Sodium channel γENaC mediates IL-17 synergized high salt induced inflammatory stress in breast cancer cells.
Chronic inflammation is known to play a critical role in the development of cancer. Recent evidence suggests that high salt in the tissue microenvironment induces chronic inflammatory milieu. In this report, using three breast cancer-related cell lines, we determined the molecular basis of the potential synergistic inflammatory effect of sodium chloride (NaCl) with interleukin-17 (IL-17). Combined treatment of high NaCl (0.15M) with sub-effective IL-17 (0.1 nM) induced enhanced growth in breast cancer cells along with activation of reactive nitrogen and oxygen (RNS/ROS) species known to promote cancer. Similar effect was not observed with equi-molar mannitol. This enhanced of ROS/RNS activity correlates with upregulation of γENaC an inflammatory sodium channel. The similar culture conditions have also induced expression of pro-inflammatory cytokines such as IL-6, TNFα etc. Taken together, these data suggest that high NaCl in the cellular microenvironment induces a γENaC mediated chronic inflammatory response with a potential pro-carcinogenic effect.


Budd-chiari syndrome causing acute liver failure: A multicenter case series.
Budd-Chiari syndrome (BCS) is a rare disease resulting from obstruction of the hepatic venous outflow tract that typically presents with abdominal pain, jaundice, and ascites without frank liver failure. However, BCS may also evolve more rapidly to acute liver failure (ALF). In this study, we describe the clinical features, treatment, and outcomes of ALF due to BCS and compare our results with those in the published literature. Twenty of the 2344 patients enrolled in the Acute Liver Failure Study Group (ALFSG) registry since 1998 presented with a clinical diagnosis of BCS. An additional 19 patients of ALF-BCS in the English language literature were reviewed and compared with the ALFSG cases. Most ALF-BCS patients were white (84%) and female (84%) in their fourth decade. A hypercoagulable state was noted in 63% of patients. BCS was diagnosed by Doppler ultrasonography or abdominal computed tomography in all patients. Liver biopsies (n = 6) all had evidence of severe pericentral necrosis. Treatments used included most commonly anticoagulation (71%), but also transjugular intrahepatic portosystemic shunt (TIPS; 37%) and orthotopic liver transplantation (37%). In-hospital mortality was approximately 60%. In conclusion, BCS is a rare cause of ALF and mandates prompt diagnosis and management for successful outcomes. Once the diagnosis is confirmed, prompt anticoagulation is recommended in conjunction with evaluation for malignancy or thrombophilic disorder. Mortality may have improved in recent years with use of TIPS and/or orthotopic liver transplantation compared with prior published reports. Liver Transplantation 23 135-142 2017 AASLD.


State transitions revisited-a buffering system for dynamic low light acclimation of Arabidopsis.
The mobile part of the light-harvesting chlorophyll (chl) a/b protein complex (LHCII), composed of the Lhcb1 and Lhcb2 proteins, is the basic unit of chloroplast state transitions--the short term tuning system in balancing the excitation energy between Photosystem (PS) II and PSI. State transitions are catalysed by the thylakoid associated STN7 kinase, and we show here that besides the phosphorylation of the Lhcb1 and Lhcb2 proteins, also the phosphorylation of Lhcb4.2 (CP29) is under the control of the STN7 kinase. Upon growth of Arabidopsis WT and stn7 mutant plants under low and moderate light conditions, the WT plants favoured state 2 whereas stn7 was locked in state 1. The lack of the STN7 kinase and state transitions in stn7 also modified the thylakoid protein contents upon long-term low light acclimation resulting, for example, in low Lhcb1 and in elevated Lhca1 and Lhca2 protein amounts as compared to WT. Adjustments of thylakoid protein contents probably occurred at post-transcriptional level since the DNA microarray experiments from each growth condition did not reveal any significant differences between stn7 and WT transcriptomes. The resulting high Lhcb2/Lhcb1 ratio in stn7 upon growth at low light was accompanied by lower capacity for NPQ than in WT. On the contrary, higher amounts of PsbS in stn7 under moderate and high light growth conditions resulted in higher NPQ compared to WT and consequently also in a protection of PSII against photoinhibition. STN7 kinase and the state transitions are suggested to have a physiological significance for dynamic acclimation to low but fluctuating growth light conditions. They are shown to function as a buffering system upon short high light illumination peaks by shifting the thylakoids from state 2 to state 1 and thereby down regulating the induction of stress-responsive genes, a likely result from transient over-reduction of PSI acceptors.


[The pathogenetic and prognostic significance of the level of class-E immunoglobulins in erysipelas].
The authors determined the content of total immunoglobulins of the E class in the blood plasma: native (IgE) and exhausted by a streptococcal allergen in the dynamics of the disease in 145 patients with erysipelas. The level of antistreptococcal reagins was evaluated. It was established that at the onset of erysipelas the concentration of IgE and a-IgE showed a short-term increase in 52 +/- 4% and 87 +/- 3% of patients correspondingly. During convalescence the level of these antibodies did not differ from that of the normal excluding high risk patients for recurrence. The participation of IgE-mediated type of allergic reactions in the pathogenesis of erysipelas is suggested. It is recommended to use the content of IgE and a-IgE for the prognosis of immediate and remote recurrences of erysipelas.


"Internet of Things" Real-Time Free Flap Monitoring.
Free flaps are a common treatment option for head and neck reconstruction in plastic reconstructive surgery, and monitoring of the free flap is the most important factor for flap survival. In this study, the authors performed real-time free flap monitoring based on an implanted Doppler system and "internet of things" (IoT)/wireless Wi-Fi, which is a convenient, accurate, and efficient approach for surgeons to monitor a free flap. Implanted Doppler signals were checked continuously until the patient was discharged by the surgeon and residents using their own cellular phone or personal computer. If the surgeon decided that a revision procedure or exploration was required, the authors checked the consumed time (positive signal-to-operating room time) from the first notification when the flap's status was questioned to the determination for revision surgery according to a chart review. To compare the efficacy of real-time monitoring, the authors paired the same number of free flaps performed by the same surgeon and monitored the flaps using conventional methods such as a physical examination. The total survival rate was greater in the real-time monitoring group (94.7% versus 89.5%). The average time for the real-time monitoring group was shorter than that for the conventional group (65 minutes versus 86 minutes). Based on this study, real-time free flap monitoring using IoT technology is a method that surgeon and reconstruction team can monitor simultaneously at any time in any situation.


Analysis of proteome bound to D-loop region of mitochondrial DNA by DNA-linked affinity chromatography and reverse-phase liquid chromatography/tandem mass spectrometry.
Mitochondrial dysfunction has been suggested as a causal factor for insulin resistance and diabetes. Previously we have shown a decrease of mitochondrial DNA (mtDNA) content in tissues of diabetic patients. The mitochondrial proteins, which regulate the mitochondrial biogensis, including transcription and replication of mtDNA, are encoded by nuclear DNA. Despite the potential function of the proteins bound to the D-loop region of mtDNA in regulating mtDNA transcription/replication, only a few proteins are known to bind the D-loop region of mtDNA. The functional association of these known proteins with insulin resistance is weak. In this study, we applied proteomic analysis to identify a group of proteins (proteome) that physically bind to D-loop DNA of mtDNA. We amplified D-loop DNA (1.1 kb) by PCR and conjugated the PCR fragments to CNBr-activated sepharose. Mitochondria fractions were isolated by both differential centrifugation and Optiprep-gradient ultracentrifugation. The D-loop DNA binding proteome fractions were enriched via this affinity chromatography and analyzed by SDS-PAGE. The proteins on the gel were transferred onto PVDF membrane and the peptide sequences of each band were subsequently analyzed by capillary reverse-phase liquid chromatography/tandem mass spectrometry (RPLC/MS/MS). We identified many D-loop DNA binding proteins, including mitochondrial transcription factor A (mtTFA, Tfam) and mitochondrial single-stranded DNA binding protein (mtSSBP) which were known to bind to mtDNA. We also report the possibility of novel D-loop binding proteins such as histone family proteins and high-mobility group proteins.


Establishing an optical flatness standard.
Methods proposed by the authors to establish a flatness standard without using a liquid mirror are proved in practice and extended. The extension is performed by a development of methods for the determination and compensation of random and systematic measuring errors by means of condition equations which must be satisfied by the measured sums of deviations from absolute planeness. Linear errors of these sums of deviations which can lead to ambiguities and errors of planeness deviations can be discovered and completely eliminated. Also nonlinear errors, for example, as a result of temperature differences or of mechanical stress, can be recognized without repeating the interference photography procedure. The deviations from absolute planeness of three fused silica plates were determined along seven diameters (angular distance 2pi/14) with an accuracy of lambda/500 (mean square error). This was performed by evaluating two sets of four different interference photographs, each with contour plane distances of lambda/50 (from fringe to fringe).


Religious affiliations and consumer behavior: an examination of hospitals.
The author re-examines the conclusions of an earlier study which contends that religious affiliation of a hospital is important in influencing hospital selection and contributes to overall patient satisfaction. In this new survey, patients ranked religious affiliation low in importance when choosing among hospitals. However, hospitals of a particular religious affiliation were more likely to be recalled, preferred, and selected by people of the same religious affiliation. Furthermore, on quality-of-care measures, religious affiliation influenced hospital evaluations.


Unusual airways management during one-lung ventilation in thoracic surgery.
Airways management in thoracic surgery is usually more difficult than in other surgery. We reported a case of a patient who underwent surgery of evacuation of empyema where after a correct insertion of a left double-lumen tube 37 Fr (DLT), one-lung ventilation was not permitted by the high airways pressure. In fact, the hole of bronchial tip was just against the left bronchial wall retracted probably from inflammatory process. We introduced blindly an Arndt blocker 9 Fr inside the tracheal lumen of DLT until the orifice of the right upper lobe bronchus, the distance was checked before. After the positioning of the blocker, the DLT was pulled up to above the carina, and the single-lung ventilation was permitted. Sometimes, an unusual use of different devices permits to manage complications. In fact, in this case, the Arndt bronchial blocker helps us to solve an important ventilatory problem.


Ion fluxes and short-circuit current in internally perfused cells of Valonia ventricosa.
Ion transport in the giant celled marine alga, Valonia ventricosa, was studied during internal perfusion and short-circuiting of the vacuole potential. The perfusing and bathing solutions were similar to natural Valonia sap and contained the following concentrations of major ions: Na 51, K 618, and Cl 652 mM. The average short-circuit current (I(sc)) was 97 pEq/cm(2) sec (inward positive current), and the average open-circuit potential difference (PD) was 74 mv (vacuole positive to external solution). Perfused and short-circuited cells showed a small net influx of Na (2.0 pEq/cm(2) sec) and large net influxes of K (80 pEq/cm(2) sec) and Cl (50 pEq/cm(2) sec). Unidirectional K influx was proportional to I(sc), but more than one-half of the I(sc) remained unaccounted for. Both the I(sc) and PD were partly light-dependent, declining rapidly during the first 1-2 min of darkness. Ouabain (5 x 10(-4)M) had little effect on the influx of Na or K and had no effect on I(inf) or PD. Fluid was absorbed at a rate of about 93 pliter/cm(2) sec. Reversing the direction of fluid movement by adding mannitol to the outside solution had little effect on ion movements. The ionic and electrical properties of normal and perfused cells of Valonia are compared.


Pharmacokinetics of the plant-derived kappa-opioid hallucinogen salvinorin A in nonhuman primates.
Salvinorin A, a potent hallucinogen isolated from the leaves of Salvia divinorum, has gained popularity among adolescents in the USA. No detailed study of the pharmacokinetics has been conducted in vivo. The present study investigates the in vivo pharmacokinetics of salvinorin A (0.032 mg/kg, i.v. bolus) in rhesus monkeys (n=4, 2 male, 2 female). The elimination t(1/2) was rapid (56.6+/-24.8 min) for all subjects. Pharmacokinetic differences (distribution t(1/2), elimination t(1/2), and AUC) were observed between males and females, suggesting potential sex differences in its pharmacologic effects. Salvinorin B, the presumed major metabolite, is observed to accumulate ex vivo; however, in this study it never reached the limit of detection.


Tuning band gaps and optical absorption of BiOCl through doping and strain: insight form DFT calculations.
Bismuth oxyhalides (BiOX, X = Cl, Br, and I) are a new family of promising photocatalysts. BiOCl and BiOBr possess large band gaps and weak absorption in visible light regions, which limit their applications. Although the band gap of BiOI is suitable to absorb most of the visible light, its redox capability is very weak. In this work, the doping and strain effects on the electronic structures and optical properties of BiOCl are explored using first principle calculations. The results show that doping in BiOCl, especially co-doping of Sb and I atoms, can obviously decrease the band gaps along with enhancing the optical absorption coefficients of pristine BiOCl because of the electronegativity difference between Sb/I atoms and Bi/Cl atoms. Meanwhile the band gap of BiOCl can be tuned under strain. This work offers potential strategies to enhance BiOCl absorption coefficients in the visible light region and its photocatalyst activity.


[Intradermal hepatitis B vaccination in workers not responsive to intramuscular vaccination].
Health care workers are at continuous risk of hepatitis B infection. Currently recommended intramuscular vaccination confers immunity in only 85-90%. We examined the immunogenicity and safety of intradermal vaccination of hepatitis B vaccine in nonresponders. 400 hospital employees who had been immunized as recommended were screened for anti-HBs antibodies and 50 were found seronegative. Each received an intramuscular booster injection and antibody level was measured a month later. Excluded were 33 employees, including 24 late responders, 2 HbsAg carriers and 7 uncooperative employees. 17 employees (mean age 47.1 yrs) then received a series of 3 intradermal injections of Energix B, 0.25 ml in the forearm, 2-3 weeks apart. The mean number of previous intramuscular injections was 4.6 +/- 1.4. A month later there was a mean titer of 315.4 +/- 347.0 miu/ml of antibody in 16/17 workers. Side effects were minimal. Intradermal injection of hepatitis B vaccine for nonresponders seems effective for inducing seroconversion. Its cost-effectiveness for the health care system warrants assessment.


Concentrations of oxygen delivered by air entrainment oxygen masks.
The air entrainment devices from oxygen masks of four manufacturers (Henleys Medical Supplies Ltd, Vickers Medical, Intersurgical Ltd, C R Bard International Ltd) were studied. All were found to deliver concentrations of oxygen close to those specified. The literature is reviewed and it is suggested that provision of a total flow in excess of 60 litres/minute is most likely to provide a constant inspired oxygen concentration, whichever nominal concentration or design of mask is selected and provided distal obstruction is avoided.


Pyometra in a Siberian Polecat (Mustela eversmanni).
A 2-year-old Siberian polecat (Mustela eversmanni) from a breeding colony presented for ultrasound evaluation for pregnancy. It was paired with a male for 2.75 months and had remained absent of pregnancy signs when it was anesthetized and clinically evaluated. Until this time, the animal had eaten well and shown no outward signs of debility. On palpation, the animal had a fluid-filled tubular structure in the caudal abdomen, consistent in location and size with the uterus. No sign of vaginal discharge was present. Ultrasonography revealed 10 fluid-filled evaginations (approximately 12 mm in diameter) of the uterine horns. A presumptive diagnosis of a fluid-filled reproductive tract and likely reproductive failure was made in light of the animal's history, its clinical signs, and the ultrasound findings. Euthanasia was performed because the animal was nonreproductive and might yield information relevant to the breeding colony as a whole. Necropsy of the polecat revealed a distended fluctuant uterus containing mildly odiferous, thick, yellow-green, purulent material. Histopathology confirmed the diagnosis of pyometra. A pure and heavy growth of Enterococcus fecalis was cultured from the uterine contents. In light of results from routine minimal inhibitory concentration antibiotic sensitivity screening, this isolate was resistant to all antibiotics tested in the standard teaching hospital screen.


Evaluation of lung lesions using FDG gamma-camera PET equipped with a one-inch crystal.
The aim of this study was to evaluate the clinical value of 18-fluorodeoxyglucose (FDG) imaging with gamma-camera positron emission tomography (GCPET) equipped with a one-inch crystal for diagnosing lung lesions and determining the stage of non-small cell lung cancer (NSCLC) in regions with a high prevalence of inflammatory disease and tuberculosis. FDG-GCPET was used to examine 103 patients with suspected malignant lesions in the lung. The results of FDG-GCPET and conventional workup (CWU) including computed tomography (CT), ultrasonography and radionuclide bone scintigraphy were compared. The final diagnosis was based on the results of a histological analysis or follow-up of at least six months. The results showed 82 patients with malignant and 21 patients with benign lesions. If a lesion to background ratio > or = 2.0 was used as the threshold, then the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of FDG-GCPET for NSCLC were 93.9, 57.1, 86.4, 89.5 and 70.6%, respectively. In 36 patients who underwent open-chest surgery, the diagnostic positive values of FDG-GCPET and CT for lymph-node involvement were 85% (17/20) and 65% (13/20), respectively. The diagnostic sensitivity, specificity, accuracy, PPV and NPV of FDG imaging were 85, 81.3, 83.3, 85 and 81.3%, respectively compared to the CT values of 65, 75, 69.4, 76.5 and 63.2%, respectively (NS). For the evaluation of distant metastases, 31 true-positive patients were identified during the follow-up. FDG imaging correctly identified 28 patients compared to 25 by CWU. In conclusion, FDG imaging with GCPET equipped with a one-inch crystal revealed a high lesion detection capability but a low level of clinical effectiveness for differentiating between malignant and benign lesions in the lung in regions with a high prevalence of inflammatory disease and tuberculosis. For N and M staging of NSCLC, this method may provide additional data that are not available from the CWU.


Impaired carotid baroreflex control of arterial blood pressure in multiple sclerosis.
Multiple sclerosis (MS), a progressive neurological disease, can lead to impairments in the autonomic control of cardiovascular function. We tested the hypothesis that individuals with relapsing-remitting MS (n = 10; 7 females, 3 males; 13 ± 4 yr from diagnosis) exhibit impaired carotid baroreflex control of blood pressure and heart rate compared with sex, age, and body weight-matched healthy individuals (CON: n = 10; 7 females, 3 males). At rest, 5-s trials of neck pressure (NP; +40 Torr) and neck suction (NS; -60 Torr) were applied to simulate carotid hypotension and hypertension, respectively, while mean arterial pressure (MAP; finger photoplethysmography), heart rate (HR), cardiac output (CO; Modelflow), and total vascular conductance (TVC) were continuously measured. In response to NP, there was a blunted increase in peak MAP responses (MS: 5 ± 2 mmHg) in individuals with MS compared with healthy controls (CON: 9 ± 3 mmHg; P = 0.005), whereas peak HR responses were not different between groups. At the peak MAP response to NP, individuals with MS demonstrated an attenuated decrease in TVC (MS, -10 ± 4% baseline vs. CON, -15 ± 4% baseline, P = 0.012), whereas changes in CO were similar between groups. Following NS, all cardiovascular responses (i.e., nadir MAP and HR and percent changes in CO and TVC) were not different between MS and CON groups. These data suggest that individuals with MS have impaired carotid baroreflex control of blood pressure via a blunted vascular conductance response resulting in a diminished ability to increase MAP in response to a hypotensive challenge.


Protozoan bacterivory and Escherichia coli survival in drinking water distribution systems.
The development of bacterial communities in drinking water distribution systems leads to a food chain which supports the growth of macroorganisms incompatible with water quality requirements and esthetics. Nevertheless, very few studies have examined the microbial communities in drinking water distribution systems and their trophic relationships. This study was done to quantify the microbial communities (especially bacteria and protozoa) and obtain direct and indirect proof of protozoan feeding on bacteria in two distribution networks, one of GAC water (i.e., water filtered on granular activated carbon) and the other of nanofiltered water. The nanofiltered water-supplied network contained no organisms larger than bacteria, either in the water phase (on average, 5 x 10(7) bacterial cells liter-1) or in the biofilm (on average, 7 x 10(6) bacterial cells cm-2). No protozoa were detected in the whole nanofiltered water-supplied network (water plus biofilm). In contrast, the GAC water-supplied network contained bacteria (on average, 3 x 10(8) cells liter-1 in water and 4 x 10(7) cells cm-2 in biofilm) and protozoa (on average, 10(5) cells liter-1 in water and 10(3) cells cm-2 in biofilm). The water contained mostly flagellates (93%), ciliates (1.8%), thecamoebae (1.6%), and naked amoebae (1.1%). The biofilm had only ciliates (52%) and thecamoebae (48%). Only the ciliates at the solid-liquid interface of the GAC water-supplied network had a measurable grazing activity in laboratory test (estimated at 2 bacteria per ciliate per h). Protozoan ingestion of bacteria was indirectly shown by adding Escherichia coli to the experimental distribution systems. Unexpectedly, E. coli was lost from the GAC water-supplied network more rapidly than from the nanofiltered water-supplied network, perhaps because of the grazing activity of protozoa in GAC water but not in nanofiltered water. Thus, the GAC water-supplied network contained a functional ecosystem with well-established and structured microbial communities, while the nanofiltered water-supplied system did not. The presence of protozoa in drinking water distribution systems must not be neglected because these populations may regulate the autochthonous and allochthonous bacterial populations.


Energy efficient hopping with Hill-type muscle properties on segmented legs.
The intrinsic muscular properties of biological muscles are the main source of stabilization during locomotion, and superior biological performance is obtained with low energy costs. Man-made actuators struggle to reach the same energy efficiency seen in biological muscles. Here, we compare muscle properties within a one-dimensional and a two-segmented hopping leg. Different force-length-velocity relations (constant, linear, and Hill) were adopted for these two proposed models, and the stable maximum hopping heights from both cases were used to estimate the cost of hopping. We then performed a fine-grained analysis during landing and takeoff of the best performing cases, and concluded that the force-velocity Hill-type model is, at maximum hopping height, the most efficient for both linear and segmented models. While hopping at the same height the force-velocity Hill-type relation outperformed the linear relation as well. Finally, knee angles between 60° and 90° presented a lower energy expenditure than other morphologies for both Hill-type and constant relations during maximum hopping height. This work compares different muscular properties in terms of energy efficiency within different geometries, and these results can be applied to decrease energy costs of current actuators and robots during locomotion.


Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor.
Although human telomerase catalytic subunit (TERT) has several cellular functions including telomere homeostasis, genomic stability, cell proliferation, and tumorigenesis, the molecular mechanism underlying anti-apoptosis regulated by TERT remains to be elucidated. Here, we show that ectopic expression of TERT in spontaneously immortalized human fetal fibroblast (HFFS) cells, which are a telomerase- and p53-positive, leads to increases of cell proliferation and transformation, as well as a resistance to DNA damage response and inactivation of p53 function. We found that TERT and a mutant TERT (no telomerase activity) induce expression of basic fibroblast growth factor (bFGF), and ectopic expression of bFGF also allows cells to be resistant to DNA-damaging response and to suppress activation of p53 function under DNA-damaging induction. Furthermore, loss of TERT or bFGF markedly increases a p53 activity and DNA-damage sensitivity in HFFS, HeLa and U87MG cells. Therefore, our findings indicate that a novel TERT-bFGF axis accelerates the inactivation of p53 and consequent increase of resistance to DNA-damage response.


Illusion of Causality in Visualized Data.
Students who eat breakfast more frequently tend to have a higher grade point average. From this data, many people might confidently state that a before-school breakfast program would lead to higher grades. This is a reasoning error, because correlation does not necessarily indicate causation - X and Y can be correlated without one directly causing the other. While this error is pervasive, its prevalence might be amplified or mitigated by the way that the data is presented to a viewer. Across three crowdsourced experiments, we examined whether how simple data relations are presented would mitigate this reasoning error. The first experiment tested examples similar to the breakfast-GPA relation, varying in the plausibility of the causal link. We asked participants to rate their level of agreement that the relation was correlated, which they rated appropriately as high. However, participants also expressed high agreement with a causal interpretation of the data. Levels of support for the causal interpretation were not equally strong across visualization types: causality ratings were highest for text descriptions and bar graphs, but weaker for scatter plots. But is this effect driven by bar graphs aggregating data into two groups or by the visual encoding type? We isolated data aggregation versus visual encoding type and examined their individual effect on perceived causality. Overall, different visualization designs afford different cognitive reasoning affordances across the same data. High levels of data aggregation by graphs tend to be associated with higher perceived causality in data. Participants perceived line and dot visual encodings as more causal than bar encodings. Our results demonstrate how some visualization designs trigger stronger causal links while choosing others can help mitigate unwarranted perceptions of causality.


Landscape evolutionary genomics.
Tremendous advances in genetic and genomic techniques have resulted in the capacity to identify genes involved in adaptive evolution across numerous biological systems. One of the next major steps in evolutionary biology will be to determine how landscape-level geographical and environmental features are involved in the distribution of this functional adaptive genetic variation. Here, I outline how an emerging synthesis of multiple disciplines has and will continue to facilitate a deeper understanding of the ways in which heterogeneity of the natural landscapes mould the genomes of organisms.


Wounding stimulates the accumulation of glycerolipids containing oxophytodienoic acid and dinor-oxophytodienoic acid in Arabidopsis leaves.
Although oxylipins can be synthesized from free fatty acids, recent evidence suggests that oxylipins are components of plastid-localized polar complex lipids in Arabidopsis (Arabidopsis thaliana). Using a combination of electrospray ionization (ESI) collisionally induced dissociation time-of-flight mass spectrometry (MS) to identify acyl chains, ESI triple-quadrupole (Q) MS in the precursor mode to identify the nominal masses of complex polar lipids containing each acyl chain, and ESI Q-time-of-flight MS to confirm the identifications of the complex polar lipid species, 17 species of oxylipin-containing phosphatidylglycerols, monogalactosyldiacylglycerols (MGDG), and digalactosyldiacylglycerols (DGDG) were identified. The oxylipins of these polar complex lipid species include oxophytodienoic acid (OPDA), dinor-OPDA (dnOPDA), 18-carbon ketol acids, and 16-carbon ketol acids. Using ESI triple-Q MS in the precursor mode, the accumulation of five OPDA- and/or dnOPDA-containing MGDG and two OPDA-containing DGDG species were monitored as a function of time in mechanically wounded leaves. In unwounded leaves, the levels of these oxylipin-containing complex lipid species were low, between 0.001 and 0.023 nmol/mg dry weight. However, within the first 15 min after wounding, the levels of OPDA-dnOPDA MGDG, OPDA-OPDA MGDG, and OPDA-OPDA DGDG, each containing two oxylipin chains, increased 200- to 1,000-fold. In contrast, levels of OPDA-hexadecatrienoic acid MGDG, linolenic acid (18:3)-dnOPDA MGDG, OPDA-18:3 MGDG, and OPDA-18:3 DGDG, each containing a single oxylipin chain, rose 2- to 9-fold. The rapid accumulation of high levels of galactolipid species containing OPDA-OPDA and OPDA-dnOPDA in wounded leaves is consistent with these lipids being the primary products of plastidic oxylipin biosynthesis.


Use of dipeptidyl peptidase 4 inhibitors and fracture risk compared to use of other anti-hyperglycemic drugs.
Dipeptidyl peptidase-4 inhibitors (DPP4-Is) are a new class of anti-hyperglycemic drugs which might have a potential beneficial effect on bone metabolism. Data on the effect of DPP4-I use and fracture risk is limited and conflicting. The aim of the present study was to investigate the association between use of DPP4-Is and fracture risk. A case-control study was conducted using data from the Danish National Health Service. Cases were those who sustained a fracture, and controls were those without a fracture during the study period (2007-2011), all aged 18 years and older. Conditional logistic regression estimated the odds ratios of fracture with current use of DPP4-I use. Analyses were adjusted for comorbidities and recent drug use. Among the cases there were 6993 current non-insulin anti-diabetic drug (NIAD) users (excluding incretin users) and 643 DPP4-I users. There were 7209 NIAD users (excluding incretin users) among the controls and 707 DPP4-I users. Current DPP4-I use was not associated with risk of any fracture (adjusted [adj.] OR: 0.97, 95% CI: 0.79-1.18) or major osteoporotic fracture (adj. OR: 0.96, 95% CI: 0.72-1.28). Stratification of current DPP4-I use to cumulative and average daily dose did not show an association. In a population-based case-control study we identified that short-term use of DPP4-I was not associated with fracture risk as compared to users of other anti-hyperglycemic drugs. Additionally, results suggest that increasing daily dose and cumulative DPP4-I exposure were not associated with fracture risk. However, more research is needed to assess the effect of long-term DPP4-I use on the risk of fracture.


Coordination properties of the oxime analogue of glycine to Cu(II).
The coordination of Cu2+ by glyoxilic acid oxime (gao)--the oxime analogue of glycine amino acid--and its deprotonated (gao- and gao2-) species has been studied with different density functional methods. Single-point calculations have also been carried out at the single- and double- (triple) excitation coupled-cluster (CCSD(T)) level of theory. The isomers studied involve coordination of Cu2+ to electron-rich sites (O,N) of neutral, anionic, and dianionic gao species in different conformations. In contrast to Cu2+-glycine, for which the ground-state structure is bidentate with the CO2(-) terminus of zwitterionic glycine, for Cu2+-gao the most stable isomer shows monodentate binding of Cu2+ with the carbonylic oxygen of the neutral form. The most stable complexes of Cu2+ interacting with deprotonated gao species (gao- and gao2-) also take place through the carboxylic oxygens but in a bidentate manner. The results with different functionals show that, for these open shell (Cu2+-L) systems, the relative stability of complexes with different coordination environments (and so, different spin distribution) can be quite sensitive to the amount of "Hartree-Fock" exchange included in the functional. Among all the functionals tested in this work, the BHandHLYP is the one that better compares to CCSD(T) results.


[Diabetic choroidopathy--a retrospective fluorescein angiography study. Preliminary report].
Both histologic studies and findings with Indocyanin green angiography furnish clear indications of the existence of diabetic choroidopathy. Out of 19,387 fluorescein angiograms made over the last 15 years at the First Ophthalmological Clinic of Vienna University, 902 were selected in which the choroidal vascular system is at least partially visible due to melanin hypopigmentation. The pathologic changes in the choroid observed in these angiograms can be allocated in two basic types of pathologic fluorescence: on the one hand hyperfluorescent lesions such as drusen in Bruch's membrane in suprisingly young diabetics, extremely hyperfluorescent lobules of the choriocapillaris, choroidal aneurysms, and neovascularizations; on the other hand, hypofluorescent lesions or structures were observed, such as delayed filling of the choriocapillaris and, in the late phase of angiography, varicose and tortuous choroidal vessels, drained and appearing dark in contrast to the diffuse background fluorescence.


Excited state non-adiabatic dynamics of pyrrole: a time-resolved photoelectron spectroscopy and quantum dynamics study.
The dynamics of pyrrole excited at wavelengths in the range 242-217 nm are studied using a combination of time-resolved photoelectron spectroscopy and wavepacket propagations performed using the multi-configurational time-dependent Hartree method. Excitation close to the origin of pyrrole's electronic spectrum, at 242 and 236 nm, is found to result in an ultrafast decay of the system from the ionization window on a single timescale of less than 20 fs. This behaviour is explained fully by assuming the system to be excited to the A2(πσ(∗)) state, in accord with previous experimental and theoretical studies. Excitation at shorter wavelengths has previously been assumed to result predominantly in population of the bright A1(ππ(∗)) and B2(ππ(∗)) states. We here present time-resolved photoelectron spectra at a pump wavelength of 217 nm alongside detailed quantum dynamics calculations that, together with a recent reinterpretation of pyrrole's electronic spectrum [S. P. Neville and G. A. Worth, J. Chem. Phys. 140, 034317 (2014)], suggest that population of the B1(πσ(∗)) state (hitherto assumed to be optically dark) may occur directly when pyrrole is excited at energies in the near UV part of its electronic spectrum. The B1(πσ(∗)) state is found to decay on a timescale of less than 20 fs by both N-H dissociation and internal conversion to the A2(πσ(∗)) state.


Does rank rule? Rank-related grooming patterns in Nicobar long-tailed macaques Macaca fascicularis umbrosus.
Primates maintain social bonds with specific individuals in the group by directing grooming toward them. Social grooming is often targeted toward individuals with whom the most benefits can be exchanged, which are usually the high-ranking individuals. We used the Seyfarth model to investigate whether dominance rank alters the distribution of grooming in a group of Macaca fascicularis umbrosus at Great Nicobar Island. We investigated whether dominance rank predicted grooming rate in both males and females. We used social network analysis to examine whether high-ranking animals maintain a central position in the grooming network. We also investigated whether adult individuals exchange grooming for social tolerance, as indicated by physical proximity. We found that more social grooming was directed toward high-ranking females, but not high-ranking males. Social network analysis suggested that high-ranking animals are not central individuals in the distribution of grooming; rather, middle-ranking animals were major contributors to the distribution of grooming. There was no relation between the grooming rate and proximity in both males and females. Overall, our findings suggest that females prefer to direct grooming toward high-ranking partners, although the dominance hierarchy is less steep than expected for Macaca fascicularis. Thus rank-related grooming patterns may be a relatively conserved trait in this isolated island population.


Measurement of disability-free survival after surgery.
Survival and freedom from disability are arguably the most important patient-centered outcomes after surgery, but it is unclear how postoperative disability should be measured. The authors thus evaluated the World Health Organization Disability Assessment Schedule 2.0 in a surgical population. The authors examined the psychometric properties of World Health Organization Disability Assessment Schedule 2.0 in a diverse cohort of 510 surgical patients. The authors assessed clinical acceptability, validity, reliability, and responsiveness up to 12 months after surgery. Criterion and convergent validity of World Health Organization Disability Assessment Schedule 2.0 were supported by good correlation with the 40-item quality of recovery scale at 30 days after surgery (r = -0.70) and at 3, 6, and 12 months after surgery with physical functioning (The Katz index of independence in Activities of Daily Living; r = -0.70, r = -0.60, and rho = -0.47); quality of life (EQ-5D; r = -0.57, -0.60, and -0.52); and pain interference scores (modified Brief Pain Inventory Short Form; r = 0.72, 0.74, and 0.81) (all P < 0.0005). Construct validity was supported by increased hospital stay (6.9 vs. 5.3 days, P = 0.008) and increased day 30 complications (20% vs. 11%, P = 0.042) in patients with new disability. There was excellent internal consistency with Cronbach's α and split-half coefficients greater than 0.90 at all time points (all P < 0.0005). Responsiveness was excellent with effect sizes of 3.4, 3.0, and 1.0 at 3, 6, and 12 months after surgery, respectively. World Health Organization Disability Assessment Schedule 2.0 is a clinically acceptable, valid, reliable, and responsive instrument for measuring postoperative disability in a diverse surgical population. Its use as an endpoint in future perioperative studies can provide outcome data that are meaningful to clinicians and patients alike.


Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins.
Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.


Systematic review of the effects of the intestinal microbiota on selected nutrients and non-nutrients.
There is considerable interest in the effects of the intestinal microbiota (IM) composition, its activities in relation with the metabolism of dietary substrates and the impact these effects may have in the development and prevention of certain non-communicable diseases. It is acknowledged that a complex interdependence exists between the IM and the mammalian host and that the IM possesses a far greater diversity of genes and repertoire of metabolic and enzymatic capabilities than their hosts. However, full knowledge of the metabolic activities and interactions of the IM and the functional redundancy that may exist are lacking. Thus, the current review aims to assess recent literature relating to the role played by the IM in the absorption and metabolism of key nutrients and non-nutrients. A systematic review (PROSPERO registration: CRD42015019087) was carried out focussing on energy and the following candidate dietary substrates: protein, carbohydrate, fat, fibre, resistant starch (RS), and polyphenols to further understand the effect of the IM on the dietary substrates and the resulting by-products and host impacts. Particular attention was paid to the characterisation of the IM which are predominantly implicated in each case, changes in metabolites, and indirect markers and any potential impacts on the host. Studies show that the IM plays a key role in the metabolism of the substrates studied. However, with the exception of studies focusing on fibre and polyphenols, there have been relatively few recent human studies specifically evaluating microbial metabolism. In addition, comparison of the effects of the IM across studies was difficult due to lack of specific analysis/description of the bacteria involved. Considerable animal-derived data exist, but experience suggests that care must be taken when extrapolating these results to humans. Nevertheless, it appears that the IM plays a role in energy homeostasis and that protein microbial breakdown and fermentation produced ammonia, amines, phenols and branch chain fatty acids, and a greater diversity in the microbes present. Few recent studies appear to have evaluated the effect of the IM composition and metabolism per se in relation with digestible dietary carbohydrate or fat in humans. Intakes of RS and prebiotics altered levels of specific taxa that selectively metabolised specific prebiotic/carbohydrate-type substances and levels of bifidobacteria and lactobacilli were observed to increase. In controlled human studies, consistent data exist that show a correlation between the intake of fibre and an increase in bifidobacteria and short-chain fatty acids, in particular butyrate, which leads to lower intestinal pH. Dietary polyphenols rely on modification either by host digestive enzymes or those derived from the IM for absorption to occur. In the polyphenol-related studies, a large amount of inter-individual variation was observed in the microbial metabolism and absorption of certain polyphenols. The systematic review demonstrates that the IM plays a major role in the breakdown and transformation of the dietary substrates examined. However, recent human data are limited with the exception of data from studies examining fibres and polyphenols. Results observed in relation with dietary substrates were not always consistent or coherent across studies and methodological limitations and differences in IM analyses made comparisons difficult. Moreover, non-digestible components likely to reach the colon are often not well defined or characterised in studies making comparisons between studies difficult if not impossible. Going forward, further rigorously controlled randomised human trials with well-defined dietary substrates and utilizing omic-based technologies to characterise and measure the IM and their functional activities will advance the field. Current evidence suggests that more detailed knowledge of the metabolic activities and interactions of the IM hold considerable promise in relation with host health.


Understanding neural signals of post-decisional performance monitoring: An integrative review.
Performance monitoring is a key cognitive function, allowing to detect mistakes and adapt future behavior. Post-decisional neural signals have been identified that are sensitive to decision accuracy, decision confidence and subsequent adaptation. Here, we review recent work that supports an understanding of late error/confidence signals in terms of the computational process of post-decisional evidence accumulation. We argue that the error positivity, a positive-going centro-parietal potential measured through scalp electrophysiology, reflects the post-decisional evidence accumulation process itself, which follows a boundary crossing event corresponding to initial decision commitment. This proposal provides a powerful explanation for both the morphological characteristics of the signal and its relation to various expressions of performance monitoring. Moreover, it suggests that the error positivity -a signal with thus far unique properties in cognitive neuroscience - can be leveraged to furnish key new insights into the inputs to, adaptation, and consequences of the post-decisional accumulation process.


In pursuit of physician/organization linkage.
A friend of mine once said that medical staff/administrative relationships are the Bermuda Triangle of health care management. The Bermuda Triangle, as I recall it, is an area of the Atlantic Ocean into which ships and planes disappear without a trace, for no apparent reason. Sometimes, especially late at night on reruns of "Twilight Zone," these planes reappear years later, crew intact and youthful. Sometimes, salt and sharks get the ships, planes, and voyagers. In a like manner, problems in medical staff/administrative relations draw consultants into a vortex. Sometimes, the consultants and their reports float to the surface a long afterward. Sometimes, they are digested by the organization and become a part of its mythology. Sometimes, they vanish forever. This is the story of three consultations. All were intended to make recommendations concerning the structural relationship of management to the physicians and their groups in our HMO: How to link the physician organization to the corporate structure. Like any narrative, this story is constructed to provide a context for reflection and is not intended to question the value of the contribution of specific individuals or companies.


A 140-kDa glycopeptide from the sperm ligand of the vitelline coat of the freshwater bivalve Unio elongatulus, only contains O-linked oligosaccharide chains and mediates sperm-egg interaction.
In previous studies we found that sperm binding activity in the vitelline coat of the freshwater bivalve Unio elongatulus is located on the O-linked oligosaccharide chains of gp273, one of the two major components of the extracellular coat, and that fucose plays a key role in this interaction. In this paper we report the partial characterization of a large glycopeptide (about 140 kDa) obtained by cyanogen bromide fragmentation of gp273, that maintains sperm binding activity. Lectin blotting revealed that the glycopeptide reacted with lectins from Arachis hypogaea (PNA) and Lotus tetragonolobus (LTA) but not Canavalia ensiformis (ConA). No other PNA-positive fragments could be detected in the electrophoretic pattern of fragmented gp273 but several ConA-positive fragments of lower molecular weight were present indicating that all the O-linked chains are clustered together in this fragment. Two-dimensional gel electrophoresis of the fragment revealed it to be acidic in nature in contrast with the neutral character of the whole gp273 molecule. Competition binding assay showed that this fragment is a strong inhibitor of the interaction, whereas no effect was detected using the ConA-positive peptides. This confirms that the sperm receptor activity of gp273 is related to its O-linked chains. The immunodominance of this fragment is also discussed.


Fucoidan from Ecklonia maxima is a powerful inhibitor of the diabetes-related enzyme, α-glucosidase.
Ecklonia maxima, an endemic South African seaweed, is a potential source of beneficial bioactive compounds. Among these compounds, fucoidan, a sulphated polysaccharide has a wide range of bioactivities including anti-diabetic activity. In this study, fucoidan was extracted from E. maxima by the hot water extraction method and then characterised by colorimetric assays for sugar composition. The extraction from E. maxima yielded 6.89% fucoidan which was found to contain 4.45 ± 0.25% L-fucose and 6.01 ± 0.53% sulphate. The water extracted E. maxima fucoidan had a low molecular weight of approximately 10 kDa. Structural studies (FT-IR, NMR and XRD) confirmed the structure and integrity of the fucoidan to be similar to previously studied fucoidans in literature. Finally, the activities of starch digestive enzymes; α-amylase and α-glucosidase, were investigated in the presence of the E. maxima fucoidan extract. Fucoidan from E. maxima was observed to be a potent mixed-type inhibitor of α-glucosidase with an IC50 range of 0.27-0.31 mg.ml-1, which was significantly lower than the commercial anti-diabetic standard, acarbose. Our present study demonstrated that fucoidan from E. maxima is a more powerful inhibitor compared to some standard anti-diabetic compounds and thus shows great potential for managing type 2 diabetes.


Control of lytic function by mitogen-activated protein kinase/extracellular regulatory kinase 2 (ERK2) in a human natural killer cell line: identification of perforin and granzyme B mobilization by functional ERK2.
The signal pathways that control effector function in human natural killer (NK) cells are little known. In this study, we have identified the critical role of the mitogen-activated protein kinase (MAPK) pathway in NK lysis of tumor cells, and this pathway may involve the mobilization of granule components in NK cells upon interaction with sensitive tumor target cells. Evidence was provided by biological, biochemical, and gene transfection methods. NK cell binding to tumor cells for 5 min was sufficient to maximally activate MAPK/extracellular signal-regulatory kinase 2 (ERK2), demonstrated by its tyrosine phosphorylation and by its ability to function as an efficient kinase for myelin basic protein. MAPK activation was achieved in NK cells only after contact with NK-sensitive but not NK-resistant target cells. In immunocytochemical studies, cytoplasmic perforin and granzyme B were both maximally redirected towards the tumor contact zone within 5 min of NK cell contact with tumor cells. A specific MAPK pathway inhibitor, PD098059, could block not only MAPK activation but also redistribution of perforin/granzyme B in NK cells, which occur upon target ligation. PD098059 also interfered with NK lysis of tumor cells in a 5-h 51Cr-release assay, but had no ability to block NK cell proliferation. Transient transfection studies with wild-type and dominant-negative MAPK/ERK2 genes confirmed the importance of MAPK in NK cell lysis. These results document a pivotal role of MAPK in NK effector function, possibly by its control of movement of lytic granules, and clearly define MAPK involvement in a functional pathway unlinked to cell growth or differentiation.


Development of methionine methylation profiling and relative quantification in human breast cancer cells based on metabolic stable isotope labeling.
Methylation of components involved in one-carbon metabolism is extremely important in cancer; comprehensive studies on methylation are essential and may provide us with a better understanding of tumorigenesis, and lead to the discovery of potential biomarkers. Here, we present an improved methodology for methylated metabolite profiling and its relative quantification in breast cancer cell lines by isotope dilution mass spectrometry based on 13CD3-methionine metabolic labeling using ultra-high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UPLC-HRMS/MS). First, all the methylated metabolites related to methionine were first screened and profiled by introducing 13CD3-methionine as the only medium into breast cancer cell growth cultures for both cellular polar metabolites and lipids. In total, we successfully found 20 labeled methylated metabolites and most of them were identified, some of which have not been reported before. We also developed a relative quantification method for all identified methylated metabolites based on isotope dilution mass spectrometry assays. Finally, the developed method was used for different breast cancer cells and mammary epithelial cells. Most methylated metabolites were disrupted in cancer cells. 1-Methyl-nicotinamide was decreased significantly, while trimethylglycine-glutamic acid-lysine and trimethyl-lysine were increased more than five times. This method offers a new insight into the methylation process, with several key pathways and important new metabolites being identified. Further investigation with biological assays should help to reveal the overall methylation metabolic network.


A study of anterior pituitary hormones secretion in patients with glioma receiving interferon-beta treatment.
Human interferon beta (IFN-beta) has been used for the treatment of patients with benign and malignant astrocytomas. The effect of IFN-beta on pituitary function, however, has not been precisely evaluated before. In this study the serum levels of various anterior pituitary hormones including GH, PRL, ACTH, and TSH were measured to determine the effects of IFN-beta on pituitary endocrine function in 19 consecutive glioma patients receiving IFN-beta. Daily doses of 3 x 10(6) U of IFN-beta were administered as a 30-min intravenous drip infusion beginning at 0800 h every morning during the first week and then 4 times a week for additional 6 weeks. Blood samples were taken on the day prior to administration as controls (0900 h and 1500 h), and on the first day of administration (0900 h and 1500 h) and after 7 days of administration (0900 h) in order to determine the acute and chronic or integrated effects of IFN-beta on the above pituitary hormones. No significant change in serum concentrations of any of the pituitary hormones examined was observed, suggesting that human natural IFN-beta used for the treatment of gliomas has no significant effect on the secretion of these hormones from the pituitary in these patients.


The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia.
Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7) or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11)). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11)). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20), allelic risk = 1.54, 95% Confidence Interval (CI) 1.41-1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87), and 2.35 (95% CI: 1.95-2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.


Rapid detection of bacterial endotoxins in drinking water and renovated wastewater.
A pilot study was conducted to determine the feasibility of using the Limulus endotoxin assay to detect endotoxins in potable waters and from reclaimed advanced waste treatment (AWT) plant effluents. Water samples were tested using both Limulus lysates prepared in our laboratory and a commercial product, Difco Pyrotest. The Limulus assay procedure was easily adapted to the testing of water samples for endotoxin. Measured endotoxin concentrations varied from 0.78 ng/ml to 1,250 ng/ml. Levels of endotoxin were not predictable based on whether the water was drinking water or AWT water, i.e., some AWT water samples had less endotoxin activity than some samples of drinking water, and some AWT waters had greater endotoxin activity than drinking water. Only three of the water samples tested were free of any detectable endotoxin. Breakpoint chlorination procedures seemed to reduce measurable endotoxin content, whereas passage through activated carbon columns was associated with greater final endotoxin concentrations in test waters.


The modifying effects of Food Stamp Program participation on the relation between food insecurity and weight change in women.
Food insecurity has been associated with overweight status in women. A number of hypotheses have been proposed to explain this association, some of which assume that household food insecurity is a cause of overweight. Similar to food insecurity, Food Stamp Program (FSP) participation has been associated with overweight status in women. One longitudinal study has also found a small effect of program participation on obesity status in women. Modeling FSP participation without accounting for the effect of need to participate in the program, as estimated by household food insecurity status, may lead to confounded findings. To estimate the direction and timing of the relation between food insecurity, this study reports on recently available longitudinal data from the Panel Study of Income Dynamics. The major finding of this paper is that persistent food insecurity was associated with a smaller weight change, controlling for other income and health-related risk factors for weight change. Among persistently food-insecure women, full participation in the FSP offset the weight change. There were no significant associations between change in food insecurity status and weight change in these data.


Occupational Therapy's efficacy in children with Asperger's syndrome: a systematic review of randomized controlled trials.
This systematic review of randomized controlled trials (RCTs) aims at evaluating the efficacy of Occupational therapy (OT) interventions in Asperger's syndrome (AS) pediatric patients. We conducted a systematic review according to PRISMA guidelines. The screening of the literature was carried out on PUBMED, SCOPUS, WEB OF SCIENCE and OT SEEKER databases, TO December 2018. We selected three RCTs having the common objective to evaluate whether children with AS can improve their social skills thanks to OT treatments. The interventions targeted by the three selected studies were: LEGO therapy, Social Use of Language Programme, Let's Face It! software and Parent Training combined with the administration of risperidone. All the studies showed that the intervention groups improved their overall social ability.This review shows that OT interventions can help concretely AS children in overcoming their social issues. Nevertheless, more RCTs are needed to better understand the OT's benefits and limitations in AS patients.


Fatal neurological disease in scrapie-infected mice induced for experimental autoimmune encephalomyelitis.
During the years or decades of prion disease incubation, at-risk individuals are certain to encounter diverse pathological insults, such as viral and bacterial infections, autoimmune diseases, or inflammatory processes. Whether prion disease incubation time and clinical signs or otherwise the pathology of intercurrent diseases can be affected by the coinfection process is unknown. To investigate this possibility, mice infected with the scrapie agent at both high and low titers were subsequently induced for experimental autoimmune encephalomyelitis, an immune system-mediated model of central nervous system (CNS) inflammation. We show here that co-induced mice died from a progressive neurological disease long before control mice succumbed to classical scrapie. To investigate the mechanism of the co-induced syndrome, we evaluated biochemical and pathological markers of both diseases. Brain and spleen PrP(Sc) levels in the dying co-induced mice were comparable to those observed in asymptomatic scrapie-infected animals, suggesting that co-induced disease is not an accelerated form of scrapie. In contrast, inflammatory markers, such as demyelination, immune cell infiltrates, and gliosis, were markedly increased in co-induced mouse spinal cords. Activated astrocytes were especially elevated in the medulla oblongata. Furthermore, PrP(sc) depositions were found in demyelinated white matter areas in co-induced mouse spinal cords, suggesting the presence of activated infected immune cells that infiltrate into the CNS to facilitate the process of prion neuroinvasion. We hypothesize that inflammatory processes affecting the CNS may have severe clinical implications in subjects incubating prion diseases.


Effects of denture teeth on the dimensional accuracy of acrylic resin denture bases.
The Michigan Computer-Graphics Coordinate Measurement System was used to determine the effects of artificial denture teeth on the accuracy of acrylic resin denture bases. Two poly(methyl methacrylate) acrylic resins and two processing techniques were tested. Groups processed with denture teeth reproduced more accurate points than groups processed without denture teeth. Groups processed with a conventional heat-polymerized acrylic resin reproduced more accurate points than groups polymerized with an injection pressing type of acrylic resin.


Cochrane Consumers and Communication Review Group: leading the field on health communication evidence.
This paper presents an overview of the history and achievements of the Cochrane Consumers and Communication Review Group, part of the international Cochrane Collaboration. It surveys the Group's establishment and structure, the scope of its Cochrane Reviews and the growth in its publication output over its 16-year history. The paper examines the Group's developmental work in interventions and outcomes related to patient communication and involvement, as well as methodological resources for review authors. It also outlines the Review Group's research partnerships with state, national and international agencies, particularly in the areas of chronic disease management, medicines use, public involvement, and vaccines communication. The Group's strong contribution to an evidence-base for health communication and participation are acknowledged.


Clinical and urodynamic evaluation in women with stress urinary incontinence treated by periurethral collagen injection.
To evaluate the success of treatment with periurethral collagen injections in patients suffering from stress urinary incontinence (SUI) with bladder neck hypermobility and intrinsic sphincter deficiency. Forty women suffering from (SUI) were selected and divided into GI (consisting of 13 women with SUI and bladder neck hypermobility) and GII (consisting of 27 women with SUI and intrinsic sphincter deficiency). Periurethral collagen was injected followed by a subjective evaluation (the need for urinary protectors) and an objective evaluation through urodynamic study before and after the treatment. It was noticed that after 9 months there was a decrease in the need of urinary protectors in the two groups. It was observed through the urodynamic study that either cure or improvement was achieved in 46% in GI and 40.7% in GII. There was a significant increase in the leak pressure in GII. Moreover, there was a decrease in the volume of urine leak in the two groups, being the results in GII statistically significant. It was concluded that the periurethral collagen injection is useful for the treatment of the SUI. The results in hypermobility are similar to those in intrinsic sphincter deficiency. In fact, it is a very simple out patient's procedure, with little side effects.


Evaluating palliative care needs in Middle Eastern countries.
Cancer incidence in Middle Eastern countries, most categorized as low- and middle-income, is predicted to double in the next 10 years, greater than in any other part of the world. While progress has been made in cancer diagnosis/treatment, much remains to be done to improve palliative care for the majority of patients with cancer who present with advanced disease. To determine knowledge, beliefs, barriers, and resources regarding palliative care services in Middle Eastern countries and use findings to inform future educational and training activities. Descriptive survey. Fifteen Middle Eastern countries; convenience sample of 776 nurses (44.3%), physicians (38.3%) and psychosocial, academic, and other health care professionals (17.4%) employed in varied settings. Palliative care needs assessment. Improved pain management services are key facilitators. Top barriers include lack of designated palliative care beds/services, community awareness, staff training, access to hospice services, and personnel/time. The nonexistence of functioning home-based and hospice services leaves families/providers unable to honor patient wishes. Respondents were least satisfied with discussions around advance directives and wish to learn more about palliative care focusing on communication techniques. Populations requiring special consideration comprise: patients with ethnic diversity, language barriers, and low literacy; pediatric and young adults; and the elderly. The majority of Middle Eastern patients with cancer are treated in outlying regions; the community is pivotal and must be incorporated into future plans for developing palliative care services. Promoting palliative care education and certification for physicians and nurses is crucial; home-based and hospice services must be sustained.


Can Platelet and Leukocyte Indicators Give Us an Idea about Distant Metastasis in Nasopharyngeal Cancer?
This study aimes to evaluate platelet and leucocyte indicators, such as the mean platelet volume, platelet distribution width, plateletcrit, white blood cell count, neutrophil to lymphocyte ratio in nasopharyngeal cancer patients and also to evaluate the relationship between these indicators and nasopharyngeal cancer with distant metastasis. The medical records of 118 patients diagnosed with nasopharyngeal cancer in our hospital between January 2006 and August 2015 were reviewed. The nasopharyngeal cancer group was further sub grouped according to the presence or absence of distant metastasis and TNM (tumour - T, node - N, metastasis - M) classification. A control group consisted of 120 healthy patients. The platelet and leucocyte values at the time of the initial diagnosis were recorded. Neutrophil to lymphocyte ratio and platelet distribution width values were significantly higher in the nasopharyngeal cancer group. But only platelet distribution width values were significantly higher in the nasopharyngeal cancer group with distant metastasis compared to the nasopharyngeal cancer group without distant metastasis. Neutrophil to lymphocyte ratio and platelet distribution width values may increase in nasopharyngeal cancer. But only the platelet distribution width values may give us an idea about the distant metastasis in nasopharyngeal cancer.


A comparison between two powder compaction parameters of plasticity: the effective medium A parameter and the Heckel 1/K parameter.
The purpose of the research was to introduce a procedure to derive a powder compression parameter (EM A) representing particle yield stress using an effective medium equation and to compare the EM A parameter with the Heckel compression parameter (1/K). 16 pharmaceutical powders, including drugs and excipients, were compressed in a materials testing instrument and powder compression profiles were derived using the EM and Heckel equations. The compression profiles thus obtained could be sub-divided into regions among which one region was approximately linear and from this region, the compression parameters EM A and 1/K were calculated. A linear relationship between the EM A parameter and the 1/K parameter was obtained with a strong correlation. The slope of the plot was close to 1 (0.84) and the intercept of the plot was small in comparison to the range of parameter values obtained. The relationship between the theoretical EM A parameter and the 1/K parameter supports the interpretation of the empirical Heckel parameter as being a measure of yield stress. It is concluded that the combination of Heckel and EM equations represents a suitable procedure to derive a value of particle plasticity from powder compression data.


1D and 2D diffusion pore imaging on a preclinical MR system using adaptive rephasing: Feasibility and pulse sequence comparison.
Diffusion pore imaging (DPI) has recently been proposed as a means to acquire images of the average pore shape in an image voxel or region of interest. The highly asymmetric gradient scheme of its sequence makes it substantially demanding in terms of the hardware of the NMR system. The aim of this work is to show the feasibility of DPI on a preclinical 9.4T animal scanner. Using water-filled capillaries with an inner radius of 10μm, four different variants of the DPI sequence were compared in 1D and 2D measurements. The pulse sequences applied cover the basic implementation using one long and one temporally narrow gradient pulse, a CPMG-like variant with multiple refocusing RF pulses as well as two variants splitting up the long gradient and distributing it on either side of the refocusing pulse. Substantial differences between the methods were found in terms of signal-to-noise ratio, contrast, blurring, deviations from the expected results and sensitivity to gradient imperfections. Each of the tested sequences was found to produce characteristic gradient mismatches dependent on the absolute value, direction and sign of the applied q-value. Read gradients were applied to compensate these mismatches translating them into time shifts, which enabled 1D DPI yielding capillary radius estimations within the tolerances specified by the manufacturer. For a successful DPI application in 2D, a novel gradient amplitude adaption scheme was implemented to correct for the occurring time shifts. Using this adaption, higher conformity to the expected pore shape, reduced blurring and enhanced contrast were achieved. Images of the phantom's pore shape could be acquired with a nominal resolution of 2.2μm.


MR cisternography: is it useful in the diagnosis of normal-pressure hydrocephalus and the selection of "good shunt responders"?
The aim of this study was to evaluate the efficiency of MR cisternography (MRC) in the diagnosis of idiopathic normal-pressure hydrocephalus (INPH) and in the prediction of the response to shunt treatment. Thirty-six patients with the diagnosis of "probable INPH" were included in the study group and 15 asymptomatic age-matched individuals were included in the control group. Pre-contrast T1-weighted (T1W) imaging was followed by intrathecal administration of 1 ml gadopentetate dimeglumine. Post-contrast T1W images were taken at the 12th, 24th and 48th hours. The presence of contrast material in the lateral ventricles for more than 24 hours was accepted as a positive diagnosis of INPH. Data from both groups were compared statistically. Statistical significance was accepted for P < 0.05. All of the INPH patients had remaining contrast material in their lateral ventricles at the 12th and 24th hours, while only 28 (78%) patients had contrast material remaining at the 48th hour after MRC. Only 3 (20%) of the control cases had remaining contrast material in their lateral ventricles at the 24th hour. No contrast material was present in the control cases at the 48th hour. The contrast material was found to be significantly more prevalent in the INPH patients at the 24th and the 48th hours compared with the control cases (P < 0.001). Shunt placement was performed in 14 INPH patients, and eight improved after shunt placement. All patients (100%) who improved after shunt placement had remaining contrast material in their lateral ventricles at the 24th and at the 48th hours. The sensitivity and specificity of MRC in the prediction of the response to shunt treatment were 100% and 17%, respectively. MRC does not use ionizing radiation and is generally a useful procedure to diagnose NPH and to predict a positive response to shunt treatment; thus, we recommend MRC after routine MRI in patients with the presumed diagnosis of NPH.


Low-Energy Electron Irradiation Efficiently Inactivates the Gram-Negative Pathogen Rodentibacter pneumotropicus-A New Method for the Generation of Bacterial Vaccines with Increased Efficacy.
Bacterial pathogens cause severe infections worldwide in livestock and in humans, and antibiotic resistance further increases the importance of prophylactic vaccines. Inactivated bacterial vaccines (bacterins) are usually produced via incubation of the pathogen with chemicals such as formaldehyde, which is time consuming and may cause loss of immunogenicity due to the modification of structural components. We evaluated low-energy electron irradiation (LEEI) as an alternative method to generate a bacterin. Rodentibacter pneumotropicus, an invasive Gram-negative murine pathogen, was inactivated with LEEI and formaldehyde. LEEI resulted in high antigen conservation, and LPS activity was significantly better maintained when compared with formaldehyde treatment. Immunization of mice with LEEI-inactivated R. pneumotropicus elicited a strong immune response with no detectable bacterial burden upon sublethal challenge. The results of this study suggest the inactivation of bacteria with LEEI as an alternative, fast and efficient method to generate bacterial vaccines with increased efficacy.


Determination of hydrocarbons using sapphire fibers coated with poly(dimethylsiloxane).
A poly(dimethylsiloxane) (PDMS) coated sapphire fiber has been investigated as a sensor for hydrocarbons (HCs) in the mid-infrared region around 3000 cm(-1). In order to optimize and predict sensor response, the diffusion behavior of the analytes into the PDMS preconcentration medium has been examined. A diffusion model based on Fickian diffusion was used to quantify diffusion. The model incorporated such factors as film thickness, refractive index of the polymer and the fiber core, and principal wavelength at which the analyte absorbs. A range of hydrocarbons, from hexane to pentadecane, was analyzed at 2930 cm(-1) using both fiber-coupled Fourier transform infrared spectroscopy and a modular prototype system. Diffusion coefficients were determined for these compounds and diffusion behavior examined and related to factors such as analyte polarity and molecular size. The diffusion coefficients were found to range from 6.41 x 10(-11) 5 x 10(-12) to 5.25 x 10(-11) +/- 9 x 10(-13) cm2 s(-1) for hexane and pentadecane into a 2.9 microm PDMS film, respectively. The diffusion model was also used to examine the effect of changing system parameters such as film thickness in order to characterize sensor response.


Divergence in the epidemiological estimates of traumatic brain injury in the United States: comparison of two national databases.
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the US, but the true incidence of TBI is unknown. The National Trauma Data Bank National Sample Program (NTDB NSP) was queried for 2007 and 2013, and population-based weighted estimates of TBI-related emergency department (ED) visits, hospitalizations, and deaths were calculated. These data were compared to the 2017 Centers for Disease Control and Prevention (CDC) report on TBI, which used the Healthcare Cost and Utilization Project's National ("Nationwide" before 2012) Inpatient Sample and National Emergency Department Sample. In the NTDB NSP the incidence of TBI-related ED visits was 59/100,000 in 2007 and 62/100,000 in 2013. However, in the CDC report there were 534/100,000 in 2007 and 787/100,000 in 2013. The CDC estimate for ED visits was 805% higher in 2007 and 1169% higher in 2013. In the NTDB NSP, the incidence of TBI-related deaths was 5/100,000 in 2007 and 4/100,000 in 2013. In the CDC report, the incidence was 18/100,000 in both years. The CDC estimate for deaths was 260% higher in 2007 and 325% higher in 2013. The databases disagreed widely in their weighted estimates of TBI incidence: CDC estimates were consistently higher than NTDB NSP estimates, by an average of 448%. Although such a discrepancy may be intuitive, this is the first study to quantify the magnitude of disagreement between these databases. Given that research, funding, and policy decisions are made based on these estimates, there is a need for a more accurate estimate of the true national incidence of TBI.


Bovine Teat Cistern Microbiota Composition and Richness Are Associated With the Immune and Microbial Responses During Transition to Once-Daily Milking.
The relationship between microbiota and health has been widely reported in humans and animals. We established a link between teat cistern microbiota composition and bovine mastitis, an inflammatory disease often due to bacterial infections. To further decipher the relationships between teat cistern microbiota and immune and microbial responses, a switch from twice- to once-daily milking (ODM) in 31 initially healthy quarters of dairy cows was used to trigger an udder perturbation. In this study, a temporal relationship was reported between initial teat cistern microbiota composition and richness, the immune response to ODM, and mastitis development. Quarters with a low initial microbiota richness and taxonomic markers such as Bacteroidetes and Proteobacteria were associated with a higher rate of mastitis during ODM. Quarters with a higher richness and taxonomic markers such as Firmicutes, including the Lachnospiraceae family, and genera such as Bifidobacterium and Corynebacterium displayed early inflammation following transition to ODM but without developing mastitis (no infection). Short-term compositional shifts of microbiota indicates that microbiotas with a higher initial richness were more strongly altered by transition to ODM, with notably the disappearance of rare OTUs. Microbiota modifications were associated with an early innate immune system stimulation, which, in turn, may have contributed to the prevention of mastitis development.


A fluorometric method for measurement of oxygen radical-scavenging activity of water-soluble antioxidants.
The relative activities of the antioxidants Trolox, ascorbic acid, uric acid, quercetin, and rutin, and the activities of total antioxidants in serum samples were determined using a fluorometric assay based on the dye 6-carboxyfluoroscein (6C-Fl) as a fluorescent indicator; 2,2'-azobis-2-amidinopropane hydrochloride (AAPH) as a peroxyl radical generator; 6-hydroxy-2,5,7, 8-tetramethyl-1-chroman-2-carboxylic acid (Trolox) as a calibrator; and phosphate buffer (pH 7.0) as a solvent. Incubation of 6C-Fl in 0. 075 M phosphate buffer, in the presence of AAPH at 37 degrees C, resulted in loss of its fluorescence signal at 520 nm with excitation at 495 nm. The antioxidants Trolox, ascorbic acid, and uric acid provided protection of the fluorescence of 6C-Fl, and the relative antioxidant activities, determined by the net protection area under curve technique, were found to be 1:0.4:1, respectively. Trolox and ascorbic acid were used to validate this assay. A linear correlation of the net protection value with the concentration of serum, Trolox, ascorbic acid, and uric acid was demonstrated. Quercetin and rutin were shown to have strong antioxidant activities, nearly 10 times those of vitamin C. This assay is simple, reliable, and suitable for automation to handle many samples and requires few microliters of serum samples.


An optimized protocol for hip joint centre determination using the functional method.
The functional method identifies the hip joint centre (HJC) as the centre of rotation of the femur relative to the pelvis during an ad hoc movement normally recorded using stereophotogrammetry. This method may be used for the direct determination of subject-specific HJC coordinates or for creating a database from which regression equations may be derived that allow for the prediction of those coordinates. In order to contribute to the optimization of the functional method, the effects of the following factors were investigated: the algorithm used to estimate the HJC coordinates from marker coordinates, the type and amplitude of the movement of the femur relative to the pelvis, marker cluster location and dimensions, and the number of data samples. This was done using a simulation approach which, in turn, was validated using experiments made on a physical analogue of the pelvis and femur system. The algorithms used in the present context were classified and, in some instances, modified in order to optimize both accuracy and computation time, and submitted to a comparative evaluation. The type of movement that allowed for the most accurate results consisted of several flexion-extension/abduction-adduction movements performed on vertical planes of different orientations, followed by a circumduction movement. The accuracy of the HJC estimate improved, with an increasing rate, as a function of the amplitude of these movements. A sharp improvement was found as the number of the photogrammetric data samples used to describe the movement increased up to 500. For optimal performance with the recommended algorithms, markers were best located as far as possible from each other and with their centroid as close as possible to the HJC. By optimizing the analytical and experimental protocol, HJC location error not caused by soft tissue artefacts may be reduced by a factor of ten with a maximal expected value for such error of approximately 1mm.


Tools to Evaluate the Eco-efficiency of Analytical Methods in the Context of Green and White Analytical Chemistry: A Review.
The release of a product in the consumer market requires an analysis by quality control. This sector makes use of reliable analytical methods, by high performance liquid chromatography (HPLC), spectrophotometry in the ultraviolet and visible regions (UV-Vis), spectrophotometry in the infrared region (IR) or thin layer chromatography (TLC), for example, to reach a result. The analysis conditions of most of these analytical methods currently still use toxic reagents, generate a greater amount of waste, sample preparation has more steps, the need for instrumentation and consumables in greater quantity, generating a cost and impact on health and the environment greater than if there were adoption of the Green Analytical Chemistry (GAC) and the White Analytical Chemistry (WAC). The objective of this review is to show the relationship of analytical choices for current pharmaceutical analyzes with the GAC and the WAC. Analytical methods can be evaluated for greenness and whiteness using tools such as the National Environmental Method Index (NEMI), Eco-Scale Assessment (ESA), Analytical Greenness Metric (AGREE) and Green Analytical Procedure Index (GAPI). The use of NEMI, ESA, AGREE and GAPI tools brings the objective evidence needed to discuss the greenness and whiteness of an analytical method, leaving the subjective level. Furthermore, semi or quantitative data facilitate the choice of an analytical method and its conditions, when the target is the concern with eco-efficiency.


Study on molecular mechanism of MiRNA-29a in promoting proliferation and invasion of non-small-cell lung cancer by inhibiting MTSS1.
To investigate the biological role of micro-ribonucleic acid (miR)-29a in non-small-cell lung cancer (NSCLC). 55 cases of NSCLC tissue specimens and paired normal lung tissue specimens collected in the Department II of Oncology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from July 2012 to April 2015 were randomly included. The fluorescent quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect the expression levels of miR-29a and metastasis suppressor 1 (MTSS1). Pearson correlation analysis was utilized to investigate the relationship between miR-29a expression and MTSS1 expression in NSCLC tissues, and the Kaplan-Meier survival curves were constructed to analyze the association of miR-29a expression with the survival time of NSCLC patients. A54 proliferation and invasion abilities were measured by means of plate clone formation assay, and transwell assay after the miR-29a was suppressed by miRNA inhibitor. Luciferase assay was used to detect the target gene of miR-29a. In NSCLC tissues, the miR-29a expression level was higher than that in normal lung tissues (p<0.05), while the expression level of MTSS1 protein was remarkably lower than that in normal lung tissues (p<0.05). The median survival time of the patients was 15.1 months in high miR-29a expression group and 18.3 months in low miR-29a expression group (p<0.05). The miR-29a expression was negatively correlated with the expression level of MTSS1 protein in NSCLC tissues (r=-0.762, p<0.05). Luciferase results suggest that miR-29a binds to the promoter region of MTSS1 and inhibits its transcription level. The expression of MTSS1 protein was up-regulated notably after miR-29a knockdown by an inhibitor. It was revealed in the results of transwell assay and plate clone formation assay that the proliferative and invasive capacity of A549 cells was significantly decreased after knockdown of miR-29a. The transcribed miR-29a down-regulates the protein level of MTSS1, suppressor of tumor proliferation and invasion, thereby promoting the proliferative and invasive capacity of NSCLC cells. Both miR-29a and MTSS1 are expected to become potential therapeutic targets for NSCLC.


Permeability shapes bacterial communities in sublittoral surface sediments.
The first interaction of water column-derived organic matter with benthic microbial communities takes place in surface sediments which are acting as biological filters catalyzing central steps of elemental cycling. Here we analyzed the bacterial diversity and community structure of sediment top layers at seven sites in the North Sea where sediment properties ranged from coarse-grained and highly permeable to fine-grained and impermeable. Bacterial communities in surface sediments were richer, more even and significantly different from communities in bottom waters as revealed by Illumina tag sequencing of 16S rRNA genes. Sediment permeability had a clear influence on community composition which was confirmed by CARD-FISH. Sulfate-reducing Desulfobacteraceae (2-5% of total cells), Flavobacteriaceae (3-5%) were more abundant in impermeable than in highly permeable sediments where acidobacterial Sva0725 dominated (11-15%). Myxobacterial Sandaracinaceae were most abundant in medium permeable sediments (3-7%). Woeseiaceae/JTB255 and Planctomycetes were major groups in all sediments (4-6%, 8-22%). Planctomycetes were highly diverse and branched throughout the phylum. We propose Planctomycetes as key bacteria for degradation of high molecular weight compounds and recalcitrant material entering surface sediments from the water column. Benthic Flavobacteriaceae likely have restricted capabilities for macromolecule degradation and might profit with Sandaracinaceae and Acidobacteria from low molecular weight compounds.


Multiple aneurysms of the anterior communicating artery.
Multiple aneurysms of the anterior communicating artery are rare. The authors describe a patient who was admitted with a sudden, severe headache with radiation to the neck. Angiograms demonstrated filling of both anterior cerebral arteries and bilateral aneurysms arising from the origin of the anterior communicating artery. Both aneurysms were surgically verified and clipped.


Osteoarticular infections in young children: what has changed over the last years?
Osteoarticular infections remain a significant cause of morbidity worldwide in young children. They can have a devastating impact with a high rate of serious and long-lasting sequelae, especially on remaining growth. Depending on the localisation of infection, they manifest as osteomyelitis, septic arthritis, a combination of both (i.e., osteomyelitis with adjacent septic arthritis) or spondylodiscitis. Osteoarticular infections can be divided into three types according to the source of infection: haematogenous; secondary to contiguous infection; or secondary to direct inoculation. During the last few years, many principles regarding diagnostic assays and the microbiological causes of these infections have evolved in a significant manner. In the present current-opinion review, we discuss recent concepts regarding epidemiology, physiopathology, and the microbiology of bone and joint infections in young children, as well as clinical presentations, diagnosis, and treatment of these infections. Clinicians caring for children need to be especially well versed in these newer concepts as they can be used to guide evaluation and treatment.


Magneto-Optical Detection of the Spin Hall Effect in Pt and W Thin Films.
The conversion of charge currents into spin currents in nonmagnetic conductors is a hallmark manifestation of spin-orbit coupling that has important implications for spintronic devices. Here we report the measurement of the interfacial spin accumulation induced by the spin Hall effect in Pt and W thin films using magneto-optical Kerr microscopy. We show that the Kerr rotation has opposite sign in Pt and W and scales linearly with current density. By comparing the experimental results with ab initio calculations of the spin Hall and magneto-optical Kerr effects, we quantitatively determine the current-induced spin accumulation at the Pt interface as 5×10^{-12} μ_{B} A^{-1} cm^{2} per atom. From thickness-dependent measurements, we determine the spin diffusion length in a single Pt film to be 11±3 nm, which is significantly larger compared to that of Pt adjacent to a magnetic layer.


ANO9/TMEM16J promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer.
Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer. In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pancreatic cancer cells, and its role in the pathogenesis of pancreatic cancer was evaluated using an integrated in vitro and in vivo approach. To determine clinical relevance of the experimental findings, the prognostic value of ANO9 was evaluated in patients with pancreatic cancer. The ANO9 mRNA and protein levels were increased in pancreatic cancer-derived cells. Exogenous expression of ANO9 in PANC-1 cells significantly increased cell proliferation in cell cultures and in mice. In contrast, knockdown of ANO9 in AsPC-1, BxPC-3, and Capan-2 cells strongly inhibited cell proliferation. Mechanistic analysis suggested that physical association of ANO9 with epidermal growth factor receptor (EGFR) underlies ANO9-induced cell proliferation. Knockdown of ANO9 augmented the effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell proliferation. In addition, high ANO9 expression is a poor prognostic factor in patients with pancreatic cancer. The ANO9/TMEM16J appears to be a clinically useful prognostic marker for pancreatic cancer and a potential therapeutic target.


Individual knock out of glycine receptor alpha subunits identifies a specific requirement of glra1 for motor function in zebrafish.
Glycine receptors (GlyRs) are ligand-gated chloride channels mediating inhibitory neurotransmission in the brain stem and spinal cord. They function as pentamers composed of alpha and beta subunits for which 5 genes have been identified in human (GLRA1, GLRA2, GLRA3, GLRA4, GLRB). Several in vitro studies showed that the pentameric subtype composition as well as its stoichiometry influence the distribution and the molecular function of the receptor. Moreover, mutations in some of these genes are involved in different human conditions ranging from tinnitus to epilepsy and hyperekplexia, suggesting distinct functions of the different subunits. Although the beta subunit is essential for synaptic clustering of the receptor, the specific role of each alpha subtype is still puzzling in vivo. The zebrafish genome encodes for five glycine receptor alpha subunits (glra1, glra2, glra3, glra4a, glra4b) thus offering a model of choice to investigate the respective role of each subtype on general motor behaviour. After establishing a phylogeny of GlyR subunit evolution between human and zebrafish, we checked the temporal expression pattern of these transcripts during embryo development. Interestingly, we found that glra1 is the only maternally transmitted alpha subunit. We also showed that the expression of the different GlyR subunits starts at different time points during development. Lastly, in order to decipher the role of each alpha subunit on the general motor behaviour of the fish, we knocked out individually each alpha subunit by CRISPR/Cas9-targeted mutagenesis. Surprisingly, we found that knocking out any of the alpha2, 3, a4a or a4b subunit did not lead to any obvious developmental or motor phenotype. However, glra1-/- (hitch) embryos depicted a strong motor dysfunction from 3 days, making them incapable to swim and thus leading to their premature death. Our results infer a strong functional redundancy between alpha subunits and confirm the central role played by glra1 for proper inhibitory neurotransmission controlling locomotion. The genetic tools we developed here will be of general interest for further studies aiming at dissecting the role of GlyRs in glycinergic transmission in vivo and the hitch mutant (hic) is of specific relevance as a new model of hyperekplexia.


Spinal accessory nerve palsy following gunshot injury: a case report.
Injuries to the spinal accessory nerve are rare and mostly iatrogenic. Pain, impaired ability to raise the ipsilateral shoulder, and scapular winging on abduction of the arm are the most frequently noted clinical manifestations. As a seldom case, a 20 year-old male with spinal accessory nerve palsy after penetrating trauma by gunshot was reported. Three months after the injury, he was complaining about left arm pain in abduction to shoulder level and a decreased range of movement. On physical examination, wasting of the left trapezium with loss of nuchal ridge and drooping of the shoulder were found. On neurological examination of the left trapezius and sternomastoid muscles, motor function were 3/5 and wide dysesthesia on the neck, shoulder and arm was present. The bullet entered just above the clavicle and exited from trapezium. Radiological studies were normal, where electromyography (EMG) showed neuropathic changes. Surgical exploration showed the intact nerve lying on its natural course and we performed external neurolysis for decompression. The postoperative period was uneventful. Dysesthesia has diminished slowly. He was transferred to physical rehabilitation unit. In his clinical control after 3 months he had no dysesthesia and neurological examination of the left trapezius and sternomastoid muscles motor function were 4/5. EMG showed recovery in the left spinal accessory nerve.


[Use of contraceptive methods among university adolescents].
The objective of this study was to identify the use of contraceptive methods among teenagers at a public University in São Paulo, as well as to describe their profile concerning social and demographic characteristics. A questionnaire was used and the sample was composed by 295 teenagers. The initiation of sexual activity was reported by 48.8%. The mean age was seventeen and most of them reported that they used some type of contraceptive method. The method used with highest frequency was the preservative, and this in combination with the pill. It could be observed that teenagers seek information through health professionals, teachers or books, and mainly media. It was concluded that the students had sexual initiation late and seek information about contraception.