Study of the Morphogenesis of Granulomas in the Liver of Mice in Different Age Periods Treated with Oxidized Dextran.
We studied granuloma formation and its outcomes in BCG-induced granulomatosis in the liver of mice of different age periods treated with oxidized dextran. Newborn C57BL/6 mice were intraperitoneally injected with BCG vaccine on the first day of life (group 1) or BCG vaccine solution on first day of life and oxidized dextran on the second day of life (group 2). Analysis was carried out on 3, 5, 10, 28, and 56 days of life. After injection of BCG vaccine, granulomas in the liver appeared starting from the day 28. In mice treated with oxidized dextran, granulomas on day 28 were smaller and less numerous than in group 1 animals. In BCG granulomatosis, fibroplastic processes in the liver develop mainly at the site of granulomas. Injection of oxidized dextran under conditions of BCG granulomatosis reduced the manifestations of fibrosis in the liver.


Prevention of foodborne diseases and home safety.
Injuries and infectious diseases show high levels of morbidity at home. It is known that diseases associated with the consumption of contaminated or poorly preserved food, can be significantly reduced if proper hygiene practices are observed. This article analyzes the main risks associated with household food consumption and aims to highlight some of the recommendations that are still widely disregarded. In particular, we highlight the issues concerning the management of food (especially cooking and storage) and water (mineral and tap water), as well as good manufacturing practices that the consumer have to take to avoid food contamination. For this purpose, a detailed information on prevention would provide people with a greater awareness of risk and, therefore, a improved perception to the real dangers.


Evaluation of the Relationship between Social Desirability and Minor Psychiatric Disorders among Nurses in Southern Iran: A Robust Regression Approach.
Social desirability may affect different aspects of people's quality of life. One of the impressive dimensions of quality of life is mental health. The prevalence of Minor Psychiatric Disorders (MPD) among health care workers is higher than other health workers. This article aims at evaluating the relationship between social desirability and MPD among nurses in southern Iran. A cross-sectional study was carried out on 765 nurses who had been employed in hospitals in the southern provinces of Iran. The 12-item General Health Questionnaire (GHQ-12) and Marlowe-Crowne Social Desirability Scale (MC-SDS) were used for evaluating the MPD and social desirability in nurses, respectively. The Robust Regression was used to determine any quantified relationship between social desirability and the level of MPD with adjusted age, gender, work experience, marital status, and level of education. The mean scores of GHQ-12 and MC-SDS were 13.02±5.64 (out of 36) and 20.17±4.76 (out of 33), respectively. The result of Robust Regression indicated that gender and social desirability were statistically significant in affecting MPD. The prevalence of MPD in female nurses was higher than males. Nurses with higher social desirability scores had the tendency to report lower levels of MPD.


Adaptive finite-time control for switched nonlinear systems subject to multiple objective constraints via multi-dimensional Taylor network approach.
The finite-time control of switched nonlinear systems subject to multiple objective constraints is investigated in this article. Firstly, with the aim of dealing with the major challenge brought by multiple objective constraints, the time-varying and asymmetric barrier function is designed, which transforms multiple objective constrained systems into unconstrained systems. Secondly, the dynamic surface control technique is introduced into the backstepping design process, and the error generated in the filtering process is reduced by constructing the error compensation systems. Then, an adaptive finite-time controller based on multi-dimensional Taylor network (MTN) is proposed. The controller proposed in this article can avoid the "singularity" problem and ensure that the objective functions never violate constraints. Finally, the effectiveness of the finite-time control strategy proposed in this article is verified by the aircraft system simulation.


Mapping of a functional recombination motif that defines isotype specificity for mu-->gamma3 switch recombination implicates NF-kappaB p50 as the isotype-specific switching factor.
Ig class switch recombination (CSR) requires expression of activation-induced deaminase (AID) and production of germline transcripts to target S regions for recombination. However, the mechanism of CSR remains unclear. Here we show that an extrachromosomal S plasmid assay is AID dependent and that a single consensus repeat is both necessary and sufficient for isotype-specific CSR. Transfected switch substrates specific for mu-->gamma3 and mu-->gamma1 are stimulated to switch with lipopolysaccharide (LPS) alone or LPS and interleukin-4, respectively. An Sgamma3/Sgamma1 substrate containing only three Sgamma3-associated nucleotides reconstituted LPS responsiveness and permitted mapping of a functional recombination motif specific for mu-->gamma3 CSR. This functional recombination motif colocalized with a binding site for NF-kappaB p50, and p50 binding to this site was previously established. We show a p50 requirement for plasmid-based mu-->gamma3 CSR using p50-deficient B cells. Switch junctions from p50-deficient B cells showed decreased lengths of microhomology between Smu and Sgamma3 relative to wild-type cells, indicating a function for p50 in the mechanics of CSR. We note a striking parallel between the affects of p50 and Msh2 deficiency on Smu/Sgamma3 junctions. The data suggest that p50 may be the isotype-specific factor in mu-->gamma3 CSR and epistatic with Msh2.


Effects of foot-ankle exercises on foot-ankle kinematics, plantar pressure, and gait kinetics in people with diabetic neuropathy: Secondary outcomes from a randomized controlled trial.
Follow-up report of secondary outcomes of a randomized, single-blinded, parallel controlled trial that investigated the benefits of a foot-ankle therapeutic exercise program on foot-ankle kinematics, plantar pressure, and lower limb kinetics during gait in individuals with diabetic neuropathy (DPN). Sixty-six participants with DPN were randomly allocated into a control group (CG; n = 31), which received usual care, and an intervention group (IG; n = 35), which received usual care plus a 12-week group-based foot-ankle exercise program. Outcomes were assessed at baseline and 12 weeks by an assessor blinded to group allocation. The generalized linear mixed model and intention-to-treat analysis revealed a greater hip extensor moment at push-off and greater hallux contact area in the IG than CG after 12 weeks. A within-group analysis revealed a larger arch height during stance and higher peak pressure and pressure-time integral at the central forefoot region in the IG after 12 weeks compared to baseline. There were no other significant group difference or changes over time in foot-ankle kinematics or in any other joint moment related to overall lower limb biomechanics. The increases in hip moment at push-off and hallux surface contact area suggest an improvement in the propulsion phase with greater participation of the toes in foot rollover after 12 weeks of a group-based foot-ankle exercises program for people with DPN. Individual face-to-face, longer-term, and more intensive interventions may be needed to positively influence foot-ankle biomechanics and pressure parameters in other plantar areas.


Correction: Ono, K. Calibration Methods of Acoustic Emission Sensors. Materials 2016, 9, 508.
The author wishes to make the following corrections to this paper [1].[...].


Evaluation of Community Perceptions and Prevention Practices Related to Ebola Virus as Part of Outbreak Preparedness in Uganda, 2020.
During the 2018-2020 Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo, risk communication and community engagement (RCCE) were prioritized in geographic areas in Uganda considered at high risk of introduction of EVD. To inform EVD preparedness in Uganda, we evaluated community perceptions and prevention practices related to EVD in 6 districts in Uganda. In March 2020, we conducted a population-based survey in 6 purposively selected districts in Uganda using multistage cluster sampling. We examined differences between districts classified as high- versus low risk for EVD in terms of their message exposure from RCCE; risk perception; and EVD knowledge, attitudes, and prevention practices. A total of 3,485 respondents were interviewed (91% response rate). EVD message exposure was more common in the high- versus low-risk districts. EVD risk perceptions were low overall but greater in the high- versus low-risk districts. Comprehensive knowledge was significantly greater in the high- versus low-risk districts (adjusted prevalence ratio [aPR] 1.61, 95% confidence interval [CI]=1.35, 1.93). Respondents' engagement in all 3 EVD prevention practices (frequent handwashing with soap, avoiding physical contact with suspected Ebola patients, and avoiding burials involving contact with a corpse) was very low (4%). However, respondents with comprehensive knowledge were more likely to engage in all 3 EVD prevention practices compared to respondents without comprehensive knowledge (aPR 1.87, 95% CI=1.08, 3.25). Our findings suggest that while RCCE efforts as part of EVD outbreak preparedness may have contributed to higher EVD knowledge in the targeted high-risk districts, uptake of prevention behaviors was similarly low across districts. In a non-outbreak setting, implementing targeted RCCE strategies may not be sufficient to motivate people to adopt protective behaviors in the absence of a high threshold of perceived threat such as in an active outbreak.


Correlation of Antibodies to Neurotransmitters in the Sera of Women with Alcohol Dependence and Depressive Disorders.
Comparative analysis of blood sera from women with alcohol dependence and depressive disorders or from conditionally healthy women revealed reduced level of antibodies to dopamine, norepinephrine, serotonin, glutamate, and GABA in blood serum in women with dysthymic disorder and a depressive episode and their increased content in women with alcohol dependence in combination with depressive disorders.


Proximity-dependent biotinylation identifies a suite of candidate effector proteins from Fusarium graminearum.
Fusarium graminearum is a fungal pathogen that causes Fusarium head blight in cereal crops. The identification of proteins secreted from pathogens to overcome plant defenses and cause disease, collectively known as effectors, can reveal the etiology of a disease process. Proximity-dependent biotin identification (BioID) was used to identify potential effector proteins secreted in planta by F. graminearum during the infection of Arabidopsis. Mass spectrometry analysis of streptavidin affinity-purified proteins revealed over 300 proteins from F. graminearum, of which 62 were candidate effector proteins (CEPs). An independent analysis of secreted proteins from axenic cultures of F. graminearum showed a 42% overlap with CEPs, thereby assuring confidence in the BioID methodology. The analysis also revealed that 19 out of 62 CEPs (approx. 30%) had been previously characterized with virulence function in fungi. The functional characterization of additional CEPs was undertaken through deletion analysis by the CRISPR/Cas9 method, and by overexpression into Triticum aestivum (wheat) leaves by the Ustilago hordei delivery system. Deletion studies of 12 CEPs confirmed the effector function of three previously characterized CEPs and validated the function of another four CEPs on wheat inflorescence or vegetative tissues. Lastly, overexpression in wheat showed that all seven CEPs enhanced resistance against the bacterial pathogen Pseudomonas syringae DC3000.


Use of Theoretical Frameworks as a Pragmatic Guide for Mixed Methods Studies: A Methodological Necessity?
There is a growing acceptance of the utility of mixed methods in health sciences but there is no widely accepted set of ideas in regard to use of a conceptual or theoretical framework to guide inquiry. Few mixed methods health science articles report the use of such a framework. Lack of available conceptual maps provided by theoretical frameworks, necessary intricacy of design, and the qualitative "black box" tradition all contribute to a dearth of methodological guidance in such studies. This article uses a funded National Institutes of Health study as an example to explain the utility of a theoretical framework in conceptualizing a study, making design decisions such as sampling and recruitment, collecting and analyzing data, and data interpretation.


Endosomal type Iγ PIP 5-kinase controls EGF receptor lysosomal sorting.
Endosomal trafficking and degradation of epidermal growth factor receptor (EGFR) play an essential role in the control of its signaling. Phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P(2)) is an established regulator of endocytosis, whereas PtdIns3P modulates endosomal trafficking. However, we demonstrate here that type I gamma phosphatidylinositol phosphate 5-kinase i5 (PIPKIγi5), an enzyme that synthesizes PtdIns4,5P(2), controls endosome-to-lysosome sorting of EGFR. In this pathway, PIPKIγi5 interacts with sorting nexin 5 (SNX5), a protein that binds PtdIns4,5P(2) and other phosphoinositides. PIPKIγi5 and SNX5 localize to endosomes, and loss of either protein blocks EGFR sorting into intraluminal vesicles (ILVs) of the multivesicular body. Loss of ILV sorting greatly enhances and prolongs EGFR signaling. PIPKIγi5 and SNX5 prevent Hrs ubiquitination, and this facilitates the Hrs association with EGFR that is required for ILV sorting. These findings reveal that PIPKIγi5 and SNX5 form a signaling nexus that controls EGFR endosomal sorting, degradation, and signaling.


[Occupationally acquired SARS-CoV-2 infections among healthcare personnel in Frankfurt am Main from March to August 2020].
Standardised surveillance of COVID-19 infections among healthcare personnel during the current pandemic was and is not available. In particular, the proportion of occupational infections among healthcare personnel and which workers among them are most at risk remains unclear. The aim of this study was to analyse the reported COVID-19 cases among healthcare personnel in Frankfurt/Main during the first six months of the pandemic, to determine the number of occupational infections and thus to allow a better interpretation of the data published by the Robert Koch Institute. Data from the Frankfurt/Main Health Protection Authority was analysed for the period from 1 March to 31 August 2020, and healthcare personnel were recruited for a cross-sectional survey. Three subgroups were defined and analysed according to whether the infectious contact occurred at work, in private or in an unknown setting. Healthcare personnel accounted for 11.8% (319/2700) of all reported COVID-19 cases in Frankfurt/Main during the period studied. In the survey, 47.2% of respondents reported that their infection was acquired in the workplace. There was an association of contact with COVID-19 patients as well as employment in the internal medicine ward and a reported work-related infection. Also apparent was an association between suspected occupational infections and consequently filed reports for alleged occupational disease. Health protection authorities are in a position to collect relevant data on work-related transmissions in healthcare occupations and workplaces and should generate standardised data on infected healthcare personnel. This data is necessary to take targeted infection control and prevention measures that protect healthcare personnel and their patients.


Expression and Clinicopathological Significances of lncRNAs: Could ARA and ZEB2NAT be the Potential Breast Cancer-Related Biomarkers?
Pieces of evidence have shown that a significant proportion of cancer-prone factors are not attributed to alterations in protein-coding sequences. Adriamycin resistance-related (ARA) and natural antisense of ZEB2 (ZEB2NAT) long non-coding RNAs (lncRNAs) have been indicated with oncogenic properties by regulating various signaling pathways and epithelial-to-mesenchymal transition (EMT), which may have diagnostic and prognostic potential as a novel group of biomarkers. The current study aimed to evaluate the expression status of ARA and ZEB2NAT lncRNAs and their clinicopathological significance in a population with breast cancer (BC). Total RNA was extracted from 60 tumor samples and their normal adjacent tissues (NATs). The lncRNA expressions were measured using quantitative reverse transcription PCR (RT-qPCR) and statistical analyses were performed by SPSS version 25. Our data showed a significant upregulation of ARA and ZEB2NAT lncRNAs in tumor tissues compared to NATs (p <0.001; p = 0.021, respectively). ARA and ZEB2NAT expression were observed to be significantly associated with tumor grade, nuclear grade, tumor stages, and lymph node metastasis (p <0.05). Additionally, ARA expression was significantly correlated with breastfeeding status (p = 0.027). our data revealed that ARA and ZEB2NAT lncRNAs were overexpressed in BC. Furthermore, the selected lncRNAs were found to might be the potential biomarkers for BC diagnosis and prognosis. However, the findings of the current research are required to be replicated in other studies with larger sample sizes.


Synthetic promoter for efficient and muscle-specific expression of exogenous genes.
Synthetic promoters (SPs) have many advantages over their natural counterparts, especially with regard to transcriptional activity and tissue specificity. Here, we report a new strategy to construct SPs for efficient and muscle-specific gene expression. First, 19 nucleic acid motifs classified to 3 kinds of transcriptional regulatory elements were rationally selected. A recombinant promoter library was constructed by randomly assembling these motifs. Second, the transcriptional activities of ~1200 SPs were screened by intramuscular expression of several reporter genes in different cell lines for activity higher than that of the cytomegalovirus (CMV) promoter, with SP-301 finally identified as the strongest. A single intramuscular injection of mice with an SP-301 plasmid expressing mouse growth hormone releasing hormone accelerated mouse growth significantly over 24 days. Third, the muscle specificity of SP-301 was confirmed in transgenic mice. Finally, in comparison with the CMV promoter, SP-301 accelerated translocation and increased the level of plasmid in the nuclei of myoblast cells to a greater extent than in non-muscle cells. Altogether, the study has provided a more rational strategy to construct efficient and tissue-specific promoters, with the promoter SP-301 exhibiting promising potential for establishing an intramuscular gene expression system for therapeutic applications.


Comparing transcriptional initiation by RNA polymerases I and III.
We comment on the current understanding of transcriptional initiation by RNA polymerases I and III, and look for common modes of operation of these enzymes, emphasizing selected recent developments. These include definitive experiments on the constitution of the human RNA polymerase I transcription factor SL1/TIF-IB, the development of a genetic system for analyzing the function of RNA polymerase I in yeast, the elucidation of the structure of the human snRNA gene transcription factor SNAPc, and initial stages of mapping the protein-protein interactions involved in the assembly of transcriptional initiation complexes.


Lipogenesis as related to endocrine control of adipose cellularity in the rat.
The incorporation rate of 3H from 3H2O in the total lipids of rat retroperitoneal adipose tissue (RPAT) according to age was followed in slightly hyperthyroid rats, in type-2 diabetic rats and in control rats. Until 12 weeks of age, the RPAT of the hyperthyroid animals exhibited hyperplasia and an increase in lipogenesis per g of wet weight or per whole fat pad. Fat cel number and lipogenesis per g of wet weight or per whole fat pad were reduced in adult diabetic rats. The concomitant changes in fat cell number and lipid synthesis in the RPAT of the two groups of treated rats have been discussed.


Complementation of peptides of barnase, extracellular ribonuclease of Bacillus amyloliquefaciens.
Recovery of ribonuclease activity by complementation of peptides of barnase is reported. Activity is restored to barnase-(1-102), which lacks eight amino acids from its COOH terminus, by combination with peptides-(88-110), -(95-110), or -(99-108), and also with succinylated peptide-(88-110). The dissociation constants are about 8 X 10(-6) M for the first two combinations and little, if any, greater for the other two. Based on barnase-(1-102) concentration, up to 80% of native activity is obtained with peptide-(88-110) but only 5 to 20% with the others. The octapeptide-(103-110), equivalent to the residues missing from barnase-(1-102), does not complement barnase-(1-102), suggesting that an intact sequence about His-102 and Tyr-103 is required for activity. Barstar, the natural inhibitor of barnase, completely inhibits all activity of the complementing peptides.


Cloning and sequence analysis of genes encoding Staphylococcus hyicus exfoliative toxin types A, B, C, and D.
Exfoliative toxins produced by certain strains of Staphylococcus hyicus mediate exudative epidermitis in pigs. In this study the genes coding for four different exfoliative toxin from S. hyicus (ExhA, ExhB, ExhC, and ExhD) were cloned and sequenced. The coding sequence of the four toxin genes ranged from 816 to 834 bp. The amino acid sequences of these four toxins were homologous to the earlier described exfoliative toxins SHETB from S. hyicus and ETA, ETB, and ETD from Staphylococcus aureus. The homology between the S. hyicus toxins was at the same level as the homology to the exfoliative toxins from S. aureus. The toxins showed similarity to serine proteases, including preservation of the catalytic tract in ExhA, ExhB, and ExhC. However, in ExhD, Asp in the putative catalytic tract was replaced with Glu. The recombinant toxins could be expressed in Escherichia coli, and three of the four toxins were recognized by monoclonal antibodies raised against native exfoliative toxins.


Hearing aid use in 11-year-old children with mild bilateral hearing loss: Associations between parent and child ratings and datalogging.
This study examined the hearing aid use in older school-aged children with mild bilateral hearing loss. More specifically, it investigated children's and parents' estimation of use in comparison to datalogging as well as explored the situations children used their hearing aids. Sixteen children with mild bilateral hearing loss and their parents participated. Of those, 14 children used hearing aids. Children and parents completed a questionnaire on hours of hearing aid use and situations hearing aids were used. Datalogging of the hearing aids was recorded and compared to the outcome of the questionnaires. Datalogging indicated average hearing aid use time was 6.6 h. Children significantly overestimated their use of their hearing aids while approximately half the parents overestimated their child's use. Children used their hearing aids most often at school and in the car. Children with mild bilateral hearing loss overestimate the amount of time they are wearing their hearing aids. This may impact counselling and intervention on the use of hearing aids. Therefore, school-aged children should be included in the discussions around potentially increasing use of hearing aids.


Real-time quality control of optical backscattering data from Biogeochemical-Argo floats.
Biogeochemical-Argo floats are collecting an unprecedented number of profiles of optical backscattering measurements in the global ocean. Backscattering (BBP) data are crucial to understanding ocean particle dynamics and the biological carbon pump. Yet, so far, no procedures have been agreed upon to quality control BBP data in real time. Here, we present a new suite of real-time quality-control tests and apply them to the current global BBP Argo dataset. The tests were developed by expert BBP users and Argo data managers and have been implemented on a snapshot of the entire Argo dataset. The new tests are able to automatically flag most of the "bad" BBP profiles from the raw dataset. The proposed tests have been approved by the Biogeochemical-Argo Data Management Team and will be implemented by the Argo Data Assembly Centres to deliver real-time quality-controlled profiles of optical backscattering. Provided they reach a pressure of about 1000 dbar, these tests could also be applied to BBP profiles collected by other platforms.


Outcomes of a Single-Segment Intrastromal Corneal Ring in Early Keratoconus and Early Pellucid Marginal Degeneration.
To determine the effect of a single-segment intrastromal corneal ring segment (ICRS; Intacs SK) on early keratoconus (KCN) and pellucid marginal degeneration (PMD). It is a prospective interventional study. One hundred twenty-four eyes (99 patients) with KCN and 36 eyes (26 patients) with PMD at early stage (the maximum keratometric reading less than 55 diopters) were included to ICRS implantation using femtosecond laser at a tertiary university-based hospital and a private outpatient center. The uncorrected distance and spectacle-corrected visual acuity (UDVA and SCDVA), manifest spherical and cylindrical refractions, and keratometry indices were measured preoperatively and postoperatively, 1 week, 2 and 6 months. One week after surgery, significant improvements were observed in UDVA, SCDVA, cylinder and keratometry readings of both KCN and PMD groups (all P < 0.05) with no significant changes afterward. No significant change occurred in the sphere refraction of PMD group (P = 0.10) in contrast to KCN group (P < 0.001). Corneal irregularity of KCN group in central 3 and 5 mm zones increased at 1 week (both P < 0.001) and then started to decrease up to 6 months. However, the corneal irregularity of PMD group had significant reduction only at 1 week in 5-mm zone (P = 0.02) and 2 months in 3-mm zone (P = 0.01) postoperatively. The final efficacy indexes were 1.44 ± 0.71 and 0.87 ± 0.40 in KCN and PMD groups, respectively. Visual acuity, refractive errors and keratometry values have been improved after one-segment Intacs SK implantation in early KCN and PMD patients.


Lateral prefrontal activity as a compensatory strategy for deficits of cortical processing in Attention Deficit Hyperactivity Disorder.
Attention Deficit Hyperactivity Disorder (ADHD) is the most common neuropsychiatric disorder in childhood and is characterized by a delay of cortical maturation in frontal regions. In order to investigate interference control, which is a key function of frontal areas, a functional MRI study was conducted on 17 ADHD boys and 17 typically developing (TD) boys, while solving the multi source interference task (MSIT). This task consists of two conditions, a "congruent condition" and an "incongruent condition". The latter requires to inhibit information that interferes with task-relevant stimuli. Behavioral results showed that ADHD subjects committed more errors than TD children. In addition, TD children presented a larger MSIT effect -a greater difference in reaction times between the incongruent and the congruent conditions- than ADHD children. Associated to the MSIT effect, neuroimaging results showed a significant enhancement in the activation of the right lateral prefrontal cortex (rlPFC) in ADHD than in TD subjects. Finally, ADHD subjects presented greater functional connectivity between rlPFC and bilateral orbitofrontal cortex than the TD group. This difference in connectivity correlated with worse performance in both groups. Our results could reflect a compensatory strategy of ADHD children resulting from their effort to maintain an adequate performance during MSIT.


Lipid analysis of a novel type of cell secretion in the exocrine pancreas: the pancreasomes.
A novel type of cell secretion termed 'microvesicular secretion' has been described recently in the exocrine pancreas. According to this process, microvesicles are released by acinocytes in the pancreas acinar lumen. These microvesicles, identified as 'pancreasomes', were characterized by the presence of a major glycoprotein component originating in the exocrine acinar cell. In the present work, phospholipids of pancreasomes have been identified. Five classes of phospholipid were found: phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylcholines, sphingomyelins and another minor class of ninhydrin-positive phospholipid (phosphatidylserines or lysophosphatidylethanolamines). The ratios of neutral lipids to phospholipids were particularly high (3:1), as estimated by GLC of their fatty acid content. Analysis of fatty acid composition of pancreasomes lipids revealed a very high proportion of two saturated fatty acids, palmitic (40%) and stearic (24%), whereas two main unsaturated fatty acids, oleic (17%) and linoleic (8%), were found in smaller proportions. Differential scanning calorimeter studies on washed pancreasomes indicated that there was no lipid phase transition in their membrane, despite the absence of cholesterol. Our observations show that pancreasomes have an unusual lipid composition and confirm our previous conclusion based on protein analysis that the release of pancreasomes occurs according to an hitherto undescribed type of secretion, in which a glycoprotein is released associated with specific domains of the luminal plasma membrane.


A pediatric case of an unusual type of annular pancreas presenting with duodenopancreatic reflux.
Pancreatitis, a late complication of an annular pancreas (AP), results from coexisting pancreaticobiliary malformations including pancreas divisum (PD), and pancreaticobiliary maljunction (PBM). The authors report the case of a 3-year-old boy with an unusual type of AP in which the dorsal anlage encircled the duodenum. The patient developed duodenal obstruction as well as duodenopancreatic reflux with resulting hyperamylasemia and hyperlipasemia. This type of AP associated with duodenopancreatic reflux in AP has not been reported previously. The patient was successfully treated by duodenoduodenostomy, which, by correcting the duodenopancreatic reflux, prevented the later development of pancreatitis.


Bidirectional alterations in antibiotics susceptibility in Staphylococcus aureus-Pseudomonas aeruginosa dual-species biofilm.
In mixed infections, the bacterial susceptibility differs significantly compared to monocultures of bacteria, and generally the concentrations of antibiotics required for the treatment increases drastically. For S. aureus and P. aeruginosa dual species biofilms, it has been numerously reported that P. aeruginosa decreases S. aureus susceptibility to a broad range of antibiotics, including beta-lactams, glycopeptides, aminoglycosides, macrolides, while sensitizes to quinolones via secretion of various metabolites. Here we show that S. aureus also modulates the susceptibility of P. aeruginosa to antibiotics in mixed cultures. Thus, S. aureus-P. aeruginosa consortium was characterized by tenfold increase in susceptibility to ciprofloxacin and aminoglycosides compared to monocultures. The same effect could be also achieved by the addition of cell-free culture of S. aureus to P. aeruginosa biofilm. Moreover, similar increase in antibiotics efficacy could be observed following addition of S. aureus suspension to the P. aeruginosa mature biofilm, compared to P. aeruginosa monoculture, and vice versa. These findings open promising perspectives to increase the antimicrobial treatment efficacy of the wounds infected with nosocomial pathogens by the transplantation of the skin residential microflora.


Recurrent Cerebral Hemorrhage in Normal Pregnancy Secondary to Mycotic Pseudoaneurysms Related to Choriocarcinoma.
Choriocarcinoma coexisting with or after normal pregnancy is extremely rare. To our knowledge, our case report is the first time cerebral mycotic pseudoaneurysms from choriocarcinoma have been proven angiographically. A 38-week pregnant 26-year-old woman presented with an acute left frontal hemorrhage. She underwent emergency cesarean section, followed by hematoma evacuation and resection of what grossly appeared to be a medium-sized arteriovenous malformation at the time of surgery. Angiogram before and after resection showed no obvious vascular pathology. One month later, she returned with status epilepticus, and an acute parenchymal hematoma posterior to the surgical resection cavity was identified. Angiography showed a multilobulated pseudoaneurysm along the left middle cerebral artery. This was resected and found on histopathology to have choriocarcinoma within and around the blood vessels. Serum human chorionic gonadotrophin levels increased daily. Pan computed tomography showed a left lung lobular mass. The diagnosis was stage 4 World Health Organization score 9 high-risk metastatic choriocarcinoma requiring radiation followed by multiagent chemotherapy. Two weeks later, she had another seizure. An angiogram showed an unruptured pseudoaneurysm along the right posterior cerebral artery, which was embolized. Metastatic choriocarcinoma is rarely considered during a viable pregnancy but is almost always fatal if unrecognized. Early recognition enhances the chances of cure with chemotherapy. Arteriovenous malformations are typically considered in young women with intracerebral hemorrhages and have higher risk of rupture in pregnant women, but physicians should also be aware of metastatic choriocarcinoma and the development of mycotic aneurysms in peripartum women with intracerebral hemorrhages.


Restorative treatment in a case of amelogenesis imperfecta and 9-year follow-up: a case report.
Amelogenesis imperfecta is a hereditary malformation showing various manifestations regarding enamel dysplasia. This case report shows a 9-year follow-up after restorative treatment of a 16-year old female patient affected by a hypoplastic type of amelogenesis imperfecta. The caries-free, hypersensitive teeth of the patient were restored by direct dentin adhesive composite restorations performed in total etch technique. After rehabilitation the patient reported a marked improvement of the mastication ability and quality of life especially during food intake. Accumulation of plaque was reduced and the ability to perform adequate oral hygiene was improved. During follow-up of 9 years recurring secondary caries and debonding of fillings were recognized and retreated. The retrospective assessment exhibits that the performed restorative treatment prolonged the time until further treatment has to be considered, such as prosthetic treatment.


STI-571 must select for drug-resistant cells but 'no cell breathes fire out of its nostrils like a dragon'.
Seemingly disappointing, the Bcr-Abl kinase inhibitor STI-571 shares an 'unfortunate' characteristic with conventional cancer drugs: the development of drug resistance. I argue that the resistance must develop even faster to STI-571 than to conventional drugs, because STI-571 is so effective. This is predictable, but is it inevitable? And how do mechanisms of resistance in relapse depend on a degree of remission. In addition to mutation rate and number of tumor cells, one additional factor determines relapse vs. 'extinction' of the leukemia cell population.


[Changes in cytomembrane and surface cells of the large intestine resulting from the action of sweetening agents].
Saccharin and cyclamates have been proved to cause organic damage. This work attempt to describe drug-induced changes brought about by drugs in 1/1000 saccharin and cyclamate-fed rats for 90 days. The ultrastructural findings show: microvilli hypertrophy; membranous mitochondrial increase in absorptive cells; and secretion changes in calciform cells. Such changes are cell-response phenomena to interference or mutagenic action on nuclear DNA or on cytoplasmatic metabolism.


Intracranial injury after moderate head trauma in children.
We retrospectively evaluated the records of 459 children who had normal findings on a neurologic examination after moderate head injury characterized by brief loss of consciousness. Skull x-ray examination had been performed in 358 children, and 52 (14%) had fractures. Intracranial complications developed in six children (1.3%); five had extradural hematomas and one had bifrontal contusions. All six had skull fractures. Three children required surgical evacuation of hematomas between approximately 24 and 72 hours after injury. On the basis of these results, we conclude that in the absence of a skull fracture, most alert children without symptoms who have sustained moderate head injury may be safely discharged from the emergency department in the care of a competent observer.


Spectrophotometry of cerebral cytochrome a, a3 in bloodless rats.
Bloodless, anesthetized Sprague-Dawley rats produced by perfluorochemical exchange transfusion and splenectomy were used to obtain cerebral mitochondrial difference spectra directly through the skull by both reflectance and transmission spectrophotometry. Reflectance peaks were about one-third in amplitude compared to transmission peaks, however percentage reduction levels of cytochrome a, a3 in animals breathing 100% oxygen were comparable. Cytochrome a, a3 was 13-14% reduced under these conditions as determined by the ratio of the optical density difference at 605 minus 620 nm to the optical density difference at the same wavelength pair with maximal cytochrome a, a3 oxidation during respiration on 95% oxygen + 5% carbon dioxide at 3 and 4 atm. absolute pressure.


The value of PLA2R antigen and IgG subclass staining relative to anti-PLA2R seropositivity in the differential diagnosis of membranous nephropathy.
The diagnostic performance of PLA2R and IgG subclass staining of kidney biopsies relative to anti-PLA2R seropositivity in the differentiation of primary and secondary membranous nephropathy (pMN, sMN) was examined. Besides PLA2R staining - which has a lower specificity than anti-PLA2R antibody serology - there is insufficient knowledge to decide which IgG1-4 subtype immunohistological patterns (IgG4-dominance, IgG4-dominance/IgG1-IgG4-codominance or IgG4-dominance/IgG4-codominance with any IgG subtype) could be used to distinguish between pMN and sMN. 87 consecutive Hungarian patients (84 Caucasians, 3 Romas) with the biopsy diagnosis of MN were classified clinically as pMN (n = 63) or sMN (n = 24). The PLA2R and IgG subclass staining was part of the diagnostic protocol. Anti-PLA2R antibodies were determined by an indirect immunofluorescence test in 74 patients with disease activity. For pMN, the sensitivity of anti-PLA2R seropositivity was 61.1%, and the specificity was 90.0%; and similar values for PLA2R staining were 81.0%, and 66.7%, respectively. In all stages of pMN, IgG4-dominance was the dominant subclass pattern, while the second most frequent was IgG3/IgG4-codominance. The sensitivity and specificity scores were: IgG4-dominance 52.2% and 91.7%, IgG4-dominance/IgG3-IgG4-codominance 76.2% and 87.5%, IgG4-dominance/IgG1-IgG4-codominance 64.2% and 75%, and IgG4-dominance/codominance with any IgG subclass 92.1% and 70.8%, respectively. Anti-PLA2R seropositivity, glomerular PLA2R, and IgG4-dominance/codominance significantly correlated with each other. The IgG4 subclass was rarely encountered in sMN. In our series, IgG4-dominance had the highest specificity in the differentiation of MN, just as high as that for anti-PLA2R seropositivity. The specificity values of PLA2R staining and IgG4-dominance/codominance with any IgG subclass or IgG4-dominance/IgG1-IgG4 codominance were ≤ 75%. Apart from IgG4 dominance, IgG4-dominance/IgG3-IgG4-codominance also had good statistical value in differentiating pMN from sMN. As IgG subclass switching during the progression of pMN was not the feature of our cohort, pMN in Hungarian patients is presumed to be an IgG4-related disorder right from the start. Although anti-PLA2R seropositivity has become the cornerstone for diagnosing pMN, if a kidney biopsy evaluation is conducted, besides the staining of PLA2R antigen, the evaluation of IgG subclasses provides relevant information for a differential diagnosis. Even in cases with IgG4-dominance, however, malignancy should be thoroughly checked.


Sexual behaviors and vulnerability to sexually transmitted infections among transgender women in Iran.
Transgender people are at serious risk for HIV infection and other sexually transmitted infections (STIs), they are four times more likely to experience HIV infection than the general population. The aim of this study was to assess sexual behaviors and vulnerability of transgender women to STIs including HIV. A cross-sectional study was conducted using convenient sampling from August 2019 to March 2020 in Iran at "Support center for Iranian transgender" and "Shiraz Forensic Medicine" where transgender individuals refer to follow the steps of gender affirmation. 127 transgender women participated in this study. A researcher-made questionnaire was applied for evaluating sexual behaviors, STIs and HIV. The mean age of participants and their age of sexual debut were 27.6 and 16.9, respectively. 92.1% of participants were single with experience of sex and 59.3% had one sex partner in the last 2 years. 96.9% of the participants were heterosexual with 67.2% reporting experiencing orgasm in at least 50% of their sexual intercourse. However, 42.5% reported sexual pain and the same percentage reported low or very low sexual satisfaction. About half of the participants used condoms occasionally during sex (48.7%) and the most important reason for not using condoms in most cases was not having a condom (37.9%). Some of participants had little knowledge of the symptoms (33.9%) and complications (44.1%) of STIs. Although 87.4% and 72.4% of participants had never been tested for a STI and HIV, 1.6% were HIV positive and 18.1% had a history of STIs. Also, 26% of people had undergone vaginoplasty and a significant association was observed between vaginoplasty with sexual satisfaction (p < 0. 01(. Some of transgender women in this study were involved in high-risk sexual behaviors while unaware of the signs and symptoms of STIs. Also, despite reaching orgasm in most of their sexual relationships, they had little sexual satisfaction that could probably be related to body dissatisfaction, and lack of vaginoplasty in the majority of them. The need for gender affirming surgeries and psychiatric interventions affecting body satisfaction was identified in this group.


Comparison of MRI and ¹⁸F-NaF PET/CT in patients with patellofemoral pain.
To determine whether bone metabolic activity corresponds to bone and cartilage damage in patients with patellofemoral pain. We acquired magnetic resonance imaging (MRI) and (18) F-NaF positron emission tomography (PET) / computed tomography (CT) scans of the knees of 22 subjects. We compared locations of increased tracer uptake on the (18) F-NaF PET images to bone marrow edema and cartilage damage visualized on MRI. We found that increased bone activity on (18) F-NaF PET does not always correspond to structural damage in the bone or cartilage as seen on MRI. Our results suggest that (18) F-NaF PET/CT may provide additional information in patellofemoral pain patients compared to MRI.


Time-domain fluorescence lifetime imaging for intracellular pH sensing in living tissues.
pH sensing in living cells represents one of the most prominent topics in biochemistry and physiology. In this study we performed one-photon and two-photon time-domain fluorescence lifetime imaging with a laser-scanning microscope using the time-correlated single-photon counting technique for imaging intracellular pH levels. The suitability of different commercial fluorescence dyes for lifetime-based pH sensing is discussed on the basis of in vitro as well of in situ measurements. Although the tested dyes are suitable for intensity-based ratiometric measurements, for lifetime-based techniques in the time-domain so far only BCECF seems to meet the requirements of reliable intracellular pH recordings in living cells.


Ruptured subcapsular liver hematoma in pregnancy: a case report of nonsurgical management.
Ruptured subcapsular liver hematoma in pregnancy is a rare condition that is usually managed surgically. Recently, however, surgical and obstetric literature has discussed conservative management. We describe successful conservative management of ruptured subcapsular liver hematoma in a woman with preeclampsia who had hemoperitoneum seen at cesarean section.


Comparison of once- versus twice-daily administration of insulin detemir, used with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes: assessment of detemir administration in a progressive treat-to-target trial (ADAPT).
The purpose of this study was to compare effects of insulin detemir once daily versus twice a day in a basal-bolus insulin regimen. In this open-label, 7-month study, 520 patients with type 1 diabetes were randomly assigned to receive detemir once daily or twice daily with mealtime insulin aspart. Insulin doses were titrated over 1 month, with patients followed up over the subsequent 3 months. Thereafter, patients were able to switch from one regimen to the other, with an additional nonrandomized 3-month follow-up, to a total of 7 months. The primary end point was A1C at 4 months, with noninferiority defined as a difference <0.4% between groups. A1C at 4 months was 8.1 +/- 0.9 versus 8.0 +/- 1.0% with once- and twice-daily detemir, respectively, with an adjusted between-group difference of 0.12% (95% CI -0.01 to 0.25%), showing noninferiority for once-daily dosing. Similar results were found in the per protocol population. Improvement in A1C was similar in both groups (-0.4 +/- 0.8 vs. -0.5 +/- 0.8%; P = 0.09, NS) but with differences in the 7-point glucose profile. Detemir doses were lower (29 +/- 18 vs. 39 +/- 20 units/day, P < 0.001), but aspart doses were higher (34 +/- 17 vs. 26 +/- 14 IU/day, P < 0.001) with once-daily detemir. At 7 months, A1C decreased slightly in patients switched from once-daily to twice-daily administration (8.2 +/- 0.8 vs. 8.0 +/- 0.8%; P = 0.34, NS) in association with increased total insulin doses (P < 0.05), but A1C increased in those switched from twice-daily to once-daily administration (7.2 +/- 0.9 vs. 7.6 +/- 0.8%, P < 0.05) in association with decreased doses (P < 0.05). Although some individuals may benefit from twice-daily dosing, the most suitable routine starting schedule for detemir in a basal-bolus regimen for type 1 diabetes is once-daily injection.


Adapted dietary inflammatory index and differentiated thyroid carcinoma risk in two French population-based case-control studies.
Thyroid cancer is the most common endocrine cancer and its etiology is still not well understood. The aim of the present study was to assess the association between an adapted dietary inflammatory index and differentiated thyroid cancer (DTC) risk in two population-based case-control studies (CATHY and YOUNG-THYR) conducted in France. These studies included a total of 1321 DTC cases and 1502 controls, for which an adapted dietary inflammatory index (ADII) was computed based on food frequency questionnaires in each study separately. The association between ADII and thyroid cancer risk was assessed using logistic regression models controlling for potential confounders. Higher ADII scores, corresponding to a higher pro-inflammatory potential of the diet, were associated with higher DTC risk (odds ratio (OR) for 1 standard deviation (SD) increase: 1.09, 95% confidence interval (CI): 1.01, 1.18, P: 0.03). Associations were stronger in analyses restricted to women (OR for 1-SD increase: 1.14, 95% CI 1.04, 1.25, P: 0.005), as well as in women with lower education level, current smoking, or high body mass index. Our study suggests that a pro-inflammatory diet is associated with an increased risk of DTC, especially when combined with other inflammatory conditions such as tobacco smoking or overweight. Our findings will help better understand the role of diet-induced inflammation in DTC etiology.


4D-Flow Cardiac Magnetic Resonance Imaging in Chronic Aortic Dissection Assessment: A Powerful Qualiquantitative Diagnostic Tool.
4-dimensional-flow cardiac magnetic resonance in patients with aortic dissection in chronic/post repair phase as a complementary diagnostic tool for anatomic-functional evaluation. Quali-quantitative analysis of 3 patients with this pathology clearly showing the true/false lumen, quantitative flow in false lumen, and helping in discerning lumen origin from different arterial vessels. (Level of Difficulty: Advanced.).


Post-translational modification of hemoglobin in alcoholism.
Hemolysates from a majority of alcoholic individuals contain a hemoglobin fraction having chromatographic properties resembling those of hemoglobin AIc, a normally occurring glycosylated hemoglobin, but differing from the latter in not being bound by boronated agarose. A hemoglobin fraction having similar properties was also isolated from human erythrocytes exposed to acetaldehyde. These observations and other evidence suggest that the abnormal hemoglobin fraction present in men and women addicted to alcohol is produced by addition to hemoglobin Ao of an aldehyde or ketone formed metabolically from ethanol and thus may serve as a diagnostic indicator of alcoholism.


An intramedullary capillary hemangioma of the spine with an underlying plasmocytoma.
In contrast to vertebral hemangiomas, which are very common within the general population, only 3% to 5% of patients with plasma cell dyscrasia show a single osteolytic bone lesion due to plasma cell infiltration without the evidence of generalized myeloma. The vast majority of these hemangiomas are completely asymptomatic and only discovered incidentally. In rare occasions, representing only 1% to 2% of the known lesions, a locally aggressive subtype can cause problems analogous to the ones triggered by a plasmocytoma, ranging from back pain to vertebral compression fractures to neurologic deficit, resulting from nerve root or spinal cord compression. Both entities are extensively discussed in the literature, but finding both lesions in one is rare if not described for the first time. To advise colleagues that the differential diagnosis between benign and malignant vertebral tumors can be harder than expected and has to be definitely made to avoid severe consequences for the patient. A 46-year-old healthy man presented to the emergency department with an acute onset of thoracic back pain after a trivial incident. Although his medical history included no known diseases and no history of back pain, plain X-rays raised the clear suspicion of a fracture of T6 that was verified in computed tomography scans. Visual analog scale; neurologic status; tumor recurrence. The case of the patient was evaluated retrospectively according to standard procedures, clinical outcome, and in review of the literature. Because there is still controversy about the best treatment (local radiation vs. operation vs. combination) of a solitary skeletal plasmocytoma, no gold standard has been established until now. Especially if a patient needs an emergency operation before all test results are obtained, each surgeon has to decide individually. Capillary hemangiomas can hide underlying plasmocytomas, which might demand totally different treatment strategies. Although our patient did not match the common criteria for a solitary plasmocytoma, one has to discuss whether a stand-alone decompression and biopsy would have been the emergency treatment of choice. Such a strategy would have reduced the risk of tumor spreading and would have made radiotherapy easier, whereas on the other hand requiring a secondary stabilization procedure later on.


The diagnostic specificity of creatine kinase isoenzymes after transurethral operations.
It has been suggested recently that increases in the concentration of the MB isoenzyme of creatine kinase after transurethral operations could result from release of creatine kinase-MB by prostatic or bladder tissues and, therefore, that creatine kinase-MB is not specific for myocardial damage. Our study of 53 patients undergoing transurethral operations and 37 undergoing urethral dilations showed that creatine kinase-MB is not released in significant quantities from the prostate or bladder. Therefore, we believe that an elevated creatine kinase-MB concentration is specific for myocardial infarction in these patients. We also concluded that the increase in total serum creatine kinase activity in these patients probably results from release of the creatine kinase-MM isoenzyme from periurethral muscle damage by electrocautery.


Cell-lineage-specific expression of the mouse hsp68 gene during embryogenesis.
Transcription of the mouse hsp68 and hsc70 genes in embryonal carcinoma cells, various embryonic and extraembryonic tissues, and some adult tissues has been assessed using cloned probes to the mouse hsp68 gene. The results from Northern blots showed that both F9 and P19 cells respond in the expected manner to a heat shock. Hsp68 expression was only detected in heat-induced F9 and P19 cells. Hsc70 transcripts were present in uninduced cells and their levels increased after induction. In adult tissues, the hsp68 gene was expressed constitutively in the kidney. A different hsp68-like transcript was detected at significant levels in adult testes. Constitutive expression of hsp68 was observed in both the placenta (beginning at Day 8.5) and yolk sac (beginning at Day 11.5). No hsp68 expression was detected in embryonic tissues until Day 15.5. Expression of the mouse hsp68 gene during embryogenesis suggests that it may play some role in development.


The evidence-based clinical decision support guide: mucogingival/esthetics making clinical decisions in the absence of strong evidence.
Although evidence-based decision-making in dentistry is quickly evolving, large gaps remain in our clinical knowledge base regarding every day decisions and procedures. Especially in the absence of strong evidence, as is the case with mucogingival conditions, risk assessment and identification are important components of the clinical decision-making process. Utilization of clinical decision support (CDS) guides, frameworks and systems enhances chairside decision-making and improves delivery of patient care. This article introduces an Evidence-Based Clinical Decision Support Guide for mucogingival/esthetic situations. This CDS guide delineates treatment strategies based upon evidence-based risk assessment and when possible, risk management. It provides the clinician with a framework that will support decision-making at the point of care. Recommendations for consultation, treatment and referral are reviewed.


An electrochemical sensing platform based on a modified carbon paste electrode with graphene/Co3O4 nanocomposite for sensitive propranolol determination.
A simple and sensitive method for the determination of propranolol using a modified carbon paste electrode with graphene/Co3O4 nanocomposite was presented. The electrochemical measurements of propranolol are studied using differential pulse voltammetry, cyclic voltammetry and chronoamperometry. The graphene/Co3O4 nanocomposite exhibits excellent catalytic activity towards the electrochemical oxidation of propranolol in phosphate buffer solution of pH 7.0. The graphene/Co3O4 nanocomposite facilitates the determination of propranolol in the concentration range 1.0-300.0 μM and a detection limit and sensitivity of 0.3 μM. and 0.1275 μA/μM were achieved.


Rare Cutaneous Malignancies in Skin of Color.
There is a scarcity of information regarding the clinical characteristics of rare cutaneous malignancies in skin of color that has yet to be comprehensively explored. To review and compile the racial differences in epidemiology, clinical presentation, histology, treatments, and outcomes of 3 rare skin cancers: dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). Several searches with keywords denoting specific skin cancer type and race were conducted on PubMed to complete this narrative review. We analyzed 50 sources that were relevant to the initial objective. The literature demonstrates that there are nuances in DFSP, MCC, and SC unique to African Americans, Asians/Pacific Islanders, and Hispanics that may differ significantly from Caucasian counterparts. African Americans consistently suffer from the worst clinical outcomes in all 3 rare cutaneous malignancies reviewed. Greater physician awareness and knowledge of the discussed racial differences is the preliminary step to address these disparities.


Soil bacteria showing a potential of chlorpyrifos degradation and plant growth enhancement.
Since 1960s, the organophosphate pesticide chlorpyrifos has been widely used for the purpose of pest control. However, given its persistence and toxicity towards life forms, the elimination of chlorpyrifos from contaminated sites has become an urgent issue. For this process bioremediation is the method of choice. Two bacterial strains, JCp4 and FCp1, exhibiting chlorpyrifos-degradation potential were isolated from pesticide contaminated agricultural fields. These isolates were able to degrade 84.4% and 78.6% of the initial concentration of chlorpyrifos (100mgL(-1)) within a period of only 10 days. Based on 16S rRNA sequence analysis, these strains were identified as Achromobacter xylosoxidans (JCp4) and Ochrobactrum sp. (FCp1). These strains exhibited the ability to degrade chlorpyrifos in sterilized as well as non-sterilized soils, and were able to degrade 93-100% of the input concentration (200mgkg(-1)) within 42 days. The rate of degradation in inoculated soils ranged from 4.40 to 4.76mg(-1)kg(-1)d(-1) with rate constants varying between 0.047 and 0.069d(-1). These strains also displayed substantial plant growth promoting traits such as phosphate solubilization, indole acetic acid production and ammonia production both in absence as well as in the presence of chlorpyrifos. However, presence of chlorpyrifos (100 and 200mgL(-1)) was found to have a negative effect on indole acetic acid production and phosphate solubilization with percentage reduction values ranging between 2.65-10.6% and 4.5-17.6%, respectively. Plant growth experiment demonstrated that chlorpyrifos has a negative effect on plant growth and causes a decrease in parameters such as percentage germination, plant height and biomass. Inoculation of soil with chlorpyrifos-degrading strains was found to enhance plant growth significantly in terms of plant length and weight. Moreover, it was noted that these strains degraded chlorpyrifos at an increased rate (5.69mg(-1)kg(-1)d(-1)) in planted soil. The results of this study clearly demonstrate that the chlorpyrifos-degrading strains have the potential to develop into promising candidates for raising the productivity of crops in pesticide contaminated soils.


Immunocytokines: a promising approach to cancer immunotherapy.
Recombinant antibody-cytokine fusion proteins are immunocytokines that achieve high cytokine concentrations in the tumor microenvironment and thereby effectively stimulate cellular immune responses against malignancies. The activation and expansion of immune effector cells, such as CD8+ T lymphocytes, by interleukin-2 immunocytokines resulted in the eradication of established pulmonary and hepatic metastases of murine melanoma and colorectal carcinoma in syngeneic mouse models. These immunocytokines were equally effective in eliminating established bone marrow and liver metastases of murine neuroblastoma by activating natural killer cells. The effective eradication of metastases by immunocytokines resulted in significant prolongation in life span of mice over that of controls receiving equivalent mixtures of antibody and interleukin-2, which failed to reduce the growth of disseminated metastases. Proof of concept was established, indicating that immunocytokine-induced activation and expansion of immune effector cells in the tumor microenvironment can effectively eradicate established tumor metastases. This promising new approach to cancer immunotherapy may lead to clinical applications that improve treatment of cancer patients with minimal residual disease in an adjuvant setting.


Potential benefit of the cathepsin S inhibitor, ASP1617, as a treatment for systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the dysregulation of various cell types and immunological pathways. Autoantibodies play an important role in its pathogenesis. The presence of autoantibodies suggests that self-antigen presentation through major histocompatibility complex (MHC) class II on antigen presenting cells is involved in the pathogenesis of autoimmune diseases, including SLE. Cathepsin S (CatS) is a key protease for antigen peptide loading onto lysosomal/endosomal MHC class II molecules through invariant chain degradation to promote antigen presentation. Inhibition of CatS is therefore expected to suppress antigen presentation via MHC class II, T and B cell activation, and antibody production from B cells. Here, we report the pharmacological profile of ASP1617, a novel CatS inhibitor. ASP1617 induced invariant chain accumulation and decreased the expression level of MHC class ΙΙ on the cell surface in both mouse and human B cells. Further, ASP1617 prevented DO11.10 mice T cell proliferation to ovalbumin antigen. We investigated the effects of ASP1617 and mycophenolate mofetil (MMF) on the development of lupus-like nephritis in NZB/W F1 mice, a widely used SLE mouse model. Oral administration of ASP1617 suppressed anti-dsDNA IgG, prevented progression of lupus-like glomerulonephritis, and significantly prevented proteinuria excretion. In contrast, MMF did not suppress anti-dsDNA IgG. Further, we found that plasma and/or urine CatS levels were increased in specimens from NZB/W F1 mice and several SLE patients. These results indicate that CatS may be an attractive therapeutic target for the treatment of SLE.


Structural characterization of ultra-stable higher-ordered aggregates generated by novel guanine-rich DNA sequences.
Guanine-rich oligonucleotides (GROs) often show a strong tendency of self-aggregation based on G-quartets and thus form a family of stable higher-ordered structures such as G-wire. Such a structure is specially high-lighted due to the connection with the telomere structure, which is well known to be related with the regeneration mechanism of shortened chromosomal DNAs and to contain GRO repeats such as d(TTAGGG). In this paper, we analyze a new series of GROs by gel electrophoresis and circular dichroism and report a finding of a novel GRO sequence, d(G(11)T), which forms ultra-stable aggregates of higher-ordered structures. The structure of these aggregates was durable against the exposure to denaturants (8 M urea and 40% formamide) at the boiling temperature and even the treatment with an excess amount of nucleases, which was confirmed by assay of electrophoretic mobility. Systematic substitution of nucleotides was introduced to this sequence in order to examine the sequence effect on this phenomenon. Based on the facts thus revealed, we constructed a model for the aggregation phenomenon: successively attaching of a unitary G-quartet block through a switching of Hoogsteen-type pairing like a modular toy 'lego'. Whatever the true structure is, the unusual bonding characteristics and properties of the self-assembling of GROs must be exploited for various purposes related to nano-technology and thus worthy of further investigation from both scientific and technological interest.


Nanobody GPS by PCS: An Efficient New NMR Analysis Method for G Protein Coupled Receptors and Other Large Proteins.
NMR chemical shift changes can report on the functional dynamics of biomacromolecules in solution with sizes >1 MDa. However, their interpretation requires chemical shift assignments to individual nuclei, which for large molecules often can only be obtained by tedious point mutations that may interfere with function. We present here an efficient pseudocontact shift NMR method to assign biomacromolecules using bound antibodies tagged with lanthanoid DOTA chelators. The stability of the antibody allows positioning the DOTA tag at many surface sites, providing triangulation of the macromolecule nuclei at distances >60 Å. The method provides complete assignments of valine and tyrosine 1H-15N resonances of the β1-adrenergic receptor in various functional forms. The detected chemical shift changes reveal strong forces exerted onto the backbone of transmembrane helix 3 during signal transmission, which are absorbed by its electronic structure. The assignment method is applicable to any soluble biomacromolecule for which suitable complementary binders exist.


Renal glutathione depletion and nephrotoxicity of cadmium-metallothionein in rats.
Renal glutathione (GSH) concentrations were reduced approximately 80% at 4 hr after a single injection of buthionine sulfoxime (BSO) (4 mmol/kg body wt) and remained reduced for at least 16 hr in male rats. Following BSO injection, rats were injected with a nephrotoxic dose of cadmium-metallothionein (Cd-MT) (0.3 mg Cd as Cd-MT/kg body wt) and killed 1, 4, or 12 hr later. Damage to the kidney was assessed histologically and by measurement of p-aminohippuric acid (PAH) uptake into renal cortical slices. Although the renal accumulation of Cd following Cd-MT injection was significantly lower in BSO-pretreated rats as compared to nonpretreated rats, the damage to kidney was more severe. At 4 and 12 hr, both Cd-MT-induced inhibition of PAH uptake and morphological damage were significantly increased in BSO-pretreated rats. In certain experiments, the induction of renal intracellular MT synthesis by zinc pretreatment slightly decreased the renal toxicity of Cd-MT in the BSO-treated rats. The results demonstrate that although GSH depletion decreases the renal accumulation of Cd in rats injected with Cd-MT, the nephrotoxicity of Cd-MT is increased. Preinduction of MT in the kidney can only partially overcome this increase in toxicity. Therefore both GSH and intracellular MT levels can influence the renal toxicity of injected Cd-MT.


Trying times: an experience of early pandemic COVID-19 diagnosis and enduring long COVID.
COVID-19 has affected us all, but for those with long COVID there is a need for patience and compassion as we learn to treat this emerging condition. https://bit.ly/3A7JCpZ.


Associations between milk progesterone concentration on different days and with embryo survival during the early luteal phase in dairy cows.
The relationships between the concentration of milk progesterone and early embryo survival on Days 4-8 inclusive and between the concentration of progesterone on different days from Days 0-8 inclusive following ovulation and insemination were examined in dairy cows. The relationships were examined following 77 randomly chosen artificial inseminations to cows in standing oestrus. There was a significant (P < 0.05) linear and quadratic relationship between the concentration of milk progesterone on each of Days 4-6 after ovulation and the probability of embryo survival. There was no association (P > 0.05) between milk progesterone concentration and probability of embryo survival on Days 7 and 8 after ovulation. There were no associations between milk progesterone concentration on Days 0-2 and the concentrations on Days 4-7, however, progesterone concentrations on Days 4 and 5 were highly predictive of the concentration on Days 6 and 7, respectively. Overall, the results indicate that suboptimal progesterone support during the early luteal phase is likely to deleteriously affect embryo viability and in addition, that it is possible to predict milk progesterone concentrations during the early luteal phase based on earlier stage concentrations and thus identify cows at risk of early embryo loss.


Retirement risk factors, exercise management and muscle mass in US senior horses.
Information on the management and health of US senior horses (≥15 years of age) is currently limited. Provide information on (1) primary use of US senior horses, (2) reasons and risk factors for horse retirement, (3) exercise management, (4) prevalence of low muscle mass and (5) risk factors for, and owner-perceived consequences of, low muscle mass. Online survey. Survey responses from 2717 owners of U.S.-resident senior horses (≥15 years of age) were analysed descriptively and inferentially, using ordered and binomial logistic regression, ANOVA and the Kruskal-Wallis test. The most frequently reported primary uses were pleasure riding/driving (38.5%) and full retirement (39.8%). Most horses (61.5%) were retired between 15 and 24 years of age, with health problems being the main reason. Age, female sex, Thoroughbred breed and various medical conditions were identified as risk factors for retirement. In working horses (i.e., those not retired or semi-retired), exercise intensity was negatively associated with age. The owner-reported prevalence of low muscle mass in all horses was 17.2% (95%CI = 15.7-18.7). In those affected by low muscle mass, the ability to work and welfare-related aspects were commonly perceived to be impaired. Increasing age, sex (gelding), pituitary pars intermedia dysfunction, osteoarthritis, laminitis and primary use (retired and semi-retired vs. use for competition) were identified as risk factors for owner-reported low muscle mass. Potential response, recall and sampling bias. Causal relationships cannot be established. Although structured exercise into old age may provide health benefits (as seen in elderly people), a large proportion of horses were fully retired in the current study. Senior horses were mainly retired for health problems and characterising these problems may aid in extending their work/active life. Low muscle mass was perceived to affect horses' welfare and ability to work, and identification of prevention and treatment strategies is therefore warranted.


Characterization of the Treponema denticola Virulence Factor Dentilisin.
Treponema denticola is a potent periodontal pathogen that forms a red complex with Porphyromonas gingivalis and Tannerella forsythia. It has many virulence factors, yet there are only a few reports detailing these factors. Among them, dentilisin is a well-documented surface protease. Dentilisin is reported to be involved in nutrient uptake, bacterial coaggregation, complement activation, evasion of the host immune system, inhibition of the hemostasis system, and cell invasion as a result of its action, in addition to its original proteolysis function. Therefore, characterization of dentilisin, and clarifying the relationship between T. denticola and the onset of periodontal disease will be important to better understanding this disease. In this chapter, we explain the methods for analysis of dentilisin activity and pathogenicity.


Cellular hypersensitivity to UV-A: a clue to the aetiology of actinic reticuloid?
Fibroblasts cultured from six patients with actinic reticuloid (AR) showed striking cytopathic changes and inhibition of RNA synthesis after exposure to near-ultraviolet radiation that had no effect on normal and other photosensitive cell strains, such as those of xeroderma pigmentosum and Bloom syndrome. An abnormal pattern of DNA fragmentation was observed after doses insufficient to cause cytopathic effects. These results suggest a cellular defect in the prevention or repair of some damage caused by free radicals and other photoproducts. In order to explain the pathogenesis of AR, it is proposed that a deficiency in the cellular mechanisms dealing with oxygen radicals leads to the establishment of a vicious circle favouring the persistence of a lymphohistiocytic infiltrate and hence the chronic clinical course characteristic of the disease.


The Tensile Behavior of High-Strength Carbon Fibers.
Carbon fibers exhibit exceptional properties such as high stiffness and specific strength, making them excellent reinforcements for composite materials. However, it is difficult to directly measure their tensile properties and estimates are often obtained by tensioning fiber bundles or composites. While these macro scale tests are informative for composite design, their results differ from that of direct testing of individual fibers. Furthermore, carbon filament strength also depends on other variables, including the test length, actual fiber diameter, and material flaw distribution. Single fiber tensile testing was performed on high-strength carbon fibers to determine the load and strain at failure. Scanning electron microscopy was also conducted to evaluate the fiber surface morphology and precisely measure each fiber's diameter. Fiber strength was found to depend on the test gage length and in an effort to better understand the overall expected performance of these fibers at various lengths, statistical weak link scaling was performed. In addition, the true Young's modulus was also determined by taking the system compliance into account. It was found that all properties (tensile strength, strain to failure, and Young's modulus) matched very well with the manufacturers' reported values at 20 mm gage lengths, but deviated significantly at other lengths.


Lead-210 in vegetables and soils from an area of high natural radioactivity in Brazil.
Contamination of vegetables and associates soils by 210Pb, originating either by natural fallout from uranium or by the processing mills of Poços de Caldas (CIPC), State of Minas Gerais, Brazil is estimated by comparison with similar control samples collected from areas distant from the mining and milling operations. For lichens and bryophytes, the mean values of 210Pb concentrations were significantly higher than those of the control region. Similarly, vegetables and soils from kitchen-gardens located near the mill contained much higher concentrations of 210Pb than those observed for other regions.


Oncogenic Drivers in Myeloproliferative Neoplasms: From JAK2 to Calreticulin Mutations.
During the past 10 years, major progress has been accomplished with the discovery of activating mutations that are associated with the vast majority of BCR-ABL negative human myeloproliferative neoplasms (MPNs). The identification in 2005 of JAK2 V617F triggered great interest in the JAK2-STAT5/STAT3 pathway. Discovery in 2006 of mutants of thrombopoietin receptor (TPO-R/MPL) and later on of mutants in negative regulators of JAK-STAT pathway led to the notion that persistent JAK2 activation is a hallmark of MPNs. In 2013, mutations in the gene coding for the chaperone calreticulin were reported in 20-30% of essential thrombocythemia and primary myelofibrosis patients. Here, we will address the question: what do we know about calreticulin that could help us understand its role in MPNs? In addition to oncogenic driver mutations, certain MPNs also exhibit epigenetic mutations. Targeting of both oncogenic drivers and epigenetic defects could be required for effective therapy.


Paracetamol use and risk of epithelial ovarian cancer: A nationwide nested case-control study.
To investigate whether paracetamol use is associated with a reduced risk of epithelial ovarian cancer (EOC). A nationwide nested case-control study. Danish female population. A total of 9589 EOC cases diagnosed from 2000 to 2019 were age-matched with 383 549 randomly selected female controls using risk set sampling. Paracetamol use, reproductive history, history of medication and history of surgery were retrieved from Danish national registers. Paracetamol use was defined as at least two prescriptions for up to 1 year before the index date, and was further classified according to recency, duration, cumulative dose and intensity of dose. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between paracetamol and EOC risk, overall and by histological subtypes. 'Ever' use of paracetamol was associated with a reduced EOC risk after adjusting for potential confounding factors (OR 0.92, 95% CI 0.87-0.97). The association was only significant among recent users (OR 0.89, 95% CI 0.84-0.95). The risk declined further with the increasing level of cumulative dose and intensity; women from the group with a high cumulative dose and a high intensity had a 13% (OR 0.87, 95% CI 0.80-0.94) and 14% (OR 0.86, 95% CI 0.79-0.93) reduced risk, respectively. In the histological subtype analysis, reduced risk with 'ever' use was most pronounced for serous and clear cell tumours. Paracetamol use was associated with a decreased risk of EOC in a dose-response manner. Future studies are needed to validate the findings and investigate the mechanisms behind the association.


Risk factors of acromial and scapular spine stress fractures differ by indication: a study by the ASES Complications of Reverse Shoulder Arthroplasty Multicenter Research Group.
Both patient and implant related variables have been implicated in the incidence of acromial (ASF) and scapular spine fractures (SSF) following reverse shoulder arthroplasty (RSA); however, previous studies have not characterized nor differentiated risk profiles for varying indications including primary glenohumeral arthritis with intact rotator cuff (GHOA), rotator cuff arthropathy (CTA), and massive irreparable rotator cuff tear (MCT). The purpose of this study was to determine patient factors predictive of cumulative ASF/SSF risk for varying preoperative diagnosis and rotator cuff status. Patients consecutively receiving RSA between January 2013 and June 2019 from 15 institutions comprising 24 members of the American Shoulder and Elbow Surgeons (ASES) with primary, preoperative diagnoses of GHOA, CTA and MCT were included for study. Inclusion criteria, definitions, and inclusion of patient factors in a multivariate model to predict cumulative risk of ASF/SSF were determined through an iterative Delphi process. The CTA and MCT groups were combined for analysis. Consensus was defined as greater than 75% agreement amongst contributors. Only ASF/SSF confirmed by clinical and radiographic correlation were included for analysis. Our study cohort included 4764 patients with preoperative diagnoses of GHOA, CTA, or MCT with minimum follow-up of 3 months (range: 3-84). The incidence of cumulative stress fracture was 4.1% (n = 196). The incidence of stress fracture in the GHOA cohort was 2.1% (n = 34/1637) compared to 5.2% (n = 162/3127) (P < .001) in the CTA/MCT cohort. Presence of inflammatory arthritis (odds ratio [OR] 2.90, 95% confidence interval [CI] 1.08-7.78; P = .035) was the sole predictive factor of stress fractures in GHOA, compared with inflammatory arthritis (OR 1.86, 95% CI 1.19-2.89; P = .016), female sex (OR 1.81, 95% CI 1.20-2.72; P = .007), and osteoporosis (OR 1.56, 95% CI 1.02-2.37; P = .003) in the CTA/MCT cohort. Preoperative diagnosis of GHOA has a different risk profile for developing stress fractures after RSA than patients with CTA/MCT. Though rotator cuff integrity is likely protective against ASF/SSF, approximately 1/46 patients receiving RSA with primary GHOA will have this complication, primarily influenced by a history of inflammatory arthritis. Understanding risk profiles of patients undergoing RSA by varying diagnosis is important in counseling, expectation management, and treatment by surgeons.


Superfused pituitary cell cultures: comparative responsiveness of cells derived from various stages of the estrous cycle to LHRH stimulation administered as short duration pulses.
We have reinvestigated the question of maintenance of differential LHRH sensitivity in culture and further investigated the role of pulsatile LHRH in the in vitro release of pulsatile LH and FSH at different stages of the estrous cycle. Pituitaries were collected on each day of the 4 day cycle at 0800. In addition, pituitaries were also collected at 1500 and 1900 on proestrous. The cells were dispersed and exposed 48 hrs later to short duration 4 ng LHRH pulses; this dose was optimized for LH release and was applied at a frequency of 1 pulse/60 min. In terms of absolute magnitude of LH response, observed responsiveness was ranked in the following order: proestrous 1900 greater than estrous 0800 greater than diestrous 1 0800 greater than proestrous 1500 greater than diestrous 2 0800. Responsiveness was significantly greater at proestrous 1900 (p greater than 0.01), estrous 0800 (p greater than 0.05) and diestrous 1 0800 (p greater than 0.05) when compared to either of the other stages tested. The heightened LHRH sensitivity of proestrous was therefore maintained in cell culture indicating that the system should be valid for conducting studies on the control of gonadotropin secretion during this period. FSH did not respond in pulsatile manner to the LHRH levels employed further substantiating recent evidence that LHRH seems to function somehow less directly in FSH as compared to LH secretion.


Calix[4]arenes linked to multiple bidentate N-donors: potential ligands for synthetic modeling of multinuclear metalloenzymes.
A series of calix[4]arenes incorporating three or four bidentate diamines or pyridylamines attached at the "upper rim" were synthesized via practical protocols. Proof of structure was obtained in one instance by X-ray crystallography. These molecules are designed for general use as ligands for the preparation of multinuclear active site models of metalloenzymes. [reaction: see text]


Laparoscopic surgery induced interleukin-6 levels in serum and gut mucosa: implications of peritoneum integrity and gas factors.
The peritoneum serves as an integral part of host immunity, and the homeostasis of intraperitoneal environment is held to be beneficial for patient recovery after abdominal surgery. How minimal invasive access to the abdomen by laparoscopy and incisions would alter the intraperitoneal immune response is not fully defined. This study examined the levels of IL-6 in serum and gut mucosa following laparoscopic surgery with reference to the peritoneum integrity and gas factors. BALB/c mice were divided into three groups (ten animals in each group) that underwent different abdominal surgical treatments: laparotomy (open group), laparoscopy with atmospheric air (air group) or carbon dioxide pneumoperitoneum (CO(2) group). A 3-cm incision of the skin and muscle was made in all animals except the peritoneum was left intact in the latter two animal groups in order to cancel out the incisional tissue injury present in laparotomy. Four hours after surgery, serum, and jejunal mucosa were extracted for IL-6 measurement by enzyme-linked immunosorbent assay (ELISA). Open laparotomy resulted in significant elevation of serum IL-6 level when compared to the laparoscopic procedures in the descending order of open > air > CO(2) groups. For the mucosal IL-6 level, both the open and air groups were significantly higher than the CO(2) group. Data from multivariate analysis revealed that breaching or incision of the peritoneum was an important factor for the elevated levels of IL-6 in serum (p < 0.001) and jejunal mucosa (p = 0.032). The present study suggests that laparoscopic techniques to minimize the size of the peritoneal incision as well as exposure to atmospheric air can potentially reduce postoperative stress responses associated with abdominal surgery and prompt early recovery.


Association of US County-Level Eviction Rates and All-Cause Mortality.
Housing instability is a key social determinant of health and has been linked to adverse short- and long-term health. Eviction reflects a severe form of housing instability and disproportionately affects minority and women residents in the USA; however, its relationship with mortality has not previously been described. To evaluate the independent association of county-level eviction rates with all-cause mortality in the USA after adjustment for county demographic, socioeconomic, and health-related characteristics. Cross-sectional. Six hundred eighty-six US counties with available 2016 county-level eviction and mortality data. 2016 US county-level eviction rate. 2016 US county-level age-adjusted all-cause mortality. Among 686 counties (66.1 million residents, 50.5% [49.7-51.2] women, 2% [0.5-11.1] Black race) with available eviction and mortality data in 2016, we observed a significant and graded relationship between county-level eviction rate and all-cause mortality. Counties in the highest eviction tertile demonstrated a greater proportion of residents of Black race and women and a higher prevalence of poverty and comorbid health conditions. After adjustment for county-level sociodemographic traits and prevalent comorbid health conditions, age-adjusted all-cause mortality was highest among counties in the highest eviction tertile (Tertile 3 vs 1 (per 100,000 people) 33.57: 95% CI: 10.5-56.6 p=.004). Consistent results were observed in continuous analysis of eviction, with all-cause mortality increasing by 9.32 deaths per 100,000 people (4.77, 13.89, p<.0001) for every 1% increase in eviction rates. Significant interaction in the relationship between eviction and all-cause mortality was observed by the proportion of Black and women residents. In this cross-sectional analysis, county-level eviction rates were significantly associated with all-cause mortality with the strongest effects observed among counties with the highest proportion of Black and women residents. State and federal protections from evictions may help to reduce the health consequences of housing instability and address disparities in health outcomes.


KV channels and the regulation of vascular smooth muscle tone.
VSMCs in resistance arteries and arterioles express a diverse array of KV channels with members of the KV 1, KV 2 and KV 7 families being particularly important. Members of the KV channel family: (i) are highly expressed in VSMCs; (ii) are active at the resting membrane potential of VSMCs in vivo (-45 to -30 mV); (iii) contribute to the negative feedback regulation of VSMC membrane potential and myogenic tone; (iv) are activated by cAMP-related vasodilators, hydrogen sulfide and hydrogen peroxide; (v) are inhibited by increases in intracellular Ca2+ and vasoconstrictors that signal through Gq -coupled receptors; (vi) are involved in the proliferative phenotype of VSMCs; and (vii) are modulated by diseases such as hypertension, obesity, the metabolic syndrome and diabetes. Thus, KV channels participate in every aspect of the regulation of VSMC function in both health and disease.


The Immunotherapy Roadmap.
As new active agents are discovered and approved, it is clear that combinations of these immunotherapies will be needed to reject most human cancers. The era of personalized patient tumor analysis has arrived just in time to guide these combinations.


Expression of TRAIL, DR4, and DR5 in bladder cancer: correlation with response to adjuvant therapy and implications of prognosis.
To explore the interrelationship of human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptors DR4 and DR5 expressions level with patient prognosis and the response to adjuvant therapy in bladder cancer, the synergism function that is between chemotherapy and TRAIL on apoptosis induction in tumor cells. The expression of TRAIL, DR4, and DR5 was studied using immunohistochemistry of paraffin-embedded tumor specimens from 229 bladder cancer patients who had undergone transurethral resection. Cytoplasmic TRAIL, DR4, and DR5 expressions were detected in 35%, 75.1%, and 74.2% of bladder cancer patients, respectively. Patients with bladder cancer with either high DR4 or DR5 expression had a significantly longer postoperative recurrence-free rate than those with low expression of both during the 10-year follow-up. Multivariate analysis revealed that the expression of DR4 (P < .001), DR5 (P < .001) and epirubicin therapy (P = .034) were independent prognostic indicators of bladder cancer. Furthermore, epirubicin therapy significantly improved recurrence-free rate for the patients with DR4-high (P = .006) or DR5-high (P = .042) tumor. The results of the present study have shown for the first time that a combination of DR4 and DR5 expression have significant value in predicting the prognosis of bladder cancer. In addition, patients with high expression of both DR4 and DR5 might benefit from epirubicin therapy.


Limited impact of chytridiomycosis on juvenile frogs in a recovered species.
The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) has caused catastrophic frog declines on several continents, but disease outcome is mediated by a number of factors. Host life stage is an important consideration and many studies have highlighted the vulnerability of recently metamorphosed or juvenile frogs compared to adults. The majority of these studies have taken place in a laboratory setting, and there is a general paucity of longitudinal field studies investigating the influence of life stage on disease outcome. In this study, we assessed the effect of endemic Bd on juvenile Mixophyes fleayi (Fleay's barred frog) in subtropical eastern Australian rainforest. Using photographic mark-recapture, we made 386 captures of 116 individuals and investigated the effect of Bd infection intensity on the apparent mortality rates of frogs using a multievent model correcting for infection state misclassification. We found that neither Bd infection status nor infection intensity predicted mortality in juvenile frogs, counter to the expectation that early life stages are more vulnerable to disease, despite average high infection prevalence (0.35, 95% HDPI [0.14, 0.52]). Additionally, we found that observed infection prevalence and intensity were somewhat lower for juveniles than adults. Our results indicate that in this Bd-recovered species, the realized impacts of chytridiomycosis on juveniles were apparently low, likely resulting in high recruitment contributing to population stability. We highlight the importance of investigating factors relating to disease outcome in a field setting and make recommendations for future studies.


Neurosurgical management of brain metastases.
Brain metastases present a significant public health issue, affecting more than 100,000 patients per year in the U.S. and result in significant morbidity. Brain metastases can occur in a variety of clinical situations ranging from multiple brain metastases with uncontrolled systemic disease to a solitary metastasis in the setting of controlled systemic disease. Additionally, advances in genomics have broadened the opportunities for targeted treatment options and potentially more durable systemic responses. As such, the treatment of brain metastases is now more tailored and multimodal, involving systemic, radiation, and surgical therapies, often in combination. This review discusses the historical and current role of neurosurgical techniques in the treatment of brain metastases.


Bilateral internal thoracic artery grafting with and without cardiopulmonary bypass: six-year clinical outcome.
We sought to evaluate whether early and late results in patients who underwent off-pump or on-pump myocardial revascularization with bilateral internal thoracic artery grafting were similar. From November 1994 through December 2001, 1835 patients underwent isolated myocardial revascularization with bilateral internal thoracic artery grafting. By applying propensity score pairwise matching, 1194 patients were selected and operated on either off pump (n = 597) or on pump (n = 597). The overall 30-day mortality was 1.5% (1.2% in the off-pump group and 1.8% in the on-pump group, P = .342). There was no difference for all the other complications between the 2 groups. Mean follow-up was 5.2 +/- 1.8 years. Forty-two patients died over the follow-up period (22 in the off-pump group and 20 in the on-pump group), 15 of them of cardiac causes (7 in the off-pump group and 8 in the on-pump group). Six-year outcomes (freedom from death, cardiac death, acute myocardial infarction and reoperation in all or in the grafted area, target cardiac events, and any other event) were similar for both categories. After a mean of 30.7 +/- 20.1 months, 202 patients had a postoperative angiography showing similar results. Our results with extensive arterial revascularization clearly show that with the technical improvements achieved in the most recent years, off-pump operations can be performed safely with the same quality of late results as those obtained with on-pump operations.


Growing fast food consumption and obesity in Asia: Challenges and implications.
It is widely believed that better access to fast food (FF) outlets increases FF consumption and thus the risk of obesity; yet, thus far, there are limited results to support this conclusion in Asian countries. A recent study by Hall and his colleagues (in press) examined the cross-sectional relationship between FF restaurant density and the likelihood of being overweight or obese among 1388 female Filipino migrant workers living in Macao, China. It found that FF restaurant density within a 0.5-mile buffer zone around one's home was significantly associated with a 7% increase (95% CI: 1%-14%) in the odds of being overweight or obese in this population. Based on these findings, the authors suggested improving access to healthy foods as one of the means to fight the obesity epidemic. The current article examines literature 1) on the relationship between obesity, FF consumption, and access to FF outlets; 2) on different measures of access to FF outlets; 3) on potential confounders and effect modifiers such as neighborhood deprivation and transportation; and 4) on challenges and implications for researchers and policymakers. Considering the growing consumption of FF and obesity rates in many countries especially in developing countries, it is important to regulate the FF industry and help consumers improve their related knowledge and behaviors. We also recommend that government policies abate obesogenic environments and thus curb the obesity epidemic in the future.


A computational approach to calculate the heat of transport of aqueous solutions.
Thermal gradients induce concentration gradients in alkali halide solutions, and the salt migrates towards hot or cold regions depending on the average temperature of the solution. This effect has been interpreted using the heat of transport, which provides a route to rationalize thermophoretic phenomena. Early theories provide estimates of the heat of transport at infinite dilution. These values are used to interpret thermodiffusion (Soret) and thermoelectric (Seebeck) effects. However, accessing heats of transport of individual ions at finite concentration remains an outstanding question both theoretically and experimentally. Here we discuss a computational approach to calculate heats of transport of aqueous solutions at finite concentrations, and apply our method to study lithium chloride solutions at concentrations >0.5 M. The heats of transport are significantly different for Li+ and Cl- ions, unlike what is expected at infinite dilution. We find theoretical evidence for the existence of minima in the Soret coefficient of LiCl, where the magnitude of the heat of transport is maximized. The Seebeck coefficient obtained from the ionic heats of transport varies significantly with temperature and concentration. We identify thermodynamic conditions leading to a maximization of the thermoelectric response of aqueous solutions.


Heterologous expression of human prostatic acid phosphatase and site-directed mutagenesis of the enzyme active site.
Earlier covalent modification experiments indicated that histidine, arginine, and carboxylic acid residues were involved in the catalytic mechanism of the acid phosphatase enzyme from human prostate. The present study utilizes site-directed mutagenesis to evaluate the catalytic importance of 7 residues of human prostatic phosphatase, namely His12, His257, Asp258, Arg11, Arg15, Arg54, and Arg79, which are highly conserved in the sequences of high molecular weight acid phosphatases. Both wild type and mutant enzymes were expressed in the yeast Saccharomyces cerevisiae as fusions to a leader peptide of prepro-alpha-factor, which resulted in the secretion of processed proteins into the culture media. The kinetic parameters of the recombinant wild type enzyme were shown to be effectively identical with those of the native protein. The circular dichroism spectra of wild type and mutant proteins were effectively superimposable. Replacement of His12, which was previously shown to be transiently phosphorylated during catalysis, as well as the adjacent Arg11, both resulted in > 10(4) reductions of enzyme activity. Consistent with a postulated involvement of arginine residues in substrate binding, large reductions in Vmax caused by the R15A and R79A mutations were accompanied by marked increases in Km. However, the mutation R54A had only small effects on kinetic parameters. Essential roles for both His257 and Asp258 were also established. The D258A mutation not only caused larger decreases of Vmax toward p-nitrophenyl phosphate compared to the effect of the H257A mutation, but it also caused the reaction to become more sensitive to the nature of the leaving group. It is concluded that His12 and Asp258 are involved in the formation of the phosphoenzyme intermediate as an acceptor of the phospho group and a proton donor for the substrate leaving group, respectively, while His257 may participate in substrate binding or may facilitate the breakdown of the phosphoenzyme by maintaining the protonated state of the phosphorylated His12 residue.