[Appraisal of cerebral atrophy in multiple sclerosis by means of the corpus callosum index].
The course of multiple sclerosis is characterised by the development of cerebral atrophy. It is of interest to monitor it in order to evaluate the treatment response, and the preferred technique consists in performing brain volume analyses, which are currently restricted to the field of research. To analyse the corpus callosum index (CCI) as a possible alternative to the methods based on brain segmentation. Our sample was made up of 109 patients with recently diagnosed demyelinating diseases (90 relapsing-remitting multiple sclerosis, 7 primary progressive forms and 12 isolated demyelinating syndromes), and the CCI was calculated in their first magnetic resonance brain scan, together with 101 healthy controls. The sequences of the patients were submitted to a volumetric analysis using the software package MSmetrix. The mean value of the CCI was 0.377 in patients and 0.411 in the controls, and the difference was statistically significant (p < 0.001). The CCI also showed a statistically significant correlation with the brain volume (p < 0.001; r = 0.444) and with the lesional volume in the FLAIR sequence (p < 0.001; r = -0.521), while no association was observed with the volume of grey matter (p = 0.058). The CCI is related to the overall brain volume obtained by volumetric techniques and may reflect the presence of atrophy in the initial stages of demyelinating diseases, which makes it a fast and easy to calculate alternative.


Cervical spine injuries in football.
The game of football, as it is played today, poses serious risk of injury for players of all ages. Injury may occur to any structure of the spinal column, including its bony, ligamentous and soft tissue components. The majority of cervical spine injuries occurring in football are self limited, and a full recovery can be expected. While these injuries are relatively uncommon, cervical spine injuries represent a significant proportion of athletic injuries that can produce permanent disability. The low incidence of cervical spine injuries has lead to a lack of emergency management experience of on-site medical staff. This paper will review the numerous injuries sustained by the cervical spine in football players and provide insights into prevention and guidelines for return to play.


Analysis of two sampling treatments of beef for microbiome studies based on metataxonomic.
Microbial enumeration by serial dilution is one of the best resources to estimate cellular density for microbiological analysis. However, for metataxonomic analysis, it is not clear if serially diluted samples may accurately be used for metataxonomic analysis to represent species composition in beef samples. In this study, the effect of sampling preparation of beef samples on the bacterial composition was evaluated by the comparison of dilution and exudate. Based on the obtained results, data obtained from the exudate of the samples were more robust in terms of number of generated reads, but no significant differences in terms of biological diversity were observed (P < .05, Wicoxon Test). Besides, both sample preparation procedures evidenced equivalent results of bacterial composition as well as its relative abundances. In conclusion, the use of exudate allows bacterial enumeration and metataxonomic analysis, which is interesting for the point of view of food microbiologists as cellular loads and microbial composition of culturable and unculturable bacteria could be compared.


Regulation of angiotensin II receptors and PKC isoforms by glucose in rat mesangial cells.
It has been shown that glomerular angiotensin II (ANG II) receptors are downregulated and protein kinase C (PKC) is activated under diabetic conditions. We, therefore, investigated ANG II receptor and PKC isoform regulation in glomerular mesangial cells (MCs) under normal and elevated glucose concentrations. MCs were isolated from collagenase-treated rat glomeruli and cultured in medium containing normal or high glucose concentrations (5.5 and 25.0 mM, respectively). Competitive binding experiments were performed using the ANG II antagonists losartan and PD-123319, and PKC analysis was conducted by Western blotting. Competitive binding studies showed that the AT1 receptor was the only ANG II receptor detected on MCs grown to either subconfluence or confluence under either glucose concentration. AT1 receptor density was significantly downregulated in cells grown to confluence in high-glucose medium. Furthermore, elevated glucose concentration enhanced the presence of all MC PKC isoforms. In addition, PKCbeta, PKCgamma and PKCepsilon were translocated only in cells cultured in elevated glucose concentrations following 1-min stimulation by ANG II, whereas PKCalpha, PKCtheta, and PKClambda were translocated by ANG II only in cells grown in normal glucose. Moreover, no changes in the translocation of PKCdelta, PKCiota, PKCzeta, and PKCmu were detected in response to ANG II stimulation under euglycemic conditions. We conclude that MCs grown in high glucose concentration show altered ANG II receptor regulation as well as PKC isoform translocation compared with cells grown in normal glucose concentration.


Paeoniflorin Enhances the Sensitivity of ER-Positive Breast Cancer Cells to Tamoxifen through Promoting Sirtuin 4.
Tamoxifen is an effective drug for treating patients with advanced estrogen receptor-positive (ER+) breast cancer (BC), but not for all ER + BC patients. Drug tolerance is the biggest obstacle. In this study, we designed an experiment to investigate whether paeoniflorin affects the ER + BC cell's sensitivity to tamoxifen in the T47D and MCF-7 cell lines. Herein, we found that paeoniflorin inhibited cell proliferation without inducing apoptosis. However, it enhanced tamoxifen-induced apoptosis in both cell lines. Immunoblotting revealed that paeoniflorin significantly increased the already elevated Bax/Bcl2 protein expression ratio and the caspase 3 activity levels, both induced by tamoxifen. Paeoniflorin was also found to increase SIRT4 expression, and deletion of SIRT4 could significantly reverse the inhibition of cell proliferation induced by paeoniflorin and significantly decrease paeoniflorin-enhanced apoptosis induced by tamoxifen. Moreover, protein expression detection revealed that paeoniflorin enhanced the tamoxifen-induced inhibition of STAT3 activation. Besides, the deletion of SIRT4 could significantly increase STAT3 activation in the T47D and MCF-7 cells. In conclusion, paeoniflorin suppressed STAT3 activation to enhance the sensitivity of ER-positive breast cancer cells to tamoxifen through promoting SIRT4 expression.


MR connectomics: Principles and challenges.
MR connectomics is an emerging framework in neuro-science that combines diffusion MRI and whole brain tractography methodologies with the analytical tools of network science. In the present work we review the current methods enabling structural connectivity mapping with MRI and show how such data can be used to infer new information of both brain structure and function. We also list the technical challenges that should be addressed in the future to achieve high-resolution maps of structural connectivity. From the resulting tremendous amount of data that is going to be accumulated soon, we discuss what new challenges must be tackled in terms of methods for advanced network analysis and visualization, as well data organization and distribution. This new framework is well suited to investigate key questions on brain complexity and we try to foresee what fields will most benefit from these approaches.


NAS-SGAN: A Semi-Supervised Generative Adversarial Network Model for Atypia Scoring of Breast Cancer Histopathological Images.
Nuclear atypia scoring (NAS), forms a significant factor in determining individualized treatment plans and also for the prognosis of the disease. Automation of cancer grading using quantitative image-based analysis of histopathological images can circumvent the shortcomings of the prevailing manual grading and can assist the pathologists in cancer diagnosis. However, developing such a robust classifier model require sufficient amount of annotated data, while the labeled histopathological images are scarce and expensive to procure as annotation forms a time-consuming and laborious task. Hence, a semi-supervised learning framework combined with the deep neural network based generative adversarial training, that can improve the performance of the classification model with limited annotated data, is proposed in this paper. The proposed NAS-SGAN model consists of discriminator and generator models that are trained in an adversarial manner using both labeled and unlabeled samples. The discriminator model is designed as an unsupervised model stacked over the supervised model sharing the model parameters and learns the data distribution by extracting the discriminative features. The generator model is trained over a stable feature matching objective function following a composite GAN architecture, and its for the first time the semi-supervised GAN model is explored for the grading of breast cancer. Experimental analysis shows that the proposed model could better discriminate different cancer grades thereby improving the robustness and accuracy of the system, even with limited amount of labeled samples.


Production of monoclonal antibodies against the 8 kDa subunit of Echinococcus granulosus Antigen B (EgAgB8/2) using DNA immunization.
Cystic echinococcosis (CE), an endemic cosmopolitan zoonotic helminthic disease caused by the larval stage of Echinococcus granulosus, lacks reliable diagnostic tools that fulfill the criteria of high sensitivity and specificity. Antigen B (AgB), a thermostable lipoprotein that constitutes a considerable fraction of the cystic hydatid fluid (HF), is being considered as a suitable source for vaccination and immunodiagnosis of CE due to its high specificity. Genetic immunization was used to immunize BALB/c mice with the second subunit of antigen B (EgAgB8/2) for the production of monoclonal antibodies (MAb). Fusion products between the spleen cells and myeloma cells produced six MAbs of the following isotypes: IgG2a (two clones), IgG2b (three clones), and IgM (one clone). The MAbs were tested for their specificity to crude sheep hydatid fluid (CSHF) versus other antigens prepared from other helminthic parasites including Toxocara canis, Acanthocheilonema viteae, Fasciola hepatica, Schistosoma mansoni, and Taenia. Five MAbs reacted with E. granulosus antigens, one showed cross reactivity with S. mansonia antigens, and one showed a high reactivity with E. granulosus but was cross reactive with all helminthic antigens tested. Using SDS-PAGE and immunoblotting under reducing conditions, all MAbs identified the four AgB subunits with molecular weights of 8, 16, 24, and 36 kDa. Further work on the specificity and sensitivity of these MAbs as well as their use in detecting circulating parasite antigens and in antigen purification will be assessed in future studies.


Frequency and importance of small amount of isolated pelvic free fluid detected with multidetector CT in male patients with blunt trauma.
To retrospectively determine the frequency and importance of a small amount of isolated pelvic free fluid seen at multidetector computed tomography (CT) in male patients who have blunt trauma without an identifiable cause. Institutional review board approval was obtained, and the requirement for informed consent was waived for this HIPAA-compliant study. One thousand male patients with blunt trauma who underwent abdominopelvic CT at a level 1 trauma center between January 2004 and June 2006 were entered into this study. The CT images of the 1000 patients were reviewed independently by two abdominal radiologists. CT scan assessment included evaluation for presence or absence of pelvic free fluid, any traumatic or nontraumatic cause of the free fluid, pelvic free fluid attenuation and volume measurements, and determination of the location of pelvic free fluid. Interobserver agreement was determined with kappa statistics, and the Student t test was used to assess differences in the mean volume and mean attenuation of the pelvic free fluid in the patients with and those without injury. Pelvic free fluid was identified in 10.2% (102 of 1000) of patients. A small amount of isolated pelvic free fluid without any identifiable cause was identified in 4.8% (48 of 1000) of patients by reader 1 and in 5.0% (50 of 1000) of patients by reader 2 (kappa value, 0.76) and was located at or below the level of the third sacral vertebral body in all 49 patients with isolated pelvic free fluid. The mean volume and mean attenuation of the small amount of isolated pelvic free fluid were 2.3 mL +/- 1.5 (standard deviation) and 8.1 HU +/- 3.9, respectively. None of the patients in this group had an undiagnosed bowel and/or mesenteric injury. In male patients with blunt trauma, a small amount of isolated pelvic free fluid with attenuation equal to that of simple fluid and located in the deep region of the pelvis likely is not a sign of bowel and/or mesenteric injury.


The vulnerability of shellfish farmers to HAB events: An optimal matching analysis of closure decrees.
Harmful Algal Blooms (HAB) events may have serious economic consequences for shellfish farmers. When toxic algae blooms threaten human health, public authorities may decide to shut down the farming business for a while, i.e. ranging from a few days to several weeks or months, according to the severity of risks. The impact of closures being temporally and spatially distributed, shellfish farmers can avoid the risky zones or develop adaptive strategies to mitigate the economic consequences and therefore reduce significantly their business sensitivity to HABs. A sequential approach by optimal matching analysis is applied to an original data set of shellfish area closure decrees between April 2004 and December 2018 in Southern Brittany and Pays de la Loire (France) to build a typology of 79 aquaculture zones affected by various HAB and microbiological hazards (ASP, DSP, Norovirus, E. Coli, oil spills). The hypothesis is that the degree of exposure to the HAB hazard assessed by zonal closures may not be correlated to the level of sensitivity revealed by the economic results of the shellfish farming industry which can develop avoidance strategies.


Adaptive classifiers, topic drifts and GO annotations.
Gene annotations with Gene Ontology codes offer scientists important options in their study of genes and their functions. Automatic GO annotation methods have the potential to supplement the intensive manual annotation processes. Annotation approaches using MEDLINE documents are generally two-phased where the first is to annotate documents with GO codes and the second is to annotate gene products via the documents. In this paper we study document annotation with GO codes using a temporal perspective. Specifically, we build adaptive code-specific classifiers. We also study topic drift i.e., changes in the contextual characteristics of annotations over time. We show that topic drift is significant especially in the biological process GO hierarchy. This at least partially explains the particular challenges faced with codes of this hierarchy.


Hypoxia inducible-factor1alpha regulates the metabolic shift of pulmonary hypertensive endothelial cells.
Severe pulmonary hypertension is irreversible and often fatal. Abnormal proliferation and resistance to apoptosis of endothelial cells (ECs) and hypertrophy of smooth muscle cells in this disease are linked to decreased mitochondria and preferential energy generation by glycolysis. We hypothesized this metabolic shift of pulmonary hypertensive ECs is due to greater hypoxia inducible-factor1alpha (HIF-1alpha) expression caused by low levels of nitric oxide combined with low superoxide dismutase activity. We show that cultured ECs from patients with idiopathic pulmonary arterial hypertension (IPAH-ECs) have greater HIF-1alpha expression and transcriptional activity than controls under normoxia or hypoxia, and pulmonary arteries from affected patients have increased expression of HIF-1alpha and its target carbonic anhydrase IX. Decreased expression of manganese superoxide dismutase (MnSOD) in IPAH-ECs paralleled increased HIF-1alpha levels and small interfering (SI) RNA knockdown of MnSOD, but not of the copper-zinc SOD, increased HIF-1 protein expression and hypoxia response element (HRE)-driven luciferase activity in normoxic ECs. MnSOD siRNA also reduced nitric oxide production in supernatants of IPAH-ECs. Conversely, low levels of a nitric oxide donor reduced HIF-1alpha expression in normoxic IPAH-ECs. Finally, mitochondria numbers increased in IPAH-ECs with knockdown of HIF-1alpha. These findings indicate that alterations of nitric oxide and MnSOD contribute to pathological HIF-1alpha expression and account for lower numbers of mitochondria in IPAH-ECs.


HBOC-201, hemoglobin glutamer-250 (bovine), Hemopure (Biopure Corporation).
Producing an alternative to human erythrocytes has been one the most exciting dreams of medicine. Hemoglobin-based oxygen carriers (HBOCs) derived from purified human or bovine hemoglobin have been studied for clinical use and one product is currently available in the United States and European Union for veterinary use, and another in South Africa for human use. HBOC-201, bovine purified hemoglobin crosslinked and polymerized with glutaraldehyde, has been studied extensively in patients. We describe HBOC-201's potential market share, the history of HBOCs in general and of this compound, its pharmacology, published studies in patients and HBOCs that are currently being studied. A literature review using PubMed listed publications and official product websites. While HBOC-201 may not replace allogenic blood transfusions, it may serve to allow critically ill patients to be resuscitated in the field or hospital setting until either regeneration of red cell occurs or a transfusion is available.


Will the wave finally break? A brief view of the adoption of electronic medical records in the United States.
For over thirty years, there have been predictions that the widespread clinical use of computers was imminent. Yet the "wave" has never broken. In this article, two broad time periods are examined: the 1960's to the 1980's and the 1980's to the present. Technology immaturity, health administrator focus on financial systems, application "unfriendliness," and physician resistance were all barriers to acceptance during the early time period. Although these factors persist, changes in clinicians' economics, more computer literacy in the general population, and, most importantly, changes in government policies and increased support for clinical computing suggest that the wave may break in the next decade.


Changing response to chloroquine of Plasmodium falciparum in Saradidi, Kenya, from 1981 to 1984.
From 1981 through 1984, the response of Plasmodium falciparum to chloroquine was monitored in Saradidi, Kenya, as a part of a community-based health programme to provide treatment for malaria in each village. Before 1983, all 71 infections treated with chloroquine were sensitive in vivo; parasitaemia cleared by day 3 and remained absent to day 7. In June 1983, 23.1% of 26 infections treated with chloroquine base 10 mg kg-1 either recrudesced in seven days (RI resistance, five infections) or decreased but failed to clear (RII resistance, one infection). In September 1983, 16.2% of 68 and in February 1984, 13.2% of 53 infections were resistant in vivo after treatment with chloroquine base 10 mg kg-1. A course of chloroquine base 25 mg kg-1 over three days remained effective; only two (1.6%) of 129 infections examined were resistant in vivo; in both, parasitaemia cleared then recurred (RI). In September 1984, however, nine (10.2%) infections were resistant after treatment with chloroquine base 25 mg kg-1; in four of these parasitaemia decreased but never cleared (RII). Similar results were observed in vitro. In the Rieckmann macro in vitro test, 63.3% of 30 P. falciparum isolates tested were resistant to chloroquine (minimal inhibitory concentration (MIC) greater than or equal to 1.25 X 10(-6) mol 1(-1) blood) in June 1983, as were 61.8% of 34 isolates in the Rieckmann micro test (MIC greater than or equal to 1.14 X 10(-6) mol 1(-1) blood).(ABSTRACT TRUNCATED AT 250 WORDS)


The evaluation of relationship between adiponectin levels and epicardial adipose tissue thickness with low cardiac risk in Gilbert`s syndrome: an observational study.
Atherosclerotic heart diseases are less frequently seen in patients with Gilbert's syndrome (GS). We aimed to investigate whether serum adiponectin (APN) and epicardial adipose tissue (EAT) thickness have an effect beside the antioxidant effect of bilirubin in lowering the incidence of the atherosclerotic process. Sixty-eight patients diagnosed with GS (39 females and 29 males) who had applied at the internal medicine clinic of the hospital were included in this cross-sectional, observational study. The control group included 63 healthy people (39 females and 24 males). EAT thickness was measured by echocardiography. The serum APN levels were also checked. Statistical analysis was performed by using independent sample t-test, Pearson correlation and linear regression analyses. The mean age of the GS group was 28 ± 9 years, and the average EAT thickness was found to be 2.5 ± 0.1 mm. The mean age of the control group was 26 ± 6 years, and the average EAT thickness was found to be 4.2 ± 0.5 mm. When comparing the two groups, the EAT thickness of the GS group was found to be significantly lower (p<0.001) than that of the control group. In the GS group the APN was 14.9 ± 4.2 mg/L, and in the control group the APN was 12.6 ± 4.5 mg/L (p<0.022). We found that total bilirubin (β=-1,607, p<0,001) and indirect bilirubin (β=1,086, p<0,001) have an independent association with decreased EAT thickness. EAT thickness is associated with coronary atherosclerosis. Low EAT thickness may be related with low release of proinflammatory cytokine. High levels of APN may be related high anti-inflammatory effect. Therefore, low EAT thickness and high levels of APN may demonstrate protective effect on atherosclerotic heart diseases in GS patients.


Using cystoscopy to segment bladder tumors with a multivariate approach in different color spaces.
Nowadays the diagnosis of bladder lesions relies upon cystoscopy examination and depends on the interpreter's experience. State of the art of bladder tumor identification are based on 3D reconstruction, using CT images (Virtual Cystoscopy) or images where the structures are exalted with the use of pigmentation, but none uses white light cystoscopy images. An initial attempt to automatically identify tumoral tissue was already developed by the authors and this paper will develop this idea. Traditional cystoscopy images processing has a huge potential to improve early tumor detection and allows a more effective treatment. In this paper is described a multivariate approach to do segmentation of bladder cystoscopy images, that will be used to automatically detect and improve physician diagnose. Each region can be assumed as a normal distribution with specific parameters, leading to the assumption that the distribution of intensities is a Gaussian Mixture Model (GMM). Region of high grade and low grade tumors, usually appears with higher intensity than normal regions. This paper proposes a Maximum a Posteriori (MAP) approach based on pixel intensities read simultaneously in different color channels from RGB, HSV and CIELab color spaces. The Expectation-Maximization (EM) algorithm is used to estimate the best multivariate GMM parameters. Experimental results show that the proposed method does bladder tumor segmentation into two classes in a more efficient way in RGB even in cases where the tumor shape is not well defined. Results also show that the elimination of component L from CIELab color space does not allow definition of the tumor shape.


Human Papillomavirus Oral Infection: Review of Methodological Aspects and Epidemiology.
Oral infection by Human Papillomavirus (HPV) has recently gained great attention because of its involvement in the development of a subset of head and neck squamous cell carcinoma. The role of specific Alpha-HPVs in this regard has been well established, whereas the contribution of other genera is under investigation. Despite their traditional classification as "cutaneous" types, Beta and Gamma HPVs are frequently detected in oral samples. Due to the lack of a standardized protocol, a large variety of methodologies have been used for oral sample collection, DNA extraction, HPV detection and genotyping. Laboratory procedures influence the evaluation of oral HPV prevalence, which largely varies also according to the population characteristics, e.g., age, gender, sexual behavior, Human Immunodeficiency Virus (HIV) status. Nevertheless, oral infection by Beta and Gamma HPVs seems to be even more common than Alpha-HPVs. The latter is 5-7% in the general population, and increases up to 30% approximately in HIV-infected men who have sex with men. Despite major advances in the evaluation of oral HPV prevalence, its natural history is still little understood, especially for Beta and Gamma HPVs. The latest technologies, such as Next Generation Sequencing (NGS), can be exploited to gain new insights into oral HPV, and to improve the identification of novel HPV types.


[Vasoplegic syndrome and its treatment with vasopressin during cardiac surgery with cardiopulmonary bypass].
Cardiac surgery with cardiopulmonary bypass is associated with systemic inflammatory response. In some cases this clinical condition is characterized by severe hypotension due to low systemic vascular resistance during and after cardiopulmonary bypass. A few of these cases do not respond to volume or catecholamines. This condition is known as vasoplegic syndrome. Its etiology is not fully understood today and carries associated morbidity and mortality In this syndrome, vasopressin levels are reduced, as in septic and hypovolemic shock. Supplementary vasopressin improves blood pressure and might be considered as an alternative treatment. Several reports have shown benefits when used alone or in combination with catecholamines. However, further studies are necessary to find the most appropriate use of the drug for vasoplegic syndrome.


Flexion contracture of the fingers caused by sarcoidosis: an 11-year follow-up.
We report the long-term result of operative treatment of a flexion contracture of the fingers resulting from sarcoidosis, in which the contracture recurred. Even with complete excision of the granulomatous lesion, a new lesion may appear in a previously healthy area, so a radical cure by operation alone is difficult.


Epithelial supporting cells can differentiate into outer hair cells and Deiters' cells in the cultured organ of Corti.
The organ of Corti is a complex structure containing a single row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs), supported respectively by one row of inner phalangeal cells and three rows of Deiters' cells. When fetal rat organ of Corti explants are cultured, supernumerary OHCs and supernumerary Deiters' cells are produced, without any additional cell proliferation. Analysis of semi- and ultrathin sections revealed that supernumerary OHCs are produced at the distal edge of the organ of Corti. Quantitative analysis of cell types present in the organ of Corti demonstrates that when the number of OHCs increases: (i) the total number of cells remains constant; (ii) the number of Deiters' cells increases; (iii) the number of tectal cells decreases and of Hensen's cells decreases. Using specific HC markers, i.e. jagged2 (Jag2) and Math1, we showed that in addition to existing OHCs, supernumerary OHCs, tectal cells and Hensen's cells expressed these markers in embryonic day 19 organ of Corti explants after 5 days in vitro. The results of this study suggest that Hensen's cells retain the capacity to differentiate into either tectal cells, which differentiate into OHCs, or into undertectal cells which differentiate into Deiters' cells.


Metallothionein messenger RNA levels in the macular mutant mouse: an animal model of Menkes' kinky-hair disease.
Levels of metallothionein-1 (MT-1) messenger RNA (mRNA) in various tissues from normal and macular mutant mice at different stages of development (17 days of gestation, 1-, 3-, 7- and 14-day-old) were determined by Northern blot analysis. Renal MT-1 mRNA levels in mutant mice were slightly elevated at 3 stages compared to normal mice, with the exception of mutant fetus and 3-day-old mutant mice. Intestinal MT-1 mRNA levels in mutant mice were elevated at 3 stages compared to normal mice with the exception of mutant fetus and 3-day-old mutant mice. Hepatic MT-1 mRNA levels in mutant fetus and 1-day-old mutant mice were approximately the same compared to normal mice. In 3- and 7-day-old mutant mice, hepatic MT-1 mRNA levels were depressed and in 14-day-old mutant mice, they were increased compared to normal mice. Brain MT-1 mRNA could not be detected in normal and mutant mice at the 4 stages with the exception of 14-day-old mice. MT-1 mRNA in 14-day-old mice was detected and the level of that in mutant mice was slightly elevated compared to normal mice. After injection of Cu, MT-1 mRNA levels in kidney, liver and intestine were determined. The injection of Cu increased the level of MT-1 mRNA in the tissues of normal and mutant mice compared to control (saline-injected) mice. Significant differences in MT-1 mRNA levels in the tissues of both Cu-injected mice were not observed.


Unusual ribulose 1,5-bisphosphate carboxylase/oxygenase of anoxic Archaea.
The predominant pool of organic matter on earth is derived from the biological reduction and assimilation of carbon dioxide gas, catalyzed primarily by the enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO). By virtue of its capacity to use molecular oxygen as an alternative and competing gaseous substrate, the catalytic efficiency of RubisCO and the enzyme's ability to assimilate CO2 may be severely limited, with consequent environmental and agricultural effects. Recent genomic sequencing projects, however, have identified putative RubisCO genes from anoxic Archaea. In the present study, these potential RubisCO sequences, from Methanococcus jannaschii and Archaeoglobus fulgidus, were analyzed in order to ascertain whether such sequences might encode functional proteins. We also report the isolation and properties of recombinant RubisCO using sequences obtained from the obligately anaerobic hyperthermophilic methanogen M. jannaschii. This is the first description of an archaeal RubisCO sequence; this study also represents the initial characterization of a RubisCO molecule that has evolved in the absence of molecular oxygen. The enzyme was shown to be a homodimer whose deduced sequence, along with other recently obtained archaeal RubisCO sequences, differs substantially from those of known RubisCO molecules. The recombinant M. jannaschii enzyme has a somewhat low, but reasonable kcat, however, unlike previously isolated RubisCO molecules, this enzyme is very oxygen sensitive yet it is stable to hyperthermal temperatures and catalyzes the formation of the expected carboxylation product. Despite inhibition by oxygen, this unusual RubisCO still catalyzes a weak yet demonstrable oxygenase activity, with perhaps the lowest capacity for CO2/O2 discrimination ever encountered for any RubisCO.


Determination of nitrite in cured meats by ion-exclusion chromatography with electrochemical detection.
A rapid liquid chromatographic (LC) method was developed for a sensitive determination of nitrite in cured meats, using ion-exclusion chromatographic separation and electrochemical detection (IEC-EC). The current AOAC colorimetric method requires 2 h shaking in a steam bath to eliminate interference from reducing compounds such as ascorbic acid. In the present method, nitrite was analyzed in the presence of ascorbic acid without interference, and the extraction time was reduced to 1 min. The extracted nitrite was determined by ion chromatography using anion-exclusion/HS column and amperometric detector equipped with platinum or glassy carbon electrode operating at +1.0 V vs Ag/AgCl reference electrode. The detection limit was 1 ppb as NO2-. The recoveries of 50 ppm nitrite added to frankfurter and meat stick were 103 and 99.6%, respectively, with relative standard deviations less than 4%. The high speed, sensitivity, and selectivity make the new method a useful alternative to the AOAC colorimetric method.


Prevention of cytomegalovirus following solid organ transplantation: a literature review.
CMV is the most common opportunistic infection affecting SOT recipients. Although current strategies to prevent both CMV infection and disease have been effective, CMV related complications continue to occur, particularly late-onset CMV disease. This literature review article examines the benefits and disadvantages of different prevention modalities, and presents emerging strategies to better prevent CMV in organ transplant recipients.


Osteoid osteoma: CT-guided percutaneous treatment.
Seven patients with presumed osteoid osteoma were treated with percutaneous destruction or drill resection with computed tomographic (CT) guidance. The diagnosis of osteoid osteoma was made on the basis of findings in the clinical history and results at plain radiography, bone scintigraphy, and CT. In four patients, histologic confirmation was obtained. Hospital stay lasted from 1 to 3 days. After 11-38 months of follow-up examinations, all patients were asymptomatic. The authors report this simple procedure as an alternative to the more traditional open surgery technique.


Assessment of cytochrome P450 3A4 activity during the menstrual cycle using alfentanil as a noninvasive probe.
Gender-dependent differences in cytochrome P450 activity, drug metabolism, drug elimination, and their clinical consequences are increasingly apparent. P450 3A4 is the most abundant P450 isoform in the human liver and is responsible for metabolizing a vast and diverse assortment of therapeutic agents, including opioids, benzodiazepines, and local anesthetics. P450, 3A4 activity is higher in women, influenced by steroid hormone levels, and is speculated to vary during the menstrual cycle. This investigation tested the hypothesis that P450 3A4 activity varies during the menstrual cycle. Alfentanil clearance was used as a metabolic probe for P450 3A4 activity. Alfentanil (20 micrograms/kg bolus) was administered to nine nonsmoking, nonpregnant female volunteers (age, 26 +/- 5 yr) with normal menstrual cycles on three separate occasions during the same menstrual cycle: days 2 (menstrual phase), 13 (estrogen peak), and 21 (progesterone peak). Venous plasma alfentanil concentrations were determined by gas chromatography-mass spectrometry. Alfentanil clearance was determined by noncompartmental methods and by a three-compartment model with both pooled population and two-stage analysis. There was no significant difference in any measure of alfentanil clearance. Noncompartmental clearances (mean +/- SD) were 3.62 +/- 0.76, 3.81 +/- 0.96, and 3.60 +/- 0.84 ml/kg/ min, respectively, on days 2, 13, and 21 of the menstrual cycle. Alfentanil clearances were not different on menstrual cycle days 2, 13, and 21, strongly suggesting no change in P450 3A4 activity. Menstrual cycle differences in alfentanil clearances do not contribute to interindividual variability in alfentanil disposition in women. If other P450 3A4 substrates are comparable, then menstrual cycle variability in their metabolism may not be a consideration in dosing or in the design of pharmacokinetic investigations.


Icosahedral Carbaboranes with Peripheral Hydrogen-Chalcogenide Groups: Structures from Gas Electron Diffraction and Chemical Shielding in Solution.
Carbaboranes 1,2-(EH)2 -closo-1,2-C2 B10 H10 (E=S, Se) were prepared, in the case of E=Se for the first time. Their semi-experimental equilibrium molecular structures were established by the concerted use of quantum-chemical calculations and gas electron diffraction. A method was developed and implemented to quantify the contribution of experimental data to each refined structural parameter. The accuracy of the experimental structures and those calculated at the MP2 level of theory were gauged by comparison of experimental 11 B NMR chemical shifts with quantum-chemically computed values; the inclusion of electron correlation (GIAO-MP2) provided superior results. For the purpose of geometrical prediction, the remaining group 16 elements were considered, and the icosahedral structures for E=O and Te were also computed; for E=O the same theoretical approach was used as for E=S, and for E=Te a description similar to that for E=Se was employed.


Engineering of papain: selective alteration of substrate specificity by site-directed mutagenesis.
The S2 subsite specificity of the plant protease papain has been altered to resemble that of mammalian cathepsin B by site-directed mutagenesis. On the basis of amino acid sequence alignments for papain and cathepsin B, a double mutant (Val133Ala/Ser205Glu) was produced where Val133 and Ser205 are replaced by Ala and Glu, respectively, as well as a triple mutant (Val133Ala/Val157Gly/Ser205Glu), where Val157 is also replaced by Gly. Three synthetic substrates were used for the kinetic characterization of the mutants, as well as wild-type papain and cathepsin B: CBZ-Phe-Arg-MCA, CBZ-Arg-Arg-MCA, and CBZ-Cit-Arg-MCA. The ratio of kcat/KM obtained by using CBZ-Phe-Arg-MCA as substrate over that obtained with CBZ-Arg-Arg-MCA is 8.0 for the Val133Ala/Ser205Glu variant, while the equivalent values for wild-type papain and cathepsin B are 904 and 3.6, respectively. This change in specificity has been achieved by replacing only two amino acids out of a total of 212 in papain and with little loss in overall enzyme activity. However, further replacement of Val157 by Gly as in Val133Ala/Val157Gly/Ser205Glu causes an important decrease in activity, although the enzyme still displays a cathepsin B like substrate specificity. In addition, the pH dependence of activity for the Val133Ala/Ser205Glu variant compares well with that of cathepsin B. In particular, the activity toward CBZ-Arg-Arg-MCA is modulated by a group with a pKa of 5.51, a behavior that is also encountered in the case of cathepsin B but is absent with papain.(ABSTRACT TRUNCATED AT 250 WORDS)


Gait speed and prognosis in patients with idiopathic pulmonary fibrosis: a prospective cohort study.
The 4-m gait speed (4MGS), a simple physical performance measure and surrogate marker of frailty, consistently predicts adverse prognosis in older adults. We hypothesised that 4MGS could predict all-cause mortality and nonelective hospitalisation in patients with idiopathic pulmonary fibrosis (IPF).4MGS and lung function were measured at baseline in 130 outpatients newly diagnosed with IPF. Survival status and nonelective hospital admissions were recorded over 1 year. We assessed the predictive value of 4MGS (as a continuous variable and as a binary variable: slow versus preserved 4MGS) by calculating hazard ratios using Cox proportional regression, adjusting for potential confounding variables. Receiver operating characteristic curves assessed discrimination between the multivariable regression models and established prognostic indices.Continuous 4MGS and slow 4MGS were independent predictors of all-cause mortality (4MGS: HR 0.03, 95% CI 0.01-0.31; p=0.004; slow 4MGS: 2.63, 95% CI 1.01-6.87; p=0.049) and hospitalisation (4MGS: HR 0.02, 95% CI 0.01-0.14; p<0.001; slow 4MGS: 2.76, 95% CI 1.16-6.58; p=0.02). Multivariable models incorporating 4MGS or slow 4MGS had better discrimination for predicting mortality than either the gender, age and lung physiology index or Composite Physiologic Index.In patients with IPF, 4MGS is an independent predictor of all-cause mortality and nonelective hospitalisation.


Genomic comparisons of Brucella spp. and closely related bacteria using base compositional and proteome based methods.
Classification of bacteria within the genus Brucella has been difficult due in part to considerable genomic homogeneity between the different species and biovars, in spite of clear differences in phenotypes. Therefore, many different methods have been used to assess Brucella taxonomy. In the current work, we examine 32 sequenced genomes from genus Brucella representing the six classical species, as well as more recently described species, using bioinformatical methods. Comparisons were made at the level of genomic DNA using oligonucleotide based methods (Markov chain based genomic signatures, genomic codon and amino acid frequencies based comparisons) and proteomes (all-against-all BLAST protein comparisons and pan-genomic analyses). We found that the oligonucleotide based methods gave different results compared to that of the proteome based methods. Differences were also found between the oligonucleotide based methods used. Whilst the Markov chain based genomic signatures grouped the different species in genus Brucella according to host preference, the codon and amino acid frequencies based methods reflected small differences between the Brucella species. Only minor differences could be detected between all genera included in this study using the codon and amino acid frequencies based methods. Proteome comparisons were found to be in strong accordance with current Brucella taxonomy indicating a remarkable association between gene gain or loss on one hand and mutations in marker genes on the other. The proteome based methods found greater similarity between Brucella species and Ochrobactrum species than between species within genus Agrobacterium compared to each other. In other words, proteome comparisons of species within genus Agrobacterium were found to be more diverse than proteome comparisons between species in genus Brucella and genus Ochrobactrum. Pan-genomic analyses indicated that uptake of DNA from outside genus Brucella appears to be limited. While both the proteome based methods and the Markov chain based genomic signatures were able to reflect environmental diversity between the different species and strains of genus Brucella, the genomic codon and amino acid frequencies based comparisons were not found adequate for such comparisons. The proteome comparison based phylogenies of the species in genus Brucella showed a surprising consistency with current Brucella taxonomy.


Substrate and product inhibition of hydrogen production by the extreme thermophile, Caldicellulosiruptor saccharolyticus.
Substrate and product inhibition of hydrogen production during sucrose fermentation by the extremely thermophilic bacterium Caldicellulosiruptor saccharolyticus was studied. The inhibition kinetics were analyzed with a noncompetitive, nonlinear inhibition model. Hydrogen was the most severe inhibitor when allowed to accumulate in the culture. Concentrations of 5-10 mM H(2) in the gas phase (identical with partial hydrogen pressure (pH(2)) of (1-2) x 10(4) Pa) initiated a metabolic shift to lactate formation. The extent of inhibition by hydrogen was dependent on the density of the culture. The highest tolerance for hydrogen was found at low volumetric hydrogen production rates, as occurred in cultures with low cell densities. Under those conditions the critical hydrogen concentration in the gas phase was 27.7 mM H(2) (identical with pH(2) of 5.6 x 10(4) Pa); above this value hydrogen production ceased completely. With an efficient removal of hydrogen sucrose fermentation was mainly inhibited by sodium acetate. The critical concentrations of sucrose and acetate, at which growth and hydrogen production was completely inhibited (at neutral pH and 70 degrees C), were 292 and 365 mM, respectively. Inorganic salts, such as sodium chloride, mimicked the effect of sodium acetate, implying that ionic strength was responsible for inhibition. Undissociated acetate did not contribute to inhibition of cultures at neutral or slightly acidic pH. Exposure of exponentially growing cultures to concentrations of sodium acetate or sodium chloride higher than ca. 175 mM caused cell lysis, probably due to activation of autolysins.


The effect of plausibility on eye movements in reading.
Readers' eye movements were monitored as they read sentences describing events in which an individual performed an action with an implement. The noun phrase arguments of the verbs in the sentences were such that when thematic assignment occurred at the critical target word, the sentence was plausible (likely theme), implausible (unlikely theme), or anomalous (an inappropriate theme). Whereas the target word in the anomalous condition provided evidence of immediate disruption, the effect of the target word in the implausible condition was considerably delayed. The results thus indicate that when a word is anomalous, it has an immediate effect on eye movements, but that the effect of implausibility is not as immediate.


An exploration of the application of social role valorization in special hospitals.
The set of ideas known as 'social role valorization' (SRV) has been highly influential in services for some client groups, but has rarely been applied in contexts of security. A framework of questions was designed to assist the application of the theory and principles of SRV in work with patients in special hospitals. Small-scale exercises in its use were introduced to explore the relevance and usefulness of SRV ideas in special hospital work. Evaluation indicated potential usefulness in a variety of contexts, especially when allied to consideration of values issues. No attempt was made in these exercises to incorporate SRV in the operational structures of the hospitals, a task that would require much more thought and work at an organizational level.


A monoclonal antibody that recognizes a neo-antigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives: its application to the measurement of soluble fibrin in plasma.
Using urea-solubilized human fibrin monomer as an immunogen, we raised in mice a battery of monoclonal antibodies that reacted with the immunogen but not with urea-treated or native fibrinogen. Although they all failed to react with acid-solubilized fibrin monomer (acid-FM) alone, an antibody designated as IF-43 was found to recognize acid-FM, which was bound with fibrinogen or its derivatives to form a 1:2 complex of soluble fibrin. The epitope for this antibody, thus, appears to be exposed most probably by conformation changes induced in the acid-FM molecule upon formation of the complex. Because IF-43 was able to recognize fibrin-derived plasmic fragment E treated with urea but not the thrombin- and urea-treated amino-terminal disulfide knot of fibrinogen, the presence of the A alpha (52-78) residue segment seems to be prerequiste for the epitope expression. The antibody was found to react with soluble fibrin monomer spiked to normal plasma dose-dependently up to 200 micrograms/mL. By an aggregation assay using latex beads coated with IF-43, we found that concentrations of soluble fibrin monomer in plasma derived from patients with thrombotic diseases were mostly elevated, but not necessarily correlated with those of the D-dimer, reflecting another aspects of the disease. Furthermore, the soluble fibrin monomer in plasma derived from patients with thrombotic diseases was found to be depleted solely of the A peptides, but not the B peptides, based on its subunit polypeptide compositions lacking the beta-chain on immunoblotting.


Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, part 1: oral solutions.
To enable more precise prediction of oral drug absorption, an existing physiologically based absorption model was revised. The revised model reflects detailed knowledge of human gastrointestinal (GI) physiology including fluid secretion and absorption, and comprises an elaborate representation of the intestinal mucosa. The alimentary canal from the stomach to the rectum was divided into 12 compartments. A mucosal compartment was added to each luminal segment of the intestine. A training set of 111 passively absorbed drugs with reported fractions of dose absorbed was used to optimize the semiempirical equation, which calculates intestinal permeability coefficients. The model was subsequently integrated into an established physiologically based pharmacokinetic software and validated by prediction of plasma concentration-time profiles of eight test compounds with diverse physicochemical properties. A good correlation between the simulated and experimental fractions of dose absorbed was established for the 111 compounds in the training set. Subsequently, the concentration-time profiles of six out of eight test compounds were predicted with high accuracy. The detailed model for GI transit and absorption presented in this study can help to understand the complex processes of oral absorption better and will be useful during the drug development process.


Esophageal Pressure and Clinical Assessments in the Gastroesophageal Reflux Disease Patients with Laryngopharyngeal Reflux Disease.
Laryngopharyngeal reflux disease (LPRD) might be associated with reflux symptoms, and its severity is correlated with the Reflux Symptoms Index. Diagnosis is often challenging because of a lack of accurate diagnostic tools. Although an association between LPRD and gastroesophageal reflux disease (GERD) exists, the extent to which esophageal pressure changes in patients with LPRD with GERD has been unknown. Therefore, this study surveys the clinical assessments and extent of esophageal pressure changes in LRPD patients with various GERD severities, and compares esophageal sphincter pressures between ages, genders, and body mass index (BMI). This observational study assessed patients with LPRD and GERD. High-resolution esophageal manometry was used to gather data pertaining to the area pressure on the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), and the correlation between such pressure and symptom severity was determined. We compared the esophageal pressure of different UES and LES levels in the following categories: gender, age, BMI, and GERD severity. We analyzed correlations between esophageal pressure and clinical assessments among 90 patients with throat globus with laryngitis with LPRD. LPRD was measured using laryngoscopy, and GERD was measured using esophagoscopy and 24 h PH monitoring. There were no significant differences in the clinical assessments among the four grades of GERD. The LPRD patients with serious GERD had a lower UES and LES pressure. The lowest pressure and longer duration of LES and UES were also observed among patients with LPRD of grade D GERD. No significant differences in UES and LES pressures among ages, genders, or BMIs were noted.


A comparative method for both discrete and continuous characters using the threshold model.
The threshold model developed by Sewall Wright in 1934 can be used to model the evolution of two-state discrete characters along a phylogeny. The model assumes that there is a quantitative character, called liability, that is unobserved and that determines the discrete character according to whether the liability exceeds a threshold value. A Markov chain Monte Carlo algorithm is used to infer the evolutionary covariances of the liabilities for discrete characters, sampling liability values consistent with the phylogeny and with the observed data. The same approach can also be used for continuous characters by assuming that the tip species have values that have been observed. In this way, one can make a comparative-methods analysis that combines both discrete and continuous characters. Simulations are presented showing that the covariances of the liabilities are successfully estimated, although precision can be achieved only by using a large number of species, and we must always worry whether the covariances and the model apply throughout the group. An advantage of the threshold model is that the model can be straightforwardly extended to accommodate within-species phenotypic variation and allows an interface with quantitative-genetics models.


Stem Cell-Derived Extracellular Vesicles and Immune-Modulation.
Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system.


Estimating virus production rates in aquatic systems.
Viruses are pervasive components of marine and freshwater systems, and are known to be significant agents of microbial mortality. Developing quantitative estimates of this process is critical as we can then develop better models of microbial community structure and function as well as advance our understanding of how viruses work to alter aquatic biogeochemical cycles. The virus reduction technique allows researchers to estimate the rate at which virus particles are released from the endemic microbial community. In brief, the abundance of free (extracellular) viruses is reduced in a sample while the microbial community is maintained at near ambient concentration. The microbial community is then incubated in the absence of free viruses and the rate at which viruses re-occur in the sample (through the lysis of already infected members of the community) can be quantified by epifluorescence microscopy or, in the case of specific viruses, quantitative PCR. These rates can then be used to estimate the rate of microbial mortality due to virus-mediated cell lysis.


Structural basis for the interaction between yeast Spt-Ada-Gcn5 acetyltransferase (SAGA) complex components Sgf11 and Sus1.
Sus1 is a central component of the yeast gene gating machinery, the process by which actively transcribing genes such as GAL1 become associated with nuclear pore complexes. Sus1 is a component of both the SAGA transcriptional co-activator complex and the TREX-2 complex that binds to nuclear pore complexes. TREX-2 contains two Sus1 chains that have an articulated helical hairpin fold, enabling them to wrap around an extended alpha-helix in Sac3, following a helical hydrophobic stripe. In SAGA, Sus1 binds to Sgf11 and has been proposed to provide a link between SAGA and TREX-2. We present here the crystal structure of the complex between Sus1 and the N-terminal region of Sgf11 that forms an extended alpha-helix around which Sus1 wraps in a manner that shares some similarities with the Sus1-Sac3 interface in TREX-2. However, the Sus1-binding site on Sgf11 is somewhat shorter than on Sac3 and is based on a narrower hydrophobic stripe. Engineered mutants that disrupt the Sgf11-Sus1 interaction in vitro confirm the importance of the hydrophobic helical stripe in molecular recognition. Helix alpha1 of the Sus1-articulated hairpin does not bind directly to Sgf11 and adopts a wide range of conformations within and between crystal forms, consistent with the presence of a flexible hinge and also with results from previous extensive mutagenesis studies (Klöckner, C., Schneider, M., Lutz, S., Jani, D., Kressler, D., Stewart, M., Hurt, E., and Köhler, A. (2009) J. Biol. Chem. 284, 12049-12056). A single Sus1 molecule cannot bind Sgf11 and Sac3 simultaneously and this, combined with the structure of the Sus1-Sgf11 complex, indicates that Sus1 forms separate subcomplexes within SAGA and TREX-2.


A survey of the coccidian parasites of reptiles from islands of the Galápagos Archipelago: 1990-1994.
From 1990 through 1994, fecal samples were collected and examined for coccidian parasites from 26 giant land tortoises Geochelone nigra, from 715 lava lizards Tropidurus spp., from 139 land iguanas Conolophus subcristatus, and from 128 marine iguanas Amblyrhynchus cristatus, all of which inhabit various islands in the Galápagos Archipelago. None of the samples from A. cristatus or from C. subcristatus was infected with coccidia. Only 1 of 26 (4%) G. nigra was infected with a single Eimeria species that we describe here as new. A total of 262 of 715 (37%) individuals representing 3 species of Tropidurus discharged oocysts of 1-3 different coccidian species; these included 2 previously described species Eimeria tropidura and Isospora insularius, and an eimerian that we describe here as new. Additionally, 104 fecal samples from Tropidurus spp. were from 51 animals recaptured in either 2 or 3 yr; 21 had no infections in any year, 15 were infected at least once, 14 were infected in 2 yr, and only 1 was infected during 3 yr. No animal was recaptured and sampled during each of the 4 yr of this study. Of the 262 infected individuals, 30 (12%) had multiple coccidial infections at the time of collection (eimerian and isosporan, or 2 eimerians). Where determination of the sexes was possible in the lava lizards, there was no difference in prevalence rates between males (39%) and females (41%). Sporulated oocysts of the new eimerian from Tropidurus are ellipsoidal, 27.1 x 15.6 (25-31 x 14-18) microns, with a polar body, but without a micropyle or oocyst residuum; they contain ellipsoidal sporocysts, 11.8 x 6.7 (10-14 x 6-8) microns, without Stieda, sub-, or parastieda bodies, but with a sporocyst residuum. Sporulated oocysts of the new eimerian from G. nigra are ellipsoidal to ovoidal, 21.6 x 18.1 (18-25 x 16-20) microns, with a large polar body, but without a micropyle or oocyst residuum; they contain ellipsoidal sporocysts 10.7 x 7.0 (8-12 x 5-8) microns, with Stieda body but no sub- or parastieda bodies. Also present is a sporocyst residuum of medium to large granules randomly distributed among the sporocysts.


9-(4-Bromo-phen-yl)-3,6-di-tert-butyl-9H-carbazole.
The asymmetric unit of the title compound, C(26)H(28)BrN, contains two independent mol-ecules in which the carbazole rings are almost planar, with r.m.s. deviations of 0.0212 (1) and 0.0229 (1) Å. The dihedral angles between the carbazole ring system and the pendent benzene ring are 60.5 (1) and 56.3 (1)° in the two mol-ecules. In the crystal, mol-ecules are linked into chains along the b axis by C-H⋯π inter-actions.


Short communication: Effect of heat stress on nonreturn rate of Italian Holstein cows.
The data set consisted of 1,016,856 inseminations of 191,012 first, second, and third parity Holstein cows from 484 farms. Data were collected from year 2001 through 2007 and included meteorological data from 35 weather stations. Nonreturn rate at 56 d after first insemination (NR56) was considered. A logit model was used to estimate the effect of temperature-humidity index (THI) on reproduction across parities. Then, least squares means were used to detect the THI breakpoints using a 2-phase linear regression procedure. Finally, a multiple-trait threshold model was used to estimate variance components for NR56 in first and second parity cows. A dummy regression variable (t) was used to estimate NR56 decline due to heat stress. The NR56, both for first and second parity cows, was significantly (unfavorable) affected by THI from 4 d before 5 d after the insemination date. Additive genetic variances for NR56 increased from first to second parity both for general and heat stress effect. Genetic correlations between general and heat stress effects were -0.31 for first parity and -0.45 for second parity cows.


Bats, emerging infectious diseases, and the rabies paradigm revisited.
The significance of bats as sources of emerging infectious diseases has been increasingly appreciated, and new data have been accumulated rapidly during recent years. For some emerging pathogens the bat origin has been confirmed (such as lyssaviruses, henipaviruses, coronaviruses), for other it has been suggested (filoviruses). Several recently identified viruses remain to be 'orphan' but have a potential for further emergence (such as Tioman, Menangle, and Pulau viruses). In the present review we summarize information on major bat-associated emerging infections and discuss specific characteristics of bats as carriers of pathogens (from evolutionary, ecological, and immunological positions). We also discuss drivers and forces of an infectious disease emergence and describe various existing and potential approaches for control and prevention of such infections at individual, populational, and societal levels.


Physical and functional interaction between integrins and hERG potassium channels.
Integrins are adhesion receptors capable of transmitting intracellular signals that regulate many different cellular functions. Among integrin-mediated signals, the activation of ion channels can be included. We demonstrated that a long-lasting activation of hERG (human ether-a-go-go-related gene) potassium channels occurs in both human neuroblastoma and leukaemia cells after the activation of the beta1 integrin subunit. This activation is apparently a determining factor inducing neurite extension and osteoclastic differentiation in both the cell types. More recently, we provided evidences that beta1 integrins and hERG channels co-precipitate in both the cell types. Preliminary results suggest that a macromolecular signalling complex indeed occurs between integrins and the hERG1 protein and that hERG channel activity can modulate integrin downstream signalling.


Expression of p27 and PTEN and clinical characteristics in early laryngeal squamous cell carcinoma and their correlation with recurrence.
Laryngeal squamous cell carcinoma is a common malignant tumor of otolaryngeal region. At present, effective treatment of laryngeal squamous cell carcinoma still depends on surgery and radiotherapy. In recent years, application of CO2 laser resection in the treatment of stage T1 glottic carcinoma can remove the tumor completely and reduce the injury of laryngeal tissues. But recurrence still happened in some postoperative patients. Here, we selected 131 patients to compare the therapeutic effects of CO2 laser resection and traditional split laryngeal surgery on the early laryngeal cancer, examined the expression of p27 and PTEN by immunohistochemistry in early laryngeal squamous cell carcinoma tissues in correlation to clinical outcome. After two years follow-up 14/85 (16.5%) of CO2 laser treatment group presented with local recurrence (recurrent group), while that of split laryngeal surgery group was 6/46 (13.0%). There was no statistical significance in recurrence rate between the two groups (P>0.05). 10 of all the 111 (9.0%) non-recurrent patients did not follow the doctor's advice to quit smoking after the operation, while 12 in the 20 (60.0%) recurrent patients did not; the difference between the two groups was statistically significant (P<0.01). The positive rates of p27 were 80.2% (105/131) and 43.5% (57/131), and that of PTEN were 83.2% (109/131) and 48.9% (64/131) in the cancer adjacent tissues (negative surgical margin tissues) and in laryngeal carcinoma tissues, respectively (P<0.001). The expression rates of p27 and PTEN in laryngeal carcinoma tissues of the recurrent group were 20.0% (4/20), 10.0% (2/20) and that in non recurrent group were 47.7% (53/111) and 55.9% (62/111), respectively, with a significant difference (P<0.001). In addition, the expression of p27 and PTEN in tumor resected marginal tissues of the recurrence group was 50.0% (10/20), 40.0% (8/20) and that in non recurrence group was 85.6% (95/111) and 91.0% (101/111), respectively; the difference was also statistically significant between both groups (P<0.001). In conclusion, there is no statistically significant difference in tumor recurrence rate between CO2 laser surgery and traditional split laryngeal surgery. Postoperative recurrence is closely related to resume smoking. The recurrence rate of p27 and/or PTEN-negative patients was higher than that of the positive ones,that should be followed up closely after treatment.


Plasma metabolomic study in perinatally HIV-infected children using 1H NMR spectroscopy reveals perturbed metabolites that sustain during therapy.
Perinatally HIV-infected children on anti-retroviral treatment (ART) are reported to have metabolic abnormalities such as dyslipidemia, lipodystrophy, and insulin resistance which potentially increase the risk of diabetes, kidney, liver and cardiovascular disease. To elucidate HIV-mediated metabolic complications that sustain even during ART in perinatally HIV-infected children. We have carried out metabolic profiling of the plasma of treatment-naïve and ART-suppressed perinatally HIV-infected children and uninfected controls using 1H nuclear magnetic resonance (NMR) spectroscopy followed by statistical analysis and annotation. Validated multivariate analysis showed clear distinction among our study groups. Our results showed elevated levels of lactate, glucose, phosphoenolpyruvic acid, propionic acid, 2-ketobutyric acid and tricarboxylic acid (TCA) cycle metabolites in untreated HIV-infected children compared to uninfected controls. ART normalized the levels of several metabolites, however the level of lactate, phosphoenolpyruvic acid, oxoglutaric acid, oxaloacetic acid, myoinositol and glutamine remained upregulated despite ART in HIV-infected children. Pathway analysis revealed perturbed propanoate metabolism, amino acid metabolism, glycolysis and TCA cycle in untreated and ART-suppressed HIV-infected children. Developing therapeutic strategies targeting metabolic abnormalities may be beneficial for preventing diabetes, cardiovascular disease or other associated complications in perinatally HIV-infected children.


Targeted evolution of pinning landscapes for large superconducting critical currents.
The ability of type II superconductors to carry large amounts of current at high magnetic fields is a key requirement for future design innovations in high-field magnets for accelerators and compact fusion reactors, and largely depends on the vortex pinning landscape comprised of material defects. The complex interaction of vortices with defects that can be grown chemically, e.g., self-assembled nanoparticles and nanorods, or introduced by postsynthesis particle irradiation precludes a priori prediction of the critical current and can result in highly nontrivial effects on the critical current. Here, we borrow concepts from biological evolution to create a vortex pinning genome based on a genetic algorithm, naturally evolving the pinning landscape to accommodate vortex pinning and determine the best possible configuration of inclusions for two different scenarios: a natural evolution process initiating from a pristine system and one starting with preexisting defects to demonstrate the potential for a postprocessing approach to enhance critical currents. Furthermore, the presented approach is even more general and can be adapted to address various other targeted material optimization problems.


A mouse model of reverse cardiac remodelling following banding-debanding of the ascending aorta.
Myocardial remodelling during pressure overload might contribute to development of heart failure. Reverse remodelling normally occurs following aortic valve replacement for aortic stenosis; however, the details and regulatory mechanisms of reverse remodelling remain unknown. Thus, an experimental model of reverse remodelling would allow for studies of this process. Although models of aortic banding are widely used, only few reports of debanding models exist. The aim of this study was to establish a banding-debanding model in the mouse with repetitive careful haemodynamic evaluation by high-resolution echocardiography. C57Bl/6 mice were subjected to ascending aortic banding and subsequent debanding. Cardiac geometry and function were evaluated by echocardiography, and left ventricular myocardium was analysed by histology and quantitative real-time polymerase chain reaction. The degree of aortic banding was controlled by non-invasive estimation of the gradient, and we found a close correlation between left ventricular mass estimated by echocardiography and weight at the time of killing. Aortic banding led to left ventricular hypertrophy, fibrosis and expression of foetal genes, indicating myocardial remodelling. Echocardiography revealed concentric left ventricular remodelling and myocardial dysfunction. Following debanding, performed via a different incision, there was rapid regression of left ventricular weight and normalization of both cardiac geometry and function by 14 days. We have established a reproducible and carefully characterized mouse model of reverse remodelling by banding and debanding of the ascending aorta. Such a model might contribute to increased understanding of the reversibility of cardiac pathology, which in turn might give rise to new strategies in heart failure treatment.


Somatic mutations in RET exons 12 and 15 in sporadic medullary thyroid carcinomas: different spectrum of mutations in sporadic type from hereditary type.
Germline mutations in the RET proto-oncogene are responsible for multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Point mutations or in-frame deletions of exons 10, 11, 13, 14 and 16 are associated with sporadic medullary thyroid carcinoma (MTC). To understand further the role of the RET gene in sporadic MTC, we examined mutations in exons 12 and 15 of RET in patients with sporadic MTC. DNAs were extracted from 39 formalin-fixed tumor tissues and corresponding normal thyroid tissues or peripheral blood leukocytes. DNA sequencing was used to identify mutations in exons 12 and 15 of RET. In this study, one novel somatic mutation was found in exon 12 and five novel mutations or deletions were found in exon 15. Of the patients with mutations, one had an in-frame 12-bp deletion (nt. 2625-2636), one had point mutations in both codons 884 and 908, and the remaining three had point mutations in codons 748, 876 and 901, respectively. Together with our previous identification of somatic mutations in exons 10, 11, 13, 14 and 16, somatic alterations were found in 10 out of 39 (25.6%) sporadic MTCs. There was no association of RET gene mutations with tumor recurrence or prognosis. These results suggest that mutations occur frequently in the RET coding region in addition to the previously reported mutation hot spots, and there is a different spectrum of mutations between sporadic and hereditary MTC.


Modelling inter-ward migration in Hereford and Worcester: the importance of housing growth and tenure.
"In this paper, we use the 1991 Special Migration Statistics to analyse inter-ward flows in the British county of Hereford and Worcester. New modelling techniques...based on the Poisson distribution are used in this research which partially overcome the under-dispersion problem resulting from modelling zero and very small flows.... Analysis at this scale provides the potential for more detailed generalization about migration processes such as suburbanization, counterurbanization, intra-urban mobility, rural depopulation and the relationship between housing and demographic change at the local level. Unlike migration flows over long distances, which are often employment related, these flows are primarily motivated by residential requirements and housing type and growth are identified as key variables in the interpretation of these migration patterns."


Neoadjuvant chemoradiotherapy with capecitabine based regimen in locally advanced rectal cancer: A retrospective study.
Capecitabine-based neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer. The objective of this study is to analyze overall survival (OS), disease-free survival (DFS) and prognostic factors of patients with stage II to III rectal cancer treated with nCRT in our institution. Between March 2014 to June 2020, 121 locally advanced rectal cancer patients were retrospectively reviewed and analyzed. All of the enrolled patients were treated with capecitabine-based nCRT (pelvic radiotherapy: 45-50.4 Gy, 1.8 Gy/d plus concomitant capecitabine-based chemotherapy), total mesorectal excision surgery (surgery was carried out 8-12 weeks after the end of CRT), and capecitabine-based adjuvant chemotherapy. We examined the pathological complete response rate, 3-year OS, 3-year DFS and the other prognostic factors. Kaplan-Meier method and Log-rank test were used to estimate and compare survival rate. With a median follow-up of 36 months, 3-year DFS and 3-year OS was 74.4% and 83.2%, respectively. Among the 121 patients, 24 achieved pathological complete remission (19.8%). After multivariate analysis, ypTNM stage (TNM stage after neoadjuvant therapy) was significantly associated with DFS. Positive mesorectal fasciae (MRF) status on magnetic resonance imaging and ypTNM stage were significantly related to OS. CRT with capecitabine based regimen provides high rates of survival and sphincter preservation with acceptable toxicity. YpTNM stage was significantly associated with DFS; magnetic resonance imaging MRF status and ypTNM stage were significant factors for OS after multivariate analysis. Distant metastasis is the dominant mode of treatment failure, and it is crucial to optimize systemic treatment for newly diagnosed patients.


Binding of lactoferrin and transferrin to the human promonocytic cell line U937. Effect on iron uptake and release.
We have compared the ability of lactoferrin and transferrin to interact with and donate iron to the monocytic cell line U937. About 10 times more lactoferrin was bound than transferrin, but most lactoferrin bound nonspecifically, and the degree of specific binding was similar for both proteins (2-3 x 10(6) sites/cell). The binding affinity for lactoferrin (83 nM) was about 4-fold lower than for transferrin (21 nM). Lactoferrin did not inhibit binding of transferrin, or vice versa. Binding of lactoferrin was not inhibited by 30 mM glucose or fucose nor by incubating the cells with heparinase. Transferrin, but not lactoferrin, was internalized, and 3 mM primaquine caused intracellular accumulation of transferrin but not lactoferrin. The cells rapidly acquired iron from transferrin, but uptake from lactoferrin was 10-fold slower and probably resulted from transfer of 59Fe from lactoferrin to unlabeled transferrin during culture. Lactoferrin, but not transferrin, released iron to the extracellular medium when bound to U937 cells. Lactoferrin inhibited cellular uptake of iron from Fe-nitrilotriacetate but not from transferrin. It is concluded that transferrin, but not lactoferrin, acts as an iron donor to U937 cells. Lactoferrin may regulate uptake of potentially toxic non-transferrin-bound iron.


Integrating horizontal gene transfer and common descent to depict evolution and contrast it with "common design".
Horizontal gene transfer (HGT) and common descent interact in space and time. Because events of HGT co-occur with phylogenetic evolution, it is difficult to depict evolutionary patterns graphically. Tree-like representations of life's diversification are useful, but they ignore the significance of HGT in evolutionary history, particularly of unicellular organisms, ancestors of multicellular life. Here we integrate the reticulated-tree model, ring of life, symbiogenesis whole-organism model, and eliminative pattern pluralism to represent evolution. Using Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a bifunctional enzyme in the glycolytic pathway of amoeba, we illustrate how EhADH2 could be the product of both horizontally acquired features from ancestral prokaryotes (i.e. aldehyde dehydrogenase [ALDH] and alcohol dehydrogenase [ADH]), and subsequent functional integration of these enzymes into EhADH2, which is now inherited by amoeba via common descent. Natural selection has driven the evolution of EhADH2 active sites, which require specific amino acids (cysteine 252 in the ALDH domain; histidine 754 in the ADH domain), iron- and NAD(+) as cofactors, and the substrates acetyl-CoA for ALDH and acetaldehyde for ADH. Alternative views invoking "common design" (i.e. the non-naturalistic emergence of major taxa independent from ancestry) to explain the interaction between horizontal and vertical evolution are unfounded.


Regulated HIV-2 RNA dimerization by means of alternative RNA conformations.
The dimer initiation site (DIS) hairpin of the HIV-2 untranslated leader RNA mediates in vitro dimerization through 'loop-loop kissing' of a loop-exposed palindrome sequence. Premature RNA dimerization must be prevented during the retroviral life cycle. A regulatory mechanism has been proposed for the HIV-1 leader RNA that can adopt an alternative conformation in which the DIS motif is effectively masked by long-distance base pairing with upstream leader sequences. We now report that HIV-2 RNA dimerization is also regulated. Sequestering of the DIS motif by base pairing interactions with downstream leader sequences mediates a switch to a dimerization-impaired conformation. The existence of two alternative conformations of the HIV-2 leader RNA is supported by UV melting experiments. Furthermore, the equilibrium between the two conformations can be shifted by annealing of antisense oligonucleotides or by deletion of certain leader regions. These measures have a profound impact on the dimerization properties of the transcript, demonstrating a mutual exclusivity between the alternative conformation and dimerization, similar to what has been described for the HIV-1 leader. The overall resemblance in regulation of HIV-1 and HIV-2 RNA dimerization suggests that a similar mechanism may be operating in other lentiviruses and perhaps all retroviridae.


Organophosphorus pesticide tolerance of transgenic Arabidopsis thaliana by bacterial ophB gene encode organophosphorus hydrolase.
Organophosphate hydrolase (OphB) gene from Pseudomonas sp. was transferred into Arabidopsis plants to observe the bioremediation ability and tolerance level of the transgenic plant to organophosphate pesticides contaminants. Gene transfer was observed by PCR of the transgenic Arabidopsis plants' genomic DNA. Expression of ophB gene and protein levels in the transgenic Arabidopsis plants was observed by western blot analysis. The transgenic plants were resistant and tolerant to chlorpyrifos (an organophosphate pesticide), as evidenced by a toxicity test, where the transgenic plants produced greater shoot and root biomass than that of wild type plants. The fresh weight of transgenic Arabidopsis plants' did not reduced significantly till 400 ppm chlorpyrifos treatment, but fresh weight of wild type Arabidopsis plants' significantly reduced by the application of 100 ppm chlorpyrifos. Moreover, in 600 ppm chlorpyrifos liquid culture, transgenic Arabidopsis plants' produced 1.34 g biomass from 100 seeds, but wild type Arabidopsis plants' produced only 0.24 g biomass from 100 seeds. This study indicates that transgenic Arabidopsis plants having ophB gene increase the tolerance level of organophosphate pesticides.


[Herpes simplex virus type 1 ICP27 induces apoptotic cell death by increasing intracellular reactive oxygen species].
HSV-1 ICP27, an immediate early protein of herpes simplex virus type 1, is involved in viral replication, transcriptional activation, RNA stability, apoptosis, and reactivation from viral latency. The reactivation from viral latency is closely related to apoptosis and oxidative stress. To understand the effect of ICP27 upon apoptosis, we tested for cell death of ICP27-expressing cells (3-3) in the presence of hydrogen peroxide. Under oxidative stress, 3-3 cells were sensitive to death, displaying typical apoptosis features such as oligonucleosomal DNA fragmentation, chromatin condensation, and G0/G1 accumulation. To dissect the sensitizing mechanism of ICP27 in apoptosis, we analyzed the level of intracellular reactive oxygen species (ROS) in 3-3 cells. We found that 3-3 cells exhibited increased ROS levels compared to Vero cells devoid of ICP27. We also observed that the increased levels of intracellular ROS in 3-3 cells were caused by disturbances in antioxidant enzymes. In 3-3 cells, the elevated ROS increased the AP-1 activity, subsequently the expression of Bax increased, and the expression of Bcl2 was reduced. In addition, 3-3 cells were sensitive to various apoptotic agents. Taken together, these results indicate that HSV-I ICP27 sensitizes the cells to apoptosis by elevating the intracellular levels of ROS.


Basic behavioral science research priorities in minority health and health disparities.
Achieving health equity among disparity populations has been a national, regional, and local priority for several years. Health promotion and disease prevention behaviors play an important role in achieving health equity; the first generation of behavioral science studies in minority health and health disparities have provided important insights about the nature and distribution of risk exposure behaviors in disparity populations. Interventions have also been developed to enhance health promotion and disease prevention behaviors using behavioral counseling, tailored health communications, and interventions that are developed collaboratively with community stakeholders. Although intervention development and evaluation are components of transdisciplinary translational behavior research, discovery science is a critical first step in translational research. Consistent with this, conceptual models and frameworks of minority health and health disparities have evolved to include multilevel determinants that include basic behavioral mechanisms such as stress responses and stress reactivity that have physiological, psychological, and behavioral components that are relevant to minority health and health disparities. This report describes priorities, opportunities, and barriers to conducting transdisciplinary translational behavioral research during the next generation of minority health and health disparities research.


[Clinical significance of autoantibodies against ubiquitin carboxyl hydrolase L1 epitopes in the screening and diagnosis of Sjögren syndrome].
Objective: To study the clinical significance of autoantibodies against different ubiquitin carboxyl hydrolase L1 (UCH-L1) epitopes in Sjogren syndrome (SS). Methods: The serum levels of different UCH-L1 epitope autoantibodies in 98 SS patients [SS group, 17 males and 81 females, aged (49.1±12.3) years] in the Fifth Affiliated Hospital of Zhengzhou University and Peking University People's Hospital from January 2017 to January 2020 and 37 healthy controls [control group, 6 males and 31 females, aged (46.3±5.8) years] were determined by enzyme-linked immunosorbent assay (ELISA). Three potential epitopes of UCH-L1 protein were analyzed and synthesized and anti-UCH-L1203-214 and anti-UCH-L158-69 antibodies were studied between the two groups. The levels of the two anti-UCH-L1 antibodies in the two groups were compared. The correlation between the levels of UCH-L1 antibodies and clinical data of SS patients were analyzed by Pearson correlation analysis. Results: The serum levels of anti-UCH-L1203-214 and anti-UCH-L158-69 antibody in SS patients were significantly higher than those in healthy controls (HCs) (anti-UCH-L1203-214: 108.2±54.3 vs 78.9±25.8, P<0.001, anti-UCH-L158-69: 86.8±33.3 vs 60.4±21.5, P<0.001). The positive rates of anti-UCH-L1203-214 and anti-UCH-L158-69 antibodies in serums of SS patients were 27.6 % (27/98) and 25.5% (25/98), and those in HCs were 2.7%(1/37) and 5.4 %(2/37), respectively. In SS patients with positive serum anti-UCH-L158-69 antibody, the levels of IgG, γ globulin and rheumatoid factor (RF) and anti-SS-related antigen B (anti-SSB) antibody positive rate were all significantly higher than those in patients with negative antibody (all P<0.05). In SS patients with negative antinuclear antibody (ANA), anti-RNA binding protein (anti-RNP) antibody, anti-SS-related antigen A (anti-SSA) antibody and anti-SSB antibody, the positive rates of anti-UCH-L1203-214 antibody was 32.1%(9/28), 27.2%(25/92), 36.4%(12/33), 28.6%(18/63), respectively; and the positive rates of anti-UCH-L158-69 antibody was 21.4%(6/28), 30.4%(28/92), 30.3%(10/33), 20.6%(13/63), respectively. The level of serum anti-UCH-L1203-214 antibody in SS patients was positively correlated with the IgA level (r=0.21, P=0.024). The level of anti-UCH-L158-69 antibody in SS patients was positively correlated with the levels of γ-globulin, IgG and RF (r=0.35, 0.33, 0.32, all P<0.01). Conclusion: Autoantibodies against UCH-L1 epitopes are correlated with some clinical parameters of SS patients, which is of promising significance in the screening and diagnosis of SS.


Mapping of the autosomal dominant cataract mutation (Coc) on mouse chromosome 16.
To characterize the mouse cataract mutation Coc. Coc is an X-radiation-induced autosomal dominant cataract mutation maintained on a murine C3H inbred strain. The affected heterozygotes were outcrossed to C57BL/6, and (C3H Coc/+ x C57BL/6) mice that were Coc/+ were then backcrossed to C57BL/6 to generate a panel of 103 progeny for mapping. For linkage analysis, microsatellites from each autosome were selected. The maximum distance between markers was 30 centimorgans (cM). The initial genome-wide screen of 14 backcrossed progeny indicated that the Coc locus resides on chromosome 16. Further mapping with additional markers from chromosome 16 for all 103 backcrossed progeny positioned Coc between markers D16Mit134 and D16Mit63. This region is syntenic to human chromosome 3. Mapping of the Coc locus to mouse chromosome 16 provides the positional information necessary to identify the candidate gene responsible for the Coc phenotype. The molecular characterization of the gene disrupted in the Coc mutation will provide insight into the mechanisms involved in cataract formation.


Free radicals, antioxidants, and nutrition.
Radiation hazards in outer space present an enormous challenge for the biological safety of astronauts. A deleterious effect of radiation is the production of reactive oxygen species, which result in damage to biomolecules (e.g., lipid, protein, amino acids, and DNA). Understanding free radical biology is necessary for designing an optimal nutritional countermeasure against space radiation-induced cytotoxicity. Free radicals (e.g., superoxide, nitric oxide, and hydroxyl radicals) and other reactive species (e.g., hydrogen peroxide, peroxynitrite, and hypochlorous acid) are produced in the body, primarily as a result of aerobic metabolism. Antioxidants (e.g., glutathione, arginine, citrulline, taurine, creatine, selenium, zinc, vitamin E, vitamin C, vitamin A, and tea polyphenols) and antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidases) exert synergistic actions in scavenging free radicals. There has been growing evidence over the past three decades showing that malnutrition (e.g., dietary deficiencies of protein, selenium, and zinc) or excess of certain nutrients (e.g., iron and vitamin C) gives rise to the oxidation of biomolecules and cell injury. A large body of the literature supports the notion that dietary antioxidants are useful radioprotectors and play an important role in preventing many human diseases (e.g., cancer, atherosclerosis, stroke, rheumatoid arthritis, neurodegeneration, and diabetes). The knowledge of enzymatic and non-enzymatic oxidative defense mechanisms will serve as a guiding principle for establishing the most effective nutrition support to ensure the biological safety of manned space missions.


Perceptions and Motivating Factors Regarding COVID-19 Vaccination in Latinx Older Adults in Chicago: A Local, Qualitative Perspective.
Historically marginalized communities disproportionately impacted by the pandemic are demonstrating lower uptake of COVID-19 vaccines. To facilitate the development of culturally tailored, language concordant educational materials promoting COVID-19 vaccination, we first explored older Latinx adults' awareness, attitudes, and beliefs about COVID-19 vaccines and factors involved in vaccination decisions within their communities. Individual, semi-structured interviews were conducted with 15 participants who self-identified as Latinx/Hispanic, aged 50 and older, and living in Chicago. Eight interviews were conducted in English and seven in Spanish. Thematic analysis was used to analyze participants' responses. Participants revealed four key factors influencing vaccination decisions: 1. protecting oneself and loved ones (against COVID-19 (n=14), or from perceived dangers of the vaccine (n=9)); 2. trust in authorities (trusting information (n=9), or worrying the vaccine is being manipulated (n=5)); 3. access and availability (gratitude to live in a country where vaccines are available (n=5), or fear of going to vaccination sites due to immigration and insurance status (n=4)); and 4. Employment and semblance of normalcy (vaccination to create opportunities (n=6), or concern about missing out due to side effects (n=9)). Our findings illuminate key factors influencing decisions for COVID-19 vaccination among Latinx older adults in Chicago. Vaccination information aiming to increase vaccination rates among this important population may benefit from leveraging collective pronouns and spirituality, language concordance, low-tech options, building trust, and addressing insurance and immigration doubts. Next steps include developing educational materials based on these themes, followed by dissemination and evaluation. Lessons learned may be of interest to public health experts responding to the ongoing pandemic and other public health crises experienced by historically marginalized communities.


Stapled Full-Thickness Diaphragm Resection: A Novel Approach to Diaphragmatic Resection in Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.
Full-thickness diaphragm resection (FT-DR) during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is sometimes required to achieve a complete cytoreduction. It is conventionally performed with electrocautery with primary repair or mesh repair. FT-DR using a linear cutting stapler is a novel technique that avoids entry to the chest cavity and minimizes the use of electrocautery on the diaphragm. We performed an institutional retrospective review of a prospectively maintained database of 145 patients who underwent CRS-HIPEC between 2013 and 2019. Patients were divided into the Conventional or Stapled group based on the FT-DR approach indicated in the operative report. Of the 145 patients who underwent CRS-HIPEC, 27 underwent FT-DR, with 63% (n = 17) in the Stapled group. There were no significant demographic or oncologic differences between the 2 groups. Patients in the Stapled group underwent tube thoracostomy (13.3% vs 60%; p = 0.008), were diagnosed with pneumonia (12% vs 50%; p = 0.04), required reintubation (6% vs 40%; p = 0.03), and required mechanical ventilation more than 48 hours (6% vs 50%; p = 0.02) less frequently than the Conventional group. There was no difference in pleural recurrence between the 2 groups (Conventional 20% vs Stapled 12%, p = 0.56). Stapled full-thickness diaphragm resection is a novel approach to achieving a complete cytoreduction that excludes the pleural cavity, minimizes diaphragm manipulation, and is associated with improved postoperative pulmonary outcomes in patients undergoing CRS-HIPEC.


Validation of the Norwegian versions of the Implementation Leadership Scale (ILS) and Multifactor Leadership Questionnaire (MLQ) in a mental health care setting.
The implementation of evidence-based practices (EBPs) is of crucial importance in health care institutions and requires effective management from leaders. However, there is a lack of assessment tools sufficient to evaluate the degree to which the employees´ rate how well their leaders are at implementing EBPs. This emphasises the need for validated and widely used scales relevant for EBPs. The current study evaluated the psychometric properties of the Multifactor Leadership Questionnaire (MLQ) and Implementation Leadership Scale (ILS) in a Norwegian mental health care setting. Results from confirmatory factor analyses indicate that the MLQ and ILS are valid instruments for measuring general and implementation leadership. The scales demonstrate good convergent validity. In addition, attitudes towards EBPs did not seem to be associated with the ILS and MLQ, further supporting the applicability of the instruments. The two scales demonstrate good psychometric properties in a Norwegian mental health care setting, which suggests that the MLQ and ILS are valid and reliable tools for measuring leadership in an implementation setting. More research is greatly needed to disentangle the link between perceived leadership and objective measures of successful implementation of EBPs. Trial registration NSD 690,133, NSD 60,059/3/OOS.


Activity of neutral endopeptidase and aminopeptidase N in mouse thymic stromal cells which bind double-positive thymocytes.
The activity of two peptidases was determined in immortalized lines of thymic stromal cells. A line of total stromal cells (T-TG-St) was grown from transgenic mouse expressing temperature-sensitive SV40 T antigen under the control of the regulatory elements of the mouse major histocompatibility complex class I gene. From these cells we isolated a subset (DP-TG-St) that binds thymocytes which are mainly CD4+8+. We also assayed a clone of fetal thymic epithelial cells (BA/10) that binds CD4+8+ thymocytes. Both lines of double -positive cell-binding stroma exhibited strong activity of two peptidases, neutral endopeptidase (NEP; EC 22.214.171.124) and aminopeptidase N (APN; EC 18.104.22.168). In contrast, the activity of both enzymes was very low in the total thymic stromal line. Use of the specific inhibitors confirmed that these two enzymes were responsible for the activity observed but also suggested the presence of additional unidentified aminopeptidase(s) in the same stromal cells. The high activity of the two peptidases on stromal cells that bind thymocytes at the double-positive stage raises the possibility that they might contribute to the microenvironment of the developing thymocytes.


Quantitative analysis of CEA expression in colorectal adenocarcinoma and serum: lack of correlation.
Tissues and sera from 110 patients diagnosed with colorectal primary carcinoma, 20 patients with benign colorectal diseases and 31 healthy donors were subjected to quantitative CEA analysis. Multiple samples from tumor lesions and autologous histologically normal mucosa (10 cm from the tumor) were obtained at the time of surgery (cancer patients) or endoscopy (benign patients and healthy volunteers). CEA content was measured in protein extracts obtained from these tissues using a quantitative RIA method. A limit of normality for CEA content was established as 300 ng/mg of protein. When this was taken as cut-off, 104 of 110 (94.5%) tumor lesions and 51 of 110 (46.4%) autologous histologically normal colonic mucosa from cancer patients had elevated CEA levels. No correlation with stage of disease was found, while a correlation was observed with degree of tumor differentiation. A statistically significant difference between CEA content in tumor lesions and in histologically normal mucosa from cancer patients was observed (p = -0.001). Moreover, CEA content was statistically higher in the normal mucosa from cancer patients than in that from healthy donors (p = 0.005). CEA content in tissue specimens from benign lesions differed significantly from that in tissue from healthy donors (p = 0.005) and in carcinoma lesions (p < 0.001). The highest CEA content was observed in benign lesions with severe dysplasia. No statistical correlation between CEA content in carcinoma tissues and serum CEA levels (r = 0.195, p = .13) was found. Therefore, in considering diagnosis or therapy with anti-CEA MAbs for colorectal-carcinoma patients, or potential therapies with anti-CEA recombinant vaccines, serum CEA levels should not be taken as indicating CEA expression in tumor lesions.