Role of gastric mucus secretion, oxinitrergic system and sulfhydryl groups on the gastroprotection elicited by Polygala cyparissias (Polygalaceae) in mice.
This study has aimed to assess the mechanisms of action for the gastroprotective effect of the acetone extract (PCAE) and methanol fraction (PCMF) of Polygala cyparissias, as well as to evaluate the activity of 1,3,6,8-tetrahydroxy-2,7-dimethoxyxanthone (1), 1,7-dihydroxy-2,3-dimethoxyxanthone (2) and astragalin (3). Gastric secretion and mucus content were determined by pylorus ligation in mice. Nitric oxide (NO) and sulfhydryl group participation were observed by the pretreatment of mice with L-NAME or NEM. Acute ulcer was induced by ethanol/HCl and chronic ulcer by acetic acid. Anti-Helicobacter pylori activity was evaluated by the agar solid dilution assay. Neither PCAE nor PCMF had the ability to reduce H(+) concentration. However, both of them enhanced mucus secretion. PCAE demonstrated its gastroprotection in a NO-dependent manner, while PCMF exerted the activity depending on the sulfhydryl group. In chronic ulcer, the curative ratios for the PCAE and PCMF were 67.5 and 58.4%, respectively. No effect over H. pylori was detected. Compounds 1, 2 and 3 were able to reduce lesions in the order of 79.6, 73.8 and 67.6%, respectively. The data suggested that PCAE and PCMF displayed antiulcer activity due to different mechanisms and with the participation of phenolic compounds obtained from the plant.


Characterization of a polysaccharide from Polygala tenuifolia willd. with immune activity via activation MAPKs pathway.
Polysaccharides from the Polygala tenuifolia Willd. have been shown multiple biological activities, however the structural feature and immunomodulatory activity are still rarely reported. In this study, a polysaccharide was obtained by purification, and its structural characteristics and immune activity were analyzed. The polysaccharide was a homogeneous macromolecular polysaccharide with smooth flat flakes surface structure and molecular weight of 2.34 × 105 Da, and composed of Rha, Ara, Xyl, Man, Glc, Gal. Methylation and NMR analyses confirmed that the repeating unit of polysaccharide was [→3)-α-Araf-(1 → 3)-α-Araf-(1 → 5)-α-Araf-(1 → 5)-α-Araf-(1 → 3)-α-Araf-(1 → ]n, and the side chain was α-Araf-(1 → 6)-β-Galp-(1 → 6)-β-Glcp-(1 → 6)-α-Manp-(1→, which was attached to the C3 of → 3,5)-α-Araf-(1 →. In vitro, the RAW 264.7 cells were co-cultivated with LPS and polysaccharide, and the results revealed that the polysaccharide can promote cell proliferation, activate effectors to release cytokines (TNF-α, IL-6, IL-1β), and then activate macrophages for immune activity. Therefore, we can infer that the polysaccharide might regard as a potential immunomodulator.


Microplastics: Sources and distribution in surface waters and sediments of Todos Santos Bay, Mexico.
Microplastics (MPs) are ubiquitous and a threat to marine and freshwater environments. Effluent waters from secondary wastewater treatment plants (WWTPs) into Todos Santos Bay (TSB) were investigated as sources of MPs. MPs were detected in all analyzed matrices and presented variable morphologies. MPs from surface water samples (n = 18) varied from 0.01 to 0.70 plastic particles/m3 (pp/m3). Fragments (47 ± 23%) and fibers (47 ± 23%) were the most abundant particles found in the surface water samples. In sediment samples (n = 11), MPs varied from 85 to 2494 pp/0.1 m2. Sediment samples showed fragments of 70 ± 19%, fibers 28 ± 18% in mean. The range of MP values from WWTP effluents (n = 24) was 81 to 1556 pp/m3, and fibers (65 ± 28%) were the most abundant MP particles. Several synthetic polymers (polypropylene, polyethylene, polyethylene-propylene, polyvinyl chloride, cellophane), and natural fibers (cotton and wood) were identified. The surface currents and the parameters that modulate them, are the main factors that dominate the distribution of MPs in surface waters. While in the sediments the parameters such as bathymetry and grain size distribution have more influence on their distribution in the marine environment, where the effluent waters from WWTPs only contributes MPs to the TSB.


Acid-sensing ion channels are tuned to follow high-frequency stimuli.
Acid-sensing ion channels (ASICs) act as neurotransmitter receptors by responding to synaptic cleft acidification. We investigated how ASIC1a homomers and ASIC1a/2a heteromers respond to brief stimuli, jumping from pH 8.0 to 5.0, approximating the time course of neurotransmitter in the cleft. We find that ASICs deactivate surprisingly fast in response to such brief stimuli from pH 8.0 to 5.0, whereas they desensitize comparatively slowly to prolonged activation. The combination of unusually fast deactivation with slow desensitzation enables recombinant ASIC1a homomers and ASIC1a/2a heteromers, as well as native ASICs of sensory neurons, to follow trains of such brief pH 8.0 to 5.0 stimuli at high frequencies. This capacity for high-frequency signalling persists under a physiological pH of 7.4 with ASIC1a/2a heteromers, suggesting that they may sustain postsynaptic responses when other receptors desensitize. The neurotransmitter-gated ion channels that underlie rapid synaptic transmission are often subjected to bursts of very brief neurotransmitter release at high frequencies. When challenged with such short duration high-frequency stimuli, neurotransmitter-gated ion channels generally exhibit the common response of desensitization. Recently, acid-sensing ion channels (ASICs) were shown to act as neurotransmitter-gated ion channels because postsynaptic ASICs can be activated by the transient acidification of the synaptic cleft accompanying neurotransmission. In the present study, we examined the responses of recombinant ASIC1a homomers, ASIC1a/2a heteromers and native ASICs from sensory neurons to 1 ms acidification stimuli, switching from pH 8.0 to 5.0, as either single pulses or trains of pulses at physiologically relevant frequencies. We found that ASIC deactivation is extremely fast and, in contrast to most other neurotransmitter-gated ion channels, ASICs show no desensitization during high-frequency stimulus trains under these conditions. We also found that accelerating ASIC desensitization by anion substitution can induce depression during high-frequency trains. When using a baseline physiological pH of 7.4, the ASIC1a responses were too small to reliably measure, presumably as a result of steady-state desensitization. However, ASIC1a/2 heteromers gave robust responses when using a baseline pH of 7.4 and were also able to sustain these responses during high-frequency stimulus trains. In conclusion, we report that the slow desensitization and fast deactivation of ASIC1a/2a heteromers enables them to sustain postsynaptic responses to bursts at high frequencies at a physiological pH that may desensitize other receptors.


Is it Worth to Evaluate the Fetal Heart With Color Doppler Scan at 11 to 13+6 Weeks?
This study was conducted to try to achieve the success rate to detect fetal cardiac malformations and/or tricuspid regurgitation with color Doppler during first trimester ultrasound scan within a short period (less than 3 minutes) in a general low-risk population. For this purpose, we started a prospective study, evaluating 240 consecutive single pregnancies, by a single examiner, during the first trimester ultrasound scan (crown to rump length between 45 and 84 mm) using a Voluson E8 system (GE Healthcare, Zipf, Austria) with a 2- to 8-MHz RAB 4-8-D transabdominal probe. Pulsed-wave and color Doppler flow mapping was used to assess the blood flow through the tricuspid valve. In addition, color Doppler was used to evaluate the 4-chamber view, the great vessels ("V sign"), and the right subclavian artery. Blood flow in the tricuspid valve could be examined in 206 cases (85.8%). Of these, tricuspid regurgitation was detected in 17 cases (7.1%) with both pulsed-wave and color Doppler. The 4-chamber view, the V sign, and the right subclavian artery could be evaluated in 188 cases (78.3%). One case of aberrant right subclavian artery and 2 suspicious of cardiac malformations were detected. In our opinion, using color Doppler during first trimester ultrasound scan, even for a short period (<3 minutes), probably adds important information about the fetal heart.


The effects of a national, voluntary agreement for a more inclusive working life on work participation following long-term sickness absence: a Norwegian cohort study.
This study aimed to estimate the average individual effect of the company-level Norwegian Agreement on a More Inclusive Working Life (IA Agreement) on individuals' (i) sustained return to work after a sickness absence (SA) episode, and (ii) recurrent SA. Using register data, 79 253 men and 94 914 women born in Norway 1967-1976 were followed for one year between 2005 and 2010 after returning to work from an SA episode (>16 days). Weighted Cox proportional hazard models analysed time to first exit from work by companies' IA status (IA/non-IA). Weighted cumulative incidence differences between IA and non-IA groups with 95% bootstrapped confidence intervals (CI) were calculated for the competing events of full SA, graded (<100%) SA, unemployment/economic inactivity, education, disability pension, and death/emigration. Stabilised inverse probability of treatment weights balanced IA/non-IA groups according to nine covariates. Analyses were stratified by gender, and separately for two initial SA diagnoses (musculoskeletal and psychological). Both men [adjusted hazard ratio (HR) 0.96, 95% CI 0.93-0.99] and women (adjusted HR 0.97, 95% CI 0.94-0.99) in IA companies were less likely to exit work in the year following SA. Similar findings were seen among individuals with musculoskeletal diagnoses and women with psychological diagnoses. Men with psychological diagnoses were more likely to exit work. Recurrent full and graded SA were more likely, and unemployment/economic inactivity less likely, in IA companies. However, the estimated effects were small and the CI often included the null. Individuals working in IA companies were more likely to remain in work. This was mainly due to reduced unemployment/economic inactivity, suggesting the IA Agreement may have influenced work participation through other means than reduced SA.


An innovative immunosensor for detection of tumor suppressor protein p53 in unprocessed human plasma and cancer cell lysates.
An innovative mediator-free electrochemical immunosensor for quantitation of p53 tumor suppressor protein based on signal amplification strategy was fabricated. In this work, biotin conjugated p53-antibody (anti-p53) was immobilized onto a green and biocompatible nanocomposite containing poly l-cysteine (P-Cys) as conductive matrix and 3D gold nanoparticles (GNPs) as signal amplification element. Therefore, a novel nanocomposite film based on P-Cys and GNPs was exploited to develop a highly sensitive immunosensor for detection of p53 protein. Importantly, GNPs prepared by sonoelectrodeposition method which lead to compact morphology. Fully electrochemical methodology was used to prepare a new transducer on a gold surface which provided a high surface area to immobilize a high amount of the anti-p53. The surface morphology of electrode was characterized by high-resolution field emission scanning electron microscope (FE-SEM) and energy dispersive spectroscopy (EDX). The immunosensor was employed for the detection of p53 in physiological pH using square wav voltammetry and differential pulse voltammetry (DPVs) techniques. Under optimized condition the calibration curve for p53 concentration by SWV and DPV was linear in 0.0369-50pM and 0.018-2.5pM with lower limit of quantification of 48fM and 18fM, respectively. The method was successfully applied assay of the p53 in unprocessed human plasma samples. Also, the method was applied to the assay of p53 in human plasma sample and normal and malignant cell line lysates such as (L929 normal cell Line from mouse C3H (L929), colon cancer cell-HCT, prostate cancer cell line PC-3, and human breast adenocarcinoma cell line-MCF7).


The chicken B-cell receptor complex and its role in avian B-cell development.
The bursa of Fabricius is critical to normal B-lymphocyte development in birds. During embryonic life, B-cell precursors migrate to the bursal rudiment and those which have undergone productive V(D)J recombination colonize lymphoid follicles and undergo immunoglobulin V gene diversification by gene conversion. The chicken surface IgM complex appears structurally and functionally equivalent to its mammalian counterpart, with homologs to CD79a and CD79b. Expression of a truncated Igmu chain is sufficient to drive the early stages of B-cell development in the embryo bursa. Bursal cells expressing the truncated mu receptor complex proliferate in bursal follicles, and those which contain V gene rearrangements undergo V gene diversification by gene conversion. The bursa is a gut-associated organ and antigen is focused to bursal lymphoid follicles after hatch. While expression of the truncated mu chain is sufficient to support B-cell development in the embryo, B cells expressing this receptor are rapidly eliminated after hatch. We suggest the possibility that B-cell development in the bursa after hatch is driven by encounter with antigen leading to redistribution of B cells within the lymphoid follicle, B-cell proliferation and V gene repertoire development by gene conversion.


From hypoxia and hypoxia-inducible factors (HIF) to oxidative stress: A new understanding of the toxic mechanism of mycotoxins.
This October, the Nobel Prize in Physiology or Medicine 2019 was jointly awarded to William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza for their discoveries of "how cells sense and adapt to oxygen availability." Importantly, the protein named hypoxia-inducible factors (HIF) were revealed in the molecular machinery that how cells regulate the activity of genes in response to hypoxia. Hypoxia has a close relationship with oxidative stress and its related diseases including cancer. Actually, accumulating evidence and recent advances show that mycotoxins, including ochratoxin A, trichothecene mycotoxins T-2 toxin, deoxynivalenol, and diacetoxyscirpenol have the potential of triggering hypoxia in cells. Moreover, HIF-1α activation is involved in the mycotoxin-induced oxidative stress response. As is known, oxidative stress is considered to be a common mechanism of various toxicities of mycotoxins; however, an in-depth molecular mechanism, especially the molecular target in this context is not fully understood. Therefore, in this work, we have discussed the underlying mechanism(s) of hypoxia and HIF-1α in the mycotoxin-induced oxidative stress effect. We believe that the explanation of hypoxia and HIF-1α would open up new avenues for early diagnosis and treatment of mycotoxicosis. More importantly, under these circumstances, we compile a special issue, "Mycotoxins in Food: New Determination Methods, Toxic Mechanisms, and Control Strategies" for Food and Chemical Toxicology. Researchers are encouraged to submit their newest research articles and excellent work within this topic for the readers of Food and Chemical Toxicology.


[Preventional and therapeutic effects of aldose reductase inhibitor FR74366 on rat galactose cataract].
Preventional and reversal effects of a new aldose reductase inhibitor FR74366 on the rat galactose cataract were examined biochemically and light microscopically. A high concentration (0.075%) FR74366 showed sufficient effects both to prevent and reverse cataract, but low concentrations (0.025%) FR74366 was not effective as 0.075% FR74366. These results indicate that FR74366 can be useful drug for cataract.


[Treatment of humeral shaft nonunion with interlocking nail and percutaneous injection of bone marrow].
To investigate the effect of treatment of humeral shaft nonunion with interlocking nail and percutaneous injection of bone marrow after operation. Twenty-five adult patients with humeral shaft nonunion, initially treated with plates, intramedullary nails, or external fixators changed to use RussellTaylor reamed antegrade intramedullary nails with autologous bone grafting and percutaneously bone marrow injection into the fracture sites ten days after the operation to promote union. All patients achieved a solid union with good function. The union period was a median of 4.5 months. We believe that the procedure may provide firm internal fixation and improve activity of osteoblasts in fracture sites for accelerating fracture healing.


Chikungunya virus with E1-A226V mutation causing two outbreaks in 2010, Guangdong, China.
CHIKV is a mosquito-borne emerging pathogen that has a major health impact in humans in tropical zones around the globe. A new variant of the virus, E1-A226V caused a large outbreak in the Indian Ocean islands and India from 2004-2007. CHIKV outbreak was initially reported in Dongguan region of Guangdong in 2010 in China, another smaller CHIKV outbreak was found in Yangjiang region of Guangdong two weeks later. The viral agent causing the two outbreaks was inferred to be the new E1-A226V variant and Yangjiang CHIKV might be introduced from Dongguan. To confirm the hypothesis and determine the origin of CHIKV causing the outbreaks, we described Yangjiang outbreak in this study, and the molecular characterization of CHIKV from Yangjiang and Dongguang outbreaks were analyzed. 27 clinical cases of CHIK fever were reported in outbreak in Yangjiang region. Sera sample from 12 clinical cases were collected from the outbreak, and nucleic acid and antibody tests for CHIKV were performed using Real-time RT-PCR and indirect immunofluorescence. Positive samples of Real-time RT-PCR were subjected to viral isolation. The results showed 3/12 samples positive for Real-time RT-PCR. 7/12 and 4/12 samples were positive for IgM and IgG against CHIKV respectively, two virus strains were isolated. Four viral genomes from Dongguan and Yangjiang were sequenced, characterized and phylogeneticly analyzed. Phylogenetic analysis revealed that the four seqeunced viruses had the closest relationship (99.4~99.6% identify) with the Singapore 2008 isolate belonging to the Indian ocean clade. A common mutation at the site of the E1-A226V was observed among four viruses. Four and three aa substitutions were detected in the CHIKV sequence from the Dongguan and Yangjiang outbreak strains respectively. CHIKV with an E1-A226V mutation that originated from Southeast Asia isolates caused two outbreaks in China in 2010, and originated from two different infectious sources.


Anthocyanin accumulation enhanced in Lc-transgenic cotton under light and increased resistance to bollworm.
Breeding of naturally colored cotton fiber has been hampered by the limited germplasm, an alternative way is to use transgenic approach to create more germplasm for breeding. Here, we report our effort to engineer anthocyanin production in cotton. The maize Lc gene, under the control of the constitutive 35S promoter, was introduced into cotton through genetic transformation. Our data showed that the expression of the Lc gene alone is sufficient to trigger the accumulation of anthocyanin in a variety of cell types including fiber cells in cotton. However, the accumulation of colored anthocyanin in cotton fibers requires the participation of light signaling. These data indicate that it is feasible to engineer colored fibers through transgenic approach in cotton. Furthermore, we showed that the Lc-transgenic cotton plants are resistant to cotton bollworm. These transgenic plants are, therefore, potentially useful for cotton breeding against cotton bollworm.


Caucasian emmetropic aged subjects have reduced corneal thickness values: emmetropia, CCT and age.
We aimed to analyze the possible changes in corneal thickness values according to age in emmetropic subjects. The central corneal thickness values of 100 emmetropic subjects (n = 100) were analyzed with the DGH 2000 AP ultrasonic pachymeter (DGH Technology, Inc., San Diego, CA, USA) by one experienced physician. The mean age of the subjects was 40.6 +/- 12.1 years old (range, 21-64). Analysis of the central corneal thickness (CCT) values by age subgroups indicated that subjects aged between 20 and 30 years had the higher CCT values. Differences in CCT values between the age groups were significant (p < 0.001; 1-way ANOVA test). A significant correlation between CCT values and age was found (r = -0.974; p < 0.001). In sum, it seems that there is a decrease in CCT values with age in emmetropic subjects.


TBBPA stimulated cell migration of endometrial cancer via the contribution of NOX-generated ROS in lieu of energy metabolism.
Due to the extensive applications and deleterious effects of Tetrabromobisphenol A (TBBPA), the health risk and possible mechanisms have been a topic of concern. However, the knowledge on carcinogenic risk of TBBPA and corresponding mechanisms remains scarce. In this study, endometrial cancer cells were exposed to low doses of TBBPA and its main derivatives including TBBPA bis (2,3-dibromopropyl ether) (TBBPA-BDBPE) and TBBPA bis (2-hydroxyethyl ether) (TBBPA-BHEE). The data from wound healing and transwell assays demonstrated that TBBPA treatment exhibited the strongest enhanced effect on cell migration among other tested treatments. Of note, the process of invasion rather than epithelial-mesenchymal transition (EMT) was accompanied by the occurrence of migration elevated by TBBPA. Furthermore, the levels of several metabolite indicators were measured to assess the underlying mechanisms involved in TBBPA-induced cell migration. The findings suggested that NADPH oxidase (NOX)-driven ROS instead of energy metabolism was sensitive to TBBPA stimulation. In addition, molecular docking supported a link between TBBPA ligand and NOX receptor. Accordingly, this study has provided new insights for TBBPA-induced carcinogenic effects and may arise peoples' vigilance to environmental pollution of brominated flame retardant.


Protonophoric and Photodynamic Effects of Fluorescein Decyl(triphenyl)phosphonium Ester on the Electrical Activity of Pond Snail Neurons.
Uncouplers of oxidative phosphorylation in mitochondria, which have been essential in elucidating the basic principles of cell bioenergetics, have recently attracted a considerable interest as compounds with therapeutic, e.g., neuroprotective, properties. Here, we report the effect of mitofluorescein (mitoFluo), a new protonophoric uncoupler representing a conjugate of fluorescein with decyl(triphenyl)phosphonium, on the electrical activity of neurons from Lymnaea stagnalis. Incubation with mitoFluo in the dark led to a decrease in the absolute value of the resting membrane potential of the neurons and alterations in their spike activity, such as spike broadening, spike amplitude reduction, and increase in the spike frequency. Prolonged incubation at high (tens micromoles) mitoFluo concentrations resulted in complete suppression of neuronal electrical activity. The effect of mitoFluo on the neurons was qualitatively similar to that of the classical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) but manifested itself after much longer incubation and at higher concentrations. The distinctive feature of mitoFluo is its light-induced effect on the electrical activity of neurons. Changes in the parameters of the neuronal activity upon illumination in the presence of mitoFluo were similar to the light-induced effects of the well-known photosensitizer Rose Bengal, although less pronounced. It was suggested that the effects of mitoFluo on the electrical activity of neurons, both as a mitochondrial uncoupler and a photosensitizer, are mediated by the changes in the cytoplasmic calcium concentration.


Late coronary stent thrombosis: early vs. late stent thrombosis in the stent era.
The incidence of coronary stent thrombosis is < 1%-2% in recent studies, with the highest-risk period considered to be the first 30 days following stent implantation. Recently, stent thrombosis after 30 days has been reported in patients undergoing brachytherapy with stenting. We reviewed the incidence of stent thrombosis causing myocardial infarction in nonbrachytherapy patients at our institution between 1 January 1996 and 30 November 1999. A case control methodology was employed with a 1:3 ratio of stent thrombosis to control patients. Of 1,191 patients undergoing coronary stenting, acute (< 24 hr) plus subacute (1-30 days) stent thrombosis occurred in 0.92% (11 of 1,191 patients). A further 0.76% (9 of 1,191 patients) developed late stent thrombosis after 30 days. There were no clinical or angiographic features at the time of the initial procedure that were associated with stent thrombosis as an entire group compared with control group, but early (acute and subacute) stent thrombosis patients had a smaller final stent minimal lumen diameter and longer stent length compared with patients who had late stent thrombosis or controls. Late stent thrombosis occurs in nonbrachytherapy patients and is almost as frequent as early stent thrombosis. Further studies are required to determine whether longer-term poststent pharmacological treatment may decrease or prevent this complication.


Acetabular development after reduction in congenital dislocation of the hip.
A study of acetabular development in 148 patients with 185 congenitally dislocated hips treated by closed reduction from 1940 to 1968 showed that eight years after reduction the acetabular index was normal (less than 20 degrees) in 49.2 per cent, satisfactory (from 20 to 24 degrees) in 34 per cent, and poor (more than 24 degrees) in 16.7 per cent. Early treatment led to the best acetabular development. Significant and continuing improvement of the acetabular index was observed between two and eight years after reduction when the femoral head remained concentrically reduced. Failure to maintain proper reduction and necrosis of the femoral head led to poor results.


Effects of cytochalasin H on the embryonic endodermal cells of Microhyla ornata.
Cytochalasin H (CH) like CB causes disaggregation of embryonic endodermal cells and reduces their adhesivity to the glass surface. These cells reaggregate on removal of the drug from the medium. Reversibility depends on the duration of drug treatment. The mechanism of drug action is explained.


The transmembrane semaphorin Sema6A controls cerebellar granule cell migration.
The transmembrane semaphorin protein Sema6A is broadly expressed in the developing nervous system. Sema6A repels several classes of developing axons in vitro and contributes to thalamocortical axon guidance in vivo. Here we show that during cerebellum development, Sema6A is selectively expressed by postmitotic granule cells during their tangential migration in the deep external granule cell layer, but not during their radial migration. In Sema6A-deficient mice, many granule cells remain ectopic in the molecular layer where they differentiate and are contacted by mossy fibers. The analysis of ectopic granule cell morphology in Sema6a-/- mice, and of granule cell migration and neurite outgrowth in cerebellar explants, suggests that Sema6A controls the initiation of granule cell radial migration, probably through a modulation of nuclear and/or soma translocation. Finally, the analysis of mouse chimeras suggests that this function of Sema6A is primarily non-cell-autonomous.


Anti-inflammatory effect of atorvastatin (80 mg) in unstable angina pectoris and non-Q-wave acute myocardial infarction.
In this randomized trial, C-reactive protein increased during the first 5 days of an acute coronary syndrome in patients treated with placebo, but this phenomenon was not observed in those randomized to atorvastatin 80 mg/day. This suggests that short-term statin therapy inhibits inflammation in patients with non-ST-elevation acute coronary syndromes.


Thoracoscopy-thoracotomy approach for an aortoesophageal fistula: a case report.
An aortoesophageal fistula is often fatal, and standard radical surgery is highly invasive because both bilateral thoracotomy and laparotomy are required. We successfully incorporated thoracoscopic esophagectomy into this procedure for a 43-year-old man with an aortoesophageal fistula. After detaching the esophagus from the adjacent tissue, and leaving just the fistula in the right thoracoscopic procedure, we performed an open aortic graft replacement. Subsequently, we created an omental pedicle graft and wrapped it over the graft. Through this thoracoscopy-thoracostomy approach, minimal destruction of the right thoracic wall was achieved and the successful dissection of the diseased esophagus could be carried out while reducing the amount of bleeding during anticoagulation for cardiopulmonary bypass, and the field of view for the aortic replacement was not disturbed during left thoracotomy. Four months later, we reconstructed the esophagus by a pedunculated small intestinal graft through the ante-thoracic route. A thoracoscopy-thoracotomy approach is therefore considered to be effective and useful for treating a patient with an aortoesophageal fistula.


Historical and Contemporary Patterns of Mercury in a Hydroelectric Reservoir and Downstream Fishery: Concentration Decline in Water and Fishes.
Mercury (Hg) contamination can pose risks to human and animal health as well as commercial fisheries. Reservoir construction in riverine systems produces flooded conditions amenable to Hg(II)-methylating bacteria, which can transform this relatively benign environmental contaminant into the bioaccumulative, environmentally relevant, and neurotoxic methyl-Hg (MeHg). Hg concentrations ([Hg]) in fishes from reservoirs can take decades to decrease to pre-dam levels, but less is known about Hg exported downstream and its dynamics within downstream fish populations. We examined and compared the multidecadal rates of biotic [Hg] decrease and contemporary factors affecting [Hg] in fish collected from a hydroelectric reservoir (Tobin Lake) and a related downstream fishery (Cumberland Lake) along the Saskatchewan River, Canada. Rates of [Hg] decrease were considered in four species-northern pike (Esox lucius), sauger (Sander canadensis), goldeye (Hiodon alosoides), and walleye (S. vitreus)-all of which showed a significant decrease over time (p < 0.001) and are now lower than Health Canada consumption guidelines (0.5 μg/g). Rates of decrease ranged from 0.5 to 3.9 %/year and were similar between sites in the cases of northern pike and sauger. Contemporary factors affecting [Hg] in walleye collected downstream include fish length (p < 0.001), fish age (p < 0.001), and trophic magnification through the food web (p < 0.001), and relationships between [Hg] and trophic level in predatory and prey fish are now similar to those found in non-Hg-inundated systems at a similar latitude. Together, these results suggest connected contamination between the two sites and delineate the timeline during which [Hg] in a variety of fish species decreased to nontoxic levels in both locations.


Evidence for a preferential targeting of 3'-UTRs by cis-encoded natural antisense transcripts.
Although both the 5'- and 3'-untranslated regions (5'- and 3'-UTRs) of eukaryotic mRNAs may play a crucial role in posttranscriptional gene regulation, we observe that cis-encoded natural antisense RNAs have a striking preferential complementarity to the 3'-UTRs of their target genes in mammalian (human and mouse) genomes. A null neutral model, evoking differences in the rate of 3'-UTR and 5'-UTR extension, could potentially explain high rates of 3'-to-3' overlap compared with 5'-to-5' overlap. However, employing a simulation model we show that this null model probably cannot explain the finding that 3'-to-3' overlapping pairs have a much higher probability (>5 times) of conservation in both mouse and human genomes with the same overlapping pattern than do 5'-to-5' overlaps. Furthermore, it certainly cannot explain the finding that overlapping pairs seen in both genomes have a significantly higher probability of having co-expression and inverse expression (i.e. characteristic of sense-antisense regulation) than do overlapping pairs seen in only one of the two species. We infer that the function of many 3'-to-3' overlaps is indeed antisense regulation. These findings underscore the preference for, and conservation of, 3'-UTR-targeted antisense regulation, and the importance of 3'-UTRs in gene regulation.


A close consideration of effect sizes reviewed by Jussim (2012).
This commentary on Jussim (2012) makes two points: (1) Effect sizes often reflect artifacts of experimental design rather than real-world relevance, and (2) any argument dependent on effect sizes must correct for attenuation due to instrument reliabilities. A formula for making this correction is presented, and its ramifications on the debate over accuracy in person perception are discussed.


Deficiency in plasma membrane calcium ATPase isoform 2 increases susceptibility to noise-induced hearing loss in mice.
Susceptibility to noise-induced hearing loss (NIHL) is poorly understood at the genetic level. Mice homozygous for a null mutation in the plasma membrane Ca2+-ATPase isoform 2 (PMCA2) gene are deaf (Kozel et al., 1998). PMCA2 is expressed on outer hair cell stereocilia (Furuta et al., 1998). Fridberger et al. (1998) observed that the outer hair cell cytoplasmic Ca2+ concentration rises following acoustic overstimulation. We hypothesized that Pmca2+/- mice may be more susceptible to NIHL. Since the auditory brainstem response (ABR) thresholds of Pmca2+/- mice vary with the presence of a modifier locus (Noben-Trauth et al., 1997), Pmca2+/- mice were outcrossed to normal hearing CAST/Ei mice. The pre-exposure ABR thresholds of the resulting Pmca2+/+ and Pmca2+/- siblings were indistinguishable. Groups of these mice were exposed to varying intensities of broadband noise, and ABR threshold shifts were calculated. Fifteen days following an 8 h, 113 dB noise exposure, the Pmca2+/- mice displayed significant (P < or = 0.0007) permanent threshold shifts at 16 and 32 kHz that were 15 or 25 dB greater than those observed in Pmca2+/+ littermates. Pmca2 may be the first gene with a known mutated protein product that confers increased susceptibility to NIHL.


One piece of the puzzle: Modeling vector presence and environment reveals seasonality, distribution, and prevalence of sandflies and Leishmania in an expansion area.
The recent geographic spread of Leishmania infantum along the borders of Argentina, Brazil and Paraguay has been highlighted. In our previous study, Lutzomyia longipalpis was found in 55 of 123 patches surveyed, and in some patches, sandflies were found at higher densities, forming hotspots. Based on the One Health approach, we investigated the seasonality of the vector, the presence of parasite DNA, and the environmental factors that contribute to vector and parasite dispersal in these previously described hotspots in Foz do Iguaçu, Brazil. Entomological surveys were conducted monthly for one year. Fourteen hotspots peridomicile and six intradomicile were sampled. PCR was used to assess the prevalence of Leishmania DNA in sandflies. Zero-inflated negative binomial regression was used to determine the association of micro- and mesoscale environmental variables with the occurrence and abundance of the three most abundant sandfly species sampled. A total of 3543 species were captured, with Lutzomyia longipalpis being the predominant species (71.78%) of the 13 species found. Evandromyia edwardsi, Expapillata firmatoi, Micropygomyia ferreirana and Pintomyia christenseni were reported for the first time in the region. NDVI, distance to water, precipitation, west-to-east wind, wind speed, maximum and minimum relative humidity, and sex were significant variables associated with vector presence/abundance in the environment. Vector presence/abundance in the peridomicile was associated with precipitation, altitude, maximum temperature, minimum and maximum relative humidity, west-to-east wind, wind speed, and sex. Leishmania DNA was detected in an average of 21% of Lu. longipalpis throughout the year. Vector abundance is concentrated in urban and peri-urban areas, with some specimens present in different parts of the city and some sites with high vector abundance. This distribution suggests that the risk of actual contact between humans and parasite vectors in urban areas during the epidemic period is associated with patches of peri-urban vegetation and then extends into urban areas.


Assembly of gold nanoparticles on functionalized Si(100) surfaces through pseudorotaxane formation.
The assembly of gold nanoparticles (AuNPs) on a hydrogenated Si(100) surface, mediated by a series of hierarchical and reversible complexation processes, is reported. The proposed multi-step sequence involves a redox-active ditopic guest and suitable calix[n]arene-based hosts, used as functional organic monolayers of the two inorganic components. Surface reactions and controlled release of AuNPs have been monitored by application of XPS, atomic force microscopy (AFM), field-emission scanning electron microscopy (FESEM) and electrochemistry.


Coronary fistula to the right atrium: a challenge for the interventional cardiologist.
Congenital coronary fistulas are rare conditions, frequently diagnosed as an incidental finding when a patient is referred for cardiac surgery for another reason. Treatment can be conservative, surgical or more recently through transcatheter closure, depending on local experience and the morphology of the fistula. The authors present the case of a pediatric patient with a large coronary artery fistula from the aorta to the right atrium. Transcatheter closure with a 16 mm Amplatzer(®) vascular plug II and a 6 mm Amplatzer(®) duct occluder was performed, with complete occlusion.


The association between leftover food consumption and depression among older adults: Findings from a cross-sectional study.
Leftover food consumption is very prevalent among the Chinese older adults, however, the potential effects of leftover eating consumption on depression have not yet been investigated. The study aims to determine the association between leftover consumption on depression among older adults. Data of leftover consumption frequency was collected in a cross-sectional study with a provincial representative sample of 5992 older adults (aged 60 or older) in 2019. Depression symptoms were assessed by the 9-item screener Patient Health Questionnaire (PHQ-9). Multiple logistic regression models were applied to analyze the association of the frequency of leftover eating consumption and the presence and the severity of depression. After controlling for all the covariates, the participants who consume leftover food everyday had higher risk of having depression symptom comparing to those who had the lowest frequency of leftover eating (OR: 1.675, 95% CI: 1.435-1.956, p < 0.001). The participants who consume leftover food every day was also associated with more severe depression symptoms (OR: 1.621, 95% CI: 1.397-1.881, p < 0.001), when comparing to the reference group. The associations seemed stronger in men than women. The causal relationship between leftover consumption behavior and depression could not be determined due to the cross-sectional design. Moreover, the variety or handling method of the leftover food was not specified. Leftovers eating frequency was associated with the presence and severity of depression symptoms among older adults.


Lineage plasticity and cell biology of fibrocartilage and hyaline cartilage: its significance in cartilage repair and replacement.
Cartilage repair is a major goal of modern tissue engineering. To produce novel engineered implants requires a knowledge of the basic biology of the tissues that are to be replaced or reproduced. Hyaline articular cartilage and meniscal fibrocartilage are two tissues that have excited attention because of the frequency with which they are damaged. A basic strategy is to re-engineer these tissues ex vivo by stimulating stem cells to differentiate into the cells of the mature tissue capable of producing an intact functional matrix. In this brief review, the sources of cells for tissue engineering cartilage and the culture conditions that have promoted differentiation are discussed within the context of natural cartilage repair. In particular, the role of cell density, cytokines, load, matrices and oxygen tension are discussed.


Investigation of coumarin functionality on the formation of polymeric nanoparticles.
The effect of coumarin molecules on the formation of polymeric nanoparticles is examined using a model polymer, poly(methyl methacrylate) (PMMA), functionalized with varying amounts of coumarin pendant groups (PCM). PCM nanoparticles are prepared in a continuous manner by Flash NanoPrecipitation (FNP). PCM forms spherical nanoparticles in water, while the PMMA without coumarin functionality fails to form nanoparticles. As the amount of coumarin functionality increases, the nanoparticle size and size polydispersity are decreased and the nanoparticle stability in water is enhanced. In particular, well-isolated spherical nanoparticles are generated from PCM with 20 mol% coumarin side chain functionality. These results can be explained by an observed increase in the negative surface charge with increasing coumarin content in the polymer.


Hemoglobin Pasadena: identification of the gene mutant by DNA analysis using synthetic DNA probes.
Hemoglobin Pasadena [beta 75(E19)Leu----Arg] was found in a boy who had an acute episode of anemia and rapid splenic enlargement. His father was the only other member of a large family with this hemoglobinopathy. We have used gene mapping techniques for direct identification of the beta-globin gene mutation. To correlate the DNA findings with the structural identification of this variant, we have also performed globin chain separation and analysis of the tryptic peptides using high performance liquid chromatography and secondary ion mass spectral analysis.


Pediatric SubQ-ICD implantation, a single center review of the inter-muscular technique.
Pediatric patients with cardiomyopathies are at risk for sudden death and may need implantable cardioverter defibrillators (ICD's), but given their small size and duration of use, children are at increased risk for complications associated with ICD use. The subcutaneous ICD presents a favorable option for children without pacing indications. Unfortunately, initial pediatric studies have demonstrated a high complication rate, likely due to the 3-incision technique employed. Patients with ICD but no pacing indication were retrospectively reviewed after implantation of subcutaneous ICD via the two-incision technique. In half of the patients, 10-J impedance test was also performed to compare with impedance obtained after defibrillation threshold testing with 65-J. Twelve patients were included. The median age was 14 years (range 10-16 years) with eight males included (72.7%). The median weight was 55 kg (range 29 kg-75.1 kg). Follow-up had a median of 11.5 months (range 2-27 months). The median body mass index was 18.4 kg/m squared (range 15.5-27.9 kg/m squared). One patient suffered a minor complication after tearing off the incisional adhesive strips early and required a non-invasive repair in clinic. Shock impedance had a median of 55 J (range 48-68 J). There was one appropriate shock/charge and no inappropriate shocks during follow-up. The two-incision, intermuscular technique appears to have a lower acute complication rate than prior reports, in our cohort of 12 pediatric patients.


Biological evaluation of N-octyl-O-sulfate chitosan as a new nano-carrier of intravenous drugs.
An amphiphilic chitosan derivate, N-octyl-O-sulfate chitosan (NOSC) was prepared by octylation of amino group at C-2 position and sulfonylation at C-6 position. Micelle formed by NOSC has great capability in solubilization of water-insoluble drug paclitaxel. Enormous attention was attracted by the potential application of NOSC as a new drug delivery system. Tritium labeled NOSC ((3)H NOSC) was injected by tail vein at dose of 13.44 mg/kg in mice; kidney retained the maximum amount of NOSC all the time even after 24h following the injection. Pharmacokinetic parameters (the area under the plasma concentration-time curve, maximum plasma concentration, apparent plasma half-life of distribution phase and elimination phase, mean residence time, apparent volume of distribution, total body clearance) were obtained by fluorometric method in rats. The results showed a linear pharmacokinetics proceeding of FITC-NOSC in vivo. 75.4+/-11.6% (3)H NOSC of dose was excreted in urine over a 7-day period, urinary excretion was the predominant way of excretion of NOSC compared with bilary or fecal pathway. A series of safety studies consisted of acute toxicity study, intravenous stimulation study, injection anaphylaxis study, hemolysis study and cell viability assay were performed to warrant the biocompatibility of the NOSC as intravenous materials. The LD(50) value of NOSC administrated by i.v. and i.p. were calculated as 102.59 and 130.53 mg/kg, respectively. No intravenous stimulation, injection anaphylaxis, hemolysis and cytotoxicity were observed in the safety studies. The tissue distribution, pharmacokinetics, excretion and safety study were persuasive for the potential application of NOSC as a new drug carrier.


Effects of progressive muscle relaxation on cerebral activity: An fMRI investigation.
Progressive muscle relaxation (PMR) is one of the self-management relaxation techniques that can be used in the general population and patients with specific issues. However, no study to date has revealed the brain activity associated with PMR. Therefore, we assessed the changes in brain activity induced by PMR using functional magnetic resonance imaging (fMRI). We conducted an intervention study with PMR and control sessions. The subjects were twelve healthy adult men who had no prior experience of PMR. Subjects performed a control session in which muscles were repeatedly simply tensed and relaxed. Subsequently, a PMR session took place, during which muscle tension was reduced through a systematic procedure of tensing and relaxing of muscle groups combined with structured breathing. We identified and visualised brain activity based on individual and group-level analysis of fMRI data. Eleven subjects' data were analysed. In the control session, brain activity broadly changed, while the change was limited to specific parts of the cerebral cortex and limbic system in the PMR session. PMR gradually decreased activity in the superior frontal gyrus (SFG), inferior frontal gyrus (IFG), and posterior cingulate cortex (PCC). In a region of interest (ROI) analysis, interactions between sessions were observed in the putamen, anterior cingulate cortex (ACC), postcentral gyrus (PCG), and insula. That PMR led to few areas showing changed activity suggests that the technique may suppress brain activity. Even novices may be able to induce such a focused mental state.


Preparation of tuna skin collagen-chitosan composite film improved by sweep frequency pulsed ultrasound technology.
To produce a natural food packaging film from tuna skin collagen (TSC) and chitosan (CTS) and improve its mechanical and physicochemical properties, the sweep frequency pulsed ultrasound (SFPU) was introduced as a new technology and compared with the conventional method. The optimum preparation conditions of the SFPU-TSC-CTS film were sweep frequency of 28 ± 0.5 kHz, power density of 100 W/L, sweep frequency cycle of 100 ms, pulse duty ratio of 77%, and ultrasonic time of 10 min. Significant increases in the tensile strength (27.14%) and elongation at break (16.54%) and a significant decrease in the water vapor permeability (12.15%) were observed by sonication. Thus, a moderate SFPU treatment can significantly improve the moisture resistance and mechanical properties of the film. These enhancements were achieved by a more ordered and compact structure, a good crystallinity and a higher thermostability of SFPU-TSC-CTS film, which were verified by the Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermal stability indexes. Moreover, SFPU-TSC-CTS film also presented good antioxidant and antibacterial activities. Therefore, SFPU was an effective auxiliary technology for improving the quality of food packaging film and can be deeply explored.


Viability and morphology of aortic and pulmonary homografts. A comparative study.
In view of possible clinical use of the pulmonary homograft for right ventricular outflow tract reconstruction a comparative study with the aortic counterpart was performed. Samples of aortic and pulmonary walls from 10 cadaveric hearts were assessed for viability and morphologic characteristics before and after storage in nutrient-antibiotic solution. The viability, as evaluated by an autoradiographic technique, was similar in both aortic and pulmonary specimens at the time of dissection, after 2 weeks, and after 4 weeks of storage. The histologic examination showed no changes in the structure of the media in all samples up to 4 weeks of storage. The total calcium content per gram of tissue in the pulmonary media was on an average less than half of that in the aortic counterpart. We conclude that the pulmonary homograft is preserved the same as the aortic homograft and, accordingly, it becomes available for clinical application. Moreover, a lesser content of elastic tissue and a lower amount of total calcium may, in all likelihood, make the pulmonary wall less prone to calcification.


Is there an optimal methodology for the microbiological analysis of effluent in CAPD peritonitis?
The definition of CAPD peritonitis and reasons for negative effluent cultures are discussed. Based on published data, present-day recommendations for an optimal culture technique of CAPD effluents are given.


Glucose metabolism in spontaneously hypertensive rats.
Serum glucose levels in SHR (especially SHR selected for a greater hyperglycemic response) tended to be higher at 'fasting' and were significantly higher after peroral glucose administration than those in normotensive WK. However, plasma immunoreactive insulin was not decreased in SHR as compared with WK. No significant acceleration of gluconeogenesis was observed in SHR.


Anatomical distribution of the degree of mineralization of bone tissue in human femoral neck: impact on biomechanical properties.
Osteoporotic hip fractures represent a major public health problem associated with high human and economic costs. The anatomical variation of the tissue mineral density (TMD) and of the elastic constants in femoral neck cortical bone specimens is an important determinant of bone fragility. The purpose of this study was to show that a Synchrotron radiation microcomputed tomography system coupled with a multiscale biomechanical model allows the determination of the 3-D anatomical dependence of TMD and of the elastic constants (i.e. the mechanical properties of an anisotropic material) in human femoral neck. Bone specimens from the inferior femoral neck were obtained from 18 patients undergoing standard hemiarthroplasty. The specimens were imaged using 3-D synchrotron micro-computed tomography with a voxel size of 10.13 μm, leading to the determination of the anatomical distributions of porosity and TMD. The elastic properties of bone tissue were computed using a multiscale model. The model uses the experimental data obtained at the scale of several micrometers to estimate the components of the elastic tensor of bone at the scale of the organ. Statistical analysis (ANOVA) revealed a significant effect of the radial position on porosity and TMD and a significant effect of axial position on TMD only. Porosity was found to increase in the radial direction moving from the periosteum inwards (p<10(-5)). At any given distance from the periosteum, porosity does not vary noticeably along the bone axis. TMD was found to be significantly higher (p<10(-5)) in the periosteal region than in other bone locations and decreases from the periosteal to the endosteal region with an average slope of 10.05 g.cm(-3).m(-1), the decrease being faster in the porous part of the samples (average slope equal of 30.04 g.cm(-3).m(-1)) than in dense cortical bone. TMD was found to decrease from the distal to the proximal part of the femur neck (average slope of 6.5 g.cm(-3).m(-1)). Considering TMD variations in the radial direction induces weak changes of bone properties compared to constant TMD. TMD variations in the axial direction are responsible for a significant variation of elastic constants. These results demonstrate that the anatomical variations of TMD affect the bone elastic properties, which could be explained by the complex stress field in bone affecting bone remodeling. TMD spatial variations should be taken into account to properly describe the spatial heterogeneity of elastic coefficients of bone tissue at the organ scale.


Finite-Element Modelling Based on Optical Coherence Tomography and Corresponding X-ray MicroCT Data for Three Human Middle Ears.
Optical coherence tomography (OCT) is an emerging imaging modality which is non-invasive, can be employed in vivo, and can record both anatomy and vibrations. The purpose here is to explore the application of finite-element (FE) modelling to OCT data. We recorded vibrations for three human cadaver middle ears using OCT. We also have X-ray microCT images from the same ears. Three FE models were built based on geometries obtained from the microCT images. The material properties and boundary conditions of the models were obtained from previously reported studies. Tympanic-membrane (TM) vibration patterns were computed for the three models and compared with the patterns measured using OCT. Frequency responses were also computed for all three models for several locations in the middle ear and compared with the OCT displacements and with the literature. The three models were compared with each other in terms of geometry and function. Parameter sensitivity analyses were done and the results were compared among the models and with the literature. The simulated TM displacement patterns are qualitatively similar to the OCT results. The simulated displacements are closer to the OCT results for 500 Hz and 1 kHz but the differences are greater at 2 kHz. This study provides an initial look at the combined use of OCT measurements and FE modelling based on subject-specific anatomy. The geometries and parameters of the existing FE models could be modified for individual patients in the future to help identify abnormalities in the middle ear.


Qianghuo Shengshi decoction exerts anti-inflammatory and analgesic via MAPKs/CREB signaling pathway.
Traditional Chinese Medicine Qianghuo Shengshi decoction (QSD) is widely used in the treatment of nervous headache, rheumatoid arthritis, sciatica, allergic purpura, and other clinical diseases in China. However, the underlying mechanisms of its anti-inflammatory and analgesic effects has not been elucidated. The aim of this study was to confirm the anti-inflammatory and analgesic effects and the underlying mechanism of QSD in vivo. In addition, this study was also to isolate and analyze the main active components of QSD by high performance liquid chromatography (HPLC). In this study, the acetic acid writhing test, hot plate test and ear swelling test and formalin test were carried out to explore the anti-inflammatory and analgesic effects of QSD. The doses were set to 7.8 g/kg, 15.6 g/kg and 31.2 g/kg body weight. Western blot was utilized to study further possible mechanisms of QSD. Moreover, the HPLC method was used to isolate and identify the components in the extraction of QSD. Twelve characteristic peaks were recognized in the HPLC spectrum, which all were the known compounds. The QSD exhibited dose-dependent effects in anti-inflammatory and analgesic aspects. Compared with model group, the writhing times of in groups of different doses of QSD (15.6 g/kg and 31.2 g/kg (oral administration = p.o.)) were reduced by 33.0% and 45.8% and indicated the QSD showed significant (p < 0.05) peripheral analgesic effect. QSD ((31.2 g/kg), p.o.) showed significant(p < 0.05) analgesic effect in the hot plate test. Inhibition rates of QSD ((15.6 g/kg and 31.2 g/kg), p.o.) in ear swelling test induced by p-xylene were 27.5% and 54.6% and demonstrated the significant (p < 0.05) anti-inflammatory activity. QSD ((31.2 g/kg), p.o.) significantly (p < 0.05) reduced times of paw licking in formalin test, and its inhibition rates were 34.3% and 28.0% in Phase I and Phase Ⅱ response, respectively. Western blot results showed that QSD inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) protein and cAMP response element-binding protein (CREB). These results of this study undoubtedly confirmed that QSD expressed obvious analgesic and anti-inflammatory activities. Anti-inflammatory and analgesic effects of QSD may be achieved by regulating the MAPKs protein and further regulating the expression of CREB. In all, QSD may play an anti-inflammatory and analgesic role through a variety of active ingredients.


Olefins turned alkylating agents: diastereoselective intramolecular Zr-catalyzed olefin alkylations.
The first examples of intramolecular Zr-catalyzed electrophilic alkylation of aryl olefins are disclosed. Substituted carbo- and heterocycles are prepared efficiently and diastereoselectively.


Is sufficient experience performing open gastrectomies necessary to start laparoscopic distal gastrectomy training?
Laparoscopic gastrectomy has become a standard procedure for treatment of gastric cancer, and hence, the opportunity for trainees to perform open gastrectomies may decrease. We investigated whether laparoscopic distal gastrectomy, performed by surgical trainees without sufficient experience performing open gastrectomies, was feasible and safe. We compared short-term outcomes in patients when laparoscopic distal gastrectomies were performed by experienced trainees (ET group; n = 124) and inexperienced trainees (IT group; n = 98) from 2013 to 2019. The operation time was significantly shorter in the ET group (median time: 253 minutes vs 286 minutes, P < 0.001). The incidence of grade ≥ 2 postoperative complications did not differ significantly between the groups. In the multivariate analysis, experience performing open gastrectomies was not an independent predictor of postoperative complications. Laparoscopic distal gastrectomies performed by trainees, with insufficient experience performing open gastrectomies, are as feasible and safe as that performed by ET.


Chronic cerebral ischemia induces redistribution and abnormal phosphorylation of transactivation-responsive DNA-binding protein-43 in mice.
Transactivation-responsive DNA-binding protein 43 (TDP-43) is closely involved in the pathogenesis of frontotemporal lobar degeneration. The native form, but not phosphorylated form, of TDP-43 has been reported to redistribute during acute neuronal injuries. Here, we examined whether the expression of phosphorylated TDP-43 was altered following chronic neuronal injury. C57BL/6 mice were subjected to sham operation or bilateral common carotid artery stenosis (BCAS) using microcoils, and changes in proteolytic cleavage, phosphorylation, and subcellular redistribution of TDP-43 were examined by immunoblotting and immunohistochemistry. We also monitored the expression of importin β, which is involved in the transport of TDP-43. Immunoblotting showed an increase in phosphorylated TDP-43 in the nuclear fraction after BCAS using microcoils. Moreover, immunoreactivity toward phosphorylated TDP-43 was observed in the neuronal cytoplasm in the cerebral cortex and hippocampus, and importin β levels decreased after the operation. Immunoreactivity toward phosphorylated TDP-43 was partly colocalized with immunoreactivity toward caspase 3 in the neuronal cytoplasm. These results suggested that chronic cerebral ischemia induced redistribution and abnormal phosphorylation of TDP-43, which may be triggered by downregulation of importin β and may partly result in neuronal death.


Octamer transfer and creation of stably remodeled nucleosomes by human SWI-SNF and its isolated ATPases.
Chromatin remodeling complexes help regulate the structure of chromatin to facilitate transcription. The multisubunit human (h) SWI-SNF complex has been shown to remodel mono- and polynucleosome templates in an ATP-dependent manner. The isolated hSWI-SNF ATPase subunits BRG1 and hBRM also have these activities. The intact complex has been shown to produce a stable remodeled dimer of mononucleosomes as a product. Here we show that the hSWI-SNF ATPases alone can also produce this product. In addition, we show that hSWI-SNF and its ATPases have the ability to transfer histone octamers from donor nucleosomes to acceptor DNA. These two reactions are characterized and compared. Our results are consistent with both products of SWI-SNF action being formed as alternative outcomes of a single remodeling mechanism. The ability of the isolated ATPase subunits to catalyze these reactions suggests that these subunits play a key role in determining the mechanistic capabilities of the SWI-SNF family of remodeling complexes.


Nano-biosensor based on manganese dioxide nanosheets and carbon dots for dual-mode determination of Staphylococcus aureus.
A ratiometric fluorescence and colorimetry dual-mode nano-biosensor has been established for Staphylococcus aureus (S. aureus) determination. The prepared approaches of Manganese dioxide nanosheets (MnO2 NSs) and carbon dots (BCDs) were facile, efficient and labor-saving and MnO2 NSs-mediated fluorescence quenching and oxidation could amplify detection signals. The dual-mode determination had a broad linear range of 37 ∼ 3.7 × 106 CFU/mL and low detection limits of 9 CFU/mL (ratiometric fluorescence) and 22 CFU/mL (colorimetry). Meanwhile, the method was applied in real samples with recovery ranging of 90 ∼ 102% and RSD < 4.44%, which was an insignificant difference with standard plate counting. The new dual-mode approach of S. aureus possesses the advantages of superior sensitivity, precision, accuracy and specificity. Moreover, the dual-mode nano-biosensor can be adopted in other foodborne pathogens determination by changing corresponding aptamers and provide an enlightenment in monitoring food safety.


First isolation and whole-genome sequencing of a Shewanella algae strain from a swine farm in Brazil.
Infections caused by Shewanella spp. have been increasingly reported worldwide. The advances in genomic sciences have enabled better understanding about the taxonomy and epidemiology of this agent. However, the scarcity of DNA sequencing data is still an obstacle for understanding the genus and its association with infections in humans and animals. In this study, we report the first isolation and whole-genome sequencing of a Shewanella algae strain from a swine farm in Brazil using the boot sock method, as well as the resistance profile of this strain to antimicrobials. The isolate was first identified as Shewanella putrefaciens, but after whole-genome sequencing it showed greater similarity with Shewanella algae. The strain showed resistance to 46.7% of the antimicrobials tested, and 26 resistance genes were identified in the genome. This report supports research made with Shewanella spp. and gives a step forward for understanding its taxonomy and epidemiology. It also highlights the risk of emerging pathogens with high resistance to antimicrobial formulas that are important to public health.


Modeling and Optimization of Manufacturing Process Performance using Modelica Graphical Representation and Process Analytics Formalism.
This paper concerns the development of a design methodology and its demonstration through a prototype system for performance modeling and optimization of manufacturing processes. The design methodology uses a Modelica simulation tool serving as the graphical user interface for manufacturing domain users such as process engineers to formulate their problems. The Process Analytics Formalism, developed at the National Institute of Standards and Technology, serves as a bridge between the Modelica classes and a commercial optimization solver. The prototype system includes (1) manufacturing model components' libraries created by using Modelica and the Process Analytics Formalism, and (2) a translator of the Modelica classes to Process Analytics Formalism, which are then compiled to mathematical programming models and solved using an optimization solver. This paper provides an experiment toward the goal of enabling manufacturing users to intuitively formulate process performance models, solve problems using optimization-based methods, and automatically get actionable recommendations.


Tradeoffs of estimating reaction time with absolute and relative thresholds.
Measuring the duration of cognitive processing with reaction time is fundamental to several subfields of psychology. Many methods exist for estimating movement initiation when measuring reaction time, but there is an incomplete understanding of their relative performance. The purpose of the present study was to identify and compare the tradeoffs of 19 estimates of movement initiation across two experiments. We focused our investigation on estimating movement initiation on each trial with filtered kinematic and kinetic data. Nine of the estimates involved absolute thresholds (e.g., acceleration 1000 back to 200 mm/s2, micro push-button switch), and the remaining ten estimates used relative thresholds (e.g., force extrapolation, 5% of maximum velocity). The criteria were the duration of reaction time, immunity to the movement amplitude, responsiveness to visual feedback during movement execution, reliability, and the number of manually corrected trials (efficacy). The three best overall estimates, in descending order, were yank extrapolation, force extrapolation, and acceleration 1000 to 200 mm/s2. The sensitive micro push-button switch, which was the simplest estimate, had a decent overall score, but it was a late estimate of movement initiation. The relative thresholds based on kinematics had the six worst overall scores. An issue with the relative kinematic thresholds was that they were biased by the movement amplitude. In summary, we recommend measuring reaction time on each trial with one of the three best overall estimates of movement initiation. Future research should continue to refine existing estimates while also exploring new ones.


Effect of environmental conditions on the production of two extracellular proteolytic enzymes by Vibrio SA1.
The production of two extracellular proteases, an endopeptidase and an aminopeptidase, by the marine bacterium Vibrio SA1 was studied in batch cultures. The production of the proteases was induced during growth of the organism in peptone media and by several amino acids during growth in minimal media. It was repressed by easily metabolisable carbon compounds such as glucose, lactate and succinate during growth in peptone media. During growth in a lactate basal medium, phenylalanine was one of the best inducers and this amino acid was therefore used in further experiments. That lactate did not repress the synthesis of the proteases during growth in the lactate basal medium supplement with 2mM phenylalanine as an inducer, appeared to be a consequence of the low iron content of this medium. Growth curves of Vibrio SA1 on such media showed a period of linear growth during which protease production was observed. When the iron concentration was made sufficiently high to prevent linear growth, the synthesis of the proteases remained repressed. Apparently by imposing an iron limitation on the organism, catabolite repression by lactate was relieved. Similarly, when growth was limited by very low values of the dissolved oxygen tension in the medium, a high rate of protease synthesis was found which was immediately repressed when the oxygen limitation was released. The results indicate that the growth rate and/or a factor associated with the energy metabolism play a role in the regulation of the synthesis of the enzymes.


Fundamental symmetry aspects of chirality.
Physical systems which exhibit distinguishable enantiomers under space inversion are not necessarily chiral. A new definition of chirality is proposed that enables true and false chirality to be distinguished. Although spatial enantiomorphism is sufficient to guarantee chirality in a stationary object, enantiomorphous systems are not necessarily chiral when motion is involved. Only a truly chiral influence can induce absolute asymmetric synthesis in a reaction mixture at thermodynamic equilibrium, but false chirality might suffice if equilibrium is not attained. Parity violation lifts only the degeneracy of enantiomers of truly chiral systems, the true enantiomers (i.e. strictly degenerate) being interconverted by space inversion together with charge conjugation. The time-independence of optical activity arising from parity violation is contrasted with the time-dependence of that arising from spontaneous parity breaking.


General and passenger-relevant factors of work-related musculoskeletal disorders (WMSDs) among Chinese female flight attendants.
A high prevalence of work-related musculoskeletal disorders (WMSDs) has been reported among flight attendants. Identifying the root causes of these disorders may improve the health conditions of flight attendants and further improve flight safety and service quality. In this study, we aimed to identify WMSD risk factors for a specific population, namely Chinese female flight attendants. A two-stage survey including an online questionnaire (46 flight attendants) and a semi-structured interview (16 flight attendants) was used to assess the WMSDs of Chinese female flight attendants. Text analysis tools in NVivo 11 were used to identify the main concerns and risk factors for WMSDs of Chinese flight attendants. In the online questionnaire, more than 86% of the participants reported discomfort in at least one body part. Biomechanical factors, work organizational factors, and psychosocial factors were reported by participants in this study. Chinese passengers were found to have an effect on WMSD development in Chinese flight attendants. The results of this study suggested that WMSDs are severe problems among Chinese flight attendants. General factors as well as the passenger-relevant factor were identified as the most influential causes of WMSDs.


Optimization of Enterotoxigenic Escherichia coli (ETEC) Outer Membrane Vesicles Production and Isolation Method for Vaccination Purposes.
The study addresses Enterotoxigenic Escherichia coli (ETEC), a significant concern in low-income countries. Despite its prevalence, there is no licensed vaccine against ETEC. Bacterial vesicle-based vaccines are promising due to their safety and diverse virulence factors. However, cost-effective production requires enhancing vesicle yield while considering altered properties due to isolation methods. The proposed method involves heat treatment and ultrafiltration to recover vesicles from bacterial cultures. Two vesicle types, collected from heat-treated (HT-OMV) or untreated (NT-OMV) cultures, were compared. Vesicles were isolated via ultrafiltration alone ("complete") or with ultracentrifugation ("sediment"). Preliminary findings suggest complete HT-OMV vesicles are suitable for an ETEC vaccine. They express important proteins (OmpA, OmpX, OmpW) and virulence factors (adhesin TibA). Sized optimally (50-200 nm) for mucosal vaccination, they activate macrophages, inducing marker expression (CD40, MHCII, CD80, CD86) and Th1/Th2 cytokine release (IL-6, MCP-1, TNF-α, IL12p70, IL-10). This study confirms non-toxicity in RAW 264.7 cells and the in vivo ability of complete HT-OMV to generate significant IgG2a/IgG1 serum antibodies. Results suggest promise for a cost-effective ETEC vaccine, requiring further research on in vivo toxicity, pathogen-specific antibody detection, and protective efficacy.


Current status of serotyping of Neisseria gonorrhoeae.
Protein I has become the basis of serotyping of N. gonorrhoeae. A panel of 12 anti-protein I monoclonal antibodies is supplied by Syva Company, Palo Alto, CA, through distributors for research purposes only. These distributors are responsible for storing the monoclonal antibodies, supplying research groups and training new users, particularly in the interpretation of coagglutination reactions. A European Workshop was held in Heidelberg, Federal Republic of Germany in July 1988 to discuss serotyping with these antibodies. The current uses of serotyping of N. gonorrhoeae include epidemiological studies, clinical purposes and surveillance of antibiotic resistance and plasmid carriage. Predominant serovars may be subtyped either by additional antibodies or with the use of another technique, such as auxotyping, determination of antibiotic sensitivities, plasmid analysis or genetic fingerprinting. Conversely, there is growing evidence that it may be appropriate to group certain serovars together. Data collected during prevalence studies could be combined with clinical information and an international data bank set up. This supposes a close future collaboration of all groups involved in the epidemiology of N. gonorrhoeae.


Substance P activates ADAM9 mRNA expression and induces α-secretase-mediated amyloid precursor protein cleavage.
Altered levels of Substance P (SP), a neuropeptide endowed with neuroprotective and anti-apoptotic properties, were found in brain areas and spinal fluid of Alzheimer's disease (AD) patients. One of the hallmarks of AD is the abnormal extracellular deposition of neurotoxic beta amyloid (Aβ) peptides, derived from the proteolytic processing of amyloid precursor protein (APP). In the present study, we confirmed, the neurotrophic action of SP in cultured rat cerebellar granule cells (CGCs) and investigated its effects on APP metabolism. Incubation with low (5 mM) potassium induced apoptotic cell death of CGCs and amyloidogenic processing of APP, whereas treatment with SP (200 nM) reverted these effects via NK1 receptors. The non-amyloidogenic effect of SP consisted of reduction of Aβ(1-42), increase of sAPPα and enhanced α-secretase activity, without a significant change in steady-state levels of cellular APP. The intracellular mechanisms whereby SP alters APP metabolism were further investigated by measuring mRNA and/or steady-state protein levels of key enzymes involved with α-, β- and γ-secretase activity. Among them, Adam9, both at the mRNA and protein level, was the only enzyme to be significantly down-regulated following the induction of apoptosis (K5) and up-regulated after SP treatment. In addition to its neuroprotective properties, this study shows that SP is able to stimulate non-amyloidogenic APP processing, thereby reducing the possibility of generation of toxic Aβ peptides in brain.


Ultrastructural observations in myopathy complicating Cushing's disease.
The ultrastructural findings in a muscle biopsy of a patient with Cushing's disease associated with severe myopathy are described. They included pronounced mitochondrial damage, thickening and deep invaginations of the sarcolemmal basement membrane, and thickening of the basement membrane of the capillaries. In addition, the muscle fibers showed a marked degree of disarray and wide interfibrillar spaces, containing large numbers of vacuoles, which presented degenerated mitochondria. The similarity between these findings and the ultrastructural features of corticosteroid-induced myopathy is discussed.


Depressed cladding, buried waveguide laser formed in a YAG:Nd3+ crystal by femtosecond laser writing.
Depressed cladding waveguides have been formed in laser crystals by a tightly focused beam of a femtosecond laser. A laser based on a depressed cladding waveguide in a neodymium-doped YAG crystal has been demonstrated for what is believed to be the first time.


Comparison of arterial wall integration of different flow diverters in rabbits: The CICAFLOW study.
New coated flow diverters (FDs) claim antithrombotic properties and increased arterial wall integration. The aim of this study is to compare in vivo endothelial coverage of coated and uncoated FD in the context of different antiplatelet regimens. Different FDs (Silk Vista - SV, Pipeline with Shield technology - PED shield and Surpass Evolve - SE) were implanted in the aorta of rabbits, all 3 in each animal with 3 different antiplatelet regimens: no antiplatelet therapy, aspirin alone, or aspirin and ticagrelor. Four weeks after FD implantation, angiography, flat-panel CT, and optical coherence tomography (OCT) were performed before harvesting the aorta. Extensive histopathology analyses were performed including environmental scanning electron microscopy (ESEM), multiphoton microscopy (MPM) and histological staining with qualitative and/or quantitative assessment of device coverage. All 23 FDs that were implanted remained patent without hyperplasia. Qualitative stent coverage assessment revealed that there were no statistically significant differences between the FD groups (p = 0.19, p = 0.45, p = 0.40, and p = 0.84 for OCT, ESEM, MPM and histology, respectively). Quantitative neointimal measurement of histological sections also showed similar results in all 3 FD groups (p = 0.70). However, there were significant differences between the 3 groups of antiplatelet regimens (p = 0.07) with a higher rate in the no antiplatelet group (p = 0.05 versus aspirin alone and p = 0.03 versus aspirin and ticagrelor). Our study provides evidence that FD integration into the arterial wall is similar with coated (PED shield) and uncoated devices (SV, SE), regardless of the antiplatelet regimen. FD integration with specific surface coverage should be promoted. APAFIS #2022011215518538.


First Detection of Microcystin-LR in the Amazon River at the Drinking Water Treatment Plant of the Municipality of Macapá, Brazil.
Human poisoning by microcystin has been recorded in many countries, including Brazil, where fatal cases have already occurred. The Amazon River is the main source of drinking water in municipalities such as Macapá, where there is no monitoring of cyanobacteria and cyanotoxins. This study investigated the presence of cyanobacteria and cyanotoxins in samples from a drinking water treatment plant (DWTP) that catches water from the Amazon River. The toxin analyses employed ELISA, LC/MS, and molecular screening for genes involved in the production of cyanotoxins. The sampling was carried out monthly from April 2015 to April 2016 at the intake (raw water) and exit (treated water) of the DWTP. This study reports the first detection of microcystin-LR (MC-LR) in the Amazon River, the world's largest river, and in its treated water destined for drinking water purposes in Macapá, Brazil. The cyanobacterial density and MC-LR concentration were both low during the year. However, Limnothrix planctonica showed a density peak (± 900 cells mL-1) in the quarter of June-August 2015, when MC-LR was registered (2.1 µg L-1). Statistical analyses indicate that L. planctonica may produce the microcystin.


T cell receptor signaling pathway is overexpressed in CD4(+) T cells from HAM/TSP individuals.
Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus related to the chronic neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4(+) T cells activation appears to play a key role on HTLV-1 infection. Here we investigated the expression of genes associated to T cell activation CD3e molecule, epsilon (CD3ɛ), lymphocyte-specific protein tyrosine kinase (LCK), vav 1 guanine nucleotide exchange factor (VAV1), and zeta-chain (TCR) associated protein kinase 70kDa (ZAP70) on T lymphocytes of HTLV-1-infected individuals and compared to healthy uninfected individuals (CT). We observed that CD3ɛ, LCK, ZAP70, and VAV1 gene expression were increased in CD4(+) T cells from HAM/TSP group compared to HTLV-1 asymptomatic patients (HAC). Moreover, ZAP70 and VAV1 were also upregulated in HAM/TSP compared to CT group. We detected a positive correlation among all these genes. We also observed that CD3ɛ, LCK, and VAV1 genes had a positive correlation with the proviral load (PVL) and Tax expression. These results suggest that PVL and Tax protein could drive CD3ɛ, LCK, and VAV1 gene expression in CD4(+) T cells, and these genes function on a synchronized way on the CD4(+) T cell activation. The elucidation of the mechanisms underlying T cell receptor signaling pathway is of considerable interest and might lead to new insights into the mechanism of HAM/TSP.


Post-growth economics: a must for planetary health justice.
Within the global health field, progress is being made to adopt a justice and sustainability-centred approach by advancing what has been named a planetary health agenda. Meanwhile, an increasing number of global health scholars argue for the decolonisation of the field. Yet, amongst these collective efforts to 'transform' global health thinking, a thorough analysis of political economy dimensions is often missing. 'Growthism', the belief that more production is necessarily good, continues to prevail. Truly committing to a decolonial eco-just global health agenda requires addressing the continuation of colonial arrangements within the structure of the global economy, removing growth dependencies and ushering in post-growth policies.


HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity.
Human leukocyte antigen (HLA)-A*03, hemochromatosis ancestral haplotype marker, was associated with greater iron overload in hemochromatosis cohorts reported before discovery of the HFE gene. We sought to learn whether an A*03-linked locus influences phenotypes in referred HFE p.C282Y homozygotes. We tabulated these phenotypes in probands with p.C282Y homozygosity: age, transferrin saturation (TS), serum ferritin (SF), conditions related to iron overload, fibrosis-four variables (FIB-4) index and aspartate aminotransferase-to-platelet ratio index (APRI) predictors of severe hepatic fibrosis, and iron removed to achieve depletion (QFe/age). We analyzed phenotypes of men and women separately across three A*03 subgroups. There were 104 men (57.8%) and 76 women (42.2%). Mean age (SD) was 49 ± 13 y. Mean TS was 79 ± 17%. Median SF (range) was 715 µg/L (28, 6103). Related conditions included: hemochromatosis arthropathy (21.7%); type 2 diabetes (18.9%); hypogonadotropic hypogonadism (5.8% of men); cardiomyopathy (0%); and cirrhosis (10.0%). Median QFe/age was 61 mg/y (0, 714). A*03 homozygosity, heterozygosity, and no A*03 occurred in 37 (20.6%), 104 (57.8%), and 39 probands (21.7%), respectively. In men, mean TS and median SF were significantly higher in A*03 homozygotes than heterozygotes but not A*03-negative probands. In men, median APRI was significantly lower in A*03 heterozygotes than homozygotes and A*03-negative probands. No other phenotypes, including QFe/age, differed significantly across A*03 subgroups in either men or women. Our results suggest that an A*03-linked locus does not influence phenotypes in referred HFE p.C282Y homozygotes. It is unlikely that heritable factors that modify phenotypes of p.C282Y homozygotes are linked to the hemochromatosis ancestral haplotype.


Lower mortality in magnet hospitals.
Although there is evidence that hospitals recognized for nursing excellence--Magnet hospitals--are successful in attracting and retaining nurses, it is uncertain whether Magnet recognition is associated with better patient outcomes than non-Magnets, and if so why. To determine whether Magnet hospitals have lower risk-adjusted mortality and failure-to-rescue compared with non-Magnet hospitals, and to determine the most likely explanations. METHOD AND STUDY DESIGN: Analysis of linked patient, nurse, and hospital data on 56 Magnet and 508 non-Magnet hospitals. Logistic regression models were used to estimate differences in the odds of mortality and failure-to-rescue for surgical patients treated in Magnet versus non-Magnet hospitals, and to determine the extent to which differences in outcomes can be explained by nursing after accounting for patient and hospital differences. Magnet hospitals had significantly better work environments and higher proportions of nurses with bachelor's degrees and specialty certification. These nursing factors explained much of the Magnet hospital effect on patient outcomes. However, patients treated in Magnet hospitals had 14% lower odds of mortality (odds ratio 0.86; 95% confidence interval, 0.76-0.98; P=0.02) and 12% lower odds of failure-to-rescue (odds ratio 0.88; 95% confidence interval, 0.77-1.01; P=0.07) while controlling for nursing factors as well as hospital and patient differences. The lower mortality we find in Magnet hospitals is largely attributable to measured nursing characteristics but there is a mortality advantage above and beyond what we could measure. Magnet recognition identifies existing quality and stimulates further positive organizational behavior that improves patient outcomes.


Enhanced thermostability of keratinase by computational design and empirical mutation.
Keratinases are proteolytic enzymes capable of degrading insoluble keratins. The importance of these enzymes is being increasingly recognized in fields as diverse as animal feed production, textile processing, detergent formulation, leather manufacture, and medicine. To enhance the thermostability of Bacillus licheniformis BBE11-1 keratinase, the PoPMuSiC algorithm was applied to predict the folding free energy change (ΔΔG) of amino acid substitutions. Use of the algorithm in combination with molecular modification of homologous subtilisin allowed the introduction of four amino acid substitutions (N122Y, N217S, A193P, N160C) into the enzyme by site-directed mutagenesis, and the mutant genes were expressed in Bacillus subtilis WB600. The quadruple mutant displayed synergistic or additive effects with an 8.6-fold increase in the t 1/2 value at 60 °C. The N122Y substitution also led to an approximately 5.6-fold increase in catalytic efficiency compared to that of the wild-type keratinase. These results provide further insight into the thermostability of keratinase and suggest further potential industrial applications.


[Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].
The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in < 5 % of cases. Cervical lymphadenopathy may be the first symptom particularly of (micro) PTC. In contrast follicular thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).


Ectomycorrhizal and arbuscular mycorrhizal colonization of Alnus acuminata from Calilegua National Park (Argentina).
The objective of this study was to determine patterns of ectomycorrhizas (ECM) and arbuscular mycorrhizas (AM) colonization associated with Alnus acuminata (Andean alder), in relation to soil parameters (electrical conductivity, field H(2)O holding capacity, pH, available P, organic matter, and total N) at two different seasons (autumn and spring). The study was conducted in natural forests of A. acuminata situated in Calilegua National Park (Jujuy, Argentina). Nine ECM morphotypes were found on A. acuminata roots. The ECM colonization was affected by seasonality and associated positively with field H(2)O holding capacity, pH, and total N and negatively associated with organic matter. Two morphotypes (Russula alnijorullensis and Tomentella sp. 3) showed significant differences between seasons. Positive and negative correlations were found between five morphotypes (Alnirhiza silkacea, Lactarius omphaliformis, Tomentella sp. 1, Tomentella sp. 3, and Lactarius sp.) and soil parameters (total N, pH, and P). A significant negative correlation was found between field H(2)O holding capacity and organic matter with AM colonization. Results of this study provide evidence that ECM and AM colonization of A. acuminata can be affected by some soil chemical edaphic parameters and indicate that some ECM morphotypes are sensitive to changes in seasonality and soil parameters.


Evolving Decisions: Perspectives of Active and Athletic Individuals with Inherited Heart Disease Who Exercise Against Recommendations.
Individuals with hypertrophic cardiomyopathy (HCM) and long QT syndrome (LQTS) are advised to avoid certain forms of exercise to reduce their risk of sudden death. Cardiovascular genetic counselors facilitate both adaptation to, and decision-making about, these exercise recommendations. This study describes decision-making and experiences of active adults who exercise above physicians' recommendations. Purposive sampling was used to select adults with HCM and LQTS who self-identified as exercising above recommendations. Semi-structured interviews explored participants' decision-making and the psychological impact of exercise recommendations. Fifteen individuals were interviewed (HCM: 10; LQTS: 5; mean age: 40). Transcripts were coded and analyzed for underlying themes. Despite exercising above recommendations, nearly all participants made some modifications to their prior exercise regimen. Often these decisions changed over time, underscoring the importance of shared decision-making conversations beyond the initial evaluation. The importance of exercise was frequently cited as a reason for continued exercise, as were perceptions of sudden death risk as low, acceptable, or modifiable. Many participants reported that family and friends supported their exercise decisions, with a minority having family or friends that expressed significant reservations. Genetic counselors, cardiologists, and nurses can use these data to inform their counseling regarding exercise recommendations.


The effects of eight serum lipid biomarkers on age-related macular degeneration risk: a Mendelian randomization study.
Age-related macular degeneration (AMD) is a leading cause of vision loss. Whereas lipids have been studied extensively to understand their effects on cardiovascular diseases, their relationship with AMD remains unclear. Two-sample Mendelian randomization (MR) analyses were performed to systematically evaluate the causal relationships between eight serum lipid biomarkers, consisting of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], triglycerides (TG) and non-HDL cholesterol (non-HDL-C), and the risk of different AMD stages and subtypes. We derived 64-407 genetic instruments for eight serum lipid biomarkers in 419 649 participants of European descent from the UK Biobank cohort. We conducted genome-wide association studies (GWAS) for 12 711 advanced AMD cases [8544 choroidal neovascularization (CNV) and 2656 geographic atrophy (GA) specific AMD subtypes] and 5336 intermediate AMD cases with 14 590 controls of European descent from the International AMD Genomics Consortium. Higher genetically predicted HDL-C and ApoA1 levels increased the risk of all AMD subtypes. LDL-C, ApoB, CHOL and non-HDL-C levels were associated with decreased risk of intermediate and GA AMD but not with CNV. Genetically predicted TG levels were associated with decreased risk of different AMD subtypes. Sensitivity analyses revealed no evidence for directional pleiotropy effects. In our multivariable MR analyses, adjusting for the effects of correlated lipid biomarkers yielded similar results. These results suggest the role of lipid metabolism in drusen formation and particularly in AMD development at the early and intermediate stages. Mechanistic studies are warranted to investigate the utility of lipid pathways for therapeutic treatment in preventing AMD.


Assessment of antimicrobial peptide LL-37 as a post-exposure therapy to protect against respiratory tularemia in mice.
Early activation of the innate immune response is important for protection against infection with Francisella tularensis live vaccine strain (LVS) in mice. The human cathelicidin antimicrobial peptide LL-37 is known to have immunomodulatory properties, and therefore exogenously administered LL-37 may be suitable as an early post-exposure therapy to protect against LVS infection. LL-37 has been evaluated for immunostimulatory activity in uninfected mice and for activity against LVS in macrophage assays and protective efficacy when administered post-challenge in a mouse model of respiratory tularemia. Increased levels of pro-inflammatory cytokine IL-6, chemokines monocyte chemoattractant protein 1 (MCP-1) and CXCL1 with increased neutrophil influx into the lungs were observed in uninfected mice after intranasal administration of LL-37. Following LVS challenge, LL-37 administration resulted in increased IL-6, IL-12 p70, IFNγ and MCP-1 production, a slowing of LVS growth in the lung, and a significant extension of mean time to death compared to control mice. However, protection was transient, with the LL-37 treated mice eventually succumbing to infection. As this short course of nasally delivered LL-37 was moderately effective at overcoming the immunosuppressive effects of LVS infection this suggests that a more sustained treatment regimen may be an effective therapy against this pathogen.


Methylene blue-induced Heinz body hemolytic anemia.
To describe the manifestations of methylene blue toxicity, with a review of the literature. A descriptive analysis of physical findings and significant laboratory tests in patients with methylene blue toxicity. A pediatric referral center. Two infants, one a neonate with trisomy 21 exposed to methylene blue as an intraoperative diagnostic marker and the other a neonate treated with methylene blue for type II glutaric acidemia. Laboratory tests to define the occurrence of methylene blue toxicity, phototherapy for hyperbilirubinemia, and transfusions for anemia. Within hours after exposure to methylene blue, the infants voided green-blue urine, followed by hyperbilirubinemia, recurrent anemia requiring transfusions, and red blood cell dysmorphology, including the appearance of blister cells and Heinz bodies visible in both Wright's- and supravital-stained peripheral blood smears. After the initiation of phototherapy, both infants exhibited cutaneous bullae followed by desquamation. Significant neonatal morbidity may occur following postpartum administration of methylene blue. Toxic manifestations include hyperbilirubinemia, Heinz body hemolytic anemia, and possibly desquamation of the skin. In our infants toxicity was secondary to an overdose of methylene blue, as is true for most of the previously reported cases. Methods for defining the mechanism of dye-related hemolysis and simple screening tests for elucidating the unique sensitivity of certain individuals to dye toxicity are suggested.