confirming the roles of candidate guidance molecules, exploring the phenotypes of A. thaliana pollen tube guidance mutants and characterizing interspecies pollination interactions.


Scattering of a Gaussian beam by an elliptical cylinder using the vectorial complex ray model.
The scattered waves of a shaped beam by an infinite cylinder in the far field are, stricto sensu, neither cylindrical nor spherical, so the asymptotic form of special functions involved in the theories based on the rigorous solution of Maxwell equations cannot be used to evaluate scattered intensities, even in the most simple case of Gaussian beam scattering by an infinite circular cylinder. Thus, although theories exist for the scattering of a shaped beam by infinite cylinders with circular and elliptical sections, the numerical calculations are limited to the near field. The vectorial complex ray model (VCRM) developed by Ren et al. describes waves by rays with a new property: the curvature of the wavefront. It is suitable to deal with the scattering of an arbitrarily shaped beam by a particle with a smooth surface of any form. In this paper, we apply this method to the scattering of an infinite elliptical cylinder illuminated by a Gaussian beam at normal incidence with an arbitrary position and orientation relative to the symmetric axis of the elliptical section of the cylinder. The method for calculating the curvature of an arbitrary surface is given and applied in the determination of the two curvature radii of the Gaussian beam wavefront at any point. Scattered intensities for different parameters of the beam and the particle as well as observation distance are presented to reveal the scattering properties and new phenomena observed in the beam scattering by an infinite elliptical cylinder.


Overweight or obese BMI is associated with earlier, but not later survival after common acute illnesses.
Obesity has been associated with improved short-term mortality following common acute illness, but its relationship with longer-term mortality is unknown. Observational study of U.S. Health and Retirement Study (HRS) participants with federal health insurance (fee-for-service Medicare) coverage, hospitalized with congestive heart failure (N = 4287), pneumonia (N = 4182), or acute myocardial infarction (N = 2001), 1996-2012. Using cox proportional hazards models, we examined the association between overweight or obese BMI (BMI ≥ 25.0 kg/m2) and mortality to 5 years after hospital admission, adjusted for potential confounders measured at the same time as BMI, including age, race, sex, education, partnership status, income, wealth, and smoking status. Body mass index (BMI) was calculated from self-reported height and weight collected at the HRS survey prior to hospitalization (a median 1.1 year prior to hospitalization). The referent group was patients with a normal BMI (18.5 to < 25.0 kg/m2). Patients were a median of 79 years old (IQR 71-85 years). The majority of patients were overweight or obese: 60.3% hospitalized for heart failure, 51.5% for pneumonia, and 61.6% for acute myocardial infarction. Overweight or obese BMI was associated with lower mortality at 1 year after hospitalization for congestive heart failure, pneumonia, and acute myocardial infarction-with adjusted hazard ratios of 0.68 (95% CI 0.59-0.79), 0.74 (95% CI: 0.64-0.84), and 0.65 (95%CI: 0.53-0.80), respectively. Among participants who lived to one year, however, subsequent survival was similar between patients with normal versus overweight/obese BMI. In older Americans, overweight or obese BMI was associated with improved survival following hospitalization for congestive heart failure, pneumonia, and acute myocardial infarction. This association, however, is limited to the shorter-term. Conditional on surviving to one year, we did not observe a survival advantage associated with excess weight.


Epidemiology and individual, household and geographical risk factors of podoconiosis in Ethiopia: results from the first nationwide mapping.
Although podoconiosis is one of the major causes of tropical lymphoedema and is endemic in Ethiopia its epidemiology and risk factors are poorly understood. Individual-level data for 129,959 individuals from 1,315 communities in 659 woreda (districts) were collected for a nationwide integrated survey of lymphatic filariasis and podoconiosis. Blood samples were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests. A clinical algorithm was used to reach a diagnosis of podoconiosis by excluding other potential causes of lymphoedema of the lower limb. Bayesian multilevel models were used to identify individual and environmental risk factors. Overall, 8,110 of 129,959 (6.2%, 95% confidence interval [CI] 6.1-6.4%) surveyed individuals were identified with lymphoedema of the lower limb, of whom 5,253 (4.0%, 95% CI 3.9-4.1%) were confirmed to be podoconiosis cases. In multivariable analysis, being female, older, unmarried, washing the feet less frequently than daily, and being semiskilled or unemployed were significantly associated with increased risk of podoconiosis. Attending formal education and living in a house with a covered floor were associated with decreased risk of podoconiosis. Podoconiosis exhibits marked geographical variation across Ethiopia, with variation in risk associated with variation in rainfall, enhanced vegetation index, and altitude.


Scissors-grip model for DNA recognition by a family of leucine zipper proteins.
C/EBP is a sequence-specific DNA binding protein that regulates gene expression in certain mammalian cells. The region of the C/EBP polypeptide required for specific recognition of DNA is related in amino acid sequence to other regulatory proteins, including the Fos and Jun transforming proteins. It has been proposed that these proteins bind DNA via a bipartite structural motif, consisting of a dimerization interface termed the "leucine zipper" and a DNA contact surface termed the "basic region." An evaluation of the properties of conserved amino acids within the basic region of 11 deduced protein sequences, coupled with the observation that they are located at an invariant distance from the leucine zipper, has led to the formulation of a "scissors-grip" model for DNA binding. The architectural features of this model are well suited for interaction with directly abutted, dyadsymmetric DNA sequences. Data supportive of the model were obtained with chemical probes of protein: DNA complexes.


ADAM9 is involved in pathological retinal neovascularization.
Pathological ocular neovascularization, caused by diabetic retinopathy, age-related macular degeneration, or retinopathy of prematurity, is a leading cause of blindness, yet much remains to be learned about its underlying causes. Here we used oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) to assess the contribution of the metalloprotease-disintegrin ADAM9 to ocular neovascularization in mice. Pathological neovascularization in both the OIR and CNV models was significantly reduced in Adam9(-/-) mice compared to wild-type controls. In addition, the level of ADAM9 expression was strongly increased in endothelial cells in pathological vascular tufts in the OIR model. Moreover, tumor growth from heterotopically injected B16F0 melanoma cells was reduced in Adam9(-/-) mice compared to controls. In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR. Collectively, these results suggest that ADAM9 could be an attractive target for the prevention of proliferative retinopathies, CNV, and cancer.


A comparison of normal versus low dietary carbohydrate intake on substrate oxidation during and after moderate intensity exercise in women.
We compared the effects of consuming a 2-day low-carbohydrate (CHO) diet (low-CHO; 20% CHO, 40% protein, 40% fat) versus an isocaloric 2-day moderate-CHO diet (mod-CHO; 55% CHO, 15% protein, 30% fat) on substrate oxidation during and after exercise in ten active, young women. Subjects were 24.9 ± 6.2% body fat with a VO(2max) of 68.8 ± 13.8 ml/kg FFM/min. For 2 days prior to exercise, subjects consumed either the mod-CHO or the low-CHO diet and then completed treadmill exercise at 55% of VO(2max) until 350 kcal of energy was expended. During exercise and for 2 h post-exercise, expired gases were analyzed to determine oxidation rates for CHO (CHO-OX) and fat (FAT-OX). Significant differences (p < 0.05) were found between diets for CHO-OX and FAT-OX (mg/kg FFM/min) during exercise, 1 h post-ex, and 2 h post-ex. During exercise, FAT-OX was higher (low-CHO 8.7 ± 2.2 vs. mod-CHO 6.2 ± 2.2) and CHO-OX was lower (low-CHO 25.1 ± 5.6 vs. mod-CHO 31.1 ± 6.2) following the low-CHO diet. A similar trend was observed during 1 h post-ex for FAT-OX (low-CHO 2.2 ± 0.5 vs. mod-CHO 1.6 ± 0.5) and CHO-OX (low-CHO 2.5 ± 1.2 vs. mod-CHO 4.1 ± 1.9), as well as 2 h post-ex for FAT-OX (low-CHO vs. 1.9 ± 0.5 mod-CHO 1.7 ± 0.4) and CHO-OX (low-CHO 2.5 ± 0.9 vs. mod-CHO 3.1 ± 1.1). Significant positive correlations were observed between VO(2max) and CHO-OX during exercise and post-exercise, as well as significant negative correlations between VO(2max) and FAT-OX post-exercise in the low-CHO condition. Waist circumference and FAT-OX exhibited a significant negative correlation during exercise in the low-CHO condition. Dietary macronutrient intake influenced substrate oxidation in active young women during and after moderate intensity exercise.


Src kinase has a central role in in vitro cellular internalization of Staphylococcus aureus.
Traditionally recognized as an extracellular pathogen, the Gram-positive bacterium Staphylococcus aureus can also be internalized by a variety of cell types in vitro. Internalization is known to involve binding of the host extracellular protein fibronectin to the bacterium, recognition of the fibronectin-coated bacterium by the fibronectin-binding integrin alpha5beta1 on the host cell surface, and integrin-mediated internalization. Here we examine elements of mammalian cell signalling pathways involved in S. aureus internalization. The mouse fibroblast cell line GD25, in which the gene encoding the beta1 integrin subunit is inactivated, has been complemented with a beta1 integrin cDNA encoding a tyrosine (Y) to phenylalanine (F) mutation in each of the two beta1 integrin intracellular NPXY motifs. This cell line, GD25beta1 A Y783/795F, is defective in migration on fibronectin coated surfaces and intracellular signalling activities involving the tyrosine kinase Src. GD25beta1 A Y783/795F cells have a decreased ability to internalize S. aureus compared to GD25beta1 A cells expressing wild-type beta1 integrins. Furthermore, using mouse embryo fibroblasts in which different members of the Src family kinases are genetically inactivated, we demonstrate that optimal internalization is dependent on expression of Src kinase. Interferon, which has been implicated in repression of the effects of the viral homologue of Src inhibits internalization of S. aureus indicating that internalization may be blocked by inhibitors of Src kinase function. We then demonstrate that Src family kinase specific inhibitors effectively block S. aureus internalization into HeLa cells leading to the conclusion that a function unique to Src is required for optimal internalization of S. aureus in vitro.


Yield of Repeat 3D Angiography in Patients with Aneurysmal-Type Subarachnoid Hemorrhage.
Aneurysmal-type subarachnoid hemorrhage is a serious disease with high morbidity and mortality. When no aneurysm is found, the patient remains at risk for rebleeding. Negative findings for SAH on angiography range from 2% to 24%. Most previous studies were based on conventional 2D imaging. 3D rotational angiography depicts more aneurysms than 2D angiography. The purpose of this study was to evaluate the yield of repeat 3D rotational angiography in patients with aneurysmal-type SAH with negative initial 3D rotational angiography findings and to classify the initial occult aneurysms. Between March 2013 and January 2016, 292 patients with SAH and an aneurysmal bleeding pattern were admitted. Of these 292 patients, 30 (10.3%; 95% CI, 7.3%-14.3%) had initial negative 3D rotational angiography findings within 24 hours. These patients underwent a second 3D rotational angiography after 7-10 days. In 8 of 30 patients (26.7%; 95% CI, 14.0%-44.7%) with initial negative 3D rotational angiography findings, a ruptured aneurysm was found on repeat 3D rotational angiography. Three of 8 initial occult aneurysms were very small (1-2 mm), 2 were supraclinoid carotid artery dissecting aneurysms (2 and 8 mm), 2 were small (1 and 3 mm) basilar perforator aneurysms, and 1 was a 3-mm vertebral artery dissecting aneurysm. In 10% of patients with aneurysmal-type SAH, initial 3D rotational angiography findings were negative, and in 1 in 4, repeat 3D rotational angiography demonstrated a ruptured aneurysm. Initial occult aneurysms were dissecting aneurysms of perforators or main arteries or were very small (1-2 mm) or both. Our results indicate that repeat 3D rotational angiography is mandatory in patients with initial 3D rotational angiography findings negative for aneurysmal-type SAH.


IgA plasma cells in vascular tissue of patients with Kawasaki syndrome.
The etiology and pathogenesis of Kawasaki syndrome (KS) remain unknown. Clinical and epidemiologic features of KS are consistent with an infectious cause. To search for an etiologic agent of KS, a phage cDNA expression library was constructed from the aorto-iliac junction of a patient with fatal acute KS and screened with convalescent KS serum followed by anti-human Ig. Unexpectedly, 0.1% of the clones in the library react with anti-human Ig, indicating the presence of many Ig-producing B lymphocytes in the vasculitic tissue. To confirm this finding and to determine the isotypes produced, frozen vascular tissue sections from the patient and paraffin sections from coronary arteries from six additional patients with fatal acute or subacute KS were incubated with Abs to Ig isotypes. Histopathology of the tissues revealed the presence of many plasma cells in the inflammatory infiltrate. IgA was the predominant isotype produced in vascular tissue in all seven KS patients. IgM- and IgG-producing cells were less often detected. We conclude that there is a marked plasma cell response within the vasculitic tissue in KS, with unusual IgA production locally in this nonlymphoid, nonmucosal tissue. We suggest that the prominence of IgA plasma cells in the vascular infiltrate in the early, acute, and subacute stages of KS indicates an Ag-driven immune response to an etiologic agent with a respiratory or gastrointestinal portal of entry and speculate that this unusual immune response is integral to the pathogenesis of the illness.


Asiatic acid isolated from Centella asiatica inhibits TGF-β1-induced collagen expression in human keloid fibroblasts via PPAR-γ activation.
Keloids are fibroproliferative disorders characterized by exuberant extracellular matrix deposition and transforming growth factor (TGF)-β/Smad pathway plays a pivotal role in keloid pathogenesis. Centella asiatica extract has been applied in scar management for ages. As one of its major components, asiatic acid (AA) has been recently reported to inhibit liver fibrosis by blocking TGF-β/Smad pathway. However, its effect on keloid remains unknown. In order to investigate the effects of AA on cell proliferation, invasion and collagen synthesis, normal and keloid fibroblasts were exposed to TGF-β1 with or without AA. Relevant experiments including 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2-deoxyuridine (EdU) incorporation assay, Transwell invasion assay, enzyme-linked immunosorbent assay, Western blot, quantitative polymerase chain reaction and RNA interference assay were conducted. As a result, keloid fibroblasts showed higher responsiveness to TGF-β1 stimulation than normal fibroblasts in terms of invasion and collagen synthesis. AA could suppress TGF-β1-induced expression of collagen type I, inhibit Smad 2/3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) expression, while elevate Smad 7 protein level. Noteworthy, the effects of AA on keloid fibroblasts could be abrogated by PPAR-γ antagonist GW9662 and by silencing of PPAR-γ. The present study demonstrated that AA inhibited TGF-β1-induced collagen and PAI-1 expression in keloid fibroblasts through PPAR-γ activation, which suggested that AA was one of the active constituents of C. asiatica responsible for keloid management, and could be included in the arsenal for combating against keloid.


Renewable Energy from Finite Resources: Example of Emerging Photovoltaics.
Renewable energies, such as sunlight, wind and geothermal heat, are resources that are replaced rapidly by natural processes. However, wind, hydro and solar installations strictly require raw materials that are, in fact, not renewable. Many raw materials are already facing a supply shortage which cannot be easily overcome. This work reviews the problem of critical raw material (CRM) use in photovoltaics (PV) as an example and explains why supply cannot be easily increased to meet demand. We discuss whether there is indeed a 'struggle for elements' in a Darwinian sense, which ultimately leads to a 'survival of the fittest' race in renewable energy technology. In the case of PV, the perception of the definition of 'fittest' needs to change from that considering energy conversion efficiency alone to that which holistically considers net energy produced per emission under the premise that sufficient environmentally and socially acceptable raw material supply exists for renewable energies and all other sectors.


First-order fiber Bragg grating inscription in indium fluoride fiber using a UV/Vis femtosecond laser and two-beam interferometry.
Fiber gratings are among key components in fiber-based photonics systems and, particularly, laser cavities. In the latter, they can play multiple roles, such as those of mirrors, polarizers, filters, or dispersion compensators. In this Letter, we present the inscription of highly reflective first-order fiber Bragg gratings (FBGs) in soft indium fluoride-based (InF3) fibers using a two-beam phase-mask interferometer and a femtosecond laser. We demonstrate an enhanced response of InF3-based fiber to a visible (400 nm) inscription wavelength compared to ultraviolet irradiation at 266 nm. In this way, FBGs with a reflectivity >99.7% were inscribed at around 1.9 µm with the bandwidth of 2.68 nm. After thermal annealing at 393K, the Bragg wavelength demonstrates stable thermal shift of 20 pm/K in the temperature range 293-373K. These observations suggest a potential extension of InF3 fiber-based laser components to an operational range of up to 5 µm.


In-SEM micro-machining reveals the origins of the size effect in the cutting energy.
High-precision metal cutting is increasingly relevant in advanced applications. Such precision normally requires a cutting feed in the micron or even sub-micron dimension scale, which raises questions about applicability of concepts developed in industrial scale machining. To address this challenge, we have developed a device to perform linear cutting with force measurement in the vacuum chamber of an electron microscope, which has been utilised to study the cutting process down to 200 nm of the feed and the tool tip radius. The machining experiments carried out in-operando in SEM have shown that the main classical deformation zones of metal cutting: primary, secondary and tertiary shear zones-were preserved even at sub-micron feeds. In-operando observations and subsequent structural analysis in FIB/SEM revealed a number of microstructural peculiarities, such as: a substantial increase of the cutting force related to the development of the primary shear zone; dependence of the ternary shear zone thickness on the underlaying grain crystal orientation. Measurement of the cutting forces at deep submicron feeds and cutting tool apex radii has been exploited to discriminate different sources for the size effect on the cutting energy (dependence of the energy on the feed and tool radius). It was observed that typical industrial values of feed and tool radius imposes a size effect determined primarily by geometrical factors, while in a sub-micrometre feed range the contribution of the strain hardening in the primary share zone becomes relevant.


Cryptococcus neoformans inhibits nitric oxide synthesis caused by CpG-oligodeoxynucleotide-stimulated macrophages in a fashion independent of capsular polysaccharides.
Cryptococcus neoformans is eradicated by macrophages via production of NO. Unmethylated CpG-ODN protect mice from infection with this fungal pathogen by inducing IFN-gamma. The present study was designed to elucidate the effect of C. neoformans on the synthesis of NO by alveolar macrophages. For this purpose, MH-S, an alveolar macrophage cell line, was stimulated with CpG-ODN in the presence of IFN-gamma. A highly virulent strain of C. neoformans with thick capsule suppressed the production of NO. Capsular polysaccharides were not essential for this suppression, because there was no difference between acapsular mutant (Cap67) and its parent strain. Physical or close interaction of Cap67 with MH-S was necessary, as shown by the loss of such effect when direct contact was interfered by nitrocellulose membrane. Similar effects were observed by disrupted as well as intact Cap67. Whereas the inhibitory effect of intact Cap67 was completely abrogated by heat treatment, disrupted Cap67 did not receive such influence. Finally, disrupted Cap67 did not show any inhibitory effect on the TLR9-mediated activation of NF-kappaB in a luciferase reporter assay with HEK293T cells, although the TLR4-mediated activation was suppressed. These results revealed that C. neoformans suppressed the synthesis of NO by CpG-ODN and IFN-gamma-stimulated macrophages in a fashion independent of capsular polysaccharides, although the precise mechanism remains to be elucidated.


Risk factors for persistent chronic widespread pain: a community-based study.
Chronic widespread pain is the cardinal clinical feature of the fibromyalgia syndrome, which, in the majority of clinic patients, is persistent. By contrast, in community-derived patients, pain is persistent in only half of the affected individuals, particularly those with psychological distress. Whether such distress is a consequence of the pain or a manifestation of a wider process of somatization which is associated with the persistence of pain is unclear. We tested in a large, prospective, population-based study the hypothesis that features of somatization predict the persistence of chronic widespread pain. In all, 252 (13%) of 1953 adult subjects selected from a population register were classified as having chronic widespread pain based on a detailed questionnaire which included a pain drawing. The patients also completed a number of psychosocial instruments which measure features known to be associated with somatization. Two hundred and twenty-five (91%) of the patients were successfully followed up after 12 months and provided data on pain status using the same instruments. In all, 126 (56%) patients reported chronic widespread pain at follow-up, 74 (33%) reported other pain and 25 (11%) reported no pain. Persistent chronic widespread pain was strongly associated with baseline test scores for high psychological distress and fatigue. In addition, these subjects were more likely to display a pattern of illness behaviour characterized by frequent visits to medical practitioners for symptoms which disrupt daily activities. The prevalence of persistent pain increased with the number of risk factors the subjects were exposed to. Although almost half of the cases of chronic widespread pain resolved within 1 yr, this study has demonstrated for the first time that those subjects who display features of somatization are more likely to have widespread pain which persists. These findings have implications for the identification and treatment of persons with persistent chronic widespread pain.


Mitochondrial metabolism of glucose and glutamine is required for intracellular growth of Toxoplasma gondii.
Toxoplasma gondii proliferates within host cell vacuoles where the parasite relies on host carbon and nutrients for replication. To assess how T. gondii utilizes these resources, we mapped the carbon metabolism pathways in intracellular and egressed parasite stages. We determined that intracellular T. gondii stages actively catabolize host glucose via a canonical, oxidative tricarboxylic acid (TCA) cycle, a mitochondrial pathway in which organic molecules are broken down to generate energy. These stages also catabolize glutamine via the TCA cycle and an unanticipated γ-aminobutyric acid (GABA) shunt, which generates GABA and additional molecules that enter the TCA cycle. Chemically inhibiting the TCA cycle completely prevents intracellular parasite replication. Parasites lacking the GABA shunt exhibit attenuated growth and are unable to sustain motility under nutrient-limited conditions, suggesting that GABA functions as a short-term energy reserve. Thus, T. gondii tachyzoites have metabolic flexibility that likely allows the parasite to infect diverse cell types.


Orthogonal projections to latent structures discriminant analysis modeling on in situ FT-IR spectral imaging of liver tissue for identifying sources of variability.
In this study, the orthogonal projections to latent structures discriminant analysis (OPLS-DA) method was used to assess the in situ chemical composition of two different cell types in mouse liver samples, hepatocytes and erythrocytes. High spatial resolution FT-IR microspectroscopy equipped with a focal plan array (FPA) detector is capable of simultaneously recording over 4000 spectra from 64 x 64 pixels with a maximum spatial resolution of about 5 microm x 5 microm, which allows for the differentiation of individual cells. The main benefit with OPLS-DA lies in the ability to separate predictive variation (between cell type) from variation that is uncorrelated to cell type in order to facilitate understanding of different sources of variation. OPLS-DA was able to differentiate between chemical properties and physical properties (e.g., edge effects). OPLS-DA model interpretation of the chemical features that separated the two cell types clearly highlighted proteins and lipids/bile acids. The modeled variation that was uncorrelated to cell type made up a larger portion of the total variation and displayed strong variability in the amide I region. This could be traced back to a gradient in the high intensity (high-density) areas vs the low intensity areas (close to empty areas) that as a result of normalization had an adverse effect on FT-IR spectral profiles. This highlights that OPLS-DA provides an effective solution to identify different sources of variability, both predictive and uncorrelated, and also facilitates understanding of any sampling, experimental, or preprocessing issues.


Microbial diversity and activity in the Nematostella vectensis holobiont: insights from 16S rRNA gene sequencing, isolate genomes, and a pilot-scale survey of gene expression.
We have characterized the molecular and genomic diversity of the microbiota of the starlet sea anemone Nematostella vectensis, a cnidarian model for comparative developmental and functional biology and a year-round inhabitant of temperate salt marshes. Molecular phylogenetic analysis of 16S rRNA gene clone libraries revealed four ribotypes associated with N. vectensis at multiple locations and times. These associates include two novel ribotypes within the ε-Proteobacterial order Campylobacterales and the Spirochetes, respectively, each sharing <85% identity with cultivated strains, and two γ-Proteobacterial ribotypes sharing >99% 16S rRNA identity with Endozoicomonas elysicola and Pseudomonas oleovorans, respectively. Species-specific PCR revealed that these populations persisted in N. vectensis asexually propagated under laboratory conditions. cDNA indicated expression of the Campylobacterales and Endozoicomonas 16S rRNA in anemones from Sippewissett Marsh, MA. A collection of bacteria from laboratory raised N. vectensis was dominated by isolates from P. oleovorans and Rhizobium radiobacter. Isolates from field-collected anemones revealed an association with Limnobacter and Stappia isolates. Genomic DNA sequencing was carried out on 10 cultured bacterial isolates representing field- and laboratory-associates, i.e., Limnobacter spp., Stappia spp., P. oleovorans and R. radiobacter. Genomes contained multiple genes identified as virulence (host-association) factors while S. stellulata and L. thiooxidans genomes revealed pathways for mixotrophic sulfur oxidation. A pilot metatranscriptome of laboratory-raised N. vectensis was compared to the isolate genomes and indicated expression of ORFs from L. thiooxidans with predicted functions of motility, nutrient scavenging (Fe and P), polyhydroxyalkanoate synthesis for carbon storage, and selective permeability (porins). We hypothesize that such activities may mediate acclimation and persistence of bacteria in a N. vectensis holobiont defined by both internal and external gradients of chemicals and nutrients in a dynamic coastal habitat.


The role of fibrinolytic genes and proteins in the development of allograft vascular disease.
We have previously shown that lack of plasminogen activator inhibitor-1 (PAI-1) expression in donor tissue greatly increases intimal proliferation (IP) after allogeneic transplantation. We sought to determine the relative role of PAI-1 and other fibrinolytic proteins in the development of IP. We used an abdominal aortic transplant model in mice to investigate IP in 3 groups of 6 recipients. In the isograft group, CBA/J strain mice were donors and recipients, donors for allograft group were C57BL/6J mice, and for the allograft/knockout group, C57BL/6J PAI-1 knockout mice. All groups received weekly injections of anti-CD8/CD4 monoclonal antibodies. IP was calculated at 50 days, and sections were analyzed for fibrinolytic proteins, messenger RNA (mRNA) and PAI-1 activity using immunohistochemistry (IHC), in situ hybridization (ISH), reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analysis. Significantly more IP developed in the allograft/knockout group vs the isograft (p < 0.001) and the allograft groups (p = 0.003). There was marked intimal expression of tissue plasminogen activator (tPA), urokinase PA (uPA), and uPA receptor (uPAR) proteins and mRNA in the allograft and allograft/knockout groups vs the isograft group. Allografts also showed significant intimal staining for PAI-1 protein and mRNA. RT-PCR demonstrated a stepwise increase in profibrinolytic protein mRNA from isograft to allograft to allograft/knockout groups, particularly uPA (p = 0.02) and uPAR (p = 0.016). Western blot data showed complementary findings. PAI-1 activity was persistently present in isograft and allograft animals, only. Intimas in allograft and allograft/knockout groups were primarily smooth muscle cells. PAI-1 reduces IP by limiting smooth muscle cell activity, with little change in matrix composition likely by modulating profibrinolytic protein expression.


Doxycycline-mediated inhibition of choroidal neovascularization.
Doxycycline, a broad-spectrum antibiotic, has certain antiangiogenic properties and can inhibit matrix metalloproteinases (MMPs/gelatinases). The authors investigated the effects of doxycycline on choroidal neovascularization (CNV) and regulation of MMP-2 and -9 and pigment epithelium-derived factor (PEDF). Doxycycline was orally administered to rats at 500, 50, 5, and 0.5 mg/kg/d; nontreated animals were used as controls. Experimental CNV was induced with laser 7 days after doxycycline treatment started. At 7 days after induction, animals were euthanatized, and eyes were collected. RPE/choroid flatmounts were labeled with isolectin IB4 to determine CNV lesion volumes using confocal microscopy and high-performance 3D imaging software. MMP-2, MMP-9, and PEDF protein levels were determined by ELISA. MMP catalytic activity was determined in solution using fluorogenic gelatin and peptide substrates, by gelatin zymography in SDS-PAGE, and by in situ fluorogenic substrate zymography in RPE/choroid sections. CNV complex lesion volumes decreased with doxycycline in a dose-response relationship. A dosage of 500 mg/kg/d caused a 70% inhibition of CNV complex volume compared with control animals. Doxycycline elevated PEDF levels in plasma and did not affect the active and pro-enzymes MMP-2 and MMP-9 levels. However, the in vitro enzymatic activities of purified MMP-2 and MMP-9 declined significantly with doxycycline. MMP-2, MMP-9, and gelatinolytic activities in situ increased early in CNV lesion development. Doxycycline treatments and exogenous additions inhibited gelatinolytic activities in CNV lesions. Doxycycline effectively hampered the progression of experimental CNV. The results suggest that orally administrated doxycycline can reach the choroid to attenuate proteolytic enzymes that remodel Bruch's membrane and promote the antiangiogenic PEDF to inhibit neovascularization.


Milk-derived bioactive peptides and their health promoting effects: a potential role in atherosclerosis.
Bioactive peptides derived from milk proteins are food components that, in addition to their nutritional value, retain many biological properties and have therapeutic effects in several health disorders, including cardiovascular disease. Amongst these, atherosclerosis is the underlying cause of heart attack and strokes. It is a progressive dyslipidaemic and inflammatory disease where accumulation of oxidized lipids and inflammatory cells leads to the formation of an atherosclerotic plaque in the vessel wall. Milk-derived bioactive peptides can be released during gastrointestinal digestion, food processing or by enzymatic and bacterial fermentation and are considered to promote diverse beneficial effects such as lipid lowering, antihypertensive, immnomodulating, anti-inflammatory and antithrombotic effects. In this review, an overview of the diverse biological effects of these compounds is given, particularly focusing on their beneficial properties on cardiovascular disease and proposing novel mechanisms of action responsible for their bioactivity. Attempts to prevent cardiovascular diseases target modifications of several risk factors such as high blood pressure, obesity, high blood concentrations of lipids or insulin resistance. Milk-derived bioactive peptides are a source of health-enhancing components and the potential health benefit of these compounds has a growing commercial potential. Consequently, they have been incorporated as ingredients in functional foods, as dietary supplements and as pharmaceuticals to promote health and reduce risk of chronic diseases.


PHT3D-UZF: A Reactive Transport Model for Variably-Saturated Porous Media.
A modified version of the MODFLOW/MT3DMS-based reactive transport model PHT3D was developed to extend current reactive transport capabilities to the variably-saturated component of the subsurface system and incorporate diffusive reactive transport of gaseous species. Referred to as PHT3D-UZF, this code incorporates flux terms calculated by MODFLOW's unsaturated-zone flow (UZF1) package. A volume-averaged approach similar to the method used in UZF-MT3DMS was adopted. The PHREEQC-based computation of chemical processes within PHT3D-UZF in combination with the analytical solution method of UZF1 allows for comprehensive reactive transport investigations (i.e., biogeochemical transformations) that jointly involve saturated and unsaturated zone processes. Intended for regional-scale applications, UZF1 simulates downward-only flux within the unsaturated zone. The model was tested by comparing simulation results with those of existing numerical models. The comparison was performed for several benchmark problems that cover a range of important hydrological and reactive transport processes. A 2D simulation scenario was defined to illustrate the geochemical evolution following dewatering in a sandy acid sulfate soil environment. Other potential applications include the simulation of biogeochemical processes in variably-saturated systems that track the transport and fate of agricultural pollutants, nutrients, natural and xenobiotic organic compounds and micropollutants such as pharmaceuticals, as well as the evolution of isotope patterns.


Nuclear magnetic resonance detects phosphoinositide 3-kinase/Akt-independent traits common to pluripotent murine embryonic stem cells and their malignant counterparts.
Pluripotent embryonic stem (ES) cells, a potential source of somatic precursors for cell therapies, cause tumors after transplantation. Studies of mammalian carcinogenesis using nuclear magnetic resonance (NMR) spectroscopy have revealed changes in the choline region, particularly increased phosphocholine (PCho) content. High PCho levels in murine ES (mES) cells have recently been attributed to cell pluripotency. The phosphoinositide 3-kinase (PI3K)/Akt pathway has been implicated in tumor-like properties of mES cells. This study aimed to examine a potential link between the metabolic profile associated with choline metabolism of pluripotent mES cells and PI3K/Akt signaling. We used mES (ES-D3) and murine embryonal carcinoma cells (EC-F9) and compared the metabolic profiles of 1) pluripotent mES (ESD0), 2) differentiated mES (ESD14), and 3) pluripotent F9 cells. Involvement of the PI3K/Akt pathway was assessed using LY294002, a selective PI3K inhibitor. Metabolic profiles were characterized in the extracted polar fraction by (1)H NMR spectroscopy. Similarities were found between the levels of choline phospholipid metabolites (PCho/total choline and PCho/glycerophosphocholine [GPCho]) in ESD0 and F9 cell spectra and a greater-than five-fold decrease of the PCho/GPCho ratio associated with mES cell differentiation. LY294002 caused no significant change in relative PCho levels but led to a greater-than two-fold increase in PCho/GPCho ratios. These results suggest that the PCho/GPCho ratio is a metabolic trait shared by pluripotent and malignant cells and that PI3K does not underlie its development. It is likely that the signature identified here in a mouse model may be relevant for safe therapeutic applications of human ES cells.


The spontaneous brain activity of disgust: Perspective from resting state fMRI and resting state EEG.
In recent years, more and more studies on disgust have shown the association between disgust and various psychopathologies. Revealing the spontaneous brain activity patterns associated with disgust sensitivity from the perspective of individual differences will give us an insight into the neurologic nature of disgust and its psychopathological vulnerability. Here, we used two modal brain imaging techniques (resting fMRI and resting EEG) to reveal spontaneous brain activity patterns closely related to disgust sensitivity. The amplitude of low-frequency fluctuation results showed that disgust sensitivity is negatively correlated with the spontaneous activity of the right cerebellum crus II and positively correlated with the spontaneous activity of the right superior frontal cortex, which are inhibition-related brain regions. Furthermore, the microstate results of rest EEG indicated that the corrected duration, occurrence rate, and contribution of Class C, which is related to the anterior default mode network and is considered to be related to subjective representation of one' own body by combining interoceptive information with affective salience, were significantly positively correlated with the disgust sensitivity level. This data-driven approach provides the first evidence on the intrinsic brain features of disgust sensitivity based on two resting-state brain modalities. The results represent an initial effort to uncover the neurological basis of disgust sensitivity and its connection to psychopathology.


Accuracy of Functional Movement Screen Deep Squat Scoring and the Influence of Optimized Scoring Criteria: A 3-Dimensional Kinematic Approach.
The deep squat (DS) test is a component of the functional movement screen, which is used to assess the quality of fundamental movement patterns; however, the accuracy of the DS has not been studied. The DS is a complex, total body movement pattern with evaluation required at several points along the kinematic chain. To assess the accuracy of DS scoring by an athletic trainer, physical therapist, and exercise science professional via a comparative analysis with kinematic data (KD) and to identify scoring criteria that would improve agreement between raters and KD scores. Cross-sectional study. Motion analysis laboratory. A rater from each of 3 movement science disciplines rated the DS of 23 male college athletes (20.3 [1.2] y; 70.5 [3.5] kg). Subjects were outfitted with reflective markers and asked to perform the DS. The DS performance was scored by 3 raters and kinematic analysis. Subsequently, the optimal set of criteria that minimized the difference between mode rater score and KD was determined via a Nelder-Mead simplex optimization routine. Intraclass correlation coefficients (ICCs) were calculated using SPSS (version 23; IBM, Armonk, NY) to determine tester agreement with the KD score and between the mode score and KD score. Agreement was poor for the athletic trainer (ICC = .387), physical therapist (ICC = .298), exercise science professional (ICC = .378), and raters' DS scores when compared with the KD. Agreement was poor for the mode score when compared with KD prior to optimization and good following optimization (ICC = .830), thereby allowing identification of specific scoring errors. Agreement for DS scores is poor when compared with KD; however, it may be improved with optimization of DS scoring criteria.


Introduction of newborn care within integrated community case management in Uganda.
Uganda's Ministry of Health, together with partners, has introduced integrated community case management (iCCM) for children under 5 years. We assessed how the iCCM program addresses newborn care in three midwestern districts through document reviews, structured interviews, and focus group discussions with village health team (VHT) members trained in iCCM, caregivers, and other stakeholders. Almost all VHT members reported that they refer sick newborns to facilities and could identify at least three newborn danger signs. However, they did not identify the most important clinical indicators of severe illness. The extent of compliance with newborn referral and quality of care for newborns at facilities is not clear. Overall iCCM is perceived as beneficial, but caregivers, VHTs, and health workers want to do more for sick babies at facilities and in communities. Additional research is needed to assess the ability of VHTs to identify newborn danger signs, referral compliance, and quality of newborn treatment at facilities.


Shift in Steroidogenesis in the Ovarian Follicles of the Goldfish (Carassius auratus) during Gonadotropin-Induced Oocyte Maturation: (oocyte maturation/gonadotropin/steroidogenesis/ovarian follicle/goldfish).
Both partially purified chum salmon gonadotropin and 17α-hydroxyprogesterone stimulated in vitro production of testosterone by postvitellogenic follicles of goldfish (Carassius auratus). Chum salmon gonadotropin further enhanced the conversion of exogenously supplied 17α-hydroxyprogesterone to 17α, 20β-dihydroxy-4-pregnen-3-one. The increased medium concentrations of 17α, 20β-dihydroxy-4-pregnen-3-one were associated with the induction of final oocyte maturation. The capacity of postvitellogenic follicles to produce steroids in response to exogenous 17α-hydroxyprogesterone was examined in females at various stages of final oocyte maturation following the administration of human chorionic gonadotropin in vivo combined with elevation of holding temperature. The maximum production of testosterone in response to 17α-hydroxyprogesterone was obtained in follicles from initial controls. In contrast, 17α 20β-diOHprog production was very low in initial controls and markedly increased during oocyte maturation (3-6 hr following injection), followed by a significant decrease in follicles collected at 15 hr. Estradiol-17β production by the follicles was very low at any stages of gonadotropin-induced oocyte maturation. These results suggest that gonadotropin-induced shift in the biosynthetic pathway in the follicle from the secretion of predominantly testosterone to 17α, 20β-dihydroxy-4-pregnen-3-one secretion is a prerequisite step for the induction of oocyte maturation in goldfish.


Evolutionary origins of multidrug and drug-specific efflux pumps in bacteria.
The available genomic sequences of three pathogenic and three nonpathogenic bacteria were analyzed to identify known and putative drug-specific and multidrug resistance transport systems. Escherichia coli was found to encode 29 such pumps, and with the exception of the archaebacterium Methanococcus jannaschii, the numbers of multidrug efflux pumps encoded within genomes of the other organisms were found to be approximately proportional to their total numbers of encoded transport systems as well as to total genome size. The similar numbers of chromosomally encoded multidrug efflux systems in pathogens and nonpathogens suggests that these transporters have not arisen recently in pathogens in response to antimicrobial chemotherapy. Phylogenetic analyses of the four transporter families that contain drug efflux permeases indicate that drug resistance arose rarely during the evolution of each family and that the diversity of current drug efflux pumps within each family arose from just one or a very few primordial systems. However, although the ability to confer drug efflux appears to have emerged on only a few occasions in evolutionary time and was stably maintained as an evolutionary trait, modulation of the substrate specificities of these systems has occurred repeatedly. A speculative model is presented that may explain the apparent capability of these multidrug transport systems to mediate drug transport from the cytoplasm or directly from the phospholipid bilayer.


Concentrated expression of Ca2+/ calmodulin-dependent protein kinase II and protein kinase C in the mushroom bodies of the brain of the honeybee Apis mellifera L.
We have previously used the differential display method to identify a gene that is expressed preferentially in the mushroom bodies of worker honeybees and to show that it encodes a putative inositol 1,4,5-trisphosphate receptor (IP3R) homologue (Kamikouchi et al. [1998] Biochem. Biophys. Res. Commun. 242:181-186). In the present study, we examined whether the expression of some of the genes for proteins involved in the intracellular Ca2+ signal transduction is also concentrated in the mushroom bodies of the honeybee by isolating cDNA fragments that encode the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) homologues of the honeybee. In situ hybridization analysis revealed that the expression of these genes was also concentrated in the mushroom bodies of the honeybee brain: The CaMKII gene was expressed preferentially in the large-type Kenyon cells of the mushroom bodies, whereas that for PKC was expressed in both the large and small types of Kenyon cells. The expression of the genes for IP3R and CaMKII was concentrated in the mushroom bodies of the queen and drone as well as in those of the worker bee. Furthermore, the enzymatic activities of CaMKII and PKC were found to be higher in the mushroom bodies/central bodies than in the optic and antennal lobes of the worker bee brain. These results suggest that the function of the intracellular Ca2+ signal transduction is enhanced in Kenyon cells in comparison to other neuronal cell types in the honeybee brain.


Mirrorless lasing from mesostructured waveguides patterned by soft lithography
Mesostructured silica waveguide arrays were fabricated with a combination of acidic sol-gel block copolymer templating chemistry and soft lithography. Waveguiding was enabled by the use of a low-refractive index (1.15) mesoporous silica thin film support. When the mesostructure was doped with the laser dye rhodamine 6G, amplified spontaneous emission was observed with a low pumping threshold of 10 kilowatts per square centimeter, attributed to the mesostructure's ability to prevent aggregation of the dye molecules even at relatively high loadings within the organized high-surface area mesochannels of the waveguides. These highly processible, self-assembling mesostructured host media and claddings may have potential for the fabrication of integrated optical circuits.


The Feasibility of Laparoscopic Surgery in Gynecologic Oncology for Obese and Morbidly Obese Patients.
Surgical interventions are the mainstay of treatment for many gynecological cancers. Although minimally invasive surgery offers many potential advantages, performing laparoscopic pelvic surgery in obese patients remains challenging. To overcome this, many centers have shifted their practice to robotic surgery; however, the high costs associated with robotic surgery are concerning and limit its use. This study aimed to examine the feasibility of performing laparoscopic gynecologic oncology procedures in obese and morbidly obese patients. This retrospective study evaluated patients who underwent laparoscopic surgeries by a gynecologic oncologist from January 2012 to June 2016 at a designated gynecologic oncology center. Patients were categorized as nonobese (body mass index [BMI] < 30 kg/m), obese (BMI 30-39.9 kg/m), and morbidly obese (BMI ≥ 40 kg/m). Intra and postoperative complications and outcomes were recorded. Group differences were computed with Kruskal-Wallis nonparametric test (continuous) or Fisher exact test (categorical). Of 497 patients, 288 were nonobese (58%), 162 obese (33%), and 47 morbidly obese (9%). Complex surgical procedures were performed in 57.4% of obese patients and 55.3% of morbidly obese patients. Although morbidly obese and obese patients had longer operative times (mean of 181 and 166 minutes vs 144 minutes, P = 0.014), conversion from laparoscopy to laparotomy occurred in 9.05% of all patients, with no group differences. Low intraoperative (9%-11%) and severe postoperative (2.41%) complication rates were observed overall, with no group differences. There was no statistically significant difference in the rate of emergency room visits 30 days postoperation between the 3 BMI groups (P = 0.6108). Average length of postoperative stay was statistically significant (P = 0.0003) but was low overall (1-2 days). Hospital readmission rates were low, with the lowest rate among morbidly obese patients (2.13%). Our data suggest that laparoscopic gynecologic-oncology procedures for obese patients are feasible and safe.


Effects of resin hydrophilicity on water sorption and changes in modulus of elasticity.
As acidic monomers of self-etching adhesives are incorporated into dental adhesives at high concentrations, the adhesive becomes more hydrophilic. Water sorption by polymers causes plasticization and lowers mechanical properties. The purpose of this study was to compare the water sorption and modulus of elasticity (E) of five experimental neat resins (EX) of increasing hydrophilicity, as ranked by their Hoy's solubility parameters and five commercial resins. After measuring the initial modulus of all resin disks by biaxial flexure, half the specimens were stored in hexadecane and the rest were stored in water. Repeated measurements of stiffness were made for 3 days. Water sorption and solubility measurements were made in a parallel experiment. None of the specimens stored in oil showed any significant decrease in modulus. All resins stored in water exhibited a time-dependent decrease in modulus that was proportional to their degree of water sorption. Water sorption of EX was proportional to Hoy's solubility parameter for polar forces (delta(p)) with increasing polarity resulting in higher sorption. The least hydrophilic resin absorbed 0.55 wt% water and showed a 15% decrease in modulus after 3 days. The most hydrophilic experimental resin absorbed 12.8 wt% water and showed a 73% modulus decrease during the same period. The commercial resins absorbed between 5% and 12% water that was associated with a 19-42% reduction in modulus over 3 days.


Correlation between potassium channel expression and sensitivity to drug-induced cell death in tumor cell lines.
Plasma membrane (PM) and mitochondrial (mt) ion channels - particularly potassium channels - became oncological targets soon after the discovery that they are involved both in the regulation of proliferation and apoptosis. Some members of the Kv Shaker family, namely Kv1.1, Kv1.3, Kv1.5 and Kv11.1 (Herg), and the intermediate-conductance calcium-activated potassium KCa3.1 (IK) channels have been shown to contribute to apoptosis in various cell lines. Kv1.3, Kv1.5 and IK are located in the plasma membrane but also in the mitochondrial inner membrane, where they participate in apoptotic signalling. Interestingly, an altered protein expression of some of the channels mentioned above has been reported in neoplastic cell lines/tissues, but a systematic quantification addressing the protein expression of the above potassium channels in tumor cell lines of different origin has not been carried out yet. In the present study we investigated whether expression of specific potassium channels, at the mRNA and protein level, can be correlated with cell sensitivity to various apoptotic stimuli, including chemotherapeutic drugs, in a panel of cancer cell lines. The results show correlation between the protein expression of the Kv1.1 and Kv1.3 channels and susceptibility to death upon treatment with staurosporine, C2-ceramide and cisplatin. Furthermore, we investigated the correlation between Kv channel expression and sensitivity to three distinct membrane-permeant Kv1.3 inhibitors, since these drugs have recently been shown to be able to induce apoptosis and also reduce tumor volume in an in vivo model. Higher protein expression of Kv1.3 significantly correlated with lower cell survival upon treatment with clofazimine, one of the Kv1.3 inhibitors. These results suggest that expression of Kv1.1 and Kv1.3 sensitizes tumour cells of various origins to cytotoxins. Data reported in this work regarding potassium channel protein expression in different cancer cell lines may be exploited for pharmacological manipulation aiming to affect proliferation/apoptosis of cancer cells.