Quenching of fluorescence of pyrene-substituted lecithin by tetracyanoquinodimethane in liposomes.
In this work we have applied a kinetic scheme derived from fluorescence kinetics of pyrene-labeled phosphatidylcholine in phosphatidylcholine membrane to explain the fluorescence quenching of 1-palmitoyl-2-(10-[pyrenl-yl]-sn-glycerol-3-phosphatidylchol ine (PPDPC) liposomes by tetracyanoquinodimethane (TCNQ). The scheme was also found to be applicable to neat PPDPC and the effect of the quencher could be attributed to certain steps of the proposed mechanism. The TCNQ molecules influence the fluorescence of pyrene moieties in PPDPC liposome in two ways. Firstly, an interaction between the quencher molecule and the pyrene monomer in the excited state quenches monomer fluorescence and effectively prevents the diffusional formation of the excimer. Secondly, an interaction between the quencher molecule and the excited dimer quenches the excimer fluorescence. The TCNQ molecule does not prevent the formation of the excimer in pyrene moieties aggregated in such a way that they require only a small rotational motion to attain excimer configuration. The diffusional quenching rate constant is calculated to be 1.0 x 10(8) M-1 s-1 for the pyrene monomer quenching and 1.3 x 10(7) M-1 s-1 for the pyrene excimer quenching. The diffusion constant of TCNQ is 1.5 x 10(-7) cm2 s-1 for the interaction radii of 0.8-0.9 nm. The TCNQ molecules are practically totally partitioned in the membrane phase.


Endovascular mechanical recanalization of acute ischaemic stroke in octogenarians.
Multiple studies have shown a clinical benefit of thrombectomy in acute ischaemic stroke, but most of them excluded octogenarians. The purpose of this study was to compare the outcomes between octogenarians and younger patients after thrombectomy. One hundred and sixty-six patients with large cerebral artery occlusion and consecutive thrombectomy were evaluated and divided into two patient age groups: younger than 80 years and older than 80 years. We compared recanalization rates, complications experienced, disability, death after discharge and at a 90-day follow-up between these age groups. Sixty-eight percent of octogenarians and 72 % of younger patients were registered with successful recanalization (p = 1.0). There was no significant difference in symptomatic intracerebral haemorrhage between the groups (p = 0.32). However, octogenarians had a significantly lower rate of good clinical outcome (24 % vs. 48 %; p = 0.008) and a higher mortality rate (36 % vs. 12 %; p = 0.0013). Octogenarians have a lower chance of good clinical outcome and a higher mortality rate despite successful recanalization. Nevertheless, 24 % of octogenarians were documented with mRS ≤2. As this age group of octogenarians will grow prospectively, careful patient selection should be mandatory when considering octogenarians for thrombectomy. • Careful patient selection for thrombectomy should be mandatory in octogenarians. • Octogenarians have a higher mortality rate despite successful recanalization. • Nearly one-third of octogenarians were documented with a good clinical outcome.


Engineering a lipase B from Candida antactica with efficient perhydrolysis performance by eliminating its hydrolase activity.
A Ser105Ala mutant of the lipase B from Candida antarctica enables 'perhydrolase-only' reactions. At the example of the chemoenzymatic Baeyer-Villiger oxidation of cyclohexanone, we demonstrate that with this mutant selective oxidation can be achieved in deep eutectic solvent while essentially eliminating the undesired hydrolysis reaction of the product.


Circulating endothelial progenitor cells and cardiovascular outcomes.
Endothelial progenitor cells derived from bone marrow are believed to support the integrity of the vascular endothelium. The number and function of endothelial progenitor cells correlate inversely with cardiovascular risk factors, but the prognostic value associated with circulating endothelial progenitor cells has not been defined. The number of endothelial progenitor cells positive for CD34 and kinase insert domain receptor (KDR) was determined with the use of flow cytometry in 519 patients with coronary artery disease as confirmed on angiography. After 12 months, we evaluated the association between baseline levels of endothelial progenitor cells and death from cardiovascular causes, the occurrence of a first major cardiovascular event (myocardial infarction, hospitalization, revascularization, or death from cardiovascular causes), revascularization, hospitalization, and death from all causes. A total of 43 participants died, 23 from cardiovascular causes. A first major cardiovascular event occurred in 214 patients. The cumulative event-free survival rate increased stepwise across three increasing baseline levels of endothelial progenitor cells in an analysis of death from cardiovascular causes, a first major cardiovascular event, revascularization, and hospitalization. After adjustment for age, sex, vascular risk factors, and other relevant variables, increased levels of endothelial progenitor cells were associated with a reduced risk of death from cardiovascular causes (hazard ratio, 0.31; 95 percent confidence interval, 0.16 to 0.63; P=0.001), a first major cardiovascular event (hazard ratio, 0.74; 95 percent confidence interval, 0.62 to 0.89; P=0.002), revascularization (hazard ratio, 0.77; 95 percent confidence interval, 0.62 to 0.95; P=0.02), and hospitalization (hazard ratio, 0.76; 95 percent confidence interval, 0.63 to 0.94; P=0.01). Endothelial progenitor-cell levels were not predictive of myocardial infarction or of death from all causes. The level of circulating CD34+KDR+ endothelial progenitor cells predicts the occurrence of cardiovascular events and death from cardiovascular causes and may help to identify patients at increased cardiovascular risk.


A spectral approach on mineralogy and geochemistry of garnet skarns in Arc-Type granitoids.
Garnets that common constituent of skarn type iron deposits are wide ranges of chemical compositions, and they are also important as a semi-gemstone mineral. This study has been investigated garnets and inclusions of its formed in contacts of Pertek granitoid and Keban marble by using a combination of multiple techniques including Raman spectrum, electron microprobe, petrography and LA-ICP-MS. The main mineral assemblage observed in the skarn formation is diopside, garnet, quartz, magnetite, calcite and pyrite. The garnets are in size between 1 and 7 cm and have reddish, greenish and light-dark brown colour. The compositions of the garnets are mainly grossular-andradite, andradite-grossular, less grossular and andradite. Increased porosity and horizontal flow of hydrothermal fluids during metasomatism resulted in the formation of garnets of different sizes. Raman spectroscopy studies on garnets show to be that the idiomorphic and semi-idiomorphic garnets are predominantly grosular, andradite and uvarovite in the core. Raman spectroscopy studies on garnets showed to have predominantly grossular, andradite and uvarovite composition in the core of the idiomorphic and semi-idiomorphic garnets. As for the rare earth element (REE) analysis and distribution model, the chondrite-normalized REE patterns of all garnets in the study area have similar trends and generally in the right-slopping shape depleted in HREE and enriched in LREE, mostly controlled by adsorption. High Fe2O3, CaO and MgO contents may cause to high mobility during skarn formation associated with contact metamorphism and cation exchange via hydrothermal fluids (eg uvarovite in the core). All garnets have generally positive Ce and positive Eu anomalies. These results suggest that the garnets in the studya area formed in conditions showing increase in pH and high oxygen fugacity or decrease in temperature in the source of the hydrothermal fluids.


Increase of ATP-sensitive potassium (K(ATP)) channels in the heart of type-1 diabetic rats.
An impairment of cardiovascular function in streptozotocin (STZ)-diabetic rats has been mentioned within 5 days-to-3 months of induction. ATP-sensitive potassium (K(ATP)) channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify the changes of cardiac K(ATP) channels in diabetic disorders. Streptozotocin-induced diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr) were used to examine the effect of hyperglycemia on cardiac function and the expression of K(ATP) channels. K(ATP) channels expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of K(ATP) channels by Western blot and Northern blot analysis. The result shows diazoxide produced a marked reduction of heart rate in control group. Furthermore, the methods of Northern blotting and Western blotting were employed to identify the gene expression of K(ATP) channel. Two subunits of cardiac K(ATP) channel (SUR2A and kir 6.2) were purchased as indicators and showed significantly decreased in both diabetic rats and high glucose treated rat cardiac myocytes. Correction of hyperglycemia by insulin or phlorizin restored the gene expression of cardiac K(ATP) in these diabetic rats. Both mRNA and protein expression of cardiac K(ATP) channels are decreased in diabetic rats induced by STZ for 8 weeks. This phenomenon leads to result in desensitization of some K(ATP) channel drugs.


Diazoxide enhances basal metabolic rate and fat oxidation in obese Zucker rats.
Persistent suppression of hyperinsulinemia in genetically obese (fa/fa) Zucker rats by diazoxide (DZ) reduces food intake and weight gain; improves insulin sensitivity, glycemic control, and lipid profile; and enhances beta(3)-adrenergic function and lipolysis in adipose tissue. The aim of this study was to elucidate the effects of DZ on basal metabolic rate (BMR), fat oxidation, and adrenergic function of lean and obese Zucker rats. Diazoxide (150 mg/kg/d) or vehicle (control) was administered for 4 weeks in 7-week-old obese and lean Zucker rats (n = 8-9 per subgroup). Animals underwent indirect calorimetry, body composition analysis, and determination of uncoupling proteins (UCPs) messenger RNA (mRNA) in brown and white adipose tissues (BAT and WAT) and skeletal muscle (SM), beta(3)-adrenergic receptor (AR) mRNA in BAT and WAT, beta(2)-AR in SM as well as WAT, and SM adenylate cyclase (AC) activity at the completion of study. Diazoxide treatment decreased food intake, weight gain, and body fat in obese rats (P < .01). Although DZ treatment lowered fasting plasma glucose, insulin, leptin, adiponectin, and lipids in obese rats (P < .01), it increased adiponectin-leptin ratio (P < .01). Plasma adiponectin-leptin ratio was inversely correlated with fat mass in obese and lean rats (r = -0.86, P < .0001). Diazoxide treatment resulted in higher BMR and fat oxidation rate in obese compared with control animals (P < .01), without any effect in lean animals. Furthermore, plasma adiponectin was inversely correlated with BMR (-0.56, P < .001) and lipid oxidation rate (-0.61, P < .0005) and was positively correlated with nonprotein respiratory quotient (r = 0.41, P < .01) in obese and lean rats. This was associated with increased beta(3)-AR mRNA expression in BAT and WAT (P < .01), UCP-1 and UCP-3 in BAT and AC activity in WAT (P < .02), and AC activity in SM of DZ obese rats compared with controls (P < .01), without significant change in SM beta(2)-AR mRNA expressions. Diazoxide attenuation of hyperinsulinemia decreased the rate of weight gain but enhanced insulin sensitivity, BMR, and fat oxidation in obese rats. This was associated with increased receptor- and non-receptor-mediated adrenergic function in adipose and muscle tissues in obese rats, respectively. These metabolic changes in obese Zucker rats suggest that antiobesity effects of DZ appear to be not only through its anorectic effect, modification of disturbed insulin metabolism, and inhibition of lipogenesis, but also due to augmentation of adrenergic function, energy expenditure, and fat utilization.


Ewing's sarcoma of metacarpal. A case report and review of literature.
The radiological features of a rare case of Ewing's sarcoma of right fourth metacarpal in a twenty-five years young male are described. An up date review of literature is also presented.


Isolation and partial characterization of normal and defective bacteriophages of gram-negative hydrogen bacteria.
Widespread defective lysogeny was detected in Alcaligenes eutrophus by electron microscopic analysis of cultures. Mitomycin C treatment of the cultures resulted in the production of defective (inco-) particles. Polysheaths were produced both with and without induction. With the simultaneous isolation technique six phages were isolated for hydrogen-oxidizing strains of the new species Pseudomonas pseudoflava. The phages were able to replicate under autotrophic conditions and were found to have a very restricted host range. Electron microscopic analysis allowed classification into two structural groups. Group I contained phages with contractile tails; group II contained phages with flexible, noncontractile tails. All but one (gb) of the new phages were shown to be temperate by isolation of lysogens and induction with mitomycin C.


Hospital-affiliated headache clinics in the managed care era.
Many headache clinics are affiliated with hospitals. These facilities were often started before the era of managed care. The new incentives and disincentives of managed care will force these programs to change their structures. Only those which document value are likely to survive.


High frequencies (HF) repetitive transcranial magnetic stimulation (rTMS) increase motor coordination performances in volleyball players.
It is widely demonstrated that high frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has facilitative effects and is therefore capable to inducing changes in motor responses. One of the most investigated areas is the dorsolateral prefrontal cortex (DLPFC) as it plays a special executive attention role in actively preserving access to stimulus representations and objectives in environments with plenty of distraction such as those of team sports. Volleyball is a team sport in which the attention and coordination components are essential for achieving performance. Thus, the aim of this study was to investigate if HF rTMS at DLPFC in volleyball players can improve homolateral motor coordination and cortical excitability. This study was a double-blinded (participant and evaluator) matched-pair experimental design. Twenty right-handed female volleyball players were recruited for the study and were randomly assigned either the active rTMS (n = 10) or the sham stimulation group (n = 10). The stimulation was performed in one session with 10 Hz, 80% of the resting motor threshold (RMT) of the right first dorsal interosseous muscle, 5 s of stimulation, and 15 s of rest, for a total of 1500 pulses. Before and after stimulation, the coordination and the cortical excitability were evaluated. The significant finding of this paper was that HF-rTMS of the DLPFC improved performance in terms of the homolateral interlimb coordination, with a significantly decreased in resting motor threshold and MEP latency of the ipsilateral motor cortex. It seem that HF-rTMS could increase coordination performances when the velocity of the execution is higher (120 bpm and 180 bpm). Moreover, in active rTMS group significant differences emerged after stimulation in RMT and in MEP latency, while no differences emerged after stimulation in MEP amplitude. In conclusion we believe that these results may be of great interest to the scientific community and may also have practical implications in the future.


Outlier knowledge management for extreme public health events: Understanding public opinions about COVID-19 based on microblog data.
Based on complex adaptive system theory and information theory for investigating heterogeneous situations, this paper develops an outlier knowledge management framework based on three aspects-dimension, object, and situation-for dealing with extreme public health events. In the context of the COVID-19 pandemic, we apply advanced natural language processing (NLP) technology to conduct data mining and feature extraction on the microblog data from the Wuhan area and the imported case province (Henan Province) during the high and median operating periods of the epidemic. Our experiment indicates that the semantic and sentiment vocabulary of words, the sentiment curve, and the portrait of patients seeking help were all heterogeneous in the context of COVID-19. We extract and acquire the outlier knowledge of COVID-19 and incorporate it into the outlier knowledge base of extreme public health events for knowledge sharing and transformation. The knowledge base serves as a think tank for public opinion guidance and platform suggestions for dealing with extreme public health events. This paper provides novel ideas and methods for outlier knowledge management in healthcare contexts.


Y chromosome gene expression in the blood of male patients with ischemic stroke compared with male controls.
Sex is suggested to be an important determinant of ischemic stroke risk factors, etiology, and outcome. However, the basis for this remains unclear. The Y chromosome is unique in males. Genes expressed in males on the Y chromosome that are associated with stroke may be important genetic contributors to the unique features of males with ischemic stroke, which would be helpful for explaining sex differences observed between men and women. We compared Y chromosome gene expression in males with ischemic stroke and male controls. Blood samples were obtained from 40 male patients ≤3, 5, and 24 hours after ischemic stroke and from 41 male controls (July 2003-April 2007). RNA was isolated from blood and was processed using Affymetrix Human U133 Plus 2.0 expression arrays (Affymetrix Inc., Santa Clara, California). Y chromosome genes differentially expressed between male patients with stroke and male control subjects were identified using an ANCOVA adjusted for age and batch. A P < 0.05 and a fold change >1.2 were considered significant. Seven genes on the Y chromosome were differentially expressed in males with ischemic stroke compared with controls. Five of these genes (VAMP7, CSF2RA, SPRY3, DHRSX, and PLCXD1) are located on pseudoautosomal regions of the human Y chromosome. The other 2 genes (EIF1AY and DDX3Y) are located on the nonrecombining region of the human Y chromosome. The identified genes were associated with immunology, RNA metabolism, vesicle fusion, and angiogenesis. Specific genes on the Y chromosome are differentially expressed in blood after ischemic stroke. These genes provide insight into potential molecular contributors to sex differences in ischemic stroke.


Effects of antidiabetic drugs on psoriasis: A meta-analysis.
Psoriasis, a chronic inflammatory skin disease, poses an elevated risk of developing diabetes mellitus. To investigate the effects of antidiabetic medications on psoriasis. We conducted a systemic review and meta-analysis and searched MEDLINE, EMBASE and CENTRAL for relevant randomized controlled trials. Our outcomes included 75% improvement in the psoriasis area and severity index from baseline (PASI 75), change in the psoriasis area and severity index (PASI) score, or change in the Dermatology Life Quality Index score under antidiabetic agents. Cochrane Collaboration's tool was used to evaluate the risk of bias of included studies. Subgroup analysis of different dosages of the antidiabetic agents was also performed. We included 10 randomized controlled studies examining the effect of antidiabetic agents. Eight studies were rated high risk of bias. Pioglitazone demonstrated significant increase in PASI 75 (risk difference = 0.42; 95% CI: 0.18-0.65) and decrease in mean PASI (mean difference = -3.82; 95% CI: -6.05-1.ㄍ59). In subgroup analysis, 30 mg pioglitazone group demonstrated a significantly higher portion of PASI 75 than 15 mg pioglitazone group (P = .003). Some biases are reported high risk in involved articles. The main limitation of the study is in the inclusion of only glitazones. The lack of effect was seen for rosiglitazone and metformin. In the case of metformin, there was only one study available, which is also an important issue. The current evidence demonstrates therapeutic efficacy of pioglitazone, which may be a treatment option in patients with psoriasis and diabetes mellitus.


A novel Fe-hemin-metal organic frameworks supported on chitosan-reduced graphene oxide for real-time monitoring of H2O2 released from living cells.
Herein, a kind of novel hemin-based metal organic frameworks (Fe-hemin-MOFs) with unique peroxidase-like bioactivity was developed for the first time. The synthesized Fe-hemin-MOFs exhibited satisfactory catalytic activity toward hydrogen peroxide (H2O2). When it was further supported on Chitosan-reduced graphene oxide (CS-rGO), amplified electrochemical signal could be obtained. The Fe-hemin-MOFs/CS-rGO composite was used to construct a novel H2O2 electrochemical sensor. The electrocatalytic reduction of H2O2 displayed two segments linearity range from 1 to 61 μM and 61-1311 μM, as well as a low detection limit of 0.57 μM. Furthermore, the proposed sensor was successfully used for real-time monitoring of H2O2 released from living cells, which extended the practical application of MOFs-based sensors in monitoring the pathological process in living cells.


Opsoclonus-myoclonus with Beckwith-Wiedemann syndrome and hepatoblastoma.
The association between Beckwith-Wiedemann syndrome and hepatoblastoma is well established and relatively commonplace. The occurrence of opsoclonus-myoclonus syndrome in individuals with occult neoplasia is also well documented. However, the development of opsoclonus-myoclonus syndrome in an infant with Beckwith-Wiedemann syndrome and hepatoblastoma has not been reported previously. The list of underlying causes of opsoclonus-myoclonus syndrome should be expanded to include hepatoblastoma, particularly in any child with features suggestive of Beckwith-Wiedemann syndrome.


[Tuberous iododerma from solutan].
The literature data on this condition are reviewed and a 22-year-old female patient with solutan-induced tuberous iododerma is described.


Association of demographic and clinical factors with risk of acute pancreatitis: An exposure-wide Mendelian randomization study.
The incidence of acute pancreatitis (AP) is increasing over years, which brings enormous economy and health burden. However, the aetiologies of AP and underlying mechanisms are still unclear. Here, we performed a two-sample Mendelian randomization (MR) analysis to investigate the associations between all reported possible risk factors and AP using publicly available genome-wide association study summary statistics. A series of quality control steps were taken in our analysis to select eligible instrumental single nucleotide polymorphisms which were strongly associated with exposures. To make the conclusions more robust and reliable, we utilized several analytical methods (inverse-variance weighting, MR-PRESSO method, weighted median, MR-Egger regression) that are based on different assumptions of two-sample MR analysis. The MR-Egger intercept test, radial regression and leave-one-out sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on each exposure. A two-step MR method was applied to explore mediators in significant associations. Genetic predisposition to cholelithiasis (effect estimate: 17.30, 95% CI: 12.25-22.36, p = 1.95 E-11), body mass index (0.32, 95% CI: 0.13-0.51, p < 0.001), body fat percentage (0.57, 95% CI: 0.31-0.83, p = 1.31 E-05), trunk fat percentage (0.36, 95% CI: 0.14-0.59, p < 0.005), ever smoked (1.61, 95% CI: 0.45-2.77, p = 0.007), and limbs fat percentage (0.55, 95% CI: 0.41-0.69, p < 0.001) were associated with an increased risk of AP. In addition, whole-body fat-free mass (-0.32, 95% CI: -0.55 to -0.10, p = 0.004) was associated with a decrease risk of AP. Genetic predisposition to cholelithiasis, obesity and smoking could be causally associated with an increased risk of AP, and whole body fat-free mass could be associated with a decreased risk of AP.


Inscuteable maintains type I neuroblast lineage identity via Numb/Notch signaling in the Drosophila larval brain.
In the Drosophila larval brain, type I and type II neuroblasts (NBs) undergo a series of asymmetric divisions which give rise to distinct progeny lineages. The intermediate neural progenitors (INPs) exist only in type II NB lineages. In this study, we reveal a novel function of Inscuteable (Insc) that acts to maintain type I NB lineage identity. In insc type I NB clones of mosaic analyses with a repressible cell marker (MARCM), the formation of extra Deadpan (Dpn)+ NB-like and GMC-like cells is observed. The lack of Insc leads to the defective localization and segregation of Numb during asymmetric cell division. By the end of cytokinesis, this results in insufficient Numb in ganglion mother cells (GMCs). The formation of extra Deadpan (Dpn)+ cells in insc clones is prevented by the attenuation of Notch activity. This suggests that Insc functions through the Numb/Notch signaling pathway. We also show that in the absence of Insc in type I NB lineages, the cellular identity of GMCs is altered where they adopt an INP-like cell fate as indicated by the initiation of Dpn expression accompanied by a transient presence of Earmuff (Erm). These INP-like cells have the capacity to divide multiple times. We conclude that Insc is necessary for the maintenance of type I NB lineage identity. Genetic manipulations to eliminate most type I NBs with overproliferating type II NBs in the larval brain lead to altered circadian rhythms and defective phototaxis in adult flies. This indicates that the homeogenesis of NB lineages is important for the adult's brain function.


Impact of ultrasound contrast agent on the detection of thrombi during transoesophageal echocardiography.
Atrial fibrillation (AF) carries the risk of thrombus formation in the left atrium and especially in the left atrial appendage (LAA). A transoesophageal echocardiography (TOE) is routinely performed in these patients to rule out thrombi before cardioversion or structural interventions like LAA closure or pulmonary vein isolation. However, in a certain number of cases, inconclusive results of the TOE may result. This study was performed to analyse whether the routine use of ultrasound contrast agent (UCA) has an influence on the frequency of thrombus detection. In patients with AF who were scheduled for a subsequent interventional procedure, a TOE was initially performed without contrast agent. Then, the TOE was repeated with the use of UCA. The percentage of diagnostic findings regarding the prevalence of thrombus in the LAA with and without UCA were compared (thrombus present (T+), no thrombus (T-) and inconclusive result (T+/-)). 223 patients were prospectively included into the trial. The numbers of thrombus detection were as follows: without UCA: 17 T+ (7.6%), 154 T- (69.1%), 52 T+/- (23,3%); with UCA: 16 T+ (7.2%), 179 T- (80.3%), 28 T+/- (12.6%; χ2: p<0.01). In 29 examinations (13.0%), the use of UCA had an impact on the subsequent treatment strategy. The use of UCA during TOE in patients with AF has a significant impact on the subsequent patient management especially due to an improved rule out of LAA thrombi.


Plasma HER2 (ERBB2) Copy Number Predicts Response to HER2-targeted Therapy in Metastatic Colorectal Cancer.
ERBB2 (HER2) amplification is an emerging biomarker in colon cancer, conferring sensitivity to combination anti-HER2 therapy. Measurement of HER2 copy number is typically performed using surgical specimens, but cell-free circulating tumor DNA (ctDNA) analysis may be a noninvasive alternative. We determined the sensitivity of plasma copy number (pCN) for detecting ERBB2 amplifications and whether pCN correlated with tissue-detected copy number. We also assessed response to HER2-targeted therapy based on pCN and suggest a pCN threshold predictive of response. Forty-eight pretreatment and progression plasma samples from 29 HER2-positive patients in the HERACLES A clinical trial were tested using the Guardant360 cfDNA assay. We correlated ERRB2 pCN with progression-free survival (PFS) and best objective response (BOR) and applied an adjustment method based on tumor DNA shedding using the maximum mutant allele fraction as a surrogate for tumor content to accurately determine the pCN threshold predictive of response. Forty-seven of 48 samples had detectable ctDNA, and 46 of 47 samples were ERBB2-amplified on the basis of cfDNA [2.55-122 copies; 97.9% sensitivity (95% confidence interval, 87.2%-99.8%)]. An adjusted ERBB2 pCN of ≥25.82 copies correlated with BOR and PFS (P = 0.0347). cfDNA is a viable alternative to tissue-based genotyping in the metastatic setting. The cfDNA platform utilized correctly identified 28 of 29 (96.6%) of pretreatment samples as ERBB2-amplified and predicted benefit from HER2-targeted therapy. In this study, an observed pCN of 2.4 and an adjusted pCN of 25.82 copies of ERBB2 are proposed to select patients who will benefit from HER2-targeted therapy.


Determination of residues of carazolol and a number of tranquilizers in swine kidney by high-performance liquid chromatography with ultraviolet and fluorescence detection.
A rapid and sensitive method has been set up for the determination of the beta-receptor blocker carazolol and the tranquillizers acepromazine, azaperone, chlorpromazine, haloperidol, propionylpromazine and xylazine in swine kidneys. The procedure involves extraction with acetonitrile, rapid sample clean-up with a Sep-Pak C18 cartridge and high-performance liquid chromatography with ultraviolet and fluorescence detection. The mean recoveries range from 93 to 101%, with the exception of xylazine (52%), and the coefficients of variation from 5.3 to 18.9% at a fortification level of 20 micrograms/kg. The limits of determination range from 0.3 micrograms/kg for carazolol to 1-10 micrograms/kg for the other drugs. The method has been tested in routine monitoring programmes.


Ecological footprint-technological innovations nexus: new empirical evidence from panel data estimations.
The aim of this approach is to establish a relation between ecological footprint and technological innovations by using panel data techniques and taking Union for the Mediterranean member countries as the case. On the one hand, the Mediterranean region is an alarming region when it comes to environmental degradation; on the other hand, existing intergovernmental organizations such as the Union for the Mediterranean may provide a sound ground to take common action among all members against such a degradation. The approach takes eleven member countries from the Union for the Mediterranean (Bosnia and Herzegovina, France, Greece, Israel, Italy, Jordan, Morocco, Portugal, Spain, Tunisia, Türkiye) and observes them for the time frame 1992-2020. By using panel unit root tests and cross-sectional dependency tests, the data is being analyzed for further evaluation using mean group, common correlated effect mean group, and augmented mean group analysis. Regarding the observed variables, we could not identify a common trend for these eleven countries. For the sample of eleven countries, the impact of technological innovations was not significant, but country-level augmented mean group analysis results indicated that for Portugal, this impact was significant and positive.


Cortical Spreading Depolarization, Blood Flow, and Cognitive Outcomes in a Closed Head Injury Mouse Model of Traumatic Brain Injury.
Cortical spreading depolarizations (CSDs) are associated with worse outcomes in many forms of acute brain injury, including traumatic brain injury (TBI). Animal models could be helpful in developing new therapies or biomarkers to improve outcomes in survivors of TBI. Recently, investigators have observed CSDs in murine models of mild closed head injury (CHI). We designed the currently study to determine additional experimental conditions under which CSDs can be observed, from mild to relatively more severe TBI. Adult male C57Bl/6J mice (8-14 weeks old) were anesthetized with isoflurane and subjected to CHI with an 81-g weight drop from 152 or 183 cm. CSDs were detected with minimally invasive visible light optical intrinsic signal imaging. Cerebral blood flow index (CBFi) was measured in the 152-cm drop height cohort using diffuse correlation spectroscopy at baseline before and 4 min after CHI. Cognitive outcomes were assessed at 152- and 183-cm drop heights for the Morris water maze hidden platform, probe, and visible platform tests. CSDs occurred in 43% (n = 12 of 28) of 152-cm and 58% (n = 15 of 26) of 183-cm drop height CHI mice (p = 0.28). A lower baseline preinjury CBFi was associated with development of CSDs in CHI mice (1.50 ± 0.07 × 10-7 CHI without CSD [CSD-] vs. 1.17 ± 0.04 × 10-7 CHI with CSD [CSD+], p = 0.0001). Furthermore, in CHI mice that developed CSDs, the ratio of post-CHI to pre-CHI CBFi was lower in the hemisphere ipsilateral to a CSD compared with non-CSD hemispheres (0.19 ± 0.07 less in the CSD hemisphere, p = 0.028). At a 152-cm drop height, there were no detectable differences between sham injured (n = 10), CHI CSD+ (n = 12), and CHI CSD- (n = 16) mice on Morris water maze testing at 4 weeks. At a 183-cm drop height, CHI CSD+ mice had worse performance on the hidden platform test at 1-2 weeks versus sham mice (n = 15 CHI CSD+, n = 9 sham, p = 0.045), but there was no appreciable differences compared with CHI CSD- mice (n = 11 CHI CSD-). The data suggest that a lower baseline cerebral blood flow prior to injury may contribute to the occurrence of a CSD. Furthermore, a CSD at the time of injury can be associated with worse cognitive outcome under the appropriate experimental conditions in a mouse CHI model of TBI.


Lactobacillus acidophilus attenuates Aeromonas hydrophila induced cytotoxicity in catla thymus macrophages by modulating oxidative stress and inflammation.
The pathogenesis of Aeromonas hydrophila, a potent fish pathogen, is attributed to its ability to cause motile aeromonad septicaemia leading to apoptosis in a myriad of fish species, including freshwater carp Catla catla. However, the underlying mechanism of antagonistic activity of probiotics against A. hydrophila induced apoptosis is not elucidated due to lack of appropriate in-vitro models. This study reported that the exposure of catla thymus macrophages (CTM) to A. hydrophila markedly induced cellular injuries as evidenced by elevated levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), increased apoptosis, DNA damage and decreased cellular viability. Flow cytometry analysis and Annexin-V/propidium iodide assay further confirmed increased ROS positive cells leading to cell death after infection. The quantitative real-time PCR analysis, also revealed upregulation of inducible nitric-oxide synthase (iNOS), pro-inflammatory cytokine (TNFα), cyclooxygenase2 (COX-2) and downregulation of anti-inflammatory cytokine (IL-10). Pretreatment of cells with probiotic, Lactobacillus acidophilus attenuated A. hydrophila induced apoptosis as evident from the decrease in the levels of ROS, RNS and DNA damage. Significant increase (P≤0.05) in expression of TNFα and IL-10 and decrease in iNOS and COX-2 was observed on probiotic stimulation. In-vivo study using catla fingerlings confirmed similar pattern of ROS, iNOS, NO production and cytokine expression in thymus. This study provides a comprehensive insight into the mechanistic basis of L. acidophilus induced macrophage mediated inflammatory response against A. hydrophila in CTM cells. Further, it speculates the possibility of using cost-effective in-vitro models for screening probiotic candidates of therapeutic potential in aquaculture industry.


Circulatory effects of tazolol in experimental myocardial infarction.
The hemodynamic effects of tazolol, a new long-acting beta-stimulating drug, were studied in dogs with acute pump failure caused by experimental myocardial infarction and the results were compared with the actions of isoproterenol given in small and large doses. Tazolol produced a significant and sustained increase in cardiac output and stroke volume, while causing a decrease in peripheral resistance and mean aortic pressure. Heart rate was only modestly increased. Compared with isoproterenol at equivalent doses. tazolol appeared to cause less S-T segment elevation at the margin of infarction. The increase in double product (systolic pressure X heart rate) produced by tazolol was also considerably less than that of isoproterenol. Tazolol may prove to be a useful addition to the drugs available for the treatment of myocardial failure of various causes. It is now being studied in patients with heart failure due to coronary artery disease.


ELK1/KIFC1 axis promotes breast cancer cell proliferation by regulating glutathione metabolism.
KIFC1 exerts an important function in centrosome aggregation in breast cancer (BC) cells and a variety of other cancer cells, but its potential mechanisms in BC pathogenesis are yet fully elucidated. The aim of this study was to investigate the effects of KIFC1 on BC progression and its underlying mechanisms. Expression of ELK1 and KIFC1 in BC was analyzed by The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction. Cell proliferative capacity was examined by CCK-8 and colony formation assays, respectively. Glutathione (GSH)/glutathione disulfide (GSSG) ratio and GSH level were measured using the kit. Expression of GSH metabolism-related enzymes (G6PD, GCLM, and GCLC) was detected by western blot. Intracellular reactive oxygen species (ROS) levels were measured by the ROS Assay Kit. The transcription factor ELK1 upstream of KIFC1 was identified by hTFtarget, KnockTFv2 database and Pearson correlation. Their interaction was validated by dual-luciferase reporter assay and chromatin immunoprecipitation. This study demonstrated the upregulation of ELK1 and KIFC1 in BC and found that ELK1 could bind to the KIFC1 promoter to promote KIFC1 transcription. KIFC1 overexpression increased cell proliferation and intracellular GSH levels, while decreasing intracellular ROS levels. The addition of the GSH metabolism inhibitor BSO attenuated the promotion of BC cell proliferation induced by KIFC1 overexpression. In addition, KIFC1 overexpression reversed the inhibitory effect of knockdown of ELK1 on BC cell proliferation. ELK1 was a transcriptional factor of KIFC1. ELK1/KIFC1 axis reduced ROS level by increasing GSH synthesis, thus facilitating BC cell proliferation. Current observations suggest that ELK1/ KIFC1 may be a potential therapeutic target for BC treatment.


Folding or holding?-Hsp70 and Hsp90 chaperoning of misfolded proteins in neurodegenerative disease.
The toxic accumulation of misfolded proteins as inclusions, fibrils, or aggregates is a hallmark of many neurodegenerative diseases. However, how molecular chaperones, such as heat shock protein 70 kDa (Hsp70) and heat shock protein 90 kDa (Hsp90), defend cells against the accumulation of misfolded proteins remains unclear. The ATP-dependent foldase function of both Hsp70 and Hsp90 actively transitions misfolded proteins back to their native conformation. By contrast, the ATP-independent holdase function of Hsp70 and Hsp90 prevents the accumulation of misfolded proteins. Foldase and holdase functions can protect against the toxicity associated with protein misfolding, yet we are only beginning to understand the mechanisms through which they modulate neurodegeneration. This review compares recent structural findings regarding the binding of Hsp90 to misfolded and intrinsically disordered proteins, such as tau, α-synuclein, and Tar DNA-binding protein 43. We propose that Hsp90 and Hsp70 interact with these proteins through an extended and dynamic interface that spans the surface of multiple domains of the chaperone proteins. This contrasts with many other Hsp90-client protein interactions for which only a single bound conformation of Hsp90 is proposed. The dynamic nature of these multidomain interactions allows for polymorphic binding of multiple conformations to vast regions of Hsp90. The holdase functions of Hsp70 and Hsp90 may thus allow neuronal cells to modulate misfolded proteins more efficiently by reducing the long-term ATP running costs of the chaperone budget. However, it remains unclear whether holdase functions protect cells by preventing aggregate formation or can increase neurotoxicity by inadvertently stabilizing deleterious oligomers.


Validity and reliability of the Urdu version of the 5D itching scale to assess pruritus among patients with chronic kidney disease in Pakistan.
Chronic kidney disease (CKD) has become a major public health issue worldwide in the past few years. Pruritus is a common, well-recognized complication often seen in patients with chronic renal failure. For assessment of pruritus, different tools are used but these tools are unable to identify the changes and variations in the severity of pruritus. The aim of our study was to validate the Urdu-version of the Urdu-version of the 5D itch scale among patients suffering from chronic kidney disease in Pakistan. The 5D itch scale was translated from English into Urdu following translation guidelines for translation. Face and content validity was determined by a panel of experts and piloted. For retest, the Urdu version of the 5D itch scale was administered at baseline and two weeks. A total of 50 participants with end stage renal disease were recruited, and of these, 64% were males. Exploratory factor analysis revealed that the 5D-IS had 2-factor loadings: "Pattern and activity" and "Distribution" with Kaiser-Mayer-Olkin (KMO) = 0.802, Bartlett's test of sphericity was significant (df = 28, p < 0.001). At test re-test, Cronbach's alpha was 0.914, while the intra class correlation was 0.9160 (95% confidence interval 0.941-0.975), which is a highly significant correlation (p < 0.0001). The Urdu version of the 5D itch scale was found to be a valid and reliable instrument for assessing pruritus and its severity in patients with chronic kidney disease in Pakistan.


Involvement of Cyr61 in growth, migration, and metastasis of prostate cancer cells.
Cyr61 has been reported to participate in the development and progression of various cancers; however, its role in prostate cancer (PCa) still remains poorly understood. In this study, we explored the function of Cyr61 in a series of malignant PCa cell lines, including LnCap, Du145, and PC3. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assays demonstrated that Cyr61 was essential for the proliferation of PCa cells. Soft agar assay and xenograft analysis showed that downregulation of Cyr61 suppressed the tumorigenicity of Du145 cells both in vitro and in vivo. Either silencing the cellular Cyr61 by RNA interference or neutralising the endogenous Cyr61 by antibody inhibited the migration of Du145 cells. In contrast, purified protein of Cyr61 promoted the migration of LnCap cells in a dose-dependent manner. These results suggested that Cyr61 was involved in the migration of PCa cells. We also observed the accumulation of mature focal adhesion complexes associated with the impaired migration through Cyr61 downregulation. Also, further studies showed that Cyr61 regulated the level of activated Rac1 as well as its downstream targets, including phosphorylated JNK, E-cadherin, and p27(kip1), which are key molecules involved in cell growth, migration, and invasion. The in vivo mouse tail vein injection experiment revealed that Cyr61 affected the metastatic capacity of Du145 cells, suggesting that Cyr61 was required for prostate tumour metastasis. Altogether, our results demonstrated that Cyr61 played an important role in the tumorigenicity and metastasis of PCa cells, which will benefit the development of therapeutic strategy for PCas.


A broadly applicable cross-linker for aliphatic polymers containing C-H bonds.
Addition of molecular cross-links to polymers increases mechanical strength and improves corrosion resistance. However, it remains challenging to install cross-links in low-functionality macromolecules in a well-controlled manner. Typically, high-energy processes are required to generate highly reactive radicals in situ, allowing only limited control over the degree and type of cross-link. We rationally designed a bis-diazirine molecule whose decomposition into carbenes under mild and controllable conditions enables the cross-linking of essentially any organic polymer through double C-H activation. The utility of this molecule as a cross-linker was demonstrated for several diverse polymer substrates (including polypropylene, a low-functionality polymer of long-standing challenge to the field) and in applications including adhesion of low-surface-energy materials and the strengthening of polyethylene fabric.


Effects of age and spectral shaping on perception and neural representation of stop consonant stimuli.
To determine if (1) aging affects neural representation of a dynamic spectral speech cue and (2) spectrally-shaped gain applied to the cue reduces any aging effects. Psychometric functions and cortical evoked responses were compared in young and older listeners with normal hearing. Stimuli were consonant-vowels along a /bdg/ place-of-articulation continuum in an unshaped and shaped condition. Shaped stimuli enhanced audibility of the F2 formant transition relative to the rest of the stimulus. Compared with younger listeners, older listeners had larger /d/ categories, longer P2 latencies, and larger N1 amplitudes to unshaped stimuli. To shaped stimuli, older listeners had /d/ categories and P2 latencies more similar to those measured from younger listeners, while N1 amplitudes were larger. Aging significantly affects the processing of dynamic spectral information. For some measures, differences due to aging were minimized with spectrally-shaped stimuli. Aging reduces neural responsiveness to dynamic spectral cues. If the cue is enhanced, neural responsiveness is increased and perceptual measures are more like those from the younger listeners for some stimuli. This suggests that aging may decrease responsiveness of intact neurons as opposed to destroying neurons and/or distorting spectral coding.


Per-O-methylation reaction for structural analysis of carbohydrates by mass spectrometry.
Per-O-methylation of carbohydrates is an important sample preparation step in structural analysis of complex carbohydrates, which has generated considerable interest as shown by thousands of citations in the last 10 years. This article provides a critical overview of the per-O-methylation methods applied for structural analysis of carbohydrates by mass spectrometry. The understanding of the O-methylation mechanism can help the researchers to apply the adequate O-methylation method and can generate new ideas in the effort of improving this reaction. The per-O-methylation of carbohydrates is relied upon stepwise reactions. The parameters that affect the reaction are discussed for the most important methods and are critically commented for each reaction step. The limits of each method are emphasized. The improvements of the per-O-methylation reaction are described in detail with their advantages and disadvantages and some illustrative examples are given. The methods that give complete O-methylation in non-hazardous conditions with high yields within minutes at room temperature with a very low amount of side-products are especially highlighted.


Adult case of giant sacrococcygeal teratoma: case report.
Sacrococcygeal teratomas are tumors originating from pluripotent embryonic germ cell layers located in the fetal coccyx. These tumors are highly vascular if they undergo malignant transformation. Typically, they are found in infants and children and occasionally can be diagnosed prenatally. Adult cases are very rare, and represent tumors present since birth with delayed detection. We describe a case of a giant sacrococcygeal teratoma in a 25 years old female college student presenting with right gluteal swelling of 4 months' duration. In addition to the huge disfiguring mass on the perineal area, she also had lower abdominal pain, urinary complaints, and difficulty with ambulation. Pre-operative impression was of a sacrococcygeal mass and histopathology following complete surgical excision revealed a sacrococcygeal teratoma. She recovered well after surgery with no radiologic evidence of recurrence at six months. Although rare, sacrococcygeal teratoma should be considered as a differential diagnosis for female adults presenting with perineal and/or pelvic masses. Complete surgical excision remains the mainstay of treatment.


Use of an intravaginal spacer in young girls treated with brachytherapy for bladder neck rhabdomyosarcoma: Dosimetric impact for organs at risk sparing and acute tolerance.
Interstitial brachytherapy is indicated as part of a conservative strategy for children with bladder and/or prostate rhabdomyosarcoma (RMS), providing high local control probability with acceptable functional results. Vaginal and/or rectal complications were however reported, due to the close proximity to the implanted volume. We investigated the dosimetric impact of a vaginal spacer in terms of rectal and vaginal doses. Medical records of 12 consecutive female patients with bladder neck RMS, median age 32 months (range: 1.3-6 years), were reviewed. Five patients were treated prior to 2017 without a vaginal spacer and seven patients treated after 2017 had their brachytherapy delivered with a vaginal spacer placed at time of implant. Minimal doses delivered to the most exposed 2cm3, 1cm3, and 0.5cm3 of the rectum were all statistically significantly lower among patients treated with a vaginal spacer, as compared to those treated without a spacer. Median rectal D2cm3 was 22GyEQD2 versus 38GyEQD2 (P=0.02), D1cm3 was 29GyEQD2 versus 51GyEQD2 (P=0.013), and D0.5cm3 was 32GyEQD2 versus 61GyEQD2 (P=0.017), with and without the vaginal spacer, respectively. The posterior vaginal wall D0.5cm3 dose was also significantly decreased, with median D0.5cm3 of 92GyEQD2 versus 54GyEQD2 (P<0.0001), with and without the spacer, respectively. Acute tolerance was excellent in all patients, with no need for replanning and no acute complication. The use of vaginal spacers in brachytherapy of female pediatric patients with bladder neck RMS resulted in significantly decreased doses to the rectum and the posterior vaginal wall. Though the clinical impact of such dose reduction remains undemonstrated, routine utilization of a vaginal spacer could be a method to decrease long-term morbidity in these patients.


Single and combined toxicity effects of nanoplastics and bisphenol F on submerged the macrophyte Hydrilla verticillata.
Nano- and microplastics pose severe risks to the ecological environment. Nanoplastics (NPs) not only directly affect aquatic organisms, but also adsorb to other pollutants, resulting in compound pollution. Bisphenol F (BPF), an endocrine-disrupting chemical, is increasingly replacing bisphenol A (BPA) and is therefore widely distributed in the environment. In this study, the toxic effects of polystyrene nanoplastics (PS-NPs) and BPF and their combined exposure on the submerged macrophytes Hydrilla verticillata (H. verticillata) and leaf biofilms, were investigated. Results showed that 10 mg/L PS-NPs and combined exposure to 10 mg/L PS-NPs and 10 mg/L BPF significantly decreased the relative growth rate and chlorophyll content of H. verticillata, whereas BPF exposure alone had no impact on the growth and the contents of photosynthetic pigments in H. verticillata. Individual and combined exposure to PS-NPs and BPF can trigger antioxidant responses such as increased activities of superoxide dismutase, peroxidase, and malondialdehyde, as well as higher levels of glutathione S-transferase and glutathione and decreased catalase activity. The results of the scanning electron microscopy (SEM) showed that the nanoplastics particles were adsorbed on the surface of plant leaves, explaining their toxic effects, whereas BPF increases the sorption of PS-NPs on the surface of H. verticillata, potentially leading to PS-NPs enrichment in the food chain. The diversity and richness of the microbial community were altered by exposure to PS-NPs and BPF individually and in combination. The current study is the first to assess the effects of PS-NPs and BPF exposure on the growth, physiological characteristics, and leaf biofilm properties of submerged macrophytes.


Associations between quality of life, coping styles, optimism, and anxiety and depression in pretreatment patients with head and neck cancer.
Head and neck cancer is often diagnosed at a late stage and consequently radical treatment is necessary. The pretreatment phase is a time of high anxiety and depression for patients. This study aimed to investigate whether anxiety and depression are related to quality of life, coping styles, and dispositional optimism. One hundred and three patients were recruited after diagnosis to a questionnaire study. Measures included the Hospital Anxiety and Depression Scale; SF12v2 Health Survey; Brief COPE, and the Revised Life Orientation Test. Quality of life, in particular emotional role explained a large proportion of the variance in pretreatment anxiety and depression. In addition, the use of negative coping styles was related to high anxiety levels and low levels of optimism were related to higher levels of depression. There are a small but significant proportion of pretreatment patients that may benefit from individualized support.


Melatonin and its possible role in mediating seasonal metabolic changes of Antarctic krill, Euphausia superba.
Melatonin, the chief secretory product of the vertebrate pineal gland is suspected to be a ubiquitous molecule principally involved in the transduction of photoperiodic information. Besides vertebrates, melatonin has been detected throughout phylogeny in numerous non-vertebrate taxa. In the present study, the occurrence of melatonin in Antarctic krill Euphausia superba and its possible role in mediating seasonal metabolic changes was evaluated. Melatonin was quantified by enzyme linked immunosorbent assay (ELISA) in high performance liquid chromatography (HPLC) purified extracts of eyestalks and hemolymph of krill sampled in the Lazarev Sea during the Antarctic winter and summer. In addition, oxygen uptake rates and the activities of the metabolic enzyme malate dehydrogenase (MDH) were recorded to assess the metabolic status of krill. Validation of melatonin measurements was carried out on the basis of three different extraction methods with parallel determination of melatonin by ELISA in crude extracts and in HPLC purified extracts, and after derivatization of melatonin under alkaline conditions in the presence of hydrogen peroxide. A significantly higher respiration rate and MDH activity was found in summer krill than in winter krill indicating that krill was in a state of reduced metabolic activity during winter. However, neither during winter nor during summer there were detectable melatonin concentrations in the visual system or hemolymph of krill. Based on these results, we question a mediating role of melatonin in the control of seasonal metabolic changes in Antarctic krill.


Three-dimensional modeling of the mitral valve for surgical planning in a pediatric patient: A case-based discussion of the technical challenges of segmentation and printing from 3D transthoracic echocardiographic datasets.
Abnormal atrioventricular valve present great challenges to the surgeon in achieving a successful repair, and thus present a great opportunity for enhanced 3D imaging to guide pre- and intra-operative management. Spatial and temporal resolution of 3D echocardiography enables 3D printing of valve morphology. However, non-linearity, angle dependence, speckle, blur, and resampling complicate segmentation compared to computed tomography (CT) and magnetic resonance imaging (MRI). A case of complex mitral valve disease in a pediatric patient is therefore presented to illustrate the technical challenges of segmentation and 3D printing from echocardiographic data.


Development of natamycin-loaded zein-casein composite nanoparticles by a pH-driven method and application to postharvest fungal control on peach against Monilinia fructicola.
This work fabricated natamycin-loaded zein-casein nanoparticles (N-Z/C NPs) by a pH-driven approach and applied to control postharvest peach brown rot caused by Monilinia fructicola. When casein and phosphoric acid were used as a stabilizer and neutralizing acid, respectively, NPs with mean particle sizes < 100 nm and zeta-potentials < -30 mV could be obtained. The NPs could increase the aqueous dispersibility of natamycin and showed high stability against environmental changes, which could be attributed to both hydrophobic stacking and hydrogen bonds between natamycin and zein. Besides, the effects of N-Z/C NPs on the storage of peach were assessed in vitro and in vivo. Nanoencapsulation did not affect the antifungal activities of natamycin. The NPs with 20 and 80 µg/mL of natamycin could basically inhibit the spore germination and mycelial growth of M. fructicola, respectively. The N-Z/C NPs coatings exhibited better results than natamycin in controlling of peach brown rot.


A crossover analysis of mandatory minute ventilation compared to synchronized intermittent mandatory ventilation in neonates.
Mandatory minute ventilation (MMV) is a novel ventilator mode that combines synchronized intermittent mandatory ventilation (SIMV) breaths with pressure-supported spontaneous breaths to maintain a desired minute volume. The SIMV rate is automatically adjusted to maintain minute ventilation. To evaluate MMV in a cohort of infants without parenchymal lung disease alternately ventilated by MMV and SIMV. Neonates >33 weeks' gestational age and electively intubated for medical or surgical procedures were enrolled. Exclusionary criteria included: nonintact respiratory drive or active pulmonary disease. Infants were randomized to receive 2 hours of either SIMV or MMV and then crossed over to the other mode for 2 hours. Ventilator parameters and end-tidal CO(2) (etCO(2)) were measured via inline, mainstream monitoring and recorded every minute. In total, 20 infants were evaluated. No statistically significant differences were found for overall means between etCO(2), minute volumes, peak inspiratory pressure (PIP), or positive end expiratory pressure (PEEP). However, there was a significant difference in the type of ventilator breaths given and in the mean airway pressure. Additionally, there was a statistically significant negative trend in MMV over time compared to SIMV, although this was subtle and could have been due to extreme cases. Neonates with an intact respiratory drive can be successfully managed with MMV without an increase in etCO(2). While this mode generates similar PIP and PEEP, the decrease in mechanical breaths and the mean airway pressure generated with MMV may reduce the risk of some of the long-term complications associated with mechanical ventilation.


Outcome quality standards for surgery of colorectal liver metastasis.
Liver metastases are the most common malignant solid liver lesions, approximately 40% of which stem from colorectal tumors. Liver resection is currently the only curative treatment for colorectal cancer liver metastases (CRLM). However, there is a lack of consensus criteria to assess the results of this treatment. In order to evaluate the quality of surgical outcomes, it is necessary to identify quality indicators (QIs) and their corresponding quality standards (QS). We propose a simple method to determine QI and QS in CRLM surgery (CRLMS) and establish acceptable quality limits (AQL) for each QI. A systematic review of CRLMS results published from 2006 to 2016. Clinical guidelines, consensus conferences, and publications related to the CRLMS were reviewed to identify and select QIs. Once selected, a new review of the papers including the results of at least one of the QIs was performed. Statistical process control (SPC) method was applied to calculate the QS and AQL of each QI. The limits of variability were established from mean and confidence intervals at 95% and 99.8%. The most relevant QIs and its AQLs were postoperative mortality (2%, < 4.5%), overall postoperative morbidity (33%, < 41%), liver failure (5%, < 8%), postoperative hemorrhage (1%, < 3%), biliary fistula (6%, < 10%), reoperation (3%, < 6%), R1 resection margins (18%, < 25%), and overall survival at 12 and 60 months (84%, > 77%; and 34%, > 25%, respectively). Despite its limitations, the present study constitutes the most extensive scientific evidence to date on QI and AQL in CRLMS and may constitute a reference in future studies.


Imaging stem-cell-driven regeneration in mammals.
The ability to observe biological processes continuously, instead of at discrete time points, holds great promise for the study of tissue regeneration. Ideally, single cells would be followed continuously within large tissue volumes (such as organs) over long periods of time. Technical limitations, however, preclude such studies. But, recently, there have been improvements in imaging technologies and biologically compatible labelling agents. Together with new insights into the molecular characteristics of stem cells, which are ultimately responsible for the regenerative potential of all tissues, researchers are now much closer to applying single-cell imaging approaches to research into regeneration and its clinical applications.


High-throughput and high-efficiency sample preparation for single-cell proteomics using a nested nanowell chip.
Global quantification of protein abundances in single cells could provide direct information on cellular phenotypes and complement transcriptomics measurements. However, single-cell proteomics is still immature and confronts many technical challenges. Herein we describe a nested nanoPOTS (N2) chip to improve protein recovery, operation robustness, and processing throughput for isobaric-labeling-based scProteomics workflow. The N2 chip reduces reaction volume to <30 nL and increases capacity to >240 single cells on a single microchip. The tandem mass tag (TMT) pooling step is simplified by adding a microliter droplet on the nested nanowells to combine labeled single-cell samples. In the analysis of ~100 individual cells from three different cell lines, we demonstrate that the N2 chip-based scProteomics platform can robustly quantify ~1500 proteins and reveal membrane protein markers. Our analyses also reveal low protein abundance variations, suggesting the single-cell proteome profiles are highly stable for the cells cultured under identical conditions.


Modelling of the natural chlorine cycling in a coniferous stand: implications for chlorine-36 behaviour in a contaminated forest environment.
Considered as one of the most available radionuclide in soil-plant system, ³⁶Cl is of potential concern for long-term management of radioactive wastes, due to its high mobility and its long half-life. To evaluate the risk of dispersion and accumulation of ³⁶Cl in the biosphere as a consequence of a potential contamination, there is a need for an appropriate understanding of the chlorine cycling dynamics in the ecosystems. To date, a small number of studies have investigated the chlorine transfer in the ecosystem including the transformation of chloride to organic chlorine but, to our knowledge, none have modelled this cycle. In this study, a model involving inorganic as well as organic pools in soils has been developed and parameterised to describe the biogeochemical fate of chlorine in a pine forest. The model has been evaluated for stable chlorine by performing a range of sensitivity analyses and by comparing the simulated to the observed values. Finally a range of contamination scenarios, which differ in terms of external supply, exposure time and source, has been simulated to estimate the possible accumulation of ³⁶Cl within the different compartments of the coniferous stand. The sensitivity study supports the relevancy of the model and its compartments, and has highlighted the chlorine transfers affecting the most the residence time of chlorine in the stand. Compared to observations, the model simulates realistic values for the chlorine content within the different forest compartments. For both atmospheric and underground contamination scenarios most of the chlorine can be found in its organic form in the soil. However, in case of an underground source, about two times less chlorine accumulates in the system and proportionally more chlorine leaves the system through drainage than through volatilisation.


An efficient route to alkyl chlorides from alcohols using the complex TCT/DMF.
[reaction: see text] Efficient conversion of alcohols and beta-amino alcohols to the corresponding chlorides (and bromides) can be carried out at room temperature in methylene chloride, using 2,4,6-trichloro[1,3,5]triazine and N,N-dimethyl formamide. This procedure can also be applied to optically active carbinols.


'Neurosecretion' by aminergic synaptic terminals in vivo--a study of secretory granule exocytosis in the corpus cardiacum of the flying locust.
Most nerve terminals forming typical synaptic junctions contain both synaptic vesicles and larger 'secretory granules' with electron-dense contents. Visualization of granule exocytosis from within terminals in the corpus cardiacum is facilitated by injection of tannic acid which immobilizes granule cores as they are discharged. The process of discharge is stimulated by flight-induced activation of the neurones and there is a correlated response by the innervated cells. In contrast to synapses with their vesicle clusters, granule discharge is not targeted upon the postsynaptic cells. These findings have general implications for mechanisms of discharge of neuropeptides and other transmitters from synaptic terminals.


Development of a sequential injection anodic stripping voltammetry (SI-ASV) method for determination of Cd(II), Pb(II) and Cu(II) in wastewater samples from coatings industry.
This paper describes the development and validation of a sequential injection (SI) anodic stripping voltammetry (ASV) method using the hanging mercury drop electrode for accumulation of the heavy metal cations Cu(II), Pb(II) and Cd(II). The method was applied to wastewater samples after proper acid digestion in open vessels to eliminate matrix effects. For a deposition time of 90 s at the flow rate of 10 microl s(-1), the detection limits of the method were 0.06, 0.09 and 0.16 micromol L(-1) for Cd, Pb and Cu, respectively. Under these conditions the linear dynamic range was between 0.20 and 9.0 micromol L(-1) and the sampling frequency was 30 analyses per hour. The relative standard deviation of the method was 3%(n=7) at the concentration level of 2.0 micromol L(-1). The accuracy of the method was evaluated by spiking the samples with known amounts of the metal cations, and by comparison with an independent analytical technique, the inductively coupled plasma atomic emission spectroscopy (ICP-AES). Average recoveries were around of 84%, and the results showed no evidence of systematic errors in comparison to the ICP-AES.


Affinity cryogel monoliths for screening for optimal separation conditions and chromatographic separation of cells.
Suitable conditions for separating cells using a chromatographic procedure were evaluated in parallel chromatography on minicolumns. A 96-hole minicolumn plate filled with cryogel monoliths (18.8 mm x 7.1 mm Ø) with immobilized concanavalin A was used. Chromatographic columns (113 mm x 7.1 mm Ø) were used for chromatographic resolution of a mixture of Saccharomyces cerevisiae and Escherichia coli cells. Separation of a cell mixture containing equal amounts of cells of both types performed in a column format under the determined optimal conditions, resulted in a quantitative capture of applied S. cerevisiae cells, while E. coli passed through the column. Bound S. cerevisiae cells were released by flow-induced detachment and by compression of the adsorbent in the presence of 0.3 M methyl alpha-D-manno-pyranoside. The flowthrough and the eluted fractions were analyzed by plate counting and by registering metabolic activity of S. cerevisiae cells in the eluted fractions after capturing on ConA-cryogel monoliths in a 96-minicolumn plate format. The flowthrough fraction contained E. coli cells with nearly 100% purity, whereas the fraction eluted by compression of the adsorbent contained viable S. cerevisiae cells with 95% purity. Thus, an efficient chromatographic separation of cells was achieved using affinity cryogel column.


Refractory hepatic hydrothorax is associated with increased mortality with death occurring at lower MELD-Na compared to cirrhosis and refractory ascites.
Although refractory hepatic hydrothorax (RH) is a serious complication of cirrhosis, waitlisted patients do not receive standardized MELD exemption because of inadequate evidence suggesting mortality above biochemical MELD. This study aimed to examine liver-related death (LRD) associated with RH compared to refractory ascites (RA). This was a retrospective cohort study of Veterans with cirrhosis. Eligibility criteria included participants with RH or RA, followed from their first therapeutic thoracentesis/second paracentesis until death or transplantation. The primary outcome was LRD with non-LRD or transplantation as competing risk. Of 2,552 patients with cirrhosis who underwent therapeutic thoracentesis/paracentesis, 177 met criteria for RH and 422 for RA. RH was associated with a significantly higher risk of LRD (aHR 4.63, 95% CI 3.31-6.48) than RA overall and within all MELD-Na strata (<10 aHR 4.08, 95% CI 2.30-7.24, 10-14.9 aHR 5.68, 95% CI 2.63-12.28, 15-24.9 aHR 4.14, 95% CI 2.34-7.34, ≥25 aHR 7.75, 95% CI 2.99-20.12). LRD was higher among participants requiring one (aHR 3.54, 95% CI 2.29-5.48), 2-3 (aHR 4.39, 95% CI 2.91-6.63), and ≥4 (aHR 7.89, 95% CI 4.82-12.93) thoracenteses relative to RA. Although participants with RH and RA had similar baseline MELD-Na, LRD occurred in RH versus RA at a lower MELD-Na (16.5 vs. 21.82, p=0.002) but higher MELD 3.0 (27.85 vs. 22.48, p<0.0001). RH was associated with higher risk of LRD than RA at equivalent MELD-Na. By contrast, MELD 3.0 may better predict risk of LRD in RH.


[Lactacidosis of the cerebrospinal fluid in apoplexy as indicator of prognosis (author's transl)].
Blood and CSF gases, as well as the level of lactate and pyruvate in blood and CSF were determined in 43 cases. of severe stroke with softening of the brain. It transpired that the CSF lactate level is the best prognostic indicator of survival. CSF values above 2,5 mMol/1 in apoplexy imply a very unfavourable prognosis. The CSF lactate level is also a very useful prognostic indicator in patients suffering from diabetes and/or uraemic metabolic disorders. As the determination of CSF lactate presents no tecnical difficulties and furnishes valuable prognostic information it would merit inclusion as a routine procedure in relevant cases.


Ethanol and heat-treated plasma fractionation methods in South Africa.
Modifications of the Cohn techniques are the methods of choice for the preparation fo dilute albumin (PPS) and gamma-globulin solutions on an industrial scale. For the manufacture of refined albumin solutions, however, considerable labour and material is saved if crude, ethanol-precipitated fractions are heated in the presence of stabilisers in order to purify the albumin. The technique is simple and cheap, and yields a safe product of high quality. Bacterially contaminated and highly haemoglobinized plasma can be successfully heat-treated.


Correction to: Substrate utilization and energy expenditure pattern in sepsis by indirect calorimetry.
An amendment to this paper has been published and can be accessed via the original article.


Comparison of the standard and the computerized versions of the Symptom Check List (SCL-90-R): a randomized trial.
The purpose of this study was to examine whether computer administration of the Symptom Check List (SCL-90-R) is equivalent to paper-and-pencil originals. 282 psychosomatic outpatients were randomly assigned to computer or paper-and-pencil conditions. Statistical equivalence tests were used to examine psychometric equivalence for the means. Reliabilities and correlations were compared for the two methods of administration. No systematic differences were observed in group means for most of the subscales. Subjects of the computer-administered group scored higher on the SCL-90-R subscale 'Obsessive-Compulsive' and 'Anger-Hostility' than the control subjects. Gender and administration mode interaction was observed for one subscale, while age and administration interaction was observed for another subscale. Using computer-administered tests makes administration and scoring of tests more efficient. The differences between the two administration modes were small, although noticeable. Further research is needed to determine whether computer environment, computer experience and age may influence the test results.


Histone acetyltransferase GCN5-mediated lysine acetylation modulates salt stress aadaption of Trichoderma.
Trichoderma viride has a wide range of applications in plant growth promotion, biological control, cellulase production, and biomass utilization. Salinity is a major limitation to Trichoderma strains in the natural environment and fermentation environment, and to improve the adaptability of Trichoderma to salt stress is of great significance to its applications in industry and agriculture. Histone acetylation plays important roles in the regulation of physiological and biochemical processes including various stress responses. GCN5 is the most representative histone acetylase, which plays vital roles in chromatin remodeling of promoters to facilitate the transcription activation. In this paper, we identified a GCN5-encoding gene TvGCN5 in T. viride Tv-1511, and characterized the function and regulating mechanism of TvGCN5-mediated acetylation of histone H3 in the salt adoption of Tv-1511, by constructions of the deletion mutants (Tv-1511-△GCN5) and overexpression mutants (Tv-1511-GCN5-OE) of TvGCN5. Results showed that compared with wild-type Tv-1511, the over-expression of TvGCN5 resulted in the longer mycelia diameter and more biomass under salt stress. Furthermore, Tv-1511-△GCN5 strains obtained the improved sodium (Na+) compartmentation and antioxidant capacity by upregulating the transcriptional levels of genes encoding PM H+-ATPase, vacuolar H+-ATPase, and antioxidant enzymes. Notably, the changes in the transcriptional expressions of these genes are tightly modulated by the TvGCN5-mediated acetylated level of histone H3 in their promoter regions. In all, these results reveal that TvGCN5 plays an important role in stress tolerance of T. viride Tv-1511, and provides potential insight to facilitate the application of epigenetic modulation in the expanding utilization of Trichoderma. KEY POINTS: • Overexpresison of TvGCN5 improves the adoption of T. viride Tv-1511 to salt stress by increasing acetylation level of histone H3 on the promoter regions of sodium-transport and antioxidant-related genes, at H3K9ac, H3K14ac, H3K23ac, and H3K27ac. • Overexprsison of TvGCN5 enhances the ion transport and compartmentation capacity by upregulating the expressions and activities of PM and vacuolar H+-ATPase to tolerate salt stress. • Overexprsison of TvGCN5 promotes the antioxidant capacity by increasing the expressions and activities of antioxidant enzymes in response to salt stress.


Full-time or part-time work in nursing: preferences, tradeoffs and choices.
Nursing human resources are limited; thus, effective deployment of personnel is essential to optimize staff capacity. The nursing profession competes for staff in environments where human capital is at a premium. To maximize recruitment and retention, it is imperative that nurses' work preferences be taken into account.


Experimental quantum simulation of superradiant phase transition beyond no-go theorem via antisqueezing.
The superradiant phase transition in thermal equilibrium is a fundamental concept bridging statistical physics and electrodynamics, which has never been observed in real physical systems since the first proposal in the 1970s. The existence of this phase transition in cavity quantum electrodynamics systems is still subject of ongoing debates due to the no-go theorem induced by the so-called A2 term. Moreover, experimental conditions to study this phase transition are hard to achieve with current accessible technology. Based on the platform of nuclear magnetic resonance, here we experimentally simulate the occurrence of an equilibrium superradiant phase transition beyond no-go theorem by introducing the antisqueezing effect. The mechanism relies on that the antisqueezing effect recovers the singularity of the ground state via exponentially enhancing the zero point fluctuation of system. The strongly entangled and squeezed Schrödinger cat states of spins are achieved experimentally in the superradiant phase, which may play an important role in fundamental tests of quantum theory and implementations of quantum metrology.


Association of lymph node metastases, grade and extent of mesenteric lymph node dissection in locoregional small intestinal neuroendocrine tumors with recurrence-free survival.
We aimed to assess the prognostic impact of tumor- and patient-related parameters in patients with stage I-III small intestinal neuroendocrine tumors (SI-NETs), who underwent locoregional resective surgery (LRS) with curative intent. We included 229 patients with stage I-III SI-NETs diagnosed from June 15, 1993, through March 8, 2021, identified using the SI-NET databases from five European referral centers. Mean ± SD age at baseline was 62.5 ± 13.6 years; 111/229 patients were women (49.3%). All tumors were well-differentiated; 160 were grade 1 (G1) tumors, 51 were G2, two were G3 and 18 tumors were of unspecified grade (median Ki-67: 2%, range 1%-50%). One-hundred and sixty-three patients (71.2%) had lymph node (LN) involvement. The median number of retrieved lymph nodes was 10 (0-63), whereas the median number of positive LNs was 2 (0-43). After a mean ± SD follow-up of 54.1 ± 64.1 months, 60 patients experienced disease recurrence at a median (range) of 36.2 (2.5-285.1) months. The 5- and 10-year recurrence-free survival (RFS) rates were 66.6% and 49.3% respectively. In univariable analysis, there was no difference in RFS and overall survival (OS) between LN-positive and LN-negative patients (log-rank, p = .380 and .198, respectively). However, in stage IIIb patients who underwent mesenteric lymph node dissection (MLND) with a minimum of five retrieved LN (n = 125), five or more LN metastases were associated with shorter RFS (median RFS [95% CI] = 107.4 [0-229.6] vs. 73.7 [35.3-112.1] months; log-rank, p = .048). In addition, patients with G2 tumors exhibited shorter RFS compared to patients with G1 tumors (median RFS [95% confidence interval (CI)] = 46.9 [36.4-57.3] vs. 120.7 [82.7-158.8] months; log-rank, p = .001). In multivariable Cox-regression RFS analysis in stage IIIb patients, the Ki-67 proliferation index (hazard ratio = 1.08, 95% CI = 1.035-1.131; p < .0001) and the number of LN metastases (hazard ratio = 1.06, 95% CI = 1.001-1.125; p = .047) were independent prognostic factors for RFS. In conclusion, LRS with a meticulous MLND and a minimum number of five harvested LNs appears to be critical in the surgical management of SI-NET patients with locoregional disease. In patients who underwent LRS and MLND, the Ki-67 proliferation index and the LN metastases count were independent predictors of RFS.


Is the social parasite Vespa dybowskii using chemical transparency to get her eggs accepted?
Both avian and insect cuckoos must trick their hosts into accepting foreign eggs. In birds this is achieved through egg mimicry. Within the hornets the only known social parasite is the rare Vespa dybowskii. We investigated how the V. dybowskii queen induces tens or hundreds of host workers to accept her eggs and offspring. Since hydrocarbons function as recognition cues in social insects, we investigated these compounds from the surface of eggs and workers of V. dybowskii, both host species (V. simillima and V. crabro) and an additional four non-host species. We found that chemical mimicry of the hosts' colony odour and their eggs normally associated with wasps was not being employed by V. dybowskii. Chemical insignificance is also unlikely as the amounts of hydrocarbons extracted from parasite, host and non-host eggs were similar. Eggs of V. dybowskii may survive in part due to being chemically transparent, as methyl-branched compounds only represent a tiny proportion (<1%) of the parasites hydrocarbon profile but a large proportion (26-41%) in both host species. However, the functions of various hydrocarbon groups need to be investigated in the hornets before this new acceptance mechanism of parasite eggs and adults is understood.


Clustering of mandibular organ-inhibiting hormone and moult-inhibiting hormone genes in the crab, Cancer pagurus, and implications for regulation of expression.
Development and reproduction of crustaceans is regulated by a combination of neuropeptide hormones, ecdysteroids (moulting hormones) and the isoprenoid, methyl farnesoate (MF), the unepoxidised analogue of insect juvenile hormone-III (JH-III). MF and the ecdysteroids are respectively synthesised under the negative control of the sinus gland-derived mandibular organ-inhibiting hormones (MO-IHs) and moult-inhibiting hormone (MIH) that are produced in eyestalk neural ganglia. Previous work has demonstrated the existence of two isoforms of MO-IH, called MO-IH-1 and -2, that differ by a single amino acid in the mature peptide and one in the putative signal peptide. To study the structural organisation of the crab MIH and MO-IH genes, a genomic DNA library was constructed from DNA of an individual female crab and screened with both MO-IH and MIH probes. The results from genomic Southern blot analysis and library screening indicated that the Cancer pagurus genome contains at least two copies of the MIH gene and three copies of the MO-IH genes. Upon screening, two types of overlapping genomic clone were isolated. Each member of one type of genomic clone contains a single copy of each of the convergently transcribed MO-IH-1 and MIH genes clustered within 6.5kb. The other type contains only the MO-IH-2 gene, which is not closely linked to an MIH gene. There are three exons and two introns in all MIH and MO-IH genes analysed. The exon-intron boundary of the crab MIH and MO-IH genes follows Chambon's rule (GT-AG) for the splice donor and acceptor sites. The first intron occurs within the signal peptide region and the second intron occurs in the coding region of the mature peptide. Sequence analysis of upstream regions of MO-IH and MIH genes showed that they contained promoter elements with characteristics similar to other eukaryotic genes. These included sequences with high degrees of similarity to the arthropod initiator, TATA box and cAMP response element binding protein. Additionally, putative CF1/USP and Broad Complex Z2 transcription factor elements were found in the upstream regions of MIH and MO-IH genes respectively. The implications of the presence of the latter two putative transcription factor binding-elements for control of expression of MIH and MO-IH genes is discussed. Phylogenetic analysis and gene organisation show that MO-IH and MIH genes are closely related. Their relationship suggests that they represent an example of evolutionary divergence of crustacean hormones.


Surface activity and structures of two fragments of the human antimicrobial LL-37.
Two fragments of the antimicrobial peptide LL-37 (LL-32 and LL-20) have been characterized in adsorption layers at the air/buffer interface by infrared reflection absorption spectroscopy (IRRAS) and X-ray reflectivity (XR) measurements. As shown in previous work, LL-32 exhibits an increased antimicrobial activity compared to LL-37, while LL-20 is almost not active. It is shown in this work that the peptides differ drastically in their surface activity (equilibrium adsorption pressure) and their secondary structure, when they are adsorbed to the air/buffer interface. As concluded from the CD spectra, both peptides are unstructured in bulk. That means that the adsorption of the peptides to the air/buffer interface is connected to a secondary structure change. While LL-32 transforms into an α-helix lying flat at the buffer surface, with a helix diameter of 17Å, LL-20 adopts a partly unstructured conformation. The dichroic ratio of LL-20 is reduced and the electron density profile shows the formation of a second layer. The ability of LL-32 to form a complete α-helical structure at the interface is in good agreement with its higher antimicrobial activity.


Sources of information during pregnancy and the early parenting period: Exploring the views of women and their partners.
There are a wide variety of information sources available during pregnancy and the early parenting period, but limited understanding of their usefulness, particularly for partners. We explored the views of both women and their partners regarding sources of information, their frequency of use, and their preferred formats. Data were collected as part of a large cluster randomised controlled trial at a tertiary maternity hospital in 2015-2016, in Melbourne, Australia. The overall evaluation was of a parenting kit ('Growing Together'), an evidence-based information source for prospective and new parents covering the period from conception until one year postpartum. This paper uses data collected from women when their baby was two months of age, and women's partners when the baby was six months of age, via postal or online survey. Women were eligible if they booked for pregnancy care at The Royal Women's Hospital during the recruitment period, were having their first baby, able to read and speak English without an interpreter, and <30 weeks pregnant at their first hospital appointment (n = 1034). All eligible women were included unless they opted out. In total 92 women were excluded. Of the women sent the two-month survey, 42% (392/941) responded. Partner surveys were returned by 252/791 partners (32%). Respondents received information from a range of sources, most frequently face to face from health professionals through childbirth education or midwife discussion/education, followed by friends and family members. Information received from a health professional was also reported as being the most useful. For both women and their partners, the most important factor related to information was that it was from a trusted and reliable source. Women and their partners highlighted the importance of quality and access to evidence based resources and information. The internet is frequently favoured by women and their partners due to its convenience, accessibility, and timely access to information. Overall, women and their partners reported information directly from a health care professional to be the most useful and health services should ensure that women and their partners have adequate access to their health care professional.


Prochymosin activation by non-aspartic proteinases.
Prochymosin can be converted into chymosin by an action of external proteinases. Thus, thermolysin at pH 5.05 converts calf prochymosin into active Phe-chymosin, which is one amino acid longer than chymosin from the N-terminus with a yield of 73%. Even better results were achieved with prochymosin activation by Legionella pneumophila metalloproteinase. Apparently the stretch of prochymosin polypeptide chain adjacent to the normally observed activation point becomes available for an attack by an external proteinase at pH 5.0-6.0. These data indicate that the intermolecular activation pathway might be of physiological importance.


[New data on the intervention of cyclic monophosphate in the cardiac automatogenous process].
We present here some new holistic titrations related to the demonstration of the intervention of threshold endogenous values of cAMP as a trigger biochemical factor of heart automatogenic function.


On the accuracy of unwarping techniques for the correction of susceptibility-induced geometric distortion in magnetic resonance Echo-planar images.
Rapid and efficient imaging of the brain to monitor brain activity and neural connectivity is performed through functional MRI and diffusion tensor imaging (DTI) using the Echo-planar imaging (EPI) sequence. An entire volume of the brain is imaged by EPI in a few seconds through the measurement of all k-space lines within one repetition time. However, this makes the sequence extremely sensitive to imperfections of magnetic field. In particular, the error caused by susceptibility induced magnetic field inhomogeneity accumulates over the duration of phase encoding, which in turn results in severe geometric distortion (warping) in EPI scans. EPI distortion correction through unwarping can be performed by field map based or image based techniques. However, due to the lack of ground truth it has been difficult to compare and validate different approaches. In this paper we propose a hybrid field map guided constrained deformable registration approach and compare it to field map based and image based unwarping approaches through a novel in-vivo validation framework which is based on the acquisition and alignment of EPI scans with different phase encoding directions. The quantitative evaluation results show that our hybrid approach of field map guided deformable registration to an undistorted T2-weighted image outperforms the other approaches.


Dynamic labelling of neural connections in multiple colours by trans-synaptic fluorescence complementation.
Determining the pattern of activity of individual connections within a neural circuit could provide insights into the computational processes that underlie brain function. Here, we develop new strategies to label active synapses by trans-synaptic fluorescence complementation in Drosophila. First, we demonstrate that a synaptobrevin-GRASP chimera functions as a powerful activity-dependent marker for synapses in vivo. Next, we create cyan and yellow variants, achieving activity-dependent, multi-colour fluorescence reconstitution across synapses (X-RASP). Our system allows for the first time retrospective labelling of synapses (rather than whole neurons) based on their activity, in multiple colours, in the same animal. As individual synapses often act as computational units in the brain, our method will promote the design of experiments that are not possible using existing techniques. Moreover, our strategies are easily adaptable to circuit mapping in any genetic system.


Interleukin-1 and neuronal injury.
Interleukin-1 is a pro-inflammatory cytokine that has numerous biological effects, including activation of many inflammatory processes (through activation of T cells, for example), induction of expression of acute-phase proteins, an important function in neuroimmune responses and direct effects on the brain itself. There is now extensive evidence to support the direct involvement of interleukin-1 in the neuronal injury that occurs in both acute and chronic neurodegenerative disorders. This article discusses the key evidence of a role for interleukin-1 in acute neurodegeneration - for example, stroke and brain trauma - and provides a rationale for targeting the interleukin-1 system as a therapeutic strategy.


A randomized controlled trial of the "positive diary" intervention for family caregivers of people with dementia.
We examined the effectiveness of the "positive diary," in which family caregivers of people with dementia write down three good things that happened with reasons at the end of each day. In this randomized controlled trial, the intervention group used the "positive diary," while the control group kept a record of each meal for 4 weeks. The intervention group showed improvement on several measures of wellbeing including Neuropsychiatric Inventory Questionnaire and Center for Epidemiologic Studies Depression Scale. The "positive diary" is a useful self-care tool for caregivers of people with dementia.


Suppression of BDNF-induced expression of neuropeptide Y (NPY) in cortical cultures by oxygen-glucose deprivation: a model system to study ischemic mechanisms in the perinatal brain.
The aim of this study was to establish a culture system that can serve as a model to study hypoxic-ischemic mechanisms regulating the functional expression of NPY neurons in the perinatal brain. Using an aggregate culture system derived from the rat fetal cortex, we defined the effects of oxygen and glucose deprivation on NPY expression, using BDNF-induced production of NPY as a functional criterion. NPY neurons exhibited a differential susceptibility to oxygen and glucose deprivation. Although the neurons could withstand oxygen deprivation for 16 hr, they were dramatically damaged by 8 hr of glucose deprivation and by 1-4 hr of deprivation of both oxygen and glucose (N+Glu-). One-hour exposure to N+Glu- led to a transient inhibition ( approximately 50%) of NPY production manifesting within 24 hr and recovering by 5 days thereafter, a 2-hr exposure to N+Glu- led to a sustained inhibition (50-75%) manifesting 1-5 days thereafter, and a 4-hr exposure to N+Glu- led to a total irreversible suppression of BDNF-induced production of NPY manifesting within 24 hr and lasting 8 days after re-supply of oxygen and glucose. Moreover, 1-hr exposure to N+Glu- led to a substantial and 4-hr exposure led to a total disappearance of immunostaining for MAP-2 and NPY but not for GFAP; indicating that neurons are the primary cell-type damaged by oxygen-glucose deprivation. Analysis of cell viability (LDH, MTT) indicated that progressive changes in cell integrity take place during the 4-hr exposure to N+Glu- followed by massive cell death 24 hr thereafter. Thus, we defined a culture system that can serve as a model to study mechanisms by which ischemic insult leads to suppression and eventually death of NPY neurons. Importantly, changes in NPY neurons can be integrated into the overall scheme of ischemic injury in the perinatal brain.


Chromosomal and genetic abnormalities in benign and malignant meningiomas using DNA microarray.
Meningioma is the commonest brain tumor and many genetic abnormalities, such as the loss of chromosome 22q and the mutation of NF2, have been reported. These classical abnormalities were detected using Southern blot, PCR, fluorescence in situ hybridization and comparative genomic hybridization, but these methods examine only very limited regions or limited mapping resolution of the tumor genome. In this study, we used DNA microarray assay, which detects numerous genetic abnormalities simultaneously and analyses a global assessment of molecular events in meningioma cells. We studied 31 meningiomas by GenoSensor Array 300 in order to detect the chromosomal aberrations and genetic abnormalities in the whole genome. This study demonstrated not only classical chromosomal aberration, such as loss of chromosome 22q in 19 meningiomas (61.3%), but also new genetic characteristics of meningiomas, such as amplification of MSH2 in 16 meningiomas (51.6%), deletion of GSCL in 13 meningiomas (41.9%) and deletion of HIRA in seven meningiomas (22.6%). These results suggest that DNA microarray assay is useful in research for the genetic characters of meningiomas and understanding tumorigenesis.


Chronic obstructive pulmonary disease in patients who have HIV infection.
An increased prevalence of chronic obstructive pulmonary disease (COPD) among persons who have HIV infection has raised the possibility that HIV may predispose to the development or progression of COPD. This article reviews the evidence that supports an association between HIV infection and COPD-namely emphysema and chronic bronchitis-and studies that suggest an association between HIV infection and small airways abnormalities and nonspecific airway hyper-responsiveness. Risk factors for COPD and potential reasons for an increased risk for COPD in HIV-positive patients are discussed. In addition, issues in the management of COPD in HIV-positive patients are reviewed.


Recycled aqueous ammonia expansion (RAAE) pretreatment to improve enzymatic digestibility of corn stalks.
A novel lignocellulose pretreatment method using aqueous ammonia for biofuel production was proposed in this study, which named recycled aqueous ammonia expansion (RAAE). Effects of temperature, pretreatment time, water to dry corn stalks loading and flow rate of aqueous ammonia on substrate enzymatic digestibility and sugar yield were investigated. Pretreatment temperature and time are important factors that affect RAAE process. Recirculation process could improve biomass digestibility and sugar yield compared with batch experiment. After RAAE pretreatment, about 70% of the lignin was removed, while more than 90% of the cellulose was preserved in the solids, the substrate crystallinity also increased because of the removal of amorphous portion. The maximum glucan enzymatic digestibility of pretreated biomass was 85.70%, which was obtained at 85°C, 11 min, 80% water to dry corn stalks loading and 1.5L/min aqueous ammonia flow rate.