High incidence of acute myeloid leukemia in SJL/J mice after X-irradiation and corticosteroids.
SJL/J mice which developed a high incidence of spontaneous reticulum cell neoplasms, developed a low rate incidence (20-25%) of myeloid leukemia (ML) after X-irradiation. The possible effect of adrenal steroid imbalance to radiation-induced ML in SJL/J mice was tested. Intact and thymectomized animals were exposed to a single dose of 300 r whole body irradiation and treated with either hydrocortisone acetate, prednisone, metyrapone and adrenocorticotropin as coleukemogenic agents. Hydrocortisone and prednisone exerted a marked coleukemogenic effect, increasing the ML incidence to a similar rate of about 50-70%, at a mean latent period of 300 days. Prominent leukemic infiltration were observed in the bone marrow, spleen, lymph nodes and liver of the leukemic animals. Results of cytological and histological studies, including cytochemistry and ultrastructure, were all consistent with the diagnosis of acute myeloid leukemia (AML). Since AML is the type of human secondary leukemia which appears increasingly in patients treated with alkylating drugs and/or irradiation and corticosteroids for Hodgkin's disease or other neoplastic diseases, the experimental model of AML induced in SJL/J mice could be used for elucidation of mechanisms of leukemogenesis in secondary leukemia.


Dynamic remodeling of the vascular bed precedes tumor growth: MLS ovarian carcinoma spheroids implanted in nude mice.
The goal of this study was to monitor the vascular bed during the lag phase in growth of implanted spheroids as a model of tumor dormancy. Vascular development and tumor growth were followed up by magnetic resonance imaging in a model system of MLS ovarian carcinoma spheroids implanted subcutaneously in female nude mice. Apparent vessel density in a 1-mm rim surrounding the spheroid was evaluated by gradient echo imaging as a measure of the angiogenic potential of the tumor. Vascular functionality and maturation were assessed by signal intensity changes in response to hyperoxia (elevated oxygen) and hypercapnia (elevated carbon dioxide), respectively. Tumor growth was delayed by 12 to 57 days after implantation. During this long period in which tumor volume did not change, up to 6 cycles of vascular development and regression were observed. We propose here that dynamic remodeling of the vascular bed may precede exit of tumors from dormancy. The sustained oscillations in the angiogenic response to the implanted spheroid are consistent with hypoxic regulation of vascular endothelial growth factor (VEGF), combined with the role of VEGF as an essential survival factor for newly formed blood vessels. Vascular maturation, manifested by physiological vasodilatory response to carbon dioxide, may be important for conferring vascular stability and exit from dormancy.


Integrative, genome-wide association study identifies chemicals associated with common women's malignancies.
Breast cancer, cervical cancer, and ovarian cancer are three of the most commonly diagnosed malignancies in women, and more cancer prevention research is urgently needed. Summary data of a large genome-wide association study of female cancers were derived from the UK biobank. We performed a transcriptome-wide association study and a gene set enrichment analysis to identify correlations between chemical exposure and aberrant expression, repression, or mutation of genes related to cancer using the Comparative Toxicogenomics Database. We identified five chemicals (NSC668394, glafenine, methylnitronitrosoguanidine, fenofibrate, and methylparaben) that were associated with the incidence of both breast cancer and cervical cancer. Using a transcriptome-wide association study and gene set enrichment analysis we identified environmental chemicals that are associated with an increased risk of breast cancer, cervical cancer, and ovarian cancer.


The screening of various biochars for Cd2+ removal at relevant soil pH.
Fourteen biochars from seven biomass sources were investigated on their long-term Cd2+ removal. The experiments consisted of a ten-day batch Cd2+ adsorption in a pH-buffered solution (pH = 6) to minimise pH effects. Insect frass, spent peat and chicken manure-derived biochars are promising Cd2+ adsorbents. Pyrolysis temperature was crucial for optimising Cd2+ removal by insect frass and spent peat-derived biochars. For these biochars, a pyrolysis temperature of 450 °C was optimal. In contrast, the Cd2+ removal by chicken manure biochars was independent of pyrolysis temperature. The Cd2+ removal by insect-frass and spent peat-derived biochars was associated with chemisorption on surface functionalities, while using chicken manure biochars was more associated with Cd2+ precipitation. The kinetics of Cd2+ removal over the course of ten days showed that insect frass biochar (450 °C) showed a gradual increase from 36 to 75 % Cd2+ removal, while chicken manure and spent peat-derived biochar (450 °C) already showed a higher Cd2+ removal (72 - 89 %) after day 1. This evidences that a long-term Cd2+ removal effect can be expected for some biochars. This should certainly be taken into consideration in future soil-based experiments.


Identification of human lung mast cell kininogenase as tryptase and relevance of tryptase kininogenase activity.
We have described previously the IgE-mediated release of kininogenase activity from purified human lung mast cells. Using supernatant fractions from mast cells stimulated with anti-IgE in the presence of deuterium oxide, we have purified this kininogenase to homogeneity by gel filtration and heparin-agarose chromatography and have demonstrated that it is identical to tryptase, the major neutral protease of human lung mast cells. Thus, tryptase and kininogenase activities co-chromatographed through both purification steps with equivalent yields. The final purified kininogenase was free of detectable chymotryptic and carboxypeptidase activities and was identified as tryptase on the basis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), amino acid composition and inhibition profile. Three such preparations of tryptase were all capable of releasing kinin from each of two different preparations of purified, single-chain, human low molecular weight kininogen. Interestingly, kinin generation was optimal at pH 5.5 and was enhanced by heparin, which has been reported to stabilize tryptase. SDS-PAGE analysis of kininogen hydrolysis by tryptase revealed the formation of a diffusely stained region in the molecular weight range of 60,000-65,000, rather than a discrete heavy chain band. Under optimal conditions, the three tryptase preparations released 10-12 micrograms kinin/hr/mg but released only 2 micrograms kinin/hr/mg at pH 7.2. HPLC analysis revealed that the kinin released was bradykinin. We conclude that the kininogenase activity from human lung mast cells is attributable to tryptase. The unique pH optimum of this reaction of a serine protease, however, raises doubts as to the physiologic significance of this activity.


Ammonium and nitrate as nitrogen sources in two Eriophorum species.
We compared ammonium and nitrate nutrition in Eriophorum scheuchzeri and E. vaginatum, two Alaskan sedges that are native to high- and low-fertility sites, respectively. When grown in solution culture, the two species were similar in their kinetics of NH inf4sup+ NO inf3sup- absorption: at nitrogen concentrations below 50 μM, net NH inf4sup+ and NO inf3sup- were absorbed at similar rates, but at higher concentrations, net uptake of NO inf3sup- was significantly faster than that of NH inf4sup+ . The two species also showed similar abilities to assimilate NO inf3sup- . Growth of E. vaginatum under NO inf3sup- nutrition was only slightly less than that under NH inf4sup+ . The observed similarities between these species from contrasting edaphic habitats indicate that factors other than tissue-specific rates of nitrogen acquisition and assimilation may underlie local adaptation to soil N fertility. Moreover, the capacity of these species to exploit NO inf3sup- as a N source supports the view that NO inf3sup- availability may be significant even in wet, acidic, arctic soils.


CSAST: Content self-supervised and style contrastive learning for arbitrary style transfer.
Arbitrary artistic style transfer has achieved great success with deep neural networks, but it is still difficult for existing methods to tackle the dilemma of content preservation and style translation due to the inherent content-and-style conflict. In this paper, we introduce content self-supervised learning and style contrastive learning to arbitrary style transfer for improved content preservation and style translation, respectively. The former one is based on the assumption that stylization of a geometrically transformed image is perceptually similar to applying the same transformation to the stylized result of the original image. This content self-supervised constraint noticeably improves content consistency before and after style translation, and contributes to reducing noises and artifacts as well. Furthermore, it is especially suitable to video style transfer, due to its ability to promote inter-frame continuity, which is of crucial importance to visual stability of video sequences. For the latter one, we construct a contrastive learning that pull close style representations (Gram matrices) of the same style and push away that of different styles. This brings more accurate style translation and more appealing visual effect. A large number of qualitative and quantitative experiments demonstrate superiority of our method in improving arbitrary style transfer quality, both for images and videos.


The DNA polymerase-encoding gene of Bacillus subtilis bacteriophage SPO1.
The bacteriophage SPO1 DNA polymerase-encoding gene, which contains a self-splicing intron, has been sequenced and its amino acid (aa) sequence has been deduced. The aa sequence of SPO1 DNA polymerase shows a high degree of similarity with that of DNA polymerase I from Escherichia coli (Po1I). Alignment with the sequences of Po1I, and the phi 29 and SPO1 DNA polymerases indicate that the aa residues that have been implicated in 3'----5' exonuclease activities are conserved.


Expression of Concern: Nanodimensional and Nanocrystalline Apatites and Other Calcium Orthophosphates in Biomedical Engineering, Biology and Medicine. Materials 2009, 2, 1975-2045.
We wish to make readers aware that the text in the published paper [1] contains substantial overlap with a previous paper by the same author [2].[...].


Diazo-positive metabolites in urine from workers exposed to aromatic nitro-amino compounds.
The amount of diazo-positive compounds in urine from workers at a chemical plant producing pharmaceuticals and explosives was determined in samples collected after work and after a holiday. Forty-five persons working with aromatic nitro-amino compounds (ANA) showed a statistically significant (p less than 0.01) increase in the exposed samples (1.21 +/- 1.40 mmol/mol creatinine) compared to the unexposed samples (0.56 +/- 0.31 mmol/mol creatinine). No increase in the level of diazo-positive metabolites was found in the 25 workers not exposed to ANA compounds. In a follow-up study, 32 trinitrotoluene (TNT) workers were divided into three exposure categories and seemed to show a dose-dependent increase in the level of urinary diazo-positive metabolites. However, there was a considerable interindividual variation. The method seems suitable for the biological assessment of exposure to ANA compounds--at least on a group level. This may be valuable, especially in situations where significant dermal uptake is expected.


Computer simulation of local blood flow and vessel mechanics in a compliant carotid artery bifurcation model.
To investigate the effect of the distensible artery wall on the local flow field and to determine the mechanical stresses in the artery wall, a numerical model for the blood flow in the human carotid artery bifurcation has been developed. The wall displacement and stress analysis use geometrically non-linear shell theory where incrementally linearly elastic wall behavior is assumed. The flow analysis applies the time-dependent, three-dimensional, incompressible Navier-Stokes equations for non-Newtonian inelastic fluids. In an iteratively coupled approach the equations of the fluid motion and the transient shell equations are numerically solved using the finite element method. The study shows the occurring characteristics in carotid artery bifurcation flow, such as strongly skewed axial velocity in the carotid sinus with high velocity gradients at the internal divider wall and with flow separation at the outer common-internal carotid wall and at the bifurcation side wall. Flow separation results in locally low oscillating wall shear stress. Further strong secondary motion in the sinus is found. The comparison of the results for a rigid and a distensible wall model demonstrates quantitative influence of the vessel wall motion. With respect to the quantities of main interest, it can be seen, that flow separation and recirculation slightly decrease in the sinus and somewhat increase in the bifurcation side region, and the wall shear stress magnitude decreases by 25% in the distensible model. The global structure of the flow and stress patterns remains unchanged. The deformation analysis shows that the tangential displacements are generally lower by one order of magnitude than the normal directed displacements. The maximum deformation is about 16% of the vessel radius and occurs at the side wall region of the intersection of the two branches. The analysis of the maximum principal stresses at the inner vessel surface shows a complicated stress field with locally high gradients and indicates a stress concentration factor of 6.3 in the apex region.


Characterizing Arrests and Charges Among Individuals With Serious Mental Illnesses in Public-Sector Treatment Settings.
Individuals with serious mental illnesses are overrepresented in all facets of the legal system. State-level criminal histories of patients with serious mental illnesses were analyzed to determine the proportion who had been arrested and number of lifetime arrests and charges, associations of six variables with number of arrests, and the most common charges from individuals' first two arrests and most recent two arrests. A total of 240 patients were recruited at three inpatient psychiatric facilities and gave consent to access their criminal history. Information was extracted from Record of Arrest and Prosecution (RAP) sheets for lifetime arrests in Georgia. A total of 171 (71%) had been arrested. Their mean±SD lifetime arrests were 8.6±10.1, and mean lifetime charges were 12.6±14.6. In a Poisson regression, number of arrests was associated with lower educational attainment, Black or African American race, the presence of a substance use disorder, the presence of a mood disorder, and female sex. Common early charges included marijuana possession, driving under the influence of alcohol, and burglary and shoplifting. Common recent charges included probation violations, failure to appear in court, officer obstruction–related charges, and disorderly conduct. Findings point to a need for policy and program development in the legal system (e.g., pertaining to charges such as willful obstruction of an officer), the mental health community (e.g., to ensure that professionals know about clients' legal involvement and can partner in strategies to reduce arrests), and social services sectors (to address charges, such as shoplifting, often related to material disadvantage).


High-grade serous ovarian carcinoma organoids as models of chromosomal instability.
High-grade serous ovarian carcinoma (HGSOC) is the most genomically complex cancer, characterized by ubiquitous TP53 mutation, profound chromosomal instability, and heterogeneity. The mutational processes driving chromosomal instability in HGSOC can be distinguished by specific copy number signatures. To develop clinically relevant models of these mutational processes we derived 15 continuous HGSOC patient-derived organoids (PDOs) and characterized them using bulk transcriptomic, bulk genomic, single-cell genomic, and drug sensitivity assays. We show that HGSOC PDOs comprise communities of different clonal populations and represent models of different causes of chromosomal instability including homologous recombination deficiency, chromothripsis, tandem-duplicator phenotype, and whole genome duplication. We also show that these PDOs can be used as exploratory tools to study transcriptional effects of copy number alterations as well as compound-sensitivity tests. In summary, HGSOC PDO cultures provide validated genomic models for studies of specific mutational processes and precision therapeutics.


Is the microbiological quality of the Msunduzi River (KwaZulu-Natal, South Africa) suitable for domestic, recreational, and agricultural purposes?
As little is known about the potential risks associated with the use of microbiologically contaminated river water for recreation, irrigation, or domestic purposes, the Msunduzi River in Pietermaritzburg (KwaZulu-Natal, South Africa) was evaluated. In addition to pH, temperature, and chemical oxygen demand, quantitative and qualitative microbiological analyses were performed monthly for 13 months. These included aerobic plate counts, counts of aerobic and anaerobic sporeformers, most probable numbers for total and faecal coliforms and Escherichia coli and the detection of Salmonella spp., Staphylococcus aureus, and intestinal enterococci. Presumptive E. coli and S. aureus from river water samples were confirmed using PCR and additionally matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS) for E. coli. Aerobic plate counts were above the South African Department of Water Affairs recommended guideline level for domestic use of 100 cfu/ml for all 13 months assessed. Faecal coliform (up to 63,000 MPN/100 ml) and E. coli (up to 7,900 MPN/100 ml) levels regularly exceeded stipulated limits for safe irrigation, domestic and recreational use. The presence of Salmonella spp., S. aureus, and intestinal enterococci frequently coincided with faecal coliform and E. coli levels above 1,000 MPN/100 ml. This illustrates the value of using guideline values for faecal coliforms and E. coli as indicators for the presence of potential pathogens. PCR and MALDI-TOF MS confirmation of E. coli were in agreement, thereby demonstrating the potential of MALDI-TOF MS as a suitable alternative. These data demonstrate that potential health risks are associated with using Msunduzi River water for irrigation and recreational or domestic purposes.


Integration of transcriptomic, proteomic and metabolomic data to reveal the biological mechanisms of AAI injury in renal epithelial cells.
Overexposure to aristolochic acid I (AAI) can induce aristolochic acid nephropathy (AAN). However, the comprehensive mechanisms of AAI-induced nephrotoxicity have not been entirely explicated. To investigate the toxicological mechanisms by which AAI induces renal injury, human kidney cells (HK-2 cells) were subjected to comprehensive transcriptomic, proteomic and metabolomic analyses. The transcriptomic analysis identified a total of 7749 differentially expressed genes (DEGs) after AAI treatment, while the proteomic analysis found 598 differentially expressed proteins (DEPs) after AAI treatment. The metabolomic analysis revealed 49 and 42 differentially expressed metabolites (DEMs) in the positive and negative ion modes, respectively. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on these DEGs, DEPs and DEMs. The results of the comprehensive analyses of transcripts, proteins, and metabolites indicated that the DEGs, DEPs, and DEMs were jointly regulated in three ways. These genes, proteins and metabolites and their related dysregulated pathways may be promising targets for research on the mechanisms of AAI injury in human renal epithelial cells. This study provides large-scale omics data that can be used to formulate new strategies for the prevention, rapid diagnosis, and treatment of AAI injury.


A survey of practices in infectious diseases by obstetrician-gynecologists.
To survey current practices among obstetricians and gynecologists concerning a wide range of infectious diseases to guide future efforts in continuing medical education. A survey questionnaire of multiple-choice questions was mailed to 2500 physicians, under age 65, randomly selected from the American Medical Association specialty list of obstetrician-gynecologists. The first 500 returns constituted the data set and were analyzed by computer. We found many clinical areas in which practice patterns were deemed appropriate, including antibiotic selection, universal screening for hepatitis B, and follow-up of urinary tract infection in pregnancy. In other areas, marked by controversy among "experts," practice patterns varied widely. These areas included management of premature rupture of the membranes and premature labor, and universal screening for group B streptococci. Areas in need of further continuing medical education efforts include management of perinatal viral infections and diagnosis and treatment of sexually transmitted diseases. Although this survey indicated that practice patterns of American obstetricians and gynecologists are appropriate in many clinical areas relevant to infectious diseases, there are other clinical conditions requiring future efforts in continuing medical education.


Active Surveillance for Patients With Papillary Thyroid Microcarcinoma: A Single Center's Experience in Korea.
Papillary thyroid microcarcinoma (PTMC) usually has an excellent prognosis. To evaluate the three-dimensional structures of PTMCs, using serial neck ultrasonography (US) in patients under active surveillance. A retrospective cohort study. In total, 192 patients diagnosed with PTMC under active surveillance for >1 year were included in a median 30-month follow-up. Changes in tumor size were evaluated not only using the maximal tumor diameter but also the tumor volume. The median age of patients was 51.3 years and 145 patients (76%) were female. The median initial maximal tumor diameter and tumor volume were 5.5 mm and 48.8 mm3, respectively. The tumor size increased in 27 patients (14%); 23 patients showed a tumor volume increase >50% without a maximal diameter increase of ≥3 mm. The other four patients had both an increasing tumor volume and increasing maximal tumor diameter ≥3 mm. One patient (0.5%) had newly appeared cervical lymph node (LN) metastasis at 3 years after the initial diagnosis. There were no significant risk factors associated with increased tumor size, such as age, sex, or Hashimoto thyroiditis. Twenty-four patients (13%) underwent delayed thyroid surgery at a median of 31.2 months and seven (29%) had cervical LN metastasis on pathologic examination. Some PTMCs could grow significantly after a relatively short period of active surveillance. We also found that the change in tumor volume was more sensitive to detect tumor progression than the change in the maximal tumor diameter.


[Effect of anaprilin on the clinical course of stenocardia and the carbohydrate metabolic indices of ischemic heart disease patients in relation to the nature of their glucose tolerance].
Fourteen-day anaprilin treatment of coronary patients with varying glucose tolerance has demonstrated that the drug's therapeutic efficiency was greater in patients with normal glucose tolerance. Anaprilin caused a moderate drop in baseline glucose level and considerably limited the degree of hyperglycemia in response to the glucose tolerance test in coronary patients with abnormally low glucose tolerance. Insulin content was virtually unaffected by the drug, irrespective of the type of glucose tolerance.


Total disc replacement: a modified posterior lumbar interbody fusion. Report of 750 cases.
Total disc replacement is a modification of posterior lumbar interbody fusion. A study of 750 patients treated by total disc replacement with allogeneic bone shows that the operation is complicated but uniquely effective. Successful results have occurred in over 90% of the cases.


Congenital syphilis in the 21st century.
While the prevalence of congenital syphilis continues to be low throughout most of the developed world, there has been a slight resurgence of the disease in several European countries, including Spain. In this context, we need to become more familiar with the signs and symptoms of this disease and consider its diagnosis in patients with only mild clinical manifestations. A definitive diagnosis may be difficult or even impossible in patients whose diagnostic tests reveal low positive titers or inconsistent results. The cornerstone of congenital syphilis control is prenatal screening and the treatment of infected mothers with penicillin, an effective and economical intervention. Based on a review of the literature supplemented by data from our own clinical experience, this article provides a detailed description of the clinical manifestations of congenital syphilis as well as the various diagnostic methods and treatments available.


Are facial nerve outcomes worse following surgery for cystic vestibular schwannoma?
This study sought to determine explicitly whether postsurgical facial nerve outcomes for patients with a cystic component to a vestibular schwannoma were significantly different from those with a solid tumor. Seventy patients who underwent translabyrinthine surgery for a cystic vestibular schwannoma between May 1981 and the present, and who had complete records in our database, were identified. These were compared with a group of patients with solid tumors matched to the study group on the following parameters: House-Brackmann grade at presentation, tumor size, surgical approach, age. Regional tertiary referral center. Adult patients with vestibular schwannomas. House-Brackmann score 2 years following surgery. No significant difference was found between the two groups. The perceived difference in outcomes between cystic and solid vestibular schwannomas cannot be demonstrated when confounding factors such as tumor size are taken into account.


[Hexobarbital-oxidation in vivo and in vitro in rats with bile duct ligation or ANIT-cholestasis (author's transl)].
Pharmacokinetics of hexobarbital in rats is not influenced by ligature of the common bile duct or by ANIT-cholestasis. Additional in vitro experiments with isolated liver microsomes show only slight changes of hexobarbital metabolism.


Plasma gastrin in congenitial hypertrophic pyloric stenosis. A hypothesis disproved.
Fasting plasma gastrin levels were measured in babies with pyloric stenosis and in normal babies of similar age. There was no difference in gastrin levels either before or after operation between the babies with pyloric stenosis and normal babies. Similarly, neither the fasting blood glucose nor the fasting gastric pH of the babies with pyloric stenosis differed significantly from the values obtained in normal babies. Our findings do not support the hypothesis that gastrin in the fasting baby has an aetiological role in the development of hypertrophic pyloric stenosis of infancy. An alternative hypothesis is suggested.


Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression.
The dissemination of tumour cells is the prerequisite of metastases and is correlated with a loss of epithelial differentiation and the acquisition of a migratory phenotype, a hallmark of malignant tumour progression. A stepwise, irreversible accumulation of genetic alterations is considered to be the responsible driving force. But strikingly, metastases of most carcinomas recapitulate the organization of their primary tumours. Although current models explain distinct and important aspects of carcinogenesis, each alone can not explain the sum of the cellular changes apparent in human cancer progression. We suggest an extended, integrated model that is consistent with all aspects of human tumour progression - the 'migrating cancer stem (MCS)-cell' concept.


Sonographic findings of Sister Mary Joseph's nodule from ovarian cancer.
Sister Mary Joseph's nodule (SMJN), which is known as a malignant tumor metastasized to the umbilicus, is a rare condition. We report ultrasonic findings of SMJN secondary to ovarian cancer in a 66-year-old woman. The umbilical tumor was observed as a hypoechoic mass with punctate hyperechoic foci. A pathological specimen obtained by needle biopsy confirmed adenocarcinoma with psammoma bodies. A comparison of the ultrasonographic findings with the pathological findings of the resected specimen suggested that the hyperechoic foci corresponded to psammoma bodies. When hyperechoic foci are observed inside SMJN by ultrasonography, adenocarcinoma from ovarian cancer should be included in the differential diagnosis.


Effects of a Meditation Program on Nurses' Power and Quality of Life.
This study evaluated the effects of meditation programs on nurses' power and quality of life. In this study, Barrett's power theory derived from Rogers' unitary human being science was used as a theoretical framework. A randomized controlled design with 50 recruited and randomly allocated participants was used. The results demonstrated that the eight-week meditation program significantly improved nurses' power and quality of life. These results suggest that meditation has positive effects on power and quality of life.


How breast cancer outpatients perceive mutual participation in patient-physician interactions.
This study examines correlations between observable communicative behaviors and patient perceptions of patient-physician interaction in 86 breast cancer outpatient consultations from three patient-centered perspectives: patient participation, physician collaboration, and communicative success. Analysis relied on audio tape recordings and questionnaires, and incorporated non-behavioral factors particular to each physician, patient, and consultation. Results revealed that patient perceptions of self-participation depended on the length of consultation. Physician collaboration depended on the degree to which patients were given the opportunity to speak, while communicative success reflected a patient's level of anxiety at the time of the consultation. Yet patient perceptions of mutual participation reflected observable communicative behaviors only partially. This gap suggests that perceptual and behavioral measures reveal different aspects of participation and that the study of patient-physician interaction benefits from the inclusion of both kinds of measure.


Metchnikoff-Schaumann bodies in experimental Yersin's type tuberculosis induced with Mycobacterium avium in hamster.
Structure and ultrastructure of Metchnikoff-Schaumann bodies occurring in macrophages, epithelioid cells and multinucleated giant cells in tuberculous granuloma were investigated. Their similitude with other reported intracellular calcareous bodies occurring in malakoplakia, infectious orchitis (Michaelis-Guttman' bodies or calcosphaerites), in beryllium granulomas (conchoid bodies) and sarcoidosis (Schaumann bodies) is discussed.


Biomechanics of diastolic dysfunction: a one-dimensional computational modeling approach.
Diastolic dysfunction (DD) is a major component of heart failure with preserved ejection fraction (HFpEF). Accordingly, a profound understanding of the underlying biomechanical mechanisms involved in DD is needed to elucidate all aspects of HFpEF. In this study, we have developed a computational model of DD by leveraging the power of an advanced one-dimensional arterial network coupled to a four-chambered zero-dimensional cardiac model. The two main pathologies investigated were linked to the active relaxation of the myocardium and the passive stiffness of the left ventricular wall. These pathologies were quantified through two parameters for the biphasic delay of active relaxation, which simulate the early and late-phase relaxation delay, and one parameter for passive stiffness, which simulates the increased nonlinear stiffness of the ventricular wall. A parameter sensitivity analysis was conducted on each of the three parameters to investigate their effect in isolation. The three parameters were then concurrently adjusted to produce the three main phenotypes of DD. It was found that the impaired relaxation phenotype can be replicated by mainly manipulating the active relaxation, the pseudo-normal phenotype was replicated by manipulating both the active relaxation and passive stiffness, and, finally, the restricted phenotype was replicated by mainly changing the passive stiffness. This article presents a simple model producing a holistic and comprehensive replication of the main DD phenotypes and presents novel biomechanical insights on how key parameters defining the relaxation and stiffness properties of the myocardium affect the development and manifestation of DD.NEW & NOTEWORTHY This study uses a complete and validated computational model of the cardiovascular system to simulate the two main pathologies involved in diastolic dysfunction (DD), i.e., abnormal active relaxation and increased ventricular diastolic stiffness. The three phenotypes of DD were successfully replicated according to literature data. We elucidate the biomechanical effect of the relaxation pathologies involved and how these pathologies interact to create the various phenotypes of DD.


Bacteriophage biocontrol in wastewater treatment.
Waterborne bacterial pathogens in wastewater remains an important public health concern, not only because of the environmental damage, morbidity and mortality that they cause, but also due to the high cost of disinfecting wastewater by using physical and chemical methods in treatment plants. Bacteriophages are proposed as bacterial pathogen indicators and as an alternative biological method for wastewater treatment. Phage biocontrol in large scale treatment requires adaptive and aggressive phages that are able to overcome the environmental forces that interfere with phage-host interactions while targeting unwanted bacterial pathogens and preventing biofilms and foaming. This review will shed light on aspects of using bacteriophage programming technology in wastewater plants to rapidly target and reduce undesirable bacteria without harming the useful bacteria needed for biodegradation.


[Nonpharmacological and nonsurgical therapies for osteoarthritis: orthosis, exercises].
Unloading valgus knee braces may be more effective than knee sleeves, to improve pain and disability for medial knee osteoarthritis, but have more adverse effects. A lateral-wedge insole could reduce pain in medial knee osteoarthritis. Cushioning insoles and footwear with shock absorbance could be proposed for hip osteoarthritis by authors' recommendations. Nocturnal splints for base-of-thumb osteoarthritis are recommended to reduce pain and disability. Aerobic, strengthening, range-of-motion and proprioceptive exercise are recommended to decrease pain and improve function and quality of life in knee and hip osteoarthritis. Strengthening and range-of-motion exercise is recommended for hand osteoarthritis.


Can Classification and Regression Tree Analysis Help Identify Clinically Meaningful Risk Groups for Hip Fracture Prediction in Older American Men (The MrOS Cohort Study)?
Although the WHO fracture risk algorithm (FRAX) is used to predict fracture, the utility of some simple machine-learning methods, such as classification and regression trees (CARTs) should be evaluated to determine their efficacy in fracture prediction. Follow-up time for the hip fracture analyses of 5977 community-dwelling American men aged ≥65 years old was truncated to 10 years. There were 172 (2.9%) men who had an incident nontraumatic hip fracture. The CARTs were developed using hip BMD and common clinical risk factors as follows: model 1 = using classification with continuous variables of age, total hip BMD, and femoral neck BMD, or together with common clinical risk factors; and model 2 = using classification with continuous variables of age, total hip BMD, femoral neck BMD, FRAX score, osteoporosis by T-score at the hip, and common clinical risk factors. The predictive performance of risk models derived from CARTs was compared with the basic classification of FRAX at 3% (basic model). From model 1, discriminators selected by CART were total hip BMD, age, and femoral neck BMD; no other clinical risk factors were selected. From model 2, discriminators selected by CART were FRAX score, femoral neck BMD, and age. Compared with the basic model using only a high-risk group by FRAX ≥3%, no significantly improved predictive performance was demonstrated by model 1 or model 2 as identified by CART with the area under the receiver-operating characteristic curve for each model of 0.714 (95% CI, 0.676 to 0.751) or 0.726 (95% CI, 0.690 to 0.762) versus 0.703 (95% CI, 0.667 to 0.740), respectively. The improved overall net reclassification improvement index was 0.02 (95% CI, -0.04 to 0.08) and 0.05 (95% CI, -0.01 to 0.10), respectively. Although a FRAX category is a good clinical indicator for hip fracture risk, a simple classification by age and BMD may provide an alternative way to estimate a clinical risk level of 3.0%. © 2019 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.


Unusable cotton spinning mill waste: A viable source of raw material in paper making.
Since the reserves of natural renewable resources are being inexorably diminished, the utilization of the recoverable waste in new area is gaining global attention day by day. Besides, as the cost of raw materials constitutes the majority of a production cost, the usage of undesirable but inevitable processing waste in the manufacturing process provides a considerable advantage to the manufacturers. Herein, it has been attempted to exploit unusable cotton spinning mill waste (filter waste derived from humidification plant) to convert it into paper. Handsheets of 70 g/m2 and 80 g/m2 were successfully produced from 100% cotton waste, 100% bleached cotton waste, and blends of bleached cotton waste with bleached hardwood kraft pulp (HWKP) (HWKP is typically used to produce commercial-grade papers). Morphologies and mechanical properties of handsheets were thoroughly investigated by whiteness index, brightness%, breaking length, tear index, bursting index, FTIR spectroscopy, optical microscope, and scanning electron microscope. Based on detailed observations, it is summarized that the produced handsheets, depending on the chemical treatment and blend ratio with HWKP, possess variations in appearances and properties that will have a wide range of potential applications from newsprint, tissue paper to commercial-grade writing and printing papers.


Cortisol induces apoptosis in activated B cells, not in other lymphoid cells of the common carp, Cyprinus carpio L..
In mammalian T and B cells glucocorticoids (GS) regulate development and selection through induction of apoptosis; more recently GS-induced apoptosis has also been implicated in the removal of circulating, activated T and B cells following an immune response. In an earlier report we have given the first evidence for cortisol-induced apoptosis as an immune regulator in an aquatic vertebrate, the common carp. Here we report on subpopulation-specific sensitivity of carp peripheral blood leukocytes (PBL) to cortisol-induced apoptosis. B cells, the most abundant leukocyte subpopulation in fish blood, are sensitised to cortisol-induced apoptosis by activation with the mitogens LPS or PHA. Cortisol-induced apoptosis in B cells is receptor mediated as it is blocked by the synthetic GS receptor blocker RU486. In contrast to what is known for mammalian lymphocytes, apoptosis in carp T cells is hardly affected by cortisol, both in unstimulated and in PHA-stimulated cell cultures. A culture supernatant of PHA-prestimulated PBL, containing IL-2-like activity, decreased spontaneous apoptosis in both T and B cells, but did not affect cortisol-induced apoptosis in B cells. Apoptosis in thrombocytes was unaffected by either mitogens, cortisol, or lymphocyte supernatant. The difference between mammalian and fish leukocyte sensitivity to cortisol is discussed in the light of differences in the immune response of mammals and fish.


Pericardial tamponade due to perforation with a permanent endocardial pacing catheter.
A case is presented in which shock developed suddenly during implantation of a permanent pacemaker. The cause proved to be pericardial tamponade secondary to catheter perforation. Analysis of this case and the 6 similar cases reported in the literature reveals that although perforation occurs not infrequently from immediately to many months after implantation, tamponade is quite rare and is invariably closely related temporally to catheter manipulation. Tamponade has occurred with different catheter sizes and makes. It is more likely related to local myocardial factors than to faulty technique. Closed pericardiocentesis is generally unsuccessful in relieving the tamponade, and prompt open drainage through the subxiphoid approach is recommended.


Root resorption caused by impacted permanent teeth. Case report.
A case of severe external root resorption in several teeth caused by unerupted permanent teeth is presented along with the initial surgical treatment.


Biological hazards in the activity of organ and tissue banks and in transplantation surgery.
The possibilities of infection, and other not so often occurring biohazards transmission, from the dead body or harvested organ or tissue, on the bank staff during all steps of banking and surgical usage are discussed. The opposite jeopardy originated from staff and menacing the graft is mentioned, too.


Metabolism of an anionic fluorescent dye, 1-anilino-8-naphthalene sulfonate (ANS) by rat liver microsomes.
The present study was designed to examine the metabolism of 1-anilino-8-naphthalene sulfonate (ANS), an anionic compound which is transported into liver via "multispecific organic anion transporter", with rat hepatic microsomes. TLC analysis indicated that the fluorescent metabolites were not produced to a measurable extent, which made it possible to assess the ANS metabolism by measuring the fluorescence disappearance. The metabolism of ANS was remarkably inhibited by the presence of SKF-525A as well as by the substitution of O2 by CO gas. ANS metabolism by microsomes also required NADPH as a cofactor. These results indicated that the microsomal monooxygenase system might be mainly responsible for the ANS metabolism. The maximum velocity (Vmax) and Michaelis constant (K(m)) were calculated to be 4.3 +/- 0.2 nmol/min/mg protein and 42.1 +/- 2.0 microM, respectively. Assuming that 1 g of liver contains 32 mg of microsomal protein, the Vmax value was extrapolated to that per g of liver (Vmax'). The intrinsic metabolic clearance (CLint) under linear conditions calculated from this in vitro metabolic study was 3.3 ml/min/g liver, being comparable with that (3.0 ml/min/g liver) calculated by analyzing the in vivo plasma disappearance curve in a previous study. Furthermore, the effects of other organic anions on the metabolism of ANS were examined. Bromophenolblue (BPB) and rose bengal (RB) competitively inhibited the metabolism of ANS, while BSP inhibited it only slightly. The inhibition constant (Ki) of BPB (6 microM) was much smaller than that of RB (200 microM). In conclusion, the microsomal monooxygenase system plays a major role in the metabolism of ANS, and other unmetabolizable organic anions (BPB and RB) compete for this metabolism.


Coupling of theta activity and glucose metabolism in the human rostral anterior cingulate cortex: an EEG/PET study of normal and depressed subjects.
In rodents, theta rhythm has been linked to the hippocampal formation, as well as other regions, including the anterior cingulate cortex (ACC). To test the role of the ACC in theta rhythm, concurrent measurements of brain electrical activity (EEG) and glucose metabolism (PET) were performed in 29 subjects at baseline. EEG data were analyzed with a source localization technique that enabled voxelwise correlations of EEG and PET data. For theta, but not other bands, the rostral ACC (Brodmann areas 24/32) was the largest cluster with positive correlations between current density and glucose metabolism. Positive correlations were also found in right fronto-temporal regions. In control but not depressed subjects, theta within ACC and prefrontal/orbitofrontal regions was positively correlated. The results reveal a link between theta and cerebral metabolism in the ACC as well as disruption of functional connectivity within frontocingulate pathways in depression.


'To see or not to see, that is the question' - A commentary on patient Selection for the RANZCP psychotherapy written case.
This paper aims to redress the shortage of published guidance for registrars on selecting suitable patients for the RANZCP Psychotherapy Written Case Summative Assessment. This article offers a common-sense approach to patient selection using psychiatric nomenclature and organises patients into proposed categories of likely suitable, possibly suitable, and unsuitable. A flowchart tool is offered for screening patients stressing a Global Assessment of Function (GAF) and the premorbid capacity to adhere to social frames such as school, university, employment, and relationships.


Morphokinetics and embryo aneuploidy: has time come or not yet?
Morphokinetic analysis of early human embryos in combination with trophectoderm biopsy and chromosomal enumeration by array technology has been shown to identify embryos with single and/or multiple aneuploidies. In a time-lapse imaging study, aneuploid embryos showed a delayed initiation of blastocyst formation and also reached the full blastocyst stage later compared with euploid embryos. Based on these findings, a model for a risk factor classification for aneuploidy of human embryos has been established. However, time values that allow differentiation between different risk classes have to be considered carefully as timings that are prognostic for one clinic may not apply directly to another clinic. Thus, risk models may need to be verified in specific IVF settings. Further studies are needed to verify that time-lapse imaging does allow subselection of embryos with a high aneuploidy risk and thus does hold the chance to restrict invasive biopsy procedures to those embryos where there is uncertainty regarding the chromosomal status.


Correction: Role of defective states in MgO nanoparticles on the photophysical properties and photostability of MEH-PPV/MgO nanocomposite.
Correction for 'Role of defective states in MgO nanoparticles on the photophysical properties and photostability of MEH-PPV/MgO nanocomposite' by Sangeetha Ashok Kumar et al., Phys. Chem. Chem. Phys., 2021, 23, 22804-22816, DOI: 10.1039/d1cp03035c.


An Epidemic Within the Pandemic: The Rising Tide of Trauma During COVID-19.
In the age of COVID-19 and enforced social distancing, changes in patterns of trauma were observed but poorly understood. Our aim was to characterize traumatic injury mechanisms and acuities in 2020 and compare them with previous years at our level I trauma center. Patients with trauma triaged in 2016 through 2020 from January to May were reviewed. Patient demographics, level of activation (1 versus 2), injury severity score, and mechanism of injury were collected. Data from 2016 through 2019 were combined, averaged by month, and compared with data from 2020 using chi-squared analysis. During the months of interest, 992 patients with trauma were triaged in 2020 and 4311 in 2016-2019. The numbers of penetrating and level I trauma activations in January-March of 2020 were similar to average numbers for the same months during 2016 through 2019. In April 2020, there was a significant increase in the incidence of penetrating trauma compared with the prior 4-year average (27% versus 16%, P < 0.002). Level I trauma activations in April 2020 also increased, rising from 17% in 2016 through 2019 to 32% in 2020 (P < 0.003). These findings persisted through May 2020 with similarly significant increases in penetrating and high-level trauma. In the months after the initial spread of COVID-19, there was a perceptible shift in patterns of trauma. The significant increase in penetrating and high-acuity trauma may implicate a change in population dynamics, demanding a need for thoughtful resource allocation at trauma centers nationwide in the context of a global pandemic.


Developmental and perinatal brain diseases.
This chapter briefly describes the normal development of the nervous system, the neuropathology and pathophysiology of acquired and secondary disorders affecting the embryo, fetus, and child. They include CNS manifestations of chromosomal change; forebrain patterning defects; disorders of the brain size; cell migration and specification disorders; cerebellum, hindbrain and spinal patterning defects; hydrocephalus; secondary malformations and destructive pathologies; vascular malformations; arachnoid cysts and infectious diseases. The distinction between malformations and disruptions is important for pathogenesis and genetic counseling.


Primary pulmonary glomus tumor with contiguous spread to a peribronchial lymph node.
Glomus tumors are uncommon soft tissue tumors. Rare occurrences in visceral organs including the respiratory tract have been reported. The vast majority of these tumors are biologically benign. We report a case of primary pulmonary glomus tumor with atypical features characterized by mild nuclear atypia, local infiltration, and contiguous spread to a peribronchial lymph node. The current literature is reviewed.


Acute presentation of memory loss and emotional lability.
A 35-year-old woman presented complaining of memory loss and increased emotional lability. On physical examination she was noted to be poorly oriented, have profound recent and remote memory defects, and to have mild but significant lateralizing signs. Inpatient work-up included EEG, computed tomography scan, and cerebral angiography, culminating with a brain biopsy that revealed a Grade IV left temporal astrocytoma. The patient was discharged and received outpatient radiotherapy before dying 12 weeks after presentation.


Evolving hybrid approaches: the preservation of the 'neglected' pulmonary valve function in patients with congenital heart disease.
The involvement of the hemodynamic expertise in the operating room led to the development of new strategies aimed to improve both early and long-term outcome of patients with congenital heart disease. During the last decade, with the aim of preserving the pulmonary valve function, we embarked on a new surgical approach, which combines surgical and interventional techniques, which are performed in the operating room. We believe that the preservation of the pulmonary valve function can be extended to any patients with classic tetralogy of Fallot and other selected patients with congenital pulmonary valve hypoplasia and dysfunction.


The action of hydrocarbons and carbon tetrachloride on the sodium current of the squid giant axon.
The effects of the n-alkanes propane to hexane, cyclopropane, cyclopentane and cyclohexane and carbon tetrachloride on the ionic currents and electrical capacity of the squid giant axon membrane have been examined. Both the peak inward and steady-state outward currents were reduced reversibly by each substance, though propane at 1 atm had very little effect. The membrane capacity at 100 kHz was reduced by all substances except propane at 1 atm. Na currents were recorded in intracellularly perfused axons before and during exposure to the hydrocarbons and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952). Shifts in the curves of the steady-state activation and inactivation parameters (m infinity and h infinity) against membrane potential, changes in the peak heights of the activation and inactivation time constants (tau m and tau h) and reductions in the maximum Na conductance (gNa) have been tabulated. The effects of the various hydrocarbons and carbon tetrachloride on the parameters of the Hodgkin-Huxley equations suggest that the suppression of the Na current by these substances originates from several different phenomena. The underlying physico-chemical events are considered in the light of the observed capacity changes and of information on artificial pore-containing membranes.


We Have to Be Willing to Say the World Has Changed and Now We Have to Figure Out How to Deal With That: An Interview With Charles Levenstein, About New Solutions.
New Solutions: A Journal of Environmental and Occupational Health Policyhas been published for 25 years. To acknowledge this milestone, Dr. Pia Markkanen interviewed Charles Levenstein, Editor Emeritus of the journal, in August 2015. The purpose of this interview was to review the journal's history: from its earliest roots to the present.New Solutionsbegan in 1990 as a project with the Oil, Chemical and Atomic Workers Union (OCAW). Dr. Charles Levenstein was the founding editor and Tony Mazzocchi was the original publisher. We've tapped Dr. Levenstein's memory to learn the intent of starting the journal and how it developed. The interview presents some of the challenges of sustaining a movement journal with the mission of being a bridge between academics and researchers and workers, environmentalists, as well as advocates and activists.


Histidase mRNA. Nature of translational products, tissue specificity, and differential development in male and female rat liver.
Histidase is expressed in only two tissues of the rat, liver and epidermis. Hepatic histidase synthesis and catalytic activity undergo complex sex-specific developmental courses. To determine whether changes in functional histidase mRNA levels underlie this developmental pattern, total cellular RNA was translated in a rabbit reticulocyte cell-free lysate system. Adult liver total cellular RNA directed the synthesis of three translational products immunoreactive with anti-native histidase: a polypeptide of Mr = 75,000 (75K), which corresponds to the in vivo synthesized histidase subunit, and two higher molecular weight proteins, a major and a minor peptide of Mr = 150,000 (150K) and 140,000 (140K), respectively. These latter peptides do not seem to be aggregates or dimers of the 75K polypeptide or precursors which are post-translationally hydrolyzed to Mr = 75,000; their origin and function remain to be clarified. In contrast to in vitro translation of hepatic total cellular RNA, Western blot analysis of liver cytosol confirms the presence of only the 75K histidase subunit, with no evidence of anti-histidase immunoreactive peptides of Mr = 140,000-150,000 synthesized in vivo. Quantitation of the radioactivity in the immunocomplexed 75K histidase subunit, translated using total RNA from livers of fetuses, 19-day-old males, 35-day-old males, adult males and females, and adult kidney and brain (0, 0.007, 0.010, 0.016, 0.031, 0, and 0%, respectively, of total released proteins) indicates that, in general, levels of functional histidase subunit mRNA reflected histidase catalytic activity (0, 0.20, 0.50, 1.01, 3.00, 0 and 0 units/g of tissue) during tissue differentiation and sex specific development. The above data indicate that initial expression and subsequent increases in synthesis and activity of histidase during hepatic differentiation, postnatal development, and sex hormone regulation are due to pretranslationally controlled augmentation in the levels of functional mRNA which specifies the histidase subunit. In tissues which do not express histidase no functional histidase mRNA is evident. The levels of the RNA which translate the combined 140-150K histidase-like polypeptides (0, 0.007, 0.014, 0.035, 0.034, 0, and 0% of released proteins) also paralleled the increase in enzymatic activity during tissue differentiation and development; however, no difference between males and females was evident. The significance of these observations awaits elucidation of the nature of these RNA(s).


Incidence of schizophrenia among ethnic minorities in the Netherlands: a four-year first-contact study.
There is only one previous report on the first-contact incidence of schizophrenia among immigrants in the Netherlands, which was based on a small number of cases, particularly for second generation immigrants. We conducted another two-year first-contact incidence study in the same geographical area, combined the data of both studies and compared risks over all four years. The incidence of schizophrenia was increased for all first generation non-Western immigrants. The risk was particularly high for second generation immigrants: the age- and gender-adjusted incidence rate ratio was 5.8 (95% CI, 2.9-11.4) for Moroccans, 2.9 (1.6-5.0) for Surinamese, 2.3 (1.0-5.4) for Turks, and 3.5 (1.8-6.8) for immigrants from other non-Western countries.


Extensive aganglionosis: further experience with the colonic patch graft procedure and long-term results.
During the period from 1979 to 1986, seven patients have been treated for extensive aganglionosis involving the colon and distal ileum (5 to 40 cm) employing the colonic patch graft (CPG) procedure. This consists of (1) ileostomy; (2) creation of a longitudinal side-to-side ileocolostomy between normal ileum and aganglionic ascending colon, forming a CPG; and (3) the definitive pull-through procedure. In all patients, the initial course after ileostomy was complicated by severe diarrhea, which was significantly improved by creation of the CPG. At the definitive operation several months later, the mesocolon attached to the CPG was severed to mobilize the ileocolostomy segment to the distal pelvis. Four patients in this series have been followed for 5 to 8 years. No patient has developed enterocolitis requiring hospitalization. Body weight became normal for age in all patients within 4 years of the definitive operation.


Clinical manifestations of 11 children with fronto-ocular syndrome (FOS): a case series.
Fronto-ocular syndrome (FOS) is a rarely seen trigonocephaly syndrome in which metopic synostosis features are unique. This report presents six cases with FOS. Clinical manifestations mainly involve skull and facial findings. Nearly all patients have short/upslanted palpebral fissures, hypotelorism, narrow bifrontal area, philtrum anomalies, trigonocephaly, and metopic ridge. Epicanthal folds, hypoplastic supraorbital ridges, bulbous nasal tip, thin upper lip, mandible, and ear anomalies are also frequently observed in the patients. Extrafacial findings are variable such as cardiac, extremity anomalies, and skin findings. Mild developmental delay and learning disability have been presented in almost half of patients. Age-dependent and age-independent phenotypic differences between the patients have been detected. Furthermore, it is observed the individuals with reduced phenotypic expression even in the same family. FOS has been described in two families in the literature which consist of mother-daughter dual. Thereby, its inheritance pattern and clinical spectrum have not been clarified clearly. We present here eleven patients that five of them had previously reported. We aim was to give a more comprehensive description of the clinical findings of fronto-ocular syndrome and to reveal its inheritance pattern.


Improved diagnostic confidence and accuracy of pediatric elbow fractures with digital tomosynthesis.
Pediatric elbow fractures are common but remain challenging to accurately diagnose. Digital tomosynthesis is a technique that has shown promise in difficult adult fracture patterns but has not been formally studied in the pediatric population. To assess the added value of digital tomosynthesis on the detection and diagnostic confidence of pediatric elbow fractures. A retrospective study was performed between January 2016 and December 2017 in pediatric patients (≤18 years) to assess the ability of conventional elbow radiographs and digital tomosynthesis to detect elbow fractures. One hundred twenty-one pediatric patients with concern for pediatric elbow trauma (64 males, 57 females; mean age: 8.1 years, range: 1 year to 17 years) were imaged with both conventional elbow radiographs and digital tomosynthesis. Two blinded pediatric radiologists identified fractures and indicated their diagnostic confidence. Observer agreement was assessed with Cohen's Kappa coefficient and a nonparametric Wilcoxon rank sum test was used to compare the degree of diagnostic confidence between standard radiographs alone and standard radiographs with digital tomosynthesis. McNemar's test was used to assess the difference in the rate of fracture detection between the two methods and sensitivity, specificity, precision, accuracy and diagnostic odds ratios were calculated. Compared with standard radiographs alone, standard radiographs with digital tomosynthesis improved inter-rater agreement, sensitivity, specificity, accuracy, precision and the diagnostic odds ratio for fracture detection and increased diagnostic confidence (Rater 1: P=0.01, Rater 2: P=0.003). The addition of digital tomosynthesis with conventional elbow radiographs improves diagnostic confidence and performance for the detection of pediatric elbow fractures.


Differential effects of HDL subpopulations on cellular ABCA1- and SR-BI-mediated cholesterol efflux.
Our objective was to evaluate the associations of individual apolipoprotein A-I (apoA-I)-containing HDL subpopulation levels with ABCA1- and scavenger receptor class B type I (SR-BI)-mediated cellular cholesterol efflux. HDL subpopulations were measured by nondenaturing two-dimensional gel electrophoresis from 105 male subjects selected with various levels of apoA-I in pre-beta-1, alpha-1, and alpha-3 HDL particles. ApoB-containing lipoprotein-depleted serum was incubated with [(3)H]cholesterol-labeled cells to measure efflux. The difference in efflux between control and ABCA1-upregulated J774 macrophages was taken as a measure of ABCA1-mediated efflux. SR-BI-mediated efflux was determined using cholesterol-labeled Fu5AH hepatoma cells. Fractional efflux values obtained from these two cell systems were correlated with the levels of individual HDL subpopulations. A multivariate analysis showed that two HDL subspecies correlated significantly with ABCA1-mediated efflux: small, lipid-poor pre-beta-1 particles (P=0.0022) and intermediate-sized alpha-2 particles (P=0.0477). With regard to SR-BI-mediated efflux, multivariate analysis revealed significant correlations with alpha-2 (P=0.0004), alpha-1 (P=0.0030), pre-beta-1 (P=0.0056), and alpha-3 (P=0.0127) HDL particles. These data demonstrate that the small, lipid-poor pre-beta-1 HDL has the strongest association with ABCA1-mediated cholesterol even in the presence of all other HDL subpopulations. Cholesterol efflux via the SR-BI pathway is associated with several HDL subpopulations with different apolipoprotein composition, lipid content, and size.


Progressing preclinical drug candidates: strategies on preclinical safety studies and the quest for adequate exposure.
Drug discovery lead optimization teams face many diverse challenges in the search for drug development candidates. This includes understanding the toxicology profile of a candidate, and some strategies call for in vivo preclinical safety studies to be moved increasingly earlier in the discovery phase to increase the likelihood of success in development. One of the final hurdles in these pursuits is achieving adequate exposure to support safety margins for human clinical trials. In this article, we describe several strategies on early toxicology studies along with various enabling formulation methods that can be employed to achieve optimal oral absorption. These two elements of research together can significantly increase the speed preclinical drug candidates can move through development, and the overall probability of success in identifying viable new drugs.


Ester-free thiol-ene dental restoratives--Part A: Resin development.
To detail the development of ester-free thiol-ene dental resins with enhanced mechanical performance, limited potential for water uptake/leachables/degradation and low polymerization shrinkage stress. Thiol-terminated oligomers were prepared via a thiol-Michael reaction and a bulky tetra-allyl monomer containing urethane linkages was synthesized. The experimental oligomers and/or monomers were photopolymerized using visible light activation. Several thiol-ene formulations were investigated and their performance ranked by comparisons of the thermo-mechanical properties, polymerization shrinkage stress, water sorption/solubility, and reactivity with respect to a control comprising a conventional BisGMA/TEGDMA dental resin. The ester-free thiol-ene formulations had significantly lower viscosities, water sorption and solubility than the BisGMA/TEGDMA control. Depending on the resin, the limiting functional conversions were equivalent to or greater than that of BisGMA/TEGDMA. At comparable conversions, lower shrinkage stress values were achieved by the thiol-ene systems. The polymerization shrinkage stress was dramatically reduced when the tetra-allyl monomer was used as the ene in ester-free thiol-ene mixtures. Although exhibiting lower Young's modulus, flexural strength, and glass transition temperatures, the toughness values associated with thiol-ene resins were greater than that of the BisGMA/TEGDMA control. In addition, the thiol-ene polymerization resulted in highly uniform polymer networks as indicated by the narrow tan delta peak widths. Employing the developed thiol-ene resins in dental composites will reduce shrinkage stress and moisture absorption and form tougher materials. Furthermore, their low viscosities are expected to enable higher loadings of functionalized micro/nano-scale filler particles relevant for practical dental systems.


Discrepancy between actual and ideal body images; Impact on eating and exercise behaviors.
This study examined how discrepancies between actual and ideal body images are related to eating and exercise patterns. A total of 115 college-age women completed the Body Discrepancy Scale (BDS, a measure of the discrepancy between one's "actual" vs. "ideal" weight and size), a leisure-time physical activity survey, and questionnaires assessing the intake of fat and fiber (i.e., fruits and vegetables), as well as measures of maladaptive eating attitudes and behaviors. Partial correlations (controlling for Body Mass Index, BMI) showed that scores on the BDS were significantly (P's<.05) associated with low levels of physical activity (r=-.28), with low levels of fruit and vegetable consumption (r=-.19), and with high levels of body image dissatisfaction (r=.32) and binge eating (r=.32). Collectively, these findings suggest that discrepancies between actual and ideal body images are associated with maladaptive eating and exercise patterns.


Enucleative surgery for renal malignancy.
Bilateral renal cell carcinoma, malignant tumors of a solitary kidney or renal carcinoma in the presence of a contralateral kidney with compromised function may be treated by simple enucleation of the tumor, usually pseudoencapsulated, permitting relatively avascular removal. We treated 5 such patients by surgical enucleation of renal cell carcinoma who have survived for intervals of 9 months to 5 years without evidence of recurrent local or metastic disease. The simplicity of the technique offers several advantages, primarily those of applicability to lesions of any portion of the kidney and the minimal disturbance of renal hemodynamics and renal function.


The synergetic effect of lanthanide (La and Ce) and N co-doping of ZnO NPs for high-rate photocatalytic phenol degradation.
Simultaneously, lanthanide and N-modified ZnO NPs were synthesized and applied for the photocatalytic phenol degradation under LED irradiation. Among La and Ce, Ce-doped ZnO exhibited more efficiently photocatalytic activity. XRD analysis confirmed that most of Ce3+ was oxidized to Ce2O3/CeO2 over the photocatalyst surface as a secondary phase. This is due to the larger ionic radius of Ce3+ relative to that of Zn2+. Ce and N co-doping of ZnO led to narrowing the band gap and suppressing charge recombination rate. The effect of key variables, dopant type, dopant concentration, catalyst loading, initial dye concentration, light source power, solution pH, and H2O2 content on the photocatalytic degradation of phenol was systematically investigated. The utmost conversion of phenol, 100%, was observed by ZnO-Ce5-N0.33 sample under optimum conditions. Kinetics investigation revealed that under the optimum conditions, photodegradation of phenol follows a pseudo-first-order kinetics model with rate constant of 0.0631 min-1. Given the fact that the ZnO-Ce5-N0.33 is a heterostructure composed of Zn1-xCexO1-yNy and Ce2O3 and CeO2, a double Z-scheme pattern is suggested as a plausible charge transfer mechanism.


Educating nurses to care for the incontinent patient.
Urinary incontinence among nursing home patients is a very common problem. Until quite recently, incontinence was believed to be impossible or unnecessary to treat except through the use of absorbent pads and diapers. The cost of this type of management to the facility in terms of laundry, labor, and supplies, as well as to patients' well-being, is very high. Recent data suggest that at least some incontinent nursing home patients can benefit from treatment programs that can be taught to the nurse's aide staff and that, at the very least, will reduce laundry and supply costs. The significance of an improvement in patient morale or a decrease in the incidence of complications resulting from incontinence has yet to be assessed, but should be considered. In addition, even a partially successful treatment program may be helpful to the nurses caring for these patients as the nurses' sense of hopelessness and frustration about managing incontinent patients may be reduced. Finally, an active treatment program for continence, instituted by nurses, advances the nursing care of these patients from custodial nursing care to therapeutic nursing care.


Disseminated cutaneous and peritoneal hyalohyphomycosis caused by Fusarium species: three cases and review of the literature.
Three recent cases of hyalohyphomycosis caused by Fusarium sp. illustrate differing aspects of infections produced by these organisms. One patient was undergoing continuous ambulatory peritoneal dialysis when peritonitis developed caused by Fusarium moniliforme. Removal of the catheter and amphotericin B were used in successful management. In a neutropenic patient on therapy for leukemia, multiple persistent infections occurred including JK diptheroids, and Candida albicans sepsis. Finally, numerous florid skin lesions caused by Fusarium oxysporum developed even while the patient was receiving amphotericin B and he died. In a second neutropenic patient on treatment for leukemia, sinus and cutaneous lesions developed due to Fusarium. These resolved on amphotericin B therapy following the return of circulating neutrophils. The literature on Fusarium infections and aspects of the biology of the organism are reviewed.


Screening for prostate cancer: have you had your cholesterol measured?
Screening for prostate cancer has become one of the most common topics of conversation at urological oncology meetings. Most people have a bias as to whether there should or should not be a national screening programme. Unfortunately there are many unanswered questions, which may or may not be possible to answer definitively. In a balanced and scholarly review of the subject, Professor Peter Boyle indicates several flaws in the agreement for screening, but feels that PSA testing will continue unabated. The authors from the University of Stellenbosch review the plentiful literature relating to testicular torsion and functional recovery. They also review the mechanism of injury and the effect on the contralateral testis.


Enhancement of rat hepatic macrophages by treatment with interleukin-2 and streptococcal preparation OK432, with reference to antitumor activity, soluble factor production and Ia expression.
The effect of biological response modifiers, such as interleukin-2 (IL-2) and streptococcal preparation OK432, on the functions of hepatic macrophages was investigated. The macrophages, even with no exogenous stimulation, produced superoxide anion (O2-) and tumor necrosis factor (TNF), displayed cytotoxicity against K562 cells and cytostasis against P815 cells and expressed immune-region-associated antigen (Ia). IL-2 administered in vitro or in vivo enhanced O2- production by hepatic macrophages and the intravenous injection of OK432 also enhanced O2 production. Furthermore, IL-2 added to the culture medium of hepatic macrophages isolated from OK432-injected rats augmented O2- production even more. The TNF production and Ia expression of the macrophages were also increased by the intravenous injection of OK432. As with O2- production, the cytotoxicity of the cells was enhanced by OK432 injection or by IL-2 added to the culture medium and the combination of OK432 and IL-2 augmented their cytotoxicity even more. Thus, the present study suggested that IL-2 and OK432 induce the augmentation of the antitumor activity of hepatic macrophages, partly as a result of the increase in production of O2- and TNF and Ia expression.


Anthracycline-induced histamine release from rat mast cells.
Comparisons were made of the ability of doxorubicin, daunorubicin, rubidazone and aclacinomycin A to release histamine from rat peritoneal mast cells. Preliminary in vitro experiments indicated that doxorubicin (10(-6) to 2.5 X 10(-4) M), in contrast to compound 48/80 and the calcium ionophore A23187, did not produce significant release under any condition tested when purified or unpurified rat mast cells were used. In in vitro experiments, released histamine was measured in the cell-free supernatant of peritoneal fluid of rats after intraperitoneal injection of the agents. The time course of doxorubicin-induced histamine release from the peritoneum was rapid, with maximal release occurring within 4 to 6 min. Dose-response curves of the 4 agents over the range 10(-5) to 3.3 X 10(-3) M revealed that all caused histamine release, with 10(-3) M concentrations of each causing maximal release of comparable magnitude to that produced by 9.5 X 10(-6) M A23187. Treated mast cells recovered from the peritoneal cavity showed degranulation and vacuolization when examined by electron microscopy. Increased vascular permeability by the Evans-blue test was also noted with all 4 agents, and zones were of comparable size after injection of the highest concentration of each agent. The results indicate that in vivo, doxorubicin, daunorubicin, rubidazone and aclacinomycin A cause a rapid release of histamine from rat mast cells and an increase in vascular permeability in rat sin. There also appeared to be a reasonable correlation between the blueing reaction and histamine release in the peritoneal cavity in that the doses that did not cause skin blueing also failed to cause histamine release. The lack of histamine release by doxorubicin from mast cell preparations in vitro suggests that alterations to the doxorubicin molecule or the presence of other critical substances may be necessary for this activity to commence.


Synthesis, Characterization, Tautomeric Structure and Solvatochromic Behavior of Novel 4-(5-Arylazo-2-Hydroxystyryl)-1-Methylpyridinium Iodide as Potential Molecular Photoprobe.
A novel series of the title compound 4-(5-arylazo-2-hydroxystyryl)-1-methylpyridinium iodide 6 has been synthesized via condensation reactions of the arylazosalicylaldehyde derivatives 4a-i with 1-methyl-picolinium iodide 5. The structures of the new arylazo compounds were characterized by ¹H NMR, IR, mass spectroscopy, as well as spectral and elemental analyses. The electronic absorption spectra of arylazomerocyanine compounds 6 were measured in different buffer solutions and solvents. The pK's and pK*'s in both the ground and excited states, respectively, were determined for the series and their correlations with the Hammett equation were examined. The results indicated that the title arylazomerocyanine dyes 6 exist in the azo form 6A in both ground and excited states. The substituent and solvent effects (solvatochromism) of the title compound arylazomerocyanine dyes were determined using the Kamlet-Taft equation and subsequently discussed.


HBcrAg, pg RNA and HBsAg dynamically supervise the seroconversion of HBsAg with anti-viral therapy: "Loss of HBsAg" maybe not a good end-point of anti-viral therapy.
We aimed to identify predictor of HBsAg seroconversion using serum quantitative pg-RNA, HBcrAg and HBsAg in CHB patients with anti-viral therapy. A total of 335 patients with anti-viral therapy between 2013 and 2017 were enrolled, only 23 achieved the seroconversion of HBsAg, other 138 patients without seroconversion of HBsAg were selected randomly in 312 patients. The samples date of 161 patients were analyzed at different time. We defined the decrease titer of pg-RNA, HBcrAg and HBsAg from baseline to 6 months and baseline to 12 months as Δpg-RNA, ΔHBcrAg and ΔHBsAg, then we used the Δpg-RNA, ΔHBcrAg and ΔHBsAg to predict HBsAg seroconversion. About 6.9% of patients achieved HBsAg seroconversion after a median of 3.61 years' treatment. Using ROC to predict seroconversion of HBsAg, ΔHBsAg of 0.64 log10 IU/mL with AUC of 0.886 (0.802, 0.969; 95% CI) at 6 months and ΔHBsAg of 1.45 log10 IU/mL with AUC of 0.939 (0.868, 1.000; 95% CI) at 12 months had the maximized Youden's index. The comparison of HBcrAg "conversion" rates using Kaplan-Meier method between 23 patients with HBsAg conversion and 138 patients with HBsAg no conversion indicated that the two groups had significant difference at the time of antiviral discontinuation (p = 0.0124). According to our results, we can use ΔHBsAg to pick out the appropriate patients who have the potential to achieve seroconversion by sticking to antiviral therapy, that is very important to reach the target of functional cure or even clinical cure.


Bipaddle chimaeric forehead flap: A new technique for simultaneous lining and cutaneous reconstruction in case of full thickness defects of the nose.
Many techniques have been described to treat full thickness nasal defects. The authors introduce the bipaddle chimaeric forehead flap (BCFF), a new alternative technique to achieve simultaneous lining and cutaneous reconstruction in case of full thickness hemi-nasal defects, presenting surgical details and applications for its clinical use. From June 2015 to April 2017, 10 patients presenting with oncological full thickness defects involving nasal sidewall and/or nasal ala were reconstructed with the BCFF technique. Mean age was 69.4 years. The chimaeric flap was composed of 2 paddles (cutaneous and periosteal), nourished by a single supratrochlear pedicle, which were used to independently reconstruct the deficient cutaneous and mucosal layers of the nose. Cartilage grafts were used in 8/10 patients. Mean surgical time was 114 minutes. An intermediate thinning operation was performed in 3 out of 10 patients. All the flaps survived with no partial necrosis or cartilage exposure observed. Viability and mucosalization of the periosteal paddle was documented both intra-operatively (during the 2nd stage of the operation) and postoperatively (with fiberoptic rhinoscopy performed 3 months after the procedure). Clinical follow-up period ranged from 4 to 24 months postoperatively. The final result was judged sufficient, good and excellent in 1, 5, and 4 cases, respectively. The BCFF technique may be a new alternative approach to address full thickness hemi-nasal defects with no extra donor site morbidity, allowing primary placement of structural cartilage grafts and immediate definition of the nasal subunits to be reconstructed.


The proposed terminology 'A(1c)-derived average glucose' is inherently imprecise and should not be adopted.
The proposed use of a more precise standard for glycated (A(1c)) and non-glycated haemoglobin would lead to an A(1c) value, when expressed as a percentage, that is lower than that currently in use. One approach advocated to address the potential confusion that would ensue is to replace 'HbA(1c)' with a new term, 'A(1c)-derived average glucose.' We review evidence from several sources suggesting that A(1c) is, in fact, inherently imprecise as a measure of average glucose, so that the proposed terminology should not be adopted.


3D Oxygen-Enhanced MRI at 3T MR System: Comparison With Thin-Section CT of Quantitative Capability for Pulmonary Functional Loss Assessment and Clinical Stage Classification of COPD in Smokers.
Oxygen (O2 )-enhanced MRI is mainly performed by a 2D sequence using 1.5T MR systems but trying to be obtained by a 3D sequence using a 3T MR system. To compare the capability of 3D O2 -enhanced MRI and that of thin-section computed tomography (CT) for pulmonary functional loss assessment and clinical stage classification of chronic obstructive pulmonary disease (COPD) in smokers. Prospective study. Fifty six smokers were included. 3T, 3D O2 -enhanced MRIs were performed with a 3D T1 -weighted fast field echo pulse sequence using the multiple flip angles. Smokers were classified into four stages ("Without COPD," "Mild COPD," "Moderate COPD," "Severe or very severe COPD"). Maps of regional changes in T1 values were generated from O2 -enhanced MR data. Regions of interest (ROIs) were then placed over the lung on all slices and averaged to determine mean T1 value change (ΔT1 ). Quantitative CT used the percentage of low attenuation areas within the entire lung (LAA%). ΔT1 and LAA% were correlated with pulmonary functional parameters, and compared for four stages using Tukey's Honestly Significant Difference test. Discrimination analyses were performed and McNemar's test was used for a comparison of the accuracy of the indexes. There were significantly higher correlations between ΔT1 and pulmonary functional parameters (-0.83 ≤ r ≤ -0.71, P < 0.05) than between LAA% and the same pulmonary functional parameters (-0.76 ≤ r ≤ -0.69, P < 0.05). ΔT1 and LAA% of the "Mild COPD" and "Moderate COPD" groups were significantly different from those of the "Severe or Very Severe COPD" group (P < 0.05). Discriminatory accuracy of ΔT1 (62.5%) and ΔT1 with LAA% (67.9%) was significantly greater than that of LAA% (48.2%, P < 0.05). Compared with thin-section CT, 3D O2 -enhanced MRI has a similar capability for pulmonary functional assessment but better potential for clinical stage classification in smokers. 2 TECHNICAL EFFICACY STAGE: 1.


New Attempts to Define and Clarify Lupus.
The purpose is to discuss the advances that genetics and genomics have provided to better understand the molecular mechanisms behind SLE and how to solve its heterogeneity. I propose new ideas that can help us stratify lupus in order to find the best therapies for each patient, and the idea of substituting clinical diagnosis with molecular diagnosis according to their molecular patterns, an idea that may not only include lupus but also other diseases. The study of rare mutations may provide insight into groups of lupus patients where type I interferon signature is important and help understand those with an atypical clinical presentation. Recent papers used longitudinal blood transcriptome data correlating with disease activity scores to stratify lupus into molecular clusters. The implication of neutrophils in the risk to develop nephritis was established, but also that neutrophils and lymphocytes may correlate with activity differentiating the mechanisms of flares and separating patients into clinically separate groups. The role of type I interferon signature is important; however, the stratification of SLE patients according to the genes and cellular compartments being modulated during disease activity may be even more important to define those patients who may benefit the most with new anti-type I IFN receptor therapies.


Using technology to address recruitment issues in the clinical trial process.
It takes nearly ten years to get a drug through the discovery and development pipeline and onto the market; most of this time is spent in the clinical phase. Clinical development times vary widely from drug to drug, but a drug typically spends just over 6 years going through clinical trials and regulatory processes. At least 3 years of this time is spent recruiting patients. Every month by which the development process can be shortened is worth US $25 million in additional income for the average drug. Can the recruitment time be shortened?


[EEG-spectrum analysis for documentation of depth of anaesthesia. Correlation with pharmacokinetic data of fentanyl (author's transl)].
The article reports on a study regarding the posibility of monitoring anaesthesia via EEG characteristics when using fentanyl-nitrous oxide. An alpha-delta index correlated sufficiently accurately with the plasma levels of fentanyl administered via continuous infusion.


Combined surgery, radiotherapy and regional chemotherapy in carcinoma of the maxillary sinus.
In order to avoid post-operative cosmetic and functional disabilities, we introduced simultaneous surgery, radiotherapy and regional chemotherapy in treating carcinomas of the maxillary sinus in October 1964 and have been working to perfect this procedure ever since. This combined therapy consists of 1) a "reduction operation," i.e., reduction of the tumor mass, succeeded by daily cleaning of the residual tumor, 2) six external irradiation (mean dose is 1,200 rads/over a period of nine days) treatments and 3) five intra-arterial infusions of 5-fluorouracil (5-FU) (250 mg daily) and broxuridine (BUdR) (500 mg daily). The degenerative changes of the tumor cells, as observed by histopathological examinations, appear so rapidly that, when six irradiation treatments and five infusions were given, 80% of the cases showed marked irreversible change. This degeneration is not affected by the degree of differentiation. In other words, no variation was observed between well and poorly differentiated squamous cell carcinomas. In 77 cases infused with 5-FU alone, the five-year survival rate was 55%. Seventy-six percent of 45 cases infused with BUdR as well as 5-FU were still living after five years. We want to emphasize that these survivors are able to return to normal life with their eyes and palates well rehabilitated.


A large duplication involving the IHH locus mimics acrocallosal syndrome.
Indian hedgehog (Ihh) signaling is a major determinant of various processes during embryonic development and has a pivotal role in embryonic skeletal development. A specific spatial and temporal expression of Ihh within the developing limb buds is essential for accurate digit outgrowth and correct digit number. Although missense mutations in IHH cause brachydactyly type A1, small tandem duplications involving the IHH locus have recently been described in patients with mild syndactyly and craniosynostosis. In contrast, a ∼600-kb deletion 5' of IHH in the doublefoot mouse mutant (Dbf) leads to severe polydactyly without craniosynostosis, but with craniofacial dysmorphism. We now present a patient resembling acrocallosal syndrome (ACS) with extensive polysyndactyly of the hands and feet, craniofacial abnormalities including macrocephaly, agenesis of the corpus callosum, dysplastic and low-set ears, severe hypertelorism and profound psychomotor delay. Single-nucleotide polymorphism (SNP) array copy number analysis identified a ∼900-kb duplication of the IHH locus, which was confirmed by an independent quantitative method. A fetus from a second pregnancy of the mother by a different spouse showed similar craniofacial and limb malformations and the same duplication of the IHH-locus. We defined the exact breakpoints and showed that the duplications are identical tandem duplications in both sibs. No copy number changes were observed in the healthy mother. To our knowledge, this is the first report of a human phenotype similar to the Dbf mutant and strikingly overlapping with ACS that is caused by a copy number variation involving the IHH locus on chromosome 2q35.


Comparison of pyrrolidinyl and piperidinyl benzamides for their anticonvulsant activity and inhibitory action on sodium channel.
1. A pair of benzamide analogues containing a pyrrolidinyl or piperidinyl group was examined for their anticonvulsant activity against the electroshock-induced seizures in mice and the ability to block the voltage-gated Na channel in N1E-115 cells, in comparison with the prototype compound, U-54494A, (+/-)-cis-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-ben zam ide , a potent anticonvulsant and a Na channel blocker. 2. The pyrrolidinyl benzamide (U-49524E) was found to be effective against the electroshock-induced seizures (ED50 = 35 mg kg-1, i.p.) whereas the benzamide with a piperidinyl moiety (U-49132E) was inactive (ED50 greater than 100 mg kg-1). 3. Using whole-cell patch clamp techniques we found that U-49132E was several times less potent, with an IC50 of 396 microM as compared to 118 microM for U-49524E at the holding potential of -80 mV, and was much slower in blocking Na channels with a half-time of 10.7 +/- 1.1 min vs. 2.2 +/- 0.4 min for its counterpart. 4. Qualitatively, their general modes of interaction with Na channels were similar to each other and to that of U-54494A in that they interacted with the resting and slowly-inactivated states of the channels and exhibited a use-dependent inhibition because of a slow recovery from the inactivated state in the presence of the drugs. 5. Comparison of their physicochemical properties, shows the less potent and slowly acting U-49132E is more hydrophobic and bulkier than U-49524E, but has the same pKa. This suggests that the drugs approach the Na channel through a narrow and hydrophilic pathway.6. Overall, this study underscores the importance of inhibiting the Na channel to the anticonvulsant activity of the benzamide compounds.


Calcitonin gene-related peptide: brain and spinal action on intestinal motility.
The effects of intracerebroventricular (ICV) and intrathecal (IT) administration of calcitonin gene-related peptide (CGRP) on intestinal motility were examined in conscious rats chronically fitted with intraparietal electrodes in the duodeno-jejunum and a cannula in a cerebral lateral ventricle or catheter in the subarachnoid space. ICV administration of CGRP (0.5-10 micrograms) restores the fasted pattern of intestinal motility in fed rats in a dose-related manner. Intrathecal administration of CGRP or calcitonin also induces fasted pattern but after a 30 min delay. These effects persisted after transection of the spinal cord and no change in intestinal motility appeared after intravenous administration of CGRP at a dose effective when given IT. This study suggests that CGRP, as calcitonin, has a neuromodulatory role in the control of intestinal motility at both brain and spinal cord levels.


Dual Charge Transfer Generated from Stable Mixed-Valence Radical Crystals for Boosting Solar-to-Thermal Conversion.
Realizing dual charge transfer (CT) based on stable organic radicals in one system is a long-sought goal, however, remains challenging. In this work, a stable mixed-valence radical crystal is designed via a surfactant-assisted method, namely TTF-(TTF+• )2 -RC (where TTF = tetrathiafulvalene), containing dual CT interactions. The solubilization of surfactants enables successful co-crystallization of mixed-valence TTF molecules with different polarity in aqueous solutions. Short intermolecular distances between adjacent TTF moieties within TTF-(TTF+• )2 -RC facilitate both inter-valence CT (IVCT) between neutral TTF and TTF+• , and inter-radical CT (IRCT) between two TTF+• in radical π-dimer, which are confirmed by single-crystal X-ray diffraction, solid-state absorption, electron spin resonance measurements, and DFT calculations. Moreover, TTF-(TTF+• )2 -RC reveals an open-shell singlet diradical ground state with the antiferromagnetic coupling of 2J = -657 cm-1 and an unprecedented temperature-dependent magnetic property, manifesting the main monoradical characters of IVCT at 113-203 K while the spin-spin interactions in radical dimers of IRCT are predominant at 263-353 K. Notably, dual CT characters endow TTF-(TTF+• )2 -RC with strong light absorption over the full solar spectrum and outstanding stability. As a result, TTF-(TTF+• )2 -RC exhibits significantly enhanced photothermal property, an increase of 46.6 °C within 180 s upon one-sun illumination.


A fluorometric method for mercury(II) detection based on the use of pyrophosphate-modified carbon quantum dots.
Pyrophosphate-modified carbon quantum dots (PP-CDs) are demonstrated to be a viable fluorescent nanoprobe for mercury(II) (Hg2+) detection. Hg2+ reacts with the pyrophosphate groups on the surface of PP-CDs to form a non-fluorescent complex. This results in quenching of the green fluorescence which has excitation/emission peaks at 400/513 nm. Static quenching is shown to be the dominant mechanism. The probe works in 0.1 μM to 1.4 μM Hg2+ concentration range, and the limit of detection is 2 nM. The PP-CDs were also used to visualize Hg2+ inside human hepatocyte LO2 cells. Graphical abstract Schematic representation of pyrophosphate-modified carbon quantum dots (CDs) for selective and sensitive fluorometric determination of mercury(II). Hg(II) quenches the blue fluorescence of the CDs, and glutathione restores it. The method was used to detect Hg(II) in spiked tap water and inside cells.


Efficacy of lianhuaqingwen granules in the management of chronic rhinosinusitis without nasal polyps.
Chronic rhinosinusitis (CRS) is a complicated disease with clinical symptoms that are impacted by the absence or presence of nasal polyps (CRSsNP or CRSwNP). Understanding of the different treatments of CRS is very significant in selecting appropriate therapies and preventing exacerbation relevant to this chronic inflammation. This study was aimed to evaluate the effect of Chinese traditional medicine lianhuaqingwen granules on CRSsNP. CRSsNP patients were enrolled and randomized into placebo or lianhuaqingwen (LHQW) granules treatment group (placebo or LHQW group). Their clinical symptoms were scored using Visual Analog Scale (VAS) and Sino-Nasal Outcome Test (SNOT)-22. Nitric oxide (NO) from nasal cavity and sinus and nasal resistance were also examined. Then, nasal biopsy samples and nasal lavage fluid (NLF) were obtained from these patients, and histologic characteristics of nasal mucosa and T cell subpopulations patterns in the NLF were evaluated. Finally, inflammatory mediators in the NLF were assessed in both groups. One hundred and forty patients with CRSsNP finished this one-month study. VAS and SNOT-22 scores and nasal resistance were all decreased distinctly after the treatment of LHQW, but not after placebo. However, the nasal NO concentration was increased in LHQW administration group in comparison with placebo group. There were significant differences in above parameters between these two treatments. Histologic changes in nasal mucosa were improved only in LHQW group. CD4+ and CD8+ T cells were all downregulated in the LHQW treatment group, but not in placebo group. Inflammatory mediators from the NLF were decreased in LHQW treatment group compared to placebo group. Furthermore, there were significant changes between these two groups in CD4+ and CD8+ T cell subpopulations and concentrations of inflammatory substances. These findings demonstrate that LHQW granules treatment may control the inflammation in nasal mucosa and result in the improvement of CRSsNP. This Chinese medicine might become a promising therapy in the management of this disease.


Antipyretic properties of the aqueous and ethanol extracts of the leaves of Ocimum suave and Ocimum lamiifolium in mice.
Numerous plant species are used to treat ailments associated with pyrexia in the indigenous health care delivery system of Ethiopia. Notable among these are Ocimum suave and Ocimum lamiifolium. The objective of the present study was thus to evaluate the antipyretic effects of the aqueous and ethanol extracts of the leaves of Ocimum suave and Ocimum lamiifolium in mice. Rectal temperatures were recorded before and after inducing pyrexia as well as after administration of the respective extracts every half an hour for 3h. Parallel experiments were run with a standard antipyretic (acetylsalicylic acid) and the vehicle (distilled water). All the plant extracts showed antipyretic property with reasonable onset and duration of action. Both ethanol and aqueous extracts of Ocimum suave were observed to be more potent than those of Ocimum lamiifolium. Aqueous extract of Ocimum suave and ethanol extract of Ocimum lamiifolium were more potent than their other counterpart extracts. Time dependent antipyretic effect was also observed with some extracts; reduced with time with aqueous extract of Ocimum suave and increased with time with both extracts of Ocimum lamiifolium.


Cloning of DNA corresponding to four different measles virus genomic regions.
Hybrid plasmids containing sequences corresponding to four different regions of the measles virus genome inserted in pBR322 were obtained by use of polyadenylated 50 S viral RNA as template for reverse transcription. One class of plasmids contains inserts corresponding to the 3' terminal region of the virus genome. The sequence of one of these inserts (605 nucleotides) partially overlaps with the cloned cDNA sequence corresponding to a part of the nucleocapsid protein (N) mRNA (M. Gorecki and S. Rozenblatt (1980). Proc. Natl. Acad. Sci. USA 77, 3686-3690). This insert region shows only one long open reading frame defining the N-terminal part of the nucleocapsid protein. The nucleocapsid protein mRNA starts at about 60 nucleotides from the genome end as revealed by nuclease S1 mapping. Three other classes of plasmid clones contain inserts derived from unidentified regions of the viral genome; they hybridize with viral mRNA species less abundant than those from which cDNA clones have been isolated so far (S. Rozenblatt, C. Gesang, V. Lavie, and F. S. Neumann (1982) J. Virol. 42, 790-797.