A novel approach to improve the function of FGF21.
Fibroblast growth factor 21 (FGF21) has potent effects on normalizing glucose, lipid, and energy homeostasis, and represents an attractive novel therapy for type 2 diabetes mellitus and obesity. Approaches to improve the pharmacokinetic properties of FGF21, such as conjugation with polyethylene glycol, have been explored for therapeutic development. However, not only is there room for further pharmacokinetic improvements, additional re-engineering approaches to improve the potency and stability of FGF21 have not been reported. Here, we describe a novel approach to modify and improve the function of FGF21 by altering its C-terminal βKlotho interaction domain. We first identified Avimer proteins that are capable of binding βKlotho. Then we explored replacing the C-terminal βKlotho interaction domain of FGF21 with a βKlotho-binding Avimer protein. Such a βKlotho-binding Avimer protein was able to fully complement the C-terminal domain function of FGF21. The resulting FGF21-Avimer fusion is functionally indistinguishable from wild type FGF21, and more tolerant of C-terminal modification. These results demonstrate a viable strategy to modulate the affinity, potency, and engineering of FGF21, paving the way for further improvements of FGF21 as a therapeutic.


1-Year clinical study of indirect resin composite restorations luted with a self-adhesive resin cement: effect of enamel etching.
In vitro studies have recommended enamel-etching before luting indirect restorations with self-adhesive resin cement. However, there is no scientific proof that this procedure has any clinical relevance. Thus, the aim of this study was to evaluate the effect of enamel-etching on the marginal quality of indirect composite resin restorations (inlay/onlay) using the self-adhesive cement RelyX Unicem clicker. Forty-two posterior teeth were selected from 25 patients that presented one or two teeth with large restorations in need of replacement. All teeth were prepared by the same operator and impressed with polyvinylsiloxane material. The composite resin restorations were built over plaster casts using the incremental technique with a LED device for light-curing the increments. The inlays/onlays were cemented according to one of the following protocols: 1. Etched group (ETR) - selective enamel phosphoric-acid etching + RelyX Unicem clicker; 2. Non-etched group (NER) - RelyX Unicem clicker alone. Each surface was light-cured for 60 s. Recalls occurred after 1 week (baseline), 6 and 12 months when the teeth were evaluated according to previously established scores (modified USPHS criteria). The clinical analysis showed little or no visible changes in the marginal quality after 1 year, even though a probe could detect all the restorations margins. Statistical analysis (Fisher's exact test, p<0.05) detected no differences between the groups after 12 months. No restorations failed and no secondary caries were found. Enamel acid etching had no clinical relevance on the marginal quality of indirect composite resin restorations luted with RelyX Unicem clicker after 1 year of follow up.


Evaluating a Newly Developed System for Electronic Medical Records in Tanzania: An Example of the Experience in Low-Income Countries.
The introduction of electronic medical records (EMRs) in health systems in high-income countries has streamlined access to care and quality of patient information. However, in low-income countries such as Tanzania, EMR remains in its initial stages. The aim of this study was to compare completeness of patient information in the paper medical records (PMRs) with that of the newly implemented EMRs. Using hospital records of newly diagnosed breast cancer patients treated at the Ocean Road Cancer Institute, demographic, diagnostic, and treatment data of 328 patients between January 2017 and April 2018 were abstracted and compared between PMRs and EMRs. The results showed that demographic information variables were documented significantly more in EMRs (occupation, 98.5%) compared to PMRs (occupation, 43.3%) (P < .001). However, diagnostic and treatment information variables were much less likely to be reported in EMRs (full blood panel, 8.2%) than PMRs (full blood panel:=, 93%) (P < .001.) The results showed that EMR utilization corresponded with a marked decrease in the overall documentation rate of patient information compared to the standard PMRs. Multiple barriers affected EMR use. A major one was the lack of EMR connectivity across health systems in the country. Future studies should focus on uncovering the barriers and facilitators to EMR utilization, health care workers perception of available EMR systems, and better ways to improve lifetime sustainability of EMR systems in Tanzania and similar low-income countries.


[Influence of pulse indicator continuous cardiac output in monitoring on the volume parameters of different tidal volume under pressure control ventilation mode and volume-controlled ventilation mode in sheep].
To compare the influence of pulse indicator continuous cardiac output (PiCCO) in monitoring tidal volume (V(T)) under pressure control ventilation mode and volume-controlled ventilation mode in sheep. After anesthesia and tracheotomy, 5 sheep, which were apneic and receiving mechanical ventilation. Twenty minutes later, central venous pressure (CVP) and cardiac function were monitored with different selected V(T) levels of 6, 10, 15, 20 ml/kg under bi-level positive airway pressure (BiPAP) mode by changing the pressure of inspiration, or under the synchronized intermittent mandatory ventilation (SIMV) mode with the same ventilation conditions. In both modes, the increase in V(T) led to an decrease of cardiac index (CI) and intrathoracic blood volume index (ITBVI), reaching a statistically significant difference at 15 ml/kg [SIMV mode: CI (3.94 + or - 1.03) L x min(-1) x m(-2), ITBVI (707 + or - 105) ml/m(2); BiPAP mode: CI (4.11 + or - 1.11) L x mi(-1) x m(-2), ITBVI (715 + or - 122) ml/m(2)] and 20 ml/kg [SIMV mode: CI (3.87 + or - 1.04) L x min(-1) x m(-2), ITBVI (705 + or - 116) ml/m(2); BiPAP mode: CI (3.64 + or - 0.96) L x min(-1) x m(-2), ITBVI (694 + or - 114) ml/m(2)] compared with 6 ml/kg [SIMV mode: CI (4.96 + or - 1.58) L x min(-1) x m(-2),ITBVI(811 + or - 169) ml/m(2); BiPAP mode:CI(5.67 + or - 1.96) L x min(-1) x m(-2), ITBVI (823 + or - 182) ml/m(2), all P<0.05]; an increase in systemic vascular resistance index (SVRI) and mean airway pressure (Pmean) at 15 ml/kg [SIMV mode: SVRI (237.6 + or - 56.2) kPaxs(-1) x L(-1), Pmean (14.0 + or - 3.2) cm H(2)O (1 cm H(2)O=0.098 kPa); BiPAP mode: SVRI (230.8 + or - 32.9) kPaxs(-1) x L(-1), Pmean (13.0 + or - 2.2) cm H(2)O] and 20 ml/kg [SIMV mode: SVRI (253.1 + or - 76.7) kPaxs(-1) x L(-1), Pmean (18.2 + or - 4.8) cm H(2)O ; BiPAP mode: SVRI (246.7 + or - 48.8) kPaxs(-1) x L(-1), Pmean (16.8 + or - 3.3) cm H(2)O] compared with 6 ml/kg [SIMV mode: SVRI (184.8 + or - 47.5) kPaxs(-1) x L(-1); Pmean (8.8 + or - 1.6) cm H(2)O; BiPAP mode: SVRI (184.5 + or - 51.5) kPaxs(-1) x L(-1), Pmean (8.6 + or - 0.5) cm H(2)O, all P<0.05]; but there was no significant effects on CVP, heart rate (HR), mean blood pressure (MBP). There was no significant difference of CI, ITBVI, SVRI and Pmean between the two ventilation modes with various V(T) levels. When the cardiac function was normal, the increase in V(T) led to a decrease of CI and ITBVI, but it had no significant effects on CVP. There was no significant difference of CI and ITBVI in the two ventilation modes, both were decreased. So a relatively constant V(T) should be maintained in determining ITBVI.


CryoETGAN: Cryo-Electron Tomography Image Synthesis via Unpaired Image Translation.
Cryo-electron tomography (Cryo-ET) has been regarded as a revolution in structural biology and can reveal molecular sociology. Its unprecedented quality enables it to visualize cellular organelles and macromolecular complexes at nanometer resolution with native conformations. Motivated by developments in nanotechnology and machine learning, establishing machine learning approaches such as classification, detection and averaging for Cryo-ET image analysis has inspired broad interest. Yet, deep learning-based methods for biomedical imaging typically require large labeled datasets for good results, which can be a great challenge due to the expense of obtaining and labeling training data. To deal with this problem, we propose a generative model to simulate Cryo-ET images efficiently and reliably: CryoETGAN. This cycle-consistent and Wasserstein generative adversarial network (GAN) is able to generate images with an appearance similar to the original experimental data. Quantitative and visual grading results on generated images are provided to show that the results of our proposed method achieve better performance compared to the previous state-of-the-art simulation methods. Moreover, CryoETGAN is stable to train and capable of generating plausibly diverse image samples.


Flexible structure of immunoglobulin G molecule. Fluorescence depolarization studies on hapten-antihapten antibody interactions using arylnaphthalenesulfonates as the ligands.
Fluorescence depolarization studies on immunoglobulin G, Fab'2 and Fab' fragments were carried out using isomeric anilinonaphthalenesulfonates and their corresponding rabbit antibody systems, and the values of the relaxation time rho(h) were calculated. From the results it was confirmed that the IgG and Fab'2 fragment have a certain degree of segmental flexibility, and suggested that these divalent antibody molecules have the same order of flexibilities. Furthermore, the rhoh values of the Fab' fragments from each antibody preparation were also determined and conflicting results were obtained with the samples from two different kinds of antibody systems against the isomeric ligands. The results were discussed with special references to the orientation of ligands bound to the antibody combining sites.


The optimal range of international normalized ratio for radiofrequency catheter ablation of atrial fibrillation during therapeutic anticoagulation with warfarin.
Uninterrupted anticoagulation with warfarin during radiofrequency catheter ablation (RFA) of atrial fibrillation is associated with a lower risk of periprocedural complications than when warfarin is temporarily discontinued. However, the optimal international normalized ratio (INR) levels during RFA have not been defined. In this retrospective analysis, RFA was performed in 1133 consecutive patients (mean age, 61±10 years) with paroxysmal (550) or persistent atrial fibrillation (583). Patients were grouped based on the INR on the day of RFA. There was a quadratic relationship between the INR and bleeding and vascular complications (P<0.001). Complications were less prevalent when INR was ≥2.0 and ≤3.0 (5% [31/572]) than when INR was <2.0 (10% [49/485]; P=0.004) and >3.0 (12% [9/76]; P=0.03). The prevalence of pericardial tamponade (1%) was similar at all INRs. From the quadratic model, the optimal range of INR was calculated as 2.1 to 2.5. INRs<2.0 and >3.0 were associated with a >2-fold increase in complications, with a further steep rise beyond an INR>3.5. Concomitant clopidogrel use was associated with a significant increase in complications at all INRs (odds ratio=3.1; ±95% confidence interval, 1.4-7.4). Unfractionated heparin requirements to maintain a therapeutic activated clotting time during RFA was reduced by 50% in patients with an INR>2.0. The optimal INR range during uninterrupted periprocedural anticoagulation using warfarin is narrow. Therefore, INR levels should be carefully monitored in preparation for RFA of atrial fibrillation.


Histological and immunohistochemical events during placentation in pigs.
The early morphological events in pig placental development are summarized and related to the known data on differences in placental vascular efficiency between Meishan and US breeds. The activation and localization of a number of factors, the ligands and their receptors, such as insulin-like growth factor (IGF), transforming growth factor beta (TGF beta), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), as well as retinoids and calcium, is described. The comparison between these factors gives a strong impression of their complex interactions and hormonal relationships during placentation and vascular development in pigs. This review also emphasizes that retinoids are of great importance for placental function and that the transport of vitamin A appears to take place in the areolar gland complex only, whereas based on histochemistry and electron energy dispersive analysis, the calcium transport may be confined to the interareolar route across the interhaemal barrier.


Recent Research on Different Parts and Extracts of Opuntia dillenii and Its Bioactive Components, Functional Properties, and Applications.
Opuntia dillenii (O. dillenii) is a plant belonging to the Cactaceae family that is abundant in tropical and subtropical regions worldwide. O. dillenii is consumed as a local delicacy and has no other current use. To understand the nutritional value of O. dillenii in human health and its application in the food, cosmetic, and drug industries, this review summarizes information on the chemical compounds (pure α-pyrone compounds, flavonoids, phenolic acids, polysaccharides, minerals, fatty acids, and betalains) and biological properties (anti-diabetic, anti-hyperglycemic, antihyperlipidemic, anti-atherosclerotic, anti-inflammatory, analgesic, antimicrobial, antifungal, antiviral, anti-spermatogenic, anticancer, antilarval, anti-angiogenic, and antioxidant) of extracts from each part of the plant (fruit juice, fruit peel, cladode, and seeds) (aqueous, ethanolic, and methanolic), and seed oil. In addition, data related to the recent applications of O. dillenii in various industries (e.g., edible coatings, food supplements, cosmetics, nanoparticles, and wastewater treatment) are provided.


A comparison of Iohexol and Conray-60 in peripheral angiography.
A double-blind clinical trial was performed in 61 adults in an attempt to compare the safety and efficacy of an ionic with a nonionic contrast agent in peripheral angiography. Objective clinical (vital signs) and laboratory factors (complete blood count, serum electrolytes, serum chemistry, urinalysis, and urine chemistry) were monitored before, during, and after the examination on each patient. There was no statistically significant difference in pre- and posttest laboratory and clinical parameters between those patients who received ionic and those who received nonionic contrast material. Data also were collected to evaluate pain and radiographic quality. The most striking finding was the marked diminution of perceived pain in those patients who received nonionic contrast material compared with those who did not. The data suggest that nonionic contrast agents are at least as safe as the ionic agents currently in use and produce an examination of equal quality with considerably less patient discomfort.


Effects of solar radiation on the skin.
No one would underestimate the importance of sunlight to the evolution of life on the earth and its role in human development. However, all humans - especially individuals who are lightly pigmented or whose occupation or lifestyle exposes them to excessive amounts of sunlight - are potentially susceptible to its deleterious effects. These effects can range from acute biological responses, such as sunburn and skin tanning, to conditions resulting from chronic exposure such as photoaged skin and potentially life-threatening conditions such as skin cancer. The objective of this review is to present a concise and up-to-date perspective on the effects of UVB, UVA, visible, and infrared radiation on cutaneous biochemistry and physiology.


Phylogenetic analysis of coccidia based on 18S rDNA sequence comparison indicates that Isospora is most closely related to Toxoplasma and Neospora.
The phylogenetic relationships and taxonomic affinities of coccidia with isosporan-type oocysts have been unclear as overlapping characters, recently discovered life cycle features, and even recently discovered taxa, continue to be incorporated into biological classifications of the group. We determined the full or partial 18S ribosomal RNA gene sequences of three mammalian Isospora spp., Isospora felis, Isospora ohioensis and Isospora suis, and a Sarcocystis sp. of a rattlesnake, and used these sequences for a phylogenetic analysis of the genus Isospora and the cyst-forming coccidia. Various alveolate 18S rDNA sequences were aligned and analyzed using maximum parsimony to obtain a phylogenetic hypothesis for the group. The three Isospora spp. were found to be most closely related to Toxoplasma gondii and Neospora caninum. This clade in turn formed the sister group to the Sarcocystis spp. included in the analysis. The results confirm that the genus Isospora does not belong to the family Eimeriidae, but should be classified together with the cyst-forming coccidia in the family Sarcocystidae. Furthermore, there appear to be two lineages within the Sarcocystidae. One lineage comprises Isospora and the Toxoplasma/Neospora clade which share the characters of having a proliferative phase of development preceding gamogony in the definitive host and an exogenous phase of sporogony. The other lineage comprises the Sarcocystis spp. which have no proliferative phase in the definitive host and an endogenous phase of sporogony.


Solvent smectic order parameters from solute nematic order parameters.
In liquid crystals, while the second and fourth rank orientational order parameters characterizing a nematic phase can be experimentally determined via several techniques, there is no straightforward experiment rendering the positional order parameters characterizing a smectic A phase. This work illustrates a novel method to estimate the positional order parameters of a smectogenic liquid crystal solvent from knowledge of the orientational order parameters of a number of solutes dissolved therein. The latter order parameters can be experimentally determined via liquid crystal NMR spectroscopy. These data can be then analyzed with a statistical-thermodynamic density functional theory, whose basic ingredient is a model for solute-solvent intermolecular interactions. Its parametrization and the subsequent fitting procedure eventually permit one to obtain the positional order parameters of the solvent besides the positional-orientational distribution function of the solutes. The method is applied to the smectogen 4,4(')-di-n-heptyl-azoxybenzene, in which the solutes 1,4-dichlorobenzene and naphthalene have been dissolved. With the help of this exploratory practical example, pros and cons of the method are pointed out and further developments prospected.


Laparoscopic Gastric Plication: An Emerging Bariatric Procedure with High Surgical Revision Rate.
Introduction: Laparoscopic gastric plication (LGCP) reduces gastric volume without resecting or implanting a foreign body. Although still considered investigational, it could be appropriate for young patients with a low body mass index (BMI) and for those unwilling to undergo sleeve gastrectomy, gastric banding, or bypass. Objectives: The aim of this study was to assess the mid-term results (2 years) of LGCP in terms of safety and efficacy. Methods: A total of 56 obese patients (47 female; mean age=30.5±11.7 years; mean BMI=40.31±4.7 kg/m2) were candidates for LGCP from January 2011 to October 2013. Early and late complications, BMI, and excess BMI loss (EBL) were prospectively recorded at 3, 6, 9, 12, 18, and 24 months follow-up. Results: Mean operative time was 72.4±15.6 minutes. No conversion was required. Mean hospital stay was 3 days. Mean %EBL was 34.3±18.40%, 40.1±24.5%, 47.4±30.2%, 46.5±34.6%, 47.8±43.2%, and 55.3±53.6% at 3, 6, 9, 12, 18, and 24 months, respectively. The overall complication rate was 32.14%. Perioperative mortality was zero. Surgical revision was needed in 30 patients: 12 for unsatisfactory weight loss and 18 for gastric prolapse (one acute within 30 days), respectively. Conclusion: LGCP showed high complication rates requiring surgical revision.


NF-kappaB activation is associated with homocysteine-induced injury in Neuro2a cells.
Perinatal exposure to hyperhomocysteinemia might disturb neurogenesis during brain development and growth. Also, high levels of homocysteine trigger neurodegeneration in several experimental models. However, the putative mechanisms of homocysteine-induced toxicity in the developing nervous system have poorly been elucidated. This study was aimed to investigate homocysteine effects in undifferentiated neuroblastoma cells, Neuro2a. A 4 h exposure to homocysteine in a concentration range of 10-100 microM did not affect cell viability and ROS production in Neuro2a cell cultures. Instead, ROS levels were increased by two-three folds in cells treated with 250 microM and 500 microM homocysteine, respectively, in comparison with control cells. Also, the highest homocysteine dose significantly reduced the viable cell number by 40%. Notably, the treatment with homocysteine (250 microM-500 microM) in the presence of antioxidants, such as N-acetylcysteine and IRFI 016, a synthetic alpha-tocopherol analogue, recovered cell viability and significantly reduced homocysteine-evoked increases in ROS production. Moreover, antioxidants, particularly IRFI 016, were able to counteract NF-kappaB activation induced by 250 microM homocysteine. Cell treatment with 250 microM homocysteine also triggered the onset of apoptosis, as demonstrated by the increased expression of early apoptotic markers such as Bax, caspase-3 and p53. In contrast, Bcl2 expression was not affected by homocysteine exposure. Interestingly, the specific inhibition of NF-kappaB nuclear translocation by the synthetic peptide SN50 was able to almost completely suppress the homocysteine-evoked rises in pro-apoptotic protein expression as well as in caspase-3 activity. Further, also IRFI 016 and N-acetylcysteine were able to significantly reduce caspase-3 activation induced by homocysteine treatment. These observations suggest an involvement of redox state alterations and activated NF-kappaB in apoptosis onset triggered by homocysteine in neuroblastoma cells Neuro2a. However, further investigations are needed to characterize molecular events involved in the NF-kappaB activation induced by homocysteine.


Monte Carlo point process estimation of electromyographic envelopes from motor cortical spikes for brain-machine interfaces.
Representation of movement in the motor cortex (M1) has been widely studied in brain-machine interfaces (BMIs). The electromyogram (EMG) has greater bandwidth than the conventional kinematic variables (such as position, velocity), and is functionally related to the discharge of cortical neurons. As the stochastic information of EMG is derived from the explicit spike time structure, point process (PP) methods will be a good solution for decoding EMG directly from neural spike trains. Previous studies usually assume linear or exponential tuning curves between neural firing and EMG, which may not be true. In our analysis, we estimate the tuning curves in a data-driven way and find both the traditional functional-excitatory and functional-inhibitory neurons, which are widely found across a rat's motor cortex. To accurately decode EMG envelopes from M1 neural spike trains, the Monte Carlo point process (MCPP) method is implemented based on such nonlinear tuning properties. Better reconstruction of EMG signals is shown on baseline and extreme high peaks, as our method can better preserve the nonlinearity of the neural tuning during decoding. The MCPP improves the prediction accuracy (the normalized mean squared error) 57% and 66% on average compared with the adaptive point process filter using linear and exponential tuning curves respectively, for all 112 data segments across six rats. Compared to a Wiener filter using spike rates with an optimal window size of 50 ms, MCPP decoding EMG from a point process improves the normalized mean square error (NMSE) by 59% on average. These results suggest that neural tuning is constantly changing during task execution and therefore, the use of spike timing methodologies and estimation of appropriate tuning curves needs to be undertaken for better EMG decoding in motor BMIs.


Transfer ribonucleic acid genes in the chloroplast deoxyribonucleic acid of pea leaves.
The saturation hybridization between pea ctDNA and 125I-labeled pea ct-tRNAs has shown that 1.2% of the peak ctDNA codes for tRNA genes. The observed level of hybridization has been found to result from specific base pairings between ctDNA and ct-RNA as shown by competition hybridization experiments and thermal stability studies on DNA-tRNA hybrids. The level of hybridization obtained in this study amounts to the presence of approximately 40 tRNA genes in pea ctDNA. The tRNAs from the cytoplasm of the pea leaves, Escherichia coli, yeast, and calf thymus did not compete with the pea ct-tRNAs for the common base sequences in pea ctDNA. The presence of 17 aminoacyl-tRNA synthetases and their corresponding tRNAs was demonstrated in chloroplast. The acylation of ct-tRNAs proceeds with the same rate whether the partially purified tRNA synthetases from chloroplasts of E. coli are used. The aminoacylation of the three amino acids glutamic acid, glutamine, and cysteine proceeded very slowly in chloroplasts. The individually labeled aminoacyl-tRNAs hybridized with pea ctDNA. The hybridization follows true saturation rates, and the melting profiles of aminoacyl-tRNA-ctDNA indicate the formation of specific base pairs between the ctDNA and tRNA. Seventeen aminoacyl-tRNA genes have been identified in the pea ctDNA.


Applicant reactions and faking in real-life personnel selection.
Faking may affect hiring decisions in personnel selection. All the antecedents of faking are still not known. The present study investigates the association between applicants' reactions about the selection procedure and their tendency to fake. The subjects (N = 180) were real-life applicants for a fire and rescue personnel school. After completing the selection process, the applicants filled out a questionnaire about their test reactions (Chan, Schmitt, Sacco & DeSohon, 1998b) and a faking scale, the Balanced Inventory of Desirable Responding (Paulhus, 1991). The results based on Structural Equation Modelling (SEM) indicated that the more positive reactions applicant had about the selection procedure the more impression management they had. The applicant reactions were not associated with self-deception.


Cross-protective efficacy of bivalent recombinant baculoviral vaccine against heterologous influenza H5N1 challenge.
The present study demonstrates the cross-protective efficacy of baculovirus displayed HAs of A/Indonesia/669/06 and A/Anhui/01/05 against heterologous H5N1 challenges in a mouse model. Mice orally or subcutaneously immunized with live bivalent-BacHA vaccine significantly induced higher HA-specific humoral and cellular immune responses when compared with inactivated bivalent-BacHA. In addition, oral administration of live bivalent-BacHA vaccine was able to induce significant level of antigen-specific mucosal IgA levels. Microneutralization assay indicated that live bivalent-BacHA vaccine was able to induce strong cross-clade neutralization titer against distinct H5N1 clades (1, 2.1.3, 188.8.131.52, 2.3.2, 2.3.4, 4, 7 and 9). The production of both interferon-gamma (IFN-γ) and interleukin-4 (IL-4) by splenocytes from vaccinated mice indicated that mice vaccinated orally or subcutaneously with live bivalent-BacHA stimulated both IFN-γ secreting Th1 cells and IL-4 secreting Th2 cells, whereas mice immunized subcutaneously with inactive adjuvanted bivalent-BacHA stimulated only IL-4 secreting Th2 cells. Cross-protective immunity study also showed that mice immunized either orally or subcutaneously with live bivalent-BacHA were completely protected against 5MLD50 of clade 1 and clade 188.8.131.52 H5N1 viral infections. The protective immune response elicited by bivalent-BacHA vaccine against H5N1 variants demonstrates the possibility of protection against a broad range of H5N1 strains.


[Hemodynamic instability and long-term lithium therapy].
Lithium is known to be responsible for many adverse events on the cardiovascular system. Among these events, it was experimentally noted that lithium could block the action of catecholamines on myocardium. The authors report the case of a patient under lithium therapy developing a myocardial infarction secondarily complicated of a severe cardiac failure. The inotropic support essential to balance hemodynamic could be raised only after lithium's stop. This example could be a clinical translation of the experimental effect previously observed.


A single-centre retrospective observational study to evaluate the change in total cholesterol and LDL cholesterol in hyperlipidaemic patients switched from atorvastatin to simvastatin.
The clinical effects of switching from one HMG Co-A reductase inhibitor (atorvastatin) to another therapeutic agent within the same class (simvastatin) were examined in this observational study. Levels of total-C, LDL-C, HDL-C and triglycerides from 100 patients were compared before and after switching, and the maintenance, improvement or loss of lipid control was assessed. There was a significant increase in total-C and triglycerides (p < 0.05) following the switch from atorvastatin to simvastatin. A number of patients showed > or = 10% variation in lipid levels after switching. The high intrapatient variation seen in this study strongly suggests that therapeutic substitution is associated with an unpredictable response in plasma lipid levels and their control. This would have practical implications for physicians who are considering a switch of this nature.


Identification and characterization of associated with lipid droplet protein 1: A novel membrane-associated protein that resides on hepatic lipid droplets.
Alcoholic and nonalcoholic liver steatosis and steatohepatitis are characterized by the massive accumulation of lipid droplets (LDs) in the cytosol of hepatocytes. Although LDs are ubiquitous and dynamic organelles found in the cells of a wide range of organisms, little is known about the mechanisms and sites of LD biogenesis. To examine the participation of these organelles in the pathophysiological disorders of steatotic livers, we used a combination of mass spectrometry (matrix-assisted laser desorption ionization-time of flight and LC-MS electrospray) and Western blot analysis to study the composition of LDs purified from rat liver after a partial hepatectomy. Fifty proteins were identified. Adipose differentiation-related protein was the most abundant, but other proteins such as calreticulin, TIP47, Sar1, Rab GTPases, Rho and actin were also found. In addition, we identified protein associated with lipid droplets I ALDI (tentatively named Associated with LD protein 1), a novel protein widely expressed in liver and kidney corresponding to the product of 0610006F02Rik (GI:27229118). Our results show that, upon lipid loading of the cells, ALDI translocates from the endoplasmic reticulum into nascent LDs and indicate that ALDI may be targeted to the initial lipid deposits that eventually form these droplets. Moreover, we used ALDI expression studies to view other processes related to these droplets, such as LD biogenesis, and to analyze LD dynamics. In conclusion, here we report the composition of hepatic LDs and describe a novel bona fide LD-associated protein that may provide new insights into the mechanisms and sites of LD biogenesis.


π-Conjugate Fluorophore-Tagged and Enzyme-Responsive l-Amino Acid Polymer Nanocarrier and Their Color-Tunable Intracellular FRET Probe in Cancer Cells.
The present investigation accounts one of the first example of enzyme-responsive and π-conjugate-tagged l-amino acid amphiphilic polymer and their fluorescence resonance energy transfer (FRET) probes for color-tunable intracellular bioimaging in cancer cells. Melt polymerizable oligo-phenylenevinylene (OPV) π-conjugated diol was tailor-made and subjected to thermo-selective melt transesterification reaction with multifunctional l-aspartic acid monomer to yield OPV-tagged amphiphilic luminescent polyesters. These amphiphilic polyesters self-assembled through strong aromatic π-π stacking and hydrophilic/hydrophobic noncovalent forces into <200 nm size blue-luminescent nanoparticles in aqueous medium. The OPV-tagged polymer nanoparticles served as FRET donor and encapsulated water insoluble Nile Red (NR) fluorophore as a FRET acceptor. Detail photophysical studies revealed that both the OPV and NR were confined within Förster distance in the polymer nanocontainer and the nanodomains provided appropriate geometry for efficient excitation energy transfer from OPV to NR. Cytotoxicity studies in breast cancer (MCF 7), cervical cancer (HeLa) and normal (Wild-type MEF) cell lines revealed that both the nascent luminescent OPV nanoparticles and OPV-NR FRET probes were nontoxic to cells up to 100 μg/mL. Confocal microscope images confirmed the efficient transportation of polymer and FRET probes across the cell membranes and their preferable accumulation in the cytoplasm of the cells. Lysosomal tracker assisted live cell imaging provided direct evidence for the localization of the polymer nanoparticles at the lysosomal compartments in the cytoplasm. In vitro enzyme-responsive studies revealed that the aliphatic polyester backbone in the polymer nanoparticles was readily biodegradable by lysosomal enzymes like esterase, chymotrypsin, trypsin, and also redox GSH species in the cytoplasm. Selective photoexcitation in confocal microscope exhibited bright OPV blue-luminescence and strong red-emission from NR followed by the excitation energy transfer and occurrence of FRET process at the intracellular environment in cancer cell lines. Both the polymer design and the biodegradable polymer FRET concept are completely new; thus, the present approach opens up new platform of research opportunities for natural l-amino acid based luminescent polymer probes for color-tunable bioimaging in cancer cells.


Subspecies composition and founder contribution of the captive U.S. chimpanzee (Pan troglodytes) population.
Chimpanzees are presently classified into three subspecies: Pan troglodytes verus from west Africa, P.t. troglodytes from central Africa, and P.t. schweinfurthii from east Africa. A fourth subspecies (P.t. vellerosus), from Cameroon and northern Nigeria, has been proposed. These taxonomic designations are based on geographical origins and are reflected in sequence variation in the first hypervariable region (HVR-I) of the mtDNA D-loop. Although advances have been made in our understanding of chimpanzee phylogenetics, little has been known regarding the subspecies composition of captive chimpanzees. We sequenced part of the mtDNA HVR-I region in 218 African-born population founders and performed a phylogenetic analysis with previously characterized African sequences of known provenance to infer subspecies affiliations. Most founders were P.t. verus (95.0%), distantly followed by the troglodytes schweinfurthii clade (4.6%), and a single P.t. vellerosus (0.4%). Pedigree-based estimates of genomic representation in the descendant population revealed that troglodytes schweinfurthii founder representation was reduced in captivity, vellerosus representation increased due to prolific breeding by a single male, and reproductive variance resulted in uneven representation among male P.t.verus founders. No increase in mortality was evident from between-subspecies interbreeding, indicating a lack of outbreeding depression. Knowledge of subspecies and their genomic representation can form the basis for phylogenetically informed genetic management of extant chimpanzees to preserve rare genetic variation for research, conservation, or possible future breeding.


Mechanisms and Molecular Targets of Artemisinin in Cancer Treatment.
The major problems with cancer therapy are drug-induced side effects. There is an urgent need for safe anti-tumor drugs. Artemisinin is a Chinese herbal remedy for malaria with efficacy and safety. However, several studies reported that artemisinin causes neurotoxicity and cardiotoxicity in animal models. Recently, nanostructured drug delivery systems have been designed to improve therapeutic efficacy and reduce toxicity. Artemisinin has been reported to show anticancer properties. The anticancer effects of artemisinin appear to be mediated by inducing cell cycle arrest, promoting ferroptosis and autophagy, inhibiting cell metastasis. Therefore, the review is to concentrate on mechanisms and molecular targets of artemisinin as anti-tumor agents. We believe these will be important topics in realizing the potential of artemisinin and its derivatives as potent anticancer agents.


Fighting Fires and Battling the Clock: Advance Care Planning in Family Medicine Residency.
Few family physicians treating patients with life-limiting illness report regularly initiating advance care planning (ACP) conversations about illness understanding, values, or care preferences. To better understand how family medicine training contributes to this gap in clinical care, we asked how family medicine residents learn to engage in ACP in the workplace. We coded semistructured interviews with family medicine residents (n=9), reflective memos (n=9), and autoethnographic field notes (n=37) using a constructivist-grounded theory approach. We next used the constant comparative method of grounded theory to develop two composite narratives describing participants' experiences that we then member-checked with participants. We identified six core categories of social process to describe how participants were taught to engage in advance care planning. These social processes included previously unidentified barriers to ACP that were specific to their role as learners. These barriers appeared to lead to cultural avoidance of prognosis, conflation of ACP and goals of care (GOC) conversations, and deferral of difficult conversations to nonprimary care settings. Family medicine educators should consider developing interventions such as flexible clinic schedules, dedicated ACP time, deliberate observed practice, and structured teaching to address potential barriers identified in this exploratory research. Family medicine leaders may wish to consider directly teaching residents and preceptors about crucial differences between ACP and GOC discussions. Shifting curricular focus toward eliciting values and illness understanding during ACP could help resolve a cultural avoidance of prognosis that limits family medicine residents' attempts to engage in ACP.


Diabetic foot ulcer due to scedosporium apiospermum.
We report a case of diabetic foot ulcer caused by Scedosporium apiospermum in a seventy year old male patient with uncontrolled diabetes. Scedosporium apiospermum, the asexual phase of Pseudallescheria boydii a fungus isolated from a variety of natural substrates throughout the world including soil, polluted water, sewage and manure of poultry and cattle. P.boydii is now recognized as a medically important opportunistic fungus. This case has been reported for its rarity.


Dietary Fibre Supplementation Improves Semen Production by Increasing Leydig Cells and Testosterone Synthesis in a Growing Boar Model.
Testicular development is imperative to spermatogenesis, and pre-puberty is the key period for testis development. This study, therefore, investigated the effects of fibre supplementation on testis development and its possible mechanism in a growing boar model. Thirty Yorkshire boars were randomly divided into a control group (Control) and a fibre group (Fibre) from day 0 to 90 after weaning, with three pigs per pen and five pens per treatment. Blood and testes were collected for analysis. Dietary fibre supplementation had no significant effect on growth performance, testicular volume, or libido but increased the semen production of boars. Boars fed with fibre had lower serum cholesterol (CHO) and low-density lipoprotein (LDL) levels compared to those on the Control diet; however, testicular CHO, triglyceride (TG), and LDL concentration in the Fibre group were significantly higher than the Control group (P < 0.01). Testicular histological analysis showed that seminiferous tubules and testicular germ cells of 120-day-old boars were densely arranged in the Fibre group, and the number of Leydig cells was significantly higher than that of the Control group (P < 0.001). Furthermore, the diet supplemented with fibre significantly decreased leptin, leptin receptor (Leptor), and luteinising hormone (LH) concentrations in boar serum (P < 0.05), whereas follicle-stimulating hormone (FSH) and testosterone concentrations were significantly increased (P < 0.05). Meanwhile, the expression of AMH, AMHR2, and SYCP3 genes related to proliferation and differentiation, and hormone-related genes STAR and SOCS3, were significantly up-regulated (P < 0.05). OCCLUDIN expression was up-regulated, whereas CDH2 expression was down-regulated. In conclusion, increased fibre intake during the pre-puberty period in growing boar is crucial for Leydig cell proliferation, up-regulating the expression of genes related to hormone synthesis and thereby promoting the secretion of testosterone and semen production.


How much GK is in the NKLM? A comparison between the catalogues of exam-relevant topics (GK) and the German National Competence-based Learning Objectives Catalogue for Undergraduate Medical Education (NKLM).
Background: The German National Competence-Based Learning Objectives for Undergraduate Medical Education (NKLM) being adopted in 2015 is designed to contribute to improve the quality of teaching and learning in medicine with respect to competence orientation. For departments, the coherence between teaching, assessment and the content of the catalogues of exam-relevant topics (GK) is a crucial factor. Before making use of the NKLM seriously in curricular development, many faculties demand more transparency regarding the representation in the NKLM of GK topics and in what aspects the NKLM exceeds the GK. Therefore, the aim of the study was to assign the NKLM competencies and objectives to the systematic GK terms, to reveal gaps in their congruence and to determine the percentage of agreement between GK and NKLM. Additionally, the distribution among the NKLM chapters (chap.), of GK content and further competencies relevant for medical practice were analysed. Methods: The textual comparison of GK and NKLM was done by advanced students that were familiar with the NKLM from previous analyses. The comparison was done independently (keyword search, face validity), afterwards consented and matched with independent ratings of GK-2 and chapter 21 done by experts as well as with cross-references to the GK indicated in chapter 12, 13 and 15 of the NKLM. Detailed data is available online: www.merlin-bw.de/gk-nklm-abgleich.html. Results: The degree of correspondence of the GK's six preclinical parts with the NKLM ranges between 94% and 98%, with the clinical GK the degree of correspondence ranging between 84% and 88%. This demonstrates a consistently very high congruence of content. Only 6-16% of the content per GK part could not be assigned to NKLM equivalents. Regarding the distribution of GK content among NKLM chapters, the chapters with classic medical expertise (chapters 12, 13, 16, 17 as well as 20 and 21) show the highest correspondences. Practical medical skills (chapter 14b) can be found in the clinical GK "Health Disorders". Doctor-patient interaction (chapter 14c) and medical scientific skills (chapter 14a) are represented only marginally in the GK. As expected, there were no equivalents to be found in the GK for the new professional roles for medical doctors (chapter 06-11). Discussion: The results presented provide faculties with a useful and detailed data base to evaluate the NKLM more reliably, especially with respect to its relevance for exams. The increased transparency supports the implementation process of the NKLM by reducing content-related uncertainties of departments, invalidating sweeping arguments against the NKLM resulting from uncertainties and thereby minimizing resistance. At the same time a critical review process of the NKLM is encouraged.


CERA (Continuous Erythropoietin Receptor Activator): a new erythropoiesis-stimulating agent for the treatment of anemia.
Anemia is a common and debilitating condition in patients with chronic kidney disease and patients with cancer. Over the last 10 to 15 years, the introduction of erythropoietic therapy has transformed the management of anemia in both these conditions. The first therapeutic agent to be used for the stimulation of erythropoiesis was recombinant human erythropoietin (epoetin). At the turn of this century, darbepoetin alfa, a second-generation erythropoietic agent, became available. Darbepoetin alfa contains two additional N-linked carbohydrate chains, which confer greater metabolic stability in vivo. More recently, a third-generation molecule, Continuous Erythropoietin Receptor Activator (CERA), incorporating a large polymer chain, has been developed. CERA has an elimination half-life in humans that is considerably longer than the half-life of either epoetin or darbepoetin alfa. CERA may also have different receptor binding characteristics and pharmacology from other erythropoietic agents; these characteristics are the subject of ongoing investigation. CERA is currently in phase III clinical trials.


Temporal Expression Patterns of Clock Genes and Aquaporin 5/Anoctamin 1 in Rat Submandibular Gland Cells.
Circadian rhythms are essential for health and regulate various physiological functions. These rhythms are regulated by a negative-feedback loop involving clock genes in the suprachiasmatic nucleus (SCN) and peripheral tissues. The rate of secretion of salivary substances, ions, and water follows a circadian rhythm, however, the relationship between the molecular mechanism of salivary secretion and peripheral circadian rhythm is not yet clear. Anoctamin 1 (ANO1, also known as TMEM16A) and Aquaporin 5 (AQP5) play an important role in the transport of ions and water in the submandibular glands (SGs). We examined the interaction between the rhythmic expression pattern of the clock genes, Ano1 and Aqp5, in rat whole SGs as well as isolated acinar and ductal cells. Circadian rhythmic expression for Bmal1, Per1, Per2, Clock, Cry1, Cry2, Rorα, and Rev-erbα mRNAs, also called the clock genes, was observed in rat SGs by semi-quantitative RT-PCR analysis. We also observed rhythmic patterns in Ano1 and Aqp5 mRNA expression. The expression of ANO1 protein also showed circadian rhythm, as confirmed by western blot analysis. We could not observe any time delay between the peak expression of ANO1 protein and its mRNA. Expression levels of the clock gene mRNAs in the ductal cells was higher than that in acinar cells, however, rhythmic oscillations were observed in both. Our results suggest that SGs have peripheral clocks, and rhythmic expressions of Ano1 and Aqp5 along with the clock genes, may play an important role in the circadian regulation of salivary secretion.


Deuterium spin probes of side-chain dynamics in proteins. 1. Measurement of five relaxation rates per deuteron in (13)C-labeled and fractionally (2)H-enriched proteins in solution.
New pulse sequences are presented for the measurement of the relaxation of deuterium double quantum, quadrupolar order, and transverse antiphase magnetization in (13)CH(2)D methyl groups of (15)N-, (13)C-labeled, fractionally deuterated proteins. Together with previously developed experiments for measuring deuterium longitudinal and transverse decay rates [Muhandiram, D. R.; Yamazaki, T.; Sykes, B. D.; Kay, L. E. J. Am. Chem. Soc. 1995, 117, 11536], these schemes allow measurement of the five unique decay constants of a single deuteron, providing an unprecedented opportunity to investigate side-chain dynamics in proteins. All five deuterium relaxation rates have been measured for deuterons in the methyl groups of the B1 immunoglobulin binding domain of peptostreptococcal protein L and the N-terminal SH3 domain from the protein drk. Since values of the spectral density function at only three different frequencies contribute to the five relaxation rates, the self-consistency of the relaxation data is readily established. Very good agreement is obtained between calculated parameters describing the amplitudes and time scales of motion when different subsets of the relaxation data are employed.


The fourth transmembrane domain of the Helicobacter pylori Na+/H+ antiporter NhaA faces a water-filled channel required for ion transport.
Cysteine-scanning mutagenesis was performed from Ser-130 to Leu-160 in the fourth transmembrane domain (TM4) of the Na+/H+ antiporter NhaA from Helicobacter pylori to determine the topology of each residue and to identify functionally important residues. All of the mutants were based on cysteine-less NhaA (Cys-less NhaA), which functions very similarly to the wild-type protein, and were expressed at a level similar to Cys-less NhaA. Discontinuity of [14C]N-ethylmaleimide (NEM)-reactive residues suggested that TM4 comprises residues Gly-135 to Val-156. Even within TM4, NEM reactivity was high for I136C, D141C to A143C, L146C, M150C, and G153C to R155C. These residues are thought to be located on one side of the -helical structure of TM4 and to face a putative water-filled channel. Pretreatment of intact cells with membrane-impermeable maleimide did not inhibit [14C]NEM binding to the NEM-reactive residues within TM4, suggesting that the putative channel opens toward the cytoplasm. NEM reactivity of the A143C mutant was significantly inhibited by Li+. The T140C and D141C mutants showed lower affinity for Na+ and Li+ as transport substrates, but their maximal antiporter velocities (Vmax) were relatively unaffected. Whereas the I142C and F144C mutants completely lost their Li+/H+ antiporter activity, I142C had a lower Vmax for the Na+/H+ antiporter. F144C exhibited a markedly lower Vmax and a partially reduced affinity for Na+. These results suggest that Thr-140, Asp-141, and Phe-144 are located in the end portion of a putative water-filled channel and may provide the binding site for Na+, Li+, and/or H+. Furthermore, residues Ile-142 to Phe-144 may be important for the conformational change that accompanies ion transport in NhaA.


Different binding of stimulatory-type and blocking-type TSH receptor antibody with guinea-pig testis membrane.
A receptor assay using [125I]bTSH-binding to guinea-pig testis membrane was developed. Unlabelled hCG and FSH inhibited [125I]bTSH binding. In patients with Graves' disease and in untreated hyperthyroid patients, almost all long-acting thyroid stimulators and thyroid-stimulating antibodies, respectively did not inhibit [125I]bTSH binding, which on the other hand was inhibited by thyroid stimulation blocking antibodies in patients with primary hypothyroidism. When the inhibitory effect on the binding of [125I]hCG and 125I-synthetic alpha-subunit peptide (alpha 26-46) of hCG to testis membrane was examined, bTSH resulted in a significant inhibition. However, all three kinds of TSH receptor antibodies had no inhibitory effect. This study demonstrated 1. interaction of alpha-subunit of TSH and hCG with the testicular receptor; 2. binding of thyroid stimulation-blocking antibody and lack of binding of thyroid-stimulating antibody to the testicular TSH receptor in spite of binding of these TSH receptor antibodies to the thyroidal TSH receptor, and 3. lack of binding of thyroid-stimulating antibody and thyroid stimulation-blocking antibody to the testicular gonadotropin receptor.


Tracing and quantifying contributions of end members to karst water at a coalfield in southwest China.
Karst water, which provides 25% of the world's drinking water, is especially vulnerable to anthropogenic contamination. Such is the case in southwestern China with trace element pollution in important karst aquifers. Approximately 20% of the total study area consisted of abandoned mine tailings with elevated concentrations of Fe, S, Mn, As, Cu, and Cr. Acid mine drainage (AMD) water originating from pyrite oxidation of the tailings was characterized by low pH and high concentrations of Fe, SO42-, and As. Concentrations of Fe, Mn, Al, SO42-, As, Cd, and Pb in spring water in wet and dry seasons were greater than WHO and USEPA drinking water guidelines. Based on the results of mineral characterizations, hydrogeochemistry, and isotopic compositions (δ34SSO4, δ18OSO4, and δ18OH2O), the chemistry of AMD water was primarily controlled by pyrite oxidation, river water by atmospheric precipitation, and spring water by carbonate rock dissolution and mixing with river and AMD waters. A three-end-member mixing model identified the contributions of these different end members to spring water quality. Although AMD water was characterized by the lowest mixing percentages during the wet (14.1%) and dry (26.9%) seasons, it played a very important role in degrading spring water quality. Based on these findings, an investigation strategy was developed for illuminating seasonal water quality and potential remediation methods corresponding to the contaminants in the spring water are also proposed to manage this seriously polluted karst system. Results could benefit remediation planning for these distinctively complex and vulnerable systems in other regions of the world.


Predicting the immunogenicity of human leukocyte antigen class I alloantigens using structural epitope analysis determined by HLAMatchmaker.
Human leukocyte antigen (HLA) matching strategies for kidney transplantation assign equal weighting to mismatches at a particular locus and take no account of variation in immunogenicity according to recipient HLA type. We examined the ability of intra- and interlocus analysis of amino-acid polymorphisms at continuous (triplet) and discontinuous positions (eplet) defined by the HLAMatchmaker program to predict alloantigen immunogenicity. Sera from highly sensitized patients were screened for HLA class-I alloantibodies and mismatched combinations were analyzed using HLAMatchmaker to determine the number of triplet or extended-triplet and eplet mismatches. Logistic regression analysis revealed a strong correlation between the number of triplet or extended-triplet and eplet mismatches and both the presence and magnitude of alloantibody to mismatched HLA-A and -B specificities. The additional structural information provided by eplet analysis gave increased discrimination of mismatched-HLA specificities for alloantigens with greatest sequence disparity but this did not further improve the ability of triplet analysis to predict alloantigen immunogenicity. High antibody levels were observed for several mismatched-HLA combinations with zero triplet or eplet mismatches indicating that self triplets or eplets expressed in different conformations do not always predict nonimmunogenic epitopes. Analysis of recipient HLA type and mismatched-HLA alloantigens using the HLAMatchmaker algorithm allows prediction of immunogenic donor HLA types.


Biotin production by bifidobacteria.
Biotin production and the growth of the strains of Bifidobacterium adolescentis, B. bifidum, B. breve, B. infantis, and B. longum were studied. These five strains showed heavy growth on BL medium. But when yeast extract medium (carbon source, glucose) was used, the extent of their growth was significantly decreased, one-half or less than that of the growth on BL medium. B. bifidum grew well on yeast extract medium containing oligosaccharides, such as isomaltooligosaccharide, and produced biotin extracellularly. The utilization of oligosaccharides in biotin production by these five strains was investigated.


Mental health and psychological impacts from the 2011 Great East Japan Earthquake Disaster: a systematic literature review.
On March 11, 2011, Japan experienced an unprecedented combination of earthquake/tsunami/nuclear accidents (the Great East Japan Earthquake; GEJE). We sought to identify mental health and psychosocial consequences of this compound disaster. A systematic literature review was conducted of quantitative research articles addressing mental health of survivors and the psychological impact of the GEJE. For articles between March 2011 and December 2014, PubMed, PsychINFO, and EMBASE databases were searched with guidance on literature review method. Forty-nine studies met the inclusion criteria. A substantial proportion of the affected individuals experienced considerable psychological distress. Mental health outcomes included, but were not limited to, posttraumatic stress disorder, depression, and anxiety symptoms. Physical health changes, such as sleeping and eating disturbances, also occurred. In Fukushima, radioactive release induced massive fear and uncertainty in a large number of people, causing massive distress among the affected residents, especially among mothers of young children and nuclear plant workers. Stigma was additional challenge to the Fukushima residents. The review identified several groups with vulnerabilities, such as disaster workers, children, internally displaced people, patients with psychiatric disorders, and the bereaved. Following the GEJE, a considerable proportion of the population was mentally affected to a significant degree. The affected individuals showed a wide array of mental and physical consequences. In Fukushima, the impact of nuclear disaster was immense and complex, leading to fear of radiation, safety issues, and stigma issues.


Dosimetric effect of photon beam energy on volumetric modulated arc therapy treatment plan quality due to body habitus in advanced prostate cancer.
The purpose of this study was to dosimetrically compare 6- and 10-MV photon beam energies in high-risk prostate cancer patients of various body habitus using a volumetric modulated arc therapy (VMAT) radiation delivery technique. The objectives of the study were to evaluate whether dosimetric differences exist and to investigate whether differences are dependent on patient body habitus. Forty patients with various body habitus who had previously received treatment to the prostate and pelvic lymph nodes with VMAT techniques were chosen. Patients were planned in the Pinnacle(3) treatment planning system with double or triple SmartArc plans with 6- and 10-MV photon energies. All patients were optimized with the same planning objectives and normalized such that 95% of the planning target volume (PTV) received the prescription dose. Patients were evaluated for PTV and organ at risk (OAR) parameters for the bladder, rectum, small bowel, penile bulb, and sigmoid colon. Metrics used for comparison were D2%, D98%, homogeneity, conformity, and dose falloff for the PTV and D(2%), D(mean), V(80%), V(60%), and V(40%) for OARs. Statistical differences were evaluated with a paired-sample Wilcoxon signed rank test with a significance level of .05. For the PTV, there were no statistically significant differences in D(mean), D(2cc), conformation number, and homogeneity index values, but the dose falloff parameters, R50 and R25, showed a median improvement of 6.7% (P<.01) and 6.2% (P<.01), respectively, with 10 MV. A correlation between patient anterior-posterior distance (d(AP)) and percentage reduction in R50 of 0.436% per centimeter (P<.01) was determined. For OARs, statistically significant reductions in dose metrics were found in the small bowel and bladder, but increases in the D(2cc) of 3.5% in the penile bulb (P<.01) and 0.2% in the rectum (P=.02) were shown with 10 MV. The use of 10 MV also demonstrated a statistically significant reduction in the total number of monitor units of 15.9% (P<.01) compared with 6 MV. The study showed that 10 MV provides a faster dose falloff than 6 MV for patients whose prostate and pelvic lymph nodes are treated using a VMAT technique irrespective of body habitus; however, the improvement in dose falloff is dependent on body habitus and increases as the patient body habitus increases.


Midchildhood acne associated with inhaled corticosteroids: report of two cases and review of the literature.
Midchildhood acne has been attributed to a number of causes in the literature, including adrenocortical tumor, hyperandrogenemia due to hypothalamic dysfunction, and contact with greasy topical skin care products. There are only a few case reports of inhaled steroids causing acneiform eruptions, all of which occurred in adults and with symptoms suggesting that the acne resulted from systemic absorption. We present two cases of comedonal and inflammatory midchildhood acne temporally associated with the use of inhaled corticosteroids administered through face masks, implicating a causative relationship between topical steroid exposure and midchildhood acne that does not necessitate systemic absorption.


Melatonin as a Pleiotropic Molecule with Therapeutic Potential for Type 2 Diabetes and Cancer.
The incidence of both type 2 diabetes (T2DM) and cancer is increasing worldwide, making these diseases a global health problem along with increasing healthcare expenditures. The current therapeutic approaches for treating these multifactorial diseases are far from satisfactory. As increasing evidence shows beneficial effects of melatonin (MLT) on typical pathological changes occurring during the development of T2DM and cancer, the present review focuses on molecular aspects of antidiabetic and anticancer activities of MLT and, moreover, discusses several future directions of research regarding MLT application as potential therapeutic agent. Critical literature analysis in PubMed central combined with personal expertise. Numerous in vitro and in vivo studies have revealed that MLT possesses a number of antidiabetic health benefits by diminishing hyperglycemia, insulin resistance, oxidative stress, and inflammation through modulating various intracellular signaling pathways or other targets involved in the pathophysiology of this disease. Mounting evidence also indicates that MLT exhibits multi-targeted anticancer effects in numerous human malignancies, mainly resulting from its ability to modulate several signal transduction pathways associated with cell survival, proliferation, and apoptosis. Furthermore, beneficial synergistic action of MLT with chemotherapy and radiotherapy has also been observed. Importantly, no adverse outcomes have been found from the clinical use of MLT, which highlights its therapeutic usefulness, either alone or in combination with other conventional therapies, in cancer treatment. The findings described in this review suggest that MLT may confer potential benefits to human health, particularly in respect to T2DM and cancer.


The anterior paraventricular thalamus modulates neuronal excitability in the suprachiasmatic nuclei of the rat.
The suprachiasmatic nucleus (SCN) in mammals is the master clock which regulates circadian rhythms. Neural activity of SCN neurons is synchronized to external light through the retinohypothalamic tract (RHT). The paraventricular thalamic nucleus (PVT) is a neural structure that receives synaptic inputs from, and projects back to, the SCN. Lesioning the anterior PVT (aPVT) modifies the behavioral phase response curve induced by short pulses of bright light. In order to study the influence of the aPVT on SCN neural activity, we addressed whether the stimulation of the aPVT can modulate the electrical response of the SCN to either retinal or RHT stimulation. Using in vitro and in vivo recordings, we found a large population of SCN neurons responsive to the stimulation of either aPVT or RHT pathways. Furthermore, we found that simultaneous stimulation of the aPVT and the RHT increased neuronal responsiveness and spontaneous firing rate (SFR) in neurons with a low basal SFR (which also have more negative membrane potentials), such as quiescent and arrhythmic neurons, but no change was observed in neurons with rhythmic firing patterns and more depolarized membrane potentials. These results suggest that inputs from the aPVT could shift the membrane potential of an SCN neuron to values closer to its firing threshold and thus contribute to integration of the response of the circadian clock to light.


Interaction of a defect with the reference curvature of an elastic surface.
The morphological response of two-dimensional curved elastic sheets to an isolated defect (dislocation/disclination) is investigated within the framework of Föppl-von Kármán shallow shell theory. The reference surface, obtained as a shell configuration in the absence of defect and external forces, accordingly has a finite non-zero curvature. The interaction of the defect with the curvature of the reference surface is emphasized through the problem of defect driven buckling of an elastic sheet. Detailed bifurcation diagrams, including the post-buckling deformation behaviour, are plotted for several combinations of defect types, reference curvatures, and boundary conditions. A pitchfork bifurcation is obtained when the reference surface is flat irrespective of the defect type and boundary condition. For curved reference surfaces there are some cases where the pitchfork bifurcation persists and others where it does not. The varied response demonstrates the rich interaction of the defects with the curvature of the reference surface.


Hyaluronic Acid-Coated Nanomedicine for Targeted Cancer Therapy.
Hyaluronic acid (HA) has been widely investigated in cancer therapy due to its excellent characteristics. HA, which is a linear anionic polymer, has biocompatibility, biodegradability, non-immunogenicity, non-inflammatory, and non-toxicity properties. Various HA nanomedicines (i.e., micelles, nanogels, and nanoparticles) can be prepared easily using assembly and modification of its functional groups such as carboxy, hydroxy and N-acetyl groups. Nanometer-sized HA nanomedicines can selectively deliver drugs or other molecules into tumor sites via their enhanced permeability and retention (EPR) effect. In addition, HA can interact with overexpressed receptors in cancer cells such as cluster determinant 44 (CD44) and receptor for HA-mediated motility (RHAMM) and be degraded by a family of enzymes called hyaluronidase (HAdase) to release drugs or molecules. By interaction with receptors or degradation by enzymes inside cancer cells, HA nanomedicines allow enhanced targeting cancer therapy. In this article, recent studies about HA nanomedicines in drug delivery systems, photothermal therapy, photodynamic therapy, diagnostics (because of the high biocompatibility), colloidal stability, and cancer targeting are reviewed for strategies using micelles, nanogels, and inorganic nanoparticles.


[Influence of diet in COVID-19 infection and severity risk: a systematic review].
Introduction: the risk and/or prognosis of COVID-19, caused by the SARS-CoV-2 virus, have been related to chronic diseases such as obesity, diabetes mellitus, and cardiovascular diseases, with poor-quality diet being a predisposing factor for these diseases. Objective: to synthesize the scientific evidence on the effect of diet on the risk of SARS-CoV-2 infection and severe COVID-19. Methods: a systematic review was carried out following the PRISMA guidelines. The bibliographic search was made in the databases Web of Science, Scopus and Medline (through the PubMed search engine). Risk of bias analysis was performed using the Newcastle-Ottawa and Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies scales. Results: 14 studies were included. Good adherence to the Mediterranean diet was associated with a decreased risk of SARS-CoV-2 infection (OR = 0.44; 95 % CI, 0.22-0.88, for high versus low adherence, and significant ORs of 0.88 and 0.95 in studies that analyzed adherence quantitatively) but not with the severity of COVID-19. A plant-based diet also had a protective association against both COVID-19 infection and severity. Specifically, a high consumption of vegetables, legumes and cereals, and a low intake of dairy products and red meat showed a protective effect against infection and/or COVID-19 severity, depending on the study. Vitamin and probiotic supplements also lowered the risk of infection. Conclusion: the available evidence suggests that a healthy diet, based on a Mediterranean or plant-based diet, with moderate consumption of dairy and red meat, exerts a protective effect against COVID-19.


Single-strand and double-strand deoxyribonucleic acid breaks produced by several bleomycin analogues.
Production of single-strand breaks (ssb) and double-strand breaks (dsb) of PM2 phage DNA by several structurally related bleomycin (BLM) analogues was studied by gel electrophoresis. BLM A2 and BLM B2 produced a comparable extent of dsb. In various experiments, BLM A2 and BLM B2, at 22-41 ng/mL, degraded 50% of the form I DNA into 33-38% form II and 12-17% form III DNA. BLM B1' produced ssb and dsb at a ratio similar to that of BLM A2, but both at a rate less than half that of BLM A2. Phleomycin (PLM) D1 induced an equivalent amount of ssb but only one-eighth of dsb induced by BLM B2. The relatively lower extent dsb production for PLM D1 was observed either in borate buffer (pH 9.5) or in Tris-HCl buffer (pH 7.5) and in the presence or absence of exogenous Fe(II). Deamido-BLM A2 produced ssb to an extent approximately half that of BLM A2 and dsb to less than one-eighth that of BLM A2. The following conclusions were drawn. (1) BLM analogues produced ssb and dsb to different extents and ratios. (2) The ratio of dsb to ssb varied depending on the analogue, indicating a lack of a direct correlation between ssb and dsb. (3) The extent of ssb and dsb was affected by modifications on both the C- and N-terminal half-molecules of BLM: modification of either the N-terminal amide or the bithiazole greatly reduced dsb, whereas changes in structure or charge in the C-terminal amine affected ssb and dsb to a similar extent.


Application of nano-sized TiO2 as an inhibitor of stress corrosion cracking in the steam generator tube materials.
Several chemicals were studied to suppress the damage due to a stress corrosion cracking (SCC) of the steam generator (SG) tubes in nuclear power plants. SCC tests were carried out to investigate the performance of TiO2 on several types of SG tube materials. The SCC tests were conducted by using an m-RUB specimen in a 10% NaOH solution at a temperature of 315 degrees C. The test with the addition of TiO2 showed a decrease in the SCC rate for the SG tubing materials. In order to improve the inhibition property in a crevice of TiO2, a sonochemical technique was applied to reduce the size of the TiO2 particle. From the SCC tests with the RUB specimen, the SG tube materials showed an enhanced cracking resistance with the addition of nano-sized TiO2 and the surface property was also changed.


Expression of constitutive nitric oxide synthase isoforms in varicose vein wall; preliminary results.
There are conflicting findings in literature about the structural changes of the primary varicose veins. NO (a potent vasodilatator) is synthesized by nitric oxide synthase (NOS). From 3 known NOS isoforms the two are constitutional: eNOS (endothelial NOS) and nNOS (neuronal NOS). 10 varicose and 10 control vein samples were processed by standard light microscopy and immuno-histochemica techniques using rabbit polyclonal antibodies against eNOS and nNOS. Antibodies expression was evaluated semiquantitatively and proved morphometrically by 2D-image analysis. total area of NOS isoforms expressions was determined by color analysis and color digital subtraction. The results showed discontinuous and significantly lower expression of both NOS isoforms the in the tunica media of varicose veins compared with the control group. For the statistical analysis the unpaired t-test was used. Our results suppose lower NO levels in varicose vein wall, deducing that varicose dilatation is due to other mechanism, and they contradict the results of previously published similar works.


[Postoperative mortality after gastrectomy for gastric cancer: analysis of 1142 cases].
To analyze postoperative morbidity and mortality after gastrectomy for gastric carcinoma and identify main risk factors influencing mortality. A total of 1142 patients with gastric cancer received gastrectomy between January 1989 and April 2004. The patients were divided into three groups according to different period, the first group (n=405): from January 1989 to January 1994; the second group (n=377): from February 1994 to January 1999; the third group (n=360): from February 1999 to March 2004. Postoperative morbidity and mortality were compared among three groups, the risk factors influencing postoperative mortality were determined by multiple logistic regression analysis. The total postoperative morbidity and mortality for all patients were 11.2% (128/1142) and 3.6% (41/1142), respectively. The postoperative morbidity was 13.1%, 10.1%, and 10.3% in the first, second, and third group respectively, there was no significant difference in morbidity among the three groups (P > 0.05). The postoperative mortality was 4.7%, 3.4%, and 2.5% respectively (P > 0.05), there was no significant difference in mortality among the three groups (P > 0.05). The most common postoperative complication was anastomotic leakage (24.2%, 31/128). The following clinicopathologic factors were found to be correlated with postoperative mortality: stage IV; palliative excision; multivisceral resection; and preoperative complications (P< 0.05). Multivariate analysis revealed that the extent of lymph node dissection or surgical procedure were not main risk factors influencing mortality. Patients with advanced gastric cancer have a high risk of postoperative mortality. Unnecessary lymph node dissection or multivisceral resection should be avoided for patients with stage IV gastric cancer.


Neural Mechanisms of Body Awareness in Infants.
The ability to differentiate one's body from others is a fundamental aspect of social perception and has been shown to involve the integration of sense modalities attributable to the self. Though behavioral studies in infancy have investigated infants' discrimination of body-related multisensory stimuli, whether they attribute this information as belonging to the self is still unknown. In human adults, neuroimaging studies have demonstrated the recruitment of a specific set of brain regions in response to body-related multisensory integration. To test whether the infant brain integrates this information similarly to adults, in a first functional near-infrared spectroscopy study we investigated the role of visual-proprioceptive feedback when temporal cues are manipulated by showing 5-month-old infants an online video of their own face while the infant was performing movements. To explore the role of body-related contingency further, in a second study we investigated whether cortical activation in response to self-initiated movements and external tactile stimulation was similar to that found in the first study. Our results indicate that infants' specialized cortical activation in response to body-related contingencies is similar to brain activation seen in response to body awareness in adults.


Can patients with McArdle's disease run?
Patients with McArdle's disease commonly adopt a sedentary lifestyle. This sedentary behaviour, however, usually worsens the limited exercise capacity of these patients. Although eccentric muscle work can be associated with rhabdomyolysis, supervised eccentric training with gradually increasing loads has important advantages compared with conventional concentric work, particularly for patients with a poor cardiorespiratory system. We report the beneficial effects (particularly, increased VO(2peak) (from 14.6 to 30.8 ml/kg/min) and increased gross muscle efficiency (from 13.8% to 17.2%)) induced by a supervised aerobic training programme of 7 months duration including 3-4 running sessions (< or =60 min/session) per week in a 38-year-old patient. These preliminary data suggest the potential therapeutic value of this type of exercise in these patients.


Dopamine activity on the perceptual salience for recognition memory.
To survive, animals must recognize relevant stimuli and distinguish them from inconspicuous information. Usually, the properties of the stimuli, such as intensity, duration, frequency, and novelty, among others, determine the salience of the stimulus. However, previously learned experiences also facilitate the perception and processing of information to establish their salience. Here, we propose "perceptual salience" to define how memory mediates the integration of inconspicuous stimuli into a relevant memory trace without apparently altering the recognition of the physical attributes or valence, enabling the detection of stimuli changes in future encounters. The sense of familiarity is essential for successful recognition memory; in general, familiarization allows the transition of labeling a stimulus from the novel (salient) to the familiar (non-salient). The novel object recognition (NOR) and object location recognition (OLRM) memory paradigms represent experimental models of recognition memory that allow us to study the neurobiological mechanisms involved in episodic memory. The catecholaminergic system has been of vital interest due to its role in several aspects of recognition memory. This review will discuss the evidence that indicates changes in dopaminergic activity during exposure to novel objects or places, promoting the consolidation and persistence of memory. We will discuss the relationship between dopaminergic activity and perceptual salience of stimuli enabling learning and consolidation processes necessary for the novel-familiar transition. Finally, we will describe the effect of dopaminergic deregulation observed in some pathologies and its impact on recognition memory.


A study on the prevalence of depression and the severity of depression in patients of chronic obstructive pulmonary disease in a semi-urban Indian population.
Chronic obstructive pulmonary disease (COPD) is one of the few respiratory diseases which is associated with a number of comorbidities. Psychiatric disease like depression is a very important comorbidity of COPD because it decreases the feeling of wellbeing in the patient and also interferes with the compliance with medication thereby increasing the risk of hospitalization in the COPD patient. A cross-sectional study was done for two years in the department of pulmonary medicine at Era's Lucknow medical college and hospital, Lucknow. A total of 150 patients were enrolled for the study after a clinico-radiological screening for the diagnosis confirmed on spirometry. After the confirmation of the diagnosis of COPD in these patients, they were screened for depression using the PHQ-9 scale in our department of pulmonary medicine. The confirmation of the diagnosis of depression was done according to the ICD-10 guidelines for depression and the severity of depression was graded using HAM-D scale in the department of psychiatry at our institute. The most common age group enrolled in the study was 51-60 years of age (40.67%). One hundred and fifteen patients (76.7%) of the enrolled patients were smokers while the remaining 35 patients (23.3%) were non-smokers. Depression was found to be present in 46 out of the total 150 patients in the study. Thus, the prevalence of depression in our study was 30.67%. Depression was seen in COPD groups B,C and D. Out of the 46 patients of COPD with depression,18 had mild depression (39.13%), 26 had moderate depression (56.52%) and 2 had severe depression (4.35%). Hence, depression of all grades (i.e., mild, moderate and severe depression) is seen in COPD groups B, C and D.


Circulating tumor cells in pancreatic cancer patients: methods of detection and clinical implications.
The poor prognosis of pancreatic cancer patients is associated with the frequent and early dissemination of the disease, as well as late detection due to unspecific and late symptoms from the primary tumor. Pancreatic cancers frequently spread to the liver, lung and skeletal system, suggesting that pancreatic tumor cells must be able to intravasate and travel through the circulation to distant organs. Circulating tumor cells (CTCs) are tumor cells that have acquired the ability to enter the circulatory system; this cell population is ultimately responsible for the development of metastases in distant organs. Clinical studies have revealed that the presence of CTCs in blood is correlated with disease progression for other cancers, such as breast, colorectal and prostate cancer. However, as CTCs are extremely rare, both enrichment and sensitive methods of detection are required for their enumeration. This review highlights various enrichment procedures and methods for the detection of CTCs. Furthermore, we systematically review previously reported studies of the clinical relevance of CTC detection in pancreatic cancer patients. There is evidence that the presence of CTCs also correlates with an unfavorable outcome in pancreatic cancer patients. However, technical/methodological issues may explain why some studies only show a trend toward an association between CTC detection and disease progression. Larger studies, as well as characterization of the CTC population, are required to achieve further insight into the clinical implications of CTC detection in pancreatic cancer patients.


Immune Cell Repertoire and Their Mediators in Patients with Acute Myocardial Infarction or Stable Angina Pectoris.
Background: To evaluate the natural innate and adaptive immunity through gene expression and cytology levels in peripheral blood mononuclear cells in patients with acute myocardial infarction (AMI), stable angina pectoris (SAP) and controls. Methods: 210 patients with AMI, 210 with SAP, and 250 clinical controls were recruited. Whole human genome microarray analysis was performed in 20 randomly chosen subjects per group were examined to detect the expressions of complement markers, natural killer cells, T cells and B cells. The quantity of these cells and related cytokines as well as immunoglobulin levels were measured in all subjects. Results: In AMI group, the mRNA expressions of late complement component, markers of natural killer cells, CD3+, CD8+ T cells and B cells were down-regulated, while those of early complement component and CD4+T cells were up-regulated (p<0.05). In both AMI and SAP patients, the quantity of natural killer cells, CD3+, CD8+ T cells, B cells, IgM and IgG were significantly lower than those of the controls. CD4+ T cells, CH50, C3, C4, IL-2, IL-4, IL-6 and IFN-γ were significantly higher (p<0.05). Conclusions: In AMI patients, both of gene expressions related to complement, natural killer cells, CD3+, CD8+ T cells, B cells and the quantity of these immune cells decreased while cell number reduced in SAP patients. Immune function in both AMI and SAP patients decreased especially in AMI patients with declined gene and protein levels. To improve the immune system is a potential target for medical interventions and prevention in AMI.


Preparation and characterization of letrozole-loaded poly(d,l-lactide) nanoparticles for drug delivery in breast cancer therapy.
Letrozole (LTZ), an aromatase inhibitor used for the treatment of hormonally-positive breast cancer in postmenopausal women, has poor water solubility, rapid metabolism, and a range of side effects. In this study, polymer-based nanoparticles (NPs) incorporating the drug have been designed and characterized, aimed to control the release, potentially maximize the therapeutic efficiency, and minimize the side effects of the drug. LTZ was incorporated into poly(d,l-lactide) (PDLLA) NPs by employing the emulsion-solvent evaporation technique using a range of drug concentrations. Loaded drug and drug-polymer interactions were studied using X-ray diffraction and NPs morphology was evaluated using scanning electron microscopy (SEM). Particle size distribution (PSD) and zeta potential of the NPs were analyzed using dynamic light scattering (DLS) and laser Doppler velocimetry (LDV), respectively. Drug content and release profile studies were carried out and determined using ultra performance liquid chromatography (UPLC). The yield of LTZ-PDLLA NPs reached as high as 85%. The NPs were spherical and smooth, regardless of LTZ concentration in the formulation. However, particle size increased from 241.6 ± 1.2 to 348.7 ± 6.1 nm upon increasing LTZ concentration from 0 to 30% w/w, with entrapment efficiencies reaching up to 96.8%. Drug release from the polymeric matrix was best described by Higuchi model with a predominant diffusion-based mechanism. More than 15, 46, and 86% of LTZ was released in a controlled fashion over 30 d from the 10, 20, and 30% LTZ-PDLLA NPs, respectively. Overall, LTZ-PDLLA NPs were designed with appropriate size and surface charge, high drug loading, superior entrapment efficiency, and prolonged release profile.


Some aspects of the structure and organization of child nutrition in a number of regions Russia.
This research aims to assess catering arrangements and dietary patterns of children at preschool educational institution and at home. The article analyses catering arrangements for pre-school children (3-7-year-old) from Ekaterinburg, Nizhny Tagil, Kamensk-Uralsky, Vladikavkaz and Krasnoyarsk. Based on menu production records provided by preschool educational institution, and family nutrition questionnaires we have examined their compliance with the nutritional physiological standards. The summarized data on menu production records from preschool educational institutions showed whether they met food basket requirements (net weight), as well as nutritional value requirements (proteins, fats, carbohydrates, calories content). The assessment was carried out in Ekaterinburg, Nizhny Tagil and Krasnoyarsk using Public catering calculations software (version 5) and a proprietary database of childreris food formulae. Childrens food basket assessment in Ekaterinburg and Kamensk-Uralsky revealed underconsumptionof vegetables (17.9-38% decrease), milk (52.7-62% decrease), curd (40.2-45.3% decrease). We have also observed decreased consumption of fruits, including dried fruit, by 31.8%, as well as cereals and legumes by 43% in Kamensk-Uralsky. Macronutrient analysis has shown underconsumption of total carbohydrates (by 19%) and animal proteins. The assessment of children nutrition at home has been carried out using NUTRITEST-IP diagnostic system in Nizhny Tagil, Kamensk-Uralsky, Vladikavkaz and Krasnoyarsk. The results showed overconsumption of most foods except vegetables. Excessive intake of fats and sugars (3.6 and 3.5 fold higher, respectively) accounted for higher than normal energy consumption by children at home. The evaluation has also revealed a significant difference in the consumption of saturated fats, mono - and disaccharides, food fibers and vitamin C by the children from the locations included in the study. The excessive intake of simple carbohydrates was typical for family diets and excessive fat intake was characteristic for child diet in preschool educational institution.


Abdominal aortic aneurysm is a specific antigen-driven T cell disease.
To determine whether monoclonal/oligoclonal T cells are present in abdominal aortic aneurysm (AAA) lesions, we amplified beta-chain T cell receptor (TCR) transcripts from these lesions by the nonpalindromic adaptor (NPA)-polymerase chain reaction (PCR)/V-beta-specific PCR followed by cloning and sequencing. Sequence analysis revealed the presence of substantial proportions of identical beta-chain TCR transcripts in AAA lesions in 9 of 10 patients examined, strongly suggesting the presence of oligoclonal populations of alphabeta TCR+ T cells. We have also shown the presence of oligoclonal populations of gammadelta TCR+ T cells in AAA lesions. Sequence analysis after appropriate PCR amplification and cloning revealed the presence of substantial proportions of identical VgammaI and VgammaII TCR transcripts in 15 of 15 patients examined, and of Vdelta1 and Vdelta2 TCR transcripts in 12 of 12 patients. These clonal expansions were very strong. All these clonal expansions were statistically significant by the binomial distribution. In other studies, we determined that mononuclear cells infiltrating AAA lesions express early- (CD69), intermediate- (CD25, CD38), and late- (CD45RO, HLA class II) activation antigens. These findings suggest that active ongoing inflammation is present in the aortic wall of patients with AAA. These results demonstrate that oligoclonal alphabeta TCR+ and gammadelta TCR+T cells are present in AAA lesions. These oligoclonal T cells have been clonally expanded in vivo in response to yet unidentified antigens. Although the antigenic specificity of these T cells remains to be determined, these T cells may play a significant role in the initiation and/or the propagation of the AAA. It appears that AAA is a specific antigen-driven T cell disease.


[Effect of interferon-gamma on transforming growth factor beta/Smad signal pathway and expression of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinase-2 in cultured rat mesangial cells].
To study the effect of interferon-gamma (IFN-gamma) on the proliferation of mesangial cells (MsC) and transforming growth factor (TGF)-beta/Smad signal pathway, the mRNA and protein expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2), and to provide an experimental basis for IFN-gamma treatment of renal fibrosis. Cultured MsC were treated with IFN-gamma at different concentrations and the proliferation of MsC was examined by MTT. Protein and RNA samples were extracted from MsC at 0, 0.5, 1, 2, 4, 6, 12, 24 h after treated by 100 IU/ml IFN-gamma. The mRNA and protein expression of Smad3, Smad7, MMP-2 and TIMP-2 were analyzed by real-time RT-PCR and Western blot, respectively. The expression of Smad7 mRNA and protein were promptly elevated at 0.5 hour after the IFN-gamma treatment and lasted for 6 hours, but the proliferation of MsC was not altered. The elevated expression of Smad3, MMP2 mRNA and proteins persisted after 6 hours, whereas the expression of TIMP-2 mRNA and protein decreased. The therapeutic effect of IFN-gamma of renal fibrosis may be mediated by TGF-beta/smads signal pathway through up-regulation of MMP-2 expression, coupled with down-regulation of TIMP-2 expression.


Focal adhesion kinase tyrosine phosphorylation is associated with myogenesis and modulated by insulin.
Focal adhesion kinase (FAK) was heavily phosphorylated as a function of differentiation of C2C12 mouse skeletal muscle cells. Insulin caused increases in FAK phosphorylation before stabilization in proliferated cells, while in differentiated cells there was a consistent transient inhibition of FAK phosphorylation before stimulation. The expression level of FAK was unaltered. Specific inhibition of insulin receptor tyrosine kinase activity abolished the insulin-mediated dephosphorylation of FAK. The data strongly indicate that FAK tyrosine phosphorylation, necessary for skeletal muscle differentiation, is modulated by insulin. Thus, for the first time, we report the differential regulation of FAK tyrosine phosphorylation by insulin during skeletal muscle differentiation.


Redescription of Alopecosa albostriata (Araneae: Lycosidae) based on specimens from Siberia.
Alopecosa albostriata (Grube, 1861), originally described from Western Yakutia, is redescribed based on specimens from Siberia. Although A. albostriata is known to be distributed in Kazakhstan, Russia, China and Korea, with records attributed to more than 30 taxonomic entries, and is considered as a senior synonym of nine species (all described from China), it is actually restricted to Siberia and was illustrated only in two publications. All synonyms and records from China, Kazakhstan and Korea refer to species related to Mustelicosa dimidiata (Thorell, 1875). Among Palaearctic species, A. albostriata is most similar to A. mutabilis (Kulczyński, 1908). Comparative figures are provided for the latter species. These two species, together with A. exasperans (O. Pickard-Cambridge, 1877) form the albostriata species group occurring across Siberia and the northern Nearctic. Male palps in this species group are most similar to those in Mustelicosa Roewer, 1960, and most likely that species group will be transferred to this genus. Distribution records of A. albostriata are shown on map.


Behavior of CHO cells on phosphated cellulose membranes.
Phosphate groups (negatively charged chemical groups) were grafted onto the surface of cellulose membranes by a reaction between hydroxyl groups of cellulose and phosphorus pentoxide to observe the effect of phosphate groups on cellular behavior. X-ray photoelectron spectroscopy (XPS) was used to determine phosphorylation. Captive bubble contact angle measurement was used to determine surface wettability. XPS was also used to analyze serum protein adsorption. Chinese hamster ovary (CHO) cells were maintained in Ham's F-12 nutrient mixture with and without fetal calf serum. Total cell area and shape factor were analyzed using image-analyzing software. Serum proteins showed higher adsorption on phosphated cellulose. Cell spreading on phosphated membranes was greater than on the cellulose membrane that served as control. The cell growth rate was faster compared to the control. Large cell aggregates were not found on the phosphated membranes, in contrast to the control membrane. The cells on the control were aggregated regardless of the existence of divalent cations in the medium.


KARTAGENER'S SYNDROME: A CASE REPORT.
Kartagener's syndrome is a rare autosomal recessive genetic disorder that causes a defect in the action of the cilia lining the respiratory tract. Patients usually present with chronic recurrent rhinosinusitis, otitis media, pneumonia, and bronchiectasis caused by Pseudomonas infection. In this case report, we present a 12-year old female with Kartagener's syndrome from Tikur Anbessa Teaching Hospital which to our knowledge is the first of it's kind to be reported in Ethiopia. The clinical and imaging findings are discussed.


VCD configuration of enantiopure/-enriched tetrasubstituted alpha-fluoro cyclohexanones and their use for epoxidation of trans-olefins.
The configurations of three enantiopure tetrasubstituted alpha-fluoro cyclohexanones (-)-5Ia, (-)-5IIa and (-)-6a were determined by VCD and proved to be (-)-(2S,5R)-5Ia, (-)-(2R,5R)-5IIa, and (-)-(2R,5R)-6a. The VCD study also identified the conformers populated in CDCl3 solution, including higher-energy gas-phase conformers with equatorial fluorine for 5Ia and 5IIa that are stabilized in CDCl3 solution. Used as catalysts for epoxidation of trans olefins (beta-methylstyrene, stilbene, methyl p-methoxy cinnamate) by oxone, it was found that (-)-5Ia is the most efficient for all trans olefins (providing, respectively, 62%, 90% and 66% ee) but that all three ketones provide high ee% with stilbene (78-90% ee). Moreover, the configurations predicted from the stereo outcome of the epoxidation reaction are identical to those determined by VCD.


Accuracy of Stereovision-Updated Versus Preoperative CT-Based Image Guidance in Multilevel Lumbar Pedicle Screw Placement: A Cadaveric Swine Study.
Change in vertebral position between preoperative imaging and the surgical procedure reduces the accuracy of image-guided spinal surgery, requiring repeated imaging and surgical field registration, a process that takes time and exposes patients to additional radiation. We developed a handheld, camera-based, deformable registration system (intraoperative stereovision, iSV) to register the surgical field automatically and compensate for spinal motion during surgery without further radiation exposure. We measured motion-induced errors in image-guided lumbar pedicle screw placement in 6 whole-pig cadavers using state-of-the-art commercial spine navigation (StealthStation; Medtronic) and iSV registration that compensates for intraoperative vertebral motion. We induced spinal motion by using preoperative computed tomography (pCT) of the lumbar spine performed in the supine position with accentuated lordosis and performing surgery with the animal in the prone position. StealthStation registration of pCT occurred using metallic fiducial markers implanted in each vertebra, and iSV data were acquired to perform a deformable registration between pCT and the surgical field. Sixty-eight pedicle screws were placed in 6 whole-pig cadavers using iSV and StealthStation registrations in random order of vertebral level, relying only on image guidance without invoking the surgeon's judgment. The position of each pedicle screw was assessed with post-procedure CT and confirmed via anatomical dissection. Registration errors were assessed on the basis of implanted fiducials. The frequency and severity of pedicle screw perforation were lower for iSV registration compared with StealthStation (97% versus 68% with Grade 0 medial perforation for iSV and StealthStation, respectively). Severe perforation occurred only with StealthStation (18% versus 0% for iSV). The overall time required for iSV registration (computational efficiency) was ∼10 to 15 minutes and was comparable with StealthStation registration (∼10 min). The mean target registration error was smaller for iSV relative to StealthStation (2.81 ± 0.91 versus 8.37 ± 1.76 mm). Pedicle screw placement was more accurate with iSV registration compared with state-of-the-art commercial navigation based on preoperative CT when alignment of the spine changed during surgery. The iSV system compensated for intervertebral motion, which obviated the need for repeated vertebral registration while providing efficient, accurate, radiation-free navigation during open spinal surgery.