Electronic transport of recrystallized freestanding graphene nanoribbons.
The use of graphene and other two-dimensional materials in next-generation electronics is hampered by the significant damage caused by conventional lithographic processing techniques employed in device fabrication. To reduce the density of defects and increase mobility, Joule heating is often used since it facilitates lattice reconstruction and promotes self-repair. Despite its importance, an atomistic understanding of the structural and electronic enhancements in graphene devices enabled by current annealing is still lacking. To provide a deeper understanding of these mechanisms, atomic recrystallization and electronic transport in graphene nanoribbon (GNR) devices are investigated using a combination of experimental and theoretical methods. GNR devices with widths below 10 nm are defined and electrically measured in situ within the sample chamber of an aberration-corrected transmission electron microscope. Immediately after patterning, we observe few-layer polycrystalline GNRs with irregular sp(2)-bonded edges. Continued structural recrystallization toward a sharp, faceted edge is promoted by increasing application of Joule heat. Monte Carlo-based annealing simulations reveal that this is a result of concentrated local currents at lattice defects, which in turn promotes restructuring of unfavorable edge structures toward an atomically sharp state. We establish that intrinsic conductance doubles to 2.7 e(2)/h during the recrystallization process following an almost 3-fold reduction in device width, which is attributed to improved device crystallinity. In addition to the observation of consistent edge bonding in patterned GNRs, we further motivate the use of bonded bilayer GNRs for future nanoelectronic components by demonstrating how electronic structure can be tailored by an appropriate modification of the relative twist angle of the bonded bilayer.


Is the soluble KDI domain of gamma1 laminin a regeneration factor for the mammalian central nervous system?
Regeneration of adult mammalian CNS is poor as a result of environmental factors that prevent axon growth. The major factors hampering regeneration of central axons include proteins released from the damaged myelin sheets of the injured neuronal pathways and formation of the glial scar. By using an experimental model of human CNS injury, we show that survival and neurite outgrowth of human central neurons are significantly enhanced by the soluble KDI domain of gamma1 laminin. Our results indicate that the KDI domain appears to neutralize both glia-derived inhibitory signals and inhibitory molecules released from the myelin of the adult human spinal cord. We propose that the KDI domain may enhance regeneration of injuries in the adult mammalian CNS.


Recurrent Endocrine Cycles.
The chaotic nature of blood glucose creates a formidable clinical challenge for diabetes healthcare. The recent discovery of recurrent endocrine cycles offers the advantage of advanced-prediction (proactive) health care. Historical studies covering 111 patients and 1 subject collected several months of glucose readings and their daily metrics. Phase portraits and phase analytics can detect recurrent metric cycles and test their ability to anticipate serious glycemic conditions. Recurrent patterns were detected having a rate of ~7 days per complete cycle. Plots and risk models based on these cycles produced advanced alerts for acute glycemia, capturing greater than 96% of true-positive days with a 5% false-positive rate. This method can be implemented graphically and functionally within a BG monitoring system to warn doctors and patients of impending serious glycemic levels.


Environmental Salmonella in agricultural fair poultry exhibits in Colorado.
Salmonella enterica is a common zoonotic pathogen in humans. Transmission typically occurs through consumption of contaminated food products or contact with infected animals, including poultry or their environment. The objective of this study was to estimate the frequency of Salmonella contamination in the environment in poultry exhibits at agricultural fairs. Samples were collected from cages, feed, floors and tables in the exhibit and cultured for Salmonella. At least one environmental sample was positive for Salmonella in 10 of 11 fairs (91%), and Salmonella was isolated from 28 of 55 environmental samples (50.9%). Eleven different serotypes were detected. Results of this study demonstrate that environmental surfaces at agricultural fairs can be contaminated with Salmonella and could potentially serve as a route of transmission to bird owners and the general public. Poultry owners and the general public should be educated about the risks of Salmonella infection from the poultry exhibit environment. Agricultural fairs should consider instituting policies and practices to improve hygiene and mitigate the risk of zoonotic salmonellosis.


Minimizing Reference Bias with an Impute-First Approach.
Pangenome indexes reduce reference bias in sequencing data analysis. However, a greater reduction in bias can be achieved using a personalized reference, e.g. a diploid human reference constructed to match a donor individual's alleles. We present a novel impute-first alignment framework that combines elements of genotype imputation and pangenome alignment. It begins by genotyping the individual from a sub-sample of the input reads. It next uses a reference panel and efficient imputation algorithm to impute a personalized diploid reference. Finally, it indexes the personalized reference and applies a read aligner, which could be a linear or graph aligner, to align the full read set to the personalized reference. This frame-work has higher variant-calling recall (99.54% vs. 99.37%), precision (99.36% vs. 99.18%), and F1 (99.45% vs. 99.28%) compared to a graph-based pangenome. The personalized reference is also smaller and faster to query compared to a pangenome index, making it an overall advantageous choice for whole-genome DNA sequencing experiments.


Mesenchymal stem cell treatment for chronic renal failure.
Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Despite advances in renal replacement therapies and organ transplantation, poor quality of life for dialysis patients and long transplant waiting lists remain major concerns for nephrologists treating this condition. There is therefore a pressing need for novel therapies to promote renal cellular repair and tissue remodeling. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cells (MSCs) are undifferentiated cells that possess immunomodulatory and tissue trophic properties and the ability to differentiate into multiple cell types. Studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. Nevertheless, several limitations pertaining to inadequate engraftment, difficulty to monitor, and untoward effects of MSCs remain to be addressed. Adverse effects observed following intravascular administration of MSCs include immune rejection, adipogenic differentiation, malignant transformation, and prothrombotic events. Nonetheless, most studies indicate a remarkable capability of MSCs to achieve kidney repair. This review summarizes the regenerative potential of MSCs to provide functional recovery from renal failure, focusing on their application and the current challenges facing clinical translation.


Phytoestrogens modulate binding response of estrogen receptors alpha and beta to the estrogen response element.
Binding of estrogen receptor (ER) to estrogen response element (ERE) induces gene activation and is an important step in estrogen-induced biological effects. Here, we investigated the effects of some dietary phytoestrogens such as the isoflavones genistein and daidzein, its metabolite equol, and the coumestane coumestrol on the binding rate of ERalpha and ERbeta to ERE by a nonradioactive real-time method, the Biacore Technology. ERalpha and ERbeta were able to bind to ERE immobilized on the surface of a sensor chip even in the absence of estrogens. 17beta-Estradiol and phytoestrogens induced an increase in ER binding to ERE in a concentration-dependent manner. 17beta-Estradiol was a more potent activator of binding than the phytoestrogens studied. The concentrations of 17beta-estradiol inducing an increase in the binding response of ERalpha and ERbeta to ERE by 50% (EC(50)) as compared to unliganded ER were 0.03 and 0.01 microM, respectively. Regarding the efficacy of activation of ERalpha, from the most to the least effective compound, the sequence and the EC(50) were as follows: 17beta-estradiol (0.03 microM) > coumestrol (0.2 microM) > equol (3.5 microM) > genistein (15 microM) > daidzein (>300 microM) and for ERbeta 17beta-estradiol (0.01 microM) > coumestrol (0.025 microM) > genistein (0.03 microM) > daidzein (0.35 microM) > equol (0.4 microM). The ratios EC(50)alpha/EC(50)beta were calculated to be for 17beta-estradiol, 3; coumestrol, 8; equol, 8.8; genistein, 500; daidzein > 850. These ratios indicate that genistein and daidzein preferentially activate the binding of ERbeta to ERE. The endogenous hormone 17beta-estradiol as well as coumestrol and daidzein metabolite equol activate the binding of ERbeta to ERE only slightly more effectively than the binding of ERalpha to ERE. Thus, the effect of daidzein can be changed from a specific activator of ERbeta to an activator of both ER isotypes alpha and beta in humans who are able to convert daidzein to equol. While the results of the measurements with ERalpha were in line with the binding affinities of compounds tested for ER, there was a distinct difference between our results and the binding affinities of phytoestrogens for the ERbeta. This leads to the conclusion that phytoestrogens differ not only in their binding affinities for the ER, but also in their potential to increase the rate of receptor binding to the ERE.


Extra neurofilament NF-L subunits rescue motor neuron disease caused by overexpression of the human NF-H gene in mice.
Previous studies demonstrated that transgenic mice overexpressing human neurofilament heavy (hNF-H) protein develop a progressive motor neuron disease characterized by the perikaryal accumulations of neurofilaments resembling those found in amyotrophic lateral sclerosis (ALS). To further investigate this neurofilament-induced pathology, we generated transgenic mice expressing, solely or concomitantly, the hNF-H and the human neurofilament light (hNF-L) proteins. We report here that the motor neuron disease caused by excess hNF-H proteins can be rescued by overexpression of hNF-L in a dosage-dependent fashion. In hNF-H transgenic mice, the additional hNF-L led to reduction of perikaryal swellings, relief of axonal transport defect and restoration of axonal radial growth. A gene delivery approach based on recombinant adenoviruses bearing the hNF-L gene also demonstrated the possibility to reduce perikaryal swellings after their formation in adult mice. The finding that extra NF-L can protect against NF-H-mediated pathogenesis is of potential importance for ALS, particularly for cases with NF-H abnormalities.


Helicobacter pylori-driven modulation of NK cell expansion, intracellular cytokine expression and cytotoxic activity.
During Helicobacter pylori (Hp) infections, innate immune cells may be positively or negatively modulated by Hp compounds or by Hp-induced cytokines. We have shown previously that the natural cytotoxic activity of PBMC was lower in Hp-infected [Hp(+)] than Hp-uninfected individuals [Hp(-)]. Here, we asked whether the Hp-modulated cytotoxic amplitude is associated with changes in the number of NK cells, their activation or intracellular cytokine expression. Flow cytometry immunophenotyping of PBMC was performed with regard to the surface receptors CD3, CD56 and CD25, and intracellular cytokine expression of IL-2, IFN-γ and IL-10 after in vitro stimulation with Hp glycine acid extract (GE), Hp LPS or standard Escherichia coli LPS. Hp GE-driven enhancement of lymphocyte cytotoxic activity was associated with the expansion of CD3(-)CD56(+)CD25(+) NK cells and the up-regulation of IFN-γ and/or IL-2 synthesis, up to the higher level in Hp(-) than in Hp(+), while Hp LPS-mediated decrease in lymphocyte cytotoxicity was accompanied by the lack of CD3(-)CD56(+)CD25(+) NK propagation, the inhibition of pro-inflammatory cytokine expression and intense expansion of IL-10-producing NK cells. Thus, the cytotoxic and cytokine activities of NK cells were dependent on the type of antigenic challenge and the Hp status, that is, NK cells could be modulated positively by Hp GE Ags and negatively by Hp LPS.


Model-based identification and diagnosis of a porcine model of induced endotoxic shock with hemofiltration.
A previously validated cardiovascular system (CVS) model and parameter identification method for cardiac and circulatory disease states are extended and further validated in a porcine model (N=6) of induced endotoxic shock with hemofiltration. Errors for the identified model are within 10% when the model is re-simulated and compared to the clinical data. All identified parameter trends over time in the experiments match clinically expected changes both individually and over the cohort. This work represents a further clinical validation of these model-based cardiovascular diagnosis and therapy guidance methods for use with monitoring endotoxic disease states.


Molecular cloning and characterization of a tocopherol cyclase gene from Lactuca sativa (Asteraceae).
Tocopherol cyclase is a rate-limiting enzyme involved in tocopherol biosynthesis. The full-length cDNA encoding tocopherol cyclase (designated as LsTC) was cloned from lettuce (Lactuca sativa) for the first time by rapid amplification of cDNA ends (RACE) and characterized by means of quantitative RT-PCR. The full-length cDNA of LsTC was 1675 bp, with an open reading frame of 1521 bp, encoding a tocopherol cyclase protein of 506 amino acids, with a calculated molecular mass of 56.76 kD and an isoelectric point of 6.49. Comparative analysis revealed that LsTC has a close similarity with tocopherol cyclases from other plant species. Bioinformatic analysis indicated that LsTC shares a common evolutionary origin based on sequence and has the closest relationship to tocopherol cyclase from Helianthus annuus. Quantitative RT-PCR analysis suggested that expression of LsTC is induced and strengthened by oxidative stresses, such as strong light and drought. This cloning and characterization of LsTC will be helpful for further understanding of its role in the tocopherol biosynthesis pathway and provide a candidate gene for metabolic engineering of vitamin E.


[Evidence-based practice: strategies for its implementation in nursing].
Evidence-based practice is an approach that enables the improvement of health care quality. The use of research findings on founded practice is one of the pillars of such approach; however, there are various barriers that hinder this nursing process, such as the lack of nurses' skills, lack of time and organizational support (human, material and financial resources). Therefore, based on the literature, this article presents some strategies that allow for the implementation of evidence-based practice in nursing in whatever area the nurse may perform.


Self-imagery and advertising effectiveness: the role of sense of presence.
The purpose of this study was to assess whether self-imagery is more effective than other-imagery, and if so, to investigate the mechanism of how self-imagery generates more increased positive responses from consumers. Furthermore, we explored the boundary conditions associated with reduced positive effects of self-imagery on consumer responses. The results of Experiment 1 suggest that self-imagery was more effective than other-imagery in generating a favorable attitude toward an advertisement and purchase intention, since it enhanced a sense of presence, and consequently, imagery engagement. However, based on the results of Experiment 2, when an advertisement evoked a sense of high-risk, self-imagery generated a less favorable attitude toward the advertisement than other-imagery due to the emotion of fear evoked by the advertisement.


AIP1 recruits phosphatase PP2A to ASK1 in tumor necrosis factor-induced ASK1-JNK activation.
Previously we have shown that AIP1 (apoptosis signal-regulating kinase [ASK]1-interacting protein 1), a novel member of the Ras-GAP protein family, facilitates dephosphorylation of ASK1 at pSer967 and subsequently 14-3-3 release from ASK1, leading to enhanced ASK1-JNK signaling. However, the phosphatase(s) responsible for ASK1 dephosphorylation at pSer967 has not been identified. In the present study, we identified protein phosphatase (PP)2A as a potential phosphatase in vascular endothelial cells (ECs). Tumor necrosis factor (TNF)-induced dephosphorylation of ASK1 pSer967 in ECs was blocked by PP2A inhibitor okadaic acid. Overexpression of PP2A catalytic subunit induced dephosphorylation of ASK1 pSer967 and activation of c-Jun N-terminal kinase (JNK). In contrast, a catalytic inactive form of PP2A or PP2A small interfering RNA blunted TNF-induced dephosphorylation of ASK1 pSer967 and activation of JNK without effects on NF-kappaB activation. Whereas AIP1, via its C2 domain, binds to ASK1, PP2A binds to the GAP domain of AIP1. Endogenous AIP1-PP2A complex can be detected in the resting state, and TNF induces a complex formation of AIP1-PP2A with ASK1. Furthermore, TNF-induced association of PP2A with ASK1 was diminished in AIP1-knockdown ECs, suggesting a critical role of AIP1 in recruiting PP2A to ASK1. TNF-signaling molecules TRAF2 and RIP1, known to be in complex with AIP1 and activate AIP1 by phosphorylating AIP1 at Ser604, are critical for TNF-induced ASK1 dephosphorylation. Finally, PP2A and AIP1 cooperatively induce activation of ASK1-JNK signaling and EC apoptosis, as demonstrated by both overexpression and small interfering RNA knockdown approaches. Taken together, our data support a critical role of PP2A-AIP1 complex in TNF-induced activation of ASK1-JNK apoptotic signaling.


CD4+ cell count recovery following initiation of HIV antiretroviral therapy in older childhood and adolescence.
To investigate CD4 cell count recovery following ART initiation in perinatally HIV-infected children diagnosed in later childhood. Observational prospective cohort study of newly diagnosed children aged 6-15 in Harare, Zimbabwe. Participants were enrolled into a cohort at seven primary healthcare clinics between January 2013 and January 2015. ART was initiated according to national guidelines and CD4 cell counts were performed 6-monthly over 18 months. The relationship between CD4 cell count and time on ART was investigated using regression analysis with fixed (population) and random (individual) effects, and age at ART initiation as a covariate. Of the 307 participants who initiated ART, the median age at initiation was 11.7 years (interquartile range 9.6-13.8). The addition of an individual intercept and slope as random effects significantly improved the model fit compared with a fixed effects-only model. CD4 response (using a square-root transformation) was best modelled using a two-knot linear spline, with significant effects of time on ART and age at ART initiation. Younger children had a higher CD4 cell count at ART initiation (-17.9 cells/μl per year of age), an accelerated increase during the first 3 months on ART (-38.9 cells/μl per year of age at day 84), and a sustained higher CD4 cell count. Earlier ART initiation in older children is associated with accelerated CD4 cell count recovery and lasting immune reconstitution. Our findings support WHO guidance recommending ART initiation in all children, irrespective of disease stage and CD4 cell count.


c-FLIP protects mature T lymphocytes from TCR-mediated killing.
Although c-FLIP has been identified as an important player in the extrinsic (death receptor-induced) apoptosis pathway, its endogenous function in mature T lymphocytes remains undefined. c-FLIP may inhibit or promote T cell death as previous data demonstrate that the c-FLIP(L) isoform can promote or inhibit caspase 8 activation while the c-FLIP(S) isoform promotes or inhibits T cell death when overexpressed. Although the c-FLIP(R) isoform inhibits cell death in cell lines, its function in T cells remains unknown. To investigate the function of c-FLIP in mature T cells, we have generated several genetic mouse models with c-FLIP or its individual isoforms deleted in mature T cells. Surprisingly, we found that c-FLIP protects mature T cells not only from apoptosis induced by the death receptors Fas and TNFR but also from TCR-mediated and spontaneous apoptosis. Thus, c-FLIP plays an essential role in protecting mature T cells from a death signal induced through the TCR itself and is required for naive T cell survival. Our results demonstrate that c-FLIP functions beyond the extrinsic death pathway.


Adverse psychological effects of corticosteroids in children and adolescents.
Children and adolescents treated with oral, inhaled, and intravenous corticosteroids (CS) may experience adverse psychological side effects (APSE), including psychotic symptoms. These can occur at any point during treatment, including withdrawal. In this paper the literature on these effects in children and adults is reviewed. From the evidence available, it is not possible to give reliable estimates for incidence or prevalence of APSE, nor clear risk factors. Some evidence is reported to suggest that oral dexamethasone treatment may carry a higher risk of APSE than other CS, but this requires further investigation. There is evidence from the adult literature that higher CS doses increase the risk of APSE. However, the dose response effect is not straightforward or predictable for individuals or groups. This is likely to be a reflection of the complex effects of CS on the central nervous system and the probable interplay between individual susceptibility, disease factors, and external environmental stressors in the emergence of APSE. More research is required to further our understanding of the adverse effects of these clinically valuable agents.


Cardiac anomalies complicating congenital contractural arachnodactyly.
A newborn boy with congenital contractural arachnodactyly (CCA) was found to have an atrial septal defect, ventricular septal defect, patent ductus arteriosus, and aortic arch anomalies. These resulted in congestive failure but subsequent progressive dilatation of both great arteries and development of aortic regurgitation were associated with eventual cardiorespiratory failure and death at 11.5 months. Others have noted that cardiac anomalies in CCA may be comparable with those of infantile Marfan's syndrome. Our case further extends the spectrum of cardiac abnormalities in CCA and substantiates that there is overlap with infantile Marfan's syndrome. This fact and our literature review suggest that early and complete cardiac assessment is necessary for appropriate management and evaluation of prognosis in any newborn infant with findings suggestive of either condition.


Intermediate TCR cells in mouse lung: their effector function to induce pneumonitis in mice with autoimmune-like graft-versus-host disease.
The lung comprises lymphocytes even under noninflammatory conditions. We investigated the presence of NK cells, extrathymic T cells, and thymus-derived T cells in this organ. As shown previously in mouse liver, two-color staining for CD3 and IL-2R beta-chain (IL-2Rbeta) identifies CD3- IL-2Rbeta+ NK cells, CD3int IL-2Rbeta+ cells (int indicates intermediate; of extrathymic origin), and CD3high IL-2Rbeta- cells (high indicates high; of thymic origin). These populations were present in the lungs of normal mice in a unique manner (i.e., NK cells > CD3high cells > CD3int cells). The proportion of CD3int cells increased in the lung with age. In athymic mice, only CD3int cells were detected in the lung. In contrast to CD3int cells in the liver, the majority of these cells in the lung did not express NK1.1 Ags. Other properties of CD3int cells in the lung were the same as those in the liver, e.g., double-negative CD4- 8- cells and gammadelta T cells. CD3int cells in the lung contained forbidden clones similar to those in other organs. When (B6 x bm12) F1 mice (Ly5.2) were injected with CD3high cells of B6-Ly5.1 origin, F1 mice fell victim to chronic graft-vs-host disease and pneumonitis, showing the expansion of CD3int cells. Almost all of them were of recipient origin (Ly5.2+). More importantly, such CD3int cells induced autoimmune-like pneumonitis when injected into irradiated F1 mice. CD3int cells isolated from the lung in mice with graft-vs-host disease exerted autologous cytotoxicity against thymocytes in vitro. These results suggest that extrathymic T cells exist in the lung and that their expansion may be responsible for inflammatory lung diseases.


Inflammatory bowel disease in the Bedouin Arabs of southern Israel: rarity of diagnosis and clinical features.
A prospective epidemiological and clinical study of ulcerative colitis and Crohn's disease was undertaken in the Bedouin Arabs of southern Israel between 1981 and 1990. There were six patients with ulcerative colitis and the prevalence rate in 1990 was calculated to be 9.8/10(5) (95% confidence intervals 3.6-17.4) in the total population, or 6.2/10(5) (0.8-22.5) in men and 13.7/10(5) (3.7-35.0) in women. Two cases of Crohn's disease occurred, both in women; the prevalence rate was 3.2/10(5) (0.4-11.8) in the entire population, and 6.8/10(5) (0.8-17.5) in women. The prevalence rates (age adjusted) in Arabs were significantly lower (p less than 0.01) than the corresponding rates in the local Jewish populations. The Bedouin patients were aged mean (SD) 34.0 (16.4) years at time of diagnosis. The clinical features of both diseases resembled those in the Jewish and other reported populations. It is suggested that the exposure of the Bedouin Arabs to the environmental causative factors of ulcerative colitis and Crohn's disease has hitherto been limited and thereby accounts for the rarity of these diseases in this population.


Evaluation of polymyxin B in an ex vivo model of endotoxemia in horses.
To evaluate effects of polymyxin B sulfate (PMB) on response of horses to endotoxin, using an ex vivo model. 8 healthy horses. In a crossover design, 3 doses of PMB (100, 1,000, and 10,000 U/kg of body weight) and physiologic saline solution (control) were evaluated. Prior to and for 24 hours after administration of PMB, blood samples were collected into heparinized tubes for use in 2 assays. For the endotoxin-induced tumor necrosis factor (TNF) assay, blood samples were incubated (37 C for 4 h) with 1 ng of Escherichia coli or Salmonella Typhimurium endotoxin/ml of blood. Plasma was harvested and assayed. For the residual endotoxin activity assay, plasma was collected into sterile endotoxin-free borosilicate tubes, diluted 1:10 with pyrogen-free water, and incubated for 10 minutes at 70 C. Escherichia coli endotoxin (0.1 or 1 ng/ml of plasma) was added to the thawed samples prior to performing the limulus ameobocyte lysate assay. Serum creatinine concentrations were monitored for 1 week. Compared with baseline values, PMB caused a significant dose- and time-dependent decrease in endotoxin-induced TNF activity. Compared with baseline values, residual endotoxin activity was significantly reduced after administration of 10,000 U of PMB/kg. Compared with baseline values, 1,000 and 5,000 U of PMB/kg should inhibit 75% of endotoxin-induced TNF activity for 3 and 12 hours, respectively. Serum creatinine concentrations remained within the reference range. Results of the study suggest that PMB is a safe, effective inhibitor of endotoxin-induced inflammation in healthy horses.


Diet and risk of gastric cancer. A population-based case-control study in Sweden.
A case-control study to evaluate risk factors of gastric cancer was carried out in areas with contrasting incidence rates in Sweden. Face-to-face interviews were conducted with 338 of 456 eligible histologically confirmed gastric-cancer cases and 669 of 880 eligible control subjects, sampled from population registers and frequency-matched by age and gender. We focused on 2 periods, adolescence and 20 years prior to interview. The association of gastric-cancer risk with dietary habits during adolescence were similar to that found for the period 20 years before interview; high consumption of wholemeal bread, fruit and vegetables was associated with reduced gastric-cancer risk. In addition, cheese, fish and tea had a protective effect during adolescence. Increased gastric-cancer risk was related to whole-milk consumption, but this association decreased substantially in a multivariate analysis including vegetables. There was a positive relationship between gastric-cancer risk and the age at which the interviewees started using refrigerators. This population-based study confirmed the protective effect of a high consumption of vegetables and fruit in the development of gastric cancer, but failed to find any association between intake of meat, sausage, cold cuts, liver, salt, coffee, the habit of frying, smoking or grilling foods, and risk of gastric cancer.


Celiac Plexus Block Complications: A Case Report and Review of the Literature.
Celiac plexus block (CPB) has been widely used as a treatment option for chronic intractable abdominal pain resulting from intra-abdominal malignancies as well as benign conditions. Complications resulting from CPB have been long reported and include diarrhea, back pain, paraplegia, postural hypotension, pneumothorax, and local anesthesia toxicity. Diarrhea and postural hypotension are two most common complications with studies reporting incidences occurring in 44% to 60% and 10% to 52% of patients, respectively. Diarrhea is most often transient, resolving within 48 hours; however, literature reports cases in which diarrhea was chronic, debilitating, and in some instances life threatening. Persistent diarrhea proves difficult to treat. We report a case of a 76-year-old male with unresectable pancreatic adenocarcinoma who underwent computed tomography-guided CBP complicated by persistent diarrhea and fecal incontinence. After conventional antidiarrheal failed to improve the symptoms, octreotide proved to be beneficial and the patient reported significant improvement in symptoms.


Three-year surveillance of community onset health care-associated staphylococcus aureus infections in children.
Staphylococcus aureus causes skin and soft tissue or invasive infections in children in the community, in the hospital or in other ways associated with the health care system (HCA). Prospective community-acquired S. aureus infection surveillance at Texas Children's Hospital was initiated on August 1, 2001. Community onset HCA (CO HCA) infections were identified. Demographic and clinical data were collected. Antibiotic susceptibilities were determined. Data were analyzed by chi or Student's t test. CO HCO-isolates were characterized by pulsed field gel electrophoresis and staphylococcal chromosomal cassette carrying the mecA methicillin-resistant gene (SCCmec) typing. From August 1, 2001 to July 31, 2004, 61.5% of 322 in year 1, 62.9% of 259 in year 2 and 56.9% of 318 in year 3 of CO HCA isolates were methicillin-resistant S. aureus (MRSA). Among the CO HCA-MRSA isolates, 8.9% of 542 were from children with invasive infections compared with 24.1% of 357 CO HCA-methicillin-susceptible S. aureus (MSSA; P < 0.001). Sixty-six percent of children with CO HCA-S. aureus isolates were admitted to the hospital. Clindamycin resistance increased over the 3 years (CO HCA-MRSA, from 3.5% to 18.8%, P < 0.001; CO HCA-MSSA, from 3.2% to 10.2%, P = 0.053). Thirty-three of 35 (94.3%) CO HCA-MRSA carried SCCmecIV; 30 were USA300. Only 3 of 35 MSSA were related to USA300 by pulsed field gel electrophoresis. CO HCA-S. aureus infections remained steady over the 3-year study at Texas Children's Hospital. Clindamycin resistance increased >4-fold for CO HCA-S. aureus isolates over the 3 years and is no longer appropriate for empiric treatment of invasive infections suspected to be caused by CO HCA-MRSA at our hospital. In our setting, CO HCA-MRSA infections are steady in number despite substantial increases in community-acquired MRSA infections and both being related to the same clone.


Malaria case management among Primary Health Care workers in Sokoto.
INTRODUCTION AND OBJECTIVES OF THE STUDY: Among the current strategies for malaria control in Nigeria include early recognition and adequate treatment of cases through capacity building of health workers. This therefore forms the basis of this study; so that an evidence based intervention programme will be designed for area and cadre specific identified gaps among PHC Workers in Sokoto with a view to achieve better control measures. A total of 195 PHC Health workers in Sokoto who met the eligibility and inclusion criteria were enlisted and enrolled into the study (descriptive cross-sectional) using table of random numbers. The data was collected using a self-administered questionnaire containing relevant questions on respondent biodata and Knowledge on the management of cases of malaria. Overall, only 71 (36.4%) of respondents were found to have adequate and effective treatment practices of malaria infection. However, age (p=0.4294), professional cadre (p=0.2988) and years of experience (p=0.1922) are not important determinants of malaria treatment pattern observed among respondents. This finding highlights ineffective treatment practices that may hinder the attainment of the goals of roll back malaria to reduce malaria cases by 50% by the year 2015. Hence periodic training and re-training of health workers based on identified gaps must be undertaken.


Microarray analyses of gene expression during chondrocyte differentiation identifies novel regulators of hypertrophy.
Ordered chondrocyte differentiation and maturation is required for normal skeletal development, but the intracellular pathways regulating this process remain largely unclear. We used Affymetrix microarrays to examine temporal gene expression patterns during chondrogenic differentiation in a mouse micromass culture system. Robust normalization of the data identified 3300 differentially expressed probe sets, which corresponds to 1772, 481, and 249 probe sets exhibiting minimum 2-, 5-, and 10-fold changes over the time period, respectively. GeneOntology annotations for molecular function show changes in the expression of molecules involved in transcriptional regulation and signal transduction among others. The expression of identified markers was confirmed by RT-PCR, and cluster analysis revealed groups of coexpressed transcripts. One gene that was up-regulated at later stages of chondrocyte differentiation was Rgs2. Overexpression of Rgs2 in the chondrogenic cell line ATDC5 resulted in accelerated hypertrophic differentiation, thus providing functional validation of microarray data. Collectively, these analyses provide novel information on the temporal expression of molecules regulating endochondral bone development.


The complement system at the fetomaternal interface.
The placenta has a unique structural organization that allows fetal cells expressing paternal alloantigens to establish a peaceful cohabitation with the maternal immune system. The fetal cells are continuously exposed to the humoral and cellular components of the maternal immune system present in the maternal blood that circulates in the intervillous space and in the decidual vessels. This review deals with the role played by the complement system at the placental level both in physiological and pathological conditions of pregnancies. Complement components found in the placental tissue derive to a large extent from blood circulating in placental vessels. However, some complement components may also be produced locally by macrophages and other cell types. Deposition of complement components at tissue level is usually found in association with inflammatory diseases. This is not the case in placentae in which deposits of complement components can also be documented in physiological conditions not resulting in fetal damage. Protection of the semiallogenic human conceptus against maternal complement activation products is achieved by surface expression of complement regulators that act at different steps of the complement sequence. These complement regulators are localized in a strategic position on the surface of villous trophoblast protecting the fetus from the damage that may derive from uncontrolled complement activation. However, pathological conditions of pregnancies may lead to deposition of a higher amount of complement activation products that may exceed the protection of local complement regulators.


Comparison of professionalism between emergency medicine resident physicians and faculty physicians: A multicenter cross-sectional study.
Professionalism is a critical competency for emergency medicine (EM) physicians, and professional behavior affects patient satisfaction. However, the findings of various studies indicate that there are differences in the interpretation of professionalism among EM resident physicians and faculty physicians. Using a cross-sectional survey, we aimed to analyze common challenges to medical professionalism for Japanese EM physicians and survey the extent of professionalism coursework completed during undergraduate medical education. We conducted a multicenter cross-sectional survey of EM resident physicians and faculty physicians at academic conferences and eight teaching hospitals in Japan using the questionnaire by Barry and colleagues. We analyzed the frequency of providing either the best or second-best answers to each scenario as the main outcome measure and compared the frequencies between EM resident physicians and EM faculty physicians. Fisher's exact test and the Wilcoxon rank sum test were used to analyze data. A total of 176 physicians (86 EM resident physicians and 90 EM faculty physicians) completed the survey. The response rate was 92.6%. The most challenging scenario presented to participants dealt with sexual harassment, and only 44.5% chose the best or second-best answers, followed by poor responses to the confidentiality scenario (69.9%). The frequency of either the best or second-best responses to the confidentiality scenario was significantly greater for EM resident physicians than for EM faculty physicians (77.1% versus 62.9%, p = 0.048). More participants in the EM resident physician group completed formal courses in medical professionalism than those in the EM faculty physician group (25.8% versus 5.5%, p < 0.01). Further, EM faculty physicians were less likely than EM resident physicians to provide acceptable responses in terms of confidentiality, and few of both had received professionalism training through school curricula. Continuous professionalism education focused on the prevention of sexual harassment and gender gap is needed for both EM resident physicians and faculty physicians in Japan.


Folic Acid Fortification Prevents Morphological and Behavioral Consequences of X-Ray Exposure During Neurulation.
Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known. In addition, the efficacy of folic acid (FA) in preventing radiation-induced birth defects and persistent radiation-induced anomalies has remained unexplored. To assess the efficacy of FA in preventing radiation-induced defects, pregnant C57BL6/J mice were X-irradiated at embryonic day (E)7.5 and were fed FA-fortified food. FA partially prevented radiation-induced (1.0 Gy) anophthalmos, exencephaly and gastroschisis at E18, and reduced the number of pre-natal deaths, fetal weight loss and defects in the cervical vertebrae resulting from irradiation. Furthermore, FA food fortification counteracted radiation-induced impairments in vision and olfaction, which were evidenced after exposure to doses ≥0.1 Gy. These findings coincided with the observation of a reduction in thickness of the retinal ganglion cell and nerve fiber layer, and a decreased axial length of the eye following exposure to 0.5 Gy. Finally, MRI studies revealed a volumetric decrease of the hippocampus, striatum, thalamus, midbrain and pons following 0.5 Gy irradiation, which could be partially ameliorated after FA food fortification. Altogether, our study is the first to offer detailed insights into the long-term consequences of X-ray exposure during neurulation, and supports the use of FA as a radioprotectant and antiteratogen to counter the detrimental effects of X-ray exposure during this crucial period of gestation.


Anti-inflammatory effects of anethole in lipopolysaccharide-induced acute lung injury in mice.
Anethole, the major component of the essential oil of star anise, has been reported to have antioxidant, antibacterial, antifungal, anti-inflammatory, and anesthetic properties. In this study, we investigated the anti-inflammatory effects of anethole in a mouse model of acute lung injury induced by lipopolysaccharide (LPS). BALB/C mice were intraperitoneally administered anethole (62.5, 125, 250, or 500 mg/kg) 1 h before intratracheal treatment with LPS (1.5 mg/kg) and sacrificed after 4 h. The anti-inflammatory effects of anethole were assessed by measuring total protein and cell levels and inflammatory mediator production and by histological evaluation and Western blot analysis. LPS significantly increased total protein levels; numbers of total cells, including macrophages and neutrophils; and the production of inflammatory mediators such as matrix metalloproteinase 9 (MMP-9), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in bronchoalveolar lavage fluid. Anethole (250 mg/kg) decreased total protein concentrations; numbers of inflammatory cells, including neutrophils and macrophages; and the inflammatory mediators MMP-9, TNF-α and NO. In addition, pretreatment with anethole decreased LPS-induced histopathological changes. The anti-inflammatory mechanism of anethole in LPS-induced acute lung injury was assessed by investigating the effects of anethole on NF-κB activation. Anethole suppressed the activation of NF-κB by blocking IκB-α degradation. These results, showing that anethole prevents LPS-induced acute lung inflammation in mice, suggest that anethole may be therapeutically effective in inflammatory conditions in humans.


Brain Modulyzer: Interactive Visual Analysis of Functional Brain Connectivity.
We present Brain Modulyzer, an interactive visual exploration tool for functional magnetic resonance imaging (fMRI) brain scans, aimed at analyzing the correlation between different brain regions when resting or when performing mental tasks. Brain Modulyzer combines multiple coordinated views-such as heat maps, node link diagrams and anatomical views-using brushing and linking to provide an anatomical context for brain connectivity data. Integrating methods from graph theory and analysis, e.g., community detection and derived graph measures, makes it possible to explore the modular and hierarchical organization of functional brain networks. Providing immediate feedback by displaying analysis results instantaneously while changing parameters gives neuroscientists a powerful means to comprehend complex brain structure more effectively and efficiently and supports forming hypotheses that can then be validated via statistical analysis. To demonstrate the utility of our tool, we present two case studies-exploring progressive supranuclear palsy, as well as memory encoding and retrieval.


An integrated system for DNA sequencing by synthesis using novel nucleotide analogues.
The Human Genome Project has concluded, but its successful completion has increased, rather than decreased, the need for high-throughput DNA sequencing technologies. The possibility of clinically screening a full genome for an individual's mutations offers tremendous benefits, both for pursuing personalized medicine and for uncovering the genomic contributions to diseases. The Sanger sequencing method, although enormously productive for more than 30 years, requires an electrophoretic separation step that, unfortunately, remains a key technical obstacle for achieving economically acceptable full-genome results. Alternative sequencing approaches thus focus on innovations that can reduce costs. The DNA sequencing by synthesis (SBS) approach has shown great promise as a new sequencing platform, with particular progress reported recently. The general fluorescent SBS approach involves (i) incorporation of nucleotide analogs bearing fluorescent reporters, (ii) identification of the incorporated nucleotide by its fluorescent emissions, and (iii) cleavage of the fluorophore, along with the reinitiation of the polymerase reaction for continuing sequence determination. In this Account, we review the construction of a DNA-immobilized chip and the development of novel nucleotide reporters for the SBS sequencing platform. Click chemistry, with its high selectivity and coupling efficiency, was explored for surface immobilization of DNA. The first generation (G-1) modified nucleotides for SBS feature a small chemical moiety capping the 3'-OH and a fluorophore tethered to the base through a chemically cleavable linker; the design ensures that the nucleotide reporters are good substrates for the polymerase. The 3'-capping moiety and the fluorophore on the DNA extension products, generated by the incorporation of the G-1 modified nucleotides, are cleaved simultaneously to reinitiate the polymerase reaction. The sequence of a DNA template immobilized on a surface via click chemistry is unambiguously identified with this chip-SBS system. The second generation (G-2) SBS system was developed based on the concept that the closer the structures of the added nucleotide and the primer are to their natural counterparts, the more faithfully the polymerase would incorporate the nucleotide. In this approach, the polymerase reaction is performed with the combination of 3'-capped nucleotide reversible terminators (NRTs) and cleavable fluorescent dideoxynucleotides (ddNTPs). By sacrifice of a small amount of the primers permanently terminated by ddNTPs, the majority of the primers extended by the reversible terminators are reverted to the natural ones after each sequencing cycle. We have also developed the 3'-capped nucleotide reversible terminators to solve the problem of deciphering the homopolymeric regions of the template in conventional pyrosequencing. The 3'-capping moiety on the DNA extension product temporarily terminates the polymerase reaction, which allows only one nucleotide to be incorporated during each sequencing cycle. Thus, the number of nucleotides in the homopolymeric regions are unambiguously determined using the 3'-capped NRTs. It has been established that millions of DNA templates can be immobilized on a chip surface through a variety of approaches. Therefore, the integration of these high-density DNA chips with the molecular-level SBS approaches described in this Account is expected to generate a high-throughput and accurate DNA sequencing system with wide applications in biological research and health care.


Composition and diversity of soil bacterial communities under identical vegetation along an elevational gradient in Changbai Mountains, China.
Soil bacteria play important roles in biogeochemical cycling and biodiversity in mountain ecosystems. Past studies have investigated the bacterial community composition and diversity in elevation gradations covered by different vegetation types, but for a better assessment of elevation effects, here we studied bacterial communities in soil under identical vegetation cover. High-throughput amplicon sequencing of the V3-V4 region of bacterial 16S rDNA was used to investigate the diversity and composition bacterial communities in soil from 700 to 1,000 m above sea level collected on the north slope of Changbai Mountains, Northeast China. Obviously differences (p < 0.05) in soil physicochemical parameters (i.e., total nitrogen, nitrate and ammonium nitrogen, soil moisture content, available potassium, microbial biomass carbon and nitrogen) were observed at different elevations. Soil bacterial abundance indices (Richness, Chao1, ACE) differed significantly along the elevation gradient, whereas the Shannon index remained unchanged. Principal Coordinates Analysis indicated separated soil bacterial communities of the different elevations. The dominant phyla in all soil samples were Proteobacteria, Acidobacteria, Actinobacteria, Verrucomicrobia, and Bacteroidetes, which in combination reached 80%-85%. Soil pH to some extend related to soil bacterial community along altitude gradations. The relative abundance of a multiple phyla was negatively affected by the soil nutrients, such as ammonium and nitrate nitrogen, available potassium, soil moisture content, available phosphorus, microbial biomass nitrogen and soil organic C. The strongest effects were seen for Proteobacteria. The pH either positively or negatively correlated with specific genera. The soil bacterial function differed significantly among four elevations. The chemoheterotrophy, aerobic chemoheterotrophy and nitrification were the most dominant functions of soil bacteria among four elevations. Overall, the changes in soil physicochemical properties with elevation are important in shaping the bacterial diversity, composition and function in soil with the same above-ground vegetation of Changbai Mountains.


Perilipin polymorphism interacts with dietary carbohydrates to modulate anthropometric traits in hispanics of Caribbean origin.
Perilipin (PLIN) is the major protein surrounding lipid droplets in adipocytes and regulates adipocyte metabolism by modulating the interaction between lipases and triacylglycerol stores. Associations between PLIN gene polymorphisms and obesity risk have been described, but interactions with dietary macronutrients require further attention. We examined whether dietary macronutrients (e.g. carbohydrates and fats) modulated the associations of the common PLIN 11482G > A (rs894160) single nucleotide polymorphism with obesity. We studied a population-based sample of Caribbean-origin Hispanics (n = 920, aged 45-74 y) living in the Boston area. Obesity measures (waist and hip circumference, BMI) did not differ between GG subjects and carriers of the A allele (GA and AA). In multivariate linear regression models, we found a significant interaction between complex carbohydrate intake as a continuous variable and PLIN 11482 G > A genotype for waist circumference (P = 0.002). By dichotomizing complex carbohydrate intake, we found significantly different effects across PLIN 11482G > A genotypes. When complex carbohydrate intake was <144 g/d, waist circumference was larger in PLIN 11482G > A carriers (P = 0.024). Conversely, when complex carbohydrate intake was >/=144 g/d, waist and hip circumferences were less in PLIN 11482G > A carriers (P < 0.05). These interactions were not found for simple sugars or total carbohydrates. We identified a significant gene-diet interaction associated with obesity at the PLIN locus. In subjects with higher complex carbohydrate intake, the minor allele was protective against obesity, whereas in subjects with lower carbohydrate intake, the minor allele was associated with increased obesity. These interactions may be relevant to dietary management of obesity.


A reverse transcriptase-polymerase chain reaction assay for the diagnosis of turkey coronavirus infection.
This study reports on the development of a reverse transcriptase-polymerase chain reaction (RT-PCR) for the specific detection of turkey coronavirus (TCoV). Of the several sets of primers tested, 1 set of primers derived from the P gene and 2 sets derived from the N gene of TCoV could amplify the TCoV genome in the infected samples. The RT-PCR was sensitive and specific for TCoV and did not amplify other avian RNA and DNA viruses tested except the infectious bronchitis virus (IBV). To overcome the problem of IBV amplification, a set of separate primers was designed from the spike protein gene of IBV. The RT-PCR under the same conditions as above could effectively differentiate between TCoV and IBV. The closely related bovine coronavirus and transmissible gastroenteritis virus of pigs were differentiated from TCoV using the same RT-PCR with slight modifications. The results of RT-PCR correlated well with the results of the immunofluorescent test for the same samples tested at the Purdue University Animal Disease Laboratory, West Lafayette, Indiana. The nucleotide sequence and projected amino acid sequence comparison of the P gene of different isolates of TCoV from 5 different states in the United States revealed a close association among the different isolates of TCoV.


Novel TCAP mutation c.32C>A causing limb girdle muscular dystrophy 2G.
TCAP encoded telethonin is a 19 kDa protein, which plays an important role in anchoring titin in Z disc of the sarcomere, and is known to cause LGMD2G, a rare muscle disorder characterised by proximal and distal lower limb weakness, calf hypertrophy and loss of ambulation. A total of 300 individuals with ARLGMD were recruited for this study. Among these we identified 8 clinically well characterised LGMD2G cases from 7 unrelated Dravidian families. Clinical examination revealed predominantly proximo-distal form of weakness, scapular winging, muscle atrophy, calf hypertrophy and foot drop, immunoblot showed either complete absence or severe reduction of telethonin. Genetic analysis revealed a novel nonsense homozygous mutation c.32C>A, p.(Ser11*) in three patients of a consanguineous family and an 8 bp homozygous duplication c.26_33dupAGGTGTCG, p.(Arg12fs31*) in another patient. Both mutations possibly lead to truncated protein or nonsense mediated decay. We could not find any functionally significant TCAP mutation in the remaining 6 samples, except for two other polymorphisms, c.453A>C, p.( = ) and c.-178G>T, which were found in cases and controls. This is the first report from India to demonstrate TCAP association with LGMD2G.


PADÉ APPROXIMANTS AND EXACT TWO-LOCUS SAMPLING DISTRIBUTIONS.
For population genetics models with recombination, obtaining an exact, analytic sampling distribution has remained a challenging open problem for several decades. Recently, a new perspective based on asymptotic series has been introduced to make progress on this problem. Specifically, closed-form expressions have been derived for the first few terms in an asymptotic expansion of the two-locus sampling distribution when the recombination rate ρ is moderate to large. In this paper, a new computational technique is developed for finding the asymptotic expansion to an arbitrary order. Computation in this new approach can be automated easily. Furthermore, it is proved here that only a finite number of terms in the asymptotic expansion is needed to recover (via the method of Padé approximants) the exact two-locus sampling distribution as an analytic function of ρ; this function is exact for all values of ρ ∈ [0, ∞). It is also shown that the new computational framework presented here is flexible enough to incorporate natural selection.


A genome-wide assessment of the role of untagged copy number variants in type 1 diabetes.
Genome-wide association studies (GWAS) for type 1 diabetes (T1D) have successfully identified more than 40 independent T1D associated tagging single nucleotide polymorphisms (SNPs). However, owing to technical limitations of copy number variants (CNVs) genotyping assays, the assessment of the role of CNVs has been limited to the subset of these in high linkage disequilibrium with tag SNPs. The contribution of untagged CNVs, often multi-allelic and difficult to genotype using existing assays, to the heritability of T1D remains an open question. To investigate this issue, we designed a custom comparative genetic hybridization array (aCGH) specifically designed to assay untagged CNV loci identified from a variety of sources. To overcome the technical limitations of the case control design for this class of CNVs, we genotyped the Type 1 Diabetes Genetics Consortium (T1DGC) family resource (representing 3,903 transmissions from parents to affected offspring) and used an association testing strategy that does not necessitate obtaining discrete genotypes. Our design targeted 4,309 CNVs, of which 3,410 passed stringent quality control filters. As a positive control, the scan confirmed the known T1D association at the INS locus by direct typing of the 5' variable number of tandem repeat (VNTR) locus. Our results clarify the fact that the disease association is indistinguishable from the two main polymorphic allele classes of the INS VNTR, class I-and class III. We also identified novel technical artifacts resulting into spurious associations at the somatically rearranging loci, T cell receptor, TCRA/TCRD and TCRB, and Immunoglobulin heavy chain, IGH, loci on chromosomes 14q11.2, 7q34 and 14q32.33, respectively. However, our data did not identify novel T1D loci. Our results do not support a major role of untagged CNVs in T1D heritability.


The dynamic disulphide relay of quiescin sulphydryl oxidase.
Protein stability, assembly, localization and regulation often depend on the formation of disulphide crosslinks between cysteine side chains. Enzymes known as sulphydryl oxidases catalyse de novo disulphide formation and initiate intra- and intermolecular dithiol/disulphide relays to deliver the disulphides to substrate proteins. Quiescin sulphydryl oxidase (QSOX) is a unique, multi-domain disulphide catalyst that is localized primarily to the Golgi apparatus and secreted fluids and has attracted attention owing to its overproduction in tumours. In addition to its physiological importance, QSOX is a mechanistically intriguing enzyme, encompassing functions typically carried out by a series of proteins in other disulphide-formation pathways. How disulphides are relayed through the multiple redox-active sites of QSOX and whether there is a functional benefit to concatenating these sites on a single polypeptide are open questions. Here we present the first crystal structure of an intact QSOX enzyme, derived from a trypanosome parasite. Notably, sequential sites in the disulphide relay were found more than 40 Å apart in this structure, too far for direct disulphide transfer. To resolve this puzzle, we trapped and crystallized an intermediate in the disulphide hand-off, which showed a 165° domain rotation relative to the original structure, bringing the two active sites within disulphide-bonding distance. The comparable structure of a mammalian QSOX enzyme, also presented here, shows further biochemical features that facilitate disulphide transfer in metazoan orthologues. Finally, we quantified the contribution of concatenation to QSOX activity, providing general lessons for the understanding of multi-domain enzymes and the design of new catalytic relays.


Biobanking-Budgets and the Role of Pathology Biobanks in Precision Medicine.
Biobanks have become an important component of the routine practice of pathology. At the 2016 meeting of the Association of Pathology Chairs, a series of presentations covered several important aspects of biobanking. An often overlooked aspect of biobanking is the fiscal considerations. A biobank budget must address the costs of consenting, procuring, processing, and preserving high-quality biospecimens. Multiple revenue streams will frequently be necessary to create a sustainable biobank; partnering with other key stakeholders has been shown to be successful at academic institutions which may serve as a model. Biobanking needs to be a deeply science-driven and innovating process so that specimens help transform patient-centered clinical and basic research (ie, fulfill the promise of precision medicine). Pathology's role must be at the center of the biobanking process. This ensures that optimal research samples are collected while guaranteeing that clinical diagnostics are never impaired. Biobanks will continue to grow as important components in the mission of pathology, especially in the era of precision medicine.


Specification of neurepithelium and surface epithelium in avian transplantation chimeras.
Previous studies of the avian blastoderm have revealed that extensive displacements occur within the epiblast during gastrulation and neurulation. The present study had two main purposes: (1) to map the origin and movement of prospective surface epithelial cells, and (2) to ask whether neurepithelial and surface epithelial cell fates are determined prior to cell movement, or whether they arise later as a result of the ultimate position attained by cells through their movement. Our results show that the rostral and lateral intraembryonic and extraembryonic surface epithelium originates as far laterally as at the area pellucida-area opaca interface of the early epiblast. Intraembryonic surface epithelial cells rearrange relative to one another, extending medially to contribute to the formation of the neural folds, whereas extraembryonic surface epithelial cells maintain their lateral positions, spreading uniformly as the epiblast expands. Our results further show that surface epithelial and neurepithelial cell fates are labile at the onset of neurulation, suggesting that cell fate is specified following cell movement.


Folic acid therapy reduces the risk of mortality associated with heavy proteinuria among hypertensive patients.
We aimed to evaluate whether proteinuria and estimated glomerular filtration rate (eGFR) levels can modify the efficacy of folic acid therapy on the risk of all-cause mortality among hypertensive patients in the China Stroke Primary Prevention Trial, a randomized, double-blind, and controlled trial. A total of 20 702 hypertensive patients without a history of major cardiovascular diseases were randomly assigned to a double-blind daily treatment of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (n = 10 348), or 10-mg enalapril alone (n = 10 354). All-cause mortality, a prespecified endpoint of the China Stroke Primary Prevention Trial, was the main outcome in this analysis. Over a median treatment duration of 4.5 years, in the enalapril alone group, both heavy proteinuria [vs. absent, 10.8 vs. 2.7%; hazard ratio = 3.30; 95% confidence interval (CI): 2.10-5.18] and lower eGFR levels (<60 vs. ≥90 ml/min per 1.73 m, 13.0 vs. 2.2%; hazard ratio = 1.93; 95% CI: 1.19-3.12) were significantly associated with increased risk of all-cause mortality. Folic acid supplementation significantly reduced the risk of all-cause mortality in patients with heavy proteinuria (6.4% in the enalapril-folic acid vs. 10.8% in the enalapril alone group, hazard ratio = 0.49; 95% CI: 0.26-0.94), but not in those with absent or mild proteinuria (2.8 vs. 2.9%, hazard ratio = 0.99; 95% CI: 0.84-1.17; P for interaction = 0.040). However, eGFR levels did not significantly modify the effect of folic acid supplementation in reducing the risk of all-cause mortality (P for interaction = 0.228). Among hypertensive patients without a history of major cardiovascular diseases, folic acid therapy could reduce the mortality risk associated with heavy proteinuria.


From the factory model to the classroom-workshop: Learning from practice in the fields of health and education.
In this article, we engage in a dialogue about structural competencies based on the proposal of the classroom-workshop, aimed at educational and work environments in the fields of health and education. Our starting point is the notion that practical experiences do not merely represent a collection of specialised technical knowledge, as they are part of the complexity of the social game. Drawing from the theoretical frameworks of Pierce, Gadamer, Freire, and others, the proposal of the classroom-workshop recovers the power of collective praxis. Learning from and with others becomes central in the social game in order to collectively appropriate knowledge by making the autonomy of learning as horizontal as possible. By centering the relational world of learning and working, the classroom-workshop recovers the circular structure of understanding that enables a reflective appropriation of the territory - understood as the social space where life takes place - while de-instrumentalizing the reading of theoretical traditions and resignifiying the practice of writing. It establishes connections, links, and anchors that enable a dialogue between theory and practice, so often dissociated and fragmented.


Development of a solid-phase assay for measurement of sulfated glycosaminoglycan concentrations in equine synovial fluid.
To develop a new 1,9-dimethylmethylene blue (DMMB) assay for measurement of sulfated glycosaminoglycan (sGAG) concentrations in equine synovial fluid (SF) by use of membrane technology and to compare the assay's ability to measure sGAG concentrations with that of 2 other established DMMB assays. 25 samples of SF collected from affected joints of 14 horses and 13 samples of SF collected from nonaffected (control) joints of 4 horses. A solid-phase DMMB assay was developed to measure sGAG concentrations in SE Results for the assay were then compared with results obtained by use of the direct spectrophotometric method (ie, Famdale method) and microplate DMMB assay. The solid-phase assay and direct spectrophotometric assay measured the same sGAG concentrations in identical equine SF, but those concentrations differed significantly from results obtained by use of the microplate DMMB assay. All other aspects of the solid-phase DMMB assay were comparable to both the direct spectrophotometric and microplate DMMB assays. The new solid-phase assay can be used interchangeably with the direct spectrophotometric method to measure sGAG concentrations in equine SF samples, but it cannot be interchanged with the microplate DMMB assay. Results can be rapidly obtained with the solid-phase assay. Also, the solid-phase assay can detect nanogram quantities of sGAGs in SF, circumvent the problem of premature precipitation of sGAG-dye complexes, and provide quantitative or qualitative results. The solid-phase assay may replace other DMMB assays for measuring sGAG concentrations in SF obtained from horses.


IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells.
The role of immune responses in tumor development is a central issue for tumor biology and immunology. IL-17 is an important cytokine for inflammatory and autoimmune diseases. Although IL-17-producing cells are detected in cancer patients and tumor-bearing mice, the role of IL-17 in tumor development is controversial, and mechanisms remain to be fully elucidated. In the current study, we found that the development of tumors was inhibited in IL-17R-deficient mice. A defect in IFN-gammaR increased tumor growth, whereas tumor growth was inhibited in mice that were deficient in both IL-17R and IFN-gammaR compared with wild-type animals. Further experiments showed that neutralization of IL-17 by Abs inhibited tumor growth in wild-type mice, whereas systemic administration of IL-17 promoted tumor growth. The IL-17R deficiency increased CD8 T cell infiltration, whereas it reduced the infiltration of myeloid-derived suppressor cells (MDSCs) in tumors. In contrast, administration of IL-17 inhibited CD8 T cell infiltration and increased MDSCs in tumors. Further analysis indicated that IL-17 was required for the development and tumor-promoting activity of MDSCs in tumor-bearing mice. These data demonstrate that IL-17-mediated responses promote tumor development through the induction of tumor-promoting microenvironments at tumor sites. IL-17-mediated regulation of MDSCs is a primary mechanism for its tumor-promoting effects. The study provides novel insights into the role of IL-17 in tumor development and has major implications for targeting IL-17 in treatment of tumors.


Serologic survey of swine workers for exposure to H2N3 swine influenza A.
Of the 16 influenza A hemagglutinin (H) subtypes, only H1, H2 and H3 viruses have been shown to cause sustained human infection. Whereas H1 and H3 viruses currently circulate seasonally in humans, H2 viruses have not been identified in humans since 1968. In 2006, an H2N3 influenza virus was isolated from ill swine in the United States. To assess the potential for zoonotic influenza transmission, the current study looked for serologic evidence of H2 influenza infection among workers at two swine facilities, some exposed and some unexposed to H2N3-positive pigs. The sera were assessed for antibodies to swine H2 influenza and currently circulating seasonal human influenza A subtypes H1N1 and H3N2. Workers were interviewed to obtain details such as age, influenza vaccination history, experiences of influenza-like-illness, and use of personal protective equipment and hygiene when working with pigs. Exposure and risk factors for positive antibody titers were compared for exposed and unexposed individuals as well as for H2 antibody-positive and H2 antibody-negative individuals. Blood was taken from 27 swine workers, of whom four had positive H2 antibody titers (> or = 1:40). Three of the positive employees were born before 1968 and one had an unknown birth date. Only one of these workers had been exposed to H2N3-positive pigs, and he was born in 1949. These data do not support the hypothesis that swine workers were infected with the emergent swine H2N3 influenza A virus.


The regulation of distention-induced ATP release from urothelium by the adenylyl cyclase-cyclic AMP pathway.
Distention of the bladder during urine storage induces ATP release from urothelium, thereby facilitating transmission of visceral sensory signals to afferent nerve fibers. An excess of urothelial ATP release was found in interstitial cystitis, a condition accompanied by hyperesthesia of the urinary bladder; it remains unclear which signals are involved in this upregulation. The present study demonstrated that the adenylyl cyclase pathway enhances distention-induced ATP release in mouse bladder. In the absence of distention, adenylyl cyclase activation by forskolin or cyclic AMP increases by rolipram did not induce significant ATP release. However, forskolin or rolipram significantly enhanced ATP release from urothelium by a physiologically normal urine storage pressure (5 cmH(2)O). Blockade of adenylyl cyclases did not alter pressure-induced ATP release in normal condition. Thus, the adenylyl cyclase-cAMP pathway might be activated in pathological conditions and cause an excess of ATP release.


Glutamine protects ischemia-reperfusion induced acute lung injury in isolated rat lungs.
Glutamine has been used to treat a number of diseases via modulating the inflammatory response. The purpose of this study is to investigate whether glutamine has a beneficial effect in ischemia-reperfusion (IR) induced acute lung injury in an isolated rat lung model. Typical acute lung injury in rats was successfully induced by 60 min of ischemia and 60 min of reperfusion. At the end of experiment, bronchoalveolar lavage fluid (BALF), perfusate and lung tissues were collected to evaluate the degree of lung injury. Glutamine (20 mM) was administrated before ischemia or after ischemia. IR caused a significant increase in the capillary filtration coefficient; lung weight gain; lung weight to body weight ratio; wet to dry weight ratio; pulmonary arterial pressure; and protein concentration and lactate dehydrogenase level in BALF. Tumor necrosis factor-α and cytokine induced neutrophil chemoattractant-1 in perfusate, and malondialdehyde levels, carbonyl content and myeloperoxidase activities in lung tissue were also significantly increased. In addition, the lung tissues showed increased septal thickness and neutrophil infiltration. Furthermore, NF-κB activity and degradation of IκB-α were significantly increased in the lungs. Treatment with glutamine before ischemia or after ischemia significantly decreased the increase in these parameters. Our study showed that glutamine treatment decreased IR-induced acute lung injury. The protective mechanism may be due to the inhibition of NF-κB activation and the attenuation of oxidative stress.


Intraoperative use of low-field magnetic resonance imaging for brain tumors: A systematic review.
Low-field magnetic resonance imaging (LF-MRI) has become a valuable tool in the diagnosis of brain tumors due to its high spatial resolution and ability to acquire images in a short amount of time. However, the use of LF-MRI for intraoperative imaging during brain tumor surgeries has not been extensively studied. The aim of this systematic review is to investigate the impact of low-field intraoperative magnetic resonance imaging (LF-IMRI) on the duration of brain tumor surgery and the extent of tumor resection. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar from February 2000 to December 2022. The studies were selected based on the inclusion criteria and reviewed independently by two reviewers. The gathered information was organized and analyzed using Excel. Our review of 21 articles found that low-field intraoperative MRI (LF-IMRI) with a field below 0.3T was used in most of the studies, specifically 15 studies used 0.15T LF-IMRI. The T1-weighted sequence was the most frequently reported, and the average scanning time was 24.26 min. The majority of the studies reported a positive impact of LF-IMRI on the extent of tumor resection, with an increase ranging from 11% to 52.5%. Notably, there were no studies describing the use of ultra-low-field (ULF) intraoperative MRI. The results of this systematic review will aid neurosurgeons and neuroradiologists in making informed decisions about the use of LF-MRI in brain tumor surgeries. Further, research is needed to fully understand the impact of LF-MRI in brain tumor surgeries and to optimize its use in the clinical setting. There is an opportunity to study the utility of ULF-MRI in brain tumor surgeries.


Primary apocrine adenocarcinoma of scrotum suspected as urothelial carcinoma metastasis: A clinical and pathological dilemma.
A 78-year-old man presented with an enlarging, tender mass in the scrotum separate to the testes. This was on the background of radical cystoprostatectomy, urethrectomy, and ileal conduit formation for high-grade urothelial carcinoma of the bladder invading submucosa 3 years prior. Examination revealed a 4 × 5 cm lesion, which was hard, fixed to the overlying skin and nodular to palpation. Ultrasound confirmed a solid mass in the scrotum extending into the perineum. Computerized tomography of the chest, abdomen, and pelvis revealed enlargement of inguinal lymph nodes but no other metastases. Complete resection of the scrotal lesion and selective removal of regional lymph nodes was performed. Rather than a cutaneous scrotal metastasis from the bladder urothelial carcinoma, histological examination suggested a primary apocrine adenocarcinoma of the scrotum. This case report explores the clinical and pathological features associated with both of these unusual differential diagnoses.


Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes.
For most intracellular structures with larger than molecular dimensions, little is known about the connection between underlying molecular activities and higher order organization such as size and shape. Here, we show that both the size and shape of the amphibian oocyte nucleolus ultimately arise because nucleoli behave as liquid-like droplets of RNA and protein, exhibiting characteristic viscous fluid dynamics even on timescales of < 1 min. We use these dynamics to determine an apparent nucleolar viscosity, and we show that this viscosity is ATP-dependent, suggesting a role for active processes in fluidizing internal contents. Nucleolar surface tension and fluidity cause their restructuring into spherical droplets upon imposed mechanical deformations. Nucleoli exhibit a broad distribution of sizes with a characteristic power law, which we show is a consequence of spontaneous coalescence events. These results have implications for the function of nucleoli in ribosome subunit processing and provide a physical link between activity within a macromolecular assembly and its physical properties on larger length scales.


Transitioning from Adolescent to Adult Mental Health Services: An Integrative Literature Review.
This article aims to present a review of the peer-reviewed, published literature related to the transition from adolescent mental health services to adult mental health services. Six databases (PubMED, Medline, PsycINFO, CINAHL, EMBASE, and Google Scholar) were searched for peer-reviewed, published literature on the transition from adolescent to adult mental health services. Articles on primary research were included in the review if they were published in English between 2000 and 2018, and if they were explicitly about alignment and/or transition between adolescent and adult mental health services. Fifty articles were included in the final review. The findings are discussed in two overarching streams of research from the literature: evaluations of transition arrangements, and the perspectives of various stakeholders (including consumers, carers, and health professionals). The results emphasise the problematic siloes of adolescent and adult mental health services. While there are still no randomised controlled trials on transition to assess transition pathways, our findings have implications to inform best practice in the sector. Given that transitioning to adult mental health services is seen as a point of vulnerability for young people, this review contributes to understandings about how services can offer better support during transition periods.


Male crickets adjust their aggressive behavior when a female is present.
Communication in nature often occurs within a broad social network, as signals can be perceived by other individuals beyond the primary intended receiver. Because signals often contain information about the signaller's quality, receivers other than the primary intended receiver may use this information in future interactions with the signaller. As a result, individuals who adjust their behavior depending on who is present may experience a selective advantage. The social environment can therefore have an important influence on the evolution of communication signals. We examined how the presence of a female audience influenced male aggressive behavior and post-contest victory displays in the Jamaican field cricket, Gryllus assimilis. We found a significant effect of female audience on aggressive interactions. When there was a female audience present, males were more likely to initiate and escalate fights, but they spent less time producing victory displays, compared to when there was no audience present. Our experiment suggests that the social environment is important in shaping the behavior of individuals during aggressive interactions.


Renal insufficiency in elderly cancer patients: International Society of Geriatric Oncology clinical practice recommendations.
Elderly cancer patients commonly have renal function decline. This warrants particular caution during the administration of renally excreted cancer drugs or those with established nephrotoxicity. An International Society for Geriatric Oncology task force was formed to discuss treatment recommendations for this group of patients. Before drug therapy, the assessment and optimization of hydration status and evaluation of renal function is required. Serum creatinine alone is insufficient as a means of evaluating renal function, and creatinine clearance should at least be calculated in every patient by the abbreviated modification of diet in renal disease or Cockcroft-Gault equations. In the extremes of obesity and cachexia and at very high and low creatinine values, no single tool is really accurate. In these patients, the best estimate of glomerular filtration rate is provided by direct methods such as (51)Cr-EDTA or inulin measurement. Within each drug class, preference may be given to agents less likely to be influenced by renal clearance, which are minimally nephrotoxic, or for which appropriate methods of prevention for renal toxicity exist. Coadministration of known nephrotoxic drugs should be avoided or minimized. Future trials should be designed to present data in a way that allows evaluation of the contribution of renal function to toxicity and efficacy.


Aminated Graphene-Graft-Oligo(Glutamic Acid) /Poly(ε-Caprolactone) Composites: Preparation, Characterization and Biological Evaluation.
Biodegradable and biocompatible composites are of great interest as biomedical materials for various regeneration processes such as the regeneration of bones, cartilage and soft tissues. Modification of the filler surface can improve its compatibility with the polymer matrix, and, as a result, the characteristics and properties of composite materials. This work is devoted to the synthesis and modification of aminated graphene with oligomers of glutamic acid and their use for the preparation of composite materials based on poly(ε-caprolactone). Ring-opening polymerization of N-carboxyanhydride of glutamic acid γ-benzyl ester was used to graft oligomers of glutamic acid from the surface of aminated graphene. The success of the modification was confirmed by Fourier-transform infrared and X-ray photoelectron spectroscopy as well as thermogravimetric analysis. In addition, the dispersions of neat and modified aminated graphene were analyzed by dynamic and electrophoretic light scattering to monitor changes in the characteristics due to modification. The poly(ε-caprolactone) films filled with neat and modified aminated graphene were manufactured and carefully characterized for their mechanical and biological properties. Grafting of glutamic acid oligomers from the surface of aminated graphene improved the distribution of the filler in the polymer matrix that, in turn, positively affected the mechanical properties of composite materials in comparison to ones containing the unmodified filler. Moreover, the modification improved the biocompatibility of the filler with human MG-63 osteoblast-like cells.


The costs and benefits of positive illusions.
Positive illusions are associated with unrealistic optimism about the future and an inflated assessment of one's abilities. They are prevalent in normal life and are considered essential for maintaining a healthy mental state, although, there are disagreements to the extent to which people demonstrate these positive illusions and whether they are beneficial or not. But whatever the situation, it is hard to dismiss their existence and their positive and/or negative influence on human behavior and decision making in general. Prominent among illusions is that of control, that is "the tendency for people to overestimate their ability to control events." This paper describes positive illusions, their potential benefits but also quantifies their costs in five specific fields (gambling, stock and other markets, new firms and startups, preventive medicine and wars). It is organized into three parts. First the psychological reasons giving rise to positive illusions are described and their likely harm and benefits stated. Second, their negative consequences are presented and their costs are quantified in five areas seriously affected with emphasis to those related to the illusion of control that seems to dominate those of unrealistic optimism. The costs involved are huge and serious efforts must be undertaken to understand their enormity and steps taken to avoid them in the future. Finally, there is a concluding section where the challenges related to positive illusions are noted and directions for future research are presented.


Targeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer.
Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro. In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway. The inhibition efficiency of PI3K/Akt/mTOR pathway was detected by RT-PCR and Western blot. Cell proliferation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8, Transwell, and flow cytometry assays. The expression of apoptosis-related proteins (cleavage caspase 3, Bcl-2, Bax, and Bim) were also detected. We found that in HT-29 and HCT-116 cells, the treatment of BEZ235 (1 μM) and PI3KCA knockdown inhibited the activation of PI3K/Akt/mTOR pathway and significantly suppressed cell proliferation, migration, and invasion of HT-29 and HCT-116 cells. In addition, we confirmed that knockdown of BEZ235 and PI3KCA induced cell apoptosis through the upregulated levels of cleavage caspase 3 and Bax and downregulated expression of Bcl-2 and Bim. Our results indicated that targeted inhibition of the PI3K/Akt/mTOR pathway impaired cell proliferation, survival, and invasion in human colon cancer.


Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors.
A National Cancer Institute summit meeting on gastroenteropancreatic neuroendocrine and carcinoid tumors was held in September 2007 to present the currently accepted standards of care for patients with these tumors and to identify areas requiring investigation and development. These tumors are clinically and pathologically heterogeneous, present commonly with obscure symptoms that lead to delays in diagnosis of years, and have an incidence in the United States of 2.5 to 5 cases per 100,000. The 5-year survival rates range between 15% and 95%, depending on the site and extent of disease. This report delineates the main conclusions of the meeting, including the best practice diagnosis and treatment strategies for gastropancreatic neuroendocrine tumors, and the identification of clinical and scientific areas that are most in need of attention. The most pressing needs were public and physician education, identification of molecular markers for early diagnosis and therapeutic monitoring, improved imaging modalities and molecular prognostication, development of a standardized pathological classification system, and creation of regional centers of expertise with tumor and laboratory data banks. In addition, adequately validated neuroendocrine tumor models and cell lines should be established to investigate the molecular mechanisms involved in the control of their growth and secretion, and to facilitate the development of specific therapies that should be examined in well-designed multicenter studies of defined patient groups.


Developing consistent data and methods to measure the public health impacts of ambient air quality for Environmental Public Health Tracking: progress to date and future directions.
Environmental Public Health Tracking (EPHT) staff at the state and national levels are developing nationally consistent data and methods to estimate the impact of ozone and fine particulate matter on hospitalizations for asthma and myocardial infarction. Pilot projects have demonstrated the feasibility of pooling state hospitalization data and linking these data to The United States Environmental Protection Agency (EPA) statistically based ambient air estimates for ozone and fine particulates. Tools were developed to perform case-crossover analyses to estimate concentration-response (C-R) functions. A weakness of analyzing one state at a time is that the effects are relatively small compared to their confidence intervals. The EPHT program will explore ways to statistically combine the results of peer-reviewed analyses from across the country to provide more robust C-R functions and health impact estimates at the local level. One challenge will be to routinely share data for these types of analyses at fine geographic and temporal scales without disclosing confidential information. Another challenge will be to develop C-R estimates which take into account time, space, or other relevant effect modifiers.


The impact of host's genetic susceptibility on Helicobacter pylori infection in children.
The aim of our study was to investigate the impact of interleukin (IL)-6 190C/T, IL-6 174G/C, IL-6 572G/C, tumor necrosis factor-alpha (TNF-α) 308G/A, and angiotensin-converting enzyme (ACE) I/D gene polymorphisms on Helicobacter pylori (H. pylori) infection in children.A cross-sectional study was performed on 126 children (57 children with H. pylori infection and 69 children without H. pylori infection) aged between 3 and 18 years presenting to a Pediatrics Tertiary Hospital from Romania. Children were assessed clinically, endoscopically, histopathologically, and genetically.In our study, we found that the presence of the CT and CT+TT genotypes of IL-6 190C/T (P < .002 and P = .04), allele G of IL-6 572 G/C polymorphism (P = .01), genotypes GA and AA of TNF-α 308 G/A polymorphism (P = .04, P = .01), and genotype II of ACE I/D polymorphism (P = .02) were associated with H. pylori infection, while the CC genotype of IL-6 174G/C polymorphism was scarcely encountered in children with H. pylori infection [P = .02, odds ratio (OR) = 0.06; 95% confidence interval (95% CI): 0.003-0.128]. Taking under consideration the 4 variant genotypes (IL-6 572G/C, IL-6 190C/T, TNF-α 308G/A, and ACE I/D), we noticed a 2 times higher incidence of H. pylori infection (OR = 6.34; 95% CI: 2.15-25.8).We may consider that the IL-6 190C/T, IL-6 174G/C, IL-6 572G/C, TNF-α 308G/A, and ACE I/D gene polymorphisms may increase the children's susceptibility for acquiring H. pylori infection; therefore, they may contribute to the pathogenesis of H. pylori gastritis.


Caught in the snare of deception: an exploration of the psychology of being deceived through two novels of Henry James.
Although all of us become deceived at times, certain individuals are particularly prone to be caught in the snare of deception. The author uses novels by Henry James to explore two pathways by which these vulnerable individuals become deceived. The Portrait of a Lady (1881) illustrates the dynamics of someone who is not chronically deceived, but who surrenders to a deceptive object in order to escape from conflict and pain. The Golden Bowl (1904) illuminates the situation of someone for whom being deceived is a more chronic state, one that mirrors a false internal world. The author considers the obstacles that one encounters when one attempts to emerge from the state of being deceived and the difficulties that the deceived patient presents for the analyst.


Coping strategies in a strongly schooling fish, the common carp Cyprinus carpio.
Individual common carp Cyprinus carpio were screened repeatedly for risk taking (rate of exploration of a novel, potentially dangerous environment) and for competitive ability (success in gaining access to a spatially restricted food source). Marked differences in behaviour were evident, and significant consistency in individual responses across trials was found for both risk taking and competitive ability. In addition, there was a significant positive relationship between individual performance in these two contexts, with fish that explored more quickly in the novel environment tending to be among the first to gain access to restricted food. In two follow-up studies, resting metabolic rate, blood lactate and glucose and the expression of the cortisol receptor gene in the head kidney and brain were compared in fish from the two extremes of the risk-taking spectrum. Mass-specific metabolic rate was significantly higher in risk-taking than in risk-avoiding fish, while plasma lactate and glucose concentrations and expression of the cortisol receptor gene were lower. It was concluded that a behavioural syndrome based on boldness and aggression exists in C. carpio, as it does in many other animals, and that this is associated with differences in metabolic and stress physiology (down to the genomic level) similar to those described in animals with different coping strategies.


Effect of codon optimisation on the production of recombinant fish growth hormone in Pichia pastoris.
This study was established to test the hypothesis of whether the codon optimization of fish growth hormone gene (FGH) based on P. pastoris preferred codon will improve the quantity of secreted rFGH in culture supernatant that can directly be used as fish feed supplements. The optimized FGH coding sequence (oFGH) and native sequence (nFGH) of giant grouper fish (Epinephelus lanceolatus) were cloned into P. pastoris expression vector (pPICZαA) downstream of alcohol oxidase gene (AOX1) for efficient induction of extracellular rFGH by adding 1% of absolute methanol. The results showed that recombinant P. pastoris was able to produce 2.80 ± 0.27 mg of oFGH compared to 1.75 ± 0.25 of nFGH in one litre of culture supernatant. The total body weight of tiger grouper fingerlings fed with oFGH increased significantly at third (P < 0.05) and fourth weeks (P < 0.01) of four-week experiment period compared to those fed with nFGH. Both oFGH and nFGH significantly enhanced the final biomass and fish survival percentage. In conclusion, codon optimization of FGH fragment was useful to increase rFGH quantity in the culture supernatant of P. pastoris that can be directly used as fish feed supplements. Further studies are still required for large scale production of rFGH and practical application in aquaculture production.


Surgical recanalisation of thrombosed M2 trunk after coil embolisation of a ruptured middle cerebral artery aneurysm.
Thromboembolic events are known complications of endovascular coiling of intracerebral aneurysms. We report a case of a 50-year-old patient whose ruptured middle cerebral artery aneurysm was treated with endovascular coiling, which was complicated by occlusion of the inferior M2 trunk during the procedure. An emergency craniotomy was performed to enable coil retrieval, evacuation of the thrombus and clipping of the aneurysm. All the middle cerebral artery branches were recanalised and the patient recovered with no neurological deficits. Our experience suggests that an emergency salvage operation for thrombosis after endovascular coiling is a treatment option offering a good clinical outcome.


The renal medullary thick ascending limb as a model for understanding lipid mediators in sepsis.
Cytokines are an essential component in those mechanisms that depress renal function in response to inflammatory diseases of the kidney. We have addressed the role of tumor necrosis factor (TNF) in mediating changes in renal function by isolating a nephron segment, the medullary thick ascending limb of Henle's loop (mTAL), and studying the effects of TNF on ion transport via changes in the activity of two epoxygenases, cyclooxygenase (COX) and cytochrome P450 (CYP450) monooxygenase. This nephron segment generates 20-hydroxyeicosatetraenoic acid (20-HETE) as a principal arachidonate metabolite. However, when challenged with lipopolysaccharide (LPS), the mTAL expresses a considerable capacity to metabolize arachidonic acid (AA) via a COX pathway to form PGE2.


Particle conformation regulates antibody access to a conserved GII.4 norovirus blockade epitope.
GII.4 noroviruses (NoVs) are the primary cause of epidemic viral acute gastroenteritis. One primary obstacle to successful NoV vaccination is the extensive degree of antigenic diversity among strains. The major capsid protein of GII.4 strains is evolving rapidly, resulting in the emergence of new strains with altered blockade epitopes. In addition to characterizing these evolving blockade epitopes, we have identified monoclonal antibodies (MAbs) that recognize a blockade epitope conserved across time-ordered GII.4 strains. Uniquely, the blockade potencies of MAbs that recognize the conserved GII.4 blockade epitope were temperature sensitive, suggesting that particle conformation may regulate functional access to conserved blockade non-surface-exposed epitopes. To map conformation-regulating motifs, we used bioinformatics tools to predict conserved motifs within the protruding domain of the capsid and designed mutant VLPs to test the impacts of substitutions in these motifs on antibody cross-GII.4 blockade. Charge substitutions at residues 310, 316, 484, and 493 impacted the blockade potential of cross-GII.4 blockade MAbs with minimal impact on the blockade of MAbs targeting other, separately evolving blockade epitopes. Specifically, residue 310 modulated antibody blockade temperature sensitivity in the tested strains. These data suggest access to the conserved GII.4 blockade antibody epitope is regulated by particle conformation, temperature, and amino acid residues positioned outside the antibody binding site. The regulating motif is under limited selective pressure by the host immune response and may provide a robust target for broadly reactive NoV therapeutics and protective vaccines. In this study, we explored the factors that govern norovirus (NoV) cross-strain antibody blockade. We found that access to the conserved GII.4 blockade epitope is regulated by temperature and distal residues outside the antibody binding site. These data are most consistent with a model of NoV particle conformation plasticity that regulates antibody binding to a distally conserved blockade epitope. Further, antibody "locking" of the particle into an epitope-accessible conformation prevents ligand binding, providing a potential target for broadly effective drugs. These observations open lines of inquiry into the mechanisms of human NoV entry and uncoating, fundamental biological questions that are currently unanswerable for these noncultivatable pathogens.