Discrepant DNA analysis in three patients with inherited arrhythmia: molecular genetic test results deserve a second glance.
Molecular results provide a basis for diagnosis, risk assessment, medical management and genetic counseling. Unlike other areas of laboratory medicine, molecular genetic tests are rarely repeated. We describe three patients with suspected inherited arrhythmia in whom genetic testing was arranged via clinical and/or research laboratories. In all three instances, initial test results appeared falsely negative, with no deleterious mutations detected by various methodologies in selected long-QT or catecholaminergic polymorphic ventricular tachycardia-related genes. Discordant results emerged upon repeat analysis in separate laboratories. The cases highlight the importance of clinical judgment and assessment of genetic test results and methodology, in addition to the role of re-testing in molecular genetic medicine, particularly in the case of uninformative negative results.


Apple phenolics as inhibitors of the carbonylation pathway during in vitro metal-catalyzed oxidation of myofibrillar proteins.
The effect of apple phenolics on the oxidative damage caused to myofibrillar proteins by an in vitro metal-catalyzed oxidation system was investigated. Three pure phenolic compounds (chlorogenic acid, (-)-epicatechin and phloridzin) and an apple peel extract were added to myofibrillar proteins in three concentrations (50, 100 and 200μM), and a blank treatment was included as a control. All suspensions were subjected to Fe(3+)/H2O2 oxidation at 37°C during 10days, and protein oxidation was evaluated as carbonylation (α-amino adipic and γ-glutamic semialdehydes) and Schiff base cross-links. Significant inhibition by apple phenolics was found as compared to the control treatment, with (-)-epicatechin being the most efficient antioxidant and phloridzin showing the weakest antioxidant effect. The higher concentrations of apple extract showed effective antioxidant activity against protein oxidation in myofibrillar proteins, emphasizing the potential of apple by-products as natural inhibitors of protein oxidation in meat products.


Acute inflammatory demyelinating optic neuritis: current concepts in diagnosis and management.
Optic neuritis (ON), defined as an inflammatory demyelinating optic neuropathy, is a frequent cause of visual loss owing to optic nerve dysfunction in young or middle-aged patients. ON can be seen in isolation or in association with multiple sclerosis (MS). Highlighting the importance of this association is the fact that approximately 20% of patients with MS will present with ON. Review was conducted of the literature and pertinent clinical trials. Although the vision prognosis of patients with ON is excellent, with or without the use of corticosteroids, a minority of patients will suffer from significantly poor vision. ON may be the heralding manifestation of MS; the risk stratification for the future development of MS in patients presenting with ON can be determined by the number of white matter lesions on the baseline cerebral magnetic resonance imaging study. To date, 2 randomized, placebo-controlled studies have found that patients with a clinically isolated demyelinating syndrome, such as ON, at risk for MS, may benefit from the early institution of a disease-modifying drug.


Combined growth hormone stimulation testing: Could the tests be shortened?
Growth hormone stimulation tests (GHST) remain the cornerstone for diagnosing growth hormone deficiency (GHD), yet they can be lengthy and costly. We aimed to examine whether the combined clonidine and glucagon stimulation test (CGST) and l-dopa and glucagon stimulation test (LDGST) can be shortened without compromising the test's specificity. We retrospectively analyzed the baseline characteristics, auxological and laboratory data of children with short stature who had undergone a CGST and an LDGST for GHD. We compared the diagnostic accuracy for the standard test and shortened test, eliminating time points of 0 and 210 min. We reviewed 830 charts (8.17 ± 2.92 years old; 56.27% males), with 431 (57.0%) children in the CGST group, and 38 (51.35%) in the LDGST group who tested negative for GHD. The peak and maximum GH levels occurred at the 60-min time point for both the CGST and LDGST. Eliminating the 0-min time point was the only time that did not affect the specificity of the CGST, with a false-positive rate of 2 (2.99%), specificity of 0.99 (0.99-0.99), and p value of 0.25. Eliminating the 0- and 210-min time points did not affect the specificity of the LDGST, with a false-positive rate of 2 (5.26%), specificity of 0.95 (0.95-0.95), and p value of 0.24. We concluded that 0-min time point could be eliminated without compromising the combined GHST diagnostic value, thus resulting in cost reduction. Larger studies are needed for the combined LDGST to explore whether the 30- and 210-min time points could be eliminated, thus resulting in cost and time savings.


Comparison of serum hydroquinidine determination by fluorescence polarization immunoassay and liquid chromatography.
Hydroquinidine is a structural analogue of quinidine. It is used in the treatment and prevention of cardiac arrhythmias and necessitates serum monitoring. Fluorescence polarization immunoassay (FPIA) of quinidine has been proposed and we have tested the performance of this assay for hydroquinidine using its cross-reaction with quinidine. Tracer (quinidine labelled with fluorescein) and anti-serum were purchased from Abbott S.A. Standard curves were obtained using specifically prepared hydroquinidine calibrators and within-run and run-to-run precision values (expressed as relative standard deviation) (RSD) lower than 5.3% (n = 10). In order to evaluate specificity of this assay in the clinical situation, FPIA and liquid chromatography results were compared.


Characterization of purine nucleotide metabolism in primary rat muscle cultures.
The synthesis and metabolic fate of purine nucleotides were studied, employing labeled precursors, in primary rat muscle cultures. The cultures were found to produce purine nucleotides, by de novo and salvage pathways, both exhibiting dependence on cellular availability of substrate 5-phosphoribosyl-1-pyrophosphate (PPRibP). Depletion of cellular PPRibP decelerated the rate of purine synthesis, whereas increasing PPRibP generation by high Pi concentration in the incubation medium, accelerated purine synthesis. Ribose accelerated purine synthesis, indicating that ribose 5-phosphate availability in the cultured muscle is limiting for PPRibP synthesis. The study in the muscle cultures of the metabolic fate if IMP formed from [14C]formate and that of nucleotides formed from labeled purine bases, revealed that the main flow in the nucleotide interconversions pathways is from AMP to IMP. The flow from IMP to GMP and to AMP appeared to be of a lesser magnitude and virtually no flow could be detected from GMP to IMP. The greatest proportion of radioactivity of purine nucleotides following synthesis by either de novo or salvage pathways, accumulated in IMP, reflecting the relative rates of flows between the various nucleotides and probably also a relatively low, or inhibited activity of the IMP nucleotidase. The results suggest that primary muscle cultures are a plausible model for the study of the role of purine metabolism in muscle work.


In Vitro and Ex Vivo Evaluation of Capparis spinosa Extract to Inactivate Protoscoleces During Hydatid Cyst Surgery.
Hydatidosis is one of the most dangerous zoonosis diseases in the world caused by the larval stage of the broad-worm or Echinococcus granulosus parasite. Today, cysts' rupture or content leakage during surgery and involvement of organs adjacent to the organ involved, and consequently secondary cysts, are the major concern for hydatid cyst surgeons. Therefore, using scolicidal substances such as hypertonic saline 20%, silver nitrate and formalin has been considered to reduce the risk of protoscoleces spread and recurrence of disease in recent years. The current work was designed to assess the antiparasitic effects of Capparis spinose L. extract against hydatid cyst protoscoleces. Collected protoscoleces from liver fertile hydatid cysts of infected sheep were exposed to the different concentrations of the essential oil (150, 300, 600 mg/mL) for 5-60 min in vitro and ex vivo. Then by using the eosin exclusion assay, the viability of protoscoleces was studied. The primary phytochemical analysis of the C. spinosa extract was done to assess the presence of tannins, alkaloids, saponins, flavonoids, terpenoids and glycosides. C. spinosa extract exhibited a powerful protoscolicidal activity in vitro so at the dose of 300 and 600 mg/ml, it entirely eliminated the parasite after 10 and 5 minutes; whereas at lower doses, it demonstrated weak protoscolicidal activity. In ex vivo assay, no similar effect to in vitro assay was observed, so more time was required to show a potent protoscolicidal activity. C. spinosa extract, at the concentrations of 300 and 600 mg/mL after an exposure time of 20 and 12 min, killed 100% of protoscoleces within the hydatid cyst, respectively. The findings of primary phytochemical screening of the C. spinosa extract demonstrated the existence of flavonoids, tannins, terpenoids, glycosides and alkaloids in this plant. The obtained results in vitro and ex vivo exhibited potent protoscolicidal effects of C. spinosa extract particularly at the concentrations of 600 and 300 mg/ml, which entirely eliminated the parasite after 5-20 min exposure. However, more supplementary works are required to verify these findings through assessing in animal models and clinical subjects.


Invertebrate turnover along gradients of anthropogenic salinisation in rivers of two German regions.
Rising salinity in freshwater ecosystems can affect community composition. Previous studies mainly focused on changes in freshwater communities along gradients of absolute levels of electrical conductivity (EC). However, both geogenic and anthropogenic drivers contribute to the EC level and taxa may regionally be adapted to geogenic EC levels. Therefore, we examined the turnover in freshwater invertebrates along gradients of anthropogenic EC change in two regions of Germany. The anthropogenic change of EC was estimated as the difference between the measured EC and the modeled background EC driven by geochemical and climate variables. Turnover in freshwater invertebrates (β-diversity) was estimated using the Jaccard index (JI). We found that invertebrate turnover between EC gradient categories is generally greater than 47%, with a maximum of approximately 70% in sites with a more than 0.4 mS cm-1 change compared to the baseline (i.e. no difference between predicted and measured EC). The invertebrates Amphinemura sp., Anomalopterygella chauviniana and Leuctra sp. were reliable indicators of low EC change, whereas Potamopyrgus antipodarum indicated sites with the highest EC change. Variability within categories of EC change was slightly lower than within categories of absolute EC. Elevated nutrient concentrations that are often linked to land use may have contributed to the observed change of the invertebrate richness and can exacerbate effects of EC on communities in water. Overall, our study suggests that the change in EC, quantified as the difference between measured EC and modeled background EC, can be used to examine the response of invertebrate communities to increasing anthropogenic salinity concentrations in rivers. However, due to the strong correlation between EC change and observed EC in our study regions, the response to these two variables was very similar. Further studies in areas where EC change and observed EC are less correlated are required. In addition, such studies should consider the change in specific ions.


Daily carbon gain by Adenocaulon bicolor (Asteraceae), a redwood forest understory herb, in relation to its light environment.
The relationships between carbon gain and availability of sunfleck- and diffuse-light were determined for Adenocaulon bicolor by following the daily courses of assimilation and incident PFD on different days and locations in a redwood forest understory. Total PFD for the days sampled ranged from 1 to 4% of full sun values. Sunflecks accounted for 50 to 90% of the total PFD and were responsible for the majority of variation among days and locations. Each day had several clusters of sunfleck activity separated by relatively long intervals of diffuse light. Most sunflecks had maximum PFDs below the photosynthetic light-saturation point, and they had a median length and diffuse light interval separating them of 2 s. Daily carbon gain varied from 14 to 40 mmol m-2d-1 and was more strongly correlated with differences among days in total sunfleck PFD (r 2=0.81) than with variation in diffuse PFD (r 2=0.54). The assimilation that was attributable to sunflecks ranged from essentially zero on one day to 30 to 65% of the total on the other days. Carbon gain on most days was 70 to 80% of that predicted by a model based on the measured light dependences of assimilation. This model assumed an instantaneous response to changes in PFD, whereas incomplete photosynthetic induction probably limited the capacity to respond to sunflecks and therefore limited carbon gain on most days.


Conversion from tacrolimus to cyclosporine A for new-onset diabetes after transplantation: a single-centre experience in renal transplanted patients and review of the literature.
Tacrolimus (TRL) increases the incidence of new-onset diabetes mellitus after transplantation (NODAT). Little is known about whether conversion from TRL to cyclosporine A (CsA) improves glucose metabolism in patients with NODAT. We retrospectively analysed glucose metabolism parameters in 54 TRL-treated renal transplant patients who developed NODAT. Thirty-four were converted to CsA whereas 20 patients continued TRL. After conversion, fasting plasma glucose decreased from 146 +/- 64 to 104 +/- 20 mg/dl (P < 0.0001) and HbA1c levels decreased from 6.8 +/- 0.8% to 6.0 +/- 0.6% (P < 0.0001) after 1 year of follow-up. The remission rate of NODAT reached 42% (95% confidence interval 24-59%) 1 year after conversion versus 0% in the control group (P = 0.001). Blood pressure and lipid levels were stable after conversion although the use of statins significantly increased (P < 0.01). The conversion was safe in terms of graft function and acute rejection episodes. The 1-year patient survival and graft survival rate were 100%. In conclusion, our results suggest a significant improvement of glucose metabolism after conversion to CsA in renal transplant patients with NODAT.


The Predictive and Prognostic Value of Early Metabolic Response Assessed by Positron Emission Tomography in Advanced Gastric Cancer Treated with Chemotherapy.
To evaluate the feasibility of early metabolic change assessed by PET in predicting clinical response to chemotherapy and investigate its prognostic value in patients with advanced gastric cancer. A total of 64 patients with advanced gastric cancer were prospectively enrolled and examined by PET with (18)F-fluorodeoxyglucose (FDG) and (18)F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT) at baseline and 14 days after treatment initiation. PET findings were analyzed for the correlation with best clinical response of patients, disease control status, and survival after identifying the threshold of metabolic change percentage by ROC analysis. For FDG-PET, the total uptake value reduction percentage (δ-SUV) of 40% was the cut-off point with the maximum of sensitivity (70%) and specificity (83%) to predict clinical responding and that of prediction for disease control status was 30%, with the highest sensitivity (58%) and specificity (100%). The δ-SUV of FLT-PET played no predictive role for clinical response (AUC = 0.62; P= 0.134) and disease control (AUC = 0.66; P= 0.157). The univariate Cox regression analysis revealed no significant prognostic impact. FDG uptake reduction in liver metastases could predict both clinical response (P= 0.010) and disease control status (P= 0.002) at thresholds of 35% and 15%, respectively. Those with greater FDG uptake reduction in liver lesions had a longer overall survival (P= 0.004). Early metabolic change in FDG-PET might be a predictive marker for response and disease control in advanced gastric cancer. Early FDG uptake change in liver metastases might be a useful prognostic factor and needs further exploration.


Treatment of lobar pneumonia in Papua New Guinea: short course chemotherapy with penicillin or chloramphenicol.
In an attempt to reduce the costs of treatment we treated 203 patients with clinical lobar pneumonia either with penicillin or chloramphenicol for periods of up to 24 hours after remission of fever (mean 2.4 days). The results show that for patients with moderately severe pneumonia short-course treatment is as effective as the more traditional treatment. Patients with severe pneumonia may respond to such treatment but require careful evaluation before stopping treatment.


Simultaneous saccharification and co-fermentation (SSCF) of AFEX(TM) pretreated corn stover for ethanol production using commercial enzymes and Saccharomyces cerevisiae 424A(LNH-ST).
Xylose consumption by Saccharomyces cerevisiae 424A(LNH-ST) during simultaneous saccharification and co-fermentation (SSCF) of AFEX(TM) pretreated switchgrass was inhibited by unhydrolyzed solids. Such inhibitory effects were not found in unhydrolyzed solids from AFEX(TM) pretreated corn stover (AFEX(TM)-CS). However, the xylose consumption was still unsatisfactory during 6h pre-hydrolysis SSCF. By extending the pre-hydrolysis time to 24h or longer, the xylose consumption was improved significantly. In order to better understand the reasons for such improvement, the hydrolysate slurries after 6h pre-hydrolysis and 24h pre-hydrolysis were studied and compared. We found that the glucose concentration after pre-hydrolysis was the critical factor that determined cell viability and hence xylose consumption during SSCF. Low temperature (30°C) and ethanol inhibition were shown to be the factors limiting hydrolysis rate and hence productivity during SSCF.


Transfection of TRK-A into human neuroblastoma cells restores their ability to differentiate in response to nerve growth factor.
Human neuroblastoma cell lines frequently express the TRK-A proto-oncogene and bind nerve growth factor (NGF) but do not differentiate when exposed to NGF. Transient transfection of an exogenous TRK-A gene into SH-SY5Y and LA-N-5 neuroblastoma cells restored the ability of these tumor cells to differentiate with NGF. Stable TRK-A-transfected SH-SY5Y cell clones were isolated, and they responded to NGF by autophosphorylation of p140trk-A, c-fos induction, morphological differentiation, and increased expression of two neuronal marker genes, neuropeptide tyrosine and GAP-43. In phorbol ester-induced differentiated wild-type cells, TRK-A expression was increased with no change in NGF responsiveness. Thus, the restoration of the NGF-induced differentiation pathway by exogenous TRK-A presents a system of NGF-responsive human cultured cells and focuses attention on the trk-A protein and its function or malfunction in neuroblastoma.


The starvation-stress response (SSR) of Salmonella.
Salmonella serovars are common etiologic agents of intestinal-based disease of animals and humans. As a result of their lifestyle, salmonellae occupy and survive in a wide range of niches where they can encounter an even broader range of environmental stresses. One of the most common stresses is starvation for an essential nutrient such as a carbon/energy (C)-source. The genetic and physiologic changes that the bacterium undergoes in response to starvation-stress are referred to as the starvation-stress response or SSR. The genetic loci whose expression increases in response to the starvation-stress compose the SSR stimulon. Several loci of the SSR stimulon have been identified in Salmonella typhimurium and grouped, based on putative or known functions or products, into transport systems, C-compound catabolic enzymes, known protective enzymes, respiratory enzyme systems, regulatory proteins, virulence loci and unclassified products. The majority of loci identified are under positive control by the rpoS-encoded sigma factor, sigma S. However, a few are under (indirect) negative control by sigma S, but only during starvation-induced stationary phase. Most of the loci identified are also under either positive or negative control by the cAMP:CRP complex. For many, additional regulatory proteins (e.g. FadR, OxyR, and RelA and others) play a role in their regulation as well. Furthermore, most of the SSR loci identified are induced during other stresses or environmental conditions. For example, some are induced during P- or N-starvation, in addition to C-starvation; some are induced by extremes in pH or osmolarity; and some are induced in the intracellular environment of epithelial cells, and/or macrophages, and/or medium designed to mimic the intracellular milieu of mammalian cells (ISM). Several SSR loci are required for long-term starvation-survival (core SSR loci), e.g. narZ, dadA, stiC and rpoS. In addition, a few of the core SSR loci are also required for stress-specific-inducible and/or C-starvation-inducible resistance to H2O2 (e.g. stiC), thermal (e.g. stiC), and/or acid pH (e.g. narZ), challenge. Interestingly, C-starved cells are resistant to challenge with the antimicrobial peptide, polymyxin B. However, this resistance mechanism(s) is different from the resistance mechanisms for H2O2 and other environmental stresses. Furthermore, a link between the SSR and Salmonella virulence can be hypothesized since the two major regulators of the SSR, sigma s and cAMP:CRP, are required for full virulence of Salmonella. Moreover, the spv (Salmonella plasmid-associated virulence) genes, required for Salmonella to cause systemic disease, are C (and P- and N-)-starvation-inducible. However, a direct link between starvation-stress and virulence has not been established conclusively.


The opinions and experiences of nurses on frailty screening among older hospitalized patients. An exploratory study.
Routine screening for frailty at admission by nurses may be useful to detect geriatric risks and problems at an early stage. However, the added value of this screening is not clear yet. Information about the opinions and attitudes of nurses towards this screening is also lacking. As they have a crucial role in conducting this screening, an exploratory study was performed to examine hospital nurses' opinions and perspectives about this screening and how it influences their daily work. A qualitative, exploratory approach was employed, using semi-structured interviews with 13 nurses working on different general medical wards (surgical and internal medicine) in three Dutch hospitals. Frailty screening had been implemented for several years in these hospitals. The participating nurses reported that frailty screening can be useful to structure their work, create more awareness of frail older patients and as starting point for pro-active nursing care. At the same time, they assess their clinical view as more important than the results of a standard screening tool. The nurses hardly used the overall screening scores, but were particularly interested in information regarding specific items, such as delirium or fall risk. Screening results are partly embedded systematically and in daily nursing care, e.g., in team briefings or during transfer of patients to other wards. The majority of the nurses had received little training about the background of frailty screening and the use of screening tools. Most nurses stated that frailty screening tools are helpful in daily practice. However, nurses did not use the frailty screening tools in the referred way; tools were particularly used to evaluate patients on separate items of the tool instead of the summative score of the tool. When frailty screening tools are implemented in daily practice, training needs to be focused on. Additional research in this field is necessary to gain more insight into nurses' opinions on frailty screening.


A multispecialty approach to the excision and reconstruction of eyelid tumors.
An ongoing study indicates that the Mohs' fresh tissue technique of tumor removal followed by eyelid reconstruction may be the most efficacious management of eyelid malignancies. Forty-seven recurrent, invasive or large eyelid and canthal tumors were excised by this method followed by eyelid reconstruction. The advantages of this approach are (1) a high cure rate, (2) conservation of tissue, (3) reduced operating room time, and (4) maximum utilization of specialty training.


Ruptured sinus of Valsalva aneurysm: transaortic repair may cause sinus of Valsalva distortion and aortic regurgitation.
Recurrent or newly developing aortic regurgitation is a critical problem after the repair of ruptured sinus of Valsalva aneurysm. A retrospective review of 56 patients who underwent surgical repair of ruptured sinus of Valsalva aneurysm between June 1990 and August 2006 was performed. Rupture of the right coronary sinus into the right ventricle was the most common anatomic type (39/56, 69.6%). Preoperative aortic regurgitation equal to or greater than grade II (n = 8, 17.9%) was managed by repair (aortic valvuloplasty, n = 5) or replacement (n = 3). Ruptured sinus of Valsalva aneurysm was repaired primarily (n = 7) or by patching (n = 10) through an aortotomy in 17 patients (transaortic group). In the remaining patients (n = 39), ruptured sinus of Valsalva aneurysm was repaired primarily from the chamber into which the corresponding aortic sinus ruptured, and the aneurysmal sac was reinforced with a supporting patch (non-transaortic group). Median follow-up duration was 46 months (0.4-177 months). There were 2 late deaths. Excluding 3 patients with aortic valve replacement on aneurysm repair, 11 patients (11/53, 21%) had recurrent or new-onset significant aortic regurgitation (> or = II/IV) during the follow-up period. By multivariable analysis, aortic valvuloplasty at initial operation was the only significant risk factor for postoperative aortic regurgitation (P < .001). After adjustment, the non-transaortic approach appeared to be associated with a lower risk of postoperative aortic regurgitation, with marginal significance (hazard ratio 0.28; P = .058). Five-year freedom from significant aortic regurgitation in the transaortic and non-transaortic groups was 68% +/- 12% and 94% +/- 4%, respectively. Transaortic repair of ruptured sinus of Valsalva aneurysm may cause postoperative aortic regurgitation by progressive distortion of the aortic sinus geometry.


Portal venous gas following chemotherapy for colorectal cancer liver metastasis.
The standard of care for patients with colorectal liver metastases is a combination of chemotherapy and surgery. New chemotherapy regimens with biologic agents (cetuximab, bevacizumab) have been shown to increase tumor response rates. Although this might be beneficial and this is an expected endpoint, it should be noted that patients with synchronous colorectal and liver metastases are at risk of septic complications. We recently encountered a case of hepatic portal venous gas after two cycles of chemotherapy in a patient with right colon cancer liver metastases. Complete necrosis of the liver metastasis subsequently turned into a liver abscess, which fistulized in the right portal vein. Infection of the necrotized metastasis was thought to be promoted by the colic tumor. Although this is a dramatic situation, it does not contraindicate a curative surgical resection.


Phantom materials for single point imaging pulse sequences.
The popularity of pure phase encode MRI techniques, including single point imaging (SPI), is steadily increasing, particularly in instances where the samples of interest are solid-like, or for other reasons possess short effective transverse relaxation times, T2*. As the interest in these techniques grows, so too does the need for a phantom material which is representative of this class of samples. The characteristics of such a phantom should include chemical and physical stability, straightforward preparation, high signal to noise ratio and relaxation times which are both easily manipulated and representative. To this end, we have developed a gelatin/sucrose-based gel which addresses the above criteria and behaves as a very flexible short T2* phantom. An order of magnitude variation in T1 and T2 can be achieved over a reasonable range of sucrose concentration. Even larger changes can be achieved with the addition of further doping agents.


Enfuvirtide: antiretroviral class 4, drug 1.
With the licensing of enfuvirtide, physicians prescribing antiretroviral medications now have available the first of a new class of drugs, the fusion inhibitors. In this article, enfuvirtide is discussed with particular emphasis on the clinical trials that led to the drug's licensing. The possible placement of enfuvirtide in the sequence of treatment is also discussed.


Exploration of synthesizing fluorescent silicon nanoparticles and label-free detection of sulfadiazine sodium.
Herein, silica nanoparticles (SiNPs) with blue-fluorescence have been originally synthesized through one facile hydrothermal way, and this kind of SiNPs were water-soluble with the relative quantum yield of around 6%. Meanwhile, N-(triethoxysilylpropyl) urea severed as the silica source, while potassium hydrogen phthalate as the doping reagent. Also, SiNPs exhibited the acceptable stability and excitation-dependent fluorescence property. Moreover, their surfaces of the obtained SiNPs were equipped with multiple functional groups including -Si-O-Si-, -Si-H, -COOH, -NH2 and -OH. Importantly, the fluorescence of SiNPs could be specifically quenched by sulfadiazine sodium (SD-Na), thus achieving a label-free detection of SD-Na, which displayed a wide linear response in the range of 0.8 μM-800 μM with a detection limit of 1.02 μM. Additionally, we explored the mechanism of SiNPs sensing SD-Na on the basis of aggregation-induced quenching. To be specific, the particle size of SiNPs increased from 29.9 nm to 203.7 nm induced by the electrostatic interactions between SiNPs and SD-Na, which was further confirmed by high resolution transmission electron microscopy. Consequently, the proposed strategy here broadened the ways of assaying sulfadiazine sodium.


Raman-induced noiselike pulses in a highly nonlinear and dispersive all-fiber ring laser.
Dual-wavelength noiselike pulses are generated in a fiber ring laser. A first series of pulses is induced at a wavelength of 1550 nm by the interplay of an erbium-doped fiber and nonlinear polarization rotation. From the Raman gain of these pump pulses emerges a second series of Stokes pulses at 1650 nm. With adequate control of the polarization states in the cavity, the noiselike Stokes pulses extend over 84 nm in the Ultralong-wavelengths band (U-band), while the pump pulses span over 46 nm.


Discovery and Targeting of a Noncanonical Mechanism of Sarcoma Resistance to ADI-PEG20 Mediated by the Microenvironment.
Many cancers lack argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme of arginine biosynthesis. This deficiency causes arginine auxotrophy, targetable by extracellular arginine-degrading enzymes such as ADI-PEG20. Long-term tumor resistance has thus far been attributed solely to ASS1 reexpression. This study examines the role of ASS1 silencing on tumor growth and initiation and identifies a noncanonical mechanism of resistance, aiming to improve clinical responses to ADI-PEG20. Tumor initiation and growth rates were measured for a spontaneous Ass1 knockout (KO) murine sarcoma model. Tumor cell lines were generated, and resistance to arginine deprivation therapy was studied in vitro and in vivo. Conditional Ass1 KO affected neither tumor initiation nor growth rates in a sarcoma model, contradicting the prevalent idea that ASS1 silencing confers a proliferative advantage. Ass1 KO cells grew robustly through arginine starvation in vivo, while ADI-PEG20 remained completely lethal in vitro, evidence that pointed toward a novel mechanism of resistance mediated by the microenvironment. Coculture with Ass1-competent fibroblasts rescued growth through macropinocytosis of vesicles and/or cell fragments, followed by recycling of protein-bound arginine through autophagy/lysosomal degradation. Inhibition of either macropinocytosis or autophagy/lysosomal degradation abrogated this growth support effect in vitro and in vivo. Noncanonical, ASS1-independent tumor resistance to ADI-PEG20 is driven by the microenvironment. This mechanism can be targeted by either the macropinocytosis inhibitor imipramine or the autophagy inhibitor chloroquine. These safe, widely available drugs should be added to current clinical trials to overcome microenvironmental arginine support of tumors and improve patient outcomes.


Representation of dark skin tones in foundational nursing textbooks: An image analysis.
This study aimed to analyze and quantify the representation of dark skin tones (DST) images/graphics across fifteen foundational and clinical nursing textbooks to understand the degree of portrayed diversity in current nursing texts. The United States (U.S.) population is becoming more ethnically and racially diverse. There is a scarcity of nursing literature, studies, and educational materials on the assessment and early recognition of common skin assessment in patients with dark skin tones (DST). The underrepresentation of people with DST images in didactic material suggests that omissions of these images in educational resources may introduce bias in health care provider education and practice. Fifteen popular foundational and clinical nursing textbooks were selected and analyzed. All the photo images and drawn graphics in these textbooks were coded according to Fitzpatrick's skin phototype (FSP) scale, which categorizes skin tone as (a) "Light" or Fitzpatrick scale I or II, (b) "Medium" or Fitzpatrick scale III or IV, and (c) "Dark" or Fitzpatrick scale V or VI. The training was provided for data collectors before analysis to ascertain good inter-rater reliability (Cohen's kappa = 0.960 for light skin tone, Cohen's kappa = 0.899 for medium skin tone, and Cohen's kappa = 0.913 for dark skin tone). Analysis of 14,192 photo images and drawn graphics depicting skin tone was completed across 15 foundational and clinical nursing textbooks. 12.3 % of photo images and 2.4 % of drawn graphics depicted dark skin tones, compared to 60.9 % of photo images and 82.8 % of drawn graphics that displayed light skin tones in these textbooks. Nursing textbooks overrepresent light skin tones and underrepresent dark skin tones. While the approximate racial distribution of the U.S. population is 59.3 % non-Hispanic-White, 13.6 % Black/African American, and 26.6 % Person of Color, the images and graphics of skin tones represented 68 % light, 15 % medium, and 9.4 % dark. All healthcare providers are expected and required to deliver competent clinical care to an increasingly diverse population. For teaching-learning, more visual representations of DST and comparative images between what to expect in dark, medium, and light skin tones can help improve knowledge deficits and increase health equity.


Traffic of p24 Proteins and COPII Coat Composition Mutually Influence Membrane Scaffolding.
Eukaryotic protein secretion requires efficient and accurate delivery of diverse secretory and membrane proteins. This process initiates in the ER, where vesicles are sculpted by the essential COPII coat. The Sec13p subunit of the COPII coat contributes to membrane scaffolding, which enforces curvature on the nascent vesicle. A requirement for Sec13p can be bypassed when traffic of lumenally oriented membrane proteins is abrogated. Here we sought to further explore the impact of cargo proteins on vesicle formation. We show that efficient ER export of the p24 family of proteins is a major driver of the requirement for Sec13p. The scaffolding burden presented by the p24 complex is met in part by the cargo adaptor Lst1p, which binds to a subset of cargo, including the p24 proteins. We propose that the scaffolding function of Lst1p is required to generate vesicles that can accommodate difficult cargo proteins that include large oligomeric assemblies and asymmetrically distributed membrane proteins. Vesicles that contain such cargoes are also more dependent on scaffolding by Sec13p, and may serve as a model for large carrier formation in other systems.


[Experience in 712 cases of tuberculosis of chest wall by surgical treatment].
From 1976 to 1987, 712 cases of tuberculosis of chest wall were treated surgically in our hospital. The primary cure rate was 97.2% (692/712). In 20 cases, the disease recurred and were cured after the second operations. The Diagnostic criteria, operative methods and causes of recurrence are discussed.


Proliferation to apoptosis ratio as a prognostic marker in adenocarcinoma of uterine cervix.
To determine the Mitotic Index (MI), Apoptotic Index (AI), the ratio of the two indices (MI/AI) in normal endocervical glands, adenocarcinoma in situ (AIS) and invasive adenocarcinoma of cervix, and to evaluate the relationship among these indices with various clinicopathological features. The MI, AI and MI/AI ratio in cervical adenocarcinoma were evaluated based on: (1) cell morphology in hematoxylin and eosin-stained sections; (2) immunohistochemical study for Ki67 antigen and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). Eighty cases of invasive adenocarcinoma and eighteen cases of adenocarcinoma in situ (AIS) adjacent to invasive adenocarcinoma were included. Adjacent normal endocervical epithelium in 26 cases of adenocarcinoma was included as control. The MI, AI and MI/AI in normal endocervical glands, AIS and invasive carcinomas showed statistically significant differences (P<0.001). A significant positive correlation was found between AI and MI, as assessed by morphological features (P<0.001) and immunohistochemistry (P=0.006). The MI/AI ratio, determined by morphology, significantly correlated with staging (P=0.023) and survival (P=0.0045). Multivariate survival analysis showed that both MI/AI ratio determined by morphology (P<0.001) and stage of tumor (P=0.03) had independent prognostic value in invasive adenocarcinoma. Tumor proliferation significantly correlated with apoptotic activity in cervical adenocarcinoma. The MI/AI ratio was an independent prognostic factor associated with patient survival. Histological determination of MI/AI ratio proved to be an economical and potentially useful adjunct in predicting clinical outcome of patients with cervical adenocarcinoma.


Gene network analysis reveals a core set of genes involved in the immune response of Japanese flounder (Paralichthys olivaceus) against Vibrio anguillarum infection.
Japanese flounder (Paralichthys olivaceus) is one of the most economically important marine fish cultured in north Asia. Vibrio anguillarum is a severe bacterial pathogen to Japanese flounder and many other aquaculture species. In order to understand the immune response of flounder during bacterial infection, we systematically examined the transcriptome profiles of flounder spleen at three time points after V. anguillarum challenge. More than one billion high quality reads were obtained, approximately 80.70% of which were successfully mapped to the reference genome of flounder. A total of 6060, 4688 and 4235 differentially expressed genes (DEGs) were captured at 6, 12 and 24-h post-infection, respectively. The DEGs exhibited dynamic changes in expression and were assigned into four different profiles based on expression trend. GO and KEGG analysis showed that the DEGs were enriched in various immune-related terms, including response to stimulation, immune system and pathways of cytokine-cytokine receptor interaction, Jak-STAT signaling and Toll-like receptor signaling. Furthermore, a network of highly interactive DEGs involved in 11 immune-related pathways was detected by utilizing the weighted co-expressing network analysis (WGCNA). Accordingly, 26 hub genes were discovered that constituted an elaborate immune regulatory network and functioned mainly in pathogen recognition, antigen processing, and molecular signaling. The results of this study provided the first systematical transcriptome profile of flounder in association with V. anguillarum infection and can serve as a valuable resource of target genes for future studies on the molecular mechanisms underlying the immune defense of flounder against bacterial infection.


Bipolar incompatibility system of an ectomycorrhizal basidiomycete, Rhizopogon rubescens.
The mating systems of most ectomycorrhizal fungi have not been elucidated because of two reasons. One is the difficulty of obtaining homokaryotic isolates for mating tests caused by the low germination rate of basidiospores, and another is the difficulty of checking dikaryotization caused by the absence or inconsistent production of clamp connections on heterokaryotic mycelia under laboratory conditions. Basidiospore germination of a few ectomycorrhizal fungi has been induced by living roots of their host plants. Based on this information, we examined methods to obtain homokaryotic isolates of Rhizopogon rubescens using its host plant, Pinus thunbergii. The basidiospores of R. rubescens appeared to germinate well on an agar plate, on which axenic pine seedlings were grown in advance to induce germination, even when the seedlings were removed from the plate at the time of spore inoculation. To enhance the production rate of clamp connections on the heterokaryotic mycelia of R. rubescens, the culture medium composition was modified. The pH of the medium was critical for the production of clamp connections, and the optimal pH was higher for the production of clamp connections than for mycelial growth. These findings made it possible to conduct mating tests, and we found that the mating system of R. rubescens is bipolar with a multiallelic mating type factor.


Factors contributing to low weight in community-living older adults.
To investigate the factors that influence the dietary practices and eating patterns of low-weight, community-living older adults (aged 65 and older) and to examine the nutritional advice given to them by healthcare providers (HCPs) (e.g., nurse practitioner, medical doctor). A qualitative approach was used to study a convenience sample of older women. Semistructured interviews were conducted. Thematic analysis and open coding were used to analyze data. Eating alone, social isolation, and stressors are the main reasons reported by participants for low weight. Data gathered in this study provide important insights into possible reasons for low weight in community-living older adults. As HCPs, it is important to bring low weight to the attention of older adults and educate them regarding appropriate weight for their age (body mass index [BMI] range >21 to <27 kg/m2 for age 65 and older), to understand that older adults with a BMI of <24 may be at increased risk for poor nutritional status, and to weigh older adults at each office visit to assess change in BMI. Small changes in eating patterns and food intake can potentially play an important role in stabilizing weight. Strategies that address eating alone, social isolation, and stressors need to be pursued.


Abdominal ultrasound combined with histological and cytological fine needle biopsy of suspected ovarian tumors.
To investigate, in a population of women suspected of an ovarian mass, whether pelvic ultrasound (US) and US combined with US-guided fine needle biopsy (FNB) increased the detection rate and whether tumor specific diagnoses could be obtained, a cohort of 307 patients suspected of an ovarian mass underwent US examination as part of routine gynecologic work-up. In cases of solid or solid/cystic lesions a US guided FNB for histology as well as cytology was proposed. All 35 primary ovarian cancers, 6 of 7 secondary ovarian cancers, and 3 of 4 non-ovarian cancers were demonstrated on US. Among 17 cases with normal palpation and an ovarian mass on US, operation disclosed 3 ovarian cancers. FNB identified 24 of 27 primary ovarian cancers and 7 of 7 cancers of extra-ovarian origin. The use of US, in this study, increased the detection of masses in the pelvis and FNB provided a reliable verification.


Therapeutic embolization of pelvic metastases of renal cell carcinoma.
The results of arterial embolization of symptomatic pelvic osseous metastases associated with extensive soft tissue tumors in 5 patients with renal cell carcinoma are presented. Of the 5 patients 4 experienced significant relief of pain and improved performance status, as well as objective evidence of bone recalcification or tumor reduction at an average followup of 10 months. One significant complication occurred in a patient with previous local irradiation. Possible advantages over conventional external beam radiation therapy of metastatic renal cell carcinoma and future applications of arterial embolization of bulky metastatic tumors are discussed briefly.


Reduction of the C2 and C4 vinyl groups of Sn-protoporphyrin to form Sn-mesoporphyrin markedly enhances the ability of the metalloporphyrin to inhibit in vivo heme catabolism.
Sn (tin)-mesoporphyrin (Sn-protoporphyrin in which the vinyl groups at C2 and C4 have been reduced to ethyl groups) when incubated with rat splenic microsomal heme oxygenase proved to be a potent competitive inhibitor of enzyme activity in vitro, with a Ki of 0.014 microM. Sn-mesoporphyrin (1 mumol/kg body wt) also inhibited hepatic, renal, and splenic heme oxygenase activity in vivo in adult animals for extended periods of time. Sn-mesoporphyrin (1 mumol/kg body wt) prevented the transient increase in serum bilirubin 24 h after birth in the rat neonate and substantially reduced the levels of serum bilirubin in ALA (delta-aminolevulinic acid) induced hyperbilirubinemia in the 7-day-old suckling neonate. Tissue heme oxygenase activity was decreased in both animal models of hyperbilirubinemia. Sn-mesoporphyrin administration led to a prolonged increase in the heme saturation of hepatic tryptophan pyrrolase indicating an increase in the "heme pool" related to tryptophan pyrrolase and the compound also suppressed chemically induced hepatic porphyria. The administration of Sn-mesoporphyrin to bile duct-cannulated rats was followed by a prompt and sustained decrease in bilirubin output in bile. In addition the excretion of heme in bile was enhanced in these animals. These studies indicate that Sn-mesoporphyrin, like Sn-protoporphyrin, decreases serum bilirubin by inhibiting the production of bilirubin in vivo and its mode of action is through a sustained competitive inhibition of heme oxygenase. However, when a direct comparison of Sn-protoporphyrin and Sn-mesoporphyrin was made, these studies clearly established that the reduction of the C2 and C4 vinyl groups of the porphyrin macrocycle to ethyl groups increases the effectiveness of the Sn-mesoporphyrin derivative 10-fold or more as compared with Sn-protoporphyrin in inhibiting heme catabolism in the animal model systems examined. Thus alterations in the side chain substituents as well as of the central metal atom can influence in a significant manner the potency of the resultant synthetic heme analog as an agent capable of inhibiting heme degradation in vivo.


Endoscopic alterations in Peyer's patches in patients with ulcerative colitis: A prospective, multicenter study.
Peyer's patches (PPs) play a major role in intestinal mucosal immunity; however, their role in ulcerative colitis (UC) is not well investigated. We evaluated endoscopic features of PPs on narrow-band imaging with magnifying endoscopy (NBI-ME) and investigated their association with clinical factors. We prospectively recruited 105 patients with UC, 18 with Crohn's disease, 16 with disease control, and 33 healthy control subjects at three institutions from 2014 to 2017. NBI-ME images of the villi of PPs were evaluated according to the Villi Index, and patients were divided into the Villi Index low (L) and high (H) types. The 1-year sustained clinical remission rate was evaluated between L-type and H-type PPs in patients with UC. The proportions of patients with H-type PPs were significantly higher among UC, Crohn's disease, and disease control patients than among healthy control patients (P = 0.0125, 0.018, 0.0007). In UC, age, gender, endoscopic score, and extent of disease involvement were not significantly different between L-type and H-type PPs, whereas the sustained clinical remission rate was significantly higher in L-type PPs than in H-type PPs (88% [57/65] vs 65% [17/26], P = 0.019). Multivariate analysis revealed that the L type of PPs was a significant factor for sustained clinical remission (odds ratio 3.8, 95% confidence interval 1.1-12.9, P = 0.033). Patients with UC showed endoscopic alterations in PPs on NBI-ME, and highly altered appearance of PPs can be associated with a high risk of clinical relapse in patients with UC.


A single-cell multiomic analysis of kidney organoid differentiation.
Kidney organoids differentiated from pluripotent stem cells are powerful models of kidney development and disease but are characterized by cell immaturity and off-target cell fates. Comparing the cell-specific gene regulatory landscape during organoid differentiation with human adult kidney can serve to benchmark progress in differentiation at the epigenome and transcriptome level for individual organoid cell types. Using single-cell multiome and histone modification analysis, we report more broadly open chromatin in organoid cell types compared to the human adult kidney. We infer enhancer dynamics by cis-coaccessibility analysis and validate an enhancer driving transcription of HNF1B by CRISPR interference both in cultured proximal tubule cells and also during organoid differentiation. Our approach provides an experimental framework to judge the cell-specific maturation state of human kidney organoids and shows that kidney organoids can be used to validate individual gene regulatory networks that regulate differentiation.


[Prevention of decubitus ulcer by an elastomere matrix cushion].
We have measured and compared the mechanical properties of the skin, muscles and of a cushion designed to prevent bedsores. The mechanical properties of the tested material are intermediate to those of skin and muscles. They permit an even and optimal distribution of the pressures on the skin.


Type 1 diabetes immunotherapy using polyclonal regulatory T cells.
Type 1 diabetes (T1D) is an autoimmune disease that occurs in genetically susceptible individuals. Regulatory T cells (Tregs) have been shown to be defective in the autoimmune disease setting. Thus, efforts to repair or replace Tregs in T1D may reverse autoimmunity and protect the remaining insulin-producing β cells. On the basis of this premise, a robust technique has been developed to isolate and expand Tregs from patients with T1D. The expanded Tregs retained their T cell receptor diversity and demonstrated enhanced functional activity. We report on a phase 1 trial to assess safety of Treg adoptive immunotherapy in T1D. Fourteen adult subjects with T1D, in four dosing cohorts, received ex vivo-expanded autologous CD4(+)CD127(lo/-)CD25(+) polyclonal Tregs (0.05 × 10(8) to 26 × 10(8) cells). A subset of the adoptively transferred Tregs was long-lived, with up to 25% of the peak level remaining in the circulation at 1 year after transfer. Immune studies showed transient increases in Tregs in recipients and retained a broad Treg FOXP3(+)CD4(+)CD25(hi)CD127(lo) phenotype long-term. There were no infusion reactions or cell therapy-related high-grade adverse events. C-peptide levels persisted out to 2+ years after transfer in several individuals. These results support the development of a phase 2 trial to test efficacy of the Treg therapy.


Asthma: the pulse is not the paradox.
Some interesting, unusual features of asthma are discussed: that patients may be better able to evaluate the severity of their asthma than physicians; that expiratory obstruction indirectly increases the work of inspiration; that 1 of the responses to airflow obstruction is hyperventilation; that localized areas of airflow obstruction may cause increased ventilation/perfusion ratios by decreasing perfusion more than ventilation; that increasing tidal volume may cause a reduction in alveolar ventilation; and, finally, that there is evidence that asthma has worsened in recent years, despite advances in the understanding and treatment of this disease.


A combinatorial approach to chemical modification of subtilisin Bacillus lentus.
The reaction between methanethiosulfonate reagents and cysteine mutants of subtilisin is quantitative and can be used to prepare chemically modified mutant enzymes (CMMs) with novel properties. The virtually unrestricted structural variations possible for CMMs presents a preparative and screening challenge. To address this, a rapid combinatorial method for preparing and screening the activities of CMMs has been developed.


Cost of surgery in a low-income setting in eastern Uganda.
Operative interventions have traditionally been seen as expensive; therefore, surgery has been given low priority in global health care planning in low-income countries. A growing body of evidence indicates that surgery can also be highly cost effective in low-income settings, but our current knowledge of the actual cost of surgery in such settings is limited. This study was carried out to obtain data on the costs of commonly performed operative procedures in a rural/semiurban setting in eastern Uganda. A prospective, facility-based study carried out at a general district hospital (public) and a mission hospital (private, not-for-profit) in the Iganga and Mayuge districts in eastern Uganda. Items included in the cost calculations were staff time, materials and medicines, overhead costs, and capital costs. The cost of surgery was higher at the mission hospital, with higher expenditure and lower productivity than the public hospital. The most commonly performed major procedures were caesarean section, uterine evacuation, and herniorrhaphy for groin hernia. The costs for these interventions varied between $68.4 and $74.4, $25.0 and $32.6, and $58.6 and $66.0, respectively. The most commonly performed minor procedures were circumcision, suture of cuts and lacerations, and incision and drainage of abscess. The costs for these interventions varied between $16.2 and $24.6, $15.8 and $24.3, and $10.1 and $18.6, respectively. The cost of surgery in the study setting compares favorably with other prioritized health care interventions, such as treatment for tuberculosis, human immunodeficiency virus/AIDS, and childhood immunization. Surgery in low-income settings can be made more cost effective, leading to increased quantity and improved quality of surgical services.


Gallbladder containing incisional hernia in an elderly woman.
Gallbladder herniation is a rare phenomenon with risk factors of being female, older age, and previous history of hernias. Imaging modalities can confirm the diagnosis. Cholecystectomy and hernia repair to prevent strangulation may be warranted.


Disulfide bond requirements for assembly of the platelet glycoprotein Ib-binding domain of von Willebrand factor.
von Willebrand factor (vWF) is a multimeric glycoprotein of plasma and the subendothelial matrix that interacts with specific platelet receptors to establish platelet adhesion at a site of vascular injury. The vWF domain containing the platelet receptor glycoprotein Ib-binding site can be expressed in heterologous cells as a recombinant homodimeric fragment that mediates platelet-platelet interaction, analogous to multimeric vWF. The recombinant domain, r116, contains 7 Cys residues within its 290-residue monomeric subunit paired in an unidentified intra- and intermolecular disulfide bond arrangement. In this report we define the disulfide bond-dependent framework of r116 that provides the domain with its essential structural features that support dimer formation and the generation of a disulfide bond-dependent epitope. The results demonstrate that a triplet of Cys residues at positions 459, 462, and 464 are essential for efficient dimer formation. An intramolecular Cys509/Cys695 disulfide loop is required for generating a functional dimeric molecule, and monomeric molecules containing a Cys509/Cys695 intramolecular disulfide bond are unable to support ristocetin-mediated platelet aggregation. The disulfide arrangement in r116 is similar, if not identical, to the proposed arrangement within the corresponding region of plasma vWF, and these studies document the inherent Cys-dependent maturation of an isolated vWF domain.


Acute Neurologic Deterioration in Mobile Spinal Schwannoma.
Spinal schwannomas are commonly presented with minor symptoms, including radicular pain, sensory deficits, and minor neurologic deficit. Acute neurologic deterioration is uncommon. In this study, a case of cauda equina schwannoma presented with acute neurologic deficit after movement of spinal schwannoma is presented. It is noted that movement of spinal schwannoma and resultant acute neurologic deterioration should be considered during the follow-up.


Assessment of the validity of the beta-lactam antibiotic allergy assessment tool for use in the rural context, QLD.
The objective of the study was to validate a clinical aid to guide the assessment and management of a patient's listed beta-lactam antibiotic allergy for use in rural areas of Australia. Rural generalists, pharmacists and junior doctors completed an online assessment of eight patient case studies using the tool. The study was conducted in the Southern Downs, QLD. Twenty-seven rural generalists, nine pharmacists and eight junior doctors. The sensitivity of the selected allergy phenotype and management option for each case study was calculated by profession and overall. Hazardous responses were reported by management category and profession. The sensitivity overall for phenotype selection was 82.4% (95% CI, 78.0-86.2) and for management 88.1% (95% CI, 84.2-91.2). The sensitivity for phenotype selection was lower for junior doctors than other professions 73.4% (95% CI, 60.9-83.7), but did not reach statistical significance (p = 0.08). A total of 10/308 responses for management recommended the least restrictive option of direct delabelling or oral challenge, where the correct answer was skin prick testing or referral to an allergist. With further education the tool could be a key component of increased antimicrobial stewardship in rural areas in Australia.


Struggling for independence: a grounded theory study on convalescence of ICU survivors 12 months post ICU discharge.
To explore and explain the challenges, concerns, and coping modalities in ICU-survivors living with a partner or spouse during the first 12 months post ICU discharge. Qualitative, longitudinal grounded theory study. Five ICUs in Denmark, four general, one neurosurgical. Thirty-five interviews with patients and their partners at three and 12 months post ICU discharge plus two group interviews with patients only and two with partners only. The ICU survivors struggled for independence and focussed chiefly on 'recovering physical strength', 'regaining functional capacity', and 'resuming domestic roles'. The first year of recovery evolved in three phases characterised by training, perseverance and continued hope for recovery. The ICU survivors did not seem to worry about traumatic experiences. Rather, their focus was on a wide range of other aspects of getting well. The study offers new insight into post-ICU convalescence emphasising patients' motivation for training to recover. The findings may contribute to defining the best supportive measures and timing of rehabilitation interventions in ICU and post ICU that may help ICU-survivors in their struggle for independence throughout recovery.


Ethnic Disparities in Treatment of Chronic Pain in Individuals with Parkinson's Disease Living in the United Kingdom.
Over 80% people with Parkinson's disease (PD; PwP) live with chronic pain. Whether ethnic disparities in receipt of appropriate analgesia exist among PwP with chronic pain living in the United Kingdom (UK). A retrospective datamining of an existing King's PD Pain Questionnaire validation study dataset enrolling 300 PwP. 69 PwP: 23 Black (57% female), 23 Asian (57% female) and 23 White (65% female) had similar pain burden on the King's PD Pain Scale. Significantly more White PwP (83%) received pain relief compared to Black (48%) and Asian (43%) PwP (p = 0.016). The difference was most evident for opioid analgesics (White 43% vs. Black 4% vs. Asian 4%, p ≤ 0.001). Ethnic disparities in the analgesic use among PwP with chronic pain living in the UK are evident in this retrospective analysis, prompting large-scale studies and reinforcement of interventions to tackle the impact ethnicity might have on the successful analgesia.


Preparation of polyhedral oligomeric silsesquioxane based cross-linked inorganic-organic nanohybrid as adsorbent for selective removal of acidic dyes from aqueous solution.
A cross-linked polyhedral oligomeric silsesquioxane (POSS) nanohybrid is synthesized through Schiff base chemistry by using octa-amino POSS as building blocks and glutaraldehyde as dual functional reagent. The obtained nanohybrid is characterized by FT-IR, solid-state 29Si NMR, SEM, TEM, TGA and N2 adsorption-desorption isotherm, and the results demonstrate the successful cross-linkage between POSS molecules, forming block-like irregular nanoparticles with a specific surface area of 42.8m2g-1. As a novel solid-phase adsorbent, cross-linked POSS nanohybrid exhibits selective adsorption properties for acidic dyes, i.e., methyl orange (MO) in the present case. The strong electrostatic interactions between MO species and the nanohybrid are the main driving forces for MO adsorption. The kinetic data are well described by the pseudo-second-order kinetic model. The adsorption isotherm studies demonstrate that the data are well fit with Langmuir model at 293K and a maximum adsorption capacity of 237.5mgg-1 is obtained. Thermodynamic studies indicate that the adsorption of MO is spontaneous and exothermal, along with reduced randomness. The adsorbed MO species could be effectively recovered by using methanol/NaOH (9/1, v/v, 0.1molL-1 NaOH) as eluent. The practical application for textile wastewater treatment demonstrates that cross-linked POSS nanohybrid appears to be a promising material in dye removal field.


Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia.
Molecular typing of 964 specimens from patients in Ethiopia with lymph node or pulmonary tuberculosis showed a similar distribution of Mycobacterium tuberculosis strains between the 2 disease manifestations and a minimal role for M. bovis. We report a novel phylogenetic lineage of M. tuberculosis strongly associated with the Horn of Africa.


Depression and major weight gain: a 6-year prospective follow-up of outpatients.
Depression and weight change are linked, but there is a paucity of studies on their association during clinical treatment. The present study investigated how risk factors for a weight gain of at least 10% (major weight gain) and mental health modify their mutual association during a 6-year prospective follow-up of depressed outpatients. The study sample consisted of 121 depressed treatment-seeking outpatients with a mean age of 44.9 years. A 6-year follow-up started in January 1996. At baseline and on follow-up after 2 and 6 years, psychiatric diagnoses were obtained using the Structured Clinical Interview for DSM-III-R (SCID-I), while cluster C personality disorders (PD) were assessed on 6-month follow-up (SCID-II). Depression was also assessed with the Hamilton Rating Scale for Depression (HAM-D) and general psychopathology with the Symptom Checklist-90 (SCL-90) at baseline and at the end of the 6-year follow-up. Weight changes were based on measurements at baseline and at the end of the follow-up. Logistic regression was used to study the factors associated with major weight gain (≥ 10%). Altogether, 16% of the study sample experienced major weight gain during the 6-year follow-up. Adverse childhood/adolescent experiences as a self-perceived cause of depression (OR 3.72, 95% CI 1.06-13.1, p=0.040), higher scores in the HAM-D (OR 1.11, 95% CI 1.02-1.22, p=0.019) and the SCL-90 subscale of anxiety (OR 2.22, 95% CI 1.11-4.42, p=0.023) at baseline, and cluster C PD at 6 months (OR 3.16, 95% CI 1.11-8.97, p=0.031) were separately associated with major weight gain after adjusting for age, gender, and baseline body mass index (BMI). The severity of depressive and anxiety symptoms and linking adverse childhood with depression at the beginning of treatment, as well as cluster C PD at 6 months, were predictors of major weight gain.


Mitochondrial DNA "common deletion" in post-fine needle aspiration infarcted oncocytic thyroid tumors.
Thyroid fine needle aspiration (FNA) can rarely induce morphological changes potentially hindering the histopathological diagnosis, especially in Hurthle cell tumors (HCTs), which may easily undergo post-FNA infarction or necrosis. HCTs contain mitochondrion (mt)-rich cells that may bear mtDNA mutations, the most frequent being the so-called common deletion (CD). The aim of this study was to determine the presence and extent of the mtDNA CD in a series of thyroid HCTs that underwent extensive infarction following FNA procedure in comparison with a control series of HCTs lacking post-FNA ischemic/hemorrhagic alterations. Of 257 HCTs with available matched FNA and surgical specimens, 8 cases showed extensive (≥80%) infarction or necrosis in the resected nodule (4 adenomas, 1 carcinoma, 3 HCTs undefined for malignancy). Noninfarcted tumors in the control series included 9 adenomas, 1 carcinoma, and 1 follicular tumor of uncertain malignant potential. These lesions were significantly (P = .03) larger than infarcted nodules. The mtDNA CD was identified using semiquantitative real-time polymerase chain reaction in 2 of 8 (25%) infarcted tumors. In HCTs lacking infarction/necrosis of the control series, the CD was significantly (P = .05) more common (8/11 cases, 72.7%). In 7 of the 10 deleted cases, the CD was present also in the adjacent nonneoplastic parenchyma. In conclusion, the rare oncocytic tumors undergoing extensive infarction are smaller than those lacking ischemic changes and bear the mtDNA CD in a significantly lower proportion compared with control noninfarcted HCTs. This may suggest that mtDNA deletion confers a survival advantage to oncocytic cells in stress conditions, including FNA procedures.


[Ultrasonographic monitoring of ovarian hyperstimulation by exogenous gonadotropins and subsequent twin-pregnancies (author's transl)].
In contrast to estrogen-monitoring the ultrasonographic monitoring of the ovaries renders possible the estimation of individual follicular growth stimulated by gonadotropins. In two patients suffering from anovulation and additional factors inhibiting fertility, ultrasonographic monitoring was used in order to induce a pregnancy after moderate hyperstimulation nevertheless.


De novo design of a fluorescence-activating β-barrel.
The regular arrangements of β-strands around a central axis in β-barrels and of α-helices in coiled coils contrast with the irregular tertiary structures of most globular proteins, and have fascinated structural biologists since they were first discovered. Simple parametric models have been used to design a wide range of α-helical coiled-coil structures, but to date there has been no success with β-barrels. Here we show that accurate de novo design of β-barrels requires considerable symmetry-breaking to achieve continuous hydrogen-bond connectivity and eliminate backbone strain. We then build ensembles of β-barrel backbone models with cavity shapes that match the fluorogenic compound DFHBI, and use a hierarchical grid-based search method to simultaneously optimize the rigid-body placement of DFHBI in these cavities and the identities of the surrounding amino acids to achieve high shape and chemical complementarity. The designs have high structural accuracy and bind and fluorescently activate DFHBI in vitro and in Escherichia coli, yeast and mammalian cells. This de novo design of small-molecule binding activity, using backbones custom-built to bind the ligand, should enable the design of increasingly sophisticated ligand-binding proteins, sensors and catalysts that are not limited by the backbone geometries available in known protein structures.


Diagnostic value of carotid intima-media thickness and clinical risk scores in determining etiology of ischemic stroke.
In the general population, carotid intima-media thickness (CIMT) is associated with atherosclerosis as well as atrial fibrillation (AF). However, the extent to which CIMT might be of diagnostic value in clarifying stroke etiology is currently unclear. In this retrospective cohort study, we included 800 consecutive patients with acute ischemic stroke. We compared CIMT-values between stroke etiologies. The association between CIMT and cardioembolic stroke was investigated via logistic regression analysis adjusting for vascular risk factors. Receiver operating characteristic analyses were conducted to investigate the diagnostic value of CIMT in comparison to vascular risk factors and clinical AF risk scores (CHA2DS2VASc, HAVOC, and AS5F). CIMT-values were highest in patients with cardioembolic or atherosclerotic stroke origin. CIMT was associated with newly diagnosed AF compared against cryptogenic strokes (crude odds ratio (OR) per 0.1 mm-increase of CIMT: 1.26 (95% confidence interval (CI): 1.13-1.41)). After adjustment for vascular risk factors, the effect of CIMT on AF-diagnosis, however, was weakened (adjusted OR: 1.10 (95% CI: 0.97-1.25)). The diagnostic value of CIMT for detection of AF (AUC: 0.60, 95% CI: 0.54-0.65) was outperformed by AF risk scores. Among the scores investigated, the AS5F-score yielded best accuracy and calibration to predict newly diagnosed AF (AUC: 0.71, 95% CI: 0.65-0.78). CIMT may help in the diagnosis of stroke etiology. However, compared with vascular risk factors or clinical AF risk scores, CIMT does not provide substantial additional information on the risk of newly detected AF. Thus, stratification of AF risk based on scores, such as the AS5F, is advisable.


Dynamics of Antagonistic Potency of Rhodobacter capsulatus PG Lipopolysaccharide against Endotoxin-Induced Effects.
The dynamics of antagonistic potency of lipopolysaccharide (LPS) isolated from Rhodobacter capsulatus PG on the synthesis of proinflammatory (TNF-α, IL-1β, IL-8, IL-6, IFN-γ) and antiinflammatory (IL-10, IL-1Ra) cytokines induced by highly stimulatory endotoxins from Escherichia coli or Salmonella enterica have been studied. Using human whole blood, we have shown that R. capsulatus PG LPS inhibited most pronouncedly the endotoxin-induced synthesis of TNF-α, IL-1β, IL-8, and IL-6 during the first 6 h after endotoxin challenge. Similarly, the endotoxin-induced release of IFN-γ was abolished by R. capsulatus PG LPS as well (24 h). In contrast to the above-mentioned cytokines, the relatively weak antagonistic activity of R. capsulatus PG LPS against endotoxin-triggered production of IL-6 and IL-8 was revealed. Since R. capsulatus PG LPS displays more potent antagonistic activity against deleterious effects of S. enterica LPS than those of E. coli LPS in the cases of such cytokines as IL-1β (6 and 24 h), IL-6 and IL-8 (4 h), we conclude that the effectiveness of protective action of antagonist is mostly determined by the primary lipid A structure of the employed agonist.


Efficient removal of black henna tattoos.
Para-phenylenediamine, a dye frequently added to henna tattoos to create the black color, is a potent contact allergen. Severe contact dermatitis may arise within days even after the first application. Our objective was to develop a method for rapid and complete removal of para-phenylenediamine-containing black henna tattoos from the skin, an important problem many physicians are confronted with, but for which no simple method exists. A database search revealed polyethylene glycol 400, described in removal of ortho-phenylenediamine from contaminated skin. We therefore investigated its use in removal of the structurally related ortholog para-phenylenediamine present in black henna tattoos. A protocol was established involving repeated cycles of rinsing of the skin with polyethylene glycol 400 solution. In 5 patients, one of whom had already developed a severe blistering contact dermatitis and another a mild erosive dermatitis, black henna tattoos were successfully removed. Removal was completed in a single session of 1 hour or less, depending on tattoo size, with a maximum of 6 rinse cycles. We provide a simple and safe method for rapid and effective removal of black henna tattoos. This procedure requires no special equipment and can be applied in virtually any setting.


Plasma amino acid concentrations in normal adults ingesting aspartame and monosodium L-glutamate as part of a soup/beverage meal.
We tested the hypothesis that ingestion of monosodium L-glutamate with aspartame produces a marked increase in plasma glutamate and aspartate concentrations. Twelve normal adults (6 males, 6 females) ingested three different soup/beverage meals in a balanced Latin square design. One meal (A) provided no aspartame (APM) or monosodium L-glutamate (MSG); a second (B) provided 50 mg MSG/kg body weight; while the third (C) provided 50 mg MSG and 34 mg APM per kg body weight. Plasma glutamate (Glu) concentrations were not significantly affected by meal A but increased significantly after meals B and C (no significant difference between B and C). Plasma aspartate (Asp) concentrations were not significantly affected by meal A but increased significantly after meals B and C (values significantly higher after meal C than meal B). Plasma Glu + Asp concentrations were not significantly affected by meal A but increased significantly from a mean (+/- SD) baseline value of 5.64 +/- 2.62 mumol/dL to high mean values of 23.1 +/- 7.29 and 26.8 +/- 9.74 mumol/dL after ingestion of meals B and C, respectively (no significant difference between meals B and C). Similarly, the area under the plasma Glu + Asp concentration-time curve did not differ significantly between meals B and C (624 +/- 197 v 763 +/- 277 mumol/dL x min, respectively). Peak plasma Glu + Asp concentrations for each subject (ignoring time) were also examined. The mean peak plasma Glu + Asp concentrations were 7.39 +/- 2.77, 23.0 +/- 6.61, and 27.3 +/- 9.07 mumol/dL, respectively after meals A, B, and C.


[Patellar pathologic fracture secondary to aneurysmal bone cyst. A case report].
Aneurysmal bone cyst is a tumor-like lesion which accounts for about 1% of all biopsied tumors and tumor-like lesions of bone. We report an extremely rare case of aneurysmal bone cyst of the patella in an 18-year-old patient revealed by a pathological fracture. The unexpected appearance of a pathological fracture affects the whole therapeutical management. However, in the case of a well-preserved articular surface, curettage and corticocancellous grafting are considered to be successful methods of treatment for aneurysmal bone cyst of the patella, as revealed in our study.


Picolinafen exerts developmental toxicity via the suppression of oxidative stress and angiogenesis in zebrafish embryos.
Picolinafen, a phytoene desaturase-inhibiting herbicide, has been used since 2001 to control the growth of broadleaf weeds. Picolinafen has lower solubility and volatility, and shows lower toxicity to non-target insect species than other types of herbicide. Although picolinafen has been detected in lakes near urban environments and induces chronic toxicity in the mammals, birds, and some aquatic organisms, no study has investigated the toxicity or mode of action of picolinafen in zebrafish. In this study, we demonstrated the lethality and acute LC50 value of picolinafen towards zebrafish embryos. Picolinafen hampered the development of embryos by the induction of morphological abnormalities via apoptosis. Additionally, picolinafen suppressed the generation of reactive oxygen species and angiogenesis. Also, the angiogenesis related genes, flt1 and flt4 mRNA expression was decreased in zebrafish embryos. This study provides a mechanistic understanding of the developmental toxicity of picolinafen in vertebrates.


Differential mechanisms for T lymphocyte recruitment in normal and neoplastic human gastric mucosa.
Worldwide, gastric adenocarcinoma (GC) is the second most common cause of death from malignant disease. The reason why immune responses are unable to clear the tumour is not fully understood, although aberrant lymphocyte recruitment to the tumour site might be one factor. Therefore, we investigated the homing phenotype of mucosal T lymphocytes in GC, compared to tumour-free mucosa. We could detect significantly decreased frequencies of mucosal homing alpha4beta7+ T cells in the tumour tissues and increased frequencies of L-selectin+ T cells. This was probably due to the correlated decrease in MAdCAM-1 positive and increase in PNAd positive blood vessels in the tumour mucosa. There were also fewer CXCR3+ T lymphocytes in the tumour tissue. These findings provide evidence that endothelial cells within tumours arising at mucosal sites do not support extravasation of typical mucosa-infiltrating T cells. This may be of major relevance for future immunotherapeutic strategies for treatment of GC.


Tissue oxygenation index is a useful monitor of histologic and neurologic outcome after cardiopulmonary bypass in piglets.
Tissue oxygenation index is a novel monitoring indicator derived by near-infrared spectroscopy. We hypothesized that tissue oxygenation index could predict a minimum safe flow rate for specific bypass conditions. Thirty-six piglets (age, 43 +/- 5 days; weight, 9.0 +/- 1.1 kg) underwent cardiopulmonary bypass with cerebral near-infrared spectroscopy (NIRO-300; Hamamatsu Photonics K.K., Hamamatsu City, Japan). Animals were cooled for 40 minutes to 15 degrees C, 25 degrees C, or 34 degrees C (pH-stat, hematocrit value of 20% or 30%, and pump flow of 100 mL . kg -1 . min -1), followed by low-flow perfusion (10, 25, or 50 mL . kg -1 . min -1) for 2 hours. Neurologic and behavioral evaluations were determined for 4 days. The brain was then fixed for histologic assessment. Tissue oxygenation index was defined as the average signal during low-flow bypass. Animals with an average tissue oxygenation index of less than 55% showed cerebral injury, whereas animals with an index of greater than 55% showed minimal or no evidence of injury. Correlations were found between average tissue oxygenation index and histologic score (Spearman rho = -0.65, P < .001) and neurologic deficit score (Pearson r = -0.50, P = .002) on the first postoperative day. Temperature (P < .001), flow rate (P < .001), and hematocrit value (P = .002) were multivariable predictors of tissue oxygenation index, as determined by means of multivariable analysis of variance. Tissue oxygenation index is a useful monitor for defining the minimum safe flow rate during cardiopulmonary bypass. An index value of less than 55% is a strong predictor of neurologic injury.


Cyr61 synthesis is induced by interleukin-6 and promotes migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis.
Interleukin-6 (IL-6) is involved in fibroblast-like synoviocyte (FLS) activation and promotes pannus formation and bone and cartilage destruction in rheumatoid arthritis (RA). Cysteine-rich 61 (Cyr61) protein regulates cell proliferation, migration, and differentiation. The aim of this study was to investigate the role of Cyr61 in RA-FLS migration and invasion after IL-6 stimulation. Western blotting, immunohistochemistry, reverse transcription-polymerase chain reaction, and real time-polymerase chain reaction were used to examine protein and mRNA levels of Cyr61, matrix metalloproteinases (MMPs), and other signalling proteins. Knockdown of gene expression was performed with siRNA, and RNA sequencing was performed for differential gene analysis. Migration and invasion were assessed by wound healing and Boyden chamber assays. Cyr61 levels were elevated in FLSs from RA patients compared to those in osteoarthritis patients. Control and IL-6-treated FLSs showed differential gene expression. IL-6 stimulated protein synthesis of Cyr61, which was attenuated by the extracellular signal-related kinase 1/2 (ERK 1/2) inhibitor, PD98059, and knockdown of early growth response 3 (EGR3), but not of JUN. IL-6-induced Cyr61 protein synthesis increased expression of MMP2. Cyr61 promoted FLS migration and invasion in an autocrine manner. Knockdown of CYR61 and a neutralising antibody attenuated Cyr61 synthesis and IL-6-induced FLS migration. By modulating the ERK/EGR3 pathway, IL-6 stimulated Cyr61 production and in turn increased invasiveness of FLS. Our data suggest that Cyr61 might be a potential target to prevent the progression of joint damage in RA.


Irreversible myocardial damage after coronary air embolism--a case report.
This case report describes the complication of an air embolism in the right coronary artery that developed during coronary angiography in a patient with acute anterior myocardial infarction. Follow-up left ventriculography, 4 months later, showed irreversible inferior wall damage. Incomplete aspiration of the angiographic catheter was the cause of this complication and should be avoided.


Effects of Diets Based on Hydrolyzed Chicken Liver and Different Protein Concentrations on the Formation and Deamination of Biogenic Amines and Total Antioxidant Capacity of Dogs.
Biogenic amines are synthesized through the bacterial decarboxylation of amino acids, commonly found in high levels in animal by-product meals due to spoilage. Furthermore, biogenic amines and other metabolites can be produced by the fermentation of proteins in the hindgut according to the protein source and concentration of crude protein (CP) in the diet. Thus, this study aimed to evaluate two protein sources (poultry by-product meal (PBPM) and hydrolyzed chicken liver powder (HCLP)) and three CP concentrations (24, 32, and 40%) and their effects on the consumption and fecal excretion of biogenic amines, plasma monoamine oxidase (MAO) and diamine oxidase (DAO) activities, and total antioxidant capacity (TAC) of healthy adult dogs after 30 days of feeding the experimental diets. Twelve dogs were randomly distributed into six treatments (n = 6/treatment): PBPM24 (PBPM with 24% CP); PBPM32 (PBPM with 32% CP); PBPM40 (PBPM with 40% CP); HCLP24 (HCLP with 24% CP); HCLP32 (HCLP with 32% CP); HCLP40 (HCLP with 40% CP). The PBPM and PBPM-based diets had higher concentrations of putrescine, cadaverine, tyramine, histamine, agmatine, and total biogenic amines. In contrast, HCLP and HCLP-based diets contained higher concentrations of spermidine, phenylethylamine, and spermine. The PBPM and PBPM-diets had higher biogenic amine index (BAI) indicating lower quality due to the high content of putrescine, cadaverine and tyramine. Dogs fed diets with PBPM and higher protein concentrations consumed more putrescine, cadaverine, tyramine, agmatine, and total amines (p < 0.0001), while dogs fed with HCLP consumed more spermidine, phenylethylamine, and spermine (p < 0.0001). Fecal excretion of phenylethylamine was greater in dogs fed HCLP32 and HCLP40 diets (p = 0.045). Dogs fed with HCLP tended to excrete more spermidine and tryptamine via feces, while higher protein concentrations tended to increase fecal excretion of cadaverine (p < 0.10). Plasma MAO activity was higher in dogs fed HCLP24 and PBPM32 diets (p = 0.024). The plasma activities of DAO and TAC were not different between diets (p > 0.05). Although we did not evaluate the intestinal activities of MAO and DAO, our results suggest that healthy adult dogs have an efficient deamination process on the gut epithelium.


Aortic root replacement for bicuspid aortopathy following heart transplantation.
Although donors with well-functioning bicuspid aortic valves (BAV) are not a contraindication for transplantation, BAV patients are at risk for long-term aortopathy and valve dysfunction. We report a case of a patient status-post heart transplant 13 years ago who presented to our institution with a BAV and severe aortic regurgitation associated with an aortic root aneurysm and underwent aortic root replacement.


Changes in glutathione status and the antioxidant system in blood and in cancer cells associate with tumour growth in vivo.
The relationship among cancer growth, the glutathione redox cycle and the antioxidant system was studied in blood and in tumour cells. During cancer growth, the glutathione redox status (GSH/GSSG) decreases in blood of Ehrlich ascites tumour-bearing mice. This effect is mainly due to an increase in GSSG levels. Two reasons may explain the increase in blood GSSG: (a) the increase in peroxide production by the tumour that, in addition to changes affecting the glutathione-related and the antioxidant enzyme activities, can lead to GSH oxidation within the red blood cells; and (b) an increase of GSSG release from different tissues into the blood. GSH and peroxide levels are higher in the tumour cells when they proliferate actively, however GSSG levels remain constant during tumour growth in mice. These changes associate with low levels of lipid peroxidation in plasma, blood and the tumour cells. The GSH/GSSG ratio in blood also decreases in patients bearing breast or colon cancers and, as it occurs in tumour-bearing mice, this change associates with higher GSSG levels, especially in advanced stages of cancer progression. Our results indicate that determination of glutathione status and oxidative stress-related parameters in blood may help to orientate cancer therapy in humans.


Instantaneous thickness measurement of multilayer films by single-shot angle-resolved spectral reflectometry.
In this Letter, we describe a new, to the best of our knowledge, concept of angle-resolved spectral reflectometry with a pixelated polarizing camera for determination of the thickness of each film layer in multilayer films. We can measure the changes in the phase and amplitude of p- and s-polarized light over a broad spectral range and a wide incident angle at a time. The proposed method is verified by measuring a sample of multilayer film and comparing our measurement results with an ellipsometer. The comparison results show that our proposed technique enables real-time inspection of multilayer films with high precision.


In vitro models of collagen biomineralization.
Over the last several years, significant progress has been made toward understanding the mechanisms involved in the mineralization of hard collagenous tissues, such as bone and dentin. Particularly notable are the identification of transient mineral phases that are precursors to carbonated hydroxyapatite, the identification and characterization of non-collagenous proteins that are involved in controlling mineralization, and significant improvements in our understanding of the structure of collagen. These advances not only represent a paradigm shift in the way collagen mineralization is viewed and understood, but have also brought new challenges to light. In this review, we discuss how recent in vitro models have addressed critical questions regarding the role of the non-collagenous proteins in controlling mineralization, the nature of the interactions between amorphous calcium phosphate and collagen during the early stages of mineralization, and the role of collagen in the mineralization process. We discuss the significance of these findings in expanding our understanding of collagen biomineralization, while addressing some of the limitations that are inherent to in vitro systems.


Exploiting CRISPR-Cas immune systems for genome editing in bacteria.
The CRISPR-Cas immune system is a DNA-encoded, RNA-mediated, DNA-targeting defense mechanism, which provides sequence-specific targeting of DNA. This molecular machinery can be engineered into the sgRNA:Cas9 technology, for programmable cleavage of DNA. Following the genesis of double-stranded DNA breaks, the DNA repair machinery generates mutations at the cleavage site using various pathways. This technology has revolutionized eukaryotic genome editing, and we are at the cusp of full exploitation in bacteria. Here, we discuss the potential of CRISPR-based technologies for use in bacteria, and highlight the application of single stranded DNA recombineering combined with CRISPR-Cas selection to edit the genome of a probiotic organism. We envision that CRISPR-Cas technologies will play a key role in the development of next-generation industrial bacteria.


Fate and removal efficiency of polystyrene nanoplastics in a pilot drinking water treatment plant.
Occurrence of microplastics and nanoplastics in aquatic systems, as well as in water compartments used to produce drinking water have become a major concern due to their impact on the environment and public health. Nanoplastics in particular, in regard to their fate and removal efficiency in drinking water treatment plants (DWTP), which ensure water quality and supply drinking water for human consumption have been, by far, rarely investigated. This study investigates the removal efficiency of polystyrene (PS) nanoplastics in a conventional water treatment plant providing drinking water for 500'000 consumers. For that purpose, a pilot-scale DWTP, located within the main treatment plant station, reproducing at a reduced scale the different processes and conditions of the main treatment plant is used. The results show that filtration process through sand and granular activated carbon (GAC) filters in the absence of coagulation achieves an overall nanoplastic removal of 88.1%. The removal efficiency of filtration processes is mainly attributed to physical retention and adsorption mechanisms. On the other hand, it is found that coagulation process greatly improves the removal efficiency of nanoplastics with a global removal efficiency equal to 99.4%. The effective removal efficiency of sand filtration increases considerably from 54.3% to 99.2% in the presence of coagulant, indicating that most of PS nanoplastics are removed during sand filtration process. The higher removal efficiency with the addition of coagulant is related to nanoplastics surface charge reduction and aggregation thus significantly increasing their retention in the filter media.


Contributions of the National Institute of Parasitic Diseases to the control of visceral leishmaniasis in China.
Visceral leishmaniasis (VL) caused by Leishmania spp. is an important vector-borne disease prevalent in China. VL was rampant in the vast area of China north of the Yangtze River before the founding of the People's Republic of China in 1949. As a result of strenuous interventions, the disease was basically eliminated in most of the former epidemic areas in 1958-60. At present, only sporadic cases occur in the western regions of China. In the process, National Institute of Parasitic Diseases at China CDC and the Chinese Center for Tropical Diseases Research (NIPD-CTDR) have achieved great impact in controlling the diseases as well as in research on Leishmania spp. This review summarized the contribution of experts from NIPD-CTDR to the control and elimination of VL in various aspects, such as understanding the epidemiological features of VL, confirmation of VL vectors and their distribution, development of control tools including diagnostics and insecticides, monitoring and evaluation supported by information management, technical supports to the control programmes, as well as analysis of the challenges faced. At the same time, it puts forward constructive suggestions for the ultimate interruption of VL transmission in China.


Diagnosis of peripheral arterial disease in general practice: can the ankle-brachial index be measured either by pulse palpation or an automatic blood pressure device?
Despite its validity as a screening test for peripheral arterial disease (PAD), and its prognostic value, the ankle-brachial index (ABI) is infrequently used in primary care, probably because a Doppler device is required, along with the requisite skill for its use. We hypothesized that ABI could be accurately measured either by pulse palpation (pABI) or automatic blood pressure devices (autoABI) instead of Doppler method (dABI). In 54 subjects, we compared the results and the intra-observer reproducibility of pABI to dABI, as well as the inter-observer reproducibility of both pABI and autoABI to dABI. Arm and ankle systolic pressures were measured by the three methods by two observers. The first observer repeated pABI and dABI measurements. The results were compared by the Student paired t-test. Reproducibility was assessed by the intra-class correlation coefficient of agreement (R) and the Bland and Altman method. The mean dABI obtained by the first observers was 1.03 +/- 0.26 vs. a pABI of 0.85 +/- 0.44 (p < 0.0001) and an autoABI of 1.09 +/- 0.31 (p < 0.05). The intra-observer R-coefficient was at 0.89 for dABI vs. 0.60 for pABI (p < 0.05). The inter-observer R-coefficients were 0.79 for dABI vs. 0.40 for pABI (p < 0.05) and 0.44 for autoABI (p < 0.05). Neither pulse palpation nor automatic oscillometric devices can be recommended as reliable methods for ABI measurement.


Proteins in the plasma membranes of rat peritoneal mast cells.
Plasma membranes of peritoneal mast cells from rats specifically bred for resistance to the dextran anaphylactoid reaction contain a polypeptide of molecular weight about 74,000 daltons which is deficient in those from rats which react to dextran. This polypeptide may modify the dextran receptor on the mast cell membranes of resistant rats so that histamine release does not take place when these cells are challenged with clinical dextran.


Metabolic mapping with bioluminescence: basic and clinical relevance.
This review is focused on metabolic mapping in biological tissue with quantitative bioluminescence and single photon imaging. Metabolites, such as ATP, glucose and lactate, can be imaged quantitatively and within microscopic dimensions in cryosections from shock frozen biological specimens using enzyme reactions and light emission by luciferases. The technique has been applied in numerous targets and models of experimental biomedical research, such as multicellular spheroids, various organs of laboratory animals in a physiological or pathophysiological state, and even in plant seeds. Among numerous other aspects, data obtained with this method have contributed to the elucidation of mechanisms that are involved in the development of necrosis in multicellular spheroids. The combination of the bioluminescence technique with immunohistochemistry, autoradiography or in situ hybridization can considerably reduce ambiguities in the interpretation of the experimental results. Although, an invasive technique, bioluminescence imaging has been used most intensively in clinical oncology using tumor biopsies taken at the first diagnosis of the disease. It has been shown for squamous cell carcinomas of the head and neck and of the uterine cervix that accumulation of high levels of lactate in the primary lesions is associated with a high risk of metastasis formation and a reduced overall and disease-free patient survival. Thus, metabolic imaging can provide additional information on the degree of malignancy and the prognosis of tumors which may help the oncologist in improving specific treatment approaches for each individual malignant disease. Last but not least, metabolic mapping in clinical oncology has stimulated a number of investigations in basic cancer research on mechanisms that underlie the correlation between tumor metabolism and malignancy.


Teaching about death and dying-A national mixed-methods survey of palliative care education provision in Swedish undergraduate nursing programmes.
In coming decades, the number of people affected by illnesses who need palliative care will rise worldwide. Registered Nurses are in a central position in providing this care, and education is one of the necessary components for meeting coming requirements. However, there is a lack of knowledge about palliative care in undergraduate nursing education curricula, including the extent of the education provided and the related pedagogical methods. The aim was to investigate the extent, content and pedagogical methods used and to explore lecturers' experiences of being responsible for teaching and learning about palliative care for undergraduate nursing students on nursing programmes at Swedish universities. All 24 universities responsible for providing undergraduate nursing education in Sweden participated. One lecturer with in-depth knowledge about palliative care or end-of-life care education participated in the quantitative (n = 24) and qualitative (n = 22) parts of the study. A mixed-method research study with an explorative design was used. Descriptive statistics were used to analyse quantitative data, and content analysis for qualitative, with both also analysed integratively. Few undergraduate nursing programmes included a specific course about palliative care in their curricula, however, all universities incorporated education about palliative care in some way. Most of the palliative care education was theoretical, and lecturers used a variety of pedagogical strategies and their own professional and personal experience to support students to understand the palliative care approach. Topics such as life and death were difficult to both learn and teach about. There is a need for substantial education about palliative care. Lecturers strive on their own to develop students' understanding and increase the extent of palliative care education with innovative teaching strategies, but must compete with other topics. Palliative care teaching must be prioritised, not only by the universities, but also by the national authority.