[AIDS through blood contamination (early 1980s) and urethane shock (1975)].
1) AIDS contracted through contaminated blood was first discovered in the early 1980s, and related law suits are now underway. The contamination of the blood is considered to ba a shared responsibility of the "government," "medical establishments" and "industry." The revision of the Pharmaceutical Affairs Law in 1979 gave the authority for commanding the recall of products to the Health and Welfare Ministry. This was a lesson learned from past cases of drug-induced suffering. However, the ministry did nothing regarding the blood contaminated with the AIDS virus. 2) "Urethane shock (drug-induced suffering)" occurred in 1975. Although it occurred before the revision of the Pharmaceutical Affairs Law, the Health and Welfare Ministry took the administrative measure of "an immediate recall," because the antipyretic analgesic injections used all over the country at that time contained 0.15 to 0.3g of urethane which is a carcinogenic substance, per ampoule. 3) Even the revision of the Pharmaceutical Affairs Law could not prevent cases of drug-induced suffering. I think that all concerned should have a full understanding, receive fair judgement and be encouraged to prevent such mistakes in the future.


On the mechanism of action of the antifungal agent propionate.
Propionate is used to protect bread and animal feed from moulds. The mode of action of this short-chain fatty acid was studied using Aspergillus nidulans as a model organism. The filamentous fungus is able to grow slowly on propionate, which is oxidized to acetyl-CoA via propionyl-CoA, methylcitrate and pyruvate. Propionate inhibits growth of A. nidulans on glucose but not on acetate; the latter was shown to inhibit propionate oxidation. When grown on glucose a methylcitrate synthase deletion mutant is much more sensitive towards the presence of propionate in the medium as compared to the wild-type and accumulates 10-fold higher levels of propionyl-CoA, which inhibits CoA-dependent enzymes such as pyruvate dehydrogenase, succinyl-CoA synthetase and ATP citrate lyase. The most important inhibition is that of pyruvate dehydrogenase, as this affects glucose and propionate metabolism directly. In contrast, the blocked succinyl-CoA synthetase can be circumvented by a succinyl-CoA:acetate/propionate CoA-transferase, whereas ATP citrate lyase is required only for biosynthetic purposes. In addition, data are presented that correlate inhibition of fungal polyketide synthesis by propionyl-CoA with the accumulation of this CoA-derivative. A possible toxicity of propionyl-CoA for humans in diseases such as propionic acidaemia and methylmalonic aciduria is also discussed.


Colonoscopy in the management of diseases of the colon and rectum.
This report covers a 2.5-year experience with colonoscopy in the management of 208 patients (104 men and 98 women, average age 58 years). Colonic bleeding of unknown cause and abnormal barium-enema findings were the most common indications for colonoscopic examination. During this period, 110 colonoscopic polypectomies were performed. Among the few complications was one case of perforation of the sigmoid from transcolonoscopic removal of a small carcinoma; the perforation was incidentally discovered at the time of subsequent laparotomy. Bleeding occurred in 6 patients, but only one of them required surgical intervention to arrest the hemorrhage. Colonoscopy is a safe, effective and reliable diagnostic and therapeutic procedure. Its use can reduce expense for the patient and obviate a long painful postoperative period.


Fit-for-purpose phosphorus management: do riparian buffers qualify in catchments with sandy soils?
Hillslope runoff and leaching studies, catchment-scale water quality measurements and P retention and release characteristics of stream bank and catchment soils were used to better understand reasons behind the reported ineffectiveness of riparian buffers for phosphorus (P) management in catchments with sandy soils from south-west Western Australia (WA). Catchment-scale water quality measurements of 60 % particulate P (PP) suggest that riparian buffers should improve water quality; however, runoff and leaching studies show 20 times more water and 2 to 3 orders of magnitude more P are transported through leaching than runoff processes. The ratio of filterable reactive P (FRP) to total P (TP) in surface runoff from the plots was 60 %, and when combined with leachate, 96 to 99 % of P lost from hillslopes was FRP, in contrast with 40 % measured as FRP at the large catchment scale. Measurements of the P retention and release characteristics of catchment soils (<2 mm) compared with stream bank soil (<2 mm) and the <75-μm fraction of stream bank soils suggest that catchment soils contain more P, are more P saturated and are significantly more likely to deliver FRP and TP in excess of water quality targets than stream bank soils. Stream bank soils are much more likely to retain P than contribute P to streams, and the in-stream mixing of FRP from the landscape with particulates from stream banks or stream beds is a potential mechanism to explain the change in P form from hillslopes (96 to 99 % FRP) to large catchments (40 % FRP). When considered in the context of previous work reporting that riparian buffers were ineffective for P management in this environment, these studies reinforce the notion that (1) riparian buffers are unlikely to provide fit-for-purpose P management in catchments with sandy soils, (2) most P delivered to streams in sandy soil catchments is FRP and travels via subsurface and leaching pathways and (3) large catchment-scale water quality measurements are not good indicators of hillslope P mobilisation and transport processes.


Prevalence of Fusarium species of the Liseola section on selected Colombian animal feedstuffs and their ability to produce fumonisins.
A total of 57 samples of feedstuffs commonly used for animal nutrition in Colombia (corn, soybean, sorghum, cottonseed meal, sunflower seed meal, wheat middlings and rice) were analyzed for Fusarium contamination. Fusarium fungi were identified at species level by means of conventional methods and the ability to produce fumonisins of the most prevailing species was determined. A total of 41 of the feedstuffs analyzed (71.9%) were found to contain Fusarium spp. Most contaminated substrates were corn (100%), cottonseed meal (100%), sorghum (80%), and soybean (80%). Wheat middlings and rice showed lower levels of contamination (40% and 20%, respectively), while no Fusarium spp. could be isolated from sunflower seed meal. The most prevalent species of Fusarium isolated were F. verticilliodes (70.8%), F. proliferatum (25.0%), and F. subglutinans (4.2%). All of them correspond to section Liseola. Production of fumonisins on corn by the isolated Fusarium was screened through liquid chromatography. Almost all strains of F. verticilliodes (97.1%) produced FB1 (5.6-25, 846.4 mg/kg) and FB2 (3.4-7507.5 mg/kg). Similarly, almost all strains of F. proliferatum (91.7%) produced fumonisins but at lower levels than F. verticilliodes (FB1 from 6.9 to 3885.0 mg/kg, and FB2 from 34.3 to 373.8 mg/kg), while F. subglutinans did not produce these toxins. This is the first study in Colombia describing toxigenic Fusarium isolates from animal feedstuffs.


CLImAT-HET: detecting subclonal copy number alterations and loss of heterozygosity in heterogeneous tumor samples from whole-genome sequencing data.
Copy number alterations (CNA) and loss of heterozygosity (LOH) represent a large proportion of genetic structural variations of cancer genomes. These aberrations are continuously accumulated during the procedure of clonal evolution and patterned by phylogenetic branching. This invariably results in the emergence of multiple cell populations with distinct complement of mutational landscapes in tumor sample. With the advent of next-generation sequencing technology, inference of subclonal populations has become one of the focused interests in cancer-associated studies, and is usually based on the assessment of combinations of somatic single-nucleotide variations (SNV), CNA and LOH. However, cancer samples often have several inherent issues, such as contamination of normal stroma, tumor aneuploidy and intra-tumor heterogeneity. Addressing these critical issues is imperative for accurate profiling of clonal architecture. We present CLImAT-HET, a computational method designed for capturing clonal diversity in the CNA/LOH dimensions by taking into account the intra-tumor heterogeneity issue, in the case where a reference or matched normal sample is absent. The algorithm quantitatively represents the clonal identification problem using a factorial hidden Markov model, and takes an integrated analysis of read counts and allele frequency data. It is able to infer subclonal CNA and LOH events as well as the fraction of cells harboring each event. The results on simulated datasets indicate that CLImAT-HET has high power to identify CNA/LOH segments, it achieves an average accuracy of 0.87. It can also accurately infer proportion of each clonal population with an overall Pearson correlation coefficient of 0.99 and a mean absolute error of 0.02. CLImAT-HET shows significant advantages when compared with other existing methods. Application of CLImAT-HET to 5 primary triple negative breast cancer samples demonstrates its ability to capture clonal diversity in the CAN/LOH dimensions. It detects two clonal populations in one sample, and three clonal populations in one other sample. CLImAT-HET, a novel algorithm is introduced to infer CNA/LOH segments from heterogeneous tumor samples. We demonstrate CLImAT-HET's ability to accurately recover clonal compositions using tumor WGS data without a match normal sample.


A comprehensive evaluation of hemodynamic energy production and circuit loss using four different ECMO arterial cannulae.
Pulsatile-flow veno-arterial extracorporeal membrane oxygenation (V-A ECMO) has shown encouraging results for microcirculation resuscitation and left ventricle unloading in patients with refractory cardiogenic shock. We aimed to comprehensively assess different V-A ECMO parameters and their contribution to hemodynamic energy production and transfer through the device circuit. We used the i-cor® ECMO circuit, which composed of Deltastream DP3 diagonal pump and i-cor® console (Xenios AG), the Hilite 7000 membrane oxygenator (Xenios AG), venous and arterial tubing and a 1 L soft venous pseudo-patient reservoir. Four different arterial cannulae (Biomedicus 15 and 17 Fr, Maquet 15 and 17 Fr) were used. For each cannula, 192 different pulsatile modes were investigated by adjusting flow rate, systole/diastole ratio, pulsatile amplitudes and frequency, yielding 784 unique conditions. A dSpace data acquisition system was used to collect flow and pressure data. Increasing flow rates and pulsatile amplitudes were associated with significantly higher hemodynamic energy production (both p < 0.001), while no significant associations were seen while adjusting systole-to-diastole ratio (p = 0.73) or pulsing frequency (p = 0.99). Arterial cannula represents the highest resistance to hemodynamic energy transfer with 32%-59% of total hemodynamic energy generated being lost within, depending on pulsatile flow settings used. Herein, we presented the first study to compare hemodynamic energy production with all pulsatile ECLS pump settings and their combinations and widely used yet previously unexamined four different arterial ECMO cannula. Only increased flow rate and amplitude increase hemodynamic energy production as single factors, whilst other factors are relevant when combined.


pH is an intracellular effector controlling differentiation of oligodendrocyte precursors in culture via activation of the ERK1/2 pathway.
We reported previously that onset of oligodendrocyte precursor cell (OPC) differentiation is accompanied by an increase in intracellular pH (pH(i)). We show that OPC differentiation is dependent primarily on a permissive pH(i) value. The highest differentiation levels were observed for pH(i) values around 7.15 and inhibition of differentiation was observed at slightly more acidic or alkaline values. Clamping the pH(i) of OPCs at 7.15 caused a transient activation of ERK1/2 that was not observed at more acidic or alkaline values. Furthermore, inhibition of ERK activation with the UO126 compound totally prevented OPC differentiation in response to pH(i) shift. These results indicate that pH(i), acting through the ERK1/2 pathway, is a key determinant for oligodendrocyte differentiation. We also show that this pH(i) pathway is involved in the process of retinoic acid-induced OPC differentiation.


Potential Economic Benefits of Paid Sick Leave in Reducing Absenteeism Related to the Spread of Influenza-Like Illness.
Most U.S. employers are not required to provide paid sick leave (PSL), and there is limited information on the economic return of providing PSL. We estimated potential benefits to employers of PSL in reducing absenteeism related to the spread of influenza-like illness (ILI). We used nationally representative data and a negative binomial random effects model to estimate the impact of PSL in reducing overall absence due to illness or injury. We used published data to compute the share of ILI from the total days of absence, ILI transmission rates at workplaces, wages, and other parameters. Providing PSL could have saved employers $0.63 to $1.88 billion in reduced ILI-related absenteeism costs per year during 2007 to 2014 in 2016 dollars. These findings might help employers consider PSL as an investment rather than as a cost without any return.


Two unusual causes of peripatellar nonmetastatic positive bone scans in patients with malignancies: case reports.
Bone scans performed with 99mTc-polyphosphate in two patients with epidermoid carcinoma of the lung each showed activity in one knee area. In the first case, radiographs of the area revealed Pellegrini-Stieda calcification over the internal femoral condyle. Uptake corresponded to this process, rather than to a lesion deep in the bone. In the second case, the activity accumulation in the right tibia was the only abnormality noted in the scan. An open biopsy revealed Paget's disease, and no radiographic evidence of Paget's disease was found in any other bone. These cases again illustrate that localized accumulation of a bone-scanning agent, in patients with known primary tumors, does not necessarily denote malignancy in bone.


A conservation planning approach to mitigate the impacts of leakage from protected area networks.
Protected area networks are designed to restrict anthropogenic pressures in areas of high biodiversity. Resource users respond by seeking to replace some or all of the lost resources from locations elsewhere in the landscape. Protected area networks thereby perturb the pattern of human pressures by displacing extractive effort from within protected areas into the broader landscape, a process known as leakage. The negative effects of leakage on conservation outcomes have been empirically documented and modeled using homogeneous descriptions of conservation landscapes. Human resource use and biodiversity vary greatly in space, however, and a theory of leakage must describe how this heterogeneity affects the magnitude, pattern, and biodiversity impacts of leakage. We combined models of household utility, adaptive human foraging, and biodiversity conservation to provide a bioeconomic model of leakage that accounts for spatial heterogeneity. Leakage had strong and divergent impacts on the performance of protected area networks, undermining biodiversity benefits but mitigating the negative impacts on local resource users. When leakage was present, our model showed that poorly designed protected area networks resulted in a substantial net loss of biodiversity. However, the effects of leakage can be mitigated if they are incorporated ex-ante into the conservation planning process. If protected areas are coupled with nonreserve policy instruments such as market subsidies, our model shows that the trade-offs between biodiversity and human well-being can be further and more directly reduced.


Interleukin 18 receptor 1 expression distinguishes patients with multiple sclerosis.
Definition of dysregulated immune components in multiple sclerosis may help in the identification of new therapeutic targets. Deviation of the interleukin 18 receptor 1 (IL18R1) is of particular interest since the receptor is critical for experimental neuroinflammation. The objective of this study was to determine whether expression of IL18R1 varies between multiple sclerosis patients and controls, and to test genetic association of IL18R1 with multiple sclerosis. We used quantitative real-time PCR to assess mRNA levels of IL18R1 in cerebrospinal fluid and peripheral blood mononuclear cells of 191 patients with multiple sclerosis, 61 patients with clinically isolated syndrome and 168 controls having other neurological disorders. Association was tested in 2153 patients with multiple sclerosis and 1733 controls using 13 tagging single nucleotide polymorphisms within the IL18R1 gene. We found that patients with multiple sclerosis had increased IL18R1 mRNA expression in both cerebrospinal fluid cells (p < 0.05) and peripheral blood mononuclear cells (p < 0.05) compared with controls. Patients with clinically isolated syndrome had elevated levels compared with controls in cerebrospinal fluid cells (p < 0.001) but not in peripheral blood mononuclear cells. The gene was not associated to multiple sclerosis. We conclude that the increased expression of IL18R1 may contribute pathogenically to disease and is therefore a potential therapeutic target. The absence of a genetic association in the IL18R1 gene itself suggests regulation from other parts of the genome, or as part of the inflammatory cascade in multiple sclerosis without a prime genetic cause.


Concentrations of the vitamin D metabolite 1,25(OH)2D and odds of metabolic syndrome and its components.
Few epidemiological studies have investigated the association between circulating concentrations of the active vitamin D metabolite 1,25(OH)2D and metabolic syndrome. We sought to determine whether blood levels of 1,25(OH)2D are associated with metabolic syndrome and its individual components, including waist circumference, triglycerides, blood pressure, and glucose, and high-density lipoprotein. We also investigated these associations for the more abundant precursor vitamin D metabolite, 25(OH)D. Participants from two completed clinical trials of colorectal neoplasia with available metabolic syndrome data and blood samples for measurement of 1,25(OH)2D (n=1048) and 25(OH)D (n=2096) were included. Cross-sectional analyses of the association between concentrations of 1,25(OH)2D, 25(OH)D, metabolic syndrome, and its components were conducted. A statistically significant inverse association was observed for circulating concentrations of 1,25(OH)2D and metabolic syndrome, with adjusted ORs (95% CIs) of 0.73 (0.52-1.04) and 0.52 (0.36-0.75) for the second and third tertiles of 1,25(OH)2D, respectively (p-trend <0.001). Significant inverse relationships were also observed between 1,25(OH)2D and high triglycerides (p-trend <0.001), and low high-density lipoprotein (p-trend <0.001). For 25(OH)D concentrations, significant inverse associations were found for metabolic syndrome (p-trend <0.01), high waist circumference (p-trend <0.04) and triglyceride levels (p-trend <0.01). Participants with 25(OH)D ≥30 ng/ml and in the highest tertile of 1,25(OH)2D demonstrated significantly lower odds of metabolic syndrome, with an OR (95% CI) of 0.38 (0.19-0.75) compared to those in the lowest category for both metabolites. These results provide new evidence that the relatively rarely-studied active hormonal form of vitamin D, 1,25(OH)2D, is associated with metabolic syndrome and its components, and confirm prior findings for 25(OH)D. The finding that 1,25(OH)2D is related to high-density lipoprotein, while 25(OH)D is not, suggests that there may be an independent mechanism of action for 1,25(OH)2D in relation to metabolic dysregulation.


[The connections between structure, pharmacokinetics and effects of glucocorticoids].
Corticosteroids above all have an influence on the metabolism of proteins, lipids and carbohydrates. Inflammatory and immunological reactions are suppressed. The effects are based on the induction of both primary and secondary responses. Examples in catabolic and anabolic reactions are described. The significance of bioavailability is illustrated and hints to discriminate the types of corticosteroids for therapeutic requirement are given.


Deleterious effects of adrenocorticotrophic hormone administration during late pregnancy upon offspring somatic, neurological, and sexual development in mice.
The influence of administration of adrenocorticotrophic hormone (ACTH) during days 12-17 of pregnancy upon somatic, neurological, and neuromuscular development of offspring in mice was studied. The effects upon the onset of puberty in female offspring was also examined. Litters from mice given the higher of two doses of ACTH (1 IU/day or 8 IU/day) showed lower body weights at birth and weaning than controls. This treatment also increased pre- and postnatal mortality rates, although not significantly. Litters from mice treated with either dose of ACTH showed retarded development of the forelimb and hindlimb grasp reflexes, the body righting reflex, the auditory startle response, and eye opening. Although ear opening was delayed in litters from ACTH-treated mice, results did not achieve statistical significance. Study of female offspring housed in small groups revealed that one indicator of puberty, vaginal opening, was delayed in female offspring of ACTH-treated mice. Experiments were conducted to identify factors mediating this syndrome: ACTH did not depress maternal food intake or alter the length of pregnancy, therefore fetal undernutrition or premature birth can be excluded as mediating factors. All litters were fostered to untreated mice to control for postnatal factors influencing development. As ACTH cannot cross the placenta, the syndrome is likely to result from in utero exposure to abnormally high concentrations of glucocorticosteroids of maternal origin. It is concluded that such alterations to the fetal environment can exert a deleterious influence upon somatic, neurological, and sexual development, and that hormones of the maternal pituitary-adrenocortical axis may naturally act to regulate general development of the fetus.


Local Insulin Improves Wound Healing: A Systematic Review and Bayesian Network Meta-Analysis.
Wounds are a significant health issue, and reliable and safe strategies to promote repair are needed. Clinical trials have demonstrated that local insulin promotes healing in acute and chronic wounds (ie, reductions of 7% to 40% versus placebo). However, the trials' sample sizes have prevented drawing solid conclusions. Furthermore, no analysis has focused on safety concerns (ie, hypoglycemia). Under the hypothesis that local insulin promotes healing through proangiogenic effects and cellular recruitment, the aim of this systematic review and network meta-analysis (NMA) was to assess its safety and relative effectiveness using a Bayesian approach. Medline, CENTRAL, Embase, Scopus, LILACS, and gray literature sources were searched for human studies assessing the local use of insulin versus any comparator since inception to October of 2020. Data on glucose changes and adverse events, wound and treatment characteristics, and healing outcomes were extracted, and an NMA was conducted. A total of 949 reports were found, of which 23 ( n = 1240 patients) were included in the NMA. The studies evaluated six different therapies, and most comparisons were against placebo. NMA showed -1.8 mg/dL blood glucose level change with insulin and a lack of reported adverse events. Statistically significant clinical outcomes identified include reduction in wound size (-27%), increased healing rate (23 mm/day), reduction in Pressure Ulcer Scale for Healing scores (-2.7), -10 days to attain complete closure, and an odds ratio of 20 for complete wound closure with insulin use. Likewise, significantly increased neoangiogenesis (+30 vessels/mm 2 ) and granulation tissue (+25%) were also found. Local insulin promotes wound healing without significant adverse events.


The effects of systemic magnesium sulfate infusion on brain magnesium concentrations and energy state during hypoxia-ischemia in newborn miniswine.
The mechanism of neuroprotection associated with systemically administered magnesium remains unclear. This investigation examined the acute effects of systemically administered MgSO4 on brain extracellular ([Mg]ecf) and intracellular ([Mg]i) fluid Mg concentrations, specific brain phosphorylated metabolites, and brain intracellular pH. Miniswine were studied with P-31 magnetic resonance spectra, to derive [Mg]i, and brain microdialysis probes, to measure [Mg]ecf. Animals were infused with MgSO4 (n = 5, 275 mg/kg over 30 min followed by 100 mg/kg over 30 min, designated MgHI) or Na2SO4 (n = 5, designated NaHI), and both groups underwent hypoxia-ischemia (HI) over the last 15 min of the infusions. Groups differed in plasma [Mg] at the completion of HI (9.1 +/- 1.5 versus 1.1 +/- 0.6 mM for MgHI and NaHI, respectively, p < 0.05). MgHI had elevations of [Mg]ecf (0.23 +/- 0.11 and 0.40 +/- 0.14 mM at control and completion of HI, respectively), and [Mg]ecf was unchanged for NaHI (p < 0.05 versus MgHI). At the completion of HI, MgHI had greater decreases in nucleoside triphosphate (NTP) (48 +/- 6% of control), and more brain acidosis after HI (6.01 +/- 0.07) compared with NaHI (NTP, 70 +/- 3% of control; brain pH, 6.51 +/- 0.14, both p < 0.05 versus MgHI). [Mg]i increased to elevated values during HI in both MgHI and NaHI (p < 0.05 versus control of each group) and remained higher in MgHI over the next 25 min (p < 0.05 versus NaHI). There were inverse correlations during HI between [Mg]i and brain NTP (r2 = 0.73 and 0.59 for MgHI and NaHI, respectively), and brain acidosis (r2 = 0.85 and 0.85 for MgHI and NaHI, respectively) in each group. These findings indicate complex effects of Mg on the brain. Elevation of [Mg]ecf may be beneficial with regards to excitatory neurotransmitters. However, greater disturbance of brain NTP concentration, more acidosis, and the increase in [Mg]i may offset any benefit. The results warrant further investigation using indicators of neuronal injury to determine whether Mg supplementation provides neuroprotection.


First line treatment of advanced non-small-cell lung cancer - specific focus on albumin bound paclitaxel.
Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007) is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel). A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.


Non-identity and authentication of two major reference strains of Candida albicans.
It has been suggested recently that the two most widely used reference strains of Candida albicans (NCPF 3153 and B311) were derived from the same parental strain. However, records maintained at the PHLS Mycological Reference Laboratory suggest otherwise. In an attempt to resolve this contradiction, assessments were made of biotypes, resistogram patterns, morphotypes and restriction fragment length polymorphisms (RFLP) for nine isolates of NCPF 3153 and six of B311, obtained from 11 different centres. Biotyping results showed that with one exception (isolate No. 3, putatively derived from NCPF 3153), only strains derived from B311 were resistant to flucytosine at 12.5 micrograms ml-1 in agar. Moreover, strain No. 3 differed from other NCPF 3153 derivatives in its resistogram and RFLP patterns, which were indistinguishable from B311 isolates. It was concluded that the two reference strains were not derived from the same parental strain, and that they could be distinguished from each other by biotype, resistogram and RFLP patterns. Strains designated as B311 resembled each other closely, in contrast to NCPF 3153 isolates, which had variable resistogram and RFLP patterns. The simplest screening procedure for distinguishing B311 isolates was their resistance to flucytosine. Since test isolate No. 3 differed consistently from other putative NCPF 3153 isolates, it was concluded that its status was uncertain and that its designation as = NCPF 3153 should be discontinued.


Flavisolibacter tropicus sp. nov., isolated from tropical soil.
A Gram-stain-negative, non-motile, deep yellow, rod-shaped bacterium, designated strain LCS9T, was isolated from a soil sample at the tropical zone within the Ecorium of the National Institute of Ecology in Seocheon, central-western Korea. 16S rRNA gene sequence analysis showed that strain LCS9T clustered with members of the genus Flavisolibacter of the family Chitinophagaceae, phylum Bacteroidetes. Sequence similarities between strain LCS9T and the type strains of the genus Flavisolibacter ranged from 94.6 to 94.9 %. Strain LCS9T grew at 10-37 °C (optimum, 25 °C) and at pH 6.0-10.0 (optimum, pH 7); was positive for catalase and oxidase; and negative for nitrate reduction and production of indole. Cells showed pigment absorbance peaks at 451 and 479 nm, and had 0.03 % survival following exposure to 3 kGy gamma radiation. Strain LCS9T had the following chemotaxonomic characteristics: the major quinone was menaquinone-7 (MK-7); the major fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH; polar lipids included phosphoatidylethanolamine, an unidentified aminophospholipid, unidentified aminolipidsand unidentified lipids. The DNA G+C content was 39.4 mol%. Based on polyphasic analysis, the type strain LCS9T (=KCTC 42070T=JCM 19972T) represents a novel species for which the name Flavisolibacter tropicus sp. nov. is proposed. Radiation resistance in the genus Flavisolibacter has not been reported to date, and so this is the first report of low-level radiation resistance of a member of the genus.


Disseminated Erysipelothrix rhusiopathiae with Secondary Prosthetic Hip Joint Infection: A Case of Successful Identification and Management in a Regional Hospital.
This article reports a case of a 72-year-old man with bilateral total hip joint replacements who suffered cuts to his hands while butchering a wild boar. He presented to the emergency department with fevers and unilateral hip pain. Erysipelothrix rhusiopathiae (E. rhusiopathiae) was isolated on hip aspirate and blood cultures. E. rhusiopathiae is a well-recognized zoonotic infection in humans, particularly in at-risk hosts, most commonly infecting swine. Infection is spread by ingestion or through skin abrasion. This illustrates an example of successful operative and perioperative management of prosthetic joint infection secondary to E. rhusiopathiae, particularly microbiological identification, within a multispecialty team of physicians and surgeons.


Comparison of quantitative parameters and radiomic features as inputs into machine learning models to predict the Gleason score of prostate cancer lesions.
The classification of prostate cancer (PCa) lesions using Prostate Imaging Reporting and Data System (PI-RADS) suffers from poor inter-reader agreement. This study compared quantitative parameters or radiomic features from multiparametric magnetic resonance imaging (mpMRI) or positron emission tomography (PET), as inputs into machine learning (ML) to predict the Gleason scores (GS) of detected lesions for improved PCa lesion classification. 20 biopsy-confirmed PCa subjects underwent imaging before radical prostatectomy. A pathologist assigned GS from tumour tissue. Two radiologists and one nuclear medicine physician delineated the lesions on the mpMR and PET images, yielding 45 lesion inputs. Seven quantitative parameters were extracted from the lesions, namely T2-weighted (T2w) image intensity, apparent diffusion coefficient (ADC), transfer constant (KTRANS), efflux rate constant (Kep), and extracellular volume ratio (Ve) from mpMR images, and SUVmean and SUVmax from PET images. Eight radiomic features were selected out of 109 radiomic features from T2w, ADC and PET images. Quantitative parameters or radiomic features, with risk factors of age, prostate-specific antigen (PSA), PSA density and volume, of 45 different lesion inputs were input in different combinations into four ML models - Decision Tree (DT), Support Vector Machine (SVM), k-Nearest-Neighbour (kNN), Ensembles model (EM). SUVmax yielded the highest accuracy in discriminating detected lesions. Among the 4 ML models, kNN yielded the highest accuracies of 0.929 using either quantitative parameters or radiomic features with risk factors as input. ML models' performance is dependent on the input combinations and risk factors further improve ML classification accuracy.


Combining multi-catalysis and multi-component systems for the development of one-pot asymmetric reactions: stereoselective synthesis of highly functionalized bicyclo[4.4.0]decane-1,6-diones.
We have developed a direct amine/acid-catalyzed stereoselective hydrogenation of a variety of Wieland-Miescher (W-M) ketones, Hajos-Parrish (H-P) ketones and their analogs with organic hydrides (Hantzsch esters) as the hydrogen source. This astonishingly simple and biomimetic approach was used to construct highly functionalized chiral bicyclo[4.4.0]decane-1,6-diones in a diastereoselective fashion. This is an example of the development of a new technology by the combination of multiple catalysts and components in one pot to deliver highly functionalized chiral molecules.


High frequencies of circulating memory T cells specific for calreticulin exon 9 mutations in healthy individuals.
Mutations in exon 9 of the calreticulin gene (CALR) frequently occur in patients with chronic myeloproliferative neoplasms (MPN). Patients exhibit spontaneous cellular immune responses to epitopes derived from the mutant CALR C-terminus, and CALR-mutant-specific T cells recognize autologous CALR-mutant malignant cells. This study investigated whether CALR-mutant-specific T cells occur naturally in CALRwt MPN-patients and in healthy individuals. Specific immune responses against epitopes in the mutant CALR peptide sequence were detected in both CALRwt MPN-patients and in healthy individuals. Healthy donors displayed more frequent and stronger CALR-mutant specific T-cell responses compared to the responses identified in CALR-mutant MPN-patients. Several T-cell responses were identified in healthy donors directly ex vivo. Importantly, by running functional analyses on live-sorted immune cells from healthy donors, we showed that circulating CALR-mutant-specific immune cells are T-memory cells. These findings suggest, that healthy individuals acquire a CALR exon 9 mutation, but the immune system reacts and clears the mutant cells, and during this reaction generates CALR-mutant specific T-memory cells. We believe that these findings provide the evidence for tumor immune surveillance in MPN.


An assessment of the translational relevance of Drosophila in drug discovery.
Drosophila melanogaster offers a powerful expedient and economical system with facile genetics. Because of the high sequence and functional conservation with human disease-associated genes, it has been cardinal in deciphering disease mechanisms at the genetic and molecular level. Drosophila are amenable to and respond well to pharmaceutical treatment which coupled to their genetic tractability has led to discovery, repositioning, and validation of a number of compounds. Areas covered: This review summarizes the generation of fly models of human diseases, their advantages and use in elucidation of human disease mechanisms. Representative studies provide examples of the utility of this system in modeling diseases and the discovery, repositioning and testing on pharmaceuticals to ameliorate them. Expert opinion: Drosophila offers a facile and economical whole animal system with many homologous organs to humans, high functional conservation and established methods of generating and validating human disease models. Nevertheless, it remains relatively underused as a drug discovery tool probably because its relevance to mammalian systems remains under question. However, recent exciting success stories using Drosophila disease models for drug screening, repositioning and validation strongly suggest that fly models should figure prominently in the drug discovery pipeline from bench to bedside.


Evaluation of ventilated sanders in the autobody repair industry.
Orbital and reciprocating sanders were evaluated in autobody shops to obtain information on the ability of the sanders to control worker dust exposures. Air is exhausted from ventilated sanders at a rate of 0.25 to 1.0 m3/min. When unventilated sanders were used, short-term total dust exposures ranged between 2 and 170 mg/m3. When ventilated sanders were used, short-term total exposures ranged between 0.22 and 1.2 mg/m3. Aerosol photometer measurements showed that ventilation decreased dust exposure by a factor of 10 when body-filling compound was sanded. These results indicate that the use of sanders equipped with high-velocity, low-volume ventilation should be encouraged in the autobody repair industry.


Osteology of Pseudochampsa ischigualastensis gen. et comb. nov. (Archosauriformes: Proterochampsidae) from the early late triassic ischigualasto formation of Northwestern Argentina.
Proterochampsids are crocodile-like, probably semi-aquatic, quadrupedal archosauriforms characterized by an elongated and dorsoventrally low skull. The group is endemic from the Middle-Late Triassic of South America. The most recently erected proterochampsid species is "Chanaresuchus ischigualastensis", based on a single, fairly complete skeleton from the early Late Triassic Ischigualasto Formation of northwestern Argentina. We describe here in detail the non-braincase cranial and postcranial anatomy of this species and revisit its taxonomy and phylogenetic relationships. The phylogenetic analysis recovered 'Chanaresuchus ischigualastensis' as part of a trichotomy together with Gualosuchus reigi and Chanaresuchus bonapartei. Accordingly, "Chanaresuchus ischigualastensis" can be potentially more closely related to Gualosuchus reigi, or even Rhadinosuchus gracilis, than to Chanaresuchus bonapartei. In addition, after discussing previously claimed synapomorphies of Chanaresuchus, we could not find unambiguous support for the monophyly of the genus. As a result, we propose here the erection of the new genus Pseudochampsa for 'Chanaresuchus ischigualastensis', which results in the new combination Pseudochampsa ischigualastensis. The information provided here about the anatomy and taxonomy of Pseudochampsa ischiguaslastensis will be useful for future quantitative analyses focused on the biogeography and macroevolutionary history of proterochampsids.


Validating activity indices from camera traps for commensal rodents and other wildlife in and around farm buildings.
Indices of rodent activity are used as indicators of population change during field evaluation of rodenticides. We investigated the potential for using camera traps to determine activity indices for commensal rodents living in and around farm buildings, and sought to compare these indices against previously calibrated survey methods. We recorded 41 263 images of 23 species, including Norway rats (Rattus norvegicus Berk.) and house mice (Mus musculus L.). We found a positive correlation between activity indices from camera traps and activity indices from a method (footprint tracking) previously shown to have a linear relationship with population size for Norway rats. Filtering the camera trap data to simulate a 30-s delay between camera trigger events removed 59.9% of data and did not adversely affect the correlation between activity indices from camera traps and footprint tracking. The relationship between activity indices from footprint tracking and Norway rat population size is known from a previous study; from this, we determined the relationship between activity indices from camera traps and population size for Norway rats living in and around farm buildings. Systematic use of camera traps was used to determine activity indices for Norway rats living in and around farm buildings; the activity indices were positively correlated with those derived from a method previously calibrated against known population size for this species in this context. © 2017 Crown copyright. Pest Management Science © 2017 Society of Chemical Industry.


Hippophae rhamnoides L.: A Comprehensive Review on the Botany, Traditional Uses, Phytonutrients, Health Benefits, Quality Markers, and Applications.
Hippophae rhamnoides L. (sea buckthorn), consumed as a food and health supplement worldwide, has rich nutritional and medicinal properties. Different parts of H. rhamnoides L. were used in traditional Chinese medicines for relieving cough, aiding digestion, invigorating blood circulation, and alleviating pain since ancient times. Phytochemical studies revealed a wide variety of phytonutrients, including nutritional components (proteins, minerals, vitamins, etc.) and functional components like flavonoids (1-99), lignans (100-143), volatile oils (144-207), tannins (208-230), terpenoids (231-260), steroids (261-270), organic acids (271-297), and alkaloids (298-305). The pharmacological studies revealed that some crude extracts or compounds of H. rhamnoides L. demonstrated various health benefits, such as anti-inflammatory, antioxidant, hepatoprotective, anticardiovascular disease, anticancer, hypoglycemic, hypolipidemic, neuroprotective, antibacterial activities, and their effective doses and experimental models were summarized and analyzed in this paper. The quality markers (Q-markers) of H. rhamnoides L. were predicted and analyzed based on protobotanical phylogeny, traditional medicinal properties, expanded efficacy, pharmacokinetics and metabolism, and component testability. The applications of H. rhamnoides L. in juice, wine, oil, ferment, and yogurt were also summarized and future prospects were examined in this review. However, the mechanism and structure-activity relationship of some active compounds are not clear, and quality control and potential toxicity are worth further study in the future.


Dietary supplementation of brown seaweed (Sargassum latifolium) alleviates the environmental heat stress-induced toxicity in male Barki sheep (Ovis aries).
Heat stress (HS) is the most potent environmental stressors for livestock in tropical and subtropical regions. HS induced splanchnic tissue hypoxia and intestinal oxidative damage, leading to endotoxemia and systemic inflammation. The present study evaluated and compared the modulatory effects of feeding Barki male sheep (Ovis aries) on a standard concentrated diet containing 2% or 4% of the brown seaweed (Sargassum latifolium) followed by roughage for 40 consecutive days on the toxicity-induced by exposure to severe environmental HS (temperature-humidity index = 28.55 ± 1.62). The present study showed that the diet containing Sargassum latifolium (especially 4%) modulated significantly (P < 0.05-0.001) almost all changes shown in the HS-exposed sheep including the increase in the thermo-respiratory responses (skin and rectal temperatures, and respiration rate) and the resulted dyslipidemia, anemia, and systemic inflammation (blood leukocytosis, the elevation in the erythrocyte sedimentation rate, and the increase in serum proinflammatory cytokines and heat shock protein-70 concentrations). In addition, Sargassum latifolium improved significantly (P < 0.05-0.001) the body-weight gain, kidney functions (especially at the high dose), and blood antioxidant defense system (total antioxidant capacity, and the activities of catalase and superoxide dismutase) in the HS-exposed sheep, as well as protected the animals from oxidative tissue damage and the risk of atherosclerosis. In conclusion, feeding sheep with the diet containing 4% of Sargassum latifolium was safe and suitable for animal nutrition, as well as efficiently alleviated the harmful effects of the environmental HS in Barki sheep through improving the animal antioxidant defense system, and regulating the thermo-respiratory and inflammatory responses.


Causal variance decompositions for institutional comparisons in healthcare.
There is increasing interest in comparing institutions delivering healthcare in terms of disease-specific quality indicators (QIs) that capture processes or outcomes showing variations in the care provided. Such comparisons can be framed in terms of causal models, where adjusting for patient case-mix is analogous to controlling for confounding, and exposure is being treated in a given hospital, for instance. Our goal here is to help identify good QIs rather than comparing hospitals in terms of an already chosen QI, and so we focus on the presence and magnitude of overall variation in care between the hospitals rather than the pairwise differences between any two hospitals. We consider how the observed variation in care received at patient level can be decomposed into that causally explained by the hospital performance adjusting for the case-mix, the case-mix itself, and residual variation. For this purpose, we derive a three-way variance decomposition, with particular attention to its causal interpretation in terms of potential outcome variables. We propose model-based estimators for the decomposition, accommodating different link functions and either fixed or random effect models. We evaluate their performance in a simulation study and demonstrate their use in a real data application.


Mental rotation training in older adults: The role of practice and strategy.
There is evidence of mental rotation (MR) abilities responding to training even in older adults, but it is still not clear whether such training would have generalized and maintained effects. The aim of the present study was to examine the specific short- and long-term gains, and any transfer effects, induced by rotation training in healthy older adults. The study involved 43 healthy older adults: 14 practiced with 2 MR tasks, that is, a 3D same/different comparisons task and a Tetris game (the Mental Rotation [MR] group); 15 were trained to use a strategy based on concrete object manipulation and imagery, then practiced with the 2 rotation tasks (Strategy [S] + MR group); and 14 were involved in alternative nonspatial activities (active control group). Transfer and maintenance effects were assessed (after 1 month) using tasks similar to those used in the training (criterion tasks), different spatial tasks (mental rotation and perspective taking tasks) and a fluid intelligence task. The results showed a trend toward an improvement in successive training sessions. The S + MR and MR groups both gained substantially more than the active control group in the short- and long-term, in the criterion tasks and most of the tasks testing transfer effects. The S + MR group showed greater long-term gains than the MR group in most tasks. These findings support a positive effect of rotation training in older adults, particularly when associated with strategy use. (PsycINFO Database Record


The inhibitory effects of monovalent ions on force development in detergent-skinned ventricular muscle from guinea-pig.
Trabeculae from guinea-pig ventricles were bathed in a physiological saline, were stimulated electrically and were stretched until isometric force production was maximal. They were then 'skinned' by superfusion for 30 min with a solution containing the non-ionic detergent, Triton X-100. The steady isometric force generated by these skinned trabeculae was measured in solutions of different pCa (-log10 [Ca2+]) and salt concentration to investigate the influence of salt concentration on (i) the maximum Ca2+-regulated force (at pCa approximately 3.8), (ii) the resting force (at pCa greater than 8) and (iii) the pCa required for 50% Ca2+ activation (pCa50). The apparent affinity constants of EGTA (ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetraacetic acid) for Ca2+ were measured in the solutions of different salt composition by a pH-metric method and these constants were used in the calculation of solution pCa. Increases in ionic strength (gamma/2) (and osmolarity) over the range 0.1-0.4 mol/l produced by the addition of various monovalent Cl or K salts resulted in an approximately linear decrease in the maximum Ca2+-regulated force. The inhibitory actions of the different salts were similar despite the differences in size and structure of their constituent ions. Increases in solution osmolarity alone, produced by the addition of sucrose up to 0.6 mol/l, did not significantly alter the maximum Ca2+-regulated force. It was concluded that the influence of monovalent salts on the maximum Ca2+-regulated force was due entirely to the changes in ionic strength and was not related to changes in solution osmolarity or to specific ion effects. Resting force was little affected by changes in salt concentration at ionic strengths of 0.2 mol/l and above. At lower ionic strengths the muscles exhibited an elevated resting force and an inability to relax completely after a Ca2+ -regulated contracture. A decrease in ionic strength from 0.2 to 0.1 mol/l produced by a reduction in KCl concentration raised the pCa50 from 5.56 to 5.85, i.e. the Ca2+ sensitivity was increased. However, the same increase in pCa50 was observed when the [K+] was lowered at constant ionic strength, osmolarity and [Cl-] by the replacement of KCl with tetramethylammonium Cl or choline Cl. Therefore, the change in pCa50 induced by an alteration in KCl concentration was due entirely to a specific inhibitory action of K+ on the Ca2+ sensitivity of cardiac myofibrils and was unrelated to changes in ionic strength, osmolarity and [Cl-]. Substitution of KCl 0.1 mol/l in the solutions by NaCl did not significantly alter the pCa50.(ABSTRACT TRUNCATED AT 400 WORDS)


Fluctuating dimension in a discrete model for quantum gravity based on the spectral principle.
The spectral principle of Connes and Chamseddine is used as a starting point to define a discrete model for Euclidean quantum gravity. Instead of summing over ordinary geometries, we consider the sum over generalized geometries where topology, metric, and dimension can fluctuate. The model describes the geometry of spaces with a countable number n of points, and is related to the Gaussian unitary ensemble of Hermitian matrices. We show that this simple model has two phases. The expectation value <n>, the average number of points in the Universe, is finite in one phase and diverges in the other. We compute the critical point as well as the critical exponent of <n>. Moreover, the space-time dimension delta is a dynamical observable in our model, and plays the role of an order parameter. The computation of <delta> is discussed and an upper bound is found, <delta> < 2.


Stroke risk reduction with oral anticoagulation using CHA2DS2-VASc in a Japanese AF population: A modeling analysis.
Current clinical guidelines recommend that risk stratification for ischaemic stroke in patients with nonvalvular AF (NVAF) should be performed using the CHA2DS2-VASc score (Congestive heart failure, Hypertension, Age≥ 75years [double], Diabetes mellitus, previous thromboembolism [double], Vascular disease, Age 65-74years, and female gender) to aid decision making for antithrombotic treatment, with a preference for Non-Vitamin K Oral Anticoagulants (NOACs) in those with CHA2DS2-VASc score ≥1. However, CHA2DS2-VASc score is not recommended in the 2014 Japanese Circulation Society (JCS) guidelines for patients with NVAF. To assess the impact of the JCS approach to stroke prevention in AF, and model the impact of using a CHA2DS2-VASc based 2-step decision making strategy, we calculated the incidence of ischaemic stroke in NVAF patients without OAC on basis of the CHADS2 and CHA2DS2-VASc scores using published Japanese data, and estimated the preventable number of stroke events. Using a CHA2DS2-VASc-based approach, the potential annual stroke events based on the estimated total number of NVAF patients in Japan was 889,000, as follows: 4369 for dabigatran 150 mg, 6049 for dabigatran 110mg, 5918 for rivaroxaban (intention-to-treat; ITT), 5302 for apixaban, 5843 for edoxaban 60mg (ITT), and 7598 for edoxaban 30 mg (ITT), respectively. Using a CHADS2 score-based approach, the number of potential stroke events was much greater for each agent. Our modelling analysis has shown that when considering antithrombotic treatment for Japanese NVAF patients, using a CHA2DS2-VASc-based approach would allow greater opportunities for stroke prevention.


The DRY motif and the four corners of the cubic ternary complex model.
Recent structural data on GPCRs using a variety of spectroscopic approaches suggest that GPCRs adopt a dynamic conformational landscape, with ligands stabilizing subsets of these states to activate one or more downstream signaling effectors. A key outstanding question posed by this emerging dynamic structural model of GPCRs is what states, active, inactive, or intermediate are captured by the numerous crystal structures of GPCRs complexed with a variety of agonists, partial agonists, and antagonists. In the early nineties the discovery of inverse agonists and constitutive activity led to the idea that the active receptor state (R⁎) is an intrinsic property of the receptor itself rather than of the RG complex, eventually leading to the formulation of the cubic ternary complex model (CTC). Here, by a careful analysis of a series of data obtained with a number of mutants of the highly conserved E/DRY motif, we show evidences for the existence of all the receptor states theorized by the CTC, four 'uncoupled (R, R⁎ and HR and HR⁎), and, consequently four 'coupled' (RG, R⁎G, HRG and HR⁎G). The E/DRY motif located at the cytosolic end of transmembrane helix III of Class A GPCRs has been widely studied and analyzed because it forms a network of interactions believed to lock receptors in the inactive conformation (R), and, thus, to play a key role in receptor activation. Our conclusions are supported by recent crystal and NMR spectra, as well as by results obtained with two prototypical GPCRs using a new FRET technology that de-couples G protein binding to the receptor from signal transduction. Thus, despite its complexity and limitations, we propose that the CTC is a useful framework to reconcile pharmacological, biochemical and structural data.


Osteoblastomas of the spine: a comprehensive review.
Osteoblastomas are primary bone tumors with an affinity for the spine. They typically involve the posterior elements, although extension through the pedicles into the vertebral body is not uncommon. Histologically, they are usually indistinguishable from osteoid osteomas. However, there are different variants of osteoblastomas, with the more aggressive type causing more pronounced bone destruction, soft-tissue infiltration, and epidural extension. A bone scan is the most sensitive radiographic examination used to evaluate osteoblastomas. These osseous neoplasms usually present in the 2nd decade of life with dull aching pain, which is difficult to localize. At times, they can present with a painful scoliosis, which usually resolves if the osteoblastoma is resected in a timely fashion. Neurological manifestations such as radiculopathy or myelopathy do occur as well, most commonly when there is mass effect on nerve roots or the spinal cord itself. The mainstay of treatment involves surgical intervention. Curettage has been a surgical option, although marginal excision or wide en bloc resection are preferred options. Adjuvant radiotherapy and chemotherapy are generally not undertaken, although some have advocated their use after less aggressive surgical maneuvers or with residual tumor. In this manuscript, the authors have aimed to systematically review the literature and to put forth an extensive, comprehensive overview of this rare osseous tumor.


[Unsolved problems in the surgical treatment of complicated ulcers of the stomach and duodenum].
The article generalizes an experience of a number of surgical collectives of the Military Medical Academy with the surgical treatment of complicated gastroduodenal ulcers by organ-preserving operations. The authors recommend wider use of such interventions in acute complications of ulcer disease (perforation and bleedings). It is important to abstain from performing such operations on planned patients with very high gastric secretion in order to decrease the amount of recurrences after vagotomy, to choose an adequate draining operation in stenosis. In young patients vagotomy should be combined with antrumresection.


On-chip reconfigurable optical add-drop multiplexer for hybrid wavelength/mode-division-multiplexing systems.
A silicon-based on-chip reconfigurable optical add-drop multiplexer (ROADM) is presented for hybrid wavelength-division-multiplexing-mode-division-multiplexing systems. The present ROADM consists of a four-channel mode demultiplexer, four wavelength-selective thermo-optic switches based on microring resonators, and a four-channel mode multiplexer. With the present ROADM, one can add/drop one of wavelength channels of any mode to/from the multimode bus waveguide successfully with an excess loss of 2-5 dB and an extinction ratio of ∼20 dB over a wavelength range of 1525-1555 nm.


Lack of competition results in efficient packaging of heterologous murine retroviral RNAs and reticuloendotheliosis virus encapsidation-minus RNAs by the reticuloendotheliosis virus helper cell line.
We constructed recombinant reticuloendotheliosis virus (Rev)-derived and murine leukemia virus-derived vectors to characterize the specificity of packaging retroviral RNAs in Rev proteins. Using this approach, we further localized the Rev encapsidation sequence (E) to a 144-nucleotide region and determined that there are sequences in both the 5' and 3' halves of this region which are necessary in cis for viral replication. We found that the Rev E, like the murine leukemia virus E (psi), is position independent (R. Mann and D. Baltimore, J. Virol. 54:401-407, 1986). Also, a 156-nucleotide region of the Rev intron enhanced replication in a cis-acting fashion in the presence, but not in the absence, of helper virus. Finally, we showed that packaging of E- and heterologous retroviral genomes occurred efficiently in the Rev helper cell in the absence of competing E-containing (E+) viral RNAs.


Use of life cycle assessment as decision-support tool for water reuse and handling of residues at a Danish industrial laundry.
This analysis presents the results of a life cycle assessment (LCA) carried out on six alternative options for the recycling of water at a Danish industrial laundry for workwear. The study focuses on the handling and disposal of the wet residues generated when wastewater is treated for recycling, and in accounting for long-term potential toxicity impacts. The analysed options are a combination of two water-upgrading technologies: biofilter and ultrafiltration, and three residue disposal alternatives: biogas followed by incineration of sludge at local wastewater treatment plant, thermal vitrification treatment for production of vitrified sand, and mineralization in a sludge bed. It is concluded from the results that with the current Danish environmental policy priorities, the environmental impacts of highest priority are the toxicity effects derived from the presence of heavy metals in the residues. Heavy metals originate from the dirt in the workwear that is washed in the laundry. It is further concluded that the studied water treatment technologies satisfy both the need of clean water for recycling and simultaneously help controlling a safe disposal of pollutants by concentration of the residues. The results of the study also confirm the potential of LCA as a decision-support tool for assisting water recycling initiatives and for residue handling management. The handling of residues has been identified as a stage of the water recycling strategy that bears important environmental impacts. This holistic perspective provided by LCA can be used as input for the definition of environmental management strategies at an industrial laundry, and the prioritization of investments to the environmental profile of laundry processes. In this case-study, the results of the LCA are made operational by, for example, selecting the water treatment technology which is associated wih a safe disposal of the wet residue. It is important to bear in mind that such prioritization depends on national boundary conditions. In the case study analysed, the boundary conditions steer the weighing of the environmental impacts, following the current Danish environmental policy priorities.


Prospective evaluation of the G8 screening tool for prognostication of survival in elderly patients with lung cancer: A single-institution study.
The G8 questionnaire is a quick and easy-to-use screening tool. Several studies reported that the G8 questionnaire had a high sensitivity for predicting abnormalities in the full comprehensive geriatric assessment and predicted functional decline and survival in elderly cancer patients. The present study aimed to evaluate the role of the G8 questionnaire for predicting clinical outcomes and overall survival (OS) in elderly patients with lung cancer, who received chemotherapy or chemoradiotherapy. The data of 101 lung cancer patients aged ≥70 years, who were hospitalized between September 2011 and August 2014, were analyzed. Of these patients (median age, 77 years), 83 (82%) had impaired G8 scores. The proportion of patients with an impaired G8 score was significantly higher in patients aged ≥80 years than those aged <80 years (p = 0.04). All 18 patients with a normal G8 score possessed an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, and none of the patients with a normal G8 score had an ECOG PS of ≥2 (p < 0.0001). An impaired G8 score tended to correlate with a relative dose intensity of <0.65 in patients who received chemotherapy or chemoradiotherapy (p = 0.05, odds ratio = 5.40). In the univariate analysis, an ECOG PS of ≥2 and an impaired G8 score were significantly associated with a poor OS (p = 0.009 and p = 0.003, respectively). Moreover, in the multivariate analysis, an ECOG PS of ≥2 (HR 2.55; 95% CI, 1.23-5.30; p = 0.01) and an impaired G8 score (HR 3.86; 95% CI, 1.44-13.36; p = 0.006) were remained independent prognostic factor for OS. G8 screening tool is useful for the prognostication of elderly lung cancer patients treated with chemotherapy. These finding suggest that the G8 questionnaire could be a useful tool in treatment decision-making to predict prognosis and prevent patients from receiving inappropriate anti-cancer treatment near the end of life.


Distinct Persistence Fate of Mycobacterium tuberculosis in Various Types of Cells.
Mycobacterium tuberculosis can invade different cells with distinct persistence fates because cells are equipped with different host restriction factors. However, the underlying mechanisms remain elusive. Here, we infected THP1 and Raw264.7 macrophages cell lines, A549 epithelial cell line, and hBMEC and bEnd.3 endothelial cell lines with M. tuberculosis and demonstrated that M. tuberculosis significantly inhibited lysosome acidification in THP1, hBMEC, A549, and Raw264.7 cells, while, in bEnd.3 cells, M. tuberculosis was mainly delivered into acidified phagolysosomes and auto-lysosomes. The systematic gene profile analysis of different cells and intracellular M. tuberculosis showed that the phagosome autophagy-pathway-related genes itgb3 and atg3 were highly expressed in bEnd.3 cells. Knockdown of these genes significantly increased the number of viable intracellular M. tuberculosis bacilli by altering phagosomal trafficking in bEnd.3 cells. Treatment with itgb3 agonist significantly decreased M. tuberculosis survival in vivo. These findings could facilitate the identification of anti-M. tuberculosis host genes and guide M. tuberculosis-resistant livestock breeding. IMPORTANCE As an intracellular pathogen, Mycobacterium tuberculosis could avoid host cell immune clearance using multiple strategies for its long-term survival. Understanding these processes could facilitate the development of new approaches to restrict intracellular M. tuberculosis survival. Here, we characterized the detailed molecular events occurring during intracellular trafficking of M. tuberculosis in macrophage, epithelial, and endothelial cell lines and found that ITGB3 facilitates M. tuberculosis clearance in endothelial cells through altering phagosomal trafficking. Meanwhile, the treatment with ITGB3 agonist could reduce bacterial load in vivo. Our results identified new anti-M. tuberculosis restriction factors and illuminated a new anti-M. tuberculosis defense mechanism.


Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss.
In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP) staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR). Furthermore, we assessed the effects of methyl gallate on the characteristics of mature osteoclasts. We found that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca2+ signaling. The blockade of these pathways was confirmed through transduction of cells with a CA-Akt retrovirus and evaluation of Ca2+ influx intensity (staining with Fluo-3/AM). Indeed, methyl gallate downregulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of lipopolysaccharide in vivo according to micro-computed tomography and histological analysis. Our data strongly indicate that methyl gallate may be useful for the development of a plant-based antiosteoporotic agent.


Studies on the protective effect of the artichoke (Cynara scolymus) leaf extract against cadmium toxicity-induced oxidative stress, hepatorenal damage, and immunosuppressive and hematological disorders in rats.
Our objective was to explore the protective effect of artichoke leaf extract (ALE) against cadmium (Cd) toxicity-induced oxidative organ damage in rats. Male albino Wistar rats were divided into four equal groups of eight animals each. The first group was assigned as a control. Groups 2-4 were orally administered with ALE (300 mg/kg bw), Cd (CdCl2, 100 mg/L drinking water), and ALE plus Cd, respectively, daily for 4 weeks. After treatment with Cd, the liver and kidney malondialdehyde (MDA) increased significantly compared with the control rats. The sera interleukin (IL)-1β, tumor necrosis factor (TNF-α), and IL-10, liver transaminase, urea, creatinine, and peripheral neutrophil count were significantly increased in Cd-exposed rats compared to the control group. The reduced glutathione (GSH), glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) decreased in the liver and kidney in Cd-exposed group. In combination treatment, Cd and ALE significantly improved immune response, an antioxidant system, and hepatorenal function with a significant decline in MDA. In conclusion, ALE ameliorates the immunosuppressive and hepatorenal oxidative injury stimulated by Cd in rats. These results suggest that artichoke has shown promising effects against adverse effects of Cd toxicity.


Reducing substance use risk and mental health problems among sexually assaulted adolescents: a pilot randomized controlled trial.
The current study reports results from a pilot randomized controlled trial evaluating the feasibility and efficacy of Risk Reduction through Family Therapy (RRFT) for reducing substance use risk and trauma-related mental health problems among sexually assaulted adolescents. Thirty adolescents (aged 13-17 years; M = 14.80; SD = 1.51) who had experienced at least one sexual assault and their caregivers were randomized to RRFT or treatment as usual (TAU) conditions. Participants completed measures of substance use, substance use risk factors (e.g., family functioning), mental health problems (i.e., posttraumatic stress disorder, depression, and general internalizing/externalizing symptoms) and risky sexual behavior at four time points (baseline, posttreatment, and 3- and 6-month follow-up). Mixed-effects regression models yielded significantly greater reductions in substance use, specific substance use risk factors, and (parent-reported) PTSD, depression, and general internalizing symptoms among youth in the RRFT condition relative to youth in the TAU condition. However, significant baseline differences in functioning between the two conditions warrant caution in interpreting between-groups findings. Instead, emphasis is placed on replication of feasibility findings and within-group improvements over time among the RRFT youth.


Wireless transfer between antenna arrays at the Talbot distance.
In modern multiple input multiple output (MIMO) wireless communication systems arrays of antennas are employed to enhance the data transfer rate. Scattering of the waves in the medium between the antennas can actually enhance the transfer capacity by decorrelating the available channels. Here it is shown that the transfer capacity between arrays of regularly spaced antennas depends intricately on the distance between the arrays and on the arrangement of scatterers. The relevant length scale is the Talbot distance L(Talbot) =2 d2/lambda known from optics as the distance where the self-imaging occurs of coherently illuminated gratings with d the grating period and lambda the wavelength. The modulation of singular values of the channel transfer matrix occurs at fractions of L(Talbot) .


A T-cell-specific transcriptional enhancer element 3' of C alpha in the human T-cell receptor alpha locus.
A transcriptional enhancer element has been identified 4.5 kilobases 3' of C alpha (constant region alpha chain) in the human T-cell receptor (TCR) alpha-chain locus. This enhancer is active on both a TCR V alpha (variable region alpha chain) promoter and the minimal simian virus 40 promotor in TCR alpha/beta Jurkat and EL4 cells but is inactive on a V alpha promoter in human TCR gamma/delta PEER and Molt-13 cells, clone 13 B cells, and HeLa fibroblasts. The enhancer has been localized to a 116-base-pair BstXI/Dra I restriction enzyme fragment, which lacks immunoglobulin octamer and kappa B enhancer motifs but does contain a consensus cAMP-response element (CRE). DNase I footprint analyses demonstrated that the minimal enhancer contains two binding sites for Jurkat nuclear proteins. One of these sites corresponds to the CRE, while the other does not correspond to a known transcriptional enhancer motif. These data support a model in which TCR alpha gene transcription is regulated by a unique set of cis-acting sequences and trans-acting factors, which are differentially active in cells of the TCR alpha/beta lineage. In addition, the TCR alpha enhancer may play a role in activating oncogene expression in T-lymphoblastoid tumors that have previously been shown to display chromosomal translocations into the human TCR alpha locus.


On sources of error in the biochemical study of perilymph (guinea-pig).
Contamination of perilymph with other fluids (cerebrospinal fluid, tissue fluid, blood, endolymph) together with sampling, anaesthesia, surgical intervention or food intake of the animals may considerably affect the analytical result. The numerous possible artefacts seem to be the main reason why varying values are given in the literature for the same chemical component of perilymph. This is also partly true of cerebrospinal fluid and blood. The effect of some sources of error on selected chemical components of perilymph, cerebrospinal fluid and blood is briefly summarized.


Tissue engineering solutions for traumatic bone loss.
Tissue engineering strategies for the repair, replacement, or augmentation of bone defects involves the use of cells, matrices, and bioregulatory factors. The source (endogenous, exogenous) and character of these factors, however, may vary greatly among the many approaches taken by current investigators. Although the results of current tissue engineering methods for regenerating bone have shown great promise, the extent of damage to extremities associated with war injuries may require the development of techniques that differ substantially from current practice.


Eukaryotic DNA Replication Fork.
This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase ε (Pol ε) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases α and δ carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. This review also discusses alternative proposals, including cellular processes during which alternative forks may be utilized, and new biochemical studies with purified proteins that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integrated replication fork.


Capsule endoscopy in Crohn's disease: are we seeing any better?
Crohn's disease (CD) is a complex, immune-mediated disorder that often requires a multi-modality approach for optimal diagnosis and management. While traditional methods include ileocolonoscopy and radiologic modalities, increasingly, capsule endoscopy (CE) has been incorporated into the algorithm for both the diagnosis and monitoring of CD. Multiple studies have examined the utility of this emerging technology in the management of CD, and have compared it to other available modalities. CE offers a noninvasive approach to evaluate areas of the small bowel that are difficult to reach with traditional endoscopy. Furthermore, CE maybe favored in specific sub segments of patients with inflammatory bowel disease (IBD), such as those with IBD unclassified (IBD-U), pediatric patients and patients with CD who have previously undergone surgery.


[IgM diagnosis in syphilis serology].
The methods in use for the detection of T pallidum-specific antibodies in human sera are the 19S-(IgM-)FTA-ABS and the IgM-SPHA test. Encouraging results have been obtained with the IgM-ELISA-TP technique using new antigens. The development of the different methods up to the present time are described. The margin of error is low, 3.4% of the 19S-(IgM-)-FTA-ABS results are false-positive and 3.6% false-negative, the respective figures for the IgM-SPAH test are 1% (false-positive) and 8% (false-negative). The agreement with the clinical diagnosis is excellent in the secondary stage (94 to 95% reactivity), the reasons for lower rates in the primary and late phases are discussed. The half-life period of reactivity after adequate treatment amounts to 2 to 6 months in all stages except for the IgM-SPHA test in neurosyphilis, where reactivity remains for 24 months (mean value) due to the production of autoantibodies.


Polymorphism of human B-cell alloantigens: evidence for three loci within the HLA system.
The B-cell alloantigens of an HLA-DR3-homozygous, MB2-homozygous, MT2-positive lymphoblastoid cell line were studied by two-dimensional gel electrophoresis. Analysis of gel patterns suggested assignment of the HLA-DR3 determinant to the larger (35,000-dalton) subunit (alpha) of the B-cell alloantigen. MB2 was found to be either a determinant on the small (27,000 dalton) subunit (beta) or a crossreactive determinant(s) on the HLA-DR3 alpha subunit and an additional alpha subunit. MT2 was found to be a determinant on Ia antigen-like molecules distinct from those carrying the MB and HLA-DR determinants. The results are consistent with the existence in the major histocompatibility complex of at least three loci encoding B-cell alloantigens.


Incidence and epidemiology of methicillin-resistant Staphylococcus aureus infection in a Saudi Arabian Hospital, 1999-2003.
During 1999-2003 in a Saudi Arabian Hospital, methicillin-resistant Staphylococcus aureus constituted 6% of all S. aureus isolates; the proportion had increased from 2% in 1999, to 9.7% in 2002, to 8% in 2003. Of all MRSA isolates, 62% represented community-acquired infection, 20.4% represented healthcare-associated infection, and 17.6% represented nosocomial infection. The proportion of community-acquired isolates increased from 41.7% in 1999 to 66.6% in 2002, and the proportion representing nosocomial infection decreased from 33% in 1999 to 19% in 2003. Isolates representing nosocomial infection showed higher rates of resistance to ciprofloxacin (76.6%), clindamycin (76.6%), erythromycin (68%) and trimethoprim-sulfamethoxazole (68%) than did isolates in the other categories (P<.001).


Regulation of blood volume in lowlanders exposed to high altitude.
Humans ascending to high altitude (HA) experience a reduction in arterial oxyhemoglobin saturation and, as a result, arterial O2 content ([Formula: see text]). As HA exposure extends, this reduction in [Formula: see text] is counteracted by an increase in arterial hemoglobin concentration. Initially, hemoconcentration is exclusively related to a reduction in plasma volume (PV), whereas after several weeks a progressive expansion in total red blood cell volume (RCV) contributes, although often to a modest extent. Since the decrease in PV is more rapid and usually more pronounced than the expansion in RCV, at least during the first weeks of exposure, a reduction in circulating blood volume is common at HA. Although the regulation of hematological responses to HA has been investigated for decades, it remains incompletely understood. This is not only related to the large number of mechanisms that could be involved and the complexity of their interplay but also to the difficulty of conducting comprehensive experiments in the often secluded HA environment. In this review, we present our understanding of the kinetics, the mechanisms and the physiological relevance of the HA-induced reduction in PV and expansion in RCV.


Social processes underlying acculturation: a study of drinking behavior among immigrant Latinos in the Northeast United States.
STUDY GOALS: To identify social processes that underlie the relationship of acculturation and heavy drinking behavior among Latinos who have immigrated to the Northeast United States of America (USA). METHOD: Community-based recruitment strategies were used to identify 36 Latinos who reported heavy drinking. Participants were 48% female, 23 to 56 years of age, and were from South or Central America (39%) and the Caribbean (24%). Six focus groups were audiotaped and transcribed. RESULTS: Content analyses indicated that the social context of drinking is different in the participants' countries of origin and in the United States. In Latin America, alcohol consumption was part of everyday living (being with friends and family). Nostalgia and isolation reflected some of the reasons for drinking in the USA. Results suggest that drinking in the Northeastern United States (US) is related to Latinos' adaptation to a new sociocultural environment. Knowledge of the shifting social contexts of drinking can inform health interventions.


ACTIVE 'JUVENILE' CIRRHOSIS CONSIDERED AS PART OF A SYSTEMIC DISEASE AND THE EFFECT OF CORTICOSTEROID THERAPY.
This is a clinical study of 81 patients (32 male and 49 female), who are not alcoholics, with jaundice of hepato-cellular type lasting longer than three months. Forty-nine of these patients were under 21 years of age. The natural history of the condition and the response to corticosteroid therapy is described; good symptomatic relief can be achieved with corticosteroids but they do not seem to prolong life. The aetiology is discussed with special reference to the relationship to viral hepatitis, to systemic lupus erythematosus, and to other disturbances of immunity.


Cdh1/Hct1-APC is essential for the survival of postmitotic neurons.
Cell division at the end of mitosis and G1 is controlled by Cdh1/Hct1, an activator of the E3-ubiquitin ligase anaphase-promoting complex (APC) that promotes the ubiquitylation and degradation of mitotic cyclins and other substrates. Cdh1-APC is active in postmitotic neurons, where it regulates axonal growth and patterning in the developing brain. However, it remains unknown whether Cdh1-APC is involved in preventing cell-cycle progression in terminally differentiated neurons. To address this issue, we used the small hairpin RNA strategy to deplete Cdh1 in postmitotic neurons. We observed that Cdh1 silencing rapidly triggered apoptotic neuronal death. To investigate the underlying mechanism, we focused on cyclin B1, a major Cdh1-APC substrate. Our results demonstrate that Cdh1 is required to prevent the accumulation of cyclin B1 in terminally differentiated neurons. Moreover, by keeping cyclin B1 low, Cdh1 prevented these neurons from entering an aberrant S phase that led to apoptotic cell death. These results provide an explanation for the mechanism of cyclin B1 reactivation that occurs in the brain of patients suffering from neurodegenerative diseases, such as Alzheimer's disease.


Vitreous humor in the pathologic scope: insights from proteomic approaches.
The vitreous humor (VH) is the largest component of the eye. It is a colorless, gelatinous, highly hydrated matrix that fills the posterior segment of the eye between the lens and retina in vertebrates. In VH, a diversity of proteins that can influence retinal physiology is present, including growth factors, hormones, proteins with transporter activity, and enzymes. More importantly, the protein composition of VH has been described as being altered in a number of disease states. Therefore, attempts aiming at establishing a map of VH proteins and detecting putative biomarkers for ocular illness or protein fluctuations with putative physiologic significance were conducted over the last two decades, using proteomic approaches. Proteomic strategies often involve gel-based or LC techniques as sample fractioning approaches, subsequently coupled with MS procedures. This set of studies resulted in the proteomic characterization of a range of ocular disease samples, with particular incidence on diabetic retinopathy. However, practical therapeutic applications arising from these studies are scarce at the moment. A pertinent example of therapeutic targets arising from VH proteomics has emerged concerning vasoproliferative factors present in the vitreous, which should be involved in neovascularization and subsequent fibrovascular proliferation of the retina, in ocular disease context. Therefore, this review attempts to sum up the information acquired from the proteomic approaches to ocular disease conducted in VH samples, highlighting its clinical potential for disclosing ocular disease mechanisms and engendering pharmacological therapeutic treatments.


Loneliness in Psychosis: A Meta-analytical Review.
Loneliness may be related to psychotic symptoms but a comprehensive synthesis of the literature in this area is lacking. The primary aim of the current study is to provide a systematic review and meta-analysis of the association between loneliness and psychotic symptoms in people with psychosis. A search of electronic databases was conducted (PsychINFO, MEDLINE, EMBASE, and Web of Science). A random effects meta-analysis was used to compute a pooled estimate of the correlation between loneliness and psychotic symptoms. Study and outcome quality were assessed using adapted versions of the Agency for Healthcare Research and Quality (AHRQ) tool and GRADE approach, respectively. Thirteen studies were included, providing data from 15 647 participants. A moderate association between psychosis and loneliness was observed (k = 13, N = 15 647, r = .32, 95% CI 0.20, 0.44; I2 = 97.56%; moderate quality evidence). Whether loneliness was assessed by a single-item or a more comprehensive measure had no moderating effect on the estimate. Results indicate that there is a significant positive relationship between loneliness and psychosis. Further studies are needed to determine the causal status of this relationship, but this robust finding should be considered in clinical practice and treatment provision for those with psychotic disorders.


Ionic Liquid-based Hollow Fiber Liquid-Liquid-Liquid Microextraction Combined with Capillary Electrophoresis for the Determination of Sulfonamides in Aquaculture Waters.
Ionic liquid-based hollow-fiber liquid-liquid-liquid microextraction (IL-HF-LLLME) coupled to capillary electrophoresis (CE) has been developed for the determination of six sulfonamides (SAs) in aquaculture waters. A series of extraction parameters was optimized to enhance the extraction efficiency, which included type and pore size of hollow fiber, type and composition of extraction solvent, pH value of donor phase, the concentration of acceptor phase and the mass ratio of donor phase to acceptor phase along with extraction temperature and time. Under optimal conditions, the IL-HF-LLLME-CE method provided a wide liner range for six SAs from 2 to 1,000 μg L-1 (r2 ≥ 0.9995), the limits of the detection from 0.25 to 0.48 and the enrichment factors from 122 to 230, respectively. Relative standard deviations for intra- and interday precision were 1.4-5.3% and 1.8-7.5% (n = 5), respectively. The proposed method was successfully applied for the determination of trace-level SAs in seven real-world aquaculture water samples with good recoveries (80.4-100.7%). Also, sulfamerazine and sulfamethoxazole were detected at the level of 0.52-1.60 μg L-1 in two water samples. Due to its good sensitivity, simple operation, short analysis time and eco-friendliness, the developed method has a great application potential in analysis of trace SA residues in aquaculture waters.


Pertussis in an infant adopted from Russia--May 2002.
On May 2, 2002, the North Carolina Department of Health and Human Services notified CDC about an infant aged 10 months adopted from Russia who had culture-confirmed pertussis diagnosed. On April 8, the adoptive parents picked him up in the orphan ward at hospital A in Bryansk and noticed that the child had upper respiratory congestion and cough. The adoptive parents reported that the infant had not received any vaccinations and that another infant living in the same room in hospital A had a severe cough. The adopted infant subsequently was examined by a local physician, who diagnosed his condition as a "cold," and the infant was taken to the U.S. Embassy in Moscow, where the parents were interviewed for an immigrant visa for the child.


Food Choice Behaviors of Lactating Women: Association with Body Mass Index and Fruits and Vegetables Intake in Central Amhara Region, Ethiopia-An Observational Study.
What food people choose to eat is embraced by circumstances that are essentially influenced by the underlying motives of food choices which are important to a healthful dietary change. Therefore, this study aimed to explore food choice behaviors associated with nutritional status and FVs intake in women during lactation from central Amhara. A multistage sampling technique was applied to select study participants. A study was conducted among 423 randomly selected lactating women using a face-to-face interview of the questionnaire. A community-based cross-sectional, quantitative study with descriptive and analytical components was done. Anthropometrics measurements such as weight, height, waist, and hip circumference were taken from all participants. Body mass index was calculated to determine the nutritional status of women. Data were analyzed using SPSS version 20 computer software program. Association between dependent and independent variables was identified by logistic regression analysis, and a P-value< 0.05 was taken as statistically significant. About 21.7% of women were underweight. Approximately 37.4% of women had good consumption trends to fruits and vegetables. Healthy meal eating motivation, price-consciousness, and mood concern were identified as the most significant behaviors of food choice, influencing the nutritional status of women with AOR (95% CI) of 2.1 (1.21-3.62), 3.01 (1.32-6.9), and 0.5 (0.30-0.95), respectively. Natural content (AOR (95%): 2.37 (1.39-4.06)), mood concern (AOR (95%): 2.29 (1.15-4.56)), religion concern (AOR (95%): 2.45 (1.37-4.4)), husband encouragement (AOR (95%): 2.26 (1.04-4.89)), and availability of milk and milk products (AOR (95%): 1.6 (1.39-2.74)) and fruits and vegetables (AOR (95%): 1.66 (1.16-3.48)) in home were associated significantly with a good intake of fruit and vegetables. This finding provides a useful insight into the food choice motivations of a group of women with preference for natural foods, mood concern, religion concern, and husband support with good fruit and vegetable intake. This can help practitioners make recommendations for health promotion strategies. Emphasis on assisting women with healthy meal eating and avoiding psychological stress is important. Nutrition education about healthy food choice is recommended for communities.


An Old World leaf-cutting, fungus-growing ant: A case of convergent evolution.
The African myrmicine ant Crematogaster clariventris is a territorially dominant arboreal species that constructs very hard carton nests. Noting that workers cut off leaves from different plant species while building or repairing their nests, we asked ourselves if there was a correlation. We conducted scanning electron microscopic observations of nest walls that revealed the presence of fungal mycelia. As the presence of filamentous Ascomycota has been shown on arboreal ant nests worldwide, we used a metabarcoding approach and, indeed, noted the presence of Operational Taxonomic Unit (OTU) Cre_006041 of the Capnodiales known to reinforce large nests of an unidentified African Crematogaster. This OTU was also recorded in the workers' bodies. At a very low level, we also noted OTU Cre_320021 of the Chaetothyriales known for their relationships with the African plant-ant species C. margaritae. Therefore, by cutting leaves and growing fungus, C. clariventris illustrates a case of convergent evolution with higher New World leaf-cutting, fungus-growing Attina of the genera Acromyrmex, Amoimyrmex and Atta. However, there are notable differences. Leaf-cutting Attina cultivate Agaricaceae (Basidiomycota) for food, whereas C. clariventris uses Capnodiales to reinforce their nests (i.e., after the mycelium died, the hyphae's cell walls remained sturdy forming a natural composite material), have a distinct geographical origin (i.e., New World vs. Old World) and belong to a distinct ant tribe in the subfamily Myrmicinae (i.e., Attini vs. Crematogastrini). Furthermore, leaf-cutting Attina evolved an efficacious means of cutting leaves by using their mandibles asymmetrically, whereas C. clariventris workers, typically, use their mandibles symmetrically.


[Comparison of the complement-binding activity of model immune complexes of different molecular weights].
The authors studied and compared the complement-fixing activity of model immune complexes with different molecular mass. The complement-fixing activity of the complexes was found to be linearly independent of the molecular mass, being mainly determined by the size of the complex, and to be slightly dependent on the concentration of aggregated immunoglobulins. As far as the aggregates with a molecular mass over 20 IgG are concerned, addition of complement leads to the dissociation of the complexes.


A comparative voltage and current-clamp analysis of feedback and feedforward synaptic transmission in the striatal microcircuit in vitro.
Striatal spiny projection (SP) neurons control movement initiation by integrating cortical inputs and inhibiting basal ganglia outputs. Central to this control lies a "microcircuit" that consists of a feedback pathway formed by axon collaterals between GABAergic SP neurons and a feedforward pathway from fast spiking (FS) GABAergic interneurons to SP neurons. Here, somatically evoked postsynaptic potentials (PSPs) and currents (PSCs) were compared for both pathways with dual whole cell patch recording in voltage- and current-clamp mode using cortex-striatum-substantia nigra organotypic cultures. On average, feedforward inputs were 1 ms earlier, more reliable, and about twice as large in amplitude compared with most feedback inputs. On the other hand, both pathways exhibited widely varying, partially overlapping amplitude distributions. This variability was already established for single FS neurons targeting many SP neurons. In response to precisely timed action potential bursts, feedforward and feedback inputs consistently showed short-term depression < or =50-70% in voltage-clamp, although feedback inputs also displayed strong augmentation in current-clamp in line with previous reports. The augmentation of feedback inputs was absent in gramicidin D perforated-patch recording, which also showed the natural reversal potential for both inputs to be near firing threshold. Preceding depolarizing feedback inputs during the down state did not consistently change subsequent postsynaptic action potentials. We conclude that feedback and feedforward inputs have their dominant effect during the up-state. The reversal potential close to the up-state potential, which supports shunting operation with millisecond precision and the strong synaptic depression, should enable both pathways to carry time-critical information.


Neutral bis(1,4-diaza-1,3-butadiene)nickel complexes and their corresponding monocations: molecular and electronic structures. A combined experimental and density functional theoretical study.
The reaction of 2 equivalents of 2-methyl-1,4-bis(2,6-dimethylphenyl)-1,4-diaza-1,3-butadiene, ((1)L(Ox))(0), or 2-methyl-1,4-bis(2,6-diisopropylphenyl)-1,4-diaza-1,3-butadiene, ((2)L(Ox))(0), in diethyl ether or n-hexane with 1 equivalent of Ni(cdt) where (cdt)(0) is the ligand cyclododecatriene affords dark red, diamagnetic precipitates of [Ni(II)((1)L )(2)] () and of [Ni(II)((2)L )(2)] (). The ligands ((1)L )(1-) and ((2)L )(1-) are the one-electron reduced, monoanionic pi radicals of the above neutral 1,4-diaza-1,3-butadienes. and have been structurally characterized by X-ray crystallography; both possess a distorted tetrahedral geometry where the dihedral angle theta between the two metallacycles Ni-N-C-C-N is 47.9 degrees and 53 degrees , respectively, (theta = 0 degrees for square planar and 90 degrees for a regular tetrahedral geometry). The reaction of and with 1 equivalent of ferrocenium hexafluorophosphate gives the paramagnetic (S(t) = 1/2) complexes and , respectively: [Ni(I)((1)L(Ox))(2)](PF(6)) (), [Ni(I)((2)L(Ox))(2)](PF(6)) (). Their EPR spectra indicate the presence of a central Ni(i) ion (d(9); S(Ni) = 1/2). Thus, the one-electron oxidation of and by [Fc]PF(6) induces an intramolecular one-electron reduction of the central Ni ion and a concomitant one-electron oxidation of the second pi radical (L )(1-)--> (L(Ox))(0) + e. Broken symmetry DFT calculations (B3LYP) corroborate the correctness of the electronic structure descriptions of . The reaction of ((1)L(Ox))(0) with NiI(2) (1 : 1) in tetrahydrofuran yields tetrahedral [Ni(II)((1)L(Ox))I(2)] () with an S(t) = 1 ground state.


Snake bite by Cerastes vipera in children: report of two cases.
Two children, ages 2 and 4 years, envenomed by the snake Cerastes vipera are presented. Both children suffered from local pain and swelling of the hand that spread up to the shoulder in the 2-year-old and up to the elbow in the 4-year-old. A hemorrhagic blister was noted on the bitten finger in the younger patient. Urinary retention, tachycardia, and a slight prolongation of prothrombin time was noted in the 2-year-old, whereas hypertension and fever were observed in the 4-year-old. In both cases, the swelling receded gradually and the patients were discharged from the hospital after several days without any complications and in a good condition.