Ground reaction force metrics are not strongly correlated with tibial bone load when running across speeds and slopes: Implications for science, sport and wearable tech.
Tibial stress fractures are a common overuse injury resulting from the accumulation of bone microdamage due to repeated loading. Researchers and wearable device developers have sought to understand or predict stress fracture risks, and other injury risks, by monitoring the ground reaction force (GRF, the force between the foot and ground), or GRF correlates (e.g., tibial shock) captured via wearable sensors. Increases in GRF metrics are typically assumed to reflect increases in loading on internal biological structures (e.g., bones). The purpose of this study was to evaluate this assumption for running by testing if increases in GRF metrics were strongly correlated with increases in tibial compression force over a range of speeds and slopes. Ten healthy individuals performed running trials while we collected GRFs and kinematics. We assessed if commonly-used vertical GRF metrics (impact peak, loading rate, active peak, impulse) were strongly correlated with tibial load metrics (peak force, impulse). On average, increases in GRF metrics were not strongly correlated with increases in tibial load metrics. For instance, correlating GRF impact peak and loading rate with peak tibial load resulted in r = -0.29±0.37 and r = -0.20±0.35 (inter-subject mean and standard deviation), respectively. We observed high inter-subject variability in correlations, though most coefficients were negligible, weak or moderate. Seventy-six of the 80 subject-specific correlation coefficients computed indicated that higher GRF metrics were not strongly correlated with higher tibial forces. These results demonstrate that commonly-used GRF metrics can mislead our understanding of loading on internal structures, such as the tibia. Increases in GRF metrics should not be assumed to be an indicator of increases in tibial bone load or overuse injury risk during running. This has important implications for sports, wearable devices, and research on running-related injuries, affecting >50 scientific publications per year from 2015-2017.


Association of Smoking, Alcohol Use, and Betel Quid Chewing with Epigenetic Aberrations in Cancers.
Numerous environmental factors such as diet, alcohol use, stress, and environmental chemicals are known to elicit epigenetic changes, leading to increased rates of cancers and other diseases. The incidence of head and neck cancer, one of the most common cancers in Taiwanese males, is increasing: oral cancer and nasopharyngeal carcinoma are ranked fourth and tenth respectively, among the top ten cancers in this group, and a major cause of cancer-related deaths in Taiwanese males. Previous studies have identified smoking, alcohol use, and betel quid chewing as the three major causes of head and neck cancers; these three social habits are commonly observed in Taiwanese males, resulting in an increasing morbidity rate of head and neck cancers in this population. In this literature review, we discuss the association between specific components of betel quid, alcohol, and tobacco, and the occurrence of head and neck cancers, lung cancer, gastrointestinal cancers, and urethral cancer. We focus on regulatory mechanisms at the epigenetic level and their oncogenic effects. The review further discusses the application of FDA-approved epigenetic drugs as therapeutic strategies against cancer.


Enhanced detection of quantum dots labeled protein by simultaneous bismuth electrodeposition into microfluidic channel.
In this study, we propose an electrochemical immunoassay into a disposable microfluidic platform, using quantum dots (QDs) as labels and their enhanced detection using bismuth as an alternative to mercury electrodes. CdSe@ZnS QDs were used to tag human IgG as a model protein and detected through highly sensitive stripping voltammetry of the dissolved metallic component (cadmium in our case). The modification of the screen printed carbon electrodes (SPCEs) was done by a simple electrodeposition of bismuth that was previously mixed with the sample containing QDs. A magneto-immunosandwich assay was performed using a micromixer. A magnet placed at its outlet in order to capture the magnetic beads used as solid support for the immunoassay. SPCEs were integrated at the end of the channel as detector. Different parameters such as bismuth concentration, flow rate, and incubation times, were optimized. The LOD for HIgG in presence of bismuth was 3.5 ng/mL with a RSD of 13.2%. This LOD was about 3.3-fold lower than the one obtained without bismuth. Furthermore, the sensitivity of the system was increased 100-fold respect to experiments carried out with classical screen-printed electrodes, both in presence of bismuth.


Anti-secretory and cyto-protective effects of chebulinic acid isolated from the fruits of Terminalia chebula on gastric ulcers.
In continuation of our drug discovery program on Indian medicinal plants, the gastro protective mechanism of chebulinic acid isolated from Terminalia chebula fruit was investigated. Chebulinic acid was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of chebulinic acid was observed against CRU (62.9%), AS (55.3%), AL (80.67%) and PL (66.63%) induced ulcer models. The reference drug omeprazole (10 mg/kg, p.o.) showed 77.73% protection against CRU, 58.30% against AS and 70.80% against PL model. Sucralfate, another reference drug (500 mg/kg, p.o.) showed 65.67% protection in AL induced ulcer model. Chebulinic acid significantly reduced free acidity (48.82%), total acidity (38.29%) and upregulated mucin secretion by 59.75% respectively. Further, chebulinic acid significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 65.01 μg/ml as compared to the IC50 value of omeprazole (30.24 μg/ml) confirming its anti-secretory activity.


Predicting Soil Salinity with Vis-NIR Spectra after Removing the Effects of Soil Moisture Using External Parameter Orthogonalization.
Robust models for predicting soil salinity that use visible and near-infrared (vis-NIR) reflectance spectroscopy are needed to better quantify soil salinity in agricultural fields. Currently available models are not sufficiently robust for variable soil moisture contents. Thus, we used external parameter orthogonalization (EPO), which effectively projects spectra onto the subspace orthogonal to unwanted variation, to remove the variations caused by an external factor, e.g., the influences of soil moisture on spectral reflectance. In this study, 570 spectra between 380 and 2400 nm were obtained from soils with various soil moisture contents and salt concentrations in the laboratory; 3 soil types × 10 salt concentrations × 19 soil moisture levels were used. To examine the effectiveness of EPO, we compared the partial least squares regression (PLSR) results established from spectra with and without EPO correction. The EPO method effectively removed the effects of moisture, and the accuracy and robustness of the soil salt contents (SSCs) prediction model, which was built using the EPO-corrected spectra under various soil moisture conditions, were significantly improved relative to the spectra without EPO correction. This study contributes to the removal of soil moisture effects from soil salinity estimations when using vis-NIR reflectance spectroscopy and can assist others in quantifying soil salinity in the future.


Bcl-2 expression during T-cell development: early loss and late return occur at specific stages of commitment to differentiation and survival.
During T-cell development CD3-CD4-CD8- (double-negative) thymocytes proliferative and produce an enormous number of CD3loCD4+CD8+ (double-positive) thymocytes which are destined to die intrathymically unless rescued by positive selection. Those which survive become mature CD3hiCD4/8+ (single-positive) cells and are the precursor of peripheral blood lymphocytes. The product of the bcl-2 protooncogene has been implicated in preventing programmed cell death and is required for prolonged lymphocyte survival following maturation. Previously we and others have reported that Bcl-2 protein expression is biphasic, being high in proliferating double-negative stem cells, low in all double-positive thymocytes except for 1-5% of these cells, and restored in mature, single-positive thymocytes. However, it remained unclear which signaling and selection events regulate Bcl-2 during T-cell maturation. Now we have utilized four-color flow cytometry in normal and genetically altered mice for a detailed analysis of Bcl-2 expression as it relates to T-cell receptor (TCR) expression and positive selection. These studies show that (i) expression of a transgenic TCR in double-negative thymocytes does not lead to premature loss of Bcl-2; thus, Bcl-2 downregulation is not solely due to TCR expression; (ii) Bcl-2 expression is lost at the early transitional CD3-/loCD4-CD8+ stage, prior to expression of CD4; (iii) the Bcl-2+ double-positive thymocytes are those which have undergone positive selection; and (iv) upregulation of Bcl-2 during positive selection requires participation of the CD4 or CD8 co-receptor. These results demonstrate that Bcl-2 and TCR expression are regulated independently during T-cell development, and suggest a role for the CD4 or CD8 co-receptor in Bcl-2 induction during positive selection.


A Method for Reconstructing Individual Patient Data From Kaplan-Meier Survival Curves That Incorporate Marked Censoring Times.
Introduction. Access to individual patient data (IPD) can be advantageous when conducting cost-effectiveness analyses or indirect treatment comparisons. While exact times of censoring are often marked on published Kaplan-Meier (KM) curves, an algorithm for reconstructing IPD from such curves that allows for their incorporation is presently unavailable. Methods. An algorithm capable of incorporating marked censoring times was developed to reconstruct IPD from KM curves, taking as additional inputs the total patient count and coordinates of the drops in survival. The reliability of the algorithm was evaluated via a simulation exercise, in which survival curves were simulated, digitized, and then reconstructed. To assess the reliability of the reconstructed curves, hazard ratios (HRs) and quantiles of survival were compared between the original and reconstructed curves, and the reconstructed curves were visually inspected. Results. No systematic differences were found in HRs and quantiles in the original versus reconstructed curves. Upon visual inspection, the reconstructed IPD provided a close fit to the digitized data from the published KM curves. Inherent to the algorithm, censoring times were incorporated into the reconstructed data exactly as specified. Conclusion. This new algorithm can reliably be used to reconstruct IPD from reported KM survival curves in the presence of extractable censoring times. Use of the algorithm will allow health researchers to reconstruct IPD more closely by incorporating censoring times exactly as marked, requiring as additional inputs the total patient count and coordinates of the drops in survival.


A novel carissic acid from fruits of Carissa carandas induced apoptotic cell death in A-549 cells following the activation of caspases.
This study was designed to identify cytotoxic compounds from Carissa carandas extract. The cytotoxic activity of extract and fractions were assessed against eight cancer cell lines. The chloroform fraction obtained from methanolic extract exhibited significant activity against MCF-7, HT-29, A-549 with IC50 values of 3.98 µg/mL (MCF-7), 1.28µg/mL (HT-29) and 1.48 µg/mL (A-549) respectively. Further investigation led to the isolation of novel compound carissic acid (CA), which was confirmed by detailed spectroscopy studies. CA exhibited notable activity with IC50 values of 3.47 µM for A-549, 2.65 µM for HT-29 and 13.58 ± 0.59 µM for MCF-7 cells. CAcaused chromatin condensation with decrease of mitochondrial membrane potential and also confirmed cell death via Reactive Oxygen Species (ROS) generation and significantly decreased the colony formation in dose-dependent manner. The overall findings suggested that CA demonstrates cytotoxic effect by inhibiting cell proliferation and promoting apoptosis in lung (A-549) carcinoma cell line.


Plasmodium falciparum genetic variation of var2csa in the Democratic Republic of the Congo.
The Democratic Republic of the Congo (DRC) bears a high burden of malaria, which is exacerbated in pregnant women. The VAR2CSA protein plays a crucial role in pregnancy-associated malaria (PAM), and hence quantifying diversity at the var2csa locus in the DRC is important in understanding the basic epidemiology of PAM, and in developing a robust vaccine against PAM. Samples were taken from the 2013-14 Demographic and Health Survey conducted in the DRC, focusing on children under 5 years of age. A short subregion of the var2csa gene was sequenced in 115 spatial clusters, giving country-wide estimates of sequence polymorphism and spatial population structure. Results indicate that var2csa is highly polymorphic, and that diversity is being maintained through balancing selection, however, there is no clear signal of phylogenetic or geographic structure to this diversity. Linear modelling demonstrates that the number of var2csa variants in a cluster correlates directly with cluster prevalence, but not with other epidemiological factors such as urbanicity. Results suggest that the DRC fits within the global pattern of high var2csa diversity and little genetic differentiation between regions. A broad multivalent VAR2CSA vaccine candidate could benefit from targeting stable regions and common variants to address the substantial genetic diversity.


Opioid receptors inhibit the spinal AMPA receptor Ca2+ permeability that mediates latent pain sensitization.
Acute inflammation induces sensitization of nociceptive neurons and triggers the accumulation of calcium permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) in the dorsal horn of the spinal cord. This coincides with behavioral signs of acute inflammatory pain, but whether CP-AMPARs contribute to chronic pain remains unclear. To evaluate this question, we first constructed current-voltage (IV) curves of C-fiber stimulus-evoked, AMPAR-mediated EPSCs in lamina II to test for inward rectification, a key characteristic of CP-AMPARs. We found that the intraplantar injection of complete Freund's adjuvant (CFA) induced an inward rectification at 3 d that persisted to 21 d after injury. Furthermore, the CP- AMPAR antagonist IEM-1460 (50 μM) inhibited AMPAR-evoked Ca2+ transients 21d after injury but had no effect in uninflamed mice. We then used a model of long-lasting vulnerability for chronic pain that is determined by the balance between latent central sensitization (LCS) and mu opioid receptor constitutive activity (MORCA). When administered 21 d after the intraplantar injection of CFA, intrathecal administration of the MORCA inverse agonist naltrexone (NTX, 1 μg, i.t.) reinstated mechanical hypersensitivity, and superfusion of spinal cord slices with NTX (10 μM) increased the peak amplitude of AMPAR-evoked Ca2+ transients in lamina II neurons. The CP-AMPAR antagonist naspm (0-10 nmol, i.t.) inhibited these NTX-induced increases in mechanical hypersensitivity. NTX had no effect in uninflamed mice. Subsequent western blot analysis of the postsynaptic density membrane fraction from lumbar dorsal horn revealed that CFA increased GluA1 expression at 2 d and GluA4 expression at both 2 and 21 d post-injury, indicating that not just the GluA1 subunit, but also the GluA4 subunit, contributes to the expression of CP-AMPARs and synaptic strength during hyperalgesia. GluA2 expression increased at 21 d, an unexpected result that requires further study. We conclude that after tissue injury, dorsal horn AMPARs retain a Ca2+ permeability that underlies LCS. Because of their effectiveness in reducing naltrexone-induced reinstatement of hyperalgesia and potentiation of AMPAR-evoked Ca2+ signals, CP-AMPAR inhibitors are a promising class of agents for the treatment of chronic inflammatory pain.


Study on the expression and clinical significances of lewis y antigen and integrin αv, β3 in epithelial ovarian tumors.
To detect the expression and clinical significances of Lewis y antigen and integrin αv, β3 in epithelial ovarian tumors, and to explore the expression correlation between Lewis y antigen and integrin αv, β3. Immunohistochemical staining was performed in 95 cases of epithelial ovarian cancer, 37 cases of borderline tumors, 20 cases of benign tumors, and 20 cases of normal ovarian tissue, for the detection of Lewis y antigen and integrin αv, β3 expressions, and to analyze the relationship between Lewis y antigen and integrin, and the relationship between clinical and pathological parameters of ovarian cancer. In addition, immunofluorescence double labeling was utilized to detect the expression correlation between Lewis y antigen and integrin αv, β3 in ovarian cancer. In epithelial ovarian tumors, the expression rate of Lewis y antigen was 81.05%, significantly higher than that of borderline (51.53%) (P < 0.05) and benign (25%) (P < 0.01) tumors, and normal ovarian tissues (0) (P < 0.01). The expression rate of integrin αv, β3 in malignant epithelial ovarian tumors was 78.95% and 82.11%, respectively, significantly higher than that of the borderline (45.94%, 40.54%) (both P < 0.05), benign group (10.00%, 15.00%) (both P < 0.01) and normal ovary group (5%, 15%) (both P < 0.01). Lewis y and integrins αv, β3 are relevant to pelvic and abdominal diffusion and metastasis of ovarian cancer cells, suggesting that these two molecules mediate a boosting function for tumor metastasis.


Human leukocyte antigen-G expression after heart transplantation is associated with a reduced incidence of rejection.
Human leukocyte antigen (HLA)-G, a nonclassic major histocompatibility complex class I molecule expressed in the extravillous cytotrophoblast at the feto-maternal interface, is known to protect the fetus from maternal cellular immunity. In a preliminary study, we showed that HLA-G is expressed in the hearts of some patients after heart transplantation. In the present study, a larger number of patients was investigated to confirm this finding and to look for possible correlations between HLA-G expression and the number and types of rejection. Expression of HLA-G in endomyocardial biopsy specimens was investigated by immunohistochemical analysis, and detection of the soluble HLA-G in the serum was performed by immunoprecipitation followed by Western blot analysis. HLA-G was detected in the biopsy specimens and serum of 9 of 51 patients (18%). The number of episodes of acute rejection was significantly lower in HLA-G-positive patients (1.2+/-1.1) as compared with HLA-G-negative patients (4.5+/-2.8) (P<0.001). No chronic rejection was observed in HLA-G-positive patients, whereas 15 HLA-G-negative patients had chronic rejection (P<0.032). A longitudinal study of these patients reveals that the status of HLA-G expression was maintained after 6 months both in serum and in biopsy specimens. During this period, HLA-G-positive patients did not have chronic rejection. There is a significant correlation between rejection and HLA-G expression in the heart after transplantation. HLA-G expression and its effect in reducing the incidence and severity of rejection seem to be stable throughout the evolution.


An investigation of network growth principles in the phonological language network.
This article investigated how network growth algorithms-preferential attachment, preferential acquisition, and lure of the associates-relate to the acquisition of words in the phonological language network, where edges are placed between words that are phonologically similar to each other. Through an archival analysis of age-of-acquisition norms from English and Dutch and word learning experiments, we examined how new words were added to the phonological network. Across both approaches, we found converging evidence that an inverse variant of preferential attachment-where new nodes were instead more likely to attach to existing nodes with few connections-influenced the growth of the phonological network. We suggest that the inverse preferential attachment principle reflects the constraints of adding new phonological representations to an existing language network with already many phonologically similar representations, possibly reflecting the pressures associated with the processing costs of retrieving lexical representations that have many phonologically similar competitors. These results contribute toward our understanding of how the phonological language network grows over time and could have implications for the learning outcomes of individuals with language disorders. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


[Feasibility of radiofrequency ablation for cancer patients with atrial fibrillation].
Objective: To analyze the impact of cancer on the recurrence rate of atrial fibrillation (AF) after AF radiofrequency ablation and further evaluate the feasibility of radiofrequency ablation therapy in cancer patients with AF. Methods: This study was a single-center, retrospective study. Cancer patients with AF undergoing radiofrequency ablation for the first time in the First Affiliated Hospital of Dalian Medical University from May 30, 2008 to September 30, 2018 were included (cancer group). AF patients without cancer undergoing radiofrequency ablation for the first time during the same period served as non-cancer group. Clinical data including age, gender, past history, cancer and AF-related parameters, etc. were analyzed. Patients were followed up after radiofrequency ablation. The primary endpoints were AF recurrence or all-cause death. Kaplan-Meier survival analysis was used to analyze the effect of cancers on the recurrence after AF ablation. The multivariate cox regression analysis was further applied to correct for other confounding factors to analyze whether the impact of cancers on the recurrence of atrial fibrillation was statistically significant. Results: A total of 90 patients were enrolled, there were 30 patients in the cancer group (mean age (64.8±6.6) years, 16 (53.3%) males) and 60 patients in the non-cancer group (mean age (63.6±6.2) years, 32 (53.3%) males). Clinical data, such as age, gender, and cancer treatment, were similar between the two groups. During an average follow-up period of (328.7±110.2) days, there were 6 AF recurrences (recurrence rate 20.0%) in the cancer group, and 17 AF recurrences (recurrence rate 28.3%) in the control group. AF recurrence rate was similar between the two groups (P>0.05). During the follow-up period, there was no all-cause death in the two groups. Kaplan-Meier survival analysis showed that cancer was not related to AF recurrence after radiofrequency ablation (P = 0.383). After adjusting for other confounding factors, the multivariate Cox regression analysis showed that cancer was not an independent predictor of AF recurrence after radiofrequency ablation (HR=0.508, 95%CI: 0.192-1.342, P = 0.172). Conclusions: The combination of cancer has no impact on the recurrence of AF after radiofrequency ablation. For cancer patients with AF, radiofrequency ablation therapy can be considered as a feasible heart rhythm control treatment strategy.


Shame and Guilt-Proneness as Mediators of Associations Between General Causality Orientations and Depressive Symptoms.
The present study examined the roles of shame- and guilt-proneness as mediators of associations between general causality orientations and depressive symptoms. We expected autonomy would be associated with less depressive symptoms based on higher guilt-proneness and lower shame-proneness, whereas control would be associated with more depressive symptoms based on lower guilt-proneness and higher shame-proneness. Undergraduates (N = 354) completed assessments of general causality orientations, shame- and guilt-proneness, and depressive symptoms in exchange for extra credit. Results of mediation analyses were generally supportive of the framework indicating that shame- and guilt-proneness mediate associations between self-determination and depressive symptoms. Autonomy was indirectly associated with less depressive symptoms through positive associations with guilt-proneness, in spite of unexpected positive associations with shame-proneness. Control and impersonal orientation were indirectly associated with more depressive symptoms through positive associations with shame-proneness. Results extend previous research relating self-determination to mental health in providing preliminary support suggesting that individual differences in self-determination facilitate differential tendencies in experiencing guilt and shame.


Expression of the Rous sarcoma virus env gene from a simian virus 40 late-region replacement vector: effects of upstream initiation codons.
Expression of the Rous sarcoma virus envelope gene (env) from a simian virus 40 (SV40) late-region replacement vector is dependent on the position of env within the SV40 late-region sequences. The difference in expression levels appeared to be due to differences in the efficiency with which the env-specific transcripts were translated, because transcription levels from different constructions were similar. Deletion of the nucleotides encoding the agnoprotein initiator codon, located upstream of the env sequences in the poorly expressed construct, resulted in high levels of env expression. The agnoprotein initiator codon and overlapping open reading frame thus act as strong barriers to further ribosome scanning and prevent initiation at the env AUG codon. We conclude that AUG codons present in the late region of SV40 can reduce expression of inserted genes positioned downstream. Nevertheless, intrinsic properties of the gene may determine its ultimate level of expression.


Role of functional MR in determining language dominance in epilepsy and nonepilepsy populations: a Bayesian analysis.
To determine the role of functional magnetic resonance (MR) imaging in assessing hemispheric language dominance in epilepsy and nonepilepsy populations. A Bayesian analysis study was performed. The study was based on data from the published literature; thus, institutional review board approval was not required. The literature was reviewed to obtain pretest probabilities and likelihood ratios, which were analyzed to determine the posttest probability of language dominance by using functional MR imaging. Pretest probabilities of different hand dominances in epilepsy and nonepilepsy populations were obtained from the largest studies available in the literature. Likelihood ratios were derived from the sensitivity and specificity of functional MR imaging by using electrocortical stimulation (ECS) and the Wada test as reference standards. Likelihood ratios for functional MR in determining language dominance were 9.3 and 12.3 with ECS and the Wada test as reference standards, respectively. Use of functional MR increased the final posttest probabilities of hemispheric language dominance in epilepsy and nonepilepsy populations. In the nonepilepsy population, regardless of hand dominance, there was very high posttest probability (>or=96%) of a correlation between functional MR hemisphere activation and definite left-hemisphere language dominance. In the epilepsy population with right-hand dominance or ambidexterity, there was very high posttest probability (>or=95%) of a correlation between functional MR hemisphere activation and definite left-hemisphere language dominance. In the left-handed nonepileptic subjects, there was high posttest probability (81%-83%) of a correlation between functional MR hemisphere activation and definite right-hemisphere language dominance. In the left-handed epilepsy population, there was high posttest probability (80%-97%) of a correlation between functional MR hemisphere activation and definite left-hemisphere language dominance. In the epilepsy population with ambidexterity, there was high posttest probability (80%-87%) of correlations between functional MR hemisphere activation and both definite right-hemisphere and bilateral language dominance. Use of functional MR increases importantly the posttest probabilities of hemispheric language dominance in multiple subgroups of individuals with and without epilepsy.


Measures to test placement of nasogastric and nasointestinal feeding tubes: a review.
A literature review regarding commonly recommended bedside measures to test nasogastric and nasointestinal feeding tube placement is presented in this article. Among the methods discussed are: aspiration of recognizable gastrointestinal contents, auscultation of insufflated air, measurement of pH of gastrointestinal secretions, and observing for coughing and choking, inability to speak, and the appearance of bubbles from the end of the tube when it is held under water. Fallibilities in these methods as well as discrepancies in recommendations for their implementation and interpretation are discussed along with implications for current practice and needed areas for research.


Phylogenomic assessment of the role of hybridization and introgression in trait evolution.
Trait evolution among a set of species-a central theme in evolutionary biology-has long been understood and analyzed with respect to a species tree. However, the field of phylogenomics, which has been propelled by advances in sequencing technologies, has ushered in the era of species/gene tree incongruence and, consequently, a more nuanced understanding of trait evolution. For a trait whose states are incongruent with the branching patterns in the species tree, the same state could have arisen independently in different species (homoplasy) or followed the branching patterns of gene trees, incongruent with the species tree (hemiplasy). Another evolutionary process whose extent and significance are better revealed by phylogenomic studies is gene flow between different species. In this work, we present a phylogenomic method for assessing the role of hybridization and introgression in the evolution of polymorphic or monomorphic binary traits. We apply the method to simulated evolutionary scenarios to demonstrate the interplay between the parameters of the evolutionary history and the role of introgression in a binary trait's evolution (which we call xenoplasy). Very importantly, we demonstrate, including on a biological data set, that inferring a species tree and using it for trait evolution analysis in the presence of gene flow could lead to misleading hypotheses about trait evolution.


Bilateral Synchronous Olecranon Apophyseal Fracture in a Teenager: A Case Report.
While elbow fractures are frequently observed in children, isolated apophyseal detachments of the olecranon are rare, accounting for just 1.7% of all elbow fractures in healthy children. These fractures have been found to have a large positive likelihood ratio for osteogenesis imperfecta (OI). Within the population of patients with OI, the incidence is 13.5%, with 6% sustaining bilateral fractures. There are, however, very few reports of synchronous bilateral fractures. A 15-year-old boy sustained a bilateral olecranon apophyse fracture, AO/OTA 21u-M/7 (displaced on the right side and minimal displacement on the left) after a low-energy fall. The patient was submitted on the same day to surgical treatment (open reduction and internal fixation with AO tension band wiring technique) on the right elbow and nonoperative treatment with a cast on the left side. Exome sequencing excluded mutations related to OI. Apophyseal avulsion fractures of the olecranon may not be pathognomonic of OI, However, orthopedists should exercise caution and remain alert to the potential occurrence in patients who experience displaced, isolated olecranon fractures due to low-energy mechanisms, particularly if they have a history of previous fractures. The clinical genetic evaluation was recommended because of clinical suspicion of OI and because patient management can be significantly influenced by genetic testing, particularly when a genetic syndrome is identified.


Emerging compounds and therapeutic strategies to treat infections from Trypanosoma brucei: an overhaul of the last 5-years patents.
Human African Trypanosomiasis is a neglected disease caused by infection from parasites belonging to the Trypanosoma brucei species. Only six drugs are currently available and employed depending on the stage of the infection: pentamidine, suramin, melarsoprol, eflornithine, nifurtimox, and fexinidazole. Joint research projects were launched in an attempt to find new therapeutic options for this severe and often lethal disease. After a brief description of the recent literature on the parasite and the disease, we searched for patents dealing with the proposal of new antitrypanosomiasis agents and, following the PRISMA guidelines, we filtered the results to those published from 2018 onwards returning suitable entries, which represent the contemporary landscape of compounds/strategies against Trypanosoma brucei. In addition, some relevant publications from the overall scientific literature were also discussed. This review comprehensively covers and analyzes the most recent advances not only in the discovery of new inhibitors and their structure-activity relationships but also in the assessment of innovative biological targets opening new scenarios in the MedChem field. Finally, also new vaccines and formulations recently patented were described. However, natural and synthetic compounds were analyzed in terms of inhibitory activity and selective toxicity against human cells.


Monte Carlo dose calculations in homogeneous media and at interfaces: a comparison between GEPTS, EGSnrc, MCNP, and measurements.
Three Monte Carlo photon/electron transport codes (GEPTS, EGSnrc, and MCNP) are bench-marked against dose measurements in homogeneous (both low- and high-Z) media as well as at interfaces. A brief overview on physical models used by each code for photon and electron (positron) transport is given. Absolute calorimetric dose measurements for 0.5 and 1 MeV electron beams incident on homogeneous and multilayer media are compared with the predictions of the three codes. Comparison with dose measurements in two-layer media exposed to a 60Co gamma source is also performed. In addition, comparisons between the codes (including the EGS4 code) are done for (a) 0.05 to 10 MeV electron beams and positron point sources in lead, (b) high-energy photons (10 and 20 MeV) irradiating a multilayer phantom (water/steel/air), and (c) simulation of a 90Sr/90Y brachytherapy source. A good agreement is observed between the calorimetric electron dose measurements and predictions of GEPTS and EGSnrc in both homogeneous and multilayer media. MCNP outputs are found to be dependent on the energy-indexing method (Default/ITS style). This dependence is significant in homogeneous media as well as at interfaces. MCNP(ITS) fits more closely the experimental data than MCNP(DEF), except for the case of Be. At low energy (0.05 and 0.1 MeV), MCNP(ITS) dose distributions in lead show higher maximums in comparison with GEPTS and EGSnrc. EGS4 produces too penetrating electron-dose distributions in high-Z media, especially at low energy (<0.1 MeV). For positrons, differences between GEPTS and EGSnrc are observed in lead because GEPTS distinguishes positrons from electrons for both elastic multiple scattering and bremsstrahlung emission models. For the 60Co source, a quite good agreement between calculations and measurements is observed with regards to the experimental uncertainty. For the other cases (10 and 20 MeV photon sources and the 90Sr/90Y beta source), a good agreement is found between the three codes. In conclusion, differences between GEPTS and EGSnrc results are found to be very small for almost all media and energies studied. MCNP results depend significantly on the electron energy-indexing method.


Catalytically increased prebiotic peptide formation: ditryptophan, dilysine, and diserine.
"Mutual" amino acid catalysis of glycine on the formation of ditryptophan, dilysine, and diserine in the prebiotically relevant Salt-Induced Peptide Formation (SIPF) Reaction was investigated varying the starting concentration and chirality of the educt amino acid, and analyzing the increase of yield resulting from this catalytic effect. Our results show the possibility of an amplified diverse pool of peptides being available for chemical evolution of larger peptides and proteins using also these more complicated amino acids for the evolution of more complex functions in future biochemical cycles and thus for the emergence of life. Catalytic effects are especially high in the case of serine, the most basic amino acid of the three, but are also significant for the other two examples investigated in the present work. Besides that, especially for serine, but also in the case of tryptophan, differences in catalytic yield increase according to the chiral form of the amino acid used could be observed.


Trapping or tethering stones (TS): A multifunctional device in the Pastoral Neolithic of the Sahara.
The Pierres de Ben Barour, also known as trapping or tethering stones (TS), are stone artefacts with notches or grooves usually interpreted as hunting devices on the basis of rock art engravings. Though their presence is a peculiar feature of desert landscapes from the Sahara to the Arabian Peninsula, we know little about their age, context and function. Here we present a new approach to the study of these artefacts based on a large dataset (837 items) recorded in the Messak plateau (SW Libya). A statistically-based geoarchaeological survey carried out between 2007 and 2011 in Libya, alongside landscape and intra-site analyses of specific archaeological features (such as rock art, settlement and ceremonial contexts), reveal that these artefacts were used for a prolonged period, probably from the early Holocene. This was followed by a multifunctional use of these devices, particularly during the Pastoral Neolithic phase (ca. 6400-3000 cal BC), with the highest concentrations being found near ceremonial contexts related to cattle burials.


Primary central nervous system lymphoma.
Primary central nervous system lymphoma (PCNSL) comprises approximately 5 % of all primary brain tumors. During the past two decades the incidence of PCNSL has increased, and as a result clinical research to determine the optimal treatment for PCNSL patients also has increased. Diagnosis is based on histopathologic findings traditionally established by biopsy only. More recent data raise controversy and challenges this biopsy-only paradigm, showing a potential advantage for surgical resection with progression-free survival (PFS) and overall survival (OS). Using high-dose intravenous (IV) methotrexate-based chemotherapy alone or as part of a regimen can lead to disease cure. The role of whole brain radiotherapy (WBRT) remains controversial and more frequently is omitted to avoid potential delayed neurocognitive effects, especially in patients older than age 60 years. Newer data from Memorial Sloan Kettering Cancer Center (MSKCC) using five cycles of Rituximab, Methotrexate, Vincristine, and Procarbazine (R-MVP) followed by low-dose WBRT (2,340 cgy), and then two cycles of Ara-C had excellent disease control with low neuro-toxicity and is now the basis of an ongoing RTOG (Radiation Treatment Oncology Group) trial comparing early versus delayed WBRT. Other chemotherapeutics and novel treatments, such as autologous stem cell transplantation, are being studied for potential use in PCNSL. Unlike many other primary brain tumors seen in adults, PCNSL is potentially curable; therefore, balancing treatment decisions with long-term neurocognitive effects and toxicities is crucial.


Leiomyosarcoma of the ureter.
Primary ureteral tumors occur relatively infrequently compared to tumors of the kidney and bladder. Smooth muscle tumors of the ureter are very rare and only 9 cases of leiomyosarcoma have been reported in the literature. The treatment of choice is total nephroureterectomy with en bloc excision of the tumor. Prognosis is unfavorable as indicated by the short survival of the reported cases.


Sources of support and psychological distress among academically successful inner-city youth.
Study 1 examined the relationships between parental attachment, academic achievement, and psychological distress among a multiethnic sample of academically successful inner-city high school students (19 White, 54 Black, 9 Asian, 18 Hispanic). These students participated in an enrichment program designed to prepare high school students for college success. The results suggest that the affective quality of maternal attachment is positively associated with grade point average, and the affective quality of paternal attachment is negatively associated with depressive symptoms. In Study 2, case examples provide an examination of sources of support, life stress, and patterns of resilience. Implications for prevention and intervention are also discussed.


Investigating the Ability of Radiomics Features for Diagnosis of the Active Plaque of Multiple Sclerosis Patients.
Multiple sclerosis (MS) is the most common non-traumatic disabling disease. The aim of this study is to investigate the ability of radiomics features for diagnosing active plaques in patients with MS from T2 Fluid Attenuated Inversion Recovery (FLAIR) images. In this experimental study, images of 82 patients with 122 MS lesions were investigated. Boruta and Relief algorithms were used for feature selection on the train data set (70%). Four different classifier algorithms, including Multi-Layer Perceptron (MLP), Gradient Boosting (GB), Decision Tree (DT), and Extreme Gradient Boosting (XGB) were used as classifiers for modeling. Finally, Performance metrics were obtained on the test data set (30%) with 1000 bootstrap and 95% confidence intervals (95% CIs). A total of 107 radiomics features were extracted for each lesion, of which 7 and 8 features were selected by the Relief method and Boruta method, respectively. DT classifier had the best performance in the two feature selection algorithms. The best performance on the test data set was related to Boruta-DT with an average accuracy of 0.86, sensitivity of 1.00, specificity of 0.84, and Area Under the Curve (AUC) of 0.92 (95% CI: 0.92-0.92). Radiomics features have the potential for diagnosing MS active plaque by T2 FLAIR image features. Additionally, choosing the feature selection and classifier algorithms plays an important role in the diagnosis of active plaque in MS patients. The radiomics-based predictive models predict active lesions accurately and non-invasively.


An investigation of psychological factors involved in the predisposition to auditory hallucinations.
Previous research by the author (Slade, 1972, 1973) and others has suggested that psychological stress plays an important role in triggering off the experience of auditory hallucinations. Clearly, however, predispositional factors are involved as well. The present study is an attempt to investigate some of the psychological factors which may predispose the individual to such experiences. A battery of tests involving cognitive, personality and mental imagery variables and the verbal transformation effect was administered to two small groups of psychotic patients differing only in respect of a history of auditory hallucinations and a normal control group. The main conclusion was that the results lend direct support to the proposition of Mintz & Alpert (1972) that a combination of vivid mental imagery and poor reality-testing in the auditory modality provides the basic predisposition for the experience of auditory hallucinations.


Nitrogen utilization of lactating sows fed increasing dietary protein1.
The objectives of the study were 1) to quantify dietary N utilized for milk N and N loss in urine and feces, in sows fed increasing dietary CP with a constant amount of Lys, Met, Thr, and Trp to meet their standardized ileal digestible (SID) requirement and 2) to determine the optimal dietary CP concentration based on dietary N utilization for milk production. Seventy-two sows were fed 1 of 6 dietary treatments, formulated to increase the SID CP as followed: 11.8, 12.8, 13.4, 14.0, 14.7, and 15.6% and formulated to be isocaloric (9.8 MJ NE/kg). Diets were fed from day 2 after parturition until weaning at day 28 (± 3 d). Litters were equalized to 14 piglets and weighed within 48 h following parturition. Sows were weighed and back fat scanned, at day 18 (± 3 d) and day 28 (weaning; ± 3 d). Litter weight was recorded at day 11, 18 (± 3 d), and 28 (± 3 d). Nitrogen balances were conducted on approximately day 4, 11, and 18 (± 3 d). Daily milk yield was estimated from recorded litter gain and litter size. To calculate sows mobilization of fat and protein, body pools of fat and protein were estimated by D2O (deuterated water) enrichment on day 4 and 18 (± 3 d). No linear, quadratic, or cubic effects of increasing dietary CP was observed for sows total feed intake, sow BW, body pools of protein and fat, protein and fat mobilization, total milk yield, and piglet performance. The protein content in milk increased linearly with increasing dietary CP in week 1 (P < 0.05), week 2 (P < 0.05), and week 3 (P < 0.001). Urine production did not differ among treatments and N output in urine increased linearly with increasing dietary CP concentration in week 1 (P = 0.05), week 2 (P < 0.001), and week 3 (P < 0.001). Urine N excretion relative to N intake increased linearly with increasing dietary CP (P < 0.001). Milk N utilization relative to N intake decreased linearly from 77.8% to 63.1% from treatment 1 through 6 (P < 0.001). Corrected milk N utilization decreased from 68.6% to 64.2% from treatment 1 through 6 (P < 0.05). In conclusion, a low dietary CP concentration for lactating sows with supplemented crystalline AA improved the efficiency of dietary N utilization and reduced the N output in urine without affecting lactation performance.


Diabetes and cognitive dysfunction.
Cognitive dysfunction in type 1 and type 2 diabetes share many similarities, but important differences do exist. A primary distinguishing feature of type 2 diabetes is that people with this disorder often (but not invariably) do poorly on measures of learning and memory, whereas deficits in these domains are rarely seen in people with type 1 diabetes. Chronic hyperglycaemia and microvascular disease contribute to cognitive dysfunction in both type 1 and type 2 diabetes, and both disorders are associated with mental and motor slowing and decrements of similar magnitude on measures of attention and executive functioning. Additionally, both types are characterised by neural slowing, increased cortical atrophy, microstructural abnormalities in white matter tracts, and similar, but not identical, changes in concentrations of brain neurometabolites. Disconcertingly, the rapid rise in obesity and type 2 diabetes in all age groups might result in a substantial increase in prevalence of diabetes-related cognitive dysfunction.


Distinct IL-6 signal transduction leads to growth arrest and death in B cells or growth promotion and cell survival in myeloma cells.
In B cell development, interleukin-6 (IL-6) induces terminal maturation of B lymphocytes into antibody producing plasma cells. Terminal differentiated B cells cell cycle arrest and death follows. In contrast, IL-6 acts as a growth factor for malignant myeloma plasma cells and in some cases protects them from therapeutic treatment. In this study, we examined two cell lines that show different responses to IL-6. Lymphoblastoid CESS cells respond to IL-6 by terminally differentiating into antibody producing plasma cells, cell cycle arrest, and undergo cell death. Continuous addition of IL-6 to these cells induces transient activation of STAT3, SHP-2 phosphorylation, and does not alter bcl-X(L) and c-myc expression. In contrast, the myeloma line ANBL6 proliferates when stimulated with IL-6 and this correlates with prolonged STAT3 activation and up-regulation of bcl-X(L) and c-myc. Interestingly, gp130-associated SHP-2 phosphorylation was detected in the IL-6-induced CESS cells but not myeloma cell lines. The data show a very distinct IL-6 signal transduction and kinetics in these cell lines and the distinct molecular events correlate closely to the cell fate of the lymphoblast and myeloma cell lines.


Genetic analysis of somatic cell scores in US Holsteins with a Bayesian mixture model.
The objective of this study was to apply finite mixture models to field data for somatic cell scores (SCS) for estimation of genetic parameters. Data were approximately 170,000 test-day records for SCS from first-parity Holstein cows in Wisconsin. Five different models of increasing level of complexity were fitted. Model 1 was the standard single-component model, and the others were 2-component Gaussian mixtures consisting of similar but distinct linear models. All mixture models (i.e., 2 to 5) included separate means for the 2 components. Model 2 assumed entirely homogeneous variances for both components. Models 3 and 4 assumed heterogeneous variances for either residual (model 3) or genetic and permanent environmental variances (model 4). Model 5 was the most complex, in which variances of all random effects were allowed to vary across components. A Bayesian approach was applied and Gibbs sampling was used to obtain posterior estimates. Five chains of 205,000 cycles were generated for each model. Estimates of variance components were based on posterior means. Models were compared by use of the deviance information criterion. Based on the deviance information criterion, all mixture models were superior to the linear model for analysis of SCS. The best model was one in which genetic and PE variances were heterogeneous, but residual variances were homogeneous. The genetic analysis suggested that SCS in healthy and infected cattle are different traits, because the genetic correlation between SCS in the 2 components of 0.13 was significantly different from unity.


The effect of treating method of pithed pheasant on the content of biogenic amines in the meat during the course of storage.
The study monitored the effect of various methods of treating pheasant carcasses after killing on the hygienic quality of the venison. Pithed pheasants treated by evisceration (n = 60), drawing (n = 60), or left untreated (n = 60) were stored for a period of 21 d at temperatures of 0, 7, and 15°C. For determination of biogenic amines, samples of breast and thigh muscles were taken on d 1, 7, 14, and 21 after killing of the pheasants. Biogenic amines were separated by reverse-phase liquid chromatography and consequently detected by tandem mass spectrometry. The sum of determined biogenic amine concentrations (cadaverine, putrescine, histamine, tyramine, tryptamine, phenylethylamine) was compared with the value of the index for meat of high hygienic quality (5 mg/kg). At a storage temperature of 0°C, the sum of biogenic amine concentrations did not exceed the value of 5 mg/kg in either breast or thigh muscle at any time during the storage period in untreated and drawn pheasants, and for a period of 14 d in eviscerated pheasants. At a storage temperature of 7°C, values lower than the limit of 5 mg/kg were recorded throughout the storage period in untreated pheasants, for a period of 14 d of storage in drawn pheasants, and for a period of just 7 d of storage in eviscerated birds. At the highest storage temperature (15°C), a value of 5 mg/kg was exceeded in eviscerated and untreated pheasants during the course of the first week of storage, and in drawn pheasants after the first week of storage. Our results indicate that the most suitable method of treatment to ensure high hygienic quality of the meat (assessed according to concentration of biogenic amines) for the longest period during the storage of pithed pheasants is to leave the pheasant carcasses untreated, followed by the drawing, with the least suitable method being the widely recommended method of evisceration.


Escherichia coli Isolates Harboring blaNDM Variants and 16S Methylases Belonging to Clonal Complex 131 in Southern Punjab, Pakistan.
The emergence of carbapenem-resistant Escherichia coli (CREC) especially harboring the New Delhi Metallo-β-lactamase (blaNDM) variants are increasingly being reported from many countries, however, the data from Pakistan is limited. In the present study, 109 CREC isolates were obtained from 4,091 E. coli isolates in five tertiary care hospitals in southern Punjab, Pakistan. The antimicrobial susceptibility profiling and screening for the resistance determinants were performed followed by blaNDM typing and multilocus sequence typing (MLST) to characterize the CREC strains. Among the carbapenemases, 57 CREC isolates were found to harbor blaNDM. The blaNDM-1, blaNDM-5, blaNDM-7, and blaNDM-4 variants were identified in 30 (52.6%), 18 (31.6%), (12.3%), 2 (3.5%) isolates, respectively. The ESBL genes, such as blaCTX-M and blaTEM, were also found in different combinations, whereas the 16S methylases that is, rmtB and armA were found in 69 (63.3%) and 55 (50.5%) CREC isolates, respectively. The MLST of blaNDM carrying E. coli revealed eight different sequence types (STs) with ST131 belonging to 21 isolates being the most prevalent. The clonal complex 131 was the predominant complex corresponding to 47 (82.5%) of blaNDM-positive strains. Large-scale surveillance studies coupled with active infection control policies are suggested on an urgent basis to avoid an epidemic in the future.


Clinical trial of nitroglycerin-induced controlled hypotension with or without acupoint electrical stimulation in microscopic middle ear surgery under general anesthesia with halothane.
Transcutaneous electrical stimulation (ES) has been shown to produce long-lasting fall of arterial blood pressure in animal or human models. Previous reports have shown that ES of acupuncture points (acupoints) enhances the hypotensive effect of isoflurane anesthesia. This study was designed to investigate the combined effect of acupoint ES and different infusion rates of nitroglycerin on controlled hypotension. Fifty-one adult ASA I patients undergoing elective mastoeidectomy were randomly divided into two groups, to receive either true or sham ES of ST36 (Zusanli) and ST38 (Tiaokou) acupoints. Each group was further subdivided into four groups to receive four different rates of nitroglycerin infusion (1.5, 2, 2.5 and 3 microg/kg/min). Steady state mean arterial blood pressure (MAP) and time to reach it were compared between two groups. The amount of bleeding in microscopic surgical field was quantitatively assessed and compared between two groups. Steady state MAP was significantly lower in true ES group compared with sham ES group (60 +/- 4 mmHg in true ES vs. 66 +/- 5 mmHg in sham ES, P = 0.000) and the difference was significantly greater in lower dosage of nitroglycerin compared with higher dosage. In addition time to reach steady state MAP was significantly shorter in true ES compared with sham group (10 +/- 3 min in true ES vs. 15.8 +/- 4 min in sham ES, P = 0.000). Heart rate decreased significantly in true ES compared with sham ES group after commencement of ES and nitroglycerin infusion. Quality of operative ischemia was excellent in 20 (83.3%) patients of true ES compared with 6 (25%) patients in sham ES group (P = 0.000). The result of this study shows that ES of ST36 combined with nitroglycerin infusion facilitates lowering of blood pressure and produces a bloodless surgical field. The mechanism of blood pressure lowering effect of acupoint ES may be reducing of norepinephrine and other sympathomimetic substances in the blood.


Extracellular domain of myelin oligodendrocyte glycoprotein (MOG) exhibits solvent-dependent conformational transitions.
The conformation of the non-glycosylated recombinant form of the extracellar domain of rat MOG (rMOG(1-125)) dissolved in different solvent conditions was studied by CD spectroscopy. The results show that rMOG(1-125) exhibits a predominantly beta sheet conformation in aqueous buffer solution at pH 7.5 and that this 'beta-form' is stabilized by zwitterionic phospholipids, DPC and LPCP. The alpha helical content of the protein can increase from 9% to up to 20% when TFE or anionic detergent LPAP and SDS are added.


Relationship Quality and Perceived Partner's Body Appreciation Is Related to Women's Own Body Appreciation and Sexual Functioning.
Research on body appreciation is limited, especially when examining its relationship to sexual functioning. The aim of this study was to explore the relationship between body appreciation and sexual functioning, while measuring perceived partner's body appreciation and general relationship quality. A sample of 244 women aged 18 to 30 completed measures of sexual functioning, relationship quality, and body image online. General relationship quality and perceived partner's appreciation of one's body predicted levels of sexual functioning. Levels of body appreciation did not predict sexual functioning over and above general relationship quality and perceived partner's appreciation of one's body. This study is the first to demonstrate the significance of general relationship quality and perceived partner's body appreciation in relation to levels of body appreciation and sexual functioning. The findings highlight the importance of understanding body appreciation and its role in buffering the harmful impacts of viewing idealized images within the media.


SYSTOMONAS--an integrated database for systems biology analysis of Pseudomonas.
To provide an integrated bioinformatics platform for a systems biology approach to the biology of pseudomonads in infection and biotechnology the database SYSTOMONAS (SYSTems biology of pseudOMONAS) was established. Besides our own experimental metabolome, proteome and transcriptome data, various additional predictions of cellular processes, such as gene-regulatory networks were stored. Reconstruction of metabolic networks in SYSTOMONAS was achieved via comparative genomics. Broad data integration is realized using SOAP interfaces for the well established databases BRENDA, KEGG and PRODORIC. Several tools for the analysis of stored data and for the visualization of the corresponding results are provided, enabling a quick understanding of metabolic pathways, genomic arrangements or promoter structures of interest. The focus of SYSTOMONAS is on pseudomonads and in particular Pseudomonas aeruginosa, an opportunistic human pathogen. With this database we would like to encourage the Pseudomonas community to elucidate cellular processes of interest using an integrated systems biology strategy. The database is accessible at http://www.systomonas.de.


Influence of treatment on the maturation of the somesthetic pathway in infants with primary congenital hypothyroidism during the first year of life.
To assess the influence of treatment on the development of the somesthetic pathway in infants with congenital hypothyroidism receiving early treatment, median nerve somatosensory evoked potentials were measured during the 1st y of life. Twenty-nine infants were studied with six to seven somatosensory evoked potential tests per infant. The cervical latency (N13) divided by arm length and the first (N19) and second (N32) cephalic latencies as well as N13-N32 latency were measured. At diagnosis, all components showed a small but significant delay, which was not related to thyroxine (T4) levels before treatment. During treatment, T4 ranged from 50 to 290 nmol/L. At 12 mo, the cervical latency divided by arm length had normalized, whereas N19 and N13-N32 were more abnormal than at diagnosis. For N19, these abnormalities were related to a slow initial rise of T4 (< or = 100 nmol/L after 1 wk of treatment) and the initial N19 values. Abnormal N13-N32 values were associated with high T4 values during treatment (> 200 nmol/L) and the type of congenital hypothyroidism (partial or total deficiency in T4 production). Induction of therapy with l-triiodothyronine rather than l-thyroxine and the occurrence of low T4 values (< 100 nmol/L) after the 4th wk of therapy had no such effect. Our data suggest that, for normal CNS development, euthyroidism should be reached as soon as possible by adequate induction therapy. Thereafter, T4 supplementation should be strictly dosed, keeping the serum T4 values within narrow limits around the mean normal for age, because overtreatment, like initial undertreatment, may lead to CNS abnormalities at the end of the first year.


Monocular transparency and unpaired stereopsis.
Howard and Duke [Howard, I. P. & Duke, P. A. (2003). Monocular transparency generates quantitative depth. Vision Research, 43, 2615-2621] recently proposed a new source of binocular information they claim is used to recover depth in stereoscopic displays. They argued that these displays lack conventional disparity and that the metrical depth experienced results from transparency rather than occlusion relations. Using a variety of modified versions of their stimuli, we show here that the conditions for transparency are not required to elicit the depth experienced in their stereograms. We demonstrate that quantitative and precise depth depended not on the presence of transparency but horizontal contours of the same contrast polarity. Depth was attenuated, particularly at larger target offsets, when horizontal contours had opposite contrast polarity for at least a portion of their length. We also show that a demonstration they used to control for the role of horizontal contours can be understood with previously identified mechanisms involved in the computations associated with stereoscopic occlusion. These results imply that the findings reported by Howard and Duke can be understood with mechanisms responsible for the computation of binocular disparity and stereoscopic occlusion.


Point Cloud Based Relative Pose Estimation of a Satellite in Close Range.
Determination of the relative pose of satellites is essential in space rendezvous operations and on-orbit servicing missions. The key problems are the adoption of suitable sensor on board of a chaser and efficient techniques for pose estimation. This paper aims to estimate the pose of a target satellite in close range on the basis of its known model by using point cloud data generated by a flash LIDAR sensor. A novel model based pose estimation method is proposed; it includes a fast and reliable pose initial acquisition method based on global optimal searching by processing the dense point cloud data directly, and a pose tracking method based on Iterative Closest Point algorithm. Also, a simulation system is presented in this paper in order to evaluate the performance of the sensor and generate simulated sensor point cloud data. It also provides truth pose of the test target so that the pose estimation error can be quantified. To investigate the effectiveness of the proposed approach and achievable pose accuracy, numerical simulation experiments are performed; results demonstrate algorithm capability of operating with point cloud directly and large pose variations. Also, a field testing experiment is conducted and results show that the proposed method is effective.


Spontaneous pneumomediastinum in a dermatomyositis patient with anti-melanoma differentiation-associated gene-5 antibody and interstitial lung disease despite an initial response to immunosuppressant.
We report a 24-year-old man with anti-melanoma differentiation-associated gene-5 (MDA5) antibody-positive dermatomyositis (DM) and interstitial lung disease (ILD) who developed spontaneous pneumomediastinum. By comparing serial thoracic high-resolution computed tomography scans, we demonstrated the distinct time course showing a paradoxical occurrence of pneumomediastinum despite a radiological improvement of ILD. Our case shows that pneumomediastinum in DM can occur regardless of associated ILD and it is a serious complication that should be considered in DM patients presenting with pulmonary manifestations. Cutaneous vasculopathy may be associated with pneumomediastinum and could potentially be a useful indicator of future disease.


Nicotinic acid adenine dinucleotide phosphate: a new intracellular second messenger?
Nicotinic acid adenine dinucleotide phosphate (NAADP) is one of the most potent stimulators of intracellular Ca2+ release known to date. The role of the NAADP system in physiological processes is being extensively investigated at the present time. Exciting new discoveries in the last 5 years suggest that the NAADP-regulated system may have a significant role in intracellular Ca2+ signaling. The NAADP receptor and its associated Ca2+ pool have been hypothesized to be important in several physiological processes including fertilization, T cell activation, and pancreatic secretion. However, whether NAADP is a new second messenger or a tool for the discovery of a new Ca2+ channel is still an unanswered question.


Vaccination demonstration zone successfully controls rabies in Guangxi Province, China.
Guangxi is the province most seriously affected by rabies virus (RABV) in China. Those most affected by RABV each year are people in rural areas, where dogs are the main cause of human infection with the virus. In this study, we established a rabies vaccination demonstration program that included eradication, core, and peripheral areas. This program was implemented for 9 years and comprised three stages: 12 counties in the first stage (2008-2010), 21 counties in the second stage (2011-2013), and then extending to all counties of Guangxi Province in the third stage (2014-2016). The program included a dog vaccination campaign, surveillance of clinically healthy dogs who may be potential RABV carriers, monitoring anti-RABV antibody titers in vaccinated dogs, and compiling and reporting statistics of human rabies cases. The target effectiveness was achieved in the eradication, core, and peripheral areas in all three stages. The vaccination demonstration program successfully promoted RABV vaccination of domestic dogs throughout Guangxi Province by drawing upon the experience gained at key points. Compared with a vaccination coverage rate of 39.42-46.85% in Guangxi Province overall during 2003-2007, this rate gradually increased to 48.98-52.67% in 2008-2010, 60.24-69.67% in 2011-2013, and 70.09-71.53% in 2014-2016, thereby meeting World Health Organization requirements. The total cases of human rabies in the province decreased from 602 in 2004 to 41 cases in 2017. The present pilot vaccination program obviously increased the rabies vaccination and seroconversion rates, and effectively reduced the spread of rabies from dogs to humans as well as the number of human rabies cases, thus successfully controlling rabies in Guangxi.


Phosphoryl transfer by protein kinase A is captured in a crystal lattice.
The catalytic (C) subunit of cAMP-dependent protein kinase (PKA) is a serine/threonine kinase responsible for most of the effects of cAMP signaling, and PKA serves as a prototype for the entire kinase family. Despite multiple studies of PKA, the steps involved in phosphoryl transfer, the roles of the catalytically essential magnesium ions, and the processes that govern the rate-limiting step of ADP release are unresolved. Here we identified conditions that yielded slow phosphoryl transfer of the γ-phosphate from the generally nonhydrolyzable analog of ATP, adenosine-5'-(β,γ-imido)triphosphate (AMP-PNP), onto a substrate peptide within protein crystals. By trapping both products in the crystal lattice, we now have a complete resolution profile of all the catalytic steps. One crystal structure refined to 1.55 Å resolution shows two states of the protein with 55% displaying intact AMP-PNP and an unphosphorylated substrate and 45% displaying transfer of the γ-phosphate of AMP-PNP onto the substrate peptide yielding AMP-PN and a phosphorylated substrate. Another structure refined to 2.15 Å resolution displays complete phosphoryl transfer to the substrate. These structures, in addition to trapping both products in the crystal lattice, implicate one magnesium ion, previously termed Mg2, as the more stably bound ion. Following phosphoryl transfer, Mg2 recruits a water molecule to retain an octahedral coordination geometry suggesting the strong binding character of this magnesium ion, and Mg2 remains in the active site following complete phosphoryl transfer while Mg1 is expelled. Loss of Mg1 may thus be an important part of the rate-limiting step of ADP release.


Dietary patterns and the risk of rhinitis in primary school children: a prospective cohort study.
This study was to investigate the association between dietary patterns and rhinitis in primary school children. 1,599 students without rhinitis at baseline survey were selected from a primary school children cohort. Information on food consumption, respiratory symptoms, and confounders was collected using questionnaires. Dietary patterns were defined using principal component analysis. Logistic regression was performed to calculate odds ratio (OR) with 95% confidence intervals (95% CI). The incidence of rhinitis during 12 months follow-up was 21.2%. Three patterns were extracted and labeled as pattern I, II and III. Dietary pattern II which had higher factor loadings of legumes, butter, nuts and potatoes was associated with an increased risk of rhinitis (OR: 1.34, 95% CI: 1.01-1.87) when the highest tertile of pattern score was compared to the lowest tertile, after adjusted for confounders. Besides, every 1-unit increase of score of pattern II was also associated with an increased risk of rhinitis (OR: 1.19, 95% CI: 1.05-1.35). Neither pattern I nor Pattern III was observed to be associated with risk of rhinitis. A diet with higher levels of consumption of legumes, butter, nuts and potatoes may increase the risk of allergic rhinitis in primary school children.


Detecting Changes in Newspaper Reporting of Suicide after a Statewide Social Marketing Campaign.
A social marketing campaign was introduced in California in 2012, promoting media adherence to consensus-based guidelines on reporting about suicide. We examine adherence to these guidelines by applying quantitative scores to articles in California and a national control group in two six-month intervals prior to and following campaign implementation. Utilizing a difference-in-difference approach, we found no significant effect of the campaign, though the type of article content was a significant indicator of the overall score. Findings also demonstrated a nation-wide downward trend in the quality of reporting. Qualitative results suggest a need for more flexible guidelines in light of a technologically driven news culture.


Immunochromatography using colloidal gold-antibody probe for the detection of atrazine in water samples.
An immunochromatography (ICG) strip test for rapid detection of atrazine in water samples was developed. A monoclonal antibody (MAb) specific to atrazine was produced from the cloned hybridoma cell (AT-1-M3) and used to develop a direct competitive enzyme-linked immunosorbent assay (DC-ELISA) and ICG strip. MAb conjugated to colloidal gold, and that was applied to the conjugate pad of the ICG strip. The visual detection limit for the ICG strip was 3 ng/mL. This test required only 10 min to get results and one step of sample to perform the assay. The results of water samples spiked with 5, 10, 20, and 50 ng/mL of atrazine by ICG strip were in good agreement with those obtained by DC-ELISA. The ICG strip was sufficiently sensitive and accurate to be useful for rapid screening of atrazine in various water samples.


Effects of Temperature and Volume of Intraoperative Normal Saline Irrigation on Postoperative Pain, Swelling, and Serum Markers of Inflammation in Patients After Elective, Arthroscopic, Single-Bundle Surgical Reconstruction of the Anterior Cruciate Ligament: A Retrospective, Single-Center Study.
BACKGROUND Arthroscopic single-bundle surgical reconstruction of the anterior cruciate ligament (ACL) is often performed electively after 3 weeks of mobilization therapy. The present single-center retrospective study aimed to investigate the effects of temperature and volume of intraoperative normal saline irrigation on postoperative pain and swelling and on serum markers of inflammation following elective, arthroscopic, single-bundle surgical reconstruction of the ACL. MATERIAL AND METHODS Clinical data from 716 patients with non-acute ACL injuries who met the criteria between March 2015 and May 2020 were retrospectively analyzed. The patients were broken into 5 groups, depending on the volume or temperature of intraoperative irrigation with normal saline. At specific times after surgery, pain, knee swelling, and skin temperature were assessed. Postoperative levels of serum C-reactive protein (CRP), interleukin (IL)-1, IL-6, and IL-10 also were measured. RESULTS Visual analog scale (VAS) scores for pain, rates of swelling, and skin temperature differed significantly among the 5 groups at all postoperative time points (P<0.001). The VAS scores(P=0.322) and ratings for swelling (P=0.245), and skin temperature (P=0.093) were not significantly different among the volume groups. There were no significant differences in the VAS scores (P=0.055), swelling ratings (P=0.570), or skin temperatures (P=0.321) among the groups that received irrigation with normal saline at different temperatures. There were no significant differences in postoperative serum levels of CRP, IL-1, IL-6, or IL-10 among the groups (P>0.05). CONCLUSIONS Irrigation with different volumes and temperatures of normal saline did not have a significant effect on postoperative pain, swelling, or serum markers of inflammation.


Whole person care: Outcomes from a 5-year care model integrating primary care into a behavioral health clinic.
Integrated mental and physical health care has the potential to improve health outcomes. A behavioral health organization established a reverse integration program site using a co-located model to provide primary care services to patients receiving behavioral health services. We ask whether this model of co-located care was effective in improving a range of physical health outcomes for clients. This program was funded with a grant from the Substance Abuse and Mental Health Services Administration Primary and Behavioral Health Care Integration. Patients received services in a community mental health setting that embedded primary care services. The population included adult patients with mental illness, substance use disorder (SUD), or co-occurring medical diagnoses in an urban setting. Just under half of the patients identified as non-White, and over one quarter identified as Hispanic. These characteristics demonstrate a medically complex and underserved population. This description and exploratory analysis utilized National Outcome Measures data and clinical health measures from electronic health records. We stratified data by SUD and mental illness diagnoses. We measured changes in health outcomes for this complex population of 532 patients from 2015 to 2019. From enrollment to last visit, patient outcomes improved for blood pressure and cholesterol. Conversely, waist circumference and breath carbon monoxide levels significantly worsened. This reverse integration co-location program demonstrates that positive health outcomes can be achieved through evidence-based care, adaptable clinic arrangements, and robust community connections and support. More work is needed to generate positive health outcomes in medically complex patients. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Gossypiboma mimicking gastrointestinal stromal tumor causing intestinal obstruction: a case report.
A 41-year-old woman was admitted to our hospital with abdominal pain that developed about 1 year after a Cesarean section. Pelvic computed tomography (CT) revealed diffuse dilation of the small intestine with fluid shadows and a pelvic tumor 55 mm in diameter. The density of the tumor, which was not enhanced by intravenous contrast medium, was diffuse and similar to that of muscular tissue, whereas the density of a capsule surrounding the mass was relatively high. T1- and T2-weighted pelvic magnetic resonance imaging (MRI) of the tumor revealed the same diffuse low-intensity signals as muscular tissue, and diffuse high-intensity signals, respectively. The CT and MRI findings were consistent with those of a gastrointestinal stromal tumor (GIST) causing ileus of the small intestine. As inserting an ileus tube did not improve her symptoms, the patient was scheduled for tumor resection. The operative findings revealed a hard, solid tumor adhering to the surrounding small intestine. The macroscopic findings revealed that the tumor consisted of layers of stratified gauze surrounded by a thick granulomatous wall. The gossypiboma was considered to have originated from gauze that had been left behind after the Cesarean section. If a patient has a history of surgery, the possibility of gossypiboma should be considered when CT or MRI findings indicate features of GIST.


[Molecular typing of the pathogenic Yersinia enterocolitica strains with pulsed field gel electrophores isolated in China].
To investigate the epidemiological and molecular typing features of the pathogenic Yersinia enterocolitica strains isolated in China,using pulsed field gel electrophoresis(PFGE) and standardized PFGE method as well as typing database of Yersinia enterocolitica. PFGE analysis was performed as Laboratory Directions for molecular subtyping of Salmonella by PFGE (PulseNet,USA) with some modifications and the results of PFGE were analyzed by BioNumerics soft (Version 4.0, Applied Maths BVBA, Belium). 114 O:3 Yersinia enterocolitica strains were typed by 25 patterns to have found that K6GN11C30012 (50 strains), K6GN11C30015(19 strains) and K6GN11C30016(10 strains) were the major patterns. K6GNllC30012 had 92.2% cluster similarity with K6GN11C30009-K6GN11C30023. This clone included 91.23% strains of 114 0:3 Yersinia enterocolitica strains. 51 0:9 Yersinia enterocolitica strains were typed by 14 patterns; K6GN11C90004 (22 strains) and K6GN11C90010 (13 strains)were the major patterns. K6GN11C90004 had 81.8% cluster similarity with K6GN11C90010 patterns. The major patterns of 0:3 and 0:9 serotypes were quite different. O:3 Yersinia enterocolitica strains might originate from the same clone and had very few variation in different years and provinces but O:9 Yersinia enterocolitica strains from two different clones with some changes.


Interleukin-17a Induces Neuronal Differentiation of Induced-Pluripotent Stem Cell-Derived Neural Progenitors From Autistic and Control Subjects.
Prenatal exposure to maternal immune activation (MIA) has been suggested to increase the probability of autism spectrum disorder (ASD). Recent evidence from animal studies indicates a key role for interleukin-17a (IL-17a) in promoting MIA-induced behavioral and brain abnormalities reminiscent of ASD. However, it is still unclear how IL-17a acts on the human developing brain and the cell types directly affected by IL-17a signaling. In this study, we used iPSC-derived neural progenitor cells (NPCs) from individuals with ASD of known and unknown genetic cause as well as from neurotypical controls to examine the effects of exogenous IL-17a on NPC proliferation, migration and neuronal differentiation, and whether IL-17a and genetic risk factors for ASD interact exacerbating alterations in NPC function. We observed that ASD and control NPCs endogenously express IL-17a receptor (IL17RA), and that IL-17a/IL17RA activation modulates downstream ERK1/2 and mTORC1 signaling pathways. Exogenous IL-17a did not induce abnormal proliferation and migration of ASD and control NPCs but, on the other hand, it significantly increased the expression of synaptic (Synaptophysin-1, Synapsin-1) and neuronal polarity (MAP2) proteins in these cells. Also, as we observed that ASD and control NPCs exhibited similar responses to exogenous IL-17a, it is possible that a more inflammatory environment containing other immune molecules besides IL-17a may be needed to trigger gene-environment interactions during neurodevelopment. In conclusion, our results suggest that exogenous IL-17a positively regulates the neuronal differentiation of human NPCs, which may disturb normal neuronal and synaptic development and contribute to MIA-related changes in brain function and behavior.


Carcinoma of the choroid plexus: a pediatric experience.
Carcinoma of the choroid plexus (CCP) is a rare tumor of the central nervous system which occurs more frequently in patients under 3 years of age. We report 10 cases of CCP in children. There were 5 males and 5 females, aged 5 to 84 months at diagnosis (median 32 months). Eight CCP were located in the lateral ventricle and 2 in the fourth ventricle. All patients underwent initial surgery, with complete resection in 5 cases. Postoperative treatment included radiotherapy alone in 4 patients, chemotherapy alone in 4, both in 1 patient, and no further treatment in one patient. Six patients remain in first continuous complete remission with a follow-up of 12 to 156 months (mean 34 months). Five of these six patients had a complete surgical resection of their tumor and 4 of them received chemotherapy alone. A comparison with the series in the literature suggests that total resection of the tumors is the major prognostic factor for survival. Recourse to additional treatments to prevent local relapses and CNS dissemination seems necessary. In our opinion, radiotherapy should be avoided as far as possible because of its deleterious effect in very young children. As some of the long term survivors did not receive radiation treatment, we conclude that CCP can be treated post operatively using chemotherapy protocols designed for infants with malignant brain tumors.


A Glycopeptidyl-Glutamate Epimerase for Bacterial Peptidoglycan Biosynthesis.
d-Glutamate (Glu) supplied by Glu racemases or d-amino acid transaminase is utilized for peptidoglycan biosynthesis in microorganisms. Comparative genomics has shown that some microorganisms, including Xanthomonas oryzae, perhaps have no orthologues of these genes. We performed shotgun cloning experiments with a d-Glu auxotrophic Escherichia coli mutant as the host and X. oryzae as the DNA donor. We obtained complementary genes, XOO_1319 and XOO_1320, which are annotated as a hypothetical protein and MurD (UDP-MurNAc-l-Ala-d-Glu synthetase), respectively. By detailed in vitro analysis, we revealed that XOO_1320 is an enzyme to ligate l-Glu to UDP-MurNAc-l-Ala, providing the first example of MurD utilizing l-Glu, and that XOO_1319 is a novel enzyme catalyzing epimerization of the terminal l-Glu of the product in the presence of ATP and Mg2+. We investigated the occurrence of XOO_1319 orthologues and found that it exists in some categories of microorganisms, including pathogenic ones.


Profile of Roche's cobas® HCV tests.
Molecular assays for detection and accurate quantitation of hepatitis C virus (HCV) RNA have been important for identification and management of the hepatitis C. Furthermore, the HCV genotype should be assessed prior to treatment initiation. Recently, Roche developed the cobas® HCV tests for use on the cobas® 6800/8800 Systems and the cobas® 4800 System and the cobas® HCV genotyping (GT) test for use on the cobas® 4800 System. Areas covered: The analytic and clinical performance of the newly-developed tests is described according to the currently existing literature. Both tests for detection and quantitation of HCV RNA have been shown to be sensitive and linear, and correlate well with established Roche tests used in the routine diagnostic laboratory. The cobas® HCV GT test shows a good performance and is suitable for identification of HCV genotypes 1 to 6 and genotype 1 subtypes a and b in clinical specimens from individuals with chronic HCV infection. Expert commentary: The new tests are effective in screening for hepatitis C infection and in the management of patients with chronic HCV infection ensuring full HCV genotype coverage. They will replace the established Roche tests within the next few years.


Immunological mechanisms of allergen-specific immunotherapy.
Allergen-specific immunotherapy has been carried out for almost a century and remains one of the few antigen-specific treatments for inflammatory diseases. The mechanisms by which allergen-specific immunotherapy exerts its effects include the modulation of both T-cell and B-cell responses to allergen. There is a strong rationale for improving the efficacy of allergen-specific immunotherapy by reducing the incidence and severity of adverse reactions mediated by IgE. Approaches to address this problem include the use of modified allergens, novel adjuvants and alternative routes of administration. This article reviews the development of allergen-specific immunotherapy, our current understanding of its mechanisms of action and its future prospects.


ASSORTATIVE MATING AND THE ADAPTIVE LANDSCAPE.
The ability of a population to shift from one adaptive peak to another was examined for a two-locus model with different degrees of assortative mating, selection, and linkage. As expected, if the proportion of the population that mates assortatively increases, so does its ability to shift to a new peak. Assortative mating affects this process by allowing the mean fitness of a population to increase monotonically as it passes through intermediate gene frequencies on the way to a new, higher, homozygotic peak. Similarly, if the height of the new peak increases or selection against intermediates becomes less severe, the population becomes more likely to shift to a new peak. Close linkage also helps the shift to a new adaptive peak and acts similarly to assortative mating, but it is not necessary for such a shift as was previously thought. When a population shifts to a new peak, the number of generations required is significantly less than that needed to return to the original peak when that happens. The short period of time required may be an explanation for rapid changes in the geological record. Under extremely high degrees of assortative mating, the shift takes longer, presumably because of the difficulty of breaking up less favored allelic combinations.


Lysophosphatidic acid as a lipid mediator with multiple biological actions.
Lysophosphatidic acid (LPA) is one of the simplest glycerophospholipids with one fatty acid chain and a phosphate group as a polar head. Although LPA had been viewed just as a metabolic intermediate in de novo lipid synthetic pathways, it has recently been paid much attention as a lipid mediator. LPA exerts many kinds of cellular processes, such as cell proliferation and smooth muscle contraction, through cognate G protein-coupled receptors. Because lipids are not coded by the genome directly, it is difficult to know their patho- and physiological roles. However, recent studies have identified several key factors mediating the biological roles of LPA, such as receptors and producing enzymes. In addition, studies of transgenic and gene knockout animals for these LPA-related genes, have revealed the biological significance of LPA. In this review we will summarize recent advances in the studies of LPA production and its roles in both physiological and pathological conditions.


Differential regulation of human and murine P-selectin expression and function in vivo.
Leukocytes roll on P-selectin after its mobilization from secretory granules to the surfaces of platelets and endothelial cells. Tumor necrosis factor (TNF), IL-1β, and lipopolysaccharide increase synthesis of P-selectin in murine but not in human endothelial cells. To explore the physiological significance of this difference in gene regulation, we made transgenic mice bearing the human Selp gene and crossed them with mice lacking murine P-selectin (Selp(-/-)). The transgenic mice constitutively expressed human P-selectin in platelets, endothelial cells, and macrophages. P-selectin mediated comparable neutrophil migration into the inflamed peritoneum of transgenic and wild-type (WT) mice. Leukocytes rolled similarly on human or murine P-selectin on activated murine platelets and in venules of the cremaster muscle subjected to trauma. However, TNF increased murine P-selectin in venules, slowing rolling and increasing adhesion, whereas it decreased human P-selectin, accelerating rolling and decreasing adhesion. Both P- and E-selectin mediated basal rolling in the skin of WT mice, but E-selectin dominated rolling in transgenic mice. During contact hypersensitivity, murine P-selectin messenger (m) RNA was up-regulated and P-selectin was essential for leukocyte recruitment. However, human P-selectin mRNA was down-regulated and P-selectin contributed much less to leukocyte recruitment. These findings reveal functionally significant differences in basal and inducible expression of human and murine P-selectin in vivo.


Monoclonal antibodies to two different epitopes in a 30-kD CNBr peptide of the K1 and K2 keratins.
Two anti-keratin monoclonal antibodies, Kab-2 and Kab-3, with specificities for different epitopes of type II (basic) human epidermal keratins, were produced. These antibodies had different immunofluorescent staining patterns on human fetal epidermis. Western blots and solid phase RIA showed both antibodies bound to 65-67-kD basic keratins (K1 and K2) extracted from foreskin epidermis. Competitive binding studies with the two Kab antibodies and other anti-keratin monoclonal antibodies showed that Kab-2 and Kab-3 recognized related epitopes, distinct from the epitopes recognized by other anti-keratin antibodies AE-1, 2, and 3. Kab-2 and Kab-3 epitopes were distinguished by differences in their reactivity with peptides generated by Staphylococcus aureus V8 protease digestion of the K1 keratin; the antibodies recognized both common and unique peptides. Western blots of cyanogen bromide digests of the K1 keratin showed that both Kab antibodies reacted with a 30-kD fragment of the molecule presumed to be the N-terminal CNBr peptide. We interpret these data to indicate that in tissues, portions of the N-terminal region of the K1 keratin are differentially available for reaction with these monoclonal antibodies and that morphologic differences in staining with monoclonal antibodies to the same molecule can reflect epitope specificity or epitope availability related to supramolecular organization.


Observed differences in dextran and polyvinylpyrrolidone as rouleaux-inducing agents.
The effectiveness of dextran fractions (Dx-500, Dx-100, Dx-70) and polyvinylpyrrolidone (PVP-360, PVP-40) in inducing aggregation of red blood cells (RBC) was studied in a nonflowing environment. The Dx fractions, at low concentrations, induced aggregation of human RBC but failed to do so at high concentrations (concentrations greater than 70 g/L). The effect was different on RBC from animal species (cat and rabbit); aggregation increased steadily with the Dx concentration and there was no critical concentration beyond which Dx failed to induce aggregation. The PVP was found to be very effective, at all concentrations, in inducing aggregation of RBC from both human and the animal species. These results have a twofold significance (1) they suggest that Dx and PVP, both neutral polymers, interact differently with the human RBC membrane; and (2) the association of Dx with the human RBC membrane is different from that with cat and rabbit RBC membranes.


Dose Calculation Accuracy of AAA and AcurosXB Algorithms for Small Central and Interface Lung Lesions - Verification with Gafchromic Film Dosimetry
Dose calculation for small field radiotherapy with heterogeneity often involves discrepancies, so that algorithms used by treatment planning systems (TPS) should be evaluated with reference to achieving optimal treatment results. Accuracy of two model based algorithms, AcurosXB (AcXB) and the analytical anisotropic algorithm (AAA) from Eclipse TPS, were here tested. Measurements are made using Gafchromic EBT3 films with indigenously generated lung phantoms irradiated with 6 MV photons. Lung phantoms contained two types of tumor plugs, one kept at an interface attached to the chest wall in right lung (RIT) and the other at the centre of the left lung (LCT). RIT and LCT were studied with two different tumor diameters, 1.5 cm and 2.5 cm. Scanned images were planned in TPS with 3D-CRT, IMRT and VMAT and individual plans for each tumor were irradiated keeping the Gafchromic film at the centre of the tumor to evaluate the dose distribution in the central plane. Both algorithms, irrespective of delivery techniques, showed more deviation with smaller than larger diameter tumors. Also, both demonstrated maximum deviation at the junction of tumor and lung in both RIT and LCT cases. However, the deviation observed was higher with AAA and a minimal acceptable deviation of within 4 % was achieved with AcurosXB.


15N-labelled yeast protein--a valid tracer for calculating whole-body protein parameters in infants: a comparison between [15N]-yeast protein and [15N]-glycine.
The validity of [15N]-glycine and 15N-labelled yeast protein as tracers for investigating the parameters of nitrogen metabolism in man was studied by comparisons of each tracer in three infants on different diets. Both tracers were administered with the food as a single oral dose of 0.2 mmol 15N-excess nitrogen per kg body weight. Cumulative 15N-excess excretion in the urine was measured by emission spectrometry and a three-compartment model was used to calculate the pool sizes by computer. In all three comparisons the values calculated for protein synthesis, protein breakdown, protein turnover and reutilization after administration of 15N-labelled yeast protein were slightly lower than those calculated after administration of [15N]-glycine. The particular advantage of applying a highly enriched, completely labelled [15N]-protein instead of [15N]-glycine as a tracer is that the protein, containing some 20 amino acids, doubtless gives a more accurate picture of protein metabolism than the use of a single amino acid labelled with heavy nitrogen. However, the small differences between the whole-body parameters calculated from 15N-labelled yeast protein and [15N]-glycine do not justify the general replacement of [15N]-glycine by 15N-labelled protein.


MicroRNA166 Monitors SPOROCYTELESS/NOZZLE for Building of the Anther Internal Boundary.
The internal boundary between inner and outer microsporangia within anthers is essential for male fertility of vascular plants. Dehiscence zones embedded in the boundary release pollen for fertilization. However, the molecular mechanism underlying boundary formation in anthers remains poorly understood. Here, we report that microRNA166 (miR166) and its target PHABULOSA (PHB) regulate SPOROCYTELESS/NOZZLE (SPL/NZZ), which controls microsporogenesis. In developing anthers of Arabidopsis (Arabidopsis thaliana), the expression domains of miR165/6 and SPL/NZZ are overlapped and rearranged synchronously. Dominant mutation of PHB suppresses SPL/NZZ expression on the adaxial sides of stamens, resulting in a thickened boundary, whereas activation of MIR166g up-regulates SPL/NZZ expression, leading to ectopic microsporogenesis in the boundary. PHB limits the expression domains of SPL/NZZ to facilitate construction of the boundary, while miR166 preserves the expression domains of SPL/NZZ by inhibiting PHB to allow the inner microsporangia to take shape. Subsequently, PHB activates the key stem cell maintainer WUSCHEL in anthers to restrict the stomium cells to the boundary so that dehiscence zones develop and release pollen properly. These findings link adaxial/abaxial polarity to microsporogenesis in building of the internal boundary of anthers and thus advance the concepts underlying the establishment of the internal structure of male organs.


Underreporting of dietary intake by body mass index in premenopausal women participating in the Healthy Women Study.
Underreporting patterns by the level of obesity have not been fully assessed yet. The purpose of this study was to examine the differential underreporting patterns on cardiovascular risk factor, macronutrient, and food group intakes by the level of Body Mass Index (BMI). We analyzed cross-sectional baseline nutritional survey data from the population-based longitudinal study, the Healthy Women Study (HWS) cohort. Study subjects included 538 healthy premenopausal women participating in the HWS. Nutrient and food group intakes were assessed by the one-day 24-hour dietary recall and a semi-quantitative food frequency questionnaire, respectively. The ratio of reported energy intake (EI) to estimated basal metabolic rate (BMR) was used as a measure of relative energy reporting status and categorized into tertiles. Overweight group (BMI>/=25kg/m(2)) had a higher ratio of EI to BMR (EI/BMR) than normal weight group (BMI<25kg/m(2)). Normal weight and overweight groups showed similar patterns in cardiovascular risk factors, nutrient intake, and food group intake by the EI/BMR. Fat and saturated fat intakes as a nutrient density were positively associated with the EI/BMR. Proportion of women who reported higher consumption (>/=4 times/wk) of sugar/candy, cream and red meat groups was greater in higher tertiles of the EI/BMR in both BMI groups. Our findings suggest similar patterns of underreporting of cardiovascular risk factors, and macronutrient and food group intakes in both normal and overweight women.