ERK1 and ERK2 activation modulates diet-induced obesity in mice.
Obesity is a worldwide problem, and dietary lipids play an important role in its pathogenesis. Recently, Erk1 knock-out (ERK1-/-) mice have been shown to exhibit low preference for dietary fatty acids. Hence, we maintained Erk1-/- mice on a high-fat diet (HFD) to assess the implication of this mitogen-activated protein (MAP) kinase in obesity. The Erk1-/- mice, fed the HFD, were more obese than wild-type (WT) animals, fed the same diet. Erk1-/- obese mice gained more fat and liver mass than WT obese animals. No difference was observed in daily food and energy intake in HFD-fed both group of animals. However, feed efficiency was higher in Erk1-/- than WT animals. Blood cholesterol, triglyceride and insulin concentrations were higher in Erk1-/- obese mice compared to WT obese animals. Accordingly, homeostatic model assessment of insulin resistance (HOMA-IR) value was higher in Erk1-/- obese mice compared to WT obese animals. Interestingly, only Erk1-/- obese mice, but not WT-obese animals, exhibited high degree of phosphorylation of liver MEK, the upstream regulator of ERK1/2. This phenomenon was associated with high liver ERK2 phosphorylation in Erk1-/- obese mice which also had high liver acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) mRNA expression, suggesting high lipogenesis in these animals. The Erk1-/- obese mice also had low PPAR-α and CPT1β mRNA, indicating low fatty acid oxidation. Our observations suggest that ERK1 and ERK2 might play key roles in the regulation of obesity.


Ceftizoxime vs. cefotaxime--a comparative randomized multicenter study.
One hundred and fourteen hospitalized patients with moderate or severe infections were assigned at random, in four medical centers, to receive either ceftizoxime or cefotaxime, administered intravenously in a dosage of 1 to 2 g every 8 h. Of 96 patients evaluable for efficacy, 24 (25%) had bacteremia, 46 (48%) had urinary tract infections and 9 (9%) had pneumonias. Half the patients had been treated ineffectively by other antibiotics prior to the study drug treatment. The overall clinical efficacy was 90% in both treatment groups and 83% in both groups with bacteremia. All patients with urinary tract infection were cured by both agents. Bacteriological eradication rate was 95% in both groups. Adverse reactions, though mild, were more frequent in the cefotaxime group (13.5%) than in the ceftizoxime group (6.8%); superinfection rate was higher in the ceftizoxime group. Both antibiotics were highly and equally efficacious in the therapy of severe infections in hospitalized patients.


Activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating Klotho.
Cardiovascular diseases are common in patients with chronic kidney disease. One of the key symptoms is the calcification of the vascular smooth muscle cells (VSMCs), which is induced by dysregulated mineral metabolism with high circulating levels of inorganic phosphate (Pi) and calcium. Klotho, which was originally identified as an aging suppressor gene, has been shown to be associated with vascular calcification. Since Klotho was recently identified as a target for nuclear receptor peroxisome proliferator-activated receptor (PPAR) γ, the present study aimed to determine whether PPARγ regulates VSMC calcification through modulating the expression levels of Klotho. It was demonstrated that the expression of PPARγ was downregulated during Pi-induced VSMC calcification. In addition, treatment with PPARγ agonists inhibited the calcification and enhanced the expression of Klotho in VSMCs in a PPARγ-dependent manner. Of note, loss of Klotho expression by RNA interference abolished the ability of PPARγ activation to inhibit VSMC calcification. Furthermore, activation of Klotho as well as PPARγ inhibited the expression of Pi transporter 1/2 and reduced Pi influx into VSMCs. To the best of our knowledge, the present study was the first to demonstrate that PPARγ regulates VSMC calcification through activating Klotho.


rAAV9--a human-derived adeno-associated virus vector for efficient transgene expression in mouse cingulate cortex.
The rostro-medial cortex of the mouse and rat, considered the functional homolog to the primate prefrontal cortex (PFC), is of growing importance for preclinical models of schizophrenia and other neurodevelopmental diseases for which symptoms typically emerge in adolescence and early adulthood. Therefore, in order to explore molecular mechanisms operating during these critical stages of PFC development, it will be important to develop an efficient gene delivery system for the PFC of juvenile animals. To this end, adeno-associated virus (AAV)-based systems are increasingly used in mice for targeted gene delivery in specific brain regions such as the hippocampus. Strikingly, there is very little literature on vector-mediated gene expression in the rostro-medial cortex. In addition, multiple AAV serotypes exist based on differences in their envelope capsid proteins. However, to date, the large majority of studies in the central nervous system (CNS) have utilized the AAV2 serotype. This is typically limited to a very focal transduction pattern and therefore is not ideal for the murine PFC, which occupies several square millimeters in the rostral hemisphere. Here, we introduce a protocol for efficient, AAV9-serotype-mediated gene delivery in juvenile (postnatal day 21) and young adult PFC, resulting in long-lasting transgene expression.


Screening for Bowel Cancer: Increasing Participation via Personal Invitation.
Participation rates in bowel cancer screening programs in Germany continue to be low. In a model project, a logistically simple procedure for inviting patients to participate was tested as a means of increasing participation. A randomized trial was performed involving persons residing in the German federal state of Saarland who had either their 50th or their 55th birthday in the year beginning on 1 April 2012 (18 560 and 16 824 persons, respectively). The 50-year-olds received a written invitation to undergo a test for blood in the stool, either with or without a stool test attached, or else no invitation at all. The 55-year-olds received either an invitation to undergo colonoscopy or no invitation. Participation rates within one year were determined from billing data of the Saarland Association of Statutory Health. Insurance Physicians. The trial was registered in the German Registry of Clinical Trials, no. DRKS00006098. A written invitation to undergo testing of the stool for blood, together with an accompanying test, increased the participation rate within one year by 62% (from 15% to 25%, p <0.001, especially among men (+158% vs. +39% for women). The participation rate was higher in general among women than among men (33% vs. 17%). On the other hand, a written invitation with no accompanying test did not increase the participation rate. A written invitation to undergo colonoscopic screening increased the participation rate within one year by 32% (5.9% vs 4.4%, p <0.001). Targeted invitations can markedly increase participation rates in cancer screening. Written invitations to undergo stool testing for blood should be accompanied by an actual test. Further trials should also include information about the number of adenomas and carcinomas detected by screening.


Immuno-derived opioids as mediators of the immuno-enhancing and anti-stress action of melatonin.
The pineal neurohormone melatonin was shown to stimulate the release of opioid peptides from activated CD4+, T lymphocytes. These immuno-derived opioids or "lymphomorphins" crossreact with anti-beta-endorphin and anti-metenkephalin antisera, bind to opioid receptors in the thymus and are the mediators of the immunoenhancing and anti-stress action of endogenous and/or exogenous melatonin. These findings proved the existence of a novel immunoneuroendocrine physiological mechanism which may be related for the long range maintenance of the immune homeostasis in spite of the unavoidable stress and/or infectious events occurring during the span of life in a normal unprotected environment.


[Anti-tumor effect of LAK (lymphokine activated killer) cells against human bladder tumors transplanted to nude mouse].
The effect of lymphokine-activated killer (LAK) cells on bladder tumor was examined in vivo and in vitro. In the in vitro experiment, 51Cr-cytotoxic assay was performed for which PBL were used as effector cells. A LAK activity of 26.6% was observed in PBL cultured with IL2 for 4 days, whereas OK-432-induced LAK activity was 22%. Furthermore, in the in vivo experiment, the anti-tumor effect of LAK cells was evaluated in human bladder tumor transplanted into nude mouse. IL2, OK432-induced LAK cells were injected intratumorally. In the LAK-treated group, inhibition of tumor growth was seen. Histologically, it was demonstrated that infiltrating lymphocytes were scattered around tumor cells. The augmentation of NK activity in spleen cells was observed in the LAK-treated group. Although further studies are required to establish its full significance, these findings suggest that immunotherapy against bladder tumors is hopeful.


On the drive-rootedness of psychoanalytic ego psychology.
This paper attempts, hypothetico-deductively, to conceptualise psychoanalysis on the level of fundamental theory. I begin by exploring the relevance for psychoanalytic theory of recent developments in the brain and cognitive sciences. Their site of articulation is identified as the concept of consciousness. I proceed to develop a conceptual integration of consciousness into psychoanalytic drive theory. This reveals the wish as the original psychical entity, with a self-process imbricated in its structure. Narcissism in shown to be sexually grounded, vitally constitutive, and intrinsically aggressive. It becomes possible, using the neighbouring sciences as well, to work out a theory of the origin of the secondary process and early ego formation. My approach provides a view of mental development in which identification and repression represent two aspects of a unitary activity that structures the mind. This allows the unconscious and consciousness to be brought into dialectical relation. Implications follow for the 'activity of the repressed' and the theory of paranoia.


Going beyond: an adventure- and recreation-based group intervention promotes well-being and weight loss in schizophrenia.
To undertake a preliminary study to assess the feasibility of clinical implementation and evaluate the effectiveness of a novel adventure- and recreation-based group intervention in the rehabilitation of individuals with schizophrenia. In a 2-year, prospective, case-control study, 23 consecutively referred, clinically stabilized schizophrenia patients received the new intervention over an 8-month period; 31 patients on the wait list, considered the control group, received standard clinical care that included some recreational activities. Symptom severity, self-esteem, self-appraised cognitive abilities, and functioning were documented for both groups with standardized rating scales administered at baseline, on completion of treatment, and at 12 months posttreatment. Treatment adherence was 97%, and there were no dropouts. Patients in the study group showed marginal improvement in perceived cognitive abilities and on domain-specific functioning measures but experienced a significant improvement in their self-esteem and global functioning (P < 0.05), as well as a weight loss of over 12 lb. Improvement was sustained over 1 year with further occupational and social gains. In the context of overcoming barriers to providing early intervention for youth and preventing metabolic problems among older adults with schizophrenia, adventure- and recreation-based interventions could play a useful complementary role.


Validation of Self-Assessed Form of Diagnostic Criteria for Psychosomatic Research Adapted from Diagnostic Criteria for Psychosomatic Research - Structured Interview.
As the diagnostic criteria for psychosomatic research-structured interview (DCPR-SI) is a rater-assessed questionnaire, it has not been used vastly in community-based studies and clinics. Describing and investigating self-assessed form of DCPR are an attempt to apply it easier and more worthwhile for medical settings. The aim of this study was to describe and present self-assessed form of DCPR self-assessed (DCPR-SA) and test its validity and reliability. The DCPR-SI was translated to Persian according to the best practice methodology and the guideline for adaptation of self-report measures. In this cross-sectional study, 540 patients and healthy individuals were recruited and answered DCPR-SA and some related questionnaires. Inter-rater (test-interview) and test-retest reliability were determined. Construct, concurrent, discriminant, and known-group validity were tested. The kappa coefficients were expressed substantial and almost perfect agreement (0.617-0.784, P ≤ 0.05). In addition, phi correlation coefficients were indicated adequate test-retest reliability for each cluster (0.548-0.754, P ≤ 0.05). Three domains (anxiety-related symptoms, functional symptoms, and dysfunctional traits and emotional patterns) were confirmed by factor analysis. The results of the discriminate validity analysis were promising. The findings show that the DCPR-SA is valid and reliable and can be used by medical professionals as a psychosomatic screening tool and can be used properly in Persian-speaking population.


[Alteration of ion channel gene expression profile in rat model of post-myocardial infarction heart failure].
To investigate the ion channel genes related with the genesis and development of heart failure after myocardial infarction through analyzing the differential gene expressions in non-infarcted myocardial tissues of post-myocardial infarction heart failure (PIHF) rat model, and that of normal rat, and the bio-informatics Stc-GO analysis on them. Rat model of PIHF was established by left anterior descending coronary artery ligation in six SD rats, and a control group with six sham-operative rats was set. Myocardial samples were taken in two batches from them (three rats in each group) at the heart failure formation stage and the stable stage (10 days and 8 weeks after operation) respectively. Total RNA extraction, probe preparation with reverse transcription, hybridization with double-channel cDNA microarray of rat's ion channel genes, and computerized differential gene expression screening were conducted, and Stc-GO functional clustering analysis was performed on the outcomes obtained to search out the GO sort of significance in them. At 10 days after operation, 319 common differential expressed genes were found from the 746 target genes, all of them were up-regulated. At 8 weeks after operation, in the 276 differential expressed genes, 274 were up-regulated while the other two down-regulated. The up-regulated genes were those concerning receptors of various hormones, cytokines, neuro-hormones, growth factors and nuclear receptor, protein phosphorylase, G protein, various ion channels mediated by ligand or voltage, transport protein, receptor interfering protein, etc. The down-regulated genes concerning the potassium channel and transport protein, etc. Stc-GO analysis found that the six genes concerning adrenergic receptor kinase beta 1 (betaARK1), amiloride-sensitive cation channel 2 neuronal (Accn2), voltage-dependent calcium ion channel gamma subunit 1 (Cacng1), cyclic nucleotide gated channel alpha 1 (Cnga1), Glutamate receptor ionotropic kainite 2 (Grik 2) and neurotrophic tyrosine kinase receptor type 2 (Ntrk 2), were all the significantly up-regulated differential genes of the model group related with the sham-operative group, and all showed a down-regulating trend as time goes on, and four genes in them were validated by the RT-PCR test. Ion channel genes concerning Accn2, Grik2, Ntrk2 and Cacng1 were up-regulated in PIHF, and its mechanism is waiting for further study.


The effect of beta-naphthoflavone on the metabolism of amiodarone by hepatic and extra-hepatic microsomes.
Amiodarone is a potent antiarrhythmic drug with several limiting side effects, some of which have been correlated with increased levels of its more toxic metabolite, desethylamiodarone. Elevated serum desethylamiodarone to amiodarone ratios are associated with a risk of amiodarone-induced pulmonary toxicity. Polycyclic aromatic hydrocarbons such as beta-naphthoflavone are known to increase desethylamiodarone levels in rat in vivo. In this article we investigated if this increase was solely due to increased formation as a result of cytochrome P450 (CYP) 1A1 and 1A2 induction in different rat hepatic and extra-hepatic tissues. Additionally, the effect of amiodarone treatment on CYP1A1 and 1A2 gene expression and activity was investigated. In rats, beta-naphthoflavone was found to increase desethylamiodarone forming activity in lung and kidney microsomes. Amiodarone increased beta-naphthoflavone mediated induction of CYP1A1 gene expression in liver, lung and kidney. However, there was no significant change in CYP1A activity. As expected, the data indicated that the increase in desethylamiodarone levels in vivo was partly due to increased formation through CYP1A1 induction, although increased formation was only evident in some extra-hepatic tissues. Amiodarone treatment did not affect basal or induced CYP1A activity.


Food Allergens and Essential Oils in Moisturizers Marketed for Children in Japan.
Introduction Personal skincare leave-on products increase the risk of food allergies. Parents must be imparted with an elevated degree of cognizance regarding the allergenic nature of pediatric skincare products. Material and methods We aimed to examine the data inferred from the promotional material on labeling these products about their proclivity to elicit skin sensitization. This study investigated the relationship between food allergens and essential oil ingredients and highlighted marketing terms, product prices, and ratings of moisturizers for children that are sold on Amazon, Japan. We searched and recorded the product labels and website marketing terms, price (per gram or milliliter), the number of reviews, and allergens and investigated the relationship between the percentage of food allergens in those products and marketing terms, price, and the number of Amazon reviews. Results Among the 164 pediatric skincare products we included, 144 (87.8%) that were manufactured in Japan were the most common; 7 (4.3%), 15 (9.1%), 23 (14.0%), 24 (14.6%), and 54 (32.9%) contained the eight regulated food allergens, grain, nut, fruit, and essential oils, respectively. Marketing terms emphasizing "natural/organic" were more likely to contain grain allergens and essential oils and were more expensive with and without "organic" labeling, respectively, whereas those labeled with marketing terms emphasizing "hypoallergenic" were less likely to contain fruit allergens or essential oils. Products with fewer Amazon reviews were more likely to use the marketing term "natural/organic" and had a higher grain allergen content. Conclusion In Japan, 4.3% of children's skincare products sold on Amazon contain eight food allergens that should obligatorily be labeled when included in food products. In addition, more than 10% of these children's skin care products contain ingredients derived from nuts, while more than 30% contain fruit extracts or essential oils.


[The clinico-morphological characteristics, diagnosis and treatment of early stomach cancer].
Data on 90 patients with gastric carcinoma involving only the mucosa of the stomach wall are presented. All the patients were operated upon according to oncological principles. No regional metastasizing was observed at this level of invasion. Squamous-infiltrative tumors were found to be most typical (46.7%). Five-years survival after radical surgical treatment was 90.3%.


Small heterodimer partner deletion prevents hepatic steatosis and when combined with farnesoid X receptor loss protects against type 2 diabetes in mice.
Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are important regulators of bile acid, lipid, and glucose homeostasis. Here, we show that global Fxr -/- Shp-/- double knockout (DKO) mice are refractory to weight gain, glucose intolerance, and hepatic steatosis when challenged with high-fat diet. DKO mice display an inherently increased capacity to burn fat and suppress de novo hepatic lipid synthesis. Moreover, DKO mice were also very active and that correlated well with the observed increase in phosphoenolpyruvate carboxykinase expression, type IA fibers, and mitochondrial function in skeletal muscle. Mechanistically, we demonstrate that liver-specific Shp deletion protects against fatty liver development by suppressing expression of peroxisome proliferator-activated receptor gamma 2 and lipid-droplet protein fat-specific protein 27 beta. These data suggest that Fxr and Shp inactivation may be beneficial to combat diet-induced obesity and uncover that hepatic SHP is necessary to promote fatty liver disease. (Hepatology 2017;66:1854-1865).


Knee Viscosupplementation: Cost-Effectiveness Analysis between Stabilized Hyaluronic Acid in a Single Injection versus Five Injections of Standard Hyaluronic Acid.
Given the wide difference in price per vial between various presentations of hyaluronic acid, this study seeks to compare the effectiveness and treatment cost of stabilized hyaluronic acid (NASHA) in a single injection with standard preparations of hyaluronic acid (HA) in five injections in osteoarthritis (OA) of the knee. Fifty-four patients with knee osteoarthritis (Kellgren-Lawrence Grade II and III) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score greater than 7, with a homogeneous distribution of age, sex, BMI, and duration of disease, were included in this study. Patients were randomized into two groups: Group I was treated with NASHA (Durolane®) and Group II with HA (Go-ON®). Patient's evolution was followed up at the 1st, 2nd, 4th, 8th, 12th, and 26th week after treatment. A statistically significant improvement in WOMAC score was observed for patients treated with NASHA versus those who received HA at Week 26. In addition, the need for analgesia was significantly reduced at Week 26 in the NASHA-treated group. Finally, the economic analysis showed an increased cost of overall treatment with HA injections. Our data support the use of the NASHA class of products in the treatment of knee OA.


[Study on the status of oral pharyngeal carriage of Haemophilus influenzae in healthy preschool children in Fuzhou city].
To study the status of oral pharyngeal carriage and characteristics of Haemophilus influenzae (Hi) in healthy preschool children in Fuzhou. Six hundred and three healthy children in two representative kindergartens in Fuzhou were studied as research subjects, and the rates of oral pharyngeal carriage of Hi were studied in four seasons. All Hi strains were serotyped and biotyped. The oral pharyngeal carriage of Hi in day care nursery healthy children were 36.7% in winter, 18.0% in autumn, 12.4% in summer and 10.9% in spring respectively. Serotype Hib was preponderant in autumn (6.9%). In winter, the carriage rates of NTHi and Hib were 17.1%, 5.4% respectively. The carriage rates of other serotypes were low. Biotype VII and VIII were preponderant in autumn, spring and summer but biotype VII and VIII were decreasing evidently in winter. There was evident seasonal difference in the rates of oral pharyngeal carriage and type of Hi in healthy preschool children. The carriage rate of Hi strains was high in autumn and winter. Results suggested that while the inoculation of Hib-binding bacterial vaccine was expanded the study on new bacterial vaccine of Hi still needs to be augmented.


miR-5003-3p promotes epithelial-mesenchymal transition in breast cancer cells through Snail stabilization and direct targeting of E-cadherin.
One of the initial steps in metastatic dissemination is the epithelial-mesenchymal transition (EMT). Along this line, microRNAs (miRNAs) have been shown to function as important regulators of tumor progression at various stages. Therefore, we performed a functional screening for EMT-regulating miRNAs and identified several candidate miRNAs. Among these, we demonstrated that miR-5003-3p induces cellular features characteristic of EMT. miR-5003-3p induced upregulation of Snail, a key EMT-promoting transcription factor and transcriptional repressor of E-cadherin, through protein stabilization. MDM2 was identified as a direct target of miR-5003-3p, the downregulation of which induced Snail stabilization. E-cadherin was also demonstrated to be a direct target of miR-5003-3p, reinforcing the EMT-promoting function of miR-5003-3p. In situ hybridization and immunohistochemical analyses using tissue microarrays revealed that miR-5003-3p expression was higher in paired metastatic breast carcinoma tissues than in primary ductal carcinoma tissues, and was inversely correlated with the expression of MDM2 and E-cadherin. Furthermore, miR-5003-3p enhanced the formation of metastatic nodules in the lungs of mice in a tail vein injection experiment. Collectively, our results suggest that miR-5003-3p functions as a metastasis activator by promoting EMT through dual regulation of Snail stability and E-cadherin, and may therefore be a potential therapeutic target in metastatic cancers.


Sleep quality, stress level and COVID-19 in university students; the forgotten dimension.
COVID-19 is a novel pandemic that has had a profound impact on global physical and psychological health. We aimed to investigate the impact of COVID-19 on stress, sleep quality, and insomnia among South Valley University students in Egypt during the quarantine period. A questionnaire, including the Pittsburgh sleep quality index, the insomnia severity index, the perceived stress scale and COVID-19 fear index was distributed to the undergraduate students through the online platforms of South Valley University during the period of 1st to 15th June 2020. Of a total respondent sample of 2,474 students, 24.5% had high-perceived stress levels, 31.3% had clinical insomnia, and about 80% were identified as generally poor sleepers by the PSQI. Being female, having a chronic disease, having a sleep disorder before the quarantine, or consuming caffeine were the main factors associated with high stress levels, clinical insomnia, and poor sleep quality. Also, levels of fear of COVID-19 were higher among people with high stress levels, clinical insomnia, and poor sleep quality. Considerable levels of stress and poor sleep quality were identified among undergraduate university students during the pandemic/home isolation period. The effect was more obvious among certain demographic groups and among the students who scored higher in the fear of COVID-19 scale.


An Efficient and Secure Alert System for VANETs to Improve Crosswalks' Security in Smart Cities.
A key characteristic of Smart Cities is the ability to reduce conflicts between different agents coexisting in a dynamic system, such as the interaction between vehicles and pedestrians. This paper presents a system to augment the awareness of vehicle drivers regarding the presence of pedestrians in nearby crosswalks. The proposed system interconnects Road Side Units (RSUs), which are informed about the state of the crosswalks, and vehicles, in order to spread to vehicles, the information about the presence of pedestrians in crosswalks. To prevent false information spreading, RSUs sign the alert messages they broadcast and all vehicles can validate the signatures. This poses strong security requirements, such as non-repudiation of alert messages, as well as strong real-time requirements, such as minimum message validation delays among vehicles approaching a crosswalk of interest. To manage the signed alert messages, we are proposing Nimble Asymmetric Cryptography (NAC), which authenticates implicit broadcast messages. NAC minimizes the usage of asymmetric ciphers, which are fundamental to assure non-repudiation but increase performance penalties and uses hash chaining for source authentication of implicit messages.


Evidence that HetR protein is an unusual serine-type protease.
The hetR gene plays a very important role in cell differentiation of heterocystous cyanobacteria. To understand the mechanism of the hetR gene product in regulation of heterocyst differentiation, the recombinant HetR protein (rHetR) was overproduced in Escherichia coli. Purified rHetR was unstable and degraded easily in solution. Phenylmethanesulfonyl fluoride, a serine-type protease inhibitor, prevented the degradation and was shown to modify covalently rHetR. Dansyl fluoride (DnsF), another serine-type protease inhibitor, also covalently modifies rHetR as shown by electrophoresis and electroblotting of the labeled rHetR and by MS. The labeling of rHetR with phenylmethanesulfonyl fluoride and DnsF was at the same site of rHetR and required Ca2+. S179N-rHetR, a mutant protein from strain 216 of Anabaena PCC 7120, which cannot differentiate heterocysts because of the mutation, was also overproduced and characterized. Although S170N-rHetR still can be labeled with DnsF, no proteolysis was observed, suggesting that Ser179 is involved in proteolytic activity. DnsF-labeled rHetR was digested with trypsin, and the labeled peptide was isolated and sequenced. The labeled peptide matches a sequence from HetR. These results show that HetR is a protease.


A molecular genetics laboratory course applying bioinformatics and cell biology in the context of original research.
Research based laboratory courses have been shown to stimulate student interest in science and to improve scientific skills. We describe here a project developed for a semester-long research-based laboratory course that accompanies a genetics lecture course. The project was designed to allow students to become familiar with the use of bioinformatics tools and molecular biology and genetic approaches while carrying out original research. Students were required to present their hypotheses, experiments, and results in a comprehensive lab report. The lab project concerned the yeast casein kinase 1 (CK1) protein kinase Yck2. CK1 protein kinases are present in all organisms and are well conserved in primary structure. These enzymes display sequence features that differ from other protein kinase subfamilies. Students identified such sequences within the CK1 subfamily, chose a sequence to analyze, used available structural data to determine possible functions for their sequences, and designed mutations within the sequences. After generating the mutant alleles, these were expressed in yeast and tested for function by using two growth assays. The student response to the project was positive, both in terms of knowledge and skills increases and interest in research, and several students are continuing the analysis of mutant alleles as summer projects.


The clinical pharmacology of antihypertensive drugs.
Antihypertensive drugs act centrally (methyldopa, clonidine, guanabenz), peripherally (prazosin, guanadrel, guanethedine, hydralazine, minoxidil), centrally and peripherally (beta-adrenergic blocking drugs) and systemically [angiotensin converting enzyme (ACE) inhibitors and diuretics]. Centrally-acting antihypertensives decrease blood pressure by diminishing sympathetic outflow from the vasomotor centre. Peripherally-acting antihypertensives act by depleting or inhibiting the release of catecholamines from the peripheral nerve ending or altering the response at alpha 1- and alpha 2-receptor sites. Beta-adrenergic blocking drugs act through a variety of mechanisms by either decreasing cardiac output, decreasing renin release, inhibiting prejunctional release of norepinephrine or through central mechanisms. Diuretics act as indirect vasodilators by depleting salt and water not only within the intravascular compartment but within the intramural portion of the arteriole, thereby diminishing its responsiveness to catecholamine and angiotensin II stimulation. ACE inhibitors such as captopril and enalapril act by inhibiting the conversion of angiotensin I to angiotensin II thereby decreasing the vasoconstrictor effect of angiotensin II and the aldosterone production secondary to angiotensin II stimulation. The main differences between captopril and enalapril is that enalapril does not possess the potentially toxic sulphydryl group and can be given twice-daily. Both drugs may show accumulation in patients with impaired renal function.


Rapid Quantitative Point-Of-Care Diagnostic Test for Post COVID-19 Vaccination Antibody Monitoring.
Point-of-care (POC) quantification of antibody responses against SARS-CoV-2 spike protein can enable decentralized monitoring of immune responses after infection or vaccination. We evaluated a novel POC microfluidic cartridge-based device (ViroTrack Sero COVID-19 Total Ab) for quantitative detection of total antibodies against SARS-CoV-2 spike trimeric spike protein compared to standard laboratory chemiluminescence (CLIA)-based tests. Antibody responses of 101 individuals were measured on capillary blood, venous whole blood, plasma, and diluted plasma samples directly on the POC. Results were available within 7 min. As the reference, plasma samples were analyzed on DiaSorin LIAISON XL CLIA analyzer using LIAISON SARS-CoV-2 IgM, LIAISON SARS-CoV-2 S1/S2 IgG, and LIAISON SARS-CoV-2 TrimericS IgG assays. The Spearman rank's correlation coefficient between ViroTrack Sero COVID-19 Total Ab and LIAISON SARS-CoV-2 S1/S2 IgG and LIAISON SARS-CoV-2 TrimericS IgG assays was found to be 0.83 and 0.89, respectively. ViroTrack Sero COVID-19 Total Ab showed high correlation between the different matrixes. Agreement for determination of samples of >230 binding antibody units (BAU)/mL on POC and CLIA methods is estimated to be around 90%. ViroTrack Sero Covid Total Ab is a rapid and simple-to-use POC test with high sensitivity and correlation of numerical results expressed in BAU/mL compared to those of a commercial CLIA assay. IMPORTANCE Serological testing is an important diagnostic support tool in the fight against COVID-19. So far, serological testing has been performed on either lateral flow assays, which perform only qualitatively and can be difficult for the individual to read, or standard laboratory assays, which are time- and resource-consuming. The purpose of the study was to evaluate the performance of a new POC microfluidic cartridge-based device based on immunomagnetic agglutination assay that can provide an accurate numerical quantification of the total antibodies within only 7 min from a single drop of capillary blood. We demonstrated a high level of correlation between the POC and the two CLIA laboratory-based immunoassays from Diasorin, thus allowing a potentially wider use of quantitative serology tests in the COVID-19 pandemic.


[Indoleamine 2,3-Dioxygenase Activity during Fulvestrant Therapy for Aromatase Inhibitor-Resistant Metastatic Breast Cancer].
We evaluated the clinical significance of indoleamine 2,3-dioxygenase (IDO) during fulvestrant therapy for aromatase inhibitor (AI)-resistant metastatic breast cancer. IDO activity can be measured by the tryptophan (Trp)/kynurenine (Kyn) ratio. Trp and Kyn were measured with high performance liquid chromatography (HPLC). Patients with AI resistant metastatic breast cancer had a 28.6% response rate to fulvestrant therapy, and the clinical benefit rate was 76.2%. AI-resistant metastatic breast cancer patients with distant metastases had a lower serum Trp/Kyn level than patients who had local recurrences. During fulvestrant therapy, IDO activity significantly decreased in the fulvestrant responder group compared to that in the fulvestrant non-responder group. During fulvestrant therapy, the IDO activity correlated with the number of metastatic lesions. These results suggest that measuring the Trp/Kyn ratio is useful for evaluating immunological metastatic status during endocrine therapy.


Constraining cyclic peptides to mimic protein structure motifs.
Many proteins exert their biological activities through small exposed surface regions called epitopes that are folded peptides of well-defined three-dimensional structures. Short synthetic peptide sequences corresponding to these bioactive protein surfaces do not form thermodynamically stable protein-like structures in water. However, short peptides can be induced to fold into protein-like bioactive conformations (strands, helices, turns) by cyclization, in conjunction with the use of other molecular constraints, that helps to fine-tune three-dimensional structure. Such constrained cyclic peptides can have protein-like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three-dimensional structures of strand, turn or helical segments of peptides and proteins, and identifies some additional restraints incorporated into natural product cyclic peptides and synthetic macrocyclic peptidomimetics that refine peptide structure and confer biological properties.


[Estimation of past infection HAV frequency among health personnel].
There were made inquires about estimating of past HAV infection frequency among people working in Province Hospital for Infectious Diseases, Surgery Clinics and in Intensive Medical Care Department of Medical School in Gdańsk. Frequency of antibody-HAV Ig "total" prevalence was a little lower compared to other inquiries of adults population in Poland. Its dependence on age of examined people was very essential. In statistical estimation of examined groups of workers being employed on different posts, it has not been stated any difference in anti-HAV Ig "total" prevalence for people over 35 years old. For people under 35-evidence of HAV infection in the past was really found out more often for workers of infectious departaments.


Defective expression of beta 1-integrins in cells with constitutively active alpha L beta 2-integrins.
We have investigated a potential relationship between expression of beta 1-integrins and adhesiveness of the beta 2-integrin LFA-1 (alpha L beta 2, CD11a/CD18). By an approach of random mutagenesis and selection we established clones from the human acute lymphatic leukemia cell line HPB-ALL with (i) constitutively active LFA-1 and (ii) with no apparent integrin-beta 1 cell surface expression. Thirty-seven of 42 clones selected for activated LFA-1 were found to have lost apparent integrin-beta 1 expression. Conversely, 7 of 21 clones selected for lack of beta 1 expression were found to have activated LFA-1. Since this pointed toward a possible coupling between beta 1 expression and LFA-1 activity, we further analyzed at which level beta 1 expression was blocked. We focused on one clone, HAP4, with activated LFA-1 and no detectable beta 1 cell surface expression and found, surprisingly, that it expressed wild-type levels of beta 1 mRNA and, in Western blots of whole cell lysates, apparently normal levels of beta 1 protein. However, in addition to beta 1 of the expected molecular weight, HAP4 expressed a unique 48-kDa band recognized by the polyclonal anti-beta 1 antiserum. Immunoprecipitation experiments revealed that the epitope recognized by the anti-beta 1 antibody 4B4 was hidden or lost. The alpha 4-chain was found in its precursor form but it did not associate with any beta-chain, and it was not processed to its mature form. Instead alpha 4-chains were eventually degraded. Taken together this showed that beta 1-chains were produced but not properly processed in HAP4. From this we propose that HAP4 is deficient in a gene product required both for proper beta 1 folding and for repression of LFA-1 adhesiveness.


[Molecular mechanisms of the action of local anesthetics].
Raman spectroscopy revealed a suppression of the polyene chain of C40-carotenoids in membrane of the frog nerve during local action of an anesthetic agent in resting and excitation. The phosphatidylcholine binding decreased during rhythmic excitation and local anesthetic action. A mechanism of potential-dependent changes of the carotenoid conformation during local anesthetic action, was discussed.


Long-term toxicological effects of persistent luminescence nanoparticles after intravenous injection in mice.
The ZnGa1.995Cr0.005O4 persistent luminescence nanoparticles offer the promise of revolutionary tools for biological imaging with applications such as cell tracking or tumor detection. They can be re-excited through living tissues by visible photons, allowing observations without any time constraints and avoiding the undesirable auto-fluorescence signals observed when fluorescent probes are used. Despite all these advantages, their uses demand extensive toxicological evaluation and control. With this purpose, mice were injected with a single intravenous administration of hydroxylated or PEGylated persistent luminescence nanoparticles at different concentrations and then a set of standard tests were carried out 1day, 1 month and 6 months after the administration. High concentrations of hydroxylated nanoparticles generate structural alterations at histology level, endoplasmic reticulum damage and oxidative stress in liver, as well as rising in white blood cells counts. A mechanism involving the endoplasmic reticulum damage could be the responsible of the observed injuries in case of ZGO-OH. On the contrary, no toxicological effects related to PEGylated nanoprobes treatment were noted during our in vivo experiments, denoting the protective effect of PEG-functionalization and thereby, their potential as biocompatible in vivo diagnostic probes.


Effect of high concentrations of bile acids on cultured hepatocytes.
High concentrations of bile acids have been reported as injurious to hepatocytes. We report the influence of various combinations of bile acids on the liver-specific function of cultured rat hepatocytes. Using 4 bile acids (glycocholate [GC], taurocholate [TC], glycohenodeoxycholate [GCDC], and taurochenodeoxycholate [TCDC]), we obtained 6 bile-acid mixtures, each containing equal amounts of 2 bile acids (total bile acids [TBA], 2 mM). Changes in gluconeogenesis, ureagenesis, DNA contents, medium alanine aminotransferase, and morphologies were compared among the paired bile acid compositions by measuring the C/CDC ratio ([GC + TC]/[GCDC + TCDC]) of each. In terms of their relative impairments of ureagenesis from greatest to least, the acids were GCDC, TCDC, and GC, which was almost the same as TC. When the C/CDC ratio was 0, the values of all parameters measured deteriorated. When the C/CDC ratio was 1 in the presence of 1 mM GCDC, only the rate of ureagenesis was diminished. When the C/CDC ratio was infinite, no hepatocellular injury was observed. GCDC and TCDC, together or separately, showed significant hepatocellular injury when the TBA concentration was 2 mM.


Genetic Transformation of Artemisia carvifolia Buch with rol Genes Enhances Artemisinin Accumulation.
The potent antimalarial drug artemisinin has a high cost, since its only viable source to date is Artemisia annua (0.01-0.8% DW). There is therefore an urgent need to design new strategies to increase its production or to find alternative sources. In the current study, Artemisia carvifolia Buch was selected with the aim of detecting artemisinin and then enhancing the production of the target compound and its derivatives. These metabolites were determined by LC-MS in the shoots of A. carvifolia wild type plants at the following concentrations: artemisinin (8μg/g), artesunate (2.24μg/g), dihydroartemisinin (13.6μg/g) and artemether (12.8μg/g). Genetic transformation of A. carvifolia was carried out with Agrobacterium tumefaciens GV3101 harboring the rol B and rol C genes. Artemisinin content increased 3-7-fold in transgenics bearing the rol B gene, and 2.3-6-fold in those with the rol C gene. A similar pattern was observed for artemisinin analogues. The dynamics of artemisinin content in transgenics and wild type A.carvifolia was also correlated with the expression of genes involved in its biosynthesis. Real time qPCR analysis revealed the differential expression of genes involved in artemisinin biosynthesis, i.e. those encoding amorpha-4, 11 diene synthase (ADS), cytochrome P450 (CYP71AV1), and aldehyde dehydrogenase 1 (ALDH1), with a relatively higher transcript level found in transgenics than in the wild type plant. Also, the gene related to trichome development and sesquiterpenoid biosynthesis (TFAR1) showed an altered expression in the transgenics compared to wild type A.carvifolia, which was in accordance with the trichome density of the respective plants. The trichome index was significantly higher in the rol B and rol C gene-expressing transgenics with an increased production of artemisinin, thereby demonstrating that the rol genes are effective inducers of plant secondary metabolism.


Noninvasive detection of airway constriction in awake guinea pigs.
Tidal volume measured by the barometric method is very sensitive to increases in compression and expansion of alveolar gas, such as would be expected to occur during airway narrowing or closure. By comparing a barometric method tidal volume signal (VT') with a reference tidal volume (VT) obtained with a head-out pressure plethysmograph, a simple index related to gas compressibility effects was calculated (VT/VT'). Changes in this index were compared with decreases in dynamic compliance (Cdyn) during histamine aerosol challenge of 15 Charles River Hartley guinea pigs. Decreases in VT/VT' occurred during all aerosol challenges and were correlated with decreases in Cdyn (r = 0.84, P less than 0.001). Decreases in VT/VT' were most marked at Cdyn values of less than 50% of base line. At Cdyn of less than 15% of base line, VT' was 3.1-4.8 times the VT reference signal. No increase in total pulmonary resistance was noted, and Cdyn and VT/VT' returned to base line after histamine exposure was stopped. We conclude that gas compressibility effects become substantial during histamine-induced airway constriction in the guinea pig and that the VT/VT' ratio appears to provide a simple noninvasive method of detecting these changes.


Comparative Analysis of Urinary Total Proteins by Bicinchoninic Acid and Pyrogallol Red Molybdate Methods.
The concentration of total proteins in urine is a good index of renal function, but its determination is found to be unreliable. The pyrogallol red molybdate (PRM) method for urine total proteins is being widely used in most of the hospitals because of its high sensitivity, better precision and its practicability. Bicinchoninic acid method (BCA) is also used for protein estimation and there have been no studies comparing this method with the PRM method in human urine samples. BCA method overestimates the urinary protein concentration in the presence of interfering substances. After removing the interfering substances present in the human urine samples the results of BCA method were compared with the PRM method. The purpose of the study is to identify whether the results of urine total proteins by BCA method are comparable to PRM method and can be used as an alternative to the PRM method. This is a cross-sectional study done on fresh urine specimens from the hospital laboratory, covering a wide range of protein concentrations. Fresh urine specimens covering a wide range of protein concentrations (urine dipstick: nil, trace, 1+, 2+ and ≥ 3+) of 36 patients were analysed by both the methods. Imprecision was determined by repeated analysis study and Inaccuracy was assessed by comparing the results of the patient's urine samples by both the methods using correlation plots, Bland and Altman, and Passing and Bablok regression analyses. The coefficient of variation and mean (SD) for the BCA method were 4.6% and 799.1 (882.5) mg/L and for the PRM method were 5.1% and 802.1 (911.9) mg/L. The Pearson correlation coefficient, r was 0.93 (p < 0.0001). Method agreement studies showed no significant constant and proportional bias between both the methods. In urine which is subjected to removal of interfering substances, the BCA results are comparable to PRM method.


Choosing Inpatient vs Home Treatment: Why Patients Accept or Decline Hospital at Home.
Hospital at home (HaH) provides interdisciplinary acute care in the home as a substitute for inpatient hospitalization. Studies have demonstrated that HaH care is associated with better quality care, fewer complications, and better patient and caregiver experience. Still, some patients decline HaH. The objective of the study was to characterize patients who accept vs decline HaH care and describe reasons for their decisions in the context of a Center for Medicare and Medicaid Innovation demonstration of HaH. A total of 442 patients with Medicare or other eligible insurance, 18 years or older, who met study eligibility criteria were offered HaH at Mount Sinai Hospitals in New York, NY, between September 1, 2014, and August 31, 2017. Reasons for accepting or declining HaH were recorded. Age, sex, insurance type, and admission diagnoses of HaH acceptors and refusers were compared in univariate analyses. Of the 442 patients offered HaH, 66.7% accepted. Main reasons for enrolling in HaH included being more comfortable at home (78.2%) and being near family (40.7%). Specific reasons given for refusing HaH included preferring in-hospital care (15.0%) and concern that HaH would not meet care needs (12.9%). Two-thirds of patients offered HaH care opted to receive it. The reasons for declining HaH provided by those who chose not to participate should be considered for quality improvement, and reasons for acceptance may be helpful in marketing and other efforts to promote HaH participation. J Am Geriatr Soc 68:1579-1583, 2020.


Transgastral retroperitoneal endoscopy in septic patients with pancreatic necrosis or infected pancreatic pseudocysts.
Peripancreatic fluid collections are common complications of acute pancreatitis or acute exacerbations of chronic pancreatitis. Surgery is required when these fluid collections become infected or cause obstruction or pain. However, morbidity and mortality after surgery in these cases are still too high, therefore minimally invasive approaches have been encouraged. The aim of this study was to evaluate the feasibility of endoscopic ultrasound-guided transmural drainage with intracystic endoscopy and necrosectomy. From 2000 to 2006 30 patients (age: 57 +/- 10 years, range: 34 - 74 years) with an infected pancreatic pseudocyst or infected pancreatic necrosis were included in the study. The diagnosis of infection in patients who had fever despite an adequate antibiotic regime was confirmed by endoscopic fine needle aspiration with a positive bacterial or mycological result. The mean C-reactive protein value before treatment was 202 +/- 58 mg/L and the mean leukocyte count was 13.25 +/- 4.75 GPt/L. Transgastric cyst drainage was performed using a therapeutic endoscopic ultrasound probe (Pentax 38 UX or Olympus GF UCT 140) with insertion of an 8-Fr double pigtail prosthesis. After balloon dilatation (12 mm) a normal gastroscope was inserted into the cavity and all the fluid and easy removable necrosis were removed. The prosthesis was removed 4 weeks after the end of the endoscopic treatment. Clinical and ultrasound follow-up were carried out 3 and 6 months after removal of the prosthesis. The mean follow-up was 60 weeks. The technical success of the procedure was 96.7 %, the long-term success was 83.4 %. On average 2.7 (range: 1 - 16) procedures were necessary for complete removal of necrosis and the remaining fluid. Major complications (bleeding, perforation, fistulation) occurred in 10 %. In 10 % a secondary operation was necessary. The overall mortality rate was 6.6 %. Endoscopic treatment of infected pseudocysts and infected postacute pancreatic necrosis using transgastral retroperitoneal endoscopy with fluid and necrosis removal is a minimally invasive and effective procedure in patients with acute pancreatitis or acute exacerbation of chronic pancreatitis. However, the mortality rate of 6.6 % has to be taken into account.


Nutrient fluxes through sponges: biology, budgets, and ecological implications.
Marine sponges are able to process a variety of carbon (C), nitrogen (N), phosphorous (P), and silicon (Si) dissolved compounds, in addition to the particulate C, N, and P obtained through regular feeding. While Si fluxes through sponges are exclusively related to the elaboration of their skeleton of biogenic silica, C, N, and P fluxes derive from a complex combination of metabolic processes that include feeding, respiration, egestion, excretion, as well as hosting of large microbial populations within the sponge body. Because of the remarkable abundance of sponges in many benthic marine communities, they have the potential to impact the availability of the compounds they take up and release, affecting the benthic-pelagic coupling and cycling rates of chemical elements that are crucial to determine growth of bacterioplankton and primary producers at the ecosystem level. Unfortunately, our knowledge and understanding of the magnitude of the sponge-meditated nutrient fluxes and their ecological implications depends much on the compound type (i.e. C, N, P, or Si). Herein, we review the available knowledge on the subject with emphasis on recent developments.


DNA Barcode Authentication and Library Development for the Wood of Six Commercial Pterocarpus Species: the Critical Role of Xylarium Specimens.
DNA barcoding has been proposed as a useful tool for forensic wood identification and development of a reliable DNA reference library is an essential first step. Xylaria (wood collections) are potentially enormous data repositories if DNA information could be extracted from wood specimens. In this study, 31 xylarium wood specimens and 8 leaf specimens of six important commercial species of Pterocarpus were selected to investigate the reliability of DNA barcodes for authentication at the species level and to determine the feasibility of building wood DNA barcode reference libraries from xylarium specimens. Four DNA barcodes (ITS2, matK, ndhF-rpl32 and rbcL) and their combination were tested to evaluate their discrimination ability for Pterocarpus species with both TaxonDNA and tree-based analytical methods. The results indicated that the combination barcode of matK + ndhF-rpl32 + ITS2 yielded the best discrimination for the Pterocarpus species studied. The mini-barcode ndhF-rpl32 (167-173 bps) performed well distinguishing P. santalinus from its wood anatomically inseparable species P. tinctorius. Results from this study verified not only the feasibility of building DNA barcode libraries using xylarium wood specimens, but the importance of using wood rather than leaves as the source tissue, when wood is the botanical material to be identified.


Unprecedented therapeutic potential with a combination of A2A/NR2B receptor antagonists as observed in the 6-OHDA lesioned rat model of Parkinson's disease.
In Parkinson's disease, the long-term use of dopamine replacing agents is associated with the development of motor complications; therefore, there is a need for non-dopaminergic drugs. This study evaluated the potential therapeutic impact of six different NR2B and A2A receptor antagonists given either alone or in combination in unilateral 6-OHDA-lesioned rats without (monotherapy) or with (add-on therapy) the co-administration of L-Dopa: Sch-58261+ Merck 22; Sch-58261+Co-101244; Preladenant + Merck 22; Preladenant + Radiprodil; Tozadenant + Radiprodil; Istradefylline + Co-101244. Animals given monotherapy were assessed on distance traveled and rearing, whereas those given add-on therapy were assessed on contralateral rotations. Three-way mixed ANOVA were conducted to assess the main effect of each drug separately and to determine whether any interaction between two drugs was additive or synergistic. Additional post hoc analyses were conducted to compare the effect of the combination with the effect of the drugs alone. Motor activity improved significantly and was sustained for longer when the drugs were given in combination than when administered separately at the same dose. Similarly, when tested as add-on treatment to L-Dopa, the combinations resulted in higher levels of contralateral rotation in comparison to the single drugs. Of special interest, the activity observed with some combinations could not be described by a simplistic additive effect and involved more subtle synergistic pharmacological interactions. The combined administration of A2A/NR2B-receptor antagonists improved motor behaviour in 6-OHDA rats. Given the proven translatability of this model such a combination may be expected to be effective in improving motor symptoms in patients.


The effect of target speed on perception of visual motion direction in a patient with akinetopsia.
Although much research has been devoted to the neural correlates of motion perception, the processing of speed of motion is still a topic of discussion. Apart from patient LM, no in-depth clinical research has been done in the past 20 years on this topic. In the present study, we investigated patient TD, who suffered from the rare disorder akinetopsia due to bilateral lesions of V5 after stroke. By means of a Random-Dot-Kinematogram (RDK) in which speed was varied systematically, it was found that TD was impaired in perceiving the direction of movement at speeds exceeding 9 deg/s. Our study suggests that V5 plays an important role in processing high-speed visual motion and further implies that V5 does not play a crucial role in processing low-speed visual motion. A remarkable finding, which has not been shown before, was that TD always reported the opposite direction of the actual movement at a speed of 24 deg/s. This suggests a form of the continuous wagon wheel illusion, which might have been caused by intact brain areas operating at different sampling rates than area V5.


Japanese experience in ablation therapies for hepatocellular carcinoma.
In the treatment of hepatocellular carcinoma, only 20-30% of patients are candidates for surgery. Still worse, even after curative surgical resection, 80% of patients develop recurrence within 5 years. Thus, various non-surgical therapies have developed. Among them, image-guided local ablation therapies, such as percutaneous ethanol injection, microwave coagulation and radiofrequency ablation, have been widely used for small hepatocellular carcinoma, because they are potentially curative, minimally invasive and easily repeatable. Percutaneous ethanol injection was a standard therapy. However, there has been a drastic shift from ethanol injection to radiofrequency ablation in recent years. In Japan, 1500 institutes have already introduced radiofrequency ablation in the treatment of liver tumors and the cool-tip electrode system has an 80% share of the market. Radiofrequency ablation can achieve complete tumor necrosis in most cases.Long-term survival seems considerably good, and complications are not frequent in radiofrequency ablation. Randomized controlled trials have proved that radiofrequency ablation is superior to ethanol injection in the treatment of small hepatocellular carcinoma from the viewpoint of, not only treatment response, but also long-term survival. Radiofrequency ablation seems feasible, efficacious and considerably safe. Radiofrequency ablation will be more widely performed in the treatment of primary and metastatic liver tumors in Japan.


Mobile Phone Apps for Smoking Cessation: Quality and Usability Among Smokers With Psychosis.
Smoking is one of the top preventable causes of mortality in people with psychotic disorders such as schizophrenia. Cessation treatment improves abstinence outcomes, but access is a barrier. Mobile phone apps are one way to increase access to cessation treatment; however, whether they are usable by people with psychotic disorders, who often have special learning needs, is not known. Researchers reviewed 100 randomly selected apps for smoking cessation to rate them based on US guidelines for nicotine addiction treatment and to categorize them based on app functions. We aimed to test the usability and usefulness of the top-rated apps in 21 smokers with psychotic disorders. We identified 766 smoking cessation apps and randomly selected 100 for review. Two independent reviewers rated each app with the Adherence Index to US Clinical Practice Guideline for Treating Tobacco Use and Dependence. Then, smokers with psychotic disorders evaluated the top 9 apps within a usability testing protocol. We analyzed quantitative results using descriptive statistics and t tests. Qualitative data were open-coded and analyzed for themes. Regarding adherence to practice guidelines, most of the randomly sampled smoking cessation apps scored poorly-66% rated lower than 10 out of 100 on the Adherence Index (Mean 11.47, SD 11.8). Regarding usability, three common usability problems emerged: text-dense content, abstract symbols on the homepage, and subtle directions to edit features. In order for apps to be effective and usable for this population, developers should utilize a balance of text and simple design that facilitate ease of navigation and content comprehension that will help people learn quit smoking skills.


The super-excess energy dissipation in diatom algae: comparative analysis with higher plants.
When grown at intermittent light regime, diatom alga Phaeodactylum tricornutum is able to form photoprotective non-photochemical chlorophyll fluorescence quenching (NPQ) three to five times larger than that observed in the higher plants. This quenching is sustained in the dark for 5 to 10 min, reverses completely within approximately 1 h and seems to be very tightly related to the presence of the zeaxanthin analogue, diatoxanthin. Addition of the uncoupler NH4Cl before illumination can completely abolish formation of NPQ, revealing the DeltapH-dependency of the xanthophyll cycle activity. Once established, NPQ can also be almost completely reversed by the uncoupler. However, the higher NPQ is formed the more time is required for its reversal. At the point when the fluorescence was approximately 90% recovered the level of illumination-induced diatoxanthin was found to be only partially reduced. This indicates that the proton gradient is a key triggering factor of NPQ. It was also noticed that NPQ in Phaeodactylum cells was absent even when majority of reaction centers were closed and the plastoquinone pool was significantly reduced. The absence of NPQ at these conditions could be due to very low levels of DeltapH. It is likely that in diatoms alternative sources of protons such as the PS I cyclic electron transfer and/or chlororespiration are important in generating the proton gradient sufficient to trigger NPQ. Absorption changes associated with the xanthophyll cycle activity were found to be larger than those for higher plants. The position of the positive maximum in the difference spectrum illuminated-minus-dark was 512-514 nm in comparison to the 505-508 nm for leaves. The 535 nm band associated with NPQ in plants is absent in Phaeodactylum. An uncoupler-sensitive absorption change at 522 nm was discovered. Kinetics of NPQ showed linear correlation with the 522 nm absorption change.


Bone stress injuries.
Bone stress injuries are due to cyclical overuse of the bone. They are relatively common in athletes and military recruits but also among otherwise healthy people who have recently started new or intensive physical activity. Diagnosis of bone stress injuries is based on the patient's history of increased physical activity and on imaging findings. The general symptom of a bone stress injury is stress-related pain. Bone stress injuries are difficult to diagnose based only on a clinical examination because the clinical symptoms may vary depending on the phase of the pathophysiological spectrum in the bone stress injury. Imaging studies are needed to ensure an early and exact diagnosis, because if the diagnosis is not delayed most bone stress injuries heal well without complications.


Integrated analysis of zone-specific protein and metabolite profiles within nitrogen-fixing Medicago truncatula-Sinorhizobium medicae nodules.
Symbiotic nitrogen fixation (SNF) between rhizobia and legumes requires metabolic coordination within specialized root organs called nodules. Nodules formed in the symbiosis between S. medicae and barrel medic (M. truncatula) are indeterminate, cylindrical, and contain spatially distinct developmental zones. Bacteria in the infection zone II (ZII), interzone II-III (IZ), and nitrogen fixation zone III (ZIII) represent different stages in the metabolic progression from free-living bacteria into nitrogen fixing bacteroids. To better understand the coordination of plant and bacterial metabolism within the nodule, we used liquid and gas chromatography coupled to tandem mass spectrometry (MS) to observe protein and metabolite profiles representative of ZII, IZ, ZIII, whole-nodule, and primary root. Our MS-based approach confidently identified 361 S. medicae proteins and 888 M. truncatula proteins, as well as 160 metabolites from each tissue. The data are consistent with several organ- and zone-specific protein and metabolite localization patterns characterized previously. We used our comprehensive dataset to demonstrate how multiple branches of primary metabolism are coordinated between symbionts and zones, including central carbon, fatty acid, and amino acid metabolism. For example, M. truncatula glycolysis enzymes accumulate from zone I to zone III within the nodule, while equivalent S. medicae enzymes decrease in abundance. We also show the localization of S. medicae's transition to dicarboxylic acid-dependent carbon metabolism within the IZ. The spatial abundance patterns of S. medicae fatty acid (FA) biosynthesis enzymes indicate an increased demand for FA production in the IZ and ZIII as compared to ZI. These observations provide a resource for those seeking to understand coordinated physiological changes during the development of SNF.


Anxiolytic properties of certain annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones.
Modification of the benzodiazepine (BZ) receptor binding template 2-aryl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one by replacement of the annelated benzene ring with various alicyclic and heterocyclic moieties led to novel structures with potent BZ receptor binding affinity. High affinity was found in some cycloalkyl-annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones and in some 7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin- 5(6H)-ones, in which the degree of activity was strongly dependent on the N-substituent in the 9-position. Nine compounds with BZ receptor IC50 binding affinity values equal or superior to diazepam were evaluated in secondary screening. One of these, 9-benzyl-2-phenyl-7,8,9,10-tetrahydropyrido[3,4-e] [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one, showed good activity in rats as a potential anxiolytic agent without sedative liability. However, it increased the rotorod deficit produced by ethanol at anxiolytic doses, an indication of alcohol interaction. Thus, none of the compounds showed an advantage over CGS 9896 (Yokoyama et al. J. Med. Chem. 1982, 25, 337-339), which is free of sedative and alcohol interaction potential as measured by the test procedures described.


Primary thyroid leiomyosarcoma: a case report and review of the literature.
Primary thyroid leiomyosarcoma (LMS) is an extremely rare tumor. We report a case of a 47-year-old male with a rapidly growing neck mass and disfagia. Preoperative investigations were diagnostic of anaplastic carcinoma. Total thyroidectomy with partial esophagectomy and dissection of right infrahyoid muscles was performed. Through histolological and immunohistochemical evaluations a primary thyroid high-grade LMS was diagnosed. At 2 months of follow-up a local recurrence was detected and consequently the patient was submitted to chemotherapy with partial response. He is still alive 9 months after surgery. Diagnosis of primary thyroid LMS is difficult due to its similarity to other more common thyroid tumors. To date, there is no standard therapy and prognosis is poor.


Shortened Nonword Repetition Task (NWR-S): A Simple, Quick, and Less Expensive Outcome to Identify Children With Combined Specific Language and Reading Impairment.
The purpose of this research note was to validate a simplified version of the Dutch nonword repetition task (NWR; Rispens & Baker, 2012). The NWR was shortened and scoring was transformed to correct/incorrect nonwords, resulting in the shortened NWR (NWR-S). NWR-S and NWR performance were compared in the previously published data set of Rispens and Baker (2012; N = 88), who compared NWR performance in 5 participant groups: specific language impairment (SLI), reading impairment (RI), both SLI and RI, one control group matched on chronological age, and one control group matched on language age. Analyses of variance showed that children with SLI + RI performed significantly worse than other participant groups in NWR-S, just as in NWR. Logistic regression analyses showed that both tasks can predict an SLI + RI outcome. NWR-S holds a sensitivity of 82.6% and a specificity of 95.4% in identifying children with SLI + RI. The sensitivity of the original NWR is 87.0% with a specificity of 87.7%. As the original NWR, the NWR-S comprising a subset of 22 nonwords scored with a simplified scoring system can identify children with combined SLI and RI while saving a significant amount of the needed assessment time. https://doi.org/10.23641/asha.5150116.


[Cancer of the oral cavity in three brothers of the whole blood in Mauritania].
Major risk factors for cancers of the oral cavity are alcohol and tobacco, but hereditary factors were also identified. This case study aims to illustrate this last component among the most known risk factors. We here report three cases of brothers of the whole blood presenting with cancer of the oral cavity showing rapid development in less than a year in each of them. Additional risk factors other than hereditary factors were: smoking, poor oral hygiene, low fruit and vegetable intake. Hereditary risk has been a controversial issue for a long period of time, but several recent studies have suggested the existence of this risk factor which is consistent with our observation. These studies even showed that hereditary component for carcinomas of the upper aerodigestive tract seems likely; it is important that family members at risk understand that their vulnerability to these tumors can be greatly reduced by stopping smoking, by a moderate consumption of alcohol and a frequent consumption of raw fruits and vegetables. Further studies should be carried out in our country to clarify the respective role of these different risk factors in developing this type of cancer Meanwhile, prevention and early diagnosis are the most appropriate means to fight against this type of cancer.


Long-term follow-up of patients with conjunctival melanoma.
Data from long-term follow-up examinations of patients with conjunctival melanoma are limited. A retrospective study of survival rates and local tumor relapse rates was performed on 85 patients initially treated between 1958 and 1993. Therapeutic procedures were local excision, local excision followed by brachytherapy, local excision combined with cryotherapy, and local excision followed by either irradiation or cryotherapy and adjuvant mitomycin C (MMC) application. The Kaplan-Meier method was used to estimate cumulative survival rates and event rate curves. Clinical parameters of the patients and the tumors were obtained and analyzed for their relation to tumor recurrence and death from metastatic melanoma using the multivariate Cox hazards modeling. The median follow-up duration among the surviving patients was 13.1 years (mean 13.8 years). The cumulative 10-year survival rate of the 85 patients based on all causes of death was 62.5%, and that based on tumor-related death was 77.7%. Patient age greater than 55 years, higher TNM category, and unfavorable tumor location (palpebral conjunctiva, fornix, caruncle, corneal stroma, eyelid) were identified as prognostic factors for death from metastatic melanoma. Tumors with unfavorable location, higher TNM grade, and excision alone as initial therapy showed a higher cumulative probability of local relapse than favorably located (bulbar and limbal conjunctiva) tumors, lower TNM grade, and excision plus adjuvant therapy. The behavior of conjunctival melanomas remains unpredictable in individual cases. To minimize local recurrence rate surgical excision should be combined with an adjunctive procedure such as irradiation, cryotherapy, or local chemotherapy with MMC. Randomized prospective multicentric studies are required.


Factor structure and psychometric properties of Chinese version of Beck Anxiety Inventory in Chinese doctors.
This study analyses the factor structure and psychometric properties of the Chinese version of Beck Anxiety Inventory on Chinese doctors. Participants include 762 doctors sampled in 18 public hospitals in three cities in Eastern China. Exploratory factor analysis is employed to identify the potential factor structure of the inventory. Confirmatory factor analysis is referred to for model fit. The results indicate that the Chinese version of Beck Anxiety Inventory has satisfactory reliability and validity, but its factor structure is unstable and has great differences compared with international versions. Naming the four extracted factors is difficult. In general, the Chinese version of Beck Anxiety Inventory is appropriate for Chinese doctors and can be used as a good screener to detect the anxiety of Chinese doctors.


Fibrinolysis in glomerulonephritis treated with ancrod: renal functional, immunologic and histopathologic effects.
The effects of a 14-day course of ancrod on fibrinolysis, renal function and structure, and immunologic findings are reported in 37 patients with glomerulonephritis. Patients were divided into two groups. In the first, the level of fibrin degradation products within 48 h was relatively low (less than 1 mg/ml). In these patients there was a linear relationship between changes in levels of fibrin degradation products and fibrinogen, suggesting that fibrin degradation products derived from ancrod-cleaved-fibrinogen in the circulating pool; in most, level of plasma alpha 2-antiplasmin before treatment was elevated. In the second, the level of fibrin degradation products within 48 h was high (greater than 1 mg/ml). Compared with the change in fibrinogen, a disproportionate increase in levels of fibrin degradation products suggested that a significant amount derived from sources other than plasmin digested ancrod-cleaved-fibrinogen, thus reflecting effective fibrinolysis, perhaps also in tissues; in most, the level of plasma alpha 2-antiplasmin was normal before treatment. In those with initial high levels of fibrin degradation products, higher levels persisted throughout treatment, changes in other fibrinolysis components were greater, and plasminogen activator inhibitor levels became normal. In patients with initial high but not with initial low response in fibrin degradation products renal function improved within 24 to 48 h and continued to improve thereafter; there was an immediate but temporary increase in proteinuria. Microvascular thrombosis decreased significantly, indicating effective removal of fibrin from glomeruli. The relation of early fibrinolysis to changes in immunologic and histopathologic findings was analyzed in patients with lupus nephritis. With ancrod, there was an increase toward normal of serum C3 and C4, a decrease in serum Igs, gamma globulin and anti-dsDNA antibody and in glomerular C3 and Ig deposits, suggesting that ancrod had favorable effects on immunologic factors. There were no clinical differences in patients with initial high and low responses, but the relationship of microvascular and inflammatory indexes before treatment differed. Initial renal biopsies and those after treatment were carried out on average 28 days apart. Inflammatory and microvascular indexes and glomerular thrombi decreased in patients with initial high levels of fibrin degradation products; fibrosclerosis index and glomerular sclerosis increased in patients with initial low levels of fibrin degradation products. Fibrinolysis expressed as the 48 h (fibrin degradation products/fibrinogen) ratio, correlated inversely with change in fibrosclerosis index and glomerular sclerosis in the whole group, and especially in those with initial high levels of fibrin degradation products.(ABSTRACT TRUNCATED AT 400 WORDS)


Will Automated Compressing Devices Save More Lives in Recalcitrant Ventricular Fibrillation Cardiac Arrest?
We present a 55-year-old male that developed ventricular fibrillation cardiac arrest in the setting of ST-elevation acute myocardial infarction with recalcitrant and persistent ventricular fibrillation arrest that was successfully resuscitated with a good neurological outcome. The persistent chest compressions were performed in our intensive care unit with an automated chest compression system. The patient required defibrillations and nonstop chest compressions which were the key factors for his survival. This is an example we should consider in all our intensive care units. It's time for a paradigm shift in replacing the compressor of a code team with an automated system. The out-of-hospital evidence in acute care is compelling to bring this technology that has been proven crucial in transports from hospital areas, ambulances, helicopters, and ships to the inpatient ICU bedside. In ventricular tachycardia and ventricular fibrillation (Vt/Vf), the electrical storm created is the perfect example of the need to have the best compressions to provide the best care possible with the best survival and neurological outcomes.


Correction: Rate constants, processivity, and productive binding ratio of chitinase A revealed by single-molecule analysis.
Correction for 'Rate constants, processivity, and productive binding ratio of chitinase A revealed by single-molecule analysis' by Akihiko Nakamura et al., Phys. Chem. Chem. Phys., 2018, DOI: .


Alternative Shaker transcripts express either rapidly inactivating or noninactivating K+ channels.
Two members of the Shaker K+ channel family designated ShA2 and ShD2 were characterized in the Xenopus oocyte expression system. The predicted amino acid sequences of ShA2 and ShD2 differ only in the amino terminus, which is located intracellularly according to the present topological model of K+ channels. The differing amino termini have profound effects on the electrophysiological and pharmacological properties of the K+ channel. Most markedly, the nature of the amino terminus determines whether the K+ channel mediates rapidly inactivating or noninactivating K+ currents. It also affects the 4-aminopyridine, tetraethylammonium, and charybdotoxin sensitivities of the K+ channels. These results suggest that the amino terminus of Shaker proteins affects K+ channel structures on both sides of the membrane.


Deep Learning Prediction for Distal Aortic Remodeling After Thoracic Endovascular Aortic Repair in Stanford Type B Aortic Dissection.
This study aimed to develop a deep learning model for predicting distal aortic remodeling after proximal thoracic endovascular aortic repair (TEVAR) in patients with Stanford type B aortic dissection (TBAD) using computed tomography angiography (CTA). A total of 147 patients with acute or subacute TBAD who underwent proximal TEVAR at a single center were retrospectively reviewed. The boundary of aorta was manually segmented, and the point clouds of each aorta were obtained. Prediction of negative aortic remodeling or reintervention was accomplished by a convolutional neural network (CNN) and a point cloud neural network (PC-NN), respectively. The discriminatory value of the established models was mainly evaluated by the area under the receiver operating characteristic curve (AUC) in the test set. The mean follow-up time was 34.0 months (range: 12-108 months). During follow-up, a total of 25 (17.0%) patients were identified as having negative aortic remodeling, and 16 (10.9%) patients received reintervention. The AUC (0.876) by PC-NN for predicting negative aortic remodeling was superior to that obtained by CNN (0.612, p=0.034) and similar to the AUC by PC-NN combined with clinical features (0.884, p=0.92). As to reintervention, the AUC by PC-NN was significantly higher than that by CNN (0.805 vs 0.579; p=0.042), and AUCs by PC-NN combined with clinical features and PC-NN alone were comparable (0.836 vs 0.805; p=0.81). The CTA-based deep learning algorithms may assist clinicians in automated prediction of distal aortic remodeling after TEVAR for acute or subacute TBAD. Negative aortic remodeling is the leading cause of late reintervention after proximal thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection (TBAD), and possesses great challenge to endovascular repair. Early recognizing high-risk patients is of supreme importance for optimizing the follow-up interval and therapy strategy. Currently, clinicians predict the prognosis of these patients based on several imaging signs, which is subjective. The computed tomography angiography-based deep learning algorithms may incorporate abundant morphological information of aorta, provide with a definite and objective output value, and finally assist clinicians in automated prediction of distal aortic remodeling after TEVAR for acute or subacute TBAD.


Prospective study on the association between serum amino acid profiles and depressive symptoms among the Japanese working population.
Accumulating evidence suggests that amino acids, particularly tryptophan and glutamate, play an important role in the pathology of depression, but prospective epidemiologic data on this issue is scarce. We examined the association between circulating amino acids and the risk of depressive symptoms in a Japanese working population. Participants were 841 workers who were free from depressive symptoms and provided blood at baseline and completed 3-yr follow-up survey. 30 varieties of amino acid concentrations in serum were measured using liquid chromatography/mass spectrometry. Depressive symptoms were defined using the Center for Epidemiologic Studies Depression Scale. Logistic regression was used to calculate the odds ratios of depressive symptoms according to serum amino acids with adjustment for lifestyle factors. A total of 151 (18.0%) workers were newly identified as having depressive symptoms at the follow-up. Baseline tryptophan and glutamate concentrations in serum were not appreciably associated with the risk of depressive symptoms. Risk of depressive symptoms tended to increase with increasing arginine concentrations; the multivariable-adjusted odds ratio for the highest versus lowest tertile of serum arginine was 1.65 (95% confidence interval: 0.96-2.83; P for trend = 0.07). No clear association was found for other amino acids. Results of the present study do not support a significant role of circulating amino acids in the development of depressive symptoms among Japanese.


Laparoscopic proximal gastrectomy with double tract reconstruction is superior to laparoscopic total gastrectomy for proximal early gastric cancer.
Laparoscopic proximal gastrectomy (LPG) with double tract reconstruction (DTR) is known to reduce reflux symptoms, which is a major concern after proximal gastrectomy. The aim of this study is to compare retrospectively the clinical outcomes of patients undergoing LPG with DTR with those treated by laparoscopic total gastrectomy (LTG). Ninety-two and 156 patients undergoing LPG with DTR and LTG for proximal stage I gastric cancer were retrospectively analyzed for short- and long-term clinical outcomes. There were no significant differences in the demographics, T-stage, N-stage, and complications between the groups. The LPG with DTR group had a shorter operative time and lower estimated blood loss than the LTG group (198.3 vs. 225.4 min, p < 0.001; and 84.7 vs. 128.3 mL p = 0.001). The incidence of reflux symptoms ≥ Visick grade II did not significantly differ between the groups during a mean follow-up period of 37.2 months (1.1 vs. 1.9%, p = 0.999). The hemoglobin change was significantly lower in the LPG with DTR group compared to in the LTG group in the first and second postoperative years (5.03 vs. 9.18% p = 0.004; and 3.45 vs. 8.30%, p = 0.002, respectively), as was the mean amount of vitamin B12 supplements 2 years after operation (0.1 vs. 3.1 mg, p < 0.001). The overall survival rate was similar between the groups. LPG with DTR maintained comparable oncological safety and anastomosis-related late complications compared to LTG and is preferred over LTG in terms of preventing postoperative anemia and vitamin B12 deficiency.


A Critical Review on Ultrasensitive, Spectroscopic-based Methods for High-throughput Monitoring of Bacteria during Infection Treatment.
The world is in the midst of a pre-emptive public health emergency, one that is just as dramatic as the global aggressive viruses-related crises (Ebola, Zika, or SARS), but not as visible. The "superbugs" and their antimicrobial resistance do not cause much public alarm or awareness, but provoke financial losses of $100 trillion annually (WHO, http://www.who.int/mediacentre/commentaries/superbugs-action-now/en/ ). This status quo review offers an overview of ultrasensitive methods for high-throughput monitoring of bacteria during infection treatment, the effects of antibiotics on bacteria at single-cell level and the challenges we will face in their detection due to the extraordinary capability of these "superbugs" to gain and constantly improve multiresistance to antibiotics. A special emphasis is put on the ultrasensitive spectroscopic-based analysis techniques, using nanotechnology or not necessarily, that are more and more promising alternatives to conventional culture-based ones. The particular case of Mycobacteria detection is discussed based on recent reported work.


HTLV-I virus in Europeans: the continuous spread. A meta-analysis.
Published and unpublished data on the HTLV-I seroprevalence in 13 European countries (sample a total of 79.549 persons) was subject to meta-analysis. HTLV-I infection was significantly associated with intravenous drug use, HIV-I seropositivity, geographical area and immigration from endemic areas outside of Europe. Significant percentage of HTLV-I seropositivity was observed in all groups of HIV-I seropositive individuals studies. The overall HTLV-I seroprevalence was 4.16% in intravenous drug abusers, 0.66% in male homosexuals, 0.62% in immigrants from HTLV-I endemic areas and 0.015% in the general population. A major problem in these epidemiological considerations is the uncertain delineation of the serology of HTLV-I versus that of HTLV-II. There have, been no reports from Europe of the specific leukaemic and neurologic indicator diseases associated with the HTLV-I seropositivity. Presently, the HTLV-I/HIV-I co-infected individuals represent an urgent medical problem. The information available shows a need for self-exclusion of all blood donor groups at risk for HTLV-I infection and for active seroepidemiological surveillance in all parts of Europe. However, improvements in diagnostic methods, increased knowledge about the pathogenesis of infection by HTLV-I or HTLV-II virus and the probable detection of new human retroviruses may markedly influence the future requirements for preventive measures.


Further kinetic characterization of alginate-entrapped cells of Mucuna pruriens L.
Alginate-entrapped cells of Mucuna pruriens L. hydroxylate L-tyrosine, tyramine, para-hydroxyphenylpropionic acid, and para-hydroxyphenylacetic acid to their corresponding catechols, which were released into the incubation medium. Michaëlis-Menten kinetics was applied for each bioconversion. The apparent affinity constants were comparable with the affinity constants obtained with a homogenate directly prepared from the cells used for entrapment and with a derived partly purified phenoloxidase. The values found for the apparent maximum rates of bioconversion of the entrapped cells were ca. 50% of the values of the maximum rates of bioconversion of the cell homogenate, indicating that the entrapped cell system was not operating optimally. The effective diffusivities of the substrates and products were measured with alginate-entrapped, inactivated cells. From the five inactivation methods tested, glutaric aldehyde treatment was chosen as the general procedure. Calculated effective diffusivities for the monophenols and catechols demonstrated that these compounds could diffuse freely into and out of the beads. For each bioconversion, the observable modulus was calculated from the initial rate of bioconversion and the effective diffusivity of the substrate. The resulting values indicated that the diffusional supply rate of the substrates was not the limiting factor, except for the conversion of tyramine for which a modulus higher than one was obtained. Analogously, the observable moduli were calculated for oxygen, which was utilized for bioconversion and cell respiration, and these values pointed towards strong oxygen limitation in all cases. The bioconversion rates of the entrapped cells increased with decreasing cell aggregate size. Therefore, it was concluded that direct cell-matrix contact determined the amount of phenoloxidase involved in the bioconversions. The bioconversion rate on a protein basis was constant with enhancement of the bead charge and thus, in spite of limitations, the mixing conditions as such were relatively optimal. In conclusion, the nonoptimal efficiency of the plant cell system studied was caused by oxygen limitation and a partial phenoloxidase participation, but not by mass transfer limitations for substrates and products with the exception of the conversion of tyramine into dopamine.


Mental wellbeing amongst younger and older migrant workers in comparison to their urban counterparts in Guangzhou city, China: a cross-sectional study.
There has been a dramatic increase in internal migrant workers in China over recent decades, and there is a recent concern of poor mental health particularly amongst younger or "new generation" migrants who were born in 1980 or later. A cross-sectional study was conducted in Guangzhou city between May and July in 2012. Mental wellbeing was measured using the World Health Organization Five-item Well-Being Index Scale and the 36 Item Short Form Health Survey mental health scale. Linear and logistic regression models were used to investigate the differences between migrant workers and their urban counterparts and between younger and older migrants. Migrant workers (n = 914) showed a small but significant advantage in mental wellbeing compared to their urban counterparts (n = 814). There was some evidence for age modification effect (p for interaction = 0.055-0.095); better mental wellbeing in migrants than urbanites were mainly seen in the older compared to the younger group, and the difference attenuated somewhat after controlling for income satisfaction. Older migrants showed better mental health than younger migrants. Factors that were independently associated with poor mental health in migrants included being male, longer working hours, and income dissatisfaction, whilst older age, factory job, high income, and increased use of social support resources were associated with reduced risk. Efforts to promote mental health amongst migrant workers may be usefully targeted on younger migrants and include measures aimed to improve working conditions, strengthen the social support network, and address age-specific needs.


Inhibition of electroacupuncture on nociceptive responses of dorsal horn neurons evoked by noxious colorectal distention in an intensity-dependent manner.
The transmission of visceral nociception can be inhibited by electroacupuncture (EA) at the spinal level. However, relationships between current intensity and EA-induced analgesia are still lacking. This study compares the effects of different intensities of EA at local acupoints and heterotopic acupoints on nociceptive responses of spinal wide dynamic range (WDR) neurons induced by noxious colorectal distension (CRD). Experiments were conducted on 40 Sprague Dawley rats anesthetized with 10% urethane. Discharges of WDR neurons in the L1-L3 segments of the dorsal horn of the spinal cord were recorded extracellularly by glass micropipettes. Different intensities of EA (0.5, 1, 2, 4, 6, and 8 mA, 0.5 ms, 2 Hz) were applied to contralateral "Zusanli" (ST 36) or "Neiguan" (PC 6), with either the same or different segmental innervation of the colon. In local acupoints, the increased discharges of WDR neurons evoked by CRD were significantly inhibited by EA at 0.5-8 mA. A positive relationship between current intensity and the inhibiting rate was observed within 0.5-4 mA, but the inhibiting rate reached a plateau when EA exceeded 4 mA. In heterotopic acupoints, the increased discharges of WDR neurons evoked by CRD were significantly inhibited by EA at 2-8 mA. A positive relationship between current intensity and the inhibiting rate was observed within 2-6 mA. Further increase in the current beyond 6 mA also resulted in a plateau effect. Within a certain range, the nociceptive responses of dorsal horn neurons induced by CRD could be inhibited by EA in an intensity-dependent manner.


Predictors of adverse events in uncomplicated type B aortic dissection: a systematic review with meta-analysis.
Thoracic endovascular aortic repair (TEVAR) has been selectively used for uncomplicated acute type B aortic dissection (TBAD); however, not all cases will benefit from TEVAR. A search for high risk clinical and radiographic predictors for complications is ongoing. This systematic review and meta-analysis aimed to identify predictors of major adverse events during follow-up of uncomplicated TBAD, in order to identify who might benefit from elective TEVAR. A systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) Statement. 16 studies were included in a qualitative synthesis and 10 in the meta-analysis. Several risk factors associated to major adverse events have been described, including: 1) aortic diameter ≥40 mm; 2) greater false lumen diameter (>22 mm); 3) patent false lumen; 4) primary entry tear >10 mm; and 5) greater number of false lumen vessels origin. Quantitative synthesis identified an aortic diameter ≥40 mm significantly associated with major adverse events (HR=3.56; P<0.00001). Reporting of false lumen status, aortic diameters and growth, and demographic data was not always congruent with the most recent recommendations by Society for Vascular Surgery and Society of Thoracic Surgeons, published in 2020. Acute and subacute patients with uncomplicated TBAD presenting with an aortic diameter ≥40 mm and solely treated with BMT have an increased hazard of developing major adverse events (HR), making them potential candidates for TEVAR. Remaining risk factors analysed have weaker evidence.


Tetrodotoxin in Asian newts (Salamandridae).
Tetrodotoxin (TTX) and its analogues occur in a wide range of marine animals but also in terrestrial vertebrates such as frogs, toads and newts. Despite numerous studies on TTX in New World newts (Notophthalmus viridescens, Taricha spp.), few data only exist for Asian newts. Methanolic extracts of newts from China (Cynops orientalis, Pachytriton labiatus, Paramesotriton chinensis), Vietnam (Paramesotriton deloustali, P. guangxiensis), and Laos (Laotriton laoensis) were analyzed by liquid-chromatography-fluorescent detection (LC-FLD) and mass-spectrometry (LC-MS). In all species, variable amounts of TTX were detected, in most specimens also TTX-analogues like 6-epiTTX, in C. orientalis 11-oxoTTX, confirming the presence of these toxins in modern Asian newts.


Modulation of Langerhans cell surface antigen expression by recombinant cytokines.
This study examined the influence of cytokines on surface antigen expression by gingival Langerhans cells (LC) in organ culture, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) upregulated the expression of CD1a, HLA-DR and HLA-DP antigens on LC. TNF-alpha, interleukin-4 (IL-4), and transforming growth factor beta (TGF-beta) suppressed CD29 expression, while other cytokines, including interleukin-3 and granulocyte-macrophage colony stimulating factor, were without effect. No cytokines induced CD3, CD4, CD23, CD25 or CD45 RA antigen expression in organ culture. Since TNF-alpha and IL-6 can be secreted by keratinocytes, these molecules, together with interleukin-1, are likely to play a role in the local control of LC number and function within the epithelial milleu. Thus, alterations in cytokine secretion by keratinocytes may at least in part be responsible for variations in LC number and antigen expression which occur in oral mucosal disorders.


Meta-Atom Behavior in Clusters Revealing Large Spin Ground States.
The field of single molecule magnetism remains predicated on super- and double exchange mechanisms to engender large spin ground states. An alternative approach to achieving high-spin architectures involves synthesizing weak-field clusters featuring close M-M interactions to produce a single valence orbital manifold. Population of this orbital manifold in accordance with Hund's rules could potentially yield thermally persistent high-spin ground states under which the valence electrons remain coupled. We now demonstrate this effect with a reduced hexanuclear iron cluster that achieves an S = 19/2 (χ(M)T ≈ 53 cm(3) K/mol) ground state that persists to 300 K, representing the largest spin ground state persistent to room temperature reported to date. The reduced cluster displays single molecule magnet behavior manifest in both variable-temperature zero-field (57)Fe Mössbauer and magnetometry with a spin reversal barrier of 42.5(8) cm(-1) and a magnetic blocking temperature of 2.9 K (0.059 K/min).