Is high-intensity interval training more effective on improving cardiometabolic risk and aerobic capacity than other forms of exercise in overweight and obese youth? A meta-analysis.
The scientific interest in high-intensity interval training (HIIT) has greatly increased during recent years. The objective of this meta-analysis was to determine the effectiveness of HIIT interventions on cardio-metabolic risk factors and aerobic capacity in overweight and obese youth, in comparison with other forms of exercise. A computerized search was made using seven databases. The analysis was restricted to studies that examined the effect of HIIT interventions on cardio-metabolic and/or aerobic capacity in pediatric obesity (6-17 years old). Nine studies using HIIT interventions were selected (n = 274). Standarized mean difference (SMD) and 95% confidence intervals were calculated. The DerSimonian-Laird approach was used. HIIT interventions (4-12 week duration) produced larger decreases in systolic blood pressure (SMD = 0.39; -3.63 mmHg) and greater increases in maximum oxygen uptake (SMD = 0.59; 1.92 ml/kg/min) than other forms of exercise. Also, type of comparison exercise group and duration of study were moderators. HIIT could be considered a more effective and time-efficient intervention for improving blood pressure and aerobic capacity levels in obese youth in comparison to other types of exercise. © 2016 World Obesity.


Analysis of BRCAness with multiplex ligation-dependent probe amplification using formalin-fixed and paraffin-embedded pancreatic ductal adenocarcinoma tissue obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy.
A breakthrough in chemotherapy for pancreatic ductal adenocarcinoma (PDAC) may be achieved using precision medicine, which involves identifying cases that are highly likely to respond to a certain treatment and then performing that treatment. BRCAness has been receiving attention as a novel predictor of anticancer drug sensitivity in PDAC, making the screening of BRCAness paramount. We conducted the first-ever examination of the feasibility of analyzing BRCAness using multiplex ligation-dependent probe amplification (MLPA). Formalin-fixed paraffin-embedded (FFPE) tissue samples obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) from 20 patients with the highest pancreatic carcinoma cell counts in tissue samples out of 40 consecutive PDAC patients who underwent EUS-FNAB at our hospital were analyzed by MLPA for BRCAness. We were able to accurately analyze BRCAness in 75% of the 20 cases of PDAC using FFPE tissue obtained by EUS-FNAB. BRCAness was observed in one of the 20 cases. In PDAC, analyzing BRCAness by MLPA using FFPE tissue obtained by EUS-FNAB offers the remarkable benefit of yielding results in a short period of time and at a low cost. In addition, this method of BRCAness analysis may prove to be a feasible and effective approach for performing precision medicine.


Foregone Opportunities? Time to Treatment Intensification Among Adults With Type 2 Diabetes and Elevated Glycated Hemoglobin on Metformin Monotherapy, 2009-2018.
In this study, we aimed to characterize time to treatment intensification (TTI) in people on metformin with uncontrolled hyperglycemia, and estimated the frequency of physician visits until intensification. This work was a cohort study of Albertan adults with glycated hemoglobin (A1C) of >7.5% after at least 3 months of metformin monotherapy, using administrative databases from 2009 to 2018, with each subject followed for up to 4 years. Therapeutic intensification was defined as dispensation of an additional class of antihyperglycemic medication. Median TTI and the median number of physician visits were estimated from Kaplan-Meier functions within age/A1C strata. A Cox proportional hazards model was fitted to examine predictors of therapeutic intensification. We included 38,846 people (average age, 57 years; 37% female; mean A1C, 8.8%). Overall, therapeutic intensification was observed in 23,077 (59%; 40% at 1 year). Median TTI was 1.4 years, varying from 0.7 years (A1C >8.5%, age <65 years) to 3.3 years (age ≥75 years, any A1C). The median number of physician visits until intensification was 9, varying between 5 (A1C >8.5%, age <65 years) and ≥30 (age ≥75 years); 93% of people awaiting intensification had at least 2 visits by 1 year. Higher A1C and younger age were the strongest predictors of intensification. Results were similar in people with ischemic heart disease. Despite ample contacts with community physicians, TTI exceeds the 6-month target recommended by guidelines, particularly in older adults. Further study is needed to better understand these foregone opportunities as guidelines call for wider promulgation of agents with cardiorenal benefits.


A case of recurrent acute cholecystitis caused by Actinomyces odontolyticus, rare actinomycosis.
Actinomyces species are gram-positive, obligate anaerobic rods and are rare causes of cholecystitis. Because Actinomyces species are anaerobic bacteria, it is difficult for Actinomyces to survive in bile apart from A. naeslundii. We experienced a case of recurrent acute cholecystitis caused by A. odontolyticus. A patient had been diagnosed with acute cholecystitis and treated one month before and after that, admitted to our hospital because of recurrent cholecystitis. Gram stain of the bile revealed gram-positive rods and gram-positive cocci. We found A. odontolyticus and MRSA in bile culture and MRSA in blood culture. We administered piperacillin-tazobactam and then changed it to ampicillin-sulbactam and vancomycin. The patient underwent laparoscopic cholecystectomy and was discharged safely. To our knowledge, this is the first case of cholecystitis caused by A. odontolyticus. Cholecystitis caused by Actinomyces species is rare. In addition, we may overlook it with the low positivity of bile cultures of Actinomyces. Whenever the cholecystitis recurs without any obstruction of the biliary tract, we should search for the gram-positive rods hidden in the bile, such as A. odontolyticus, as the causative organism, even if the bile culture is negative.


Mood instability and activity/energy instability in patients with bipolar disorder according to day-to-day smartphone-based data - An exploratory post hoc study.
Alterations and instability in mood and activity/energy has been associated with impaired functioning and risk of relapse in bipolar disorder. The present study aimed to investigate whether mood instability and activity/energy instability are associated, and whether these instability measures are associated with stress, quality of life and functioning in patients with bipolar disorder. Data from two studies were combined for exploratory post hoc analyses. Patients with bipolar disorder provided smartphone-based evaluations of mood and activity/energy levels from day-to-day. In addition, information on functioning, perceived stress and quality of life was collected. A total of 316 patients with bipolar disorder were included. A total of 55,968 observations of patient-reported smartphone-based data collected from day-to-day were available. Regardless of the affective state, there was a statistically significant positive association between mood instability and activity/energy instability in all models (all p-values < 0.0001). There was a statistically significant association between mood and activity/energy instability with patient-reported stress and quality of life (e.g., mood instability and stress: B: 0.098, 95 % CI: 0.085; 0.11, p < 0.0001), and between mood instability and functioning (B: 0.045, 95 % CI: 0.0011; 0.0080, p = 0.010). Findings should be interpreted with caution since the analyses were exploratory and post hoc by nature. Mood instability and activity/energy instability is suggested to play important roles in the symptomatology of bipolar disorder. This highlight that monitoring and identifying subsyndromal inter-episodic fluctuations in symptoms is clinically recommended. Future studies investigating the effect of treatment on these measures would be interesting.


Pregnancy-maintaining antibodies: workshop report (Giessen, 1988).
To analyse the nature of antibodies which are purported to be essential for the maintenance of normal human pregnancy, six centers participated in a workshop of "blind" tests on 19 allosera. Fc-receptor dependent assays detected antibodies with specificity only for HLA. In addition to cytotoxic antibodies, the Fc-receptor dependent immune phagocytosis inhibition test revealed two non-cytotoxic alloantibodies with HLA specificity. These antibodies had high titers and may, therefore, be essentially non-cytotoxic. Murine monoclonal antibodies to HLA-A, B, C or DR (W6/32 and 2MC3) were used to evaluate the methods. These antibodies inhibited immune rosette formation as well as immune phagocytosis. Diluted to concentrations below the threshold of complement-dependent cytotoxicity, the monoclonal antibodies still inhibited the mixed lymphocyte reaction and the immune phagocytosis. A human monoclonal immunoglobulin M with specificity for monomorphic non-HLA lymphocyte antigens inhibited the mixed lymphocyte reaction. The immune rosette inhibition test exhibited several false positive reactions, e.g. three out of four with a serum that did not contain alloantibodies to blood cells. Non-cytotoxic antibodies were therefore rare in the selected sera of the workshop and they exhibited HLA specificity only. No participant was able to identify pregnancy-maintaining non-HLA-antibodies.


Effects of copper on the tyrosinase of liver pigment cells from Rana esculenta L.
1. The liver pigment cells of R. esculenta L. constitute a peculiar pigment cell system of histiocytic nature and contain a tyrosinase-like activity localized in the protein component of melanosomes. 2. The effects of addition and/or removal of Cu on the DOPA-oxidase activity of the system were studied. 3. It was concluded that: (a) this tyrosinase behaves as a Cu-enzyme; (b) Cu could be involved in the regulation of the enzyme activity; and (c) mixtures of apoenzyme and active enzyme coexist in the melanosomes.


Multi-level attention graph neural network based on co-expression gene modules for disease diagnosis and prognosis.
Advanced deep learning techniques have been widely applied in disease diagnosis and prognosis with clinical omics, especially gene expression data. In the regulation of biological processes and disease progression, genes often work interactively rather than individually. Therefore, investigating gene association information and co-functional gene modules can facilitate disease state prediction. To explore the gene modules and inter-gene relational information contained in the omics data, we propose a novel multi-level attention graph neural network (MLA-GNN) for disease diagnosis and prognosis. Specifically, we format omics data into co-expression graphs via weighted correlation network analysis, and then construct multi-level graph features, finally fuse them through a well-designed multi-level graph feature fully fusion module to conduct predictions. For model interpretation, a novel full-gradient graph saliency mechanism is developed to identify the disease-relevant genes. MLA-GNN achieves state-of-the-art performance on transcriptomic data from TCGA-LGG/TCGA-GBM and proteomic data from coronavirus disease 2019 (COVID-19)/non-COVID-19 patient sera. More importantly, the relevant genes selected by our model are interpretable and are consistent with the clinical understanding. The codes are available at https://github.com/TencentAILabHealthcare/MLA-GNN.


Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology.
Transmembrane (TMEM)-176A and 176B proteins belong to the MS4A family of proteins whose function in the immune system remains unclear. TMEM176A transcripts were previously shown to be elevated in liver cancer or kidney tissue with proteinuria, while marked changes in TMEM176B transcripts have been found in tolerated tissue allografts and neoplastic fibroblasts. To study the functional relationship between human TMEM176A and 176B and their putative link to cancer, we used polymerase chain reaction and biochemical assays. Here, we show that TMEM176A and 176B are widely expressed in all human tissues examined. Co-immunoprecipitation of heterologously expressed TMEM176A and 176B revealed direct physical interaction. To determine the relevance of such interaction to cancer pathology, we analyzed biopsied tissue samples from a variety of normal and cancer tissues. Our data reveal that human TMEM176A and 176B protein levels are significantly elevated in lymphoma, but not in normal tissues. The protein levels of TMEM176A are also significantly increased in lung carcinoma. Finally, analysis of the protein expression ratio of TMEM176A over 176B showed significant differences between normal and cancer tissues of the breast, lymph, skin, and liver, which indicates that both TMEM proteins could be potential useful markers for certain human cancers.


Interlocking-interface-enabled thermally deformable liquid metal/polymer membrane with high bonding strength.
The high surface tension of liquid metal (LM) causes interface incompatibility and poor bonding strength with many substrates. Fine adjustment towards the properties of the surface area is sufficient to introduce strong bonding. Hence, we hypothesize that the interlocking structure using hydrophilic polyvinyl alcohol (PVA) as a "bridge" should be helpful for tight interfacial bonding of LM with polymeric substrates, thus achieving high-performance LM/polymer membranes, which have wide applications in the field of soft sensors and robotics. The bulk EGaIn was fabricated into LM nanoparticles (LMNPs@PVA) solution. Then, PVA molecules were "doped" into the surface crosslink of the plasma treated polymer substrate by an interfacial penetrating method. Afterward, the solution was evenly dropped on the surface of the treated substrate to obtain the LMNP/polymer membrane after the water evaporated. Photothermal actuators were fabricated based on the membranes. During the interlocking structure, PVA macromolecules could be doped and trapped onto the top surfaces of various polymer substrates as binding "bridges" between the LMNPs and the matrix materials. The achieved LMNP membrane exhibites satisfactory bonding strength, durability and water-assisted erase-reprint, which can be used as soft photothermal actuators with remote laser control.


Sex differences in aortic stenosis: Identification of knowledge gaps for sex-specific personalized medicine.
This review summarizes sex-based differences in aortic stenosis (AS) and identifies knowledge gaps that should be addressed by future studies. AS is the most common valvular heart disease in developed countries. Sex-specific differences have not been fully appreciated, as a result of widespread under diagnosis of AS in women. Studies including sex-stratified analyses have shown differences in pathophysiology with less calcification and more fibrosis in women's aortic valve. Women have impaired myocardial perfusion reserve and different compensatory response of the left ventricle (LV) to pressure overload, with concentric remodeling and more diffuse fibrosis, in contrast to men with more focal fibrosis and more dilated/eccentrically remodeled LV. There is sex difference in clinical presentation and anatomical characteristics, with women having more paradoxical low-flow/low-gradient AS, under-diagnosis and severity underestimated, with less referral to aortic valve replacement (AVR) compared to men. The response to therapies is also different: women have more adverse events with surgical AVR and greater survival benefit with transcatheter AVR. After AVR, women would have more favorable LV remodeling, but sex-related differences in changes in myocardial reserve flow need future research. Investigation into these described sex-related differences in AS offers potential utility for improving prevention and treatment of AS in women and men. To better understand sex-based differences in pathophysiology, clinical presentation, and response to therapies, sex-specific critical knowledge gaps should be addressed in future research for sex-specific personalized medicine.


[How should we follow end-stage glaucoma?].
End-stage glaucoma is characterized by a near total structural loss and similarly deteriorated visual function. It is very difficult to follow patients in this stage of the disease by standard automated perimetry. The purpose of this article is to discuss how to better follow patients with end-stage glaucoma. Monitoring of glaucoma must take into account the measurement of intraocular pressure, structural evaluation and functional assessment. Structural evaluation has only minor importance at this stage, and the most useful tool is qualitative analysis, especially through stereo disc photography, looking for disc hemorrhages. Conversely, functional assessment is of major importance. Specific techniques and strategies should be used. Patients' complaints are very important in this stage of glaucoma. Trial frames are very useful for accurate testing of visual acuity, and are preferable to phoropters. Visual field measurement must be adapted to this end stage of glaucoma, by using targeted strategies, such as: testing the central 10 degrees, testing a 24-2 field with a size V stimulus, and Goldmann perimetry. Any slight sign of worsening must be taken into account, so as to detect any progression of the disease.


Cytochemical characterization of secretory and cell surface glycoconjugates by light and electron microscopy.
Lectin methods have increased the capacity for histochemical characterization and differentiation of glycoproteins and have demonstrated, for example, greater reactivity of gastrointestinal than of respiratory tract secretions with the periodate-concanavalin A-horseradish peroxidase method for localizing mannose-rich glycoprotein. Application of a battery of ultrastructural cytochemical methods with specificity for the constituents characteristically present in the complex carbohydrates provides knowledge of the distribution of the various recognizable types of glycoconjugates in tissues and cells showing, for example, marked differences in glycoconjugates of the apical compared with the basolateral plasmalemma in a given cell type and differences between apical plasmalemmas or basement membranes of different cell types. Such information raises questions as to the biologic significance of the different complex carbohydrates in various sites and, hopefully, will lead to a clearer understanding of their physiologic roles.


Rapid phosphorylation of microtubule-associated proteins through distinct mitogenic pathways.
Mitogenic stimulation of sparse quiescent Swiss 3T3 cells with serum induces a transient reorganization of microtubules which may be necessary for generation or transduction of the mitogenic signal(s). Recently, several studies have shown that microtubule-associated proteins (MAPs) modulate microtubule-mediated functions in vitro and in vivo. We have analyzed, by two-dimensional electrophoresis, the molecular changes in MAPs associated with microtubules in situ following cell activation. By as early as 15 min after addition of serum, several of the MAPs present in quiescent cells are lost from the assembled microtubule fraction while one additional MAP becomes evident. This new MAP is a phosphoprotein whose appearance is independent of protein synthesis. Four additional MAPs also become phosphorylated, and this phosphorylation is accompanied by a partial redistribution of MAPs into the unassembled soluble fraction. Stimulation of cells with purified platelet-derived growth factor or phorbol tumor promoter, a direct activator of protein kinase C, also induces phosphorylation of the same MAPs and DNA synthesis. These results demonstrate that activation of the protein kinase C pathway is sufficient to promote the phosphorylation of MAPs and mitogenesis. However, epidermal growth factor, which does not activate protein kinase C, also stimulates phosphorylation of MAPs and DNA replication. Furthermore, down-regulation of the protein kinase C pathway does not prevent these responses. We conclude that phosphorylation of MAPs and mitogenesis can proceed through protein kinase C-dependent and -independent pathways in 3T3 cells.


Comparison between cells and cancer stem-like cells isolated from glioblastoma and astrocytoma on expression of anti-apoptotic and multidrug resistance-associated protein genes.
This study is to explore and compare the features of the cells and cancer stem-like cells (CSCs) isolated from both glioblastoma and astrocytoma on expression of anti-apoptotic and multidrug resistance-associated protein (MRP) genes. As a result, the mRNA expression of livin, livinalpha and MRP1 was up-regulated in human CSCs from 2 times to 85 times, but the gene expression of MRP3 was down-regulated from 0.09 times to 0.5 times. After just differentiation the mRNA expression of livin, livinalpha and MRP3 was up-regulated from 9 times to 64 times, but the mRNA expression of MRP1 was down-regulated from 0.01 times to 0.03 times. It is a rare report that glioma stem-like cells can be induced successfully from a grade 2-3 astrocytoma tissue. The properties of glioblastoma and astrocytoma stem-like cells on anti-apoptotic and MRP genes are: anti-apoptotic gene livin and survivin are elevated in CSCs but are the most increased in just differentiated CSCs; MRP1 gene is significantly increased and MRP3 is decreased in CSCs, but when differentiating the MRP3 gene starts a remarkable increase in CSCs; the expression of anti-apoptotic and MRP genes shows no differences between the CSCs isolated from glioblastoma and astrocytoma tissues.


Effect of botulinum toxin injection on length and lengthening velocity of rectus femoris during gait in hemiparetic patients.
In hemiparetic patients, rectus femoris spasticity is one of the main causes of reduced knee flexion in swing phase, known as stiff knee gait. Botulinum toxin is often used to reduce rectus femoris spasticity and to increase knee flexion during swing phase. However, the mechanisms behind these improvements remain poorly understood. The aim of this study was (1) to quantify maximal rectus femoris length and lengthening velocity during gait in ten adult hemiparetic subjects with rectus femoris spasticity and stiff knee gait and to compare these parameters with those of ten healthy subjects and (2) to study the effect of botulinum toxin injection in the rectus femoris muscle on the same parameters. 10 patients with stiff knee gait and rectus femoris spasticity underwent 3D gait analysis before and one month after botulinum toxin injection of the rectus femoris (200 U Botox, Allergan Inc., Markham, Ontario, CANADA). Rectus femoris length and lengthening velocity were quantified using a musculoskeletal model (SIMM, MusculoGraphics, Inc., Santa Rosa, California, USA). Maximal length and lengthening velocity of the rectus femoris were significantly reduced on the paretic side. There was a significant increase in muscle length as well as lengthening velocity during gait following botulinum toxin injection. This study showed that botulinum toxin injection in the spastic rectus femoris of hemiparetic patients improves muscle kinematics during gait. However maximal rectus femoris length did not reach normal values following injection, suggesting that other mechanisms are likely involved.


Circular dichroism study of enzymatic manipulation on magnetic and metallic DNA template nanowires.
Circular dichroism spectroscopy (CD) was used to examine the mechanism of endonuclease clipping and ligation of the DNA template nanowires. The biomolecular manipulation of the DNA template is compared for both metallic (Au) and magnetic (Fe(2)O(3) and CoFe(2)O(4)) nanowires. The dependence of nanoparticle (NP) concentration on enzymatic clipping and DNA ligation was studied, in addition to performing absorbance and thermal melting experiments. Low-NP concentration preserved and digested the DNA template structure. Yet, at higher NP concentrations, the DNA template began to denature before enzyme addition. It was also observed that ligation of the digested DNA occurred more efficiently at low-NP concentrations. These results provide significant information on structural alteration and biorecognition effectiveness of the DNA template after enzymatic manipulation.


Inpatient violence: trait and state.
This study compared patients who showed persistent violence, transient violence and no violence. The presence of neurological abnormalities was found to be the factor that differentiated most clearly among the three groups. The persistently violent patients, in addition to showing significantly more neurological abnormalities, also evidenced a more disturbed family background. Both violent groups had a higher incidence of violent crime prior to hospitalization than the nonviolent controls. A logistic regression model simultaneously relating the effects of six factors on violent behavior was developed and used to predict violent group membership.


Autoregulated, bidirectional and multicistronic gas-inducible mammalian as well as lentiviral expression vectors.
We present a novel set of autoregulated, bidirectional and multicistronic mammalian as well as lentiviral expression vectors which enable transgene expression fine-tuning by gaseous acetaldehyde. The acetaldehyde-inducible regulation (AIR) technology capitalizes on Aspergillus nidulans components evolved to convert ethanol into metabolic energy. AIR is based on functional interaction of the fungal transactivator AlcR and AlcR-specific chimeric promoters (P(AIR)) which drive desired transgene expression in mammalian cells only in the presence of gaseous acetaldehyde. We have engineered AIR technology into a variety of different mammalian and lentiviral expression vector systems including (i) a most compact autoregulated expression format harboring alcR and the transgene in a single P(AIR)-driven transcription unit, (ii) a bidirectional P(AIR) derivative supporting expression of two transgenes with strict 1:1 transcription stoichiometry and (iii) a multicistronic expression arrangement providing simultaneous translation of three independent transgenes from a single P(AIR)-controlled transcript. All expression vectors have been validated in Chinese hamster ovary (CHO-K1), baby hamster kidney (BHK-21) and human HeLa cells for gas-inducible (co-)expression of the reporter transgenes such as Bacillus stearothermophilus-derived secreted alpha-amylase (SAMY), human vascular endothelial growth factor 121 (VEGF121), human placental-secreted alkaline phosphatase (SEAP) and Escherichia coli-derived chloramphenicol acetyl-transferase (CAT). The panoply of mammalian/lentiviral vectors presented here provides a robust and versatile expression platform for the first gas-inducible transgene control system which we expect to foster future advances in gene therapy, tissue engineering as well as biopharmaceutical manufacturing.


Quantitative sensory testing and skin biopsy findings in late-onset ATTRv presymptomatic carriers: Relationships with predicted time of disease onset (PADO).
Hereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN) presymptomatic carriers often show preclinical abnormalities at small fiber-related diagnostic tests. However, no validated biomarker is currently available to use for presymptomatic carriers' follow-up, thus helping therapeutic decision making. Our study aimed at assessing nerve conduction study (NCS), quantitative sensory testing (QST), and skin biopsy parameters in a large cohort of late-onset ATTRv presymptomatic carriers and to evaluate whether they correlated with predicted age of disease onset (PADO). Late-onset ATTRv presymptomatic carriers were consecutively enrolled and underwent NCS, QST, and skin biopsy with intraepidermal nerve fiber density (IENFD) evaluation from a distal and a proximal site. Douleur Neuropathique-4 (DN4) and Small Fiber Neuropathy-Symptoms Inventory (SFN-SIQ) were used to assess painful and small fiber neuropathy-related symptoms. PADO and time-to-PADO (delta-PADO) were estimated for each carrier, and correlations with diagnostic test measures were analyzed. Forty presymptomatic ATTRv subjects were enrolled. Twenty carriers (50%) had distal IENFD reduction, with a non-length-dependent distribution in 73% of cases. Eleven subjects (27.5%) had cold and/or warm detection threshold (CDT and/or WDT) abnormalities at QST. Delta-PADO positively correlated with sural sensory nerve action potential (SNAP) amplitude (r = .416, p = .004), and z-values of QST parameters like CDT (r = .314, p = .028), WDT (r = -.294, p = .034), and mechanical detection threshold (MDT; r = -.382, p = .012). Simple linear regression models showed a linear relation between delta-PADO and sural SAP, CDT, and MDT. Our findings confirm that IENFD reduction and QST abnormalities may occur early in ATTRv presymptomatic carriers, often with a non-length-dependent pattern. However, only sural SAP amplitude and QST parameters correlated with delta-PADO, suggesting that serial combined QST and NCS evaluation could be useful in ATTRv presymptomatic carriers' follow-up.


Hydroxyaluminium tetra-3-phenylthiophthalocyanine is a new effective photosensitizer for photodynamic therapy and fluorescent diagnosis.
We studied the possibility of using liposomal forms of hydroxyaluminium tetra-3-phenylthiophthalocyanine as a near infrared band photosensitizer. Experiments on mice with solid Ehrlich tumor and subcutaneously transplanted P-388 leukemia revealed high selectivity of accumulation of the photosensitizer in tumors in comparison with normal tissues and high photodynamic activity of the preparation. This photosensitizer can be used as the basis for creating an effective preparation for photodynamic therapy and fluorescent diagnosis.


RmtF, a new member of the aminoglycoside resistance 16S rRNA N7 G1405 methyltransferase family.
Multidrug-resistant clinical isolate Klebsiella pneumoniae BM4686 was highly resistant to 4,6-disubstituted 2-deoxystreptamines and to fortimicin. Resistance was due to the presence, on the 40-kb non-self-transferable plasmid pIP849, of the rmtF gene which was cotranscribed with the upstream aac(6')-Ib gene. The deduced RmtF protein had 25 to 46% identity with members of the N7 G1405 family of aminoglycoside resistance 16S rRNA methyltransferases.


Helicase89B is a Mot1p/BTAF1 homologue that mediates an antimicrobial response in Drosophila.
We have identified a novel component, Helicase89B, that is required for the inducible antimicrobial response in Drosophila larvae by means of a P-element insertional genetic screen. Helicase89B belongs to the Mot1p/BTAF1 subfamily of SNF2-like ATPases. This subfamily can interact with TATA-binding proteins, but whether the interaction leads to gene activation or repression is being debated. We found that Helicase89B is required for the inducible expression of antimicrobial peptide genes but not for the inducible expression of heat-shock genes. The antimicrobial peptide genes are activated by the Toll and immune deficiency (IMD) signalling pathways. Genetic experiments show that Helicase89B acts downstream of DIF and Relish, the two nuclear factor-kappaB (NF-kappaB)-related transcription factors that mediate Toll- and IMD-stimulated antimicrobial response. Thus, Helicase89B positively regulates gene expression during innate immune response and may act as a link between NF-kappaB-related transcription factors and the basal transcription machinery.


10-year long-term survival (LTS) of induction chemotherapy with three cycles cisplatin/paclitaxel followed by concurrent chemoradiation cisplatin/etoposide/45 Gy (1.5 Gy bid) plus surgery in locally advanced non-small-cell lung cancer (NSCLC)-a multicenter phase-II trial (CISTAXOL).
Induction chemoradiotherapy plus surgery remains an option to study in IIIA(N2) and selected IIIB NSCLC. Here we report ten-year long-term survival of a prospective multicenter German-French phase-II trial with trimodality. Mediastinoscopically proven IIIA(N2)/selected IIIB NSCLC received three cycles cisplatin (50 mg/m(2) day 1+8) and paclitaxel (175 mg/m(2)d1) qd 22. Concurrent CTx/RTx followed: 45 Gy (1.5 Gy bid) with cisplatin 50 mg/m(2) day 2+9 and etoposide 100 mg/m(2) d 4-6. Surgery was planned three to five weeks after RTx. If evaluated inoperable/irresectable at the end of RTx, definitive RTx-boost (20 Gy; 2 Gy qd) followed. Here we report 10-year-LTS for this cohort. All 64 patients were accrued 3/99 to 2/02. Patients characteristics: IIIA(N2)/IIIB 25/39; m/f 48/16; adeno/squamous/large-cell/adenosquamous/NOS 15/26/18/3/2; age: median 52.5 (range 33-69). 36 operated: R0 32/36 (89%); pCR 16/36 (44%). 10-year-LTS%; all 26.0; IIIA(N2) 37.1; IIIB 17.9; relevant prognostic factors (exploratory): pretreatment - histopathology (squamous/adeno) - age (<50/≥50) - Charlson-CI: 1/>1 - BMI (≥25/<25) - pack years smoking (≥10/<10); treatment-dependent - R0/no-R0. This regimen achieves substantial LTS. Interestingly, adenocarcinomas, older patients, unfavorable comorbidity scores, higher BMI and light smokers demonstrate poor long-term outcome even with aggressive trimodality. This dataset defines the rationale for our ongoing randomized trial with surgery after induction therapy in IIIA(N2)/selected IIIB (ESPATÜ).


[The plasmic translocation and release of high mobility group box chromosomal protein 1 in peripheral blood monocytes of patients with rheumatoid arthritis and the effect of thalidomide].
To investigate the release and intracellular localization of high mobility group box chromosomal protein 1 (HMGB1) in the peripheral blood monocytes of rheumatoid arthritis (RA) patients and the inhibitive effect of thalidomide. 19 RA patients and 20 healthy controls were included in the study. Monocytes were separated from peripheral blood with Ficoll density gradient centrifugation. Monocytes were treated with 100 ng/ml tumor necrosis factor alpha (TNFalpha) or 100 ng/ml TNFalpha plus 40 microg/ml thalidomide and grown in an incubator at 37 degrees C with 5% CO2 for 24 hours. The culture supernatants of the monocytes were collected. HMGB1 level in the culture medium was detected with Western blot. In addition, the intracellular localization of HMGB1 in the monocytes was investigated with immunocytochemical analysis. Without stimulation, the release of HMGB1 protein was significantly increased in the culture supernatants of peripheral blood monocytes from RA patients as compared with that from healthy controls (P < 0.05). TNFalpha (100 ng/ml) did not further increase the release of HMGB1 in the monocytes from the patients with RA. Thalidomide (40 microg/ml) could inhibit the release of HMGB1 in the monocytes from RA patients stimulated with TNFalpha (P < 0.05). In the monocytes from RA patients, HMGB1 was mainly localized in the nucleus. Treatment with TNFalpha (100 ng/ml) for 24 hours resulted in a cytoplasmic translocation of HMGB1, which was inhibited significantly by thalidomide. TNFalpha induces the release and cytoplasmic translocation of HMGB1 in the peripheral blood monocytes of RA patients and thalidomide inhibits the release and translocation of HMGB1.


Bacteriophage therapy--cooked goose or phoenix rising?
Recent animal and human trials of bacteriophage therapy have demonstrated its potential to alleviate bacterial diseases, both in internal and in external applications. The regulatory requirements are becoming clearer as more examples are presented. A core of GLP (Good Laboratory Practice) studies will be needed to validate safety and clinical trials to validate efficacy. GMP (Good Manufacturing Practice) production requirements and quality issues will mean that comparable costs to the production of conventional antibiotics should be anticipated. The definition of the 'active substance' will be central to the success of bacteriophage therapy to ensure that the variety and evolutionary potential of bacteriophages are exploited.


Comprehensive analysis of the immunogenic cell death-related signature for predicting prognosis and immunotherapy efficiency in patients with lung adenocarcinoma.
Although immunotherapy has been considered as a potent strategy for lung adenocarcinoma (LUAD), only a small part of patients was served as potentially clinical benefiters. Immunogenic cell death (ICD), a type of regulated cell death (RCD), which enable to reshape the tumor immune microenvironment and contribute to the immunotherapy efficiency. Developing a novel ICD-based signature may be a potential strategy to differentiate prognosis of patients with LUAD and predict efficacy of immunotherapy. In this study, 34 ICD-related genes (ICDRGs) were identified and analyzed in LUAD samples from the Cancer Genome Atlas (TCGA). 572 patients with LUAD were divided into two distinct clusters according to ICDRGs expression levels. Patients were subsequently classified into two distinct gene subtypes based on differentially expressed genes (DEGs) analyzed between two ICD-related clusters. We further developed and validated a novel ICD-related score (ICDRS) followed by comprehensive investigation about the landscape of the prognosis, immune-based features, immunotherapautic responses and sensitivity of target drugs in patients with LUAD. After confirming transcriptomic aberrations and appraising prognostic value of ICDRGs, two ICD-associated subtypes were initially determined by consensus clustering in accordance with differentially expressional levels of ICDRGs. It was shown that patients in the ICD high-subtype possessed the superior clinical prognosis, abundant immune cell infiltration and higher involvement in immune-related signaling compared with the ICD low-subtype. A signature of ICD-related score (ICDRS) was further established and validated, which was served as an independent prognostic indicator for LUAD patients. These comprehensive results revealed that the high-score patients represented better clinical prognosis, higher immune infiltration-related characteristics, stronger expression of immune checkpoints, and better response to immune checkpoint inhibitor therapy and multiple targeted drugs. To further verify our analysis, we selected TLR4 as the representative of ICDRGs and evaluated its expression on the lung normal cells and cancer cells in vitro. Then, relative animal experiments were performed in vivo, with results of that the stimulation of TLR4 suppressed the growth of lung cancer. In conclusion, our comprehensive analysis of ICDRGs in LUAD demonstrated their function in serving as a biomarker of predicting prognosis and clinical effects of immunotherapy and targeted drugs, which is meaningful to improve our understanding of ICDRGs and brought inspirations about evaluating prognosis and developing effective therapeutic strategies to patients with LUAD.


Loss of a single methylation in 23S rRNA delays 50S assembly at multiple late stages and impairs translation initiation and elongation.
Ribosome biogenesis is a complex process, and dozens of factors are required to facilitate and regulate the subunit assembly in bacteria. The 2'-O-methylation of U2552 in 23S rRNA by methyltransferase RrmJ is a crucial step in late-stage assembly of the 50S subunit. Its absence results in severe growth defect and marked accumulation of pre50S assembly intermediates. In the present work, we employed cryoelectron microscopy to characterize a set of late-stage pre50S particles isolated from an Escherichia coli ΔrrmJ strain. These assembly intermediates (solved at 3.2 to 3.8 Å resolution) define a collection of late-stage particles on a progressive assembly pathway. Apart from the absence of L16, L35, and L36, major structural differences between these intermediates and the mature 50S subunit are clustered near the peptidyl transferase center, such as H38, H68-71, and H89-93. In addition, the ribosomal A-loop of the mature 50S subunit from ΔrrmJ strain displays large local flexibility on nucleotides next to unmethylated U2552. Fast kinetics-based biochemical assays demonstrate that the ΔrrmJ 50S subunit is only 50% active and two times slower than the WT 50S subunit in rapid subunit association. While the ΔrrmJ 70S ribosomes show no defect in peptide bond formation, peptide release, and ribosome recycling, they translocate with 20% slower rate than the WT ribosomes in each round of elongation. These defects amplify during synthesis of the full-length proteins and cause overall defect in protein synthesis. In conclusion, our data reveal the molecular roles of U2552 methylation in both ribosome biogenesis and protein translation.


Relation of statin use to the 5-year incidence and progression of age-related maculopathy.
To examine the association of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) with the 5-year incidence of age-related maculopathy (ARM). Population-based cohort study. Participants included persons 48 to 91 years old examined March 1, 1993, through June 14, 1995, living in Beaver Dam, Wis (N = 3684), of whom 2780 participated in a follow-up 5 years later. Standardized procedures were used for physical examinations, blood sample collection, and questionnaire administration. Age-related maculopathy was determined by grading images of the posterior pole using a standard protocol. Standard univariate and multivariate analyses were performed. Incidence and progression of ARM was measured over the 5-year interval. While controlling for age and sex, statin use was not found to be associated with the 5-year incidence of early ARM (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.47-2.67), progression of ARM (OR, 1.22; 95% CI, 0.54-2.76), or incidence of late ARM (OR, 0.41; 95% CI, 0.12-1.45). These findings do not suggest an association between statin use and incident ARM over a 5-year period. Further investigation of these relationships in larger studies over a longer period is needed.


[Comparative study of the expression and phosphorylation of neurofilament proteins of brain gray matter in Alzheimer's disease].
To explore the role of abnormal modification of neurofilament proteins (NFPs) in the pathogenesis of Alzheimer disease (AD), and the characteristics of NFPs in distribution and solubility. Ultra-centrifugation and Western blot were utilized to isolate and analyze NF subunits. Ultra-centrifugation and Western blot were utilized to observe the effect of abnormal modification of neurofilament proteins (NFPs) on the characteristics of NFPs in distribution and solubility in the pathogenesis of Alzheimer disease. In human brain gray matter, NF subunits were mainly detected in particular fraction. Compared with Huntington's disease (HD), the content of NF subunits was increased in AD brain gray matter and the increased level of NF-H and NF-M were mainly in abnormal hyper-phosphorylate form. Abnormal phosphorylation and accumulation of NFPs are involved in pathology of AD brain.


[Hereditary breast and ovarian cancers].
Hereditary factors are responsible for 5-10% of all breast cancers and 10% of all ovarian cancer cases and are predominantly caused by mutations in the high risk genes BRCA1 and BRCA2 (BRCA: breast cancer). Additional moderate and low penetrance gene variants are currently being analyzed via whole genome association studies. Interdisciplinary counseling, quality managed genetic testing and intensified prevention efforts in specialized medical centres are essential for members of high risk families considering the high prevalence of malignant tumors and the early age of onset. Furthermore, the identification of BRCA-deficient carcinomas is of particular clinical interest, especially regarding new specific therapeutic options, e.g. treatment with poly (ADP-ribose) polymerase (PARP) inhibitors. There are presently no valid surrogate markers verifying the association of BRCA1/BRC2 in tumors. However, breast cancers harboring pathogenic BRCA1 mutations in particular display specific histopathological features.


The outer limits of the welfare state: discrimination, racism and their effect on human services.
The European social democracies have been more generous than the United States in social provision, including services to aged. The momentum of provision has slowed down in recent years. We suggest that prosperity which has led to use of foreign laborers in menial jobs has caused this slow down. The dynamics are similar to the historical U.S. use of "non-100% Americans" as our menial workers. Changes in social policy strategies are needed: 1) universal provision, rather than programs aimed at minorities, is needed to enlist support of stable working and middle classes; 2) tax reforms, which lower progressive income-tax structures for middle incomes, and value-added tax, may be necessary to overcome anti-tax ideologies; 3) clear priorities as to most necessary services must be established by the gerontological community.


IL-12 p40 monomer is different from other IL-12 family members to selectively inhibit IL-12Rβ1 internalization and suppress EAE.
Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system. The IL-12 family of cytokines has four members, which are IL-12 (p40:p35), IL-23 (p40:p19), the p40 monomer (p40), and the p40 homodimer (p402). Since all four members contain p40 in different forms, it is important to use a specific monoclonal antibody (mAb) to characterize these molecules. Here, by using such mAbs, we describe selective loss of p40 in serum of MS patients as compared to healthy controls. Similarly, we also observed decrease in p40 and increase in IL-12, IL-23, and p402 in serum of mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS, as compared to control mice. Interestingly, weekly supplementation of mouse and human recombinant p40 ameliorated clinical symptoms and disease progression of EAE. On the other hand, IL-12, IL-23, and p402 did not exhibit such inhibitory effect. In addition to EAE, p40 also suppressed collagen-induced arthritis in mice. Using IL-12Rβ1-/-, IL-12Rβ2-/-, and IL-12Rβ1+/-/IL-12Rβ2-/- mice, we observed that p40 required IL-12Rβ1, but not IL-12Rβ2, to suppress EAE. Interestingly, p40 arrested IL-12-, IL-23-, or p402-mediated internalization of IL-12Rβ1, but neither IL-12Rβ2 nor IL-23R, protected regulatory T cells, and suppressed Th1 and Th17 biasness. These studies identify p40 as an anti-autoimmune cytokine with a biological role different from IL-12, IL-23, and p402 in which it attenuates autoimmune signaling via suppression of IL-12Rβ1 internalization, which may be beneficial in patients with MS and other autoimmune disorders.


Hepatitis disease diagnosis using a novel hybrid method based on support vector machine and simulated annealing (SVM-SA).
In this study, diagnosis of hepatitis disease, which is a very common and important disease, is conducted with a machine learning method. We have proposed a novel machine learning method that hybridizes support vector machine (SVM) and simulated annealing (SA). Simulated annealing is a stochastic method currently in wide use for difficult optimization problems. Intensively explored support vector machine due to its several unique advantages is successfully verified as a predicting method in recent years. We take the dataset used in our study from the UCI machine learning database. The classification accuracy is obtained via 10-fold cross validation. The obtained classification accuracy of our method is 96.25% and it is very promising with regard to the other classification methods in the literature for this problem.


Human orbitofrontal cortex signals decision outcomes to sensory cortex during behavioral adaptations.
The ability to respond flexibly to an ever-changing environment relies on the orbitofrontal cortex (OFC). However, how the OFC associates sensory information with predicted outcomes to enable flexible sensory learning in humans remains elusive. Here, we combine a probabilistic tactile reversal learning task with functional magnetic resonance imaging (fMRI) to investigate how lateral OFC (lOFC) interacts with the primary somatosensory cortex (S1) to guide flexible tactile learning in humans. fMRI results reveal that lOFC and S1 exhibit distinct task-dependent engagement: while the lOFC responds transiently to unexpected outcomes immediately following reversals, S1 is persistently engaged during re-learning. Unlike the contralateral stimulus-selective S1, activity in ipsilateral S1 mirrors the outcomes of behavior during re-learning, closely related to top-down signals from lOFC. These findings suggest that lOFC contributes to teaching signals to dynamically update representations in sensory areas, which implement computations critical for adaptive behavior.


Evaluation of nerve capture using classical landmarks for genicular nerve radiofrequency ablation: 3D cadaveric study.
Radiofrequency (RF) denervation of the superolateral genicular nerve (SLGN), superomedial genicular nerve (SMGN) and inferomedial genicular nerve (IMGN) is commonly used to manage chronic knee joint pain. However, knowledge of articular branches captured, using classical landmarking techniques, remains unclear. In order to enhance and propose new RF procedures that conceivably capture a greater number of articular branches, more detailed cadaveric investigation is required. The objectives were to (1) determine which articular branches are captured or spared using classical landmarking techniques, and (2) evaluate the anatomical feasibility of classical landmarking techniques using three-dimensional (3D) modeling technology. Ultrasound-guided classical superolateral/superomedial/inferomedial landmarking techniques were used to position RF cannulae in five specimens. The articular branches, bony and soft tissue landmarks, and cannula tip position, were meticulously dissected, digitized and modeled in 3D. Simulated lesions were positioned at the cannula tip, on the 3D models, to determine which articular branches were captured or spared. Capture rates of articular branches were compared. In all specimens, classical superolateral/superomedial techniques captured the transverse deep branches of SLGN and SMGN, and articular branches of lateral and medial nerve to vastus intermedius, while sparing distal branches of SLGN/SMGN. The inferomedial technique captured anterior branches of IMGN while sparing the posterior and inferior branches. This study provides anatomical evidence supporting the effectiveness of classical landmarking for genicular nerve ablation; however, each technique resulted in sparing of articular branches. The extensive innervation of the knee joint suggests the use of supplementary landmarks to improve capture rates and potentially patient outcomes.


Increased detection of HPV 16 virus in invasive, but not in early cervical cancers.
Human papilloma virus type 16 (HPV 16) DNA is found in about 50% of cervical squamous cell carcinomas (SCCs), and this association has raised the possibility of a causal role for HPV 16 in cervical carcinogenesis. We have tested this hypothesis by assaying a series of biopsies (n = 119) ranging from normal mucosa to infiltrating SCC with the PCR-technique for the presence of HPV 16 DNA. While HPV 16 DNA was detected in 50% of our cases with invasive SCC, the incidence of HPV 16-positive samples was about 10% in all other biopsies ranging from normal mucosa to cases of carcinoma in situ. HPV 16 therefore appears to be involved in late tumor promotion but not in early tumor development.


Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel.
During 1996 and 1997 a panel of European haematologists, oncologists, and neonatologists developed specific paediatric guidelines for the use of colony stimulating factors based on published literature and the clinical experience of these specialists within each of 13 countries. Well established indications for use comprise intervention in patients with life-threatening infection, adjunctive therapy post autologous bone marrow transplantation (BMT), mobilization of peripheral blood progenitor cells for autologous BMT, patients with acquired aplastic anaemia on anti-lymphocyte globulin and cyclosporin regimen, and severe congenital neutropenia. Less clear indications include primary prophylaxis to support dose intensification in children with high risk/advanced malignancies, secondary prophylaxis to prevent neutropenia in patients with a history of severe neutropenia, support therapy in cases of poor marrow function following BMT and for deteriorating marrow function following successful BMT, in neonatal sepsis and non infectious neonatal neutropenia, in drug induced neutropenia and in HIV-positive patients. Treatment is generally well tolerated and granulocyte colony stimulating factor appears better tolerated than granulocyte and macrophage colony stimulating factor. Economically colony stimulating factors have not been shown to induce excessive costs for a given patient. In general the adult guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasms, specific indications, neonatal use, congenital disorders) must be taken into account.


Computed tomography of complicated psoas abscess with intraabscess contrast medium injection.
Computed tomography in a case of tuberculous psoas abscess is described. Additional information useful in planning surgical drainage was obtained by intraabscess contrast medium injection through a draining sinus.


Pontederia sagittata and Cyperus papyrus contribution to carbon storage in floating treatment wetlands established in subtropical urban ponds.
Carbon sequestration is considered an ecosystem service of regulation provided by diverse ecosystems, including wetlands. It has been widely evaluated in the soil of natural wetlands while in constructed wetlands, there is scanty information. In Floating Treatment Wetlands (FTW) there is none. Previously, our research group reported the efficient performance of FTW in an urban polluted pond for two years. As a follow up, the aim of this work was to investigate the contribution of Cyperus papyrus and Pontederia sagittata to carbon storage (CS) in four FTW established in eutrophic urban ponds in a subtropical region. Plant growth, productivity, and CS were assessed in the aboveground biomass of C. papyrus and P. sagittata and the belowground biomass (root mix from C. papyrus and P. sagittata), throughout 26 months in 2 FTW with an area of 17.5 m2 (FTW1) and 33 m2 (FTW2) and throughout 19 months in 2 FTW with an area of 25 m2 (FTW3) and 33 m2 (FTW4), respectively. The macrophyte growth depended on various factors, such as the season, the plant species, and the location of the FTW. High relative growth rate values were found for both species (0.125 and 0.142 d-1 for P. sagittata and C. papyrus, respectively), especially during summer and early autumn. The highest values of productivity were 337 ± 125 gdw m-2d-1 for the aboveground biomass of C. papyrus in FTW2, 311 ± 96.90 gdwm-2d-1 for the aboveground of P. sagittata in FTW1, and 270 ± 107 gdw m-2d-1 for the belowground biomass in FTW2. The mean values of CS for P. sagittata found in FTW1 were 1.90 ± 0.94 kg m-2, while for C. papyrus in FTW2 they were 4.09 ± 0.73 kg m-2. The contribution of the belowground biomass to CS was also significant in FTW2 (4.58 ± 0.59 kg m-2).


A combined top-down and bottom-up MS approach for the characterization of hemoglobin variants in Rhesus monkeys.
Sickle cell disease is caused by one of the 1200 known hemoglobin variations. A single-point mutation β6(A3)Glu→Val leads to sickling of red blood cells, which in turn causes a lack of oxygen supply to tissue and organs. Although sickle cell disease is well understood, treatment options are currently underdeveloped. The only Food and Drug Administration-approved drug is hydroxyurea, an inducer of fetal γ-hemoglobin, which is known to have a higher oxygen affinity than adult hemoglobins and thus alleviates symptoms. In the search for better cures, Rhesus monkeys (Macaca mulatta) serve as models for monitoring success of induction of fetal γ-hemoglobins and with recent advances in proteomics, MS has become the leading technique to determine globin expression. Similar to humans, Rhesus monkeys possess hemoglobin variants that have not been sufficiently characterized to initiate such a study. Therefore, we developed a combined bottom-up and top-down approach to identify and characterize novel hemoglobin variants of the umbilical cord blood of Rhesus monkeys. A total of four different variants were studied: α, β, γ1 and γ2. A new α- and β-hemoglobin variant was identified, and the two previously hypothesized γ-hemoglobins were identified. In addition, glutathionylation of both γ-hemoglobin variants at their cysteines has been characterized. The combined approach outperformed either bottom-up or top-down alone and can be used for characterization of unknown hemoglobin variants and their PTMs.


Sorption of Cu and Zn by bone charcoal.
Bone charcoal is being developed as a treatment for decontaminating polluted water. In particular, its potential to adsorb metal species from contaminated water supplies is being examined. In this study, bone charcoal was used in batch and column experiments designed to investigate the sorption of two cationic metals Cu and Zn. The data from batch experiments fitted the Langmuir isotherm and so theoretical maximum binding capacities could be obtained. These values were compared with experimental values derived from the column experiments. The mechanisms involved in the immobilisation were also investigated.


Postradiation sarcoma: case report and review of the potential complications of therapeutic ionizing radiation.
Radiation therapy is an acceptable treatment choice for many cutaneous malignancies. A potential late sequela of ionizing radiation is the development of secondary neoplasms within the treatment field. Although there are well-known cutaneous syndromes in which the use of ionizing radiation is contraindicated, in other clinical situations, physicians may not fully realize the risks associated with this therapeutic modality. Through a case report presentation, a potential adverse consequence of radiation therapy will be discussed. A subsequent review of the literature should allow clinicians to better understand the potential risks of therapeutic radiation. A case report and review of the literature are provided. A healthy black male with an unusual distribution of lower extremity squamous cell carcinomas in situ developed a malignant fibrous histiocytoma after radiation therapy. Postradiation sarcomas are uncommon complications of radiation therapy; however, the significant metastatic capabilities of these tumors demand that clinicians be aware of the potential risks of primary radiation therapy in the treatment of cutaneous tumors.


Neurocognitive Development in Children at Familial High Risk of Schizophrenia or Bipolar Disorder.
Neurocognitive impairments exist in children at familial high risk (FHR) of schizophrenia and bipolar disorder. Studies on preadolescent developmental courses of neurocognition are important to describe shared and distinct neurodevelopmental pathways in these groups. To assess the development in specific neurocognitive functions from age 7 to 11 years in children at FHR of schizophrenia or bipolar disorder compared with children in a population-based control (PBC) group. The Danish High Risk and Resilience Study is a prospective, longitudinal, cohort study that collected data from January 1, 2013, to January 31, 2016 (phase 1), and from March 1, 2017, to June 30, 2020 (phase 2). Data were collected at 2 university hospitals in Denmark, and participants included 520 children at FHR of schizophrenia or bipolar disorder along with a PBC group matched with the group of children at FHR of schizophrenia by age, sex, and municipality. Parental schizophrenia, bipolar disorder, or neither. Neurocognitive functioning was assessed with validated tests of intelligence, processing speed, attention, memory, verbal fluency, and executive functioning. Multilevel mixed-effects linear regression models with maximum likelihood estimation were used to estimate neurocognitive development from age 7 to 11 years. At 4-year follow-up, a total of 451 children (mean [SD] age; 11.9 [0.2] years; 208 girls [46.1%]) underwent neurocognitive testing. There were a total of 170 children at FHR of schizophrenia (mean [SD] age, 12.0 [0.3]; 81 girls [47.7%]), 103 children at FHR of bipolar disorder (mean [SD] age, 11.9 [0.2] years; 45 girls [43.7%]), and 178 children in the PBC group (mean [SD] age, 11.9 [0.2] years; 82 girls [46.1%]). At either age 7 or 11 years or at both assessments, 520 children participated in the neurocognitive assessment and were therefore included in the analyses. When correcting for multiple comparisons, no statistically significant time × group interactions were observed across the 3 groups. Compared with the PBC group at 4-year follow-up, children at FHR of schizophrenia showed significant neurocognitive impairment in 7 of 24 neurocognitive measures (29.2%; Cohen d range, 0.29-0.37). Compared with children at FHR of bipolar disorder, children at FHR of schizophrenia had significant neurocognitive impairment in 5 of 24 measures (20.8%; Cohen d range, 0.29-0.38). Children at FHR of bipolar disorder and those in the PBC group did not differ significantly. In this cohort study, findings suggest that neurocognitive maturation was comparable across groups of children at FHR of schizophrenia or bipolar disorder compared with PBCs from age 7 to 11 years. Compared with the PBC group, children at FHR of schizophrenia demonstrated widespread, stable, neurocognitive impairments during this period, whereas children at FHR of bipolar disorder showed no neurocognitive impairments, which may indicate distinct neurodevelopmental pathways in children at FHR of schizophrenia and bipolar disorder.


Catheter atherectomy: functional results in peripheral arterial disease.
In 10 patients with peripheral arterial disease (PAD) atherectomy was performed with the Simpson atherectomy catheter. PAD was diagnosed by clinical evaluation, oxzillography, Doppler ultrasound examination, treadmill walking, and angiography. Eight patients belonged to stage II and 2 to stage IV. Two stenoses were located in the iliac artery, and the others in the superficial femoral artery or popliteal artery or both. The treadmill walking distance before the intervention ranged from 24 to 67 m before and 105 to 115 m after the procedure (speed 2 mph; gradient 12.5%). After atherectomy, the walking distance improved by 35% to 126%. No patient in stage II perceived pain. In these patients treadmill exercise was terminated because of dyspnea. The ankle/arm ratio (Doppler ultrasound) ranged from 0.4 to 1.0 before atherectomy with a mean improvement of 0.15 afterward (stages II and IV). Control angiography within three to six months in 4 patients did not reveal any significant change at the site of the original stenosis.


CDH13 promoter region is specifically methylated in poorly differentiated colorectal cancer.
It has recently become clear that CDH13 (H-cadherin, T-cadherin) expression is frequently silenced by aberrant methylation in colorectal cancers and adenomas. In this study, we investigated the methylation status of CDH13 gene and detected aberrant promoter methylation in 27 of 84 (32%) colorectal cancers. We then correlated the results with the clinicopathological features of affected patients. We found a significant difference in histology (P=0.0053) when we compared the CDH13 methylation of poorly differentiated colorectal cancers to that of differentiated ones. This result suggested that poorly differentiated colorectal cancers specifically exhibited CDH13 methylation, and since CDH13 might be responsible for selective cell recognition and adhesion, inactivation of CDH13 could lead to the formation of scattered carcinoma cells in these cancers.


The search for spontaneous edge currents in Sr2RuO4 mesa structures with controlled geometrical shapes.
Scanning Hall microscopy has been used to search for spontaneous edge fields in geometrically shaped mesa structures etched into the ab surface of Sr2RuO4 single crystals in order to test recent theories of the direction of edge current flow as a function of facet orientation and band filling. We find no evidence for spontaneous edge fields in any of our mesa structures above our experimental noise floor of ± 25 mG. We do, however, observe pronounced vortex clustering at low fields and temperatures, consistent with the established semi-Meissner scenario whereby a long range attractive component to the vortex-vortex interaction arises due, for example, to the multiband nature of the superconductivity. We also see clear evidence for the formation of a square vortex lattice inside square mesa structures above 1.3 K. Our results are discussed in terms of recent relevant experimental results and theoretical predictions.


Surgical Treatment of Benign Prostatic Hyperplasia-Lift or Laser?
We review modern office based therapies for the management of lower urinary tract symptoms secondary to benign prostatic hyperplasia. A search was performed for the literature between 2005 and 2014 on office based therapies for benign prostatic hyperplasia focusing on prostatic urethral lift and office based laser therapies. Prostatic urethral lift is a novel technology that functions on mechanical compression alone. Initial trials have demonstrated improvement in symptom scores by 42% and in maximum flow by 30% at 2 years of followup. The prostatic urethral lift device represents a novel approach in the array of office based technologies to treat benign prostatic hyperplasia, although additional information on ease of insertion, reproducibility and durability is needed.


Hormonal regulation of beta2-adrenergic receptor level in prostate cancer.
Androgen deprivation is the only effective systemic therapy available for patients with prostatic carcinoma, but is associated with a gradual transition to a hormone-refractory prostate cancer (HRCAP) in which ligand-independent activation of the androgen receptor has been implicated. The beta(2)-adrenergic receptor (beta(2)-AR) is a well-known activator of the androgen receptor. Prostatic cell lines were analyzed using cDNA micro-array, real time RT-PCR, radioligand binding assay, cAMP measurements, transfection and thymidine incorporation assay. Clinical specimens were studied by immunohistochemistry and Affymetrix microarrays. Here, we show that beta(2)-AR was transiently down-regulated both at mRNA- and protein levels when hormone-sensitive prostate cancer cells, LNCaP, were cultured in steroid stripped medium (charcoal-stripped fetal calf serum) or when the cells were treated with the anti-androgen, bicalutamide (Casodex). The number of beta-adrenergic receptors was modestly up-regulated in androgen independent cell lines (LNCaP-C4, LNCaP-C4-2 and DU145) compared to LNCaP. Triiodothyronine (T3) increased the level of beta(2)-AR and the effect of T3 was inhibited by bicalutamide. Immunohistochemical staining of human prostate specimens showed high expression of beta(2)-AR in glandular, epithelial cells and increased expression in malignant cells compared to benign hyperplasia and normal tissue. Interestingly, beta(2)-AR mRNA was strongly down-regulated by androgen ablation therapy of prostate cancer patients. The level of beta(2)-AR was increased by T3 in prostatic adenocarcinoma cells and reduced in prostate cancer patients who had received androgen ablation therapy for 3 months.


Media use and perceived risk as predictors of marijuana use.
To assess the influence of media use and perceived risk on marijuana use outcomes. With survey data from 750 US young adults, structural equation modeling tested how attitudes, behaviors, and behavioral intention specific to marijuana use are influenced by perceived personal and societal risk of marijuana use, media campaign exposure, and news use. Perceived societal risk had significant effects, though not as strong as perceived personal risk. Campaign exposure had favorable effects whereas those of news use were mixed. Perceived personal risk and perceived societal risk should be considered when designing preventive media campaigns.


Orthostatic hypotension is associated with decreased cerebrospinal fluid levels of chromogranin A in early stage of Parkinson disease.
An association between the CSF chromogranin A (CgA) and orthostatic blood pressure changes was investigated in 20 patients in the early stage of Parkinson disease (PD). There was a positive correlation between the CSF CgA and diastolic blood pressure change, when CSF CgA levels were lower in patients with orthostatic hypotension (OH). Decreased CSF CgA may be useful in predicting OH in the early stage of PD.


Increasing the Specificity of AAV-Based Gene Editing through Self-Targeting and Short-Promoter Strategies.
Our group previously used adeno-associated viral vectors (AAVs) to express an engineered meganuclease specific for a sequence in the PCSK9 gene (M2PCSK9), a clinical target for treating coronary heart disease. Upon testing this nuclease in non-human primates, we observed specific editing characterized by several insertions and deletions (indels) in the target sequence as well as indels in similar genomic sequences. We hypothesized that high nuclease expression increases off-target editing. Here, we reduced nuclease expression using two strategies. The first was a self-targeting strategy that involved inserting the M2PCSK9 target sequence into the AAV genome that expresses the nuclease and/or fusing the nuclease to a specific peptide to promote its degradation. The second strategy used a shortened version of the parental promoter to reduce nuclease expression. Mice administered with these second-generation AAV vectors showed reduced PCSK9 expression due to the nuclease on-target activity and reduced off-target activity. All vectors induced a stable reduction of PCSK9 in primates treated with self-targeting and short-promoter AAVs. Compared to the meganuclease-expressing parental AAV vector, we observed a significant reduction in off-target activity. In conclusion, we increased the in vivo nuclease specificity using a clinically relevant strategy that can be applied to other genome-editing nucleases.


Hierarchical Architecture Engineering of Branch-Leaf-Shaped Cobalt Phosphosulfide Quantum Dots: Enabling Multi-Dimensional Ion-Transport Channels for High-Efficiency Sodium Storage.
New-fashioned electrode hosts for sodium-ion batteries (SIBs) are elaborately engineered to involve multifunctional active components that can synergistically conquer the critical issues of severe volume deformation and sluggish reaction kinetics of electrodes toward immensely enhanced battery performance. Herein, it is first reported that single-phase CoPS, a new metal phosphosulfide for SIBs, in the form of quantum dots, is successfully introduced into a leaf-shaped conductive carbon nanosheet, which can be further in situ anchored on a 3D interconnected branch-like N-doped carbon nanofiber (N-CNF) to construct a hierarchical branch-leaf-shaped CoPS@C@N-CNF architecture. Both double carbon decorations and ultrafine crystal of the CoPS in-this exquisite architecture hold many significant superiorities, such as favorable train-relaxation, fast interfacial ion-migration, multi-directional migration pathways, and sufficiently exposed Na+ -storage sites. In consequence, the CoPS@C@N-CNF affords remarkable long-cycle durability over 10 000 cycles at 20.0 A g-1 and superior rate capability. Meanwhile, the CoPS@C@N-CNF-based sodium-ion full cell renders the potential proof-of-feasibility for practical applications in consideration of its high durability over a long-term cyclic lifespan with remarkable reversible capacity. Moreover, the phase transformation mechanism of the CoPS@C@N-CNF and fundamental springhead of the enhanced performance are disclosed by in situ X-ray diffraction, ex situ high-resolution TEM, and theoretical calculations.


Prognostic Significance of Lymph Node Count Removed at Sublobar Resection in Pathologic Stage IA Non-Small-cell Lung Cancer: A Population-Based Analysis.
We sought to elucidate the associations between the examined lymph node (ELN) count and survival after sublobar resection (SLR) in pathologic stage IA non-small-cell lung cancer and assess the survival efficacy for patients undergoing SLR with an adequate ELN count compared with lobar resection (LR). The newly released U.S. Surveillance, Epidemiology, and End Results database was queried. The association between the ELN count in SLR and survival was analyzed using Cox regression and propensity score matching analyses. The optimal cutoff for the ELN count in SLR was determined using the Chow test and "segmented" function. Survival differences between SLR with an adequate ELN count and LR were compared using the log-rank test. A total of 16,630 lobectomies, 3979 wedge resections, and 1119 segmentectomies were included in the present study. The median ELN count was 3 (interquartile range [IQR], 1-7), 1 (IQR, 0-4), and 7 (IQR, 4-12) for segmentectomy, wedge resection, and lobectomy, respectively (P < .001). The optimal cutoff for ELNs was 2.40 (IQR, 2.15-2.65) and 2.59 (IQR, 2.19-3.00) for patients undergoing wedge and segmental resection. SLR patients with ≥ 3 ELNs showed better overall survival and lung cancer-specific survival compared with those with < 3 ELNs. SLR patients with ≥ 3 ELNs had a noninferior prognosis compared with LR patients after matching of potential confounders. In SLR, an adequate ELN count (≥ 3) could confer an improved prognosis compared with an inadequate ELN count (< 3). SLR patients with an adequate ELN count had noninferior survival outcomes compared with LR patients when the ELNs were well matched.


Facile modulation the sensitivity of Eu2+/Eu3+-coactivated Li2CaSiO4 phosphors through adjusting spatial mode and doping concentration.
Series of Eu2+/Eu3+-coactivated Li2CaSiO4 phosphors were prepared by solid-state reaction technique. All the samples emitted the unique emissions of Eu2+ and Eu3+ ions when excited by 395 nm, while the strongest emission intensity was received when x = 0.03. On the basis of theoretical discussion, it is evident that crossover relaxation should be responsible for the thermal quenching mechanism which was further proved by the unchanged lifetime at elevated temperature. Besides, through analyzing the inconsistent responses of the emission intensities of the Eu2+ and Eu3+ ions to the temperature, the optical thermometric properties of the designed phosphors were studied. By selecting different emissions of Eu3+ ions and combining with that of the Eu2+ ions, adjustable sensitivities were realized in the resultant phosphors. Furthermore, the sensitivities of the studied compound were also found to be greatly affected by the doping concentration. The maximum absolute and relative sensitivities of the synthesized compounds were 0.0025 K-1 and 0.289% K-1, respectively. These achieved results implied that the Eu2+/Eu3+-coactivated Li2CaSiO4 phosphors were promising candidates for optical thermometry. Additionally, this work also provided promising methods to modulate the sensitivities of the luminescent compounds by adjusting spatial mode and doping concentration.


Unusual cases of human myiasis due to Old World screwworm fly acquired indoors in Hong Kong.
Myiasis is the infestation of tissue by the larvae of flies. We report eight cases of human myiasis in Hong Kong. All patients were nursing home residents with an average age of 81.8 years. Seven patients were bedridden with advanced dementia. Four patients had pre-existing wounds. Five had poor oral hygiene and four of those were on tube feeding. All of the five patients with poor oral hygiene suffered from oral myiasis. Two patients had vaginal infestations and one had wound myiasis in his diabetic foot ulcer. Seven cases were infested by Chrysomya bezziana, an obligatory parasite that requires living mammalian tissue for its larval development. Larvae of the Calliphoridae family were responsible for the remaining case. Patients were managed with manual removal of larvae and irrigation of the site of infestation with saline. All infestations were nosocomial, being acquired in nursing homes. Carers of the old and debilitated should be made aware of the need for better oral care, especially for those on tube feeding. The use of window screens in nursing homes should be encouraged to reduce the chance of flies entering the vicinity of these patients. Electrocuters could also be mounted indoors to kill flies that do enter.


Iron-induced decomposition of perfluorohexanesulfonate in sub- and supercritical water.
Decomposition of perfluorohexanesulfonate (PFHS), a bioaccumulative analogue of perfluorooctanesulfonate (PFOS), in sub- and supercritical water was investigated. Although PFHS was only slightly reactive in pure subcritical water at 350 degrees C, it decomposed to F(-) and SO(4)(2-) ions when the temperature was increased to 380 degrees C, at which temperature the water became supercritical state. Addition of zerovalent iron to the reaction system dramatically accelerated PFHS decomposition to F(-) ions in both sub- and supercritical water: for example, when the initial PFHS concentration was 741microM, the F(-) yields at 350 degrees C were 4.13-16.0 times as high as those in the absence of iron, depending on the amount and the particle size of the iron powder. After the reactions, small amounts of CO(2) and CF(3)H were also detected in the gas phase; these increased with temperature, and the amount of CF(3)H increased markedly when the reaction was carried out in supercritical water. Increasing the specific surface area of the iron powder markedly increased PFHS consumption and F(-) formation in the aqueous phase, which indicates that the reactions occurred on the iron surface and that the increased specific surface area was a key factor in accelerating the decomposition of PFHS to F(-) ions.


Conformational search of antisense nucleotides. Part 2.
In this study is presented the phosphorotioate nucleotide compound (1) possessing an unusual moiety with a chiral P and a Se atoms double bonded. It required a force field parameterization for carrying out standard molecular mechanics calculations. A new set of MMFF parameters was developed and applied for the complete conformational search of the diastereoisomers, using both Monte Carlo and molecular dynamics, with the purpose to validate them by the comparison between calculated structural properties and NMR measurements.


miRNA-Mediated Suppression of a Cardioprotective Cardiokine as a Novel Mechanism Exacerbating Post-MI Remodeling by Sleep Breathing Disorders.
Obstructive sleep apnea-hypopnea syndrome, a sleep breathing disorder in which chronic intermittent hypoxia (CIH) is the primary pathology, is associated with multiple cardiovascular diseases. However, whether and how CIH may affect cardiac remodeling following myocardial infarction (MI) remains unknown. To determine whether CIH exposure at different periods of MI may exacerbate post-MI heart failure and to identify the mechanisms underlying CIH-exacerbated post-MI remodeling. Adult male mice were subjected to MI (4 weeks) with and without CIH (4 or 8 weeks). CIH before MI (CIH+MI) had no significant effect on post-MI remodeling. However, double CIH exposure (CIH+MI+CIH) or CIH only during the MI period (MI+CIH) significantly exacerbated pathological remodeling and reduced survival rate. Mechanistically, CIH activated TGF-β (tumor growth factor-β)/Smad (homologs of both the Drosophila protein MAD and the C. elegans protein SMA) signaling and enhanced cardiac epithelial to mesenchymal transition, markedly increasing post-MI cardiac fibrosis. Transcriptome analysis revealed that, among 15 genes significantly downregulated (MI+CIH versus MI), Ctrp9 (a novel cardioprotective cardiokine) was one of the most significantly inhibited genes. Real-time polymerase chain reaction/Western analysis confirmed that cardiomyocyte CTRP9 expression was significantly reduced in MI+CIH mice. RNA-sequencing, real-time polymerase chain reaction, and dual-luciferase reporter assays identified that microRNA-214-3p is a novel Ctrp9 targeting miRNA. Its upregulation is responsible for Ctrp9 gene suppression in MI+CIH. Finally, AAV9 (adeno-associated virus 9)-mediated cardiac-specific CTRP9 overexpression or rCTRP9 (recombinated CTRP9) administration inhibited TGF-β/Smad and Wnt/β-catenin pathways, attenuated interstitial fibrosis, improved cardiac function, and enhanced survival rate in MI+CIH animals. This study provides the first evidence that MI+CIH upregulates miR-214-3p, suppresses cardiac CTRP9 (C1q tumor necrosis factor-related protein-9) expression, and exacerbates cardiac remodeling, suggesting that CTRP9 may be a novel therapeutic target against pathological remodeling in MI patients with obstructive sleep apnea-hypopnea syndrome.


Draft Genome Sequences of Four Xanthomonas arboricola pv. juglandis Strains Associated with Walnut Blight in Chile.
Xanthomonas arboricola pv. juglandis is an important pathogen responsible for walnut blight outbreaks globally. Here, we report four draft genome sequences of X. arboricola pv. juglandis strains isolated from Chilean walnut trees.


ZnO nanorod array-coated mesh film for the separation of water and oil.
Dense and vertically aligned ZnO nanorod arrays with a large area have been fabricated successfully on the stainless steel mesh by a simple chemical vapor deposition method. The coated mesh exhibited both superoleophilic and superhydrophobic properties, even if it was not modified by low surface energy materials. The separation efficiencies were more than 97% in the filtration of water and oil. Besides, the wettability of the coated mesh was still stable after it was soaked in the corrosive solutions for 1 h. A detailed investigation showed that the coated mesh has the best superhydrophobic property when the stainless steel mesh pore size was about 75 μm.


Double immunochemical screening test (hemoglobin and albumin) for the detection of occult intestinal bleeding.
The authors have developed a combined electrophoretic-immunoprecipitation technique suitable for the simultaneous demonstration of two blood proteins, i.e., hemoglobin and albumin, in the feces. The analytical sensitivity of the method is 2 micrograms hemoglobin and albumin/ml. The technique is simple, inexpensive, and suitable for the reliable demonstration of occult intestinal bleeding for either inpatients or mass screening. This technique is an aid not only to the fact that bleeding can be detected, but to its intensity, as well. This new technique improves the diagnostic accuracy of early detection of carcinomas and polyps, presumably without raising significantly the number of "false-positive" reactions.


Unipolar sensing in contemporary pacemakers: using myopotential testing to define optimal sensitivity settings.
Bipolar lead use has increased due to oversensing concerns with older unipolar systems. Data on contemporary unipolar devices with improved hardware design and greater programming flexibility is lacking. Using a randomized crossover design, unipolar and bipolar sensing characteristics of 22 atrial and 16 ventricular leads were compared in 34 patients who had pulse generators of programmable polarity. Unipolar and bipolar intracardiac electrogram amplitudes, pacing and sensing thresholds at rest were similar. Provocative maneuvers were used to assess for myopotential inhibition. At atrial sensitivities of 0.625-1.50 mV, myopotential inhibition occurred in 11 (50%) atrial leads in the unipolar mode compared to 1 (5%) in the bipolar mode (p < 0.001). At sensitivities of > 1.50 mV myopotential inhibition occurred in only 1 ventricular (unipolar) lead. An optimal sensitivity setting for each polarity was derived using clinic test results and assessed by ambulatory ECG (AECG). At these optimal settings, oversensing occurred in 1 (6%) atrial and 1 (8%) ventricular unipolar lead during AECG monitoring, whereas oversensing was not seen in any leads programmed to the bipolar mode. Undersensing occurred in 5 (29%) atrial unipolar versus 1 (6%) bipolar lead (p = 0.08). Undersensing was not observed in any of the ventricular leads. Myopotential inhibition may be frequently provoked by provocative maneuvers at higher sensitivity settings in atrial unipolar leads. The frequency of oversensing can be significantly reduced by defining an optimal sensitivity setting using simple isometric maneuvers. Given present day concerns over bipolar lead longevity, increased utilization of unipolar ventricular leads should be considered.


Effect of acidic erosion on properties of solidified sewage sludge.
Solidified sludge can be regarded as a new type of earth cover material for domestic waste landfill. But the acidic environment result from the leachate in landfill is a potential threat to cement-based material. In order to evaluate the deterioration risk of solidified sludge in acidic environment, the leaching process of solidified sludge components under different pH conditions was investigated by taking Ni and Cr as the indexes of semi-dynamic leaching test. Under strongly acid environment (pH = 2), the leaching rate of Cr is significantly higher than that in the weakly acid environment or nearly neutral environment, and the diffusion coefficient increased by an order of magnitudes. The leaching and diffusion coefficients of Ni undergo a small influence from the adding amount of cement and pH value. Both Ni and Cr have relatively low migration ratio.


[Three dimensional optimization method for the interstitional afterloading therapy (author's transl)].
The authors present a new method for the interstitial therapy working with an Ir-192 source which is displaced step by step. After having been fed with the tumor parameters, the computer calculates for every stopping point the duration of stay of the source which provides a threedimensional optimization. The practical application of the method is discussed and the optimization procedure is compared with other similar methods.


Taurine, analogues and ethanol elicited responses.
The effect of taurine, of some of its precursors and major metabolic products on spontaneous locomotor activity were studied in mice. The effect of taurine and some analogues on certain ethanol-mediated responses were observed. Administration of taurine, 50 mg/kg, IP, did not significantly alter motility in experimental animals compared to controls. Behavioral depression was evident subsequent to injection of cysteine hydrochloride or taurocholic acid (50 mg/kg). Administration of taurocholic acid, 50 mg/kg, IP, 30 min prior to a narcotic dose of ethanol, 5 g/kg, IP, reduced the time required for the onset of ethanol-narcosis. Pretreatment with cysteic acid, 50 mg/kg, IP, prolonged ethanol-produced narcosis. Treatment with cysteic acid 30 min prior to ethanol, 2.5 g/kg, IP, was found to decrease whole blood ethanol concentration as compared to the respective controls without a concomitant changes in brain ethanol levels. Administration of taurocholic acid, 100 mg/kg, IP, decreased the intake of an ethanol solution in rats preferring 5% ethanol solution over water as the drinking fluid of choice. None of the compounds tested altered endogenous specific activity of mouse liver alcohol dehydrogenase when given once daily (50 mg/kg, IP) for 10 consecutive days. The results suggest that both taurocholic acid and cysteic acid exert additive action to some ethanol-elicited responses studied.


The clinical skills laboratory: a cost-effective venue for teaching clinical skills to third-year medical students.
The authors taught clinical examination and procedural skills using manikins in a clinical skills laboratory as a part of an integrated curriculum in the third-year clerk-ship. This teaching modality was effective and well received by students and faculty.


Radionuclide Meckelogram with particular reference to false-positive results.
Abdominal imaging 99mTc-pertechnetate is a most sensitive and noninvasive procedure for detecting Meckels diverticulum. However, false-positive results are unavoidable. We report two in which false-positive results were obtained and present a summary of reported false-positive results.


Microsecond protein dynamics measured by 13Calpha rotating-frame spin relaxation.
NMR spin relaxation in the rotating frame (R1rho) is a unique method for atomic-resolution characterization of conformational (chemical) exchange processes occurring on the microsecond timescale. We present a rotating-frame 13C(alpha) relaxation dispersion experiment for measuring conformational dynamics in uniformly 13C-labeled proteins. The experiment was validated by using the E140Q mutant of the C-terminal fragment of calmodulin, which exhibits significant conformational exchange between two major conformations, as gauged from previous 15N and 1H relaxation studies. Consistent with previous work, the present 13C(alpha) R1rho experiment detects conformational-exchange dynamics throughout the protein. The average correlation time of <tau(ex)>=25+/-8 micros is in excellent agreement with those determined previously from 1H and 15N R1rho relaxation data: <tau(ex)>=19+/-7 and 21+/-3 micros, respectively. The extracted chemical-shift differences between the exchanging states reveal significant fluctuations in dihedral angles within single regions of Ramachandran phi-psi space, that were not identified from the 1H and 15N relaxation data. The present results underscore the advantage of using several types of nuclei to probe exchange dynamics in biomolecules.


Microcalorimetric study of the adsorption of native and mono-PEGylated bovine serum albumin on anion-exchangers.
The adsorption of native bovine serum albumin (BSA) and 12 kDa-PEG-BSA on 12 different commercially available strong and weak anion-exchange resins is studied at 25 °C and pH 7. The resins differ in their base matrix material, their functional groups and the type of polymer modification. A combination of equilibrium measurements and microcalorimetric experiments is used to determine the specific enthalpy of adsorption of the proteins. From these data, the entropic contributions to the specific Gibbs energy of adsorption are determined. The results strongly differ for different resins. They also depend on the loadings. The adsorption of BSA on strong (Q) anion-exchangers is exothermic and enthalpy-driven. The adsorption of BSA on weak (DEAE) anion-exchangers is endothermic and entropy-driven. The adsorption of PEG-BSA on strong (Q) anion-exchangers is exothermic or endothermic, depending on the resin, while the adsorption of PEG-BSA on weak (DEAE) anion-exchangers is exothermic for all studied resins. The present study provides a large body of new experimental data that contribute to the understanding of the nature of protein adsorption on ion exchange resins and the influence of the resin properties and polymer modification of the proteins on this process.


The estimation of bladder volume by sonocystography.
Real-time ultrasonography was used to measure bladder volumes. Volumes were calculated as the product of 3 internal bladder diameters (height, width and depth). The true bladder volume was obtained from the voided volume or by catheterization. There was a good correlation between calculated and true volumes provided a correction factor of 0.6 was applied. It also was found that a simpler method using only 2 diameters and a correction factor of 0.15 was nearly as reliable. The accuracy of this quantitative method was shown to be limited to an average error of plus or minus 25 per cent for bladder volumes between 100 and 500 ml. Smaller volumes could be assessed only qualitatively. False negative readings were common for bladder volumes less than 50 ml.


Fast evolution of SARS-CoV-2 driven by deamination systems in hosts.
As an RNA virus, the fast evolution of SARS-CoV-2 is driven by the extensive RNA deamination by the host cells.


Edoxaban for treatment of venous thromboembolism in patient groups with different types of cancer: Results from the Hokusai VTE Cancer study.
The safety and efficacy of edoxaban and dalteparin is unclear for several cancer groups. We evaluated the occurrence of the primary outcome in large cancer groups. The primary outcome was the composite of recurrent VTE or major bleeding over 12 months. In patients with gastrointestinal cancer, the primary outcome occurred in 19.4% patients given edoxaban and in 15.0% given dalteparin (risk difference [RD], 4.4%; 95%-CI, -4.1% to 12.8%). The corresponding rates for edoxaban and dalteparin were 10.4% and 10.7% for lung cancer (RD, -0.3%; 95%-CI, -10.0% to 9.5%), 13.6% and 12.5% for urogenital cancer (RD, 1.1; 95%-CI, -10.1-12.4), 3.1% and 11.7% for breast cancer (RD, -8.6; 95%-CI, -19.3-2.2), 8.9% and 10.9% for hematological malignancies (RD, -2.0; 95%-CI, -13.1-9.1), and 10.4% and 17.4% for gynecological cancer (RD, -7.0; 95%-CI, -19.8-5.7). In the subgroup of gastrointestinal cancer, edoxaban was associated with a 3.5% lower absolute risk of recurrent VTE and a 7.9% higher risk of major bleeding. Edoxaban has a similar risk-benefit ratio to dalteparin in most cancer groups. In those with gastrointestinal cancer, the lower risk of recurrent VTE and the advantages of oral therapy need to be balanced against the increased risk of major bleeding.


A Study on Effect of Surface Treatments on the Shear Bond Strength between Composite Resin and Acrylic Resin Denture Teeth.
Visible light-cured composite resins have become popular in prosthetic dentistry for the replacement of fractured/debonded denture teeth, making composite denture teeth on partial denture metal frameworks, esthetic modification of denture teeth to harmonize with the characteristics of adjacent natural teeth, remodelling of worn occlusal surfaces of posterior denture teeth etc. However, the researches published on the bond strength between VLC composite resins and acrylic resin denture teeth is very limited. The purpose of this study is to investigate the effect of five different methods of surface treatments on acrylic resin teeth on the shear bond strength between light activated composite resin and acrylic resin denture teeth. Ninety cylindrical sticks of acrylic resin with denture teeth mounted atop were prepared. Various treatments were done upon the acrylic resin teeth surfaces. The samples were divided into six groups, containing 15 samples each. Over all the treated and untreated surfaces of all groups, light-cured composite resin was applied. The shear strengths were measured in a Universal Testing Machine using a knife-edge shear test. Data were analyzed using one way analysis of variance (ANOVA) and mean values were compared by the F test. Application of bonding agent with prior treatment of methyl methacrylate on the acrylic resin denture teeth resulted in maximum bond strength with composite resin.


Selective sensitivity of the gut microbiome to iron chelators in polybacterial abdominal sepsis.
Iron chelation has been proposed as a potential therapy for polybacterial abdominal sepsis. Treatment with iron chelation is known to be able to attenuate bacterial growth. It is hypothesized that the different types of bacteria will exhibit variations in their sensitivity to iron chelation based on differences in their iron metabolism. Bacteria with weaker iron access systems might have their growth reduced initially, but stronger species may also be suppressed. Gram-positive and Gram-negative bacteria are known to possess different iron acquisition systems, which may affect their response to iron chelation. Bacteria which can produce siderophores are at a particular advantage for iron acquisition. Novel iron chelators, which do not act as xenosiderophores, may be effective in depriving these bacteria of iron. This has implications for the treatment of polybacterial sepsis, which might be enhanced if the sensitivity to iron chelation of the primary causative agents is known.


Characteristics of the shark fisheries of Fiji.
Limited information is available on artisanal and subsistence shark fisheries across the Pacific. The aim of this study was to investigate Fiji's inshore fisheries which catch sharks. In January and February 2013, 253 semi-directive interviews were conducted in 117 villages and at local harbours on Viti Levu, Vanua Levu, Taveuni, Ovalau and a number of islands of the Mamanuca and Yasawa archipelagos. Of the 253 interviewees, 81.4% reported to presently catch sharks, and 17.4% declared that they did not presently catch any sharks. Of the 206 fishers that reported to catch sharks, 18.4% targeted sharks and 81.6% caught sharks as bycatch. When targeted, primary use of sharks was for consumption or for sale. Sharks caught as bycatch were frequently released (69.6%), consumed (64.9%) or shared amongst the community (26.8%). Fishers' identification based on an identification poster and DNA barcoding revealed that at least 12 species of elasmobranchs, 11 shark and one ray species (Rhynchobatus australiae) were caught. This study, which is the first focused exploration of the shark catch in Fiji's inshore fisheries, suggests that the country's artisanal shark fisheries are small but have the potential to develop into larger and possibly more targeted fisheries.


A contribution to the concept "the exception" as a developmental phenomenon.
The sense of "entitlement" or of being an exception has been noted in people who have suffered from severe childhood deformities or from other forms of severe deprivation. In such cases it constitutes a restitution for earlier suffering. In this vignette from the treatment of a patient who, because of sexual abuse by her mother, did not feel that she owned her own genitals, the sense of entitlement represented a developmental step toward ownership of her own body.