Fixed-dose combination antidiabetic therapy: real-world factors associated with prescribing choices and relationship with patient satisfaction and compliance.
Compliance with antidiabetic therapy has the potential to impact on the risk for complications by an effect on glycemic control. Fixed-dose combinations (FDCs) offer a simplified dosing regimen that may improve patient compliance. We undertook a retrospective database analysis to understand the real-world association between FDCs, treatment practices, glycated hemoglobin (HbA(1c)) levels, and patient perspectives in type 2 diabetes. Data were drawn from the Adelphi Diabetes Disease Specific Programme (DSP), a multicenter, patient recordbased market research study of primary care physicians and diabetologists/endocrinologists in Europe. The study is based on physician interviews, completion of detailed patient record forms by physicians, and a self-completion questionnaire by patients. Regression analyses were used to identify factors associated with (1) physician-reported dipeptidyl peptidase-4 inhibitor (DPP-4)/metformin FDC prescribing in dual or triple therapy regimens; (2) HbA1c of patients prescribed a DPP-4 FDC alone versus free-form DPP-4 plus metformin dual therapy regimens; and (3) differences between patients prescribed any oral antidiabetic therapy (OAD) FDC therapy (alone or in combination with one other OAD) versus those prescribed dual or triple OAD free-form combination therapy. Physician-reported data were available for 5891 patients (mean age 61.5 years, 43% female, mean duration since diagnosis 5.7 years). Factors associated with DPP-4 FDC usage included physicians' reason for choice being "improves patient compliance." The relative mean % HbA(1c) level associated with being on a DPP-4 FDC rather than free-form independent of the physician perception of patient compliance was 0.25 lower (CI -0.40 to -0.09). When physician-perceived patient compliance was described as "fairly compliant" rather than "poorly compliant" or "not at all compliant," the relative mean % HbA1c level was 0.42 lower (CI -0.67 to -0.18). Similarly, being perceived as "fully compliant" rather than "fairly compliant" was associated with a relative mean % HbA(1c) level that was 0.17 lower (CI -0.31 to -0.02). A significant predictor for the current regimen being any FDC (alone or in combination with one other OAD) regimen was patients' satisfaction with treatment (odds ratio 1.32; 95% CI 1.10 to 1.58; P=0.003). These results suggest that DPP-4 FDC prescribing is considered to be a positive prescribing choice to improve compliance and that choice is associated with improved glycemic control. From the patient's perspective, the decision to prescribe an FDC is associated with improved satisfaction with treatment.


A sensitive determination of terbutaline in pharmaceuticals and urine samples using a composite electrode based on zirconium oxide nanoparticles.
An accurate and precise determination of terbutaline has been carried out using a glassy carbon electrode (GCE) modified with a composite of multi-walled carbon nanotubes (MWCNTs) and nanoparticles of zirconium oxide (ZrO2NPs). Energy dispersive X-ray and scanning electron microscopic techniques were utilized for the characterization of the composite layer. Terbutaline exhibited a broad oxidation peak at 770mV on a GCE. However, MWCNTs/GCE presented an electrocatalytic effect toward the oxidation of terbutaline with a better anodic peak at 660mV. Furthermore, the electrochemical behavior of terbutaline has greatly been improved at a GCE modified with a composite of MWCNTs and nanoparticles of ZrO2. The ZrO2NPs/MWCNTs/GCE exhibited a sharp anodic wave at 645mV with a large enhancement of the current response for terbutaline. Square wave voltammetry (SWV) was performed for the determination of terbutaline at ZrO2NPs/MWCNTs/GCE. A linear plot was obtained for the current responses of terbutaline against concentrations in the range of 10-160nM yielding a detection limit of 2.25nM (based on 3Sb/m). Improved voltammetric behavior, long-time stability and good reproducibility were obtained for terbutaline at the proposed electrode. A mean recovery of 101.2% with an RSD% of 1.9 was obtained for the analysis of the drug formulation. The accurate and precise quantification of terbutaline makes the ZrO2NPs/MWCNTs/GCE system of great interest for monitoring its therapeutic use.


Development and experimental verification of an ergonomic shopping bag handle.
Plastic shopping bags are used world over. However, users may suffer pain in or injury to their fingers because of the relatively thin plastic handles of those bags. Due to such drawbacks of the available bag handles, new designs are needed. The purpose of this study was to develop a handle that can be used to carry many bags simultaneously. This handle was ergonomically designed and manufactured with soft grip. Then, an experiment was performed to test the usefulness of the developed handle. The cardiac cost, discomfort ratings, activity levels of eight muscles, and peak plantar pressure (PPP) were the response variables in the experiment. The carrying style (with or without the handle), carrying method (dominant hand or both hands), and weight carried (5%, 10%, or 15% of the subject's body weight) were the independent variables in the experiment. Twenty-six healthy, young volunteers participated in the experiment. It was found that carrying grocery bags in both hands using the bag handle was preferable to the other carrying methods because it reduced the cardiac cost, muscular stress, PPP, and average discomfort ratings. The results of this study demonstrated that the developed shopping bag handle provides an ergonomic solution for carrying multiple heavy plastic bags.


Biases in read coverage demonstrated by interlaboratory and interplatform comparison of 117 mRNA and genome sequencing experiments.
High-throughput sequencing of whole genomes and transcriptomes allows one to generate large amounts of sequence data very rapidly and at a low cost. The goal of most mRNA sequencing studies is to perform the comparison of the expression level between different samples. However, given a broad variety of modern sequencing protocols, platforms and versions thereof, it is not clear to what extent the obtained results are consistent across platforms and laboratories. The comparison of 117 human mRNA and genome high-throughput sequencing experiments performed on the Illumina and SOLiD platforms at 26 institutions all over the world demonstrated high dependency of the gene coverage profiles on the producing laboratory. Gene coverage profiles showed laboratory-specific non-uniformity that survived the 3'-bias correction and mappability normalization, suggesting that there are other yet unknown mRNA-associated biases.


Stent thrombosis after primary percutaneous coronary intervention in comatose survivors of out-of-hospital cardiac arrest: Are the new P2Y12 inhibitors really more effective than clopidogrel?
High rates of stent thrombosis (ST) have been reported in patients with out-of-hospital cardiac arrest (OHCA) who require a primary percutaneous coronary intervention (PCI). The aim of this study was to assess risk factors of ST in this population with a special focus on antiplatelet therapy administered during the acute phase. We conducted a retrospective observational study in patients treated with primary PCI after OHCA between 2011 and 2013 in our center. All consecutive patients were treated with mild therapeutic hypothermia and dual antiplatelet therapy after primary angioplasty. A total of 101 consecutive patients were included in the present analysis. Mean age was 61.3 ± 12.7 years and 75% of patients had an initial ventricular fibrillation. All patients received aspirin before PCI. P2Y12 inhibitors were administered after PCI and included clopidogrel (47.5%), prasugrel (21.8%) or ticagrelor (29.7%). The survival rate at discharge was 44.5%. We identified 11 cases (10.9%) of definite or probable ST (clopidogrel (n=2), prasugrel (n=4) and ticagrelor (n=5)) occurring at a median of 2 days after PCI. No specific predictors were found to be significantly associated with ST. New P2Y12 inhibitors were associated with more ST compared to clopidogrel (17.3% vs. 4.2%; respectively, p=0.05). ST was associated with a decreased left ventricular ejection fraction (p=0.007) and with a trend toward a higher mortality compared to patients without ST (82% vs. 52%, p=0.06). The incidence of ST in OHCA survivors is high and associated with poor clinical outcome. The use of new oral P2Y12 inhibitors does not appear to be associated with a reduction in ST compared to clopidogrel.


Cropland nitrous oxide emissions exceed the emissions of RCP 2.6: A global spatial analysis.
Nitrous oxide (N2O), as a potent greenhouse gas, must be limited to prevent the global temperature increasing by >2 °C. Cropland is the largest source of anthropogenic N2O emissions; however, earlier estimates for emissions and their exceedances still remain uncertainties. Here, we used a spatially explicit model to estimate cropland N2O emission in 2014 by refined grid-level crop-specific EFs and considered the background emission. We also sought to determine where N2O emissions exceed the "boundary" through analysis of spatial data from representative concentration pathway (RCP) 2.6. The global cropland N2O emission was 2.92 ± 0.59 Tg N yr-1, which far exceeds the 0.82 Tg N yr-1 boundary, over 90 % of cropland areas exceeded the boundary. Western Europe, Southeastern China, Pakistan, and the Ganges Plain exceeded the boundary by >2 kg N ha-1 yr-1. The boundary exceedances showed a positive linear response with respect to total cropland emission and a quadratic response to GDP per capita at the country level. Our study highlights the necessity of accurate estimations of spatial variations in cropland N2O emissions and evaluation of exceedances, to facilitate the development of more effective mitigation measures in different regions.


[NSAID-use delays the diagnosis of 'acute abdomen'].
In three patients with abdominal pain, two men aged 63 and 18 years and a woman aged 46 years, the use of NSAIDs reduced the symptoms. They were in fact suffering from peritonitis due to gastrointestinal perforation, but the decision to operate was delayed because of the relatively mild presentation. The strong analgesic, antipyretic and anti-inflammatory properties of NSAIDs can reduce the symptoms, signs and laboratory findings of peritonitis.


Machine learning for genetics-based classification and treatment response prediction in cancer of unknown primary.
Cancer of unknown primary (CUP) is a type of cancer that cannot be traced back to its primary site and accounts for 3-5% of all cancers. Established targeted therapies are lacking for CUP, leading to generally poor outcomes. We developed OncoNPC, a machine-learning classifier trained on targeted next-generation sequencing (NGS) data from 36,445 tumors across 22 cancer types from three institutions. Oncology NGS-based primary cancer-type classifier (OncoNPC) achieved a weighted F1 score of 0.942 for high confidence predictions ([Formula: see text]) on held-out tumor samples, which made up 65.2% of all the held-out samples. When applied to 971 CUP tumors collected at the Dana-Farber Cancer Institute, OncoNPC predicted primary cancer types with high confidence in 41.2% of the tumors. OncoNPC also identified CUP subgroups with significantly higher polygenic germline risk for the predicted cancer types and with significantly different survival outcomes. Notably, patients with CUP who received first palliative intent treatments concordant with their OncoNPC-predicted cancers had significantly better outcomes (hazard ratio (HR) = 0.348; 95% confidence interval (CI) = 0.210-0.570; P = [Formula: see text]). Furthermore, OncoNPC enabled a 2.2-fold increase in patients with CUP who could have received genomically guided therapies. OncoNPC thus provides evidence of distinct CUP subgroups and offers the potential for clinical decision support for managing patients with CUP.


Finding a common core microbiota in two Brazilian dairies through culture and DNA metabarcoding studies.
Dairy foods are complex ecosystems composed of microorganisms from different origins that can affect flavor and safety of final products. The objective of this paper is to assess the in-house microbiota of two Brazilian dairies and to discuss the possible implications of the taxa determined for food protection. In total, 27 samples from dairies were cultured in selective (Baird Parker, de Man, Rogosa and Sharpe) and non-selective (Brain Heart Infusion) media, and the isolates were identified by Sanger sequencing. Moreover, metagenomic DNA was directly extracted from samples and the structure of the bacterial community was determined by massive DNA sequencing followed by bioinformatics analyses. The results showed the majority of isolates belonged to the group of lactic acid bacteria, but Enterobacteriaceae, Staphylococcacceae, Bacillaceae, Pseudomonadaceae and Moraxellaceae were also detected. From the reads obtained in metataxonomics analyses, a heatmap was constructed and the top 20 OTUs (operational taxonomic units) were determined. Besides, 12 most prevalent bacterial taxa were assigned to the core microbiota of the dairies evaluated, which included Thiomonas thermosulfata, Alkalibacillus salilacus, Pseudomonas clemancea, Erythrobacter aquimans, Tetragenococcus doogicus, Macrococcus brunensis, Pseudomonas ludensis, Streptococcus dentinousetti, Serratia entomophila, Vagococcus teuberi, Lactococcus fujiensis and Tolumonas auensis. In conclusion, the results reveal the presence of bacteria that may be related to spoilage and also foodborne diseases, in microbial niches that also present rare taxa, highlighting the importance to consider culture-independent results to evaluate and improve food safety.


Sandwich osteotomy of the atrophic posterior mandible with interpositional autogenous bone block graft compared with bone substitute material: a systematic review and meta-analysis.
The objective of the present systematic review was to test the hypothesis that there were no differences in outcome of implant treatment after sandwich osteotomy in the atrophic posterior mandible with interpositional autogenous bone block graft, compared with bone substitute material. A MEDLINE/PubMed, Embase and Cochrane Library search in combination with hand-search of selected journals was conducted. Two short-term randomised controlled trials with a split-mouth study design and low risk of bias fulfilled the inclusion criteria. High survival rate of suprastructures and implants was disclosed with no significant difference between interpositional autogenous bone block graft compared with bone substitute material. Meta-analysis revealed patient-based implant survival risk ratio of 1.05 (95% CI: 0.88 to 1.25) and peri-implant marginal bone loss of 0.31mm (95% CI: -0.29 to 0.90) indicating no significant differences between the two treatments. High implant stability values, gain in vertical alveolar ridge height, bone formation, and few complications were reported with both treatments. Sandwich osteotomy with interpositional grafting material appears to be a predictable surgical technique for enhancement of the vertical alveolar ridge height in the atrophic posterior mandible prior to implant placement.


From Conventional Angle Surgery to 360-Degree Trabeculotomy in Pediatric Glaucoma.
To describe the transition from conventional angle surgery (CAS), trabeculotomy with rigid probe or goniotomy, to 360-degree trabeculotomy assisted with microcatheter (MCT). Retrospective comparative interventional case series. Review of consecutive children with glaucoma undergoing angle surgery, including cases with previous surgery, from January 2012 until March 2018 at Moorfields Eye Hospital. Main outcome measure was success rate, defined as intraocular pressure (IOP) ≤21 mm Hg with a minimum of 20% of IOP reduction and no further glaucoma surgery (complete success: without the need of glaucoma drops; qualified success: drops were needed to keep the IOP under control). Among the 106 eyes (77 patients) included were 54 MCT and 52 CAS eyes. At last visit, after a single surgery, qualified success was 85% (46 eyes) in MCT and 37% (19 eyes) in CAS. Complete success was 69% (37 cases) in MCT and 23% (12 cases) in CAS. The mean (95% confidence interval) change in axial length after surgery was -0.03 mm (-0.34 to 0.40) for MCT and +1.35 mm (-0.64 to 1.62) for CAS (P < .001). The percentage of IOP reduction was 52.1% in MCT and 45.5% in CAS (P = .1616). Further glaucoma surgery was required in 5.5% (3) in MCT and 63.4% (33) in CAS. At 1 year, 94.3% of MCT cases achieved qualified success compared to 34.6% of CAS (P < .0001). No significant complications were found on either group. MCT achieved better results with significantly lower reoperation rates. The transition from CAS to MCT can be easily achieved, even in difficult cases or those previously operated.


Percutaneous endopyelotomy in infants and young children after failed open pyeloplasty.
We assessed the efficacy and safety of percutaneous endopyelotomy in infants and young children with secondary ureteropelvic junction obstruction after previous open pyeloplasty. Three boys and 2 girls with persistent ureteropelvic junction obstruction after open pyeloplasty underwent percutaneous antegrade cold knife endopyelotomy via an 18F nephrostomy tract. Percutaneous endopyelotomy was successfully performed in all 5 children with minimal complications. At a mean followup of 2.5 years endopyelotomy was successful in 4 of the 5 children based on the absence of symptoms, normal pressure-perfusion studies and normal or improved diuretic renal scintigraphy studies. One child in whom endopyelotomy failed underwent successful ureterocalicostomy. Percutaneous antegrade endopyelotomy is a safe and efficacious method of treating secondary ureteropelvic junction obstruction in children. This method offers a minimally invasive alternative to conventional repeat open pyeloplasty.


Identification, localization, and relative quantitation of pseudouridine in RNA by tandem mass spectrometry of hydrolysis products.
The constitutional isomers uridine (U) and pseudouridine (Ψ) cannot be distinguished from each other by simple mass measurements of RNA or its fragments because the conversion of U into Ψ is a "mass-silent" post-transcriptional modification. Here we propose a new mass spectrometry based method for identification, localization, and relative quantitation of Ψ in RNA consisting of ∼20 nucleotides that does not require chemical labeling. Our approach takes advantage of the different fragmentation behavior of uridine (N-glycosidic bond) and pseudouridine (C-glycosidic bond) residues in RNA upon collisionally activated dissociation.


Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide.
Covalent multistep coating of poly(methylpentene), the membrane material in lung ventilators, by using a copper-free "click" approach with a modified cyclic RGD peptide, leads to a highly biocompatible poly(methylpentene) surface. The resulting modified membrane preserves the required excellent gas-flow properties while being densely seeded with lung endothelial cells.


Protective HLA alleles against severe COVID-19: HLA-A*68 as an ancestral protection allele in Tapachula-Chiapas, Mexico.
HLA is a polymorphic antigen presenter which has provided valuable information on the susceptibility of populations to viruses. Therefore, the study of HLA can reveal specific susceptibility or resistance alleles to severe COVID-19 in an ethnically dependent manner. This pilot study investigated HLA alleles associated with COVID-19 severity in Tapachula, Chiapas, Mexico. A total of 146 Mexican Mestizos were typed for HLA class I and II using PCR-SSP. The patients were classified according to the outcome (death or improvement) and the infection's severity (mild or severe). In addition, a group of exposed uninfected individuals was included. HLA-A*68 was found to be a protective allele against the severe infection and fatal outcome; pC = 0.03, OR = 0.4, 95% CI =0.20-0.86, and pC =0.009, OR = 0.3, 95% CI =0.13-0.71 respectively. HLA-DRB1*03 also appears to be a protective factor against fatal outcome pC = 0.009, OR = 0.1, 95%IC = 0.01-0.66; however, the low frequency of this allele in the studied population limits the statistical power. The severity and fatal outcome of COVID-19 patients in Tapachula, Chiapas depend more on the lack of resistance than susceptibility HLA alleles.


[The use of nimodipine in comatose patients with different types of cerebrovascular pathology].
The authors report on the use of nimodipine in 36 patients for coma due to severe cerebral (20 haemorrhagic, 2 ischaemic, 9 post-anoxic, 4 traumatic, 1 neoplastic) lesions. In addition to resuscitative therapy, all patients were given nimodipine per os, 60 mg every 4 hrs for 21 days. In all patients, survival, duration of the coma and degree of disability, according G.O.S., were evaluated. Decrease of mortality was highly significant, decrease of disability of surviving patients was significant if compared with comatose patients suffering from similar diseases, but not treated with nimodipine.


Glial fibrillary acidic protein, vimentin and fibronectin in primary cultures of human glioma and fetal brain.
The expression of glial fibrillary acidic protein (GFAP), vimentin and fibronectin (Fn) was studied in cells cultured from human glioma and fetal brain by indirect immunofluorescence (IIF) microscopy and multiple labelling experiments. In the primary cultures a major part (20%-70%) of the cells usually displayed both GFAP and vimentin and the rest of the cells only vimentin. A prominent variation in GFAP and vimentin fluorescence intensity sometimes made interpretation of double IIF stainings difficult. However, occasional GFAP-positive cells appeared vimentin negative in primary glioma cultures, whereas in fetal brain primary cultures cells that were preferentially GFAP positive also showed at least a weak vimentin immunoreactivity. Only a fraction of the cells, roughly corresponding to the GFAP-negative cells, were Fn positive in the primary cultures. As judged by double IIF, the GFAP-positive cells were usually Fn negative, while the Fn-positive cells were vimentin positive. This could also be demonstrated in triple IIF experiments. During serial subcultivation the amount of cells expressing GFAP decreased, while the number of Fn-positive cells increased. By the third to fourth passage GFAP positivity was usually lost, all cells expressed vimentin and most cells also Fn. The results of the present study demonstrate a general coexpression of GFAP and vimentin in cultured astroglial cells, in addition to cells expressing only vimentin. Interestingly, occasional glioma cells seem to contain GFAP as the only intermediate filament protein as detected by immunocytochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)


Saponin rich fractions from Polygonatum odoratum (Mill.) Druce with more potential hypoglycemic effects.
The root of Polygonatum odoratum (YuZhu), also a medicinal food has long been used for the treatment of diabetes. The objective of the study was to characterize the anti-diabetic active fractions or compounds in this herb. Fractions with a different polarity were prepared by solvent extraction and macroporous absorptive resin (D101) column and their anti-diabetic potentials were evaluated by glucose uptake in HepG2 cells and STZ-induced diabetic rats. In addition, α-glycosidase inhibitory activities of active fractions were measured in vitro and chemical compositions including saponin, total flavonoids and total sugar in the fractions were determined. The n-buthanol fraction, a saponin-rich fraction obtained by partitioning the ethanol extract with n-buthanol after petroleum ether and acetic ether showed the highest anti-diabetic potential in glucose uptake in HepG2 cells followed by acetic ether fraction which was rich in flavonoids. Further fractionation the saponin-rich fraction using macroporous resin column (D101), polysaccharide, flavonoid and saponin rich fractions were obtained by elution with water, 40% and 60% ethanol, respectively and their anti-diabetic potentials proved by glucose uptake test in HepG2 cells and STZ-induced diabetic rats were in the order of saponin rich fraction>flavonoid rich fraction>polysaccharide rich fraction. Long-term therapy test (60d) in severe diabetic rats indicated that saponin-rich fraction significantly ameliorated clinical symptoms of diabetes including the elevated blood glucose, body weight loss as well as the increased food and water intake while flavonoid-rich fraction was more potential than saponin-rich fraction to increase superoxide dismutase (SOD) activity and decrease malondialdehyde (MDA) level in rat plasma. Additionally, saponin-rich fraction and flavonoid-rich fraction showed α-glycosidase inhibitory activity with IC(50) value of 2.05±0.32 and 3.92±0.65mg/ml, respectively. The results suggested that saponin in this herb was more important than flavonoid in exhibiting anti-diabetic activity and flavonoid contributed more to anti-oxidant activity in vivo.


Robotic radical hysterectomy versus open radical hysterectomy for cervical cancer: a single-centre experience from India.
To compare the disease-free survival (DFS) and overall survival (OS) at 3 years and 5 years in patients undergoing treatment for early-stage cervical cancer with either robotic (RRH) or open radical hysterectomy (ORH). This retrospective study compared all patients with stage IA1 (lymphovascular invasion), IA2, IB1, IB2 and II A cervical cancer in accordance with International Federation of Gynaecology and Obstetrics staging (FIGO 2009) of cancer of the cervix uteri. Patients who underwent Radical Hysterectomy at our centre from January 2011 till January 2018 were included in the study. One hundred and eighty-nine patients ( ORH = 67, RRH = 122) were included. The median follow-up time was 46.3 months in RRH group and 70.0 months in the ORH group. The 3-year DFS was comparable in both the arms, 91.5% in RRH and 91.6% in ORH. The 5-year DFS was 88.9% and 85.9% in robotic and open approaches, respectively (P = 0.258), hazard ratio (HR) 0.616 (CI = 0.266-1.427). The 3-year overall survival for robotic approach was 93.4% and for open was 95%, whereas 5-year overall survival was 84.7% and 87.4% in robotic and open approaches, respectively (P = 0.813). The median estimated blood loss for robotics was lower (100 ml vs 300 ml, P < 0.001) and median operative time was less (162.5 min vs. 180 min, P = 0.005) in robotics. The patients in RRH cohort had shorter median hospital stay (3.9 days vs. 6.3 days, P < 0.001). Robotic radical hysterectomy had comparable survival outcomes to open radical hysterectomy in cancer cervix. RRH is associated with improved peri-operative surgical outcomes and better resource utilisation.


Characterization of prokineticin system in Crohn's disease pathophysiology and pain, and its modulation by alcohol abuse: A preclinical study.
Crohn's disease-(CD) pathogenesis is still unknown and chronic pain is a frequent symptom in CD-patients. Identifying novel therapeutic targets and predisposing factors is a primary goal. In this regard, prokineticin system-(PKS) appears a promising target. TNBS-model was used. DAI, abdominal and visceral pain, and muscle strength were monitored. CD-mice were sacrificed at two times (day 7 and 14 after TNBS) in order to identify PKS involvement in CD pathophysiology and pain. PKS characterization was performed in mesenteric lymph nodes-(MLN), colon, myenteric plexus-(MP), dorsal root ganglia-(DRGs) and spinal cord-(SC). Inflammation/neuroinflammation was also assessed in the same tissues. In order to evaluate alcohol abuse as a possible trigger for CD and its effect on PKS activation, naïve mice were administered (oral-gavage) with ethanol for 10 consecutive days. PKS as well as inflammation/neuroinflammation were evaluated in MLN, colon and MP. TNBS treated-mice showed a rapid increase in DAI, abdominal/visceral hypersensitivity and a progressive strength loss. In all tissue analysed of CD-mice, a quick and significant increase of mRNA of PKs and PKRs was observed, associated with an increase of pro-inflammatory cytokines (IL-1β, IL-6 and TNFα) and macrophage/glia markers (iba1, CD11b and GFAP) levels. In alcohol abuse model, ethanol induced in colon and MP a significant PKS activation accompanied by inflammation/neuroinflammation. We can assume that PKS may be involved in CD development and pain. Furthermore, alcohol appears to activate PKS and may be a trigger factor for CD.


Age-related characteristics of brain development in children living in the north.
The morphofunctional age-related development of the brain was studied in schoolchildren living in the difficult climatological-geographic and socioeconomic conditions of the north (Arkhangel'sk region). Of the 62 students in country middle schools, EEG amplitude-frequency, time, and spatial measures corresponded to age norms (European norms) in only 10 cases (16%). A further 26 children (53%) showed minor abnormalities in the form of an inadequate degree of organization of the temporospatial EEG pattern, mainly in the frontal and temporal lobes of the brain, with increases in the levels of the theta and delta rhythms, and the absence of any marked "functional nucleus" in the alpha rhythm. In the remaining 14 children (29%), EEG measures showed more marked delays in mental development (DMD), which were combined with learning difficulties and abnormal behavior. The retardation in the morphofunctional development of the brain in northern children averaged 1.5-2 years, which coincides with delays in hormonal and physical development described by other authors.


Plant volatile ligands for male-biased MmedOBP14 stimulate orientation behavior of the parasitoid wasp Microplitis mediator.
As an important class of chemosensory-associated proteins, odorant binding proteins (OBPs) play a key role in the perception of olfactory signals for insects. Parasitoid wasp Microplitis mediator relies on its sensitive olfactory system to locate host larvae of Noctuidae and Geometridae. In the present study, MmedOBP14, a male-biased OBP in M. mediator, was functionally investigated. In fluorescence competitive binding assays, the recombinant MmedOBP14 showed strong binding abilities to five plant volatiles: β-ionone, 3,4-dimethylacetophenone, 4-ethylacetophenone, acetophenone and ocimene. Homology modeling and molecular docking results indicated that the binding sites of all five ligands were similar and concentrated in the binding pocket of MmedOBP14. Except acetophenone, the remaining four ligands at 1, 10 and 100 μg/μL caused strong antennal electrophysiological responses in adults M. mediator, and males showed more obvious EAG responses to most ligands than females. In behavioral trials, males were attracted by low concentrations of MmedOBP14 ligands, whereas high doses of β-ionone and acetophenone had a repellent effect on males. Moreover, 1 μg/μL of 3,4-dimethylacetophenone showed the strongest attractiveness to female wasps. These findings suggest that MmedOBP14 may play a more important role in the perception of plant volatiles for male wasps to locate habitat, supplement nutrition and search partners.


Mapping of cerebral metabolic rate of oxygen using dynamic susceptibility contrast and blood oxygen level dependent MR imaging in acute ischemic stroke.
MR-derived cerebral metabolic rate of oxygen utilization (CMRO(2)) has been suggested to be analogous to PET-derived CMRO(2) and therefore may be used for detection of viable tissue at risk for infarction. The purpose of this study was to evaluate MR-derived CMRO(2) mapping in acute ischemic stroke in relation to established diffusion- and perfusion-weighted imaging. In 23 patients (mean age 63 ± 18.7 years, 11 women) with imaging findings for acute ischemic stroke, relative oxygen extraction fraction was calculated from quantitative transverse relaxation times (T2, T2*) and relative cerebral blood volume using a quantitative blood oxygenation level dependent (BOLD) approach in order to detect a local increase of deoxyhemoglobin. Relative CMRO(2) (rCMRO(2)) maps were calculated by multiplying relative oxygen extraction fraction (rOEF) by cerebral blood flow, derived from PWI. After co-registration, rCMRO(2) maps were evaluated in comparison with apparent diffusion coefficient (ADC) and time-to-peak (TTP) maps. Mean rCMRO(2) values in areas with diffusion-restriction or TTP/ADC mismatch were compared with rCMRO(2) values in the contralateral tissue. In tissue with diffusion restriction, mean rCMRO(2) values were significantly decreased compared to perfusion-impaired (17.9 [95 % confidence interval 10.3, 25.0] vs. 58.1 [95 % confidence interval 50.1, 70.3]; P < 0.001) and tissue in the contralateral hemisphere (68.2 [95 % confidence interval 61.4, 75.0]; P < 0.001). rCMRO(2) in perfusion-impaired tissue showed no significant change compared to tissue in the contralateral hemisphere (58.1 [95 % confidence interval 50.1, 70.3] vs. 66.7 [95 % confidence interval 53.4, 73.4]; P = 0.34). MR-derived CMRO(2) was decreased within diffusion-restricted tissue and stable within perfusion-impaired tissue, suggesting that this technique may be adequate to reveal different pathophysiological stages in acute stroke.


The diadenosine homodinucleotide P18 improves in vitro myelination in experimental Charcot-Marie-Tooth type 1A.
Charcot-Marie-Tooth 1A (CMT1A) is a demyelinating hereditary neuropathy whose pathogenetic mechanisms are still poorly defined and an etiologic treatment is not yet available. An abnormally high intracellular Ca(2+) concentration ([Ca(2+)]i) occurs in Schwann cells from CMT1A rats (CMT1A SC) and is caused by overexpression of the purinoceptor P2X7. Normalization of the Ca(2+) levels through down-regulation of P2X7 appears to restore the normal phenotype of CMT1A SC in vitro. We recently demonstrated that the diadenosine 5',5'''-P1, P2-diphosphate (Ap2A) isomer P18 behaves as an antagonist of the P2X7 purinergic receptor, effectively blocking channel opening induced by ATP. In addition, P18 behaves as a P2Y11 agonist, inducing cAMP overproduction in P2Y11-overexpressing cells. Here we investigated the in vitro effects of P18 on CMT1A SC. We observed that basal levels of intracellular cAMP ([cAMP]i), a known regulator of SC differentiation and myelination, are significantly lower in CMT1A SC than in wild-type (wt) cells. P18 increased [cAMP]i in both CMT1A and wt SC, and this effects was blunted by NF157, a specific P2Y11 antagonist. Prolonged treatment of organotypic dorsal root ganglia (DRG) cultures with P18 significantly increased expression of myelin protein zero, a marker of myelin production, in both CMT1A and wt cultures. Interestingly, P18 decreased the content of non-phosphorylated neurofilaments, a marker of axonal damage, only in CMT1A DRG cultures. These results suggest that P2X7 antagonists, in combination with [cAMP]i-increasing agents, could represent a therapeutic strategy aimed at correcting the molecular derangements causing the CMT1A phenotype.


Small interfering RNA of alkaline phosphatase inhibits matrix mineralization.
To investigate the cascade of matrix mineralization, cells expressing high and low alkaline phosphatase (ALP) were separated from human osteoblast-like (HOS) cells by fluorescence-activated cell sorting with an ALP antibody. After these cells had been recloned from single cells and then cultured under osteogenic conditions, high-ALP-expressing HOS (H-HOS) cells showed matrix mineralization, but low-ALP-expressing HOS (L-HOS) cells did not. The interaction among osteogenic-related genes, such as runt-related transcription factor 2 (RUNX2), collagen type I alpha1 chain (COL1A1), tissue non-specific ALP, and osteocalcin (OCN), is well known as being related to matrix mineralization. Quantitative real-time polymerase chain reaction revealed that the gene expression of ALP was higher in H-HOS cells than in L-HOS, whereas the gene expression of RUNX2, COL1A1, and OCN was lower in H-HOS cells than in L-HOS cells. When small interfering RNAs (siRNAs) of these osteogenic-related genes were introduced into H-HOS cells by transfection, only ALP siRNA inhibited matrix mineralization. Furthermore, the expression of not only the ALP gene, but also the COL1A1 and RUNX2 genes was influenced by the inhibition of ALP, although the expression of OCN was not affected by the inhibition of ALP. We have been able to confirm that the ALP gene is a strong candidate as the trigger of matrix mineralization. These results indicate the usefulness of cloned osteogenic cells in investigating the molecular mechanisms of matrix mineralization, the function of which can be modulated by using a variety of siRNAs.


[Effect of Ganoderma japonicum (Fr.) Lloyd mixture on experimental thrombosis].
The therapeutic effect of Ganoderma japonicum(Fr.) Lloyd mixture on thrombosis and its mechanism were studied. The results showed that Ganoderma japonicum(Fr.) Lloyd mixture inhibited thrombus formation in vitro and in vivo, the thrombus weight and length formed in the rabbit common carotid artery and external jugular vein were significantly decreased in the experimental group compared with the control (P < 0.01). The results suggest that Ganoderma japonicum(Fr.) Lloyed mixture has anti-thrombotic effect, blood coagulation and platelet activation were inhibited, and the ability of vascular endothelial cells against the process of thrombosis was enhanced.


Analgesics as reinforcers with chronic pain: Evidence from operant studies.
Previously preclinical pain research has focused on simple behavioral endpoints to assess the efficacy of analgesics in acute and chronic pain models, primarily reflexive withdrawal from an applied mechanical or thermal stimulus. However recent research has been aimed at investigating other behavioral states in the presence of pain, including spontaneous, non-elicited pain. One approach is to investigate the reinforcing effects of analgesics in animals with experimental pain, which should serve as reinforcers by virtue of their ability to alleviate the relevant subjective states induced by pain. The gold standard for assessing drug reinforcement is generally accepted to be drug self-administration, and this review highlights the ability of drugs to serve as reinforcers in animals with experimental neuropathic pain, and the extent to which this behavior is altered in chronic pain states. Additionally, intracranial self-stimulation is an operant procedure that has been used extensively to study drug reinforcement mechanisms and the manner in which neuropathic pain alters the ability of drugs to serve as reinforcers in this paradigm will also be discussed. Drug self-administration and intracranial self-stimulation have promise as tools to investigate behavioral effects of analgesics in animals with chronic pain, particularly regarding the mechanisms through which these drugs motivate consumption in a chronic pain state.


Cell death pathways in juvenile Batten disease.
Apoptosis, Golgi fragmentation and elevated ceramide levels occur in Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) neurons, lymphoblasts and fibroblasts. Our purpose was to examine whether apoptosis is the mechanism of cell death in JNCL. This was tested by analyzing caspase-dependent/independent pathways and autophagy, and caspase effects on ceramide and Golgi fragmentation. zVAD prevented caspase activation, but not all cell death. Inhibiting caspase-8 suppressed caspases more than inhibition of any other caspase. Inhibiting caspase-8/6 was synergistic. zVAD suppressed autophagy. 3-methyladenine suppressed caspase activation less than zVAD did. Blocking autophagy/caspase-8/or-6 was synergistic. Blocking autophagy/caspase-3/or-9 was not. Inhibiting caspase-9/3 suppressed autophagy. Golgi fragmentation was suppressed by zVAD, and blocked by CLN3. CLN3, not zVAD, prevented ceramide elevation. caspase-dependent/independent apoptosis and autophagy occur caspase-dependent pathways initiate autophagy Golgi fragmentation results from apoptosis ceramide elevation is independent of caspases, and CLN3 blocks all cell death, prevents Golgi fragmentation and elevation of ceramide in JNCL.


Apelin-13 facilitates mitochondria homeostasis via mitophagy to prevent against airway oxidative injury in asthma.
Oxidative stress is a major mediator in the pathogenesis of allergens-induced asthma. Mitochondria damage and dysfunction is considered to be closely related with oxidative stress. Apelin-13 is a novel multifunctional protein with anti-inflammatory and anti-oxidative properties in neuroinflammation and ischemia-reperfusion injury. However, its role in mitochondria homeostasis under asthma-associated airway oxidative injury and the potential mechanisms have not been elucidated. A murine model of asthma was established by house dust mite (HDM) allergen sensitization and challenge. The mice were received Apelin-13 protein through intraperitoneal administration before HDM challenge. Airway inflammation, histopathological changes and oxidative stress were examined. The regulatory effects of Apelin-13 on mitochondria function were evaluated using airway epithelial BEAS-2B cells, including mitochondria membrane potential (MMP), mitophagy and the possible signaling pathway. The HDM-challenged mice group exhibited robust inflammation and apoptosis in airway epithelium compared to the control group. The airway impairment in asthmatic mice was partly lessened after Apelin-13 administration. Meanwhile, protein expressions of mitophagy-related markers PINK1, Parkin, Tomm20 and LC3 were significantly increased in the lungs of Apelin-13-treated asthmatic mice. In vitro, Apelin-13 treatment significantly improved MMP levels and reduced ROS production in BEAS-2B cells exposed to HDM, accompanied with the increase of cell viability. Furthermore, Apelin-13 was found to promote the activation of PINK1/Parkin signaling in BEAS-2B cells, thereby increasing mitophagy activity and facilitating mitochondria homeostasis. These results demonstrate that Apelin-13 acts as a regulator of mitochondria homeostasis by driving mitophagy to protect against HDM allergen-induced airway oxidative injury. Apelin-13 may serve as a promising protective agent for treating asthma.


Correction to: The rumen microbiome as a reservoir of antimicrobial resistance and pathogenicity genes is directly affected by diet in beef cattle.
Following publication of the original article [1], the authors reported an error in the Additional file 1.


Current management of the amenorrhea-galactorrhea syndrome.
Management of the amenorrhea-galactorrhea syndrome has changed considerably in the last 5 years. Better understanding of the neuroendocrine physiology of the central nervous system in general, and of the hypothalamic-pituitary region in particular, have contributed significantly to our understanding of the pathophysiology of this syndrome. Greater awareness by physicians, improved neuroradiologic techniques, and the development of immunoassays for prolactin have markedly improved our diagnostic abilities. Many more patients are being diagnosed as having a pituitary tumor. The recent introduction of microneurosurgical techniques and the new medications (ergolines) are changing the treatment of this syndrome. Women in the childbearing age--who are affected most often--can expect successful treatment in the majority of cases with resumption of normal menstrual function and fertility. However, certain risks are still posed, particularly during pregnancy. In spite of improved diagnosis and treatment, the natural history of prolactin-secreting pituitary tumors and the long-range effects are still not fully appreciated. More experience in time will be needed before the indications for and the efficacy of various treatment regimens are fully known.


Serological and clinical associations of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus.
To study the clinical significance of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus (SLE), we enrolled 526 new-onset patients who met the 1997 Updated American College of Rheumatology SLE Classification Criteria for a retrospective cohort study. Chi-square test and Wilcoxon rank-sum test were used to detect the relationship of autoantibodies with clinical manifestations and serological results respectively. Our results demonstrated that the positive rate of anti-ribosomal P protein (anti-P) antibody in female patients was higher than that in male patients (41.2% vs. 22%, P = 0.008). Patients with anti-SSB (43.95 ± 73.12 vs. 40.92 ± 75.75, P = 0.004; 63.93 ± 103.56 vs. 55.06 ± 120.84, P = 0.008 respectively) antibodies had higher levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), whereas those with anti-P antibody (28.90 ± 25.70 vs. 50.08 ± 93.00, P = 0.014; 38.51 ± 48.19 vs. 69.95 ± 142.67, P = 0.047, respectively) had lower levels of them. Anti-dsDNA antibody (P = 0.021) was associated with pulmonary arterial hypertension (PAH). The patients with anti-Ro60 (P = 0.044), anti-P (P = 0.012) and anti-dsDNA (P = 0.013) antibodies were less likely to develop Interstitial lung disease. Anti-SmRNP antibody was correlated to lower prevalence of neuropsychiatric symptoms (P = 0.037), and patients with anti-centromere antibody (ACA) were more likely to develop serositis (P = 0.016).We identified five clusters of SLE-related autoantibodies, confirmed previously reported associations of autoantibodies, and discovered new associations.


Nuclear phosphatidylinositols decrease during S-phase of the cell cycle in HeLa cells.
In the current study we have measured phosphatidylinositols during the cell cycle. HeLa cells were labeled with [3H]myoinositol to a steady state, synchronized to the G1/S boundary, and the levels of phosphatidylinositol (PtdIns) lipids were measured at various times after release from the block. The levels of total cellular PtdIns, PtdIns(4)P, and PtdIns(4,5)P2 relative to total cellular phospholipid did not vary throughout the cell cycle. We then isolated nuclei from synchronized cells using a non-detergent method and found that the levels of nuclear PtdIns lipids decreased by over 50% at 2 and 4 h after release from the G1/S boundary (S-phase of the cell cycle) and returned to the original levels by 9 h. Separation of individual inositol-containing nuclear lipids showed that PtdIns decreased by 50% while levels of PtdIns(4)P and PtdIns(4,5)P2 decreased by 66%. Levels of the cytoplasmic PtdIns lipids remained constant throughout this period. This experiment indicates that there is specific nuclear. PtdIns turnover that is activated during DNA synthesis.


Quantification of infection with Schistosoma haematobium in relation to epidemiology and selective population chemotherapy. II. Mass treatment with a single oral dose of metrifonate.
Determination of the efficacy of mass treatment of schistosomiasis is usually based on the rate of cure. However, schistosomes do not multiply in the human host, disease tends to cluster in the small proportion of individuals with heavy infections, and reinfection continually occurs in endemic areas. Thus drastic reduction in worm burdens can be a reasonable goal for mass treatment campaigns. The standard dose and regimen of metrifonate for the treatment of schistosomiasis haematobia is 7.5 mg/kg administered in three doses two weeks apart. This treatment results in a cure rate of approximately 50% and a reduction in egg output of 94.5%. In the present study, 72 infected children with egg counts before treatment that averaged from 0.1 to 2,334/10 ml of urine were treated with a single oral dose of 10 mg of metrifonate/kg: the cure rate was 22%, and the reduction in egg output was 96.5%. No side effects were recorded.


Effects of stimulant medication on the lateralisation of line bisection judgements of children with attention deficit hyperactivity disorder.
Deficits in the maintenance of attention may underlie problems in attention deficit hyperactivity disorder (ADHD). Children with ADHD also show asymmetric attention deficits in traditional lateralisation and visuospatial orienting tasks, suggesting right hemispheric (and left hemispace) attentional disturbance. This study aimed to examine the lateralisation of selective attention in ADHD; specifically, the effect of a moving, random dot background, and stimulant medication in the line bisection task. The performance of children with ADHD, on and off methylphenidate, was examined using a computerised horizontal line bisection task with moving and blank backgrounds. Twenty children with a DSM-IV diagnosis of ADHD participated with 20 controls, individually matched for age, sex, grade at school, and IQ. Twelve of the 20 children with ADHD were on stimulant medication at the time of testing. Horizontal lines of varying length were presented in the centre of a computer screen, with either a blank background, or a moving, random dot field. The random dots moved either leftward or rightward across the screen at either 40 mm/s or 80 mm/s. The children with ADHD off medication bisected lines significantly further to the right compared with controls, who showed a small leftward error. Methylphenidate normalised the performance of the children with ADHD for the task with the moving dots. These results support previous evidence for a right hemispheric hypoarousal theory of attentional dysfunction, and are consistent with the emerging picture of a lateralised dysfunction of frontostriatal circuitry in ADHD.


Ultrastructural changes in the air-blood barrier in mice after intratracheal instillations of Asian sand dust and gold nanoparticles.
The purpose of this study was to investigate a possible translocation pathway of intratracheally instilled gold nanoparticles after the induction of acute pulmonary injury by Asian sand dust. ICR mice were intratracheally instilled with 800μg Asian sand particles (CJ-2 particles) 24h before instillation of 50-nm gold nanoparticles. Lungs from mice treated with Asian sand particles and gold nanoparticles showed an acute focal inflammation with an increased expression of proinflammatory cytokines (IL-6 and TNF-α) and oxidative stress markers (Cu/Zn SOD and iNOS) in alveolar macrophages, type I alveolar epithelial cells, and endothelial cells at the alveolar walls. Electron microscopy revealed a destruction of the alveolar walls with an increased number of endocytic vesicles in the cytoplasm of both type I epithelial cells and endothelial cells; gold nanoparticles were demonstrated in these endocytic vesicles. These findings suggest that translocation of the exposed nanoparticles may be enhanced in the lung tissues with acute inflammatory changes.


Brain templates and atlases.
The core concept within the field of brain mapping is the use of a standardized, or "stereotaxic", 3D coordinate frame for data analysis and reporting of findings from neuroimaging experiments. This simple construct allows brain researchers to combine data from many subjects such that group-averaged signals, be they structural or functional, can be detected above the background noise that would swamp subtle signals from any single subject. Where the signal is robust enough to be detected in individuals, it allows for the exploration of inter-individual variance in the location of that signal. From a larger perspective, it provides a powerful medium for comparison and/or combination of brain mapping findings from different imaging modalities and laboratories around the world. Finally, it provides a framework for the creation of large-scale neuroimaging databases or "atlases" that capture the population mean and variance in anatomical or physiological metrics as a function of age or disease. However, while the above benefits are not in question at first order, there are a number of conceptual and practical challenges that introduce second-order incompatibilities among experimental data. Stereotaxic mapping requires two basic components: (i) the specification of the 3D stereotaxic coordinate space, and (ii) a mapping function that transforms a 3D brain image from "native" space, i.e. the coordinate frame of the scanner at data acquisition, to that stereotaxic space. The first component is usually expressed by the choice of a representative 3D MR image that serves as target "template" or atlas. The native image is re-sampled from native to stereotaxic space under the mapping function that may have few or many degrees of freedom, depending upon the experimental design. The optimal choice of atlas template and mapping function depend upon considerations of age, gender, hemispheric asymmetry, anatomical correspondence, spatial normalization methodology and disease-specificity. Accounting, or not, for these various factors in defining stereotaxic space has created the specter of an ever-expanding set of atlases, customized for a particular experiment, that are mutually incompatible. These difficulties continue to plague the brain mapping field. This review article summarizes the evolution of stereotaxic space in term of the basic principles and associated conceptual challenges, the creation of population atlases and the future trends that can be expected in atlas evolution.


Enhancing the versatility of wireless biopotential acquisition for myoelectric prosthetic control.
A significant challenge in rehabilitating upper-limb amputees with sophisticated, electric-powered prostheses is sourcing reliable and independent channels of motor control information sufficient to precisely direct multiple degrees of freedom simultaneously. In response to the expressed needs of clinicians, we have developed a miniature, batteryless recording device that utilizes emerging integrated circuit technology and optimal impedance matching for magnetic resonantly coupled (MRC) wireless power transfer to improve the performance and versatility of wireless electrode interfaces with muscle. In this work we describe the fabrication and performance of a fully wireless and batteryless EMG recording system and use of this system to direct virtual and electric-powered limbs in real-time. The advantage of using MRC to optimize power transfer to a network of wireless devices is exhibited by EMG collected from an array of eight devices placed circumferentially around a human subject's forearm. This is a comprehensive, low-cost, and non-proprietary solution that provides unprecedented versatility of configuration to direct myoelectric prostheses without wired connections to the body. The amenability of MRC to varied coil geometries and arrangements has the potential to improve the efficiency and robustness of wireless power transfer links at all levels of upper-limb amputation. Additionally, the wireless recording device's programmable flash memory and selectable features will grant clinicians the unique ability to adapt and personalize the recording system's functional protocol for patient- or algorithm-specific needs.


TEMPRANILLO genes link photoperiod and gibberellin pathways to control flowering in Arabidopsis.
In Arabidopsis, FLOWERING LOCUS T (FT) promotes flowering in response to long days in the photoperiod pathway, while signalling downstream gibberellin (GA) perception is critical for flowering under short days. Previously we have established that the TEMPRANILLO (TEM) genes have a pivotal role in the direct repression of FT. Here we show that TEM genes directly regulate the expression of the GA(4) biosynthetic genes GA 3-oxidase1 and 2 (GA3OX1 and GA3OX2). Plants overexpressing TEM genes resemble GA-deficient mutants, and conversely, TEM downregulation give rise to elongated hypocotyls perhaps as a result of an increase in GA content. We consistently find that TEM1 represses GA3OX1 and GA3OX2 by directly binding a regulatory region positioned in the first exon. Our results indicate that TEM genes seem to link the photoperiod and GA-dependent flowering pathways, controlling floral transition under inductive and non-inductive day lengths through the regulation of the floral integrators.


A photothermal therapy enhanced mechano-bactericidal hybrid nanostructured surface.
Polymeric materials that have been extensively applied in medical devices, wearable electronics, and food packaging are readily contaminated by bothersome pathogenic bacteria. Bioinspired mechano-bactericidal surfaces can deliver lethal rupture for contacted bacterial cells through mechanical stress. However, the mechano-bactericidal activity based only on polymeric nanostructures is not satisfactory, especially for the Gram-positive strain which is generally more resistant to mechanical lysis. Here, we show that the mechanical bactericidal performance of polymeric nanopillars can be significantly enhanced by the combination of photothermal therapy. We fabricated the nanopillars through the combination of low-cost anodized aluminum oxide (AAO) template-assisted method with an environment-friendly Layer-by-Layer (LbL) assembly technique of tannic acid (TA) and iron ion (Fe3+). The fabricated hybrid nanopillar exhibited remarkable bactericidal performances (more than 99%) toward both Gram-negative Pseudomonas aeruginosa (P. aeruginosa) and stubborn Gram-positive Staphylococcus aureus (S. aureus) bacteria. Notably, this hybrid nanostructured surface displayed excellent biocompatibility for murine L929 fibroblast cells, indicating a selective biocidal activity between bacterial cells and mammalian cells. Thus, the concept and antibacterial system described here present a low-cost, scalable, and highly repeatable strategy for the construction of physical bactericidal nanopillars on polymeric films with high performance and biosafety, but without any risks of causing antibacterial resistance.


Harnessing the therapeutic potential of anticancer drugs through amorphous solid dispersions.
The treatment of cancer is still a major challenge. But tremendous progress in anticancer drug discovery and development has occurred in the last few decades. However, this progress has resulted in few effective oncology products due to challenges associated with anticancer drug delivery. Oral administration is the most preferred route for anticancer drug delivery, but the majority of anticancer drugs currently in product pipelines and the majority of those that have been commercially approved have inherently poor water solubility, and this cannot be mitigated without compromising their potency and stability. The poor water solubility of anticancer drugs, in conjunction with other factors, leads to suboptimal pharmacokinetic performance. Thus, these drugs have limited efficacy and safety when administered orally. The amorphous solid dispersion (ASD) is a promising formulation technology that primarily enhances the aqueous solubility of poorly water-soluble drugs. In this review, we discuss the challenges associated with the oral administration of anticancer drugs and the use of ASD technology in alleviating these challenges. We emphasize the ability of ASDs to improve not only the pharmacokinetics of poorly water-soluble anticancer drugs, but also their efficacy and safety. The goal of this paper is to rationalize the application of ASD technology in the formulation of anticancer drugs, thereby creating superior oncology products that lead to improved therapeutic outcomes.


Content Validation of the Quality and Safety Framed Clinical Evaluation for Nurse Practitioner Students.
Clinical performance evaluation is a high-stakes assessment that requires a valid and reliable instrument. There appear to be no identified clinical evaluation instruments developed for nurse practitioner (NP) students that have undergone content validation. This study describes the process to develop, validate, and pilot a clinical evaluation instrument for NP students framed in the Quality and Safety Education of Nurses Competencies for advanced practice. Six expert nurse educators were recruited for the purpose of rating items for relevance for inclusion in the Quality and Safety Framed Clinical Evaluation Instrument for NP Students using the content validity index. The instrument was pilot tested in a primary care clinical course. Two rounds of review yielded a 34-item content validated instrument. Evidence suggests that the Quality and Safety Framed Clinical Evaluation for NP Students is a valid and reliable instrument to evaluate the clinical performance of NP students.


Measurement of Crassostrea gigas hemocyte oxidative metabolism by flow cytometry and the inhibiting capacity of pathogenic vibrios.
A flow cytometric method to measure the production of oxidative metabolism products was adapted for use with Crassostrea gigas hemocytes. The method is based upon the oxidation, by hydrogen peroxide (H2O2), of intracellular 2',7'-dichlorofluorescin (DCFH) to green-fluorescent dichlorofluorescein. Activation of the respiratory burst (RB) was tested using phorbol myristate acetate with no success. By contrast, activation by zymosan particles increased oxidation of DCFH in C. gigas hemocytes, mainly granulocytes, and optimization tests showed a good response with 20 zymosan particles per hemocyte. Anti-aggregant solution, used to prevent hemocytes from clumping during bleeding, inhibited the RB activity measured by DCFH oxidation. The flow cytometric method developed during this work was used to evaluate the DCFH oxidation-inhibiting capacity of four strains of vibrio bacteria, known or suspected to be pathogenic for bivalves.


An evaluation of the wire mesh prosthesis in primary reconstruction of the mandible.
A stainless steel wire mesh prosthesis was used as a primary mandibular replacement in 102 patients after resection of malignant neoplasms arising in the head and neck. In sixty-seven patients the prosthesis was considered successful. Failure of the host to tolerate the prosthesis was associated with a history of previous irradiation, extensive resections, and loss of distant skin flaps used for coverage of the prosthesis. We conclude that the wire mesh mandibular prosthesis is an excellent means to accomplish prompt functional and cosmetic reconstruction after mandibular loss and does not preclude the use of a more complex modality of reconstruction if the initial implant is removed.


Structure and localization of synaptic complexes in the cardiac ganglion of a portunid crab.
The cardiac ganglion of Portunus sanguinolentus exhibits spontaneous rhythmic activity when isolated. The ganglion contains five large and four small intrinsic neurons and is innervated by three pairs of fibres originating in the thoracic ganglia. We have identified the processes of the large neurons in electron micrographs by injecting these cells with two electron-dense markers, horseradish peroxidase (HRP) and Procion Rubine (PR). In addition we have studied the processes of the four smaller neurons by light microscopy serial reconstructions and by electron microscopy of selected regions. Both markers were found only in neuronal processes and not in glial cells nor in the extracellular space, except close to the soma of the injected cell. We found contacts between the small secondary (collateral) processes of the large cells but not between their somata or their primary processes (axons and dendrites). Two specialized structures present at the contacts between the collateral processes were small membrane close appositions, possibly the site of electrotonic junctions, and chemical synapses. Contacts between processes marked by HRP and those marked by PR were common, as were contacts between processes marked by either HRP or PR and those of the other intrinsic neurons. Adjacent processes stained by PR could contain PR deposits of different densities, but it is unclear whether this finding was due to intercellular diffusion of the dye or to its diffusing at different rates into branches of the same process. Identified processes of all the intrinsic neurons contained the same type of vesicles, which were different from those found in processes of the extrinsic fibres. Chemical synapses were present at contacts between processes of the extrinsic and intrinsic neurons, as well as at contacts between processes of the intrinsic neurons. The axons of three small cells made a series of contacts at which extensive arrays of membrane close appositions, but not chemical synapses, were found. These three axons also formed contacts, either directly or through their collateral branches, with processes of the large cells, at which both membrane close appositions and chemical synapses were present. The axon of the fourth small cell could not be followed in our series.


Spatial structure of peptides determined by residual dipolar couplings analysis.
The gated decoupled (13)C NMR spectra of a dipeptide (Glu-Trp) and a tetrapeptide (NAc-Ser-Phe-Val-Gly-OMe) were recorded in D(2)O and in a lyotropic alignment medium (pentaethylene glycol monododecyl ether/n-hexanol). The residual dipolar couplings were extracted as the differences between the observed couplings for the magnetic nuclei dissolved in the latter and former media. Using a computational optimization, the spatial structures of the compounds were calculated starting from their respective low energy conformations obtained on a semiempirical basis. The uniformity of each conformation was confirmed by the solid-state (13)C NMR spectra of powder samples. Differences between the starting structures and final ones, optimized when employing residual dipolar couplings, are discussed.


Impact of chronic coronary syndromes on cardiovascular hospitalization and mortality: the ESC-EORP CICD-LT registry.
In Europe, global data on guideline adherence, geographic variations, and determinants of clinical events in patients with chronic coronary syndrome (CCS) remain suboptimal. The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischemic Cardiovascular Disease Long-Term (CICD-LT) registry is a prospective European registry, and was designed to describe the profile, management, and outcomes of patients with CCS across the ESC countries. We aimed to investigate clinical events at 1-year follow-up from the ESC EORP CICD-LT registry.One-year outcomes of 6655 patients from the 9174 recruited in this European registry were analysed. Overall, 168 patients (2.5%) died, mostly from cardiovascular (CV) causes (n = 97, 1.5%). Northern Europe had the lowest CV mortality rate, while southern Europe had the highest (0.5 vs. 2.0%, P = 0.04). Women had a higher rate of CV mortality compared with men (2.0 vs. 1.3%, P = 0.02). During follow-up, 1606 patients (27.1%) were hospitalized at least once, predominantly for CV indications (n = 1220, 20.6%). Among the population with measured low-density lipoprotein-cholesterol level at 1 year, 1434 patients (66.5%) were above the recommended target. Age, history of atrial fibrillation, previous stroke, liver disease, chronic obstructive pulmonary disease or asthma, increased serum creatinine, and impaired left ventricular function were associated with an increased risk of CV death or hospitalization. In the CICD registry, the majority of patients with CCS have uncontrolled CV-risk factors. The 1-year mortality rate is low, but these patients are frequently hospitalized for CV causes. Early identification of comorbidities may represent an opportunity for enhanced care and better outcomes.


Existential aspects documented in older people's patient records in the context of specialized palliative care: a retrospective review.
Documentation of older people's end-of-life care should cover the care given and provide an overview of their entire situation. Older people approaching the end of life often have complex symptoms, live with bodily losses, and face an unknown future in which existential aspects come to the forefront. Knowledge of the existential aspects recorded in palliative care documentation is sparse and merits improvement. This knowledge is relevant to the development of more holistic documentation and is necessary in order to promote reflection on and discussion of documentation of the sensitive existential considerations arising in palliative care. The aim of this study was to describe the documentation of existential aspects in the patient records of older people receiving specialized palliative care. Data were obtained from a retrospective review of the free-text notes in 84 records of randomly selected patients aged ≥75 years enrolled in specialized palliative care units who died in 2017. The notes were analysed using an inductive qualitative content analysis. The notes documented existential aspects in terms of connotations of well-being and ill-being. Documented existential aspects were related to the patients' autonomy concerning loss of freedom and self-determination, social connectedness concerning loneliness and communion, emotional state concerning anxiety and inner peace, and state of being concerning despair and hope. The notes on existential aspects were, however, not recorded in a structured way and no care plans related to existential aspects were found. Existential aspects concerning both ill-being and well-being were sparsely and unsystematically documented in older people's patient records, but when notes were extracted from these records and analysed, patterns became evident. Existential aspects form an important basis for delivering person-centred palliative care. There is a need to develop structured documentation concerning existential aspects; otherwise, patients' thoughts and concerns may remain unknown to healthcare professionals.


Dermatology Training in Africa: Successes and Challenges.
This article analyzes various dermatology training programs in Africa by region and country. There is a paucity of dermatologists for the African population. West Africa has a harmonized curriculum, adopted by some anglophone and most francophone countries in the region. Algeria, Egypt, Ethiopia, Morocco, South Africa, Sudan, Tanzania, and Tunisia have national curricula. In the remaining countries for which information is available and programs exist, a university-specific curriculum is followed. Of the 55 countries in Africa, there is no opportunity for dermatology specialization in 30. Local and ethnic skin curricula content appropriate for Africa, developed through continent-wide collaborations, are recommended.


Progressive degradation of serial grooming chains by descending decerebration.
Rule-governed behavioral chains occur predictably within the grooming sequences of rats. Descending levels of decerebration were used to identify the minimum brain substrate needed to generate the sequential structure of a chain that connects up to 25 actions into a stereotyped grooming pattern. Full brain transections in the coronal plane isolated the decerebrate brainstem of rats at one of 3 different levels: mesencephalic (above the midbrain), metencephalic (above the hindbrain), and myelencephalic (above the medulla oblongata). Complete chain sequences were produced successfully by higher decerebrates, demonstrating that brainstem circuitry suffices for the basic generation of this sequential pattern. The pattern of sequential degradation across lower transection levels was gradual and continuous, raising the possibility that the generating circuitry for this chain may not be localized at a single level within the brainstem but rather may be distributed across the hindbrain as a degenerate or parallel network. The competence of this network appears to be reduced merely in increments by descending transections. This possibility is compared to localized generator alternatives.


Continuous infusion epidural analgesia during labor: a randomized, double-blind comparison of 0.0625% bupivacaine/0.0002% fentanyl versus 0.125% bupivacaine.
The analgesic efficacy of the continuous epidural infusion of 0.0625% bupivacaine/0.0002% fentanyl was compared with the infusion of 0.125% bupivacaine alone in a randomized, double-blind study of nulliparous women. Each patient received, in sequence: 1) 3 ml of 0.5% bupivacaine with 1:200,000 epinephrine; 2) 6 ml of study solution 1 (bupivacaine-fentanyl group: 0.125% bupivacaine/0.0008% fentanyl; bupivacaine-only group: 0.25% bupivacaine alone); and 3) a continuous epidural infusion of study solution 2 at a rate of 12.5 ml/h (bupivacaine-fentanyl group: 0.0625% bupivacaine/0.0002% fentanyl; bupivacaine-only group: 0.125% bupivacaine alone). The epidural infusion was discontinued at full cervical dilatation, but patients who lacked perineal anesthesia received one or two 5-ml boluses of study solution 3 (bupivacaine-fentanyl group: 0.0625% bupivacaine alone; bupivacaine-only group: 0.125% bupivacaine alone). During the first stage of labor, 36 of 41 (88%) women in the bupivacaine-fentanyl group, and 37 of 39 (95%) women in the bupivacaine-only group, had analgesia of excellent or good quality (P = NS). During the second stage, 22 of 37 (59%) women in the bupivacaine-fentanyl group, and 23 of 35 (66%) women in the bupivacaine-only group, rated their analgesia as excellent or good (P = NS). Women in the bupivacaine-only group were more likely to have motor block at full cervical dilatation (P less than .001). There was no significant difference between groups in duration of the second stage of labor, duration of pushing, position of the vertex before delivery, method of delivery, Apgar scores, or umbilical cord blood gas and acid-base values.(ABSTRACT TRUNCATED AT 250 WORDS)


Perceptual load modifies processing of unattended stimuli both in the presence and absence of attended stimuli.
This study explored effects of perceptual load on stimulus processing in the presence and absence of an attended stimulus. Participants were presented with a bilateral or unilateral display and asked to perform a discrimination task at either low or high perceptual load. Electrophysiological responses to stimuli were then compared at the P100 and N100. As in previous studies, perceptual load modified processing of attended and unattended stimuli seen at occipital scalp sites. Moreover, perceptual load modulated attention effects when the attended stimulus was presented at high perceptual load for unilateral displays. However, this was not true when the attended and unattended stimulus appeared simultaneously in bilateral displays. Instead, only a main effect of perceptual load was found. Reductions in processing contralateral to the unattended stimulus at the N100 provide support for Lavie's (1995) theory of selective attention.


Aluminum accumulation in tangle-bearing neurons of Alzheimer's disease with Balint's syndrome in a long-term aluminum refiner.
Progressive dementia had developed since the age of 55 in a male patient, who had worked as an aluminum refiner for 30 years. Balint's syndrome was observed from at 60 and he died of bronchopneumonia at 65. Neuropathological examination revealed characteristic features of Alzheimer's disease with marked atrophy of the occipito-temporal lobes and senile plaques of the cerebellum. Wavelength-dispersive X-ray microanalysis disclosed focal aluminum accumulation within the nucleus and cytoplasm of the tangle-bearing neurons. Microanalysis by the same method failed to disclose aluminum accumulation in the tangle-bearing neurons in a case of senile dementia of Alzheimer's type who had no possible inhalation of aluminum.


Faculty development projects for international health professions educators: Vehicles for institutional change?
Projects are an important tool in faculty development, and project emphasis may offer insights into perceived education priorities. Impact of projects has been focused on individuals, not institutions or health. Education innovation projects of Fellows in an international faculty development program were examined to better understand perceived needs in health professions education and institutional impact of projects. Four hundred and thirty-five projects were analyzed to identify focus areas. Fellows were asked to identify changes in their schools and communities resulting from their projects. New education methods and curriculum change were common project focus areas. Regional differences were evident with a higher percentage of education methods projects by Fellows residing in India (52%), compared with South Africa (25%) and Brazil (24%). Fifty-six percent of projects were incorporated into the curriculum and/or incorporated as institutional policy. One-third to two-thirds of respondents noted improved teaching quality, collaboration, education research interest, assessment, student performance, and curriculum alignment with community health needs. National differences in project focus may offer insight into local conditions and needs. High rates of diffusion of projects and impact on faculty, students, and curriculum suggest that faculty development projects may be a strategy for institutional change in resource limited environments.


Clinical course and outcome of schizoaffective disorders. A three-year follow-up study.
Four samples of patients (fulfilling at the index episode, respectively, Research Diagnostic Criteria for schizoaffective disorder manic type, schizoaffective disorder depressed type, manic disorder and major depressive disorder) were followed up for 3 years. At the end of the follow-up period, no significant difference with respect to the mean scores on the Disability Assessment Schedule (DAS) and on the Strauss-Carpenter Outcome Scale was observed between schizomanics and manics (although the global outcome was slightly poorer in the former group). In contrast, significant differences between schizodepressives and depressives were found both on some DAS subscales (the schizodepressives were more socially withdrawn, had less social contacts and poorer work performance) and on the Strauss-Carpenter Outcome Scale (the mean total score and the mean scores on the items "social contacts" and "employment" were significantly lower in schizodepressives). The most frequent pattern of course in patients diagnosed cross-sectionally as schizomanic was a bipolar one. Some patients had only recurrent schizomanic episodes and others more an alternance of schizomanic and schizophrenic episodes. In patients diagnosed cross-sectionally as schizodepressives, the most frequent pattern of course was that characterized by recurrent schizodepressive episodes. In some patients an alternance of schizodepressive and depressive or schizodepressive and schizophrenic episodes was observed. These data confirm that patients diagnosed cross-sectionally as schizoaffective represent a very heterogeneous group when they are studied longitudinally, and support the usefulness of a "multiaxial" approach to the classification of schizoaffective disorders, taking into account both cross-sectional symptomatology and clinical course.


Antibiofilm and immunomodulatory resorbable nanofibrous filing for dental pulp regenerative procedures.
Multifunctional scaffolds with host defense peptides designed for regenerative endodontics are desirable nanobiotechnological tools for dentistry. Here, different scaffolds were tested for use during the pulp revascularization process, including poly(vinyl alcohol)-PVA hydrogels or resins, collagen hydrogels and poly(vinyl alcohol) PVA/Chitosan (PVA/CS) nanofibers. Based on time to degradation (21 days), nanofibers were chosen to be incorporated with ciprofloxacin and IDR-1002 (each at 50 mg/g). Nanofibers containing ciprofloxacin and IDR-1002 had anti-biofilm activity against Enterococcus faecalis, Staphylococcus aureus and a multispecies oral biofilm, besides anti-inflammatory activities. The in vivo subcutaneous tissue response to tooth fragments filled with nanofibers demonstrated a pulp-like tissue formation, when compared to empty teeth fragments. Thus, we designed a strong antimicrobial, immunomodulatory and regenerative candidate for pulp revascularization and regeneration procedures.


Glycogen synthase kinase-3 inhibitors augment TRAIL-induced apoptotic death in human hepatoma cells.
Hepatocellular carcinoma (HCC) displays a striking resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Therefore, the characterization of pharmacological agents that overcome this resistance may provide new therapeutic modalities for HCC. Here, we examined whether glycogen synthase kinase-3 (GSK-3) inhibitors could restore TRAIL sensitivity in hepatoma cells. To this aim, the effects of two GSK-3 inhibitors, lithium and SB-415286, were analyzed on TRAIL apoptotic signaling in human hepatoma cell lines in comparison with normal hepatocytes. We observed that both inhibitors sensitized hepatoma cells, but not normal hepatocytes, to TRAIL-induced apoptosis by enhancing caspase-8 activity and the downstream recruitment of the mitochondrial machinery. GSK-3 inhibitors also stabilized p53 and the down-regulation of p53 by RNA interference abolished the sensitizing effect of lithium on caspase-3 activation. Concomitantly, GSK-3 inhibitors strongly activated c-Jun N-terminal kinases (JNKs). The pharmacological inhibition of JNKs with AS601245 or SP600125 resulted in an earlier and stronger induction of apoptosis indicating that activated JNKs transduced protective signals and provided an anti-apoptotic balance to the pro-apoptotic effects of GSK-3 inhibitors. These findings demonstrate that GSK-3 exerts a negative and complex constraint on TRAIL apoptotic signaling in hepatoma cells, which can be greatly alleviated by GSK-3 inhibitors. Therefore, GSK-3 inhibitors may open new perspectives to enhance the anti-tumor activity of TRAIL in HCC.


Palladium and the electrochemical quartz crystal microbalance: a new method for the in situ analysis of the precious metal in aqueous solutions.
A new method for the quantitative determination of palladium(II) by the electrochemical quartz crystal microbalance (EQCM) technique has been developed. Using a bare carbon-coated quartz crystal, Pd(II) ions are directly deposited from aqueous solution as palladium metal onto the crystal surface, and the Pd(II) concentration is determined with a detection limit of 0.0156 mM, or 1.66 ppm. No complexing agent or preconcentration of palladium is required for the analysis. The palladium is stripped from the crystal through its electrochemical oxidation, regenerating the crystal for subsequent multi-cycle palladium analyses. A conventional gold-coated quartz crystal was incapable of carrying out the same measurements. The EQCM technique presented is simple, sensitive, and reproducible for the detection of this widely used precious metal.


Structure-activity relationship studies of the two-component lantibiotic haloduracin.
The lantibiotic haloduracin consists of two posttranslationally processed peptides, Halalpha and Halbeta, which act in synergy to provide bactericidal activity. An in vitro haloduracin production system was used to examine the biological impact of disrupting individual thioether rings in each peptide. Surprisingly, the Halalpha B ring, which contains a highly conserved CTLTXEC motif, was expendable. This motif has been proposed to interact with haloduracin's predicted target, lipid II. Exchange of the glutamate residue in this motif for alanine or glutamine completely abolished antibacterial activity. This study also established that Halalpha-Ser26 and Halbeta-Ser22 escape dehydration, requiring revision of the Halbeta structure previously proposed. Extracellular proteases secreted by the producer strain can remove the leader peptide, and the Halalpha cystine that is dispensable for bioactivity protects Halalpha from further proteolytic degradation.


Distinct effects of interferon-gamma and MHC class I surface antigen levels on resistance of the K562 tumor cell line to natural killer-mediated lysis.
Various investigators have examined the relationship between tumor cell susceptibility to natural killer (NK) cell lysis and the expression of HLA class I antigens on the tumor cell. There is controversy as to whether or not an inverse relationship exists, and if so, the basis of the relationship between these two phenomena remains undefined. To address these questions, the genomic clones for two HLA antigens were transfected into the erythroleukemia cell line K562, a cell line that is used as the standard to assess human NK and major histocompatibility complex (MHC) nonrestricted cytolysis. Susceptibility to NK lysis was not affected by the de novo expression of HLA antigens on the K562 after DNA mediated gene transfer. Interferon-gamma (IFN-gamma) treatment of K562 induced levels of MHC class I antigen surface expression comparable to those found on the transfected cells; however, the IFN-gamma-treated cells were resistant to NK lysis. When very high levels of surface HLA antigens were induced on the transfectants, a potential effect of class I MHC expression on K562 lysis could be discerned that was distinct from the resistance to NK lysis induced by IFN-gamma-treatment.


Novel clinical manifestations and treatment of hereditary apoA-I amyloidosis: when a good protein turns bad.
Amyloidoses are life-threatening diseases caused by the deposition of various proteins including apolipoprotein A-I, the major protein of plasma high-density lipoprotein. Timely diagnostics of amyloidoses are crucial for their treatment. Colombat et al. reported novel aspects of the hereditary apolipoprotein A-I amyloidosis, including its unexpected clinical presentation and genetic origins, as well as life- and vision-saving hepatorenal transplantation. This study improves the diagnostics of apolipoprotein A-I amyloidosis, optimizes its treatment, and expands our understanding of the molecular basis of this multipronged disease.


Angiotensin convertase activities in human alveolar macrophages: effects of cigarette smoking and sarcoidosis.
Angiotensin I convertase activity has been found in human alveolar macrophages from normal volunteers and patients with pulmonary sarcoidosis. This activity is higher in the alveolar macrophages from smokers than from nonsmokers, and is even more elevated in sarcoid patients. The activity can be detected with both angiotensin I and bradykinin analogs and appears to require protein synthesis, but the enzyme is not secreted by alveolar macrophages in culture.


Bis-cyclometallated gold(III) complexes as efficient catalysts for synthesis of propargylamines and alkylated indoles.
Stable bis-cyclometallated gold(III) complexes were developed as efficient catalysts for organic transformation reactions by using two strategies: (1) construction of distorted square planar gold(III) complexes and (2) dual catalysis by gold(III) complexes and silver salts.


Hide and seek: the theory of mind of visual concealment and search.
Researchers have investigated visual search behavior for almost a century. During that time, few studies have examined the cognitive processes involved in hiding items rather than finding them. To investigate this, we developed a paradigm that allowed participants to indicate where they would hide (or find) an item that was to be found (or hidden) by a friend or a foe. We found that (i) for friends more than foes, participants selected the pop-out item in the display, and (ii) when the display was homogeneous, they selected nearby and corner items. These behaviors held for both hiding and finding, although hide and find behaviors were not identical. For pop-out displays, decision times were unusually long when hiding an item from a foe. These data converge on the conclusion that the principles of search and concealment are similar, but not the same. They also suggest that this paradigm will provide researchers a powerful method for investigating theory of mind in adults.


Transforming poison into medicine: the role of dualism in psychiatry.
This article draws attention to a generalizable phenomenon called "transforming poison into medicine," illustrating both literal and figurative applications. The purpose of such illustrations is to support a strong philosophical claim, namely the currently incomplete reduction (if not the ultimate irreducibility) of intentional mind-states - e.g., beliefs, desires, volitions - to electro-chemical brain-states. Such incomplete reduction (or irreducibility) holds profound implications for the ineluctable role of dualism in neuroscience and psychiatry alike.


Microarray detection of food-borne pathogens using specific probes prepared by comparative genomics.
In order to design a method for the accurate detection and identification of food-borne pathogens, we used comparative genomics to select 70-mer oligonucleotide probes specific for 11 major food-borne pathogens (10 overlapping probes per pathogen) for use in microarray analysis. We analyzed the hybridization pattern of this constructed microarray with the Cy3-labeled genomic DNA of various food-borne pathogens and other bacteria. Our microarray showed a highly specific hybridization pattern with the genomic DNA of each food-borne pathogen; little unexpected cross-hybridization was observed. Microarray data were analyzed and clustered using the GenePix Pro 6.0 and GeneSpring GX 7.3.1 programs. The analyzed dendrogram revealed the discriminating power of constructed microarray. Each food-borne pathogen clustered according to its hybridization specificity and non-pathogenic species were discriminated from pathogenic species. Our method can be applied to the rapid and accurate detection and identification of food-borne pathogens in the food industry. In addition, this study demonstrates that genome sequence comparison and DNA microarray analysis have a powerful application in epidemiologic and taxonomic studies, as well as in the food safety and biodefense fields.


Cell-free DNA in the management of prostate cancer: Current status and future prospective.
With the escalating prevalence of prostate cancer (PCa) in China, there is an urgent demand for novel diagnostic and therapeutic approaches. Extensive investigations have been conducted on the clinical implementation of circulating free DNA (cfDNA) in PCa. This review aims to provide a comprehensive overview of the present state of cfDNA as a biomarker for PCa and to examine its merits and obstacles for future clinical utilization. Relevant peer-reviewed manuscripts on cfDNA as a PCa marker were evaluated by PubMed search (2010-2022) to evaluate the roles of cfDNA in PCa diagnosis, prognosis, and prediction, respectively. cfDNA is primarily released from cells undergoing necrosis and apoptosis, allowing for non-invasive insight into the genomic, transcriptomic, and epigenomic alterations within various PCa disease states. Next-generation sequencing, among other detection methods, enables the assessment of cfDNA abundance, mutation status, fragment characteristics, and epigenetic modifications. Multidimensional analysis based on cfDNA can facilitate early detection of PCa, risk stratification, and treatment monitoring. However, standardization of cfDNA detection methods is still required to expedite its clinical application. cfDNA provides a non-invasive, rapid, and repeatable means of acquiring multidimensional information from PCa patients, which can aid in guiding clinical decisions and enhancing patient management. Overcoming the application barriers of cfDNA necessitates increased data sharing and international collaboration.


Effect of light deprivation on the ERG responses of taurine-deficient rats.
The decrease of taurine levels in the retina of taurine-depleted rats treated with guanidinoethane sulfonate (GES) reduced the amplitude of the a- and b-waves of the electroretinogram, registered as a function of the log relative intensity stimulus. The effect was observed either in rats exposed to a light-darkness cycle or to continuous darkness; this effect was somewhat more pronounced in retinas of rats exposed to light. Values obtained from the Naka-Rushton equation for the V-log I curve for the a-wave showed that the half-saturating intensity was unchanged but Vmax was decreased by GES treatment. Implicit times for the b-wave delayed whereas those for the a-wave were unaffected by the treatment.


Can across-treatment changes in cumulative puff duration predict treatment outcome during nicotine fading.
The smoking behavior of 10 male and 15 female smokers was assessed weekly during a standardized nicotine fading program to examine the relationship between compensatory smoking (i.e., increases in the number of cigarettes smoked per day, expired air carbon monoxide (CO), or the frequency and duration of puffs) and posttreatment abstinence from tobacco. Subjects who continued to smoke or relapsed immediately following treatment (Nonabstainers) smoked significantly more cigarettes per day during the program (p less than .05) and exhibited greater across-treatment increases in the time spent puffing a cigarette (i.e., cumulative puff duration) (p less than .05) than subjects who successfully quit smoking (Abstainers). Both Nonabstainers and Abstainers exhibited across-treatment decreases in expired air CO (p less than .001). Similar analyses conducted between subjects who were abstinent versus relapsed 3-6 months following treatment revealed no significant differences in smoking behavior, although both groups exhibited similar across-treatment decreases in CO (p less than .001) and time spent smoking a cigarette (i.e., time alite) (p less than .05). The findings are discussed in reference to their relevance to (a) the development of differential assessment procedures to match smokers to appropriate treatments; (b) the determination of appropriate procedural modifications in the nicotine fading protocol; and (c) nicotine regulation research.


Amplitude and fall-time discrimination of unit spike activity using TTL.
An inexpensive and reliable window discriminator simply constructed using TTL integrated circuits is described. The device will discriminate between unit spikes on the basis of amplitude alone or amplitude and fall-time, and simultaneous analysis of two separate spikes is possible. All pulse outputs and amplitude and fall-time windows may be displayed allowing the setting up of window criteria to proceed under direct visual control.


An overview of the genetics, mechanisms and management of NAFLD and ALD.
Alcoholic liver disease (ALD) and, increasingly, non-alcoholic fatty liver disease (NAFLD) are common causes of advanced liver disease in many developed countries including the UK. Both diseases share parallel natural histories, progressing from steatosis, to steatohepatitis and fibrosis/cirrhosis; and are characterised by substantial interindividual variation in disease outcome. This article will provide an overview of disease mechanisms, genetic modifiers and management, focusing principally on NAFLD, while drawing parallels between the two conditions where appropriate.


Barriers and facilitators of electronic patient-reported outcome measures (e-PROMs) for patients in home palliative cancer care: a qualitative study of healthcare professionals' perceptions.
Patient-reported outcomes in palliative care enable early monitoring and management of symptoms that most impact patients' daily lives; however, there are several barriers to adopting electronic Patient-reported Outcome Measures (e-PROMs) in daily practice. This study explored the experiences of health care professionals (HCPs) regarding potential barriers and facilitators in implementing e-PROMs in palliative cancer care at home. This was a qualitative descriptive study. The data were collected from two focus groups structured according to the conceptual framework of Grol. HCPs involved in home palliative cancer care of Fondazione IRCCS Istituto Nazionale dei Tumori of Milan were enrolled. Data were analyzed using a reflexive thematic analysis. A total of 245 codes were generated, 171 for the first focus group and 74 for the second focus group. The results were subdivided into subthemes according to Grol's themes: Innovation, Individual professional, Patient, Social context, Organizational context, except Economic Political context. Nine HCPs attended the first focus group, and ten attended the second. According to these participants, e-PROMs could be integrated into clinical practice after adequate training and support of HCPs at all stages of implementation. They identified barriers, especially in the social and organizational contexts, due to the uniqueness of the oncological end-of-life setting and the intangible care interventions, as well as many facilitators for the innovation that these tools bring and for improved communication with the patient and the healthcare team. e-PROMs are perceived by HCPs as adding value to patient care and their work; however, barriers remain especially related to the fragility of these patients, the adequacy of technological systems, lack of education, and the risk of low humanization of care.


Indoor particles and symptoms among office workers: results from a double-blind cross-over study.
We studied the effects of removing small airborne particles in an office building without unusual contaminant sources or occupant complaints. We conducted a double-blind crossover study of enhanced particle filtration in an office building in the Midwest United States in 1993. We replaced standard particle filters, in separate ventilation systems on two floors, with highly efficient filters on alternate floors weekly over 4 weeks. Repeated-measures models were used to analyze data from weekly worker questionnaires and multiple environmental measurements. Bioaerosol concentrations were low. Enhanced filtration reduced concentrations of the smallest airborne particles by 94%. This reduction was not associated with reduced symptoms among the 396 respondents, but three performance-related mental states improved; for example, the confusion scale decreased (-3.7%; 95% confidence limits (CL) = -6.5, -0.9). Most environmental dissatisfaction variables also improved; eg, "stuffy" air, -5.3% (95% CL = -10.3, -0.4). Cooler temperatures within the recommended comfort range were associated with remarkably large improvement in most outcomes; for example, chest tightness decreased -23.4% (95% CL = -38.1, -8.7) for every 1 degrees C decrease. Benefits of enhanced filtration require assessment in buildings with higher particulate contaminant levels in studies controlling for temperature effects. Benefits from lower indoor temperatures need confirmation.