Influence of lignin content in cellulose pulp on paper durability.
Paper degradation on a macroscopic scale is characterised primarily by yellowing, an increase in brittleness, and other destructive changes caused by the hydrolysis of glycoside bonds and oxidation reactions. Until now, lignin has been believed to cause these changes. However, contemporary analysis has not confirmed this assumption and has attributed low paper resistance to ageing with acidification owing to the production in acid environments that involve aluminium sulfate. In view of the common belief this manuscript presents studies on the accelerated ageing of papers with different lignin contents that are produced in neutral environments. To achieve the objective, artificially aged papers under conditions of increased humidity and temperature were investigated using chromatographic (SEC) and spectroscopic (FTIR and UV-Vis spectroscopy) techniques. Mechanical tests were used to determine the decrease in tensile properties of the samples. We observed no effects of the lignin content on the ageing rate of paper produced at neutral pH. This work also reveals the extent to which spectroscopic methods are useful for studying the papers containing lignin.


Performance evaluation of an amplicon-based next-generation sequencing panel for BRCA1 and BRCA2 variant detection.
As next-generation sequencing (NGS) technology matures, various amplicon-based NGS tests for BRCA1/2 genotyping have been introduced. This study was designed to evaluate an NGS test using a newly released amplicon-based panel, AmpliSeq for Illumina BRCA Panel (AmpliSeq panel), for detection of clinically significant BRCA variants, and to compare it to another amplicon-based NGS test confirmed by Sanger sequencing. We reviewed BRCA test results done by NGS using the TruSeq Custom Amplicon kit from patients suspected of hereditary breast/ovarian cancer syndrome (HBOC) in 2018. Of those, 96 residual samples with 100 clinically significant variants were included in this study using predefined criteria: 100 variants were distributed throughout the BRCA1 and BRCA2 genes. All target variants were confirmed by Sanger sequencing. Duplicate NGS testing of these samples was performed using the AmpliSeq panel, and the concordance of results from the two amplicon-based NGS tests was assessed. Ninety-nine of 100 variants were detected in duplicate BRCA1/2 genotyping using the AmpliSeq panel (sensitivity, 99%; specificity, 100%). In the discordant case, one variant (BRCA1 c.3627dupA) was found only in repeat 1, but not in repeat 2. Automated nomenclature of all variants, except for two indel variants, was in consensus with Human Genome Variation Society nomenclature. Our findings confirm that the analytic performance of the AmpliSeq panel is satisfactory, with high sensitivity and specificity.


The clinical value of exhaled nitric oxide in patients with lung cancer.
To investigate the clinical value of fractional exhaled nitric oxide (FeNO) in lung cancer patients. A total of 172 healthy control subjects and 164 patients with histopathologically confirmed lung cancer were enrolled in this study. The FeNO measurements and pulmonary function tests were conducted in the Chinese PLA General Hospital. The recorded data included FeNO, the forced expiratory volume in one second (FEV1 ), the forced vital capacity (FVC), FEV1 /FVC, the FEV1 (% predicted), the demographic characteristics, the presence of complications and the smoking status. The patients with lung cancer had a significantly higher level of eNO than the healthy control subjects (33.85 ± 15.63 ppb, n = 163; 16.83 ± 4.17 ppb, n = 172; P < 0.01). The areas under receiver operating characteristic curves for eNO predicting airway inflammation in lung cancer subjects and healthy control subjects was 0.932 (95% confidence interval: 0.904-0.961). In the lung cancer group, the eNO levels in the squamous cell carcinoma, adenocarcinoma, small-cell lung cancer and lung carcinoid tumor groups were significantly different (P < 0.01). Lung cancer patients with a predicted FEV1 % value <80% had a higher level of eNO than the patients with a predicted FEV1 % value ≥80%. The eNO levels in patients with lung cancer were higher than the normal level, especially in the patients with squamous cell carcinoma and small-cell lung cancer. The differences in eNO among the lung cancer subtypes were statistically significant. Measuring eNO will be helpful in diagnosing airway inflammation in lung cancer and in the classification of lung cancer.


Comparison of complication rates of porous anophthalmic orbital implants.
Porous anophthalmic orbital implants are used widely. This study evaluates risk factors for porous anophthalmic orbital implant complications and compares complication rates of hydroxyapatite, porous polyethylene, and polyglactin mesh-wrapped aluminum oxide implants. The records of 105 patients (110 eyes) who received porous anophthalmic orbital implants for any indication were reviewed retrospectively. Complications were recorded and correlated with potential risk factors, including implant material. All patient records were de-identified to protect privacy. Porous polyethylene and aluminum oxide implants were associated with higher exposure rates (porous polyethylene: odds ratio 6.1 [1.29, 29.1]; aluminum oxide: odds ratio 6.0 [1.58, 23.1]; P = .004) and higher overall complication rates compared to hydroxyapatite implants. Implant material may be a risk factor for several anophthalmic clinical outcomes.


Distribution and fine structure of ependymal cells possessing intracellular cysts in the aqueductal wall of the rat brain.
The wall of the cerebral aqueduct was examined in 20 male rats at the light- and electron-microscopic levels. Disorder in ciliary orientation was occasionally seen in ordinary ependymal cells. Ependymal cells possessing intracellular cysts of 5 to 30 micron in diameter were observed within and beneath the aqueductal ependyma in all animals examined. Light-microscopic reconstruction from serial, 10-micron thick frontal sections revealed an extensive distribution of cystic ependymal cells (CECs), especially along the ependymal ridges in the rostral half of the aqueduct, and along the dorsal region of the aqueductal lining in the caudal half. Both cystic and surface membranes of CECs bore microvilli and cilia. Ectopic ependymal cells (EECs) characterized by densely packed microvilli, well-developed intermediate junctions and cilia, but without cysts, were situated in the subependymal region adjacent to a CEC or another EEC. The ependymal ridges were long, narrow and sporadically stratified ependymal linings extending rostrocaudally and bilaterally along the aqueductal surface. Tanycyte-like cells filled the surface region of the ridge, and CECs and EECs were frequently seen in the core. Intraventricularly injected microperoxidase was detected among densely packed microvilli but not in the cystic lumina of CECs, indicating that EECs and CECs are distinct entities.


Development and Validation of a Risk Scoring Model for Early Prediction of Severe Colon Ischemia.
Colon ischemia (CI) is injury to the intestines secondary to insufficient blood flow. Its clinical severity can range from mild to life-threatening. To investigate predictive risk factors for CI and propose a scoring model for severe outcomes. We retrospectively analyzed the medical records of patients admitted to Chungnam National University Hospital from January 2010 to December 2018. CI was defined as severe when patients required surgery immediately or after initial conservative management, death occurred after hospitalization, or symptoms persisted after 2 weeks. By controlling for possible confounders from the logistic regression analysis, we obtained a new risk scoring model for the early prediction of severe CI. Furthermore, using the area under the receiver operating characteristics curve (AUROC), we assessed the accuracy of the model. A total of 274 patients endoscopically diagnosed with CI were included, of whom 181 had severe CI. In the multivariate analysis, tachycardia, elevated C-reactive protein, Favier endoscopic classification stage ≥ 2, and history of hypertension were independently and significantly associated with severe CI. The AUROC of the model was 0.749. This risk scoring model based on the presence of tachycardia, elevated C-reactive protein level, unfavorable endoscopic findings by Favier's classification, and the history of hypertension could be used to predict severe CI outcomes at an early stage.


Concanavalin A modulates tyrosine phosphorylation and activation of a type II phosphatidylinositol 4-kinase in rat splenic lymphocytes.
Activation of rat splenic lymphocytes by concanavalin A resulted in two-fold increase in Ptdlns 4-kinase activity and rapid tyrosine phosphorylation of the enzyme. The activation kinetics showed a strong correlation with tyrosine phosphorylation state of the enzyme. Characterization of the enzyme activity suggests that it is a type II PtdIns 4-kinase. Kinetic analysis of the enzyme reaction showed three-fold decrease in Km for PtdIns and two-fold increase in Vmax in Con A stimulated cells. These results suggest that a type II PtdIns 4-kinase is an integral component of the early signal transduction machinery during T-cell activation by concanavalin A and is actively regulated by protein tyrosine phosphorylation-dephosphorylation.


Evolution and Outcomes of a Canadian Pediatric Bariatric Surgery Program.
An interdisciplinary obesity management program was established in 2007 at our quaternary hospital, including bariatric surgery for selected adolescent patients. We report the evolution of surgical management within the program and outcomes following bariatric surgery. This was a retrospective review of adolescents who underwent bariatric surgery between 2007 and 2017. All cases were performed by a pediatric surgeon and an adult bariatric surgeon. Baseline demographics, BMI, co-morbidities, and post-operative outcomes were recorded. Thirty-eight patients underwent bariatric surgery. Median age at entrance into the program was 16.5 (range, 12.1-17.4) years and at time of surgery was 17.4 (range, 13.6-18.8) years. Eight patients had laparoscopic adjustable gastric banding (LAGB) from 2007 to 10. Between 2011 and 2017, 18 had laparoscopic sleeve gastrectomy (LSG), and 12 had laparoscopic Roux-en-Y gastric bypass (RYGB). There were no intraoperative complications or conversions. Postoperative complications included wound infection, bleeding requiring transfusion and re-exploration, and internal hernia. Of patients who had LAGB, 2 required surgical revision, and 3 underwent subsequent removal. Adolescent bariatric surgery in the context of a multidisciplinary obesity management program is safe and effective. RYGB and sleeve gastrectomy are associated with superior weight loss in the immediate post-operative period and at most recent follow-up and lower reoperation rates than gastric banding. III.


[The evolution of the relations between brain development, secondary temporomandibular joint and facial development in mammals].
Comparing the development of the face in mammals and sauropsida only in mammals the maxillary process reach forward to fuse with the medial nasal fold. This is the supposition for the maxillary and mandibular process to fuse forming the cheeks. The phylogenetically relations for these developmental events are discussed.


Heterocyclic methylsulfone hydroxamic acid LpxC inhibitors as Gram-negative antibacterial agents.
The synthesis and antibacterial activity of heterocyclic methylsulfone hydroxamates is presented. Compounds in this series are potent inhibitors of the LpxC enzyme, a key enzyme involved in the production of lipopolysaccharide (LPS) found in the outer membrane of Gram-negative bacteria. SAR evaluation of compounds in this series revealed analogs with potent antibacterial activity against challenging Gram-negative species such as Pseudomonas aeruginosa and Klebsiella pneumoniae.


Active involvement and intervention in patients exposed to whiplash trauma in automobile crashes reduces costs: a randomized, controlled clinical trial and health economic evaluation.
To examine and compare the costs and consequences in a partial economic evaluation of two competing interventions in patients exposed to whiplash trauma in automobile crashes. The interventions were an active involvement and intervention using early mobilization and a standard intervention of rest, recommended short-term immobilization in a cervical collar and a cautious, gradual self-exercise program according to a leaflet. The study was randomized and controlled. The aim of the study was to compare the costs of an active involvement and intervention versus a standard intervention and to relate them to the clinical benefits in patients exposed to whiplash trauma in automobile crashes to facilitate decision-making regarding intervention and resource allocation. There is very little known about the health economic aspects of various interventions in the target treatment group of patients. Based on a prospective, randomized, clinical trial, data on clinical effectiveness and resources used for the active involvement and intervention and standard intervention were collected for a comparative analysis of the costs related to physical therapy treatment and sick leave. A cost-consequence analysis consisting of a modified cost-effectiveness analysis was used. The costs were significantly lower after 6 and 36 months with an active involvement and intervention as compared with the standard intervention. The active involvement and intervention were significantly superior in reducing experienced pain and reducing sick leave. For patients exposed to whiplash trauma in a motor vehicle collision, an active involvement and intervention were both less costly and more effective than a standard intervention.


Isolated splenic granuloma: report of a case with an emphasis on ultrasound findings.
There is a marked paucity of reports on contrast-enhanced ultrasonography (US) for focal splenic disease in the literature, and there are no previously reported contrast-enhanced US findings for splenic granuloma. We report the case of a 77-year-old cirrhotic woman with isolated splenic granulomas. We detail the diagnostic difficulty encountered in this case and briefly review the literature.


Interfacially Polymerized Polyamide Interlayer onto Ozonated Carbon Nanotube Networks for Improved Stability of Sulfur Cathodes.
Lithium-sulfur (Li-S) batteries are considered promising energy-storage devices owing to the high specific capacity and low cost of the S cathode. However, they suffer from capacity decay and poor coulombic efficiency arising from the dissolution of long-chain polysulfides and their shuttling. A facile and scalable method was developed to directly coat a thin (≈57.3 nm) and porous polyamide (PA) interlayer onto a S cathode by interfacial polymerization. This PA interlayer prevented the shuttling of polysulfides by creating a physical barrier and, through chemical interactions between the amide functionalities of PA and the polysulfides, allowing access to the S electrode by the Li ions. The resulting PA-coated cathode exhibited approximately 64.2 % capacity retention over 1000 cycles at 1 C with only 0.0358 % decay per cycle and a moderate capacity of 1008 mAh g-1 at 0.1 C.


Reduced Sensitivity to Background Reward Underlies Apathy After Traumatic Brain Injury: Insights From an Ecological Foraging Framework.
Altered reward processing is increasingly recognised as a crucial mechanism underpinning apathy in many brain disorders. However despite its clinical relevance, little is known about the mechanisms of apathy following moderate-to-severe traumatic brain injury (TBI). In real-life situations, reward representations encompass both foreground (gains from current activity) and background (potential gains from the broader environment) elements. This latter variable provides a crucial set-point for switching behaviour in many naturalistic settings. We hypothesised apathy post-TBI would be associated with disrupted background reward sensitivity. We administered a computer-based foraging task to 45 people with moderate-to-severe TBI (20 with apathy, 39 males) and 37 matched controls. Participants decided when to leave locations (patches) where foreground reward rates depleted at differing rates, to pursue greater rewards from other patches in the environment, which had either a high or low background reward rate. Primary analysis was performed using linear mixed effects models, with patch leaving time the dependent variable. Findings showed a significant interaction between apathy and background reward sensitivity, driven by apathetic TBI participants not altering patch-leaving decisions as environmental reward rate changed. In contrast, although TBI was associated with reduced sensitivity to changing foreground rewards, this did not vary as a function of apathy. These results provide the first evidence directly linking disrupted background reward processing to apathy in any brain disorder. They identify a novel mechanism for apathy following moderate-to-severe TBI, and point towards novel interventions to improve this debilitating complication of head injury.


Phase II trial of pyrazoloacridine in recurrent platinum-resistant ovarian cancer: a Gynecologic Oncology Group study.
The Gynecologic Oncology Group performed a Phase II study to determine the response rate of pyrazoloacridine (PZA) in patients with platinum-resistant ovarian cancer. PZA was administered at a dose of 750 mg/m2 intravenously over 3 hours every 3 weeks. Among 24 evaluable patients, there was 1 (4.2%) complete and 1 (4.2%) partial response. The major toxicities were hematologic. With the dose and schedule used, PZA had only modest activity in this population.


The Distress Questionnaire-5: Population screener for psychological distress was more accurate than the K6/K10.
The K6 and K10 are well-validated screening measures for psychological distress and are widely used. However, the accuracy of these scales in identifying common mental disorders may be suboptimal. This study aimed to develop a brief scale of psychological distress--the Distress Questionnaire-5 (DQ5)--and validate its diagnostic accuracy in identifying common mental disorders, relative to the K6 and K10. The DQ5 was developed from a pool of 347 items reflecting a range of mental health symptoms. Validation of the DQ5 was conducted concurrently, on the basis of DSM-5 criteria for seven common mental disorders. A population-based sample of Australian adults (n = 3,175) was recruited online, with data weighted to reflect population estimates of disorder prevalence, age, and gender. At specified cut points, the DQ5 was significantly more accurate in identifying individuals who met criteria for each of the disorders examined relative to the K6, with the exception of major depression where there was no significant difference in sensitivity or specificity. The DQ5 is a promising tool for identifying psychological distress in the community, with potential for use in a range of clinical settings.


Development of INSOL-tag for proteome-wide protein handling and its application in protein array analysis.
Proteomic analysis requires protein tags that enable high-throughput handling; however, versatile tags that can be used in in vitro expression systems are currently lacking. In this study, we developed an insoluble protein tag, INSOL-tag, derived from human transcription factor MafG. The INSOL-tagged target protein is expressed in a eukaryotic in vitro expression system and recovered as a pellet following centrifugation at 19,000 × g for 20 min. Comparisons of the target protein recovery rates of GST-tag and INSOL-tag using 111 cytoplasmic proteins revealed a fourfold increase in the yield of INSOL-tagged proteins. Using 267 cancer antigens purified with INSOL-tag, we subsequently developed an INSOL-CTA array method, for profiling autoantibodies in sera of cancer patients. The detection limit of the array was approximately 11.1 pg IgG, and the correlation with ELISA was high (R2 = .993, .955). Moreover, when autoantibody profiling of digestive cancer patient sera was performed, antigen spreading was observed. These data suggest that INSOL-tag is a versatile tag that can insolubilize a wide range of target proteins. It is therefore expected to become a powerful tool in comprehensive protein preparation for protein arrays, antibody production, and mass spectrometry.


Serum testosterone concentration in combat-related chronic posttraumatic stress disorder.
The primary aim of this study was to assess the testosterone levels of soldiers with posttraumatic stress disorder (PTSD), without considering their comorbid conditions, compared with the ones in the control group with combat experience. The secondary aim was to determine whether there was a difference in testosterone levels when the same group of soldiers with PTSD was divided according to their comorbid conditions into those with major depressive disorder (MDD) or alcohol dependence (ETOH) compared to the soldiers with PTSD with no comorbid conditions and the controls. We analyzed serum testosterone in soldiers with PTSD without the division according to comorbid conditions (n = 66) in comparison to the controls (n = 34). We also analyzed testosterone in pure PTSD (n = 17), PTSD comorbid with MDD (n = 18), PTSD comorbid with ETOH (n = 31), and in the controls. Soldiers with PTSD, without considering comorbid conditions, did not show any difference in testosterone levels in comparison to the controls. However, when we divided the same PTSD sample based on comorbid conditions, pure PTSD showed significantly higher serum testosterone levels in comparison to PTSD comorbid with MDD, comorbid with ETOH, or controls. Also, there was no difference in testosterone levels between the PTSD groups with comorbid MDD, with comorbid ETOH, and the controls. We did not find any differences in testosterone levels between the soldiers with PTSD without considering comorbid conditions and the controls. Considering comorbid conditions, soldiers with PTSD without comorbid conditions had higher testosterone levels compared to soldiers with PTSD with comorbid MDD or ETOH, or the controls.


Short Communication: Stellate Ganglion Blockade for Persistent Olfactory and Gustatory Symptoms Post-COVID-19.
One hundred ninety-five patients presenting with post-COVID symptomology, including parosmia and dysgeusia, underwent reversible stellate ganglion blockade. Stellate ganglion blockade was performed at an outpatient facility, and patients were evaluated via survey at seven days post-injection. Of the 195 participants, ages ranged from 18-69 years of age with the breakdown of sexes being females n = 157 and males n = 38. The most significant finding was a reported improvement in olfaction post-injection in 87.4% of subjects. The effectiveness of this novel treatment for post-COVID is promising and warrants further investigation.


Pediatric patient with hyperketotic hypoglycemia diagnosed with glycogen synthase deficiency due to the novel homozygous mutation in GYS2.
Glycogen synthase deficiency (glycogen storage disease 0 - GSD 0) caused by mutations in the GYS2 gene is characterized by a lack of glycogen synthesis in the liver. It is a rare condition of disturbed glycogen homeostasis in the liver with less than 30 cases reported in the literature so far. We report a 9 year old boy diagnosed with GSD 0 due to the newly identified, highly pathogenic homozygous mutation: NM_021957.3:p.Phe574Leu/c.1720T > C in ex. 14. A random, asymptomatic hypoglycemia with ketonuria was found in this patient at the age of 7. His developmental parameters were within normal ranges. Oral glucose tolerance test showed normal baseline blood levels of glucose, insulin and lactate, and their increase following glucose intake. Eight-hour fasting plasma glucose test, revealed glucose blood level of 34 mg/dl with no clinical symptoms. The results of these tests suggested GSD 0. Molecular analysis of the GYS2 gene was not feasible, but this particular gene was included in the panel of hypoglycemia of whole exome sequencing (WES) which was at our disposal.


STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS: NOVEL FINDINGS AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY ANALYSIS.
To present novel findings in stellate nonhereditary idiopathic foveomacular retinoschisis, including the largest series of optical coherence tomography angiography findings to date. A retrospective case series with multimodal imaging was obtained and reviewed. All three patients were women, aged 59-63. Two cases were unilateral, and one was bilateral. Vision ranged from 20/20 to 20/60 in the affected eyes. Peripheral retinoschisis was observed in all three patients. All patients were followed for a minimum of 1 year. In one case, progressive macular retinoschisis leading to foveal involvement was observed over two years, with an associated vision decline from 20/25 to 20/60. Attempted interventions included topical dorzolamide in all cases and intravitreal bevacizumab in one patient; however, no treatment effect was observed. The foveal avascular zone size was within normal limits (mean 280 µ m). In all stellate nonhereditary idiopathic foveomacular retinoschisis eyes, the retinoschisis cavities were nonvascular. Novel findings regarding stellate nonhereditary idiopathic foveomacular retinoschisis include the progressive nature of foveal involvement and the lack of response to topical dorzolamide and intravitreal bevacizumab. Foveal avascular zone was normal in all eyes, consistent with the relatively preserved vision in these cases. Retinoschisis cavities were nonvascular in all eyes, a finding which may give insight into the mechanism of this disease.


Experience with intermediate-dose (110-120 mg/m2) epirubicin.
A total of 23 patients with advanced malignancies received escalating doses of epirubicin (100-120 mg/m2) i.v. at 3-week intervals; 15 had received previous chemotherapy. In all, 46 courses of chemotherapy were given. Mucositis (grade II or III) occurred in 47% of courses at 120 mg/m2, but in only 15% of courses at 115 mg/m2. Myelotoxicity was manifest as leucopenia, with a median white blood count nadir of 1.9 (range, 0.8-7.0) x 10(9)/l. Nausea and vomiting were generally well controlled by prophylactic antiemetic therapy. Alopecia was WHO grade 0 in 2 patients, grade I in 1, grade II in 5 and grade III in 14. No renal or hepatic toxicity was noted, and there were no episodes of congestive cardiac failure. One fatal coronary thrombosis (proven at post-mortem examination) occurred 48 h after a dose of 115 mg/m2. Four patients developed thrombophlebitis at the injection site that was not dose-related; it occurred at doses between 100 and 120 mg/m2. Two patients who had been given chemotherapy in the past had complete responses (one penile carcinoma, one gastric carcinoma). Six patients had partial responses, including two with breast cancer, one with gastric cancer and three with sarcoma. Intermediate-dose epirubicin was well tolerated up to 120 mg/m2, when mucositis became a significant clinical problem. Preliminary data suggest promising activity in gastric cancer, breast cancer and a variety of sarcomas.


Combination of a 755-nm picosecond laser and hydroquinone 2% cream versus hydroquinone 2% cream alone for the treatment of melasma: A randomized, split-face, and controlled trial.
While combined laser and topical treatments are currently a common approach to melasma treatment, data on the efficacy and safety of this combined therapy remain scarce, with studies showing varied results. To compare the efficacy and safety of hydroquinone (HQ) cream alone versus HQ cream combined with 755-nm picosecond (PS) laser in the treatment of melasma. Twenty subjects presenting with mixed-type melasma were enrolled in the study. All patients were instructed to apply 2% HQ cream to both sides of the face for 4 weeks. Randomly assigned hemifaces of all patients thereafter received 5 biweekly PS laser treatments. Objective (measurement of average melanin content and melanin index) and subjective (grading of modified melasma area and severity index [mMASI] score and global percentage of pigment clearance) assessments of melasma clearance, and occurrence of adverse effects were evaluated at 1-, 3-, and 6-months after the final laser treatment. mMASI scores were significantly improved from baseline for both sides (p = 0.006 HQ alone, p < 0.001 HQ + PS laser), with no statistically significant difference when comparing HQ alone versus HQ + PS laser. Objective assessments (measurements of average melanin content and melanin index) of melasma clearance corresponded to the clinical evaluation using mMASI score. Mild postinflammatory hyperpigmentation was observed in 15% of the patients on the laser-treated side, while no adverse effects were reported on the HQ monotherapy side. Adjunctive treatment with a 755-nm PS laser does not provide additional benefit to topical HQ in the treatment of melasma. ClinicalTrail.gov PRS. number: NCT04597203.


Efficacy of apheresis platelets treated with riboflavin and ultraviolet light for pathogen reduction.
Pathogen reduction technologies for platelet (PLT) components offer a means to address continued viral transmission risks and imperfect bacterial detection systems. The efficacy of apheresis PLTs treated with riboflavin (vitamin B2) plus ultraviolet (UV) light (Mirasol, Navigant Biotechnologies) was investigated in a single-blind, crossover study in comparison to untreated PLTs. Normal subjects (n = 24) donated PLTs by apheresis on two occasions at least 2 weeks apart. Units were randomized to control or test arms, the latter receiving the addition of 28 mL of 500 micromol per L B2 and exposure to 6.2 J per mL UV light. PLTs were stored for 5 days with biochemical and hematologic analyses performed before and after illumination on Day 0 and at the end of storage. An aliquot of each unit was radiolabeled and returned to determine recovery and survival. The PLT content of treated units was maintained from Day 0 (4.1 x 10(11) +/- 0.4 x 10(11)) to Day 5 (4.0 x 10(11) +/- 0.4 x 10(11)). Treatment with B2 plus UV light was associated with an increase in lactate production with concomitant increases in glucose consumption. pH (control, 7.38 +/- 0.07; test, 7.02 +/- 0.10) was well maintained throughout storage. Recovery of treated PLTs (50.0 +/- 18.9%) was reduced from that of control PLTs (66.5 +/- 13.4%); survival was similarly shortened (104 +/- 26 hr vs. 142 +/- 26 h; p < 0.001). PLTs treated with B2 plus UV light demonstrate some alterations in in vitro measures but retain in vitro and in vivo capabilities similar to pathogen-reduced and licensed PLT components that have been shown to have useful clinical applicability. The recovery, survival, and metabolic properties of Mirasol PLTs should provide sufficient hemostatic support in thrombocytopenia to justify patient clinical trials.


An evaluation of the Norwegian Salmonella surveillance and control program in live pig and pork.
Population data and apparent prevalence data from the Salmonella surveillance and control program in pigs (NSSCP) from 1998 and 1999 were used in a simulation model to evaluate the efficacy of the program. The model consists of three parts: modelling of individual prevalence at the abattoir (abattoir part), modelling of the number of sampled herds of different sizes when carcasses are randomly sampled at the abattoir (sampling strategy part) and finally, modelling of the within herd prevalence (within herd part). A total of 136,550 sows and 2,866,550 finishing pigs slaughtered, 4446 herds and 11 herds positive for Salmonella in 1994/1995-2000 were included in the abattoir part, sampling strategy part and the within herd part of the model, respectively. The abattoir part showed an average estimated prevalence of Salmonella in sows and finishing pigs of (median) 0.4% (5-95 percentiles = 0.03-2%) and 0.1% (0.04-0.2%) respectively. The estimated number of infected sow carcasses that entered the market was 502 (37-2157) while the estimated number of finishing pig carcasses was 2919 (1218-5771). The probability of being sampled for the 10% smallest herds was (mean) 1.9% (1.6-2.2), to 25% (24.7-26.5%) for the 10% largest herds. The within herd prevalence was estimated to be from 1% to 4% for Norwegian pig herds. The conclusions drawn from this evaluation are that the NSSCP does not have any significant consumer protection effect, and that the documentation could be done more effectively using the herd rather than the individual animal as the unit of sampling. Sampling should focus on the larger herds supplying most of the meat on the market and on herds that produce breeding sows and piglets and thus can contribute to the spread of Salmonella among herds.


Sulfur oxidation by Achromobacter xylosoxidans strain wsp05 reveals ecological widening over which thiotrophs are distributed.
Achromobacter xylosoxidans is a versatile bacterium known for its ability to degrade aromatic compounds. However, its ability to oxidize sulfur compounds for electron and energy source is not reported much. In the present work, the Gram-negative bacterium Achromobacter xylosoxidans strain wsp05 isolated from a waste stabilization ponds (WSPs) system was studied for its ability to oxidize reduced sulfur compounds. The strain was able to oxidize thiosulfate and sodium sulfite. To observe the effect of physicochemical parameters on the rate of sulfur oxidation, strain wsp05 was grown in thiosulfate (20 mM) containing minimal salt medium at varied pH, temperature and ammonium and phosphate ions concentration. Maximum thiosulfate oxidation was observed at 30 °C with initial pH of 7-7.2. The strain was characterized using universal 16S rRNA gene primers revealing high similarity (> 99%) with Achromobacter xylosoxidans NBRC 15126T belonging to β-proteobacteria. In the present study, we investigated the sulfur oxidation properties of the Achromobacter xylosoxidans strain wsp05, which revealed an ecological and phylogenetic widening over which the thiotrophs are distributed.


Development and validation of a 21-gene prognostic signature in neuroblastoma.
Survival outcomes for patients with neuroblastoma vary markedly and reliable prognostic markers and risk stratification tools are lacking. We sought to identify and validate a transcriptomic signature capable of predicting risk of mortality in patients with neuroblastoma. The TARGET NBL dataset (n = 243) was used to develop the model and two independent cohorts, E-MTAB-179 (n = 478) and GSE85047 (n = 240) were used as validation sets. EFS was the primary outcome and OS was the secondary outcome of interest for all analysis. We identified a 21-gene signature capable of stratifying neuroblastoma patients into high and low risk groups in the E-MTAB-179 (HR 5.87 [3.83-9.01], p < 0.0001, 5 year AUC 0.827) and GSE85047 (HR 3.74 [2.36-5.92], p < 0.0001, 5 year AUC 0.815) validation cohorts. Moreover, the signature remained independent of known clinicopathological variables, and remained prognostic within clinically important subgroups. Further, the signature was effectively incorporated into a risk model with clinicopathological variables to improve prognostic performance across validation cohorts (Pooled Validation HR 6.93 [4.89-9.83], p < 0.0001, 5 year AUC 0.839). Similar prognostic utility was also demonstrated with OS. The identified signature is a robust independent predictor of EFS and OS outcomes in neuroblastoma patients and can be combined with clinically utilized clinicopathological variables to improve prognostic performance.


A critical review of effect modeling for ecological risk assessment of plant protection products.
A wide diversity of plant protection products (PPP) is used for crop protection leading to the contamination of soil, water, and air, which can have ecotoxicological impacts on living organisms. It is inconceivable to study the effects of each compound on each species from each compartment, experimental studies being time consuming and cost prohibitive, and animal testing having to be avoided. Therefore, numerous models are developed to assess PPP ecotoxicological effects. Our objective was to provide an overview of the modeling approaches enabling the assessment of PPP effects (including biopesticides) on the biota. Six categories of models were inventoried: (Q)SAR, DR and TKTD, population, multi-species, landscape, and mixture models. They were developed for various species (terrestrial and aquatic vertebrates and invertebrates, primary producers, micro-organisms) belonging to diverse environmental compartments, to address different goals (e.g., species sensitivity or PPP bioaccumulation assessment, ecosystem services protection). Among them, mechanistic models are increasingly recognized by EFSA for PPP regulatory risk assessment but, to date, remain not considered in notified guidance documents. The strengths and limits of the reviewed models are discussed together with improvement avenues (multigenerational effects, multiple biotic and abiotic stressors). This review also underlines a lack of model testing by means of field data and of sensitivity and uncertainty analyses. Accurate and robust modeling of PPP effects and other stressors on living organisms, from their application in the field to their functional consequences on the ecosystems at different scales of time and space, would help going toward a more sustainable management of the environment. Graphical Abstract Combination of the keyword lists composing the first bibliographic query. Columns were joined together with the logical operator AND. All keyword lists are available in Supplementary Information at https://doi.org/10.5281/zenodo.5775038 (Larras et al. 2021).


Effects of LDL Receptor Modulation on Lymphatic Function.
Atherosclerosis is driven by the accumulation of immune cells and cholesterol in the arterial wall. Although recent studies have shown that lymphatic vessels play an important role in macrophage reverse cholesterol transport, the specific underlying mechanisms of this physiological feature remain unknown. In the current report, we sought to better characterize the lymphatic dysfunction that is associated with atherosclerosis by studying the physiological and temporal origins of this impairment. First, we assessed that athero-protected Pcsk9(-/-) mice exhibited improved collecting lymphatic vessel function throughout age when compared to WT mice for up to six months, while displaying enhanced expression of LDLR on lymphatic endothelial cells. Lymphatic dysfunction was present before the atherosclerotic lesion formation in a mouse model that is predisposed to develop atherosclerosis (Ldlr(-/-); hApoB100(+/+)). This dysfunction was presumably associated with a defect in the collecting lymphatic vessels in a non-specific cholesterol- but LDLR-dependent manner. Treatment with a selective VEGFR-3 agonist rescued this impairment observed early in the onset of this arterial disease. We suggest that LDLR modulation is associated with early atherosclerosis-related lymphatic dysfunction, and bring forth a pleiotropic role for PCSK9 in lymphatic function. Our study unveils new potential therapeutic targets for the prevention and treatment of atherosclerosis.


Novel suppression of an L-type calcium channel in neurones of murine dorsal root ganglia by 2,3-butanedione monoxime.
1. Voltage-activated currents through calcium channels in primary cultures of murine dorsal root ganglion cells (DRG) were studied with the whole-cell and cell-attached patch recording techniques. 2. The chemical phosphatase 2,3-butanedione monoxime (BDM) reversibly reduced the amplitude of L-type calcium current (ICa) in a dose-dependent manner; at a concentration of 20 mM, BDM caused a 47% suppression of ICa. 3. Application of 10 mM-8-bromo-cyclic AMP or 50 microM-isoprenaline onto DRG treated with BDM completely restored ICa to the pre-BDM level. 4. In striking contrast, bath application of Bay K 8644 (0.5-5 microM) had no effect on the BDM-suppressed ICa. As expected, Bay K 8644 alone caused a two- to threefold increase of the maximal ICa and shifted its I-V relationship to the left. Interestingly, if a cell was first exposed to Bay K 8644 further treatment with 20 mM-BDM resulted in 100% suppression of ICa. This suggests that Bay K 8644 changes the conformation of the calcium channel to one which is more sensitive or more accessible to the action of the phosphatase. 5. Pre-treatment of DRG with an activator of protein kinase C, 12-O-tetradecanoyl-phorbol-13-acetate, did not antagonize BDM's effect on ICa. 6. The depressant action of BDM on ICa was distinct from that of nifedipine in that it did not exhibit use dependence. 7. When single calcium channel currents were recorded in cell-attached patches (barium as the charge carrier), bath application of BDM reduced the percentage of time that the channel spent in the open state. 8. Superfusion with 8-bromo-cyclic AMP restored the ensemble macroscopic 'ICa' to the pre-BDM amplitude. This was due to a dramatic enhancement of the frequency of channel openings. 9. We suggest that BDM acts through the cytoplasm to alter cyclic AMP-dependent protein kinase modulation of neuronal L-type calcium channels. The brief, high-frequency openings which 8-bromo-cyclic AMP activates in the presence of BDM may reflect a rapid phosphorylation-dephosphorylation sequence which controls channel gating.


Enantioselective Approach to (-)-Hamigeran B and (-)-4-Bromohamigeran B via Catalytic Asymmetric Hydrogenation of Racemic Ketone To Assemble the Chiral Core Framework.
A new strategy featuring an iridium-catalyzed asymmetric hydrogenation of a racemic ketone via dynamic kinetic resolution to generate a cyclopentanol with three contiguous stereocenters and a SmI2-promoted pinacol coupling to install the six-membered ring with correct stereochemistry has been described for the enantioselective total synthesis of (-)-hamigeran B (19 steps, 10.6% overall yield) and (-)-4-bromohamigeran B (19 steps, 12.3% overall yield).


Voiding and incontinence frequencies: variability of diary data and required diary length.
Frequencies of voiding and urinary incontinence are commonly measured by a patient's recall or a diary. The recommended diary length varies from 1 to 14 days, with 7 days apparently being most common. To examine the statistical precision of these different modalities, we analyzed recall data and diary data of 74 patients with urinary frequency, incontinence, or both. Recall data on voiding and incontinence frequency were systematically higher and more variable than diary data. Longer diary length provided less variable diary data. The confidence interval of diary data was calculated by applying the normal distribution to daytime voiding frequency and the Poisson distribution to daytime incontinence frequency. For daytime voiding frequency, the 95% confidence interval was estimated to be (x - 2.65, x + 2.65) (x - 1.53, x + 1.53) (x - 1, x + 1), where x is the 1-day, 3-day, and 7-day diary mean, respectively. For daytime incontinence frequency, the confidence interval depended on both the diary length and the diary mean. It was estimated to be (0, 6.39), (1.72, 4.28), (2.36, 3.64), by using a diary mean of 3 or 1-day, 7-day, and 28-day diaries, respectively. Also, it was estimated to be (0, 1.02), (1.72, 4.28), (7.66, 12.34), when the 7-day diary mean was 0.5, 3, and 10, respectively. Studies with different samples of genuine stress incontinence (n = 37) and urge incontinence (n = 25) confirmed these results. In conclusion, we believe the 7-day diary is highly reliable for estimating voiding frequency and is a reasonable option for predicting incontinence episodes. However, the diary length should be extended in a patient with rarer events of incontinence, and it should be shortened for those who are incontinent more often or who are diagnosed with voiding frequency only.


Theoretical studies on nonlinear optical properties of formaldehyde oligomers by ab initio and density functional theory methods.
The first and second hyperpolarizability beta and gamma are obtained for formaldehyde oligomers (H2CO)n (n = 1-7) using computational methods. We have used the finite field (FF) approach and hyperpolarizability density analysis (HDA) to predict the microscopic first and second nonlinear hyperpolarizability of the formaldehyde oligomers. The spatial contributions of electrons to the hyperpolarizability by using plots of HDA are presented. It has been found from the numerical stability checking of the hyperpolarizability calculations that the calculated values by FF method are more stable than those by HDA approach. The values of beta are zero when n is even as the molecule possesses centrosymmetry, and when n is odd, the differences among beta values are not clear. The gamma values are increased with increase in n.


Gold nanoparticles as localization markers for direct and live imaging of particle absorption through a Caco-2 cell monolayer using dark-field microscopy.
Recently, efforts have been made to reduce the size of food particles containing functional ingredients, since reducing the size is expected to improve intestinal absorption. However, the absorption mechanisms have yet to be fully clarified. Therefore, a microscopy-based method for studying interactions between the particles and intestinal cells is required. We optimized the experimental conditions for observing gold nanoparticles (AuNPs) on the surface of an unfixed Caco-2 cell using dark-field microscopy (DFM). Tight junctions were clearly visible with AuNPs on the cells, producing intense scattered light under DFM. This suggests that AuNPs could be used as localization markers to visualize particle absorption through Caco-2 cells.


A randomized trial comparing INR monitoring devices in patients with anticoagulation self-management: evaluation of a novel error-grid approach.
In addition to the metrological quality of international normalized ratio (INR) monitoring devices used in patients' self-management of long-term anticoagulation, the effectiveness of self-monitoring with such devices has to be evaluated under real-life conditions with a focus on clinical implications. An approach to evaluate the clinical significance of inaccuracies is the error-grid analysis as already established in self-monitoring of blood glucose. Two anticoagulation monitors were compared in a real-life setting and a novel error-grid instrument for oral anticoagulation has been evaluated. In a randomized crossover study 16 patients performed self-management of anticoagulation using the INRatio and the CoaguChek S system. Main outcome measures were clinically relevant INR differences according to established criteria and to the error-grid approach. A lower rate of clinically relevant disagreements according to Anderson's criteria was found with CoaguChek S than with INRatio without statistical significance (10.77% vs. 12.90%; P = 0.787). Using the error-grid we found principally consistent results: More measurement pairs with discrepancies of no or low clinical relevance were found with CoaguChek S, whereas with INRatio we found more differences with a moderate clinical relevance. A high rate of patients' satisfaction with both of the point of care devices was found with only marginal differences. A principal appropriateness of the investigated point-of-care devices to adequately monitor the INR is shown. The error-grid is useful for comparing monitoring methods with a focus on clinical relevance under real-life conditions beyond assessing the pure metrological quality, but we emphasize that additional trials using this instrument with larger patient populations are needed to detect differences in clinically relevant disagreements.


Amygdalin based G-6-P synthase inhibitors as novel preservatives for food and pharmaceutical products.
G-6-P synthase enzyme has been involved in the synthesis of the microbial cell wall, and its inhibition may lead to the antimicrobial effect. In the present study, we designed a library of amygdalin derivatives, and two most active derivatives selected on the basis of various parameters viz. dock score, binding energy, and ADMET data using molecular docking software (Schrodinger's Maestro). The selected derivatives were synthesized and evaluated for their antioxidant and antimicrobial potential against several Gram (+ ve), Gram (-ve), as well as fungal strains. The results indicated that synthesized compounds exhibited good antioxidant, antimicrobial, and better preservative efficacy in food preparation as compared to the standard compounds. No significant differences were observed in different parameters as confirmed by Kruskal-Wallis test (p < 0.05). Docking results have been found in good correlation with experimental wet-lab data. Moreover, the mechanistic insight into the docking poses has also been explored by binding interactions of amygdalin derivative inside the dynamic site of G-6-P synthase.


Ruxolitinib: A Review in Polycythaemia Vera.
Ruxolitinib (Jakavi(®), Jakafi(®)) is an orally administered, first-in-class Janus Kinase (JAK) 1 and 2 inhibitor that was recently approved for the treatment of patients with polycythaemia vera (PV) who have responded inadequately to or are intolerant of hydroxyurea. By inhibiting JAK 1 and 2, ruxolitinib reduces hyperactive JAK-signal transducers and activators of transcription (STAT) signalling that is implicated in the pathogenesis of PV. This article briefly reviews the pharmacology of the drug, focusing on its clinical use in patients with PV. In the phase III RESPONSE trial in PV patients who had an inadequate response to or unacceptable adverse effects from hydroxyurea, ruxolitinib was superior to best available therapy in reducing haematocrit without phlebotomy and reducing spleen size after 32 weeks of treatment. Ruxolitinib was also associated with reducing leukocyte and platelet counts and improving symptoms. Patient follow-up demonstrated that response to ruxolitinib was durable, including preliminary results after up to 80 weeks of treatment. The drug is generally well tolerated, although mild to moderate anaemia, thrombocytopenia and lymphopenia were common in the RESPONSE trial. These effects can usually be managed with dosage modification and did not lead to therapy discontinuation in the RESPONSE trial. Thus, for a subgroup of PV patients for whom few treatment options have existed previously, ruxolitinib provides a valid option.


1-Methoxy-agroclavine from Penicillium sp. WC75209, a novel inhibitor of the Lck tyrosine kinase.
A high-throughput screen was developed and implemented to identify inhibitors of the Lck tyrosine kinase. This report describes the identification of a specific inhibitor of this enzyme from the solid fermentation culture of the Penicillium sp., WC75209. The active compound was isolated and structurally characterized as 1-methoxy-5R, 10S-agroclavine, a new member of the ergot alkaloid family.


Evaluation of depression, anxiety and posttraumatic stress response levels of children and adolescents treated with COVID-19.
We aimed to evaluate stress level reactions to depression, anxiety, and posttraumatic stress in paediatric patients' post-COVID-19 infection. A total of two hundred consecutive patients aged 8 to 18 years were prospectively enrolled in the study between March 2020 and June 2021. One hundred patients were diagnosed with a positive COVID-PCR test and had inpatient management. Another hundred patients had positive COVID-PCR results and completed their care and isolation for 14 days at home. We used the child posttraumatic stress reaction index (CPTS-RI), child depression inventory (CDI), and screen for child anxiety-related disorders (SCARED) to evaluate their post-COVID-19 infection mental health state. In the study population, the mean age was 13.4 years, and 50.5% were male. Sixty-seven patients were paediatric, and the rest were adolescents. Based on our scaling system, 10% of patients had depression. Forty-one percent of patients had at least one high subscale of SCARED. Forty-four percent of patients' CPTS-RI was above the normal limit, while 4% had a severe stress reaction level. In the female patient population, SCARED and CPTS-RI were significantly high (p = 0.01). There was no significant correlation between hospitalization duration and test scores. The CPTS-RI score was significantly higher in the outpatient group than in the other groups (p = 0.01). The inpatient group had significantly higher social phobia, while the outpatient group had significantly higher school phobia (p = 0.01 and p = 0.05, respectively). The present study showed that COVID-19 infection is a significant risk factor for psychopathology in children and adolescents. • COVID-19 causes multiple physical complications in the body along with significant harmful physiologic mental health effects. After being diagnosed with COVID-19, paediatric and adolescent patients have been engaging in social isolation. • Shutdowns, school closings, minimizing social interaction, and isolating behaviour are some of the measures used to control the pandemic. For kids to develop into healthy individuals, they need social interaction and a safe environment. • The present study showed that COVID-19 infection is a significant risk factor for childhood and adolescent psychopathology. Based on our scaling system, 10% of patients had depression. Forty-four percent of patients' CPTS-RI was above the normal limit, while 4% had a severe stress reaction level. In the female patient population, SCARED and CPTS-RI were significantly high. • These patients need to be evaluated and monitored by paediatric and adolescent psychiatry clinics simultaneously with paediatric clinics.


What are the effects of PFAS exposure at environmentally relevant concentrations?
The group of synthetic chemicals known as poly and per-fluoroalkyl substances (PFAS) are currently of high concern to environmental regulators and the public due to their widespread occurrence, resistance to degradation and reported toxicity. However, little data exists on the effects of exposure to PFAS at environmentally relevant concentrations and this hampers the effective management of these compounds. This paper reviews current research on the occurrence and ecotoxicology of PFAS at environmentally relevant doses to assess their potential biological impacts. Hazard Quotient (HQ) analysis was undertaken as part of this assessment. Most PFAS detected in the environment were found to have a HQ risk value of <1 meaning their reported concentrations are below their predicted no effect concentration. This indicates many reported toxic effects of PFAS are, theoretically, unlikely to occur outside the laboratory. However, lack of information on new PFAS as well as their precursors and degradation products, coupled with lack of knowledge of their mixture toxicity means our understanding of the risks of PFAS is incomplete, especially in regard to sub-lethal and/or chronic effects. It is proposed that the development of molecular markers for PFAS exposure are needed to aid in the development of environmental PFAS regulations that are effective in fully protecting the environment.


Mechanotransduction pathways linking the extracellular matrix to the nucleus.
Cells contain several mechanosensing components that transduce mechanical signals into biochemical cascades. During cell-ECM adhesion, a complex network of molecules mechanically couples the extracellular matrix (ECM), cytoskeleton, and nucleoskeleton. The network comprises transmembrane receptor proteins and focal adhesions, which link the ECM and cytoskeleton. Additionally, recently identified protein complexes extend this linkage to the nucleus by linking the cytoskeleton and the nucleoskeleton. Despite numerous studies in this field, due to the complexity of this network, our knowledge of the mechanisms of cell-ECM adhesion at the molecular level remains remarkably incomplete. Herein, we present a review of the structures of key molecules involved in cell-ECM adhesion, along with an evaluation of their predicted roles in mechanical sensing. Additionally, specific binding events prompted by force-induced conformational changes of each molecule are discussed. Finally, we propose a model for the biomechanical events prominent in cell-ECM adhesion.


A 4D Printable Shape Memory Vitrimer with Repairability and Recyclability through Network Architecture Tailoring from Commercial Poly(ε-caprolactone).
Vitrimers have shown advantages over conventional thermosets via capabilities of dynamic network rearrangement to endow repairability as well as recyclability. Based on such characteristics, vitrimers have been studied and have shown promises as a 3D printing ink material that can be recycled with the purpose of waste reduction. However, despite the brilliant approaches, there still remain limitations regarding requirement of new reagents for recycling the materials or reprintability issues. Here, a new class of a 4D printable vitrimer that is translated from a commercial poly(ε-caprolactone) (PCL) resin is reported to exhibit self-healability, weldability, reprocessability, as well as reprintability. Thus, formed 3D-printed vitrimer products show superior heat resistance in comparison to commercial PCL prints, and can be repeatedly reprocessed or reprinted via filament extrusion and a handheld fused deposition modeling (FDM)-based 3D printing method. Furthermore, incorporation of semicrystalline PCL renders capabilities of shape memory for 4D printing applications, and as far as it is known, such demonstration of FDM 3D-printed shape memory vitrimers has not been realized yet. It is envisioned that this work can fuel advancement in 4D printing industries by suggesting a new material candidate with all-rounded capabilities with minimized environmental challenges.


Clinical benefit of graduated compression stockings for prevention of venous thromboembolism after total knee arthroplasty: post hoc analysis of a phase 3 clinical study of edoxaban.
Guidelines from the Japanese Circulation Society recommend prophylaxis with anticoagulation plus intermittent pneumatic compression or graduated compression stockings (GCS) among patients at the highest risk for developing venous thromboembolism (VTE). However, the benefits of concomitant GCS use for patients undergoing total knee arthroplasty (TKA) and receiving anticoagulation remain unknown. In this study, the efficacy of GCS plus anticoagulation compared with anticoagulation alone was evaluated among patients undergoing TKA. This study is a post hoc analysis of a previously reported phase 3 trial involving patients undergoing TKA. In the primary study, which permitted the use of GCS for mechanical prophylaxis, patients were randomized to receive edoxaban 30 mg once daily or enoxaparin 20 mg twice daily for 11 to 14 days following TKA. The primary endpoint was the incidence of VTE, a composite of symptomatic deep vein thrombosis (DVT), symptomatic pulmonary embolism (PE), and asymptomatic DVT. Treatment comparisons were performed using the chi-square test, and the 95 % confidence intervals were calculated. Among patients receiving edoxaban, the incidence of VTE was 3.8 and 5.8 % for patients with and without GCS, respectively. For patients receiving enoxaparin, VTE incidence was 8.4 and 20.8 % among those with and without GCS, respectively. Overall, VTE incidence was 6.0 and 13.0 % for anticoagulated patients with and without GCS mechanical prophylaxis, respectively. No deaths or symptomatic PE were reported during this study. Although the incidence of VTE was >2-fold lower among patients receiving anticoagulation plus GCS compared with those receiving anticoagulation alone, statistical significance was not achieved. Further studies are required to confirm the findings of this preliminary analysis. ClinicalTrials.gov Identifier: NCT01181102.


Loss of LKLF function results in embryonic lethality in mice.
Lung Kruppel-like factor (LKLF) is a member of the Kruppel-like family of zinc finger transcription factors and is closely related to erythroid kruppel-like factor (EKLF), which is necessary for beta-globin gene expression. While EKLF is expressed exclusively in erythroid cells, LKLF is expressed temporally during early embryonic development and predominantly in the adult mouse lung. To understand the role this novel transcription factor plays in development as well as tissue differentiation and function, animals lacking LKLF were produced using gene targeting technology. Mice lacking LKLF die in utero between day 11.5 and 13.5 of embryonic life and exhibit retarded growth, craniofacial abnormalities, abdominal bleeding and signs of anaemia. Although the yolk sac erythropoiesis is normal in mutant embryos, in vitro fetal liver cultures of these embryos fail to give rise to erythroid cells. Expression of other erythroid specific genes such as EKLF, GATA1 and GATA3 is unaltered in these animals. These findings demonstrate the LKLF function is indispensable during normal embryonic development, and although both LKLF and EKLF recognize common DNA motifs, they do not substitute for each other.


Splenic stiffness and platelet count to predict varices needing treatment in pediatric extrahepatic portal vein obstruction.
Surveillance endoscopy to detect varices needing treatment (VNT) is important to prevent bleeding and morbidity in portal hypertension. In adult and pediatric cirrhosis, platelet count and liver stiffness measurement (LSM) are useful in selecting patients for endoscopy. Such recommendations do not exist for extrahepatic portal vein obstruction (EHPVO). Splenic stiffness measurement (SSM) has been studied in adult and pediatric EHPVO with conflicting results and methodological errors. This study evaluates the role of platelet counts and SSM to predict VNT and bleeding in pediatric EHPVO while comparing LSM and SSM between pediatric EHPVO and controls. One hundred and seven children (55 with EHPVO and 52 controls) were recruited. Clinical, biochemical, hematological, and radiographic parameters of all children were noted. All children with EHPVO underwent endoscopy. Of the 55 children with EHPVO, 48 (87.3%) had VNT. There was no difference in the platelet counts (85,000/mm3 vs. 120,000/mm3, p = 0.58) and SSM (3.62 vs. 3.19, p = 0.05) between EHPVO children with VNT and those without. They had poor sensitivity and specificity to predict VNT. EHPVO children with bleeding had higher SSM that those without. LSM was higher among EHPVO than among controls (1.19 vs. 1.10, p = 0.003). Those with LSM higher than controls had normal liver histology. SSM is higher in EHPVO bleeders but SSM and platelet counts are unreliable to predict VNT in pediatric EHPVO. Surveillance endoscopies may be needed in all pediatric EHPVO until better screening strategies are available. Not applicable.


In vitro studies of intragastric digestion.
Following consumption of a meal, 99% of the large food particles are emptied only after intragastric fragmentation has reduced their diameter to less than 2 mm. An in vitro model was constructed to evaluate some of the factors which may play a role in the process of intragastric digestion. Gastric mixing of food was simulated in a silicone rubber tube (ID 19 mm) placed in a peristaltic pump. Peristaltic waves progressed upwards along the tube at a frequency of 0, 1, or 3/min, reducing the internal diameter of the tube to 5 mm. Cooked chicken liver particles (2-2.8 mm in diameter) were placed in the tube with one of the following: (1) 150 mM NaCl, (2) 150 mM HCl with or without pepsin, or (3) phosphate buffer at pH 7, 5.4, or 2.6 + pepsin. After 30 min, the extent of particle reduction and of solubilization of proteins were determined and expressed as percent of the initial liver weight. The diameter of liver particles was reduced to a greater extent in NaCl than in pH 7 buffer or acid solutions with or without pepsin. In contrast, the amount of proteins solubilized was enhanced two- to threefold by acid pepsin solutions compared to NaCl or pH 7 phosphate. The present in vitro studies suggest that changes in motor and/or secretory activity of the stomach significantly modify intragastric digestion.


Editorial: Translating the advances of biosensors from bench to bedside.
Biosensors have been found with numerous applications in many areas including genetic analysis, detection of infectious diseases, environmental monitoring and forensic analysis. We have witnessed rapid advances in this field, especially with the emergence of nanotechnology in the past decade.


Sulphate sequestered in the sulphate-binding protein of Salmonella typhimurium is bound solely by hydrogen bonds.
An important question in understanding substrate binding by proteins is how charged groups are stabilized in the absence of their solvation shell. We have addressed this question here by solving the structure of the sulphate-binding protein of Salmonella typhimurium with bound substrate at 2.0 A resolution. The results are remarkable in that the charged oxygen atoms of the sulphate molecule, which is buried and completely inaccessible to the solvent, are not stabilized by the formation of salt-bridges but by hydrogen bonds donated by specific residues of the protein. These hydrogen bonds are in turn coupled via peptide units to several resonating hydrogen bonding systems. These findings may be of general significance for the role of electrostatic interactions in protein structure and function.


Dietary Supplement Labels May Be Inaccurate and Misleading.
According to this study: The labeling on dietary supplements marketed to support or boost the immune system is often inaccurate and inconsistent with Food and Drug Administration requirements.Quality control measures appear to be insufficient for most of these products.


Evidence for the denaturation of recombinant hepatitis B surface antigen on aluminium hydroxide gel.
Despite the complexity of the subject of protein-alum interactions, a valuable information can be obtained by analyzing the adsorbed and desorbed protein by common physico-chemical methods. In the present work, to approach the adsorption of hepatitis B surface antigen (HBsAg) on alum, the experimental data were supported by complementary analyses of the adsorbed protein by immunoelectron microscopy and the desorbed protein by denaturing size-exclusion chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. First, the depletion of HBsAg was investigated. The aspects assessed were the conditions, recovery and chromatographic performance of the desorbed protein. The results obtained strongly suggested the loss of particulate structure of HBsAg after adsorption on alum. This conclusion was further reinforced by direct immunoelectron microscopic visualization of HBsAg in the adsorbed state.


Cooperative care as origins of the "happy ape"?
Grossmann proposes an interesting framework to explain how heightened fearfulness among humans could be evolutionarily adaptive in the context of cooperative care. I would like to propose that cooperative care may also be a potential mechanism promoting enhanced happiness expression among humans, shedding light on questions about the scope and boundary of the fearful ape hypothesis.


Slaughterhouse Workers, Animals, and the Environment: The Need for a Rights-Centered Regulatory Framework in the United States That Recognizes Interconnected Interests.
The COVID-19 pandemic has shone a bright light on industrial slaughterhouses in the United States and their impacts on the vulnerable beings-both human and animal-they exploit. But the severity of these impacts is the result of a long history of failed regulatory oversight. This paper highlights the inadequacies of the current regulatory system in the United States and how they have contributed to dangerous conditions for slaughterhouse workers, environmental degradation, and severe animal suffering. Further, it argues that a rights-centered One Health approach would provide the necessary conceptual foundation for a new regulatory framework that can meaningfully address the interconnected rights, health, and well-being of humans, animals, and the environment. As a first step in establishing this new framework, the United States should create a federal Slaughterhouse Oversight Commission to strengthen the rights, health, and well-being of humans and animals.


Seasonal exposure to PM2.5-bound polycyclic aromatic hydrocarbons and estimated lifetime risk of cancer: A pilot study.
Limited researches are available on seasonal variation of inhalation exposure of polycyclic aromatic hydrocarbons (PAHs) and its cancer risk assessment in China. We recruited 20 fresh postgraduates and measured outdoor and indoor (dormitories, offices and laboratories) daily PM2.5 concentrations in four seasons (seven consecutive days in every season) during 2014 -2015, calculated daily potential doses of personal exposure to total Benzo[a]pyrene equivalent concentration (BaPeq) in the microenvironments based on the total BaPeq and the time-activity patterns, and estimated incremental lifetime cancer risk (ILCR) using Monte Carlo method. Daily average concentrations of PM2.5-bound ∑PAHs on the campus ranked from high to low were winter, autumn, spring, summer in the dormitories and offices. Daily average concentration of PM2.5-bound ∑PAHs were higher in indoor environments than outdoor in the same season, except for that of PM2.5-bound ∑PAHs in laboratories in the winter. Median values of ILCR in both sexes from high to low were winter (men vs. women: 5.35e-9 vs. 4.96e-9), spring (3.71e-9 vs. 4.00e-9), autumn (2.92e-9 vs. 3.02e-9), summer (1.71e-9 vs. 1.87e-9). Indoor and outdoor PM2.5-bound PAHs concentrations showed seasonal and spatial variations. The ILCR value for PM2.5-bound PAHs was higher in women than in men.


In vivo proton magnetic resonance spectroscopy (MRS) study of post polio residual paralysis (PPRP) patients.
In-vivo proton MR spectroscopy carried out on post polio residual paralysis (PPRP) patients indicate that the presence or absence of intra-myocellular lipids (IMCL) is related to the severity of the paralysis. It is observed that mildly paralyzed patients are comparable (p > 0.05) with the control subjects in relation to the presence of IMCL, while moderate and severely paralysed patients are comparable (p > 0.05) in relation to the absence of IMCL. In addition, there is reduction or complete absence of creatine, carnitine and choline metabolites in severely paralyzed patients. The ability to detect noninvasively the subtle differences in in vivo, the lipid compartments of muscle may prove to be a valuable tool in understanding the pathogenesis of muscle diseases. This could open up the possibilities in designing effective rehabilitative exercise programs or development of new drug therapies.


Homocysteine and methylenetetrahydrofolate reductase genotype: association with risk of coronary heart disease and relation to inflammatory, hemostatic, and lipid parameters.
It has been suggested that homocysteine (tHcy) levels and methylenetetrahydrofolate reductase (MTHFR) genotype are primary risk factors for coronary heart disease (CHD). We performed a case-control study to investigate whether tHcy levels and MTHFR genotype (677 C-->T mutation and 1298 A-->C mutation) are associated with CHD under special consideration of the possibility for confounding. German speaking patients aged 40-68 years who underwent coronary angiography at the University of Ulm between April 1996 and November 1997 and who had at least one coronary stenosis greater than 50% were included in the study. Controls were sampled from voluntary blood donors and were matched for sex and age. tHcy levels were measured by high performance liquid chromatography and MTHFR genotype by means of polymerase chain reaction. In addition, C-reactive protein, fibrinogen, plasma viscosity, leukocytes, HDL-cholesterol and Lp(a) were determined. Overall, 312 patients and 479 controls were enrolled in the study (response in patients 78%, in controls 84%). Mean tHcy value was 9.43 micromol/l in CHD patients and 8.91 micromol/l in controls (P=0.145). Prevalence of 677TT-polymorphism was 9.9% in patients and 10.4% in controls (P=0.295). Prevalence of 1298CC-polymorphism was 9.7% in patients and 13.8% in controls (P=0.346). There was a clear association of tHcy-values, but not of 677TT- or 1298CC-genotype with conventional CHD risk factors. After adjustment for these risk factors no increased risk for CHD could be associated with increased tHcy-values, with 677TT or 1298CC-genotype, or with their combination. Also no statistically significant relationships of these parameters to inflammatory, rheologic or hemostatic parameters or lipids were detectable. These results do not confirm an independent relationship of tHcy values and MTHFR genotype with risk of CHD in the population studied.


Alkane hydroxylation by peroxy acids: a comparison with the cytochrome P450 hydroxylation.
Alkane hydroxylation by peroxy acids proceeds by a synchronous nonconcerted peroxy oxygen insertion into the C-H bond according to density functional theory. A comparable reaction sequence, initiated by homolytic peroxy bond cleavage, can be formulated for the alkane hydroxylation by the cytochrome P450 hydroperoxo-heme Compound 0. This hydroxylation reaction proceeds by a two-step process because the formed reactive intermediate, Compound II, is significantly stabilized.


Chemical characterization of variably degraded fibre glass reinforced plastic from the marine environment.
Glass reinforced plastic (GRP) constitutes the commonest component of small sea going craft of all descriptions. This study provides a baseline molecular and elemental account of GRP's recovered from the marine environment. Fourteen samples of GRP sourced from scrapyards and one sample sourced from a GRP boat manufacturer were examined. Samples were analysed by x-ray fluorescence and mid infrared (MIR). The latter technique confirmed that all samples contained the same polyester resin, poly diallyl phthalate (PDP). The two techniques in combination indicate the presence of aluminium calcium borosilicate E-glass fibres (E denotes electrical) of variable origins. MIR results are consistent with hydrolysis of polyester, weakening of the glass fibre resin interface facilitating exposure of e-type fibres to water which accelerates fibre breakage. The implication being that aging of GRP in the marine environment represent sources for micro (<5 mm) and macro plastic release, plus fragmented asbestiform-like silicate fibres.


Posterior Tibial Tendoscopy: Endoscopic Synovectomy and Assessment of the Spring (Calcaneonavicular) Ligament.
A tear of the spring ligament is frequently associated with posterior tibial tendon dysfunction. Repair of the damaged spring ligament is an important component of surgical reconstruction in the treatment of posterior tibial tendon dysfunction because it is a major anatomic contributor to the integrity of the medial longitudinal arch, particularly if the dynamic support of the posterior tibial tendon is compromised. Extensive dissection is required for exposure and repair of the ligament because it is a deep-seated structure. It is beneficial to confirm the presence of ligament tears before surgical exploration to avoid unnecessary dissection. Preoperative magnetic resonance imaging and ultrasound studies have moderate sensitivity in the detection of these tears. We report an arthroscopic technique for assessment of the integrity of the spring ligament during endoscopic or open reconstruction of the posterior tibial tendon. This allows the surgeon to confirm the presence of a ligament tear before additional dissection to explore and repair the ligament.


Is preoperative physical activity related to post-surgery recovery?-a cohort study of colorectal cancer patients.
An increasing interest is seen in the role of preoperative physical activity (PA) in enhancing postoperative recovery. The short-term effect of preoperative PA on recovery after colorectal cancer is unknown. The aim of this study was to evaluate the association of the preoperative level of PA with postoperative recovery after surgery due to colorectal cancer disease. This is a prospective observational cohort study, with 115 patients scheduled to undergo elective colorectal surgery. The self-reported level of preoperative PA was compared to measures of recovery. Regular self-reported preoperative PA was associated with a higher chance of feeling highly physically recovered 3 weeks after surgery (relative chance 3.3, p = 0.038), compared to physical inactivity. No statistically significant associations were seen with length of hospital stay, self-assessed mental recovery, re-admittances or with re-operations. In clinical practice, evaluating the patients' level of PA is feasible and may potentially be used as a prognostic tool for patients undergoing colorectal cancer surgery. Given the study design, the results from this study cannot prove causality. The present study found that the preoperative level of PA was associated with a faster self-assessed physical recovery after colorectal cancer surgery. PA did not show any associations with the primary outcome measure length of hospital stay or any of the other secondary outcome measures. Assessment of PA level preoperatively could be used for prognostic reasons. If systematic preoperative/postoperative physical training will enhance recovery, this remains to be studied in a randomized controlled study. We examined preoperative physical activity and the recovery after colorectal cancer surgery. Physically active individuals had faster self-assessed physical recovery. Assessment of preoperative physical activity may provide prognostic clinical information.


Sex differences in effect of patients-centered intervention on blood pressure in patients with hypertension.
Hypertension exhibits sex-related differences in its causes, symptoms, and complications. In this study, we aimed to confirm the efficacy of hypertension intervention by applying a patient-centered approach based on sex differences. We enrolled 95 hypertensive patients in this prospective quasi-experimental pretest-posttest study. The patient-centered lifestyle intervention included penalized nutrition and exercise education in 30-min one-on-one sessions. Before the intervention, we conducted a pretest to evaluate physical examination, behavioral status, quality of life (QoL), blood pressure (BP) measurements, and routine blood tests. The same evaluations were conducted again in a posttest after 3 months. After 3 months of patient-centered intervention, all patients showed a decrease in systolic BP by 2.87 mmHg and diastolic BP by 1.04 mmHg. However, there was no significant difference in BP between men and women after the 3-month follow-up. There were differences in lipid profiles based on sex, with total cholesterol and low-density lipoprotein cholesterol levels decreasing in men and increasing in women. Behavioral and QoL scores improved after the intervention; however, there was no significant difference based on sex. A patient-centered lifestyle intervention for hypertensive patients can effectively lower BP, and sex-specific risk factors affecting its efficacy have been identified.


Vacancy-mediated anomalous phononic and electronic transport in defective half-Heusler ZrNiBi.
Studies of vacancy-mediated anomalous transport properties have flourished in diverse fields since these properties endow solid materials with fascinating photoelectric, ferroelectric, and spin-electric behaviors. Although phononic and electronic transport underpin the physical origin of thermoelectrics, vacancy has only played a stereotyped role as a scattering center. Here we reveal the multifunctionality of vacancy in tailoring the transport properties of an emerging thermoelectric material, defective n-type ZrNiBi. The phonon kinetic process is mediated in both propagating velocity and relaxation time: vacancy-induced local soft bonds lower the phonon velocity while acoustic-optical phonon coupling, anisotropic vibrations, and point-defect scattering induced by vacancy shorten the relaxation time. Consequently, defective ZrNiBi exhibits the lowest lattice thermal conductivity among the half-Heusler family. In addition, a vacancy-induced flat band features prominently in its electronic band structure, which is not only desirable for electron-sufficient thermoelectric materials but also interesting for driving other novel physical phenomena. Finally, better thermoelectric performance is established in a ZrNiBi-based compound. Our findings not only demonstrate a promising thermoelectric material but also promote the fascinating vacancy-mediated anomalous transport properties for multidisciplinary explorations.


Use of Psychotropic Medication in an Outpatient CAMHS Over a 5-Year Period.
Psychotropic medication is being prescribed with increasing frequency for children and adolescents but there are very few prescription reviews on the extent of use in the UK. A retrospective prescriptions' survey was carried out in an outpatient CAMHS in three time-bands between 1997 and 2002. We found a five-fold increase in the number of prescriptions, a ten-fold increase in the number of young people prescribed medications, and a dramatic increase in the range of psychotropics prescribed. There is a need to further evaluate prescribing for children and adolescents in the UK. Clearer guidelines should be developed to ensure safe practices.


Arsenic behavior in groundwater in Hanoi (Vietnam) influenced by a complex biogeochemical network of iron, methane, and sulfur cycling.
The fate of arsenic (As) in groundwater is determined by multiple interrelated microbial and abiotic processes that contribute to As (im)mobilization. Most studies to date have investigated individual processes related to As (im)mobilization rather than the complex networks present in situ. In this study, we used RNA-based microbial community analysis in combination with groundwater hydrogeochemical measurements to elucidate the behavior of As along a 2 km transect near Hanoi, Vietnam. The transect stretches from the riverbank across a strongly reducing and As-contaminated Holocene aquifer, followed by a redox transition zone (RTZ) and a Pleistocene aquifer, at which As concentrations are low. Our analyses revealed fermentation and methanogenesis as important processes providing electron donors, fueling the microbially mediated reductive dissolution of As-bearing Fe(III) minerals and ultimately promoting As mobilization. As a consequence of high CH4 concentrations, methanotrophs thrive across the Holocene aquifer and the redox transition zone. Finally, our results underline the role of SO42--reducing and putative Fe(II)-/As(III)-oxidizing bacteria as a sink for As, particularly at the RTZ. Overall, our results suggest that a complex network of microbial and biogeochemical processes has to be considered to better understand the biogeochemical behavior of As in groundwater.


Macrophages in human uteroplacental tissues: a review.
Macrophages are major cellular components of the uterus, the placenta, and the extra-placental membranes throughout pregnancy. Many macrophages in normal uteroplacental tissues are in an activated state as evidenced by their expression of class II major histocompatibility antigens. Activated macrophages are capable of synthesizing and releasing an impressive array of potent "monokines" and other molecules with dramatic effects on receptive cells. Macrophage activation levels can be further enhanced by exposure to either endotoxin from gram-negative organisms or to interferon-gamma from stimulated lymphocytes. Since prostaglandin E2 is one of the products of activated macrophages and can stimulate contraction of smooth muscle, macrophages may be responsible in part for the induction of preterm labor in cases of infection. Thus, understanding the conditions of uncomplicated pregnancy as well as the consequences of local infections requires exploration of the temporal, spatial, and functional characteristics of macrophages residing in uteroplacental tissues.


Chemotherapy of metastatic ameloblastoma. A case report and review of the literature.
A case of metastatic ameloblastoma is presented which was resistant to treatment with adriamycin (doxorubicin), platinol (cis-platinum), cytoxan (cyclophosphamide), dacarbazine (DTIC), and 5-fluorouracil (5-FU). The literature about treatment with chemotherapeutic agents is reviewed.


Ethylene oxide derived glycol ethers: A review of the alkyl glycol ethers potential to cause endocrine disruption.
The 'ethylene glycol ethers' (EGE) are a broad family of solvents and hydraulic fluids produced through the reaction of ethylene oxide and a monoalcohol. Certain EGE derived from methanol and ethanol are well known to cause toxicity to the testes and fetotoxicity and that this is caused by the common metabolites methoxy and ethoxyacetic acid, respectively. There have been numerous published claims that EGE fall into the category of 'endocrine disruptors' often without substantiated evidence. This review systematically evaluates all of the available and relevant in vitro and in vivo data across this family of substances using an approach based around the EFSA/ECHA 2018 guidance for the identification of endocrine disruptors. The conclusion reached is that there is no significant evidence to show that EGE target any endocrine organs or perturb endocrine pathways and that any toxicity that is seen occurs by non-endocrine modes of action.


Superbases-templated carbons doped with electrochemically active oxygen as advanced supercapacitor electrodes.
Templating techniques have been widely adopted for the synthesis of porous carbons, such as oxygen-doped porous carbon nanosheets (O-PCNs), but the effect of the surface characteristics of templates on the surface functionality and performance of a derived carbon has not been well studied. Herein, a series of laboratory-made superbases of K/Mg(OH)2 with different K/Mg ratios were employed as template to fabricate nanocarbon materials. The aim is to find out how the strength of template basicity could influence the surface functionalities and the supercapacitor performances of the derived O-PCNs. The resulting materials are rich in conjugated hydroxyl and carbonyl groups that are electrochemically active owing to the protection of the conjugated hydroxyl group by KOH and the dehydrogenation step catalyzed by magnesium oxide. Systematic investigations revealed that with the increase of basic strength, the content of the derived electrochemically active oxygen species in the forms of conjugated carbonyl (CO) and hydroxyl (COH) first increases from 8.4 atom% to 11.4 atom% then decreases to 9.25 atom%. Moreover, the microporosity of the O-PCNs stepwise increases with the rise of KOH loading, ascribable to the effect of KOH etching on the carbon skeleton. The O-PCN-20 templated by 20 % K/Mg(OH)2 is rich in porosity, large in surface area (930 m2/g) and high in active oxygen content (11.4 atom%). With high active surface area and extra Faradaic capacitance, O-PCN-20 exhibited superior supercapacitor performances including large specific capacitance of 375 firstname.lastname@example.com A/g, high rate capability of 81.1 % (from 1.0 A/g to 20 A/g), energy density of 25.7 Wh/kg@900 W/kg and excellent cycling stability with near 100 % capacitance retentions after 10 000 cycles and more than 86.2 % capacitance retention over 20 000 cycles at large current density of 10 A/g, indicating O-PCN-20 has potential to be used as electrode material for energy storage devices.


Impact of training level of urology residents on the detection of prostate cancer on TRUS biopsy.
The objective of this study is to evaluate the performance of urology residents at each training level in detecting prostate cancer with transrectal ultrasound-guided (TRUS) biopsy. The inclusion criteria were: (1) prostate-specific antigen (PSA) 4-10 ng/ml; and (2) 10-12 cores per biopsy session. Data from repeat biopsy sessions were excluded. Overall prostate cancer detection rate for 170 patients was 39.4%. PSA, digital rectal examination (DRE), and prostate volume were predictors of cancer detection. There were no significant differences in overall cancer detection rates, PSA, DRE, or prostate volume between resident levels. In conclusion, urology residents at all levels of training perform equally well at detecting cancer using TRUS prostate biopsy technology.


RNA secondary structure diagrams for very large molecules: RNAfdl.
There are many programs that can read the secondary structure of an RNA molecule and draw a diagram, but hardly any that can cope with 10(3) bases. RNAfdl is slow but capable of producing intersection-free diagrams for ribosome-sized structures, has a graphical user interface for adjustments and produces output in common formats. Source code is available under the GNU General Public License v3.0 at http://sourceforge.net/projects/rnafdl for Linux and similar systems or Windows using MinGW. RNAfdl is implemented in C, uses the Cairo 2D graphics library and offers both command line and graphical user interfaces. firstname.lastname@example.com


Protection of mice against Brucella abortus by immunization with polyclonal anti-idiotype antibodies.
Polyclonal goat anti-idiotypic antibodies containing internal images which mimic Brucella abortus antigens were generated from rabbit polyclonal idiotypes specific for partially purified extract of B. abortus (PX III). The anti-idiotypic antibodies were purified using two-step immunoaffinity column chromatography. The presence of internal images was demonstrated by competitive inhibition analysis using an enzyme-linked immunosorbent assay. Several groups of BALB/c mice were vaccinated with the anti-idiotypic antibodies. The vaccinated mice showed a high serum titer of antibodies specific for B. abortus. When the vaccinated mice were challenged with a virulent B. abortus strain 2308, greater than 90% reduction of bacteria in the spleen as compared to the unvaccinated control groups was seen. Immunoblotting experiments using antiserum from vaccinated mice demonstrate the ability to distinguish vaccinated mice from B. abortus infected mice. Our data indicate that the anti-idiotypic antibody containing internal images of B. abortus may be used as a vaccine and the induced antibody can be distinguished by immunoblotting from antibodies generated by natural infection with B. abortus.


The role of plasminogen in angiogenesis in vivo.
Plasminogen, by virtue of its role in the degradation of extracellular matrix proteins and by facilitation of cell migration, may contribute to angiogenesis. the purpose of this study was to evaluate the contribution of plasminogen to angiogenesis in vivo. Angiogenesis was assessed in gene-targeted mice with deficiencies of plasminogen, urokinase plasminogen activator (uPA), and urokinase receptor (uPAR) in a mouse corneal model. In wild-type mice, female and young mice showed a trend toward increased angiogenesis compared to males and old mice. Because of this influence of age and gender on angiogenesis, young, female mice (6-13 weeks of age) were used for this study. In response to angiogenic stimulation by basic fibroblast growth factor (bFGF), uPA deficient mice exhibited a decrease in new vessel formation as reflected by vessel length (0.47 in control vs. 0.33 mm in uPA-/- mice, P = 0.043), but new vessel formation was not altered (P = 0.107) in the uPAR deficient mice compared to control mice. A significantly decreased angiogenic response of new vessel formation to both vascular endothelial growth factor (VEGF) (P < 0.02) and bFGF (P < 0.007) was observed in Plg deficient (Plg-/-) mice (VEGF - 0.36 mm, bFGF - 0.67 mm) compared to Plg+/+ mice (VEGF - 0.56 mm, bFGF - 0.85 mm). These results demonstrate the importance of plasminogen, as well as of uPA, in angiogenesis in vivo.


Subtype classification of the presynaptic alpha-adrenoceptors which regulate [3H]-noradrenaline secretion in guinea-pig isolated urethra.
1. The following experiments were carried out to investigate the presence and type of functional presynaptic receptors in adrenergic nerves of the guinea-pig urethra. 2. The urethra from male guinea-pigs was incubated with [3H]-noradrenaline and superfused with Tyrode solution in vitro. The fractional secretion of [3H]-noradrenaline evoked by 300 electrical pulses was measured. 3. The [3H]-noradrenaline secretion was positively frequency-dependent, yielding a half-maximal secretion at 8 +/- 5 Hz. Stimulation was usually applied at 5 Hz. 4. The [3H]-noradrenaline secretion was not altered by noradrenaline (1 or 100 microM), norephedrine (1 microM), isoprenaline (0.1 microM), 5-hydroxytryptamine (10 microM), oxotremorine (10 microM), adenosine (0.2 mM), propranolol (1 microM), atropine (1 microM) or 8-phenyltheophylline (10 microM). 5. The [3H]-noradrenaline secretion was enhanced by clonidine (3 microM), chlorpromazine (10 microM), metitepine (1 microM), 4-aminopyridine (0.5 mM), tetraethylammonium (2 mM), 3-isobutyl-1-methylxanthine (4 mM), 8-bromo cyclic AMP (1 mM) and forskolin (25 microM). 6. The alpha-adrenoceptor antagonists rauwolscine, yohimbine, phentolamine, prazosin and AR-C 239 maximally enhanced the [3H]-noradrenaline secretion to about 300% of control. The partial alpha-adrenoceptor agonist oxymetazoline maximally enhanced the secretion to about 200% of control. The order of apparent EC50 values was rauwolscine less than yohimbine less than phentolamine less than oxymetazoline less than prazosin less than AR-C 239.7. The enhancing effects of yohimbine (1 microM) with tetraethylammonium (2mM), 8-bromo cyclic AMP (1 mM), or forskolin (25,microM) were additive, but not those of yohimbine (1 microM) with prazosin (10 microM), 4-aminopyridine (0.5 mM), or 3-isobutyl-1-methylxanthine (4 mM).8. These results suggest that the [3H]-noradrenaline secretion in the guinea-pig urethra is regulated by presynaptic alpha2A-adrenoceptors which may, in a cyclic AMP-independent manner, be coupled to a 4-aminopyridine-sensitive potassium channel. The secretion is not influenced by compounds acting at beta-adrenoceptors, muscarinic cholinoceptors or adenosine receptors.


Conventional diatom testing using strong acid: (II) Number and types of diatoms detected in closed organs and lungs of 80 autopsy cases using only new Kjeldahl flasks.
The number of diatoms detected in the kidneys and liver varies considerably when comparing various reports, but the reason remains unclear. We previously showed that the reuse of Kjeldahl flasks is susceptible to generating false positives; false-positive results were observed in 17 of 60 tested flasks, and a maximum of 290 diatoms were detected. Furthermore, these data suggested that the number of diatoms in kidney and liver tissue may be much lower than previously thought. Therefore, only new Kjeldahl flasks were used to perform diatom tests on 80 autopsy cases (drowning and non-drowning victims) in this study. When combined with the 20 cases in a previous study, a total of 100 cases were analyzed. Four grams of lung, 10-30 g each of kidney and liver, 10 mL of blood, and 50-100 mL of water (discovery site) were examined. A large number of diatoms (n = 400) were found in organs other than the lungs in only 1 of 56 cases of suspected drowning (excluding cases of suspected drowning in baths). Together with the previous 20 cases, this single case represented only 1 of 76 cases (1.3 %). In closed organs and blood samples, 3 diatoms were found in 2 of 56 victims (3.6 %), and 1 or 2 diatoms were found in 8 victims (14 %). However, 5 diatoms were found in 1 of 10 bathtub drowning victims and 12 non-drowning victims (4.5 %), and 1 or 2 diatoms were found in 6 victims (27 %). Moreover, 1 or 2 diatoms were found in negative control flasks in 3 of 80 victims (3.8 %). The results showed that distinguishing false-positive results is difficult when a small number of diatoms are found in the kidneys and liver. Thus, the presence of diatoms in closed organs and blood seems to be unreliable as evidence of death by drowning, at least in the water environments in our region (freshwater areas: 23-26,000 diatoms/mL, median 200 diatoms; brackish water areas: 26-1200 diatoms/mL, median 210 diatoms; seawater area: 2-1000 diatoms/mL, median 24 diatoms). These results also reconfirmed that the reuse of flasks is the most important cause of false positives. Conversely, the presence of a large number of diatoms in lung samples (1-850,000 diatoms/g lung tissue; median (right lung): 440 diatoms, (left lung): 320 diatoms) is very informative and is an effective diagnostic aid in many cases.


Germline polymorphisms in genes involved in the Hippo pathway as recurrence biomarkers in stages II/III colon cancer.
The Hippo pathway regulates tissue growth and cell fate. In colon cancer, Hippo pathway deregulation promotes cellular quiescence and resistance to 5-Fluorouracil (5-Fu). In this study, 14 polymorphisms in 8 genes involved in the Hippo pathway (MST1, MST2, LATS1, LATS2, YAP, TAZ, FAT4 and RASSF1A) were evaluated as recurrence predictors in 194 patients with stages II/III colon cancer treated with 5-Fu-based adjuvant chemotherapy. Patients with a RASSF1A rs2236947 AA genotype had higher 3-year recurrence rate than patients with CA/CC genotypes (56 vs 33%, hazard ratio (HR): 1.87; P=0.017). Patients with TAZ rs3811715 CT or TT genotypes had lower 3-year recurrence rate than patients with a CC genotype (28 vs 40%; HR: 0.66; P=0.07). In left-sided tumors, this association was stronger (HR: 0.29; P=0.011) and a similar trend was found in an independent Japanese cohort. These promising results reveal polymorphisms in the Hippo pathway as biomarkers for stages II and III colon cancer.The Pharmacogenomics Journal advance online publication, 15 September 2015; doi:10.1038/tpj.2015.64.