URGCP/URG4 promotes apoptotic resistance in bladder cancer cells by activating NF-κB signaling.
Cisplatin is a well-known chemotherapeutic agent, it could cause DNA damage and induce apoptotic cell death, but the cisplatin resistance also appears, it's important to reveal the mechanisms of cisplatin resistance [1]. URGCP/URG4 is overexpressed in various tumors and plays critical role during tumor development. We found URGCP/URG4 was upregulated in bladder cancer cells and tissues, URGCP/URG4 overexpression increased the resistance to cisplatin-induced apoptosis in bladder cancer, and promoted anti-apoptotic genes expression, such as Bcl-2, Survivin, MCL-1, FLIP, and downregulated Caspase-3 expression, Knockdown of URGCP/URG4 decreased the resistance to cisplatin-induced apoptosis, and inhibited anti-apoptotic genes expression, such as Bcl-2, Survivin, MCL-1, FLIP, and upregulated Caspase-3 expression. Mechanism analysis found URGCP/URG4 activated NF-κB pathway which is a well-known anti-apoptotic pathway and promoted the expression of NF-κB targeted genes. So we speculated URGCP/URG4 regulates cisplatin-induced apoptosis by activating NF-κB pathway. We also analyzed the correlation between URGCP/URG4 expression and clinical clinicopathologic, and found its expression was positively correlated with bladder cancer progression, it can serve as a valuable prognostic factor. In summary, URGCP/URG4 promotes the resistance to cisplatin-induced apoptosis by activating NF-κB pathway, and is an unfavorable prognostic factor for bladder cancer.


Platelet-derived growth factor D: tumorigenicity in mice and dysregulated expression in human cancer.
Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes, as well as in human cancer and other proliferative disorders. We have recently isolated and characterized a novel protease-activated member of the PDGF family, PDGF D. PDGF D has been shown to be proliferative for cells of mesenchymal origin, signaling through PDGF receptors. Comprehensive and systematic PDGF D transcript analysis revealed expression in many cell lines derived from ovarian, renal, and lung cancers, as well as from astrocytomas and medulloblastomas. beta PDGF receptor profiling further suggested autocrine signaling in several brain tumor cell lines. PDGF D transforming ability and tumor formation in SCID mice was further demonstrated. Exploiting a sensitive PDGF D sandwich ELISA using fully human monoclonal antibodies, PDGF D was detected at elevated levels in the sera of ovarian, renal, lung, and brain cancer patients. Immunohistochemical analysis confirmed PDGF D localization to ovarian and lung tumor tissues. Together, these data demonstrate that PDGF D plays a role in certain human cancers.


Kiloniella antarctica sp. nov., isolated from a polynya of Amundsen Sea in Western Antarctic Sea.
A taxonomic study was conducted on strain soj2014T, which was isolated from the surface water of a polynya in the Antarctic Sea. Comparative 16S rRNA gene sequence analysis showed that strain soj2014T belongs to the family Kiloniellaceae and is closely related to Kiloniella spongiae MEBiC09566T, 'Kiloniella litopenaei' P1-1T and Kiloniella laminariae LD81T (98.0 %, 97.8 % and 96.2 % 16S rRNA gene sequence similarity, respectively). The DNA-DNA hybridization values between strain soj2014T and closely related strains were below 28.6 %. The G+C content of the genomic DNA of strain soj2014T was 45.5 mol%. The predominant cellular fatty acids were summed feature 8 (composed of C18 : 1ω6c/C18 : 1ω7c, 57.0 %) and summed feature 3 (composed of C16 : 1ω6c/C16 : 1ω7c, 23.5 %). Strain soj2014T was Gram-stain-negative, slightly curved, spiral-shaped, and motile with a single polar flagellum. The strain grew at 0-30 °C (optimum, 25 °C), in 1.5-5.1 % (w/v) NaCl (optimum, 2.1-2.4 %) and at pH 5.5-9.5 (optimum, 7.5-8.0). It also had differential carbohydrate utilization traits and enzyme activities compared with closely related strains. Based on these phylogenetic, phenotypic and chemotaxonomic analyses, strain soj2014T represents a distinct species, separable from the reference strains, and is, therefore, proposed as a novel species, Kiloniella antarctica sp. nov. The type strain is soj2014T (=KCTC 42186T=JCM 30386T).


Modulation of thymus-leukemia antigens on mouse leukemia cells induced by IgG, but not IgM, antibody.
Exposure of mouse leukemia cells bearing thymus-leukemia (TL) surface antigens to whole TL alloantiserum has previously been shown to desensitize the cells to subsequent lysis by guinea pig complement (C) and fresh antiserum (antigenic modulation) and to correlate with the ability of cells to escape immune destruction in mice immunized against TL antigens. Tested in vitro, IgG of TL.1,2,3,5 antiserum modulated RADA1 leukemia cells (TL.1,2,3,5) completely within 2 hours at 37 degrees C when fully sensitizing amounts were used, with normal mouse serum as a source of C3. Similar results were obtained with IgG1, IgG2a, and IgG2b fractions of TL antiserum. An IgG2a monoclonal TL.3 antibody also completely modulated TL.3 antigens and partially modulated all antigens detected with TL.1,2,3,5 antiserum. IgM anti-TL.1,2,3,5 failed to modulate RADA1 cells even after 6 hours in vitro when fully sensitizing amounts of antibody were used. An IgM monoclonal TL antibody also failed to induce modulation. Modulation did occur on cells incubated with fully sensitizing amounts of IgG and IgM TL.1,2,3,5 antibody simultaneously, and nearly all cell-bound immunoglobulins were IgG. In mice passively immunized with IgG TL antibody, RADA1 cells modulated completely within 24 hours, whereas no modulation occurred during 4 days in mice immunized with IgM antibody. However, in both instances, tumor cells grew actively, which indicated that tumor escape did not depend on achievement of a modulated state.


Genome-wide scanning for linkage in Finnish breast cancer families.
Only a proportion of breast cancer families has germline mutations in the BRCA1 or BRCA2 genes, suggesting the presence of additional susceptibility genes. Finding such genes by linkage analysis has turned out to be difficult due to the genetic heterogeneity of the disease, phenocopies and incomplete penetrance of the mutations. Isolated populations may be helpful in reducing the level of genetic heterogeneity and in providing useful starting points for further genetic analyses. Here, we report results from a genome-wide linkage analysis of 14 high-risk breast cancer families from Finland. These families tested negative for BRCA1 and BRCA2 germline mutations and showed no linkage to the 13q21 region, recently proposed as an additional susceptibility locus. Suggestive linkage was seen at marker D2S364 (2q32) with a parametric two-point LOD score of 1.61 (theta=0), and an LOD score of 2.49 in nonparametric analyses. Additional genotyping of a 40 cM chromosomal region surrounding the region of interest yielded a maximum parametric two-point LOD score of 1.80 (theta=0) at D2S2262 and a nonparametric LOD score of 3.11 at an adjacent novel marker 11291M1 in BAC RP11-67G7. A nonparametric multipoint LOD score of 3.20 was seen at 11291M1 under the assumption of dominant inheritance. While not providing proof of linkage considering the small number of families and large number of laboratory and statistical analyses performed, these results warrant further studies of the 2q32 chromosomal region as a candidate breast cancer susceptibility locus. Both linkage and association studies are likely to be useful, particularly in other isolated populations.


Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder.
Metabolic and functional alterations of neurons in the dorsolateral prefrontal cortex (dlPFC) are thought to contribute to impulsivity, which is a hallmark of addictive behaviors that underlie compulsive drug seeking and taking in humans. To determine if there is a transcriptional signature in dlPFC neurons of humans with cocaine use disorder, we performed total RNA-sequencing on neuronal nuclei isolated from post-mortem dlPFC of cocaine addicts and healthy controls. Our results point toward a transcriptional mechanism whereby cocaine alters specific gene networks in dlPFC neurons. In particular, we identified an AP-1 regulated transcriptional network in dlPFC neurons associated with cocaine use disorder that contains several differentially expressed hub genes. Several of these hub genes are GWAS hits for traits that might involve dysfunction of brain reward circuitry (Body-Mass Index, Obesity) or dlPFC (Bipolar disorder, Schizophrenia). Further study is warranted to determine their potential pathophysiological role in cocaine addiction.


[Study on the microstructure of acellular dermal matrix and its biocompatibility with MG63 osteoblast-like cells].
To study the microstructue of acellular dermal matrix (ADM) and the attachment and proliferation of MG63 osteoblast-like cells on the membrane. ADM was experimental group and expanded polytetrafluoroethylene (e-PTFE) membrane was control group. Light microscope and scanning electronic microscope (SEM) were used to observe the microstructure of the two kinds of membrane. MG63 osteoblast-like cells were cultured on the two kinds of membrane and the blank group. The cell viability was checked by cell viability analyzer (CVA) and alkaline phosphatase (ALP) activity was detected by ELISA. SEM was used to observe the adhesion and proliferation of the MG63 osteoblast-like cells on the two kinds of membrane. The ADM was composed of the tissular side and basal lamina side. The tissue side showed scale-shaped structure and the basal lamina side demonstrated many digitations and some pores of folliculus pili. The e-PTFE showed many tiny lined cracks in elliptic structure. The viability of the MG63 osteoblast-like cells on the two kinds of membranes and ALP measurement showed that there was no significant difference between each of the two membrane groups and the blank. The adhesion and proliferation of osteoblast-like cells on the two kinks of membranes were both well. ADM has no negative effects on the growth of osteoblast-like cells. ADM is biocompatibile and its microstructure is appropriate for guided bone regeneration materials.


Effect of internal structures on the accuracy of 3D printed full-arch dentition preparation models in different printing systems.
The objective of this study was to investigate how internal structures influence the overall and marginal accuracy of full arch preparations fabricated through additive manufacturing in different printing systems. A full-arch preparation digital model was set up with three internal designs, including solid, hollow, and grid. These were printed using three different resin printers with nine models in each group. After scanning, each data was imported into the 3D data processing software together with the master cast, aligned and trimmed, and then put into the 3D data analysis software again to compare the overall and marginal deviation whose results are expressed using root mean square values and color maps. To evaluate the trueness of the resin model, the test data and reference data were compared, and the precision was evaluated by comparing the test data sets. Color maps were observed for qualitative analysis. Data were statistically analyzed by one-way analysis of variance and Bonferroni method was used for post hoc comparison (α = .05). The influence of different internal structures on the accuracy of 3D printed resin models varied significantly (P < .05). Solid and grid models showed better accuracy, while the hollow model exhibited poor accuracy. The color maps show that the resin models have a tendency to shrink inwards. The internal structure design influences the accuracy of the 3D printing model, and the effect varies in different printing systems. Irrespective of the kind of printing system, the printing accuracy of hollow model was observed to be worse than those of solid and grid models.


TreeSnatcher: coding trees from images.
TreeSnatcher is a GUI-driven JAVA application for the semi-automatic recognition of multifurcating phylogenetic trees in pixel images. The program accepts an image file as input and analyzes the topology and the metrics of a tree depicted. The analysis is carried out in a multiple-stage process using algorithms from image analysis. In the end, TreeSnatcher produces a Newick tree code that represents the tree structure optionally including branch lengths. TreeSnatcher can process trees with 100 leaves or more in a few seconds. TreeSnatcher was developed in JAVA under Mac OS X and is executable on UNIX/Linux, Windows and Mac OS X systems. The application and its documentation can be freely downloaded from http://www.cibiv.at/software/treesnatcher.


Flow characteristics and film thickness of flowable resin composites.
Flowable resin composites have been recommended for many clinical uses and have been formulated in a variety of compositions and viscosities to meet various uses. This study compared the variation in viscosity of flowable resin composites using the ADA Flow Test and measured film thickness with a test to simulate flow during cementation. The film thickness test for the flowable resin composites was performed at three different seating pressures to simulate pressure variation during seating of porcelain veneers, one of the potential uses of flowable resin composites that may favor a lower viscosity. The following flowable resin composites were evaluated: Revolution, StarFlow, Aeliteflo LV, Aelite, Flow-It, FloRestore, Versaflo, Durafill Flow and Tetric Flow, with Nexus2, a composite luting resin used as a control. Flow characteristic measurements suggest that resin composites may be divided into high flow (StarFlow, Revolution, Aeliteflo LV), medium flow (FloRestore, Durafill Flow, Flow-It) and low flow (Tetric Flow, Versaflo, Nexus2, Aelite) groupings. The film thickness measurements agreed with the ADA flow test, except for two exceptions. Durafill Flow resin composite had a higher film thickness than expected based on the ADA flow test. Also, Aeliteflo unexpectedly had a lower film thickness. At the lowest seating pressure (.016MPa) tested, eight out of the nine resin composites tested as well as the control luting resin had a film thickness greater than the 25 microns used as the clinical standard for cement film thickness. However, at the highest seating pressure (.038 MPa) tested, only two and the control, Versaflo, Durafill Flow and Nexus2, had film thicknesses significantly greater than 25 microns. The highly filled Nexus2 luting resin had the highest film thickness at all seating pressures.


Acquired superoxide-scavenging ability of ceria nanoparticles.
Ceria nanoparticles (nanoceria) are well known as a superoxide scavenger. However, inherent superoxide-scavenging ability has only been found in the nanoceria with sizes of less than 5 nm and with very limited shape diversity. Reported herein is a strategy to significantly improve the superoxide-scavenging activity of nanoceria sized at greater than 5 nm. The nanoceria with sizes of greater than 5 nm, with different shapes, and with a negligible Ce(3+)/Ce(4+) ratio can acquire remarkable superoxide-scavenging abilities through electron transfer. This method will make it possible to develop nanoceria-based superoxide-scavengers with long-acting activity and tailorable characteristics.


The incidence and spectrum of congenital hand differences in patients with Fanconi anaemia: analysis of 48 patients.
We analysed the spectrum of congenital hand differences in a cohort of patients with Fanconi anaemia (FA). Data of 48 FA patients at the National Cancer Institute were reviewed focusing on age at diagnosis, type and severity of limb difference and any potential association with other known clinical anomalies that are part of the FA phenotype, specifically VACTERL-H and PHENOS. Twenty-eight patients had an upper limb difference, which always included thumb hypoplasia. Twenty-three patients had bilateral upper limb differences, including varying combinations and severities of thumb hypoplasia, radial dysplasia and thumb duplication. Patients with a limb difference were diagnosed at a younger age (<2 years: 15/28 with limb anomaly versus 4/20 without a limb anomaly). However, 7/28 with limb anomalies, usually thumb hypoplasia, were not diagnosed until after 6 years of age. This study demonstrates the broad spectrum of radial ray anomalies within the FA phenotype along with the possibility of either unilateral or bilateral upper limb differences and adds further merit to consideration of screening for FA in all cases of radial ray anomaly.Level of evidence: II.


Recombinant gamma interferon induces class II major histocompatibility complex antigens on insulinoma cells.
Aberrant expression of major histocompatibility (MHC) antigens has been implicated as a factor contributing to organ-specific autoimmunity, such as progressive loss of pancreatic beta cells in type 1 diabetes. We investigated the potential of a rat beta cell tumour, RINM5F, to express enhanced levels of MHC antigens in vitro. To this purpose we treated RINM5F cells in vitro with recombinant rat gamma interferon (rIF gamma). We used monoclonal antibodies to RT1.A (class I) and RT1.B (class II) antigens of the rat MHC in conjunction with flowcytometry and immunoperoxidase techniques to analyse the expression of MHC antigens. Untreated RINM5F cells express low levels of RT1.A, whereas they are negative for RT1.B. Treatment with rIF gamma appeared to increase the expression of RT1.A antigens substantially. Most importantly, RT1.B antigens were newly expressed by rat insulinoma cells in vitro after treatment with rIF gamma. To our knowledge this is the first documentation of the potential of beta cells or their derivatives to express class II MHC antigens following IF gamma-treatment. This mechanism may play an important role in the augmentation and perpetuation of insulitis leading to type 1 diabetes mellitus.


Choreographed swimming of copepod nauplii.
Small metazoan paddlers, such as crustacean larvae (nauplii), are abundant, ecologically important and active swimmers, which depend on exploiting viscous forces for locomotion. The physics of micropaddling at low Reynolds number was investigated using a model of swimming based on slender-body theory for Stokes flow. Locomotion of nauplii of the copepod Bestiolina similis was quantified from high-speed video images to obtain precise measurements of appendage movements and the resulting displacement of the body. The kinematic and morphological data served as inputs to the model, which predicted the displacement in good agreement with observations. The results of interest did not depend sensitively on the parameters within the error of measurement. Model tests revealed that the commonly attributed mechanism of 'feathering' appendages during return strokes accounts for only part of the displacement. As important for effective paddling at low Reynolds number is the ability to generate a metachronal sequence of power strokes in combination with synchronous return strokes of appendages. The effect of feathering together with a synchronous return stroke is greater than the sum of each factor individually. The model serves as a foundation for future exploration of micropaddlers swimming at intermediate Reynolds number where both viscous and inertial forces are important.


M wave and H-reflex of soleus muscle before and after electrical muscle stimulation in healthy subjects.
This study was the preliminary research for applying the evaluation of muscle fatigue using the evoked electromyography in the field of physical therapy. In this study, we speculated that muscle fatigue was induced by electrical muscle stimulation (EMS). And we studied the M wave and amplitude ratio of H/M before and after EMS because the M wave and amplitude ratio of H/M have been often used as the parameter in the study of muscle fatigue. Subjects were five healthy males. In this study, the intermittent EMS (30 Hz) was administered to the soleus muscle of dominant leg for 10 minutes and we analyzed the amplitude of maximal M wave and the amplitude ratio of H/M in this study. The amplitude of maximal M wave after EMS significantly decreased compared with that before the EMS (p < 0.05). And the results of amplitude ratio of H/M varied as follows; decrease in two subjects, increase in one subject and unchanged results in two subjects. M wave reflects the excitability of muscle membrane related to the change in force during muscle fatigue and the amplitude ratio of H/M has been considered as the index of a relative excitability of alpha motoneuron pool. From the results of this study, we considered that muscle fatigue was induced by EMS as predictability because the amplitude of maximal M wave significantly decreased after EMS. And it was considered that the excitability of spinal neural function corresponding to fatigued soleus muscle by EMS was not consist change in this study. Therefore we thought that results of amplitude ratio of H/M might be influenced by excitability of spinal neural function in subject's ordinary state. It was suggested that the muscle fatigue was induced because the amplitude of maximal M wave significantly decreased after EMS in this study. And also it was suggested the excitability of spinal neural function corresponding with fatigued soleus muscle by EMS was not consist change in this study.


TERATOMA OF THE OVARY IN A FREE-RANGING JAPANESE RACCOON DOG (NYCTEREUTES PROCYONOIDES VIVERRINUS).
A young adult, female, free-ranging Japanese raccoon dog ( Nyctereutes procyonoides viverrinus) with scabies infection was found dead as a result of traumatic injuries presumed to reflect vehicular trauma. Necropsy showed a large solid mass located on the left ovarian region, occupying a third of the abdominal cavity. Histologically, the mass contained complex tissues derived from three germinal layers, with areas of cuboidal or columnar epithelium, keratinized squamous epithelium, bone, cartilage, and adipose tissue. This paper presents the first morphologic description of ovarian teratoma in a raccoon dog.


Effects of thermal denaturation on protein glycation.
Protein denaturation occurs at sites of inflammation. We hypothesized that denatured protein may provide a more susceptible target for glycation, which is a known mediator of inflammation. We examined the effects of thermal denaturation on the susceptibility of protein glycation using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and aspartate aminotransferase (AAT) as our target proteins. GAPDH and AAT are ubiquitous proteins that exhibited very different thermal stabilities. Glycating agents, methylglyoxal (MG) and glyceraldehyde (Glyc), caused an increase in the formation of advanced glycation endproducts (AGEs) in native and denatured GAPDH and AAT. The effects of the glycating agents were more pronounced with the denatured proteins. In addition to nitroblue tetrazolium (NBT)- reactivity, our measured endpoints were absorbance (lambda = 365 nm) and fluorescence (lambda(ex) = 370 nm; lambda(em) = 470 nm) properties that are typically associated with protein glycation. We also looked at carnosine's ability to prevent glycation of native and denatured protein. Carnosine, an endogenous histidine dipeptide, exhibits anti-inflammatory activity presumably due to its anti-oxidant and anti-glycation properties. Carnosine prevented Glyc-induced AGE formation in both native and denatured AAT suggesting that carnosine's anti-inflammatory activity may be due in part to carnosine's ability to prevent glycation of denatured protein.


Interactive effects of family functioning and sleep experiences on daily lung functioning in pediatric asthma: An ecological momentary assessment approach.
Objectives: Children living in urban, underserved settings are at risk for experiencing sleep difficulties as well as poor asthma outcomes. The family is important for both asthma management and ensuring children are getting the necessary amount of sleep, but how family functioning and sleep patterns influence children's asthma remains unclear. Methods: Fifty-nine children (7-12 years old; 90% African American) diagnosed with asthma, and their primary caregivers, participated in this study. In a single research session, caregivers rated overall family functioning via the Family Assessment Device. Caregivers also completed daily diaries delivered via smartphone for a two-week period rating their children's daily sleep quantity and quality; a home-based spirometer (AM2) was used to assess children's pulmonary functioning across that same period. Two-level multilevel models tested associations among overall family functioning, children's sleep quality/quantity, and pulmonary functioning. Results: Child sleep quality, quantity, and general family functioning did not predict child pulmonary functioning directly. Family functioning and sleep quality interacted to predict children's pulmonary functioning; children with poor family functioning and bad/very bad sleep quality had the poorest levels of lung functioning. Conclusions: These findings highlight a subset of children who are at higher risk for poor lung functioning based on sleep quality and family functioning. Results may inform routine monitoring of family functioning and sleep difficulties at pediatric asthma visits and intervention strategies to augment children's lung functioning.


The host specificity of ape malaria parasites can be broken in confined environments.
Recent studies have revealed a large diversity of Plasmodium spp. among African great apes. Some of these species are related to Plasmodium falciparum, the most virulent agent of human malaria (subgenus Laverania), and others to Plasmodium ovale, Plasmodium malariae and Plasmodium vivax (subgenus Plasmodium), three other human malaria agents. Laverania parasites exhibit strict host specificity in their natural environment. Plasmodium reichenowi, Plasmodium billcollinsi, Plasmodium billbrayi and Plasmodium gaboni infect only chimpanzees, while Plasmodium praefalciparum, Plasmodium blacklocki and Plasmodium adleri are restricted to gorillas and Plasmodium falciparum is pandemic in humans. This host specificity may be due to genetic and/or environmental factors. Infrastructures hosting captive primates, such as sanctuaries and health centres, usually concentrate different primate species, thus favouring pathogen exchanges. Using molecular tools, we analysed blood samples from captive non-human primates living in Gabon to evaluate the risk of Plasmodium spp. transfers between host species. We also included blood samples from workers taking care of primates to assess whether primate-human parasite transfers occurred. We detected four transfers of Plasmodium from gorillas towards chimpanzees, one from chimpanzees to gorillas, three from humans towards chimpanzees and one from humans to mandrills. No simian Plasmodium was found in the blood samples from humans working with primates. These findings demonstrate that the genetic barrier that determines the apparent host specificity of Laverania is not completely impermeable and that parasite exchanges between gorillas and chimpanzees are possible in confined environments.


Coordination during Cholera Outbreak Response: Critical Insights from Yemen.
Within the humanitarian arena and since the introduction of the humanitarian reform process in 2005, the cluster approach was introduced to strengthen the cooperation and accountability between agencies working in the same field. Such an integrated approach is particularly needed and relevant in emergencies like cholera, especially in countries undergoing internal conflicts like Yemen. Several areas of concern have been identified during the past field experiences, which include dysfunctional cooperation as a result of different mandates as well as the relationship between nongovernmental organizations and their donors. Control of environmental health services is, for instance, the responsibility of several clusters/agencies and stakeholders, which usually results in a complicated and sometimes confusing approaches to address gaps and barriers. As far as the drinking water quality monitoring and surveillance are concerned, sampling and testing and compilation of data are usually carried out by many agencies included in the health and water sanitation and hygiene (WASH) clusters. We believe that the cluster theoretical approach for emergency response remains a turning point for the humanitarian arena. However, lessons from the recent past, especially in the management of a cholera outbreak in fragile settings, may serve as a serious reflection on roles and dynamics within the blurred border between health and WASH. Specifically, cluster leads in the field have the responsibility for ensuring that humanitarian actors working in their sectors remain actively engaged in addressing crosscutting concerns such as the environment.


Ignoring dependency between linking variables and its impact on the outcome of probabilistic record linkage studies.
OBJECTIVES This study sought to examine the differences between ignoring (naïve) and incorporating dependency (nonnaïve) among linkage variables on the outcome of a probabilistic record linkage study. DESIGN AND MEASUREMENTS We used the outcomes of a previously developed probabilistic linkage procedure for different registries in perinatal care assuming independence among linkage variables. We estimated the impact of ignoring dependency by re-estimating the linkage weights after constructing a variable that combines the outcomes of the comparison of 2 correlated linking variables. The results of the original naïve and the new nonnaïve strategy were systematically compared for 3 scenarios: the empirical dataset using 9 variables, the empirical dataset using 5 variables, and a simulated dataset using 5 variables. RESULTS The linking weight for agreement on 2 correlated variables among nonmatches was estimated considerably higher in the naïve strategy than in the nonnaïve strategy (16.87 vs. 13.55). Therefore, ignoring dependency overestimates the amount of identifying information if both correlated variables agree. The impact on the number of pairs that was classified differently with both approaches was modest in the situation in which there were many different linking variables but grew substantially with fewer variables. The simulation study confirmed the results of the empirical study and suggests that the number of misclassifications can increase substantially by ignoring dependency under less favorable linking conditions. CONCLUSION Dependency often exists between linking variables and has the potential to bias the outcome of a linkage study. The nonnaïve approach is a straightforward method for creating linking weights that accommodate dependency. The impact on the number of misclassifications depends on the quality and number of linking variables relative to the number of correlated linking variables.


[Effects of Helicobacter pylori and Helicobacter pylori-related cytokines on apoptosis of gastric epithelial cells and mechanisms thereof].
To investigate the influence of Helicobacter pylori (H. pylori) and H. pylori-related cytokines on the apoptosis of gastric epithelial cells and mechanisms thereof. (1) Human gastric cancer cells of the line AGS and human gastric epithelial cells of the line GES-1 were cultured as control group, or incubated with H. pylori alone or H. pylori in combination with exogenous cytokines: interleukin (IL)-1beta, IL-8, or IL-10 for 24 hours. Then flow cytometry (FCM) was used to determine the rate of apoptosis. (2) The GES-1 and AGS cells were incubated with H. pylori for 24 hours and exogenous cytokines for 2 hours respectively. Then RT-PCR was used to examine the level of Fas mRNA expression. (3) Another GES-1 and AGS cells were cultured as control group, or incubated with FasL alone or FasL + exogenous cytokine for 2 hours (incubated with IL-1beta, IL-8, or IL-10 for 2 hours before being added with FasL). Then FCM was used to detect the apoptosis rate. (1) In comparison to the apoptosis level of control group, H. pylori induced an increase in the apoptosis rate of GES-1 and AGS cells by 113.0% and 47.0% respectively (both P < 0.05). The H. pylori-induced apoptosis rates of GES-1 cells (by 29.6% or 25.8%) and AGS cells (by 19.7% or 21.1%) were reduced by IL-1beta or IL-10 (all P < 0.05). IL-8 increased the H. pylori-induced apoptosis level of GES-1 cells by 19.9% (P < 0.05). (2) In the baseline status, both GES-1 and AGS cells showed Fas mRNA expression. The Fas mRNA expressions of the GES-1 and AGS cells incubated with H. pylori were increased by 89.0% and 36.0% respectively (both P < 0.05) in comparison to that of the control group. IL-1beta and IL-10 had no significant effect on the basal Fas mRNA expressions in both GES-1 and AGS cells (all P > 0.05). IL-8 up-regulated the basal Fas mRNA expression level of the GES-1 cells by 33.0% (P < 0.05). (3) IL-1beta and IL-10 inhibited the FasL-induced apoptosis rate of the GES-1 cells (by 30.3% and 32.5% respectively) and AGS cells (by 44.2% and 51.5% respectively) (all P < 0.05). IL-8 enhanced the FasL-induced apoptosis level of the GES-1 cells by 100% (P < 0.05). The gastric epithelium apoptosis induced by H. pylori may be in association with Fas receptor. IL-8 may enhance the H. pylori-induced apoptosis by up-regulating the Fas receptor expression. IL-1beta and IL-10 may modulate the apoptosis through other mechanisms.


Co-Targeting FASN and mTOR Suppresses Uveal Melanoma Growth.
Uveal melanoma (UM) displays a high frequency of metastasis; however, effective therapies for metastatic UM are limited. Identifying unique metabolic features of UM may provide a potential targeting strategy. A lipid metabolism protein expression signature was induced in a normal choroidal melanocyte (NCM) line transduced with GNAQ (Q209L), a driver in UM growth and development. Consistently, UM cells expressed elevated levels of fatty acid synthase (FASN) compared to NCMs. FASN upregulation was associated with increased mammalian target of rapamycin (mTOR) activation and sterol regulatory element-binding protein 1 (SREBP1) levels. FASN and mTOR inhibitors alone significantly reduced UM cell growth. Concurrent inhibition of FASN and mTOR further reduced UM cell growth by promoting cell cycle arrest and inhibiting glucose utilization, TCA cycle metabolism, and de novo fatty acid biosynthesis. Our findings indicate that FASN is important for UM cell growth and co-inhibition of FASN and mTOR signaling may be considered for treatment of UM.


Models of adjustment to chronic illness: using the example of rheumatoid arthritis.
There are a number of theoretical frameworks that attempt to explain how individuals may adjust to threats to health and serious physical illness. The three major paradigms that attempt to organize key components of health and adaptation to illness include the following: the biomedical model which emphasizes disease; psychological models of adaptation to illness; and biopsychosocial models with the latter two emphasizing health, functioning, and well-being. Each of these three major paradigms, including biomedical, psychosocial, and biopsychosocial frameworks, is discussed and critiqued in turn, and contributions and theoretical issues in terms of adjustment to chronic illness, particularly rheumatoid arthritis (RA), are highlighted. Furthermore, a biopsychosocial framework for conceptualizing adjustment to physical illness is proposed that incorporates elements from key existing biomedical and psychosocial models of adaptation to chronic physical health issues.


Previous chronic blockade of NMDA receptors intensifies morphine dependence in rats.
Chronic exposure of receptors to antagonists generally results in upregulation and/or supersensitivity. On the other hand, the noncompetitive NMDA receptor antagonists ketamine (K) and dextromethorphan (DM) suppress opiate abstinence syndrome by blocking NMDA receptors. Therefore, 40 mg/kg ketamine (K), 5 mg/kg dextromethorphan (DM), 5 mg/kg morphine (M) and 2 mg/kg naloxone (NL) alone or in combination with NL were IP administered to the rats five times during the daytime only for five days to see whether they would intensify abstinence syndrome through upregulation and/or supersensitivity of NMDA receptors. Three days following the implantation of three M-containing pellets, abstinence syndrome was brought about by 2 mg/kg NL injection. Jumping, wet dog shake, writhing, teeth chattering, diarrhoea, defecation and ptosis were observed for ten min. All drugs used alone or in combination with NL increased the intensity of abstinence syndrome. Since K and DM are noncompetitive NMDA receptor antagonists, the intensifying effect of NL or M was considered to be related to their interactions with NMDA receptors. Furthermore, on the basis of the results of the previous and present study, NL was claimed to act on NMDA receptors, like other opioids, but with higher affinity for and weaker blocking effect on NMDA receptors.


Effect of zoledronic acid on metastatic hormone-refractory prostate cancer resistant to taxane, estramustine, carboplatin, and dexamethasone.
This case report demonstrates the effect of zoledronic acid (ZA) on a patient with bone metastatic hormone-refractory prostate cancer (HRPC) resistant to taxane, estramustine phosphate, carboplatin, and dexamethasone. The pathogenesis, diagnosis, and management of bone metastasis on HRPC are also reviewed.


Roaming dynamics in acetone dissociation.
DC slice imaging has been employed to study the photodissociation dynamics of acetone at 230 nm, with detection of the CO photoproduct via the B (v' = 0) (1)Sigma(+) <-- X (v'' = 0) (1)Sigma(+) transition. A bimodal translational energy distribution observed in the CO fragments points to two distinct dissociation pathways in the 230 nm photolysis of acetone. One pathway results in substantial translational energy release (E(ave) approximately 0.3 eV) along with rather high rotational excitation (up to J'' = 50) of CO, and is attributed to the thoroughly investigated stepwise mechanism of bond cleavage in acetone. The other dissociation pathway leads to rotationally cold CO (J'' = 0-20) with very little energy partitioned into translation (E(ave) approximately 0.04 eV) and in this way it is dynamically similar to the recently reported roaming mechanism found in formaldehyde and acetaldehyde dissociation. We ascribe the second dissociation pathway to an analogous roaming dissociation mechanism taking place on the ground electronic state following internal conversion. For acetone, this would imply highly vibrationally excited ethane as a coproduct of rotationally cold CO, with the ethane formed above the threshold for secondary decomposition. We estimate that about 15% of the total CO fragments are produced through the roaming pathway. Rotational populations were obtained using a new Doppler-free method that simply relies on externally masking the phosphor screen under velocity map conditions in such a way that only the products with no velocity component along the laser propagation direction are detected.


Effects of external loading on lumbar extension moment during squat lifting.
The main objective of this study has been qualitative investigation of the effects of external loading on the lumbar extension moment during squat lifting. Findings of this study may allow to determine the factor with the most considerable effect on the lumbar extension moment and may help determine the lumbar spine risk factors at temporo-spatial coordination during squat lifting. Twelve healthy men volunteered to perform slow and fast squat lifting of a box of varied mass (4 kg, 8 kg and 12 kg). The eight-channel electromyography was applied to detect the activities of abdominal (rectus abdominis and external oblique) and lower back muscles (iliocostalis lumborum and multifidus). The lumbar extension moment was calculated using 3D linked segment model. Ground reaction forces and kinematic data were recorded using a Vicon system with 2 parallel Kistler force-plates. Significant increases (both p-values < 0.05) were detected for the peak lumbar extension moment with increases in the lift speed and box weight. Moreover, a significant interaction (p = 0) was detected between the lift speed and box weight. Furthermore, insignificant differences (all p-values > 0.05) were detected between the lumbar angles related to the lower trunk muscles peak activities and lumbar angle related to the peak lumbar extension moment in most of the lifts. According to the findings, the inertial force of the lifted box is the most important factor that affects the lumbar extension moment during squat lifting. Moreover, critical lumbar angles are seemingly those ones in which the lifted box reaches the peak acceleration. Int J Occup Med Environ Health 2017;30(4):665-679.


A method of transoral finger dissection for a giant epiglottic lipoma.
Background. Subcutaneous lipomas that occur in the trunk and proximal extremities are commonly dissected by low-invasive method. However, a standard surgical method for lipomas of the epiglottis has been absent. Microscopic laryngeal surgery is appropriate to extirpate small epiglottic lipomas. However, microscopic laryngeal surgery may be insufficient for giant epiglottic lipomas because there is restricted visualization of the operating field of the tumor under the microscope. Furthermore, microscopic surgical instruments are very small to manipulate giant lipomas, and it would be excessive to approach these lipomas via external cervical incisions. Case Presentation. A 57-year-old female presented with a giant lipoma on the lingual surface of the epiglottis. Following a tracheotomy, microscopic surgery was inadequate to manipulate the epiglottic lipoma. Instead, we performed macroscopic surgery in which the epiglottic lipoma was pulled into the oral cavity with forceps and then separated from the surrounding tissues using the surgeon's finger to dissect the tumor en bloc. Conclusion. The low-invasive method of transoral finger dissection enabled the giant lipoma to be extirpated without leaving any remnants or causing excessive epiglottic damage.


A wave finite element analysis of the passive cochlea.
Current models of the cochlea can be characterized as being either based on the assumed propagation of a single slow wave, which provides good insight, or involve the solution of a numerical model, such as in the finite element method, which allows the incorporation of more detailed anatomical features. In this paper it is shown how the wave finite element method can be used to decompose the results of a finite element calculation in terms of wave components, which allows the insight of the wave approach to be brought to bear on more complicated numerical models. In order to illustrate the method, a simple box model is considered, of a passive, locally reacting, basilar membrane interacting via three-dimensional fluid coupling. An analytic formulation of the dispersion equation is used initially to illustrate the types of wave one would expect in such a model. The wave finite element is then used to calculate the wavenumbers of all the waves in the finite element model. It is shown that only a single wave type dominates the response until this peaks at the best place in the cochlea, where an evanescent, higher order fluid wave can make a significant contribution.


United States life tables, 2009.
This report presents complete period life tables for the United States by race, Hispanic origin, and sex based on age-specific death rates in 2009. Data used to prepare the 2009 life tables are 2009 final mortality statistics; July 1, 2009, population estimates based on the 2000 decennial census; and 2009 Medicare data for persons aged 66-99. The methodology used to estimate the 2009 life tables is the same as that used for data year 2008, which was revised from that used for data years 2000-2007. The methodology used to estimate the life tables for the Hispanic population remains unchanged from that developed for the publication of life tables by Hispanic origin for data year 2006. In 2009, the overall expectation of life at birth was 78.5 years. Between 2008 and 2009, life expectancy at birth increased for all groups considered. Life expectancy increased for both males (from 75.6 to 76.0) and females (80.6 to 80.9) and for the white population (78.5 to 78.8), the black population (74.0 to 74.5), the Hispanic population (81.0 to 81.2), the non-Hispanic white population (78.4 to 78.7), and the non-Hispanic black population (73.7 to 74.2).


Hepatic release of tumor necrosis factor in the endotoxin-treated conscious dog.
The effects of a 4 h intraportal infusion of Escherichia coli lipopolysaccharide (LPS, .21 mu g/kg/min) on the release of tumor necrosis factor (TNF) by hepatic and nonhepatic splanchnic tissues was assessed in the chronically catheterized conscious dog (n = 7) using arteriovenous difference techniques. TNF levels were measured using both a WEHI-164 cytotoxicity assay (WEHI) and a h-TNF-alpha EIA kit (ELISA; Biosource, Camarillo, CA). Using WEHI, arterial TNF levels increased from 10 + or - 6 pg/mL to a peak of 4667 + or - 1442 pg/mL 100 min after LPS and fell to 443 + or - 199 pg/mL by 240 min. Using ELISA, arterial TNF levels increased from 5 + or - 5 pg/mL to a peak of 12,234 + or - 2046 pg/mL at 100 min and fell to 3511 + or - 991 pg/mL by 240 min. WEHI could not be used to assess organ TNF release due to excessive assay variability. Based upon ELISA, net hepatic TNF output increased from undetectable release at basal to 23.0 + or - 10.7 ng/kg/min at 60 min and returned toward basal by 240 min (4.7 + or - 3.8 ng/kg/min). Net release of TNF by the nonhepatic splanchnic bed was not observed. One compartment analysis of the arterial TNF response indicated that net release of TNF by the liver accounted for the majority of the increase in the arterial TNF levels. In summary, after intraportal LPS infusion, it was determined that 1) both assays predict similar qualitative TNF response, while the quantitative response differs, 2) the liver is the major site of TNF production, and 3) the nonhepatic splanchnic bed is not a net producer of TNF.


Serum Pepsinogen as a Predictor for Gastric Cancer Death: A 16-Year Community-based Cohort Study.
The purpose of this article is to validate the long-term association between initial serum pepsinogen (PG) measurements and subsequent gastric cancer-specific deaths from a long-term longitudinal cohort. Endoscopic surveillance can be effective and efficient in reducing gastric cancer mortality if a biomarker such as serum PG is available to identify high-risk individuals and if the biomarker also is specific to gastric cancer risk. Between 1995 and 1998, a gastric cancer-screening program was conducted in a high-risk population: The first stage involved PG testing, and the second stage involved upper endoscopy. The outcome was gastric cancer death, which was monitored until December 31, 2010; results were expressed as the hazard ratio (HR) and corresponding 95% confidence interval (CI) using the Cox proportional hazards regression model. Other causes of death were used as comparators. Among participants (n=3514) aged ≥30 years, 1682 (47.9%) were screened to determine serum PG levels. After 16 years of follow-up, 14 deaths from gastric cancer were documented. Multivariate analyses adjusted for age, sex, and Helicobacter pylori serological positivity showed that PG-I <30 μg/L and PG-I <30 μg/L or PG-I/II ratio <3 were significantly associated with the risk of gastric cancer death (HR, 3.27; 95% CI, 1.11-9.61 and HR, 3.45; 95% CI, 1.18-10.12, respectively). In contrast, there were no significant associations between PG and other causes of death, including neoplastic and non-neoplastic diseases. This long-term cohort study shows the usefulness of PG measurement as a biomarker that is specific to the risk of gastric cancer death.


Structural and thermodynamic insights into the binding mode of five novel inhibitors of lumazine synthase from Mycobacterium tuberculosis.
Recently published genomic investigations of the human pathogen Mycobacterium tuberculosis have revealed that genes coding the proteins involved in riboflavin biosynthesis are essential for the growth of the organism. Because the enzymes involved in cofactor biosynthesis pathways are not present in humans, they appear to be promising candidates for the development of therapeutic drugs. The substituted purinetrione compounds have demonstrated high affinity and specificity to lumazine synthase, which catalyzes the penultimate step of riboflavin biosynthesis in bacteria and plants. The structure of M. tuberculosis lumazine synthase in complex with five different inhibitor compounds is presented, together with studies of the binding reactions by isothermal titration calorimetry. The inhibitors showed the association constants in the micromolar range. The analysis of the structures demonstrated the specific features of the binding of different inhibitors. The comparison of the structures and binding modes of five different inhibitors allows us to propose the ribitylpurinetrione compounds with C4-C5 alkylphosphate chains as most promising leads for further development of therapeutic drugs against M. tuberculosis.


Unravelling feeding territoriality in the Little Blue Heron, Egretta caerulea, in Cananéia, Brazil.
Habitat use by the Little Blue Heron (Egretta caerulea) and discovery of feeding territoriality are discussed here. The results showed the existence of a territorial individual defending an area (2,564.46 +/- 943.56 m(2)) close to the mangrove, and non-territorial individuals (9.17 +/- 2.54) in the rest of a demarcated area (mean area for the non-territorial: 893.25 +/- 676.72). A weak positive correlation (r = 0.47, df = 46, p < 0.05) was found between the overlapping of territorial and non-territorial individuals (2.85 +/- 3.07 m(2)) and the mean overlapped area for territorial individuals (171.41 +/- 131.40 m(2)). Higher capture (1.52 +/- 1.14 x 1.00 +/- 1.37 catches/minutes) and success rates (0.45 +/- 0.31 x 0.21 +/- 0.27) and lower energy expenditure rates (45.21 +/- 14.96 x 51.22 +/- 14.37 steps/minutes; and 3.65 +/- 2.55 x 4.94 +/- 3.28 stabs/minutes) were observed for individuals foraging in areas close to the mangrove. The results suggest that the observed territorial behaviour is more related to a number of food parameters than to intruder pressure, and also that the observed territoriality might be related to defense of areas with higher prey availability.


Genome-wide analysis of DNA methylation in tongue squamous cell carcinoma.
Tongue squamous cell carcinoma (TSCC) is one of the most common types of oral cancer; however, its molecular mechanisms remain unclear. In this study, methylated DNA immunoprecipitation (MeDIP) coupled with methylation microarray analysis was performed to screen for aberrantly methylated genes in adjacent normal control and TSCC tissues from 9 patients. Roche NimbleGen Human DNA Methylation 385K Promoter Plus CpG Island Arrays were used to detect 28,226 CpG sites. A total of 1,269 hypermethylated CpG sites covering 330 genes and 1,385 hypomethylated CpG sites covering 321 genes were found in TSCC tissue, compared to the adjacent normal tissue. Furthermore, we chose three candidate genes (FBLN1, ITIH5 and RUNX3) and validated the DNA methylation status by methylation-specific PCR (MS-PCR) and the mRNA expression levels by reverse transcription PCR (RT-PCR). In TSCC tissue, FBLN1 and ITIH5 were shown to be hypermethylated and their expression was found to be decreased, and RUNX3 was shown to be hypomethylated, however, its mRNA expression was found to be increased. In addition, another three genes (BCL2L14, CDCP1 and DIRAS3) were tested by RT-PCR. In TSCC tissue, BCL2L14 and CDCP1 expressions were markedly upregulated, and DIRAS3 expression was significantly downregulated. Our data demonstrated that aberrant DNA methylation is observed in TSCC tissue and plays an important role in the tumorigenesis, development and progression of TSCC.


Subfunctionalization of PhyB1 and PhyB2 in the control of seedling and mature plant traits in maize.
Phytochromes are the primary red/far-red photoreceptors of higher plants, mediating numerous developmental processes throughout the life cycle, from germination to flowering. In seed plants, phytochromes are encoded by a small gene family with each member performing both distinct and redundant roles in mediating physiological responses to light cues. Studies in both eudicot and monocot species have defined a central role for phytochrome B in mediating responses to light in the control of several agronomically important traits, including plant height, transitions to flowering and axillary branch meristem development. Here we characterize Mutator-induced alleles of PhyB1 and a naturally occurring deletion allele of PhyB2 in Zea mays (maize). Using single and double mutants, we show that the highly similar PhyB1 and PhyB2 genes encode proteins with both overlapping and non-redundant functions that control seedling and mature plant traits. PHYB1 and PHYB2 regulate elongation of sheath and stem tissues of mature plants and contribute to the light-mediated regulation of PhyA and Cab gene transcripts. However, PHYB1 and not PHYB2 contributes significantly to the inhibition of mesocotyl elongation under red light, whereas PHYB2 and to a lesser extent PHYB1 mediate the photoperiod-dependent floral transition. This sub functionalization of PHYB activities in maize has probably occurred since the tetraploidization of maize, and may contribute to flowering time variation in modern-day varieties.


Incidence of atrial fibrillation and its risk prediction model based on a prospective urban Han Chinese cohort.
Prediction models of atrial fibrillation (AF) have been developed; however, there was no AF prediction model validated in Chinese population. Therefore, we aimed to investigate the incidence of AF in urban Han Chinese health check-up population, as well as to develop AF prediction models using behavioral, anthropometric, biochemical, electrocardiogram (ECG) markers, as well as visit-to-visit variability (VVV) in blood pressures available in the routine health check-up. A total of 33 186 participants aged 45-85 years and free of AF at baseline were included in this cohort, to follow up for incident AF with an annually routine health check-up. Cox regression models were used to develop AF prediction model and 10-fold cross-validation was used to test the discriminatory accuracy of prediction model. We developed three prediction models, with age, sex, history of coronary heart disease (CHD), hypertension as predictors for simple model, with left high-amplitude waves, premature beats added for ECG model, and with age, sex, history of CHD and VVV in systolic and diabolic blood pressures as predictors for VVV model, to estimate risk of incident AF. The calibration of our models ranged from 1.001 to 1.004 (P for Hosmer Lemeshow test >0.05). The area under receiver operator characteristics curve were 78%, 80% and 82%, respectively, for predicting risk of AF. In conclusion, we have identified predictors of incident AF and developed prediction models for AF with variables readily available in routine health check-up.


A mathematical model of the dynamics of lymphatic filariasis in Caraga Region, the Philippines.
Despite being one of the first countries to implement mass drug administration (MDA) for elimination of lymphatic filariasis (LF) in 2001 after a pilot study in 2000, the Philippines is yet to eliminate the disease as a public health problem with 6 out of the 46 endemic provinces still implementing MDA for LF as of 2018. In this work, we propose a mathematical model of the transmission dynamics of LF in the Philippines and a control strategy for its elimination using MDA. Sensitivity analysis using the Latin hypercube sampling and partial rank correlation coefficient methods suggests that the infected human population is most sensitive to the treatment parameters. Using the available LF data in Caraga Region from the Philippine Department of Health, we estimate the treatment rates r 1 and r 2 using the least-squares parameter estimation technique. Parameter bootstrapping showed small variability in the parameter estimates. Finally, we apply optimal control theory with the objective of minimizing the infected human population and the corresponding implementation cost of MDA, using the treatment coverage γ as the control parameter. Simulation results highlight the importance of maintaining a high MDA coverage per year to effectively minimize the infected population by the year 2030.


Ranking and clustering of Drosophila olfactory receptors using mathematical morphology.
This article introduces an alignment-free clustering method in order to cluster all the 66 DORs sequentially diverse protein sequences. Two different methods are discussed: one is utilizing twenty standard amino acids (without grouping) and another one is using chemical grouping of amino acids (with grouping). Two grayscale images (representing two protein sequences by order pair frequency matrices) are compared to find the similarity index using morphology technique. We could achieve the correlation coefficients of 0.9734 and 0.9403 for without and with grouping methods respectively with the ClustalW result in the ND5 dataset, which are much better than some of the existing alignment-free methods. Based on the similarity index, the 66 DORs are clustered into three classes - Highest, Moderate and Lowest - which are seen to be best fitted for 66 DORs protein sequences. OR83b is the distinguished olfactory receptor expressed in divergent insect population which is substantiated through our investigation.


Effects of MS-153 on chronic ethanol consumption and GLT1 modulation of glutamate levels in male alcohol-preferring rats.
We have recently shown that upregulation of glutamate transporter 1 (GLT1) in the brain is associated in part with reduction in ethanol intake in alcohol-preferring (P) male rats. In this study, we investigated the effects of a synthetic compound, (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), known to activate GLT1 on ethanol consumption as well as GLT1 expression and certain signaling pathways in P rats. P rats were given 24-h concurrent access to 15 and 30% ethanol, water and food for 5 weeks. On week 6, P rats received MS-153 at a dose of 50 mg/kg (i.p.) or a vehicle (i.p.) for 5 consecutive days. We also tested the effect of MS-153 on daily sucrose (10%) intake. Our studies revealed a significant decrease in ethanol intake at the dose of 50 mg/kg MS-153 from Day 1 through 14. In addition, MS-153 at dose of 50 mg/kg did not induce any significant effect on sucrose intake. Importantly, we found that MS-153 upregulated the GLT1 level in the nucleus accumbens (NAc) but not in the prefrontal cortex (PFC). In accordance, we found upregulation of nuclear NFkB-65 level in NAc in MS-153-treated group, however, IkBα was downregulated in MS-153-treated group in NAc. We did not find any changes in NFkB-65 and IkBα levels in PFC. Interestingly, we revealed that p-Akt was downregulated in ethanol vehicle treated groups in the NAc; this downregulation was reversed by MS-153 treatment. We did not observe any significant differences in glutamate aspartate transporter (GLAST) expression among all groups. These findings reveal MS-153 as a GLT1 modulator that may have potential as a therapeutic drug for the treatment of alcohol dependence.


Loss of agency in apraxia.
The feeling of acting voluntarily is a fundamental component of human behavior and social life and is usually accompanied by a sense of agency. However, this ability can be impaired in a number of diseases and disorders. An important example is apraxia, a disturbance traditionally defined as a disorder of voluntary skillful movements that often results from frontal-parietal brain damage. The first part of this article focuses on direct evidence of some core symptoms of apraxia, emphasizing those with connections to agency and free will. The loss of agency in apraxia is reflected in the monitoring of internally driven action, in the perception of specifically self-intended movements and in the neural intention to act. The second part presents an outline of the evidences supporting the functional and anatomical link between apraxia and agency. The available structural and functional results converge to reveal that the frontal-parietal network contributes to the sense of agency and its impairment in disorders such as apraxia. The current knowledge on the generation of motor intentions and action monitoring could potentially be applied to develop therapeutic strategies for the clinical rehabilitation of voluntary action.


Stalling autophagy: a new function for Listeria phospholipases.
Listeria monocytogenes is a Gram-positive bacterial pathogen that induces its own uptake in non-phagocytic cells. Following invasion, Listeria escapes from the entry vacuole through the secretion of a pore-forming toxin, listeriolysin O (LLO) that acts to damage and disrupt the vacuole membrane. Listeria then replicates in the cytosol and is able to spread from cell-to-cell using actin-based motility. In addition to LLO, Listeria produces two phospholipase toxins, a phosphatidylinositol-specific phospholipase C (PI-PLC, encoded by plcB) and a broad-range phospholipase C (PC-PLC, encoded by plcA), which contribute to bacterial virulence. It has long been recognized that secretion of PI- and PC-PLC enables the disruption of the double membrane vacuole during cell-to-cell spread, and those phospholipases have also been shown to augment LLO-dependent escape from the entry endosome. However, a specific role for Listeria phospholipases during the cytosolic stage of infection has not been previously reported. In a recent study, we demonstrated that Listeria PI-PLC and PC-PLC contribute to the bacterial escape from autophagy through a mechanism that involves direct inhibition of the autophagic flux in the infected cells [Tattoli et al. EMBO J (2013), 32, 3066-3078].


Impaired warm and cold perception thresholds in leprosy skin lesions.
The aim of the present study was to determine the frequency of alteration in warm perception thresholds (WPT), cold perception thresholds (CPT) and the warm and cold perception interval (WCPI) in leprosy-suspected skin lesions, and to determine if these tests could assist in the diagnosis of leprosy. Tests were conducted using a thermal sensory analyser TSA-2001 (Medoc Ltd, Israel) and the method of levels. A cross-sectional study of 112 patients presenting leprosy-suspected skin lesions ('patch'), with no clinical evidence of peripheral nerve damage, was conducted. Leprosy diagnosis was based on clinical dermato-neurological examinations and complementary tests. One hundred and eight subjects (45 males, 63 females; average age 37.7 years) completed the tests: 82 were positively diagnosed with leprosy and 26 with diseases of different etiologies. The mean values of WPT (45-63 +/- 5.59), CPT (9.64 +/- 11.34) and WCPI 36.01 +/- 15.58) registered in leprosy-skin lesions were significantly different (P < 0.001) from lesions of diverse aetiologies and skin area without lesions. The cut-off point for WPT as determined from the ROC curve (receiver operating characteristic) was 35-10 degrees C, with a sensitivity of 90.2% and a specificity of 100%, and the corresponding cut-off point for CPT was 28.95 degrees C, with a sensitivity of 92.7% and a specificity of 100%. Nevertheless, all patients with leprosy presented a WCPI greater than 6.10 degrees C (ROC curve) in skin lesions. Increase in the thermal thresholds indicated warm hypoaesthesia, cold hypoaesthesia or both. The WCPI, which embraces both warm and cold perception thresholds, was the best indicator of thermal sensation, a term used in literature as a non-specific expression that does not describe warm and cold stimuli explicitly in terms of units of temperature.


The politics of counter-rejection: gay christians and the church.
This paper analyzes the accounts constructed by 60 gay male Christians in managing the stigma imposed on them by the Church. These accounts signify that they, having developed a positive self-image, are involved in the politics of counter-rejection of the Church and its official positions on the issue of homosexuality. Their counter-rejection of the Church as a moral arbiter is predicated on four bases: (1) the Church's ignorance of sex and sexuality, (2) the Church's ignorance of all sexualities as God's creation, (3) the Church's misinterpretation of biblical passages on homosexuality, and (4) the Church's fallibility. Having counter-rejected the Church by challenging its credibility, the counter-rejection of the Church's official positions is a matter of course. Their experiences highlight the ability of stigmatized social actors to invent social biographies not only to defend their moral choices, but also to challenge the credibility of sources that question and stigmatize their choices.


Self-care Perception in Physicians and Patients With Type 2 Diabetes.
We sought to assess self-care perception consistency between patients with type 2 diabetes mellitus and their physicians and characterize the psychosocial parameters influencing their respective perceptions. We conducted a study of 627 patients with type 2 diabetes and their physicians throughout 12 family medicine residency clinics in Texas to analyze their respective perceptions of patient self-care. We utilized linear regression testing. There was a lack of consistency in self-care perception between patients and physicians 31.2% of the time. Patient self-care perception was best predicted by the patients' diabetes distress scores (P<.001) and last HbA1c (P<.001). Measuring a patient's diabetes distress may help physicians better understand a patient's self-care perception. By understanding a patient's self-care perception, the physician may be able to explore these notions of positive or negative self-care perception and even gently correct them when necessary. This may allow physicians to better align themselves with the patient, provide behavioral health interventions, and better target and communicate effective plans. We suggest periodic assessment of diabetes distress and self-care perception to inform the need for education to improve self-efficacy.


Chest Pain: If It Is Not the Heart, What Is It?
Noncardiac chest pain is an angina-type discomfort without indication of ischemia. Diagnosis can be difficult because of its heterogeneous nature. Classification varies by specialty; gastroenterology uses the terminology gastroesophageal reflux disease related versus non-gastroesophageal reflux disease related. Other disciplines recognize noncardiac chest pain etiologies as having gastrointestinal, musculoskeletal, psychiatric, or pulmonary/other as underlying etiologies. Diagnostics yield a specific cause for effective treatment, which is aimed at the underlying etiology, but it is not always possible. Some patients with noncardiac chest pain have comorbidities and ongoing pain that lead to decreased quality of life and continued health care use.


Transformation of avobenzone in conditions of aquatic chlorination and UV-irradiation.
Emerging contaminants represent a wide group of the most different compounds. They appear in the environment at trace levels due to human activity. Most of these compounds are not yet regulated. Sunscreen UV-filters play an important role among these emerging contaminants. In the present research the reactions of 4-tert-butyl-4'-methoxydibenzoylmethane (avobenzone), the most common UV filter in the formulation of sunscreens, were studied under the combined influence of active chlorine and UV-irradiation. Twenty five compounds were identified by GC/MS as transformation products of avobenzone in reactions of aquatic UV-irradiation and chlorination with sodium hypochlorite. A complete scheme of transformation of avobenzone covering all the semivolatile products is proposed. The identification of the two primary chlorination products (2-chloro-1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)-1,3-propanedione and 2,2-dichloro-1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)-1,3-propanedione) was confirmed by their synthesis and GC/MS and NMR analysis. Although the toxicities of the majority of these products remain unknown substituted chlorinated phenols and acetophenones are known to be rather toxic. Combined action of active chlorine and UV-irradiation results in the formation of some products (chloroanhydrides, chlorophenols) not forming in conditions of separate application of these disinfection methods. Therefore caring for people «well-being» it is of great importance to apply the most appropriate disinfection method. Since the primary transformation products partially resist powerful UV-C irradiation they may be treated as stable and persistent pollutants.


Secondary Raised Intracranial Pressure After Cranial Vault Remodeling for Isolated Sagittal Craniosynostosis.
The management of sagittal craniosynostosis has evolved over the decades as teams seek to refine their surgical approaches to idealize head shape with the least possible morbidity. Here, the authors identify the incidence of raised intracranial pressure (ICP) and its risk factors, requiring secondary surgical intervention after cranial vault remodeling (CVR) procedure at a single tertiary referral craniofacial unit. A retrospective case-control study was performed on the patients with isolated non-syndromic sagittal craniosynostosis. All patients who underwent CVR in our unit and had a minimum of 1.5 years follow-up were included. One hundred and eighty-four patients (134 male and 50 female) who underwent primary CVR surgery for isolated sagittal craniosynostosis were included. Thirteen patients (7.07%) had clinical evidence of late raised ICP resulting in repeat CVR procedures. Higher incidence of raised ICP in patients who had primary surgery before 6 months than after or at 6 months of age (P = 0.001). There were 23.5%, 5.6%, 3.2%, and 1.9% of secondary raised ICP patients who underwent the primary surgery between 1999-2004, 2005-2010, 2011-2015 and 2016-2018, respectively (P = 0.024). The risk of secondary raised ICP was higher in patients with isolated sagittal craniosynostosis whose primary surgery occurred before the age of 6 months (two times more likely). More extensive CVR can be performed safely in sagittal synostosis with promising outcomes. The late presentation with raised ICP reinforces the importance of long-term multidisciplinary protocol-based follow-up.


Direct Stenting Versus Balloon Pre-Dilatation In Elective Percutaneous Coronary Intervention.
Stents are now deployed in almost 95% of all percutaneous coronary interventions (PCIs). Recent advances in balloon and stent technology has improved the technique of direct stent (DS) strategy, i.e., stent delivery without pre-dilatation instead of conventional stenting (CS), i.e., stent implantation after balloon pre-dilatation with multiple advantages. This randomized controlled trial was conducted at the Cardiology. Department, Punjab Institute of Cardiology, Lahore from April to September, 2017. One hundred patients who were being treated by percutaneous coronary intervention (PCI) were enrolled into two Groups e.g., Group I & group II. 50 patients undergoing direct stenting were enrolled in group I and 50 patients undergoing stenting after balloon pre-dilatation were enrolled in group II after randomization. All patients were treated by single type drug eluting or bare metal stents. Chi square test was used for association and t-test for mean difference between two groups in comparison to post dilatation, fluoroscopy time, procedure time, amount of contrast used, procedural success, side branch compromise, slow flow. The p-value of ˂ 0.05 was significant. This study consisted of 76 males and 24 females out of a total count of 100, with the average age of 52.2±0.01 years. Overall, 43 (43%) patients were diabetic and overall, 44 (44%) were hypertensive. Most of the patients 55 (55%) had PCI to LAD. Average fluoroscopy time 4.l±2.5 minutes in Group I was significantly lesser as compared to 6.7±3.8 minute group II (p-value <0.05). The average procedure time was also marginally lesser in Group I, 23.4±11.6 in comparison to the second Group 33.7±14 (p-value <0.05). Side branch compromise was observed in 10 (20%) in the first group as compared to 8 (16%) the second group. In comparison to stenting preceded by balloon predilatation, direct stenting is a safer and more feasible procedure with respect to radiation exposure, cost and time duration of the procedure.


Phenotypic and genomic variation among Staphylococcus epidermidis strains infecting joint prostheses.
We studied the SmaI and SstII macrorestriction patterns of 54 Staphylococcus epidermidis strains isolated from 14 patients infected following the implantation of joint prostheses. Multiple strains from pus and infected tissue specimens of each patient were selected on the basis of different colony morphologies and drug resistance patterns. The same criteria were used to select 23 S. epidermidis strains from hand swabs of eight healthy individuals. For 10 of the 14 patients, all the intrapatient strains appeared to be closely or possibly related, whereas related strains were detected in the skin flora of only one of the eight healthy individuals. This observation suggests that, in most cases, the patients were infected by a single S. epidermidis clone which subsequently underwent rearrangements that yielded derivatives with divergent phenotypes and, occasionally, divergent macrorestriction patterns. The four patients whose specimens contained unrelated S. epidermidis strains were probably infected with several polyclonal strains.


Surface EMG cross talk quantified at the motor unit population level for muscles of the hand, thigh, and calf.
Cross talk is an important source of error in interpreting surface electromyography (EMG) signals. Here, we aimed at characterizing cross talk for three groups of synergistic muscles by the identification of individual motor unit action potentials. Moreover, we explored whether spatial filtering (single and double differential) of the EMG signals influences the level of cross talk. Three experiments were conducted. Participants (total 25) performed isometric contractions at 10% of the maximal voluntary contraction (MVC) with digit muscles and knee extensors and at 30% MVC with plantar flexors. High-density surface EMG signals were recorded and decomposed into motor unit spike trains. For each muscle, we quantified the cross talk induced to neighboring muscles and the level of contamination by the nearby muscle activity. We also estimated the influence of cross talk on the EMG power spectrum and intermuscular correlation. Most motor units (80%) generated significant cross-talk signals to neighboring muscle EMG in monopolar recording mode, but this proportion decreased with spatial filtering (50% and 42% for single and double differential, respectively). Cross talk induced overestimations of intermuscular correlation and has a small effect on the EMG power spectrum, which indicates that cross talk is not reduced with high-pass temporal filtering. Conversely, spatial filtering reduced the cross-talk magnitude and the overestimations of intermuscular correlation, confirming to be an effective and simple technique to reduce cross talk. This paper presents a new method for the identification and quantification of cross talk at the motor unit level and clarifies the influence of cross talk on EMG interpretation for muscles with different anatomy.NEW & NOTEWORTHY We proposed a new method for the identification and quantification of cross talk at the motor unit level. We show that surface EMG cross talk can lead to physiological misinterpretations of EMG signals such as overestimations in the muscle activity and intermuscular correlation. Cross talk had little influence on the EMG power spectrum, which indicates that conventional temporal filtering cannot minimize cross talk. Spatial filter (single and double differential) effectively reduces but not abolish cross talk.


Protective effects of broccoli (Brassica oleracea) and its active components against radical-induced oxidative damage.
The radical scavenging effect and protective potential from oxidative damage by radical generator, 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), in renal epithelial LLC-PK1 cell of broccoli (Brassica oleracea) were investigated and identified the active components under the bioassay-linked fractionation method. The MeOH extract, and fractions of CH2Cl2, BuOH and H2O from broccoli showed the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect in a dose-dependent manner. In addition, they exerted the protective effect against LLC-PK1 cellular damage induced by AAPH dose-dependently. In particular, the BuOH fraction was evaluated as the most active fraction, indicating that the BuOH fraction contains the active components with antioxidative capacity. Employing a bioassay-linked fractionation method, the active principles were isolated and characterized as 1,2-disinapoylgentiobiose and 1-sinapoyl-2-feruloylgentiobiose from the BuOH fraction. These two compounds from broccoli displayed potent antioxidant effects against the DPPH radical, showing the IC50 values of 5.18 and 7.52 microg/mL, respectively. Moreover, the compounds significantly and dose-dependently recovered cell viability lowered by AAPH treatment, suggesting the protective roles from cellular oxidative damage. The present study suggests that broccoli has excellent antioxidative potential and the hydroxycinamic acid esters from broccoli, 1,2-disinapoylgentiobiose and 1-sinapoyl-2-feruloylgentiobiose, are considered as the active components with antioxidative effect.


Social and interpersonal factors relating to adolescent suicidality: a review of the literature.
This article reviews the empirical literature concerning social and interpersonal variables as risk factors for adolescent suicidality (suicidal ideation, suicidal behavior, death by suicide). It also describes major social constructs in theories of suicide and the extent to which studies support their importance to adolescent suicidality. PsychINFO and PubMed searches were conducted for empirical studies focused on family and friend support, social isolation, peer victimization, physical/sexual abuse, or emotional neglect as these relate to adolescent suicidality. Empirical findings converge in documenting the importance of multiple social and interpersonal factors to adolescent suicidality. Research support for the social constructs in several major theories of suicide is summarized and research challenges are discussed.


[Extended aortoplasty for supravalvular aortic stenosis with Williams syndrome].
We report a male case of supravalvular aortic stenosis associated with Williams syndrome requiring surgery at age 11. At 5 years of age, this boy presented with a harsh systolic heart murmur and was diagnosed as having a supravalvular aortic stenosis. In association with mental retardation, elfin face and bilateral inguinal hernias, he was diagnosed as a Williams syndrome confirmed by the chromosomal analysis revealing the deletion of 7q11.23. The pressure gradient across the stenotic lesion of the ascending aorta, which had been 35 mmHg at age 5, progressed to 80 mmHg at age 11 years. Extended aortoplasty was performed using a patch of 20 mm Hemashield graft prosthesis. Postoperative cardiac catheterization confirmed that the pressure gradient in the ascending aorta completely disappeared following surgery.


C86Y: as a destructive homozygous mutation deteriorating Pex7p function causing rhizomelic chondrodysplasia punctata type I.
Rhizomelic Chondrodysplasia Punctata (RCDP) type 1 is a peroxisomal biogenesis disorder with a genetic abnormality in PEX7 gene. In the present study, mutational analysis was performed on two Iranian RCDP patients with distinct clinical phonotype. Mutation detection was carried out by sequencing of RT-PCR product consisting the whole length of PEX7 cDNA. Sequence data revealed the same missense homozygous mutation of G to A at nucleotide 257 in exon3 of PEX7 coding sequence in both patients. Moreover, genomic analysis of the PEX7 gene confirmed the RT-PCR data. This mutation caused one amino acid residue substitution of Cys to Tyr at codon 86 located on WD1 repeat domain region of Pex7p, which severely affected the functionality of PEX7 protein. Back-transfection of vector encoding mutant Pex7p did not restore the normal peroxisomal function in RCDP patient's fibroblast cells dissimilar to the native type of PEX7.


Idarucizumab for dabigatran reversal: the first 6 months in a tertiary centre.
This retrospective audit reviews patients on dabigatran presenting with bleeding or requiring urgent surgery in the Wellington region, whether they received idarucizumab appropriately and the outcome of episodes. Eighty patients were identified with bleeding or need for urgent surgery, 14 of which received idarucizumab. In patients who received idarucizumab, use was safe, effective and overall appropriate. Idarucizumab was underutilised with patients who could have benefited not receiving it; however, some patients who were treated may not have required it. Increased awareness and use may improve outcomes.


In vitro anti-cancer effect of marmesin by suppression of PI3K/Akt pathway in esophagus cancer cells.
Marmesin, an important coumarin isolated from Broussonetia kazinoki, has been proposed to possess many pharmacological activities including anti-tumor activity. However, the anti-cancer effect of marmesin on esophageal cancer (EC) has not been characterized. The study aimed to explore the anti-cancer role of marmesin using EC cell lines in vitro. Cell proliferation was evaluated by CCK-8 and Edu cell proliferation assays and apoptosis was detected by TUNEL assay. Western blot analysis was used to determine the expression of Ki67, proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, phosphatidylinositol 3-kinase (PI3K), phosphoryrated-PI3K (p-PI3K), protein kinase B (Akt), and phosphoryrated-Akt (p-Akt). The mechanism of action of marmesin was analyzed using network pharmacology approach. Marmesin exhibited anti-proliferative effect against EC cells, which was further confirmed by the reduced expression of Ki67 and PCNA. Marmesin exerted pro-apoptotic activity on EC cells by downregulating Bcl-2 and upregulating Bax. According to the results from network pharmacology approach, we speculated that PI3K/Akt pathway may participate in the effect of marmesin on EC cells. Additionally, the PI3K/Akt pathway was suppressed by marmesin in EC cells. Moreover, forced expression of Akt reversed the inhibition of cell proliferation and induction of apoptosis induced by marmesin in EC cells. Marmesin exerted anti-cancer activity in EC cells by inhibiting the PI3K/Akt pathway.


[Case of primary Sjögren's syndrome with hypereosinophilia and elevation of serum IgE: measurements of serum IL-4, IL-5 and the IgG subclass].
A 62-year-old man admitted to our hospital because of dry eyes and thirst. On admission, his bilateral parotid and submandibular glands were swelling. Laboratory data revealed severe eosinophilia (3309/microl), elevated serum IgE (1821IU/dl) and hypergammaglobulinemia (IgG 6049 mg/dl). Interstitial pneumonia and renal dysfunction were present. He was diagnosed with Sjögren's syndrome (SjS) according to the European criteria. After the initiation of the therapy with 30 mg of prednisolone, all abnormal findings including salivation ameliorated promptly. In the absence of any other obvious causes of eosinophilia and elevation of serum IgE, these findings might be associated with SjS itself. Moreover, both serum IL-5 and IgG4 levels were elevated in this patient, suggesting that Th2 type cytokines were dominant. Elevation of serum IgE and IgG4, and hypereosinophilia were likely to be reactive. To our knowledge, there have been no reports of these cytokines and of IgG subclass in such patients. We propose the existence of Th2-type-cytokine-dominant subtype of SjS.


Imaging of chemiluminescent signals with cooled CCD camera systems.
We investigated imaging of chemiluminescent signals from 1,2-dioxetanes with cooled CCD cameras. Non-radioactive detection methods for biomolecules utilizing these chemiluminescent substrates for alkaline phosphatase have been developed. Applications which have been successfully adapted to this technology include Southern and Northern blotting, immunoblotting, ELISA methods and DNA sequencing. Dephosphorylation of the dioxetane CSPD by alkaline phosphatase generates an unstable anion that decomposes resulting in light production. The wavelength of the emitted light is approximately 460 nm. We have utilized Photometrics Star and MXC 200L cooled CCD cameras for direct imaging of chemiluminescent signals. Benefits of utilizing a CCD detector include rapid data digitization and more accurate quantitation of chemiluminescent signals compared to film-based densitometry owing to the significantly greater dynamic range. Chemiluminescent images from dot blots of biotinylated DNA, Southern blots and DNA sequencing gel blots were obtained. In a chemiluminescent microtitre plate assay, serial dilutions of alkaline phosphatase spanning four orders of magnitude can be detected. Our results indicate that the digitization of chemiluminescent signal data with cooled CCD cameras is an excellent alternative to 32P detection methods utilizing storage phosphor screen imaging systems.


Cardiac Amyloidosis, An Infiltrative Heart Disease Presenting as Arrhythmia-A Case Report.
Cardiac amyloidosis is a manifestation of amyloidosis which is a multisystem disorder. This is difficult to diagnose, rare disease which eventually leads to the mortality. Diagnosis requires a high index of clinical suspicion along with echocardiographic clues like, diastolic dysfunction, bi-atrial enlargement and ventricular thickening. Treatment is mainly supportive with disappointing outcomes. We present a case of systemic amyloidosis with negative congo red staining, presenting with predominantly cardiac features.


Robotic-assisted right hepatectomy via anterior approach for intrahepatic cholangiocarcinoma.
Major hepatic resection, especially right hepatectomy, has been successfully performed by specialized hepatobiliary centers using the robotic platform with low morbidity, conversion rates and outcomes comparable to laparoscopic and open surgery. The authors report a case of robotic-assisted right hepatectomy done for intrahepatic cholangiocarcinoma using anterior approach, after right portal vein embolisation for future liver remnant volume enhancement.


Mediastinal pancreatic pseudocyst with hemorrhage and left gastric artery pseudoaneurysm, managed with left gastric artery embolization and placement of percutaneous trans-hepatic pseudocyst drainage.
Mediastinal pancreatic pseudocyst (MPP) is a rare, but known, complication of both acute and chronic pancreatitis. Most pseudocysts are associated with alcoholic pancreatitis. Recent advances in endoscopic techniques have shown promising results, with reduced chances of infection and recurrence than with percutaneous drainage, but limited availability restricts widespread use. Left gastric artery pseudoaneurysm with mediastinal pseudocyst has not been described in the literature to date. We report a successful resolution of hemorrhagic MPP with embolization of pseudoaneurysm and percutaneous trans-hepatic pseudocyst drainage.


COVID-19 pandemic and personal protective equipment shortage: protective efficacy comparing masks and scientific methods for respirator reuse.
The abrupt outbreak of the novel coronavirus disease 2019 and its rapid spread over many healthcare systems throughout the world has led to a shortage in personal protective equipment (PPE), which cannot be solved by reducing their use or by increasing production. It is thus necessary to promote PPE rational use, highlighting possible differences in terms of efficacy and promoting an effective technique to reuse them. A literature search was performed on PubMed, Scopus, Cochrane database, and Google Scholar, and from the 25 top cited articles, 15 were selected for relevance and impact. Most studies on previous respiratory virus epidemics to date suggest surgical masks are not inferior compared with N95 respirators in terms of protective efficacy among healthcare workers. Therefore, the use of N95 respirators should be limited to high-risk situations. Concerning respirator reuse, highly energetic, short-wave, ultraviolet germicidal irradiation (UVGI) at 254 nm was determined to decontaminate N95 respirators from viral respiratory agents, but UVGI requires careful consideration of the type of respirator and of the biologic target. Rational use and successful reuse of respirators can help in the shortage of PPE during a pandemic. Further studies testing UVGI and other decontamination techniques are an unmet need. The definitive answer to pandemic issues can be found in artificial intelligence and deep learning. These groundbreaking modalities could help in identifying high-risk patients and in suggesting appropriate types and use of PPE.


High prevalence of GR2 and GR4 plasmids in Acinetobacter baumannii strains from Brazil.
Acinetobacter baumannii is Gram-negative pathogen with extensive role in healthcare-associated infections (HAIs). Plasmids in this species are important carriers of antimicrobial resistance genes. In this work, we investigated the plasmids of 227 Brazilian A. baumannii genomes. A total of 389 plasmid sequences with 424 Rep proteins typed to 22 different homology groups (GRs) were identified. The GR2 plasmid group was the most predominant (40.6%), followed by the GR4 group (16.7%), representing ∼57% of all plasmids. There is a wide distribution of plasmids among the isolates and most strains carry more than one plasmid. Our analyses revealed a significant prevalence of GR4 plasmids in Brazilian A. baumannii genomes carrying several antimicrobial resistance genes, notably to carbapenem (39.43%). These plasmids harbor a MOBQ relaxase that might confer increased spreading potential in the environment. Most plasmids of the predominant groups belong to the same plasmid taxonomic unit (PTU-Pse7) and have a AbkA/AbkB toxin-antitoxin system that has a role in plasmid stability and dissemination of carbapenem resistance genes. The results of this work should contribute to our understanding of the molecular content of plasmids in a large and populous country, highlighting the importance of genomics for enhanced epidemiological surveillance.


Bleomycin-induced DNA damage and repair in human cells permeabilized with lysophosphatidylcholine.
We have examined bleomycin-induced DNA damage and repair in confluent human fibroblasts that were reversibly permeabilized to small molecules (e.g., deoxynucleotide triphosphates and trypan blue) by a short exposure to 80 micrograms/ml lysophosphatidylcholine. We found that this treatment dramatically increases the dose effectiveness of bleomycin in inducing DNA strand breaks and DNA repair synthesis in these cells. For example, when intact cells (not treated with lysophosphatidylcholine) were incubated with 100 micrograms/ml bleomycin, only about 5% of the cell population was observed to have undergone measurable DNA repair synthesis (by autoradiography). On the other hand, when these cells were reversibly permeabilized with lysophosphatidylcholine before treatment, we observed significant repair synthesis in greater than 80% of the cells using a bleomycin dose of only 5 micrograms/ml. Furthermore, sufficient levels of single- and double-strand breaks were introduced into nucleosome linker DNA of permeabilized cells to yield a nucleosomal repeat pattern in alkaline and neutral agarose gels. However, no change in the amount of DNA less than 23 kilobases was observed on these gels when intact cells were incubated with bleomycin.


Molecular and Clinical Elucidation of the Mechanism of Action of Steroids in Idiopathic Carpal Tunnel Syndrome.
Carpal tunnel steroid injection is a nonoperative intervention for the treatment for idiopathic carpal tunnel syndrome (CTS). The antifibrotic, anti-inflammatory, and antiedematous properties of steroids account for their therapeutic effects in the context of CTS; however, their relative contribution has not been clarified. Fibroblasts from subsynovial connective tissues (SSCT) were intraoperatively collected from patients with idiopathic CTS and were incubated with or without the steroid triamcinolone acetonide (TA) for 1, 3, and 7 days; the expression of fibrosis-related genes and inflammatory cytokines was evaluated using quantitative reverse transcription-polymerase chain reaction. A clinical prospective study was conducted with patients who received carpal tunnel TA injections. We performed clinical and electrophysiological evaluations before and 1, 3, and 5 months after TA injection; and we compared the median nerve, flexor tendon, and SSCT areas and the median nerve flattening ratio before and 1 month after TA injection using 3-T magnetic resonance imaging (MRI). TA induced downregulation of the fibrosis-related genes Col1A1 (collagen type I alpha 1 chain), Col1A2, and Col3A1 but not the inflammation-related genes. The nerve flattening ratio did not change after TA injection according to the MRI-based observation of the median nerve, flexor tendon, and SSCT areas. The therapeutic effects of injected TA are apparently mediated by its antifibrotic rather than its anti-inflammatory and antiedematous properties. TA probably alters the properties but not the morphology of SSCT. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


A transient entanglement coupling mechanism for DNA separation by capillary electrophoresis in ultradilute polymer solutions.
Using capillary electrophoresis, large DNA molecules (2.0-23.1 kbp) may be rapidly separated in ultradilute polymer solutions (< 0.002% w/w) under a high-voltage, steady field (265 V/cm). At this polymer concentration, the separation mechanism appears to be significantly different from that postulated to occur in crosslinked gels. Based on experimental results obtained with DNA restriction fragments and with negatively charged latex microspheres, we conclude that the Ogston and reptation models typically used to describe gel electrophoresis are not appropriate for DNA separations in such dilute polymer solutions. Electrophoresis experiments employing solutions of both small and large hydroxyethyl cellulose polymers highlight the importance of polymer length and concentration for the optimum resolution of DNA fragments varying in size from 72 bp to 23.1 kbp. A transient entanglement coupling mechanism for DNA separation in dilute polymer solutions is developed, which suggests that there is no a priori upper size limit to DNA that can be separated by capillary electrophoresis in a constant field.


Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs.
Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1), has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1-/- mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis.


Increased risk for cancer of the breast due to previous medication.
Fifteen patients presenting one or more risk factors for cancer of the breast, who also received medication with prolactin-stimulating effects, were selected. The medication was by hormone derivatives or by non-hormone drugs used for processes other than oncologic . In all cases the medication was for long periods, three or more years, with the exception of one case, where the correlation with the unfavourable evolution of the cancer process was more evident. In patients presenting the classic risk factors for cancer of the breast, it is recommended to avoid the prescription of drugs having a prolactin-stimulating effect. The association of both circumstances (risk factors and prolactin-stimulating medication) is considered as an increased risk for cancer of the breast.


Diastereo- and enantioselective construction of spirooxindole scaffolds through a catalytic asymmetric [3 + 3] cycloaddition.
A chiral phosphoric acid-catalyzed asymmetric [3 + 3] cycloaddition of C3-substituted 2-indolylmethanols with isatin-derived azomethine ylides has been established, which afforded chiral spirooxindoles in considerable yields, moderate to good enantioselectivities and excellent diastereoselectivities (up to 85% yield, 96 : 4 er, all >95 : 5 dr).


Extracorporeal shockwave therapy (ESWT) in patients with chronic proximal plantar fasciitis.
The aim of this study was to compare the effect of extracorporeal shockwave therapy (ESWT) in patients with chronically painful proximal plantar fasciitis with a conventional conservative treatment consisting of nonsteroidal anti-inflammatory drugs, heel cup, orthoses and/or shoe modifications, local steroid injections and electrotherapy. Forty-seven patients (49 feet) with a previously unsuccessful conservative treatment of at least six months were randomized to two groups. Treatment of Group 1 (25 heels) started immediately with three sessions of ESWT (3000 shockwaves/session of 0.2 mJ/mm2) at weekly intervals. In the patients of Group 2 (24 heels) treatment was continued for 12 weeks. After this period they were treated using the protocol of Group 1. No significant difference of pain and walking time after further non-ESWT treatment (three months) was seen. Six months after ESWT pain decreased by 64% to 88% on the visual analog scale (VAS) and the comfortable walking time had increased significantly in both groups.