Prognostic significance of postoperative serum carcinoembryonic antigen levels in patients with completely resected pathological-stage I non-small cell lung cancer.
Until date, there are no clear recommendations for regular perioperative measurements of serum CEA levels for lung cancer in any guidelines. The purpose in the present study is to evaluate the prognostic significance of perioperative serum carcinoembryonic antigen (CEA) levels in patients with pathological-stage I non-small cell lung cancer (NSCLC). We retrospectively reviewed 263 completely resected pathological-stage I NSCLC patients whose preoperative and postoperative serum CEA levels were measured. Patients were subdivided according to the perioperative change of CEA levels: continuously normal CEA levels (NN group), continuously high CEA levels (HH group), and high preoperative CEA levels that returned to normal levels post-operation (HN group). The clinicopathological factors and overall survival (OS) among these 3 groups were compared. Univariate and multivariate analyses of the correlation between clinicopathological factors and OS were performed. High preoperative CEA levels significantly correlated with men aged >70 years with smoking history, high serum CYFRA 21-1 levels, greater tumor diameter, presence of visceral pleural invasion (VPI), and moderate-to-poor differentiation. Five-year OS rates in the NN and HH groups were 95.5% and 59.3%, respectively. Four-year OS rate in the HN group was 85.5%. Multivariate analyses indicated tumor diameter of more than 30 mm, presence of VPI, and the HH group were independent unfavorable prognostic factors. A high postoperative CEA level was an independent unfavorable prognostic factor in pathological-stage I NSCLC patients. Patients with high postoperative CEA levels may benefit from adjuvant chemotherapy.


Niche Differentiation of Active Methane-Oxidizing Bacteria in Estuarine Mangrove Forest Soils in Taiwan.
Mangrove forests are one of the important ecosystems in tropical coasts because of their high primary production, which they sustain by sequestering a substantial amount of CO2 into plant biomass. These forests often experience various levels of inundation and play an important role in CH4 emissions, but the taxonomy of methanotrophs in these systems remains poorly understood. In this study, DNA-based stable isotope probing showed significant niche differentiation in active aerobic methanotrophs in response to niche differentiation in upstream and downstream mangrove soils of the Tamsui estuary in northwestern Taiwan, in which salinity levels differ between winter and summer. Methylobacter and Methylomicrobium-like Type I methanotrophs dominated methane-oxidizing communities in the field conditions and were significantly 13C-labeled in both upstream and downstream sites, while Methylobacter were well adapted to high salinity and low temperature. The Type II methanotroph Methylocystis comprised only 10-15% of all the methane oxidizers in the upstream site but less than 5% at the downstream site under field conditions. 13C-DNA levels in Methylocystis were significantly lower than those in Type I methanotrophs, while phylogenetic analysis further revealed the presence of novel methane oxidizers that are phylogenetically distantly related to Type Ia in fresh and incubated soils at a downstream site. These results suggest that Type I methanotrophs display niche differentiation associated with environmental differences between upstream and downstream mangrove soils.


Gene expression during mammalian spermatogenesis. III. Changes in populations of mRNA during spermiogenesis.
Round spermatids and elongating spermatids were purified from a suspension of mouse testicular cells by sedimentation at unit gravity coupled with density gradient centrifugation through Percoll. Following separation, the two cell types were fractionated into polysomal and non-polysomal compartments. By comparison with round spermatids, elongating spermatids contain about one-half as much cytoplasmic RNA per cell, one sixth as much poly(A)+ RNA per cell and one-half the concentration of poly (A)+ mRNA in their cytoplasm. About two-thirds of the poly(A)+ messenger RNA (mRNA) was in the non-polysomal fraction in both cell types. Polypeptides whose synthesis was directed by cell-free translation of purified mRNA from each cell fraction were analyzed by two-dimensional gel electrophoresis. At the level of detection provided by the electrophoretic methods used, the majority of peptides from the polysomal and non-polysomal compartments for each cell type were similar. However, between the two cell types, approx. 5-10% of the polypeptides in the polysomal and non-polysomal fractions differed markedly in abundance. When the polypeptides encoded by the polysomal and non-polysomal mRNA from round spermatids were compared to the polypeptides encoded in the equivalent fractions from elongating spermatids, a significant reduction in number of polypeptides from elongating spermatids was seen. The presence of specific mRNAs in the non-polysomal fraction of round spermatids and in the polysomal fraction of elongating spermatids suggests that storage of mRNA in the cytoplasm and subsequent utilization provides a source of mRNA for proteins expressed at a time during spermiogenesis when transcription has terminated.


Isolation of Human Circulating Myeloid-Derived Suppressor Cells and Analysis of Their Immunosuppressive Activity.
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of myeloid cells with potent immunosuppressive activity and characterized by a pathological state of activation. The T cell suppression assay is the most common method to evaluate the suppressive capacity of MDSC. Identifying the suppressive potential of different MDSC subsets within individual donors is key for understanding the biology of MDSC and their clinical relevance. Here we describe assays to ascertain and quantify the suppression of autologous T cells by human MDSC. These include the dye dilution proliferation assay for flow cytometry and the detection of IFNγ production by T cells using flow cytometry and sandwich ELISA.


Prediction of protein secondary structure and active sites using the alignment of homologous sequences.
The prediction of protein secondary structure (alpha-helices, beta-sheets and coil) is improved by 9% to 66% using the information available from a family of homologous sequences. The approach is based both on averaging the Garnier et al. (1978) secondary structure propensities for aligned residues and on the observation that insertions and high sequence variability tend to occur in loop regions between secondary structures. Accordingly, an algorithm first aligns a family of sequences and a value for the extent of sequence conservation at each position is obtained. This value modifies a Garnier et al. prediction on the averaged sequence to yield the improved prediction. In addition, from the sequence conservation and the predicted secondary structure, many active site regions of enzymes can be located (26 out of 43) with limited over-prediction (8 extra). The entire algorithm is fully automatic and is applicable to all structural classes of globular proteins.


Resurrecting the alternative splicing landscape of archaic hominins using machine learning.
Alternative splicing contributes to adaptation and divergence in many species. However, it has not been possible to directly compare splicing between modern and archaic hominins. Here, we unmask the recent evolution of this previously unobservable regulatory mechanism by applying SpliceAI, a machine-learning algorithm that identifies splice-altering variants (SAVs), to high-coverage genomes from three Neanderthals and a Denisovan. We discover 5,950 putative archaic SAVs, of which 2,186 are archaic-specific and 3,607 also occur in modern humans via introgression (244) or shared ancestry (3,520). Archaic-specific SAVs are enriched in genes that contribute to traits potentially relevant to hominin phenotypic divergence, such as the epidermis, respiration and spinal rigidity. Compared to shared SAVs, archaic-specific SAVs occur in sites under weaker selection and are more common in genes with tissue-specific expression. Further underscoring the importance of negative selection on SAVs, Neanderthal lineages with low effective population sizes are enriched for SAVs compared to Denisovan and shared SAVs. Finally, we find that nearly all introgressed SAVs in humans were shared across the three Neanderthals, suggesting that older SAVs were more tolerated in human genomes. Our results reveal the splicing landscape of archaic hominins and identify potential contributions of splicing to phenotypic differences among hominins.


Molecular analysis of the variant alloantigen HLA-B27d (HLA-B*2703) identifies a unique single amino acid substitution.
HLA-B27 is a human major histocompatibility complex class I product defined by its antigenic specificity with conventional alloantisera. Detailed studies using monoclonal antibodies, cytotoxic T lymphocytes (CTL), and isoelectric focusing (IEF) gel electrophoresis demonstrated the heterogeneity in the B27 antigen. We have previously identified a unique variant molecule of B27 designated locally as B27d which is distinguished from other B27 variants by isoelectric point, serologic reactivity, and by a cloned CTL recognition. A gene encoding the B27d variant has been cloned and a complete nucleotide sequence has been determined. Compared to the sequence of the prototype B27a, the B27d has a single base substitution at codon 59 (B27a:TAT--B27d: CAT) in exon 2 responsible for Tyr to His substitution. A His residue at this position in the alpha 1 domain is unique among the known class I sequences and this single amino acid change is apparently sufficient to alter the epitope(s) recognized by antibody and cytotoxic T cell receptor. Previous primary structural analysis of the other five B27 variants has revealed differences of two to four amino acids. The combined structural data on the B27 variants indicate that (1) HLA-B27 represents a family of closely related B locus alleles that share the B27 allospecificity and differ by a limited number (one to four) of amino acid substitutions and (2) point mutation as well as gene conversion might be the mechanism responsible for the allelic variation of B27 antigen family.


Comparison of two methods of transporting paramedics to cardiac arrests outside hospital.
To compare the deployment of paramedics in a separate rapid response unit with their deployment in a standard emergency ambulance. A one year period of each deployment. Throughout the community in some parts of West Yorkshire. All patients receiving resuscitation for cardiac arrest by paramedics. Using the same group of paramedics and central control, 12 months with the paramedics deployed in separate cars in addition to the standard ambulances (period 1) were followed by another 12 months when they were deployed as one crew member of a standard emergency ambulance (period 2). Number of arrests attended, number of patients in ventricular fibrillation at paramedic arrival, response times, survival to leave hospital. In period 1, 580 arrests were attended with 31 survivors. In period 2, 462 arrests resulted in 25 survivors. The mean response time was shorter in period 1 (6.24 versus 6.60 min, Cl--0.01-0.73 min). In period 1, 217 patients were found in ventricular fibrillation (23 survivors): In period 2, 141 patients were found in ventricular fibrillation (11 survivors). Separating paramedics from the standard emergency ambulances increases the number of survivors of cardiac arrest but the difference may not be sufficiently large to justify the additional expenditure.


Monoclonal antibodies to tissue-specific chromatin proteins.
Antisera raised in mice to chromatins from different tissues of the chicken reacted preferentially with the chromatin type that was used for immunization. This tissue specificity was also evident in the spectrum of monoclonal antibodies generated when mice were immunized with erythrocyte chromatin. Three erythroid-specific antigens and one antigen that was present in a number of chicken tissues were characterized in further detail. These antigens, which comprised less than 0.1% of the erythrocyte chromatin proteins, were nuclear localized although three were also detected in the cytoplasm. Two of the erythroid-specific antigens existed as multiple polypeptides in isolated chromatin. The multiple chromatin forms of one antigen were derived from a precursor protein that was selectively cleaved within 1 min after erythrocyte lysis. Analysis of this antigen in extracts from erythrocytes and reticulocytes indicated that the cleavage of the precursor protein was developmentally regulated in vivo.


Leveraging secondary data for evaluation: Planning the expansion of the Illinois asthma partnership to reduce pediatric asthma related emergency department visits.
Government partnerships with community-based and healthcare organizations have historically increased the impact of public health programs. In order to strengthen and expand the Illinois Asthma Partnership (IAP), external evaluators determined the degree to which local rates of Pediatric Asthma Related Emergency Department (PARED) visits aligned with local hospital Community Health Needs Assessments (CHNA), asthma prioritization, and IAP engagement. The majority of counties with high PARED rates also had high levels of concentrated disadvantage. Combining these data enabled identification of 15 out of 102 counties where PARED visits were high and the program was not engaged. In these counties, there was an opportunity for the IAP to assist. Potential actions in these counties could include identification of a local asthma champion and development of a new program, actions to raise community awareness of asthma, and engagement with health care community leaders to discuss perceptions of need and competing priorities. This study provided a unique and cost-effective way of utilizing easily accessible data in order to plan the expansion of the IAP.


Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium.
Synovial hyperplasia, resulting in erosion of cartilage and bone, represents one of the major pathologies associated with rheumatoid arthritis. To develop an approach for efficient delivery of proteins or agents to synovium to induce targeted apoptosis of hyperplastic synovial tissue, we have screened an M13 peptide phage display library for synovial-specific transduction peptides. We identified a novel synovial-targeted transduction peptide, HAP-1, which is able to facilitate specific internalization of protein complexes into human and rabbit synovial cells in culture and rabbit synovial lining in vivo. HAP-1 and a non-tissue-specific cationic protein transduction domain, PTD-5, were fused to an antimicrobial peptide, (KLAK)(2), to generate two proapoptotic peptides termed DP2 and DP1, respectively. Administration of these peptides was able to induce apoptosis of rabbit and human synovial cells in culture, with DP2 inducing synovial cell-specific apoptosis. Intra-articular injection of DP1 and DP2 into arthritic rabbit joints with synovial hyperplasia induced extensive apoptosis of the hyperplastic synovium, while reducing the leukocytic infiltration and synovitis. These results suggest that proapoptotic peptides and, in particular, DP2 can be clinically useful for treatment of synovial hyperplasia, as well as inflammation. Moreover, the results demonstrate the feasibility of identifying tissue-specific transduction peptides capable of mediating efficient transduction in vivo.


Digoxin and nifedipine.
Many investigators have studied the potential interactions between calcium-channel antagonists and digoxin. Digoxin is usually well absorbed, and its excretion is dependent on renal mechanisms, primarily glomerular filtration. Several studies have reported a decrease in digoxin clearance and an increase of approximately 50% in digoxin levels when verapamil was added to digoxin therapy. Because renal digoxin clearance was decreased but no concomitant change in creatinine clearance was shown, the presumed major mechanism for decreased renal digoxin clearance is an alteration in renal tubular secretion of digoxin. Although an early report described a digoxin-nifedipine interaction, several subsequent studies have shown no significant changes in digoxin kinetics during nifedipine administration. Four studies found no significant decrease in creatinine clearance of digoxin during nifedipine administration. Thus significant changes in glomerular filtration are unlikely. Physiologic endpoints were measured by 2 groups describing a digoxin-nifedipine interaction and, although there was an increase in serum digoxin concentration, no changes were found in electrophysiologic correlates. Thus, if a digoxin-nifedipine interaction does exist, steady-state digoxin levels might increase from 24 to 45% when nifedipine therapy is added. Studies to date have involved small numbers of subjects with and without cardiac disease and have used different study protocols. Nonetheless, little evidence exists for any clinically significant increase in physiologic effects and no adverse effects have been found in patients receiving combined nifedipine and digoxin.


Bedside monitoring of heparin therapy.
Continuous infusion heparin therapy was monitored in twenty-five patients with simultaneously performed activated partial thromboplastin times and activated clotting times. These data were then compared by means of the coefficient of correlation. Significant correlation is demonstrated between the APTT and ACT in 88 per cent of cases.


Antifungal efficacy of herbs.
Candida carriage was reported to be common in oral cancer patients, with C. albicans being the predominant species. The prevalence of diseases caused by Candida species have been found to increase in recent years. The aim of our study was to find the antifungal activities at MIC of selected fifteen plant leaves extracts prepared in three different solutions (methanol and ethanol) against the opportunistic pathogen Candida albicans isolated from oral cavity infections. It may also help the clinician to treat the patient not only for the particular lesion that is present, but also to treat the infection by Candida albicans so as to reduce its potential to malignant transformation. Material n methods: Leaves extract of selected plant prepared in methanolic and eethanolic solution have been chosen for the investigation of in vitro antifungal activity which acts as expectorant and not having toxic properties on humans while for comparison or control, antifungal drugs have been taken. Results showed that Candida albicans shows most sensitivity towards the standard antibiotic cotrimoazol but very less towards other drugs like Fluconazole, minocycline, erythromycin respectively which indicated Candida albicans shows some resistance character towards drugs while the herbal extracts of Lawsonia inermis, Withania somnifer, Curcuma longa, Cymbopogon citrates and Zingiber officinale gives the best inhibitory effect and they have the potential to control growth of Candida albicans.


A new Polylopha species attacking cinnamon trees in Vietnam (Lepidoptera: Tortricidae: Chlidanotinae: Polyorthini).
Polylopha vietnama sp. nov. (Tortricidae: Chlidanotinae: Polyorthini), a new pest of cinnamon (Cinnamomum cassia, Lauraceae), is described from northern Vietnam. A related species, Lopharcha ditissima Diakonoff (1974) from Indonesia (Java), is transferred to the genus Polylopha, as P. ditissima (Diakonoff) comb. nov., resulting in nine species for the genus.


Inflammasomes: Intracellular detection of extracellular bacteria.
The non-canonical inflammasome triggers host cell death and inflammation upon recognition of cytosolic LPS. A recent report in Cell now shows that Outer Membrane Vesicles (OMVs) of extracellular Gram-negative bacteria can deliver LPS into the host cell cytosol.


Non-canonical Glutamate-Cysteine Ligase Activity Protects against Ferroptosis.
Cysteine is required for maintaining cellular redox homeostasis in both normal and transformed cells. Deprivation of cysteine induces the iron-dependent form of cell death known as ferroptosis; however, the metabolic consequences of cysteine starvation beyond impairment of glutathione synthesis are poorly characterized. Here, we find that cystine starvation of non-small-cell lung cancer cell lines induces an unexpected accumulation of γ-glutamyl-peptides, which are produced due to a non-canonical activity of glutamate-cysteine ligase catalytic subunit (GCLC). This activity is enriched in cell lines with high levels of NRF2, a key transcriptional regulator of GCLC, but is also inducible in healthy murine tissues following cysteine limitation. γ-glutamyl-peptide synthesis limits the accumulation of glutamate, thereby protecting against ferroptosis. These results indicate that GCLC has a glutathione-independent, non-canonical role in the protection against ferroptosis by maintaining glutamate homeostasis under cystine starvation.


Formation of a stable dicarbenoid and an unsaturated C2P2S2 ring from two-electron oxidation of the [C(PPh2S)2]2- dianion.
Two-electron oxidation of the [C(PPh(2)S)(2)](2-) dianion with iodine afforded an unexpected mixture of a dimeric Li-I carbenoid [(Et(2)O)(mu-Li)][(mu(4)-Li){IC(PPh(2)S)(2)}(2)] and a novel, unsaturated six-membered C(2)P(2)S(2) ring in [(SPh(2)P)(2)C(2)(PPh(2))(2)S(2)].


Comparative study of IFNγ and antibody tests for feline tuberculosis.
This study describes the comparison of the cell-based interferon-gamma (IFNγ) test with serological rapid antibody tests (STAT-PAK and DPP VetTB) for the ante mortem testing of tuberculosis in domestic cats. The antibody specificities of rapid antibody test-positive cats were further discerned using multi-antigen print immunoassay. A total of 62 cats with culture-confirmed Mycobacterium bovis, Mycobacterium microti, Mycobacterium avium and Mycobacterium malmoense, as well as negative controls and dangerous-contact cats were tested. Tests were also applied longitudinally to one further cat undergoing TB chemotherapy for suspected M. bovis infection. Our data from this small study show excellent test specificity (100% for all tests) and encouraging levels of test sensitivity for M. bovis and TB Complex infections (IFNγ 70-100% depending upon test interpretation criteria; rapid tests both 90% for M. bovis infection and up to 46.2% for M. microti infection). The differential diagnosis of very pathogenic TB Complex (M. bovis, Mycobacterium tuberculosis), as opposed to less-pathogenic TB Complex (M. microti) was possible where positive responses to the protein cocktail ESAT6/CFP10 were observed (80% of M. bovis-infected cats in this study showed positive IFNγ responses to ESAT6/CFP10, while 20% had antibody responses to ESAT6/CFP10 using MAPIA). Finally, preliminary data from a longitudinal study of one M. bovis-exposed cat with a positive IFNγ test pre-treatment suggest that a decrease in bacterial burden may be reflected in the IFNγ response, and thus the IFNγ test may provide a monitor for TB chemotherapy.


Heterogeneous virologic response rates to interferon-based therapy in patients with chronic hepatitis C: who responds less well?
The introduction of new agents and regimens for the treatment of chronic hepatitis C, such as pegylated interferons and combination therapy with ribavirin, has resulted in substantial improvements in sustained virologic response rates. However, treatment remains a challenge, particularly for certain patient populations, because several virus-related and patient-related factors are associated with a lower virologic response to therapy. Hepatitis C virus genotype 1 and a high baseline viral load are the major viral factors associated with lower response. Patient-related factors include previous relapse or nonresponse to treatment, the presence of cirrhosis, African-American ethnicity, older age, contraindications to treatment, and obesity. This article reviews the data on interferon-based therapies among patients with lower chances for sustained virologic response and discusses the potential of the new pegylated interferons.


Activation of apoptosis by ethyl acetate fraction of ethanol extract of Dianthus superbus in HepG2 cell line.
Dianthus superbus L. is commonly used as a traditional Chinese medicine. We recently showed that ethyl acetate fraction (EE-DS) from ethanol extract of D. superbus exhibited the strongest antioxidant and cytotoxic activities. In this study, we examined apoptosis of HepG2 cells induced by EE-DS, and the mechanism underlying apoptosis was also investigated. Treatment of HepG2 cells with EE-DS (20-80 μg/ml) for 48 h led to a significant dose-dependent increase in the percentage of cells in sub-G1 phase by analysis of the content of DNA in cells, and a large number of apoptotic bodies containing nuclear fragments were observed in cells treated with 80 μg/ml of EE-DS for 24 h by using Hoechst 33258 staining. These data show that EE-DS can induce apoptosis of HepG2 cells. Immunoblot analysis showed that EE-DS significantly suppressed the expressions of Bcl-2 and NF-κB. Treatment of cells with EE-DS (80 μg/ml) for 48 h resulted in significant increase of cytochrome c in the cytosol, which indicated cytochrome c release from mitochondria. Activation of caspase-9 and -3 were also determined when the cells treated with EE-DS. The results suggest that apoptosis of HepG2 cells induced by EE-DS could be through the mitochondrial intrinsic pathway. High performance liquid chromatography (HPLC) data showed that the composition of EE-DS is complicated. Further studies are needed to find the effective constituents of EE-DS.


[Analysis of the causes of potential wear and breakdown of elements of artificial heart valves of the disk type].
The reliability analysis of the artificial cardiac valve and experiments made it possible to establish that the ACV reliability is ensured by the physical and mechanical properties of the material, technology observance and thorough control over each operation during the manufacturing process. The accelerated testing of the new MX disk valve made in the USSR showed a satisfactory degree of the disk wear and the absence of breaks-down after 400 million working cycles which is equivalent to ten-years' work in a human body.


Usefulness of the aldehyde breath test for predicting metachronous recurrence in patients with esophageal squamous cell carcinoma and hypopharyngeal squamous cell carcinoma.
The rate of metachronous recurrence after endoscopic submucosal dissection for early-stage esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma is as high (10-15%). The acetaldehyde breath test may detect acetaldehyde dehydrogenase 2 gene polymorphisms. Therefore, we evaluated its usefulness in assessing metachronous recurrence in patients with esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma. A total of 76 patients underwent endoscopic submucosal dissection for esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma and were followed up for at least 3 years (non-recurrence group: 52 patients; recurrence group: 24 patients). The risk factors for carcinogenesis were compared between the recurrence and non-recurrence groups, and the acetaldehyde-to-ethanol ratio was assessed. The cutoff acetaldehyde-to-ethanol ratio that correlated with recurrence was established, and the cumulative recurrence rate was evaluated. The recurrence group had a higher acetaldehyde-to-ethanol ratio, daily alcohol consumption, and Lugol-voiding lesion grade than the non-recurrence group in the univariate analysis. The cutoff acetaldehyde-to-ethanol ratio for recurrence was 28.1 based on the receiver operating characteristic curve. The multivariate analysis revealed an acetaldehyde-to-ethanol ratio of > 28.1 and a Lugol-voiding lesion grade associated with carcinogenesis. Patients with an acetaldehyde-to-ethanol ratio of ≥ 28.1 had a significantly high recurrence rate using the Kaplan-Meier method. The acetaldehyde-to-ethanol ratio detected using the acetaldehyde breath test could be a novel biomarker of metachronous recurrence after endoscopic submucosal dissection in patients with esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma. UMIN000040615.


Trade-off between feed efficiency and immunity in specialized high-performing chickens.
Based on resource allocation theory, ignoring importance of immunity, and focus on growth and feed efficiency (FE) traits in breeding plans may lead to serious weakness in immune system performance. However, in poultry the adverse effects of selection for FE on the immune system are unclear. Therefore, an experiment was conducted to study the trade-off between FE and immunity using a total of 180 high-performing specialized male chickens from a commercial broiler line which were selected over 30 generations for growth (body weight gain, BWG) and FE (residual feed intake, RFI). Birds were reared for 42 d and 5 FE-related traits of the birds in the last week were considered including daily feed intake (DFI), feed conversion ratio (FCR), residual feed intake (RFI), residual BW gain (RG), and residual intake and gain (RIG). For all 180 chickens, immune system performance including humoral immune response, cell-mediated immunity (CMI), and the activity of lysozyme enzyme (L. activity) as innate immunity was measured. After ascending sort of each FE records, 10% of higher records (H-FE: N = 18) and 10% of lower records (L-FE: N = 18) were determined, and immunity between L-FE and H-FE groups were compared. Moreover, L-BWG and H-BWG were analyzed because BWG is one of components in the FE formula. Performance of the immune system was not statistically different for CMI in none of the studied FE groups. Moreover, high and low groups for DFI and BWG were not different regarding the immunity of the birds. Antibody titers against Newcastle disease virus (NDV) were different between low and high groups of FCR, RG, and RIG. Likewise, SRBC-derived antibodies were significantly different between RFI groups. Rather than humoral immunity, RIG had adversely effect on the innate immunity. Results of the present study showed that although RIG is a more appropriate indicator for FE, choosing for high RIG can weaken the performance of the both humoral and innate immune systems, while RFI had fewer adverse effects.


Appling the abdominal aortic-balloon occluding combine with blood pressure sensor of dorsal artery of foot to control bleeding during the pelvic and sacrum tumors surgery.
To investigate the feasibilities of reducing intraoperative hemorrhage and improving the safety of pelvic and sacrum tumor surgery using sizing balloon occluding abdominal aorta. From May 2001 to May 2007, 18 patients were diagnosed as sacrum or pelvic tumor and underwent surgery in our institution. Balloon catheters were placed via femoral artery to occlude the abdominal aorta of pelvic tumor and sacrum region undergoing the sacrum resection or half pelvis resection and replacement operation in 12 patients. A sizing balloon was used to occlude the abdominal aorta for 60 min in assisting with resection of pelvic and sacral tumors. After the abdominal aorta was occluded, much less intraoperative hemorrhage was found, and the average blood loss was only 280 ml (range 200-600 ml). This procedure assisted the surgeon in identifying clearly the surgical margin and neurovascular structure surrounded by the tumors. The blood pressure remained stable during the operation. And the function of the kidney, the pelvis organs and the lower extremities were normal. Intraoperative abdominal aorta occluding may effectively control intraoperative hemorrhage, thus assisting the surgeon in the complete and safe resection of pelvic and sacrum tumors.


Accuracy of a new wrist cuff oscillometric blood pressure device: comparisons with intraarterial and mercury manometer measurements.
Accurate measurement of arterial blood pressure is of great importance for the diagnosis and treatment of hypertension. Because of the chronic nature of antihypertensive drug therapy, the involvement of the patient in blood pressure control is desirable. Such an involvement, however, is only feasible if simple, user-friendly, and precise blood pressure measurement devices are available. In this study we tested a new wrist cuff oscillometric blood pressure measurement device in 100 consecutive patients undergoing cardiac catheterization. Blood pressures were simultaneously taken intraarterially (axillary artery) and with a mercury manometer and stethoscope or noninvasive measurement device (OMRON R3). Intraarterial measurements were directly compared with two measurements taken in random order with either an arm cuff mercury manometer or the wrist cuff device. Systolic and diastolic blood pressure as assessed with the mercury manometer was higher, especially when compared with the intraarterial and the wrist cuff values, which were comparable. Correlations of blood pressure values with intraarterial measurement were 0.86 systolic and 0.75 diastolic (P < .01) for the wrist cuff and 0.84 systolic (P < .01) and 0.59 diastolic (P < .05) for the mercury manometer measurements. Reproducibility of both measurements was good for the wrist cuff device ([systolic/diastolic]: r = 0.94/0.92; P < .01) and the mercury manometer (r = 0.97/0.88; P < .01). Both methods overestimated high diastolic values, whereas only the wrist cuff underestimated high systolic values. Thus, the new oscillometric wrist cuff blood pressure measurement device measures arterial blood pressure with great accuracy and reproducibility. As compared with intraarterial values, the wrist cuff device overestimated high diastolic and underestimated high systolic blood pressure values. Blood pressure values as measured by the mercury manometer were higher than intraarterial values and those of the wrist cuff. Both noninvasive devices overestimated high diastolic values.


Endocrinology of cluster headache: potential for therapeutic manipulation.
Cluster headaches have always been among the most intriguing of the commonly recognized primary headache syndromes. This clinical interest is related to a number of factors, including the intense but short-lived nature of the pain, its sexual predilection, associated trigeminal autonomic dysfunction, and the remarkable circadian and circannual periodicity of cluster periods. Recent advances in neuroimaging and neuroendocrinology have shed light on the pivotal role of the hypothalamus in the biology of cluster headache. We discuss these revelations, along with current clinical observations in headache and sleep medicine.


Outcomes of pelvic exenteration for recurrent or primary locally advanced colorectal cancer.
The objective of this study was to assess the clinical outcomes of pelvic exenteration for patients with primary locally advanced colorectal cancer (LACRC) or locally recurrent colorectal cancer (LRCRC), and to identify clinically relevant prognostic factors. Between January 2001 and December 2010, 40 consecutive patients with primary LACRC or LRCRC underwent pelvic exenteration at the National Cancer Center, Republic of Korea. We retrospectively reviewed their medical records. The median age was 59 years and the median follow-up time was 26 months (range, 1-117 months). The overall complication and in-hospital mortality rates were 70% (28/40) and 7.5% (3/40), respectively. The complication rates were similar between patients with primary LACRC (69.6%) and those with LRCRC (70.6%). The overall recurrence rate was 50% (17/34), and was lower in patients with primary LACRC than in patients with LRCRC (33.3% vs. 76.9%, P = 0.032). The 5-year overall survival was significantly different between primary LACRC and patients with LRCRC (58.7% vs. 11.8%, P = 0.022). Multivariate analysis revealed that radicality (R0 vs. R1/R2) was an independent prognostic factor for overall survival (P = 0.020). The complication and operative mortality rates of pelvic exenteration remained high, but pelvic exenteration might provide an opportunity for long-term survival and good local control. Complete (R0) resection was the only independent prognostic factor for overall survival.


[Death of neurons and glial cells, induced by a photodynamic injury: signaling processes and neurone-glial interactions].
The mechanisms of photodynamic (PD) injury of neurons and glial cells are reviewed. Neuron responses: firing stimulation at high photosensitizer concentrations and inhibition at low concentrations (< 10(-7) M) that were followed by necrosis, are described. Glial cells died from both necrosis and apoptosis. Local laser inactivation of a neuron enhanced PD-induced apoptosis of glial cells, thus indicating that neuron maintained the survival of glia. Inter- and intracellular signaling mediated photodamage of these cells. Using inhibitors or activators of signaling proteins, the involvement of Ca(2+)-, adenylate cyclase- and tyrosine kinase-mediated signaling pathways in responses of neurons and glial cells to photosensitization was shown. Their pharmacological modulation can change selectivity of PD injury of neuronal and glial cells and efficiency of PD therapy.


Circulating plasma lncRNAs as novel markers of EGFR mutation status and monitors of epidermal growth factor receptor-tyrosine kinase inhibitor therapy.
Epidermal growth factor receptor (EGFR) gene mutations predict tumor response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, even patients with EGFR-sensitive mutations in NSCLC have limited efficacy with EGFR-TKI. Studies have shown that long noncoding RNA (lncRNA) is related to diagnosis and prognosis with NSCLC. This study aimed to explore the correlation between lncRNA in NSCLC patients with EGFR mutation status and EGFR-TKI efficacy. The amplification-refractory mutation system method was used to test the EGFR mutation status in tumor tissues and pleural effusions of NSCLC patients. Three EGFR-mutant patients and three EGFR wild-type patients were selected. Differential lncRNA was performed on the pleural effusions of the two selected groups of patients using Clariom D Human chip technology. Five lncRNAs significantly associated with EGFR mutation status were screened by FC value and GO analysis, and then evaluated by real-time quantitative polymerase chain reaction in NSCLC patients' pleural effusions. Three were further analyzed in NSCLC patients' plasma. There were 61 significant differences in lncRNA between EGFR mutation-positive and wild-type patients. Among them, SCARNA7, MALAT1, NONHSAT017369, NONHSAT051892, and FTH1P2 were significantly associated with EGFR mutation status. SCARNA7, MALAT1, and NONHSAT017369 showed consistent results with plasma in pleural effusions compared to EGFR wild-type, all upregulated in the EGFR mutation group. This study shows that lncRNAs can be used not only as potential biomarkers for predicting the mutation status of EGFR and the efficacy of EGFR-TKI, but also for monitoring the efficacy of EGFR-TKI.


Use of intravenous methylprednisolone in acute idiopathic thrombocytopenic purpura.
Twenty newly diagnosed children with acute idiopathic thrombocytopenic purpura (ITP) with a platelet count (PC) of less than 20,000 were treated with intravenous methyl prednisolone (IVMP) 5 mg/kg/day in four divided doses until the platelet count increased to 50,000/mm3. They were then placed on oral prednisone at conventional doses for a total of three weeks of steroid therapy. The platelet counts increased by an average of 55,000/mm3 within 48 h of treatment. Within 72 h (day 3) of treatment all patients achieved a PC of greater than 20,000/mm3. By day 5, all 20 patients achieved a PC of greater than 50,000. IVMP is highly effective in rapidly raising the PC in acute ITP above the critical level of 20,000, thereby reducing the duration of risk for intracranial hemorrhage (ICH).


Two types of phonological dyslexia - a contemporary review.
Friedman (1995) presents a review of 6 phonological dyslexic cases in which she suggests that this reading impairment is divisible into subtypes on the basis of two straightforward behavioural profiles: (1) cases with poor function word reading and normal nonword repetition (3 cases) and (2) cases with good function word reading and poor nonword repetition (3 cases). This evidence is interpreted as support for a reading model that does not posit a non-lexical reading route (Harm and Seidenberg, 2001, 2004; Plaut, et al. 1996), with the pattern of impairment in case (1) being due to disruption of direct connections between orthography-phonology and in case (2) being due to a 'generalised' impairment of phonology. The current review re-evaluates the validity of Friedman's original criteria as a basis for identifying 'subtypes' of phonological dyslexia with a larger sample of 38 documented cases. On balance it is found that the majority does not easily fit either subtype on the basis of the expected behavioural profiles. Thus the present survey would suggest that Friedman's criteria for classification of phonological dyslexia is not particularly useful for the general population of such cases. However, subsequent correlational analyses did find evidence in support of a relationship between nonword reading impairment and nonword repetition/function word reading impairment. This finding is largely consistent with the principles of the type of reading model outlined by Friedman (1995), although other potential accounts cannot be ruled out. These findings are discussed in greater detail with relation to present models of reading and potential avenues for further research are proposed.


Erythrocyte agglomeration and survival studies in citrate-phosphate-dextrose (CPD) units.
We have previously reported increased tendency to agglomeration in CPD-stored erythrocytes. In the present study we investigated the deterioration pattern of fresh units, as detected by agglomeration, free hemoglobin levels, ATP levels, osmotic fragility, and certain enzymatic activities. When the negative test was converted to a positive one, the 24-h survival values of these units were determined by autotransfusion. A positive agglomeration occurred while viability was still above 70%. Fresh units had high ATP levels and negative agglomeration while old units had low ATP levels and positive agglomeration. However, in intermediate-storage units, no definite correlation between ATP and agglomeration was found. Agglomeration seems to reflect the degree of changes in stored erythrocytes. However, further studies are needed before this test may serve for prediction of post-transfusion viability.


Antithrombin controls tumor migration, invasion and angiogenesis by inhibition of enteropeptidase.
Antithrombin is a key inhibitor of the coagulation cascade, but it may also function as an anti-inflammatory, anti-angiogenic, anti-viral and anti-apoptotic protein. Here, we report a novel function of antithrombin as a modulator of tumor cell migration and invasion. Antithrombin inhibited enteropeptidase on the membrane surface of HT-29, A549 and U-87 MG cells. The inhibitory process required the activation of antithrombin by heparin, and the reactive center loop and the heparin binding domain were essential. Surprisingly, antithrombin non-covalently inhibited enteropeptidase, revealing a novel mechanism of inhibition for this serpin. Moreover, as a consequence of this inhibition, antithrombin was cleaved, resulting in a molecule with anti-angiogenic properties that reduced vessel-like formation of endothelial cells. The addition of antithrombin and heparin to U-87 MG and A549 cells reduced motility in wound healing assays, inhibited the invasion in transwell assays and the degradation of a gelatin matrix mediated by invadopodia. These processes were controlled by enteropeptidase, as demonstrated by RNA interference experiments. Carcinoma cell xenografts in nude mice showed in vivo co-localization of enteropeptidase and antithrombin. Finally, treatment with heparin reduced experimental metastasis induced by HT29 cells in vivo. In conclusion, the inhibition of enteropeptidase by antithrombin may have a double anti-tumor effect through inhibiting a protease involved in metastasis and generating an anti-angiogenic molecule.


Glutathione conjugation of the fluorophotometric epoxide substrate, 7-glycidoxycoumarin (GOC), by rat liver glutathione transferase isoenzymes.
The fluorophotometric substrate, 7-glycidoxycoumarin (GOC), was examined for the assay of epoxide-glutathione (GSH)-conjugating activities of seven major GSH transferases (GSTs) isolated from rat liver cytosols. GST 7-7 (GST-P), isolated from the liver cytosol of rats bearing hepatic hyperplastic nodules, catalysed the GSH conjugation of GOC at a higher rate than any other examined GST isolated from the normal rat liver cytosol. GSTs 3-3, 3-4 and 4-4 (group 3-4 enzymes) had specific activities towards GOC by one fifth to one third of that of GST 7-7. GSTs 1-1, 1-2 and 2-2 (group 1-2 enzymes) had very low activities towards this epoxide. A kinetic study indicated that GST 7-7 showed the largest kappa cat/Km value for the catalytic reaction of GOC-GSH conjugation among the GSTs. In spite of their much smaller kappa cat values, group 3-4 enzymes showed much larger kappa cat/Km values for GOC than the group 1-2 enzymes, because GOC had a much higher affinity for group 3-4 enzymes than for group 1-2 enzymes. A comparative study was also done with GSH conjugations of styrene 7,8-oxide (STO) and 1-chloro-2,4-dinitrobenzene by the GSTs. Unlike GOC, the conjugation of STO was mediated at rates about twice as high by group 3-4 enzymes than by GST 7-7. STO was also a very poor substrate for group 1-2 enzymes.


Fate of cadmium in rat renal tubules: a microinjection study.
109Cd was injected into the lumen of superficial proximal or distal tubules of rat kidneys, and recovery in the pelvic urine from the ipsilateral kidney was measured. Fractional recovery of labeled inulin always exceeded 90%. About 70% of injected inorganic Cd (CdCl2) was taken up by the epithelium of proximal tubules, while more than 90% of the injected amount was recovered after distal microinjection. The proximal fractional Cd uptake of a 1:1 (molar) Cd-L-cysteine complex was 82%, but was below 60% for a 5-10:1 molar ratio of cysteine:Cd. The chelate Cd-pentetic acid was recovered in final urine nearly quantitatively after proximal or distal microinjection. Fractional uptake of 109Cd from a Cd-metallothionein (Mt) complex, following proximal microinjection, ranged between 17 (Cd-Mt 0.19 mM) and 8% (Cd-Mt 1.5 mM). It is concluded that luminal Cd uptake by the tubular epithelium depends markedly on the chemical form of Cd and, when present, occurs mostly or exclusively in proximal tubules.


Structural dynamics of nucleosome mediated by acetylations at H3K56 and H3K115,122.
Post translational modifications have a profound role in the regulation of several biological processes such as transcription, replication, and DNA repair. Acetylation and phosphorylation form a major class of post translational modifications involved in nucleosomal regulation by modifying its structure. The effect of post translational modifications on nucleosome structure could be better explored when the molecular trajectories explaining the time dependent structural evolution over a period of time is examined at the atomic level. The present study attempts to highlight the importance of acetylation, especially at entry-exit (Lys56) and dyad (Lys115 and Lys122) regions in regulating the nucleosome accessibility and mobility using all atom simulations. It is evident from this study that acetylation at Lys56, Lys115, and Lys122 introduces local changes in the electrostatic nature of the lateral surface and thereby weakens the histone-DNA interactions. In addition, simulations also reveal significant changes in the dynamics of superhelical DNA. The acetylation at Lys56 promotes a high amplitude out-of-planar movement of entry-exit termini. Whereas, acetylation at Lys115 and Lys122 increases the flexibility of the superhelical DNA to facilitate the rolling of the superhelical DNA around the octameric histone. In essence, the present study highlights the role of acetylation at Lys56, Lys115, and Lys122 in transcriptional regulation by promoting high amplitude dynamics of superhelical DNA for a possible unwrapping as well as mobility of nucleosome.


The effects of engineering design on heterogeneous biocatalysis in microchannels.
The results of a numerical study of the fundamental interactions of engineering design and micromixing on conversion in packed microchannels are presented. Previously, channel-based microreactors made of molded silicon plastic were designed, fabricated, and experimentally tested. These reactors have enzymes immobilized on the channel walls by various methods including layer-by-layer nano self-assembly techniques. They also contain molded packing features to add reactive surface area and to redistribute the fluid. An arbitrary but intuitively sensible packing arrangement was initially chosen and used in experimental studies. The current computer simulation study was undertaken to understand how static laminar mixing affects the conversion efficiency. The reactors previously used experimentally have been simulated using CFD-ACE+multiphysics software (ESI CFD Inc., Huntsville, AL). It is found that packing significantly increases conversion when compared with empty channels over the entire flow rate range of the study (0.25<Re<62.5). The boost in conversion has an optimal point near Re=20 for the particular geometry examined.


When pregnant women and their physicians disagree on the need for cesarean section: no simple solution.
This article provides an analysis of why women might refuse cesarean sections that are advised by their physicians. It presents a review of court cases, ethical opinions, and recommendations in the literature and lists the legal requirements for informed consent. The author delineates the process of weighing whether or not a court order should be requested.


In brain, Axl recruits Grb2 and the p85 regulatory subunit of PI3 kinase; in vitro mutagenesis defines the requisite binding sites for downstream Akt activation.
Axl is a receptor tyrosine kinase implicated in cell survival following growth factor withdrawal and other stressors. The binding of Axl's ligand, growth arrest-specific protein 6 (Gas6), results in Axl autophosphorylation, recruitment of signaling molecules, and activation of downstream survival pathways. Pull-down assays and immunoprecipitations using wildtype and mutant Axl transfected cells determined that Axl directly binds growth factor receptor-bound protein 2 (Grb2) at pYVN and the p85 subunit of phosphatidylinositol-3 kinase (PI3 kinase) at two pYXXM sites (pY779 and pY821). Also, p85 can indirectly bind to Axl via an interaction between p85's second proline-rich region and the N-terminal SH3 domain of Grb2. Further, Grb2 and p85 can compete for binding at the pY821VNM site. Gas6-stimulation of Axl-transfected COS7 cells recruited activated PI3 kinase and phosphorylated Akt. An interaction between Axl, p85 and Grb2 was confirmed in brain homogenates, enriched populations of O4+ oligodendrocytes, and O4- flow-through prepared from day 10 mouse brain, indicating that cells with active Gas6/Axl signal through Grb2 and the PI3 kinase/Akt pathways.


Revision of the ununited one-bone forearm.
Between 1975 and 1995, 7 patients were surgically treated for persistent forearm pain following previously unsuccessful attempts of constructing a radioulnar synostosis using interosseous bone grafting with either cross screw or pin fixation. These prior reconstructive procedures were salvage operations to address symptomatic radioulnar instability. The time interval between index operation and revision surgery was a mean of 12.6 months (range, 4-36 months). The postoperative follow-up period averaged 29.7 months (range, 11-61 months). To address these failed radioulnar arthrodeses, plate osteosynthesis and aggressive bone grafting were used in 5 of 7 patients (group 1) (4 with autologous graft and 1 with demineralized bone matrix). Union was achieved in all 5 patients after a single revision operation. Radiographic evidence of solid union was seen at approximately 4 months. In the remaining 2 patients (group 2), revision synostosis procedures were performed; these involved local bone grafting and repeat transverse screw fixation in 1 patient and iliac crest bone grafting alone in the other. One of these 2 patients progressed to union; the other had a persistent symptomatic fibrous union. The 5 patients in group 1 reported symptomatic relief, while the 2 patients in group 2 were dissatisfied. There were no postoperative complications in our series. Based on our findings, we advocate abundant bone grafting and plating for rigid internal fixation in failed radioulnar synostosis procedures.


Effect of intensive training on heart rate variability in prepubertal swimmers.
In children, there is very limited evidence focusing on the beneficial effect of exercise training on heart rate variability (HRV) during childhood. Despite the fact that more and more children are engaged in intensive training programs, the question arises if such intensive training involves deleterious effects on the cardiac autonomic nervous system during childhood. Thus the aim of the present study was to compare HRV parameters in highly trained swimmer boys and untrained counterparts. Twenty prepubertal boys, aged 11-12 years old, took part in the study. The children were divided into 11 highly trained prepubertal swimmers (training sessions of 8-10 h weekly for at least 4 years) and 9 age-matched active boys. HRV analysis was performed on diurnal recordings in the frequency (short-term recordings 6 min the most 'vagal') and time (long-term recordings 4 h centred on the 6 min most 'vagal') domains. No significant differences were obtained between groups for all frequency variables whatever the mode of expression (absolute in ms2, relative in Ln or %). All time-domain components were not significantly different in swimmers and untrained boys. The results of the present study demonstrate that participating intensively in swimming training does not induce in children changes in HRV indices. Neither time nor domain HRV variables were significantly different between untrained and highly trained prepubertal boys. Thus, intensive training in healthy children does not involve deleterious effects on HRV.


Effect of simulated microgravity on aged pea seed vigour and related physiological properties.
We used simulated microgravity to treat aged pea seeds, in order to observe its effect on seed vigour and related physiological properties. The result shows that microgravity obviously promotes the germination rate, vitality index, germination index, and keeps the activity of protective enzyme, with conductivity and the content of MDA decreased. These effects gradually disappeared for a certain period after the microgravity administration.


RNA synthesis in neuronal and glial cell nuclei from rat cerebral hemispheres during early postnatal development.
RNA synthesis in rat cerebral hemispheres at 1, 5, and 10 days of age and the relative contribution brought by neuronal and glial nuclei to RNA synthesis was investigated. The experiments were carried out both in vivo (by i.p. injection of [3H]uridine) and in vitro (either by incubation of tissue slices with [3H]uridine or by determination of RNA polymerase activities). The labeling of RNA decreases from 1 to 10 days of age both in vivo and in vitro; the decrease is of the same extent in neuronal and glial nuclei. RNA polymerase activity Mg2+-dependent does not change significantly from 1 to 10 days of age either in total, in neuronal, or in glial nuclei, whereas the Mn2+-dependent activity increases significantly over the same developmental period studied. The significance of RNA polymerase assay as an index of in vivo RNA synthesis is discussed.


Cognitive functional therapy compared with core exercise and manual therapy in patients with chronic low back pain: randomised controlled trial.
Cognitive functional therapy (CFT) is a physiotherapy-led intervention that has evolved from an integration of foundational behavioral psychology and neuroscience within the physiotherapist practice directed at the multidimensional nature of chronic low back pain (CLBP). The current evidence about the comparative effectiveness of CFT for CLBP is still scarce. We aimed to investigate whether CFT is more effective than core training exercise and manual therapy (CORE-MT) in pain and disability in patients with CLBP. A total of 148 adults with CLBP were randomly assigned to receive 5 one-hour individualized sessions of either CFT (n = 74) or CORE-MT (n = 74) within a period of 8 weeks. Primary outcomes were pain intensity (numeric pain rating scale, 0-10) and disability (Oswestry Disability Index, 0-100) at 8 weeks. Patients were assessed preintervention, at 8 weeks and 6 and 12 months after the first treatment session. Altogether, 97.3% (n = 72) of patients in each intervention group completed the 8 weeks of the trial. Cognitive functional therapy was more effective than CORE-MT in disability at 8 weeks (MD = -4.75; 95% CI -8.38 to -1.11; P = 0.011, effect size= 0.55) but not in pain intensity (MD = -0.04; 95% CI -0.79 to 0.71; P = 0.916). Treatment with CFT reduced disability, but the difference was not clinically important compared with CORE-MT postintervention (short term) in patients with CLBP. There was no difference in pain intensity between interventions, and the treatment effect was not maintained in the mid-term and long-term follow-ups.


Cognitive and behavioural correlates of different domains of psychological adjustment in early-stage multiple sclerosis.
This study investigated a cognitive-behavioural model of adjustment to multiple sclerosis (MS). It aimed to determine the contribution of cognitions and behaviours to the explanation of two distinct adjustment outcomes above and beyond measures of MS severity. Illness-related functional impairment was anticipated to be most strongly related to unhelpful thoughts and behaviours that were specific for MS and the experience of symptoms. Psychological distress was hypothesised to be most strongly related to more general unhelpful cognitions about the self and emotions. Ninety-four people with MS completed questionnaires. Correlations and hierarchical multiple regressions determined the relative contribution of illness severity, cognitions, and behaviours to the prediction of psychological distress and functional impairment. Illness-related functional impairment was related to disease severity, progressive versus relapsing-remitting disease, and unhelpful illness perceptions and cognitive and behavioural responses to symptoms. Illness severity factors accounted for a significant 23.7% of the variance in functional impairment (P<.001). Cognitive and behavioural variables explained a further 22.6% of the variance (P<.001), with behavioural responses to symptoms emerging as the strongest predictor. The correlates of distress were unhelpful beliefs about the self, unhelpful beliefs about emotions, acceptance, and unhelpful cognitive responses to symptoms and illness perceptions. Illness severity factors explained only 2.2% of the variance in distress (P>.05), while cognitive and behavioural variables accounted for 37.1% (P<.001). Unhelpful beliefs about the self were the strongest predictor. Longitudinal and experimental research is required to investigate potential causal relationships. However, the cognitions and behaviours identified as important for adjustment are potentially modifiable and thus may be useful to address within interventions for adjustment to MS.


Phosphatidate phosphatase: activity and properties in fetal and adult rat lung.
The purpose of this work is to compare the properties of phosphatidate phosphatase (L-alpha-phosphatidate phosphohydrolase, EC 184.108.40.206) in fetal and adult rat lung and to establish the developmental profile of activity measured under optimal conditions. The maximal pH of 6.0--7.0 and the inhibition by fluoride, Ca2+ and detergents were simialr for both adult and fetal. Phosphatidate phosphohydrolase activity was located in both mitochondria and microsomes. The localizations of marker enzymes indicated that the activity in these subfractions was not a result of cross contaminations. Very low activity was detected in the supernatant fraction and no Mg2+ requirement was demonstrable. The activity in the particulate fraction was about 50% of the adult from 18 day gestation until birth. Following birth, the activity rapidly increased to adult levels. Dipalmitoyl, dioleoyl and diacyl glycerol 3-phosphates are all utilized well as substrates. 1,2-dipalmitoyl-sn-glycerol 3-phosphate was hydrolyzed faster under maximal conditions. The velocity-substrate curves tended to be sigmoidal, particularly when 1,2-dipalmitoyl-sn-glycerol 3-phosphate was the substrate. Estimated apparent Km values of 0.02--0.03 mM were obtained for fetal and adult preparations.


Receptor-mediated binding and uptake of immunoglobulin A by human liver.
We have studied the molecular mechanisms of the binding and uptake of secretory and serum immunoglobulin A (IgA) of both subclasses (1 and 2) and molecular forms (monomer and polymer) by the particulate fraction of human liver homogenate and by a human hepatoma cell line (HepG2). Inhibition by asialoorosomucoid and the requirement for the presence of calcium indicated that the binding of secretory IgA and polymeric IgA1 was mediated by the asialoglycoprotein receptor. Secretory component, which functions as a receptor for polymeric IgA in several animal species, was detected in the epithelial cells of bile ducts, but not in hepatocytes. Secretory IgA and all molecular forms and subclasses of serum IgA were bound by HepG2 cells, which do not express secretory component. The requirement for the presence of calcium, the presence of a terminal galactose residue in IgA, and the molecular weight of the major plasma membrane protein responsible for binding (41,700 daltons) indicated the involvement of asialoglycoprotein receptor. Immunoglobulin A proteins bound by HepG2 cells were endocytosed and catabolized.


Childhood depression: an explanation of a behavior disorder of children.
Depression is an important cause of behavioral disturbances in children. Childhood depression is an episodic disorder characterized by 10 criteria, symptoms of dysphoric mood, self-deprecatory ideation, agitation, loss of energy, reduced socialization, altered school performance, altered school attitude, sleep disturbance, appetite disturbance, and somatic compliants persisting for at least one month. Diagnosis and appropriate treatment can successfully alleviate the symptomatology in depressed children.


How septic is urosepsis? Clinical course of infected hydronephrosis and therapeutic strategies.
Despite rapid decompression of the upper urinary tract, some patients show signs of systemic inflammatory response syndrome (SIRS) or septic shock syndrome when infected hydronephrosis is diagnosed. Clinical and biological parameters were analyzed retrospectively in 189 patients diagnosed with hydronephrosis regarding disease severity as well as microbiological and antibiotic features. Fifty of the 189 patients had positive urine culture in the renal pelvis and were included in the study. Fifteen patients had to be placed in the intensive care unit and two patients developed severe septic signs. An initial body temperature above 38.5 degrees C (P=0.0004) and an elevated BMI (P=0.002) were the only parameters that indicated a higher risk of developing SIRS or sepsis. Typical biological parameters were not helpful in differentiating patients who will develop urosepsis. Further research is necessary to provide conclusive evidence of the value of other early prognostic markers in patients with infected hydronephrosis.


Effect of season and gonadotropins on the superovulatory response in camel (Camelus dromedarius).
The purpose of the present investigation was to study the extent to which season and the gonadotropin preparation interferes with the superovulatory response in the dromedary. Adult camels were treated for superovulation during the breeding (November to April) and non-breeding season (May to October). Animals were synchronized by daily i.m. injections of progesterone (125 mg/animal/day, Jurox, UK) for 10 to 14 days. Superovulation was induced by 400mg pFSH alone (Follitropin V, Vetrepharm, Canada) administered in eight descending doses at 12h intervals or a combination of PMSG (2000IU, Folligon, Intervet, The Netherlands), injected with last injection of progesterone and 400mg pFSH in eight descending doses. The follicular development was daily assessed by ultrasonography of the ovaries. The donors were classified as per their response to the superovulatory treatment into very good (>10 follicles), good (5-10 follicle), poor (2-4 follicles) or no response (1 or no follicle) on each ovary. Ovulation was induced by injecting 3000 IU hCG (Chorulon, Intervet) at the time of first mating. The donors were mated twice at an interval of 12h when all or most of the follicles reached to a size of about 1.0-1.7 cm. Camels were flushed non-surgically on Day 6 or 7 after the ovulation. The proportion of camels showing very good response during the breeding as well as non-breeding season was higher (P<0.05) when a combination of pFSH and eCG was used compared with pFSH only. There was no difference (P>0.05) in the proportion of donors flushed successfully (embryos recovered) when treated either with a combination of pFSH and eCG or pFSH alone during the breeding and non-breeding season. The rate of recovery of ova/embryos and proportion of transferable embryos was higher (P<0.05) when donors were treated with pFSH+eCG compared with pFSH only during the breeding as well as non-breeding season. The results may indicate that ova/embryo recovery rate of the dromedary is influenced by the gonadotropin preparation but is not appreciably affected by the season.


Biochemical and cellular characterization of cardiac valve tissue after cryopreservation or antibiotic preservation.
It has been reported that aortic homografts that have been cryopreserved before transplantation remain viable longer as an allograft than tissue stored at 4 degrees C in an antibiotic solution. In the present study, we tested the hypothesis that storage of cardiac valve tissue by cryopreservation or by antibiotic preservation may alter the metabolic status of the tissue. Initially, we collected aortic valves composed of cardiac tissue, aortic root, and valvular tissue from cadaver donors. These specimens were divided into three equal portions, and one portion was analyzed before storage while the other two parts were stored for 3 weeks at either 4 degrees C in an antibiotic solution or at -196 degrees C in liquid nitrogen. All specimens were examined with regard to the following parameters: tissue structure, tissue viability, cell proliferative capacity, metabolic function, and identification of cell-specific antigens. We found no significant alterations in the structure of any of the three tissue components after antibiotic preservation or cryopreservation; however, cell viability and cell number were decreased in all three groups. All tissue samples grew in culture before storage. When we compared activities of the following organellar marker enzymes--lysosomal acid lipase, plasma membrane 5' nucleotidase, mitochondrial cytochrome oxidase, and microsomal neutral alpha-glucosidase--we observed no major differences between tissues stored by either technique. In addition, we observed no loss of enzymic activity as a result of storage. Finally, when cell lines isolated from each tissue specimen were incubated with monoclonal antibodies against cell-specific antigens in an immunoperoxidase assay, all the cell cultures proved to be endothelial cells. These results suggest that although cardiac valve tissue stored by cryopreservation or by antibiotic preservation retained its normal structure and metabolic capabilities, both storage techniques produced significant decreases in cell numbers and viability. However, only endothelial cells from tissue stored by cryopreservation retained the capacity to proliferate in vitro. These findings have important implications for the function of aortic homografts transplanted after storage.


Three-Year Outcomes of a Phase II Study of Perioperative Capecitabine Plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601).
We previously reported the good feasibility and favorable efficacy of perioperative capecitabine plus oxaliplatin (CapeOx) in patients (pts) with clinical T3(SS)/T4a(SE) N1-3 M0 gastric cancer (GC) in a phase II study in which the pathological response rate, the primary endpoint, of 54.1% was demonstrated. Here, we report 3-year follow-up data. The eligibility criteria included clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of Gastric Carcinoma-3rd English Edition (JCGC). Three cycles of neoadjuvant CapeOx (capecitabine, 2000mg/m2 for 14 days; oxaliplatin, 130mg/m2 on day 1, every 3 weeks) were administered, followed by 5 cycles of adjuvant CapeOx after D2 gastrectomy. Three-year overall survival and relapse-free survival are presented here, and analyzed by cohorts based on pathologic response rate (pRR). Thirty-seven pts were enrolled from July 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of neoadjuvant CapeOx and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29). The overall survival (OS) rate and relapse-free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Further, the 3-year OS rate in pts with pathological response of grade 1a (n = 13) and grade 1b or higher (n = 20) was 69.2% (95% CI: 48.2-99.5%) and 100.0%, respectively, based on JCGC. Pathological response rate was classified according to JCGC as follows: grade 0, the tumor was not affected; grade 1a, less than one-third of the tumor was affected; grade 1b, one to two thirds of the tumor was affected; grade 2, greater than or equal to two thirds was affected; and grade 3, no residual tumor. A pathological response was defined as grade 1b or greater. Perioperative CapeOx showed good feasibility and favorable prognosis, especially in pts with pathological response of grade 1b or higher and was found to be useful in predicting prognosis. The data obtained using this novel approach warrant further investigation (Trial ID: UMIN000021641, jRCTs051180109).


Reduced-dose C-arm computed tomography applications at a pediatric institution.
Reduced-dose C-arm computed tomography (CT) uses flat-panel detectors to acquire real-time 3-D images in the interventional radiology suite to assist with anatomical localization and procedure planning. To describe dose-reduction techniques for C-arm CT at a pediatric institution and to provide guidance for implementation. We conducted a 5-year retrospective study on procedures using an institution-specific reduced-dose protocol: 5 or 8 s Dyna Rotation, 248/396 projection images/acquisition and 0.1-0.17 μGy/projection dose at the detector with 0.3/0.6/0.9-mm copper (Cu) filtration. We categorized cases by procedure type and average patient age and calculated C-arm CT and total dose area product (DAP). Two hundred twenty-two C-arm CT-guided procedures were performed with a dose-reduction protocol. The most common procedures were temporomandibular and sacroiliac joint injections (48.6%) and sclerotherapy (34.2%). C-arm CT was utilized in cases of difficult percutaneous access in less common applications such as cecostomy and gastrostomy placement, foreign body retrieval and thoracentesis. C-arm CT accounted for between 9.9% and 80.7% of the total procedural DAP. Dose-reducing techniques can preserve image quality for intervention while reducing radiation exposure to the child. This technology has multiple applications within pediatric interventional radiology and can be considered as an adjunctive imaging tool in a variety of procedures, particularly when percutaneous access is challenging despite routine fluoroscopic or ultrasound guidance.


Effects of unilateral nigrostriatal dopamine depletion on peripheral glucose tolerance and insulin signaling in middle aged rats.
Clinical studies indicate an increased incidence of impaired glucose tolerance in individuals with Parkinson's disease (PD). The mechanisms that underlie this co-morbidity are currently unknown. The purpose of this study was to analyze peripheral glucose tolerance following severe unilateral nigrostriatal dopamine (DA) depletion, and to determine whether central and peripheral insulin signaling was affected in the 6-hydroxydopamine (6-OHDA) middle-aged rat model of PD. Although serum insulin levels differed significantly between the 6-OHDA and sham groups over the course of a glucose tolerance test six weeks post-lesion, no significant effect on glucose tolerance or insulin signaling in skeletal muscle was observed. In contrast, markers of striatal insulin resistance were evident in the rats. These data suggest that while 6-OHDA may affect serum insulin levels and striatal insulin signaling, the unilateral 6-OHDA lesion model does not induce glucose intolerance or peripheral insulin resistance, at least at the six-week post-lesion timepoint.


Designer proteins that competitively inhibit Gαq by targeting its effector site.
During signal transduction, the G protein, Gαq, binds and activates phospholipase C-β isozymes. Several diseases have been shown to manifest upon constitutively activating mutation of Gαq, such as uveal melanoma. Therefore, methods are needed to directly inhibit Gαq. Previously, we demonstrated that a peptide derived from a helix-turn-helix (HTH) region of PLC-β3 (residues 852-878) binds Gαq with low micromolar affinity and inhibits Gαq by competing with full-length PLC-β isozymes for binding. Since the HTH peptide is unstructured in the absence of Gαq, we hypothesized that embedding the HTH in a folded protein might stabilize the binding-competent conformation and further improve the potency of inhibition. Using the molecular modeling software Rosetta, we searched the Protein Data Bank for proteins with similar HTH structures near their surface. The candidate proteins were computationally docked against Gαq, and their surfaces were redesigned to stabilize this interaction. We then used yeast surface display to affinity mature the designs. The most potent design bound Gαq/i with high affinity in vitro (KD = 18 nM) and inhibited activation of PLC-β isozymes in HEK293 cells. We anticipate that our genetically encoded inhibitor will help interrogate the role of Gαq in healthy and disease model systems. Our work demonstrates that grafting interaction motifs into folded proteins is a powerful approach for generating inhibitors of protein-protein interactions.


The role of the mental health expert witness in family law disputes.
Mental health professionals are frequently called upon to appear in Family Court as Expert Witnesses in order to help the judge make difficult decisions in disputed cases, involving issues like custody, access and abuse. The adversary system often serves to intimidate or to antagonize the expert witness, or to render his/her judgment as suspect and even invalid. An approach is suggested in which the expert is designated as an "amicus curiae" (impartial friend of the court), rather than as a "hired gun" by one of the disputants. Even with this procedure, however, the expert witness must possess specific personal and professional characteristics which lend credibility to his/her testimony. The work is difficult, and requires considerable knowledge and skill; the responsibilities are heavy, but the opportunity to do exciting and vital work on behalf of children and families make it more than worthwhile.


Nucleotide-mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptors.
ATP is the dominant messenger for astrocyte-to-astrocyte calcium-mediated communication. Definition of the exact ATP/P2 receptors in astrocytes and of their coupling to intracellular calcium ([Ca(2+)](i)) has important implications for brain physiology and pathology. We show that, with the only exception of the P2X(6) receptor, primary rat cortical astrocytes express all cloned ligand-gated P2X (i.e., P2X(1-5) and P2X(7)) and G-protein-coupled P2Y receptors (i.e., P2Y(1), P2Y(2), P2Y(4), P2Y(6), and P2Y(12)). These cells also express the P2Y-like UDP-glucose receptor, which has been recently recognized as the P2Y(14) receptor. Single-cell image analysis showed that only some of these receptors are coupled to [Ca(2+)](i). While ATP induced rapid and transient [Ca(2+)](i) increases (counteracted by the P2 antagonists suramin, pyridoxal-phosphate-6-azophenyl-2'-4'-disulfonic acid and oxidized ATP), the P2X(1)/P2X(3) agonist alphabetameATP produced no changes. Conversely, the P2X(7) agonist BzATP markedly increased [Ca(2+)](i); the presence and function of the P2X(7) receptor was also confirmed by the formation of the P2X(7) pore. ADP and 2meSADP also produced [Ca(2+)](i) increases antagonized by the P2Y(1) antagonist MRS2179. Some cells also responded to UTP but not to UDP. Significant responses to sugar-nucleotides were also detected, which represents the first functional response reported for the putative P2Y(14) receptor in a native system. Based on agonist preference of known P2 receptors, we conclude that, in rat astrocytes, ATP-induced calcium rises are at least mediated by P2X(7) and P2Y(1) receptors; additional receptors (i.e., P2X(2), P2X(4), P2X(5), P2Y(2), P2Y(4), and P2Y(14)) may also contribute.


Imaging guidance for cholesteatoma surgery using tissue autofluorescence.
Cholesteatoma is an expansile destructive lesion of the middle ear and mastoid, which can result in significant complications by eroding adjacent bony structures. Currently, there is an inability to accurately distinguish cholesteatoma tissue margins from middle ear mucosa tissue, causing a high recidivism rate. Accurately differentiating cholesteatoma and mucosa will enable a more complete removal of the tissue. Develop an imaging system to enhance the visibility of cholesteatoma tissue and margins during surgery. Cholesteatoma and mucosa tissue samples were excised from the inner ear of patients and illuminated with 405, 450, and 520 nm narrowband lights. Measurements were made with a spectroradiometer equipped with a series of different longpass filters. Images were obtained using a red-green-blue (RGB) digital camera equipped with a long pass filter to block reflected light. Cholesteatoma tissue fluoresced under 405 and 450 nm illumination. Middle ear mucosa tissue did not fluoresce under the same illumination and measurement conditions. All measurements were negligible under 520 nm illumination conditions. All spectroradiometric measurements of cholesteatoma tissue fluorescence can be predicted by a linear combination of emissions from keratin and flavin adenine dinucleotide. We built a prototype of a fluorescence imaging system using a 495 nm longpass filter in combination with an RGB camera. The system was used to capture calibrated digital camera images of cholesteatoma and mucosa tissue samples. The results confirm that cholesteatoma emits light when it is illuminated with 405 and 450 nm, whereas mucosa tissue does not. We prototyped an imaging system that is capable of measuring cholesteatoma tissue autofluorescence.


MRI metrics as surrogate markers for clinical relapse rate in relapsing-remitting MS patients.
To formally validate metrics derived from conventional MRI as surrogate endpoints for relapse rate in MS. Although metrics derived from MRI are used widely in clinical trials of MS, a formal statistical validation of MRI metrics as surrogate endpoints for clinical outcome in MS is lacking. A validation procedure was applied to clinical and MRI data collected in the context of a randomized, double-blind, placebo-controlled trial of glatiramer acetate in patients with relapsing-remitting MS. The four Prentice operational criteria were applied to assess surrogacy for the number of new enhancing lesions, the percentage change of T2 lesion volume, and a composite MRI score based on these two metrics. The results of this analysis show that all three MRI measures considered by the authors had a behavior compatible with the Prentice criteria for valid surrogates. The composite MRI score correlated with relapses and accounted for much of the treatment effect on relapse rate. This preliminary study suggests that conventional MRI metrics might serve as valid surrogate endpoints in MS trials with glatiramer acetate or treatments thought to have a similar mode of action.


Synergized N, P dual-doped 3D carbon host derived from filter paper for durable lithium metal anodes.
Lithium metal is deemed a promising anode material for the next-generation batteries with high specific energy. Unfortunately, the growth of Li dendrites and infinite volume change during cycling, caused by the "hostless" feature of metallic Li, have posed a great challenge to the commercialization of Li metal anode. The introduction of appropriate host materials for Li metal is highly desirable. In this work, a N, P dual-doped 3D carbon derived from low-cost quantitative filter paper (NPCQP) is designed and fabricated for direct using as a host for Li metal anode. The resulting NPCQP host achieves a high deposition/stripping Coulombic efficiency of above 97.5 % with a low nucleation overpotential. Moreover, the NPCQP@Li symmetric cells enable an excellent long-term cycling performance (1000 h) with an ultralow voltage hysteresis (12 mV) and stable interface behavior. When paired with the commercial LiFePO4 cathode, the full cell with NPCQP@Li anode displays impressive long-term cyclic stability and rate capability, outperforming the counter cell with bare Li anode. This contribution sheds light on the rational design of viable host for practical lithium metal anodes.


A real-time colorimetric assay for label-free detection of microRNAs down to sub-femtomolar levels.
A real-time colorimetric assay utilizing gold nanoparticle networks and a duplex-specific nuclease (DSN) for label-free detection of microRNAs is proposed. Excellent sensitivity and selectivity were accomplished through the engagement of the DSN and a cumulative signal amplification process.


Functional characterization of DnSIZ1, a SIZ/PIAS-type SUMO E3 ligase from Dendrobium.
SUMOylation is an important post-translational modification of eukaryotic proteins that involves the reversible conjugation of a small ubiquitin-related modifier (SUMO) polypeptide to its specific protein substrates, thereby regulating numerous complex cellular processes. The PIAS (protein inhibitor of activated signal transducers and activators of transcription [STAT]) and SIZ (scaffold attachment factor A/B/acinus/PIAS [SAP] and MIZ) proteins are SUMO E3 ligases that modulate SUMO conjugation. The characteristic features and SUMOylation mechanisms of SIZ1 protein in monocotyledon are poorly understood. Here, we examined the functions of a homolog of Arabidopsis SIZ1, a functional SIZ/PIAS-type SUMO E3 ligase from Dendrobium. In Dendrobium, the predicted DnSIZ1 protein has domains that are highly conserved among SIZ/PIAS-type proteins. DnSIZ1 is widely expressed in Dendrobium organs and has a up-regulated trend by treatment with cold, high temperature and wounding. The DnSIZ1 protein localizes to the nucleus and shows SUMO E3 ligase activity when expressed in an Escherichia coli reconstitution system. Moreover, ectopic expression of DnSIZ1 in the Arabidopsis siz1-2 mutant partially complements several phenotypes and results in enhanced levels of SUMO conjugates in plants exposed to heat shock conditions. We observed that DnSIZ1 acts as a negative regulator of flowering transition which may be via a vernalization-induced pathway. In addition, ABA-hypersensitivity of siz1-2 seed germination can be partially suppressed by DnSIZ1. Our results suggest that DnSIZ1 is a functional homolog of the Arabidopsis SIZ1 with SUMO E3 ligase activity and may play an important role in the regulation of Dendrobium stress responses, flowering and development.


Differential impact of missed initial wound clinic visit on 6-month wound healing by race/ethnicity among patients with chronic limb-threatening ischemia.
Chronic limb-threatening ischemia (CLTI) is associated with significant morbidity, including major limb amputation, and mortality. Healing ischemic wounds is necessary to optimise vascular outcomes and can be facilitated by dedicated appointments at a wound clinic. This study aimed to estimate the association between successful wound care initiation and 6-month wound healing, with specific attention to differences by race/ethnicity. This retrospective study included 398 patients with CLTI and at least one ischaemic wound who scheduled an appointment at our wound clinic between January 2015 and July 2020. The exposure was the completion status of patients' first scheduled wound care appointment (complete/not complete) and the primary outcome was 6-month wound healing (healed/not healed). The analysis focused on how this association was modified by race/ethnicity. We used Aalen-Johansen estimators to produce cumulative incidence curves and calculated risk ratios within strata of race/ethnicity. The final adjustment set included age, revascularization, and initial wound size. Patients had a mean age of 67 ± 14 years, were 41% female, 46% non-White and had 517 total wounds. In the overall cohort, 70% of patients completed their first visit and 34% of wounds healed within 6-months. There was no significant difference in 6-month healing based on first visit completion status for White/non-Hispanic individuals (RR [95% CI] = 1.18 [0.91, 1.45]; p-value = 0.130), while non-White individuals were roughly 3 times more likely to heal their wounds if they completed their first appointment (RR [95% CI] = 2.89 [2.66, 3.11]; p-value < 0.001). In conclusion, non-White patients were approximately three times more likely to heal their wound in 6 months if they completed their first scheduled wound care appointment while White/non-Hispanic individuals' risk of healing was similar regardless of first visit completion status. Future efforts should focus on providing additional resources to ensure minority groups with wounds have the support they need to access and successfully initiate wound care.


Asymmetrical developmental pattern of uptake of Lucifer Yellow into amacrine cells in the embryonic chick retina.
Whole chick embryo eyes between embryonic day 10.5 and 12 (E10.5-E12) were incubated in a solution of Lucifer Yellow and examined in frozen sections. Starting around day 10.5, brightly stained cells were observed in the innermost part of the inner nuclear layer. Their size, shape and location suggest that most of them represent a subclass of amacrine cells. A distinct spatio-temporal development of Lucifer Yellow-staining of this subpopulation of cells within the inner nuclear layer between E10.5 and E12 is revealed in detail using 3-dimensional models of Lucifer Yellow-stained eyes. The staining can be first observed at a specific location at the ventro-posterior side not far from the fundus. It then spreads radially in a complex pattern reaching the ora serrata first on the ventro-posterior side, then sequentially reaching into the dorso-posterior, the ventro-anterior and finally the dorso-anterior quadrants of the retina. Our results suggest that a horizontal (posterior-anterior) axis and a vertical (ventro-dorsal) axis function as a coordinate system during differentiation of the tissue. We conclude that there are precise spatio-temporal patterns of Lucifer Yellow-staining which most probably reflect spatio-temporal patterns of cell differentiation within the chicken retina. The correlation of these findings with other data on spatio-temporal patterns during differentiation of the chicken retina is discussed.


Rapid recovery of stem increment in Norway spruce at reduced SO2 levels in the Harz Mountains, Germany.
Tree-ring width of Picea abies was studied along an altitudinal gradient in the Harz Mountains, Germany, in an area heavily affected by SO(2)-related forest decline in the second half of the 20th century. Spruce trees of exposed high-elevation forests had earlier been shown to have reduced radial growth at high atmospheric SO(2) levels. After the recent reduction of the SO(2) load due to clean air acts, we tested the hypothesis that stem growth recovered rapidly from the SO(2) impact. Our results from two formerly damaged high-elevation spruce stands support this hypothesis suggesting that the former SO(2)-related spruce decline was primarily due to foliar damage and not to soil acidification, as the deacidification of the (still acidic) soil would cause a slow growth response. Increasing temperatures and deposited N accumulated in the topsoil are likely additional growth-promoting factors of spruce at high elevations after the shortfall of SO(2) pollution.


Serological and cultural studies on broiler breeder multiplier flocks infected with Mycoplasma synoviae.
Nine broiler breeder flocks found infected with Mycoplasma synoviae (MS) at 17 to 42 weeks of age were used for serological tests and isolations of MS. Five live females and 20 to 30 serums were brought to the laboratory from each flock on three occasions. Serums from flocks naturally infected reacted to the serum plate agglutination and hemagglutination-inhibition tests throughout one laying season. MS was isolated from the trachea, turbinates, sinus, lung, and air sacs throughout one laying season. The medium with 0.1 g NAD isolated MS more efficiently than the medium with 0.01 g NAD. MS was isolated more frequently from the trachea, turbinates, and sinus than from the lung and air sacs.


Inhibition of elongin C promotes longevity and protein homeostasis via HIF-1 in C. elegans.
The transcription factor hypoxia-inducible factor 1 (HIF-1) is crucial for responses to low oxygen and promotes longevity in Caenorhabditis elegans. We previously performed a genomewide RNA interference screen and identified many genes that act as potential negative regulators of HIF-1. Here, we functionally characterized these genes and found several novel genes that affected lifespan. The worm ortholog of elongin C, elc-1, encodes a subunit of E3 ligase and transcription elongation factor. We found that knockdown of elc-1 prolonged lifespan and delayed paralysis caused by impaired protein homeostasis. We further showed that elc-1 RNA interference increased lifespan and protein homeostasis by upregulating HIF-1. The roles of elongin C and HIF-1 are well conserved in eukaryotes. Thus, our study may provide insights into the aging regulatory pathway consisting of elongin C and HIF-1 in complex metazoans.


Secondary Neurulation Defect: Terminal Myelocystocele, a Biological Leviathan.
Terminal myelocystocele (TMC) has been a puzzling entity of spinal dysraphism. It is found in the sacrococcygeal region usually forming a subcutaneous hump of various sizes. The wide variation of its morphology has been clarified by defining the essential and nonessential features as described in this chapter. Although it is not a common entity, TMC is attractive in that a highly plausible hypothesis on its pathoembryogenesis has been proposed based on observations on the secondary neurulation of the chick embryo. In this chapter, the embryology will be described, followed by the surgical strategy in accordance with the embryogenesis. The clinical features and prognosis will also be presented in detail.


Short-term femoral venous dialysis catheters for autologous peripheral blood progenitor cell collection: retrospective evaluation in 276 catheter practice from a single center.
We retrospectively evaluated 276 short-term femoral venous dialysis catheters (STFVCs) used for the collection of peripheral blood progenitor cells (PBPCs). Patients were not given any prophylactic antibiotic or anti-thrombotic therapy. Totally 877 leukapheresis sessions were performed. STFVCs were sufficient for continuous flow rate in all leukapheresis session. Side effects were detected in 30 (10.86%) STFVC practice (ecchymosis and/or hematoma in 13 (4.71%), thrombophlebitis in 5 (1.81%), bleeding in 4 (1.44%), catheters were not inserted into right femoral vein in 4 (1.44%), infection in PBPC products of 3 (1.08%) and blood receiving tip of catheter was cracked in 1 (0.36%)). Our results showed that STFVCs minimized the serious side effects such as thrombophlebitis, bleeding and infection of PBPC products. The STFVCs appeared safe and effective for PBPC collection.


Multifaceted deregulation of gene expression and protein synthesis with age.
Protein synthesis represents a major metabolic activity of the cell. However, how it is affected by aging and how this in turn impacts cell function remains largely unexplored. To address this question, herein we characterized age-related changes in both the transcriptome and translatome of mouse tissues over the entire life span. We showed that the transcriptome changes govern those in the translatome and are associated with altered expression of genes involved in inflammation, extracellular matrix, and lipid metabolism. We also identified genes that may serve as candidate biomarkers of aging. At the translational level, we uncovered sustained down-regulation of a set of 5'-terminal oligopyrimidine (5'-TOP) transcripts encoding protein synthesis and ribosome biogenesis machinery and regulated by the mTOR pathway. For many of them, ribosome occupancy dropped twofold or even more. Moreover, with age, ribosome coverage gradually decreased in the vicinity of start codons and increased near stop codons, revealing complex age-related changes in the translation process. Taken together, our results reveal systematic and multidimensional deregulation of protein synthesis, showing how this major cellular process declines with age.


[Arterial pressure in female combers depending on age and the length of work service].
The arterial pressure values were examined in 111 female workers of a combing shop. Hypotension was diagnosed in 22.5% of workers and hypertension in 5.4% of workers. The authors use a complex of measures to reduce noxious effects of industrial factors with the purpose of stabilization of the arterial pressure.


End of life in intensive care: family members' acceptance of orthotanasia.
This study aimed to assess family member acceptance of orthotanasia as related to symptom management, patient preference and the influence of the medical team's communication on therapy. This was a descriptive one-year study conducted at the adult intensive care unit of the Hospital do Servidor Público Estadual. A structured questionnaire based on the Quality of Dying and Death (QODD 22) instrument and prior informal interviews were used. Sixty family members were assessed; the mean age was 51.7 + 12.1 years, and 81.7% were female. The patients were hospitalized for a mean of 31 + 26.9 days, and 17.0% of these days were spent in the intensive care unit. Most of the patients had neurological conditions. Most of the patients (53.3%) had discussed their end-of-life care wishes with family members; however, 76.7% of them had not discussed this issue with their doctors (p < 0.00). The family members reported being favorable to orthotanasia in 83.3% of the cases. Most (85.0%) desired the medical team to clearly approach the subject, and 65.0% wished to take part in the quality of end-of-life decision making process. The family members were generally satisfied with information they received from the doctors: 93.3% believed they had received appropriately frequent communications about the clinical conditions; 81.7% were able to clarify their doubts regarding the patient's clinical status; the communication was understood by 83.3% of the respondents; and 80.0% believed that clear and honest information had been provided. Only 43.3% of the respondents wished to be present at the time of their loved ones' deaths. A significant association between family member acceptance of orthotanasia and participation in end-of-life decisions (p = 0.042) was observed. Most of the respondents were favorable to orthotanasia and wished to participate in end-of-life discussions.


Comparing effects of kyphoplasty, vertebroplasty, and non-surgical management in a systematic review of randomized and non-randomized controlled studies.
To determine if differences in safety or efficacy exist between balloon kyphoplasty (BKP), vertebroplasty (VP) and non-surgical management (NSM) for the treatment of osteoporotic vertebral compression fractures (VCFs). As of February 1, 2011, a PubMed search (key words: kyphoplasty, vertebroplasty) resulted in 1,587 articles out of which 27 met basic selection criteria (prospective multiple-arm studies with cohorts of ≥ 20 patients). This systematic review adheres to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Pain reduction in both BKP (-5.07/10 points, P < 0.01) and VP (-4.55/10, P < 0.01) was superior to that for NSM (-2.17/10), while no difference was found between BKP/VP (P = 0.35). Subsequent fractures occurred more frequently in the NSM group (22 %) compared with VP (11 %, P = 0.04) and BKP (11 %, P = 0.01). BKP resulted in greater kyphosis reduction than VP (4.8º vs. 1.7°, P < 0.01). Quality of life (QOL) improvement showed superiority of BKP over VP (P = 0.04), along with a trend for disability improvement (P = 0.08). Cement extravasation was less frequent in the BKP (P = 0.01). Surgical intervention within the first 7 weeks yielded greater pain reduction than VCFs treated later. BKP/VP provided greater pain relief and fewer subsequent fractures than NSM in osteoporotic VCFs. BKP is marginally favored over VP in disability improvement, and significantly favored in QOL improvement. BKP had a lower risk of cement extravasation and resulted in greater kyphosis correction. Despite this analysis being restricted to Level I and II studies, significant heterogeneity suggests that the current literature is delivering inconsistent messages and further trials are needed to delineate confounding variables.