Motion compensation for cone-beam CT using Fourier consistency conditions.
In cone-beam CT, involuntary patient motion and inaccurate or irreproducible scanner motion substantially degrades image quality. To avoid artifacts this motion needs to be estimated and compensated during image reconstruction. In previous work we showed that Fourier consistency conditions (FCC) can be used in fan-beam CT to estimate motion in the sinogram domain. This work extends the FCC to [Formula: see text] cone-beam CT. We derive an efficient cost function to compensate for [Formula: see text] motion using [Formula: see text] detector translations. The extended FCC method have been tested with five translational motion patterns, using a challenging numerical phantom. We evaluated the root-mean-square-error and the structural-similarity-index between motion corrected and motion-free reconstructions. Additionally, we computed the mean-absolute-difference (MAD) between the estimated and the ground-truth motion. The practical applicability of the method is demonstrated by application to respiratory motion estimation in rotational angiography, but also to motion correction for weight-bearing imaging of knees. Where the latter makes use of a specifically modified FCC version which is robust to axial truncation. The results show a great reduction of motion artifacts. Accurate estimation results were achieved with a maximum MAD value of 708 μm and 1184 μm for motion along the vertical and horizontal detector direction, respectively. The image quality of reconstructions obtained with the proposed method is close to that of motion corrected reconstructions based on the ground-truth motion. Simulations using noise-free and noisy data demonstrate that FCC are robust to noise. Even high-frequency motion was accurately estimated leading to a considerable reduction of streaking artifacts. The method is purely image-based and therefore independent of any auxiliary data.


Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A.
The protease encoded by the human immunodeficiency virus (HIV) processes the viral gag and gag-pol protein precursor by posttranslational cleavage. In this study we have demonstrated by site-specific mutagenesis (Asp----Thr) and by pepstatin A inhibition that the recombinant HIV protease is an aspartic-type protease. Furthermore, incubation of HIV-infected H9 cells with pepstatin A inhibited part of the intracellular processing of the HIV gag protein yet had no apparent toxicity on HIV-infected cells during 48 hr of incubation.


Intracranial embryonal cell carcinoma.
Intracranial embryonal cell carcinoma (ECC) is a germ cell tumor most frequently found in the pineal region. However, little is known about the incidence, pattern of growth, or response to treatment of ECC. Between 1975 and 1983, 16 consecutive patients younger than age 18 with tumors of the pineal region have had biopsies performed prior to treatment, and 5 (31%) have had primary intracranial ECC. One other child had ECC in the suprasellar region. The clinical, radiographic, and histologic features of the six patients with ECC are presented and contrasted with the findings in children with other pineal region neoplasms. Pathologic confirmation is necessary to distinguish ECC from other intracranial tumors. Three patients were treated with radiation therapy (RT) plus adjuvant chemotherapy; two patients were treated with chemotherapy followed by RT; and one was treated with RT only. All patients initially responded to therapy, but only one has survived for longer than 1 year. It is concluded that biopsy is necessary for the diagnosis of ECC; that ECC is more common than currently believed; and that current treatment for intracranial ECC is unsatisfactory. Biopsy of pineal region tumors is necessary if progress is to be made in their management.


Physical Therapists' Choices, Views and Agreements Regarding Non-Pharmacological and Non-Surgical Interventions for Knee Osteoarthritis Patients: A Mixed-Methods Study.
The aims of this study are to collect the most common non-pharmacological and non-surgical interventions used by the Portuguese physical therapists in their knee osteoarthritis patients, and to deeper understand the factors associated to their intervention choices. This study incorporated a mixed-methods design. For the quantitative data it was choose an e-survey (with 25 close-end questions, plus general information of the study and a clinical vignette), retrieving sociodemographic and self-reported practice on knee osteoarthritis information. It was analysed response frequencies and associations between variables with logistic regression analyses. For the qualitative data, it was chosen to perform semi-structured interviews in purposefully selected physical therapists to include different sociodemographic factors and survey responses regarding the physical therapists' interventions chosen. After the interviews, the audios were collected, anonymised, transcribed verbatim, and the texts explored by the thematic approach. From the 277 PTs that shown interest in participating in the study, 120 fully completed the questionnaire and, from those, 10 participated in the interviews. The most chosen interventions included Resistance Exercise, Manual Therapy, Nutrition/Weight Loss, Self-care/Education, Stretching and Aquatic Exercise. Furthermore, it seems that PTs' individual characteristics (age, experience, and clinical reasoning), patient's characteristics (clinical findings and preferences), and work-related factors (facility type, work environment and available resources) are the main actors responsible for an intervention chosen. In the Portuguese PTs context the most important interventions are Exercise, Manual Therapy, Nutrition/Weight Loss, and Self-care/Education; these interventions chosen may be influenced by PT, patient and work-related factors.


Activation of NLRP3 inflammasome in alveolar macrophages contributes to mechanical stretch-induced lung inflammation and injury.
Mechanical ventilation of lungs is capable of activating the innate immune system and inducing sterile inflammatory response. The proinflammatory cytokine IL-1β is among the definitive markers for accurately identifying ventilator-induced lung inflammation. However, mechanisms of IL-1β release during mechanical ventilation are unknown. In this study, we show that cyclic stretch activates the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes and induces the release of IL-1β in mouse alveolar macrophages via caspase-1- and TLR4-dependent mechanisms. We also observed that NADPH oxidase subunit gp91(phox) was dispensable for stretch-induced cytokine production, whereas mitochondrial generation of reactive oxygen species was required for stretch-induced NLRP3 inflammasome activation and IL-1β release. Further, mechanical ventilation activated the NLRP3 inflammasomes in mouse alveolar macrophages and increased the production of IL-1β in vivo. IL-1β neutralization significantly reduced mechanical ventilation-induced inflammatory lung injury. These findings suggest that the alveolar macrophage NLRP3 inflammasome may sense lung alveolar stretch to induce the release of IL-1β and hence may contribute to the mechanism of lung inflammatory injury during mechanical ventilation.


A novel method in predicting immediate postoperative facial nerve function post acoustic neuroma excision.
To determine whether the percentage calculated by dividing the amplitude of postexcision direct facial nerve stimulus responses (at pontomedullary junction) by the amplitude of distal ipsilateral transcutaneous (stylomastoid region) maximal stimulus responses and response amplitude progression by increasing stimulus intensities have predictive value for determining normal or near-normal (House-Brackmann Grade 1 or 2) immediate postoperative facial nerve function. Intraoperative recordings of three muscle groups: 1) frontalis, 2) orbicularis oculi, and 3) orbicularis oris. Postexcision direct facial nerve stimulation at the pontomedullary junction and transcutaneous maximal facial nerve stimulation at the ipsilateral stylomastoid region and their associated response amplitudes were recorded. Tertiary referral center. Patients who underwent acoustic neuroma surgery from January 2004 to March 2006 with intraoperative facial nerve monitoring and an intact facial nerve after tumor excision were included. Recordings were available for 38 patients. With a stimulus intensity of 0.3 mA at the root exit zone, there was an 81% positive predictive value in patients that exhibited a compound action potential of greater than 20% of maximum (sensitivity, 81%). This increased to 93% when the compound action potential was greater than 50% of maximum. When the amplitude increase was greater than 5 microV, there was a 77% positive predictive value (sensitivity, 87%). The percentage of the response amplitude of direct facial nerve stimulation at the pontomedullary junction when compared with the maximum response amplitude of ipsilateral transcutaneous stimulation at the stylomastoid foramen is a good predictor of normal to near-normal immediate postoperative facial nerve function. Progression of amplitude response also seems to be a good predictor of normal to near-normal immediate postoperative facial nerve function.


Acute effects of aspartame on concentrations of brain amines and their metabolites in selected brain regions of Fischer 344 and Sprague-Dawley rats.
This study is the first in a series to define a rodent model to document the effects of amino acid-modulating compounds on central neurotransmitter function. A time-response curve for a single dose of orally intubated aspartame was determined in male Fischer 344 and Sprague-Dawley rats. Regional brain concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites were analyzed in the hypothalamus, cerebellum, pons/medulla, hippocampus, striatum, cortex, and midbrain/thalamus at 30, 60, 120, or 240 min after oral aspartame (1000 mg/kg) administration. Without consideration for time and group variables, levels of most compounds were higher in the brain regions of Fischer than Sprague-Dawley rats. Aspartame in Fischer 344 or Sprague-Dawley rats had no significant effect on levels of the catecholamines or indoleamines at any of the time points monitored following its acute administration. From the results of this study, large oral loads of aspartame do not appear to lead to regional alterations in brain biogenic amine levels.


Understanding the Role of SARS-CoV-2 ORF3a in Viral Pathogenesis and COVID-19.
The ongoing SARS-CoV-2 pandemic has shocked the world due to its persistence, COVID-19-related morbidity and mortality, and the high mutability of the virus. One of the major concerns is the emergence of new viral variants that may increase viral transmission and disease severity. In addition to mutations of spike protein, mutations of viral proteins that affect virulence, such as ORF3a, also must be considered. The purpose of this article is to review the current literature on ORF3a, to summarize the molecular actions of SARS-CoV-2 ORF3a, and its role in viral pathogenesis and COVID-19. ORF3a is a polymorphic, multifunctional viral protein that is specific to SARS-CoV/SARS-CoV-2. It was acquired from β-CoV lineage and likely originated from bats through viral evolution. SARS-CoV-2 ORF3a is a viroporin that interferes with ion channel activities in host plasma and endomembranes. It is likely a virion-associated protein that exerts its effect on the viral life cycle during viral entry through endocytosis, endomembrane-associated viral transcription and replication, and viral release through exocytosis. ORF3a induces cellular innate and pro-inflammatory immune responses that can trigger a cytokine storm, especially under hypoxic conditions, by activating NLRP3 inflammasomes, HMGB1, and HIF-1α to promote the production of pro-inflammatory cytokines and chemokines. ORF3a induces cell death through apoptosis, necrosis, and pyroptosis, which leads to tissue damage that affects the severity of COVID-19. ORF3a continues to evolve along with spike and other viral proteins to adapt in the human cellular environment. How the emerging ORF3a mutations alter the function of SARS-CoV-2 ORF3a and its role in viral pathogenesis and COVID-19 is largely unknown. This review provides an in-depth analysis of ORF3a protein's structure, origin, evolution, and mutant variants, and how these characteristics affect its functional role in viral pathogenesis and COVID-19.


Clinical outcome and adverse effect profile associated with concurrent administration of alprazolam and imipramine.
Clinical outcome and adverse effects associated with concurrent alprazolam and imipramine administration were studied in 29 patients with major depressive disorder who completed a 6-week trial in which they served as their own controls. Alprazolam was added on Day 8 in gradually escalating, then gradually tapering dosages while imipramine dosages remained unchanged. Significant decreases were observed in scores on the Hamilton Rating Scales for Depression and Anxiety at all later evaluation days with Day 8 as baseline. The mean total Symptom and Side Effects score decreased significantly from Day 8 to Day 22 when alprazolam doses were 1 mg q.i.d. For most side effects, total number of reports remained constant or decreased from Day 1 to later evaluation days. Standing diastolic blood pressures were significantly lower on Day 22 than on Day 1. No significant relationship was found between any rating scale score and plasma concentration data.


Enhanced pathogenicity of Candida albicans pre-treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis.
To investigate the relative pathogenicity of Candida albicans treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis. Previous studies indicate that these cells secrete 10 times more farnesol than do untreated cells. In our usage, subinhibitory means a concentration which causes a prominent decrease in turbidity but still allows some cell growth. C. albicans A72 cells were grown overnight in 0-5.0 microM fluconazole, washed, and inoculated in mice by tail vein injection. Groups of 15 or 16 mice were injected with 1.3 x 10(6) cells and mortality was recorded for 7 days post-inoculation. The levels of farnesol in control and treated C. albicans were determined by GC/MS. The MIC50 for strain A72 was 0.125 mg/L (0.4 microM). Mice administered C. albicans pre-treated with 0.5 to 1.0 microM fluconazole died 2.5 to 4 days earlier and had 2 to 4 times higher mortality rates than mice given untreated C. albicans. Fluconazole (0.5 to 1.0 microM) pre-treated cells were 4.2 to 8.5 times more lethal (P < 0.001) than untreated cells. The extracellular, membrane bound, and intracellular farnesol concentrations of cells pre-treated with 1.0 muM fluconazole were 12-, 2- and 6-times those of untreated cells. The effects of fluconazole on C. albicans are very concentration-dependent. The enhanced pathogenicity of fluconazole pre-treated C. albicans in mice should be relevant to the therapeutic and prophylactic use of fluconazole. Further research is needed to explore whether farnesol production by C. albicans is a virulence factor.


Combined spatio-temporal impacts of climate and longline fisheries on the survival of a trans-equatorial marine migrant.
Predicting the impact of human activities and their derivable consequences, such as global warming or direct wildlife mortality, is increasingly relevant in our changing world. Due to their particular life history traits, long-lived migrants are amongst the most endangered and sensitive group of animals to these harming effects. Our ability to identify and quantify such anthropogenic threats in both breeding and wintering grounds is, therefore, of key importance in the field of conservation biology. Using long-term capture-recapture data (34 years, 4557 individuals) and year-round tracking data (4 years, 100 individuals) of a trans-equatorial migrant, the Cory's shearwater (Calonectris diomedea), we investigated the impact of longline fisheries and climatic variables in both breeding and wintering areas on the most important demographic trait of this seabird, i.e. adult survival. Annual adult survival probability was estimated at 0.914±0.022 on average, declining throughout 1978-1999 but recovering during the last decade (2005-2011). Our results suggest that both the incidental bycatch associated with longline fisheries and high sea surface temperatures (indirectly linked to food availability; SST) increased mortality rates during the long breeding season (March-October). Shearwater survival was also negatively affected during the short non-breeding season (December-February) by positive episodes of the Southern Oscillation Index (SOI). Indirect negative effects of climate at both breeding (SST) and wintering grounds (SOI) had a greater impact on survival than longliner activity, and indeed these climatic factors are those which are expected to present more unfavourable trends in the future. Our work underlines the importance of considering both breeding and wintering habitats as well as precise schedules/phenology when assessing the global role of the local impacts on the dynamics of migratory species.


Bayesian Population Physiologically-Based Pharmacokinetic (PBPK) Approach for a Physiologically Realistic Characterization of Interindividual Variability in Clinically Relevant Populations.
Interindividual variability in anatomical and physiological properties results in significant differences in drug pharmacokinetics. The consideration of such pharmacokinetic variability supports optimal drug efficacy and safety for each single individual, e.g. by identification of individual-specific dosings. One clear objective in clinical drug development is therefore a thorough characterization of the physiological sources of interindividual variability. In this work, we present a Bayesian population physiologically-based pharmacokinetic (PBPK) approach for the mechanistically and physiologically realistic identification of interindividual variability. The consideration of a generic and highly detailed mechanistic PBPK model structure enables the integration of large amounts of prior physiological knowledge, which is then updated with new experimental data in a Bayesian framework. A covariate model integrates known relationships of physiological parameters to age, gender and body height. We further provide a framework for estimation of the a posteriori parameter dependency structure at the population level. The approach is demonstrated considering a cohort of healthy individuals and theophylline as an application example. The variability and co-variability of physiological parameters are specified within the population; respectively. Significant correlations are identified between population parameters and are applied for individual- and population-specific visual predictive checks of the pharmacokinetic behavior, which leads to improved results compared to present population approaches. In the future, the integration of a generic PBPK model into an hierarchical approach allows for extrapolations to other populations or drugs, while the Bayesian paradigm allows for an iterative application of the approach and thereby a continuous updating of physiological knowledge with new data. This will facilitate decision making e.g. from preclinical to clinical development or extrapolation of PK behavior from healthy to clinically significant populations.


Acupuncture Treatment for Low Back Pain and Lower Limb Symptoms-The Relation between Acupuncture or Electroacupuncture Stimulation and Sciatic Nerve Blood Flow.
To investigate the clinical efficacy of acupuncture treatment for lumbar spinal canal stenosis and herniated lumbar disc and to clarify the mechanisms in an animal experiment that evaluated acupuncture on sciatic nerve blood flow. In the clinical trial, patients with lumbar spinal canal stenosis or herniated lumbar disc were divided into three treatment groups; (i) Ex-B2 (at the disordered level), (ii) electrical acupuncture (EA) on the pudendal nerve and (iii) EA at the nerve root. Primary outcome measurements were pain and dysesthesia [evaluated with a visual analogue scale (VAS)] and continuous walking distance. In the animal study, sciatic nerve blood flow was measured with laser-Doppler flowmetry at, before and during three kinds of stimulation (manual acupuncture on lumber muscle, electrical stimulation on the pudendal nerve and electrical stimulation on the sciatic nerve) in anesthetized rats. For the clinical trial, approximately half of the patients who received Ex-B2 revealed amelioration of the symptoms. EA on the pudendal nerve was effective for the symptoms which had not improved by Ex-B2. Considerable immediate and sustained relief was observed in patients who received EA at the nerve root. For the animal study, increase in sciatic nerve blood flow was observed in 56.9% of the trial with lumber muscle acupuncture, 100% with pudendal nerve stimulation and 100% with sciatic nerve stimulation. Sciatic nerve stimulation sustained the increase longer than pudendal nerve stimulation. One mechanism of action of acupuncture and electrical acupuncture stimulation could be that, in addition to its influence on the pain inhibitory system, it participates in causing a transient change in sciatic nerve blood blow, including circulation to the cauda equine and nerve root.


Radiologic Correlation Between the Ischiofemoral Space and Morphologic Characteristics of the Hip in Hips With Symptoms of Dysplasia.
The purpose of this study was to investigate radiologic correlation between the ischiofemoral space and morphologic findings in the hip in patients with symptomatic developmental dysplasia of the hip (DDH), borderline DDH, and femoroacetabular impingement (FAI). In 84 patients undergoing hip arthroscopic surgery, 108 hips were divided into three groups according to lateral center-edge angle (LCEA): DDH group (LCEA < 20°; 18 hips), borderline DDH group (20° ≤ LCEA < 25°; 26 hips), and FAI group (LCEA ≥ 25°; 64 hips). Ischiofemoral distance was evaluated by radiography and ischiofemoral space and quadratus femoris space by MRI. Software was used to measure the radiographic parameters LCEA, femoral neck-shaft angle, and femoral neck anteversion on preoperative CT scans. Ischiofemoral distance, ischiofemoral space, and quadratus femoris space were significantly smaller in the DDH and borderline DDH groups than in the FAI group. The prevalence of hips with ischiofemoral space < 17 mm was significantly higher in the DDH (10 of 18 patients [56%]) and borderline DDH (8 of 26 patients [31%]) groups than in the FAI group (4 of 64 patients [6%]). In addition, the prevalence of hips with a quadratus femoris space < 8 mm was significantly higher in the DDH (2 of 18 patients [11%]) and borderline DDH (3 of 26 patients [12%]) groups than in the FAI (0 of 64 patients [0%]) group. Femoral neck-shaft angle and femoral neck anteversion were significantly greater in the DDH group than in the FAI group. Ischiofemoral impingement syndromes can be considered more likely in patients with DDH than in those with FAI.


Distinguishable Colorimetric Biosensor for Diagnosis of Prostate Cancer Bone Metastases.
Castration-resistant prostate cancer (PCa) causes severe bone metastasis (BM), which significantly increases mortality in men with PCa. Imaging tests and radiometric scanning require long analysis times, expensive equipment, specialized personnel, and a slow turnaround. New visualization technologies are expected to solve the above problems. Nonetheless, existing visualization techniques barely meet the urgency for precise diagnosis because the human eyes cannot recognize and capture even slight variations in visual information. By using dye differentiated superposition enhancement colorimetric biosensors, an effective method to diagnose prostate cancer bone metastases (PCa-BM) with excellent accuracy for naked-eye quantitative detection of alkaline phosphatase (ALP) is developed. The biomarker ALP specific hydrolytic product ascorbic acid can be detected by rhodamine derivatives (Rd) as gold nanobipyramids (Au NBPs) are deposited and grown. Color-recombining enhancement effects between Rd and Au NBPs significantly improved abundance. The 150 U L-1 threshold between normal and abnormal can be identified by color. And with color enhancement effect and double signal response, the ALP index is visually measured to diagnose PCa-BM and provide handy treatment recommendations. Additionally, the proposed colorimetric sensing strategy can be used to diagnose other diseases.


Membrane association of a protein increases the rate, extent, and specificity of chemical cross-linking.
Many cellular processes involve interactions between membrane-associated proteins, and those interactions are enhanced by membrane association. We have used cross-linking reactions to compare the extent and specificity of protein interactions in solution versus on a membrane surface. Cysteine mutants of a soluble cytoplasmic fragment (CF) of the aspartate receptor, a transmembrane receptor involved in bacterial chemotaxis, are used in disulfide bond formation with the thiol-specific oxidant diamide and chemical cross-linking reactions with the trifunctional maleimide TMEA. CF binding to membranes is mediated by its N-terminal His tag binding to vesicles containing a nickel-chelating lipid, so cross-linking reactions conducted in the presence and absence of vesicles differ only in whether CF is bound to the vesicles or is free in solution. For multiple Cys throughout the CF, membrane association is shown to increase the rate and extent of these reactions. Cross-linking specificity, which is measured as the preference for cross-linking between Cys near each other in the native structure, is also enhanced by membrane association. These results provide an experimental demonstration that membrane binding enhances protein-protein interactions, an important consideration for understanding processes involving membrane-associated proteins. The experiments further demonstrate the importance of cross-linking conditions for these reactions that are often used to probe protein structure and dynamics and the potential of membrane association to restore native interactions of membrane-associated proteins for cross-linking studies.


Growth mechanism of amorphous selenium nanoparticles synthesized by Shewanella sp. HN-41.
Shewanella sp. HN-41 was exploited for selenium nanoparticles synthesis from aqueous selenite compounds under anaerobic conditions. Various reaction conditions, including reaction time, initial biomass, and initial selenite concentration, were systematically investigated to determine their effects on particle size distribution and formation rate. The biomass concentration of Shewanella sp. HN-41 had no significant effect on average particle size but strongly influenced reduction rate and size distribution. Initial selenite concentration (0.01-1.0 mM) also had no significant effect on the average particle size, but affected the early growth stage mechanism of selenium particle production, which was modeled using a Michaelis Menten model. The HR-TEM and SAED patterns indicated that the synthesized selenium nanoparticles were amorphous.


Molding and replication of ceramic surfaces with nanoscale resolution.
The design of reproducible and more efficient nanofabrication routes has become a very active research field in recent years. In particular, the development of new methods for micro- and nanopatterning materials surfaces has attracted the attention of many researchers in industry and academia as a consequence of the growing relevance of patterned surfaces in many technological fields, ranging from optoelectronics to biotechnology. In this work we explore, discuss, and demonstrate the possibility of extending the well-known molding and replication strategy for patterning ceramic materials with nanoscale resolution. To achieve this goal we have combined physical deposition methods, molecule-thick anti-sticking coatings, and nanostructured substrates as master surfaces. This new perspective on an "old technology", as molding is, provides an interesting alternative for high-resolution, direct surface-relief patterning of materials that currently requires expensive and time-consuming lithographic approaches.


Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice.
Nonalcoholic fatty liver disease (NAFLD) in non-obese patients remains a clinical condition with unclear etiology and pathogenesis. Using a metabolomics approach in a mouse model that recapitulates almost all the characteristic features of non-obese NAFLD, we aimed to advance mechanistic understanding of this disorder. Mice fed high fat, high cholesterol, cholate (HFHCC) diet for three weeks consistently developed hepatic pathology similar to NAFLD and nonalcoholic steatohepatitis (NASH) without changes to body weight or fat pad weights. Gas- and liquid chromatography/mass spectrometry-based profiling of lipidomic and primary metabolism changes in the liver and plasma revealed that systemic mechanisms leading to steatosis and hepatitis in this non-obese NAFLD model were driven by a combination of effects directed by elevated free cholesterol, cholesterol esters and cholic acid, and associated changes to metabolism of sphingomyelins and phosphatidylcholines. These results demonstrate that mechanisms underlying cholesterol-induced non-obese NAFLD are distinct from NAFLD occurring as a consequence of metabolic syndrome. In addition, this investigation provides one of the first metabolite reference profiles for interpreting effects of dietary and hepatic cholesterol in human non-obese NAFLD/NASH patients.


Temporal recruitment of transcription factors at the 3',5'-cyclic adenosine 5'-monophosphate-response element of the human GnRH-II promoter.
GnRH-II is a potent GnRH subtype involved in modulating OVCAR-3 cell proliferation and the invasive properties of JEG-3 cells, and an atypical cAMP-response element (CRE) in the human GnRH-II promoter influences its activation. We demonstrated that the GnRH-II promoter is activated by 8-bromoadenosine-cAMP in several cell lines including alphaT3, TE671, JEG-3, and OVCAR-3 cells and that cAMP enhances GnRH-II mRNA levels in JEG-3 and OVCAR-3 cells. Moreover, 8-bromoadenosine-cAMP increases cAMP response element-binding protein (CREB) phosphorylation in JEG-3 and OVCAR-3 cells and augments CBP and CCAAT/enhancer-binding protein (C/EBP)-beta coimmunoprecipitation with phosphorylated CREB (p-CREB) in a temporally defined manner from nuclear extracts. When CREB, CBP, and C/EBPbeta levels were knocked down by small interfering RNA, reductions in any of these transcription factors reduced cAMP-enhanced GnRH-II promoter activity and GnRH-II mRNA levels in JEG-3 and OVCAR-3 cells. Importantly, chromatin immunoprecipitation assay showed that p-CREB bound the CRE within the endogenous GnRH-II promoter within 1 h and that p-CREB association with C/EBPbeta occurs within 2 h of cAMP stimulation, coincident with the first appearance of C/EBPbeta at the CRE. By contrast, maximum interactions between p-CREB and CBP do not occur until at least 4 h after cAMP stimulation, and this is reflected in the progressive loading of CBP at the CRE at 2-4 h, as demonstrated by chromatin immunoprecipitation. Taken together, these data suggest that p-CREB, C/EBPbeta, and CBP are recruited to the CRE of the GnRH-II promoter in a temporarily defined manner to enhance its transcription in JEG-3 and OVCAR-3 cells in response to cAMP.


Beneficial effects of the novel cholecystokinin agonist (pGlu-Gln)-CCK-8 in mouse models of obesity/diabetes.
Cholecystokinin (CCK) is a rapidly degraded gastrointestinal peptide that stimulates satiety and insulin secretion. We aimed to investigate the beneficial weight-lowering and metabolic effects of the novel N-terminally modified CCK analogue, (pGlu-Gln)-CCK-8. The biological actions of (pGlu-Gln)-CCK-8 were comprehensively evaluated in pancreatic clonal BRIN BD11 cells and in vivo in high-fat-fed and ob/ob mice. (pGlu-Gln)-CCK-8 was completely resistant to enzymatic degradation and its satiating effects were significantly (p < 0.05 to p < 0.001) more potent than CCK-8. In BRIN-BD11 cells, (pGlu-Gln)-CCK-8 exhibited enhanced (p < 0.01 to p < 0.001) insulinotropic actions compared with CCK-8. When administered acutely to high-fat-fed or ob/ob mice, (pGlu-Gln)-CCK-8 improved glucose homeostasis. Sub-chronic twice daily injections of (pGlu-Gln)-CCK-8 in high-fat-fed mice for 28 days significantly decreased body weight (p < 0.05 to p < 0.001), accumulated food intake (p < 0.05 to p < 0.001), non-fasting glucose (p < 0.05) and triacylglycerol deposition in pancreatic (p < 0.01), adipose (p < 0.05) and liver (p < 0.001) tissue, and improved oral (p < 0.05) and i.p. (p < 0.05) glucose tolerance and insulin sensitivity (p < 0.001). Similar observations were noted in ob/ob mice given twice daily injections of (pGlu-Gln)-CCK-8. In addition, these beneficial effects were not reproduced by simple dietary restriction and were not associated with changes in energy expenditure. There was no evidence for development of tolerance to (pGlu-Gln)-CCK-8, and analysis of histology or blood-borne markers for pancreatic, liver and renal function in mice treated with (pGlu-Gln)-CCK-8 suggested little abnormal pathology. These studies emphasise the potential of (pGlu-Gln)-CCK-8 for the alleviation of obesity and insulin resistance.


Metal-free, organocatalytic syn diacetoxylation of alkenes.
A novel method for the organocatalytic syn diacetoxylation of alkenes has been developed using aryl iodides as efficient catalysts. A broad range of substrates, including electron-rich as well as electron-deficient alkenes, are smoothly transformed by the new procedure, furnishing the desired products in good to excellent yields with high diastereoselectivity (up to >19:1 dr).


A comparative study of risk factors for corneal infection in diabetic and non-diabetic patients.
To compare the clinical characteristics of infectious keratopathy in type 2 diabetes mellitus (T2DM) and non-diabetes mellitus (NDM) and to investigate risk factors for infectious keratopathy in T2DM patients. Totally 230 patients with T2DM and 168 with NDM diagnosed as infectious keratopathy were hospitalized at Qingdao Eye Hospital from 2001 to 2015. Data including sex, age, occupation, season, smoking and alcohol consumption habits, duration between onset and treatments, duration of hospitalization were collected. Initially identified indicators were analyzed with a multivariate logistic regression. Glycosylated hemoglobin A1c (HbA1c) in patients with T2DM was analyzed. The infectious keratopathies in the two groups were categorized and compared. The diabetic group consisted of 146 (63.5%) males and 84 (36.5%) females. The NDM group consisted of 111 (66.1%) males and 57 (33.9%) females. There was no signigicantly difference in sex distribution between the two groups (P>0.05). There were significant differences in age, occupation of patients, season of the onset of diseases, duration between onset and treatment, and durations of hospitalization between the two groups (P<0.05). In most of the patients in the diabetic group, the duration between onset and treatment was ≤3mo, and most was ≥3mo in the NDM group. Multivariate logistic regression analysis revealed that age and season were related to the development of corneal infection in the T2DM group (OR=1.709, 1.706). In the T2DM group, HbA1c was 9.09%±2.12%. There were statistically significant differences in the incidences of bacterial keratitis and herpes simplex keratitis in the two groups (P<0.05), but no significant statistical difference was found between fungal keratitis and amoebic keratitis (P>0.05). Advanced age and the summer and winter seasons are identified as risk factors for infectious keratopathy in T2DM patients, and T2DM patients are more prone to bacterial keratitis.


Parental knowledge of child sexual abuse symptoms.
The purpose of this study was to investigate parental knowledge of symptoms of child sexual abuse (CSA), and to determine the factors associated with that knowledge. A total of 150 parents listed symptoms of CSA in the following areas: physical/medical, emotional, sexual behavior, and behavior towards others. Results suggest that, although most parents are familiar with some of the symptoms of CSA, they are more likely to know emotional or behavioral reactions which could be suggestive of many other life stressors. Parents with higher socioeconomic status listed more symptoms, but race and parenting experience were not significant factors. Results suggest the need to inform parents of more indicative physical or sexual symptoms, and to target parents of lower SES background in awareness efforts. doi:10.1300/ J070v15n04_01.


The effect of different milks and milk proteins on the growth of Bifidobacterium infantis ATCC 27920 in vitro.
Bifidobacteria is a well known bacteria that is found in abundance in the intestine of infants which provides several health and nutritional benefits. Realizing the many benefits of bifidobacteria to human, this study has been conducted with the objective to determine the growth promotional effect of different types of milk and milk proteins on Bifidobacterium species. One strains of Bifiodobacterium species that is B. infantis was used to study the growth promoting effect of human milk, cow's milk, goat's milk, milk based infant formula, soy-based infant formula, lactoferrin (1 mg/ml), lactoperoxidase (1p~g/ml), lysozyme (1 mg/ml) and the mixture of these three proteins. The growth promotion assay was done using the 96-well culture plates which consists of 200 (1 Trypticase-Peptone-Yeast extract (TPY) medium, 50 4 sample and 10 1il of bacteria inoculum. Control consists of PBS instead of the samples. The assay was incubated anaerobically at 370C for 18 hours before being spread on the agar plate containing TPY medium with agar. Comparison was made between the mean count (log cfu/ml) of different types of milks, between infant formula and between milk proteins. From the results, Oneway ANOVA test at P<0.05 showed that there was significant differences in the mean counts (log cfu/ml) between the milks (P = 0.0000). A similar trend was observed in the mean count (log cfu/mI) between the infant formulas (P = 0.0 124) and also between the milk proteins (P = 0.0005). Duncan Multiple Range tests showed that there was significant differences between all the milks and control and among the milks themselves. There was however, no significant difference among the two types of infant formulas. The milk proteins also showed significant differences between the proteins and control and among themselves except for lysozyme which showed no significant differences with lactoferrin. This study showed that the growth of B. infantis could be promoted by different kinds of milks and milk proteins in vitro. Comparing the differences in growth promoting effect between samples and control indicated that human milk has the highest growth promoting effect followed by cow's milk and the mixture of the three milk prtoeins. Lysozyme showed the lowest in term of differences in percentage of growth promoting effect among all these samples. In conclusion the findings of this study supported that human milk ios the best milk choice for infant in comparison to other types of milk in promoting the growth of bifidobacteria. In additon, this tudy also found that milk protein when used in combination may show better growth promoiotive effect than when used singly.


Human papillomavirus DNA in tumor-free regional lymph nodes: a potential prognostic marker in cervical carcinoma.
The medical management of women with cervical carcinoma would benefit from a test that might predict which patients have a high risk of progression or recurrence. The detection of micrometastases in regional lymph nodes may be such a test. At least 90% of cervical carcinomas worldwide contain human papillomavirus (HPV) DNA. In a pilot study, we evaluated a polymerase chain reaction-based method for the detection of human papillomavirus DNA in archival routine sections of regional lymph nodes as a marker of micrometastasis in patients with a long-term follow-up period. We analyzed 134 archival routine slides of histologically tumor-free lymph nodes derived from 21 patients with clinically and pathologically determined stage Ib, IIa, and IIb HPV-16 positive cervical carcinoma. The patients had been selected for good (still alive with a follow-up time of at least 5 years) or fatal outcome (dead of disease within 3 years). The amount of HPV-16 DNA was estimated by comparison with standards. All patients without strongly HPV-positive lymph nodes survived. In contrast, 8 of 12 women with strongly HPV-positive lymph nodes died of cervical carcinoma. In patients with cervical cancer, an approach based on a PCR test for HPV DNA in tumor-free regional lymph nodes may allow early identification of women at high risk for relapse who should receive adjuvant treatment.


Lysophosphatidic acid acyltransferase 3 tunes the membrane status of germ cells by incorporating docosahexaenoic acid during spermatogenesis.
Docosahexaenoic acid (DHA) is one of the essential ω-3 polyunsaturated fatty acids with a wide range of physiological roles important for human health. For example, DHA renders cell membranes more flexible and is therefore important for cellular function, but information on the mechanisms that control DHA levels in membranes is limited. Specifically, it is unclear which factors determine DHA incorporation into cell membranes and how DHA exerts biological effects. We found that lysophosphatidic acid acyltransferase 3 (LPAAT3) is required for producing DHA-containing phospholipids in various tissues, such as the testes and retina. In this study, we report that LPAAT3-KO mice display severe male infertility with abnormal sperm morphology. During germ cell differentiation, the expression of LPAAT3 was induced, and germ cells obtained more DHA-containing phospholipids. Loss of LPAAT3 caused drastic reduction of DHA-containing phospholipids in spermatids that led to excess cytoplasm around its head, which is normally removed by surrounding Sertoli cells via endocytosis at the final stage of spermatogenesis. In vitro liposome filtration assay raised the possibility that DHA in phospholipids promotes membrane deformation that is required for the rapid endocytosis. These data suggest that decreased membrane flexibility in LPAAT3-KO sperm impaired the efficient removal of sperm content through endocytosis. We conclude that LPAAT3-mediated enrichment of cell membranes with DHA-containing phospholipids endows these membranes with physicochemical properties needed for normal cellular processes, as exemplified by spermatogenesis.


Granular compaction under confinement.
Successive vertical vibrations can cause a granular pack to rearrange and move to more and more dense configurations. The dilation of the pack that occurs during the vibrations is important to these rearrangements and the resulting compaction of the system. This paper presents an experimental study in which a confining force is used to limit the amount of dilation of the pack. These experiments show that the compaction is greatly reduced in the presence of a confining force. Systems with different shaking accelerations and different confining forces compact in the same way if the amount of dilation is the same. Under large confining forces, there is very little dilation. The resulting compaction when dilation is inhibited is very slow and may approach a final packing fraction of approximately 0.6, consistent with ideas of a critical packing fraction for the onset of dilation.


Direct observation of stacking faults and pore connections in ordered cage-type mesoporous silica FDU-12 by electron tomography.
The porous structure and the periodic array of cavities in ordered mesoporous materials with large, three-dimensionally arranged and interconnected pores is thoroughly described by combining electron tomography, small-angle X-ray diffraction, and nitrogen sorption techniques. We used the ability of the electron tomography to provide local three-dimensional information of a nano-object and compared the results to those of the other characterization techniques which furnish global information. We showed thus that the face-centered cubic (fcc) structure usually assigned to the FDU-12 materials is in fact an intergrowth of cubic and hexagonal close-packing structures. This agrees with small-angle X-ray scattering (SAXS) modeling, but for the first time a direct visualization of these stacking faults was achieved. Three-dimensional transmission electron microscopy (3D-TEM) provides also a direct and unique evidence of peculiar stacking defects ("z-shifted [111] areas"), as well as an estimate of their density, which have never been reported elsewhere. In addition, interstitial cavities were also observed, revealing the complex defective structure of this material. A direct observation of the nature of the connecting pores was also achieved for the first time, with a resolution limit of 2 nm. Finally, the characteristics of the porous network evidenced by 3D-TEM are used to explain and validate the results obtained by nitrogen sorption experiments.


Multifactorial mediation of post norepinephrine induced intestinal hyperemia.
We evaluated several potential endogenous mediators of post norepinephrine induced hyperemia in the mesenteric circulation. Hyperemia was elicited in the anesthetized rat anterior mesenteric artery after cessation of intravenous norepinephrine infusion at 0.125 to 1.0 x 10(-8) M/min x 4 min. Arterial blood pressure was measured with a transducer, and the velocity of arterial blood flow was determined with pulsed Doppler velocimetry. Conductance at the height of mesenteric hyperemia, the post norepinephrine hyperemia volume, and the autoregulatory escape volume were calculated from recorded measurements. The higher doses of norepinephrine increased both the hyperemia volume and peak conductance in both control and capsaicin pretreated rats. Hyperemic parameters were significantly diminished by pretreatment with either yohimbine, propranolol, adenosine deaminase, or methylene blue. Combining adenosine deaminase with propranolol further reduced peak conductance and the hyperemia volume compared with enzyme pretreatment alone. The magnitude of hyperemia was related to the escape volume but not to the extent of norepinephrine induced vasoconstriction. We conclude that post norepinephrine induced hyperemia in the rat mesenteric circulation is modulated by alpha 2 and beta 2 adrenergic receptor activation, adenosine release, and endothelial factors.


Gall stones in a Danish population. Relation to weight, physical activity, smoking, coffee consumption, and diabetes mellitus.
The presence of gall stones diagnosed by ultrasonography in a cross sectional study was analysed in relation to relative weight, weight change since age 25, slimming treatment, physical activity, smoking, consumption of coffee, and diabetes mellitus. The random sample comprised 4581 men and women of Danish origin, aged 30, 40, 50, and 60 years, of whom 3608 (79%) attended the investigation. In women high body mass index, history of slimming treatment, and weight gain since the age of 25 of more than 5 body mass index units were each significantly associated with gall stones (p less than 0.05), while only body mass index was significant (p less than 0.05) in a multivariate analysis. In men history of slimming treatment was significantly associated (p less than 0.05) with gall stones in univariate and in multivariate analyses, where smoking also became significantly associated (p less than 0.05). No significant association was detected between gall stones and the other variables.


Central nervous system cladosporiosis: an account of ten culture-proven cases.
Central nervous system (CNS) cladosporiosis is a rare infection caused by Cladophialophora bantiana. It has varied presentation and poor outcome. Most of the available data in the literature are reviews of individual case reports. To describe the clinical, radiological and mycological features of 10 cases of C. bantiana managed at a single tertiary center. To analyze the various treatment options, factors associated with outcome and to review the relevant literature. This is a retrospective study of 10 patients with CNS cladosporiosis managed at National Institute of Mental Health and Neurosciences from 1979 to 2006. It is a descriptive study. The case records were reviewed for clinical presentation, radiological features, management and outcome. Only those patients in whom the fungus could be isolated on culture were included in the study. The age of the patients ranged from three to 42 years. Nine patients presented with features of space-occupying lesion and one patient with chronic meningitis. There were no specific clinical or radiological features. None of patients had impaired immune status. This infection presented as two pathomorphological forms - diffuse meningoencephalitis and focal abscesses. Burr hole tapping and excision are the surgical options. Both patients with burr hole tapping required excision of abscess subsequently. Two out of seven patients with abscess expired compared to all three patients with diffuse meningoencephalitis who expired. Recurrences occurred in four of the five patients following excision of the abscess. Combination antifungal treatment had better result than monotherapy. The outcome was poor with survival of only 50%. Thorough microbiological examination is required to diagnose CNS infection caused by C. bantiana. The outcome is better in patients with abscess. Excision of the abscess followed by combination antifungal therapy results in better outcome. Close follow-up is required due to high risk of recurrence.


Search for unknown tumor-antagonizing genes.
Following the ingenious prediction of Alfred Knudson in 1971, the first tumor suppressor gene, RB1, has been isolated. Its product, the RB1 protein, was found to play a major role in the control of the cell cycle. The loss of heterozygosity (LOH) technique, introduced by Cavenee and colleagues, was an important milestone toward the confirmation of Knudson's hypothesis and the identification of the gene. Subsequently, the LOH technique has provided important clues that have led to the discovery of other tumor suppressor genes. Most of them play important roles in the regulation of the cell cycle and/or of apoptosis. Circumstantial evidence suggests that still other and perhaps many unknown genes may participate in the protection of the organism against malignant growth. The numerous genome losses in tumors, detected by LOH, comparative genomic hybridization, and by cytogenetic techniques, support this possibility. The early work of one of us (G.K.), together with Henry Harris and Francis Wiener, had shown that the malignant phenotype can be suppressed by hybridizing malignant with low- or non-tumorigenic cells. However, analysis of this phenomenon failed to assign the inhibition of tumorigenicity to any particular gene. We have pursued the search for new tumor-antagonizing genes with two unconventional approaches, focusing on human chromosomal subband 3p21.3, a region frequently targeted by cytogenetically detectable deletions. We have detected four clusters of candidate tumor suppressor genes at 3p21.3 by a combination of deletion mapping and the "elimination test." These findings raise the question whether the number and variety of genes that may contribute to the defense against uncontrolled proliferation may have been underestimated.


Chemical Composition, Antioxidant Activity, and Antibacterial Activity of Black Poplar Buds' Hydroalcoholic Macerates from Dobrogea Area.
Black poplar buds have high contents of many compounds with therapeutic potential, which are useful in cosmetics and the treatment of various dermatitis, respiratory diseases, etc. The aim of this study was to identify and exploit the local plant resources with biologically active properties from the Dobrogea area, Romania. For this purpose, materials were collected from the mentioned area, and macerates of black poplar were prepared in order to evaluate their qualities as antioxidant and antimicrobial agents. Three different black poplar buds' hydroalcoholic macerates were analyzed by the Folin-Ciocâlteau method to estimate the total content of phenolic compounds, by the HPLC-DAD method for identification and quantification of the main bioactive compounds and by the DPPH radical scavenging method to evaluate the antioxidant activity. All hydroalcoholic macerates showed high concentrations of phenolic compounds, the main individual compounds being gallic acid, chlorogenic acid, cinnamic acid, and methyl gallic acid. The antioxidant activity of the black poplar buds' hydroalcoholic macerates, evaluated by the DPPH radical scavenging test, showed high values, between 496 and 1200 mg GAE /100 g d.w. The Cd, Cu, Zn, Ni, and Pb concentrations released in dry poplar buds, determined by AAS, were below the detection limits. Hydroalcoholic macerates of black poplar were tested against two groups of gram-positive bacteria (Enterococcus and Staphylococcus) using an agar well diffusion assay. The in vitro inhibitory activities of the macerates were important and ranged from 8.2-9.4 mm inhibition zones (Staphylococcus) to 8.6 -10 mm inhibition zones (Enterococcus).


Effects of CPT-11 (a unique DNA topoisomerase I inhibitor) on a highly malignant xeno-transplanted neuroblastoma.
Although many advances have been made in the management of neuroblastoma, the prognosis of patients with advanced neuroblastoma remains poor, and constant efforts are being made to search for newer effective drugs. CPT-11 is a newly developed derivative of camptothecin and shows a unique anti-tumor activity by inhibiting DNA topoisomerase I. In this study the effects of CPT-11 on a human neuroblastoma xenograft, TNB9, were investigated according to the standard Battelle Columbus Laboratories protocol. TNB9 is one of the most malignant strains of neuroblastoma, showing a homogeneously staining resion (HSR) on chromosome 20 and 80-fold amplification of the N-myc gene. This study disclosed that CPT-11 was highly effective against TNB9. Maximum inhibition rate (IR) was 72.5% at a standard dose and 52.8% even at half the dose. No nude mouse used in this study lost weight after an administration of CPT-11. Plasma pharmacokinetics of CPT-11 administered in this experimental model were compared to that in clinical patients. Our data suggested that CPT-11 might be a promising new drug in the treatment of high-risk neuroblastoma patients and encouraged us to employ CPT-11 in the protocol of the Study Group of Japan.


The Arcuate Estrogen-Regulated Transcriptome: Estrogen Response Element-Dependent and -Independent Signaling of ERα in Female Mice.
To influence energy homeostasis and reproduction, 17β-estradiol (E2) controls the arcuate nucleus (ARC) through multiple receptor-mediated mechanisms, but primarily via estrogen receptor (ER) α, which signals through both estrogen response element (ERE)-dependent and -independent mechanisms. To determine ERα-mediated, ERE-dependent, and ERE-independent E2 signaling in the ARC, we examined the differential regulation of the mouse arcuate transcriptome by E2 using three mice genotypes: (1) wild-type, (2) ERα knock-in/knockout (ERE-independent mechanisms), and (3) total ERα knockout (ERα-independent mechanisms). Females were ovariectomized and injected with oil or E2, and RNA sequencing on the ARC was used to identify E2-regulated genes in each genotype. Our results show that E2 regulates numerous genes involved in cell signaling, cytoskeleton structure, inflammation, neurotransmission, neuropeptide production, and transcription. Furthermore, ERE-independent signaling regulates ARC genes expressed in kisspeptin neurons and transcription factors that control the hypothalamic/pituitary/gonadal axis. Interestingly, a few genes involved in mitochondrial oxidative respiration were regulated by E2 through ERα-independent signaling. A comparison within oil- and E2-treated females across the three genotypes suggests that genes involved in cell growth and proliferation, extracellular matrices, neuropeptides, receptors, and transcription are differentially expressed across the genotypes. Comparing with previously published chromatin immunoprecipitation sequencing analysis, we found that ERE-independent regulation in the ARC is mainly mediated by tethering of ERα, which is consistent with previous findings. We conclude that the mouse arcuate estrogen-regulated transcriptome is regulated by multiple receptor-mediated mechanisms to modulate the central control of energy homeostasis and reproduction, including novel E2-responsive pathways.


Epidemiology of non-gastroenteropancreatic (neuro)endocrine tumours.
The widespread availability and reliability of immunohistochemical techniques in the last three decades have allowed researchers to identify cells with common neuroendocrine markers in virtually every organ. As a whole, these neuroendocrine cells form the so-called diffuse neuroendocrine system. Tumours arising from the cells of the diffuse neuroendocrine system are defined as (neuro)endocrine tumours (NETs). NETs have been increasingly described in recent years. However, despite the increase in the number of published papers focused on NET, we still lack adequate epidemiological data, particularly for non-gastroenteropancreatic (GEP) NETs. Furthermore, the real incidence of neuroendocrine differentiation for most sites is not completely known and is probably underestimated. As a consequence, data on the clinical features of many NET subgroups are not well known or confusing. For all of these reasons, we have attempted to evaluate the epidemiology of non-GEP NETs, reviewing the limited data available in the literature.


Distribution of complement factors Bf, C2 and C6 in the Western Pacific.
Complement components Bf, C2 and C6 have been typed in various Micronesian, Polynesian, Melanesian and Indian populations of the Western Pacific. BfS and BfF gene frequencies are heterogeneous throughout the region but the number of alleles in the Bf system is restricted. C2 is also restricted with the C22 gene frequency from 0-1.3% in all groups except Fijian Indians where it is 4.8%. The C6A and C6B frequencies of Polynesians, Melanesians and Fijian Indians are within the narrow range of frequencies reported for these alleles from other parts of the world. In the Micronesians of Nauru, a third polymorphic allele (C6Nauru) occurs together with a number of rare alleles (C6R). The Nauruan C6 gene frequencies are C6A 44.6%, C6B 45.2%, C6Nauru 6.7% and C6R 3.5% C6Nauri is present in low frequencies in most other Western Pacific populations and C6R variants occur in Polynesians.


Salinity Inhibits Rice Seed Germination by Reducing α-Amylase Activity via Decreased Bioactive Gibberellin Content.
Seed germination plays important roles in the establishment of seedlings and their subsequent growth; however, seed germination is inhibited by salinity, and the inhibitory mechanism remains elusive. Our results indicate that NaCl treatment inhibits rice seed germination by decreasing the contents of bioactive gibberellins (GAs), such as GA1 and GA4, and that this inhibition can be rescued by exogenous bioactive GA application. To explore the mechanism of bioactive GA deficiency, the effect of NaCl on GA metabolic gene expression was investigated, revealing that expression of both GA biosynthetic genes and GA-inactivated genes was up-regulated by NaCl treatment. These results suggest that NaCl-induced bioactive GA deficiency is caused by up-regulated expression of GA-inactivated genes, and the up-regulated expression of GA biosynthetic genes might be a consequence of negative feedback regulation of the bioactive GA deficiency. Moreover, we provide evidence that NaCl-induced bioactive GA deficiency inhibits rice seed germination by decreasing α-amylase activity via down-regulation of α-amylase gene expression. Additionally, exogenous bioactive GA rescues NaCl-inhibited seed germination by enhancing α-amylase activity. Thus, NaCl treatment reduces bioactive GA content through promotion of bioactive GA inactivation, which in turn inhibits rice seed germination by decreasing α-amylase activity via down-regulation of α-amylase gene expression.


Strategic Optimization of the Flushing Operations in Lubricant Manufacturing and Packaging Facilities.
Commercial lubricant industries use a complex pipeline network for the sequential processing of thousands of unique products annually. Flushing is conducted between changeovers to ensure the integrity of each production batch. An upcoming product is used for cleaning the residues of the previous batch, resulting in the formation of a commingled/mixed oil that does not match the specifications of either of the two batches. The existing operations are based on the operator's experience and trial and error. After a selected flush time, the samples are tested for their viscosity to determine the success of a flush. The approach results in long downtime, the generation of large commingled oil volumes, and huge economic losses. Hence, to overcome the drawback, our work introduces a solution strategy for systematically optimizing flushing operations and making more informed decisions to improve the resource-management footprint of these industries. We use the American Petroleum Institute-Technical Data Book (API-TDB) blending correlations for calculating the mixture viscosities in real-time. The blending correlations are combined with our first-principles models and validated against well-designed experimental data from the partnered lubricant facility. Next, we formulate an optimal control problem for predicting the optimum flushing times. We solve the problem using two solution techniques viz. Pontryagin's maximum principle and discrete-time nonlinear programming. The results from both approaches are compared with well-designed experimental data, and the economic and environmental significance are discussed. The results illustrate that with the application of a discrete-time nonlinear programming solution approach, the flushing can be conducted at a customized flow rate, and the necessary flushing volume can be reduced to over 30% as compared to the trial-and-error mode of operation.


Subclavian artery pseudoaneurysm in type IV Ehlers-Danlos syndrome.
We report case of a subclavian artery pseudoaneurysm in a patient with type IV Ehlers-Danlos Syndrome. A 16-year-old boy underwent successful repair of a subclavian artery pseudoaneurysm that occurred after a cervical hyperextension injury. Subsequent workup included skin biopsy and fibroblast culture, which were consistent with a diagnosis of type IV Ehlers-Danlos Syndrome. This condition is a dominantly inherited connective tissue disorder, which in this patient was found to be caused by a spontaneous point mutation in the COL3A1 gene that encodes the chains of type III procollagen. The clinical, genetic, and molecular characteristics of type IV Ehlers-Danlos Syndrome are briefly reviewed.


Effect of confinement on properties of stiff biological macromolecules.
The behaviour of semiflexible chains, modelling biopolymers such as DNA and actin in confined spaces, was investigated by means of Monte Carlo simulations. Simulations, based on the coarse-grained worm-like chain (WLC) model, assumed confinement length-scales comparable to those used in micro- and nanofluidic devices. The end-to-end chain elongation R was determined as a function of the channel dimensions and chain bending rigidity. Three regions of chain elongation R, identified in simulations in a cylinder and a slit, were described by current theoretical concepts. In harmony with the measurements of confined DNA, an abrupt transition between the blob region at moderate confinement and the deflection region at strong cylindrical confinement was found. The conditions for hairpin formation were elucidated as a trade-off between confinement and chain stiffness. The intrinsic persistence length of unconfined polymers was calculated by four methods that provided practically identical results. However, in confined geometries only the rigorous and WLC methods predicted the dependence of apparent persistence length P on confinement in a qualitatively correct way. It was found that the simple exponential function, suitable for the description of orientation correlations in free chains is, in confined systems, limited only to short distances along the chain contour and, thus, the apparent persistence length determined by this method just reproduces the intrinsic value of P. The orientation correlations from simulations were compared with analytical predictions in the deflection regime under strong confinement and with the measurements of actin filaments.


The Management and Outcomes of Pharmacological Treatments for Tinnitus.
Tinnitus, a phantom sensation experienced by people around the world, currently is endured without a known cure. Some find the condition tolerable, while others are tortured on a daily basis from the incessant phantom noises. For those who seek treatment, oftentimes, they have a comorbid condition (e.g., depression, anxiety, insomnia), which is treated pharmaceutically. These products aim to reduce the comorbities associated with tinnitus thereby minimizing the overall burden present. Because of the phantom nature of tinnitus, it is often compared to neurologic pain. Since pain can be managed with pharmaceutical options, it is reasonable to assume that similar agents might work to alleviate tinnitus. The effects of antidepressants, benzodiazepines, anticonvulsants, and glutamate antagonists are reviewed in this paper. Table 1 summarizes the pharmaceutical products discussed. Due to the variety of comorbid factors and potential causes of tinnitus, there may not be one pharmaceutical treatment that will combat every type of tinnitus. Nevertheless, a product that finally addresses the true cause of tinnitus, and not just its comorbidities, will benefit millions of people worldwide.


Global and regional brain mean diffusivity changes in patients with heart failure.
Heart failure (HF) patients show gray and white matter changes in multiple brain sites, including autonomic and motor coordination areas. It is unclear whether the changes represent acute or chronic tissue pathology, a distinction necessary for understanding pathological processes that can be resolved with diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures. We collected four DTI series from 16 HF (age 55.1 ± 7.8 years, 12 male) and 26 control (49.7 ± 10.8 years, 17 male) subjects with a 3.0-Tesla magnetic resonance imaging scanner. MD maps were realigned, averaged, normalized, and smoothed. Global and regional MD values from autonomic and motor coordination sites were calculated by using normalized MD maps and brain masks; group MD values and whole-brain smoothed MD maps were compared by analysis of covariance (covariates; age and gender). Global brain MD (HF vs. controls, units × 10(-6) mm(2) /sec, 1103.8 ± 76.6 vs. 1035.9 ± 69.4, P = 0.038) and regional autonomic and motor control site values (left insula, 1,085.4 ± 95.7 vs. 975.7 ± 65.4, P = 0.001; right insula, 1,050.2 ± 100.6 vs. 965.7 ± 58.4, P = 0.004; left hypothalamus, 1,419.6 ± 165.2 vs. 1,234.9 ± 136.3, P = 0.002; right hypothalamus, 1,446.5 ± 178.8 vs. 1,273.3 ± 136.9, P = 0.004; left cerebellar cortex, 889.1 ± 81.9 vs. 796.6 ± 46.8, P < 0.001; right cerebellar cortex, 797.8 ± 50.8 vs. 750.3 ± 27.5, P = 0.001; cerebellar deep nuclei, 1,236.1 ± 193.8 vs. 1,071.7 ± 107.1, P = 0.002) were significantly higher in HF vs. control subjects, indicating chronic tissue changes. Whole-brain comparisons showed increased MD values in HF subjects, including limbic, basal-ganglia, thalamic, solitary tract nucleus, frontal, and cerebellar regions. Brain injury occurs in autonomic and motor control areas, which may contribute to deficient function in HF patients. The chronic tissue changes likely result from processes that develop over a prolonged period.


Deficits in Visuo-Motor Temporal Integration Impacts Manual Dexterity in Probable Developmental Coordination Disorder.
The neurological basis of developmental coordination disorder (DCD) is thought to be deficits in the internal model and mirror-neuron system (MNS) in the parietal lobe and cerebellum. However, it is not clear if the visuo-motor temporal integration in the internal model and automatic-imitation function in the MNS differs between children with DCD and those with typical development (TD). The current study aimed to investigate these differences. Using the manual dexterity test of the Movement Assessment Battery for Children (second edition), the participants were either assigned to the probable DCD (pDCD) group or TD group. The former was comprised of 29 children with clumsy manual dexterity, while the latter consisted of 42 children with normal manual dexterity. Visuo-motor temporal integration ability and automatic-imitation function were measured using the delayed visual feedback detection task and motor interference task, respectively. Further, the current study investigated whether autism-spectrum disorder (ASD) traits, attention-deficit hyperactivity disorder (ADHD) traits, and depressive symptoms differed among the two groups, since these symptoms are frequent comorbidities of DCD. In addition, correlation and multiple regression analyses were performed to extract factors affecting clumsy manual dexterity. In the results, the delay-detection threshold (DDT) and steepness of the delay-detection probability curve, which indicated visuo-motor temporal integration ability, were significantly prolonged and decreased, respectively, in children with pDCD. The interference effect, which indicated automatic-imitation function, was also significantly reduced in this group. These results highlighted that children with clumsy manual dexterity have deficits in visuo-motor temporal integration and automatic-imitation function. There was a significant correlation between manual dexterity, and measures of visuo-motor temporal integration, and ASD traits and ADHD traits and ASD. Multiple regression analysis revealed that the DDT, which indicated visuo-motor temporal integration, was the greatest predictor of poor manual dexterity. The current results supported and provided further evidence for the internal model deficit hypothesis. Further, they suggested a neurorehabilitation technique that improved visuo-motor temporal integration could be therapeutically effective for children with DCD.


Retrievable inferior vena cava filter utilization in obstetric patients.
Objectives: The objective of this study is to evaluate patterns of use and outcomes of retrievable inferior vena cava filters (rIVCF) in obstetric patients. Methods: A single center review of consecutive patients who underwent rIVCF placement during pregnancy/postpartum in 2005-2016. A pooled analysis of the relevant cases in the English literature was conducted. Results: The current cohort comprised 24 women, median age 27 [interquartile range 24-30] years. Among 10 filters placed during pregnancy, the most common indication (n = 4) was the need to withhold anticoagulation therapy before delivery, in the presence of acute thrombosis. In the postpartum period, most filters (64%, 9/14) were an adjunct to catheter-directed thrombolytic therapy. Inferior vena cava filters (IVCF)-related complications occurred in seven (29.2%). Retrieval was attempted in 21 patients (87.5%), and was technically successful in 19 (90.5%), for an overall removal rate of 79.1%. Pooled analysis of the literature (n = 98) showed comparable rates for filter removal and complications (81.6%, p = .78 and 24.2%, p = .60, respectively). Suprarenal placement (p = .12) and elective cesarean section (p = .19) did not reduce overall complication and retrieval rates. The estimated radiation dose among pregnant patients who underwent rIVCF placement without adjunct catheter directed thrombolysis (CDT) (mean 695 Gy cm2) was significantly lower than the radiation dose used in postpartum patients (1863 Gy cm2) or in pregnant patients in whom adjunct CDT was utilized (4059 Gy cm2) (p = .001 for both comparisons). Conclusions: Frequent rIVCF-related complications, radiation exposure, and removal failure call for their cautious utilization in obstetric patients. The role of suprarenal placement and elective cesarean section to improve outcomes has yet to be established.


Promutagen activation by fish liver as a biomarker of littoral pollution.
Metabolic activation of known promutagens by liver S9 fractions of Mugil sp. (grey mullet) from two zones of the South Atlantic Spanish littoral was determined and related to their pollution levels. Sediments from the putative contaminated area contained high concentrations of PAHs, PCBs and pesticides, and animals from the polluted site exhibited higher concentrations of metals than those from the reference area. Hepatic S9 fractions of mullets from the polluted site showed 5.1-, 18.6- and 42.8-fold higher capability to activate benzo(a)pyrene, 2-acetyl-aminofluorene and 2-aminoanthracene, respectively, than those from reference animals. Cadmium, a highly toxic metal, was one of the pollutants detected in the contaminated area. Gilthead seabream (Sparus aurata) were exposed under controlled conditions to different Cd concentrations in order to investigate the effects of Cd on fish promutagen activation capability. A clear dose-response relationship was observed between Cd concentration, EROD activity and metabolic activation of 2-aminoanthracene and benzo(a)pyrene. Our data indicate that the enhanced promutagen activation by fish S9 fractions accompanying induction of EROD activity is a sensitive and reliable index of pollution in aquatic environments.


Gastrointestinal stromal tumors the assessment of malignant potential.
GISTS are the largest category of non-epithelial neoplasms of stomach and small bowel. Numerous immunohistochemical, ultrastructural and flow cytometry studies have been carried out for evaluation of prognostic factors which could predict malignant behaviour of these neoplasms. Tumor size of 5 cm and mitosis of 2/10 hpf were suggested as two important parameters which could predict the chances of recurrence and clinically aggressive course. The aim of this study is to examine predictive value of these two important parameters in assigning the tumors as high, intermediate and low risk groups. Using these two parameters we categorized 30 cases of GIST over a period of 6 years (1990-95) into low, intermediate and high risk groups and examined other features of these cases. Based on these two parameters alone we found that 4 cases each in low and intermediate group could be assigned to a higher risk group clinically as there were presence of adjacent organ infiltration, lymphatic emboli, serosal nodules, lymph node metastasis and transmural infiltration. Hence, other features like hemorrhage, necrosis and anaplasia should also be included in risk assessment. Metaplastic tissues like bone, cartilage and adipose tissues were seen only in high-risk categories.


Generalized synchronization between chimera states.
Networks of coupled oscillators in chimera states are characterized by an intriguing interplay of synchronous and asynchronous motion. While chimera states were initially discovered in mathematical model systems, there is growing experimental and conceptual evidence that they manifest themselves also in natural and man-made networks. In real-world systems, however, synchronization and desynchronization are not only important within individual networks but also across different interacting networks. It is therefore essential to investigate if chimera states can be synchronized across networks. To address this open problem, we use the classical setting of ring networks of non-locally coupled identical phase oscillators. We apply diffusive drive-response couplings between pairs of such networks that individually show chimera states when there is no coupling between them. The drive and response networks are either identical or they differ by a variable mismatch in their phase lag parameters. In both cases, already for weak couplings, the coherent domain of the response network aligns its position to the one of the driver networks. For identical networks, a sufficiently strong coupling leads to identical synchronization between the drive and response. For non-identical networks, we use the auxiliary system approach to demonstrate that generalized synchronization is established instead. In this case, the response network continues to show a chimera dynamics which however remains distinct from the one of the driver. Hence, segregated synchronized and desynchronized domains in individual networks congregate in generalized synchronization across networks.


[Chlamydia infection and CIN].
Under the hypothesis that a chronic infection of the cervical epithelium leads to a reduction in the immunological response, a study was carried out to compare the possible relationship between chlamydial infection and CIN. 187 patients were referred to hospital for histological confirmation because of a cytological smear result (PAP III and IV a). Smears were examined for chlamydia antigens using immunofluorescence. The presence of antichlamydial IgA and IgG was performed in serum using an indirect immunohistochemical method. These tests confirmed CIN in 163 patients. The infection rate with chlamydia was 52.9%, 15.9% of CIN patients showing an active chlamydial infection. Inclusion of topographical findings, together with differential evaluation of colposcopic results, with reference to the transformation zone, allow for a separation between inflammation and dysplasia. The confirmation of a positive chlamydial infection and colposcopic criteria may help to reduce the high percentage of false-positive findings in the problem-group of PAP III patients. It appears that reservations about smear controls after doxycyclin therapy--including treatment of sexual partners--is justified.


The neurotensin fragment AcNT(8-13) inhibits lowering of interstitial fluid pressure in rat trachea.
Injury to soft tissue results in the lowering of interstitial fluid pressure (P(if)), plasma protein extravasation, and increased total tissue volume. In this study, the effects of N-acetyl neurotensin(8-13) [AcNT(8-13)] on P(if) in rat trachea were examined after electrical stimulation (ES) of the vagus nerve. P(if) was measured with glass capillaries connected to a servocontrolled counterpressure system. In pentobarbital-anesthetized female Wistar rats, the P(if) after intravenous saline was -1.8 +/- 0.3 mmHg (means +/- SD) and decreased to -5.0 +/- 0.6 mmHg (P < 0.01, n = 9) after ES. AcNT(8-13) (10 microg/kg) blocked the fall in P(if) after ES (-2.5 +/- 2.3 mmHg, P < 0.01, n = 8). In tracheal tissue from animals pretreated with AcNT(8-13) at the same dose and immersed in phosphate-buffered saline (0.15 M, pH 7.4), the rate of fluid accumulation in excised tissues was significantly reduced after 2 h. The ability of AcNT(8-13) to modulate the fluid mechanics of tracheal interstitium after inflammation suggests that it may be a useful tool for studying cell adhesion and related factors that maintain structural integrity of connective tissue after injury.


Recurrent Aphthous Stomatitis: A Review.
Aphthous stomatitis is a painful and often recurrent inflammatory process of the oral mucosa that can appear secondary to various well-defined disease processes. Idiopathic recurrent aphthous stomatitis is referred to as recurrent aphthous stomatitis. The differential diagnosis for recurrent aphthous ulcerations is extensive and ranges from idiopathic benign causes to inherited fever syndromes, to connective tissue disease, or even inflammatory bowel diseases. A thorough history and review of systems can assist the clinician in determining whether it is related to a systemic inflammatory process or truly idiopathic. Management of aphthous stomatitis is challenging. For recurrent aphthous stomatitis or recalcitrant aphthous stomatitis from underlying disease, first-line treatment consists of topical medications with use of systemic medications as necessary. Herein, the authors discuss the differential diagnosis and treatment ladder of aphthous stomatitis as described in the literature.


Regulation of prostaglandin biosynthesis in dispersed choriodecidual cells in culture.
We have evaluated the prostaglandin (PG) production and PG biosynthetic gene expression in a choriodecidual dispersed cell culture system. Cells dispersed from human choriodecidual membranes by dispase and trypsin digestion were evaluated after 1,3,5 and 7 days of culture for basal and tumour necrosis factor alpha (F-alpha) stimulated PGE2 production. The highest rates of production (P < 0.05) were obtained with cells treated after 3 days of culture, (3.7 +/- 1) x 10(2) pg PGE2 per 16 h per microg total cellular protein (mean +/- SEM), which was 3.9 times basal rate after 3 days culture. In choriodecidual cells treated after 3 days in culture, expression of prostaglandin endoperoxide H synthase-2 (PGHS-2) mRNAwas similarly responsive toTNF-alpha (3.9 times basal within 3 h of 30 ng/ml TNF-alpha) while there was little effect on PGHS-1 or cytosolic phospholipase A2 expression. Hence, the dispersed choriodecidual cell culture system described retainsTNF-alpha responsive PG biosynthetic capacity which is at least in part upregulated via increased expression of PGHS-2 mRNA.


Purification and properties of the pyruvate kinase isoenzymes type L and M2 from chicken liver.
A procedure for the simultaneous purification of both isoenzymes of pyruvate kinase (type M2 and L) from chicken liver has been worked out. Each isoenzyme produces a single band in dodecylsulfate gel electrophoresis. Each has a molecular weight of 190 000 and contains four apparently identical subunits of Mr = 50 000. The isoenzymes differ in their isoelectric points (type L: 6.3; type M2: 8.3) and their kinetic behaviour. Pyruvate kinase type L had an S-shaped phosphoenolpyruvate saturation curve (K 0.5=0.79 mM) which was transformed into an hyperbola in the presence of fructose 1,6-bisphosphate, while type M2 had a phosphoenolpyruvate saturation curve of the Michaelis-Menten type (K0.5=0.2mM). Antibodies against pyruvate kinase type L from chicken liver inactivated type L from rat and partially inactivated type M2 from chicken and rat; but the antibodies against type L did not react with type M1 from chicken breast muscle. It is therefore concluded that, contrary to a previous report (Strandholm, J.J. et al. (1975) Biochemistry 14, 2242-2246), avian liver contains pyruvate kinases type M2 and L as the mammalian liver does.


Long-Term Exposure to Traffic-Related Air Pollution and Risk of Incident Atrial Fibrillation: A Cohort Study.
Atrial fibrillation is the most common sustained arrhythmia and is associated with cardiovascular morbidity and mortality. The few studies conducted on short-term effects of air pollution on episodes of atrial fibrillation indicate a positive association, though not consistently. The aim of this study was to evaluate the long-term impact of traffic-related air pollution on incidence of atrial fibrillation in the general population. In the Danish Diet, Cancer, and Health cohort of 57,053 people 50-64 years old at enrollment in 1993-1997, we identified 2,700 cases of first-ever hospital admission for atrial fibrillation from enrollment to end of follow-up in 2011. For all cohort members, exposure to traffic-related air pollution assessed as nitrogen dioxide (NO2) and nitrogen oxides (NOx) was estimated at all present and past residential addresses from 1984 to 2011 using a validated dispersion model. We used Cox proportional hazard model to estimate associations between long-term residential exposure to NO2 and NOx and risk of atrial fibrillation, after adjusting for lifestyle and socioeconomic position. A 10 μg/m3 higher 10-year time-weighted mean exposure to NO2 preceding diagnosis was associated with an 8% higher risk of atrial fibrillation [incidence rate ratio: 1.08; 95% confidence interval (CI): 1.01, 1.14] in adjusted analysis. Though weaker, similar results were obtained for long-term residential exposure to NOx. We found no clear tendencies regarding effect modification of the association between NO2 and atrial fibrillation by sex, smoking, hypertension or myocardial infarction. We found long-term residential traffic-related air pollution to be associated with higher risk of atrial fibrillation. Accordingly, the present findings lend further support to the demand for abatement of air pollution. Citation: Monrad M, Sajadieh A, Christensen JS, Ketzel M, Raaschou-Nielsen O, Tjønneland A, Overvad K, Loft S, Sørensen M. 2017. Long-term exposure to traffic-related air pollution and risk of incident atrial fibrillation: a cohort study. Environ Health Perspect 125:422-427; http://dx.doi.org/10.1289/EHP392.


Alkyne-tethered oligodeoxynucleotides that allow simultaneous detection of multiple DNA/RNA targets using Raman spectroscopy.
Detection of multiple DNA/RNA targets is essential for understanding cellular function. Herein, we propose a general method for the simultaneous detection of plural nucleic acids based on surface-enhanced Raman scattering (SERS) using gold nanoparticles bearing functional oligodeoxynucleotides (ODNs) on their surface. Modified ODNs bearing an acetylene tag hybridized with their complementary ODNs on the surface of the gold nanoparticles, inducing a strong SERS signal of the acetylene tag. The addition of the target nucleic acid to the system resulted in a spontaneous displacement of the strand on the particle and dissociation of the alkyne-tagged ODN from the particle, resulting in a dramatic decrease in signal intensity. By using an alkyne tag for each of the multiple target nucleic acids, each target could be detected simultaneously. In addition, we successfully detected cellular microRNA. Different targets showed changes with different wavenumbers in the Raman spectra, allowing for the detection of multiple nucleic acids.


Brief report: Assessing youth well-being in global emergency settings: Early results from the Emergency Developmental Assets Profile.
The 13-item Emergency Developmental Assets Profile measures the well-being of children and youth in emergency settings such as refugee camps and armed conflict zones, assessing whether young people are experiencing adequate positive relationships and opportunities, and developing positive values, skills, and self-perceptions, despite being in crisis circumstances. The instrument was found to have acceptable and nearly identical internal consistency reliability in 22 administrations in non-emergency samples in 15 countries (.75), and in 4 samples of youth ages 10-18 (n = 1550) in the emergency settings (war refugees and typhoon victims, .74) that are the measure's focus, and evidence of convergent validity. Confirmatory Factor Analysis showed acceptable model fit among those youth in emergency settings. Measures of model fit showed that the Em-DAP has configural and metric invariance across all emergency contexts and scalar invariance across some. The Em-DAP is a promising brief cross-cultural tool for assessing the developmental quality of life as reported by samples of youth in a current humanitarian crisis situation. The results can help to inform international relief program decisions about services and activities to be provided for children, youth, and families in emergency settings.


[Caring pathways of terminal cancer patients: a retrospective survey].
Caring pathways of terminal cancer patients: a retrospective survey. Introduction. The caring patways of terminal cancer patients of the Vallagarina district, dead in 2008, cared at home and/or by district services in the last 90 days of life of cancer patients, were retrospectively described. Aim. To describe the last 90 days of life of all patients dead for cancer. Methods. Data were collected from different sources: hospital discharge forms, local health unit informative systems, data bank of the palliative care service (PC), charts of PC and home care services and through interviews to caregivers, for patients cared by General practitioners (GPs). Results. Four caring pathways were identified: patients mainly cared by GPs, in nursing homes, in long term care or by the PC service. The rate of hospital admissions varies widely: 25% of potential days of care for GPs patients; 1.3% for PCs patients; same for length of hospital stay: mean duration 18.7 days for GPs and 5.6 days for PC patients. Only rarely the GPs activate other forms of care such as care by multidisciplinary teams (10.8% patients) or visits at home by GPs (12.7% patients). Caregivers would like more information on the clinical situation of the patient and on the different caring services, to be involved in the decision making process. Conclusions. Patients cared by GPs and PC Service experience different caring pathways. Lack of information to caregivers may profoundly impact the type of care received.


Agriculture and biotechnology in Pacific countries.
The Pacific countries are small in land mass and therefore represent one of the most fragile ecosystems. Due to the isolation of these island counties, these are home to unique species of plants and animals as well as crop varieties and landraces. Biosafety issues in the Pacific countries, therefore, require special attention to take these factors into account. The issues are shared with other small island nations such as the Caribbean countries. Although most Pacific countries do not have scientific capacity to develop genetically modified organisms (GMOs), they are inadvertently introduced from the developed world. As the countries do not have appropriate capacity to monitor the introduction and commerce of GMO's, it is imperative to establish biosafety legislation and capacity by pooling the resources within the Pacific countries.


Data, Social Determinants, and Better Decision-making for Health: the 3-D Commission.
More than a decade after the World Health Organization Commission on the Social Determinants of Health (SDoH), it is becoming widely accepted that social and economic factors, including but not limited to education, energy, income, race, ethnicity, and housing, are important drivers of health in populations. Despite this understanding, in most contexts, social determinants are not central to local, national, or global decision-making. Greater clarity in conceptualizing social determinants, and more specificity in measuring them, can move us forward towards better incorporating social determinants in decision-making for health. In this paper, first, we summarize the evolution of the social framing of health. Second, we describe how the social determinants are conceptualized and contextualized differently at the global, national, and local levels. With this, we seek to demonstrate the importance of analyzing and understanding SDoH relative to the contexts in which they are experienced. Third, we problematize the gap in data across contexts on different dimensions of social determinants and describe data that could be curated to better understand the influence of social determinants at the local and national levels. Fourth, we describe the necessity of using data to understand social determinants and inform decision-making to improve health. Our overall goal is to provide a path for our collective understanding of the foundational causes of health, facilitated by advances in data access and quality, and realized through improved decision-making.


Microscopic droplet formation and energy transport analysis of condensation on scalable superhydrophobic nanostructured copper oxide surfaces.
Utilization of nanotechnologies in condensation has been recognized as one opportunity to improve the efficiency of large-scale thermal power and desalination systems. High-performance and stable dropwise condensation in widely-used copper heat exchangers is appealing for energy and water industries. In this work, a scalable and low-cost nanofabrication approach was developed to fabricate superhydrophobic copper oxide (CuO) nanoneedle surfaces to promote dropwise condensation and even jumping-droplet condensation. By conducting systematic surface characterization and in situ environmental scanning electron microscope (ESEM) condensation experiments, we were able to probe the microscopic formation physics of droplets on irregular nanostructured surfaces. At the early stages of condensation process, the interfacial surface tensions at the edge of CuO nanoneedles were found to influence both the local energy barriers for microdroplet growth and the advancing contact angles when droplets undergo depinning. Local surface roughness also has a significant impact on the volume of the condensate within the nanostructures and overall heat transfer from the vapor to substrate. Both our theoretical analysis and in situ ESEM experiments have revealed that the liquid condensate within the nanostructures determines the amount of the work of adhesion and kinetic energy associated with droplet coalescence and jumping. Local and global droplet growth models were also proposed to predict how the microdroplet morphology within nanostructures affects the heat transfer performance of early-stage condensation. Our quantitative analysis of microdroplet formation and growth within irregular nanostructures provides the insight to guide the anodization-based nanofabrication for enhancing dropwise and jumping-droplet condensation performance.


Distinguishing different excitation pathways in two-dimensional terahertz-infrared-visible spectroscopy.
In condensed molecular matter, low-frequency modes (LFMs) associated with specific molecular motions are excited at room temperature and determine essential physical and chemical properties of materials. LFMs, with typical mode energies of up to ∼500 cm-1 (62 meV), contribute significantly to thermodynamic parameters and functions (e.g., heat capacity and entropy) and constitute the basis for room temperature molecular dynamics (e.g., conformational fluctuations and change). LFMs are often analyzed indirectly by the measurement of their effect on specific high-frequency modes (HFMs); the LFM-HFM coupling is reflected in the lineshape, as well as in the spectral and angular diffusion of the HFM. Two-dimensional terahertz-infrared-visible (2D TIRV) spectroscopy allows measuring the LFM-HFM coupling directly and can thereby provide new insights into the strength and nature of the coupling and the character of LFMs. However, the interference between the different signals generated by different excitation pathways can complicate 2D TIRV spectra, preventing a straightforward analysis. Here, we develop an experimental method to distinguish different excitation pathways in 2D TIRV spectroscopy and plot them separately in different quadrants of a 2D spectrum. We validate this method by measuring the spectra of CaF2 and nitrogen gas. For CaF2, only sum-frequency mixing between infrared and terahertz fields generates the signal. In contrast, for N2, only difference-frequency mixing is observed. We then use this method to separate sum- and difference-frequency pathways in the 2D TIRV spectrum of liquid water, verifying the previous interpretation of the lineshape of the 2D TIRV spectrum of water.


Skills acquisition for trainee urologists: are the Federal Medical Centers in Nigeria suitable?
Surgical training involves acquisition of knowledge and skills. The district hospitals are known to play complementary role in surgical training in many parts of the world; it is time to evaluate for the possible role Federal Medical Centers (FMC) in Nigeria can play to complement the training of urologists. Against this background, we retrospectively reviewed the relative frequency of urologic procedures performed in one of the FMC as a case study. Hospital data were retrospectively reviewed from January 2007 to June 2010 and records of urologic procedures were extracted for analysis. The total numbers of operations done within same period were also recorded. Urological procedures formed 24.6% of the surgical operation in the hospital during the study period. Uncomplicated prepuce, bladder outflow obstruction, uro-oncology and congenital urological lesion topped the list and accounted for 31.3%, 22.7%, 11.9%, and 11.0% of the cases, respectively. The most frequently performed urological operation in the center was circumcision. Nephrectomy, ureteroneocystostomy, pyeloplasty, cystectomy, and urinary diversion were other procedures performed. The varieties and volume of urologic cases recorded in this centre is comparable with those documented in other established training institutions and thus, it is recommended that the trainees should find time to visit some of these centers and acquaint themselves with hands-on surgical exposure.


[Magnetic resonance imaging and cerebrospinal fluid examinations in a case of central nervous involvement of systemic lupus erythematosus].
A 69-year-old woman was admitted to our hospital with a 7-month history of sensory disturbance of the bilateral lower extremities. Since she developed paraplegia of the extremities, urinary incontinence and left hemiplegia several days after admission, neurologic involvement both in the lumbar cord, and in the cervical cord or the brain was suspected. While no abnormalities were noted by computerized tomography of the brain. T2-weighted magnetic resonance imaging (MRI) clearly demonstrated foci in the periventricular and the basal ganglia regions bilaterally. Furthermore, the levels of immunoglobulin G and interleukin 6 were increased in the cerebrospinal fluid (CSF). From physical and other laboratory findings in addition to the MRI and CSF findings, she was diagnosed as having systemic lupus erythematosus with central nervous involvement. The administration of prednisolone resulted in marked improvement in her neurologic symptoms in two months. Thus, it is considered that the MRI and CSF examinations are useful for the diagnosis and treatment of central nervous involvement of systemic lupus erythematosus.