Systematics of the nematodes that cause ostertagiasis in cattle, sheep and goats in North America.
The systematics of the Ostertagiinae is unsettled with no agreement on how many genera and species are present in cattle and sheep. Ten species of Ostertagiinae are commonly parasitic in cattle and sheep. The males can be identified on the basis of differences in morphology of spicules and genital cones but the females of most species cannot be identified. The species-level systematics have been complicated by the proposal that the ten species are polymorphs of only five species. The systematics at genus level has been complicated by the use of numerous genera for the ten species, at present most commonly Ostertagia, Teladorsagia and Marshallagia. This report (1) describes the current knowledge of the systematics and (2) provides diagnoses of the genera recommended for the ten species. The morphology of the ten species was studied to determine whether characteristics could be found to identify females or to further differentiate the males. Characters studied included the system of longitudinal and surface cuticular ridges (synlophe), the internal morphology of the esophagus and the orientation of rays of the copulatory bursa. The study of species morphology resulted in additional support for the polymorphism proposal. All minor species were found to be identical to their major species in characteristics of the synlophe, esophagus and rays of the copulatory bursa. Two recent classifications of the Ostertagiinae both recommended the use of the genus Teladorsagia for the species T. circumcincta and the two minor species that occur with it, T. trifurcata and T. davtiani. Teladorsagia is characterized by a copulatory bursa in which the five lateral rays are arranged 2-2-1 and a ventral swelling of the genital cone (proconus) is absent. One pair of species, Marshallagia marshalli (major species) and Ostertagia occidentalis (minor species) should be included in the genus Marshallagia. This genus has been characterized by an elongated bursa in which the posterior pair of lateral rays are much longer than the ventral pair. The remaining two pairs of species (O. ostertagi and its minor species O. lyrata, and O. leptospicularis and its minor species O. kolchida) and O. bisonis belong in the genus Ostertagia which is characterized by a 2-1-2 arrangement of the five lateral rays of the copulatory bursa and the presence of a proconus.


Genetic basis of resistance to southern corn leaf blight in the maize multi-parent population and diversity panel.
Southern corn leaf blight (SLB), caused by the necrotrophic pathogen Cochliobolus heterostrophus, is one of the maize foliar diseases and poses a great threat to corn production around the world. Identification of genetic variations underlying resistance to SLB is of paramount importance to maize yield and quality. Here, we used a random-open-parent association mapping population containing eight recombinant inbred line populations and one association mapping panel consisting of 513 diversity maize inbred lines with high-density genetic markers to dissect the genetic basis of SLB resistance. Overall, 109 quantitative trait loci (QTLs) with predominantly small or moderate additive effects, and little epistatic effects were identified. We found 35 (32.1%) novel loci in comparison with the reported QTLs. We revealed that resistant alleles were significantly enriched in tropical accessions and the frequency of about half of resistant alleles decreased during the adaptation process owing to the selection of agronomic traits. A large number of annotated genes located in the SLB-resistant QTLs were shown to be involved in plant defence pathways. Integrating genome-wide association study, transcriptomic profiling, resequencing and gene editing, we identified ZmFUT1 and MYBR92 as the putative genes responsible for the major QTLs for resistance to C. heterostrophus. Our results present a comprehensive insight into the genetic basis of SLB resistance and provide resistant loci or genes as direct targets for crop genetic improvement.


Monitoring of peptide-specific and gamma interferon-productive T cells in patients with active and convalescent tuberculosis using an enzyme-linked immunosorbent spot assay.
To establish a high-efficiency gamma interferon-specific enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT assay) for detection of tuberculosis (TB), peptides (E6, E7, and C14) and peptide mixtures (E6 plus E7 and E6 plus E7 plus C14) were used to monitor peripheral blood (PBL) samples from patients with pulmonary TB (PTB), as well as control samples. The positive detection rates of the five IFN-γ ELISPOT assays were 78.38%, 74.86%, 55.83%, 90.43%, and 91.51%, respectively, and there were similar detection rates between the two combined peptide mixture IFN-γ ELISPOT assays and the tuberculin skin test (TST) (90.62% versus 95.59%). No significant difference was found between the detection rates of the two combined peptide mixture IFN-γ ELISPOT assays and the T-SPOT.TB assay for 86 patients with PTB (P > 0.05), but the median number of spot-forming cells/10(6) cells (SFP value) for positive results was higher by the former than by the latter assay (P < 0.05). In contrast, the 29.93% positive detection rate and median SFP value of 482 by the two combined peptide mixture IFN-γ ELISPOT assays were significantly higher than the corresponding values of 14.29% and 152 by T-SPOT.TB assay for the same 147 community donors (P < 0.05). For nine PTB patients tracked, the SFP value of 7 for the two peptide mixture IFN-γ ELISPOT assays began to decrease from the second month after regular treatment. A relatively low, almost normal, SFP level was reached and maintained after the third or fourth month. Two in-house IFN-γ ELISPOT assays and the T-SPOT.TB assay could reduce the false-positive and false-negative detection rates of TST and sputum acid-fast staining. Therefore, these two combined peptide mixture IFN-γ ELISPOT assays have a potential advantage, beyond their greater specificity and sensitivity, for use in screening and detection of active TB infection (TBI) and latent TB infection (LTBI) in China.


The Red Reflex Exam: Highlighting the Importance of Physical Exam Maneuvers.
A pediatric well-child physical examination consists of various assessments that screen for common abnormalities during development. Checking the red reflex is one such assessment, with the absence of a red reflex indicating a potential ocular abnormality such as a retinoschisis. Both the American Academy of Pediatrics and the American Academy of Family Physicians have guidelines that call for routine screening of the red reflex from infancy through adolescence. This exam has a high specificity if performed correctly, underlining the utility of this test. This case details a pediatric patient diagnosed with retinoschisis following an absent red reflex noted by a primary care physician. We illustrate the importance of routine exam maneuvers like the red light reflex in routine physical examinations for the screening and diagnosis of illnesses that can significantly alter a child's quality of life over time.


Thymidine-dependent effect of granulocyte-derived inhibitor on granulocyte-macrophage progenitor cells (GM-CFC).
We have compared the effect of granulocyte extract (GRE) on proliferation of hemopoietic cells from various sources, using two different cultures media, CMRL 1066 and McCoy 5A. GRE caused a strong (80-90%) inhibition of granulocyte-macrophage colony forming cells (GM-CFC) in cultures with medium CMRL 1066. GM-CFC in human blood and human and mouse bone marrow were equally sensitive to the inhibitor. The inhibitor had a maximal effect in the concentration range corresponding to GRE from 2 x 10(5) to 2 x 10(6) cells per 1 ml culture dish. At higher GRE concentration the inhibition was reduced. GM-CFC from human blood and mouse marrow were suppressed in cultures with McCoy's medium as well, but to a lesser extent than in CMRL 1066 cultures. On the other hand, in cultures with human bone marrow cells (BMC) and McCoy's medium, GRE had no inhibitory effect. CMRL 1066 medium contains a number of components not present in McCoy's medium. In a systematic study where these substances were added one by one to McCoy's medium we found that inhibition by GRE depended upon the presence of thymidine. At a thymidine concentration of 3 x 10(-5) mol/l GRE strongly suppressed GM-CFC in human blood and bone marrow. This thymidine concentration itself had no effect. Other nucleosides or components of the CMRL 1066 did not potentiate the suppressive effect of GRE.


Mathematical modeling of immune modulation by glucocorticoids.
The cellular and molecular mechanisms of immunomodulatory actions of glucocorticoids (GC) remain to be identified. Using our experimental findings, a mathematical model based on a system of ordinary differential equations for characterization of the regulation of anti-tumor immune activity by the both direct and indirect GC effects was generated to study the effects of GC treatment on effector CD8+ T cells, GC-generated tolerogenic dendritic cells (DC), regulatory T cells and the growth of lymphoma cells. In addition, we compared the data from in vivo and in silico experiments. The mathematical simulations indicated that treatment with GCs may suppress anti-tumor immune response in a dose-dependent manner. The model simulations were in line with earlier experimental observations of inhibitory effects of GCs on T and NK cells and DCs. The results of this study might be useful for predicting clinical outcomes in patients receiving GC therapy.


Smart data collection for CryoEM.
This report provides an overview of the discussions, presentations, and consensus thinking from the Workshop on Smart Data Collection for CryoEM held at the New York Structural Biology Center on April 6-7, 2022. The goal of the workshop was to address next generation data collection strategies that integrate machine learning and real-time processing into the workflow to reduce or eliminate the need for operator intervention.


Chemoenzymatic synthesis of Neu5Ac9NAc-containing α2-3- and α2-6-linked sialosides and their use for sialidase substrate specificity studies.
O-Acetylation of sialic acid (Sia) modulates its recognition by sialic acid-binding proteins and plays an important role in biological and pathological processes. 9-O-Acetylation is the most common modification of sialic acid in human. However, study of O-acetylated sialoglycans is hampered due to the instability of O-acetyl group towards pH changes and sensitivity to esterases. Our previous studies demonstrated a chemical biology method to this problem by replacing the oxygen atom in the C9 ester group of sialic acid by a nitrogen to form an amide. Here, we synthesized a library of sixteen new 9-acetamido-9-deoxy-N-acetylneuraminic acid (Neu5Ac9NAc)-containing α2-3- and α2-6-linked sialosides with various underlying glycans using efficient one-pot three-enzyme (OP3E) sialylation systems. Neu5Ac9NAc-containing compounds with a para-nitrophenol aglycon have been used together with their 9-O-acetyl analogs in microtiter plate-based high-throughput substrate specificity studies of nine different sialidases including those from humans and bacteria. In general, similar to 9-O-acetylation, 9-N-acetyl modification of sialic acid in the substrates lowers sialic acid-cleavage activity of most sialidases. In most cases, Neu5Ac9NAc is a good analog of 9-O-acetyl sialic acid. However, exceptions do exist. For example, 9-N- and 9-O-acetyl modifications have different effects on the sialosides cleave efficiencies of a commercially available C. perfringens sialidase as well as recombinant Streptococcus pneumoniae sialidase SpNanC and Bifidobacterium infantis sialidase BiNanH2. The mechanism for the difference awaits further investigation.


Structure and function of seed lipid-body-associated proteins.
Many organisms among the different kingdoms store reserve lipids in discrete subcellular organelles called lipid bodies. In plants, lipid bodies can be found in seeds but also in fruits (olives, ...), and in leaves (plastoglobules). These organelles protect plant lipid reserves against oxidation and hydrolysis until seed germination and seedling establishment. They can be stabilized by specific structural proteins, namely the oleosins and caleosins, which act as natural emulsifiers. Considering the putative role of some of them in controlling the size of lipid bodies, these proteins may constitute important targets for seed improvement both in term of oil seed yield and optimization of technological processes for extraction of oil and storage proteins. We present here an overview of the data on the structure of these proteins, which are scarce, and sometimes contradictory and on their functional roles.


From microarrays to genome duplications.
A report on the fifth annual conference of the Society for Bioinformatics in the Nordic Countries (SOCBIN), 'Bioinformatics 2003', Helsinki, Finland, 22-24 May 2003.


Semi-circular microgrooves to observe active movements of individual Navicula pavillardii cells.
We performed a trajectory analysis of movements of Navicula pavillardii diatom cells that were confined to semi-circular microgrooves with several different curvature radii. Using the semi-circular micropattern, we succeeded in observing change of velocity of the same cell before and after the stimulation by N,N-dimethyl-p-toluidine (DMT). Because the looped grooves had longer contour length than straight grooves, it was effective to achieve the long term observation of the stimulated active cells. Although average velocity of 150 cells was significantly increased with DMT, the maximum velocity (19 μm/s) of the cells was not increased after the DMT injection. This may suggest that existence of the mechanical limit of the velocity of the diatom cells. Secondly, trajectories of individual cell movements along the walls of the semi-circular microgrooves were analyzed in detail. As a result, the velocity of the cells was not affected by the curvature radii of the grooves although the trajectories indicated an obvious restriction of area of the cell motion. This suggests that the surface of the diatom is effective in minimizing the frictional force between the cell body and the wall of a groove. Finally, a simple model of cell motion in the semi-circular groove was proposed to clarify the relationships among the forces that determine cell movement.


Impairment in family caregiving: a biological perspective.
This paper focuses on patterns in the care of children and dependent elders, providing a new perspective to understand impairment in family caregiving. One concept from evolutionary theory, kin selection, has promise for providing a broad framework for understanding patterns of family caregiving. We present an application of the evolutionary model to the issue of family care decisions in the face of potential conflicts of interest. Specifically, a mathematical biological model, which was developed to understand self-preservation motivation, is applied to the kin investment decision. Using the evolutionary model, the main predictors of investment would be relatedness, reproductive value, and expected benefit from the care invested. The biological model accounts very simply for decisions between caring for an elder parent or caring for your own child, and for decisions by two daughters (one with a child, one childless) to care for an elder parent. The factors that form the basis of an evolutionary model (relatedness, reproductive value, and benefit from care) have not been widely investigated in family care studies, however, and this absence reveals new directions for future research.


Relationship between survival and histologic type in small cell anaplastic carcinoma of the lung.
Survival and histologic subtype were compared in 61 patients with small cell anaplastic lung cancer. Patients with lymphocyte-like (oat cell) and fusiform histologies treated with chemotherapy had longer median survivals than the polygonal and other varieties on the same treatment. Likewise, when detectable disease was confined to the chest and supraclavicular nodes, the patients with lymphocyte-like and fusiform types lived longer. The improved survival in the lymphocyte-like and fusiform categories accounted for most of our improved overall median survival rates with the COPP regimen in small cell lung cancer. Survival in the polygonal and other types was not appreciably different from that seen in non-small cell lung cancer (squamous and adenocarcinoma). It may be possible to refine treatment plans on the basis of cell type so as to further increase survival in small cell anaplastic lung carcinoma.


Overview of human B-cell development and antibody deficiencies.
B cells are a key component of the humoral (antibody-mediated) immune response which is responsible for defense against a variety of pathogens. Here we provide an overview of the current understanding of B cell development and function and briefly describe inborn errors of immunity associated with B cell development defects which can manifest as immune deficiency, malignancy, autoimmunity, or allergy. The knowledge and application of B cell biology are essential for laboratory evaluation and clinical assessment of these B cell disorders.


Dietary Micronutrient Adequacy and Risk of Multimorbidity in Community-dwelling Older Adults.
Multimorbidity refers to the coexistence of multiple chronic health conditions. The effect of nutritional adequacy on multimorbidity is mostly unknown. The aim of this study was to assess the prospective association between dietary micronutrient adequacy and multimorbidity among community-dwelling older adults. This cohort study included 1461 adults aged ≥65 y from the Seniors-ENRICA II cohort. Habitual diet was assessed at baseline (2015-2017) with a validated computerized diet history. The intakes of 10 micronutrients (calcium, magnesium, potassium, vitamins A, C, D, E, zinc, iodine, and folate) were expressed as percentages relative to the dietary reference intakes, with higher scores indicating greater adequacy. Dietary micronutrient adequacy was computed as the average of all the nutrient scores. Information on medical diagnosis was obtained from the electronic health records up to December 2021. Conditions were grouped into a comprehensive list of 60 categories and occurrence of multimorbidity was defined as having ≥6 chronic conditions. Analyses were conducted using Cox proportional hazard models adjusted for relevant confounders. The mean age was 71.0 y (SD: 4.2) and 57.8% of participants were males. During a median follow-up of 4.79 y, we documented 561 incident cases of multimorbidity. Participants in the highest (85.8%-97.7%) versus the lowest tertile (40.1%-78.7%) of dietary micronutrient adequacy had a low risk of multimorbidity [fully adjusted hazard ratio (95% confidence interval): 0.75 (0.59-0.95); P-trend: 0.02]. A 1-SD increment in minerals and vitamins adequacy was associated with a low risk of multimorbidity, although estimates were attenuated after additional adjustment for the opposite subindex [minerals subindex: 0.86 (0.74-1.00); vitamins subindex: 0.89 (0.76-1.04)]. No differences were observed by strata of sociodemographic and lifestyle factors. A high micronutrient index score was associated with low risk of multimorbidity. Improving the dietary micronutrient adequacy could prevent multimorbidity among older adults. clinicaltrials.govNCT03541135.


Cardiotoxicity and cancer therapy: treatment-related cardiac morbidity in patients presenting with symptoms suggestive of heart or lung disease.
Cardiac injury is one of the complications of cancer treatment. This study aimed to investigate the relationships between the types of radiotherapy of the chest (RT), chemotherapy (CT), cancer surgery (CS) and endocrine therapy (ET), and the presence of heart disease, and their associations with the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). A consecutive series of 374 patients with cancer who were referred because of symptoms suggestive of heart or lung disease prospectively underwent a diagnostic workup. The prevalence of heart disease was 36.9%. RT administered before 1995 (n = 19) was associated with both increased odds of heart disease [adjusted odds ratio 10.3, 95% confidence interval 3.1-34.0] and higher ln-transformed NT-proBNP values (p < 0.01) compared to the control group (no RT or RT for right-sided breast cancer from 1995 onwards; n = 311). Anthracycline-treated patients (n = 54) had higher adjusted values for ln(NT-proBNP) compared to the control group (no CT; n = 243; p < 0.01) but no increased odds of heart disease. While pre-1995 RT and anthracycline-containing CT were associated with cardiac effects, there was no evidence that RT using modern cardioprotective techniques, CT in the absence of anthracyclines, CS or ET had detrimental effects on the heart.


The risk of allowing blood donation from men having sex with men after a temporary deferral: predictions versus reality.
In most industrialized countries, men who had sex with men (MSM) are permanently deferred from blood donation. Some countries have adopted a temporary deferral after the MSM behavior, thus avoiding donations made during the window period of human immunodeficiency virus (HIV) infection. However, one concern with this approach is the possible increase in the number of HIV-positive donations obtained from unknowingly infected, abstinent MSM; such donations might inadvertently be made available for transfusion, a risk that was previously estimated through mathematical modeling. Model predictions were compared to the actual donor rate of HIV in three countries that went from a permanent to a temporary deferral: Australia, the United Kingdom, and Canada. Depending on the model, a temporary deferral should have increased the rate of HIV in the male donor pool by 73% to more than 3400%. In reality, the very low baseline rate of HIV before the change in these three countries (22 cases/year) remained unchanged 2 years after the revised policy (16 cases/year). These observations strongly suggest that a temporary deferral for MSM incurs zero risk to recipients, at least in jurisdictions where HIV epidemiology is comparable to that of countries where the change happened.


Urinary parabens and their derivatives associated with oxidative stress biomarkers in children from South and Central China: Repeated measures.
Previous studies implied that elevated exposure to parabens may result in increased oxidative stress. However, the association between exposure to paraben derivatives and oxidative stress biomarkers in children has been rarely studied. This study examined the associations between exposure to paraben derivatives and oxidative stress biomarkers in Chinese children. Nine targeted compounds of parabens and their derivatives including methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), butyl paraben (BuP), p-hydrox4ybenzoic acid (p-HB), 3,4-dihydroxy benzoic acid (3,4-DHB), benzoic acid, methyl 3,4-dihydroxybenzoate (rOH-MeP), and ethyl 3,4-dihydroxybenzoate (rOH-EtP) were detected in urine collected from 139 children from South and Central China. Additionally, 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 4-hydroxy-2-nonenal mercapturic acid (HNE-MA) were measured as oxidative stress biomarkers. All targeted compounds (except for BuP) were frequently detected in urine (detection frequencies ranged 80.8%-100%). Linear mixed effects model revealed that all targeted compounds (with detection frequencies >50%), except for EtP, were significantly associated with an increase in 8-OHdG. rOH-EtP was found to be significantly associated with 8-OHG (β = 0.12; 95% confidence interval [95% CI]: 0.08, 0.16) positively. In addition, PrP and benzoic acid were associated with elevated levels of HNE-MA. Weighted quantile sum regression revealed that co-exposure to the targeted compounds was positively associated with 8-OHdG (β = 0.17; 95% CI: 0.12, 0.22), 8-OHG (β = 0.14; 95% CI: 0.10, 0.18), and HNE-MA (β = 0.43; 95% CI: 0.27, 0.59); rOH-EtP and benzoic acid were the major contributors for the combined effects on oxidative stress of nucleic acids and lipid, respectively. Our findings provide new evidence for the effects of exposure to paraben derivatives on nucleic acid oxidative damage and lipid peroxidation in children.


Supracricoid partial laryngectomy in the treatment of laryngeal cancer: univariate and multivariate analysis of prognostic factors.
To evaluate the oncological results of supracricoid partial laryngectomy as a treatment for selected glottic and supraglottic cancer in a large series of patients who had undergone uniform treatment over a 16-year period and to determine the different prognostic factors that may influence local control and survival. Retrospective clinical study. Academic tertiary referral medical center. The study population comprised 253 consecutive patients (234 men and 19 women) with glottic and supraglottic squamous cell carcinoma. The mean age was 58 years for men and 59.2 years for women. Supracricoid partial laryngectomy: 180 patients had undergone cricohyoidopexy and 73 had undergone cricohyoidoepiglottopexy. Local control and overall survival. Potential prognostic factors for local control and survival were evaluated with univariate and multivariate models. The 3-, 5-, 10-, and 16-year overall survival rates in this group of 253 patients were 85.8%, 79.1%, 57.6%, and 57.6%, respectively. With regard to local control, univariate and multivariate analyses showed that a positive resection margin was the only important predictor of local control and that a dysplastic lesion at the margin of resection is just as aggressive as the presence of invasive carcinoma. When considering the prognostic factors influencing survival, univariate analysis showed that the tumor category, lymph node category, tumor stage, and recurrence all had a significant influence on the survival rate. Multivariate analysis showed that the most important predictor of survival was recurrence. Supracricoid partial laryngectomy is a valid choice in the treatment of selected glottic and supraglottic cancer while maintaining laryngeal functions and achieving a high rate of local control. T category, N category, tumor stage, positive resection margins, and recurrence are the most important predictors of oncological outcome.


The cephalic glands of Brazilian reptilia and amphibia. IV. Histology of labial, premaxillary, and Duvernoy's glands in the colubrid snake Oxyrhopus trigeminus.
A study of the morphology of the salivary glands of the colubrid snake Oxyrhopus trigeminus showed the following: The acini of supralabial, infralabial, and premaxillary glands are formed by mucous and mucoserous cells; the tubules of Duvernoy's gland are formed by seromucous cells; and mucous cells produce neutral and acid mucosubstances, mucoserous cells secrete neutral and acid mucosubstances and protein, and seromucous cells have neutral mucosubstance and protein secretions.


Role of CD64 expression on neutrophils in the diagnosis of sepsis and the prediction of mortality in adult critically ill patients.
Intensive care unit patients who developed systemic inflammatory response syndrome (SIRS) with proven microbial etiology were assigned to the infectious causes (n = 29), while patients with negative cultures and more probable other etiology were assigned to the noninfectious causes (n = 37). Flow cytometry was used to detect the presence of CD64 on neutrophils. The multivariate analysis revealed that KPC-producing Klebsiella pneumoniae rectal colonization and >1.39 mean fluorescence intensity (MFI) of CD64 expression on neutrophils upon day 1 of SIRS were significantly associated with an infectious SIRS. The overall mortality was 29% (19 patients) and was independently associated with Simplified Acute Physiology Score II >44 points and multiple-organ dysfunction syndrome, while appropriate antibiotic treatment was identified as predictor of good prognosis. MFI of CD64 expression on neutrophils showed high sensitivity, specificity, and accuracy in the diagnosis of sepsis but not for the prediction of survival.


UBE2M-mediated neddylation of TRIM21 regulates obesity-induced inflammation and metabolic disorders.
Inflammation is closely associated with obesity and related metabolic disorders. However, its origin during obesity is largely unknown. Here, we report that ubiquitin-conjugating enzyme E2M (UBE2M) is critical to obesity-related inflammation induced by macrophages. In mice with UBE2M-deficient macrophages, obesity, insulin resistance, and hepatic steatosis induced by a high-fat diet are greatly alleviated, an effect related to the decreased proinflammatory activity of macrophages due to reduced IL-1β production. Mechanistically, UBE2M deficiency inhibits the neddylation of E3 ubiquitin ligase TRIM21 on K129/134, leading to reduced recruitment and ubiquitination-mediated degradation of E3 ubiquitin ligase VHL. Subsequently, VHL reduces HIF-1α-induced IL-1β production by degrading HIF-1α. Targeting macrophage TRIM21 with Trim21 antisense oligonucleotide-loaded red blood cell extracellular vesicles effectively inhibits obesity-induced inflammation and related metabolic disorders. Thus, our results demonstrate that macrophage UBE2M is essential for obesity-induced inflammation and that TRIM21 is a proof-of-concept target for treating obesity and associated metabolic diseases.


The influence of circulating fibrinogen level on postoperative blood loss and blood transfusion in pediatric cardiac surgery: a retrospective observational study.
Pediatric patients are at high risk of massive bleeding after cardiac surgery under cardiopulmonary bypass (CPB). Fibrinogen is essential for coagulation; however, pediatric patients with congenital heart disease (CHD) present abnormal fibrinogen function. The pre- and post-operative fibrinogen level may affect the bleeding and transfusion amount in patients undergoing cardiac surgery. However, the relationship between plasma fibrinogen levels and the bleeding and transfusion amount in pediatric cardiac surgery remains unclear. This study aimed to assess the association of pre-CPB fibrinogen levels (PreFib) and post-CPB fibrinogen levels (PostFib) with postoperative bleeding and transfusion volume in pediatric cardiac surgery. We reviewed the medical records of 375 newborns and infants who underwent cardiac surgery under CPB for CHD. The primary endpoint was the correlation of the PreFib and PostFib values, as well as their difference (FibGap), with the bleeding and transfusion amount within 24 postoperative hours. There was no correlation of the PreFib, PostFib, and FibGap values with the bleeding and transfusion amounts at postoperative 24 hours. However, patients with PreFib and PostFib values of <150 and <100 mg/dL, respectively, showed a significantly higher frequency of postoperative platelet (PLT) transfusion. In patients with complex CHD, PreFib showed a weak negative correlation with the bleeding amount at postoperative 24 hours and the number of PLT-transfused patients. Our findings suggest that in pediatric patients with CHD who cannot undergo point-of-care (POC) tests, those presenting PreFib and PostFib values of <150 and <100 mg/dL, respectively, have a significantly higher frequency of postoperative PLT transfusion.


Expression of serine proteases and metalloproteinases in human pituitary adenomas and anterior pituitary lobe tissue.
Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g. MMP-9). Serine proteases have not yet been investigated in human pituitary adenomas. In this study, paraffin-embedded material from 84 human pituitary adenomas (acromegaly n=18, Cushing's disease n=21, prolactinoma n=18, thyroid-stimulating hormone-secreting adenoma n=1, nonsecreting adenoma n=26) and 9 nontumourous anterior pituitary lobes (obtained from patients with prostate cancer) was immunohistochemically analysed for expression of MMP-2, MMP-9, tissue inhibitor of metalloproteinases-2 (TIMP-2), urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and interleukin-6 (IL-6). Cavernous sinus invasion was determined by assessment of preoperative magnetic resonance imaging and intraoperative inspection (invasive n=50, noninvasive n=34). In pituitary adenomas, reactions were positive (diffuse expression) to MMP-2 (74% of cases), MMP-9 (49%), TIMP-2 (88%), uPA (89%), uPAR (90%), tPA (69%), and PAI-1 (87%). A weak expression of IL-6 was found in 12% of the adenomas. All reactions were positive (focal expression) in every sample of anterior lobe tissue, except for uPA (negative in 3 out of 9 cases), and IL-6 (faintly positive in 5 out of 8 cases). Adenomas showed remarkably greater expression of uPA than anterior lobe tissue (Chi-square P<0.05). Nonsecreting adenomas exhibited a stronger tendency towards overexpression of uPA in invasive tumours when compared to noninvasive adenomas (Chi-square P=0.053). We found no correlation of MMP-9 expression and tumour invasion. TIMP-2 was overexpressed in noninvasive as compared to invasive adenomas (Chi-square P<0.05). The interrelationship between MMPs and serine proteinases in pituitary adenomas remains to be elucidated. From our data, a correlation between IL-6 and an activation of MMP-9 cannot be proven. The uPA-system may, however, play a role in dural invasion of pituitary adenomas.


[Aspects, findings and problems in criminal cadaver dismemberment].
Nine cases of defensive corpse dismemberment are reported. Twice offensive components were regarded. All victims were identified within a short time. Eight crimes were solved, in six cases there had been a relationship between the murderer and the victim. One corpse was dismembered by means of an explosive.


Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms.
Janus kinases (JAKs) mediate responses to cytokines, hormones and growth factors in haematopoietic cells1,2. The JAK gene JAK2 is frequently mutated in the ageing haematopoietic system3,4 and in haematopoietic cancers5. JAK2 mutations constitutively activate downstream signalling and are drivers of myeloproliferative neoplasm (MPN). In clinical use, JAK inhibitors have mixed effects on the overall disease burden of JAK2-mutated clones6,7, prompting us to investigate the mechanism underlying disease persistence. Here, by in-depth phosphoproteome profiling, we identify proteins involved in mRNA processing as targets of mutant JAK2. We found that inactivation of YBX1, a post-translationally modified target of JAK2, sensitizes cells that persist despite treatment with JAK inhibitors to apoptosis and results in RNA mis-splicing, enrichment for retained introns and disruption of the transcriptional control of extracellular signal-regulated kinase (ERK) signalling. In combination with pharmacological JAK inhibition, YBX1 inactivation induces apoptosis in JAK2-dependent mouse and primary human cells, causing regression of the malignant clones in vivo, and inducing molecular remission. This identifies and validates a cell-intrinsic mechanism whereby differential protein phosphorylation causes splicing-dependent alterations of JAK2-ERK signalling and the maintenance of JAK2V617F malignant clones. Therapeutic targeting of YBX1-dependent ERK signalling in combination with JAK2 inhibition could thus eradicate cells harbouring mutations in JAK2.


Simple device for determining an index of echogenicity.
The technique reported here uses a simple electronic system adaptable to a standard manual echograph with the aim of obtaining a numerical index of echogenicity. The index is the ratio of the average echo amplitude within a gated portion of tissue at a given depth to the average echo amplitude within the same gated portion measured under the same conditions on a phantom filled with a "tissue-mimicking" material. A theoretical analysis shows that the index depends not only on the attenuation coefficient and the backscattering coefficient of the tissue but also on the depth of the measurement. It is demonstrated that it is feasible to measure the attenuation coefficient using the current system, and the reproducibility of the index measurement is evaluated on a normal thyroid.


Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) improves brain ischemia-induced pulmonary injury in rats associated to TNF-α expression.
Bone marrow mesenchymal stem cell (BMSCs)-based therapy seems to be a promising treatment for acute lung injury, but the therapeutic effects of BMSCs transplantation on acute lung injury induced by brain ischemia and the mechanisms have not been totally elucidated. This study explores the effects of transplantation of BMSCs on acute lung injury induced by focal cerebral ischemia and investigates the underlying mechanism. Acute lung injury model was induced by middle cerebral artery occlusion (MCAO). BMSCs (with concentration of 1 × 10(6)/ml) were transplanted into host through tail vein 1 day after MCAO. Then, the survival, proliferation and migration of BMSCs in lung were observed at 4 days after transplantation, and histology observation and lung function were assessed for 7 days. Meanwhile, in situ hybridization (ISH), qRT-PCR and western blotting were employed to detect the expression of TNF-α in lung. Neurobehavioral deficits and acute lung injury could be seen in brain ischemia rats. Implanted BMSCs could survive in the lung, and relieve pulmonary edema, improve lung function, as well as down regulate TNF-α expression. The grafted BMSCs can survive and migrate widespread in lung and ameliorate lung injury induced by focal cerebral ischemia in the MCAO rat models. The underlying molecular mechanism, at least partially, is related to the suppression of TNF-α.


Prospective assessment of complications on a daily basis is essential to determine morbidity and mortality in routine pediatric surgery.
We aimed to assess postoperative complications prospectively on a daily basis and hypothesized that this would lead to an increase in the number of detected complications. Surgical complications were assessed prospectively during a period of 8months. Systematic documentation was carried out daily during a team meeting (period S). Data were compared to those of a preceding period of 8-months of nonsystematic assessment (period N) in which complications had been documented in a self-reporting fashion. Complications were classified according to the Clavien-Dindo classification. A total of 1291 patients (mean age: 6.6years) were included. During period S complications were determined in 16% of 790 operations compared to 4% of 741 procedures in period N (p<0.01). This difference was owing to an increased detection of minor complications (grade I-III), i.e. wound infection, dysuria after hypospadias repair or postoperative bleeding. In contrast, the incidence of severe complications (grade IV+V) was not significantly different between the time periods (1.3% in period S and 0.8% in period N). Most frequent major complications were cardiopulmonary arrest, enterocolitis, and death. Severe complications accounted for 8% of complications discussed during weekly morbidity and mortality conferences in period S versus 22% in period N (p<0.05). Our results indicate that a systematic documentation of complications on a daily basis reveals a more realistic picture of the incidence of pediatric surgical complications and should be the method of choice.


Color appearance: neutral surrounds and spatial contrast.
The experimental data in this paper show that chromatic bars presented in alternation with equiluminant neutral-appearing bars are seen as more saturated than the same chromaticity presented as a uniform rectangle. This effect was diminished but not eliminated when test and match stimuli were presented within a slightly dimmer neutral surround. The test stimulus was a 2 x 5 degrees rectangle with a 0.7 cpd square wave grating composed of alternating equiluminant chromatic test bars and neutral bars. Asymmetric matching was used to match the test bar appearance to a uniform 2 x 5 degrees comparison rectangle. Test and comparison stimuli were presented to separate eyes in a haploscope and appeared flanking a central fixation target. Data were collected with test and inducing stimuli on the cardinal axes of color space. Test bars separated by neutral bars appeared more saturated than the comparison rectangle for both the l- and s-axis directions. Manipulation of excitation on one cardinal axis did not affect the appearance matches made for the other cardinal axis.


Stability of oestrogen receptor status in sequential biopsies from patients with breast cancer.
Sequential biopsies of breast cancer tissue were obtained from a total of 210 women in order to assess any change in oestrogen receptor (ER) status arising spontaneously or as a result of intervening therapy. A combined assay measuring both cytosol and nuclear oestrogen receptors was used for all samples. One hundred and fifty-five patients had biopsies of their primary tumour and of a later loco-regional recurrence; 26 had biopsies of their primary tumour and a recurrence or new primary in the opposite breast; and 29 had sequential biopsies of recurrent disease only. Overall only 61.2% of the primary tumours retained their original status with respect to both cytosol and nuclear oestrogen receptors on recurrence. These results were influenced by intervening therapy, however, and if only untreated patients are considered, over 70% of their recurrences contain the same combination of cytosol and nuclear receptors as found in the primary tumours. For tumours 'recurring' in the opposite breast, the pattern was similar with 69.2% retaining the same status as the first primary. The agent found most likely to alter I:R status was tamoxifen and in the samples taken from patients undergoing treatment with this drug, no tumour was found to contain measurable receptor.


Differentiation of intramural ganglia in the dissociated rectosigmoid of the rat: an organ culture study.
The distal rectosigmoid of the developing embryonic rat was studied on each gestational day from 12 to 21. Circular muscle was first recognized on day 16 and ganglion cells on day 17. When in vitro dissociated colon from as early as the day 12 embryo reached a maturational age of 17 days (embryonic age plus days in culture), circular muscle, ganglia, and peristalsis could be detected. This indicates that neuroblasts must have migrated to the indifferent mesenchyme before day 12 of gestation. Anti-nerve growth factor immunoglobulin-G ( IgG) did not inhibit differentiation of ganglia in vitro. As a result of this study we designed an in vitro assay that can serve as a useful means to study isolated ganglion cell development.


Loss of lamin A/C expression revealed by immuno-electron microscopy in dilated cardiomyopathy with atrioventricular block caused by LMNA gene defects.
Mutations of the LMNA gene encoding the lamin A and C nuclear envelope proteins cause an autosomal dominant form of dilated cardiomyopathy (DCM) with atrioventricular block (AVB). The aim of this study was to investigate ultrastructural nuclear membrane changes by conventional electron microscopy and protein expression by immuno-electron microscopy in the heart of patients with DCM and AVB due to LMNA gene mutations. Four immunohistochemical techniques were used: pre-embedding and post-embedding in Epon-Araldite resin and London Resin White (LRW), with and without silver enhancement. Parallel light microscopy immunohistochemistry studies were performed. Conventional electron microscopy showed a loss of integrity of the myocyte nuclei with blebs of the nuclear membrane, herniations and delamination of the nuclear lamina and nuclear pore clustering. Post-embedding LRW was the most informative technique for morphology and immuno-labelling. Immuno-labelling was almost absent in the nuclear envelope of patients with LMNA gene mutations, but intensely present in controls. The loss of labelling selectively affected myocyte nuclei; the endothelial cell nuclei were immunostained in patients and controls. Light immunohistochemistry confirmed the results. These findings confirm the hypothesis that LMNA gene defects are associated with a loss of protein expression in the selective compartment of non-cycling myocyte nuclei.


Local iron homeostasis in the breast ductal carcinoma microenvironment.
While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. We confirm previous results by showing that breast cancer epithelial cells present an 'iron-utilization phenotype' with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an 'iron-donor' phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context.


Study of quinones reactions with wine nucleophiles by cyclic voltammetry.
Quinones are electrophilic species which can react with various nucleophiles, like wine antioxidants, such as sulfur dioxide or ascorbic acid, thiols, amino acids, and numerous polyphenols. These reactions are very important in wine aging because they mediate oxygen reactions during both production and bottle aging phases. In this work, the major challenge was to determine the interaction between ortho-quinones and wine nucleophiles (amino acids, thiols, and the antioxidants SO2 and ascorbic acid), by cyclic voltammetry. Wine-model solutions with gallic acid, caffeic acid, or (+)-catechin and nucleophilic compounds were used. To understand the effect of nucleophilic addition in wine, a white wine with the same added nucleophiles was also analysed. Cyclic voltammograms were taken with glassy carbon electrode or screen-printed carbon electrodes, respectively, for wine-model and white wines solutions, in the absence and in the presence of nucleophiles. A nucleophilic order profile related to the cathodic current intensity decrease was observed.


Infections of the Central Nervous System in Returning Travelers and Immigrants.
This review highlights current knowledge in travel-related neuroinfectious diseases, providing insight on approaches to prevention, diagnosis, and treatment of infections of the central nervous system (CNS) in travelers and immigrants. Updates on travel vaccine recommendations including vaccine-specific interactions with immunosuppressive agents, advances in Zika virus and dengue virus vaccine development, new diagnostic criteria for neurocysticercosis, updates on treatment approaches for tuberculosis meningitis. Increasing rates of travel are leading to the spread of known infectious diseases and the emergence of new diseases in travel medicine. Among these infections, neuroinfectious diseases carry significant morbidity and mortality. To reduce the effect of travel-related illness, appropriate pre-travel measures and up-to-date diagnostic and treatment strategies are essential for optimal outcomes. This review highlights important travel information relevant to neuroinfectious diseases for several populations including immunocompetent, immunocompromised, pregnant, and infant/children travelers. It also outlines the travel risk, clinical presentation, diagnosis, and management of a select list of neuroinfectious diseases by region, including neurocysticercosis, Zika virus, tuberculosis meningitis, rabies, and tick-borne encephalitis.


Assessing severity of adult asthma and need for hospitalization.
Exacerbations of asthma requiring emergency treatment are common but, fortunately, asthma is rarely life threatening. In the course of treating acute asthmatics, however, the question of whether to admit the patient often is raised. With the current costs of hospitalization and morbidity associated with the disease, it is advantageous to be able to separate accurately those who require in-hospital treatment from those who can be treated as outpatients. The choice to hospitalize the asthmatic patient must be based on objective findings, including spirometry alone, spirometry plus history and physical signs, or index scoring (Figure). The best method awaits elucidation by prospective study. The most objective indicator of asthma severity is the indirect measurement of airways obstruction by spirometry, either by FEV1.0 or PEFR. FEV1.0 and PEFR yield comparable results. Simple, inexpensive devices for these measurements are available. An FEV1.0 less than 0.8 to 1.0 L (less than 25% predicted in women and men ages 25 to 65 years) or a PEFR less than 100 L/min (less than 20% predicted in women and men ages 25 to 65 years) accurately indicates a severe asthma exacerbation. The percentage predicted is utilized in those individuals who lack average stature. An increase in FEV1.0 to greater than 1.6 to 2.1 L (greater than 60% predicted) or a PEFR improvement to greater than 300 L/min (greater than 60% predicted) after therapy negates the need for hospitalization. In order to gain such improvement the patient may require approximately four to six hours of outpatient treatment. Some will treat patients for longer periods. Evidence of worsening obstruction or impending respiratory failure during this period mandates admission.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of PCDD/F levels and profiles in fly ash samples from multiple industrial thermal sources.
A comprehensive comparison of the levels and profiles of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) in fly ash samples from multiple industrial sources may help to prioritize sources and to understand discrepancies in profiles. In this study, PCDD/F data from 113 fly ash samples from 14 sources reported in previous studies were summarized and compared. The highest PCDD/F levels occurred in samples from secondary copper smelting (SCu). Although PCDD/F levels from secondary zinc smelting (SZn) were slightly lower than those of SCu, the PCDD/F profiles varied widely between the two sources. For SCu, more chlorinated homologs were dominant, with highest degrees of chlorination being 6.6 for PCDF and 7.2 for PCDD. For SZn, less chlorinated homologs were dominant, with lowest degrees of chlorination being 4.4 for PCDF and 4.8 for PCDD. We speculate that copper and zinc might promote PCDD/F formation by catalyzing different pathways of thermal reactions. Diagnostic ratios of specific PCDD/F congeners for different sources were suggested to identify potential sources of PCDD/Fs in the environment. Equations describing correlations between congeners and PCDD/F toxic equivalents were established, which may be useful for rapid and inexpensive screening of the toxic levels of PCDD/Fs in fly ash samples.


Development of an efficient in vitro transcription system for bloodstream form Trypanosoma brucei reveals life cycle-independent functionality of class I transcription factor A.
Trypanosomatid parasites possess extremely divergent transcription factors whose identification typically relied on biochemical, structural and functional analyses because they could not be identified by standard sequence analysis. For example, subunits of the Trypanosoma brucei mediator and class I transcription factor A (CITFA) have no sequence resemblance to putative counterparts in higher eukaryotes. Therefore, homologous in vitro transcription systems have been crucial in evaluating the transcriptional roles of T. brucei proteins but so far such systems have been restricted to the insect-stage, procyclic form (PF) of the parasite. Here, we report the development of a homologous system for the mammalian-infective, bloodstream form (BF) of T. brucei which supports accurately initiated transcription from three different RNA polymerase (pol) I promoters as well as from the RNA pol II-recruiting spliced leader RNA gene promoter. The system is based on a small scale extract preparation procedure which accommodates the low cell densities obtainable in BF culture. BF and PF systems behave surprisingly similar and we show that the CITFA complex purified from procyclic extract is fully functional in the BF system indicating that the transcriptional machinery in general is equivalent in both life cycle stages. A notable difference, however, was observed with the RNA pol I-recruiting GPEET procyclin promoter whose reduced promoter strength and increased sensitivity to manganese ions in the BF system suggests the presence of a specific transcriptional activator in the PF system.


The significance of infections with two types of viral hepatitis demonstrated by histologic features in chimpanzees.
In view of the recognized importance of necroinflammatory episodes in chronic hepatitis B virus (HBV) infection, chimpanzees, either HBV surface antigen (HBsAg) carriers or noninfected (naive), were infected with other primary hepatotropic viruses to evaluate histologic alterations and changes in virologic and biochemical markers of infection. The advantages of studies on chimpanzees are the availability of serial biopsy specimens and the viral type-specific histologic lesions, not as well recognized in humans. Infection with hepatitis A and non-A, non-B (NANB) agents produced more severe lesions in chronic HBsAg carrier chimpanzees than in naive animals. During this superinfection, the specific expression of the second agent was predominant, indicating that the exacerbation is caused by the second agent, but that carriers are prone to more severe disease than the naive chimpanzees. Hepatitis delta virus (HDV) infections were always coexistant with HBV and superinfection of carriers produced histologic changes more severe than those seen in any other type of viral hepatitis. Such HDV infections revealed less evidence of lymphocytotoxicity but rather of cytotoxicity, and sometimes resembled in appearance the histopathology of NANB. Coinfection of HDV and HBV and superinfection of HBV-carriers with NANB resulted in hepatitis that was far less severe than superinfection of HDV in HBV carriers, greatly in keeping with human experiences. HBV replication was suppressed transiently in both NANB and HDV superinfection. This implies that in exacerbations during chronic HBV infections of humans, suppression of HBV replication markers indicates superinfection, for instance, by NANB for which markers are so far not widely available; by contrast, elevated markers of HBV replication suggest reactivation of the original HBV infection.


Use of poly(vinylpyrrolidone) and poly(vinyl alcohol) for cryoultramicrotomy.
Specimens infused with or suspended in a mixture of 10-30% poly(vinylpyrrolidone) and 2.07-1.61 M sucrose can often be more easily frozen-sectioned than those infused with sucrose alone. The pH of such a mixture can be efficiently adjusted to neutrality by using Na2CO3. Use of poly(vinylpyrrolidone) causes little or no increase in the background level of immunolabelling. Adsorption staining of ultrathin frozen sections with a mixture of uranyl acetate and poly(vinyl alcohol), i.e. a simple thin-embedding of the sections in such a mixture, produces positive staining effects that are often enough to delineate structures of many organelles. When OsO4-treated frozen sections are stained with uranyl acetate and further adsorption-stained with a mixture of lead citrate and poly(vinyl alcohol), the overall staining effects are similar to those observed in double-stained conventional sections.


HIV-1 resistance to the gp41-dependent fusion inhibitor C-34.
The gp41 subunit of HIV-1 has been recently recognized as a target for antiviral therapy. C-34 is a peptide that mimics the heptad repeat 2 in the ectodomain of gp41. Here, we describe two HIV-1 strains selected after 5 and 17 passages in culture with increasing concentrations of C-34 (breakthrough concentration of 10 microg/ml). The HXB2-derived strain was more than 1000-fold resistant and contained a V38E mutation in the gp41 coding DNA sequence. The NL4-3-derived strain was more than 500-fold resistant and contained a L33S mutation in gp41. No cross-resistance to the RT inhibitor AZT, the HIV binding inhibitor dextran sulfate (DS), or the chemokine receptor antagonist ALX-40-4C was detected. These data indicate that HIV-1 can overcome C-34 inhibition through mutations at residues not involved in the formation of the hydrophobic cavity of gp41.


The role of an occlusal template during the placement of preformed metal crowns in children under general anaesthesia: a randomised control trial.
This aim was to evaluate preformed metal crowns (PMC) placed under general anaesthesia using an occlusal template in comparison to crowns placed without the use of a template. CONSORT protocols were followed in the design of the study. A total of 60 children between 4-7 years requiring pulpotomy and PMC for all primary molars met the inclusion criteria for this study. The control group comprised patients for whom the PMC were placed without the use of an occlusal template, while in the test group crowns were placed using a polyvinyl siloxane occlusal template. Patients were followed up at 24 h, 7 days, 3 and 6 months. The time taken for the placement of crowns, instances of post-operative discomfort, success or failure of the pulp therapy and loss of any crowns were compared between the groups. The mean time taken for completion of the procedure in the control group was significantly greater than the template group (t = 2.566, p = 0.013). Significantly fewer patients in the template group reported symptoms of discomfort or high points at the 24-h recall; however, these differences were not significant at the 1-week, 3- or 6-month recall. The use of an occlusal template for the placement of multiple PMC under general anaesthesia reduces the time taken for their placement and reduces the incidence of immediate post-operative discomfort.


Identification of the sites of phosphorylation in insulin-like growth factor binding protein-1. Regulation of its affinity by phosphorylation of serine 101.
Serine phosphorylation of insulin-like growth factor binding protein-1 (IGFBP-1) has been shown to alter its affinity for the insulin-like growth factors (IGF-I and IGF-II) and to modify its capacity to modulate cellular responses to the IGFs. Because of this, we determined the sites of serine phosphorylation. Purification of 32P-labeled IGFBP-1 was followed by digestion with trypsin and endoproteinase Glu-C and radiosequencing of labeled peptides. Three serines were found to be phosphorylated, with Ser101, Ser119, and Ser169 containing 70%, 5%, and 25% of the incorporated 32P, respectively. A mutated IGFBP-1, substituting alanine for serine at positions 98 and 101, was expressed in CHO cells. On nondenaturing gels, the wild type protein migrated as five isoforms (one non-phosphorylated and four phosphorylated). However, in the mutated protein, the most rapidly migrating band (a phosphorylated form) was not present. The cells containing the mutated cDNA incorporated 60% less 32P into immunoprecipitable IGFBP-1. The mutated protein had a 3-fold reduction in affinity for IGF-I compared to the wild type protein. We conclude that Ser101 represents the major site of phosphorylation containing 63% of the total 32P incorporated and that phosphorylation of Ser101 is important for maintenance of high affinity binding for this growth factor.


T-cell depletion of bone marrow does not inhibit in vitro hematopoiesis.
One approach to overcome the problem of histoincompatibility in bone marrow transplantation is to use T cell depleted marrow from a haploidentical donor in an attempt to ameliorate graft-versus-host disease. Since the T cell requirements for normal hematopoiesis are uncertain, experiments were performed to study the effects of E rosette-T cell depletion on in vitro growth of hematopoietic progenitor cells. Marrow mononuclear cells were cultured in a modified CFU-GEMM assay before and after T cell depletion. The number of 7 day granulocytic and erythrocytic colonies, and 14 day granulocytic, erythrocytic and mixed colonies were enumerated and expressed in terms of colonies per 10(5) non T cells plated. T cell depletion did not result in decreased proliferation of any of these progenitors save possibly for 14 day granulocytic colonies in one of four experiments. In two cases, T cell depletion resulted in increased growth of progenitor cells. Three of four patients transplanted with T cell depleted haploidentical marrow cells engrafted. It is concluded that E rosette depletion of T cells from marrow does not decrease the potential of these cells to establish hematopoiesis in vitro or in vivo.


Carbon footprints across transport infrastructure development and industrial output in Pakistan.
Over the past few decades, the development of transport infrastructure has attracted huge local and foreign direct investments to raise the overall industrial output in Pakistan. Meanwhile, the transport sector has emerged as one of the most emissions-intensive industrial sectors. Thus, this study is the first to investigate how Pakistan's transport infrastructure across four modes-roads, trains, ports, and airways-affects industrial value addition and carbon footprints in the country. By making use of the theoretical and empirical literature, the study builds carbon emission and economic output models to determine the economic and environmental sustainability of transport infrastructure development in the country. The empirical findings conclude long-term environmental sustainability issues in transportation infrastructure development. All means of transport infrastructure development have a significant positive impact on carbon dioxide emissions in the country. Only ports and highways, however, provide a positive contribution to industrial output. Additionally, population growth, capital, labor, and urbanization are positively linked with the industrial output and carbon dioxide emission in the country, whereas trade openness helps to offset the emission intensity to some extent. Given this evidence, we provide detailed policy implications by highlighting the significance of greener technologies under new transport-related infrastructure investment that addresses SDG-9.


Appearance of breast attenuation artifacts with thallium myocardial SPECT imaging.
The appearance of breast attenuation artifacts is described as the artifacts occur with single photon emission computed tomography (SPECT) imaging of the heart using TI-201 thallous chloride.


A novel method for automatic genotyping of microsatellite markers based on parametric pattern recognition.
Genetic mapping of loci affecting complex phenotypes in human and other organisms is presently being conducted on a very large scale, using either microsatellite or single nucleotide polymorphism (SNP) markers and by partly automated methods. A critical step in this process is the conversion of the instrument output into genotypes, both a time-consuming and error prone procedure. Errors made during this calling of genotypes will dramatically reduce the ability to map the location of loci underlying a phenotype. Accurate methods for automatic genotype calling are therefore important. Here, we describe novel algorithms for automatic calling of microsatellite genotypes using parametric pattern recognition. The analysis of microsatellite data is complicated both by the occurrence of stutter bands, which arise from Taq polymerase misreading the number of repeats, and additional bands derived form the non-template dependent addition of a nucleotide to the 3' end of the PCR products. These problems, together with the fact that the lengths of two alleles in a heterozygous individual may differ by only two nucleotides, complicate the development of an automated process. The novel algorithms markedly reduce the need for manual editing and the frequency of miscalls, and compares very favourably with commercially available software for automatic microsatellite genotyping.


Validation of the modified Graeb score in aneurysmal subarachnoid hemorrhage.
Intraventricular hemorrhage (IVH) in patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) is a known negative predictor. Scoring systems like Fisher, Le Roux, and original Graeb score (oGS) are established to quantify the volume of IVH. The aim of this study was to evaluate the validity of the recently introduced modified Graeb score (mGS) in patients with aSAH. A retrospective analysis of the validity of the oGS and mGS in 257 aSAH patients was performed to assess and compare the predictive value of hospital mortality, development of CHC, and early functional outcome. In univariate analysis, an increase in either the oGS or mGS was associated with a higher risk for hospital mortality, development of CHC, and poor early functional outcome. The correlation of the oGS and mGS was excellent using Pearson's product-moment (r = 0.918; p < 0.001). The predictive value of the oGS was superior to the predictive value of the mGS using receiver operating characteristics and corresponding area under the curve value as there was no statistical significant differences between the scores. Our study confirms the validity of the recently introduced mGS to quantify the volume of IVH and extends its value in aSAH. However, the mGS offers no additional predictive value for hospital mortality, development of CHC, and poor early functional outcome in patients with aSAH patients compared to the less complex oGS.


A novel small peptide as a targeting ligand for receptor tyrosine kinase Tie2.
Tie2 is an endothelium-specific receptor tyrosine kinase known to play an important role in tumor angiogenesis. We sought to identify a small peptide ligand against Tie2 for developing a delivery targeting agent. We used hydrophobic analysis and comparative sequence/structure analysis to select a minimal peptide based on angiopoietin-2 amino acid sequence. The resulting peptide named GA3(WTIIQRREDGSVDFQRTWKEYK) was synthesized and labeled with iodine-125 at the C-terminal tyrosine residue to characterize its binding capability. In in vitro binding assays, GA3 can not only specifically bind to SMMC7721-Tie2 but also compete with angiopoietin-2 in binding. Via mouse tail vein injection, 125I-labeled GA3 was found to favorably accumulate in SPC-A1 xenograft tumor tissues which positively express Tie2. These results demonstrated that GA3 may be useful as a drug or gene delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy.


Late rectal function after prostate brachytherapy.
Using a patient-administered quality of life instrument, to evaluate the effect of permanent prostate brachytherapy on late rectal function. One hundred eighty-nine prostate brachytherapy patients were mailed the Rectal Function Assessment Score (R-FAS), with a prestamped return envelope. The R-FAS consists of nine questions and a scoring range of 0-27, with higher scores indicative of poorer bowel function. One hundred eighty-seven (98.4%) surveys were returned. The median follow-up was 66.3 months (range 54-92 months). Clinical, treatment, and dosimetric parameters evaluated for bowel dysfunction included patient age, diabetes, hypertension, tobacco consumption, clinical T-stage, elapsed time since implant, prostate ultrasound volume, planning target volume, hormonal status, supplemental external beam radiation therapy (EBRT), isotope, average, median and maximum rectal doses, total implanted seed strength, values of the minimum dose received by 90% of the prostate gland (D(90)), and the percent prostate volume receiving 100%, 150%, and 200% of the minimum prescribed dose (V(100/150/200)). The R-FAS score for the evaluated cohort was 3.92, which represented a slight improvement from the 1999 survey score of 4.15 (p = 0.29). Of the evaluated clinical, treatment, and dosimetric parameters, the number of preimplant bowel movements, a history of tobacco consumption, and the median rectal dose correlated with the R-FAS. Although lower rectal doses were noted with Pd-103, isotope did not predict for bowel function. Only 12% (23/187) of patients reported their bowel function to be worse after implantation. Patient perception of overall rectal quality of life was inversely related to the use of supplemental EBRT (p = 0.007). Minor bowel changes are noted following prostate brachytherapy. The vast majority of patients did not report any deterioration in bowel function. In addition, the R-FAS continue to improve with time.


Unleashing the potential of nanoparticles on seed treatment and enhancement for sustainable farming.
The foremost challenge in farming is the storage of seeds after harvest and maintaining seed quality during storage. In agriculture, studies showed positive impacts of nanotechnology on plant development, seed storage, endurance under various types of stress, detection of seed damages, and seed quality. Seed's response varies with different types of nanoparticles depending on its physical and biochemical properties and plant species. Herein, we aim to cover the impact of nanoparticles on seed coating, dormancy, germination, seedling, nutrition, plant growth, stress conditions protection, and storage. Although the seed treatment by nanopriming has been shown to improve seed germination, seedling development, stress tolerance, and seedling growth, their full potential was not realized at the field level. Sustainable nano-agrochemicals and technology could provide good seed quality with less environmental toxicity. The present review critically discusses eco-friendly strategies that can be employed for the nanomaterial seed treatment and seed enhancement process to increase seedling vigor under different conditions. Also, an integrated approach involving four innovative concepts, namely green co-priming, nano-recycling of agricultural wastes, nano-pairing, and customized nanocontainer storage, has been proposed to acclimatize nanotechnology in farming.


Monolayer culture of animal cells with the gyrogen equipped with tubes.
The gyrogen with tubes has been the object of repeated trials carried out over a period of some years. The aim of these trials was essentially to multiply BHK cells in monolayer and to reproduce the FMD virus in one operation. At the laboratory stage, the gyrogen consisted of 3 rolling flasks; at the pilot stage, it equalled 100 rolling flasks; and at the industrial stage which will be tested in the coming months, it should equal 500 flasks. The culture of cells on a glass support was not in itself new; the difficulty appeared when replicating the virus in order to obtain the high parameters necessary for the production of vaccine. Everything was done so that finally cell culture and viral multiplication could be carried out in situ in the same apparatus.


Effects of an aminosteroid, ORG 6001, on various membrane phenomena of non-myelinated nerve fibres of the rat.
The aminosteroid ORG 6001 (3 alpha-amino-5 alpha-androstan-2 beta-ol-17-one hydrochloride) was shown to be a compound with a rather strong local anaesthetic action. Compound action potentials evoked in non-myelinated nerve fibres of the desheathed rat vagus with the single sucrose gap method showed, in presence of this drug, a decrease in amplitude and increase in conduction time comparable with the effect of lidocaine. Since the total membrane resistance represented by the amplitude of the electrotonic potential was not affected by ORG 6001, it is likely that ORG 6001 reduces the transient increase in sodium conductance during the action potential, a mechanism also postulated for lidocaine. This is confirmed by the decrease of the post-tetanic hyperpolarization in the presence of both ORG 6001 and lidocaine. Since neither sodium pump activity nor the Na/K coupling ratio was affected by ORG 6001, the increase of the potassium-activated response was explained by an increased sodium permeability during rest. The local anaesthetic action of these drugs was even seen with a concentration (20--40 micron) sufficient to produce antiarrhythmic effects in vivo in man if the nerve was stimulated frequently (1--4 c.p.s.).


Performance evaluation of three different types of local evaporative cooling pads in greenhouses in Sudan.
This study was conducted in Date Palm Technology Company Limited, Shambat, Khartoum State. To evaluate performance of three types of evaporative cooling pads for greenhouses (celdek pads, straw pads and sliced wood pads), as compared to the conditions outside the greenhouses (control), for pads. Performance evaluation includes environmental parameters (temperature and relative humidity at 8 am, 1 pm and 6 pm) and crop parameters (length and stem diameter, leaves number and width, fruit length and diameter, fruit weight and dry matter and yield). The results obtained for the temperature at 8 am showed that there was no significant difference (0.05) inside the greenhouses, while a high significant difference between the conditions inside and outside of the greenhouses was found. Significant differences were found at 1 pm and 6 pm between all treatments as compared to the conditions outside the greenhouses, and the results obtained for relative humidity showed high significant differences at 8 am and 1 pm inside the greenhouses and between inside and outside the greenhouse, respectively, while there was no significant difference at 6 pm inside the greenhouses and between inside and outside the greenhouses. On the other hand, the results obtained for crop parameters showed that there were significant differences between all parameters inside the greenhouses and outside the greenhouses; however, the greenhouses with sliced wood pads gave the highest yield and the greenhouses with straw pads gave the least and conditions outside gave the lowest. This study indicated that the sliced wood pads are better than the other evaporative cooling pads.


Seasonal progression of plant water relations in fynbos in the western Cape Province, South Africa.
Plant xylem pressure potentials and leaf conductances to water loss were measured in the spring and summer at two sites in the western Cape Province, Republic of South Africa. The measurements were to test the hypothesis that the fynbos of South Africa was equivalent to the chaparral of California, therefore a period of plant water stress, similar to the period measured in chaparral species, should occur in flynbos species during the dry summer. The measurements indicated little or no plant water stress in most fynbos species at both sites. The sites were similar in plant water relations in spite of a more than twofold difference in annual precipitation. The minor differences in plant water relations can be explained in terms of different vegetation cover and different vapor pressure deficits during the measurements. The results support the conclusion that the arid fynbos may be equivalent to chaparral, but the majority of the fynbos is equivalent to coniferous and broad-leaved evergreen forest in California.


Is there a way to predict failure after direct vision internal urethrotomy for single and short bulbar urethral strictures?
To identify patient and stricture characteristics predicting failure after direct vision internal urethrotomy (DVIU) for single and short (<2 cm) bulbar urethral strictures. We retrospectively analysed the records of adult patients who underwent DVIU between January 2002 and 2013. The patients' demographics and stricture characteristics were analysed. The primary outcome was procedure failure, defined as the need for regular self-dilatation (RSD), redo DVIU or substitution urethroplasty. Predictors of failure were analysed. In all, 430 adult patients with a mean (SD) age of 50 (15) years were included. The main causes of stricture were idiopathic followed by iatrogenic in 51.6% and 26.3% of patients, respectively. Most patients presented with obstructive lower urinary tract symptoms (68.9%) and strictures were proximal bulbar, i.e. just close to the external urethral sphincter, in 35.3%. The median (range) follow-up duration was 29 (3-132) months. In all, 250 (58.1%) patients did not require any further instrumentation, while RSD was maintained in 116 (27%) patients, including 28 (6.5%) who required a redo DVIU or urethroplasty. In 64 (6.5%) patients, a redo DVIU or urethroplasty was performed. On multivariate analysis, older age at presentation [odds ratio (OR) 1.017; P = 0.03], obesity (OR 1.664; P = 0.015), and idiopathic strictures (OR 3.107; P = 0.035) were independent predictors of failure after DVIU. The failure rate after DVIU accounted for 41.8% of our present cohort with older age at presentation, obesity, and idiopathic strictures independent predictors of failure after DVIU. This information is important in counselling patients before surgery.


Increasing sulfate concentration and sedimentary decaying cyanobacteria co-affect organic carbon mineralization in eutrophic lake sediments.
Sulfate (SO42-) concentrations in eutrophic lakes are continuously increasing; however, the effect of increasing SO42- concentrations on organic carbon mineralization, especially the greenhouse gas emissions of sediments, remains unclear. Here, we constructed a series of microcosms with initial SO42- concentrations of 0, 30, 60, 90, 120, 150, and 180 mg/L to study the effects of increased SO42- concentrations, coupled with cyanobacterial blooms, on organic carbon mineralization in Lake Taihu. Cyanobacterial blooms promoted sulfate reduction and released a large amount of inorganic carbon. The SO42- concentrations in cyanobacteria treatments significantly decreased and eventually reached close to 0. As the initial SO42- concentration increased, the sulfate reduction rates significantly increased, with maximum values of 9.39, 9.44, 28.02, 30.89, 39.68, and 54.28 mg/L∙d for 30, 60, 90, 120, 150, and 180 mg/L SO42-, respectively. The total organic carbon content in sediments (51.16-52.70 g/kg) decreased with the initial SO42- concentration (R2 = 0.97), and the total inorganic carbon content in overlying water (159.97-182.73 mg/L) showed the opposite pattern (R2 = 0.91). The initial SO42- concentration was positively correlated with carbon dioxide (CO2) emissions (R2 = 0.68) and negatively correlated with methane (CH4) emissions (R2 = 0.96). The highest CO2 concentration and lowest CH4 concentration in the 180 mg/L SO42- treatment were 1688.78 and 1903 μmol/L, respectively. These biogeochemical processes were related to competition for organic carbon sources between sulfate reduction bacteria (SRB) and methane production archaea (MPA) in sediments. The abundance of SRB was positively correlated with the initial SO42- concentration and ranged from 6.65 × 107 to 2.98 × 108 copies/g; the abundance of MPA showed the opposite pattern and ranged from 1.99 × 108 to 3.35 × 108copies/g. These findings enhance our understanding of the effect of increasing SO42- concentrations on organic carbon mineralization and could enhance the accuracy of assessments of greenhouse gas emissions in eutrophic lakes.


Titanium Mesh Exposure After Bone Grafting: Treatment Approaches-A Systematic Review.
A systematic review according to PRISMA statement has been designed to answer the preliminary question: "In titanium mesh exposures, is there a treatment alternative which leads to an increased graft maintenance?" and fill the PICO assessment out. To review studies published in the past 20 years (1999-2019) in which mesh exposure has occurred, detecting the suitable approaches to treat exposure allowing the graft maintenance. Initial search on PUBMED, SCOPUS, and COCHRANE databases resulted in 777 articles, and hand-searching identified 6 articles. After removing duplicates and unrelated articles, eligibility criteria were applied, and 31 studies were selected (randomized clinical trials, retrospective/prospective clinical trials, and case series). A total of 677 surgical sites and 225 cases of mesh exposure were identified. Eleven treatments have been identified. Chlorhexidine was the primary approach in 46% of cases, followed by oral hygiene instructions and follow-up with 22.5% of occurrences. In 21% of clinical situations, titanium mesh removal was the treatment of choice, associated with other measures (i.e., antibiotic prescription). There seems to be a consensus in cases of infection. When this complication was associated with tissue dehiscence, the primary treatment was mesh removal. The same does not occur when the site needs to be cleaned for long-term periods. In 2 decades of use of titanium meshes, the available treatments do not seem to have evolved, and there is not enough data to establish a guideline.


Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting.
1. Measurements have been made of whole-body and skeletal muscle protein synthesis in fed and fasted adults with L-[1-13C]leucine. 2. The marked increase in whole-body synthesis on feeding largely reflects the changes in protein synthesis in muscle, which doubles on feeding, compared with a 40% increase in that of the rest of the body. 3. Skeletal muscle in fed man contributes more than half to total protein synthesis occurring in the whole body.


Usability of a two-way personalized mobile trainer system in a community-based exercise program for adults with chronic traumatic brain injury.
To examine the usability of an Apple Watch-based, two-way Personalized Mobile Trainer (PMT) in community-based exercise programs for individuals with chronic traumatic brain injury (cTBI). This is a prospective pilot study. Twenty participants with cTBI aged 46-73 were enrolled in a 3-month individualized exercise program. After one in-person training session on PMT and exercise program, participants were prescribed either aerobic exercise training (AET) or stretching and toning (SAT) performed at home. The PMT was used to remotely deliver updated exercise prescription, track exercise progress, and communicate with the participants. The primary outcome was compliance with the exercise programs. All the participants completed the assigned exercise program with an average compliance of 76%. Nineteen (95%) participants were able to use the PMT properly during exercise sessions. After 3 months of training, the AET trended toward maintaining exercise endurance when compared with the SAT group (0.3% vs -4%, p = 0.14) with a medium effect size of 0.43. Using the PMT system to support and track exercise in community-based exercise programs is feasible. The PMT may promote compliance with the training program but testing its effectiveness with larger trials is warranted.


[Working conditions of female workers in the system of "Soiuzgostsirk" (the Soviet State Circus)].
Labour activity of those engaged in the system of Soyuzgostsirk was analyzed. It was established that unsatisfactory sanitary and hygienic situation for members of the orchestra, workers taking care of animals and others, physical and neuroemotional load of gymnasts, acrobats and their assistants, induced uncomfortable work posture of conjurers and gymnasts were in some cases regarded as the main unfavourable occupational factors. The health state of the above professional groups was assessed. Preventive measures aimed at sanitation of labour conditions and decrease of disease rates were developed.


Vessel dilator cricothyrotomy for transtracheal jet ventilation.
Needle cricothyrotomy is a safe, relatively easy procedure and has been described to enable pulmonary ventilation for patients in both elective and emergency situations. Conventional IV cannulae are short, thin-walled, and easily kinked and, therefore, do not provide a secure system to jet oxygen into the trachea. The vessel dilators of most 7-9 French introducer kits are firm, pliable, resist kinking, and can be passed easily into the tracheal lumen. We describe our experience with the use of vessel dilator cricothyrotomy to oxygenate and ventilate the lungs of patients in emergency and elective situations.


Taurine: stimulation of pineal N-acetyltransferase activity and melatonin production via a beta-adrenergic mechanism.
Pineal glands convert [3H]tryptophan to [3H]N-acetylserotonin and [3H]melatonin in organ culture. Taurine treatment increases the rate of production of these compounds 40- and 25-fold respectively by stimulating the activity of N-acetyltransferase. This stimulation is blocked stereospecifically by L-propranolol, indicating that taurine is probably acting via beta-adrenergic receptors. Taurine is active in stimulating N-acetyltransferase activity in denervated glands, suggesting that it might interact directly with the beta-adrenergic receptor, and not by causing the release of norepinephrine from nerve terminals.


Treatment of dysphasia with rTMS and language therapy after childhood stroke: Multimodal imaging of plastic change.
Expressive dysphasia accompanies left inferior frontal gyrus (IFG/Broca) injury. Recovery may relate to interhemispheric balance with homologous, contralesional IFG but is unexplored in children. We evaluated effects of inhibitory rTMS to contralesional IFG combined with intensive speech therapy (SLT). A 15year-old, right-handed male incurred a left middle cerebral artery stroke. After 30months, severe non-fluent dysphasia impacted quality of life. Language networks, neuronal metabolism and white matter pathways were explored using MRI. Language function was measured longitudinally. An intensive SLT program was combined with contralesional inhibitory rTMS of right pars triangularis. Procedures were well tolerated. Language function improved persisting to four months. Post-treatment fMRI demonstrated increased left perilesional IFG activations and connectivity at rest. Bilateral changes in inositol and glutamate metabolism were observed. Contralesional, inhibitory rTMS appears safe in childhood stroke-induced dysphasia. We observed clinically significant improvements after SLT coupled with rTMS. Advanced neuroimaging can evaluate intervention-induced plasticity.


Comparison of the results of cemented, porous-ingrowth, and threaded acetabular cup fixation. A meta-analysis of the orthopaedic literature.
A meta-analysis of the orthopaedic literature was performed to evaluate the clinical performance of cementless, threaded acetabular cups. The hypothesis for the study was that the clinical performance of the cementless, threaded acetabular cup is equivalent to that of the cemented and porous-ingrowth acetabular cups. Ninety-five articles were included in the study. There were 1,269 cases in the threaded cup group, 1,979 in the porous control group, and 10,230 in the cemented control group. The primary outcome variable tested was the rate of aseptic loosening of the acetabular components as measured by the revision rates following the index total hip arthroplasty procedure. Other measures of acetabular component loosening that were analyzed included clinical rating scores, pain scores, frequency of radiolucencies according to location and size, frequency of radiolucencies as a separately defined outcome variable, progressive radiolucencies, and component migration. The threaded cup group was found to have a significantly higher rate of revision, clinical and pain score failures, progressive radiolucencies and migrations when compared with the cemented and porous control groups (P < .05). Despite the many limitations of meta-analyses and the poor state of the orthopaedic literature database, this study provides a reasonable comparison of the clinical performance of threaded acetabular cups with that of cemented and porous-ingrowth acetabular cups.


FISH-mapping of 18S ribosomal RNA genes and telomeric sequences in the Japanese bitterlings Rhodeus ocellatus kurumeus and Tanakia limbata (Pisces, Cyprinidae) reveals significant cytogenetic differences in morphologically similar karyotypes.
The Japanese rose bitterling, Rhodeus ocellatus kurumeus, and the oily bitterling, Tanakia limbata, were cytogenetically studied by silver (Ag)- and chromomycin A3 (CMA3)-staining, by C-banding and by mapping of the 18S ribosomal genes and of the (TTAGGG)n telomeric sequence. These two representative species of related genera of the subfamily Acheilognathinae show very similar chromosome complements. Nevertheless, significant differences in the chromosomal distribution of nucleolus organizer regions (NORs) and interstitial telomeric sequences were observed. Whereas R. ocellatus kurumeus shows a single NOR-bearing chromosome pair, T. limbata is characterized by a higher number of variable NORs. Multiple telomeric sequence sites were found at the pericentromeric regions of several chromosomes in the rose bitterling. No telomeric sequence sites were detected near centromeres, but they were found to be scattered along the NORs in the oily bitterling. Two karyoevolutive trends might have been identified in the subfamily.


Inhibition of ROS-activated p38MAPK pathway is involved in the protective effect of H2S against chemical hypoxia-induced inflammation in PC12 cells.
We have demonstrated the neuroprotection of hydrogen sulfide (H2S) against chemical hypoxia-induced injury by inhibiting p38MAPK pathway. The present study attempts to evaluate the effect of H2S on chemical hypoxia-induced inflammation responses and its mechanisms in PC12 cells. We found that treatment of PC12 cells with cobalt chloride (CoCl2, a hypoxia mimetic agent) enhanced IL-6 secretion, nitric oxide (NO) generation and expression levels of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). L-canavanine, a selective iNOS inhibitor, partly blocked CoCl2-induced cytotoxicity, apoptosis and mitochondrial insult. In addition, 7-Nitroindazole (7-NI), an inhibitor of nNOS, also partly attenuated the CoCl2-induced cytotoxicity. The inhibition of p38MAPK by SB203580 (a selective p38MAPK inhibitor) or genetic silencing of p38MAPK by RNAi (Si-p38) depressed not only CoCl2-induced iNOS expression, NO production, but also IL-6 secretion. In addition, N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, conferred a similar protective effect of SB203580 or Si-p38 against CoCl2-induced inflammatory responses. Importantly, pretreatment of PC12 cells with exogenous application of sodium hydrosulfide (a H2S donor, 400 μmol/l) for 30 min before exposure to CoCl2 markedly attenuated chemical hypoxia-stimulated iNOS and nNOS expression, NO generation and IL-6 secretion as well as p38MAPK phosphorylation in PC12 cells. Taken together, we demonstrated that p38MAPK-iNOS pathway contributes to chemical hypoxia-induced inflammation and that H2S produces an anti-inflammatory effect in chemical hypoxia-stimulated PC12 cells, which may be partly due to inhibition of ROS-activated p38MAPK-iNOS pathway.


Argon laser induced single cortical responses: a new method to quantify pre-pain and pain perceptions.
The shape (amplitude and latency) of single cortical responses to argon laser stimulation was found to match six perceptual classes: three pre-pain and three pain. The amplitude of the pain related single cortical responses correlated with the perceived feeling of pain. Easy detectable responses were obtained because habituation to the stimuli was reduced and a high degree of attention was given to each stimulus. Single cortical responses to argon laser stimuli are suggested as a new quantitative technique with application in the assessment of function in the thermal and nociceptive pathways.


[The vascularization of the submucous external plexus (Schabadasch) and the submucous internal plexus (Meissner) in the small intestine of swine and cat].
Each ganglion of the plexus Schabadasch is supplied by a specific periganglionic capillary network. Within the plexus Meissner, several ganglia are connected to circulation areas. The communicating branches of the plexus Schabadasch have their own capillary system; as to the plexus Meissner, this is valid for the cat only. The results allow to conclude that the centres of the intramural nervous system of the intestinal wall are equipped with a preferred and self-acting vascularization.


The potential of the human connectome as a biomarker of brain disease.
The human connectome at the level of fiber tracts between brain regions has been shown to differ in patients with brain disorders compared to healthy control groups. Nonetheless, there is a potentially large number of different network organizations for individual patients that could lead to cognitive deficits prohibiting correct diagnosis. Therefore changes that can distinguish groups might not be sufficient to diagnose the disease that an individual patient suffers from and to indicate the best treatment option for that patient. We describe the challenges introduced by the large variability of connectomes within healthy subjects and patients and outline three common strategies to use connectomes as biomarkers of brain diseases. Finally, we propose a fourth option in using models of simulated brain activity (the dynamic connectome) based on structural connectivity rather than the structure (connectome) itself as a biomarker of disease. Dynamic connectomes, in addition to currently used structural, functional, or effective connectivity, could be an important future biomarker for clinical applications.


Selenium and rutin alone or in combination do not have stronger protective effects than their separate effects against cadmium-induced renal damage.
Selenium (Se) and rutin (RUT) are antioxidants that protect against tissue damage. In this study, the separate and combine protective effects of RUT and Se against cadmium (Cd)-induced renal damage were evaluated in rats. Wistar rats were treated by gavage to RUT (30 mg/kg) or Se (0.15 ppm) or Cd (200 ppm) in drinking water alone or in combination (30 mg/kg RUT +0.15 ppm Se + 200 ppm Cd). Corn oil was used as vehicle (2 mL/kg). After a 5-week treatment period, rat kidneys were removed for biochemical assays and histopathological examination. Se and Cd levels were evaluated by flame atomic absorption spectrophotometry. The malondialdehyde and glutathione levels as well as superoxide dismutase and catalase activities in the Cd-treated animals were increased compared with control values (0.056 ± 0.0003 versus 0.011 ± 0.0005 μmol/mg; 0.005 ± 0.0006 versus 0.00085 ± 0.0002 μg/mg; 1.62 ± 0.09 versus 0.48 ± 0.12 units/mg; 650 ± 25 versus 361.89 ± 31 μmol H2O2/mg, respectively). Cd treatment was also associated with decreased renal Se concentration (4.19 ± 0.92 versus 7.73 ± 0.7 μg/g dry weight), increased alkaline phosphatase (0.07 ± 0.0015 versus 0.033 ± 0.0019 unit/mg), acid phosphatase (0.029 ± 0.0021 versus 0.015 ± 0.0016 unit/mg), and lactate dehydrogenase (0.032 ± 0.004 versus 0.014 ± 0.0027 unit/mg) activities, respectively, and with evidence of severe renal damage. The combination of RUT and Se or their separate effects prevented the Cd-induced oxidative renal damage. However, their combine effects do not have stronger effects than their separate effect against Cd-induced renal damage. RUT and Se function as potent antioxidant in the protection of renal damage induced by Cd.


Revisiting the birth of NaCl crystals using molecular dynamics simulation.
Molecular dynamics simulations were used to investigate the initial stage of phase separation mechanisms for an oversaturated electrolytic solution. We developed a low computational cost methodology to determine the simulation frames where the first ionic clusters are formed. By discretizing the simulation box, we obtain a density profile in the moments preceding and succeeding the nuclei's formation. The growth of the clusters identified with our methodology was analyzed until the end of the simulation. Calculation of the Steinhardt parameter showed symmetry of the solid, giving indications that the classical nucleation theory explains the mechanism of the solid formation. The methodology developed was useful for identifying phase separation mechanisms in the nucleation process. At lower concentrations, there was no formation of stable clusters. At intermediate concentrations, the analyses indicate a transition of phases in one stage, from a oversaturate electrolytic solution to a crystalline solid. At high concentration, a transition of phases in two stages, initially, is the formation of a dense liquid, and only after that, crystalline solid formed inside the dense liquid. The change in phase separation mechanism due to increasing oversaturation underscores the importance of precise determination of the driving force for phase separation and concentration limits for each mechanism.


XL-ing at Induction of Apoptosis in Kidney Cancer through Inhibition of BCL-XL.
Through analysis of the cancer dependency map of CRISPR and short hairpin RNA datasets, the antiapoptotic BCL-XL was found to be a selective dependency in kidney cancer. Among kidney cancers, BCL-XL inhibition is most active in those with a mesenchymal gene signature, which portends a poor prognosis and response to current therapies. See related article by Grubb et al., p. 4689.