Spatial control of translation repression and polarized growth by conserved NDR kinase Orb6 and RNA-binding protein Sts5.
RNA-binding proteins contribute to the formation of ribonucleoprotein (RNP) granules by phase transition, but regulatory mechanisms are not fully understood. Conserved fission yeast NDR (Nuclear Dbf2-Related) kinase Orb6 governs cell morphogenesis in part by spatially controlling Cdc42 GTPase. Here we describe a novel, independent function for Orb6 kinase in negatively regulating the recruitment of RNA-binding protein Sts5 into RNPs to promote polarized cell growth. We find that Orb6 kinase inhibits Sts5 recruitment into granules, its association with processing (P) bodies, and degradation of Sts5-bound mRNAs by promoting Sts5 interaction with 14-3-3 protein Rad24. Many Sts5-bound mRNAs encode essential factors for polarized cell growth, and Orb6 kinase spatially and temporally controls the extent of Sts5 granule formation. Disruption of this control system affects cell morphology and alters the pattern of polarized cell growth, revealing a role for Orb6 kinase in the spatial control of translational repression that enables normal cell morphogenesis.


Medical-setting deaths and the coroner: laws, penalties and guidelines.
We examine the law governing the reporting of medical-setting deaths to the Coroner throughout the Australian states and territories. We use a hypothetical case report to explore the different legal requirements for reporting a medical-setting death and the varying penalties that apply for failing to report a reportable death. It is important for health practitioners to understand the law that applies in the state or territory in which they practice. Knowing when to report a medical-setting death requires not only medical knowledge but also legal analysis. On this basis, we recommend the development of coroners' guidelines in all jurisdictions to assist health practitioners in complying with their coronial reporting obligations.


Effect of in ovo feeding of l-arginine on the hatchability, growth performance, gastrointestinal hormones, and jejunal digestive and absorptive capacity of posthatch broilers.
This study was conducted to investigate the effects of in ovo feeding (IOF) of Arg solution on the hatchability, growth performance, gastrointestinal hormones, serum AA, activities of digestive enzymes, and mRNA expressions of sensing receptors and nutrient transporters in the jejunum of posthatch broilers. One thousand two hundred embryonated eggs with similar weight were randomly allocated to 5 groups consisting of 8 replicates of 40 eggs each. The 5 treatments were arranged as a noninjected control, a diluent-injected (0.75% NaCl solution) group, and Arg solution-injected groups with 0.5%, 1.0%, and 2.0% Arg, all dissolved in diluent. At 17.5 d of incubation, 0.6 mL of IOF solution was injected into the amniotic fluid of each egg of the injected groups. Results showed the hatchability of the 2% Arg group was lower (linear, = 0.025) than that of the other groups, and the BW of 21-d-old broilers increased (linear, = 0.008; quadratic, = 0.003) with increasing IOF concentration of Arg. The ADFI (linear, = 0.005; quadratic, = 0.001) and ADG (linear, = 0.010; quadratic, = 0.004) increased during d 1 to 21 with increasing IOF concentration of Arg. For 7- and 21-d-old broilers, the weights of digestive organs increased (linear, < 0.05) with increasing IOF concentrations of Arg; the greatest values were observed in the 1% Arg group. For 21-d-old broilers, IOF of the 1% Arg solution increased ( < 0.05) the concentrations of ghrelin and glucagon-like peptide 2; the activities of digestive enzymes, alkaline phosphatase, maltase, and sucrase in the jejunum; and the concentrations of serum AA of Val, Met, Ile, Leu, Arg, and Pro compared with those of the noninjected control and diluent-injected group. In ovo feeding of the 1% Arg solution also increased ( < 0.05) the mRNA expressions of jejunal sensing receptors of taste receptor type 1 members 1 and 3; the G protein-coupled receptor, class C, group 6, subtype A; nutrient transporters of solute carrier family 7, members 4, 6, and 7; sodium-glucose transporter 1; and fatty acid-binding protein 1. In conclusion, the 1% Arg solution was the appropriate injection level. In ovo feeding of the 1% Arg solution did not affect the hatchability but facilitated the release of gastrointestinal hormones, increasing the digestive and absorptive capacity and finally improving the growth performance of 21-d-old broilers. Therefore, IOF of the appropriate Arg solution could be an effective technology for regulating early nutrition supply and subsequent growth development in the poultry industry.


Characterization of Pt nanoparticles deposited onto carbon nanotubes grown on carbon paper and evaluation of this electrode for the reduction of oxygen.
Multiwalled carbon nanotubes (MWCNTs) were grown on the fibers of a commercial porous carbon paper used as carbon-collecting electrodes in fuel cells. The tubes were then covered with Pt nanoparticles in order to test these gas diffusion electrodes (GDEs) for oxygen reduction in H2SO4 solution and in H2/O2 fuel cells. The Pt nanoparticles were characterized by cyclic voltammetry, transmission electron microscopy, and X-ray photoelectron spectroscopy. The majority of the Pt particles are 3 nm in size with a mean size of 4.1 nm. They have an electrochemically active surface area of 60 m2/g Pt for Pt loadings of 0.1-0.45 mg Pt/cm2. Although the electroactive Pt surface area is larger for commercial electrodes of similar loadings, Pt/MWCNT electrodes largely outperform the commercial electrode for the oxygen reduction reaction in GDE experiments using H2SO4 at pH 1. On the other hand, when the same electrodes are used as the cathode in a H2/O2 fuel cell, they perform only slightly better than the commercial electrodes in the potential range going from approximately 0.9 to approximately 0.7 V and have a lower performance at lower voltages.


Health-related quality of life among patients with an ostomy regarding sex, disease diagnosis, health care provider, and ostomy type: a descriptive cross-sectional study.
Ostomy surgery can negatively affect quality of life; however, the lived experiences of individuals with ostomies in Saudi Arabia are not well understood. To examine how sex, ostomy type, disease diagnosis, and health care provider shape health-related quality of life (HRQOL) in individuals with ostomies in Saudi Arabia. A descriptive cross-sectional study was conducted based on self-reported data of a convenience sample of 421 patients (239 male, 182 female) with ostomies (206 temporary, 211 permanent, 4 unknown) from 5 hospitals in Riyadh, Saudi Arabia. Data were collected using the City of Hope-Quality of Life-Ostomy Questionnaire (Arabic version) and analyzed by univariate and multiple regression analyses to identify predictors of physical, psychological, social, spiritual, and overall HRQOL. HRQOL scores correlated significantly with ostomy type (temporary vs permanent), sex, and health care provider. There were no significant differences in HRQOL scores by disease diagnosis (cancer vs non-cancer). Several potential predictors of HRQOL among patients with ostomies in Saudi Arabia were identified, which may assist in developing intervention strategies to improve patients' HRQOL. Additional studies are needed to understand the specific barriers in each group.


[Total count of bacteria in the air of three different laying hen housing systems].
Bacteria in the air of animal housing is assumed to have an impact on the health of the humans and the animals in them and on the environment. The bacterial count in poultry housing systems is particularly high in comparison to those of pigs and cattle. Little is known about the bacteria in the air of new laying hen housing systems. We therefore made simple, simultaneous measurements in the air of three different systems (enriched cages, AK; conventional battery cages, BK; aviary, VOL), in the unheated scratching area of the VOL, and in the outside air over a period of one year (24-h samples were taken about once a month using polycarbonate filters) in order to determine the general bacterial count (using blood agar). The highest concentrations of bacteria were found all year long in the VOL, followed by the BK and the AK. In the VOL, there were on average 2.16 and 0.56 x 10(6) colony forming units (cfu)/m3 in the winter and summer, respectively; 0.25 and 0.38 in the BK; and 0.39 and 0.12 in the AK. These preliminary results show that air quality considerations should be included in the development and implementation of new housing systems, as should the impact on the respiratory system of the humans and animals in them and on the environment, because high concentrations of air contamination in the housing generally also lead to high emissions into the vicinity of the facility, the significance of which cannot always be estimated, as has recently been shown for antibiotics in the exhaust air from animal housing.


[The mass-spectrometric evaluation of сarbapenemase activity of Pseudomonas aeruginosa.]
The Pseudomonas aeruginosa is among number of leading opportunistic pathogens. The evaluation of sensitivity of hospital isolates of P. aeruginosa to antibiotics is an important stage in the struggle with Pseudomonas sepsis pathology. The purpose of study is to confirm diagnostic efficiency of mass spectrometry approach in evaluation of сarbapenemase activity in clinical isolates of P. aeruginosa. The study was targeted to detection of сarbapenemases in 50 clinical isolates of P. aeruginosa, non-sensitive to сarbapenemas (control group - 9 isolates of P. aeruginosa sensitive to сarbapenemas). The comparative analysis was implemented concerning the results obtained using laser desorption ionization time-of-flight mass spectrometry and using such common techniques as phenotype detection of presence of metallo-beta-lactamase using E-tests and detection of presence of genes of carbapenemases (VIM, IMP, NDM) using polymerase chain reaction in real-time. The metallo-beta-lactamase activity was established in 14 (28%) out of 50 non-sensitive to сarbapenemas strains. All of them had genes of carbapenemases VIM-type. No IMP and NDM genes were detected in any strain. The VIM genes were detected only in metallo-beta-lactamase positive strains and metallo-beta-lactamase activity was registered only in carriers of VIM genes. According data of MALDI-TOF, all metallo-beta-lactamase and VIM positive strains demonstrated increased capacity of hydrolyzing meropenem. The percentage of hydrolysis under testing of the given strains made up to from 7.6 to 59.3. The absence of carbapenemase activity was demonstrated by 36 (72%) out of 50 strains non-sensitive to сarbapenemases with percentage of hydrolysis from 0 to 4. None of 9 control isolates sensitive to сarbapenemases had metallo-beta-lactamase activity, carried analyzed genes of сarbapenemas and hydrolyzed meropenem. The MALDI-TOF mass spectrometry is a perspective technique to be applied in practice of clinical microbiology for detect isolates of P. aeruginosa, producing сarbapenemases.


Outbreak of leptospirosis among triathlon participants in Germany, 2006.
In August 2006, a case of leptospirosis occurred in an athlete after a triathlon held around Heidelberg and in the Neckar river. In order to study a possible outbreak and to determine risk factors for infection an epidemiological investigation was performed. Participants of the triathlon were contacted by e-mail and were asked to fill out a standardized questionnaire. In addition, they were asked to supply a serum sample for laboratory diagnosis of leptospirosis. A confirmed case patient was defined as a clinical case (i.e. fever and at least one additional symptom suggestive for leptospirosis) with at least two of the following tests positive: ELISA IgM, latex agglutination testing, or microscopic agglutination testing. Rainfall and temperature records were obtained. A total of 142 of 507 triathletes were contacted; among these, five confirmed leptospirosis cases were found. Open wounds were identified as the only significant risk factor for illness (p = 0.02). Heavy rains that preceded the swimming event likely increased leptospiral contamination of the Neckar River. This is the first outbreak of leptospirosis related to a competitive sports event in Germany. Among people with contact to freshwater, the risk of contracting leptospirosis should be considered by health care providers also in temperate countries, particularly in the summer after heavy rains.


The management of desmoid tumors.
To determine the efficacy of different treatment modalities for desmoid tumors. We reviewed the treatment of 40 patients with histologically confirmed desmoid tumors seen at Duke University Medical Center between 1974 and 1990. Radiotherapy was administered to 16 patients (Group I)--14 with recurrent disease s/p surgery and in two as initial treatment. The average size of the irradiated lesions was 9.3 +/- 3.9 X 8.4 +/- 3.5 cm. With a median follow-up of 57.5 months and a median administered dose of 5400 cGy (mean 5286 cGy, range 4960-5620 cGy), local control has been obtained in 15/16 patients (94%). Complete regression (5/16), partial regression (5/16), or stable disease (5/16) was produced in 15 patients while one patient failed and was salvaged via gross total resection. Continued regression has been seen up to 60 months after treatment. Fourteen patients underwent primary gross total resection and two underwent subtotal resection (Group II). None received post-operative radiotherapy. Three of 14 patients (21%) recurred after gross total resection. All three were salvaged with subsequent gross total resection. After subtotal resection, 2/2 patients recurred. With a mean follow-up of 52 months, 14 patients are without evidence of disease, one is dead with disease (unrelated cause of death), and one was lost to follow-up after recurrence. Eight patients have been treated with combinations of chemotherapy, NSAIDS, anti-estrogens, and immunotherapy with mixed results (Group III). A subset of seven patients with retroperitoneal disease taken from all three groups had large tumor burden (mean size 17 X 15 cm), an infiltrative nature, as well as a difficult location. The disease was surgically resectable in three patients. One is without evidence of disease 9 years after gross total resection alone. Disease has been stabilized with radiotherapy in the other two patients after multiple unsuccessful surgical resections. Of four patients with unresectable disease, two are dead of disease, one died of unrelated causes with disease, and regression of disease was obtained in the other with Gamma-interferon after unsuccessful treatment with tamoxifen and vincristine, doxorubicin, and cyclophosphamide chemotherapy. Gross total resection is the indicated initial therapy, if it can be performed without significant disfigurement. Radiotherapy is also excellent for obtaining local control, even in patients with a large burden of recurrent disease. Doses in the range of 50 to 55 Gy give a chance of local control equal to that obtained with higher doses previously reported.


Pipeline Impact of Radiolabeled Compounds in Drug Discovery and Development.
The long-lived radionuclides tritium and carbon-14 have been used for many years in pharmaceutical research and development for making key efficacy and toxicological decisions. Early discovery utilizes radiolabels for compound selection through radioligand binding assays and autoradiography. In preclinical safety evaluation, the use of labeled compounds for adsorption, distribution, metabolism, and excretion studies is often preferred for the added detection sensitivity. As the drug substance proceeds to the clinic, human metabolism studies are reliant on the use of labeled materials to fulfill required regulatory applications.


A pattern of care analysis: Prosthetic rehabilitation of head and neck cancer patients after radiotherapy.
While some medical associations provide guidelines for the implant-prosthetic rehabilitation of head and neck cancer patients, the circulation and implementation in the everyday routine of practicing dentists remain unknown. To analyze patterns of care for the prosthetic rehabilitation of head and neck cancer patients after radiotherapy in German speaking countries. An online survey consisting of 34 questions separated into three sections, (a) general inquiries, (b) treatment concepts, and (c) patient cases, was forwarded to university hospital departments for Prosthetic Dentistry and Oral and Maxillofacial Surgery, and members of different medical associations. Statistical differences between groups were analyzed using chi-squared test (P < .05). From May to October 2019, 118 participants completed the survey. The majority practiced in university hospitals, had more than 5 years of work experience, and reported to be involved in <10 post radiation prosthetic rehabilitation cases per year. Rehabilitation protocols involving dental implants were implemented by oral/oral- and maxillofacial surgeons and prosthetic dentists, while general dentists favored implant-free solutions. Xerostomia was recognized as a common problem for a successful prosthetic rehabilitation. The subsequent treatment choice with either fixed dental prostheses or removable dentures was divided among participants. As treatment planning differed with regard to the participants' field of expertise and work environment, and most practitioners only handle a low number of cases, patients might benefit from centralization in larger institutes with a multidisciplinary structure. A high agreement between the practitioners' treatment concepts and the current state of research was observed. While the choice between a mucosa- or tooth-supported, and an implant-supported restoration depends on numerous individual factors, guidelines derived from longitudinal studies would enhance evidence-based treatment in this field.


Glucose metabolism disorders in patients with non-functioning adrenal adenomas - single-centre experience.
The presence of glucose metabolism disorders and their possible correlation with degree of cortisol secretion were evaluated in patients with non-functioning adrenal incidentalomas (NFAIs). The study group consisted of 131 patients with hormonally inactive adrenal incidentalomas. In each patient, besides hormonal and radiological evaluation, was assessed for fasting glucose and insulin concentrations, and the oral glucose tolerance test (OGTT) was performed in all participants without previous history of glucose disturbances. The HOMA-IR, QUICKI, and TyG indices were calculated. Diabetes was diagnosed in 30.5% of the studied group. Among glucose tolerance abnormalities, impaired fasting glucose (IFG) was found in 23.7%, impaired glucose tolerance (IGT) in 4.6%, and combined IFG and IGT in 11.5%. Normoglycaemia was recognised in 29.8% of NFAIs patients. The occurrence rate of glucose aberrations increased with age. There was a significant difference in all insulin resistance indices shown between normoglycaemic patients and those with impairments in glucose tolerance. There was no significant correlation between fasting glucose, insulin resistance indices, and adrenal tumour size or degree of cortisol secretion. The prevalence of diabetes and impaired fasting glucose among NFAIs patients is much higher than in the general population. Therefore, patients with incidentally discovered adrenal tumours should be tested for glucose tolerance.


Newer anti-diabetic therapies with low hypoglycemic risk-potential advantages for frail older people.
The prevalence of diabetes is increasing due to increasing aging of the population. Hypoglycemia is a common diabetes-related complication in old age especially in patients with multiple comorbidities and frailty. Hypoglycemia and frailty appear to have a bidirectional relationship reenforcing each other in a negative downhill spiral that leads to an increased risk of adverse events including disability and mortality. The incidence of hypoglycemia in this age group is usually underestimated due to its atypical clinical presentation and difficult recognition by health care professionals. Guidelines generally recommend a relaxed glycemic control in frail older people with diabetes mainly due to the fear of anti-diabetic medications-induced hypoglycemia. The new anti-diabetic therapies of sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon like peptide-1 receptor agonists (GLP-1RA) have consistently shown a cardio-renal protective effect independent of their glycemic control. Contrary to the traditional hypoglycemic agents that either increase insulin stimulation or insulin sensitization with a potential hypoglycemic risk especially sulfonylureas, the new therapies have a novel anti-diabetic mechanisms of action that have a negligible risk of hypoglycemia. The new therapies appear to be both effective and well tolerated in old age. With appropriate patients' selection, most older people will be eligible for the new therapies if well tolerated and no contraindications. In frail older people, we suggest a pragmatic approach of the use of the new therapies based on the concept of the weight status rather than the frailty status. Frail patients with normal or excess weight are likely to gain most from the new therapies due to its favorable metabolic properties in this group, while the use in the underweight frail patients should be largely avoided especially in those with persistent anorexia and weight loss.


Examining the effects of perceived pregnancy discrimination on mother and baby health.
Over the last decade, more than 50,000 pregnancy discrimination claims were filed in the United States (United States Equal Employment Opportunity Commission [U.S. EEOC], 2018a). While pregnancy discrimination claims remain prevalent, research examining the effects of pregnancy discrimination on the well-being and health of working mothers and their babies is lacking. As such, we aim to examine the role of perceived pregnancy discrimination in the workplace on health outcomes for mothers and their babies via mother's stress. We draw on the occupational stress literature and medical research to propose that perceived pregnancy discrimination indirectly relates to mother and baby health via the mother's perceived stress. In our first study, we examine the effects of perceived pregnancy discrimination on mothers' postpartum depressive symptoms via perceived stress. In our second study, we replicate and extend our first study and examine the effects of perceived pregnancy discrimination on mothers' postpartum depressive symptoms and babies' gestational age, Apgar scores, birth weight, and number of doctors' visits, through the mechanism of perceived stress. We find that perceived pregnancy discrimination indirectly relates to increased levels of postpartum depressive symptoms for the mothers, and lower birth weights, lower gestational ages, and increased number of doctors' visits for the babies, via perceived stress of the mothers during pregnancy. Implications for theory and practice, limitations, and future research are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


In vitro BACE1 inhibitory activity of geraniin and corilagin from Geranium thunbergii.
Generation of amyloid β peptide through the proteolytic process of amyloid precursor protein by β-secretase and γ-secretase is a main casual factor of Alzheimer's disease, since amyloid β peptide is a major and crucial component of senile plaques in Alzheimer's disease brains. In the process of searching for β-secretase inhibitors from natural resources, the EtOAc soluble fraction of Geranium thunbergii exhibited significant β-secretase inhibitory activity. Two compounds, geraniin and corilagin, isolated from the most active EtOAc fraction of G. thunbergii, exhibited predominant inhibition against β-secretase with IC₅₀ values of 4.0 × 10⁻⁶ M and 3.4 × 10⁻⁵ M, respectively. Dixon plot of geraniin and corilagin demonstrated that the β-secretase inhibition was noncompetitive with the substrate, thus clearly suggesting that these compounds might bind either to the β-secretase subsites or to another regulatory domain with Ki values of 2.8 × 10⁻⁶ M and 7.9 × 10⁻⁵ M, respectively. Both compounds exhibited no significant inhibition against α-secretase and other serine proteases including trypsin and chymotrypsin, showing that they were relatively specific and selective inhibitors of β-secretase. These novel findings suggest that geraniin and corilagin from G. thunbergii may be effective therapeutic agents for further drug development in Alzheimer's disease.


[Speech-related tremor of lips: a focal task-specific tremor].
We report a 66-year-old Japanese woman in whom tremor of lips appeared during speech. Her past and family histories were unremarkable. On neurological examination, there was no abnormal finding except the lip tremor. Results of laboratory findings were all within normal levels. Her MRI and EEG were normal. Surface EMG studies revealed that regular grouped discharges at a frequency of about 4-5 Hz appeared in the orbicularis oris muscle only during voluntary speaking. The tremor was not observed under conditions of a purposeless phonation or a vocalization of a simple word, suggesting that the tremor was not a vocal tremor but a task-specific tremor related to speaking. Administration of a beta-blocker and consumption of small amount of alcohol could effectively improve the tremor, possibly suggesting that this type of tremor might be a clinical variant of essential tremor.


Cognitive style and the reading process: field-dependence differences on a lexical-decision task.
This study examined cognitive-style differences in reading strategies on a lexical-decision task. Subjects made word/nonword judgments for letter sequences consisting of either real words, English-sounding nonwords, or non-English-sounding nonwords. In line with previous findings, responses were significantly slower to English-sounding nonwords than to non-English-sounding nonwords. This effect was qualified by a significant interaction with field dependence such that field-dependent subjects were significantly slower than field-independent subjects for English-sounding nonwords but not for non-English-sounding nonwords or for real words. These findings complement a 1988 finding by Davies that field-dependent scores prefer a phonological strategy for lexical access and they provide better evidence for the role of such process differences in normal reading.


Emergence of community-associated methicillin-resistant Staphylococcus aureus at a Memphis, Tennessee Children's Hospital.
An epidemiologic investigation was performed because of a perceived increase in infections caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA) among children in the greater Memphis area. We reviewed medical records of 289 children evaluated from January 2000 to June 2002 at a children's hospital. Clinical criteria were applied to classify MRSA isolates as community-associated (n=51) or health care-associated (n=138). The relatedness of 33 archived S. aureus isolates was evaluated using pulsed field gel electrophoresis (PFGE) of Sma I-digested genomic DNA; a common pulsed field type was defined as > or = 80 % similarity based on Dice coefficients. PFGE profiles were compared with those in a national database of MRSA isolates. During the first 18 study months, 46 of 122 MRSA isolates (38%) were community-associated; this proportion increased to 106 of 167 isolates (63%) during the last 12 study months (P <.0001). Community-associated isolates were recovered from normally sterile sites as frequently as were health care-associated isolates (16% versus 13%). PFGE revealed that 15 of 16 community-associated isolates shared a common pulsed field type (USA300) observed in community-associated MRSA infections elsewhere in the United States and characterized by staphylococcal cassette chromosome mec type IV, clindamycin susceptibility and erythromycin resistance mediated by an msr A-encoded macrolide efflux pump. Community-associated MRSA has emerged as a potentially invasive pathogen among children in the greater Memphis area, and this phenomenon is not explained by spread of nosocomial strains into the community.


Occupational health aspects of the arsenic extractive industry in Britain (1868-1925).
A historical survey into the occupational hazards of mining and refining arsenic is presented together with the measures adopted for their control. The industry is placed in the social perspective of its time and it is suggested that this experience could be of value to those who may encounter similar problems where arsenic is extracted elsewhere in the world.


Effect of time delay in a bistable synthetic gene network.
The essence of logical stochastic resonance is the dynamic manipulation of potential wells. The effect of time delay on the depth of potential wells and the width of a bistable region can be inferred by logic operations in the bistable system with time delay. In a time-delayed synthetic gene network, time delay in the synthesis process can increase the depth of the potential wells, while that in the degradation process, it can reduce the depth of the potential wells, which will result in a decrease in the width of the bistable region (the reason for time delay to induce logic operations without external driving force) and the instability of the system (oscillation). These two opposite effects imply stretching and folding, leading to complex dynamical behaviors of the system, including period, chaos, bubble, chaotic bubble, forward and reverse period doubling bifurcation, intermittency, and coexisting attractors.


Liquid core waveguide for full imaging of electrophoretic separations.
We employed a liquid core waveguide to image both DNA electrophoresis separations and isoelectric focusing of proteins. The utility of the system is demonstrated for DNA fragment sizing and protein separations. The system utilizes the liquid-core waveguide as an efficient window for both the excitation of separated samples and the collection of light through total internal reflectance, with an ability to detect target molecules in the zeptomolar range. Scanning the excitation laser along the length of the electrophoresis capillary excites individually separated analyte bands, while the fluorescence is collected end-on by an optical fiber coupled to a photomultiplier, thus, creating an image of the separation along the length of the capillary.


Thoracomyoplasty in the treatment of empyema: current indications, basic principles, and results.
Empyema remains a challenge for modern medicine. Cases not amenable to lung decortication are particularly difficult to treat, requiring prolonged hospitalizations and mutilating procedures. This paper presents the current role of thoracomyoplasty procedures, which allow complete and definitive obliteration of the infected pleural space by a combination of thoracoplasty and the use of neighbourhood muscle flaps (latissimus dorsi, serratus anterior, pectoralis, rectus abdominis, omentum, etc). Recent publications show an overall rate of success of 90%, with a quick and definitive healing. Although rarely indicated in our days, this kind of procedures remain in the armamentarium of modern thoracic surgery. The importance of thoracomyoplasty derives from the fact that it may be a simple and definitive solution for complicated cases of chronic empyema not amenable to standard decortication.


[Infectious agents : current concepts and perspectives].
The authors present a detailed discussion on infectious agents and their development in the immediate future and the anti-microbial strategies which need to be developed. After describing a series of new diseases and the suspected microbial aetiology of little known syndromes, they describe the major lines of development of chemotherapy: new products which need to be developed; microbial enzyme inhibitors; selective transport. The proper use of the range of drugs already available should not be underestimated. Finally, the authors review recent developments and the prospects for the future in the immunological field: new vaccines or the improvement of existing vaccines and the immense possibilities of immunological techniques of identification.


[Active oxygen and anti-inflammatory drug: measurement by luminol dependent chemiluminescence].
The active oxygen produced from stimulated phagocytic cells emits luminol-dependent chemiluminescence (CL) upon reaction with luminol. So the active oxygen was measured by using the CL and the results of this were compared with those by the LDH-NADH method. Moreover, effects of nonsteroidal anti-inflammatory drugs (NSAID) on the generation of active oxygen were studied by both methods. Rat peritoneal and pleural exudated cells (PEEC and PLEC) emitted strong CL on incubation with zymosan, but that from rat whole blood cells was very weak. The effects of superoxide dismutase, catalase, NaN3 and L-ascorbic acid on the generation of active oxygen from rat phagocytic cells were different between CL and LDH-NADH methods. These discrepancies seem to be due to the different kinds of active oxygen that can be measured by both methods. Except for BW-755C, most of the NSAID had only a slight inhibitory effect on the generation of active oxygen measured by both methods, and the ex vivo effect was the same as that observed in vitro. It may be considered that NSAID decrease the phagocytic function of cells by non-specifically stabilizing the biological membrane and inhibit slightly the generation of active oxygen from phagocytes. On the other hand, the CL method could be performed not only in PEEC and PLEC, but also in whole blood cells. From these results, it was suggested that CL measurement can be used as a simple and valuable method for the detection of all types of active oxygen including superoxide anion radical and its metabolites and for testing cellular functions and drug actions on them.


Correlation of admitted nursing home residents' hospital length of stay and vitamin D levels.
To determine the relationship between low vitamin D levels and hospital length of stay in nursing home residents who were admitted to acute medical floors in an urban community teaching hospital. This prospective cohort study used multiple regression analysis for patients transferred from nursing homes to the hospital. On admission, patients' serum 25(OH)D levels were obtained by blood draw using partially purified lipid extracts via a competitive protein binding assay. We defined low levels of serum 25(OH)D as <30 ng/ml. Patient medical histories were compiled by retrospective chart review and/or patient interview. Medical histories were analyzed with special emphasis on history of falls, osteoporosis, comorbidities, medication profile, and hospital length of stay. The mean serum 25(OH)D level for 71 patients (N = 71) was 22.69 ng/ml (±SD 10.967); the median, 23 ng/ml. Low serum concentrations of 25(OH)D were recorded in 51 patients (72%) all of whom had a longer mean hospital length of stay (13.72 days ± SD 10.778) than the 20 patients with higher vitamin D levels (7.72 days ± SD 4.070). Low vitamin D levels in nursing home residents admitted to a community hospital were directly associated with increased hospital length of stay.


[Effects of oral administration of UFT in unresectable gastric cancer with liver metastasis].
A 62-year-old male was admitted because of upper abdominal mass. Exploratory laparotomy revealed unresectable gastric cancer, liver metastases and swelling of regional lymph nodes. Histological examination showed papillotubular adenocarcinoma. After 6 months' postoperative administration of UFT at a daily dose of 600 mg, X-ray and endoscopic examination revealed remarkable improvement of the gastric cancer. Computed tomography and ultrasonography showed disappearance of the mass in the liver and a remarkable decrease in the size of paraaortic lymph nodes. The cancer marker, serum CEA also decreased from 5.2 ng/ml to 2.1 ng/ml. At present, the abdominal mass is not palpable and the patient is asymptomatic except for pigmentation and being followed up in the outpatient department. This case suggests the possibility that UFT may be effective for advanced gastric cancer with liver metastases.


Enhanced UV-mediated free radical generation; DNA and mitochondrial damage caused by retinol supplementation.
Retinoid supplementation has been therapeutically used against various human disorders. We and others have demonstrated that retinol treatment causes free radical generation and increased iron uptake, iron storage and oxidative damage, both in vitro and in vivo. Here, we investigate the possible synergistic effect of retinol on UV-mediated free radical generation, oxidative damage to biomolecules and decreased cellular viability in primary cultured mammalian cells. Retinol treatment (7 microM) resulted in a threefold increase in UV-mediated free radical generation and a 40%, increase in lipoperoxidation. DNA fragmentation and mitochondrial oxidative damage also increased significantly in retinol-supplemented UV-irradiated cultured cells as compared to UV-irradiated control cells, which were only treated with the solvent used to deliver the retinol (0.1% ethanol). All measurements were restored to control values when an iron chelator, 1,10-phenanthroline (100 microM), or an OH* scavenger, mannitol (1 mM), was co-administrated. Rather than protecting against free radical generation, retinol seems to enhance UV-mediated oxidative damage and decreases cellular viability in cultured cells. We suggest that retinol-enhanced iron uptake and storage and increased reactive oxygen species generated by the Fenton reaction may act synergistically with UV-irradiation in causing oxidative damage to cells.


Featuring Trends in the Epidemiology of Lung Cancer Following the Publication of the National Cancer Strategy in Qatar.
Qatar has witnessed significant reforms in its health care system, including the care of cancer patients. In 2011, the National Cancer Strategy was released with the aim to deliver a high standard of care to cancer patients across the country. We sought to investigate the featuring trends in the epidemiological and clinical characteristics of lung cancer in Qatar following the publication of the National Cancer Strategy. We conducted a retrospective cohort study documenting the epidemiological and clinical characteristics of primary lung cancer cases in Qatar diagnosed from 1 January 2011 to 31 December 2018. The overall age-standardized incidence rate was 8.7 per 100 000 persons (11.6 per 100 000 and 5.4 per 100 000 persons for males and females, respectively). The one, three, and five-year overall survival rates were 67.0%, 48.0%, and 28.0%, respectively. The three-year overall survival rates for stages I, II, III, and IV were 97.0%, 78.0%, 52.0%, and 31.0%, respectively. The three-year survival rates for males and females were 43.0% and 64.0%, respectively (p = 0.029), for Qatari and non-Qatari nationals were 42.0% and 49.0%, respectively (p = 0.252), and for smokers and non-smokers were 39.0% and 69.0%, respectively (p ≤ 0.001). The overall age-standardized mortality rate was 5.5 per 100 000 persons. Adenocarcinoma was the most common histologic type. Despite the low overall lung cancer incidence rate in Qatar, there is a rise in the incidence among females when compared to previous studies. Qatar has favorable five-year lung cancer survival rates compared to many developed and neighboring countries. Policymakers in the country should consider the changing patterns in lung cancer incidence when planning future preventive strategies.


In Vitro Monocyte/Macrophage Phagocytosis Assay for the Prediction of Drug-Induced Thrombocytopenia.
Phagocytosis of platelets by monocytes and macrophages is a primary mechanism of platelet clearance in vivo and has been increasingly implicated in playing an important role in thrombocytopenia mediated by monoclonal antibodies intended for therapeutic purposes. In the present article, we describe an in vitro flow cytometry assay to assess the effect of antibody-mediated platelet phagocytosis by monocytes. Freshly isolated platelets were labeled with a fluorescent probe, 5-chloromethylfluorescein diacetate (CMFDA) and then co-cultured with isolated peripheral blood mononuclear cells (PBMCs) from the same donor in the presence of increasing concentrations of a monoclonal antibody drug. After incubation, an increase in CMFDA fluorescence intensity of CD14 positive monocytes was evaluated by flow cytometry as an assessment for drug-mediated platelet phagocytosis by monocytes. The assay has been evaluated using both human and cynomolgus monkey cells for the prediction of drug-induced thrombocytopenia. © 2019 by John Wiley & Sons, Inc.


Intravenous immunoglobulin in septic shock: review of the mechanisms of action and meta-analysis of the clinical effectiveness.
Sepsis is characterized by a complex immune response. In this study we aimed to provide a review of the mechanisms of action of immunoglobulin (Ig) related to sepsis and an updated meta-analysis of the clinical effectiveness of the Ig use in septic patients. We performed two separate searches of Medline and other databases with the keywords Ig, sepsis, septic shock, septicemia, septicemia with no language restrictions in order to review the mechanisms of action of Igs in sepsis and to update the previous meta-analysis on the effects of the Ig therapy on the mortality of adult patients with septic shock. Pathogens and toxin clearance, anti-inflammatory effects and anti-apoptotic effects on immune cells seems to be the main mechanisms of action of Ig therapy in sepsis. The meta-analysis of 18 RCTs indicated that the use of intravenous Ig reduces the mortality risk of septic patients (odds ratio=0.50 [95% CI 0.34-0.71], I2=44.68%). Low study quality, heterogeneous dosing regimens and type of Ig preparations, and different control interventions (placebo or albumin) may have influenced our results. Our study showed that the use of intravenous Ig therapy in adult septic patients may have a rationale and seems to be associated with a reduced mortality. Anyway, the treatment effect generally tended to be smaller or less consistent if considering only those studies that were deemed adequate on each indicator. So, the available evidence is not clearly sufficient to support the widespread use of Ig in the treatment of sepsis.


Two-dimensional magnetic clusters in La(n)(Ti(1-x)Fe(x))(n)O(3n+2) (n = 5 with x = 0.2 and n = 6 with x = 0.33).
Crystal structure analyses of the layered compounds La(n)(Ti(1-x)Fe(x))(n)O(3n+2), with nominal compositions x = 0.2 for n = 5 and x = 0.33 for n = 6, show that the iron is concentrated at the centers of the slabs. The spatial arrangements of the iron ions can be approximated by two-dimensional square lattices with strong magnetic interactions between neighboring sites, albeit with fractional occupancies of the sites of an average of 0.67 magnetic ions in n = 6 and 0.42 magnetic ions in n = 5 compounds. A previously described (Lichtenberg et al 2008 Prog. Solid State Chem. 36 253) crossover of magnetic behavior of n = 6 at room temperature is explained by the formation of two-dimensional, ferromagnetically organized magnetic clusters with an average size of 52 Fe(3+) ions. The absence of long-range magnetic order follows from the fractional occupancy of the sites by the magnetic ions. The lower concentration of magnetic ions in n = 5 explains why crossover behavior is not found and clusters do not form in that compound.


Polycythemia vera. V. Enhanced proliferation and phosphorylation due to vanadate are diminished in polycythemia vera erythroid progenitor cells: a possible defect of phosphatase activity in polycythemia vera.
Erythropoietin (EP) and stem cell factor (SCF) are essential growth factors for erythroid progenitor cell proliferation and differentiation in serum-free culture. It has been previously shown that burst-forming units-erythroid and colony-forming units-erythroid from patients with polycythemia vera (PV) have enhanced sensitivity to EP and SCF compared with normal erythroid progenitors, but little is known about the mechanism for this difference. In the present investigation, the effect of EP and SCF on protein tyrosine phosphorylation in day-8 normal and PV erythroid colony-forming cells, which give rise to colonies of 2-49 hemoglobinized cells, was studied. EP rapidly induced tyrosine phosphorylation of the EP receptor, whereas the most prominent phosphorylated protein induced by SCF was identified as the SCF receptor. No additional phosphorylated proteins were evident when PV cells were compared with normal cells. Culture of normal erythroid progenitors with orthovanadate, an inhibitor of protein tyrosine phosphatases, resulted in an increased number of erythroid colonies and enhanced protein tyrosine phosphorylation. However, in contrast, little enhancement was evident with PV cells. These results indicate that, although vanadate may be acting in normal erythroid progenitors as a phosphatase inhibitor that potentiates the kinase activity induced by SCF and EP, this function is diminished in PV cells. Because erythropoiesis is regulated by a balance between protein tyrosine kinase activity and protein tyrosine phosphatase activity, PV patients may have an abnormal phosphatase activity allowing increased cell proliferation.


Preparation of cross-linked biocompatible poly(2-methacryloyloxyethyl phosphorylcholine) gel and its strange swelling behavior in water/ethanol mixture.
Functional cross-linked poly(2-methacryloyloxyethyl phosphorylcholine(MPC)) gels were prepared with various cross-linkers by conventional radical polymerization in aqueous media. The poly(MPC) gels swelled in water and have a large degree of swelling compared with that of poly(2-hydroxyethyl methacrylate). The swelling degree of the poly(MPC) gel equilibrated in water depended on the chemical structure and composition of the cross-linkers, but did not change in an aqueous medium with pH and ionic concentrations. On the other hand, the volume of poly(MPC) gel changed sharply with a change in the composition of water/ethanol mixtures. Although in mixtures containing 70-90 vol% of ethanol the gel volume was nearly 10% of that in water, in pure ethanol it was almost the same as in water. The change in the volume of the poly(MPC) gel observed in a water/ethanol mixture was completely reversible. We conclude that this so-called re-entrant phenomenon was derived from the co-nonsolvency of poly(MPC) in the water/ethanol mixture triggered by an imbalance in the delicate interaction force between the molecules of water, ethanol, and poly(MPC).


Prevalence, Virulence Genes and Antimicrobial Resistance Profiles of Salmonella Serovars from Retail Beef in Selangor, Malaysia.
The aim of the present study was to investigate the prevalence of Salmonella spp., Salmonella Enteritidis and Salmonella Typhimurium in retail beef from different retail markets of Selangor area, as well as, to assess their pathogenic potential and antimicrobial resistance. A total of 240 retail beef meat samples (chuck = 60; rib = 60; round = 60; sirloin = 60) were randomly collected. The multiplex polymerase chain reaction (mPCR) in combination with the most probable number (MPN) method was employed to detect Salmonella spp., S. Enteritidis and S. Typhimurium in the meat samples. The prevalence of Salmonella spp., S. Enteritidis and S. Typhimurium in 240 beef meat samples were 7.50, 1.25, and 0.83%, respectively. The microbial loads of total Salmonella was found in the range of <3 to 15 MPN/g. Eight different serovars of Salmonella were identified among the 23 isolates, and S. Agona was the predominant serovar (26.09%). Interestingly, all the Salmonella isolates were resistant to penicillin, erythromycin and vancomycin, but the sensitivity was observed for tetracycline, gentamicin and amoxicillin/clavulanic acid. All 23 isolates were resistant to at least three antibiotics. Two S. Typhimurium isolates (8.70%) exhibited the highest multiple antibiotic resistance (MAR) index value of 0.56 which shown resistance to nine antibiotics. PCR analysis of virulence genes showed that all Salmonella isolates (100%) were positive for the invA gene. Meanwhile, pefA was only identified in S. Enteritidis and S. Typhimurium. The findings in this study indicate that retail beef products tested were widely contaminated with multi-drug resistant (MDR) Salmonella and various virulence genes are present among the isolated Salmonella serovars.


Genotype-phenotype correlation in inherited severe insulin resistance.
The insulin receptor is a ligand-activated tyrosine kinase. Mutations in the corresponding gene cause the rare inherited insulin-resistant disorders leprechaunism and Rabson-Mendenhall syndrome. Patients with the most severe syndrome, leprechaunism, have growth restriction, altered glucose homeostasis and early death (usually before 1 year of age). Rabson-Mendenhall syndrome is less severe, with survival up to 5-15 years of age. These disorders are transmitted as autosomal recessive traits. Here we report six new patients and correlate mutations in the insulin receptor gene with survival. Patients with leprechaunism were homozygous or compound heterozygous for mutations in the extracellular domain of the insulin receptor and their cells had markedly impaired insulin binding (<10% of controls). Mutations in their insulin receptor gene inserted premature stop codons (E124X, R372X, G650X, E665X and C682X), resulting in decreased levels of mature mRNA, or affected the extracellular domain of the receptor (R86P, A92V, DeltaN281, I898T and R899W). Three patients with Rabson-Mendenhall syndrome had at least one missense mutation in the intracellular domain of the insulin receptor (P970T, I1116T, R1131W and R1174W). Expression studies in CHO cells indicated that the R86P, A92V, DeltaN281, I898T, R899W and R1131W mutations markedly impaired insulin binding (<5% of control), while the P970T, I1116T and R1174W mutant receptors retained significant insulin-binding activity. These results indicate that mutations in the insulin receptor retaining residual insulin-binding correlate with prolonged survival in our series of patients with extreme insulin resistance.


The Montara Oil Spill: A 2009 Well Blowout in the Timor Sea.
A well on the Montara platform on the Australian continental shelf blew out in August 2009 and spilled oil into the Timor Sea for 74 days. The oil, estimated at as much as 23.5 million L in total volume, spread over a large area of the shelf and eventually into Indonesian waters. This paper documents, through published literature, reports of both Australian and Indonesian governments and observations of coastal residents and fishermen the spread of the oil and attempts to estimate its impact. The lack of observers on the ocean and baseline, pre-spill data on populations of marine organisms, and delays in deploying scientific surveys after the spill severely limited efforts by the Australian government to determine damage in its territorial waters. Biological survey work was not done in Indonesian waters, but coastal residents attested to relatively severe impacts to algal farms. In addition fish landings declined in one port in southwest Timor Island.


Contribution of harmonicity and location to auditory object formation in free field: evidence from event-related brain potentials.
The contribution of location and harmonicity cues in sound segregation was investigated using behavioral reports and source waveforms derived from the scalp-recorded evoked potentials. Participants were presented with sounds composed of multiple harmonics in a free-field environment. The third harmonic was either tuned or mistuned and could be presented from the same or different location from the remaining harmonics. Presenting the third harmonic at a different location than the remaining harmonics increased the likelihood of hearing the tuned or slightly (i.e., 2%) mistuned harmonic as a separate object. Partials mistuned by 16% of their original value "pop out" of the complex and were paralleled by an object-related negativity (ORN) that superimposed the N1 and P2 components. For the 2% mistuned stimuli, the ORN was present only when the mistuned harmonic was presented at a different location than the remaining harmonics. Presenting the tuned harmonic at a different location also yielded changes in neural activity between 150 and 250 ms after sound onset. The behavioral and electrophysiological results indicate that listeners can segregate sounds based on harmonicity or location alone. The results also indicate that a conjunction of harmonicity and location cues contribute to sound segregation primarily when harmonicity is ambiguous.


A rank-based approach to active diagnosis.
The problem of active diagnosis arises in several applications such as disease diagnosis and fault diagnosis in computer networks, where the goal is to rapidly identify the binary states of a set of objects (e.g., faulty or working) by sequentially selecting, and observing, potentially noisy responses to binary valued queries. Previous work in this area chooses queries sequentially based on Information gain, and the object states are inferred by maximum a posteriori (MAP) estimation. In this work, rather than MAP estimation, we aim to rank objects according to their posterior fault probability. We propose a greedy algorithm to choose queries sequentially by maximizing the area under the ROC curve associated with the ranked list. The proposed algorithm overcomes limitations of existing work. When multiple faults may be present, the proposed algorithm does not rely on belief propagation, making it feasible for large scale networks with little loss in performance. When a single fault is present, the proposed algorithm can be implemented without knowledge of the underlying query noise distribution, making it robust to any misspecification of these noise parameters. We demonstrate the performance of the proposed algorithm through experiments on computer networks, a toxic chemical database, and synthetic datasets.


Structure of putrescine aminotransferase from Escherichia coli provides insights into the substrate specificity among class III aminotransferases.
YgjG is a putrescine aminotransferase enzyme that transfers amino groups from compounds with terminal primary amines to compounds with an aldehyde group using pyridoxal-5'-phosphate (PLP) as a cofactor. Previous biochemical data show that the enzyme prefers primary diamines, such as putrescine, over ornithine as a substrate. To better understand the enzyme's substrate specificity, crystal structures of YgjG from Escherichia coli were determined at 2.3 and 2.1 Å resolutions for the free and putrescine-bound enzymes, respectively. Sequence and structural analyses revealed that YgjG forms a dimer that adopts a class III PLP-dependent aminotransferase fold. A structural comparison between YgjG and other class III aminotransferases revealed that their structures are similar. However, YgjG has an additional N-terminal helical structure that partially contributes to a dimeric interaction with the other subunit via a helix-helix interaction. Interestingly, the YgjG substrate-binding site entrance size and charge distribution are smaller and more hydrophobic than other class III aminotransferases, which suggest that YgjG has a unique substrate binding site that could accommodate primary aliphatic diamine substrates, including putrescine. The YgjG crystal structures provide structural clues to putrescine aminotransferase substrate specificity and binding.


Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [(11)C]PBR28 PET Brain Imaging Study.
The purpose of this study was to determine whether microglial activity, measured using translocator-protein positron emission tomography (PET) imaging, is increased in unmedicated persons presenting with subclinical symptoms indicating that they are at ultra high risk of psychosis and to determine whether microglial activity is elevated in schizophrenia after controlling for a translocator-specific genetic polymorphism. The authors used the second-generation radioligand [(11)C]PBR28 and PET to image microglial activity in the brains of participants at ultra high risk for psychosis. Participants were recruited from early intervention centers. The authors also imaged a cohort of patients with schizophrenia and matched healthy subjects for comparison. In total, 50 individuals completed the study. At screening, participants were genotyped to account for the rs6971 polymorphism in the gene encoding the 18Kd translocator protein. The main outcome measure was total gray matter [(11)C]PBR28 binding ratio, representing microglial activity. [(11)C]PBR28 binding ratio in gray matter was elevated in ultra-high-risk participants compared with matched comparison subjects (Cohen's d >1.2) and was positively correlated with symptom severity (r=0.730). Patients with schizophrenia also demonstrated elevated microglial activity relative to matched comparison subjects (Cohen's d >1.7). Microglial activity is elevated in patients with schizophrenia and in persons with subclinical symptoms who are at ultra high risk of psychosis and is related to at-risk symptom severity. These findings suggest that neuroinflammation is linked to the risk of psychosis and related disorders, as well as the expression of subclinical symptoms.


Influence of plasma substitutes on the concentration of tissue catecholamines in rats.
The concentration of catecholamines was determined in the brain, heart and adrenals in normovolaemic and hypovolaemic rats after reinfusion of the lost blood and after infusion of equivalent volumes of plasma substitutes (dextran and modified gelatins). After infusion of these preparations in normovolaemic rats noradrenaline concentration increased significantly in the myocardium. It was found also that restoration of normal blood volume by infusion of plasma substitutes prevented changes in catecholamine concentrations induced by hypovolaemia in the brain but not in the adrenals.


Expression of P53 and HSP70 in Chronic Hepatitis, Liver Cirrhosis, and Early and Advanced Hepatocellular Carcinoma Tissues and Their Diagnostic Value in Hepatocellular Carcinoma: An Immunohistochemical Study.
Tumor protein (P53) and heat shock protein 70 (HSP70) play key roles in chronic liver diseases. This study aimed to characterize P53 and HSP70 expression in chronic hepatitis (CH), liver cirrhosis (LC), early and advanced HCC, and to analyze their diagnostic value in hepatocellular carcinoma (HCC). Immunohistochemical staining was conducted to evaluate the expression of P53 and HSP70 in 200 human liver tissue specimens, with advanced HCC (n=80), early HCC (n=30), CH (n=30), LC (n=30), and Controls (n=30). P53 expression levels were lower in LC than those of HCC, but remained on par with those of CH and Controls. HSP70 expression levels were higher in HCC than those of LC, CH, and Controls. The sensitivity and specificity for HCC diagnosis were: 50.9% and 98.9% for P53, and 78.2 and 77.8% for HSP70, respectively. The sensitivity and specificity of different combinations were: 95.5% and 85.5% with either P53 or HSP70 being positive, and 33.6% and 98.9% if both were positive. Among the differentiation stages marked low, intermediate, and high in HCC, the P53 positive rate was higher in the low than in the intermediate, which was higher than that in the high. HSP70 positive rate was higher in the low and the intermediate than in the high, but no obvious changes were found between the low and the intermediate. P53 and HSP70 could be potential biomarkers for HCC diagnosis, and proper combinations of these 2 markers could improve diagnostic accuracy.


Solid phase radioimmunoassay for chromosomal components.
This manuscript describes the use of a solid phase radioimmunoassay for serological analysis of chromosomal components. The applicability of this assay for various studies on nonhistone chromosomal proteins, histones, and chromatin subunits is illustrated. By this technique it is possible to detect and quantify nuclear antigens in the nanogram range. The assay has all the inherent sensitivity and precision of radioimmunoassays and, as such, introduces a new, convenient method for serological analyses of chromosomal components. The results presented reconfirm the serological similarity among the HMG (high mobility group) proteins derived from various sources. The amount of HMG proteins present in mononucleosomes purified from calf thymus is similar to that present in mononucleosomes purified from HeLa cells, suggesting that various tissues contain similar amounts of these proteins. Per nucleosome, dinucleosomes and trinucleosomes contain as much HMG-1 protein as mononucleosomes, suggesting that the protein is not exclusively associated with those regions of DNA which have been solubilized by micrococcal nuclease. Part of the antigenic determinants present in HMG-1 forming a complex in the nucleosomal conformation do not interact with antibodies.


Malformation syndromes: a review of mouse/human homology.
The purpose of this paper is to review the known and possible homologies between mouse and human multiple congenital anomaly syndromes. By identifying single gene defects causing similar developmental abnormalities in mouse and man, comparative gene mapping can be carried out, and if the loci in mouse and man are situated in homologous chromosome segments, further molecular studies can be performed to show that the loci are identical. This paper puts forward tentative homologies in the hope that some will be investigated and shown to be true homologies at the molecular level, thus providing mouse models for complex developmental syndromes. The mouse malformation syndromes are reviewed according to their major gene effects. X linked syndromes are reviewed separately because of the greater ease of establishing homology for these conditions.


Genome-wide identification of the peptide transporter family in rice and analysis of the PTR expression modulation in two near-isogenic lines with different nitrogen use efficiency.
Nitrogen (N) is a major nutrient element for crop growth. In plants, the members of the peptide transporter (PTR) gene family may involve in nitrate uptake and transport. Here, we identified PTR gene family in rice and analyzed their expression profile in near-isogenic lines. We identified 96, 85 and 78 PTR genes in Nipponbare, R498 and Oryza glaberrima, and the phylogenetic trees were similar in Asian cultivated rice and African cultivated rice. The number of PTR genes was higher in peanut (125) and soybean (127). The 521 PTR genes in rice, maize, sorghum, peanut, soybean and Arabidopsis could be classified into 4 groups, and their distribution was different between monocots and dicots. In Nipponbare genome, the 25 PTR genes were distributed in 5 segmental duplication regions on chromosome 1, 2, 3, 4, 5, 7, 8, 9, and 10. The PTR genes in rice have 0-11 introns and 1-12 exons, and 16 of them have the NPF (NRT1/PTR family) domain. The results of RNA-seq showed that the number of differentially expressed genes (DEGs) between NIL15 and NIL19 at three stages were 928, 1467, and 1586, respectively. Under low N conditions, the number of differentially expressed PTR genes increased significantly. The RNA-seq data was analyzed using WGCNA to predict the potential interaction between genes. We classified the genes with similar expression pattern into one module, and obtained 25 target modules. Among these modules, three modules may be involved in rice N uptake and utilization, especially the brown module, in which hub genes were annotated as protein kinase that may regulate rice N metabolism. In this study, we comprehensively analyzed the PTR gene family in rice. 96 PTR genes were identified in Nippobare genome and 25 of them were located on five large segmental duplication regions. The Ka/Ks ratio indicated that many PTR genes had undergone positive selection. The RNA-seq results showed that many PTR genes were involved in rice nitrogen use efficiency (NUE), and protein kinases might play an important role in this process. These results provide a fundamental basis to improve the rice NUE via molecular breeding.


Management of sudden cardiac death in cardiac sarcoidosis using the wearable cardioverter defibrillator.
Patients with cardiac sarcoidosis are at increased risk of ventricular tachycardia/fibrillation. We tested the hypothesis that the wearable cardioverter defibrillator can be used to mitigate the risk of sudden cardiac death among cardiac sarcoidosis patients. A retrospective review of the commercial database identified cardiac sarcoidosis patients who wore the wearable cardioverter defibrillator. Evidence for cardiac sarcoidosis diagnosis as well as demographic, co-morbidity and left ventricular ejection fraction were provided by patient clinical records. Clinical data also included daily wearable cardioverter defibrillator wear, shock treatment and survival information. The wearable cardioverter defibrillator was worn by 46 cardiac sarcoidosis patients, 24 (52%) male. The median age was 48 years and median left ventricular ejection fraction was 30%. The wearable cardioverter defibrillator was worn a median of 23.6 hours each day. There were 11 ventricular tachycardia/fibrillation episodes occurring in 10 (22%) patients. Ventricular tachycardia/fibrillation occurred over a range of 1 to 79 days, median 24 days. First-shock success for conversion of ventricular tachycardia/fibrillation was 100%. Patient survival 24 hours after shock treatment was 100%. Follow up to determine the reason for discontinuing wearable cardioverter defibrillator use indicated that among shocked patients 7 received an implantable cardioverter defibrillator, 1 patient was admitted to the hospital ending in death 2 weeks after discontinuing wearable cardioverter defibrillator use, and 2 patients were lost to follow up. Among the not shocked patients, there were 16 who received an implantable cardioverter defibrillator while 7 achieved improved left ventricular ejection fraction. Management of sudden cardiac death among cardiac sarcoidosis patients was aided by the wearable cardioverter defibrillator resulting in successful termination of ventricular tachycardia/fibrillation upon delivery of shock.


AIDS and euthanasia.
This paper estimates the proportion of people with HIV who have considered asking assistance to end their lives and explores their motivations and plans of action to hasten death. 16/57 (28%) people with HIV have considered asking for assistance to hasten death, significantly more than seronegative controls (4/67) (3%) (p < 0.001). In follow-up interviews with seropositive respondents the figure increased to 19/57 (33%). The main motivations are fear of being dependent and losing dignity and control in the final stages of the disease. These results are discussed in the light of current legislation about euthanasia and recent evidence that about one-half of NHS doctors would be prepared to comply with requests for euthanasia were it legal to do so.


WHY DO SOCIETIES WITH HIGHER AVERAGE COGNITIVE ABILITY HAVE LOWER INCOME INEQUALITY? THE ROLE OF REDISTRIBUTIVE POLICIES.
Past studies suggest that, across nations, the average cognitive ability of a population is negatively associated with income inequality; societies with higher average cognitive ability tend to have lower levels of income inequality. However, it is not clear why. This paper proposes that social transfers from the wealthy to the poor may be a major mechanism by which some societies achieve lower income inequality than others, because more intelligent individuals may be more likely to have a preference for such transfers. Publicly available societal-level data were analysed in a series of multiple regression models. The empirical results in this study replicate the earlier finding that societies with higher cognitive ability have lower levels of income inequality, but the association is entirely mediated by social transfers. Social transfers therefore appear to be the primary mechanism by which societies with higher levels of cognitive ability achieve lower income inequality.


[The bradycardia-tachycardia syndrome].
Disorders of the heart rhythm which consist basically of sinus bradicardia or sinus arrest correspond to a syndrome which has been named the sick sinus syndrome. Within the framework of this syndrome, there is a subgroup of alternating atrial bradycardia with episodes of atrial tachyarrhythmia. Generally known as the bradycardia-tachycardia syndrome, this subgroup is both electrophysiologically interesting and therapeutically challenging. This report is concerned with the experience obtained at the emergency ward and coronary care unit of the Instituto Nacional de Cardiología de México on the diagnosis and management of 8 patients with this syndrome. Various underlying heart conditions were present with predominance of ischemic heart disease. The clinical picture was dependent upon the hypoperfusion of vital organs secondary to the cardial arrhythmia. The most common symptoms were derived from cerebral circulatory deficit and coronary insufficiency. Half of the patients had moderate cardiac failure. All patients had spontaneous and transient loss of sinus function which lasted more than 2,000 msec. in seven. The bradycardia had a rate below 50 beats per minute in all cases except one. The tachyarrhythmias observed were atrial flutter, atrial fibrillation and paroxysmal supraventricular tachycardia. Three of the patients had more than one of these these tachyarrhythmias during the period of study. A discussion is made on the diagnosis of this syndrome by means of atrial pacing and interventions which modify either vagal or sympathetic tone. Considerations are also made on the frequent associated abnormality of the A-V functional tissues. Emphasis is placed on the problems encountered in the management of these patients. It is concluded that, in most cases, a satisfactory result may be obtained by the implantation of a permanent demand pacemaker associated to the administration of antiarrhythmic drugs.


Induction of alternative fate other than default neuronal fate of embryonic stem cells in a membrane-based two-chambered microbioreactor by cell-secreted BMP4.
Cell-secreted soluble factor signaling in a diffusion dominant microenvironment plays an important role on early stage differentiation of pluripotent stem cells invivo. In this study, we utilized a membrane-based two-chambered microbioreactor (MB) to differentiate mouse embryonic stem cells (mESCs) in a diffusion dominant microenvironment of the top chamber while providing enough nutrient through the bottom chamber. Speculating that accumulated FGF4 in the small top chamber will augment neuronal differentiation in the MB culture, we first differentiated mESCs for 8 days by using a chemically optimized culture medium for neuronal induction. However, comparison of cellular morphology and expression of neuronal markers in the MB with that in the 6-well plate (6WP) indicated relatively lower neuronal differentiation in the MB culture. Therefore, to investigate whether microenvironment in the MB facilitates non-neuronal differentiation, we differentiated mESCs for 8 days by using chemically defined basal medium. In this case, differentiated cell morphology differed markedly between the MB and 6WP cultures: epithelial sheet-like morphology in the MB, whereas rosette morphology in the 6WP. Expression of markers from the three germ layers indicated lower neuronal but higher meso- and endo-dermal differentiation of mESCs in the MB than the 6WP culture. Moreover, among various cell-secreted soluble factors, BMP4 expression was remarkably upregulated in the MB culture. Inhibition of BMP4 signaling demonstrated that enhanced effect of upregulated BMP4 was responsible for the prominent meso- and endo-dermal differentiation in the MB. However, in the 6WP, downregulated BMP4 had a minimal influence on the differentiation behavior. Our study demonstrated utilization of a microbioreactor to modulate the effect of cell-secreted soluble factors by autoregulation and thereby inducing alternative self-capability of mESCs. Understanding and implementation of autoregulation of soluble factors similar to this study will lead to the development of robust culture systems to control ESC behavior.


An analysis of medical workload--evidence of patient to specialist mismatch.
The National Health Service has employed physicians since its inception, yet 46 years later there are few data on the day-to-day work done by physicians. This paper describes the case mix of general medicine in one region using data for general medical admissions to one specialty (respiratory medicine) as a working example. The pattern of general medical inpatient admissions is consistent across the 10 districts in the Mersey region: 26% have a respiratory diagnosis, 22% cardiac, and 15% gastrointestinal. For medical day cases, 60% are gastrointestinal. The average length of stay for particular conditions varies little between hospitals, and the average consultant 'cares' for 949 consultant inpatient episodes per year. In only half the Mersey districts is the respiratory consultant provision appropriate for the case mix admitted to the hospital. A simple algorithm applied to data collected routinely by regional health authorities can yield much information upon which to plan medical manpower. Applied to a specialty, it has identified mismatches between workload and consultant type. For respiratory medicine, at least six more respiratory physicians (a 30% increase) are needed to correct the underprovision in Mersey region.


Dimer-induced signal propagation in Spo0A.
Spo0A, the response regulator protein controlling the initiation of sporulation in Bacillus, has two distinct domains, an N-terminal phosphoacceptor (or receiver) domain and a C-terminal DNA-binding (or effector) domain. The phosphoacceptor domain mediates dimerization of Spo0A on phosphorylation. A comparison of the crystal structures of phosphorylated and unphosphorylated response regulators suggests a mechanism of activation in which structural changes originating at the phosphorylatable aspartate extend to the alpha4beta5alpha5 surface of the protein. In particular, the data show an important role in downstream signalling for a conserved aromatic residue (Phe-105 in Spo0A), the conformation of which alters upon phosphorylation. In this study, we have prepared a Phe-105 to Ala mutant to probe the contribution of this residue to Spo0A function. We have also made an alanine substitution of the neighbouring residue Tyr-104 that is absolutely conserved in the Spo0As of spore-forming Bacilli. The spo0A(Y104A) and spo0A(F105A) alleles severely impair sporulation in vivo. In vitro phosphorylation of the purified proteins by phosphoramidate is unaffected, but dimerization and DNA binding are abolished by the mutations. We have identified intragenic suppressor mutations of spo0A(F105A) and shown that these second-site mutations in the purified proteins restore phosphorylation-dependent dimer formation. Our data support a model in which dimerization and signal transduction between the two domains of Spo0A are mediated principally by the alpha4beta5alpha5 signalling surface in the receiver domain.


Infrared and Fluorescence Spectroscopic Investigations of the Acyl Surface Modification of Hydrogel Beads for the Deposition of a Phospholipid Coating.
The scaffolded vesicle has been employed as an alternative means of developing natural model membranes and envisioned as a potential nutraceutical transporter. Furthering the research of the scaffolded vesicle system, a nucleophilic substitution reaction was implemented to form an ester linkage between palmitate and terminal hydroxyl groups of dextran in order to hydrophobically modify the hydrogel scaffold. An average tilt angle of 38° of the hydrophobic palmitate modifying layer on the surface of the hydrogel was determined from dichroic ratios obtained from infrared spectra collected in the attenuated total reflection (ATR) configuration. ATR-IR studies of the DMPC-coated acylated hydrogel demonstrated that the hydrocarbon chains of the DMPC coating was similar to those of the DMPC bilayers and that the underlying palmitate layer had a negligible effect on the average tilt angle (26°) of the DMPC coating. The permeability of this acylated hydrogel was investigated with fluorescence spectroscopy and the terbium/dipicolinic acid assay. The hydrophobic modification on the surface of the hydrogel bead allowed for an efficient deposition of a DMPC layer that served as an impermeable barrier to terbium efflux. About 72% of DMPC-coated acylated hydrogel beads showed ideal barrier properties. The remaining 28% were leaking, but the half-life of terbium efflux of the DMPC-coated acylated hydrogel was increasing, and the total amount of leaked terbium was decreasing with the incubation time. The half-life time and the retention were considered a marked improvement relative to past scaffolded vesicle preparations. The process of acylating hydrogel beads for efficient DMPC deposition has been identified as another viable method for controlling the permeability of the scaffolded vesicle.


Presentation of early otitis media in 'Top End' Aboriginal infants.
Otitis media is highly prevalent in Aboriginal Australians. This study found that otitis media was universal in 41 Aboriginal infants from the north of the Northern Territory, who were examined monthly from birth; more than one-third had experienced eardrum perforation. The earliest age at perforation was 44 days and the mean duration was 44.3 days. All subjects had acute otitis media or otitis media with effusion before perforation and after drum healing. This study, therefore, recommends that individual medical treatment should not be postponed until drum perforation occurs because otitis media develops first behind an intact drum and then may progress to perforation.


Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia.
Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague-Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A (A2AAR) and A2B adenosine receptor (A2BAR) mRNA and protein were quantified. Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2AAR mRNA and protein concentrations remained unchanged following ischemia. A2BAR protein was increased in PA ligated lungs of SS rats after 7 days, and 4 h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes. Increased A2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A2BAR mutant rats implicate a protective role for A2BAR signaling in countering ischemic lung injury.


Visual working memory for briefly presented scenes.
Previous studies have painted a conflicting picture on the amount of visual information humans can extract from viewing a natural scene briefly. Although some studies suggest that a single glimpse is sufficient to put about five visual objects in memory, others find that not much is retained in visual memory even after prolonged viewing. Here we tested subjects' visual working memory (VWM) for a briefly viewed scene image. A sample scene was presented for 250 ms and masked, followed 1000 ms later by a comparison display. We found that subjects remembered fewer than one sample object. Increasing the viewing duration to about 15 s significantly enhanced performance, with approximately five visual objects remembered. We suggest that adequate encoding of a scene into VWM requires a long duration, and that visual details can accumulate in memory provided that the viewing duration is sufficiently long.


Effect of everolimus on the expression of Ki-67 and caspase-3 in patients with neuroendocrine tumors.
Tumors, especially neuroendocrine tumors (NETs), can cause adverse effects on human health. The expression and significance of Ki-67 and caspase-3 in NET remain to be further explored. Everolimus is an important drug used for the treatment of NETs. In this study, we aimed to investigate whether everolimus exerts anti-tumor effects by suppressing the expression of Ki-67 and caspase-3 in NET. Tumor (different developmental stages) and adjacent tissues were collected from patients with NET. The expression of Ki-67 and caspase-3 were detected in 244 paraffin sections of NET using immunohistochemistry. RT-PCR and western blot were used to detect the expression of Ki-67 and caspase-3 at mRNA and protein levels, respectively. The patients (N = 244) were randomly divided into everolimus-intervention and control groups. RT-PCR and western blot were used to measure the expression changes of Ki-67 and caspase-3 before and after everolimus treatment. The rates of Ki-67 expression in NET grades 1-6 were 14.2, 22.1, 37.5, 59.9, 69.9, and 77.8%, respectively. The difference between the groups was significant. The rates of caspase-3 expression in NET grades 1-6 were 28.6, 33.3, 31.3, 60.0, 80.0, and 88.9%, respectively, and the difference between groups was significant. Moreover, the expression of Ki-67 and caspase-3 showed a significant negative correlation. The expression of Ki-67 decreased while that of caspase-3 increased after everolimus treatment. In conclusion, the decrease in Ki-67 expression and increase in caspase-3 expression after everolimus treatment indicated that everolimus exerted its anti-cancer effect by regulating the expression of Ki-67 and caspase-3.


Quantification of variability and uncertainty in lawn and garden equipment NOx and total hydrocarbon emission factors.
Variability refers to real differences in emissions among multiple emission sources at any given time or over time for any individual emission source. Variability in emissions can be attributed to variation in fuel or feedstock composition, ambient temperature, design, maintenance, or operation. Uncertainty refers to lack of knowledge regarding the true value of emissions. Sources of uncertainty include small sample sizes, bias or imprecision in measurements, nonrepresentativeness, or lack of data. Quantitative methods for characterizing both variability and uncertainty are demonstrated and applied to case studies of emission factors for lawn and garden (L&G) equipment engines. Variability was quantified using empirical and parametric distributions. Bootstrap simulation was used to characterize confidence intervals for the fitted distributions. The 95% confidence intervals for the mean grams per brake horsepower/hour (g/hp-hr) emission factors for two-stroke engine total hydrocarbon (THC) and NOx emissions were from -30 to +41% and from -45 to +75%, respectively. The confidence intervals for four-stroke engines were from -33 to +46% for THCs and from -27 to +35% for NOx. These quantitative measures of uncertainty convey information regarding the quality of the emission factors and serve as a basis for calculation of uncertainty in emission inventories (EIs).


Glucose patterns during the OGTT and risk of future diabetes in an urban Indian population: The CARRS study.
Traditionally, fasting and 2-hour post challenge plasma glucose have been used to diagnose diabetes. However, evidence indicates that clinically relevant pathophysiological information can be obtained by adding intermediate time-points to a standard oral glucose tolerance test (OGTT). We studied a population-based sample of 3666 Asian Indians without diabetes from the CARRS-Chennai Study, India. Participants underwent a three-point (fasting, 30-min, and 2-h) OGTT at baseline. Patterns of glycemic response during OGTT were identified using latent class mixed-effects models. After a median follow-up of two years, participants had a second OGTT. Logistic regression adjusted for diabetes risk factors was used to compare risk of incident diabetes among participants in different latent classes. We identified four latent classes with different glucose patterns (Classes 1-4). Glucose values for Classes 1, 2, and 4 ranked consistently at all three time-points, but at gradually higher levels. However, Class 3 represented a distinct pattern, characterized by high 30-min (30minPG), normal fasting (FPG) and 2-h (2hPG) plasma glucose, moderately high insulin sensitivity, and low acute insulin response. Approximately 22% of participants were categorized as Class 3, and had a 10-fold risk of diabetes compared to the group with the most favorable glucose response, despite 92.5% of Class 3 participants having normal glucose tolerance (NGT) at baseline. Elevated 30minPG is associated with high risk of incident diabetes, even in individuals classified as NGT by a traditional OGTT. Assessing 30minPG may identify a subgroup of high-risk individuals who remained unidentified by traditional measures.


Dietary supplementation of finishing pigs with the docosahexaenoic acid-rich microalgae, Aurantiochytrium limacinum: effects on performance, carcass characteristics and tissue fatty acid profile.
The aim of this experiment was to evaluate the effect of dietary supplementation with the docosahexaenoic acid (DHA)-rich microalgae, Aurantiochytrium limacinum (AURA) on pig performance, carcass traits, and the fatty acid composition of pork Longissimus lumborum (LL) and backfat. A total of 144 Pig Improvement Company (PIC)×Goland finishing pigs (72 females and 72 castrated males) of mean weight 117.1 (±13.1) kg were blocked by sex and body weight and provided with 0% or 1% AURA in isonutritive and isocaloric diets. A total of 24 pens provided 12 replicates per treatment. Animals were weighed on day 0 and 28 with feed and water intake recorded per pen. After 31 days supplementation (28 days of study and 3 days until the slaughtering date) three animals per pen (n = 72) were slaughtered and the LL and backfat thickness, lean meat content and dressing percentage were recorded for the carcasses. The fatty acid (FA) profile of the LL and backfat was established by direct FA methyl ester synthesis. No differences were observed for any performance parameters or carcass traits. Supplementation with AURA resulted in significant changes to the FA profiles of both the LL and backfat with male and female pigs responding differently to supplementation in terms of particular FAs. Overall, pork LL samples had significantly higher eicosapentaenoic acid (p<0.001) and DHA concentrations (p<0.001), and higher omega-3 (n-3) FAs (p<0.001), as well as an increased omega3:omega6 (n-3:n-6) ratio (p = 0.001). For backfat, supplementation resulted in significantly higher amounts of DHA (p<0.001) and n-3 FAs (p<0.001). These results indicate that dietary supplementation with 1% AURA over a 31 day period can increase the FA composition of pork LL and backfat, specifically the DHA, with no major impact on growth performance and carcass traits.


Surgical chemotherapy against lymph node metastases: an experimental study.
Accompanying surgical resection of the primary tumor is removal of its drainage lymph nodes. However, all of the minute regional lymph nodes cannot be identified and some may be left behind. If a certain anticancer agent in the form of an emulsion is injected topically into the lymph nodes, it may suppress the lymphatic metastases. Domestic rabbits were used as experimental animals, because transplantable VX2 tumors are available. The vermiform appendix was selected as the transplantation site because of its rich supply of lymph follicles, simulating lymph nodes histologically, and because the path of lymph drainage is very simple. The drainage lymph node, which is located at the root of the appendix, was selected for study. The rate of transfer of bleomycin into lymph nodes and of its sustained release from the nodes was extremely enhanced by the use of a sphere-in-oil-type emulsion--more than two times higher than in the use of a W/O emulsion. Although prolongation of survival time did not take place in animals receiving the bleomycin solution topically or intravenously, five of the seven rabbits receiving the local administration of bleomycin as a sphere-in-oil or a water-in-oil emulsion, between which differences were not found in tumor effects, survived with complete reduction of the lymph node metastases.


[The Bothriocephalus scorpii complex (Mueller, 1776). Differentiation of species of parasites of the turbot (Psetta maxima) and the brill (Scophthalmus rhombus). Study of protein fractions and antigen complexes].
Previous electrophoretic studies (Renaud et al., 1983) carried out on the Cestode Bothriocephalus scorpii (Mueller, 1776) showed that the populations parasiting the Turbot and the Brill on the Mediterranean coast, are two distinct species: Bothriocephalus (supra sp. scorpii) gregarius and Bothricephalus (supra sp. scorpii) barbatus respectively. This work has been done with the purpose of identifying these two species by using biochemical tests. The study of whole body proteins by electrophoresis of zones of acrylamide gel shows the existence of nineteen distinct protein fractions in both populations. Among those different protein fractions, two of them (Rf 53 and Rf 87) are present only in the Cestode of the Brill and one (Rf 42) seems to be specific of the Turbot. On the other hand, the fraction of Rf 27 is present only in the Cestodes of the Brill. The immunoelectrophoretic study of antigenic components shows seven or eight major fractions depending on the source of protein, five of them being common to both. The reactions of absorption of antiserum permitted characterization of three arcs of precipitation proper in the Cestodes of the Brill corresponding to protein fractions of Rf (27, 53, 87) and three arcs in the Cestodes of the Turbot, corresponding to protein fractions of Rf (42, 21, 66).


Chemical Response of the Toxic Dinoflagellate Karenia mikimotoi Against Grazing by Three Species of Zooplankton.
We investigated the toxicity of Karenia mikimotoi toward three model grazers, the cladoceran Moina mongolica, the copepod Pseudodiaptomus annandalei, and the crustacean Artemia salina, and explored its chemical response upon zooplankton grazing. An induction experiment, where K. mikimotoi was exposed to grazers or waterborne cues from the mixed cultures revealed that K. mikimotoi might be toxic or nutritionally inadequate toward the three grazers. In general, direct exposure to the three grazers induced the production of hemolytic toxins and the synthesis of eicosapentaenoic acid (EPA). Both EPA and the hemolytic toxins from K. mikimotoi decreased the survival rate of the three grazers. In addition, the survival rates of M. mongolica, P. annandalei, and A. salina in the presence of induced K. mikimotoi that had previously been exposed to a certain grazer were lower than their counterparts caused by fresh K. mikimotoi, suggesting that exposure to some grazers might increase the toxicity of K. mikimotoi. The chemical response and associated increased resistance to further grazing suggested that K. mikimotoi could produce deterrents to protect against grazing by zooplankton and that the substances responsible might be hemolytic toxins and EPA.


Characteristics of premenstrual acne flare-up and benefits of a dermocosmetic treatment: a double-blind randomised trial.
To date, facial acne flare-ups in adult women during the luteal phase of the menstrual cycle have been poorly investigated. To clinically characterize premenstrual acne flare-up in adult women and investigate the effect of a dermocosmetic treatment. This single-centre study included 32 young adult women with declared premenstrual acne flares and was composed of two phases: (1) an observational phase (two menstrual cycles) and (2) an interventional phase (one menstrual cycle) in a controlled, randomised, double-blind, intra-individual (half-face) setting in which a dermocosmetic (containing lipohydroxyacid, nicotinamide, and piroctone-olamine) and placebo were compared. Initially, during the first part of the study, we observed that premenstrual acne flare-ups in adult women were characterized by a significant increase in the number of papules (20.2 vs. 13.7; p = 0.0008) and to a lesser extent, closed comedones (25.6 vs. 22.7; p = 0.04). Secondly, during the interventional phase, the half-face treated with the dermocosmetic formulation showed a significantly lower number of inflammatory lesions (7.6 vs 9.4; p = 0.01) during the luteal phase compared to the half-face treated with the placebo. Tolerance of the dermocosmetic formulation was rated as good or excellent. Our data indicate a significant increase in the number of papules during premenstrual acne flare-ups in adult women and the use of a dermocosmetic may be of benefit in partially reducing this premenstrual inflammatory flare-up.


Coordinatively diverse ortho-phosphinoaniline complexes of ruthenium and isolation of a putative intermediate in ketone transfer hydrogenation catalysis.
Amine-functionalized mono- and diphosphines have been used to prepare a series of ruthenium complexes which exhibit a variety of coordination modes depending on the number of donors possessed by the ligands, the degree of amine methylation, the solvent system used, and the oxidation state of the metal. Reactions of the monophosphinoanilines, Ph(2)PAr or Ph(2)PAr' (Ar = o-C(6)H(4)NHMe, Ar' = o-C(6)H(4)NMe(2)), with 0.5 equiv of [RuCl(mu-Cl)(eta(6)-p-cymene)](2) in dichloromethane result in the formation of [RuCl(2)(eta(6)-p-cymene)(P-Ph(2)PAr)] or [RuCl(eta(6)-p-cymene)(P,N-Ph(2)PAr')]Cl, respectively. In refluxing methanol, [RuCl(2)(eta(6)-p-cymene)(P-Ph(2)PAr)] gradually undergoes chloride ion dissociation to afford the P,N-chelate, [RuCl(eta(6)-p-cymene)(P,N-Ph(2)PAr)]Cl. This chelate can then be deprotonated to afford the amido complex, [RuCl(eta(6)-p-cymene)(P,N-Ph(2)PAr(-))] (Ar(-) = o-C(6)H(4)NMe(-)), which is an active ketone transfer hydrogenation catalyst. Reactions of the diphosphines, Ar(2)PCH(2)PAr(2) (mapm) or Ar'(2)PCH(2)PAr'(2) (dmapm) with 0.5 equiv of [RuCl(mu-Cl)(eta(6)-p-cymene)](2) result in the formation of [RuCl(2)(P,P',N,N'-mapm)] or [RuCl(eta(6)-p-cymene)(P,P'-dmapm)]Cl, respectively, in which increased methyl substitution in the latter actually inhibits amine coordination with retention of the p-cymene fragment. Reaction of mapm with 1 equiv of [Ru(CO)(4)(eta(2)-C(2)H(4))] in dichloromethane initially produces [Ru(CO)(4)(P-mapm)] which, over a 24 h period with exposure to ambient light, is completely converted to the P,P'-chelate, [Ru(CO)(3)(P,P'-mapm)], by photodissociation of carbon monoxide. The same reaction with 2 equiv of [Ru(CO)(4)(eta(2)-C(2)H(4))] generates a mixture of [Ru(3)(CO)(10)(mu-P,P'-mapm)] and the mononuclear P,P'-chelate. The trinuclear complex can also be synthesized by direct reaction of mapm with 1 equiv of [Ru(3)(CO)(12)].


Contribution of Moraxella catarrhalis type IV pili to nasopharyngeal colonization and biofilm formation.
Moraxella catarrhalis is a gram-negative mucosal pathogen of the human respiratory tract. Although little information is available regarding the initial steps of M. catarrhalis pathogenesis, this organism must be able to colonize the human mucosal surface in order to initiate an infection. Type IV pili (TFP), filamentous surface appendages primarily comprised of a single protein subunit termed pilin, play a crucial role in the initiation of disease by a wide range of bacteria. We previously identified the genes that encode the major proteins involved in the biosynthesis of M. catarrhalis TFP and determined that the TFP expressed by this organism are highly conserved and essential for natural transformation. We extended this initial study by investigating the contribution of TFP to the early stages of M. catarrhalis colonization. TFP-deficient M. catarrhalis bacteria exhibit diminished adherence to eukaryotic cells in vitro. Additionally, our studies demonstrate that M. catarrhalis cells form a mature biofilm in continuous-flow chambers and that biofilm formation is enhanced by TFP expression. The potential role of TFP in colonization by M. catarrhalis was further investigated using in vivo studies comparing the abilities of wild-type M. catarrhalis and an isogenic TFP mutant to colonize the nasopharynx of the chinchilla. These results suggest that the expression of TFP contributes to mucosal airway colonization. Furthermore, these data indicate that the chinchilla model of nasopharyngeal colonization provides an effective animal system for studying the early steps of M. catarrhalis pathogenesis.