Spatial resolution of Normalized Difference Vegetation Index and greenness exposure misclassification in an urban cohort.
The Normalized Difference Vegetation Index (NDVI) is a measure of greenness widely used in environmental health research. High spatial resolution NDVI has become increasingly available; however, the implications of its use in exposure assessment are not well understood. To quantify the impact of NDVI spatial resolution on greenness exposure misclassification. Greenness exposure was assessed for 31,328 children in the Greater Boston Area in 2016 using NDVI from MODIS (250 m2), Landsat 8 (30 m2), Sentinel-2 (10 m2), and the National Agricultural Imagery Program (NAIP, 1 m2). We compared continuous and categorical greenness estimates for multiple buffer sizes under a reliability assessment framework. Exposure misclassification was evaluated using NAIP data as reference. Greenness estimates were greater for coarser resolution NDVI, but exposure distributions were similar. Continuous estimates showed poor agreement and high consistency, while agreement in categorical estimates ranged from poor to strong. Exposure misclassification was higher with greater differences in resolution, smaller buffers, and greater number of exposure quantiles. The proportion of participants changing greenness quantiles was higher for MODIS (11-60%), followed by Landsat 8 (6-44%), and Sentinel-2 (5-33%). Greenness exposure assessment is sensitive to spatial resolution of NDVI, aggregation area, and number of exposure quantiles. Greenness exposure decisions should ponder relevant pathways for specific health outcomes and operational considerations.


A Layer-specific Corticofugal Input to the Mouse Superior Colliculus.
In the auditory cortex (AC), corticofugal projections arise from each level of the auditory system and are considered to provide feedback "loops" important to modulate the flow of ascending information. It is well established that the cortex can influence the response of neurons in the superior colliculus (SC) via descending corticofugal projections. However, little is known about the relative contribution of different pyramidal neurons to these projections in the SC. We addressed this question by taking advantage of anterograde and retrograde neuronal tracing to directly examine the laminar distribution, long-range projections, and electrophysiological properties of pyramidal neurons projecting from the AC to the SC of the mouse brain. Here we show that layer 5 cortico-superior-collicular pyramidal neurons act as bandpass filters, resonating with a broad peak at ∼3 Hz, whereas layer 6 neurons act as low-pass filters. The dissimilar subthreshold properties of layer 5 and layer 6 cortico-superior-collicular pyramidal neurons can be described by differences in the hyperpolarization-activated cyclic nucleotide-gated cation h-current (Ih). Ih also reduced the summation of short trains of artificial excitatory postsynaptic potentials injected at the soma of layer 5, but not layer 6, cortico-superior-collicular pyramidal neurons, indicating a differential dampening effect of Ih on these neurons.


An unusual presentation of primary amyloidosis.
A 65-year-old male patient presented with right upper-quadrant abdominal pain. Ultrasonography revealed hypoechoic lesion in the perihepatic and intraparenchymal area. Computed tomography (CT) showed hypodense lesion in the same localization. A fine needle biopsy specimen of the perihepatic lesion was hemorrhagic. On abdominal CT, the liver showed enhancement, but the spleen did not enhance. The spleen could not be detected by scintigraphic imaging using Tc99m sulfur dioxide. A diagnosis of primary amyloidosis was made by renal biopsy. Melphalan 10 mg/day for 4 days/month was started. The clinical and radiological follow up demonstrated a resorption of the hematoma. The patient is still alive at the eighth month of therapy.


A New Species of Small Water Strider in the Genus Microvelia (Hemiptera: Heteroptera: Veliidae) from Aichi Prefecture, Honshu, Japan.
A new species of small water strider (Hemiptera: Heteroptera: Veliidae), Microvelia pilosa sp. nov., is described from Aichi Prefecture, Honshu, Japan. It belongs to the subgenus Picaultia Distant, 1913 within the genus Microvelia Westwood, 1834, and is similar to Microvelia japonica Esaki and Miyamoto, 1955 and Microvelia douglasi douglasi Scott, 1874. The new species can be distinguished from these two taxa by its blackish-brown body, small punctures on the pronotum, and arcuate right paramere that is slender only in the distal part. Our molecular phylogenetic analysis using the mitochondrial COI gene revealed that M. pilosa sp. nov. is genetically separated from some of the other Japanese Microvelia and is most closely related to M. japonica.


Field evaluation of in situ source reduction of trichloroethylene in groundwater using bioenhanced in-well vapor stripping.
Two technologies in combination, cometabolic bioremediation and in-well vapor stripping, were applied to reduce trichloroethylene (TCE) concentrations in groundwater at a contaminant source area without the need to pump contaminated groundwater to the surface for treatment. The vapor-stripping well reduced source TCE concentrations (as high as 6-9 mg/L) by over 95%. Effluent from the well then flowed to two bioremediation wells, where additional reductions of approximately 60% were achieved. TCE removal was extensively monitored (for research and not regulatory purposes) using an automated system that collected samples about every 45 min at 55 locations over an area of approximately 50 x 60 m2. During 4.5 months of system operation, total TCE mass removal was 8.1 kg, 7.1 kg of which resulted from in-well vapor stripping and 1.0 kg from biotreatment. The system reduced the average TCE concentration of about 3000 microg/L in the source-zone groundwater to about 250 microg/L in water leaving the treatment zone, effecting greater than 92% TCE removal. A 6 month rebound study after system operation ceased found TCE concentrations then increased significantly in the treatment zone due to diffusion from the fractured rock below and perhaps other processes, with mass increases of about 1.5 kg in the lower aquifer and 0.3 kg in the upper aquifer.


Molecular determinants for substrate selectivity of ω-transaminases.
ω-Transaminase (ω-TA) is an industrially important enzyme for production of chiral amines. About 20 (S)-specific ω-TAs known to date show remarkably similar substrate selectivity characterized by stringent steric constraint precluding entry of a substituent larger than an ethyl group in the small binding pocket (S) and dual recognition of an aromatic substituent as well as a carboxylate group in the large pocket (L). The strictly defined substrate selectivity of the available ω-TAs remains a limiting factor in the production of structurally diverse chiral amines. In this work, we cloned, purified, and characterized three new ω-TAs from Ochrobactrum anthropi, Acinetobacter baumannii, and Acetobacter pasteurianus that were identified by a BLASTP search using the previously studied ω-TA from Paracoccus denitrificans. All the new ω-TAs exhibited similar substrate specificity, which led us to explore whether the molecular determinants for the substrate specificity are conserved among the ω-TAs. To this end, key active site residues were identified by docking simulation using the X-ray structure of the ω-TA from Pseudomonas putida. We found that the dual recognition in the L pocket is ascribed to Tyr23, Phe88*, and Tyr152 for hydrophobic interaction and Arg414 for recognition of a carboxylate group. In addition, the docking simulation indicates that Trp60 and Ile262 form the S pocket where the substituent size up to an ethyl group turns out to be sterically allowed. The six key residues were found to be essentially conserved among nine ω-TA sequences, underlying the molecular basis for the high similarity in the substrate selectivity.


Refractory pulmonary aspergillosis treated with caspofungin after heart-lung transplantation.
Invasive pulmonary aspergillosis (IPA) is a serious complication of lung transplantation. Pre-mortem diagnosis is difficult and is made according to defined criteria. Most patients with a post mortem diagnosis of IPA only reach the possible or probable levels of diagnostic certainty during life. Here, we report a case of probable IPA that was refractory to conventional treatment, including amphotericin, but which responded to therapy with caspofungin. A 23-year-old man underwent heart-lung transplantation for cystic fibrosis. Ten years after transplantation he developed IPA. His condition continued to deteriorate despite treatment with itraconazole, liposomal amphotericin and flucytosine together with treatment of a concomitant infection with Pseudomonas aeruginosa. Following treatment with caspofungin there was progressive and sustained clinical and radiological improvement. No adverse reaction occurred during treatment. Caspofungin should be considered as an alternative treatment for IPA in lung transplant recipients who fail to respond to other therapy.


The dietary intake of chronic kidney disease according to stages: Findings from the Korean National Health and Nutritional Examination Survey.
Appropriate dietary adjustment in patients with chronic kidney disease (CKD) is important, and nutritional guidelines recommend different dietary management depending on the CKD stage. However, there is no study, to our knowledge, of the characteristics of dietary intake according to CKD stages. We tried to assess the comparison of nutritional intake according to CKD stages. A cross-sectional study was conducted to reveal the characteristics of dietary intake among patients with CKD based on the Korean National Health and Nutritional Examination Survey between 2011 and 2014. Of 16,878 participants, we classified non-CKD (n = 14,952) and CKD (n = 1,926), which was stratified into five groups (I, II, IIIa, IIIb, and IV-V). We investigated the characteristics of dietary intake, such as energy, water, protein, fat, carbohydrate, sodium, potassium, calcium, and phosphorus, according to stage of CKD. We also explored nutritional intake according to CKD stage among patients with early CKD (stage I and II) and advanced CKD (stage IIIa, IIIb, and IV-V). Intake of majority of nutrients and energy tended to be decreased as CKD progressed. In early CKD stage, intake of energy, water, protein, fat, carbohydrate, potassium, calcium and phosphorus seemed to be statistically significant decreased as CKD progressed. In advanced CKD stage, intake of potassium and calcium seemed to be decreased as CKD progressed, but the intake of energy was about to be lower limit. Appropriate dietary education and CKD recognition are needed to improve nutritional intake depending on the CKD stage.


Diesel Exhaust, Respirable Dust, and Ischemic Heart Disease: An Application of the Parametric g-formula.
Although general population studies of air pollution suggest that particulate matter-diesel exhaust emissions in particular-is a potential risk factor for cardiovascular disease, direct evidence from occupational cohorts using quantitative metrics of exposure is limited. In this study, we assess counterfactual risk of ischemic heart disease (IHD) mortality under hypothetical scenarios limiting exposure levels of diesel exhaust and of respirable mine/ore dust in the Diesel Exhaust in Miners Study cohort. We analyzed data on 10,779 male miners from 8 nonmetal, noncoal mines-hired after diesel equipment was introduced in the respective facilities-and followed from 1948 to 1997, with 297 observed IHD deaths in this sample. We applied the parametric g-formula to assess risk under hypothetical scenarios with various limits for respirable elemental carbon (a surrogate for diesel exhaust), and respirable dust, separately and jointly. The risk ratio comparing the observed risk to cumulative IHD mortality risk at age 80 under a hypothetical scenario where exposures to elemental carbon and respirable dust are eliminated was 0.79 (95% confidence interval [CI]: 0.64, 0.97). The corresponding risk difference was -3.0% (95% CI: -5.7, -0.3). Our findings, based on data from a cohort of nonmetal miners, are consistent with the hypothesis that interventions to eliminate exposures to diesel exhaust and respirable dust would reduce IHD mortality risk.


Case Report: Is It Premature Ovarian Insufficiency or Swyer Syndrome After Bone Marrow Transplantation?
Introduction: Iatrogenic factor is one of the recognized causes for premature ovarian insufficiency. The aim of this case report was to present a rare case with premature ovarian insufficiency and 46, XY karyotype after bone marrow transplant (BMT) for thalassaemia major at childhood. We also reviewed some relevant literature in this report. Case Presentation: A 17-year-old girl was presented with primary amenorrhea and premature ovarian insufficiency after receiving chemotherapy and BMT from her brother due to thalassaemia major at childhood. She had poor secondary sex characteristics, assessed as stage I for the development of breasts and external genitalia based on the Tanner scale. Transabdominal ultrasound showed small uterus with visible endometrial lining and small ovaries. Laboratory data showed hypergonadotropic hypogonadism profile with low level of estrogen and high level of follicular-stimulating hormone (FSH). Patient's peripheral lymphocytes karyotype was 46, XY. Conclusions: This case was diagnosed as a chemotherapy induced premature ovarian insufficiency. Patient's peripheral lymphocytes karyotype (46, XY) after she received BMT from a male donor was a misleading finding, and the case could be easily misdiagnosed as Swyer syndrome. A correct diagnosis in such cases should depend not only on the recent clinical findings, but also on the detailed medical history. To prevent premature ovarian insufficiency in similar cases, fertility preservation should be offered to girls before they receive chemotherapy, total body irradiation and BMT.


Asymmetric N-Hydroxyalkylation of Indoles with Ethyl Glyoxalates Catalyzed by a Chiral Phosphoric Acid: Highly Enantioselective Synthesis of Chiral N,O-Aminal Indole Derivatives.
A method of SPINOL-derived chiral phosphoric acid catalyzed asymmetric intermolecular N-hydroxyalkylation of multisubstituted indoles with ethyl glyoxalates is described in this report. This protocol provides an alternative, convenient, and direct strategy for efficient access to structurally unique α-chiral indole N,O-acyclic aminals with a broad substrate scope and good to excellent enantioselectivities. The synthetic utility of this methodology is illustrated by a gram-scale experiment and the subsequent efficient synthesis of more complex chiral N,O-aminal indole derivatives.


Calcific tendinitis of the biceps-labral complex: a rare cause of acute shoulder pain.
Calcific tendinitis most commonly affects the rotator cuff and has not been previously reported affecting the biceps-labral complex. We report a case of calcific tendinitis of the biceps-labral complex attachment, a rare cause of acute, severe shoulder pain. Clinically, it can be misdiagnosed as supraspinatus tendinitis or septic arthritis of the shoulder joint. Non-operative treatment failed to resolve the symptoms. Arthroscopic debridement of the calcific deposit resulted in resolution of symptoms. Knowledge of this clinical condition and its imaging features is crucial for a correct diagnosis of this uncommon cause of shoulder pain.


PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia.
The immune checkpoint inhibitor programmed cell death protein 1 (PD-1) plays a critical role in immune regulation. Recent studies have demonstrated functional PD-1 expression in peripheral sensory neurons, which contributes to neuronal excitability, pain, and opioid analgesia. Here we report neuronal expression and function of PD-1 in the central nervous system (CNS), including the spinal cord, thalamus, and cerebral cortex. Notably, GABA-induced currents in spinal dorsal horn neurons, thalamic neurons, and cortical neurons are suppressed by the PD-1-neutralizing immunotherapeutic Nivolumab in spinal cord slices, brain slices, and dissociated cortical neurons. Reductions in GABA-mediated currents in CNS neurons were also observed in Pd1 -/- mice without changes in GABA receptor expression. Mechanistically, Nivolumab binds spinal cord neurons and elicits ERK phosphorylation to suppress GABA currents. Finally, both GABA-mediated analgesia and anesthesia are impaired by Pd1 deficiency. Our findings reveal PD-1 as a CNS-neuronal inhibitor that regulates GABAergic signaling and GABA-mediated behaviors.


Milk and rice.
The following short article is an account of Israeli nurses caring for Syrian wounded. These wounded are shuffled across the Syrian border into Israeli hospitals. Until today and including today, we are considered 'enemy countries' with no diplomatic relations and fire arms pointing at each other. Six months ago when the Syrian wounded started trickling into our hospitals, the nurses did not know how to react and stood on shaky ground. The casualties were admitted directly into the intensive care units and emergency rooms without knowledge of mechanism of injury, date or circumstances of injury, and alone with no family support. We were told not to communicate with them. However, that request was quickly overlooked and relationships developed. The following report is that of one of the bedside nurses in an Israeli border hospital and her experience of caring for a Syrian casualty.


Detection of leukotriene B4 in cardiac tissue and its role in infarct extension through leucocyte migration.
The main left coronary artery of rats was ligated near its origin under light ether anaesthesia and the infarction observed for 48 h. The ischaemic area was determined after an intravenous injection of pontamine sky blue dye 1 h before induction of cardiac arrest with potassium chloride. The unstained area (true ischaemic area) decreased with time to 27.1% of the left ventricle at 48 h, whereas the intensely stained area between the normal and the true ischaemic areas increased with time, suggesting that blood was flowing to the border from the normal surrounding tissue. The infarcted area, identified by its lack of triphenyltetrazolium chloride staining, became evident after 3 h and stabilised at 12 h (42% of left ventricle). The polymorphonuclear leucocyte counts in the hearts, differentiated by staining of their chloroacetate esterase, increased gradually up to 5500 cells per section at 24 h. The leukotriene B4 concentration, determined by radioimmunoassay after freezing of the beating heart in liquid nitrogen, increased to eight times that of the sham operated hearts and peaked at 8 h (9.4(0.6) ng per heart, mean(SEM) n = 5) before the leucocyte counts reached their maximum. A single oral dose of a selective 5-lipoxygenase inhibitor (AA-861, 80 mg.kg-1, 1 h before ligation) lowered the leukotriene B4 concentration to that of the sham operated hearts and decreased the leucocyte count by 49.4% and 41.2% at 12 and 24 h respectively. The inhibitor also reduced the infarct size at 48 h by 34.4%. It was concluded that leukotriene B4, generated in ischaemic cardiac tissue, may increase infarct size through migration of polymorphonuclear leucocytes.


Antioxidant, Anti-Inflammatory and Antithrombotic Effects of Ginsenoside Compound K Enriched Extract Derived from Ginseng Sprouts.
Partially purified ginsenoside extract (PGE) and compound K enriched extract (CKE) were prepared from ginseng sprouts, and their antioxidant, anti-inflammatory and antithrombotic effects were investigated. Compared to the 6-year-old ginseng roots, ginseng sprouts were found to have a higher content of phenolic compounds, saponin and protopanaxadiol-type ginsenoside by about 56%, 36% and 43%, respectively. PGE was prepared using a macroporous adsorption resin, and compound K(CK) was converted and enriched from the PGE by enzymatic hydrolysis with a conversion rate of 75%. PGE showed higher effects than CKE on radical scavenging activity in antioxidant assays. On the other hand, CKE reduced nitric oxide levels more effectively than PGE in RAW 264.7 cells. CKE also reduced pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β and IL-6 than PGE. Tail bleeding time and volume were investigated after administration of CKE at 70-150 mg/kg/day to mice. CKE administered group showed a significant increase or increased tendency in bleeding time than the control group. Bleeding volume in the CKE group increased than the control group, but not as much as in the aspirin group. In conclusion, ginseng sprouts could be an efficient source of ginsenoside, and CKE converted from the ginsenosides showed antioxidant, anti-inflammatory and antithrombotic effects. However, it was estimated that the CKE might play an essential role in anti-inflammatory effects rather than antioxidant effects.


The roles of immunity and autoimmunity in chronic heart failure.
Chronic heart failure (CHF) represents a major public health burden in developed countries. The introduction of new treatments has helped to improve its prognosis in recent years. However, it is still not possible to directly target the immunological aspects of the disease. In fact, chronic immune activation with the up-regulation of pro-inflammatory substances in the plasma remains an important feature of the disease, independently of its aetiology. Autoimmune mechanisms play a significant role in a subgroup of patients with dilated cardiomyopathy. The interplay between the two systems has not been established so far. This review briefly summarizes immune and autoimmune mechanisms in CHF.


What Is Value in Health and Healthcare? A Systematic Literature Review of Value Assessment Frameworks.
This study aimed to investigate how value is defined and measured in existing value assessment frameworks (VAFs) in healthcare. We searched PubMed, Embase, the Cochrane Library, and Centre for Reviews and Dissemination from 2008 to 2019. We also performed backward citation chaining of included studies and previously published systematic reviews. Studies reporting the development of a VAF in healthcare were included. For each included framework, we extracted and compared the context, target users, intended use, methods used to identify value attributes, description of the attributes, and attribute scoring approaches. Of the 8151 articles screened, 57 VAFs were included. The value attributes included in 55 VAFs were grouped into 9 categories: health benefits (n = 53, 96%), affordability (n = 45, 82%), societal impact (n = 42, 76%), burden of disease (n = 36, 65%), quality of evidence (n = 32, 58%), cost-effectiveness (n = 31, 56%), ethics and equity (n = 27, 49%), unmet needs (n = 21, 38%), and innovation (n = 15, 27%). The remaining 2 VAFs used broad attributes or user-defined attributes. Literature review was the main approach to identify value attributes in 36 VAFs. Patient or public was engaged through the development of only 11 VAFs. Weighting has been used to score 29 VAFs, of which 19 used the methods of multicriteria decision analysis. There are substantial variations in defining and measuring value. A noticeable weakness of existing VAFs is that patient or public engagement was generally very limited or missing in framework development process. Existing VAFs tend to aggregate multiple value attributes into a single index for decision making.


High prevalence of genital tract papillomavirus infection in female adolescents.
To investigate clinical condyloma, abnormal cervical cytologic findings, and evidence of human papillomavirus infections, 89 adolescent girls were examined. Cellular DNAs extracted from exfoliated cervical cells were examined for human papillomavirus genomic sequences by Southern transfer hybridization using 32P-labeled human papillomavirus DNA probes. Human papillomavirus sequences were detected in 12 (13%) young women, abnormal cytologic specimens in 21 (24%), and vulvar condylomas in 12 (13%). The human papillomavirus types identified included HPV-6/11 (four instances), which is known to be associated with benign lesions, and HPV-16, -18, and -31 (eight instances) which are considered to have oncogenic potential. Two young women were infected with both HPV-16 and -31. Human papillomavirus sequences were found in 48% of the young women with abnormal cytologic findings and in 3% of patients with normal cytologic findings (P less than .0001). Condylomatous changes in the cervical smear were associated with the presence of HPV-6/11 and mild dysplasia with the presence of HPV-16, -18, and -31. The presence of vulvar condylomas correlated with condylomatous changes in the cervical smear and with the recovery of HPV-6/11 from the cervical epithelium. The results indicate that the prevalence of human papillomavirus infections in this population is high and that a majority of the infections are with viruses associated with lower genital tract malignancies.


A case of anisakiasis causing intestinal obstruction.
A 31-year old salesman living in Seoul developed suddenly abdominal pain due to intestinal obstruction. Exploratory laparotomy exhibited segmental jejunal cellulitis caused by penetrating Anisakis larva. The patient had eaten raw fish. The typical history of intestinal anisakiasis was presented with a short review of Korean patients of anisakiasis.


UV radiation sensitivity of bacteriophage PhiX174 - A potential surrogate for SARS-CoV-2 in terms of radiation inactivation.
To minimize health risks, surrogates are often employed to reduce experiments with pathogenic microorganisms and the associated health risk. Due to structural similarities between the enveloped RNA-viruses SARS-CoV-2 and Phi6, the latter has been established as a nonpathogenic coronavirus surrogate for many applications. However, large discrepancies in the UV log-reduction doses between SARS-CoV-2 and Phi6 necessitate the search for a better surrogate for UV inactivation applications. A literature study provided the bacteriophage PhiX174 as a potentially more suitable nonpathogenic coronavirus surrogate candidate. In irradiation experiments, the sensitivity of PhiX174 was investigated upon exposure to UV radiation of wavelengths 222 nm (Far-UVC), 254 nm (UVC), 302 nm (broad-band UVB), 311 nm (narrow-band UVB) and 366 nm (UVA) using a plaque assay. The determined log-reduction doses for PhiX174 were 1.3 mJ/cm2 @ 222 nm, 5 mJ/cm2 @ 254 nm, 17.9 mJ/cm2 @ 302 nm, 625 mJ/cm2 @ 311 nm and 42.5 J/cm2 @ 366 nm. The comparison of these results with published log-reduction doses of SARS-CoV-2 in the same spectral region, led to the conclusion that the bacteriophage PhiX174 exhibits larger log-reduction doses than SARS-CoV-2, nevertheless, it is a better UV-surrogate at 222 nm (Far-UVC), 254 nm (UVC) and 302 nm (UVB) than the often applied Phi6.


Biomarkers: project update from the GRAPPA 2012 annual meeting.
For members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), an important goal has been the identification of soluble biomarkers in psoriatic arthritis that might predict the development of radiographic progression. Work over the past year has resulted in approval of a draft protocol, and an announcement is forthcoming of the outcome of an assessment process for centers that applied to manage the project. GRAPPA is now ready to commence formal negotiations with potential funding partners and intends to initiate this project in the near future.


The impact of gardening on nutrition and physical health outcomes: a systematic review and meta-analysis.
Community gardening has been widely recognized as a multicomponent approach that has affected a broad range of health and well-being outcomes. The objective of this study was to investigate the association between community gardening and nutrition and physical health among adults. A systematic review and meta-analysis were conducted. Five electronic databases were searched systematically. Quality of included studies was appraised by several quality assessment tools related to the study design of each included article. Evidence from 19 articles was included (14 cross-sectional studies, 4 quasi-experimental studies and 1 case-control study). Although the majority of included studies appeared to have moderate quality, there existed weaknesses in the methods used, including low response rate and lack of confounder controls. Due to diversity in the measurement units, only body mass index (BMI) data could be pooled to perform meta-analysis. The results suggest that gardening had a significantly positive effect on BMI reduction. Subgroup analysis showed that quasi-experimental and case-control studies produced greater pooled effect size than those of cross-sectional design. Funnel plot and Egger's test showed no significant evidence of publication bias. As robust evidence for the effect of community gardening on BMI reduction was found, this intervention should be integrated in health promoting policy to improve population health.


A highly unusual case of osmotic demyelination syndrome and extrapontine myelinolysis in a 3-month-old infant with Bartter syndrome.
Bartter syndrome (BS) is a rare autosomal recessive renal tubular disorder characterized by acute electrolyte imbalance, and similarly, osmotic demyelination syndrome (ODS) is a rather rare complication occurring during electrolyte imbalance. The pathological features of ODS include central pontine myelinolysis and extrapontine myelinolysis (EPM), which consist of severe damage to the myelin sheath of neurons. ODS is very rare in children. We describe a case of a 3-month-old infant with ODS and EPM associated with undiagnosed BS. ODS developed because of a sudden change in electrolyte levels and osmolality caused by acute dehydration during a gastrointestinal infection episode. Undiagnosed, untreated, and non-balanced BS was the cause of the neurological complication. Our patient represents the first case of ODS in BS, the ninth case of ODS in an infant less than one year old, and the third case of isolated EPM in such a young patient. This case report reminds us that in rare diseases, young patients tend to have genetic components.


Failure load of teeth restored by use of alumina copings: Influence of residual tooth structure and cementation.
To evaluate failure loads of teeth restored by use of alumina-coping, and to assess the effects of different amounts of residual tooth structure and different cements, standardized artificial alumina copings were fabricated on seventy-two molars. 24 of the copings were cemented by use of an adhesive resin cement (P-group), n=24 by use of glass-ionomer cement (K-group), and n=24 by use of a self-adhesive modified composite resin-cement (R-group). After artificial ageing (10,000 thermal-cycles between 6.5 and 60°C; 1,200,000 chewing cycles with Fmax=64 N), the specimens were loaded until failure (cross-head-speed: 0.5 mm/min). In the K-group 83% of the specimens failed during chewing simulation. Statistical analysis included chi-squared-test, unpaired-to-sample-t-test, and ANOVA. For severely damaged teeth, loads to failure in the P-group (384 N) were significantly (p=0.03) higher than in the R-group (295 N). For severely damaged teeth, use of composite resin cement resulted in higher loads to failure than use of other cements.


Design of Association Application System of Face Recognition and Test-Tube Barcode Based on CNN.
In order to improve the standardization and accuracy of business process management of laboratory department in hospitals, combined with convolutional neural networks (CNN) and face recognition technology, an association application system of laboratory face recognition and test-tube barcode is designed by inputting patient's face and blood test-tube barcode into the system for storage. When the patient logs into the system again, the system uses the patient's face to automatically search for a matching test-tube barcode to obtain the test results. The simulation results show that the system can accurately recognize the face and match the corresponding test-tube barcode, and the accuracy and ROC of face recognition are 0.85 and 0.94, respectively. In addition, when the patient's face is within 5 m from the system camera, the accuracy of face recognition can reach 100%. It can be seen that the system designed in this paper shows good performance.


Refining Diagnosis of Schistosoma haematobium Infections: Antigen and Antibody Detection in Urine.
Background: Traditional microscopic examination of urine or stool for schistosome eggs lacks sensitivity compared to measurement of schistosome worm-derived circulating antigens in serum or urine. The ease and non-invasiveness of urine collection makes urine an ideal sample for schistosome antigen detection. In this study several user-friendly, lateral-flow (LF) based urine assays were evaluated against a composite reference that defined infection as detection of either eggs in urine or anodic antigen in serum. Method: In a Tanzanian population with a S. haematobium prevalence of 40-50% (S. mansoni prevalence <2%), clinical samples from 44 women aged 18 to 35 years were analyzed for Schistosoma infection. Urine and stool samples were examined microscopically for eggs, and serum samples were analyzed for the presence of the anodic antigen. Urines were further subjected to a set of LF assays detecting (circulating) anodic (CAA) and cathodic antigen (CCA) as well as antibodies against soluble egg antigens (SEA) and crude cercarial antigen preparation (SCAP). Results: The urine LF anodic antigen assay utilizing luminescent upconverting reporter particles (UCP) confirmed its increased sensitivity when performed with larger sample volume. Qualitatively, the anodic antigen assay performed on 250 μL urine matched the performance of the standard anodic antigen assay performed on 20 μL serum. However, the ratio of anodic antigen levels in urine vs. serum of individual patients varied with absolute levels always higher in serum. The 10 μL urine UCP-LF cathodic antigen assay correlated with the commercially available urine POC-CCA (40 μL) test, while conferring better sensitivity with a quantitative result. Urinary antibodies against SEA and SCAP overlap and correlate with the presence of urinary egg and serum anodic antigen levels. Conclusions: The UCP-LF anodic antigen assay using 250 μL of urine is an expedient user-friendly assay and a suitable non-invasive alternative to serum-based antigen testing and urinary egg detection. Individual biological differences in the clearance process of the circulating antigens are thought to explain the observed high variation in the type and level of antigen (anodic or cathodic) measured in urine or serum. Simultaneous detection of anodic and cathodic antigen may be considered to further increase accuracy.


Sunitinib-resistant gastrointestinal stromal tumors harbor cis-mutations in the activation loop of the KIT gene.
Although sunitinib malate has shown significant clinical effect on imatinib-resistant gastrointestinal stromal tumors, with acceptable tolerability and improved prognosis for the patients, the mechanism of resistance to the drug is still under investigation. We analyzed findings in 8 patients (seven men and one woman, median age, 59 years) out of 17 patients with imatinib-resistant gastrointestinal stromal tumors who had been treated with sunitinib. Sunitinib was orally administered once a day at a starting dose of 37.5 mg/day, 50 mg/day, or 75 mg/day, with 4 weeks on and 2 weeks off. All imatinib- as well as sunitinib-resistant lesions showed viable tumor cells strongly re-expressing the KIT protein. Pre-imatinib samples had heterogeneous KIT mutations either in exon 9 (n = 1) or exon 11 (n = 7), and seven imatinib-resistant tumors carried a secondary mutation either in the ATP-binding domain or in the activation loop in the same allele as the primary mutation. Most patients with imatinib-resistant tumors carrying secondary mutations in the ATP-binding domain obtained clinical benefits from sunitinib, whereas some tumors with mutations in the activation loop showed resistance to the drug. A tumor with mutations in exon 11 and 13 of the KIT gene, and showing partial response to sunitinib, harbored a third mutation in the activation loop when sunitinib resistance was shown. All additional secondary and tertiary mutations were located on the same allele as the primary mutation (cis-mutation). These findings indicate that an additional cis-mutation in the activation loop of the KIT gene could be a potential cause of sunitinib resistance in gastrointestinal stromal tumors.


Performance of Legiolert Test vs. ISO 11731 to Confirm Legionella pneumophila Contamination in Potable Water Samples.
Detection and enumeration of Legionella in water samples is of great importance for risk assessment analysis. The plate culture method is the gold standard, but has received several well-known criticisms, which have induced researchers to develop alternative methods. The purpose of this study was to compare Legionella counts obtained by the analysis of potable water samples through the plate culture method and through the IDEXX liquid culture Legiolert method. Legionella plate culture, according to ISO 11731:1998, was performed using 1 L of water. Legiolert was performed using both the 10 mL and 100 mL Legiolert protocols. Overall, 123 potable water samples were analyzed. Thirty-seven (30%) of them, positive for L. pneumophila, serogroups 1 or 2-14 by plate culture, were used for comparison with the Legiolert results. The Legiolert 10 mL test detected 34 positive samples (27.6%) and the Legiolert 100 mL test detected 37 positive samples, 27.6% and 30% respectively, out of the total samples analyzed. No significant difference was found between either the Legiolert 10 mL and Legiolert 100 mL vs. the plate culture (p = 0.9 and p = 0.3, respectively) or between the Legiolert 10 mL and Legiolert 100 mL tests (p = 0.83). This study confirms the reliability of the IDEXX Legiolert test for Legionella pneumophila detection and enumeration, as already shown in similar studies. Like the plate culture method, the Legiolert assay is also suitable for obtaining isolates for typing purposes, relevant for epidemiological investigations.


The role of nursing in public policy reform.
Currently, individuals concerned about the cost and quality of health care, and the necessity of major system reform, are grappling with the concepts of managed competition, managed cooperation, sponsors, and health insurance purchasing cooperatives. Managed competition, broadly defined, is a purchasing strategy designed to obtain maximum value for consumers and employers as they acquire health care. Managed competition occurs at the level of integrated financial and delivery plans, not at the individual provider level. The goal of managed competition is to divide the providers in each community into competing economic units to motivate them to develop efficient delivery systems (Enthoven, 1993). Efficient health care delivery systems have not resulted from the fee-for-service and remote third-party reimbursement practices that currently dominate the health care system. However, more efficient delivery systems have emerged from managed care. Some of the best known models of managed care that have demonstrated cost effectiveness include Kaiser Permanente, Group Health Cooperative of Puget Sound, and Washington Group Health. The rapidly escalating consumption of US economic resources in the name of health care has led to the current pressure for health care reform. Although the public discussion about health care reform centers around the high cost of health care, we are, in truth, in the midst of both a crisis of medical care and an emergence of an era of health care for the nation's people.


In-vitro response of Plasmodium falciparum to the main alkaloids of Cinchona in northwestern Thailand.
The blood schizontocidal activity of the four main Cinchona alkaloids against Plasmodium falciparum was compared in 46 fresh parasite isolates, using an in-vitro test measuring the drug-specific inhibition of schizont maturation. The studies were conducted in June-August 2001 at Mae Sot, northwestern Thailand, an area where quinine alone is no longer able to eliminate infections with P. falciparum. Quinidine showed the highest blood schizontocidal activity, followed by cinchonine, cinchonidine and finally quinine, which was identified as the least active compound. The isolates showed marked heterogeneity in their response to the Cinchona alkaloids. There was also high correlation of activity among all four alkaloids. The mean EC50 values for quinine, quinidine, cinchonine and cinchonidine were 144 nM, 80 nM, 104 nM and 225 nM, respectively, and the EC99 values 8040 nM, 861 nM, 1176 nM and 6531 nM. The EC99 values for quinine and cinchonidine are beyond the therapeutic concentration range and those for quinidine within it. For cinchonine, values are likely to be within this range, but toxicological and pharmacokinetic studies on this compound are required for clarifying its potential future role in the treatment of falciparum malaria.


Multi-carrier synthetic aperture communication in shallow water: experimental results.
Orthogonal frequency division multiplexing (OFDM) communications in the presence of motion is investigated using data collected from the Kauai Acomms MURI 2008 (KAM08) experiment, conducted off the western side of Kauai, Hawaii, in June-July 2008. The experiment involved a vertical array moored in 106 m deep shallow water and a source towed at a speed of 3 knots at ranges between 600 m and 6 km. In order to attain reliable communications with only a single receive element, a synthetic aperture approach is applied. After combining multiple transmissions, an error-free reception is achieved with a low-density parity-check code, confirming the feasibility of coherent synthetic aperture communications using OFDM.


Post-transcriptional regulation of MTA family by microRNAs in the context of cancer.
MicroRNAs (miRNAs) are a class of 20-24 nt small non-coding RNAs that regulate a wide range of biological processes through changing the stability and translation of their target messenger RNA (mRNA) genes. Shortly after their identification, many miRNA genes have been found dysregulated in a variety of human cancers, indicating a pathological function of this gene class in mediating cancer progression. Over the past decade, accumulated literature has shown that miRNAs participate in numerous cancer-relevant processes including cell proliferation, apoptosis, differentiation, metabolism, and importantly, metastasis, which accounts for the mortality of approximately 90 % of cancer patients. Several recent publications have linked miRNAs with metastasis-associated protein (MTA) family members. Given the fact that the MTA family members are widely overexpressed in human cancers and their nature of serving as both corepressor and coactivator in gene regulation, it is intriguing to study whether certain miRNAs regulate cancer progression through modulating the expression of MTA family members. In this review, we will focus on recent advances in understanding the regulatory relationship between certain miRNAs and MTA family members.


[Pseudochylothorax. Review of 5 cases].
We undertook a retrospective review of five patients with pseudo-chylothorax diagnosed at our hospital between 1984 and 1994. Pseudo-chylothorax was diagnosed if crystals of cholesterol were observed (CC) or if cholesterol concentrations were over 150 mg/dl, but chylomicrons were absent from pleural effusions with cloudy supernatants after centrifugation. The five patients were males and their mean age was 53 years. All had history of pulmonary or pleural tuberculosis (mean 31 years since diagnosis). All had received chemotherapy and four had undergone therapeutic pneumothorax. Two patients were diagnosed in the course of examination for other reasons, Three were diagnosed while being examined for the cause of pleural effusion. The diagnosis of four patients was based on the presence of CC. Three patients received specific treatment and Mycobacterium tuberculosis was isolated in the pleural fluid of two. One patient required a pleural drain and antibiotics because of empyema related to pseudo-chylothorax. Decortication was needed by two. 1) Pseudo-chylothorax is at present rare. 2) All the cases we saw were associated with earlier tuberculosis infection with residual pleural lesions. 3) Diagnosis usually occurs in the course of examination for the other motives, but the possibility of infected pleural effusion or reactivation of tuberculosis should be considered.


High Aldehyde Dehydrogenase Levels Are Detectable in the Serum of Patients with Lung Cancer and May Be Exploited as Screening Biomarkers.
Since early detection improves overall survival in lung cancer, identification of screening biomarkers for patients at risk represents an area of intense investigation. Tumor liberated protein (TLP) has been previously described as a tumor-associated antigen (complex) present in the sera from lung cancer patients. Here, we set out to identify the nature of TLP to develop this as a potential biomarker for lung cancer screening. Beginning from the peptide epitope RTNKEASI previously identified from the TLP complex, we produced a rabbit anti-RTNKEASI serum and evaluated it in the lung cancer cell line A549 by means of immunoblot and peptide completion assay (PCA). The TLP sequence identification was conducted by mass spectrometry. The detected protein was, then, analyzed in patients with non-small cell lung cancer (NSCLC) and benign lung pathologies and healthy donors, by ELISA. The anti-RTNKEASI antiserum detected and immunoprecipitated a 55 kDa protein band in the lysate of A549 cells identified as aldehyde dehydrogenase isoform 1A1, revealing the molecular nature of at least one component of the previously described TLP complex. Next, we screened blood samples from a non-tumor cohort of 26 patients and 45 NSCLC patients with different disease stages for the presence of ALDH1A1 and global ALDH. This analysis indicated that serum positivity was highly restricted to patients with NSCLC (ALDH p < 0.001; ALDH1A1 p=0.028). Interestingly, the global ALDH test resulted positive in more NSCLC samples compared to the ALDH1A1 test, suggesting that other ALDH isoforms might add to the sensitivity of the assay. Our data indicate that ALDH levels are elevated in the sera of NSCLC patients, even with early stage disease, and may thus be evaluated as part of a marker panel for non-invasive detection of NSCLC.


Intraoperative evaluation of sentinel lymph nodes for breast carcinoma: current methodologies.
Sentinel lymph node biopsy is an important new addition to the surgical management of patients with breast carcinoma. Sentinel nodes have a higher chance of containing metastases than do nonsentinel nodes. Sentinel lymph node biopsy provides an opportunity to stage breast carcinoma patients more accurately and to modify subsequent treatment. One of the most exciting current roles of sentinel lymph node biopsy is the ability to stage patients intraoperatively, allowing a one-step axillary lymph node dissection if the sentinel lymph node contains metastatic carcinoma. Currently, intraoperative evaluation of sentinel lymph nodes is performed using imprint cytology with or without rapid cytokeratin staining, frozen sectioning with or without rapid cytokeratin staining, scrape preparations, or some combination of these techniques. We review the relative strengths and weaknesses of these different methodologies. A great deal of controversy exists regarding the management of patients with metastatic breast carcinoma, particularly those patients with occult and micrometastatic disease. These issues are beyond the scope of this article.


Vanadium in the blood and urine of workers in a ferroalloy plant.
The concentration of vanadium in the blood and urine of both nonexposed and occupationally exposed workers have been determined by neutron activation analysis. A comparison of the exposure data and the corresponding blood and urine values shows that the urine vanadium concentration adjusted for creatinine concentration is the most reliable exposure indicator. The normal levels of vanadium in blood are less than 20 nmol/l. The corresponding urine values are less than 3.5 nmol/mmol of creatinine.


Clinical Outcomes of May-Thurner Syndrome in Pediatric Patients: A Single Institutional Experience.
Introduction May-Thurner syndrome (MTS) is a vascular anatomic variant resulting in compression of the left common iliac vein by the right common iliac artery, affecting approximately 22% of the population. In adults, following acute deep vein thrombosis (DVT) of the iliofemoral veins, the incidence of postthrombotic syndrome (PTS) and recurrent DVT are high if treated with anticoagulation alone, warranting adjunctive treatment with thrombolysis and stent placement. However, there is paucity of literature documenting the course of treatment and associated outcomes in pediatric patients with MTS. Methods A retrospective chart review of pediatric patients (≤ 18 years of age) with radiologic confirmation of MTS with or without DVT evaluated and/or treated at our institution from January 1, 2005 through December 31, 2015 was conducted. Results Seventeen patients (4 male; 13 female) were identified. Median age was 15.4 years (range 8.8-17.1 years) with a median follow-up of 1.2 years (range 0.4-7.5 years). Thirteen (76.5%) patients presented with left lower extremity DVT. Management included catheter-directed thrombolysis ( n = 5), systemic thrombolysis ( n = 1), and mechanical thrombectomy ( n = 1). Fifteen patients were treated with anticoagulation including two patients with endovascular stents without DVT. Median duration of anticoagulation was 6.3 months (range 3.2-18.7 months). Ten patients (59%) underwent stent placements. Complete and partial thrombus resolution was noted in six patients each and no resolution in one patient. Four patients had recurrence/progression of thrombus ( n = 3 with stents) at a median time of 29 days (range 12-495 days). No bleeding complications were observed. Clinically documented or self-reported PTS was noted in 8 patients (62%). Conclusion There are no clear guidelines for MTS management in children and adolescents. In our cohort, thrombolysis, anticoagulation, or stent placements were not associated with bleeding risks, with recurrence/progression of DVT and signs and symptoms of PTS noted in 30 and 62%, respectively. Further studies are needed to determine a standardized treatment approach of the pediatric patient with MTS with or without thrombosis.


Patterns of Traumatic Spinal Injuries in the Developing World: A Five-Year Longitudinal Review.
Retrospective review. A 5-year longitudinal study documenting and comparing patterns of traumatic spinal injuries (TSIs) observed in developing countries. Current knowledge of the patterns and epidemiology of TSI are based on evidence from developed countries and there is a lack of data from developing countries to enable a comparison of information to formulate healthcare policies. A review of case records of all patients treated at a tertiary level trauma center over a 5-year period (2015-2019) was performed. Epidemiological, clinical, and radiological data were analyzed. The incidence of spinal trauma was 6.2% (2,065/33,072) among all trauma patients. Among these 2,065 patients, the mean age was 43.4±16.3 years and 77.3% (n=1,596) were aged 21-60 years. The major cause of injury was falls (52.1%, n=1,069) and 49.8% were high-energy falls (>10 feet [=3.048 m]). In patients with TSI due to falls, injuries occurred at the workplace (n=376), home (n=309), trees (n=151), wells (n=77), and electric poles (n=57). Road traffic accidents contributed to 42% (n=862) of TSIs and predominantly affected motorcyclists (52%, n=467). Around half (53.5%, n=1,005) of all patients were in the lower socioeconomic strata. The most common injury level was thoracic region (37.2%, n=769). Spinal cord injury (SCI) occurred in 49% (n=1,011) of patients and 49.7% (n=1,028) had injuries associated with other organs. Our study indicated different demographic patterns and epidemiological features of TSI compared with the Western literature, including a preponderance of young male patients, falls from heights, motorcycle accidents, and a larger percentage of SCI. The high number of falls at workplace indicates a lack of knowledge among the public and policy makers about safety measures.


On the mechanism of action of methylmalonyl-CoA mutase. Change of the steric course on isotope substitution.
When (methyl-2H3)methylmalonyl-CoA was reacted with partially purified methylmalonyl-CoA mutase, 1H-NMR revealed that about 24% of the migrating deuterium was lost after 88% conversion. When [methyl-3H]methylmalonyl-CoA was incubated with highly purified methylmalonyl-CoA mutase, tritium exchange with the medium depended on added methylmalonyl-CoA epimerase. With highly purified preparations of methylmalonyl-CoA mutase, effective tritium exchange from [5'-3H]adenosylcobalamin to water required the addition of methylmalonyl-CoA epimerase and of substrate (e.g. succinyl-CoA). By addition of [14C]succinyl-CoA to a partially purified preparation of methylmalonyl-CoA mutase, it was shown that the mutase binds one substrate molecule very tightly. Coupling the mutase reaction with the transcarboxylase reaction and using variously labelled succinyl-CoA as substrate, revealed that only (2R)- and not (2S)-methylmalonyl-CoA will be formed by the mutase with a kinetic isotope effect of 3.5 using (2H4)succinyl-CoA. When (1-13C) propionyl-CoA was reacted with a mixture of highly purified methylmalonyl-CoA carboxylase, epimerase and mutase, 13C-NMR signals were obtained for the thioester carbonyl of succinyl-CoA (relative intensity 100%) and of methylmalonyl-CoA (5%) as well as for the carboxyl of free succinic acid (27%) and of succinyl-CoA (less than 4.5%). Thus very little, if any, migration of the CoA from one carboxyl to the other appears to take place. (1,4-13C2)Succinic acid and (1,4-13C2)succinyl-CoA were synthesised and their 13C-NMR chemical shifts were exactly determined. Evidence is provided for a strict stereospecificity of the mutase toward the (2R)-epimer of methylmalonyl-CoA and for an incomplete stereospecificity toward the two diastereotopic 3-H atoms of succinyl-CoA. The latter, combined with a high intramolecular isotope discrimination, causes rapid washing-out of the migrating 2H and 3H to water and slow washing-in from the medium. Whenever migration of protium from the sterically less preferred 3-pro(S)- position of succinyl-CoA occurs and simultaneously a heavy isotope is maneuvered from the migratable 3-pro(R)- position into the labile alpha-position of methylmalonyl-CoA, the substitution by the COSCoA group takes place with inversion of configuration. When the sterically preferred 3-pro(R)-hydrogen atom migrates, the previously reported stereochemical retention occurs. A mechanistic and stereochemical scheme is discussed that fully accounts for all observations.


Allopolyploidization and evolution of species with reduced floral structures in Lepidium L. (Brassicaceae).
Understanding the pattern of speciation in a group of plants is critical for understanding its morphological evolution. Lepidium is the genus with the largest variation in floral structure in Brassicaceae, a family in which the floral ground plan is remarkably stable. However, flowers in more than half of Lepidium species have reduced stamen numbers, and most of these also have reduced petals. The species with reduced flowers are geographically biased, distributed mostly in the Americas and Australia New Zealand. Previous phylogenetic studies using noncoding regions of chloroplast DNA and rDNA internal transcribed spacer were incongruent in most New World species relationships. These data, combined with the presence of many polyploid Lepidium species, implied a reticulate history of the genus but did not provide enough information to infer the evolutionary pattern of flower structures. To address this question more thoroughly, sequences of the first intron of a single copy nuclear gene, PISTILLATA, were determined from 43 species. Phylogenetic analysis of the PI intron suggests that many species in the New World have originated from allopolyploidization, and that this is correlated with floral reduction. Interspecific hybrids were generated to understand why allopolyploidization is associated with reduced flowers. The phenotypes of F1 flowers indicate allelic dominance of the absence of lateral stamens, suggesting that propagation of dominant alleles through interspecific hybridization could account for the abundance of the allopolyploid species without lateral stamens.


Astragalus Polysaccharides Ameliorate Diet-Induced Gallstone Formation by Modulating Synthesis of Bile Acids and the Gut Microbiota.
Cholesterol gallstone (CG) disease has relationships with several metabolic abnormalities. Astragalus polysaccharides (APS) have been shown to have multiple benefits against metabolic disorders. We attempted to uncover the effect and mechanism of action of APS on diet-induced CG formation in mice. Animals were fed a chow diet or lithogenic diet (LD) with or without APS supplementation. The effect of APS on CG formation was evaluated. The level of individual bile acids (BAs) in gallbladder bile and ileum were measured by liquid chromatography-tandem mass spectrometry. Real-time reverse transcription-quantitative polymerase chain reaction and western blotting were used to assess expression of the genes involved in BA metabolism and the enterohepatic circulation. Cecal contents were collected to characterize microbiota profiles. APS ameliorated LD-induced CG formation in mice. APS reduced the level of total cholesterol, bile acid hydrophobicity index and cholesterol saturation index in gallbladder bile. The protective effect of APS might result from reduced absorption of cholic acid in the intestine and increased hepatic BA synthesis. APS relieved the LD-induced activation of the intestinal farnesoid X receptor and decreased ileal expression of fibroblast growth factor 15. In the liver, expression of cytochrome P450 (Cyp) enzyme Cyp7a1 and Cyp7b1 was increased, whereas expression of adenosine triphosphate-binding cassette (Abc) transporters Abcg5 and Abcg8 was decreased by APS. APS improved the diversity of the gut microbiota and increased the relative abundance of the Bacteroidetes phylum. APS had demonstratable benefits against CG disease, which might be associated with enhanced BA synthesis and improved gut microbiota. Our results suggest that APS may be a potential strategy for the prevention of CG disease.


Methionine metabolism: a window on carcinogenesis?
Recent experimental evidence links changes in methionine metabolism to the onset and progression of cancer. Aberrant methylation reactions and polyamine synthesis may alter genome stability, gene expression, and cell proliferation.


A Tailored App for the Self-management of Musculoskeletal Conditions: Evidencing a Logic Model of Behavior Change.
Musculoskeletal conditions such as joint pain are a growing problem, affecting 18.8 million people in the United Kingdom. Digital health interventions (DHIs) are a potentially effective way of delivering information and supporting self-management. It is vital that the development of such interventions is transparent and can illustrate how individual components work, how they link back to the theoretical constructs they are attempting to change, and how this might influence outcomes. getUBetter is a DHI developed to address the lack of personalized, supported self-management tools available to patients with musculoskeletal conditions by providing knowledge, skills, and confidence to navigate through a self-management journey. The aim of this study was to map a logic model of behavior change for getUBetter to illustrate how the content and functionality of the DHI are aligned with recognized behavioral theory, effective behavior change techniques, and clinical guidelines. A range of behavior change models and frameworks were used, including the behavior change wheel and persuasive systems design framework, to map the logic model of behavior change underpinning getUBetter. The three main stages included understanding the behavior the intervention is attempting to change, identifying which elements of the intervention might bring about the desired change in behavior, and describing intervention content and how this can be optimally implemented. The content was mapped to 25 behavior change techniques, including information about health consequences, instruction on how to perform a behavior, reducing negative emotions, and verbal persuasion about capability. Mapping to the persuasive system design framework illustrated the use of a number of persuasive design principles, including tailoring, personalization, simulation, and reminders. This process enabled the proposed mechanisms of action and theoretical foundations of getUBetter to be comprehensively described, highlighting the key techniques used to support patients to self-manage their condition. These findings provide guidance for the ongoing evaluation of the effectiveness (including quality of engagement) of the intervention and highlight areas that might be strengthened in future iterations.


[Ecological studies on genetically engineered microorganism in environment].
This paper discussed the main problems which should be considered on the environmental release of genetically engineered microorganism (GEM), including GEM construction, gene transfer, fitness, diffusion, translocation, potential eco-influence and so on. Moreover, aiming at the special ecological characteristic and eco-influence of GEM, this paper brought forward the policy of "respective analysis on different problems", and postulated the corresponding projects of GEM ecological research to apply GEM safely and effectively in nature.


A novel computational approach for predicting complex phenotypes in Drosophila (starvation-sensitive and sterile) by deriving their gene expression signatures from public data.
Many research teams perform numerous genetic, transcriptomic, proteomic and other types of omic experiments to understand molecular, cellular and physiological mechanisms of disease and health. Often (but not always), the results of these experiments are deposited in publicly available repository databases. These data records often include phenotypic characteristics following genetic and environmental perturbations, with the aim of discovering underlying molecular mechanisms leading to the phenotypic responses. A constrained set of phenotypic characteristics is usually recorded and these are mostly hypothesis driven of possible to record within financial or practical constraints. We present a novel proof-of-principal computational approach for combining publicly available gene-expression data from control/mutant animal experiments that exhibit a particular phenotype, and we use this approach to predict unobserved phenotypic characteristics in new experiments (data derived from EBI's ArrayExpress and ExpressionAtlas respectively). We utilised available microarray gene-expression data for two phenotypes (starvation-sensitive and sterile) in Drosophila. The data were combined using a linear-mixed effects model with the inclusion of consecutive principal components to account for variability between experiments in conjunction with Gene Ontology enrichment analysis. We present how available data can be ranked in accordance to a phenotypic likelihood of exhibiting these two phenotypes using random forest. The results from our study show that it is possible to integrate seemingly different gene-expression microarray data and predict a potential phenotypic manifestation with a relatively high degree of confidence (>80% AUC). This provides thus far unexplored opportunities for inferring unknown and unbiased phenotypic characteristics from already performed experiments, in order to identify studies for future analyses. Molecular mechanisms associated with gene and environment perturbations are intrinsically linked and give rise to a variety of phenotypic manifestations. Therefore, unravelling the phenotypic spectrum can help to gain insights into disease mechanisms associated with gene and environmental perturbations. Our approach uses public data that are set to increase in volume, thus providing value for money.


Modulation of CD8+ intraepithelial lymphocyte distribution by dietary fiber in the rat large intestine.
We studied whether ingestion of dietary fiber modifies the distribution of intraepithelial lymphocytes (IEL) in a physiological condition. Male WKAH rats were fed diets either with fiber (sugar beet fiber or crystalline cellulose, 100 g/kg diet each) or without fiber for 3 weeks. The number of CD8(+), CD4(+), and NKR-P1(+) IEL per epithelial layer in the crypt section of the cecum, proximal colon, and distal colon were scored by immunohistochemical staining. We found that the proportion of CD8(+) IEL was greater in the cecal mucosa and was gradually reduced toward the distal large intestine in general. In contrast, there was no difference in the proportion of CD4(+) and NKR-P1(+) IEL in the large intestine. Dietary sugar beet fiber, but not crystalline cellulose, increased the proportion of CD8(+) IEL, especially in the cecal mucosa, but not the CD4(+) and NKR-P1(+) IEL. Analysis of cecal organic acid concentration confirmed higher concentrations of acetate and butyrate, and lower concentration of succinate and isovalerate, in the cecum of the rats fed sugar beet fiber than other diets. These results indicate that ingestion of some dietary fiber modulates local cell proliferation of a progenitor of CD8(+) IEL or promotes homing of CD8(+) T cells into the large intestinal epithelium, most likely via the fermentation in the luminal contents.


Effects of combined exposure to dichlorvos and monocrotophos on blood and brain biochemical variables in rats.
Dichlorvos (DDVP) and monocrotophos (MC) are systemic insecticides and known to produce cholinergic and non-cholinergic effects. Individual toxic effects of these chemicals are known but their combined effects have not been studied. We studied the effect of concomitant exposure to DDVP and MC on selected biochemical variables suggestive of liver damage, changes in whole brain biogenic amines levels, acetylcholinesterase (AchE) and monoamine oxidase (MAO) activities in rats. Female rats were exposed to DDVP (2.5 mg/kg subcutaneously) and MC (1.8 mg/kg oral) either individually or in combination for 4 weeks. We observed significant decrease in more pronounced depletion in norepinephrine (NE) and dopamine (DA) levels during co-exposure to DDVP and MC. Brain AChE activity increased and activity of MAO showed significant depletion on co-exposure to DDVP and MC. Brain glutathione (GSH) and oxidized glutathione (GSSG) ratio decreased significantly during exposure to DDVP or MC while co-exposure to these toxicants led to a more pronounced depletion of GSH: GSSG ratio. Serum aspartate amino transferase (AST) and alkaline phosphatase (ALP) activities increased significantly on exposure to MC suggesting liver injury, while DDVP alone had no effect on these variables. There were no effects of DDVP and MC exposure on haematological biochemical variables except for depletion in serum glucose level after MC exposure which was more pronounced DDVP + MC during co-exposure. It can be concluded that only moderate synergistic effects occur between MC and DDVP during co-exposure. A more detailed study with variable doses, prolonged exposure and alterations in different brain regions is recommended.


Evaluation of hot compressed water pretreatment and enzymatic saccharification of tulip tree sawdust using severity factors.
Tulip tree sawdust was pretreated using hot compressed water with different pretreatment severities (LogR0, 3.05-5.01) by varying reaction temperatures (180-220°C) and residence time (1-30 min). It is found that the chemical composition and physicochemical properties of the pretreated products can be characterized and correlated with severity. Removal of most of the xylan and other hemicellulosic sugars from the raw material was observed at a severity of 4.5. Thus, the residual solids were recovered with increased cellulose and lignin contents. Nearly complete glucan conversion was achieved after 48 h of hydrolysis with 10 FPU/g of wet residual solid obtained above a severity of 4.8. The characteristics of the pretreated solids according to the pretreatment severity were strongly related with the glucose yield. The removal of structural barriers to the enzyme attack was the dominant factor affecting enzyme accessibility to the substrate.


Identifying Trajectories and Predictors of Response to Psychotherapy for Post-Traumatic Stress Disorder in Adults: A Systematic Review of Literature.
There exists considerable individual variability in the development and progression of pathological stress reactions after experiencing trauma, as well as in individuals' response to psychological interventions. Yet until recently, such individual differences had not been considered when evaluating the efficacy of therapeutic interventions for post-traumatic stress disorder (PTSD). This systematic review aims to examine the emerging literature on this subject and, specifically, to identify trajectories and predictors of psychotherapeutic response in adults with PTSD. Four databases were searched using specific keywords without date or language restrictions. For each study, independent reviewers systematically evaluated whether it met eligibility criteria and assessed risk of bias. For included studies, reviewers completed data extraction using standard formats. Those examining how subgroups of adults respond to therapy for clinical PTSD using trajectory modeling were deemed eligible. Demographic, PTSD, clinical, and trauma-related factors associated to particular trajectories were also examined. Of the 1,727 papers identified, 11 were included in this analysis. Of these studies, six focused on military-related traumas and five on civilian ones. Although studies found between two and five trajectories, most supported a three-trajectory model of response categorized as responders, nonresponders, and subclinical participants. Over 22 predictors of treatment trajectories were examined. Comorbid depression, anxiety, and alcohol abuse were the strongest predictors of poor therapeutic response. Age, combat exposure, social support, and hyperarousal were moderate predictors. This review provides valuable insight into the treatment of PTSD, as it supports the heterogeneous trajectories of psychotherapeutic responses and provides avenues for the development of interventions that consider individual-level factors in treatment response.


Additive effects of insulin-sensitizing and anti-androgen treatment in young, nonobese women with hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation.
The endocrine-metabolic hallmarks of polycystic ovary syndrome are hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation. We hypothesized that dyslipidemia and anovulation in nonobese women with polycystic ovary syndrome are essentially secondary to the concerted effects of hyperandrogenism and insulin resistance. We tested this hypothesis by comparing the efficacy of anti-androgen (flutamide) or insulin-sensitizing (metformin) monotherapy to that of combined therapy in normalizing the endocrine-metabolic and anovulatory status of nonobese, young women with hyperinsulinemic hyperandrogenism. Thirty-one young women (mean age, 18.7 yr; body mass index, 21.9 kg/m(2); hirsutism score, 16; monthly ovulation rate monitored by weekly serum progesterone, 10%) were randomly assigned to receive once daily flutamide (250 mg; n = 10), metformin (1275 mg; n = 8), or combined flutamide- metformin therapy (n = 13) for 9 months. At baseline, there were no endocrine-metabolic differences among treatment groups. Compared with monotherapy, combined flutamide-metformin therapy resulted in greater improvements in insulin sensitivity, in testosterone, androstenedione, dehydroepiandrosterone sulfate, and triglyceride levels, and in low-density lipoprotein/high-density lipoprotein-cholesterol ratio (all P < 0.005). Monthly ovulation rates increased after 9 months to 75 and 92%, respectively, with metformin alone or with combined therapy, but were unimproved with flutamide alone. All treatments were well tolerated. In conclusion, combined anti-androgen and insulin-sensitizing treatment in young, nonobese women with hyperinsulinemic hyperandrogenism had additive benefits on insulin sensitivity, hyperandrogenemia, and dyslipidemia. The data from this small study suggest that dyslipidemia is secondary to excess androgen action in concert with the hyperinsulinemia associated with insulin resistance. In contrast, anovulation seems to be mainly attributable to insulin resistance and hyperinsulinemia.


[Resilience behavior of titanium implants with integrated maintenance-free biokinetic elements].
Good functional properties are essential in dental implantology. Bio-kinetics elements are imitating dental resilience. In this study a new kind of implants with maintenance-free shock-absorbing elements was introduced and their bio-mechanic properties were tested. The mobile implant (SIS Inc, Klagenfurt, Austria) is a self-cutting conical screw implant with an integrated bio-kinetic element. The shock absorber is a central part of the implant and a titanium ring obturates the shock absorbing unit in the implant. The resilience of the implant was tested by axial and excentric loading in a special testing unit. Furthermore a survival test of the elastic titanium ring in the most exposed cervical part of the implant was performed. The region was examined by scanning electron microscopy after 12 million loading cycles in the axial and radial direction. A progressive shock absorption was registered during radial and axial loading. The maximum movements were 0.06 mm in the axial and 0.16 mm in the radial direction. No signs of material destruction were seen in the electron microscopic analysis. Thus a maintenance-free bio-kinetic implant with progressive shock-absorbing qualities is presented.


Clinical evaluation of microendoscopy-assisted extreme lateral interbody fusion.
Extreme lateral interbody fusion (XLIF) has rapidly become a popular operative procedure for lumbar canal stenosis and scoliosis. This approach provides direct access to the lateral aspect of the disc with minimal disruption of spinal structures, including ligaments and muscles. However, it involves risk of injuries to the lumbar nerve plexus, segmental artery and intestinal tract because of the limited surgical field. This study aimed to clarify the benefit of using a microendoscope to prevent these injuries. A total of 96 consecutive patients treated by a single surgeon were retrospectively analyzed. The basic approach via the psoas muscle was performed in accordance with the conventional XLIF procedure. Operative manipulations, such as insertion of the shim, discectomy, endplate preparation and intervertebral spacer placement, were performed with the assistance of a microendoscope. Preoperative and postoperative neurological status were evaluated using the Japanese Orthopedic Association (JOA) scores and the Oswestry Disability Index (ODI). Eighty-four patients underwent surgery for a single vertebral level, nine patients underwent surgery for 2 levels and three patients underwent surgery for 3 levels (average, 1.2 levels). The average age of patients was 61 years (range, 22-83 years); the mean follow-up period was 18 months (range, 3-36 months). Average preoperative and postoperative JOA scores were 11.9 and 15.6, with a mean recovery rate of 33%. Average preoperative and postoperative ODI scores were 38.6 and 19.1. There were 3 (3.1%) complications: 2 end-plate fractures and 1 deep surgical site infection. There were no bowel perforations or vascular injuries. Microendoscopy assistance is one solution for severe visceral and vascular injuries related to XLIF.


Computational prediction of the specificities of proteasome interaction with antigen protein.
In the processing and presentation of antigenic peptides bound by the major histocompatibility complex (MHC) class I molecule, the ubiquitin-proteasome system of the eukaryotic cells plays an important role in proteolysis and degradation. The ubiquitinated protein substrate is delivered into the 26S proteasome to be digested and degraded. The proteasome degrading substrate is actually protein-protein interactions. Some researches of predicting proteasome cleave site rarely gave the information of the proteasome interacting with its substrate, and so the accuracy and reliability of these proteasome cleavage predictive methods still need to be improved. This paper used support vector machine method (SVM) to predict the proteasomal cleavage sites, and the predictive accuracy of the model was 82.8%. We showed analytically that the cleavage specificities of the cleavage sites "|" and its adjacent positions, and gave the information about the proteasome interacting with its substrate from our research results. It demonstrates that the proteasome cleaving to target protein is selective, but not random.


A simplified testing system to evaluate performance after transplantation of human skin preserved in glycerol or in liquid nitrogen.
We have designed and tested a mouse recipient model for evaluation and direct comparison of skin-preservation procedures. Glycerolized skin was compared with cryopreserved and fresh cadaveric skin. Human skin samples were grafted on Balb/c mice, and primary take was evaluated after 4 and 7 days. The results demonstrate that although all grafted specimens were initially accepted as indicated by gross observations, histologic differences were evident and significant. Cryopreserved skin grafts performed better than did glycerolized skin even after a transplantation period as short as 4 days; this difference became even more pronounced after 7 days. Both methods of preservation provided a less successful product than did fresh viable cadaveric skin. However, for very short periods of grafting the performance of glycerolized skin might be considered adequate (79% compared with cryopreserved). Because the present study used an immunocompetent xenogeneic model, it is possible that the period of adequate allogeneic grafting will be prolonged in patients who are immunosuppressed. The present model is simple to use, requires a minimum of maintenance and expertise, and has inherent clinical relevance, because it is concerned primarily with the clinical performance of the skin. Thus it may be used as a quality control test for banked skin.


Protein kinase CK2 as a druggable target.
CK2 is probably the most pleiotropic Ser/Thr protein kinase with hundreds of endogenous substrates already known, which are implicated in a variety of cellular functions. At variance with most protein kinases whose activity is turned on only in response to specific stimuli, and whose genetic alterations often underlie pathological situations, CK2 is not susceptible to tight regulation and there are no mutations known to affect its constitutive activity. Nevertheless an abnormally high level of CK2 is invariably found in tumours, and solid arguments have accumulated suggesting that CK2 plays a global pro-survival function, which under special circumstances creates a cellular environment particularly favourable to the development and potentiation of the tumour phenotype. Therefore any strategy aimed at attenuating CK2 activity may represent a "master key" for the treatment of different neoplastic diseases. Waiting for the clarification of the epigenetic mechanisms promoting the rise of CK2 in cells predisposed to develop a tumour phenotype, a useful pharmacological aid can come from the improvement of a number of fairly potent and selective CK2 inhibitors already available.


Changes in synaptic plasticity and expression of glutamate receptor subunits in the CA1 and CA3 areas of the hippocampus after transient global ischemia.
Excess glutamate release from the presynaptic membrane has been thought to be the major cause of ischemic neuronal death. Although both CA1 and CA3 pyramidal neurons receive presynaptic glutamate input, transient cerebral ischemia induces CA1 neurons to die while CA3 neurons remain relatively intact. This suggests that changes in the properties of pyramidal cells may be the main cause related to ischemic neuronal death. Our previous studies have shown that the densities of dendritic spines and asymmetric synapses in the CA1 area are increased at 12h and 24h after ischemia. In the present study, we investigated changes in synaptic structures in the CA3 area and compared the expression of glutamate receptors in the CA1 and CA3 hippocampal regions of rats after ischemia. Our results demonstrated that the NR2B/NR2A ratio became larger after ischemia although the expression of both the NR2B subunit (activation of apoptotic pathway) and NR2A subunit (activation of survival pathway) decreased in the CA1 area from 6h to 48h after reperfusion. Furthermore, expression of the GluR2 subunit (calcium impermeable) of the AMPA receptor class significantly decreased while the GluR1 subunit (calcium permeable) remained unchanged at the same examined reperfusion times, which subsequently caused an increase in the GluR1/GluR2 ratio. Despite these notable differences in subunit expression, there were no obvious changes in the density of synapses or expression of NMDAR and AMPAR subunits in the CA3 area after ischemia. These results suggest that delayed CA1 neuronal death may be related to the dramatic fluctuation in the synaptic structure and relative upregulation of NR2B and GluR1 subunits induced by transient global ischemia.


Misoprostol treatment vs expectant management in women with early non-viable pregnancy and vaginal bleeding: a pragmatic randomized controlled trial.
To compare vaginal misoprostol treatment with expectant management in early non-viable pregnancy with vaginal bleeding with regard to complete evacuation of the uterine cavity within 10 days after randomization. This was a parallel randomized controlled, open-label trial conducted in Skåne University Hospital, Sweden. Patients with anembryonic pregnancy or early fetal demise (crown-rump length ≤ 33 mm) and vaginal bleeding were randomly allocated to either expectant management or treatment with a single dose of 800 μg misoprostol administered vaginally. Patients were evaluated clinically and by ultrasound until complete evacuation of the uterus was achieved (no gestational sac in the uterine cavity and maximum anteroposterior diameter of the intracavitary contents < 15 mm as measured by transvaginal ultrasound on midsagittal view). Follow-up visits were planned at 10, 17, 24 and 31 days. Dilatation and evacuation (D&E) was recommended if miscarriage was not complete within 31 days, but was performed earlier at patient's request, or if there was excessive bleeding as judged clinically. Analysis was by intention to treat. The main outcome measure was number of patients with complete miscarriage without D&E ≤ 10 days. Ninety-four patients were randomized to misoprostol treatment and 95 to expectant management. After exclusion of three patients and withdrawal of consent by two patients in the expectant management group, 90 women were included in this group. Miscarriage was complete ≤ 10 days in 62/94 (66%) of the patients in the misoprostol group and in 39/90 (43%) of those in the group managed expectantly (risk difference (RD) = 23%; 95% CI, 8-37%). At 31 days, the corresponding figures were 81/94 (86%) and 55/90 (61%) (RD = 25%; 95% CI, 12-38%). Two patients from each group underwent emergency D&E because of excessive bleeding and one of these in each group received blood transfusion. The number of patients undergoing D&E at their own request was higher in the expectantly managed group, 15/90 (17%) vs 3/94 (3%) in the misoprostol group (RD = 14%; 95% CI, 4-23%), as was the number of patients making out-of-protocol visits, 50/90 (56%) vs 27/94 (29%) (RD = 27%; 95% CI, 12-40%). Compared with the expectant management group, more patients in the misoprostol group experienced pain (71/77 (92%) vs 91/91 (100%); RD = 8%; 95% CI, 1-17%) and used painkillers (59/77 (77%) vs 85/91 (93%); RD = 17%; 95% CI, 5-29%). No major side effect was reported in any group. In women with early non-viable pregnancy and vaginal bleeding, misoprostol treatment is more effective than is expectant management for complete evacuation of the uterus. Both methods are safe but misoprostol treatment is associated with more pain than is expectant management. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Lentiviral gene transfer of TCIRG1 into peripheral blood CD34(+) cells restores osteoclast function in infantile malignant osteopetrosis.
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorptive function of IMO osteoclasts by lentiviral mediated gene transfer of the TCIRG1 cDNA. CD34(+) cells from peripheral blood of five IMO patients and from normal cord blood were transduced with lentiviral vectors expressing TCIRG1 and GFP under a SFFV promoter, expanded in culture and differentiated on bone slices to mature osteoclasts. qPCR analysis and western blot revealed increased mRNA and protein levels of TCIRG1, comparable to controls. Vector corrected IMO osteoclasts generated increased release of Ca(2+) and bone degradation product CTX-I into the media as well as increased formation of resorption pits in the bone slices, while non-corrected IMO osteoclasts failed to resorb bone. Resorption was approximately 70-80% of that of osteoclasts generated from cord blood. Furthermore, transduced CD34(+) cells successfully engrafted in NSG-mice. In conclusion we provide the first evidence of lentiviral-mediated correction of a human genetic disease affecting the osteoclastic lineage.


Comparative effects of N,N-disubstituted dithiocarbamates and dimercaptosuccinate on mobilization of methylmercury in mice.
Diethyldithiocarbamate (DDTC) and five of its N,N-disubstituted analogs were compared with dimercaptosuccinate (DMSA) for effectiveness in mobilizing and promoting excretion of methylmercury (MeHg) following administration of a sublethal dose of MeHg labeled with Me203Hg. The previously reported effectiveness of DMSA was confirmed. Of the dithiocarbamates assessed, only di(carboxymethyl)-dithiocarbamate (DCDC) was active in mobilizing MeHg, and its activity on a molar dose basis was less than that of DMSA. The disparate structural requirements of dithiocarbamates as antagonists of MeHg and of cadmium were discussed.


[Obstetrical complications of adenomyosis. Literature review and two case reports].
Adenomyosis of the uterus is a frequent disorder often associated with pregnancy. Diagnosis is difficult during pregnancy and usually is made after an obstetrical complication. In a review of the literature from 1904 to 1994, only 31 cases of obstetrical complications related to adenomyosis have been reported. We report two cases revealed by obstetrical complications: one causing spontaneous rupture of the uterus during labor in a primiparous woman and the other with cornual ectopic pregnancy diagnosed, due to an episode of massive intraperitoneal bleeding.


Environmental gamma-ray dose rate in Aomori Prefecture, Japan.
Japan's first commercial nuclear fuel cycling facilities, including a spent nuclear fuel reprocessing plant, are now under construction in Rokkasho, Aomori Prefecture (prefecture--an area of administration similar to a county in the U.S.). The reprocessing plant is due to be completed by 2004. We surveyed indoor and outdoor environmental gamma-ray dose rates throughout Aomori Prefecture from 1992 to 1996 to get background data before operation of the plant. Glass dosimeters were used to measure cumulative gamma-ray dose rate. The outdoor gamma-ray dose rates were measured at 109 locations in the prefecture. The indoor gamma-ray dose rates were measured at 81 locations, which were generally in a dwelling near the location of an outdoor measurement. The contribution of radionuclides in the ground to the outdoor dose rate was estimated by using in-situ gamma-ray spectrometry with a germanium detector. The spectra were measured at 20 locations used for the glass dosimeter measurements. The outdoor gamma-ray dose rate was higher in the Tsugaru area (western part of the prefecture) than in the Nanbu area (eastern part). Means of the dose rate were 28, 31, and 25 nGy h(-1) for the whole prefecture and Tsugaru and Nanbu areas, respectively. The dose rates in winter were lower than those in the other seasons due to the shielding effect of snow on the ground. Mean contributions of uranium series, thorium series and 40K to the dose rates were 7.7, 8.2, and 9.3 nGy h(-1), respectively. The indoor dose rate was generally higher than the outdoor one, and the mean ratio of indoor to outdoor dose rates was 1.42. Means of indoor gamma-ray dose rate were 41, 37, and 43 nGy h(-1) for the whole prefecture and Tsugaru and Nanbu areas, respectively. The average effective dose rate to people in the prefecture was estimated to be 0.24 mSv y(-1).


Dismembered pyeloplasty in infants under the age of 12 months.
To assess the impact of internal ureteric stenting on the surgical outcome of dismembered pyeloplasty in infants under the age of 12 months. The case records of 53 of 55 infants with the diagnosis of congenital pelvi-ureteric junction obstruction who underwent dismembered pyeloplasty over a 6-year period were available for review. A total of 63 renal units were treated surgically. The policy for urinary drainage changed during this period from predominantly nephrostomy or no drainage to that of internal ureteric stenting. The post-operative mean (SD) length of stay for stented and non-stented cases was 5.9 (1.8) and 12.4 (5.4) days, respectively (P < 0.001). The mean length of stay for patients with bilateral and unilateral pyeloplasty was 9.7 (4.9) and 8.0 (4.7) days, respectively (P = 0.19). Urinary leaks occurred in non-stented anastomoses and not in stented anastomoses. All three cases which later required revision pyeloplasty had had significant complications associated with urinary leaks. With a minimum follow-up of 24 months, a favourable outcome, as determined by radio-isotope imaging, was achieved in 48 of 51 infants (94%) for whom follow-up data were available. The use of internal ureteric stenting in dismembered pyeloplasty performed in infants < 12 months old has, in our hands, led to a dramatic reduction in operative morbidity. The routine use of internal ureteric stents at the time of pyeloplasty is justified.


The RADial artery International ALliance (RADIAL) extended follow-up study: rationale and study protocol.
It is generally accepted that radial artery (RA) grafts have better mid-term patency rate compared to saphenous vein grafts. However, the clinical correlates of the improved patency rate are still debated. Observational studies have suggested increased survival and event-free survival for patients who receive an RA rather than a saphenous vein, but they are open to bias and confounders. The only evidence based on randomized data is a pooled meta-analysis of 6 randomized controlled trial comparing the RA and the saphenous vein published by the RADial artery International Alliance (RADIAL). In the RADIAL database, improved freedom from follow-up cardiac events (death, myocardial infarction and repeat revascularization) was found at 5-year follow-up in the RA arm. The most important limitation of the RADIAL analysis is that most of the included trials had an angiographic follow-up in the first 5 years and it is unclear whether the rate of repeat revascularization (the main driver of the composite outcome) was clinically indicated due to per-protocol angiographies. Here, we present the protocol for the long-term analysis of the RADIAL database. By extending the follow-up beyond the 5th postoperative year (all trials except 1 did not have angiographic follow-up beyond 5 years), we aim to provide data on the role of RA in coronary artery bypass surgery with respect to long-term outcomes.


Effect of aldehyde lipid oxidation products on myoglobin.
The effects of aldehyde lipid oxidation products on myoglobin (Mb) were investigated at 37 degrees C and pH 7.2. Oxymyoglobin (OxyMb) oxidation increased in the presence of 4-hydroxynonenal (4-HNE) compared to controls (P < 0.05). Preincubation of metmyoglobin (MetMb) with aldehydes rendered the heme protein a poorer substrate for enzymatic MetMb reduction compared to controls, and the effect was inversely proportional to preincubation time; unsaturated aldehydes were more effective than saturated aldehydes (P < 0.05). The order of MetMb reduction as affected by preincubation was control > hexanal > heptanal > octanal > nonanal = decanal = hexenal > heptenal = octenal > nonenal = decenal = 4-HNE (P < 0.05). Preincubation of MetMb with 4-HNE enhanced the subsequent ability of the heme protein to act as a prooxidant in both liposomes and microsomes when compared to controls (P < 0.05); the effect was reduced in microsomes containing elevated concentrations of alpha-tocopherol (P < 0.05). MetMb preincubation with mono-unsaturated aldehydes enhanced the catalytic activity of MetMb to a greater degree than saturated aldehydes (P < 0.05). These results suggest that aldehyde lipid oxidation products can alter Mb stability by increasing OxyMb oxidation, decreasing the ability of MetMb to be enzymatically reduced and enhancing the prooxidant activity of MetMb.


Single ectopic thoracic renal artery associated with a normal kidney position and renal artery stenosis: a case report and review of literature.
There are several reports of multiple ectopic renal arteries (RA) in the literature. However, the ectopic origin of a single RA with a normal kidney position is rare. Knowledge of this variant is extremely important in clinical, surgical and radiological practice. Using MDCT angiography examination, we describe a rare case of a right kidney located in a normal lumbal position with a single ectopic thoracic renal artery originating in the thorax, above the diaphragmatic dome, at the level of the upper one-third of the T12 vertebral body. With an "S"-shaped course and a total length of 103 mm, this artery had an intratoracic portion of 38 mm. It crossed the diaphragm at 23 mm lateral to the right side of the TA, through a hiatus located on the lateral side of the right crus of the diaphragm. The right inferior phrenic artery arose from the left lateral wall of the right RA, 5 mm below the level of CT (45 mm distal to the right RA origin). Remarkably, this variant was associated with an area of proximal arterial stenosis, which produced signs and symptoms of hypertension secondary to renal arterial stenosis. To the authors' knowledge, this is the first reported case of a stenotic single ectopic thoracic renal artery associated with a normal kidney position.


Characterization of blood lipoproteins and validation of cholesterol and triacylglycerol assays for free-ranging polar bears (Ursus maritimus).
Blood triacylglycerol (TG) and lipoproteins are important variables for evaluating nutritional status of wildlife, but measurements are often expensive and difficult. Performance of a small, portable blood analyzer intended for human medical diagnostics was evaluated in measuring these variables in plasma and serum from free-ranging polar bears (Ursus maritimus), which are experiencing nutritional stress related to sea ice loss. The analyzer accurately tracked changes in concentration of total cholesterol (Ctotal), cholesterol associated with high-density lipoprotein (CHDL), and TG during a validation protocol of diluting samples and spiking them with exogenous cholesterol and glycerol. Values of Ctotal and TG agreed well with values obtained by other methods (ultracentrifugation followed by colorimetric assays); agreement was variable for values of cholesterol associated with specific lipoproteins. Similar to a study of captive polar bears, ultracentrifugation methods revealed greater TG in very low-density lipoproteins than in low-density lipoprotein, which is unusual and merits additional study.


Micro-CT based experimental liver imaging using a nanoparticulate contrast agent: a longitudinal study in mice.
Micro-CT imaging of liver disease in mice relies on high soft tissue contrast to detect small lesions like liver metastases. Purpose of this study was to characterize the localization and time course of contrast enhancement of a nanoparticular alkaline earth metal-based contrast agent (VISCOVER ExiTron nano) developed for small animal liver CT imaging. ExiTron nano 6000 and ExiTron nano 12000, formulated for liver/spleen imaging and angiography, respectively, were intravenously injected in C57BL/6J-mice. The distribution and time course of contrast enhancement were analysed by repeated micro-CT up to 6 months. Finally, mice developing liver metastases after intrasplenic injection of colon carcinoma cells underwent longitudinal micro-CT imaging after a single injection of ExiTron nano. After a single injection of ExiTron nano the contrast of liver and spleen peaked after 4-8 hours, lasted up to several months and was tolerated well by all mice. In addition, strong contrast enhancement of abdominal and mediastinal lymph nodes and the adrenal glands was observed. Within the first two hours after injection, particularly ExiTron nano 12000 provided pronounced contrast for imaging of vascular structures. ExiTron nano facilitated detection of liver metastases and provided sufficient contrast for longitudinal observation of tumor development over weeks. The nanoparticulate contrast agents ExiTron nano 6000 and 12000 provide strong contrast of the liver, spleen, lymph nodes and adrenal glands up to weeks, hereby allowing longitudinal monitoring of pathological processes of these organs in small animals, with ExiTron nano 12000 being particularly optimized for angiography due to its very high initial vessel contrast.