Presence of angiographic coronary collaterals predicts myocardial recovery after coronary bypass surgery in patients with severe left ventricular dysfunction.
Patients with coronary artery disease and left ventricular dysfunction (LVD) may have areas of hibernating myocardium that improve functionally after revascularization. Coronary collateral circulation may sustain ischemic, dysfunctional myocardium and favor myocardial recovery after revascularization. We evaluated the effect of angiographic coronary collaterals on myocardial functional recovery after coronary bypass graft (CABG) surgery in a group of patients with severe LVD. Forty-one patients with multivessel coronary artery disease and advanced LVD (left ventricular ejection fraction [LVEF] 25 +/- 5%) undergoing CABG were identified from a prospective database. Preoperative coronary angiograms were evaluated for collaterals, which were graded according to Rentrop's classification (0 to 3), and a collateral index was calculated (collateral sum divided by 3). Preoperative and postoperative radionuclide ventriculograms provided global LVEF and regional ejection fractions. Of 123 regions evaluated, 120 were dysfunctional at baseline. Virtually all (122 of 123) regions were subtended by an artery with > or = 70% stenosis that was bypassed. Thirty-eight (81%) of 47 dysfunctional regions with grade 2 or 3 collaterals improved regional ejection fraction after surgery versus 38 (52%) of 73 dysfunctional regions with grade 0 or 1 collaterals (P = 0.0018). Global LVEF was 34 +/- 10% after surgery (P < 0.001 versus before surgery). Among patients with a global LVEF increase > or = 10%, collateral index was 1.81 versus 0.83 in those with an LVEF increase < 10% (P = 0.005). In this population of patients with coronary artery disease with severe LVD, the presence of angiographic grade 2 or 3 collaterals predicted recovery of regional and global myocardial function after CABG.


Fiscal policy and CO2 emissions from heterogeneous fuel sources in Thailand: Evidence from multiple structural breaks cointegration test.
This study investigated the dynamic linkage between fiscal policy, energy and CO2 emissions from heterogeneous fossil fuel sources in the context of the environmental Kuznets curve (EKC) framework for Thailand. With annual data from 1972 to 2014 while incorporating structural breaks, the study employed a Maki cointegration test and the dynamic ordinary least squares estimation approach. The results found that a 1% increase in fiscal policy brought about a 6.5% (p < 0.05) increase in the low CO2 emitting gaseous fuel sources (natural gas), a 0.2% (p < 0.01) reduction in the intermediate CO2 emitting liquid fuel sources (crude oil derivatives), and an insignificant increase 0.2% (p > 0.05) in the high CO2 emitting solid fuel sources (coal derivatives). While a 1% increase in fiscal policy abates aggregated CO2 emissions by 0.2% (p < 0.05), the existence of the EKC hypothesis was validated in all models. The causality test revealed a bi-directional causal relationship between fiscal policy and CO2 emissions and unidirectional flow from fiscal policy to energy consumption. This confirms that fiscal policy initiatives towards energy consumption have long-run implications for environmental quality. Our findings support the energy-led growth hypothesis for the Thai economy. The implication of the finding is that increasing the share of clean and renewable energy sources should be encouraged-rather than energy conservation policies, which obstruct energy supply and utilization. This highlights a more efficient way of harnessing energy sources through the instrumentality of fiscal policy.


Initial results of QuantiFERON-TB Gold testing in patients with uveitis.
To describe the use of the second-generation QuantiFERON-TB Gold (QFT-G) test in a series of patients in an ophthalmic practice. The charts of all patients who had QFT-G tests ordered by Mayo Clinic ophthalmologists in the past 3 years were reviewed. A total of 27 QFT-G tests were ordered. Thirteen (48%) tests were negative, six (22%) were indeterminate, two (7%) tests were re-ordered after a lab accident or an improper cancellation, four (15%) were positive and represented infection, and two (7%) were positive but negative when re-tested. Of the four truly positive cases, three were treated for tuberculosis (TB): one had tuberculous iritis, one had retinal vasculitis and haemorrhage, and one had asymptomatic TB but was on immunosuppressive therapy. The fourth patient had previously been treated for latent infection. In a series of selected patients with uveitis, the QFT-G test was able to detect TB infection in 15% of the patients, though it does not differentiate between active and latent TB infection. QFT-G should be considered in place of purified protein derivative testing in those with uveitis that have had prior BCG vaccination and in immunocompromised patients. Patients with a positive QFT-G, but who have little risk for TB infection and a negative systemic work-up, should be re-tested.


Efficacy of antibiotic short course for bloodstream infections in acute myeloid leukemia patients with febrile neutropenia: A retrospective comparative study.
There is no specific recommendation about antimicrobial treatment length for documented infections in chemotherapy induced febrile neutropenia (FN). Practices have changed along time in our center regarding length of antibiotic treatment. The aim of this study was to compare long versus short antibiotic course for bloodstream infection (BSI) treatment in acute myeloid leukemia (AML) patients during FN. This monocentric retrospective comparative study included all consecutive BSI episodes among AML patients with FN for 3 years (2017-2019). Episodes were classified regarding the length of antibiotic treatment, considered as short course if the treatment lasted ≤ 7 days, except for nonfermenting bacteria and Staphylococcus aureus or lugdunensis for which the threshold was ≤ 10 days and ≤ 14 days, respectively. The primary outcome was the number of BSI relapses in both groups within 30 days of antibiotic discontinuation. Among 71 AML patients, 104 BSI episodes were included; 48 (46%) received short course treatment. Only 8 (7.6%) BSI episodes relapsed within 30 days of antibiotic discontinuation, 5 having received short course treatment. No association was found between risk of relapse and short course of antibiotic treatment (p = 0.37). The only risk factor significantly associated with BSI relapse was neutropenia duration (p = 0.005). Antibiotic short course seemed as effective as prolonged treatment for BSI in AML patients during FN, with very few relapses at day 30. These encouraging findings should be confirmed through prospective studies.


Structures and expression of mRNAs coding for major plasma proteins of Bombyx mori.
A group of structurally related proteins, referred to as '30K proteins', accumulate in a stage-dependent fashion in the larval hemolymph of the silkworm, Bombyx mori. To investigate the regulatory mechanisms of the 30K protein biosynthesis in the fat body, mRNA sequences coding for these plasma proteins were cloned and their structures and expression during the larval development were studied. Five plasmid clones, each bearing a distinct mRNA sequence coding for the 30K protein component, were isolated from a cDNA library constructed from the fat body poly(A)RNA of the mid-fifth instar larvae. These clones were remarkably similar to each other with respect to both the nucleotide and the amino-acid sequences. Each clone carried an open reading frame for amino-acid residues 251 to 264, with a typical signal sequence for transmembrane secretion at the deduced amino-terminal domain. Northern blot hybridization provided evidence that the developmental change in the amount of 30K protein mRNAs in the fat body reflects well that of the hemolymph concentration of 30K proteins, indicating that the biosynthesis of 30K proteins is developmentally regulated at a transcriptional or post-transcriptional level in the fat body.


Validation of the eighth edition American Joint Committee on Cancer staging system for human papillomavirus-associated oropharyngeal cancer.
The eighth edition American Joint Committee on Cancer (AJCC) staging manual includes major changes in staging of oropharyngeal cancer (OPC). We evaluated the new staging system in order to validate this shift in classification. We used the National Cancer Database (NCDB) to identify patients with human papillomavirus-associated (HPV-positive) OPC from 2010-2013. We restaged patients using the eighth edition guidelines and compared them with those from the seventh edition. We calculated stage-specific overall survival and concordance indices. We identified 15 116 patients with a median follow-up period of 29.1 months. Clinical and pathological staging changed for 93.9% and 91.7% of patients, respectively. Survival concordance indices for both clinical (0.621-0.656) and pathological (0.640-0.663) staging were improved in the eighth edition compared to the seventh edition. The eighth edition guidelines have profoundly altered staging of HPV-positive OPC and seem to demonstrate improved survival discrimination.


Effect of particle size and composition of suspended sediment on denitrification in river water.
Rivers with high suspended sediment (SPS) concentration are common worldwide, and previous studies reported the occurrence of denitrification on SPS. In this work, effect of particle size and composition of SPS on denitrification in river water was studied in laboratory. The (15)N isotope tracer technique was used to investigate the denitrification in water containing 8 g L(-1) SPS with different particle sizes, including <20 μm, 20-50 μm, 50-100 μm, and 100-200 μm. The results showed that the denitrification rate was negatively related to particle size, and the SPS with particle size below 20 μm had the highest (15)N2 emission rate of 0.27 mg-N/m(3) · d, which was twice that of 100-200 μm. The denitrifying bacteria population in the system decreased with the increase of particle size, which was positively correlated with denitrification rate (p<0.05). There was a positive correlation between organic carbon content of SPS and denitrifying bacteria population (p<0.01), indicating that organic carbon is a key factor influencing denitrifying bacteria. Different from the (15)N2 production, (15)N2O emission rate reached the highest of 1.02 μg-N/m(3) · d in the system containing SPS of 20-50 μm, which was 14.8 times that of 100-200 μm. This was due to the difference in denitrifying bacteria species in different systems due to different oxic/anoxic conditions around SPS. This study suggests that not only the SPS concentration but also the SPS size and composition should be considered in studying the nitrogen cycle in river systems, especially for the production of N2O.


Chemical constituents from leaves of Jatropha curcas.
To investigate the chemical constituents from the leaves of Jatropha curcas and evaluate their inhibition on lipopolysaccharide (LPS)-activated BV-2 microglia cells. The n-BuOH extract of the leaves of J. curcas was isolated by macroporous adsorption resin, silica gel, ODS, column chromatography and semi-preparative HPLC. The structures of the compounds were identified by MS, NMR, ECD, and other spectroscopic methods. In addition, anti-neuroinflammatory effects of isolated compounds were evaluated by measuring the production of nitric oxide (NO) in over-activated BV-2 cells. Seventeen compounds, including (7R,8S)-crataegifin A-4-O-β-D-glucopyranoside (1), (8R,8'R)-arctigenin (2), arctigenin-4'-O-β-D-glucopyranoside (3), (-)-syringaresinol (4), syringaresinol-4'-O-β-D-glucopyranoside (5), (-)-pinoresinol (6), pinoresinol-4'-O-β-D-glucopyranoside (7), buddlenol D (8), (2R,3R)-dihydroquercetin (9), (2S,3S)-epicatechin (10), (2R,3S)-catechin (11), isovitexin (12), naringenin-7-O-β-D-glucopyranoside (13), chamaejasmin (14), neochamaejasmin B (15), isoneochamaejasmin A (16), and tomentin-5-O-β-D-glucopyranoside (17) were isolated and identified. Compounds 2, 4 and 8 significantly inhibited the release of NO in BV-2 microglia activated by LPS, with IC50 values of 18.34, 29.33 and 26.30 μmol/L, respectively. Compound 1 is a novel compound, and compounds 2, 3, 8, 14-17 are isolated from Jatropha genus for the first time. In addition, the lignans significantly inhibited NO release and the inhibitory activity was decreased after glycosylation.


Analysis of Transurethral Resection of Bladder Tumor Efficiency Utilizing Nonprocedural Operating Room Times.
To analyze the contribution of nonprocedural operating room (OR) times to transurethral resection of bladder tumor (TURBT) operative efficiency. Over a 24-month period, all nonprocedural OR times from TURBT surgeries performed at a single institution were prospectively collected. Nonprocedural times included: in-room to anesthesia release time, anesthesia release to cut time, and close to wheels out time. Procedural OR time was cut to close time. We also analyzed the impact of time of day on TURBT efficiency (morning vs afternoon). Comparisons between groups were made using the Wilcoxon rank sum test for continuous variables. We identified 777 consecutive TURBT procedures from 2019 to 2020. The median total OR time was 63 minutes (interquartile range: 50-81 minutes). The nonprocedural time occupied a median of 49.4% of the total operating time (interquartile range: 38.9%-60.4%). Median anesthesia release to cut time was slower when 1 TURBT was performed a day compared to 2 or more (13 minutes vs 12 minutes, P = .04). Median close to wheels out time was faster when there was 1 TURBT in a day (7 minutes vs 8 minutes, P = .02). Median in-room to anesthesia release time was faster in the morning than it was in the afternoon (10 minutes vs 11 minutes, P = .02). Nonprocedural times made up roughly half of the total TURBT operating time and should be considered in OR efficiency analyses. TURBT OR efficiency may be related to the number of TURBTs performed in a day as well as the time of day of TURBT start.


Childhood internalizing and externalizing problems and cardiovascular and diabetes mellitus risk in adolescence.
Among adults, common psychopathology is a risk factor for cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM). We investigated whether childhood internalizing and externalizing problems are prospectively associated with clinically elevated CVD and T2DM risk factors in adolescence. Data were from the Avon Longitudinal Study of Parents and Children. Childhood internalizing (emotional) and externalizing (hyperactivity and conduct) problems were rated on the Strengths and Difficulties Questionnaire (parent version) (N = 6442). BMI was measured at age 15 and triglycerides, low-density lipoprotein cholesterol and homeostasis model assessment of insulin resistance, IR, were assessed at age 17. We estimated associations using multivariate log-linear regression. Models were adjusted for confounding and participants attrition. Children with hyperactivity or conduct problems were more likely to become obese and to develop clinically high levels of triglycerides and HOMA-IR in adolescence. In fully adjusted models, IR was associated with hyperactivity (relative risk, RR = 1.35, 95 % confidence interval, CI = 1.00-1.81) and conduct problems (RR = 1.37, CI = 1.06-1.78). High triglycerides were associated with hyperactivity (RR = 2.05, CI = 1.41-2.98) and with conduct problems (RR = 1.85, CI = 1.32-2.59). BMI only minimally explained these associations. Emotional problems were not associated with increased risk. Residual attrition bias, reliance on parent's reports of children's behaviors, non-diverse sample. This research suggests that childhood externalizing problems might be a novel independent risk factor for CVD/T2DM. Future research should corroborate these findings and investigate mechanisms. Pediatricians may need to assess and treat CVD/T2DM risk factors in adolescents with a history of externalizing problems.


Small intestinal bacterial overgrowth is common after gastrectomy but with little impact on nutritional status.
Available evidence assessing the impact of small intestinal bacterial overgrowth (SIBO) following gastrectomy is limited. To evaluate the prevalence of SIBO after gastrectomy and its association with malnutrition. To describe the antibiotic treatment required to correct it and if nutritional status improves. A prospective cohort study was performed at the Agencia Sanitaria Costa del Sol (Costa del Sol Health Agency) from 2012 to 2015. A hydrogen-methane breath test with oral glucose overload was performed. Demographic variables and nutritional parameters were collected at baseline and one month after effective treatment of SIBO. The antibiotic regimens and the number of treatment lines used were assessed. Sixty gastrectomy patients were analysed, 58.3% of which were male. A sub-analysis of the curve was performed at 45min to minimise possible false positives, and SIBO was identified in 61.6% of cases. SIBO patients tended to have a lower BMI, although this trend was not statistically significant. After treatment with rifaximin, 94.6% of patients were still positive for SIBO, which fell to 85.7% after metronidazole. The rate of total antibiotic treatment failure was 67.6%. No statistically significant changes were found in nutritional parameters after treatment. SIBO was identified in 61.6% of patients after gastrectomy. No correlation was found with any malnutrition parameter. Rifaximin and metronidazole were found to be largely ineffective in eradicating SIBO. When treatment was effective, the impact on malnutrition was negligible and may have been associated with other factors.


Biotinylated-spiperone ligands for quantum dot labeling of the dopamine D2 receptor in live cell cultures.
We have synthesized 3 analogs of the dopamine D2 receptor (D2 DR) antagonist spiperone that can be conjugated to streptavidin-coated quantum dots via a pegylated biotin derivative. Using fluorescent imaging we demonstrate that substitution on the spiro position is tolerated, whilst the length and rigidity of a spacer arm attached to spiperone is important in controlling specific labeling as well as minimizing nonspecific labeling to cells and the surface of cell culture dishes. The ligand with the most rigid linker IDT772 (4) had the best binding profile and had high specific binding to D2 DR expressing HEK-293T cells with low nonspecific binding to plates and HEK-293T cells that lacked the D2 DR.


The value of indium-labelled leucocytes in clinical practice.
Following intravenous injection, autologous 111In labelled-leucocytes migrate to sites of inflammation, where they can be imaged with the gamma camera. The principle underlining the labelling technique is exposure of a population of leucocytes or purified granulocytes to a lipophilic 111In complex, such as 111In oxine or 111In tropolonate. As a result of cell activation, the in vitro manipulation to which the leucocytes are subjected modifies their biodistribution early after re-injection. Separation and labelling in plasma-enriched media, however, limits this activation and promotes early migration into inflammatory foci.


Systematic development of a set of implementation strategies for transitional care innovations in long-term care.
Numerous transitional care innovations (TCIs) are being developed and implemented to optimize care continuity for older persons when transferring between multiple care settings, help meet their care needs, and ultimately improve their quality of life. Although the implementation of TCIs is influenced by contextual factors, the use of effective implementation strategies is largely lacking. Thus, to improve the implementation of TCIs targeting older persons receiving long-term care services, we systematically developed a set of viable strategies selected to address the influencing factors. As part of the TRANS-SENIOR research network, a stepwise approach following Implementation Mapping (steps 1 to 3) was applied to select implementation strategies. Building on the findings of previous studies, existing TCIs and factors influencing their implementation were identified. A combination of four taxonomies and overviews of change methods as well as relevant evidence on their effectiveness were used to select the implementation strategies targeting each of the relevant factors. Subsequently, individual consultations with scientific experts were performed for further validation of the process of mapping strategies to implementation factors and for capturing alternative ideas on relevant implementation strategies. Twenty TCIs were identified and 12 influencing factors (mapped to the Consolidated Framework for Implementation Research) were designated as priority factors to be addressed with implementation strategies. A total of 40 strategies were selected. The majority of these target factors at the organizational level, e.g., by using structural redesign, public commitment, changing staffing models, conducting local consensus discussions, and organizational diagnosis and feedback. Strategies at the level of individuals included active learning, belief selection, and guided practice. Each strategy was operationalized into practical applications. This project developed a set of theory and evidence-based implementation strategies to address the influencing factors, along further tailoring for each context, and enhance the implementation of TCIs in daily practice settings. Such work is critical to advance the use of implementation science methods to implement innovations in long-term care successfully.


An enzyme-linked immunoassay for circulating immune complexes using solid phased goat Clq.
An ELISA procedure was developed for measuring circulating immune complexes (IC), using solid phased goat Clq. The use of purified Clq from this species significantly diminished the background uptake of the enzyme-labeled goat antibodies used in the assay, in comparison with Clq isolated from human, guinea pig or rabbit serum. The test specimen results are reported as micrograms equivalent (microgram eq)/ml of heat aggregated human immunoglobulin G (HAIgG), and are based on standard curves developed with this latter reagent for each assay. The 2 World Health Organization (WHO) reference preparations for immune complex determinations (HAIgG and a human tetanus antitoxin-toxoid immune complex) were assayed by this ELISA procedure, and the results obtained were in very good agreement with the WHO established values. All the reagents in the ELISA, including the lyophilized HAIgG standard and the solid phased Clq are stable for more than one year at 4 degrees C. The range of accurate quantitation in test serum is 2-500 micrograms/ml, when using a 1:100 specimen dilution. The total incubation is less than 2 h, with no preliminary preparation of test specimens. The average concentration of IC reactivity in 126 healthy adults was 6 micrograms eq/ml, and the normal upper limit was determined to be 12 micrograms eq/ml.


Antimicrobial activity and pH measurement of calcium silicate cements versus new bioactive resin composite restorative material.
The purpose of this in vitro study is to compare the antimicrobial effect and pH of two calcium silicate cements Mineral trioxide aggregate high plasticity (Angelus PR, Brazil) and iRoot BP Plus (BioCeramix Inc., Vancouver, BC, Canada) and new bioactive restorative resin composite restorative material (ACTIVA, MA, Pulpdent, USA) against aerobic bacteria, strictly anaerobic bacteria and a yeast by using an agar diffusion test. The materials were tested immediately after manipulation and were applied to the agar plates. Sodium hypochlorite (NaOCl) 5.25% was used as a positive control group. The dry filter paper acted as a negative control group for this study. The size of the inhibition zone for each material was measured after 12, 24 and 48 h. At the time of pH measurement; materials were prepared, crushed then dispersed in distilled water. The one-way Anova test revealed that iRoot BP Plus significantly showed superior antimicrobial efficacy compared to MTA-HP against the following species; Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, Enterococcus faecium, Peptostreptococcus anaerobius and Candida albicans (P < 0.05). All of the tested materials did not show any antimicrobial effect against Porphyromonas gingivalis and Actinomyces israelii. The new bioactive resin composite material (ACTIVA) showed the least antimicrobial activity against the previously mentioned microorganisms except E. faecalis. NaOCl significantly showed the highest antimicrobial activity among the test group (P < 0.05). iRoot BP Plus was more alkaline (pH 12.1 ± 0.14/ 11.9 ± 0.25) in comparison to MTA-HP (pH 11.6 ± 0.16/ 11.2 ± 0.10) while ACTIVA was slightly acidic (pH 5.4 ± 0.09/ 6.5 ± 0.08). According to the findings of this study, it was concluded that calcium silicate- based cements showed a potential antimicrobial activity mainly due to its high alkalinity. The new bioactive resin composite restorative material exhibits less antimicrobial activity due to its resinous ingredients and slightly acidic nature. Antimicrobial effect of calcium silicate cements against strictly anaerobic bacterial species is still questionable.


Role of corneal collagen cross-linking in pseudophakic bullous keratopathy: a clinicopathological study.
To evaluate the clinical and histopathologic changes induced by collagen cross-linking (CXL) in pseudophakic bullous keratopathy (PBK). Randomized, prospective, interventional study. Twenty-four patients with PBK were included in the study. Twenty-four patients with PBK underwent CXL followed by keratoplasty at 1 or 3 months. Twelve patients underwent penetrating keratoplasty 1 month after CXL (group A) and the remaining 12 patients underwent penetrating keratoplasty 3 months after CXL (group B). The main outcome measures were assessed at 1 week and 1 month for all patients and at 3 months for 12 patients only. The corneal buttons underwent histopathologic and immunofluorescence evaluation. Visual acuity, ocular discomfort (tearing, redness, pain), corneal haze, central corneal thickness, histopathologic evaluation, and immunofluorescent microscopy. Mean visual acuity showed a significant improvement after CXL, from 1.925 ± 0.173 before surgery to 1.75±0.296 at 1 month after surgery (P = 0.010), but deteriorated to 1.81 ± 0.23 at 3 months. Symptomatic relief after CXL was at a maximum at 1 month, with a worsening trend at 3 months. Eighteen patients showed a reduction in corneal haze 1 month after CXL. The effect was maintained in 9 of 12 patients at 3 months. The mean central corneal thickness decreased significantly from 846.46 ± 88.741 to 781.0 ± 98.788 μm at 1 month (P<0.01) after CXL, but increased to 805.08±136.06 μm at 3 months. Immunofluorescence microscopy revealed anterior stromal compaction in 7 of 12 patients (58.3%) in group A and in 5 of 12 patients (41.6%) in group B. Staining of keratocyte nuclei with 4',6-diaminido-2-phenylindole dihydrochloride (Molecular Probes, Carlsband, CA) revealed a relative uniform distribution throughout the stroma. Collagen cross-linking causes symptomatic relief and a decrease in central corneal thickness and anterior stromal compaction in PBK. However, the effect decreases with time and depends on disease severity.


Value of squamous cell carcinoma antigen levels in invasive cervical carcinoma.
Squamous cell carcinoma (SCC) antigen (Ag) levels were measured by radioimmunoassay in 64 patients with invasive squamous cell cervical carcinoma and 9 patients with nonsquamous carcinoma before the initiation of treatment. The mean antigen level in the squamous group was 10.5 ng/ml compared with 1.3 ng/ml in the nonsquamous group. In the patients with squamous cell carcinoma, mean SCC Ag level correlated well with stage, except for bulky stage IB tumors (P less than 0.05), where mean level was much higher than expected. Patients with exophytic tumors had significantly higher SCC Ag levels than those with nonexophytic tumors. Follow-up on 62 evaluable patients ranged from 20 to 40 months. The mean pretreatment SCC Ag level for patients free of disease at last contact was 5.6 ng/ml, in contrast to 16.1 ng/ml for those with recurrent disease. Only 32% of patients free of disease had pretreatment levels of 4.0 ng/ml or greater, while 86% of those with recurrent disease had such values (P less than 0.05). Forty patients had follow-up samples drawn 1 to 14 months after treatment. Mean post-treatment SCC Ag levels dropped to 1.8 ng/ml in 21 patients free of disease (73% decrease), but remained elevated at 13.4 ng/ml (17% decrease) in 19 patients with recurrences. The specificity of follow-up SCC Ag levels as a predictive test for outcome was 90%, with a sensitivity of 63%. We conclude that pretreatment SCC Ag levels correlate well with tumor stage, lesion morphology, and extent of disease. SCC antigen levels may be used to follow patients to determine effectiveness of treatment.


PCSK9 and HS-CRP Predict Progression of Aortic Stenosis in Patients with Stable Coronary Artery Disease.
It is essential to study the factors associated with the evolution of aortic stenosis progression (ASP) to develop therapies that could reduce it. We studied 283 patients 6 months after acute coronary syndrome (ACS). ASP was defined as an increase in the maximum aortic velocity of at least 0.5 m/s between the echocardiogram performed during ACS hospitalization and the last one recorded in the electronic medical registry. The median follow-up was 72.4 months. Twenty patients (7%) had ASP. A multivariate binary logistic regression analysis was performed showing that PCSK9 plasma levels (OR, 0.668 CI (0.457-0.977); p = 0.038), HS-CRP (OR, 1.034 CI (1.005-1.063); p = 0.022), the presence of dyslipidemia (OR, 4.622 CI (1.285-16.618); p = 0.019), the history of PAD (OR, 9.453 CI (1.703-52.452); p = 0.010), and GFR (OR, 0.962 CI (0.939-0.986); p = 0.002) were independent predicting factors of ASP. In patients with ischemic heart disease, low plasma levels of PCSK9 and elevated levels of HS-CRP are independent predictors of ASP.


Comparing pharmaceutical and pesticide loads into a small Mediterranean river.
During 2003/2004, water samples were collected upstream and downstream of two wastewater treatment plant (WWTP) outlets in order to determine the contribution of urban centres to concentration of selected pharmaceuticals (antiphlogistics, lipid regulators and carbamazepine) and pesticides into a Mediterranean river basin (Arc river, Aix en Provence, France). Pharmaceutical loads were compared to pesticide ones. They could be nearly regarded as important as pesticide ones at least at one sampling site. The observed pollution patterns differed from pesticides to pharmaceuticals. Pesticide pollution occurred through a high pollution peak in spring while pharmaceuticals were continuously infused into the river via WWTP effluents. Carbamazepine and bezafibrate were detected in almost all samples at concentration levels ranging from ng/L to microg/L. The major pharmaceutical source could be ascribed to WWTP effluents and pharmaceutical concentrations increased during low flow rate conditions (summer), when municipal wastewater effluents accounted for the majority of the river water flow. Treated wastewaters contributed to a lesser extent to pesticide river water pollution. In an urbanized Mediterranean river basin, a deep understanding of water pollution by organic waste contaminants is required in order to set up an efficient programme of pollution reduction measures.


Sexual Dysfunction in Parkinson's Disease: A Systematic Review of the Arizona Sexual Experience Scale Sexual Dysfunction in Parkinson Disease: A Systematic Review of the Arizona Sexual Experience Scale.
Parkinson's disease (PD) affects older individuals and can cause sexual dysfunction (SD). SD is a determinant of general well-being; but is infrequently assessed in professionally. The Arizona Sexual Experience Scale (ASEX) measures SD; unlike other scales, it is minimally invasive and requires little time to complete. This review aimed to assess the prevalence of SD in patients with PD using ASEX. Were searched the keywords, "sexual dysfunction," "Parkinson's disease" and "ASEX" in 9 databases. The prevalence of SD ranged from 65%-90%. SD was associated with older age at disease onset, higher Unified Parkinson Disease Rating Scale scores, age and depression (p ranged from .001 to <.05). The most observed SD was erectile dysfunction in men. SD is common among patients with PD. ASEX, although not specific to PD, is an easy and quickly applied tool that can help evaluate SD and guide treatments in PD.


Influence of bone remodelling rate on quantitative ultrasound parameters at the calcaneus and DXA BMDa of the hip and spine in middle-aged and elderly European men: the European Male Ageing Study (EMAS).
To assess the influence of sex hormones on markers of bone turnover and to explore the association between these markers and bone health in middle-aged and elderly European men. A cross-sectional population-based survey. Men aged 40-79 years were recruited from population registers in eight European centres. Subjects completed a postal questionnaire which included questions concerning lifestyle and were invited to undergo quantitative ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β C-terminal cross-linked telopeptide (β-cTX)), total testosterone, total oestradiol (E(2)), sex hormone-binding globulin (SHBG) and insulin-like growth factor 1 (IGF1) were measured. Dual-energy X-ray absorptiometry (DXA) of the hip and lumbar spine was performed in two centres. A total of 3120, mean age 59.9 years (s.d.=11.0) were included. After adjustment for centre, age, height, weight, lifestyle factors, season and other hormones, total and free E(2) were negatively associated with β-cTX but not P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated with both β-cTX and P1NP. Total or free testosterone was not independently associated with either bone marker. After the same adjustments, higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine. E(2), SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone turnover in middle-aged and older European men. Higher rates of bone remodelling are negatively associated with male bone health.


Fully automatic segmentation of type B aortic dissection from CTA images enabled by deep learning.
This study sought to establish a robust and fully automated Type B aortic dissection (TBAD) segmentation method by leveraging the emerging deep learning techniques. Preoperative CTA images of 276 patients with TBAD were retrospectively collected from January 2011 to December 2018. Using a reproducible manual segmentation protocol of three labels (whole aorta, true lumen (TL), and false lumen (FL)), a ground truth database (n = 276) was established and randomly divided into training and testing sets in a rough 8:1 ratio. Three convolutional neural network (CNN) models were developed on the training set (n = 246): single one-task (CNN1), single multi-task (CNN2), and serial multi-task (CNN3) models. Performance was evaluated using the Dice coefficient score (DCS) and lumen volume accuracy on the testing set (n = 30). Pearson correlation, Intra-class correlation coefficients and Bland-Altman plots were used to evaluate the inter-observer measurement agreement. CNN3 performed the best, with mean DCSs of 0.93 ± 0.01, 0.93 ± 0.01 and 0.91 ± 0.02 for the whole aorta, TL, and FL, respectively (p < 0.05). Each label volume from CNN3 showed excellent agreement with the ground truth, with mean volume differences of -31.05 (-82.76 to 20.65) ml, 4.79 (-11.04 to 20.63) ml, and 8.67(-11.40 to 28.74) ml for the whole aorta, TL, and FL, respectively. The segmentation speed of CNN3 was 0.038 ± 0.006 s/image. Deep learning-based model provides a promising approach for accurate and efficient segmentation of TBAD and makes it possible for automated measurements of TBAD anatomical features.


Seasonal adaptations in energy budgeting in the primate Lepilemur leucopus.
The spiny forest of South Madagascar is one of the driest and most unpredictable habitats in Africa. The small-bodied, nocturnal primate Lepilemur leucopus lives in this harsh habitat with high diurnal and seasonal changes in ambient temperature. In this study, we investigated seasonal adaptions in energy budgeting of L. leucopus, which allow it to live under these conditions by measuring resting metabolic rate using open-flow respirometry. No signs of heterothermy were detected, and resting metabolic rate was significantly lower in the warmer wet season than in the colder dry season. In fact, L. leucopus possesses one of the lowest mass-specific metabolic rates measured so far for an endotherm, probably the result of adaptations to its habitat and folivorous and potentially toxic diet. Surprisingly, we identified a shift of the thermoneutral zone from between 25 and 30 °C in the wet season to between 29 and 32 °C in the cool dry season. L. leucopus seems to be more affected by the hot daytime temperatures during the dry season and thermoregulation seems to be more costly during this time, which makes this shift of the thermoneutral zone advantageous. Our findings suggest that L. leucopus has a very small scope to unfavorable conditions, making it highly vulnerable, e.g., to changing conditions due to climate change.


Friendships in Children with Williams Syndrome: Parent and Child Perspectives.
Although children with Williams syndrome (WS) are strongly socially motivated, many have friendship difficulties. The parents of 21 children with WS and 20 of the children themselves participated in a semi-structured interview about the children's friendships. Parents reported that their child had difficulties sustaining friendships and low levels of interaction with peers. Barriers to friendships included difficulties with play and self-regulating behaviour. However, there was within-group variability, with a small number of children reported to have strong friendships. While parents reported friendship challenges, all of the children named at least one friend, and most said that they had never felt excluded by their peers. Future research is needed to determine optimal ways to support children with WS in their friendships.


A novel pathway to the manifestations of metabolic syndrome.
Pathways leading from obesity to the manifestations of metabolic syndrome involve a number of metabolic risk factors, as well as adipokines, mediators of inflammatory response, thrombogenic and thrombolytic parameters, and vascular endothelial reactivity. Increased adipose tissue mass contributes to augmented secretion of proinflammatory adipokines, particularly tumor necrosis factor-alpha (TNF alpha), along with diminished secretion of the "protective" adiponectin. In our view, TNF alpha and adiponectin are antagonistic in stimulating nuclear transcription factor-kappa B (NF-kappa B) activation. Through this activation, TNF alpha induces oxidative stress, which exacerbates pathological processes leading to oxidized low-density lipoprotein and dyslipidemia, glucose intolerance, insulin resistance, hypertension, endothelial dysfunction, and atherogenesis. NF-kappa B activation further stimulates the formation of additional inflammatory cytokines, along with adhesion molecules which promote endothelial dysfunction. Elevated free fatty acid, glucose, and insulin levels enhance this NF-kappa B activation and further downstream modulate specific clinical manifestations of metabolic syndrome.


Ionophore properties of OmpA of Escherichia coli.
Both porins OmpA1, from wild-strain K12 Escherichia coli, and OmpA2, from a K12 derivative deficient in both OmpF and OmpC, are able to form ion channels in virtually solvent-free membranes. The conductance has been shown to vary in a discrete fashion with different single increment values especially with OmpA2. This behaviour seems to indicate, beside monomers, the presence of aggregates of different sizes. The estimated small pore diameter (0.6-0.7 nm) for the monomeric would explain the weak permeability of this narrow channel toward different solutes. OmpA protein, from experiments of ion selectivity and zero-current potential, is determined weakly anion selective.


Overexpression of chloroplastic Zea mays NADP-malic enzyme (ZmNADP-ME) confers tolerance to salt stress in Arabidopsis thaliana.
The C4 plants photosynthesize better than C3 plants especially in arid environment. As an attempt to genetically convert C3 plant to C4, the cDNA of decarboxylating C4 type NADP-malic enzyme from Zea mays (ZmNADP-ME) that has lower Km for malate and NADP than its C3 isoforms, was overexpressed in Arabidopsis thaliana under the control of 35S promoter. Due to increased activity of NADP-ME in the transgenics the malate decarboxylation increased that resulted in loss of carbon skeletons needed for amino acid and protein synthesis. Consequently, amino acid and protein content of the transgenics declined. Therefore, the Chl content, photosynthetic efficiency (Fv/Fm), electron transport rate (ETR), the quantum yield of photosynthetic CO2 assimilation, rosette diameter, and biomass were lower in the transgenics. However, in salt stress (150 mM NaCl), the overexpressers had higher Chl, protein content, Fv/Fm, ETR, and biomass than the vector control. NADPH generated in the transgenics due to increased malate decarboxylation, contributed to augmented synthesis of proline, the osmoprotectant required to alleviate the reactive oxygen species-mediated membrane damage and oxidative stress. Consequently, the glutathione peroxidase activity increased and H2O2 content decreased in the salt-stressed transgenics. The reduced membrane lipid peroxidation and lower malondialdehyde production resulted in better preservation, of thylakoid integrity and membrane architecture in the transgenics under saline environment. Our results clearly demonstrate that overexpression of C4 chloroplastic ZmNADP-ME in the C3 Arabidopsis thaliana, although decrease their photosynthetic efficiency, protects the transgenics from salinity stress.


Hypothalamic-pituitary-gonadal axis in depressed premenopausal women: elevated blood testosterone concentrations compared to normal controls.
To assess the function of the hypothalamic-pituitary-gonadal (HPG) axis in major depression, a multihormonal study was carried out in 20 depressed premenopausal women. Serum concentrations of LH, FSH, estradiol, progesterone, testosterone, and GnRH-stimulated LH and FSH were measured before initiation of treatment (on the first day after menstruation) and during clomipramine treatment (same time one menstrual cycle later). Significantly higher blood concentrations of testosterone were found in untreated patients compared to normal controls. Furthermore, there was a significant negative correlation between Hamilton depression scores and estradiol concentrations of patients. The efficacy of clomipramine treatment was not related to hormonal parameters.


Purification of hog renin by affinity chromatography using the synthetic competitive inhibitor (D-Leu6)octapeptide.
The renin substrate analog His-Pro-Phe-His-Leu-D-Leu-Val-Tyr ([D-Leu6]-octapeptide) acts as a potent inhibitor of renin because of the D-amino acid substitution at the cleavage site. This inhibitor was coupled to CNBr-activated Sepharose 4B to yield a support for affinity chromatography. Hog renin with a specific activity of 1.2 Goldblatt units/mg was in one step purified 195-fold to a final specific activity of 234 Goldblatt units/mg. Application of a pH gradient from 5.0 to 7.5 to the support was found to be the most successful elution program, probably because the [D-Leu6]-octapeptide is not an inhibitor for renin at neutral pH.


Review of clinical evidence of caudal block for postoperative analgesia in children with ketamine added local anesthetics.
Adding ketamine to local anesthetics used for caudal block in children is an emerging clinical practice. This review aims to resolve controversies related to this adjuvant for a caudal block in children who underwent sub-umbilical surgeries. Between January 2010 and November 2021, PubMed, Cochrane Review, and Google Scholar were searched for a caudal block with ketamine added local anesthetics for children. After screening for eligibility and removing duplicates, 38,187 articles were found, 13 reviewed. Despite adding ketamine to local anesthetics used for a caudal block, it is a recent technique practiced worldwide. Ketamine showed equi-efficacious as other adjuvants used for the caudal block to control postoperative pain in children. Ketamine with a 0.5 mg/kg dose is safe and effective to manage postoperative children's pain when used as an adjuvant to local anesthetics used for caudal block.


Cell transplantation-based regenerative medicine in liver diseases.
This review aims to evaluate the current preclinical state of liver bioengineering, the clinical context for liver cell therapies, the cell sources, the delivery routes, and the results of clinical trials for end-stage liver disease. Different clinical settings, such as inborn errors of metabolism, acute liver failure, chronic liver disease, liver cirrhosis, and acute-on-chronic liver failure, as well as multiple cellular sources were analyzed; namely, hepatocytes, hepatic progenitor cells, biliary tree stem/progenitor cells, mesenchymal stromal cells, and macrophages. The highly heterogeneous clinical scenario of liver disease and the availability of multiple cellular sources endowed with different biological properties make this a multidisciplinary translational research challenge. Data on each individual liver disease and more accurate endpoints are urgently needed, together with a characterization of the regenerative pathways leading to potential therapeutic benefit. Here, we critically review these topics and identify related research needs and perspectives in preclinical and clinical settings.


Chromatin Immunoprecipitation Assay in Mouse Retinal Tissue.
Chromatin immunoprecipitation (ChIP) is one of the most widely used methods for investigating interactions between proteins and DNA sequences. ChIP plays an important role in the transcriptional regulation study, which can locate the target genes of transcription factors and cofactors or monitor the sequence-specific genomic regions of histone modification. To analyze the interaction between transcription factors and several candidate genes, ChIP coupled with quantitative PCR (ChIP-PCR) assay is a basic tool. With the development of next-generation sequencing technology, ChIP-coupled sequencing (ChIP-seq) can provide the protein-DNA interaction information in a genome-wide dimension, which helps a lot in identifying new target genes. This chapter describes a protocol for performing ChIP-seq of transcription factors from retinal tissues.


Binovular follicles in the adult human ovary.
The human ovary may contain binovular or polyovular follicles at birth, but they are unusual later in life. Binbovular follicles were found in bilateral ovarian biopsies from a patient with primary amenorrhea who had been treated with exogenous gonadotropins. The fine structural morphology of these follicles has shown that both oocytes were in the resting meiotic prophase, that their respective vitelline bodies faced each other across the intervening plasma membranes, and that the adjacent oocytes made mutual contacts similar to those found between granulosa cells and oocytes. From the appearance of the multivesicular bodies in nearby stromal fibroblasts it is suggested that these follicles had formed by fusion of two adjacent primordial follicles by a mechanism similar to the depolymerization of the ground substance in the apex of the Graafian follicle that leads to ovulation.


Pneumonia: cause or symptom of postinjury multiple organ failure?
Recent studies have shown that selective gut decontamination can reduce the incidence of pneumonia, but this does not decrease multiple organ failure (MOF) or mortality. These findings have prompted the hypothesis that pneumonia is an inconsequential symptom of MOF. To test this, we prospectively evaluated 123 high-risk trauma patients (mean Injury Severity Score = 36.2 +/- 1.5). Organ dysfunction, scored daily according to a 12-point scale, ultimately developed in 28 (23%) patients. Major infections were diagnosed, based on strict criteria, in 59 patients (48%), and pneumonia developed in 52 patients (43%). Pneumonia was significantly associated with MOF (82% of patients with MOF versus 30% of patients without MOF, p < 0.0001). In 14 (50%) of the patients with MOF, pneumonia preceded a significant rise (greater than or equal to 3) in serial MOF scoring. Of note, 10 (71%) of these patients died. Among the remaining 14 patients with MOF, 10 developed pneumonia, but this was associated with a minimal increase (less than or equal to 2) in MOF scoring (3 patients died). These data, by temporal association with MOF scoring, implicate pneumonia in precipitating or significantly worsening organ failure in 50% of the patients who developed MOF.


(-)-Indolactam V activates protein kinase C and induces changes in muscarinic receptor functions in SH-SY5Y human neuroblastoma cells.
The effects of a synthetic protein kinase C (PKC) activator, (-)-indolactam V (ILV), were studied in SH-SY5Y human neuroblastoma cells. (-)-ILV induced a translocation of PKC from cytosol to plasma membrane and displaced 3H-phorbol dibutyrate binding in the micromolar range. In addition, (-)-ILV caused a decreased sensitivity of cells to muscarinic agonist-induced Ca2+ mobilization measured with quin-2 and induced a down-regulation of cell surface muscarinic receptors. All the changes induced by (-)-ILV were similar in magnitude to those seen with the phorbol ester tetradecanoyl phorbol acetate (TPA). The results suggest that (-)-ILV is a full activator of PKC and a promising alternative to phorbol esters in studies on mechanism of actions of PKC.


Functioning and quality of life in patients with somatic symptom disorder: The association with comorbid depression.
Patients with somatic symptoms often have impaired functioning and reduced quality of life (QOL), but the factors identified as responsible for these impairments vary between studies. We examined functioning and QOL in patients with somatic symptom disorder (SSD), exploring their associations with demographic factors, personality traits and psychological features. The sample comprised 107 SSD patients and 100 healthy controls. Several types of self-report instrument were administered. Group differences were assessed with independent t-tests. We used multiple linear regression to examine relationships between the independent variables and functioning and QOL. Finally, we used structural equation modeling (SEM) to perform path analysis and examine the fit of a model based on the earlier results. Most function scores were lower in SSD patients than in healthy controls. In SSD patients overall WHO Quality of Life-BREF (WHOQOL-BREF) score was correlated with exercise level and Beck Depression Inventory-II (BDI-II) score. There were also associations between Sheehan Disability Scale (SDS) score and age, novelty seeking, Cognitions About Body and Health Questionnaire (CABAH) score and BDI-II score. Family APGAR score was only related to BDI-II score. Path analysis revealed that BDI-II score was related to all three indices of functioning. Depression is associated with functioning and QOL in SSD patients. The Research Ethics Committee of National Taiwan University National Taiwan University Hospital approved this study (approval number: 201507007RINB).


Role of computerized axial tomography in diagnosis, treatment and follow-up of hydrocephalus. Preliminary communication.
The authors have summarized their experience in the application of computerized axial tomography to the overall management of hydrocephalus.


Improved cross-axis synchronous flow-through coil planet centrifuge for performing counter-current chromatography. II. Studies on retention of stationary phase in short coils and preparative separations in multilayer coils.
Performance of the apparatus was evaluated in terms of stationary phase retention, partition efficiency and sample loading capacity. Preliminary studies with short coils revealed high retention of the stationary phase under a proper combination of the head-tail elution and planetary motion. Preparative capability of the apparatus was successfully demonstrated on efficient multigram separations of 2,4-dinitrophenyl amino acids, indole auxins, and bacitracin in a pair of large multilayer coils with a total capacity of 1.5 l.


Bication lead iodide 2D perovskite component to stabilize inorganic α-CsPbI3 perovskite phase for high-efficiency solar cells.
Among various all-inorganic halide perovskites exhibiting better stability than organic-inorganic halide perovskites, α-CsPbI3 with the most suitable band gap for tandem solar cell application faces an issue of phase instability under ambient conditions. We discovered that a small amount of two-dimensional (2D) EDAPbI4 perovskite containing the ethylenediamine (EDA) cation stabilizes the α-CsPbI3 to avoid the undesirable formation of the nonperovskite δ phase. Moreover, not only the 2D perovskite of EDAPbI4 facilitate the formation of α-CsPbI3 perovskite films exhibiting high phase stability at room temperature for months and at 100°C for >150 hours but also the α-CsPbI3 perovskite solar cells (PSCs) display highly reproducible efficiency of 11.8%, a record for all-inorganic lead halide PSCs. Therefore, using the bication EDA presents a novel and promising strategy to design all-inorganic lead halide PSCs with high performance and reliability.


Anomalous optic nerve fiber convergences in the ipsilateral retinocollicular projection: a comparison of congenitally monocular and neonatally one-eye-removed rats.
Single cell responses to electrical stimuli applied to the optic chiasm and to the lateral geniculate nucleus were studied in expanded projection to the ipsilateral superior colliculus of neonatally enucleated and congenitally monocular rats. In both types of rats latencies to the afferent volleys were longer, and the latency correlation between the optic chiasm and the lateral geniculate responses was lower in the ipsilateral than in the contralateral superior colliculus cells. This was interpreted to suggest abnormal convergence of retinal axons with different conduction velocities in the ipsilateral retinocollicular projection. The deviation of ipsilateral superior colliculus cells from the high-latency correlation of the contralateral cells was more marked in congenitally monocular than in neonatally enucleated rats.


A [-2]proPSA-based artificial neural network significantly improves differentiation between prostate cancer and benign prostatic diseases.
The aim of this study was to combine the new automated Access [-2]proPSA (p2PSA) assay with a percent free PSA (%fPSA) based artificial neural network (ANN) or logistic regression (LR) model to enhance discrimination between patients with prostate cancer (PCa) and with no evidence of malignancy (NEM) and to detect aggressive PCa. Sera from 311 PCa patients and 275 NEM patients were measured with the p2PSA, total PSA (tPSA) and free PSA (fPSA) assays on Access immunoassay technology (Beckman Coulter, Fullerton, CA) within the 0-30 ng/ml tPSA range. Four hundred seventy-five patients (264 PCa, 211 NEM) had a tPSA of 2-10 ng/ml. LR models and leave-one-out (LOO) ANN models with Bayesian regularization by using tPSA, %fPSA, p2PSA/fPSA (%p2PSA), age and prostate volume were constructed and compared by receiver-operating characteristic (ROC) curve analysis. The ANN and LR model each utilizing %p2PSA, %fPSA, tPSA and age, but without prostate volume, reached the highest AUCs (0.85 and 0.84) and best specificities (ANN: 62.1% and 45.5%; LR: 53.1% and 41.2%) compared with tPSA (22.7% and 11.4%) and %fPSA (45.5% and 26.1%) at 90% and 95% sensitivity. The %p2PSA furthermore distinguished better than tPSA and %fPSA between pT2 and pT3, and Gleason sum <7 and >or=7 PCa. The automated p2PSA assay offers a new tool to improve PCa detection, and especially aggressive PCa detection. Incorporation of %p2PSA into an ANN and LR model further enhances the diagnostic accuracy to differentiate between malignant and non-malignant prostate diseases.


The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets.
The development of molecularly targeted anticancer agents relies on large panels of tumour-specific preclinical models closely recapitulating the molecular heterogeneity observed in patients. Here we describe the mutational and gene expression analyses of 151 colorectal cancer (CRC) cell lines. We find that the whole spectrum of CRC molecular and transcriptional subtypes, previously defined in patients, is represented in this cell line compendium. Transcriptional outlier analysis identifies RAS/BRAF wild-type cells, resistant to EGFR blockade, functionally and pharmacologically addicted to kinase genes including ALK, FGFR2, NTRK1/2 and RET. The same genes are present as expression outliers in CRC patient samples. Genomic rearrangements (translocations) involving the ALK and NTRK1 genes are associated with the overexpression of the corresponding proteins in CRC specimens. The approach described here can be used to pinpoint CRCs with exquisite dependencies to individual kinases for which clinically approved drugs are already available.


Chiral derivatizations applied for the separation of unusual amino acid enantiomers by liquid chromatography and related techniques.
Amino acids are essential for life, and have many functions in metabolism. One particularly important function is to serve as the building blocks of peptides and proteins, giving rise complex three dimensional structures through disulfide bonds or crosslinked amino acids. Peptides are frequently cyclic and contain proteinogenic as well as nonproteinogenic amino acids in many instances. Since most of the proteinogenic α-amino acids contain at least one stereogenic center (with the exception of glycine), the stereoisomers of all these amino acids and the peptides in which they are to be found may possess differences in biological activity in living systems. The impetus for advances in chiral separation has been highest in the past 25 years and this still continues to be an area of high focus. The important analytical task of the separation of isomers is achieved mainly by chromatographic and electrophoretic methods. This paper reviews indirect separation approaches, i.e. derivatization reactions aimed at creating the basis for the chromatographic resolution of biologically and pharmaceutically important enantiomers of unusual amino acids and related compounds, with emphasis on the literature published from 1980s. The main aspects of the chiral derivatization of amino acids are discussed, i.e. derivatization on the amino group, transforming the molecules into covalently bonded diastereomeric derivatives through the use of homochiral derivatizing agents. The diastereomers formed (amides, urethanes, urea and thiourea derivatives, etc.) can be separated on achiral stationary phases. The applications are considered, and in some cases different derivatizing agents for the resolution of complex mixtures of proteinogenic d,l-amino acids, non-proteinogenic amino acids and peptides/amino acids from peptide syntheses or microorganisms are compared.


The impact of hyperglycemia and obesity on hospitalization costs and clinical outcome in general surgery patients.
The impact of obesity on clinical outcomes and hospitalization costs in general surgery patients with and without diabetes (DM) is unknown. We reviewed medical records of 2451 patients who underwent gastrointestinal surgery at two university hospitals. Hyperglycemia was defined as BG ≥140 mg/dl. Overweight was defined by body mass index (BMI) between 25-29.9 kg/m(2) and obesity as a BMI ≥30 kg/m(2). Hospital cost was calculated using cost-charge ratios from Centers for Medicare and Medicaid Services. Hospital complications included a composite of major cardiovascular events, pneumonia, bacteremia, acute kidney injury (AKI), respiratory failure, and death. Hyperglycemia was present in 1575 patients (74.8%). Compared to patients with normoglycemia, those with DM and non-DM with hyperglycemia had higher number of complications (8.9% vs. 35.8% vs. 30.0%, p<0.0001), longer hospital stay (5 days vs. 9 days vs. 9 days, p<0.0001), more readmissions within 30 days (9.3% vs. 18.8% vs. 17.2%, p<0.0001), and higher hospitalization costs ($20,273 vs. $79,545 vs. $72,675, p<0.0001). In contrast, compared to normal-weight subjects, overweight and obesity were not associated with increased hospitalization costs ($58,313 vs. $58,173 vs. $66,633, p=0.74) or risk of complications, except for AKI (11.9% vs. 14.8% vs. 20.5%, p<0.0001). Multivariate analysis revealed that DM (OR=4.4, 95% CI=2.8,7.0) or perioperative hyperglycemia (OR=4.1, 95% CI=2.7-6.2) were independently associated with increased risk of complications. Hyperglycemia but not increasing BMI, in patients with and without diabetes undergoing gastrointestinal surgery was associated with a higher number of complications and hospitalization costs.


Effect of N-acetylcysteine on vascular endothelium function in aorta from oophorectomized rats.
1. Experiments were performed to examine and to compare vascular endothelial function in aortic rings from oophorectomized and from ovary-intact rats and to test the effect of thiol compound as N-acetylcysteine on endothelial function. 2. In precontracted aortic rings from oophorectomized and intact rats, vascular endothelial function was evaluated by measuring changes in isometric force in response to cumulative doses of superoxide dismutase, acetylcholine and sodium nitroprusside. 3. In studies designed to assess the tone-related release of nitric oxide from aortic rings moderately precontracted with phenylephrine, superoxide dismutase produced a lower concentration-related relaxant response in aortic rings from oophorectomized rats than from ovary intact rats. 4. Acetylcholine caused a concentration- and endothelium-dependent relaxation of less magnitude in aortic rings from oophorectomized animals compared with those from ovary-intact rats. Addition of N-omega-nitro-L-arginine methyl ester eliminated the relaxation induced by both superoxide dismutase and acetylcholine. 5. No differences between groups were noticed in the concentration-relaxation curve induced by sodium nitroprusside. 6. Preincubation with N-acetylcysteine normalized the depressed vasorelaxant response to acetylcholine in the aortic rings from oophorectomized rats, whereas the concentration-response curve for acetylcholine in aortic rings from ovary-intact rats did not alter. 7. These results suggest that the absence of ovary estrogens is associated with a vascular endothelium dysfunction that can be reverted by addition of N-acetylcysteine, a thiol-containing compound with a free radical scavenger effect.


Bladder recurrence of upper urinary tract cancer after laparoscopic surgery.
We reviewed our cases to determine whether laparoscopic nephroureterectomy is a risk factor for the bladder recurrence. From 1996 to 2003, 65 nephroureterectomies were performed: 47 by open and 18 by laparoscopic surgery. In 43 (28 by open, 15 by laparoscopic surgery), bladder cancer was not observed at the time of the operation. Two laparoscopic operations were converted to open surgery because of technical problems. The other 13 with laparoscopic and 28 with open surgery were enrolled into this study. Significantly higher recurrence rate was observed in laparoscopic cases (69.2%) than that in open cases (35.7%, P = 0.0484) by log rank test. However, the operation time required in laparoscopic surgery (371.5 +/- 90.8 min) was significantly longer than that in the open surgery (229.9 +/- 46.6 min, P < 0.0001). In multivariate analysis (Cox proportional hazards model), only the longer operation time (>250 min) was a significant variable (P = 0.0305), and laparoscopic surgery in itself was not a significant risk factor (P = 0.5011). Although frequent bladder recurrence was observed in laparoscopic cases, the most important risk factor was the longer operation time. Technical improvements including shortening of operation time and earlier ureteral ligation may decrease the bladder recurrence.


[Medium-chain acyl-CoA-dehydrogenase (MCAD) deficiency: French consensus for neonatal screening, diagnosis, and management].
MCAD deficiency is the most common fatty acid oxidation disorder, with the prevalence varying from 1/10,000 to 1/27,000 in the countries adjacent to France. As the High Authority for Health has recently proposed including MCAD deficiency in the panel of diseases neonatally screened for in France, a consensus was written for the management of MCAD deficiency diagnosed either clinically or by neonatal screening. Patients may present acutely with hyperammonemia, hypoglycemia, encephalopathy, and hepatomegaly, mainly after a prolonged fast of intercurrent infection. Sudden death related to heartbeat disorders may also occur. The diagnosis of MCAD deficiency is suspected on the plasma acylcarnitine and/or the urinary organic acid profile. The diagnosis is confirmed by molecular biology and the enzymatic activity for patients who are not homozygous for the main mutation c.985A>G. However, some MCAD-deficient individuals may remain asymptomatic throughout life. The mainstay of treatment consists in avoiding prolonged fast and prescribing l-carnitine for patients who exhibit a deficiency in plasma carnitine. This management has radically modified the natural history of MCAD deficiency. This consensus will allow homogeneous management of these patients once the neonatal screening of MCAD deficiency has been introduced in France.


Nomogram Predicting Locally Advanced Prostate Cancer in Patients with Clinically Organ-Confined Disease Who Underwent Robot-Assisted Radical Prostatectomy: A Retrospective Multicenter Cohort Study in Japan (The MSUG94 Group).
We created a clinically applicable nomogram to predict locally advanced prostate cancer using preoperative parameters and performed external validation using an external independent validation cohort. From a retrospective multicenter cohort study of 3622 Japanese patients with prostate cancer who underwent robot-assisted radical prostatectomy at ten institutions, the patients were divided into two groups (MSUG cohort and validation cohort). Locally advanced prostate cancer was defined as pathological T stage ≥ 3a. A multivariable logistic regression model was used to identify factors strongly associated with locally advanced prostate cancer. Bootstrap area under the curve was calculated to assess the internal validity of the prediction model. A nomogram was created as a practical application of the prediction model, and a web application was released to predict the probability of locally advanced prostate cancer. A total of 2530 and 427 patients in the MSUG and validation cohorts, respectively, met the criteria for this study. On multivariable analysis, initial prostate-specific antigen, prostate volume, number of cancer-positive and cancer-negative biopsy cores, biopsy grade group, and clinical T stage were independent predictors of locally advanced prostate cancer. The nomogram predicting locally advanced prostate cancer was demonstrated (area under the curve 0.72). Using a nomogram cutoff of 0.26, 464 of 1162 patients (39.9%) could be correctly diagnosed with pT3, and 2311 of 2524 patients (91.6%) could avoid underdiagnosis. We developed a clinically applicable nomogram with external validation to predict the probability of locally advanced prostate cancer in patients undergoing robot-assisted radical prostatectomy.


Betaine protects against heat exposure-induced oxidative stress and apoptosis in bovine mammary epithelial cells via regulation of ROS production.
Heat stress is one of the wide varieties of factors which cause oxidative stress in vivo; elevated temperature can lead to oxidative stress of dairy cows that affects milk production. The aim of this study was to determine the capacity of the betaine to act as an antioxidant against oxidative stress induced by heat exposure and apoptosis in mammary epithelial cells (mammary alveolar cells, MAC-T). The MAC-T were divided into four treatment groups: control (37 °C), heat stress (HS, 42 °C), betaine (37 °C), and HS + betaine. MAC-T under heat stress (HS) showed increased ROS accumulation, malondialdehyde (MDA) content, superoxide dismutase (SOD) concentration, and catalase (CAT) activity. During heat stress, betaine decreased the mRNA expression level of HSP70 and HSP27 in MAC-T. Bax/Bcl-2 ratio and caspase-3, the markers of apoptosis, were also elevated in MAC-T under heat stress. The markers of oxidative stress Nrf-2/HO-1 genes were also elevated in MAC-T under heat stress. Pretreatment of betaine reversed the heat-induced depletion in total antioxidant status, ROS accumulation, and SOD and CAT contents in MAC-T. Bax/Bcl-2 ratio and Nrf-2/HO-1 expression of heat-exposed MAC-T were also reduced with betaine supplementation. In conclusion, betaine alleviated oxidative stress and apoptosis of MAC-T by inhibiting ROS accumulation.


Upper Limb Ischemic Postconditioning as Adjunct Therapy in Acute Stroke Patients: A Randomized Pilot.
This study aims to observe the clinical effect of upper limb ischemic postconditioning (LIPostC) as an adjunct to treatment with acute stroke patients, possibly due to increased cerebral perfusion. We perform a randomized blinded placebo controlled trial in nonthrombolysis patients with acute ischemic stroke, within 72hours of ictus, divided into the LIPostC group and control group. The LIPostC group is induced by 4 cycles of intermittent repeated limb ischemia: alternating 5 minutes inflation (20mm Hg above systolic blood pressure) and 5 minutes deflation performed manually using a standard upper arm blood pressure cuff in the nonparetic arm. The control group receives a sham procedure (cuff inflation to 30mm Hg). Patients underwent the intervention from the time of enrollment to Day 14. Comparison of National Institutes of Health Stroke Scale (NIHSS) score, cerebral infarction volume, relative Perfusion weighted imaging (PWI) parameters (regional relative cerebral blood flow, regional relative mean transit time; preintervention [day 0], day 14, day 90), modified Rankin Scale (mRS; the preintervention score [day 0], the curative ratio at day 90 [we define 0-1 score as close to recovery or full recovery]). Sixty eligible patients with acute stroke (29 LIPostC and 31 control) are recruited age 65years (SD 12.22), blood pressure 156/74mm Hg (SD 14/10), and NIHSS score 5.98 (SD 3.35), mRS score 2.25 (SD .79). Only 1 in the LIPostC group is intolerant the first cycle to give up. All patients tolerate the sham procedure. Two patients experience recurrent stroke versus none in the LIPostC group. Day 90, compared with the control group, there is a significant decrease the NIHSS score, regional relative mean transit time (P < .05) and increase the curative ratio of mRS, regional relative cerebral blood flow(P < .05) in the LIPostC group, which infarct volume decreased by 31.3% (P < .05). LIPostC after acute stroke is well tolerated and appears safe and feasible. LIPostC may improve neurological outcome, and protective mechanisms may be increased cerebral blood flow to improve cerebral perfusion. A larger trial is warranted.


Reliability of the P3 component in a 3-stimulus concealed information test with known and unknown stimuli.
The parietal P3 amplitude of the event-related potential (ERP) has been highlighted to signal stimulus salience in concealed information tests (CITs) with known and unknown stimuli. To extend previous validity investigations in deception research, the reliability of the early parietal P3 amplitude in a 3-stimulus CIT including known and unknown stimuli has been investigated in a sample of N = 68 participants. Variations of Cronbach's Alpha and split-half reliability (odd-even, 1st vs. 2nd half) of the early parietal P3 amplitude were considered for ERP quantification method (peak-to-peak, mean, baseline-to-peak), epoch selection strategies (chronological vs. random) and number of epochs (10-40) in three stimulus types (probe, target, irrelevant). Excellent reliability coefficients have been summarized for number of epochs, P3 quantifications, and epoch selection strategies. Moreover, the best-practice recommendations highlight mandatory combinations of epoch selection strategy, number of epochs and P3 quantifications to ensure robust and excellent reliabilities of the early parietal P3 amplitude in a 3-stimulus CIT with known (probe, target) and unknown (irrelevant) stimuli. The robustness of mandatory excellent reliability coefficients for the early parietal P3 has been discussed for two data tracks in single-case analyses.


Lower heart rate variability, an index of worse autonomic function, is associated with worse beta cell response to a glycemic load in vivo-The Maastricht Study.
We investigated, using population-based data, whether worse autonomic function, estimated from lower 24-hour heart rate variability (HRV), was associated with beta cell function, assessed from beta cell response during an oral glucose tolerance test (OGTT). We used cross-sectional data from The Maastricht Study, a population-based cohort study (N = 2,007; age, mean ± SD:60 ± 8 years; 52% men; and 24% with type 2 diabetes). We used linear regression analyses with adjustment for potential confounders (demographic, cardiovascular, and lifestyle factors) to study the associations of time- and frequency-domain HRV (composite scores) with overall beta cell response (estimated from a composite score calculated from: C-peptidogenic index, overall insulin secretion, beta cell glucose sensitivity, beta cell potentiation factor, and beta cell rate sensitivity). In addition, we tested for interaction by sex and glucose metabolism status. After full adjustment, lower time- and frequency-domain HRV was significantly associated with lower overall beta cell response composite score (standardized beta, -0.055 [-0.098; -0.011] and - 0.051 [-0.095; -0.007], respectively). These associations were not modified by sex and there was no consistent pattern of interaction by glucose metabolism status. The present etiological study found that worse autonomic function, estimated from lower HRV, was associated with worse beta cell function, estimated from a composite score in a population-based sample which covered the entire spectrum of glucose metabolism. Hence, autonomic dysfunction may contribute to beta cell dysfunction and, ultimately, to the alteration of glucose metabolism status from normal glucose metabolism to prediabetes and type 2 diabetes.


An attempt to determine lipid peroxides with polyethylene glycol-modified hemin.
Hemin, having two carboxyl groups, was coupled with alpha-(3-aminopropyl)-omega-methoxypoly(oxyethylene) through the acid-amide bond formed with carbodiimide. The modified hemin catalyzed the peroxidase reaction in 1,1,1-trichloroethane using benzoyl peroxide or peroxides in unsaturated fatty acids as the hydrogen acceptor and leuco crystal violet as the hydrogen donor. A basic study on quantitative microanalysis of the lipid peroxides was attempted.


The effects of phytosterol supplementation on serum LDL-C levels and learning ability in mice fed a high-fat, high-energy diet from gestation onward.
A high-fat, high-energy (HFE) diet may be deleterious to the cardiovascular system and mental health. We previously reported that serum cholesterol levels and escape latency were significantly increased in mice by feeding them an HFE diet from gestation onward. In this study, we examined whether an HFE diet supplemented with phytosterols fed to pregnant C57BL/6j dams and their offspring would protect the HFE-diet-induced compromise of the offspring's learning capability. We measured serum cholesterol levels, brain N-methyl-D-aspartate receptor (NMDAR1) mRNA and protein expression and liver sterol 27-hydroxylase (Cyp27a1) mRNA expression, as well as a Morris water maze performance. The results showed that, compared to mice consuming the HFE diet alone, those also consuming phytosterols (the HFE + PS diet) significantly decreased mean serum low-density lipoprotein cholesterol levels and altered brain NMDAR1 mRNA and protein expression and liver Cyp27a1 mRNA expression. The Morris water maze experiments indicated that dietary phytosterol supplementation slightly decreased the escape latency (p = 0.07). Collectively, these observations suggest that consumption of phytosterols from early in life may help alleviate the detrimental effects of HFE diets in mice.


Comparison of three stool antigen tests in confirming Helicobacter pylori eradication in adults.
Reliable and readily available non-invasive methods are needed for detection of Helicobacter pylori infection and assessment of eradication therapy. In H. pylori-positive subjects we compared three stool antigen tests (Premier Platinum HpSA, Amplified IDEIA HpStAR and ImmunoCard STAT!HpSA) with invasive tests before their eradication therapy, and with non-invasive diagnostic methods after their therapy. A total of 82 adults with dyspepsia (aged 24-79 years) with an H. pylori-positive rapid urease test were enrolled in the study. Before therapy, H. pylori status was also confirmed with histology, culture and serology. After eradication, success was assessed with the [13C]-urea breath test (UBT) and usually also with serology. At baseline, sensitivities of these stool antigen tests were 90.2% for HpSA, 97.6% for HpStAR and 96.3% for ImmunoCard. Eradication therapy was successful in 66 patients and unsuccessful in 16. Sensitivity and specificity of the three stool antigen tests in the post-eradication setting were, respectively, 75.0% and 95.5% for HpSA, 93.8% and 98.5% for HpStAR and 87.5% and 95.5% for Immunocard. The performance of all three stool antigen tests in the post-treatment setting was slightly inferior to that of the UBT test and serology, with monoclonal antibody-based tests showing better results.


Double Switch Procedure and Surgical Alternatives for the Treatment of Congenitally Corrected Transposition of the Great Arteries.
We present our experience with the double switch operation in sixteen patients with congenitally corrected transposition of the great arteries. We enrolled 16 patients with congenitally corrected transposition of the great arteries operated by a single surgeon between 1995 and 2015. The mean age was 25 months (range 4 to 72 months) and the mean body weight was 8.9 kg (range 4.3 to 19 kg) at the time of operation. We encountered seven patients with moderate to severe tricuspid regurgitation, five of which had Ebstein anomaly. We performed a combination of atrial and arterial switch procedures in 11 cases, one of which had a concomitant coarctation of the aorta that was repaired along with the double switch procedure. Atrial switch and the Rastelli procedures were performed in three cases with concomitant pulmonary stenosis. A combination of arterial switch, Hemi-Mustard procedure, and bidirectional cavopulmonary anastomosis was performed in two cases. During a mean follow-up period of 67 months (range three months to 18 years), we encountered one early postoperative mortality related to intracerebral bleeding. All but one of the patients are now in NYHA class I-II. Congenitally corrected transposition of the great arteries is a rare congenital cardiac anomaly in which the results of the anatomical repair with double switch operation appear to be superior to that achieved by a physiological repair.


Fulvic acid mitigates cadmium toxicity-induced damage in cucumber seedlings through the coordinated interaction of antioxidant enzymes, organic acid, and amino acid.
Fulvic acid (FA) can significantly alleviate cadmium (Cd) stress, but the specific metabolic response of FA to Cd toxicity is still not clarified. In the present study, we used untargeted metabolomic [gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)] analysis to profile cucumber metabolism in response to Cd stress after spray application of FA. Our results showed that 331 differentially enriched metabolites (DEMs) were identified in leaf materials. These DEMs were enriched in 21 shared pathways in comparative groups of "Cd treatment vs. the control treatment" and "FA + Cd treatment vs. the Cd treatment." Specifically, treatment with FA significantly enhanced the organic acid content (citric acid, isocitric acid, 2-oxoglutaric acid, fumaric acid, and malic acid), which would contribute to provide sufficient substrates for the tricarboxylic acid (TCA) cycle and amino acid biosynthesis, thereby ensuring the normal production of energy and amino acid. At the same time, FA significantly increased the amino acid content (aspartate, citrulline, histidine, leucine, and phenylalanine). The accumulation of organic acid and amino acid can act as chelating agents for heavy metal ions and as scavengers of reactive oxygen species (ROS), thereby reducing intracellular oxidative damage. Furthermore, the application of FA improves antioxidant enzymes and accelerates ROS clearance. The improved contents of organic acid and amino acid, and the increased activity of antioxidant enzymes both played a central role in the reduction of malondialdehyde (MDA, 14.08%), hydrogen peroxide (H2O2, 61.70%) contents, and superoxide anion radical (O2-, 30.41%) production rate in plants under Cd stress. Taken together, the present study demonstrates the effects of FA on the antioxidant capacity and carbohydrate and amino acid metabolism of cucumber seedlings exposed to Cd stress, which provides comprehensive insights into the regulation of plants' response to Cd toxicity with FA was applied in cucumber.


Stresses and coping strategies of Chinese families with children with autism and other developmental disabilities.
Data from 368 families of children with autism and other developmental disabilities in the People's Republic of China were gathered to understand the stresses that families experience and the coping strategies they employ. Chinese families of children with developmental disabilities perceived high levels of stress related to pessimism, child characteristics, and parent and family problems. Regarding coping strategies, acceptance, active coping, positive reinterpretation and growth, suppression of competing activities, and planning were the most frequently employed coping strategies. Parents of children with autism experienced more stress and used planning as a coping strategy to a greater degree than parents of children with other developmental disabilities. The implications and limitations of these findings are discussed.


A comprehensive survey on gait analysis: History, parameters, approaches, pose estimation, and future work.
Human gait is a periodic motion of body segments-the analysis of motion and related studies is termed gait analysis. Gait Analysis has gained much popularity because of its applications in clinical diagnosis, rehabilitation methods, gait biometrics, robotics, sports, and biomechanics. Traditionally, subjective assessment of the gait was conducted by health experts; however, with the advancement in technology, gait analysis can now be performed objectively and empirically for better and more reliable assessment. State-of-the-art semi-subjective and objective techniques for gait analysis have limitations that can be mitigated using advanced machine learning-based approaches. This paper aims to provide a narrative and a comprehensive analysis of cutting-edge gait analysis techniques and insight into clinical gait analysis. The literature of the previous surveys during the last decade is discussed. This paper presents an elaborated schema, including gait analysis history, parameters, machine learning approaches for marker-based and marker-less analysis, applications, and performance measures. This paper also explores the pose estimation techniques for clinical gait analysis that open future research directions in this area.


Biomarkers in Rare Diseases 2.0.
It is estimated that there are over 7000 rare diseases, collectively affecting more than 350 million individuals worldwide [...].


Anisotropic charge trapping in phototransistors unlocks ultrasensitive polarimetry for bionic navigation.
Being able to probe the polarization states of light is crucial for applications from medical diagnostics and intelligent recognition to information encryption and bio-inspired navigation. Current state-of-the-art polarimeters based on anisotropic semiconductors enable direct linear dichroism photodetection without the need for bulky and complex external optics. However, their polarization sensitivity is restricted by the inherent optical anisotropy, leading to low dichroic ratios of typically smaller than ten. Here, we unveil an effective and general strategy to achieve more than 2,000-fold enhanced polarization sensitivity by exploiting an anisotropic charge trapping effect in organic phototransistors. The polarization-dependent trapping of photogenerated charge carriers provides an anisotropic photo-induced gate bias for current amplification, which has resulted in a record-high dichroic ratio of >104, reaching over the extinction ratios of commercial polarizers. These findings further enable the demonstration of an on-chip polarizer-free bionic celestial compass for skylight-based polarization navigation. Our results offer a fundamental design principle and an effective route for the development of next-generation highly polarization-sensitive optoelectronics.


The effect of continuous dialysis on platelet preservation.
Serotonin uptake and response to hypotonic shock were studied after storage of platelet-rich plasma for three days at 4, 25, and 37 C. Both properties were best maintained at 25 C. The greatly impaired serotonin uptake and hypotonic shock response of platelets stored for three days at 37 C were partly restored by resuspension of the platelets in fresh autologous plasma. No improvement was found when platelets stored at 4 C were resuspended in fresh autologous plasma. When platelet suspensions were stored for three days at 4, 25, and 37 C under continuous dialysis against plasma, the results obtained at 37 C were even better than those obtained with platelets stored at 25 C. These results indicate that if the accumulation of metabolites in the plasma milieu, which in addition to other changes results in a drop of pH, is prevented, the effective storage time of platelet concentrates can be prolonged. The use of a closed plastic dialysis system, based on the triple-bag transfusion set is suggested.


In vitro antimicrobial combination testing of and evolution of resistance to the first-in-class spiropyrimidinetrione zoliflodacin combined with six therapeutically relevant antimicrobials for Neisseria gonorrhoeae.
Resistance in Neisseria gonorrhoeae to all gonorrhoea therapeutic antimicrobials has emerged. Novel therapeutic antimicrobials are imperative and the first-in-class spiropyrimidinetrione zoliflodacin appears promising. Zoliflodacin could be introduced in dual antimicrobial therapies to prevent the emergence and/or spread of resistance. We investigated the in vitro activity of and selection of resistance to zoliflodacin alone and in combination with six gonorrhoea therapeutic antimicrobials against N. gonorrhoeae. The international gonococcal reference strains WHO F (WT) and WHO O, WHO V and WHO X (strains with different AMR profiles) were examined. Zoliflodacin was evaluated alone or combined with ceftriaxone, cefixime, spectinomycin, gentamicin, tetracycline, cethromycin or sitafloxacin in chequerboard assays, time-kill curve analysis and selection-of-resistance studies. Zoliflodacin alone or in combination with all six antimicrobials showed rapid growth inhibition against all examined strains. The time-kill curve analysis indicated that tetracycline or cethromycin combined with zoliflodacin can significantly decrease the zoliflodacin kill rate in vitro. The frequency of selected zoliflodacin-resistance mutations was low when evaluated as a single agent and further reduced for all antimicrobial combinations. All resistant mutants contained the GyrB mutations D429N, K450T or K450N, resulting in zoliflodacin MICs of 0.5-4 mg/L. Zoliflodacin, alone or in combination with sexually transmitted infection therapeutic antimicrobials, rapidly kills gonococci with infrequent resistance emergence. Zoliflodacin remains promising for gonorrhoea oral monotherapy and as part of dual antimicrobial therapy with low resistance emergence potential. A Phase III trial evaluating efficacy and safety of zoliflodacin for uncomplicated gonorrhoea treatment is planned in 2019.


The primary structure of the alpha subunit of protocatechuate 3,4-dioxygenase. II. Isolation and sequence of overlap peptides and complete sequence.
The complete primary structure of the alpha subunit of protocatechuate 3,4-dioxygenase has been determined by automated Edman degradation and carboxypeptidase digestionof the intact alpha chain and of peptides derived from trypsin (N.A. Kohlmiller and J.B. Howard (1979) J. Biol. Chem. 254, 7302-7308) and Staphylococcus aureus protease digestion, and from hydroxylamine and dilute acid cleavage. The alpha chain was found to consist of 200 residues in the following sequence from the NH2-terminal end: (formula: see text).


Palliative and end of life care for a child: Understanding parents' coping strategies.
Understanding of coping strategies that parents use before the death of their child is crucial and will enable us to best provide support. The current study aimed to explore parents' coping strategies, and map these onto an existing theoretical framework. Bereaved parents and parents of a child with a life-limiting/threatening condition were interviewed to investigate coping strategies, recruited through Intensive Care Units (2 Neonatal, 2 Paediatric, 1 Paediatric Cardiac) and a children's hospice. Analysis focused on coping strategies and mapping these onto the framework. 24 parents of 20 children were interviewed and identified. Parents use a variety of coping strategies (n = 25) such as humour, staying positive, advocating and staying strong for others, expressing emotions and preparing, while also living life to the full, supported by others. The themes were successfully mapped onto the theoretical framework, which focuses on the constructs of approach and avoidance, as well as coping for self and others. The findings have provided a detailed account of the breadth and depth of coping strategies parents use, including those classed as avoidance. The strategies were successfully mapped onto the theoretical framework. Future research should investigate changes over times, and associations to negative long-term outcomes.


'Cap' structures in maize poly(A)-containing RNA.
Poly(A)-containing RNA was isolated from maize embryos by chromatography on columns of oligo(dT)-cellulose and exhaustively digested with ribonucleases T2, T1, and A. Fractionation of the digests by two-dimensional electrophoresis revealed the presence of three 7-methylguanosine-terminated 'cap structures' of the type m7GpppNp.


An Evidence-Based Videotaped Running Biomechanics Analysis.
Running biomechanics play an important role in the development of injuries. Performing a running biomechanics analysis on injured runners can help to develop treatment strategies. This article provides a framework for a systematic video-based running biomechanics analysis plan based on the current evidence on running injuries, using 2-dimensional (2D) video and readily available tools. Fourteen measurements are proposed in this analysis plan from lateral and posterior video. Identifying simple 2D surrogates for 3D biomechanic variables of interest allows for widespread translation of best practices, and have the best opportunity to impact the highly prevalent problem of the injured runner.


Mitral valve repair with the new semirigid partial Colvin-Galloway Future annuloplasty band.
Various devices have been proposed for ring stabilization in patients with mitral valve disease. This study reports the intermediate-term results of mitral valve repair with a new semirigid partial annuloplasty ring in a large series of patients. A total of 437 consecutive patients were analyzed who underwent mitral valve reconstruction with annuloplasty using the Colvin-Galloway Future band at the German Heart Center in Munich between 2001 and 2005. A total of 237 patients (54.2%) underwent isolated mitral valve repair, and 200 patients (45.8%) underwent a combined procedure. The follow-up is 97% complete (mean follow-up of 405 survivors 2.1 +/- 1.1 years). Overall 30-day mortality was 2.7%. Twenty patients (4.6%) died later after an average of 1.1 +/- 1.1 years. Actuarial survival at 4 years after isolated mitral valve reconstruction and combined procedures was 91% +/- 4% and 87% +/- 2.5%, respectively (P < .001). Twelve patients (2.7%) required a mitral valve reoperation after an average of 4.5 +/- 4.3 months. Five of these reoperations were required for band dehiscence, and 1 reoperation was required for band fracture. Freedom from reoperation at 4 years was 97% +/- 0.9%. At the latest follow-up, 93.5% of the patients showed trivial or mild mitral valve regurgitation, and 86.4% of the patients showed New York Heart Association functional class I or II. Mitral valve annuloplasty with the Colvin-Galloway Future band can be performed with a low early and late mortality and an excellent functional outcome. The low incidence of reoperation demonstrates that the Colvin-Galloway Future band is a safe and effective device. The importance of secure anchoring of the device in the mitral annulus has to be emphasized to prevent band dehiscence.


An arachidonoyl (polyenoic)-specific phospholipase A2 activity regulates the synthesis of platelet-activating factor in granulocytic HL-60 cells.
Human promyelocytic leukemia cells (HL-60) were used as a cell model to determine how arachidonic acid stimulates the synthesis of platelet-activating factor (PAF) synthesized via the remodeling pathway. In these studies HL-60 cells were cultured over 30 passages in fatty acid-free medium to deplete them of arachidonic acid. Even though the phospholipid classes from these cells contained no arachidonate, they could still be differentiated into granulocytes by dimethyl sulfoxide (1.25%). When the differentiated HL-60 cells, depleted of arachidonic acid, were stimulated with calcium ionophore A23187 in the presence of Ca2+ and [3H]acetate, only minimal amounts of [3H]PAF were produced. In contrast, if the differentiated HL-60 cells were supplemented with 10 microM arachidonic acid for 24 h and then stimulated with the ionophore, there was a large amount of [3H]PAF formed. The increase in PAF synthesis depended on the length of time the cells were supplemented with arachidonic acid; only a small increase in PAF synthesis occurred during the early hours of supplementation whereas stimulation of PAF synthesis was maximal (3-5-fold) after a 24-h period of the 20:4 supplementation. Other polyenoic fatty acid supplements (20:5, 22:4, and 22:6 for 24 h) also stimulated PAF production in the ionophore-treated HL-60 cells depleted of 20:4, but the amount of PAF was significantly less than found for the supplements of 20:4 under identical experimental conditions. Also noteworthy is that undifferentiated cells supplemented with 20:4 or their unsupplemented controls could not be stimulated by the calcium ionophore to produce PAF. Addition of indomethacin (cyclooxygenase inhibitor), A63162 (5'-lipoxygenase inhibitor), or eicosatetraynoic acid (cyclooxygenase/lipoxygenase inhibitor) to the incubations caused little change in the production of [3H]PAF in the differentiated cells supplemented with 20:4 for 24 h. On the other hand, the addition of mepacrine, bromophenacyl bromide, or U26384 (phospholipase A2 inhibitors) resulted in very large decreases (80-90% lower than controls) in the amount of [3H]PAF produced under the same conditions. Analysis of the molecular species of [3H]alkylacyl-GroPCho (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, the precursor of PAF in the remodeling pathway) in 20:4-supplemented cells prelabeled with [3H]alkyl-lyso-GroPCho revealed that only the alkylarachidonoyl-GroPCho species were preferentially decreased after stimulation with the A23187 ionophore. These results demonstrate that arachidonate must be at the sn-2 position of alkylacyl-GroPCho in order for it to serve as a precursor of PAF.(ABSTRACT TRUNCATED AT 400 WORDS)