Evaluation of the Hemostatic Efficacy of Two Powdered Topical Absorbable Hemostats Using a Porcine Liver Abrasion Model of Mild to Moderate Bleeding.
Topical hemostatic agents, used alone or in combination, have become common adjuncts to manage tissue and organ bleeding resulting from trauma and surgical procedures. Oxidized regenerated cellulose (ORC) is one of the most commonly used adjunctive hemostatic agents. The aim of the present study was to compare the hemostatic efficacy of a novel ORC-based product, SURGICEL® Powder Absorbable Hemostat (Surgicel-P) to that of HEMOBLAST™ Bellows (Hemoblast-B), a collagen-based combination powder. Using an established porcine liver abrasion model, we randomly tested Surgicel-P and Hemoblast-B in 60 experimental lesion sites (30 per product tested). Primary endpoints included hemostatic efficacy measured by absolute time to hemostasis (TTH) within 5 minutes. We also examined number of applications required to achieve hemostasis, and sustained hemostasis following saline irrigation of test sites that achieved hemostasis. Surgicel-P demonstrated significantly higher hemostatic efficacy and lower TTH (p < 0.01) than Hemoblast-B. Surgicel-P-treated lesion sites achieved hemostasis in 73.3% of cases following one product application vs. 3.3% of Hemoblast-B-treated sites. Of all sites that were assessed, hemostasis was achieved and sustained following irrigation at 93.3% of Surgicel-P-treated sites vs. 50.0% of Hemoblast-B-treated sites. The average number of Surgicel-P applications per site was 51% lower than the average number of applications used for Hemoblast-B. Surgicel-P provided more effective and sustained hemostasis and faster TTH than Hemoblast-B. Surgicel-P represents a novel clinical alternative to provide adjunctive control of diffuse mild and moderate bleeding. Surgicel-P combines an ORC powder formulation and a delivery system in a device that is particularly useful for application on large surfaces and difficult-to-access anatomical locations where application of other forms of topical hemostats may be impractical.


Mental health policy in the liberal state: the example of the United States.
Mental health policy arises out of the interaction of many different variables. These include (but are not limited to) the composition of the population of persons with severe mental illnesses; the means of dealing with disease and dependency; concepts of the etiology and nature of mental disorders; the organization and ideology of psychiatry; funding mechanisms; and existing popular, political, cultural, and professional values. But an often neglected but crucial factor in shaping policy is the very structure of the American political system, which played a crucial role in shaping mental health policy. Rather than emphasizing the neo-liberal theory and its accompanying hostility toward "unsuccessful" people and disdain of welfare, this article suggests that an understanding of mental health policy in the latter half of the twentieth century is better served by an examination of what actually happened. Theory, however attractive, rarely can encompass the messy data of reality.


Sonochemical treatment of fly ash for dye removal from wastewater.
Fly ash samples modified by NaOH solution and sonochemical treatment were tested for a basic dye (methylene blue) adsorption in aqueous solution. It is found that sonochemical treatment of fly ash can significantly increase the adsorption capacity depending on the concentration of NaOH and treatment time. The untreated FA and the sonochemically treated sample exhibits adsorption capacity at 6 x 10(-6)mol/g and 1.2 x 10(-5)mol/g at 30 degrees C, respectively. The adsorption tests show that solution pH and adsorption temperature also influence the adsorption behaviour. The adsorption isotherms can be fitted by Langmuir and Freudlich models, while the two-site Langmuir heterogeneous model will present the best result.


[Radiosensitivity on colorectal neoplasms by recombinant adenoviral-mediated wild-type p53 gene].
To study the radiosensitization on the cells of colorectal cancer transfected with recombinant adenovirus vector-mediated wild-type p53. SW480 cells transfected by wild-type p53 were treated with 4 Gy and 6 Gy radiation. The expression of recombinant adenovirus vector-mediated wild-type p53 gene was detected by Western blotting. The inhibition rate of SW480 cells was examined by MTT, apoptotic rate by TdT-mediated dUTP nick end labeling (TUNEL) and proliferating cell nuclear antigen (PCNA) by immunohistochemical method. SW480 cells transfected by wild-type p53 were inhibited significantly by 4 Gy and 6 Gy radiation. The level of apoptosis increased and the expression of PCNA decreased. Cells of colorectal carcinoma transfected with wild-type p53 increases their radiation sensitivity.


MAP7D3, a novel prognostic marker for triple-negative breast cancer, drives cell invasiveness and cancer-initiating cell properties to promote metastatic progression.
Patients with triple-negative breast cancer (TNBC) tend to develop visceral metastasis within five years, making them the most challenging BC patients to treat. The MAP7 protein family is a group of microtubule-binding proteins with a well-known role in microtubule-related cell migration, but its role in metastasis-related properties of TNBC remains unclear. qRT-PCR and western blot were used to validate mRNA and protein expression of the MAP7 family in the isogenic pairs of TNBC cell lines with low and high metastasis potential. Functional characterization of MAP7D3 was carried out using cell-based and mouse models. The clinical association between MAP7D3 and TNBC was established using datasets in the public domain. MAP7D3 expression was consistently upregulated in the metastatic subline IV2 and 468-LN at both mRNA and protein levels. Knockdown of MAP7D3 inhibited the 3D colony-forming ability, cell migration, and invasion ability of IV2 and 468-LN, indicating its significant contribution to the metastasis phenotypes. Mechanistically, inhibition of MAP7D3 could significantly increase the sensitivity of metastatic TNBC cells to docetaxel and gemcitabine treatment by reducing the expression of proteins related to breast cancer-initiating cells (BCICs) and drug resistance, as well as suppressing the activity of Rac1. The animal study showed that the depletion of MAP7D3 drastically reduced TNBC tumor growth and impaired the metastatic capability of TNBC cells. Elevated expression of MAP7D3 was found in the metastatic lymph nodes and was significantly associated with advanced stage and higher grade TNBC. Moreover, MAP7D3 expression was significantly correlated with the TNBC population, and its high expression was significantly associated with lymph node metastasis and poor survival outcomes of patients with TNBC. Our study indicates that targeting MAP7D3 could be a promising therapeutic strategy for addressing the progression of TNBC, and MAP7D3 may serve as a novel predictive biomarker for the survival outcomes of triple-negative breast cancer.


Reading errors in patients with cerebellar vermis lesions.
Dyslexia, both developmental and acquired, has been considered the result of cerebrocortical dysfunction, affecting the temporo-parieto-occipital brain regions. However, dyslexia may involve abnormalities of the magnocellular component of the visual system, leading to binocular instability or alterations of accommodation. To test the hypothesis of cerebellar involvement in the reading process -- justified by its emergent role in language and cognition -- we studied 10 patients with cerebellar vermis/paravermis lesions using reading tests and we compared the results with those produced by 10 normal volunteers. The data obtained demonstrate an increased number of reading mistakes in the patient group, resulting from a possible alteration of the diffuse connection system from the cerebellum to different cerebrocortical and subcortical structures. Acquired dyslexia due to cerebellar impairment may be due to oculomotor alteration or, more subtly, to the intimate cerebellar-encephalic projections, connecting the cerebellum to the attentive and alerting processes and to the language system. We discuss the data with an overview of literature.


High diastereoselective vinylogous Mannich reaction induced by O-pivaloylated D-galactosylamine as the chiral auxiliary: stereoselective synthesis of 8-arylazocan-2-one.
The diastereospecific formation of β-N-glycosidically linked α,β-unsaturated δ-amino aldehyde derivatives has been achieved with high yield via a vinylogous Mannich reaction. The reaction was performed by using a O-pivaloylated galactosyl amine as a chiral template and AlCl3 as a promoter in THF. (S)-8-(p-Nitrophenyl) azocan-2-one can be stereoselective synthesized from (S) ethyl 7-galactosylamino-7-(p-nitrophenyl)hepta-2,4-dienoate by sequential hydrogenation of the double bond, cyclic lactam formation, and removal of the N-glycosidic auxiliary under basic conditions.


Alteration of vascular response to norepinephrine, calcitonin gene-related peptide, and acetylcholine in orchidectomized rats.
To determine the long-term effects of orchidectomy on vasoreactivity. Orchidectomized rats with or without hormone replacement were raised 1, 2, and 4 months. Vascular responses to norepinephrine, calcitonin gene-related peptide (CGRP), and acetylcholine were tested on three different arteries (thoracic aorta, pulmonary artery, and caudal artery) by functional experiments. Responses to norepinephrine, CGRP, and acetylcholine were not changed by 1 or 2 months deprivation of androgen. In aorta, the dose-response curve of CGRP was shifted to the left by 1 month of testosterone replacement. Response to norepinephrine was increased 4 months after orchidectomy and reversed by testosterone replacement in thoracic aorta. Orchidectomy did not affect CGRP- and acetylcholine-induced relaxation in all the arteries 4 months after orchidectomy. Compared to estrogen, the protective effects of androgen on vasoresponsiveness may be through inhibiting vasoconstriction, but is relatively weak.


Simple laparoscopic repair of perforated peptic ulcer without omental patch.
We evaluated the outcomes of laparoscopic repair of perforated peptic ulcers using simple closure only. This retrospective study included 79 patients who underwent laparoscopic repair of perforated peptic ulcers from January 2011 to February 2016. They were divided into two groups: repair with an omental patch and repair with simple closure only. All of them underwent peritoneal cavity lavage with several litres of warm normal saline. A closed suction drain system was placed for drainage of intra-abdominal abscess. Patients' age, sex, Boey score, perforation size, operation time, overall complications, and length of hospital stay were evaluated. A total of 79 patients diagnosed with perforated peptic ulcers who underwent emergency laparoscopic operations were enrolled in this study. Thirty patients underwent simple closure without an omental patch (group A), and 49 patients underwent simple closure with an omental patch (group B). Between the two groups, there were no statistically significant differences in the patients' age, size of perforation, and Boey score. However, the operation time was significantly different (p < 0.05) between the groups, with the average time being 84.4 min in group A and 106.65 min in group B. There was no statistically significant difference in the complication rate or the average length of hospital stay. No patient underwent reoperation for complications. Laparoscopic repair of a perforated peptic ulcer without an omental patch is a safe option and does not increase the morbidity and mortality rate.


Estimation of the inhibiting impact of abiraterone D4A metabolite on human steroid 21-monooxygenase (CYP21A2).
Abiraterone D4A metabolite, the product of 3β-hydroxysteroid dehydrogenase activity toward abiraterone, may serve as a potential antitumor agent for the treatment of prostate cancer. The main adverse effect of abiraterone is the disruption of corticosteroid biosynthesis, and the more pharmacologically active abiraterone D4A metabolite may have the same issues. We therefore estimated the inhibiting impact of the abiraterone D4A metabolite on one of the key corticosteroidogenic enzymes - human steroid 21-monooxygenase (CYP21A2). Molecular docking of D4A into the active site of CYP21A2 has been predicted to be similar to abiraterone binding with the enzyme. Abiraterone D4A metabolite, similar to abiraterone, induces type II spectral changes of CYP21A2. The spectral dissociation constant for the abiraterone D4A metabolite-CYP21A2 complex was calculated as 3.4 ± 0.5 μM. Abiraterone D4A metabolite demonstrates competitive/mixed type CYP21A2 inhibition with an inhibitory constant of 1.8 ± 0.8 μM, as obtained by Dixon plot. These results make it possible to predict the adverse effects of the new perspective candidate compound for antitumor therapy.


Optimization of AAV6 transduction enhances site-specific genome editing of primary human lymphocytes.
Adeno-associated virus serotype 6 (AAV6) is a valuable reagent for genome editing of hematopoietic cells due to its ability to serve as a homology donor template. However, a comprehensive study of AAV6 transduction of hematopoietic cells in culture, with the goal of maximizing ex vivo genome editing, has not been reported. Here, we evaluated how the presence of serum, culture volume, transduction time, and electroporation parameters could influence AAV6 transduction. Based on these results, we identified an optimized protocol for genome editing of human lymphocytes based on a short, highly concentrated AAV6 transduction in the absence of serum, followed by electroporation with a targeted nuclease. In human CD4+ T cells and B cells, this protocol improved editing rates up to 7-fold and 21-fold, respectively, when compared to standard AAV6 transduction protocols described in the literature. As a result, editing frequencies could be maintained using 50- to 100-fold less AAV6, which also reduced cellular toxicity. Our results highlight the important contribution of cell culture conditions for ex vivo genome editing with AAV6 vectors and provide a blueprint for improving AAV6-mediated homology-directed editing of human T and B cells.


Microscopic eye movements compensate for nonhomogeneous vision within the fovea.
Humans rely on the fovea, the small region of the retina where receptors are most densely packed, for seeing fine spatial detail. Outside the fovea, it is well established that a variety of visual functions progressively decline with eccentricity. In contrast, little is known about how vision varies within the central fovea, as incessant microscopic eye movements prevent isolation of adjacent foveal locations. Using a new method for restricting visual stimulation to a selected retinal region, we examined the discrimination of fine patterns at different eccentricities within the foveola. We show that high-acuity judgments are impaired when stimuli are presented just a few arcminutes away from the preferred retinal locus of fixation. Furthermore, we show that this dependence on eccentricity is normally counterbalanced by the occurrence of precisely directed microsaccades, which bring the preferred fixation locus onto the stimulus. Thus, contrary to common assumptions, vision is not uniform within the foveola, but targeted microscopic eye movements compensate for this lack of homogeneity. Our results reveal that microsaccades, like larger saccades, enable examination of the stimulus at a finer level of detail and suggest that a reduced precision in oculomotor control may be responsible for the visual acuity impairments observed in various disorders.


Age- and tissue-dependent expression of CYP2C23 in the rat.
A cDNA was isolated from a library prepared with 15-day-old rat liver RNA and was shown to correspond to CYP2C23 with some minor alterations which modified the open reading frame. The expression of CYP2C23 was examined in rat liver, kidney, lung and testis and during ontogenesis. An appreciable amount of CYP2C23 RNA was observed in liver and kidney but the age-dependent expression was quite different between these two tissues. In liver, expression reached its maximal value in early neonates and remained quite stable, while the increase was progressive in kidney before declining after 3 weeks of age. In the liver, classical inducers of cytochrome P-450 decreased the CYP2C23 RNA content. Experimental data confirm the classification of CYP2C23 as a constitutive member of the 2C subfamily and clearly establish its age- and tissue-dependent expression in rat.


An automated screening method for drugs and toxic compounds in human serum and urine using liquid chromatography-tandem mass spectrometry.
A fully automated screening using liquid chromatography-mass spectrometric method applying data-dependent acquisition was developed to identify toxicologically relevant substances in serum and urine. A library including more than 405 spectra of about 365 compounds (main drugs and important metabolites) was established. An easy to use program was created to automate and accelerate library search. Drugs were identified based on their relative retention times, molecular ions and fragment ions. Limits of detection were tested with 100 of the 365 compounds the majority of these were lower than 100μg/l (67%). The developed LC-MS-MS system seems to be a valuable alternative to other general unknown screening methods allowing fast and specific identification of drugs in serum and urine samples.


Minimal spanning tree analysis of biological structures.
A new approach to study order and disorder in biological membranes and more generally in biological structures is developed. It is based on a graph constructed on the set points representing the position of particles. From this graph, which is called the minimal spanning tree, it is possible to deduce two parameters, namely the average length m and the standard deviation sigma which are characteristic of the repartition to be studied. The use of a diagram involving both m and sigma makes it possible to determine the degree of order by taking a simple reading in the (m, sigma) plane.


Clinical implications of the American Joint Committee on Cancer (AJCC) 8th edition update in seminoma pT1 subclassification.
Seminoma accounts for 30-50% of testicular germ cell tumors (TGCT)-the most common solid malignancy in men aged 15-35 years. The American Joint Committee on Cancer (AJCC) 8th edition (2018) created the subclassifications pT1a (tumor size < 3 cm) and pT1b (≥ 3 cm), despite not being universally recognized. Rete testis invasion (RTI) and tumor size > 4 cm are considered features associated with a higher recurrence risk, but not formally used for staging. The authors propose further understanding the subclassification's potential impact in clinical practice, by summarizing current evidence and reviewing clinical cases in their institutions. All consecutive cases of seminoma stage I, pT1 treated in two institutions between January 2005 and December 2016 were included. Clinical data were retrieved, and variables were analyzed using SPSS. Relevant literature on the topic was reviewed. Seminoma pT1 was identified in 58 patients. By using newly AJCC criteria, 29 (50%) would have been staged as pT1a and 29 (50%) pT1b. Median age at diagnosis was similar (33 in pT1a vs 32 in pT1b). Median follow-up time 5.8 years. Almost half (45%) of pT1b patients had a tumor size < 4 cm. The majority of either pT1a or pT1b were treated with chemotherapy or radiotherapy, reflecting more intensive approaches in the past. Three retroperitoneal recurrences were recorded (two in pT1a, one in pT1b, all under surveillance protocol); no deaths occurred. RTI and extensive necrosis (EN) were associated with pT1b (P < 0.0001 and P = 0.023, respectively), known adverse biological features. In our population, the exploratory analysis of the newly created AJCC criteria showed no significant difference in recurrence or death, although pT1b was associated with adverse biomarkers, such as RTI and EN, but its clinical relevance remains incompletely understood. Our results confirm an excellent prognosis, regardless of subcategorization, thus a larger population and a longer follow-up time are needed to understand prospectively the impact of the recently updated criteria. We would recommend using the latest AJCC staging system, although the individual risk of relapse, long-term toxicities and patient preferences should be taken into account when considering surveillance or active treatment adjuvant options.


Enlarging a training set for genomic selection by imputation of un-genotyped animals in populations of varying genetic architecture.
The most common application of imputation is to infer genotypes of a high-density panel of markers on animals that are genotyped for a low-density panel. However, the increase in accuracy of genomic predictions resulting from an increase in the number of markers tends to reach a plateau beyond a certain density. Another application of imputation is to increase the size of the training set with un-genotyped animals. This strategy can be particularly successful when a set of closely related individuals are genotyped. Imputation on completely un-genotyped dams was performed using known genotypes from the sire of each dam, one offspring and the offspring's sire. Two methods were applied based on either allele or haplotype frequencies to infer genotypes at ambiguous loci. Results of these methods and of two available software packages were compared. Quality of imputation under different population structures was assessed. The impact of using imputed dams to enlarge training sets on the accuracy of genomic predictions was evaluated for different populations, heritabilities and sizes of training sets. Imputation accuracy ranged from 0.52 to 0.93 depending on the population structure and the method used. The method that used allele frequencies performed better than the method based on haplotype frequencies. Accuracy of imputation was higher for populations with higher levels of linkage disequilibrium and with larger proportions of markers with more extreme allele frequencies. Inclusion of imputed dams in the training set increased the accuracy of genomic predictions. Gains in accuracy ranged from close to zero to 37.14%, depending on the simulated scenario. Generally, the larger the accuracy already obtained with the genotyped training set, the lower the increase in accuracy achieved by adding imputed dams. Whenever a reference population resembling the family configuration considered here is available, imputation can be used to achieve an extra increase in accuracy of genomic predictions by enlarging the training set with completely un-genotyped dams. This strategy was shown to be particularly useful for populations with lower levels of linkage disequilibrium, for genomic selection on traits with low heritability, and for species or breeds for which the size of the reference population is limited.


Gender differences in glenoid anatomy: an anatomic study.
Gender differences in glenoid anatomy have not been well studied in the current literature. Previous literature demonstrates a mismatch between glenoid anatomy and glenoid implants for shoulder replacements. This may have clinical implications in that glenoid loosening after shoulder arthroplasty has been cited as a frequent cause of poor performance of shoulder implants, and perhaps the most common indication for revision. The purpose of this study was to determine any gender differences in the size and overall shape of the glenoid. Eleven measurements were taken of 363 human scapular bone specimens (equal proportions of females to males and blacks to whites). Glenoid height and width, glenoid notch location, and depth were measured for each specimen using calipers. In addition, the authors developed a classification system to describe anterior glenoid notch morphology. There was a significant difference between female and male specimens for each dimension measured (P < 0.05). Height to width ratios were also significantly different comparing men to women (P < 0.05). These differences resulted in a rounder male glenoid and more oval female glenoid. Our results showed that 80.4% of females had an anterior glenoid notch compared to only 57.6% of males. There was a significant difference between female and male specimens in the location of the anterior glenoid notch: 36.7% from the top of the glenoid in female specimens, and 28.9% in males (P < 0.0001). The clear difference between male and female glenoid anatomy may be important in various shoulder surgeries.


Telephone-linked care for cancer symptom monitoring: a pilot study.
The purpose of this pilot project was to explore the feasibility of using a telephone-based computerized system to monitor postchemotherapy symptoms and to test the mechanism of generating alert communications to healthcare providers about symptoms that are poorly controlled. Twenty-seven patients with cancer participated in the study by calling the telephone-linked care (TLC) system daily during a single cycle of chemotherapy and reporting on seven common chemotherapy-related symptoms. Using selected symptom data, symptoms that met a preset threshold for severity generated a fax notification of the patient's symptom pattern to the physician. Patients then were interviewed about their satisfaction with TLC and about suggestions for improvement. The study demonstrated that TLC is easy to learn and use and that it captures daily symptom information from patients in their homes. A majority of patients experienced symptoms that were severe enough to generate symptom-alert faxes. Patient satisfaction with TLC was high. The technique, TLC voice, and the duration of the calls were acceptable to patients. There were few technical problems. The TLC system has the potential to improve dramatically symptom monitoring and symptom care of patients with cancer at home. Further testing is needed, but the TLC chemotherapy monitoring application shows promise for improving supportive-care service delivery for cancer patients. In its initial test, the TLC chemotherapy monitoring application has been shown to be highly acceptable to patients, able to generate useful symptom data, and able to generate faxed alerts to healthcare providers, thus improving communication about poorly controlled symptoms.


Diazepam in high doses is effective in schizophrenia.
1. Diazepam in high doses, up to 400 mg per day, was administered to paranoid schizophrenic patients in a double-blind placebo-controlled study. 2. The effects of treatment were assessed by the following: the Brief Psychiatric Rating Scale (BPRS); the Clinical Global Impressions Scale (CGI); the Schizophrenia Subscale of the Present State Examination (SS-PSE); the Simpson-Angus Rating Scale (SARS) for extrapyramidal symptoms; the Nurses' Observation Scale for Inpatient Evaluation (NOSIE); and a 90 item Self-Assessment Questionnaire (SCL-90). 3. Within a few hours to a few days from the onset of diazepam treatment both positive (such as auditory hallucinations and persecutory delusions) and negative (such as emotional withdrawal and blunted affect) schizophrenic symptoms were dramatically eliminated in 5 out of the 6 patients.


Isopentenoid synthesis in isolated embryonic Drosophila cells. Farnesol catabolism and omega-oxidation.
Kc cells divert minimally 40% of their mevalonate carbon to n-fatty acids and unidentified compounds covalently linked to macromolecules (Havel, C., Rector, E. R., II, and Watson, J. A. (1986) J. Biol. Chem. 261, 10150-10156). Furthermore mevalonate carbon diversion appears to occur at the polyprenyl 1-pyrophosphate level. This report summarizes initial efforts to define the mevalonate carbon diversion pathway. We demonstrate that Kc cell extracts readily metabolize [14C]farnesyl 1-pyrophosphate and [14C]farnesol, via common intermediates, to identical 14C-products. Two of the major 14C-products were identified as trans,trans-3,7,11-trimethyl-2,6,10-dodecatrien-1,12-dioic acid and trans-3,7-dimethyl-2,6-decadien-1,10-dioic acid. Similar acids were also synthesized by supplemented rat liver extracts incubated with [14C]farnesol. We conclude that (a) mevalonate carbon diversion at the level of polyprenyl 1-pyrophosphate is a viable metabolic strategy, (b) polyprenols are oxidized to alpha,omega-prenyl dicarboxylic acids which are catabolized from the omega-terminus, and (c) this metabolic process is not limited to insect cells.


Leucine-Rich Amelogenin Peptide (LRAP) Uptake by Cementoblast Requires Flotillin-1 Mediated Endocytosis.
Basic, pre-clinical, and clinical studies have documented the potential of amelogenin, and its variants, to affect cell response and tissue regeneration. However, the mechanisms are unclear. Thus, the aim of the present study was to identify, in cementoblasts, novel binding partners for an alternatively spliced amelogenin form (Leucine-Rich Amelogenin Peptide-LRAP), which is supposed to act as a signaling molecule in epithelial-mesenchymal interactions. LRAP-binding protein complexes from immortalized murine cementoblasts (OCCM-30) were achieved by capture affinity assay (GST pull down) and proteins present in these complexes were identified by mass spectrometry and immunoblotting. Flotillin-1, which functions as a platform for signal transduction, vesicle trafficking, endocytosis, and exocytosis, was identified and confirmed by co-precipitation and co-localization assays as a protein-binding partner for LRAP in OCCM-30 cells. In addition, we found that exogenously added GST-LRAP recombinant protein was internalized by OCCM-30 cells, predominantly localized in the perinuclear region and, that inhibition of flotillin1-dependent functions by small interference RNA (siRNA) methodology significantly affected LRAP uptake and its biological properties on OCCM-30 cells, including LRAP effect on the expression of genes encoding osteocalcin (Ocn), bone sialoprotein (Bsp), and runt-related transcription factor 2 (RunX2). In conclusion, LRAP uptake by cementoblast involves flotillin-assisted endocytosis, which suggests an involvement of LRAP in lipid-raft-dependent signaling pathways which are mediated by flotillin-1. J. Cell. Physiol. 232: 556-565, 2017. © 2016 Wiley Periodicals, Inc.


Sustained Human Background Exposure to Acrolein Evidenced by Monitoring Urinary Exposure Biomarkers.
This study investigates a potential correlation between the intake of heat-processed food and the excretion of the acrolein (AC) biomarkers N-acetyl-S-(3-hydroxypropyl)-l-cysteine (HPMA) and N-acetyl-S-(carboxyethyl)-l-cysteine (CEMA) based on two human studies. Human exposure to AC is monitored using the AC-related mercapturic acids HPMA and CEMA in the urine of a) non-smoking volunteers under defined living conditions and b) of non-smoking volunteers on unrestricted or vegan diet under free living conditions. Free living volunteers in part show markedly enhanced urinary excretions of HPMA and CEMA. The intake of heat-processed food does not influence AC-related biomarker excretion. Incidentally enhanced urinary exposure biomarker levels appear to suggest AC exposure possibly from open fire, barbecuing, or tobacco smoke. However, kinetics of urinary biomarkers related to tobacco and other potential smoke exposure, do not correlate with those observed for HPMA and CEMA. This study is the first to convincingly show a sustained and substantial background exposure to AC in non-smoking humans, clearly independent from uptake of heat-processed foods. The data strongly point to endogenous AC generation by pathways of mammalian and/or microbial metabolism as yet not taken into consideration.


Safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for pediatric acute myeloid leukemia: a report from the Children's Oncology Group.
While gemtuzumab ozogamicin (GTMZ) is commonly used in the treatment of acute myeloid leukemia (AML) in combination with standard chemotherapy agents, the pediatric maximum-tolerated dose (MTD) of GMTZ in combination with chemotherapy has not been determined. The Children's Oncology Group AAML00P2 trial sought to define the MTD of GMTZ in combination with cytarabine and mitoxantrone and cytarabine and l-asparaginase chemotherapy regimens. The MTD for GMTZ in combination with cytarabine and mitoxantrone was 3 mg/m(2) while the MTD in combination with cytarabine and l-asparaginase was 2 mg/m(2). Toxicities observed in both treatment regimens were typical of those seen in the relapsed AML setting and consisted primarily of infectious complications. The overall remission response rate (mean +/- SE) was 45% +/- 15% and the 1 year event-free survival and overall survival estimates were 38% +/- 14% and 53% +/- 15%, respectively. This trial determined the pediatric MTD for GMTZ with two commonly used AML chemotherapy combinations. Based on these results, an ongoing phase III trial conducted within the Children's Oncology Group is evaluating the effect of GMTZ when added to standard AML therapy.


Postpartum scarcity-adversity disrupts maternal behavior and induces a hypodopaminergic state in the rat dam and adult female offspring.
Postpartum adversity is among the strongest predictors for the emergence of postpartum depression (PPD) in humans and a translational risk factor employed in rodent models. Parental care is disturbed under conditions of environmental adversity, including low resource environments, and in PPD. Nonetheless, the neural changes associated with these adversity-induced maladaptive behavioral states remain poorly understood. Postpartum scarcity-adversity can be modeled in rats by providing the dam with limited bedding and nesting (LBN) materials, which mimics the effects of a stressful low resource environment in potentiating maltreatment/neglect in humans. Indeed, LBN exposure from postpartum days (PD) 2-9 increased adverse maternal behaviors, impaired pup retrieval, and increased passive stress coping responses. Since mesolimbic dopamine (DA) activity is an important mechanism for motivated maternal behavior and is implicated in PPD, we assessed the impact of postpartum scarcity-adversity on in vivo electrophysiological properties of ventral tegmental area (VTA) DA neurons at two timepoints. We found reduced numbers of active VTA DA neurons in LBN dams at PD 9-10 but not PD-21, suggesting a transient impact on VTA population activity in LBN dams. Finally, we assessed the impact of early life scarcity-adversity on VTA DA function by conducting VTA recordings in adult female offspring and found a long-lasting attenuation in DA activity. These findings highlight a link between adversity-induced deficits in DA function and disrupted maternal behavior, suggesting the VTA/mesolimbic DA system as a potential mechanism by which postpartum scarcity-adversity drives aberrant maternal behavior, and early postnatal programming of adult VTA function in the offspring.


Characterization of organic matter of plants from lakes by thermal analysis in a N2 atmosphere.
Organic matter (OM) has been characterized using thermal analysis in O2 atmospheres, but it is not clear if OM can be characterized using slow thermal degradation in N2 atmospheres (STDN). This article presents a new method to estimate the behavior of OM in anaerobic environment. Seventeen different plants from Tai Lake (Ch: Taihu), China were heated to 600 °C at a rate of 10 °C min(-1) in a N2 atmosphere and characterized by use of differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). DSC chromatograms were compared with 9 standard compounds. Seven peaks were observed in DSC chromatograms, 2 main peaks strongly correlated with biochemical indices, and one main peak was a transitional stage. Energy absorbed by a peak at approximately 200 °C and total organic carbon were well correlated, while energy absorbed at approximately 460 °C was negatively correlated with lignin content. Presence of peaks at approximately 350 and 420 °C varied among plant biomass sources, providing potential evidence for biomass identification. Methods of STDN reported here were rapid and accurate ways to quantitatively characterize OM, which may provide useful information for understanding anaerobic behaviors of natural organic matters.


Postsplenectomy thrombocytosis: its association with mesenteric, portal, and/or renal vein thrombosis in patients with myeloproliferative disorders.
During the past two years, postoperative thromboses of parts or all of the splanchnic venous circulation have developed in four of 30 patients with myeloproliferative disorders who have undergone splenectomy at our institution. The patients' courses were marked by platelet abnormalities, both quantitative and qualitative. In an attempt to avoid this complication, aspirin and low-dose heparin sodium have been administered and there has been no evidence of thrombosis in the four patients so managed.


Retraction: Light-triggered nitric oxide release and targeted fluorescence imaging in tumor cells developed from folic acid-graft-carboxymethyl chitosan nanospheres.
[This retracts the article DOI: 10.1039/C4RA03034F.].


In vitro susceptibility of recent clinical isolates of pneumococci to the investigational cephalosporin cefditoren.
From February to June 2000, 2,597 isolates of Streptococcus pneumoniae were prospectively collected from 146 clinical laboratories across the United States (US) and tested to evaluate the in vitro activity of cefditoren, an investigational oral cephalosporin. In all, 2,492 isolates (96.0%) had a cefditoren MIC of 0.5 microg/mL or less, 74 isolates (2.8%) had an MIC of 1 microg/mL, 30 isolates (1.2%) had an MIC of 2 microg/mL, and 1 isolate (<0.1%) had an MIC of 4 microg/mL. Among the beta-lactams tested, the rank order of potency (MIC(90,) microg/mL) was cefditoren (0.5) > ceftriaxone (1) > amoxicillin-clavulanate (2) > cefuroxime (4) > cefprozil (8). Penicillin-resistant isolates (n = 443; 17.1%) were inhibited by lower concentrations (MIC(90,) microg/mL; MIC range,) of cefditoren (1; 0.03-4) than ceftriaxone (2; 0.25- > 2), amoxicillin-clavulanate (8; 0.5- > 8), cefuroxime (16; 2- > 16), and cefprozil (32; 2- > 32). Cefditoren MIC(90)s against cefuroxime-resistant (n = 640) and ceftriaxone-resistant (n = 89) isolates were 1 and 2 microg/mL, respectively. All isolates with reduced susceptibility to cefditoren (MIC, 2 or 4 microg/mL; n = 31) were resistant to penicillin, cefuroxime, and ceftriaxone. The potent in vitro activity of cefditoren against a recent US collection of pneumococci as demonstrated in this study supports its continued development for oral empiric therapy in outpatients with respiratory tract infections.


Characterization of a new aerosol antibiotic/adjuvant combination for the treatment of P. aeruginosa lung infections.
The lack of novel classes of antibiotics as well as the constant increase of multidrug resistant bacteria are leaving the clinicians disarmed to treat bacterial infections, especially those caused by Gram-negative pathogens. Among all the investigated solutions, the design of adjuvants able to enhance antibiotics activities appears to be one of the most promising. In this context, a polyamino-isoprenyl derivative has been recently identified to be able to potentiate, at a very low concentration the activity of doxycycline against P. aeruginosa bacterial strains by increasing its intracellular concentration. On the other hand, since aerosol therapy allows a rapid drug administration and targets the respiratory system by avoiding the first pass effect and minimizing undesirable systemic effects, we have developed the first adjuvant/antibiotic combination in an aerosolized form and demonstrated the feasibility of such an approach. Thus, combination aerosol droplets have been demonstrated in sizes suitable for inhalation (3.4 and 4.4 μm mass median aerodynamic diameter and 54 and 60% of the aerodynamic particle size distribution less than 5 μm, as measured for the adjuvant NV716 and doxycycline, respectively and with properties (stoichiometric 1:1 ratio of NV716 salt to drug) that would support further development as an inhaled dosage form. Taken together, our results suggest that these molecules could be successfully delivered at the requested concentration in the lungs and then able to decrease drug consumption as well as increase treatment efficacy.


Screened Attention Deficit/Hyperactivity Disorder as a Predictor of Substance Use Initiation and Escalation in Early Adulthood and the Role of Self-Reported Conduct Disorder and Sensation Seeking: A 5-Year Longitudinal Study with Young Adult Swiss Men.
Attention deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and sensation seeking (SS) have been consistently related to a higher risk of substance use (SU) and substance use disorder (SUD). To investigate the relationship between ADHD and prevalence rates in males at age 20 and age 25, the initiation of SU and SUD after age 20, and the escalation of SU from age 20 to age 25, and to explore the role of CD and SS in the relation of ADHD with SU and SUD initiation and escalation. Data were obtained as part of the Cohort Study on Substance Use Risk Factors (C-SURF), which focused on young Swiss men aged 20 years at baseline and 25 years at follow-up. Participants who screened positive for ADHD at baseline exhibited a higher rate of SU and SUD than participants who screened negative. The presence of ADHD symptoms at age 20 predicted initiation of all SU between age 20 and age 25, except for alcohol and smoking. After controlling for self-reported CD and SS, ADHD still predicted this late initiation of use of hallucinogens, meth-/amphetamines, and ecstasy/MDMA; non-medical use of ADHD medication and sedatives, and alcohol use disorder (AUD). No escalation of weekly drinking and smoking or annual cannabis use was observed from age 20 to age 25. Screened-positive ADHD is an independent predictor of late SU and AUD, along with self-reported CD and SS. From a public health perspective, identifying ADHD is not only important in childhood and adolescence but also in early adulthood to guide specific interventions to lower risks of drug use initiation and the development of AUD in early adulthood.


A comb laser-driven DWDM silicon photonic transmitter based on microring modulators.
We demonstrate concurrent multi-channel transmission at 10 Gbps per channel of a DWDM silicon photonic transmitter. The DWDM transmitter is based on a single quantum dot comb laser and an array of microring resonator-based modulators. The resonant wavelengths of microrings are thermally tuned to align with the wavelengths provided by the comb laser. No obvious crosstalk is observed at 240 GHz channel spacing.


Risk Factors for and Trends in Isoniazid Monoresistance at Diagnosis of Tuberculosis-United States, 1993-2016.
Resistance to isoniazid (INH) only (monoresistance), with drug susceptibility to rifampin, pyrazinamide, and ethambutol at diagnosis of tuberculosis (TB) disease, can increase the length of treatment. To describe US trends in INH monoresistance and associated patient characteristics. We performed trend and cross-sectional analyses of US National Tuberculosis Surveillance System surveillance data. We used Joinpoint regression to analyze annual trends in INH monoresistance and logistic regression to identify patient characteristics associated with INH monoresistance. Culture-positive cases reported to National Tuberculosis Surveillance System during 1993-2016 with drug susceptibility test results to INH, rifampin, pyrazinamide, and ethambutol. (1) Trends in INH monoresistance; (2) odds ratios for factors associated with INH monoresistance. Isoniazid monoresistance increased significantly from 4.1% of all TB cases in 1993 to 4.9% in 2016. Among US-born patients, INH monoresistance increased significantly from 2003 onward (annual percentage change = 2.8%; 95% confidence interval: 1.4-4.2). During 2003-2016, US-born persons with INH-monoresistant TB were more likely to be younger than 65 years; to be Asian; to be human immunodeficiency virus-infected; or to be a correctional facility resident at the time of diagnosis. Among non-US-born persons, INH resistance did not change significantly during 1993-2016 (annual percentage change = -0.3%; 95% confidence interval: -0.7 to 0.2) and was associated with being aged 15 to 64 years; being Asian, black, or Hispanic; or having a previous history of TB. INH-monoresistant TB has been stable since 1993 among non-US-born persons; it has increased 2.8% annually among US-born persons during 2003-2016. Reasons for this increase should be further investigated.


Flow-function dissociation following an acute dose of cocaine: effect of captopril on coronary flow.
Acute administration of cocaine leads to left ventricular dysfunction and a decrease in coronary blood flow. This experiment studied the relationship between function and flow over time in cocaine heart disease and examined the effects of captopril on this relationship. Dogs anesthetized with pentobarbital (n = 13) were given a 3 mg/kg body weight intravenous bolus of cocaine followed by a 7 mg/kg infusion over 10 minutes. Animals were then randomly assigned to receive either captopril (0.5 mg/kg infused over 5 minutes, followed by 0.5 mg/kg/h) or an equivalent volume of saline beginning 15 minutes after cocaine administration. Coronary blood flow (radioactive microspheres and Doppler flow probes) and left ventricular function (two-dimensional echocardiogram and dP/dt) were monitored for 2 hours. Within 15 minutes, cocaine caused a drop in dP/dt by 39% to 42% and in coronary blood flow by 35%. Cocaine also caused an increase in left ventricular end-diastolic pressures in both groups. Cocaine resulted in prolongation of an index of end-diastolic isovolumic relaxation time (tau) from a baseline of 34 milliseconds to 56 milliseconds at 15 minutes after cocaine administration in the control group and from a baseline of 35 milliseconds to 49 milliseconds in the captopril group (P < 0.05). By 2 hours after therapy, the tau in the control group remained elevated, whereas in the captopril group it returned toward baseline. At 2 hours of observation, systolic function recovered while coronary flow remained depressed. There was no difference between the captopril and control groups in coronary blood flow or systolic cardiac function at any time during the study. Cocaine caused left ventricular systolic and diastolic dysfunction as well as reduced coronary blood flow. At 2 hours there is a dissociation of systolic function, which recovers, and of coronary blood flow, which does not. Captopril had no effect on coronary blood flow or systolic left ventricular function following cocaine administration.


RNA stabilization and continued RNA processing following nuclear dissolution in maturing Xenopus laevis oocytes.
The Xenopus laevis oocyte provides a convenient system for studying cell cycle-induced changes in RNA metabolism. Initially arrested at first meiotic prophase, it can be induced in vitro to undergo maturation by incubation in the presence of progesterone, progressing to second meiotic metaphase over the course of several hours. The dissolution of the nuclear membrane before the onset of first meiotic metaphase (also known as germinal vesicle breakdown, or GVBD) provides a convenient indication of the overall rate of maturation. It is reported that all ordinarily unstable classes of nuclear RNA show substantial increases in stability following GVBD. However, some radioactivity in rRNA precursors disappears following GVBD and this is quantitatively accounted for by the appearance of label in mature rRNA. These results suggest continued processing of rRNA precursors after GVBD.


Disruption of canine jejunal interdigestive myoelectrical activity by artificial ileocolonic sphincter. Studies of intestinal motor response to surgically fashioned sphincter substitute.
We studied the effects of an ileocolonic sphincter substitute on canine small intestine motor activity. Recordings of fasting and postprandial myoelectrical activity were performed in three groups of animals in whom the following procedures had been performed: (1) electrode placement alone, intestinal continuity undisturbed (controls); (2) ileocolonic sphincter substitute fashioned in mid-jejunum; and (3) transection and reanastomosis at a similar location in mid-jejunum. Transection alone resulted in a decrease in slow-wave frequency, a shortening of the period of the interdigestive myoelectrical complex (IDMEC) and a prolongation of phase III of the IDMEC in the jejunum distal to the site of transection. The IDMEC period was also shorter at proximal electrode sites, but the incidence of IDMEC phase III complexes was similar on either side of the transection. However, in those animals in whom a sphincter substitute had been fashioned at the site of the transection, the incidence of IDMEC phase III complexes was significantly suppressed in the proximal intestine; IDMEC phase III frequency per hour (mean +/- SD transection vs sphincter substitute) was 0.59 +/- 0.20 vs 0.23 +/- 0.24, P less than 0.002; 0.61 +/- 0.24 vs 0.28 +/- 0.30, P less than 0.006; 0.61 +/- 0.24 vs 0.29 +/- 0.30, P = 0.008, at electrodes 10, 35, and 85 cm proximal to the sphincter substitute, respectively. In addition, the sphincter-substitute animals alone demonstrated, during fasting, recurrent propagated bursts of spike clusters and occasional prolonged spike bursts in electrodes proximal to the sphincter substitute.(ABSTRACT TRUNCATED AT 250 WORDS)


Cerebral metastases in patients with ovarian cancer treated with chemotherapy.
Cerebral metastases are considered an uncommon complication of ovarian carcinoma. In a series of 52 patients treated with platinum, Adriamycin, and cyclophosphamide combination chemotherapy, 6 patients developed cerebral metastases, an incidence (11.6%) higher than that reported by others. The median age of the patients with cerebral metastases was similar to that of patients without this complication. Cerebral metastases occurred as site of first relapse in three of six patients. Only one patient had extraperitoneal disease prior to chemotherapy and four of the six patients had attained a complete response following chemotherapy. Cerebral relapse occurred at 0, 21, 27, 30, 34, and 36 months from original diagnosis of ovarian carcinoma and 0, 9, 11, 19, 25 and 29 months following first treatment with combination chemotherapy. The median survival was 33 months from diagnosis and 28.5 months from first treatment with chemotherapy. This compares with a median survival from diagnosis for the entire series of 30 months (28 months from first treatment). The result of treatment of established metastases was poor. Survival from diagnosis of cerebral metastases was 2, 2, 3, 6, 10, and 41 + months. If other series confirm these findings consideration may need to be given to prophylactic central nervous system radiotherapy for patients achieving complete remission after systemic chemotherapy.


Human oligodendrocytes in dissociated cell culture.
Human oligodendrocytes have been successfully maintained in cell cultures for 14 weeks using a modification of a method used previously for animal brain cell cultures. Dissociated cell cultures from spinal cords of human foetuses of 10 to 20 weeks gestional age were investigated for up to 98 days. Oligodendrocytes were identified by monoclonal human antiserum specific for myelin-associated glycoprotein, by polyclonal rabbit antiserum against myelin basic protein, and by the mouse monoclonal antibody I6G1. Astrocytes were identified by polyclonal antibodies against glial fibrillary acidic protein. Immunocytochemical cell identification was corroborated by electron microscopy, by which glial cells were investigated both in situ and in culture. Immunocytochemical staining of myelin-associated glycoprotein showed specifically labelled oligodendrocytes on electron microscopy. The present study indicates that human oligodendrocytes, a putative target in demyelinating disease, can be studied in dissociated cell culture of human foetal spinal cord for several weeks in vitro under stable conditions.


Plant Polyphenols: Potential Antidotes for Lead Exposure.
Lead is one of the most common heavy metal elements and has high biological toxicity. Long-term lead exposure will induce the contamination of animal feed, water, and food, which can cause chronic lead poisoning including nephrotoxicity, hepatotoxicity, neurotoxicity, and reproductive toxicity in humans and animals. In the past few decades, lead has caused widespread concern because of its significant threat to health. A large number of in vitro and animal experiments have shown that oxidative stress plays a key role in lead toxicity, and endoplasmic reticulum (ER) stress and the mitochondrial apoptosis pathway can also be induced by lead toxicity. Therefore, plant polyphenols have attracted attention, with their advantages of being natural antioxidants and having low toxicity. Plant polyphenols can resist lead toxicity by chelating lead with their special chemical molecular structure. In addition, scavenging active oxygen and improving the level of antioxidant enzymes, anti-inflammatory, and anti-apoptosis are also the key to relieving lead poisoning by plant polyphenols. Various plant polyphenols have been suggested to be useful in alleviating lead toxicity in animals and humans and are believed to have good application prospects.


Intracellular metabolism and persistence of the anti-human immunodeficiency virus activity of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine, a novel thymidine analog.
The therapeutic benefits of current antiretroviral therapy are limited by the evolution of drug-resistant virus and long-term toxicity. Novel antiretroviral compounds with activity against drug-resistant viruses are needed. 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine (4'-Ed4T), a novel thymidine analog, has potent anti-human immunodeficiency virus (HIV) activity, maintains considerable activity against multidrug-resistant HIV strains, and is less inhibitory to mitochondrial DNA synthesis in cell culture than its progenitor stavudine (D4T). We investigated the intracellular metabolism and anti-HIV activity of 4'-Ed4T. The profile of 4'-Ed4T metabolites was qualitatively similar to that for zidovudine (AZT), with the monophosphate metabolite as the major metabolite, in contrast to that for D4T, with relatively poor formation of total metabolites. The first phosphorylation step for 4'-Ed4T in cells was more efficient than that for D4T but less than that for AZT. The amount of 4'-Ed4T triphosphate (4'-Ed4TTP) was higher than that of AZTTP at 24 h in culture. There was a dose-dependent accumulation of 4'-Ed4T diphosphate and 4'-Ed4TTP on up-regulation of thymidylate kinase and 3-phosphoglycerate kinase expression in Tet-On RKO cells, respectively. The anti-HIV activity of 4'-Ed4T in cells persisted even after 48 h of drug removal from culture in comparison with AZT, D4T, and nevirapine (NVP). The order of increasing persistence of anti-HIV activity of these compounds after drug removal was 4'-Ed4T > D4T > AZT > NVP. In conclusion, with the persistence of 4'-Ed4TTP and persistent anti-HIV activity in cells, we anticipate less frequent dosing and fewer patient compliance issues than for D4T. 4'-Ed4T is a promising antiviral candidate for HIV type 1 chemotherapy.


Radiofrequency catheter ablation of accessory pathways in the dog: the Italian experience (2008-2016).
Accessory pathways (APs) in dogs are mostly right-sided, display nondecremental conduction, and mediate atrioventricular reciprocating tachycardias (AVRTs). Radiofrequency catheter ablation (RFCA) is considered the first-line therapy in human patients to abolish electrical conduction along APs. Seventy-six consecutive client-owned dogs. Retrospective study to describe the precise anatomical distribution and the electrophysiologic characteristics of APs in a large population of dogs and to evaluate long-term success and complication rates of RFCA. Eighty-three APs were identified in 76 dogs (92.1% with single APs and 7.9% with multiple APs); 96.4% were right-sided, 3.6% left-sided. Conduction along the APs was unidirectional and retrograde in 68.7% of the cases and bidirectional in 31.3%. Accessory pathways presented retrograde decremental properties in 6.5% of the cases. They mediated orthodromic AVRT in 92.1% of the cases and permanent junctional reciprocating tachycardia in 6.5%. In one case, no AVRT could be induced. In 97.4% of dogs, RFCA was attempted with an acute success rate of 100%. In 7.7% of cases, recurrence of the tachycardia occurred within 18 months, followed by a second definitively successful ablation. A major complication requiring pacemaker implantation was identified in 2.6% of dogs. Accessory pathway distribution and electrophysiologic properties in these 76 dogs were similar to previous report. Long-term success and complication rates of RFCA in dogs appeared very similar to results of humans. Radiofrequency catheter ablation of APs can be performed with a high success rate and low incidence of complications.


Interleukin 1 and tumor necrosis factor potentiate angiotensin II- and calcium ionophore-stimulated prostaglandin E2 synthesis in rat renal mesangial cells.
In resting mesangial cells, angiotensin II and the calcium ionophore A23187 stimulated prostaglandin E2 (PGE2) formation. After pretreatment with interleukin 1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha), which are themselves potent stimuli for PGE2 synthesis, mesangial cells displayed an amplified response to angiotensin II and A23187. The cytokine-induced effects occurred in a time- and dose-dependent manner and were attenuated by actinomycin D, cycloheximide and dexamethasone. IL-1 beta and TNF alpha treatment also increased the amount of arachidonic acid released after stimulation of cells with angiotensin II and A23187. In addition, IL-1 beta but not TNF alpha treatment augmented the formation of PGE2 from exogenous arachidonic acid by mesangial cells. Furthermore, the conversion of prostaglandin H2 to PGE2 was not changed by IL-1 beta and TNF alpha. These results suggest that IL-1 beta and TNF alpha exert a priming effect on PGE2 production in mesangial cells.


The effect of luminance values of the edge between regions on figure-ground perception.
The present study examined whether luminance values of an edge between regions affect figure-ground perception. A dark-gray or light-gray region was presented on the left (or upper) or right (or lower) side of an edge. Observers reported which region was perceived as a figure. The results in the 0.2° edge width condition showed that dark-gray regions with low luminance edges were perceived as a figure significantly more often than dark-gray regions with high luminance edges. The edge luminance effect occurred, partly occurred, and did not occur when the edge widths were 0.2, 0.5, and 0.8° of visual angle, respectively. These results showed that luminance values of the edge between the regions affected figure-ground perception, and that regions with luminance values closer to that of the edge between the regions were perceived as a figure more often, but only when the edge width was narrow. The edge luminance effect occurred less often as the edge width was increased and would be attributed to similarity grouping between edge and region.


Single is better than double: theoretical and experimental comparison between two thermal poling configurations of optical fibers.
Thermal poling, a technique to create permanently effective second-order susceptibility in silica optical fibers, has a suite of applications including frequency conversion and mixing for high harmonic generation and phase sensitive amplification, optical switching and modulation, and polarization-entangled photon pair generation. In this work, we compare both theoretically and experimentally two different electrode configurations for poling optical fibers, namely double-anode and single-anode, for two different geometries of the cladding holes. This analysis reveals that the single-anode configuration is optimal, both for the absolute value of effective χ (2) created in the fiber core, and for the simplification of the fiber fabrication process.


Sociocultural perspectives on suicidal behaviour at the Coast Region of Kenya: an exploratory qualitative study.
To explore perceived sociocultural factors that may influence suicidality from key informants residing in coastal Kenya. We used an exploratory qualitative study design. Mombasa and Kilifi Counties of Coastal Kenya. 25 key informants including community leaders, professionals and community members directly and indirectly affected by suicidality. We conducted in-depth interviews with purposively selected key informants to collect data on sociocultural perspectives of suicide. Thematic analysis was used to identify key themes using both inductive and deductive processes. Four key themes were identified from the inductive content analysis of 25 in-depth interviews as being important for understanding cultural perspectives related to suicidality: (1) the stigma of suicidal behaviour, with suicidal victims perceived as weak or crazy, and suicidal act as evil and illegal; (2) the attribution of supernatural causality to suicide, for example, due to sorcery or inherited curses; (3) the convoluted pathway to care, specifically, delayed access to biomedical care and preference for informal healers; and (4) gender and age differences influencing suicide motivation, method of suicide and care seeking behaviour for suicidality. This study provides an in depth understanding of cultural factors attributed to suicide in this rural community that may engender stigma, discrimination and poor access to mental healthcare in this community. We recommend multipronged and multilevel suicide prevention interventions targeted at changing stigmatising attitudes, beliefs and behaviours, and improving access to mental healthcare in the community.


Influence of teniposide (VM-26) on radiation-induced damage to mouse spermatogenesis: a flow cytometric evaluation.
The effect of teniposide (VM-26) 0.05 mg/kg body weight treatment on spermatogenesis of mice exposed to 0, 0.5, 1, 2, and 3 Gy gamma-radiation was evaluated flow cytometrically. Whole body irradiation with 1 to 3 Gy resulted in a significant decline in testis weight from Day 14 to 35 post-irradiation depending on the exposure dose. Treatment of mice with teniposide before irradiation advanced the decline in testicular weight by several days, especially at 3 Gy, where a significant decline in testicular weight was observed at Day 7 post-irradiation when compared with the double distilled water (DDW)+irradiation group. The relative percentage of the 2C population declined significantly in the VM-26+irradiation group in comparison with the DDW+irradiation group at various post-irradiation time periods depending on the exposure dose. A significant depletion in the relative percentage of S-phase cells was observed as early as Day 1 post-irradiation in the VM-26+irradiation group when compared with the DDW+irradiation group after exposure to 1 to 3 Gy. This decline continued up to Day 21 post-irradiation after exposure to 2 Gy. The relative percentage of primary spermatocytes showed a consistent decline after exposure to various doses of gamma-radiation in the VM-26+irradiation group when compared with the DDW+irradiation group at different time periods, with a few exceptions, especially at higher doses. The pattern of decline in the relative percentage of round spermatids was similar to that of primary spermatocytes, where a significant decline was observed at various post-irradiation time periods in the VM-26+irradiation group in comparison with the DDW+irradiation group. These changes in the relative germ cell percentages are manifested as alterations in the ratios of various germ cell populations. The 4C:2C ratio declined consistently from Day 1 to Day 70 post-irradiation in the VM-26+irradiation group at all exposure doses. Similarly, the 4C:S-phase ratio in the VM-26+irradiation group also showed a significant decline at different post-irradiation time periods when compared with the DDW+irradiation group depending on the exposure dose. The reduction observed in the relative percentages of various cell populations was higher in the combination group when compared with the DDW+irradiation controls, indicating potentiation of damage to male germ cells by teniposide treatment before irradiation.


COVID-19 resulting in bilateral pulmonary emboli and a right ventricular thrombus: association or causation? A case report.
SARS-CoV-2 is a novel viral illness originating out of Wuhan China in late 2019. This global pandemic has infected nearly 3 million people and accounted for 200 000 deaths worldwide, with those numbers still climbing. We present a 54-year-old patient who developed respiratory failure requiring endotracheal intubation from her infection with SARS-CoV-2. This patient was subsequently found to have a right ventricular thrombus and bilateral pulmonary emboli, likely contributing to her respiratory status. On the 14th day of hospitalization, the patient was successfully extubated, and 5 days later was discharged to the rehabilitation unit. SARS-CoV-2 presents primarily with pulmonary symptoms; however, many patients, particularly those who are severely ill, exhibit adverse events related to hypercoagulability. The exact mechanism explaining this hypercoagulable state has yet to be elucidated, but these thrombotic events have been linked to the increased inflammation caused by SARS-CoV-2. This novel viral illness is still largely misunderstood, but the hypercoagulable state, seen in severely ill patients, appears to play a major role in disease progression and prognosis.


Usefulness of the BACES score in nontuberculous mycobacterial pulmonary disease for various clinical outcomes.
A uniform prognostic marker is needed for nontuberculous mycobacterial pulmonary disease (NTM-PD) due to the diverse clinical course. We aimed to seek the utility of the BACES score, originally derived to predict all-cause mortality, for various outcomes. To calculate the BACES score, one point was given for each of the following factors: body mass index < 18.5 kg/m2, age ≥ 65 years, presence of cavities, elevated erythrocyte sedimentation rate, or male sex. The study included 681 patients, of whom 97 (14.2%), 189 (27.7%), 192 (28.2%), 143 (21.0%), 47 (6.9%), and 13 (1.9%) had BACES scores of 0 to 5. Those with greater BACES scores were more likely to experience dyspnea, body weight loss, and anorexia. With severe disease, the risk of disease progression increased while the rate of treatment culture conversion decreased. After adjustment of comorbidities, higher BACES score was independently associated with the risk of mortality from respiratory causes or infection. As a simple and efficient bedside tool for assessing the severity of NTM-PD, the BACES score has the potential to be utilized as a surrogate marker for uniform severity assessment.


Molecular cloning of the estrogen and progesterone receptors of the American alligator.
Steroid hormones perform many essential roles in vertebrates during embryonic development, reproduction, growth, water balance, and responses to stress. The estrogens are essential for normal reproductive activity in female and male vertebrates and appear to have direct actions during sex determination in some vertebrates. To begin to understand the molecular mechanisms of estrogen action in alligators, we have isolated cDNAs encoding the estrogen receptors (ER) from the ovary. Degenerate PCR primers specific to ER were designed and used to amplify alligator ovary RNA. Two different DNA fragments (ERalpha and ERbeta) were obtained and the full-length alligator ERalpha cDNA was obtained using 5' and 3' RACE. The inferred amino acid sequence of alligator ERalpha (aERalpha) was very similar to the chicken ERalpha (91% identity), although phylogenetic analyses suggested profound differences in the rate of sequence evolution for vertebrate ER sequences. We also isolated partial DNA fragments encoding ERbeta and the progesterone receptor (PR) of the alligator, both of which show strong sequence similarities to avian ERbeta and PR. We examined the expression levels of these three steroid receptors (ERalpha, ERbeta, and PR) in the ovary of juvenile alligators and observed detectable levels of all three receptors. Quantitative RT-PCR showed that gonadal ERalpha transcript levels in juvenile alligators decreased after E2 treatment whereas ERbeta and PR transcripts were not changed. These results provide tools that will allow future studies examining the regulation and ontogenic expression of steroid receptors in alligators and expand our knowledge of vertebrate steroid receptor evolution.


Multiparameter fluorescence mapping of nonprotein sulfhydryl status in relation to blood vessels and hypoxia in cervical carcinoma xenografts.
Aberrant architecture of the tumor vasculature and temporal fluctuations in blood flow can result in tumor hypoxia. The aim of this study was to classify tumor hypoxia based on distance to blood vessels, and to characterize its biologic significance by determining levels of nonprotein sulfhydryls (NPSH) in hypoxic regions located proximally and distally to tumor blood vessels. A dual fluorescence method was developed for the spatial colocalization of the vasculature and hypoxia in frozen sections from SiHa cervical carcinoma xenografts. A parallel section was stained with the sulfhydryl stain mercury orange. Composite fluorescence images were generated by imaging and tiling individual fields of view into 2D image arrays. Image arithmetic techniques were combined with feature-based image segmentation to characterize expression of NPSH as a function of the hypoxic tumor microenvironment. NPSH levels were higher in hypoxic areas of the SiHa xenografts (15.1 +/- 0.5 vs. 13.5 +/- 0.5 integrated optical density [IOD], p < 0.03). When tumor hypoxia was classified by distance to the nearest visible blood vessel, significantly higher NPSH levels were found in hypoxic regions close to blood vessels than in regions at a distance from blood vessels. The results of this study indicate differential expression of NPSH levels in regions of hypoxia that are proximal or distal to blood vessels in SiHa tumors.


Higher Plasma S100B Concentrations in Schizophrenia Patients, and Dependently Associated with Inflammatory Markers.
Glial damage and immune dysfunction are involved in pathogenesis of schizophrenia. However, interaction between glial damage and immune dysfunction in schizophrenia is undefined. This study aims to compare plasma S100 calcium binding protein (S100B) levels between schizophrenia patients and healthy participants, and to determine if immune markers are independently related with concentration of S100B in schizophrenia patients. Forty-one schizophrenia patients and thirty-three healthy volunteers were enrolled. Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of plasma S100B and inflammatory markers. We found that concentrations of S100B were elevated in schizophrenia patients than healthy participants (p < 0.05), and were negatively related with the severity of symptoms (p = 0.046). Receiver operating characteristic (ROC) curve analysis showed that different S100B levels between schizophrenia and healthy participants can be used as a clinical diagnostic factor (predictive value: 0.666, p = 0.015). Multiple linear regression analysis found that length of illness (Beta = -0.161), plasma levels of inflammatory regulation factors (including TGF-β1, logIL-23 and logIL-10) (Beta = 0.119, 0.475, 0.514) were independently associated with concentrations of S100B (Adjusted R(2) = 0.897, p < 0.001). Therefore, our results suggest the possible function of S100B in pathogenesis of schizophrenia, and implicate the important role of autoimmune response and balance to glial dysfunction in patients with schizophrenia.


Gene transcript profiling in aging research.
Advances in biotechnology have led to methods for quantifying the relative concentrations of thousands of mRNAs in parallel. While these are powerful methods that can be used for both hypothesis testing and hypothesis generation, gene transcript profiling has some limitations as a tool to study aging. These include the difficulty in separating effects of aging from analytical and biological variability, statistical problems associated with simultaneous determination of so many different gene transcripts, and uncertainty about the functional significance of changes in mRNA concentrations. In this review, these issues are discussed with a focus on two methods for profiling mRNAs--serial analysis of gene expression (SAGE) and DNA arrays.


Botulinum Toxin to Improve Scar Quality in Cleft Lip Repair: A Systematic Review.
Cleft lip repair (CLR) can be complicated by hypertrophic scar or keloid. Botulinum toxin type A (BTA) may improve postoperative scarring by reducing muscle tension and cytokine activity at the scar site. This systematic review analyzes the available evidence regarding the effect of BTA on scar quality after CLR. The search was conducted in 6 different databases in accordance with PRISMA guidelines (PubMed, Scielo, Embase, Scopus, Web of Science, and Cochrane) using "botulinum toxin" and "cleft lip" as keywords. Academic hospital. Exclusive to patients who underwent CLR and BTA injection. Mean visual analog scores (VAS), mean Vancouver scar scale (VSS), scar width, and BTA or CLR-related complications. Five studies for a total of 216 patients met inclusion criteria. Four studies reported on primary CLR during infancy while 1 study recruited older patients seeking revision. All patients had BTA (range: 1-2 units/kg) injected in the orbicularis oris muscle. One study documented BTA injections in additional perioral muscles. All 4 studies that measured scar width and had a saline control arm found a significant decrease in width with BTA injection. Improvement of VAS and VSS with BTA was reported in 3 of 5 studies and 2 of 5 studies, respectively. There were no reports of complications associated with BTA or CLR. The existing studies support the use of BTA injection to improve scar quality following CLR with low concern for complication. Further investigations with a greater number of patients are necessary.


Reconstruction of complete palsies of the adult brachial plexus by root grafting using long grafts and nerve transfers to target nerves.
We report on the results we obtained with reconstruction for total paralysis of the brachial plexus using long nerve grafts that connect nonavulsed roots to the musculocutaneous and radial nerve. Nerve transfers were performed to restore function of the suprascapular nerve, triceps long head, and pectoralis major muscle. We studied 22 young adults with complete brachial plexus palsy who had surgical repair an average of 5 months after trauma. Nerve grafts connected the C5 root to the musculocutaneous nerve. The C6 root was connected by grafts to the radial nerve. When the C6 root was avulsed, the levator scapulae motor branch was connected by grafts to the triceps long head motor branch. In 13 patients, the platysma motor branch was transferred to the medial pectoralis nerve through a long nerve graft. The suprascapular nerve was repaired through transfer of the accessory nerve. Outcomes were assessed an average of 27 months after surgery, focusing on recovery of muscle strength, categorized using the Medical Research Council scale. All but one patient recovered some shoulder abduction, with a mean range of recovered shoulder abduction of 57°. Pectoralis major reinnervation was observed in 9 of the 13. Twenty patients recovered full elbow flexion and achieved at least grade M3 strength. Among the 10 patients in whom the C6 root was grafted to the radial nerve, 4 patients recovered active elbow extension with biceps co-contraction. All patients in whom the levator scapulae nerve was connected to the triceps long head recovered active elbow extension, albeit weak. Double lesions of the musculocutaneous nerve were identified in 4 patients. Accessory to suprascapular nerve transfer, levator scapulae nerve transfer to the triceps long head and C5 root grafting to the musculocutaneous nerve is now our preferred method of reconstruction in total palsies of the brachial plexus. Therapeutic IV.


Beyond assembly: the increasing flexibility of single-molecule sequencing technology.
The maturation of high-throughput short-read sequencing technology over the past two decades has shaped the way genomes are studied. Recently, single-molecule, long-read sequencing has emerged as an essential tool in deciphering genome structure and function, including filling gaps in the human reference genome, measuring the epigenome and characterizing splicing variants in the transcriptome. With recent technological developments, these single-molecule technologies have moved beyond genome assembly and are being used in a variety of ways, including to selectively sequence specific loci with long reads, measure chromatin state and protein-DNA binding in order to investigate the dynamics of gene regulation, and rapidly determine copy number variation. These increasingly flexible uses of single-molecule technologies highlight a young and fast-moving part of the field that is leading to a more accessible era of nucleic acid sequencing.


Antioxidant activity of flavonoids from Licania licaniaeflora.
In our screening program for antioxidants with DPPH radical scavenging activity we tested several flavonoids isolated from the leaves of Licania licaniaeflora (Chrysobalanaceae family) and identified by spectroscopic evidence, particularly with 1H and 13C NMR. All the isolated compounds exhibited DPPH radical scavenging activity: quercetin derivatives showed the strongest action, while the flavanone 8-hydroxy-naringenin and kaempferol 3-O-alpha-rhamnoside had the lowest.


Resonant ultrasound spectroscopy measurements of the elastic constants of human dentin.
The technique of resonant ultrasound spectroscopy (RUS) was used to measure the second-order elastic constants of hydrated human dentin. Specimens were placed between two transducers, and the resonant frequencies of vibration were measured between 0.5 and 1.4 MHz. The elastic constants determined from the measured resonant frequencies in hydrated dentin exhibited slight hexagonal anisotropy, with the stiffest direction being perpendicular to the axis of the tubules (E11 = 25.1GPA) This hexagonal anisotropy was small (E33/E11 = 0.92), and almost disappeared when the specimens were dried. In addition, there was a pronounced anisotropy in the Poisson's ratio of wet dentin: v21 = 0.45; v31 = 0.29. With drying in air, this anisotropy vanished: v21 = v31 = 0.29. The isotropic Young's modulus of dried dentin was 28.1 GPa. RUS shows promise for determining the elastic constants in mineralized tissues.


Nontraumatic intramural hematoma of the duodenum. Report of 4 cases and review of the literature.
The authors report 4 cases of nontraumatic intramural hematoma of the duodenum (IMHD), 1 of pancreatic origin, 2 due to anticoagulant therapy while the 4th was an unusual complication of periarteritis nodosa. The principal anatomical, clinical, biological and radiological characteristics of IMHD are reviewed. Therapy is discussed, emphasizing nonaggressive surgery when possible.


BRASSINOSTEROID-SIGNALING KINASE1-1, a positive regulator of brassinosteroid signalling, modulates plant architecture and grain size in rice.
Brassinosteroids (BRs) are a crucial class of plant hormones that regulate plant growth and development, thus affecting many important agronomic traits in crops. However, there are still significant gaps in our understanding of the BR signalling pathway in rice. In this study, we provide multiple lines of evidence to indicate that BR-SIGNALING KINASE1-1 (OsBSK1-1) likely represents a missing component in the BR signalling pathway in rice. We showed that knockout mutants of OsBSK1-1 are less sensitive to BR and exhibit a pleiotropic phenotype, including lower plant height, less tiller number and shortened grain length, whereas transgenic plants overexpressing a gain-of-function dominant mutant form of OsBSK1-1 (OsBSK1-1A295V) are hypersensitive to BR, and exhibit some enhanced BR-responsive phenotypes. We found that OsBSK1-1 physically interacts with the BR receptor BRASSINOSTEROID INSENSITIVE1 (OsBRI1), and GLYCOGEN SYNTHASE KINASE2 (OsGSK2), a downstream component crucial for BR signalling. Moreover, we showed that OsBSK1-1 can be phosphorylated by OsBRI1 and can inhibit OsGSK2-mediated phosphorylation of BRASSINOSTEROID RESISTANT1 (OsBZR1). We further demonstrated that OsBSK1-1 genetically acts downstream of OsBRI1, but upstream of OsGSK2. Together, our results suggest that OsBSK1-1 may serve as a scaffold protein directly bridging OsBRI1 and OsGSK2 to positively regulate BR signalling, thus affecting plant architecture and grain size in rice.


Report of the 1985 American College of Cardiology Survey of Cardiovascular Medicine Manpower.
As a first step toward cardiology manpower planning, 3,011 questionnaires were sent to a random sample of 24% of the membership of the American College of Cardiology. The response rate was 53%. The questionnaires covered personal and educational data, geographic aspects of practice, professional activities and sources of professional income. There were differences in these variables according to age. Data were also collected with regard to perceptions of manpower supply and needs. In these categories, regional differences were evident.


Mouse serum as a medium supplement for murine immune responses in vitro.
In vitro generation of secondary anti-viral H-2 restricted cytotoxic T cells (Tc cells) alloreactive Tc cells, alloantigen-induced T cell proliferation, bacterial lipopolysaccharide (LPS)-induced B cell proliferation and anti-dinitrophenyl IgM and IgG antibody responses were used to evaluate pools of mouse sera (MS) and other animal sera as medium supplements by comparison with 5-10% fetal calf serum (FCS). Some batches of normal MS were comparable with FCS while others inhibited Tc cell responses when used at 1%, particularly with limiting stimulator cell numbers. In contrast, 2 pools of nude mouse sera and several pools of MS from thioglycollate-injected mice (TMS) used at 1% were consistently comparable with FCS at 5-10% in terms of in vitro generation of effector Tc cells and antibody secreting B cells. TMS at 1% was satisfactory for Tc cell responses either fresh, after heat inactivation at 56 degrees C for 30 min, or after storage for 6 months at -70 degrees C. 0.5% or 2% heat-inactivated rat and rabbit sera (but not guinea pig sera) were also satisfactory for Tc cell generation. Total thymidine incorporation into proliferating B or T cells was 5-15-fold lower in cultures with 1% normal MS, nude MS or TMS than with 5% FCS, but stimulation indices with 1% nude MS and TMS were similar to those with 5% FCS, whereas 1% normal MS apparently completely inhibited stimulation. One percent syngeneic TMS is a convenient, reliable alternative to 5-10% FCS in culture medium, supporting all the murine responses listed above.


The sense of agency: a philosophical and empirical review of the "Who" system.
How do I know that I am the person who is moving? According to Wittgenstein (1958), the sense of agency involves a primitive notion of the self used as subject, which does not rely on any prior perceptual identification and which is immune to error through misidentification. However, the neuroscience of action and the neuropsychology of schizophrenia show the existence of specific cognitive processes underlying the sense of agency--the "Who" system--which is disrupted in delusions of control. Yet, we have to be careful in the interpretation of such clinical symptoms, which cannot be so easily reduced to deficit of action monitoring or to lack of action awareness. Moreover, we should refine the definition of the sense of agency by distinguishing the sense of initiation and the sense of one's own movements. A conceptual analysis of the empirical data will lead us to establish the taxonomy of the different levels of action representations.


Increased incidence of alcohol use disorder and alcohol-related psychiatric disorders in patients with obstructive sleep apnea: A nationwide population-based cohort study.
Obstructive sleep apnea (OSA) and alcohol-related diseases (ARDs), including alcohol use disorder, alcohol-related psychiatric disorders, alcoholic liver disease, alcoholic polyneuropathy alcoholic cardiomyopathy, and alcoholic gastritis, are both highly prevalent conditions. Alcohol consumption is associated with a higher risk of sleep apnea. However, whether OSA increases the risk of ARD has not, as yet, been studied comprehensively. Our study aimed to determine whether OSA increases the subsequent risk of ARD. This study utilized the data from Taiwan's National Health Insurance Database between 2000 and 2015. We identified 7722 individuals newly diagnosed with OSA and randomly selected sex-, age-, and index date-matched (1:3) 22,166 controls without OSA, with a total of 29,888 subjects. We used the Fine and Gray's survival analysis to estimate the effects of OSA on ARD. The OSA cohort had an adjusted hazard ratio of subsequent ARDs as 1.486 (95% Confidence Interval: 1.301-1.698), when comparing the cohort without OSA. The Kaplan-Meier analysis showed that the cumulative incidence of ARDs was significantly higher in the OSA cohort than in the controls in the first year of follow-up, till the end of the follow-up. A post-hoc analysis showed that OSA was associated with alcohol use disorder, alcohol-related psychiatric disorders, and alcoholic liver disease, but not alcoholic polyneuropathy, alcoholic cardiomyopathy, and alcoholic gastritis. The use of psychoactive medication, including the sedative-hypnotics, antidepressants or antipsychotics were associated with a lower risk of ARDs. Our study demonstrates that the OSA patients are at a higher risk of developing ARDs.


Properties of some 3-nitrotyrosyl elapid venom cardiotoxins.
Nitration of the invariant Tyr-22 in Hemachatus haemachates cardiotoxin 12B did not greatly decrease lethality, and the haemolytic potency towards guinea-pig erythrocytes remained unchanged. This residue is thus non-essential for cardiotoxin to exert its biological action. Nitration of Naja haje annulifera and Naja melanoleuca cardiotoxins VII1 decreased but did not abolish the lethalities and haemolytic potencies. Thus Tyr-25 and Tyr-51 were concluded to have no direct functional role in cardiotoxin lethality. The pKa values of the phenolic hydroxyl groups of the tyrosine residues appeared to be important for certain properties of cardiotoxin in solution. No evidence could be produced to show that Tyr-51 is unreactive to nitration under normal (non-denaturing) conditions.


Prevalence of impaired fasting glucose and type 1 and 2 diabetes mellitus in a large nationwide working population in Spain.
To report the prevalence of impaired fasting glucose (IFG), undiagnosed and diagnosed diabetes, and their association to occupational categories in a representative sample of working population in Spain. A cross-sectional study of workers who attended routine medical check-ups from January 2007 to December 2007. A structured questionnaire was completed, and physical examinations and routine serum biochemical tests were performed. IFG was defined as fasting glucose levels ranging from 100 to 125 mg/dl with no diagnosis of T1DM or T2DM; T1DM was defined as previous diagnosis of T1DM; and T2DM as previous diagnosis of T2DM, treatment with oral antidiabetic drugs or insulin or fasting glucose levels ≥126 mg/dl, according to ADA criteria. Of the 371,997 participants (median age 35 [interquartile range 29-44] years), 72.4% were male. Raw prevalence rates (95% CI) of IFG, undiagnosed (UKDM), and previously known type 2 (KDM2) and type 1 (KDM1) diabetes were 10.4% (10.3-10.5%), 1.3% (1.2-1.3%), 1.1% (1.1-1.2%), and 0.3% (0.3-0.3%), respectively. With the exception of KDM1, prevalence of these conditions increased with age and was greater among manual/blue-collar workers (12.1%, 1.5%, 1.3% and 0.3%, respectively) as compared to non-manual/white-collar workers (7.3%, 0.8%, 0.8% and 0.3%, respectively). Age- and sex-adjusted prevalence rates of IFG, UKDM and KDM2 were 13.1%, 2.0% and 2.4%, respectively. In this sample of Spanish working population, impaired glycemic profiles were common. Prevalence rates of IFG and T2DM were high among blue-collar workers (except for T1DM). These data emphasize the need for earlier structured preventive schemes.


Effect of a physical examination teaching program on the behavior of medical residents.
The reliance on physical examination as a diagnostic aid is in decline. To determine whether an educational program can increase the use of physical examination by medical residents. A series of educational workshops were provided to 47 second- and third-year medical residents at a large academic teaching hospital. Interns and students reported the frequency and depth of clinical examination performance on morning rounds by their residents before and up to six months after the workshops. Behavior before and after the workshops was compared using a mixed model. A total of 374 reports were returned (77% response). After adjusting for the type of service and observer, there was a statistically significant 23% increase (P=.02) in the performance of physical examination among residents who attended the course. Residents significantly increased the fraction of patients they examined on rounds (absolute increase 11%, P=.002) but did not increase the depth of their examination. The change was greatest on general medical teams, among whom the performance of physical examination had been least frequent. Teaching and feedback events on medicine teams by residents to their interns (2.8 and 1.1 events per 2 weeks, respectively) and medical students (5.9 and 2.8 events per 2 weeks, respectively) remained infrequent. A skills improvement program can significantly increase the frequency of physical examination, but teaching and feedback events remain sporadic and infrequent.


Missense mutation in the lacI gene of Escherichia coli. Inferences on the structure of the repressor protein.
The lac repressor has been studied extensively but a precise three-dimensional structure remains unknown. Studies using mutational data can complement other information and provide insight into protein structure. We have been using the lacI gene-repressor protein system to study the mutational specificity of spontaneous and induced mutation. The sequencing of over 6000 lacI- mutations has revealed 193 missense mutations generating 189 amino acid replacements at 102 different sites within the lac repressor. Replacement sites are not distributed evenly throughout the protein, but are clustered in defined regions. Almost 40% of all sites and over one-half of all substitutions found occur within the amino-terminal 59 amino acid residues, which constitute the DNA-binding domain. The core domain (residues 60 to 360) is less sensitive to amino acid replacement. Here, substitution is found in regions involved in subunit aggregation and at sites surrounding residues that are implicated in sugar-binding. The distribution and nature of missense mutational sites directs attention to particular amino acid residues and residue stretches.


UniTVelo: temporally unified RNA velocity reinforces single-cell trajectory inference.
The recent breakthrough of single-cell RNA velocity methods brings attractive promises to reveal directed trajectory on cell differentiation, states transition and response to perturbations. However, the existing RNA velocity methods are often found to return erroneous results, partly due to model violation or lack of temporal regularization. Here, we present UniTVelo, a statistical framework of RNA velocity that models the dynamics of spliced and unspliced RNAs via flexible transcription activities. Uniquely, it also supports the inference of a unified latent time across the transcriptome. With ten datasets, we demonstrate that UniTVelo returns the expected trajectory in different biological systems, including hematopoietic differentiation and those even with weak kinetics or complex branches.


Agricultural environmental total factor productivity in China under technological heterogeneity: characteristics and determinants.
With limited resources, growing environment constraints and downward pressure on the economy, increasing agricultural environmental total factor productivity (AETFP) and its contribution to agricultural growth is significant for transforming agricultural development to make it more resource efficient and environment-friendly. This paper considered technological heterogeneity in different regions of China and measured AETFP in 30 provinces from 1997 to 2015 using the Metafrontier Malmquist-Luenberger (MML) productivity index. Multi-dimensional analysis was made on temporal and spatial characteristics, evolution patterns, and influencing factors of AETFP in China. The results showed that: (1) AETFP increased in the Ninth, Tenth, Eleventh, and Twelfth Five-Year Plan periods, with average annual growth rates of 0.76%, 0.88%, 1.17%, and 0.87%, respectively. (2) The average annual growth rate of AETFP in the eastern, central, and western regions decreased successively. The eastern region generally had played a leading role. The central region had a catch-up effect on environmental production technologies from the eastern region, while the western region lacked the catch-up effect. (3) The dynamic evolution of AETFP had prominent features. For the whole nation, the kernel density curve of AETFP continuously moved to the right. The main peak value continuously decreased and the width of the main peak continuously increased. The internal differences of AETFP in the eastern and western regions exhibited an increasing trend, while the internal differences of AETFP in the central region showed little change. (4) There was an inverted U-shaped relationship between agricultural economic growth and AETFP. Both the disaster rate and planting structure had a negative impact on AETFP with varying degrees of significance. Income gaps between urban and rural areas can partially offset the role of urbanization in promoting the growth of AETFP. The greater the income differences between urban and rural areas, the weaker the role of urbanization in promoting the growth of AETFP. These findings can help the government determine policies to change the agricultural development mode and formulate effective measures to improve AETFP.


Problems of surgical technique for the treatment of supratentorial midline tumors in children.
In this presentation the authors describe briefly their thoughts on microsurgical management of certain typical brain tumors arising from within and adjacent to the third ventricle the surgical treatment of which has for many years been essentially conservative, not infrequently without histological verification of the type of the tumor or even of the presence of a real neoplasm.


Dietary oleic acid and adipocyte lipolytic activity in culture.
Although various studies have noted fatty-acid-mediated regulation of adipocyte lipolysis, determining the isolated effect of a single fatty acid is more difficult. We examined the influence of dietary oleic acid on adipose cell lipolytic activity and the tissue fat content independently of the variation in other dietary fatty acids. We fed 48 rats with six diets designed so that the oleic acid content was not correlated with the content of any other fatty acid and studied the lipolytic activity and fatty acid content of the tissues. There were no differences in the weight of the animals after the diet. The muscle fat content and the epinephrine-stimulated lipolytic activity varied significantly according to the dietary levels of oleic acid and the tissues, showing a dose-dependent behavior of the dietary oleic acid concentration. The results of this study show that diets rich in oleic acid have a beneficial effect on the regulation of lipid metabolism and body weight homeostasis.


[Ultrastructure of Yersinia pseudotuberculosis in the process of their reversible transition into the dormant (non-culturable) state in association with blue-green algae].
The ultrastructural organization of Y. pseudotuberculosis in the process of the transition of vegetative cells into the dormant (noncultivable) state in interaction with blue-green algae of the species Anabaena variabilis was studied by the method of transmission electron microscopy. The use of type specific Y. pseudotuberculosis serum made it possible to identify Y. pseudotuberculosis cells in the bacterial association and to find out whether their antigenic properties remained intact in time. The dormant forms of Y. pseudotuberculosis, recultivated by passage through the axenic culture of unfusoria (Tetrahymena pyryformis), were also studied with the use of electron microscopy. The revertants were found to be at different stages of restoration of their typical morphological characteristics and antigenic properties were partially retained. The fine structure of Y. pseudotuberculosis cells in the initial culture was shown to be similar to that of the revertants of dormant forms, morphological criteria of the dormant cell ultrastructure were established. The cyclic processes of reversible transition from vegetative forms to dormant ones in bacterial populations under the influence of hydrobios is regarded as an adaptive mechanism of their existence in the environment.