Community-based trial results of combination clindamycin 1%--benzoyl peroxide 5% topical gel plus tretinoin microsphere gel 0.04% or 0.1% or adapalene gel 0.1% in the treatment of moderate to severe acne.
Acne is characterized by different types of lesions at different stages of development. Therefore, combination therapy may offer numerous advantages, including enhanced efficacy and better tolerability. The addition of benzoyl peroxide (BPO) to all long-term antibiotic treatment is widely advocated to help suppress the emergence of antibiotic-resistant bacteria. Topical retinoids are recommended as early initiation treatment of most patients with acne because they target most mechanisms of acne pathogenesis. In the clinical setting, therapeutic regimens that include retinoids and topical antibiotic-BPO combination formulations frequently are prescribed. This study investigated the efficacy and safety of combination therapy with clindamycin 1%-BPO 5% topical gel plus tretinoin microsphere (RAM) gel 0.04% or 0.1% or adapalene (AP) gel 0.1% in moderate to severe acne.


[Reduced-intensity conditioning haematopoietic stem cell transplantation in genetic diseases: Experience of the Spanish Working Group for Bone Marrow Transplantation in Children].
Haematopoietic stem cell transplantation (HSCT) involves implanting cellular elements capable of generating a new and healthy haematopoietic system. Reduced intensity conditioning (RIC) consists of an immunosuppressive treatment to facilitate a progressive implant with lower morbidity. This type of conditioning can also lead to myelosuppression, which is potentially reversible over time. Reduced intensity conditioning enables HSCT to be performed on patients with genetic diseases for whom added comorbidity is undesirable due to the high doses of chemotherapy that accompanies conventional myeloablative regimens. An analysis was performed on the outcomes of 68 paediatric patients with genetic diseases who underwent HSCT with RIC between 2005 and 2013 in the of Paediatric Haematopoietic Stem Cell Transplantation Units that are part of the Spanish Working Group for Bone Marrow Transplantation in Children. A multicentre study was conducted including 68 patients, of whom 43 had Primary Immunodeficiency, 21 with congenital haematological diseases, and 4 with metabolic diseases. Fifty (73.5%) of the 68 patients were still alive. The Overall Survival (OS) at nine years was 0.74. Twenty-three (33.8%) had some event during the course of the HSCT, with an event-free survival rate of 0.66. The OS in patients with haematological diseases was 0.81, being 0.7 in primary immunodeficiencies, and 0.4 in metabolic diseases. No significant difference was observed between the 3 groups of diseases. As regards the source of haematopoietic progenitors, there was an OS rate of 0.74 in patients transplanted with peripheral blood, 0.70 with bone marrow, and 0.70 and with cord blood, with no statistically significant differences. Favourable results have been obtained in HSCT with reduced intensity conditioning in genetic diseases. It should be noted that the risks and benefits of the RIC in patients with metabolic diseases need to be assessed on an individual basis.


An iliac bone stress fracture in a basketball player.
The authors describe the case of an athlete from the Brazilian national men's basketball team (sub-16) who reported pain in the right iliac region at the end of the season. Clinical and imaging exams revealed an iliac bone stress fracture. A conservative treatment of removing the load from the fracture in combination with physical therapy was chosen. The athlete improved satisfactorily and returned to the sport at the same level as prior to the injury after 14 weeks of treatment.


Online description of services provided in adult survivorship programs across U.S. accredited cancer centers.
The American College of Surgeons Standard 4.8 requires an institution to implement a survivorship program to become a Commission on Cancer (CoC)-accredited cancer center. The online information offered by these cancer centers can help educate patients and their caregivers about available services. We assessed the content of survivorship program websites of CoC-accredited cancer centers in the United States. Of the 1245 CoC-accredited centers for adults, we sampled 325 institutions (26%) based proportionately on the 2019 new cancer cases by state. Website pages of the institutions' survivorship programs were assessed for information and services offered using the COC Standard 4.8. We included programs for adult survivors of adult- and childhood-onset cancers. 54.5% of the cancer centers did not have a survivorship program website. Of the 189 included programs, most were aimed at adult survivors in general, rather than those with specific cancer types. On average, five essential CoC-recommended services were described, most commonly nutrition, care plans, and psychology services. The least mentioned services were genetic counseling, fertility, and smoking cessation. Most programs described services offered to patients who had completed treatment, while 7.4% of described services for those with metastatic disease. More than half of CoC-accredited programs did have information about cancer survivorship programs on their websites and when included, had variable and limited description of services. Our study provides an overview of online cancer survivorship services and offers a methodology that may be used by cancer centers to review, expand, and improve the information described on their websites.


New software for searching the Cambridge Structural Database and visualizing crystal structures.
Two new programs have been developed for searching the Cambridge Structural Database (CSD) and visualizing database entries: ConQuest and Mercury. The former is a new search interface to the CSD, the latter is a high-performance crystal-structure visualizer with extensive facilities for exploring networks of intermolecular contacts. Particular emphasis has been placed on making the programs as intuitive as possible. Both ConQuest and Mercury run under Windows and various types of Unix, including Linux.


In vitro activity of SCH-56592 and comparison with activities of amphotericin B and itraconazole against Aspergillus spp.
In this study, we investigated the in vitro activity of SCH-56592 (SCH), a new triazole antifungal agent. We compared the activity of SCH with those of itraconazole (ITZ) and amphotericin B (AB) against 60 clinical isolates of Aspergillus spp. by using a microtiter format. Incubation was done at 37 degrees C for 48 h, and MIC endpoints (no growth) were read visually. The medium used for all of the drugs was RPMI 1640 buffered with morpholinepropanesulfonic acid (MOPS) and supplemented with 2% glucose. MICs and minimum fungicidal concentrations (MFCs; killing of > or = 99.99%) were measured for all isolates. The geometric mean (GM) MICs and ranges (in micrograms per milliliter) were as follows: SCH, 0.09 and < or = 0.01 to 1; ITZ, 0.25 and 0.06 to 32; AB, 1.46 and 0.25 to 32. Aspergillus terreus (n = 7) was markedly more susceptible to SCH (GM, 0.05 microg/ml) and ITZ (GM, 0.07 microg/ml) than to AB (GM, 8.8 microg/ml). For all isolates, the GM MFCs and ranges (in micrograms per milliliter) were as follows: SCH, 3.64 and 0.125 to 16; ITZ, 15.09 and 0.125 to 32; AB, 10.3 and 1 to 32. In the drug concentration range tested, 71, 32, and 64% of the isolates against which SCH, ITZ, and AB, respectively, were tested were killed. A reproducibility study was performed with 20% of the isolates; for 11 of the 12 isolates retested, the MIC was the same or within 1 well of the original MIC of each drug. Therefore, in vitro mould testing of SCH is feasible and reproducible. SCH was found to be very active against all species of Aspergillus and at lower concentrations than either ITZ or AB.


Esophageal insufflation testing in nonlaryngectomized adults.
Esophageal insufflation testing has been advocated for laryngectomized patients considered for tracheoesophageal puncture. The present work was undertaken to document the degree to which nonlaryngectomized individuals were able to produce and sustain esophageal voice in association with esophageal insufflation testing. Fifteen young, healthy adults were tested in a uniform way. Results were interpreted to support the views that (a) normal function of the pharyngoesophageal segment represents an influence detrimental to the ultimate acquisition of functionally serviceable esophageal or tracheoesophageal speech and (b) laryngectomized patients having airtight closure of the pharyngoesophageal segment during insufflation testing exhibit a normal esophageal response. Implications for completing air insufflation testing and selective myotomy are discussed.


Microbially mediated nitrogen removal and retention in the York River Estuary.
Denitrification, anaerobic ammonium oxidation and dissimilatory nitrate reduction to ammonium (DNRA) are important microbial processes determining the fate of nitrogen (N) in estuaries. This study examined these processes in sediments of the York River Estuary, a tributary of Chesapeake Bay, and investigated environmental and microbial drivers of the rates of denitrification and DNRA. Nitrate reduction followed a consistent pattern throughout the year and across the estuary with nitrogen removal, primarily through denitrification, decreasing from the head of the estuary to the mouth and nitrogen retention, through DNRA, following the opposite pattern. At the mouth of the estuary, nitrogen retention was consistently higher than nitrogen removal. Denitrification rates showed strong linear relationships with concentrations of organic matter, nitrate and chlorophyll a, and the abundance of the nirS gene. DNRA rates were best correlated with the relative abundance of three bacterial families, Anaerolineaceae,Ectothiorhodospiraceae and Prolixibacteraceae, which carry the nrfA gene. The controls responsible for retention or removal of N from an estuary are complex, involving both geochemical and microbial factors. The N retained within estuaries may support primary production and seasonal algae blooms and result in estuarine eutrophication.


MicroRNA-24 can control triacylglycerol synthesis in goat mammary epithelial cells by targeting the fatty acid synthase gene.
In nonruminants it has been demonstrated that microRNA-24 (miR-24) is involved in preadipocyte differentiation, hepatic lipid, and plasma triacylglycerol synthesis. However, its role in ruminant mammary gland remains unclear. In this study we measured miR-24 expression in goat mammary gland tissue at 4 different stages of lactation and observed that it had highest expression at peak lactation when compared with the dry period. Overexpression or downregulation of miR-24 in goat mammary epithelial cells (GMEC) strongly affected fatty acid profiles; in particular, miR-24 enhanced unsaturated fatty acid concentration. Additional effects of miR-24 included changes in triacylglycerol content and the expression of fatty acid synthase, sterol regulatory element binding transcription protein 1, stearoyl-CoA desaturase, glycerol-3-phosphate acyltransferase mitochondrial, and acetyl-CoA carboxylase. Luciferase reporter assay confirmed that fatty acid synthase is a target of miR-24. Taken together, these results not only highlight the physiological importance of miR-24 in fatty acid metabolism in GMEC, but also laid the foundation for further research on regulatory mechanisms among miR-24 and other microRNA expressed in GMEC.


MATtrack: A MATLAB-Based Quantitative Image Analysis Platform for Investigating Real-Time Photo-Converted Fluorescent Signals in Live Cells.
We introduce here MATtrack, an open source MATLAB-based computational platform developed to process multi-Tiff files produced by a photo-conversion time lapse protocol for live cell fluorescent microscopy. MATtrack automatically performs a series of steps required for image processing, including extraction and import of numerical values from Multi-Tiff files, red/green image classification using gating parameters, noise filtering, background extraction, contrast stretching and temporal smoothing. MATtrack also integrates a series of algorithms for quantitative image analysis enabling the construction of mean and standard deviation images, clustering and classification of subcellular regions and injection point approximation. In addition, MATtrack features a simple user interface, which enables monitoring of Fluorescent Signal Intensity in multiple Regions of Interest, over time. The latter encapsulates a region growing method to automatically delineate the contours of Regions of Interest selected by the user, and performs background and regional Average Fluorescence Tracking, and automatic plotting. Finally, MATtrack computes convenient visualization and exploration tools including a migration map, which provides an overview of the protein intracellular trajectories and accumulation areas. In conclusion, MATtrack is an open source MATLAB-based software package tailored to facilitate the analysis and visualization of large data files derived from real-time live cell fluorescent microscopy using photoconvertible proteins. It is flexible, user friendly, compatible with Windows, Mac, and Linux, and a wide range of data acquisition software. MATtrack is freely available for download at eleceng.dit.ie/courtney/MATtrack.zip.


Multifocal choroiditis following simultaneous hepatitis A, typhoid, and yellow fever vaccination.
The paper describes the first reported case of multifocal choroiditis following simultaneous hepatitis-A, typhoid, and yellow fever vaccinations. A 33-year-old male developed sudden onset of flashing lights and floaters in his right eye 3 weeks following hepatitis A, typhoid, and yellow fever vaccinations. Fundus examination and angiography confirmed the presence of multiple peripheral chorioretinal lesions. These lesions demonstrated characteristic morphologic changes over a period of 8 weeks which were consistent with a diagnosis of self-resolving multifocal choroiditis. Vaccine-induced intraocular inflammation has been described infrequently. We demonstrate the first case of self-resolving multifocal choroiditis following simultaneous administration of hepatitis A, yellow fever, and typhoid immunizations.


Caring for Our Human Nature.
The care for creation is an important call for all. Our human bodies form part of this created reality and should be treated with dignity and respect. Pope Benedict XVI underlined the ecology of man. Pope Francis took up this teaching in his pontificate, encouraging us to welcome the gift of our body, and critiquing ideologies which undermine the respect due our bodies. Proponents of the so-called "gender ideology" affirm surgery on the body, which generally involves the removal of healthy functioning tissues and organs, is largely mutilating, and can involve exorbitant costs. The voices of those who have "detransitioned" such as Keira Bell need also to be heard. The Congregation for Catholic Education, in its document "Male and Female He Created Them: Toward a Path of Dialogue on the Question of Gender Theory in Education" warns us against theories that aim to annihilate the concept of "nature," that is, everything we have been given as a pre-existing foundation of our being and action in the world. Our growing awareness of the importance of the environment and nature can lead us to a greater respect for our own human nature. We are all called to participate in the care for nature and creation, especially of our bodies as part of the created reality. Many voices today remind us to take care of nature and creation. Our bodies are part of this created reality. Proponents of gender ideology do not hesitate to promote surgery which radically alters and even mutilates the body. Our increasing ecological awareness can help us grow more sensitive to the ecology of man and woman, and value the gift of the nature and body given to each one of us. Let us take care of nature and creation, including our own bodies.


On the biodegradation of beta-peptides.
A consortium of microorganisms was established that was able to grow with the beta-tripeptide H-beta-HVal-beta-HAla-beta-HLeu-OH, with the beta-dipeptide H-beta-HAla-beta-HLeu-OH, and with the beta-amino acids H-beta-HAla-OH, H-beta-HVal-OH, and H-beta-HLeu-OH as the sole carbon and energy sources. This growth was achieved after several incubation-transfer cycles with the beta-tripeptide as the substrate. During degradation of the beta-tripeptide H-beta-HVal-beta-HAla-beta-HLeu-OH, the temporary formation of a metabolite was observed. The metabolite was identified as the beta-dipeptide H-beta-HAla-beta-HLeu-OH by nuclear magnetic resonance spectroscopy and mass spectrometry. This result indicates that in the course of the degradation of the beta-tripeptide, the N-terminal beta-HVal residue was cleaved off by a not yet known mechanism. During the subsequent degradation of the beta-dipeptide, formation of additional metabolites could not be detected. The growth-yield coefficients Y(x/s) for growth on the beta-di- and beta-tripeptide both had a value of 0.45. When a 1:1 mixture of the beta-tripeptide and the corresponding alpha-tripeptide H-Val-Ala-Leu-OH was added to the enrichment culture, the alpha-peptide was completely utilized in six days and thereafter growth of the culture stopped. This result indicates that even in beta-peptide enrichment cultures, alpha-peptides are the preferred substrates. Our experiments clearly show for the first time that beta-peptides and beta-amino acids are amenable to biodegradation and that a microbial consortium was able to utilize these compounds as sole carbon and energy sources. Furthermore, the preparation of beta-amino acids, of derivatives thereof, and of beta-di- and beta-tripeptides is described.


Epidemiology of soccer injuries in Korea women national team for 5 years.
The purpose of this study was to analyze the characteristics of injuries in female national soccer players. The injuries data were recorded by Korea Football Association medical staff using the Daily Medical Report provided by the Asian Football Confederation during a total 21 training camps and friendly and official matches from January 2014 to December 2018. A total of 483 players in the national team training camps and matches participated in the study, of which 377 players experienced more than one injury. Sports injuries accounted for 89% of the total 1,019 injuries; general diseases accounted for the remaining 11%. The number of injuries per 1,000 exposure hours was higher in matches than in training sessions. Most injuries that occurred during training and matches involved the lower extremities (79%). The most common injury diagnosed during training and matches was muscle rigidity (45%), followed by contusions/hematomas/bruises (22%) and sprain (15%). The largest proportions of injuries in terms of absence from soccer play were minimal injury (67%), followed by mild (29%), moderate (3.5%), and severe (1%). As conclusion, the characteristics of injuries during training sessions and matches were different. Rehabilitation and injury prevention programs need to developed for female soccer players to improve the players' performance.


[A case of multiple liver metastases after resection of gastrointestinal stromal tumor of the small intestine that was successfully treated with imatinib mesylate].
A 73-year-old man was found to have an intestinal tumor, approximately 10 cm in diameter, on computed tomography (CT). In September 2001, he underwent partial resection of the jejunum with partial colectomy and left nephrectomy. Pathological examination showed 2 mitoses per 50 high-power fields, and immunohistochemical analysis showed positive staining for c-kit. Based on the above findings, the tumor was diagnosed as a high-risk malignant gastrointestinal stromal tumor( GIST) of the small intestine; the patient was followed up and no adjuvant therapy was administered. In October 2005, an abdominal CT scan revealed 2 tumors with diameters of 21 and 28 mm in the S8 and S7 region of the liver, respectively, and the patient was diagnosed with liver metastases from GIST. After obtaining adequate informed consent, chemotherapy with imatinib (400 mg/day) was initiated. Although the patient experienced partial response (PR) 2 months after the treatment, grade 3 neutropenia and general fatigue were observed. Therefore, the treatment schedule was changed to 1 week of therapy, followed by 1 week of rest. At present, at 91 months after the diagnosis of liver metastases, the patient shows no signs of recurrence. Therefore, it is important that adjuvant chemotherapy should be considered for the treatment of patients with high-risk malignant GIST.


A Red Blood Cell Model to Estimate the Hemolysis Fingerprint of Cardiovascular Devices.
One of the most relevant and open issues within cardiovascular prosthetic hemodynamic performance is a realistic quantification of the damage sustained by red blood cells (RBCs). Specifically, the optimal design of bileaflet mechanical heart valves (BMHVs) requires both low shear stresses along the leaflets and short particle resident times. This study approaches RBC damage estimation by developing a numerical model of RBCs and computing the damage sustained by a set of passive RBCs immersed within in vitro flows. The RBC is modeled as an ellipsoidal shell with size dependent on age. Mechanically, a viscous hyper-elastic model was adopted to compute the stress-deformation transmitted by the experimental flow field to the RBC layer. The rupture parameters were calibrated using experimental results on real RBCs submitted to Couette flow. Moreover, the integrated hemolysis index (HI) through a BMHV was computed for a set of RBCs injected in a flow field derived from an in vitro study and for multiple RBC passages. The main results are (1) a good capability of the RBC model to replicate in vitro experiments performed with real RBCs, finding realistic rupture parameters; (2) the spatial distribution for the HI, maximal along the leaflet boundary layer and for long resident times; (3) 90% of HI is produced by the less damaging trajectories, which are favored by local flow dynamics; (4) cumulated HI in 8 days is about 0.01% smaller than the clinical warning threshold, the latter being obtained only after a period of time comparable with the RBC lifetime.


HGP-30, a synthetic analogue of human immunodeficiency virus (HIV) p17, is a target for cytotoxic lymphocytes in HIV-infected individuals.
Evaluation of the immune response of individuals exposed to human immunodeficiency virus (HIV) is an important component of any plan designed to lead toward the development of an AIDS vaccine. Since the levels of antibodies to HIV p17 and the synthetic p17 peptide HGP-30 correlate with stages of progression to AIDS, studies were initiated to determine whether cytotoxic lymphocytes directed toward target cells pulsed with HGP-30 and radioactive chromium were present in seropositive individuals. The significance of such cells in controlling HIV viral infection has recently been enhanced by reports that HIV p17 is on the surface of infected cells and that an inactivated virus vaccine depleted of viral envelope appears to be effective in controlling expression. The selection of HGP-30 as the p17 peptide to be evaluated in early studies is based on the presence of both T-cell and B-cell epitopes as predicted by computer modeling and mouse studies and the demonstration of in vitro neutralization activity by antibodies to the epitope. By using B-lymphoblastoid cells pulsed with HGP-30 and radioactive chromium as autologous targets and mixed leukocyte culture-expanded peripheral blood lymphocytes as effectors, CD8+ cytotoxic T lymphocytes against HGP-30-coated targets were identified in seropositive individuals. In this report we demonstrate that a synthetic p17 epitope can be a target for major histocompatibility complex-restricted cytotoxic T lymphocytes in HIV-infected individuals.


[Analysis of the mechanisms of the anti-arrhythmic action of marcaine and lidocaine].
It has been demonstrated in experiments on anesthetized cats with heart rhythm abnormalities induced by the creation of an "ectopic focus" by high-frequency electric stimulation of the ventricles that lidocaine in a dose of 5.8 mg/kg is inferior to marcaine in a dose of 1.3 mg/kg as regards the ability to inhibit the sympathetic tone. Lidocaine and marcaine have been discovered to produce different effects: lidocaine produced a dose-dependent selective inhibition of C-components of reflex discharges, whereas marcaine a more prolonged and uniform suppression of both A- and C-components of evoked responses, inhibiting both excitatory and inhibitory components of reflex responses.


Role of endogenous endothelin in endothelial dysfunction in murine model of systemic sclerosis: tight skin mice 1.
Systemic sclerosis (SSc) is a systemic inflammatory disorder, resulting in severe vascular dysfunction. The endothelin (ET) system has vasoconstrictor and profibrotic properties and has been shown to be activated in SSc. ET antagonists are currently used in SSc-related pulmonary arterial hypertension, but the endothelial impact of ET antagonists remains less known in SSc. We thus assessed the effects of the dual ET(A)-ET(B) antagonist, bosentan, on endothelial dysfunction in a murine model of SSc, the heterozygous tight-skin mice 1 (TSK1(+)). Six-week-old TSK1(+) were either untreated or treated for 6 weeks with bosentan (100 mg/kg/day), and compared with controls. Endothelial function was evaluated in isolated mesenteric resistance arteries, using a small vessel myograph. TSK1(+) displayed endothelial dysfunction, as shown by a decreased response of mesenteric arteries to acetylcholine, especially in the presence of L-nitro-arginine methyl ester (L-NAME), corresponding to NO-independent, prostaglandin-mediated relaxation. The NO-independent relaxation was partially restored in bosentan-treated TSK1(+), and this was abolished by a cyclo-oxygenase inhibitor. Therefore, the murine model of SSc, TSK1(+) exhibits severe endothelial dysfunction of peripheral resistance arteries. The ET antagonist bosentan prevents endothelial alterations, suggesting a major role of ET in the adverse vascular effects of SSc.


Insulin-like growth factor 1, its binding protein 3, and sex hormones in girls during puberty.
The aim of the study was to estimate relationships between serum concentration of insulin-like growth factor 1 (IGF-1), its binding protein (IGFBP-3), estradiol and testosterone in girls during puberty, taking into consideration gonadotropins level and nutritional status. Eighty-six girls aged 9.8-14.7 were examined. The girls were divided into three groups according to the pubertal stage. Body height, weight and thicknesses of skin folds were measured. Biochemical parameters were assessed using RIA method. It has been found that all investigated parameters are growing with pubertal development. There are significant positive correlations between IGF-1 and testosterone, IGF-1 and estradiol serum concentrations as well as between IGF-1 serum concentration, BMI and sum of skin folds thicknesses. It has been also proved that there are positive correlations between IGFBP-3 and estradiol serum concentration as well as between IGFBP-3 and age, body height and body weight in girls during puberty.


Genetic characterization of the metK locus in Escherichia coli K-12.
Three independently isolated metK mutants have been shown to have leisions lying between speB and glc near 57 min on the Escherichia coli chromosome. Two deletions result in a lack of the metC gene product but neither extends into the metK glc region. The three metK mutations are recessive to the wild-type allele carried on the KLF16 episome.


[A case of minute carcinoma associated with an atypical epithelial lesion of the stomach and histopathological analysis].
A patient with minute carcinoma associated with an atypical epithelial lesion (ATP) of the stomach is reported. The resected stomach from this 81-year-old male exhibited a 1.3 X 1.0 cm elevated ATP; microscopic examination revealed a minute (0.4 mm) carcinoma. The lesion was differentiated tubular adenocarcinoma and was suggestive of one-gland carcinoma. It consisted of one faveola in the upper half and multibranched , compound alveolar glands in the lower half, structurally mimicking the initial stage of intestinal metaplasia. The lesion existed in small metaplastic foci; the surface foveolar epithelia of the lesion showed no cancerous changes. These findings suggested that this minute carcinoma occurred in the initial stage of intestinal metaplasia.


Concanavalin A binding glycoproteins in subcellular fractions from the developing rat cerebral cortex.
Synaptic plasma membrane (SPM) and mitochondrial fractions were prepared from 3-50-day rat cerebral cortex and their purity assessed. The fractions were subjected to electrophoresis on slab gels, stained for protein, and overlaid with 125I-concanavalin A (ConA). ConA binding glycoproteins (CABGs) were revealed by autoradiography. In the SPM fraction CABGs of MW 25,000, 63,000, 80,000, 115,000, 174,000, and 239,000 increased while those of MW 47,000, 75,000, and 190,000 decreased developmentally. In the mitochondrial fraction, CABGs of MW 25,000, 44,000, 115,000 and 174,000 increased while those of 34,000, 43,000, 47,000, 51,000, 80,000, 107,000, and 195,000 decreased developmentally. CABGs of MW 32,000, 63,000, 88,000, 153,000, 190,000, and 239,000 appear to be unique to the SPM fraction and those of MW 34,000, 107,000, and 195,000 are unique to the mitochondrial fraction.


Beta blockade to prevent atrial dysrhythmias following coronary bypass surgery.
Atrial fibrillation and atrial flutter (AF) frequently complicate coronary artery bypass surgery (CABG) and increase hospital stay as well as morbidity. Studies of drug prophylaxis to prevent AF with beta-adrenergic blocking agents administered in fixed doses have had conflicting results. One hundred patients were randomized to receive metoprolol or placebo following CABG. A dosing algorithm was used to achieve clinically significant beta-adrenergic blockade. There was no significant difference between the incidence of AF in the metoprolol (24%) and placebo (26%) groups. However, the incidence of AF in all patients having CABG at this institution declined over the period of the study from 31% to 23% (P < .025), in association with the adoption of a continuous technique of cardioplegia delivery. Metoprolol is not efficacious for the prevention of post-CABG AF even when dosage is titrated to achieve clinical evidence of beta blockade. It is likely that the adoption of a continuous cardioplegia technique caused a reduction in our incidence of post-CABG AF.


Intravesical lipiodol injection technique for image-guided radiation therapy for bladder cancer.
To describe the technique of injecting Lipiodol in the submucosa of the urinary bladder wall as a novel modality to improve localization of muscle-invasive bladder tumors before image-guided radiation therapy. Eight patients underwent submucosal Lipiodol injections at transurethral bladder tumor reresection. A rigid cystoscope with a working port was used to inject Lipiodol into bladder submucosa circumferentially around the tumor bed (2-3 mm from margin of resection). Approximately 20-30 injections were used to demarcate the tumor bed for external beam radiation therapy, which was used as part of a bladder-sparing approach. All patients were diagnosed with clinically localized, high-grade, muscle-invasive carcinoma and were deemed nonsurgical candidates or were unwilling to undergo radical cystectomy. Five of the 8 patients received radiation at our institution. Lipiodol injections (95%) were visible on treatment planning computed tomographic scans and kilovoltage portal images throughout the 7-week course of image-guided radiation therapy. In 2 of 5 patients, the tumor bed based on Lipiodol extended outside a planning target volume that would have been treated with radiation therapy based on cystoscopy reports and computed tomographic scans without Lipiodol. There were no adverse events or treatment-related toxicities secondary to Lipiodol injection. Intravesical Lipiodol injection is an easy-to-perform technique that is safe and effective. Lipiodol serves as a fiducial marker that improves tumor bed localization for radiation therapy, thereby reducing the likelihood of missing the tumor.


A Modular Synthesis of 4-Aminoquinolines and [1,3] N-to-C Rearrangement to Quinolin-4-ylmethanesulfonamides.
A copper-catalyzed regiocontrolled three-component reaction afforded diversified 4-aminoquinolines using nitriles, diaryliodoniums, and ynamides. The C7-substituted regioisomers were formed regioselectively when meta-substituted phenyliodonium salts were used. [1,3] N-to-C rearrangement of the products to quinolin-4-ylmethanesulfonamides and simultaneous deprotection of benzyl and sulfonamide group were newly developed. Finally, antimalarial CK-2-68 was successfully prepared.


Adaptation and validation of a computerized neurocognitive battery in the Xhosa of South Africa.
Large-scale studies have revolutionized biomedical research, and neurocognitive tests can help elucidate the biological basis of neuropsychiatric diseases. However, studies have predominantly been conducted in Western settings. We describe the development and validation of a computerized battery (PennCNB) with the Xhosa population of South Africa. Individuals with schizophrenia (n = 525) and a normative comparison group (n = 744) were balanced on age, sex, education, and region. Participants provided blood samples, were assessed psychiatrically, and were administered a PennCNB translation to isiXhosa, including measures of executive functions, episodic memory, complex cognition, social cognition, and sensorimotor speed. Feasibility was examined with test completion rates and input from administrators, and psychometric structural validity and associations with clinical and demographic characteristics were examined. Tests were well tolerated by participants, as >87% had one (or fewer) test missing. Results suggested a similar factor structure to prior PennCNB studies in Western contexts, and expected age and sex effects were apparent. Furthermore, a similar profile of schizophrenia was observed, with neurocognitive deficits most pronounced for executive functions, especially attention, as well as memory, social cognition, and motor speed relative to complex cognition and sensorimotor speed. Results support the feasibility of implementing a culturally adapted computerized neurocognitive battery in sub-Saharan African settings and provide evidence supporting the concurrent validity of the translated instrument. Thus, the PennCNB is implementable on a large scale in non-Western contexts, shows expected factor structure, and can detect cognitive deficits associated with neuropsychiatric disorders. Obtaining valid measures of cognition by nonspecialized proctors is especially suitable in resource-limited settings, where traditional testing is prohibitive. Future work should establish normative standards, test-retest reliability, and sensitivity to treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Cerebral processing of proper and common nouns: Perception and production following left hemisphere damage.
The goal of this study was to further investigate hemispheric specialization for proper and common nouns by examining the ability of individuals with left hemisphere damage (LHD) to perceive and verbally reproduce famous names and matched common names compared with the performance of matched healthy controls (HC). Ten individuals with LHD due to stroke and 16 age- and education-matched HC completed recognition and production tasks of famous proper and common nouns. All tasks were designed as split-visual field experiments, modelled after the study done by Ohnesorge and Van Lancker. Results contribute to a better understanding of hemispheric roles in perception and production of famous proper nouns, suggesting that (1) both hemispheres can recognize famous proper nouns, possibly due to a right hemisphere role in personal relevance and (2) production of proper nouns as well as common nouns is associated with left hemisphere.


Promoter regulation in Candida albicans and related species.
Regulation of gene expression has been studied extensively in Saccharomyces cerevisiae and Schizosaccharomyces pombe. Some, but by far not all, of the findings are also applicable to Candida albicans, an important ascomycete fungal pathogen of humans. Areas of research in C. albicans include the influence of key signal transduction cascades on morphology, and the response to host-generated influences, such as host immune effector cells, blood, pH or elevated carbon dioxide. The resistance to antifungal agents and response to stress are also well researched. Conditional gene expression and reporter genes adapted to the codon usage of C. albicans are now widely used in C. albicans. Here we present a comprehensive overview of the current techniques used to investigate regulation mechanisms for promoters in C. albicans and other Candida species. In addition, we discuss reporter genes used for the study of gene expression.


[Seasonal variation of phytoplankton community and its relationship with environment in subtropical reservoirs: A comparison between two methods of functional groups classification].
Phytoplankton is the most important biological component in the reservoir ecosystem, which could indicate the status of aquatic ecosystem due to its sensitive to environmental variation. To understand the application and difference between two methods of phytoplankton functional group classification, functional groups (FG) and morphology-based functional groups (MBFG), in indicating the changes of reservoir environment, we investigated water quality and phytoplankton in Qingshitan Reservoir monthly from March 2016 to February 2017. Two phytoplankton functional groups classifications (FG and MBFG) were used to analyze phytoplankton community composition, seasonal succession, and its driving factors. We compared the application and differences of two methods of functional group classifications in indicating environmental changes. The results showed that there were 109 species belonged to seven phylum, which could be classified into 17 FG or 5 MBFG functional groups. Results from both methods indicated that the reservoir was meso-eutrophic. The phytoplankton seasonal succession under 8 or 9 steps with FG or 8 steps with MBFG. Results from the redundancy analysis showed that the response of phytoplankton community reflected with FG to environmental variation was more sensitive than that with MBFG, especially in the response to the changes of pH and nitrate concentration. In conclusion, FG was more appropriate in describing community succession and exploring the relationship between phytoplankton and environment.


Modulation of biotransformation systems and ABC transporters by benznidazole in rats.
The effect of antichagasic benznidazole (BZL; 100 mg/kg body weight/day, 3 consecutive days, intraperitoneally) on biotransformation systems and ABC transporters was evaluated in rats. Expression of cytochrome P-450 (CYP3A), UDP-glucuronosyltransferase (UGT1A), glutathione S-transferases (alpha glutathione S-transferase [GST-α], GST-μ, and GST-π), multidrug-resistance-associated protein 2 (Mrp2), and P glycoprotein (P-gp) in liver, small intestine, and kidney was estimated by Western blotting. Increases in hepatic CYP3A (30%) and GST-μ (40%) and in intestinal GST-α (72% in jejunum and 136% in ileum) were detected. Significant increases in Mrp2 (300%) and P-gp (500%) proteins in liver from BZL-treated rats were observed without changes in kidney. P-gp and Mrp2 were also increased by BZL in jejunum (170% and 120%, respectively). In ileum, only P-gp was increased by BZL (50%). The activities of GST, P-gp, and Mrp2 correlated well with the upregulation of proteins in liver and jejunum. Plasma decay of a test dose of BZL (5 mg/kg body weight) administered intraduodenally was faster (295%) and the area under the concentration-time curve (AUC) was lower (41%) for BZL-pretreated rats than for controls. The biliary excretion of BZL was higher (60%) in the BZL group, and urinary excretion of BZL did not show differences between groups. The amount of absorbed BZL in intestinal sacs was lower (25%) in pretreated rats than in controls. In conclusion, induction of biotransformation enzymes and/or transporters by BZL could increase the clearance and/or decrease the intestinal absorption of coadministered drugs that are substrates of these systems, including BZL itself.


Coarse-Grained Models for Constant pH Simulations of Carboxylic Acids.
A model for carboxylic acids, in both the protonated and deprotonated states, is developed in which hydrogen interaction sites are not used and all interactions are short-ranged. A method for constant pH simulations, which exploits these features of the model, is developed. The constant pH method samples protonation states by making discrete Monte Carlo steps and is able to efficiently move between states in two steps. The method is applied to the polymer poly(methacrylic acid), a pH-responsive polymer that undergoes structural changes as a function of pH. The model is able to reproduce the structural changes induced by pH.


[Comparison of Real Time PCR Cycle Threshold Values in Symptomatic and Asymptomatic COVID-19 Patients].
Patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) show different clinical courses ranging from asymptomatic to severe infection requiring intensive care treatment and death. Real-time reverse transcription polymerase chain reaction (rRT-PCR), used in the diagnosis, screening and surveillance of coronavirus-2019 (COVID-19), provides the viral load as a cycle threshold (Ct) value. It has been reported that the Ct value may be related to the course of the infection and the clinical condition of the patient. In this study, it was aimed to compare the Ct and C reactive-protein (CRP) results of symptomatic and asymptomatic patients who were found to be positive with rRT-PCR. Between 14 April and 29 August 2020, a total of 355 patients aged 18 years and older with positive SARS-CoV-2 rRT-PCR test were included in the study. The COVID-19 rRT-PCR test was performed with Bio-speedy SARS-CoV-2 rRT-PCR kit (Bioeksen, Turkey) versions, the kit targeting the RdRp gene region, and the dual gene kit versions targeting the N and ORF1ab gene regions were used. Patients were classified as symptomatic and asymptomatic according to their clinical findings. Ct and CRP results of the patients were analyzed statistically. Of the 355 patients included in the study, 237 (66.7%) were symptomatic and 118 (33.2%) were asymptomatic patients. The mean age of symptomatic patients (46.68 ± 18.03) was observed significantly higher than asymptomatic patients (38.27 ± 13.82) (p<0.001). When the patients are evaluated according to the age groups, the rate of asymptomatic patients was significantly higher in the 21-39 age group, while the rate of symptomatic patients was significantly higher in 65 years and older group (p<0.05). The rate of comorbidity was significantly higher in symptomatic patients (n= 69, 29.1%) than in asymptomatic patients (n= 11, 9.3%) (p<0.001). Hypertension (12.2%), diabetes mellitus (9.7%), chronic respiratory disease (9.3%) and cardiovascular diseases (5.5%) were the most common diseases in symptomatic patients. However, among these, hypertension and chronic respiratory disease were found significantly higher in symptomatic patients (p<0.05). Increased CRP rate in symptomatic patients (64.6%) was found significantly higher than asymptomatic patients (27.3%) (p<0.001). The median of Ct value was found significantly higher in asymptomatic patients (26.34, IQR= 19.78-35.48), than in symptomatic patients (21.77, IQR= 17.81-26.51) (p<0.001). Regarding the medians of Ct values obtained from target genes; RdRp gene Ct value was found significantly higher in asymptomatic patients than in symptomatic patients (p<0.001). However, no statistical difference was found between symptomatic and asymptomatic patients in the ORF1ab and N genes Ct value medians (p> 0.05). As a result, it was observed that SARS-CoV-2 PCR positive patients were symptomatic in the presence of advanced age and comorbidity. Increased CRP value at the time of admission to the hospital was found significantly higher in symptomatic patients. Ct value has been shown to be lower in symptomatic patients, as expected. Although Ct and CRP values are thought to be useful in monitoring the clinical course and prognosis of patients with COVID-19, more detailed studies are needed to prove their clinical value.


Selenium-Dependent Read Through of the Conserved 3'-Terminal UGA Stop Codon of HIV-1 nef.
The HIV-1 nef gene terminates in a 3'-UGA stop codon, which is highly conserved in the main group of HIV-1 subtypes, along with a downstream potential coding region that could extend the nef protein by 33 amino acids, if readthrough of the stop codon occurs. Antisense tethering interactions (ATIs) between a viral mRNA and a host selenoprotein mRNA are a potential viral strategy for the capture of a host selenocysteine insertion sequence (SECIS) element (Taylor et al, 2016) [1]. This mRNA hijacking mechanism could enable the expression of virally encoded selenoprotein modules, via translation of in-frame UGA stop codons as selenocysteine (SeC). Here we show that readthrough of the 3'-terminal UGA codon of nef occurs during translation of HIV-1 nef expression constructs in transfected cells. This was accomplished via fluorescence microscopy image analysis and flow cytometry of HEK 293 cells, transfected with engineered GFP reporter gene plasmid constructs, in which GFP can only be expressed by translational recoding of the UGA codon. SiRNA knockdown of thioredoxin reductase 1 (TR1) mRNA resulted in a 67% decrease in GFP expression, presumably due to reduced availability of the components involved in selenocysteine incorporation for the stop codon readthrough, thus supporting the proposed ATI. Addition of 20 nM sodium selenite to the media significantly enhanced stop codon readthrough in the pNefATI1 plasmid construct, by >100%, supporting the hypothesis that selenium is involved in the UGA readthrough mechanism.


Is Disease Intensity a Good Surrogate for Yield Loss or Toxin Contamination? A Case Study with Fusarium Head Blight of Wheat.
Sometimes plant pathologists assess disease intensity when they are primarily interested in other response variables, such as yield loss or toxin concentration in harvested products. In these situations, disease intensity potentially could be considered a surrogate of yield or toxin. A surrogate is a variable which can be used instead of the variable of interest in the evaluation of experimental treatments or in making predictions. Surrogates can be measured earlier, more conveniently, or more cheaply than the variable of primary interest, but the reliability or validity of the surrogate must be shown. We demonstrate ways of quantifying two facets of surrogacy by using a protocol originally developed by Buyse and colleagues for medical research. Coefficient-of-determination type statistics can be used to conveniently assess the strength of surrogacy on a unitless scale. As a case study, we evaluated whether field severity of Fusarium head blight (i.e., FHB index) can be used as a surrogate for yield loss and deoxynivalenol (DON) toxin concentration in harvested wheat grain. Bivariate mixed models and corresponding approximations were fitted to data from 82 uniform fungicide trials conducted from 2008 to 2013. Individual-level surrogacy-for predicting the variable of interest (yield or DON) from the surrogate (index) in plots with the same treatment-was very low. Trial-level surrogacy-for predicting the effect of treatment (e.g., mean difference) for the variable of interest based on the effect of the treatment on the surrogate (index)-was moderate for yield, and only low for DON. Challenges in using disease severity as a surrogate for yield and toxin are discussed.


Rapid colorimetric micromethod for free fatty acids.
Free fatty acids (FFA), the uranyl ion, and the basic dye Rhodamine B form colored complexes, which are extractable into toluene or benzene. Fatty acids of different chain lengths above C(10) and different degrees of unsaturation gave constant molar yield. Complexes in toluene alone are unstable, especially in the light, but a small amount of aqueous uranyl acetate stabilizes them sufficiently for determination. At constant uranyl and Rhodamine B concentrations, a plot of optical density vs. FFA concentration yields two straight lines of different slope, i.e., a biphasic standard curve. Phospholipids interfere, and must be removed with zeolite during FFA extraction. Recovery of FFA added to rat plasma was very similar to that with titration. Assay of rat and dog plasma samples under fasting and fed conditions gave good agreement with the titration method. Values of human plasma samples tended to be higher by the colorimetric procedure; a few samples gave significant disagreement. The method compares well with previous methods in sensitivity and accuracy, and offers advantages in speed, simplicity, and possibly specificity.


[Discussion on needling manipulation of Chifeng Yingyuan].
Regarding the needling manipulation, Chifeng Yingyuan, there are different descriptions in ancient medical literature and the current teaching materials or clinical reports, especially for the understanding recorded in Jinzhenfu Poem of Golden Needle). In the current teaching materials and clinical reports, it is described that the needle is inserted deeply at first, and then shallowly; afterward, the needle tip is pushed to the middle layer and manipulated with lifting, thrusting and rotating technique, combined with twisting and flying method. After analyzing the original description in the book and the feasibility of function and operation, the authors introduced their recognition on its manipulation and techniques in this article. This manipulation should be: the needle is inserted to the middle layer, afterward, the needle body is pulled and tilted toward each of the four directions, on this basis, then twisting and flying method is applied.


Selective and sensitive liquid chromatography-tandem mass spectrometry method for the determination of levonorgestrel in human plasma.
A selective, sensitive and rapid liquid chromatography-tandem mass spectrometry method for the determination of levonorgestrel in plasma was developed. An Applied Biosystems API 3000 triple quadrupole mass spectrometer set to multiple reaction monitoring (MRM) mode, using atmospheric pressure photospray ionisation (APPI) in the positive mode. Using 17-alpha-methyltestosterone as internal standard (IS), liquid-liquid extraction was followed by reversed phase liquid chromatography using a phenyl-hexyl column and tandem mass spectrometric detection. The mean recovery for levonorgestrel and 17-alpha-methyltestosterone was 99.5 and 62.9%, respectively. The method was validated from 0.265 to 130 ng levonorgestrel/ml plasma with the lower limit of quantification (LLOQ) set at 0.265 ng/ml. This assay method makes use of the increased sensitivity and selectivity of tandem mass spectrometric (MS/MS) detection, allowing for a rapid (extraction and chromatography) and selective method for the determination of levonorgestrel in human plasma. The assay method was used in a pharmacokinetic study to quantify levonorgestrel in human plasma samples generated after administrating a single oral dose of 1.5 mg levonorgestrel to healthy female volunteers for up to five half lives. The total chromatographic runtime of this method was 5.0 min per sample, allowing for analysis of a large number of samples per batch.


Allele-specific hybridization using oligonucleotide probes of very high specific activity: discrimination of the human beta A- and beta S-globin genes.
The repair activity of Escherichia coli DNA polymerase I (Klenow fragment) was used to prepare nonadecanucleotide hybridization probes which were complementary either to the normal human beta-globin (beta A) or to the sickle cell human beta-globin (beta s) gene. Template-directed polymerization of highly radiolabeled alpha[32P]deoxyribonucleoside triphosphates (dNTPs) onto nonamer and decamer primers produced probes with specific activities ranging from 1.0 X 10(10) to 2.0 X 10(10) dpm/micrograms. The extremely high specific activities of these probes made it possible to detect the beta A and beta S single-copy gene sequences in as little as 1 microgram of total human genomic DNA as well as to discriminate between the homozygous and heterozygous states.


West Nile virus meningoencephalitis: MR imaging findings.
Reports of MR imaging in West Nile virus (WNV) meningoencephalomyelitis are few and the described findings limited. The purpose of this study was to review the spectrum of MR imaging findings for WNV meningoencephalomyelitis and investigate whether any of the findings correlates with clinical presentation of flaccid paralysis. We reviewed the MR imaging findings of 17 patients with confirmed WNV encephalitis and/or myelitis. MR imaging brain studies were evaluated for location of signal intensity abnormalities, edema, hydrocephalus, or abnormal enhancement. MR imaging spine studies were evaluated for signal intensity abnormalities in cord and/or enhancement. Retrospective review of the MR imaging studies of 17 patients was performed by 2 neuroradiologists. Eleven of 16 brain MR images demonstrated abnormalities. Eight (50%) patients had abnormal studies related to meningoencephalitis. All 8 patients had abnormal findings in the deep gray matter and/or brain stem; 2 had additional white matter abnormalities. Three patients with abnormal MR studies of the spine had extremity weakness on examination. The imaging findings included abnormal signal intensity more pronounced in the ventral horns and/or enhancement around the conus medullaris and cauda equina. One patient had additional abnormalities in the pons. Abnormal MR imaging findings in patients with WNV meningoencephalomyelitis are nonspecific but not uncommon. Anatomic areas commonly affected are basal ganglia, thalami, mesial temporal structures, brain stem, and cerebellum. Extremity weakness or flaccid paralysis corresponds to spinal cord/cauda equina abnormalities.


Multiplex PCR for detection of the heat-labile toxin gene and shiga-like toxin I and II genes in Escherichia coli isolated from natural waters.
A triplex PCR method was developed to simultaneously amplify a heat-labile toxin sequence (LT) of 258 bp, a shiga-like toxin I sequence (SLT I) of 130 bp, and a shiga-like toxin II sequence (SLT II) of 346 bp from toxigenic strains of Escherichia coli. This method was used to screen 377 environmental E. coli isolates from marine waters or estuaries located in Southern California and North Carolina for enterotoxigenic or enterohemorrhagic E. coli strains. Of the 377 E. coli screened, one isolate was found to belong to the enterotoxigenic group, since it contained a LT homologous sequence, and one isolate was found to belong to the enterohemorrhagic group, since it contained a SLT I homologous sequence. None was found to contain SLT II homologous sequences. The pathogenicity of the positive environmental E. coli isolates was confirmed by standard bioassays with Y-1 adrenal cells and Vero cells to confirm toxin production. Our results suggest that toxigenic E. coli occurs infrequently in environmental waters and that there is a low public health risk from toxigenic E. coli in coastal waters.


Improved genome recovery and integrated cell-size analyses of individual uncultured microbial cells and viral particles.
Microbial single-cell genomics can be used to provide insights into the metabolic potential, interactions, and evolution of uncultured microorganisms. Here we present WGA-X, a method based on multiple displacement amplification of DNA that utilizes a thermostable mutant of the phi29 polymerase. WGA-X enhances genome recovery from individual microbial cells and viral particles while maintaining ease of use and scalability. The greatest improvements are observed when amplifying high G+C content templates, such as those belonging to the predominant bacteria in agricultural soils. By integrating WGA-X with calibrated index-cell sorting and high-throughput genomic sequencing, we are able to analyze genomic sequences and cell sizes of hundreds of individual, uncultured bacteria, archaea, protists, and viral particles, obtained directly from marine and soil samples, in a single experiment. This approach may find diverse applications in microbiology and in biomedical and forensic studies of humans and other multicellular organisms.Single-cell genomics can be used to study uncultured microorganisms. Here, Stepanauskas et al. present a method combining improved multiple displacement amplification and FACS, to obtain genomic sequences and cell size information from uncultivated microbial cells and viral particles in environmental samples.


A Novel Polysaccharide Conjugate from Bullacta exarata Induces G1-Phase Arrest and Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells.
Bullacta exarata has been consumed in Asia, not only as a part of the normal diet, but also as a traditional Chinese medicine with liver- and kidney-benefitting functions. Several scientific investigations involving extraction of biomolecules from this mollusk and pharmacological studies on their biological activities have been carried out. However, little is known regarding the antitumor properties of polysaccharides from B. exarata, hence the polysaccharides from B. exarata have been investigated here. One polysaccharide conjugate BEPS-IA was isolated and purified from B. exarata. It mainly consisted of mannose and glucose in a molar ratio of 1:2, with an average molecular weight of 127 kDa. Thirteen general amino acids were identified to be components of the protein-bound polysaccharide. Methylation and NMR studies revealed that BEPS-IA is a heteropolysaccharide consisting of 1,4-linked-α-d-Glc, 1,6-linked-α-d-Man, 1,3,6-linked-α-d-Man, and 1-linked-α-d-Man residue, in a molar ratio of 6:1:1:1. In order to test the antitumor activity of BEPS-IA, we investigated its effect against the growth of human hepatocellular carcinoma cells HepG2 in vitro. The result showed that BEPS-IA dose-dependently exhibited an effective HepG2 cells growth inhibition with an IC50 of 112.4 μg/mL. Flow cytometry analysis showed that BEPS-IA increased the populations of both apoptotic sub-G1 and G1 phase. The result obtained from TUNEL assay corroborated apoptosis which was shown in flow cytometry. Western blot analysis suggested that BEPS-IA induced apoptosis and growth inhibition were associated with up-regulation of p53, p21 and Bax, down-regulation of Bcl-2. These findings suggest that BEPS-IA may serve as a potential novel dietary agent for hepatocellular carcinoma.


Molecular characterization of Pseudomonas fluorescens isolates involved in the Italian "blue mozzarella" event.
Between June and September 2010, widespread Italian consumer reports of unusual blue spoilage on fresh dairy products were publicized, resulting in the so-called blue mozzarella event. An inordinately high number of samples from mozzarella and whey cheese products of Italian and German production subsequently tested positive for Pseudomonas fluorescens. The aim of this study was to verify whether a selected P. fluorescens strain was responsible for this apparently unusual event. Molecular characterization of 181 isolated P. fluorescens strains was conducted using a newly optimized pulsed-field gel electrophoresis protocol. Although a high number of pulsotypes was found (132), only four pulsotypes were associated with more than one production plant, and only one German isolate had the same pulsotype as was detected in two Italian plants. This is the only evidence of possible cross-contamination among cheeses from the two countries. The overall results did not support the spread of contamination from German to Italian plants or the presence of one environmental strain that spread in both countries.


Alcohol-use disorders.
Essential facts [Figure: see text] According to recent statistics from NHS Digital, there were an estimated 1.1 million hospital admissions where alcohol was the primary or secondary issue in 2015-16. In the UK, it is estimated that 24% of adults drink in a hazardous or harmful way, while around 9% of men and 4% of women show signs of alcohol dependence.


On the origin of physiologically high ratios of urinary testosterone to epitestosterone: consequences for reliable detection of testosterone administration by male athletes.
Testosterone administration to male athletes can be safely detected in the vast majority of cases by the urinary excretion ratio of testosterone to epitestosterone glucuronides (TG/EG), which may not exceed 6. Some rare cases of physiologically high TG/EG ratios (between 6 and 12) are encountered; these may be attributed to a dysregulation of the testicular secretions of epitestosterone which is decreased, and of epitestosterone sulphate (ES) which is normal or increased. Impaired hydrolysis of circulating epitestosterone sulphate by deficiency of a specific sulphatase acting on 17 alpha-sulphates must also be considered as a possible reason for the decreased availability of epitestosterone for hepatic glucuronidation. Urinary excretions of conjugates and metabolites of testosterone and epitestosterone (expressed in nmol/mmol creatinine) have been determined by gas chromatography-mass spectrometry associated with stable isotope dilution, in a reference population of 90 healthy male subjects and in 12 subjects with chronic TG/EG > 4. Urinary excretion ratios such as TG/(EG+ES), EG/ES and TG/5-androstene-3 beta,17 alpha-diol glucuronide are shown to be efficient criteria which allow discrimination between physiologically high and pharmacologically high TG/EG ratios. A simple oral loading test with deuterium-labelled epitestosterone demonstrates the difference between hepatic and total epitestosterone metabolism clearly, particularly in subjects with physiologically high TG/EG in comparison with subjects with normal TG/EG.


Development and clinical evaluation of a highly sensitive DNA microarray for detection and genotyping of human papillomaviruses.
Human papillomavirus (HPV) has been found in cervical cancer, tonsillar cancer, and certain types of head and neck cancers. We report on a DNA microarray-based method for the simultaneous detection and typing of HPVs. The genotype spectrum discriminated by this HPV DNA microarray includes 15 high-risk HPV genotypes and 12 low-risk HPV genotypes. The HPV DNA microarray showed high degrees of specificity and reproducibility. We evaluated the performance of the HPV DNA microarray by application to three HPV-positive cell lines (HeLa, Caski, and SiHa cells) and two HPV-negative cell lines (C33A and A549 cells). The HPV DNA microarray successfully identified the known types of HPV present in the cell lines. The detection limit of the HPV DNA microarray was at least 100-fold higher than that of PCR. To assess the clinical applicability of the HPV DNA microarray, we performed the HPV genotyping assay with 73 nonmalignant and malignant samples from 39 tonsillar cancer patients. Twenty-five of the 39 (64.1%) malignant samples were positive for HPV, whereas 3 of 34 (8.8%) nonmalignant samples were positive for HPV. This result shows a preferential association of HPV with tonsillar carcinomas. The correlations of the presence of HPV with the grade of differentiation and risk factors were not significant. Our data show that the HPV DNA microarray may be useful for the diagnosis and typing of HPV in large-scale epidemiological studies.


Association between AGTR1 A1166C polymorphism and the susceptibility to diabetic nephropathy: Evidence from a meta-analysis.
Diabetic nephropathy (DN) is a common complication in patients with diabetic mellitus (DM). Growing evidences have demonstrated that the polymorphisms of angiotensin II receptor type 1 (AGTR1) showed significant association with DN onset, but no consensus has been achieved yet. Therefore, we performed this meta-analysis to combine the findings of previous researches for a more comprehensive conclusion. Eligible publications were identified through electronic databases. The intensity of the correlation between AGTR1 A1166C polymorphism and DN susceptibility was evaluated through calculating pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs). Heterogeneity among included studies was examined with Q test. When P-value less than .05, significant heterogeneity presented, random-effects model was used to calculate the pooled ORs, otherwise, the fixed-effects model was used. Stratification analyses were also performed based on ethnicity and the type of DM. Seventeen eligible articles were finally included in the present meta-analysis. The analysis results showed that AGTR1 A1166C polymorphism was significantly related to increased risk of DN under CC versus AA (OR = 1.723, 95% CI = 1.123-2.644), CC + AC versus AA (OR = 1.179, 95% CI = 1.004-1.383), CC versus AA + AC (OR = 1.662, 95% CI = 1.112-2.486), and C versus A (OR = 1.208, 95% CI = 1.044-1.397) genetic models. Additionally, a similar result was also found in Asian and T2DM (type 2 diabetic mellitus) groups after subgroup analyses of ethnicity and DM type. AGTR1 A1166C polymorphism may increase the susceptibility to DN, especially in Asians and T2DM population.


A consistency-specificity trade-off to select source behavior in information fusion.
Combining pieces of information provided by several sources without or with little prior knowledge about the behavior of the sources is an old yet still important and rather open problem in the belief function theory. In this paper, we propose an approach to select the behavior of sources based on a very general and expressive fusion scheme, that has the important advantage of making clear the assumptions made about the sources. The selection process itself relies on two cornerstones that are the notions of specificity and consistency of a knowledge representation, and that we adapt to the considered fusion scheme. We illustrate our proposal on different examples and show that the proposed approach actually encompasses some important existing fusion strategies.


Exposure to soluble nickel in electrolytic nickel refining.
Past and present exposure to nickel was studied in an electrolytic nickel refinery, where an increased incidence of nasal cancer had been reported, using nickel analyses in air, blood and urine. Genotoxic effects were studied using analysis of micronuclei from acridine orange-stained smears from the buccal mucosa of the workers. Workers used respirators or masks in tasks where the exposure was expected to be high. Inside the mask, nickel concentrations were 0.9-2.4 micrograms m-3 in such tasks. In those tasks where masks were not used, nickel concentrations in the breathing zone were 1.3-21 micrograms m-3. Air-borne nickel concentrations (stationary sampling) varied between 230 and 800 micrograms m-3 in 1966-1988 with no systematic change; thereafter lower concentrations (170-460 micrograms m-3) have been observed. After-shift urinary concentrations of nickel were 0.1-2 mumol l-1; they showed no correlation with nickel concentrations in the air. Concentrations of nickel in the urine were still elevated after a 2-4 week vacation. The frequency of micronucleated epithelial cells in the buccal mucosa of nickel refinery workers was not significantly elevated by comparison with referents. No relationship was observed between micronucleus frequencies and levels of nickel in air, urine or blood.


[Twin studies with a differentiated diagnosis of endogenic psychoses - psychosocial influences in certain forms of schizophrenia].
The examination started from the premise that "systematic schizophrenias", which constitute the majority of chronic schizophrenias in "differentiated diagnostics", only very rarely have a family history of psychosis. We set out to obtain an explanation of this observation by means of investigation in twins. Surprisingly, these types were not present in identical twins. It seems, therefore, that the severe schizophrenias, which we consider to be similar in character to systemic diseases, are prevented by the influence of an identical twin partner. As, however, the illness did occur in two-egg twins, the favourable influence must be effective during a period of life, when mutual understanding between the twins is already decisive, i.e. during later childhood, probably during puberty. An interaction between individual and environment is probably necessary for normal mental development and also for the maturing of brain systems essential in the adult psyche. In autistic patients there is no interaction, thus schizophrenia may develop. With an identical twin, however, contact is always present: because of similarity in character it is impossible that the partners minds are not mutually accessible. Thus, a satisfactory mental interrelationship is maintained, by which systematic schizophrenia is prevented. For refernces see the end of the following communication.


The Use of PRISM (Pictorial Representation of Illness and Self Measure) in Patients Affected by Chronic Cutaneous Ulcers.
PRISM (Pictorial Representation of Illness and Self Measure) is a nonverbal visualization instrument. The authors chose to use this tool to avoid the limitation of the other tests for the assessment of quality of life by using interview methods that depend on the cognitive and cultural level of the patient. The aim of the study was to assess the impact on the quality of life of different types of chronic wounds using the PRISM test. The PRISM test was administered by the same medical student to each patient visiting the dermatology department for a routine visit and medication. The PRISM test was administered to 77 patients with chronic cutaneous ulcers referred to the Dermatology Department of the Spedali Civili of Brescia, Italy. The authors analyzed the "Self-llness-Separation"' (SIS) value, which resulted from the PRISM test, and related it to sex, age, and ulcer etiology. Considering all categories, the mean SIS was 9.58 cm; a different perception of the disease between the sexes was noted and also in the subgroups based on the ulcer's different etiology. In addition, the age of the affected patients influenced the SIS value. PRISM is an easy and sensitive instrument to record information about the patient's expectations and suffering in order to improve the overall physician-patient relationship.


A latent change score analysis of emotion regulation difficulties and evaluative threat in STEM.
We examined implications of evaluative threat on the ability to regulate emotions for first-time college freshmen completing Science, Technology, Engineering, and Math (STEM) majors (N = 432). Students completed the Evaluative Threat in STEM Scale (Ahlqvist, London, & Rosenthal, 2013) and the Difficulties in Emotion Regulation Scale (DERS; Gratz & Roemer, 2004) at six intervals. Cross-sectional and longitudinal measurement invariance was supported. Women reported greater evaluative threat than men, but they did not differ from men in difficulties regulating emotion. Both constructs showed moderate relative stability over time. Using latent change score analyses, significant positive deceleration change patterns indicated that four of the emotion regulation difficulties (Lack of Emotional Awareness, Lack of Emotional Clarity, Impulse Control Difficulties, and Nonacceptance of Emotional Responses) and evaluative threat tended to increase (worsen) over the year, but the increases also slowed (i.e., plateaued) over time. Compared with men, women initially reported higher evaluative threat than men did, but these differences decreased over the year, as women decelerated more quickly than men did. In terms of cross-coupling effects, we found that evaluative threat was associated with subsequent difficulty in identifying strategies to cope with unpleasant emotions. There were no cross-coupling effects for emotion regulation predicting subsequent change in evaluative threat. Gender moderated the Evaluative Threat-to-DERS coupling effects for Lack of Emotional Clarity, Difficulties in Goal-Directed Behavior, and Nonacceptance of Emotional Responses. We discuss implications of evaluative threat for depleting coping resources and some potential psychoeducational and preventive interventions to support students in STEM majors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


APYRASE1/2 mediate red light-induced de-etiolation growth in Arabidopsis seedlings.
In etiolated seedlings, red light (R) activates phytochrome and initiates signals that generate major changes at molecular and physiological levels. These changes include inhibition of hypocotyl growth and promotion of the growth of primary roots, apical hooks, and cotyledons. An earlier report showed that the sharp decrease in hypocotyl growth rapidly induced by R was accompanied by an equally rapid decrease in the transcript and protein levels of two closely related apyrases (APYs; nucleoside triphosphate-diphosphohydrolases) in Arabidopsis (Arabidopsis thaliana), APY1 and APY2, enzymes whose expression alters auxin transport and growth in seedlings. Here, we report that single knockouts of either APY inhibit R-induced promotion of the growth of primary roots, apical hooks, and cotyledons, and RNAi-induced suppression of APY1 expression in the background of apy2 inhibits R-induced apical hook opening. When R-irradiated primary roots and apical hook-cotyledons began to show a gradual increase in their growth relative to dark controls, they concurrently showed increased levels of APY protein, but in hook-cotyledon tissue, this occurred without parallel increases in their transcripts. In wild-type seedlings whose root growth is suppressed by the photosynthesis inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea, the R-induced increased APY expression in roots was also inhibited. In unirradiated plants, the constitutive expression of APY2 promoted both hook opening and changes in the transcript abundance of Small Auxin Upregulated RNA (SAUR), SAUR17 and SAUR50 that help mediate de-etiolation. These results provide evidence that the expression of APY1/APY2 is regulated by R and that APY1/APY2 participate in the signaling pathway by which phytochrome induces differential growth changes in different tissues of etiolated seedlings.


The role of aragonite matrix surface chemistry on the chondrogenic differentiation of mesenchymal stem cells.
In the present research we study the effects of surface chemistry of an aragonite crystalline biomatrix on the chondrogenesis of mesenchymal stem cells (MSCs). An aragonite matrix obtained from the coral Porites lutea and a gold-coated P. lutea matrix were seeded with MSCs, with and without the addition of growth factors (GFs). Scanning electron microscopy, histochemical staining, immunofluorescence, biochemical analyses and quantitative polymerase chain reaction showed that the chemistry of the matrix influenced the differentiation process of the MSCs. The calcium carbonate composition of the coral promoted osteogenesis, while impeding cell-material contact (by gold coating) altered the differentiation lineage of MSCs towards chondrogenic fate. Supplementation of the culture medium with GFs intensified the influence of the surface composition on the differentiation of MSCs, and the synergistic effect of the biomatrix surface composition and the GFs induced chondrogenesis and facilitated maintenance of the chondrocyte phenotype. Therefore, we suggest that scaffolding material candidates for tissue engineering should be examined for their effects on the MSCs differentiation process and their effect on signal transduction events in the cells.


Complexity of error hypersurfaces in multilayer perceptrons.
Error hypersurfaces are very valuable to study because of their unique status in multilayer perceptron research. Given the architecture of a multilayer perceptron, if the pattern sets are different, so are the respective error hypersurfaces in the multilayer perceptron. Using the theory of groups and Polya Theorem, this paper constructs classes of congruent pattern sets and classes of congruent error hypersurfaces, and proves that the number of classes of congruent pattern sets is equal to the number of congruent error hypersurfaces. Calculation results lead to much fewer classes of congruent error hypersurfaces than the total error hypersurfaces, and show that as the input dimension N increases, the former number increases at a much lower rate than the latter number, thus simplifying the understanding of the complexity of classes of error hypersurfaces.


An update on environment-induced pulmonary edema - "When the lungs leak under water and in thin air".
Acute pulmonary edema is a serious condition that may occur as a result of increased hydrostatic forces within the lung microvasculature or increased microvascular permeability. Heart failure or other cardiac or renal disease are common causes of cardiogenic pulmonary edema. However, pulmonary edema may even occur in young and healthy individuals when exposed to extreme environments, such as immersion in water or at high altitude. Immersion pulmonary edema (IPE) and high-altitude pulmonary edema (HAPE) share some morphological and clinical characteristics; however, their underlying mechanisms may be different. An emerging understanding of IPE indicates that an increase in pulmonary artery and capillary pressures caused by substantial redistribution of venous blood from the extremities to the chest, in combination with stimuli aggravating the effects of water immersion, such as exercise and cold temperature, play an important role, distinct from hypoxia-induced vasoconstriction in high altitude pulmonary edema. This review aims at a current perspective on both IPE and HAPE, providing a comparative view of clinical presentation and pathophysiology. A particular emphasis will be on recent advances in understanding of the pathophysiology and occurrence of IPE with a future perspective on remaining research needs.


Osteoid osteoma of the carpal scaphoid in the adult: a clinical case.
The authors present one case of osteoid osteoma of the carpal scaphoid, emphasizing the clinical rareness of the disease. Methods of diagnosis used and surgical treatment performed are described.


The lines and grooves of the face: a suggested nomenclature.
The lines and grooves of the face commonly recognized and used by plastic surgeons, biological anthropologists, forensic medicine specialists, artists, and others are described. Proper Latin anatomical names for them are suggested. It is hoped that eventually these will be adopted by those who use them and published by the International Anatomical Nomenclature Committee.


Biomechanical and Anatomical Validity of the Short Posterior Arch Screw.
This study was conducted to clarify the validity of the short posterior arch screw (S-PAS). The S-PAS is inserted only in the pedicle-analogue portion of the posterior arch. The S-PAS screw length is almost half that conventional C1 lateral mass screws inserted via the posterior arch (via-PAS). S-PAS reduces the risk of vertebral artery injury (VAI) because it never reaches the transverse foramen. Although the biomechanical validity of various C1 lateral mass screws (C1LMS) analyzed in young specimens have been published, that of unicortically inserted C1LMS such as the unicortical Harms screw, S-PAS, and via-PAS for elderly patients is concerning because of the high prevalence of osteoporosis in the elderly. Nine fresh frozen cadavers (average age at death, 72.1 years) were used for pullout testing. The bone mineral density of each specimen was evaluated using quantitative computed tomography. The pullout strength of via-PAS (1,048.5 N) was significantly greater than that of the unicortical Harms screw (257.9 N) (p<0.05). The pullout strength of S-PAS was 720.3 N, which was also significantly greater than that of the unicortical Harms screw (p<0.05). The via-PAS and S-PAS are valid surgical options, even in elderly patients. Along with sufficient biomechanical strength, the S-PAS screw prevents VAI.


Infantile myofibromatosis.
Infantile myofibromatosis (IMF) is a rare tumour with a wide spectrum of disease activity ranging from a solitary cutaneous nodule through to a multicentric form with widespread visceral involvement. It is characterised by its unique ability to spontaneously regress and has a typical histological appearance of actin-positive fibroblasts arranged in whorls or fascicles and vessels in a pericytomatous pattern. A male infant with multiple lesions involving the subcutaneous tissue and bone from birth is described and followed-up for two years. Treatment of IMF is dependent on the location of the tumour/s with surgery or chemotherapy reserved for rapidly progressive or symptomatic disease. However, due to the low rate of recurrence and the possibility of spontaneous tumoral regression, therapeutic abstention, as practised in our patient, is justified.


Low-Temperature Oxidation of Fine UO2 Powders: Thermochemistry and Kinetics.
The thermochemical behavior of low-temperature oxidation in fine UO2 powders has been investigated by simultaneous thermogravimetric analysis and differential scanning calorimetry. The evaluation of the thermochemical and kinetic data reveals a complex interplay between different mechanisms. The initial reaction concerns the rapid chemisorption of oxygen gas onto the surface of UO2 grains, having an activation energy of only 13.1 ± 0.6 kJ mol-1. The subsequent oxidation at temperatures between 40 and 100 °C occurs first at the surface via a field-assisted mechanism, which progresses via domain growth into the bulk. At more elevated temperatures, thermally activated diffusion becomes the dominant mechanism.


Inserting central venous catheter in emergency conditions in coagulopathic patients in comparison to noncoagulopathic patients.
The current study was designed to compare the complications and adverse effects of central venous catheter (CVC) insertion under ultrasound guidance in patients with and without coagulopathy. In this clinical trial, 59 patients who needed CVC for various reasons were enrolled. Patients were divided into two groups of those with and without coagulopathy based on complete blood count, prothrombin time, partial thromboplastin time, and international normalized ratio test results, and then, CVC was inserted with ultrasound guidance in both groups. The CVC inserting site was examined for hematoma and hemorrhage in four stages at different times. There was no significant difference in the terms of demographic features, catheter lumen size (P = 0.43), and number of attempting for CVC placement (odds ratio [OR] =2.35, 95% confidence interval [CI] = 0.36-15.3, P = 0.39) between two groups. Seven out of 59 patients suffered from complications (11.9%) that the complications in coagulopathic patients were oozing (5.7%) and superficial hematoma (8.6%) while in noncoagulopathic patients were 4.2% for both complications (OR = 0.54, 95% CI = 0.09-3.07, P = 0.767). According to our results, it can be concluded that inserting CVC with ultrasound guidance under emergency conditions causes no serious and life-threatening complications in coagulopathic patients.


Selectivity for echo spectral interference and delay in the auditory cortex of the big brown bat Eptesicus fuscus.
The acoustic environment for an echolocating bat can contain multiple objects that reflect echoes so closely separated in time that they are almost completely overlapping. This results in a single echo with a spectrum characterized by deep notches due to interference. The object of this study was to document the possible selectivity, or lack thereof, of auditory neurons to the temporal separation of biosonar signals on a coarse (ms) and fine (micros) temporal scale. We recorded single-unit activity from the auditory cortex of big brown bats while presenting four protocol designs using wideband FM signals. The protocols simulated a pair of partially overlapping echoes where the separation between the first and second echo varied between 0 and 72 micros, a pulse followed by a single echo at varying delay from 0 to 30 ms, a pulse followed at a fixed delay by a pair of partially overlapping echoes that had a varying temporal separation of 0-72 micros, and a pulse followed, with a varying delay between 0 and 30 ms, by a pair of echoes that themselves had a fixed temporal separation on a microsecond time scale. About half of the cortical units showed increased spike counts to pairs of partially overlapping echoes at particular separations (6-72 micros) compared with a baseline stimulus at 0-micros separation. For many neurons tested with a pulse followed by two overlapping echoes, we observed a sensitivity to the coarse delay between the pulse and pair of overlapping echoes and to the separation between the two echoes themselves. The sensitivity to the partial overlap between the two echoes was not tuned to a single temporal separation. For bats, this means that the absolute range to the closest reflector and range between reflectors may be jointly encoded across a small population of single units. There are several possible neuronal mechanisms for encoding the separation between two nearby echoes based on the sensitivity to spectral notches.


Extracellular Matrix Remodeling Biomarkers in Coronary Artery Disease.
Atherosclerosis and one of its most serious consequences, coronary artery disease, are important sources of morbidity and mortality globally, necessitating early detection and treatment. Considering their complex pathophysiology, including several harmful processes, a comprehensive approach to diagnosis, prognosis, and therapy is very desirable. Extracellular matrix remodeling is a major component of this dangerous cascade, including the cleavage of constituents (collagen, elastin, proteoglycans) and the propagation or exacerbation of the inflammatory response. Several extracellular matrix degradation indicators have been hypothesized to correlate with the existence, severity, and prognosis of coronary artery disease. The potency of matrix metalloproteinases, notably collagenases and gelatinases, has been the most thoroughly investigated in clinical studies. Stromelysins, matrilysins, transmembrane matrix metalloproteinases, collagen and laminin turnover indicators, as well as fibronectin, have also been studied to a lesser level. Among the most well-studied markers, MMP-1, MMP-2, MMP-8, and MMP-9 have been found increased in patients with cardiovascular risk factors such as metabolic syndrome, its components (obesity, dyslipidemia, diabetes mellitus), and smoking. Increasing concentrations are detected in acute coronary syndromes compared to stable angina pectoris and healthy control groups. It should also be stressed that those extracellular matrix biomarkers may also be detected in high concentrations in other vascular pathologies such as peripheral artery disease, carotid artery disease, aortic aneurysms, and dissections. Despite the advances gained, future research should focus on their importance and, more crucially, their added utility as biomarkers in identifying persons at risk of developing overt coronary artery disease. At the same time, determining the prognosis of coronary artery disease patients using such biomarkers may be important for their adequate care.


Interleukin-1 beta, but not interleukin-6, impairs spatial navigation learning.
The effects of the cytokines interleukin-1 and -6 (IL1 beta, IL6; 100 ng) on spatial learning were examined in the Morris water maze. Intracerebroventricular injection of IL1 or IL6 before the training on day 1 did not influence the acquisition of spatial navigation. However, IL1 administered at 60 min, but not immediately before the training, resulted in impaired performance of spatial navigation the following day. In contrast, IL6 administered at both times had no effect. In a second experiment the same doses of IL1 and IL6 increased the body temperature of rats in a time-related fashion. The temperature effect of IL1 developed after a delay of 120 min, while the IL-6-effect was immediate. Comparable behavioral changes might accompany infections or inflammatory diseases and therapeutic cytokine administration.


Professional drivers: protection needed for a high-risk occupation.
"On the job" motor vehicle deaths number more than 4,000 annually in the U.S. and comprise nearly one-third of all work-related deaths. Yet the Department of Labor has set no standards relating to on-the-road safety of the millions of workers whose jobs entail large amounts of driving, and Department of Transportation standards affecting occupational safety cover only drivers in interstate commerce. Drivers of some commercial vehicles, such as heavy trucks, are at special risk of injury because trucks have usually been exempted for many years from federal motor vehicle safety standards--such as standards for brakes and seatbelts--designed to prevent crashes or protect occupants in crashes. Observations based on a series of 150 fatal crashes involving tractor trailers illustrate the need for better protection of this large population of high-risk workers. Clarification of responsibility within the various federal agencies and application of available knowledge and technology are essential.


High-grade dysplasia in sporadic fundic gland polyps: a case report and review of the literature.
We present a case of fundic gland polyps (FGPs) containing high-grade dysplasia in a 68-year-old man. High-grade dysplasia, and even gastric adenocarcinoma, associated with FGPs have been described in patients with familial adenomatous polyposis (FAP) and attenuated familial adenomatous polyposis (AFAP) but never in non-FAP patients. Two colonoscopies in the past six years virtually rule out FAP and AFAP in our patient. Dysplasia in FGPs from non-FAP patients is extremely rare, and until now only cases of low-grade dysplasia have been described. The literature on dysplasia in FGPs is reviewed briefly. Additional immunohistochemical investigations in this case showed nuclear staining of beta-catenin, increased proliferation and apoptosis in the dysplastic areas of the FGPs. Our case suggests that the malignant potential of FGPs is not limited to FAP-associated FGPs.


Frontotemporal dementia and language networks: cortical thickness reduction is driven by dyslexia susceptibility genes.
Variations within genes associated with dyslexia result in a language network vulnerability, and in patients with Frontotemporal Dementia (FTD), language disturbances represent a disease core feature. Here we explored whether variations within three related-dyslexia genes, namely KIAA0319, DCDC2, and CNTNAP, might affect cortical thickness measures in FTD patients. 112 FTD patients underwent clinical and neuropsychological examination, genetic analyses and brain Magnetic Resonance Imaging (MRI). KIAA0319 rs17243157 G/A, DCDC2 rs793842 A/G and CNTNAP2 rs17236239 A/G genetic variations were assessed. Cortical thickness was analysed by Freesurfer. Patients carrying KIAA0319 A*(AG or AA) carriers showed greater cortical thickness atrophy in the left fusiform and inferior temporal gyri, compared to KIAA0319 GG (p ≤ 0.001). Patients carrying CNTNAP2 G*(GA or GG) showed reduced cortical thickness in the left insula thenCNTNAP2 AA carriers (p≤0.001). When patients with both at-risk polymorphisms were considered (KIAA0319 A* and CNTNAP2 G*), greater and addictive cortical thickness atrophy of the left insula and the inferior temporal gyrus was demonstrated (p ≤ 0.001). No significant effect of DCDC2 was found. In FTD, variations of KIAA0319 and CNTNAP2 genes were related to cortical thickness abnormalities in those brain areas involved in language abilities. These findings shed light on genetic predisposition in defining phenotypic variability in FTD.


Critical Care Management of Peritonitis in a Low-Resource Setting.
Management of critically ill patients is challenging in a low-resource setting. In Rwanda, peritonitis is a common surgical condition where patients often present late, with advanced disease. We aim to describe critical care management of patients with peritonitis in Rwanda. Data were collected at a tertiary referral hospital in Rwanda on patients undergoing operation for peritonitis over a 6-month period. Data included epidemiology, hospital course and outcomes. Patients requiring admission to the intensive care unit (ICU) were compared with those not requiring ICU admission using Chi-square and Wilcoxon rank-sum test. Over a 6-month period, 280 patients were operated for peritonitis. Of these, 46 (16.4%) were admitted to the ICU. The most common diagnoses were intestinal obstruction (N = 17, 37.0%) and typhoid intestinal perforation (N = 6, 13.0%). Thirty-nine (89%) patients had sepsis. The median American Society of Anesthesiologist score was 3 (range 2-4), and the median Surgical Apgar Score was 4 (range 0-6). Twenty-four (52.2%) patients required vasopressors, with dopamine and adrenaline being the only vasopressors available. Patients admitted to the ICU, compared with non-critically ill patients, were more likely to have major complications (80.4 vs. 14%, p < 0.001), unplanned reoperation (28 vs. 10%, p < 0.001) and death (72 vs. 8%, p < 0.001). Patients with peritonitis admitted to the ICU commonly presented with features of sepsis. Due to limited resources in this setting, interventions are primarily supportive with intravenous fluids, intravenous antibiotics, ventilator support and vasopressors. Morbidity and mortality remain high in this patient population.


[Diagnostic value of the protein antigens of Br. abortus and Yersinia enterocolitica type 9].
Protein antigens were obtained from Br. abortus 99 and Yersinia enterocolitica, type 9, and were titered on guinea-pigs infected with a living culture from these microbes. It was proved that the guinea-pigs infected with Yersinia reacted with a skin-allergic reaction only to an antigen obtained from Yersinia and not from Brucella. Conversely, the animals infected with Br. abortus B-19 reacted during skin treatment only to an allergen from Brucella, but not with an allergen from Yersinia. In a rabbit anti-yersinia serum were proved precipitins through the immunodiffusion test against the protein allergen from Yersinia, whereas no Brucella precipitins were detected with a protein allergen. In anti-Brucella rabbit serum (Brucella amboceptor or agglutinative serum, no precipitins were proved with Brucella and Yersinia protein allergens. In a hiperimmune rabbit serum against Brucella and Yersinia were proved precipitins against a polysaccharide both from Yersinia and Brucella. It was adopted that protein antigens in the case of Brucella and Yersinia were specific and that specificity could be used for differentiation of these two infections.


Online Customer Reviews of Assisted Living Communities: Association with Community, County, and State Factors.
Online reviews provided by users of assisted living communities may offer a unique source of heretofore unexamined data. We explored online reviews as a possible source of information about these communities and examined the association between the reviews and aspects of state regulations, while controlling for assisted living, county, and state market-level factors. Cross-sectional, observational study. Sample included 149,265 reviews for 8828 communities. Primary (eg, state regulations) and secondary (eg, Medicare Beneficiary Summary Files) data were used. County-level factors were derived from the Area Health Resource Files, and state-level factors from the integrated Public Use Microdata series. Information on state regulations was obtained from a previously compiled regulatory dataset. Average assisted living rating score, calculated as the mean of posted online reviews, was the outcome of interest, with a higher score indicating a more positive review. We used word cloud to visualize how often words appeared in 1-star and 5-star reviews. Logistic regression models were used to determine the association between online rating and a set of community, county, and state variables. Models were weighted by the number of reviews per assisted living bed. Overall, 76% of communities had online reviews. We found lower odds of positive reviews in communities with greater proportions of Medicare/Medicaid residents [odds ratio (OR) = 0.986; P < .001], whereas communities located in micropolitan areas (compared with urban), and those in states with more direct care worker hours (per week per bed) had greater odds of high rating (OR = 1.722; P < .001 and OR = 1.018, P < .05, respectively). Online reviews are increasingly common, including in long-term care. These reviews are a promising source of information about important aspects of satisfaction, particularly in care settings that lack a public reporting infrastructure. We found several significant associations between online ratings and community-level factors, suggesting these reviews may be a valuable source of information to consumers and policy makers.


Effect of annealing in hydrogen atmosphere on carbon nanocap formation in surface decomposition of 6H-SiC(000-1).
We investigated the effect of annealing in a hydrogen atmosphere on carbon nanocap formation during decomposition of a 6H-SiC(000-1) surface. It was determined that native oxides were reduced to below the detection limit of X-ray photoelectron spectroscopy after 30 min of annealing at 1200 degrees C in a hydrogen atomosphere at 10(-3) Pa. In addition, we found that the homogeneity of carbon nanocap size was improved on the SiC surface, compared with a sample annealed in ultra-high vacuum. This technique will be useful in the fabrication of homogeneous carbon nanotube layers by surface decomposition of SiC.