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A method has been developed for discovering of antibody covered bacteria in the urine by means of a coagglutination test with a protein A containing strain--St. aureus Cowan's I. The test is based on the ability of staphylococcal protein A to bind Fc-fragment of IgG. As a specificity control St. aureus Wood 46 was used. 38 patients with urinary infections were examined. As pyelonephritic criteria the following were considered: febrile episodes, lumber pains, polyuria, pollakiuria, leukocyturia, proteinuria, raised arterial pressure, anemia, diminished renal function or chronic renal failure, x-ray, ultrasound and isotopic-nephrographic changes. In the presence of antibody covered bacteria the test is positive--there is coagglutination only with st. aureus Cowan's I. If the bacteria are not antibody coated no coagglutination takes place. If there is coagglutination with both strains the reaction is considered non-specific. II samples gave non-specific reaction. In 75% of the pyelonephritic patients the test was positive. In 70% of the patients with urinary infections of the lower urinary tract, i.e. with bacteria without immunoglobulins, the test was negative. In 74.1% of the cases there is a correlation between the coagglutination test and the localization of the urinary infection by means of other clinical and paraclinical methods. It is suggested that the coagglutination test should be included in the examination of patients with urinary infections, the positive test indicates renal localization of the infection."
Antibody-Coated Bacteria Test, Urinary
Several methods have been proposed in open literatures for detecting changes in disease outbreak or incidence. Most of these methods are likelihood-based as well as the direct application of Shewhart, CUSUM and EWMA schemes. We use CUSUM, EWMA and EWMA-CUSUM multi-chart schemes to detect changes in disease incidence. Multi-chart is a combination of several single charts that detects changes in a process and have been shown to have elegant properties in the sense that they are fast in detecting changes in a process as well as being computationally less expensive. Simulation results show that the multi-CUSUM chart is faster than EWMA and EWMA-CUSUM multi-charts in detecting shifts in the rate parameter. A real illustration with health data is used to demonstrate the efficiency of the schemes.
Biosurveillance
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic(1,2). Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms that determine such variable outcomes remain unresolved. Here we investigated CD4(+) T cells that are reactive against the spike glycoprotein of SARS-CoV-2 in the peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors. We detected spike-reactive CD4(+) T cells not only in 83% of patients with COVID-19 but also in 35% of healthy donors. Spike-reactive CD4(+) T cells in healthy donors were primarily active against C-terminal epitopes in the spike protein, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared with N-terminal epitopes. Spike-protein-reactive T cell lines generated from SARS-CoV-2-naive healthy donors responded similarly to the C-terminal region of the spike proteins of the human endemic coronaviruses 229E and OC43, as well as that of SARS-CoV-2. This results indicate that spike-protein cross-reactive T cells are present, which were probably generated during previous encounters with endemic coronaviruses. The effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined in larger cohorts. However, the presence of spike-protein cross-reactive T cells in a considerable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming trials investigating COVID-19 vaccines.
Coronavirus OC43, Human
The objective of the present study was to evaluate the effects of diacylglycerol oil following long-term administration to rats. Diacylglycerol oil is an edible oil with comparable taste and physicochemical properties of several naturally occurring oils. Diacylglycerol oil can be used as a replacement for any generally used edible oil in the home and has been approved for use in cooking oil in Japan. Male and female Sprague-Dawley rats were divided into four groups and fed low-fat (1.7%) basal diets containing an edible oil composed of rapeseed, corn, high linoleic safflower and high oleic safflower oils at 5.3% (control group 1); an edible oil composed of rapeseed and soybean oils at 5.3% (control group 2); diacylglycerol oil at 2.65% plus edible oil composed of rapeseed, corn, high linoleic safflower and high oleic safflower oils at 2.65% (low-dose group); and diacylglycerol oil at 5.3% (high-dose group) for 2 years. Interim sacrifices were conducted at weeks 30 and 77 and the study was terminated following 105 weeks of feeding. No compound-related effects were noted on clinical signs, body weights, food consumption, cumulative survival rates, hematology, blood chemistry, urinalysis, organ weights or on microscopic non-neoplastic changes. Compared to control group 2, but not control group 1, there was a significant increase in the number of high-dose group females with either benign or malignant epithelial mammary gland neoplasms. These changes were not considered biologically significant, because the tumor incidence was not similar in control group 1 and 2, and the neoplastic findings were not dose related. In summary, the two-year chronic rat study revealed no toxicologically significant or treatment-related effects of diacylglycerol oil consumption at levels of up to 5.3% in the diet.
Safflower Oil
INTRODUCTION: This review was designed to make recommendations on future educational needs, principles of curricular development, and how the International Society for Sexual Medicine (ISSM) should address the need to enhance and promote human sexuality education around the world. AIM: To explore the ways in which graduate and postgraduate medical education in human sexuality has evolved and is currently delivered. METHODS: We reviewed existing literature concerning sexuality education, curriculum development, learning strategies, educational formats, evaluation of programs, evaluation of students, and faculty development. We reviewed literature relating to four main areas: (i) the current status of the international regulation of training in sexual medicine; (ii) the current delivery of education and training in sexual medicine; (iii) resident and postgraduate education in sexual medicine surgery; and (iv) education and training for allied health professionals. RESULTS: The main findings in these four areas are as follows. Sexual medicine has grown considerably as a specialty during the past 20 years, with many drivers being identified. However, the regulatory aspects of training, assessment, and certification are currently in the early stages of development and are in many ways lagging behind the scientific and clinical knowledge in the field. However, there are examples of the development of curricula with accompanying assessments that have attempted to set standards of education and training that might underlie the delivery of high-quality care to patients in sexual medicine. The development of competence assessment has been applied to surgical training in sexual medicine, and there is increasing interest in simulation as a means of enhancing technical skills training. Although the focus of curriculum development has largely been the medical profession, there is early interest in the development of standards for training and education of allied health professionals. CONCLUSION: Organizations of professionals in sexual health, such as the ISSM, have an opportunity, and indeed a responsibility, to provide and disseminate learning opportunities, curricula, and standards of training for doctors and allied health professionals in sexual medicine. Eardley I, Reisman Y, Goldstein S, et al. Existing and Future Educational Needs in Graduate and Postgraduate Education. J Sex Med 2017;14:475-485.
Sexology
Glycosylation reactions mediated by UDP-glycosyltransferases (UGTs) are common post-modifications involved in plant secondary metabolism and significantly improve the solubility and bioactivity of aglycones. Penstemon barbatus is rich in phenylethanoid glycosides (PhGs), such as echinacoside and verbascoside. In this study, a promiscuous glycosyltransferase UGT84A95 was identified from P. barbatus. In vitro enzyme assays showed that UGT84A95 catalyzed the glucosylation of the phenol hydroxyl group of PhGs efficiently as well as other structurally diverse phenolic glycosides, including flavonoids, terpenoids, stilbene glycosides, coumarins, and simple polyphenols. By using UGT84A95, 12 glycosylated products were prepared and structurally identified by NMR spectroscopy, among which 7 are new compounds. These findings suggest that UGT84A95 could be a potential biocatalyst to synthesize multi-glycosylated glycosides.
Penstemon
AIMS: To evaluate the effects of treating barley grain with lactic acid (LA) and heat on postprandial dynamics of 19 microbial taxa and fermentation in the rumen of dairy cows. METHODS AND RESULTS: This study was designed as a double 3 x 3 Latin square with six rumen-cannulated cows and three diets either containing untreated control barley or barley treated with 1% LA and 1% LA and heat (LAH, 55 degrees C). Microbial populations, pH and volatile fatty acids were assessed in rumen liquid and solids during the postprandial period. Propionate increased and butyrate decreased in rumen solids of cows fed LA and LAH treated barley compared to the control barley. The LA but not LAH treatment depressed Fibrobacter succinogenes in rumen liquid and solids, whereas the opposite effect was observed for Ruminococcus albus in both fractions and Ruminococcus flavefaciens in rumen solids. LA promoted Ruminobacter amylophilus with the effect being more pronounced with LAH. The Lactobacillus group and Megasphaera elsdenii increased in both fractions with LA but not with LAH. CONCLUSIONS: LA and LAH treatment of barley differently altered ruminal abundance of certain bacterial taxa and fungi and increased propionate fermentation in rumen solids, whereby LA and LAH effects were consistent and mostly independent of the rumen fraction and time after barley feeding. SIGNIFICANCE AND IMPACT OF THE STUDY: Results provided evidence that LA and LAH treatment of barley can enhance rumen propionate fermentation without adversely affecting rumen pH. As propionate is the major contributor to gluconeogenesis in ruminants, the present barley treatment may have practical application to enhance energy supply in dairy cows.
Fibrobacter
BACKGROUND: Human milk contains a number of nutrients and bioactive ingredients which play an important role in the growth and development of infants. One important nutrient and bioactive ingredient of human milk is L-tryptophan. L-Tryptophan is an essential aromatic alpha-amino acid and is required in the diet of children and adult humans. As an essential amino acid, it is needed for protein synthesis and as a precursor of key biomolecules such as serotonin, melatonin, tryptamine, niacin, quinolinic acid and kynurenic acid, nicotinamide adenine dinucleotide. The aim of the study was to evaluate the antioxidant, anti-inflammatory and antiproliferative properties of tryptophan isolated from enzymatic hydrolysates from human milk and its metabolites on human glioma U251 cells and to evaluate the effects of human recombinant (hrIFNgamma) on molecular ions of tryptophan and its metabolites in human glial U251 cells. METHODS: The cytotoxicity was determined by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. The antioxidant property was assessed by the oxygen radical scavenging capacity (ORAC) method. The anti-inflammatory effect was determined by the enzyme-linked immunosorbent assay (ELISA) against cytokines IL-6 and TNF-alpha. The effects of recombinant human (rhIFNgamma) on molecular ions of tryptophan and its catabolites were evaluated by mass spectrometry. The tryptophan was isolated from milk peptides following enzymatic digestion, followed by separation by chromatographic and mass spectrometric methods. RESULTS: Tryptophan from human milk exhibited profoundly higher oxygen radical absorption capacity (7,986+/-468 microm Trolox equivalent (TE)/g) than that of whole human milk (80.4+/-13.3 microm TE/g). Tryptophan showed a moderate degree of anti-inflammatory activity against TNF-alpha and IL-6. rhIFNgamma inhibited tryptophan metabolism. A low concentration of L-tryptophan (10-25 mug/mL) inhibited nearly 25% of cell growth. When U251 cells were treated with 25 mug/mL L-tryptophan and subsequently challenged with 30 ng/mL of human recombinant IFNgamma, a significant inhibitory effect on cell growth was observed. Low concentrations of Xanthurenic acid, L-kynurenine, and 3-OH DL kynurenine were found to inhibit cell growth except melatonin and 3-OH anthranilic acid. Melatonin was a strong inducer of TNF-alpha in RAW cells, whereas 3-OH kynurenine at 25, 50 and 100 microg/mL inhibited IL-6 in RAW cells. No significant change was observed in the IL-8 profile in tryptophan-treated U251 cells except that L-kynurenine at 10 microg/mL produced significantly high level of an inflammatory cytokine IL-8. Melatonin, 3-OH, DL kynurenine at high concentrations (100 microg/mL) induced proliferation of U251 cells. Melatonin seemed to show synergistic effects with recombinant human IFNgamma (rhINFgamma) in promoting growth of human glioma cells. While treatment of U251 cells with tryptophan alone and subsequent treatment with rhIFNgamma inhibited the growth of human cancer glioma cells, and conversely melatonin combined with rhIFNgamma promoted growth of the U251 cells. CONCLUSIONS: The findings from this study suggest that human milk-derived tryptophan and its metabolites possess strong antioxidant properties. Such effects might play a significant role in regulating the cell proliferation and growth of human cancer cells in a concentration-dependent manner."
Oxygen Radical Absorbance Capacity
Patent Foramen Ovale (PFO) is present in 20 - 25% of the population, and is known to be associated with a number of clinical syndromes. However, it is less clear that there is a causal (or contributory) role for the PFO in the development of thromboembolic stroke, systemic thromboembolization, decompression illness in divers, hypoxemia with obstructive sleep apnea, or migraine headaches. On-going and new randomized prospective trials are testing these relationships and are attempting to prove therapeutic benefit to closing the defects. This paper will review the existing literature on PFO, and will attempt to clarify some of the outstanding clinical management issues.
Foramen Ovale, Patent
OBJECTIVE: The aim of this study was to determine whether prehospital blood products reduce 30-day mortality in patients at risk for hemorrhagic shock compared with crystalloid only resuscitation. SUMMARY OF BACKGROUND DATA: Hemorrhage is the primary cause of preventable death after injury. Large volume crystalloid resuscitation can be deleterious. The benefits of prehospital packed red blood cells (PRBCs), plasma, or transfusion of both products among trauma patients is unknown compared with crystalloid. METHODS: Secondary analysis of the multicenter PAMPer trial was performed on hypotensive injured patients from the scene. The trial randomized 27 helicopter bases to prehospital plasma or standard resuscitation. Standard resuscitation at the sites was equally divided between crystalloid and crystalloid + PRBC. This led to 4 prehospital resuscitation groups: crystalloid only; PRBC; plasma; and PRBC+plasma. Cox regression determined the association between resuscitation groups and risk-adjusted 30-day mortality. The dose effect of resuscitation fluids was also explored. RESULTS: Four hundred seven patients were included. PRBC+plasma had the greatest benefit [hazard ratio (HR) 0.38; 95% confidence interval (95% CI) 0.26-0.55, P < 0.001], followed by plasma (HR 0.57; 95% CI 0.36-0.91, P = 0.017) and PRBC (HR 0.68; 95% CI 0.49-0.95, P = 0.025) versus crystalloid only. Mortality was lower per-unit of PRBC (HR 0.69; 95% CI 0.52-0.92, p = 0.009) and plasma (HR 0.68; 95% CI 0.54-0.88, P = 0.003). Crystalloid volume was associated with increased mortality among patients receiving blood products (HR 1.65; 95% CI 1.17-2.32, P = 0.004). CONCLUSION: Patients receiving prehospital PRBC+plasma had the greatest mortality benefit. Crystalloid only had the worst survival. Patients with hemorrhagic shock should receive prehospital blood products when available, preferably PRBC+plasma. Prehospital whole blood may be ideal in this population.
Shock, Hemorrhagic
TGF-beta induces apoptosis and inhibits the proliferation of EBV-negative B-lymphoma cell lines. In contrast, EBV-immortalized B cells are resistant to both the proapoptotic and the antiproliferative activities of TGF-beta. We have generated a lymphoblastoid cell line, in which we can switch on and off the EBV-specific transcriptional program driven by EBNA2. When these cells express the EBNA2-driven phenotype, they are resistant to TGF-beta-mediated growth arrest. We used this cell line to readdress the question of how EBV can overcome the antiproliferative TGF-beta activity. We show here that EBV-driven cells remain TGF-beta-responsive since TGF-beta target genes are readily induced. Thus, EBV can overcome TGF-beta-mediated growth arrest without interfering with the core machinery of the TGF-beta signaling pathway, which links ligand binding to the induction of TGF-beta target genes."
Epstein-Barr Virus Nuclear Antigens
The present study was to investigate whether entopeduncular nucleus (EP) is involved in caudate-putamen nucleus (CPu) stimulation-induced analgesia and in acupuncture analgesia. It was found that the foot-withdrawal latency elicited by radiant heat exposure was increased after electroacupuncture analgesia (EA), and the nociceptive responses of neurons in parafascicular nucleus (Pf) were inhibited after EA or after excitation of CPu neurons in normal rats, but the foot-withdrawal latency and nociceptive responses of Pf neurons were unchanged by EA or excitation of CPu in the rats with lesion of EP by local application of kainic acid. The results obtained with microinjeciton of saline instead of kainic acid into the EP were the same with those in the nonlesioned control group. The differences in the results between the lesion group and the other groups were significant ( <0.05). It is suggested that EP is involved in acupuncture analgesia and also plays an important role in caudate-putamen nucleus stimulation-induced analgesia.
Entopeduncular Nucleus
The inhibitory effects of several nucleoside triphosphate analogs on Rauscher murine leukemia virus (RMuLV) and human immunodeficiency virus (HIV) type 1 reverse transcriptases (RTs) were studied. With RNA as the template, the apparent K(m) and apparent K(i) values of HIV RT toward its substrates and inhibitors are 12 to 500 times lower than the corresponding values for RMuLV RT. However, the k(i)/k(m) ratios (inhibition efficiencies) for HIV and RMuLV RTs'are similar for AZTTP (zidovudine triphosphate), d4TTP [3'-deoxythymidine-2'-ene-(3'-deoxy-2',3'-didehydrothymidine) triphosphate], PMEADP [9-(2-phosphonylmethoxyethyl)adenine diphosphate], FIAUTP [1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodouracil triphosphate], and HPMPCDP [(S)-1-(3-hydroxy-2-phosphylmethoxypropyl) cytosine diphosphate]. With DNA as the template, the K(m) values are similar for HIV and RMuLV RTs. However, the K(i)/K(m) values of HIV and RMuLV RTs are significantly different for ddCTP, ddATP, and 3TCTP (2',3'-dideoxy-3'-thiacytidine). The RTs of RMuLV and HIV are sufficiently different from one another that the kinetic inhibition constants for a particular antiviral compounds should be determined to indicate whether anti-RMuLV activity is likely to be predictive for the anti-HIV activity of the compound. This information, in conjunction with species-specific drug metabolism differences and tissue culture antiviral activity, is important in determining the suitability of a particular animal model.
Rauscher Virus
The purpose of this study was to develop an alternative submicron emulsion containing three bufadienolides for oral administration and evaluate its preclinical stability, efficacy, and toxicity. The bufadienolide-loaded oral submicron emulsion (BU-OE) was prepared by high-pressure homogenization. The storage stability, in vitro cytotoxicity, in vivo antitumor efficacy, acute toxicity, and long-term toxicity of BU-OE were investigated in detail to evaluate the formulation. The stability study suggested that BU-OE was stable at room temperature and could be stored for at least 18 months at 6+/-2 degrees C. The cytotoxicity test revealed that BU-OE had marked cytotoxic activities against cancer cells, but no evident inhibitory effects on normal cells. Likewise, BU-OE exhibited significant antitumor efficacy against Hep G2, HCT-8, and EC9706 cell lines and a slight inhibitory effect on BGC 803 cell line in nude mice, while comparable antitumor activity with fluorouracil injection. The LD50 of BU-OE in mice was 29.4 mg/kg (male) and 22.8 mg/kg (female), respectively. As for the long-term toxicity, BU-OE showed no apparent toxic effects except minor cardiotoxic effects which were reversible. In conclusion, submicron emulsion is a suitable delivery system for oral administration of bufadienolides, with satisfactory stability, superior antitumor efficacy and low toxicity.
Toxicity Tests, Subacute
The bisphosphonate family with a P-C-P structure is a broad class of drugs, widely investigated as potential inhibitors in bone diseases and calcium metabolic disorders. In this study, the mass spectrometric (MS) behavior and fragmentation of clodronate and related bisphosphonate and phosphonate compounds was studied by using negative ion electrospray ionization (ESI) with triple quadrupole and ion trap instruments. The effect of pH on the degree of deprotonation of the polyprotic bisphosphonic and phosphonic acids in negative ion ESI-MS was investigated, and the degree of deprotonation in the ESI mass spectra and the dissociation in the liquid phase were compared. The results provide evidence that the measured ESI mass spectra do not correlate with the chemistry in the liquid phase owing to the decrease in the pH of the solvent droplets during the ion evaporation process and the charge state neutralization in the gas phase. Ion trap MS(n) provided useful information on the fragmentation study of clodronate and related bisphosphonate and phosphonate compounds, in which interesting fragmentation pathways including the direct elimination of carbon monoxide from deprotonated bisphosphonates and formation of a P-P bond were observed. Reactions between the product ions with a -PO(2) group and residual water in the ion trap or in the high-pressure region of the triple quadrupole instrument formed other unexpected fragmentation paths for all the bisphosphonates studied."
Spectrometry, Mass, Electrospray Ionization
BACKGROUND: We present two patients in whom a free rectus abdominis muscle flap was used to close recurrent traumatic CSF rhinorrhea. CASE DESCRIPTION: CT scan of both patients showed frontal lobe atrophy and porencephaly after contusional hematoma. In the first patient, because the site of CSF leakage was not identified and the patient underwent three unsuccessful attempts to close the fistula using the fascia lata, we treated the patient by unifying all paranasal sinuses and by filling them with a free rectus abdominis muscle flap. In the second patient, CSF rhinorrhea recurred 6 years after closure of the fistula using the fascia lata. The patient underwent separation of a porencephalic cyst from the paranasal sinus and a free muscle flap was placed extradurally, because the CSF pulse pressure in the enlarged left anterior horn eroded the previously repaired fascia lata, resulting in the recurrence of CSF leakage. CONCLUSION: Although duraplasty is the primary procedure for repairing dural fistulas, the vascularized free muscle flap is an alternative method when the location of the fistula is not identified or the patient with recurrent CSF rhinorrhea has severe frontal lobe atrophy and porencephaly.
Rhinorrhea
BACKGROUND: Habitual behavior rather than intention has been linked to food intake patterns. AIM: The purpose of this study was to examine the adherence to dietary recommendations in university students and to analyze whether habit strength predicts food consumption. METHODS: A student sample of the University (University of Hohenheim) was recruited ( n = 103; age range 18-30 years). Habit strength for consuming the food groups fruits, vegetables, whole grains, milk, meat, convenience foods, sugary and savory snacks, water and sugar-sweetened beverages was measured using a questionnaire. Food intake was measured via a self-administered online food frequency survey two weeks later, which was then compared to dietary recommendations. For associations of habit strength and consumption, Kendall's Tau-c correlation coefficient was calculated. RESULTS: The majority of students failed to meet the recommendations for all food groups except meat, eggs, oil, fat, and water. Only 4.2% of men (15.4% of women) consumed the recommended daily amount of vegetables. Fruit recommendations were met by 20.8% of men (43.6% of women). Habit strength was significantly associated with the consumption of most food groups. CONCLUSION: Adhering to dietary recommendations appeared to be difficult. Educational efforts should be undertaken to improve students' diet considering habit strength as an important determinant of food intake.
Food
Ductal carcinoma in situ has been stable in incidence for a decade and has an excellent prognosis. Breast conservation therapy is safe and effective for most patients. Adjuvant whole breast radiation therapy is recommended to reduce the risk of local recurrence. Accelerated partial breast irradiation is a promising alternative to decrease toxicity and improve cosmetic results. Adjuvant hormonal therapy can reduce local recurrence, but should be used cautiously. Future directions in management include developing predictive tools for guidance for use of adjuvant therapy and selecting low-risk patients with ductal carcinoma in situ in whom surgery may be safely omitted."
Carcinoma, Intraductal, Noninfiltrating
Gliomas are the most common primary tumors of the central nervous system (CNS). Nogo-66 is an extracellular domain of Nogo-A, which can block axon regeneration in the CNS after trauma. Some studies have indicated that Nogo-A and its receptor (NgR) are expressed in tumor tissues; however, their roles in tumors are still unknown. We report the impact of Nogo-66 and NgR on the proliferation, apoptosis, adhesion and invasion of C6 glioma cells. Short hairpin RNA (shRNA)-triggered RNA interference was used to inhibit NgR expression in C6 cells. Then, an in vitro cell adhesion assay was performed to assess the effect of NgR downregulation on the adhesion ability of C6 cells. In addition, a chamber assay and a cell scratch assay were conducted to test invasion ability. The spontaneous apoptosis of C6 cells was examined by flow cytometry, western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. NgR downregulation resulted in a significant increase of C6 adhesion and invasion activity in the presence of Nogo-66, markedly inhibited proliferation and induced spontaneous apoptosis. In conclusion, knockdown of NgR enhanced invasion and adhesion but increased cell apoptosis in C6 cells, suggesting that Nogo-66/NgR might have complex effects on glioma cells.
Nogo Receptors
Cutaneous accessory cells include dendritic cells (DCs) and macrophages. Heterogeneity, plasticity, and responsiveness to local environmental cues are hallmarks of both types of cells. Until recently, results of studies of cells that had been extracted from tissues or propagated in vitro provided the foundation for most conceptual frameworks. The availability of a variety of spontaneously occurring and genetically engineered mice has facilitated in vivo studies that have provided new insights into the developmental and functional aspects of DCs in skin and other tissues. In several instances, results of these in vivo studies have been very surprising. Existing paradigms have been modified or debunked, and new hypotheses have been generated. We can anticipate that detailed understanding of the biology of individual cutaneous accessory cells and their relationships with each other will continue to accumulate as these types of studies are actively pursued.
Dendritic Cells
The Council on Scientific Affairs of the California Medical Association presents the following epitomes of progress in anesthesiology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and clinical importance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of progress in medicine, whether in their own field of special interest or another. The epitomes included here were selected by the Advisory Panel to the Section on Anesthesiology of the California Medical Association, and the summaries were prepared under the direction of Dr Jackson and the panel.
Androstanols
INTRODUCTION: Fractional CO(2) has many indications in medicine including in treatment of acne scars and rejuvenation. The aim of this study was to evaluate the safety, efficacy, and cost-effectiveness of Fractional CO(2) Laser in comparison with other methods of rejuvenation and acne scar treatment. MATERIALS AND METHODS: Several databases including Medline, OVID, EMBASE, CINHAL, SCOPUS, Web of science, CRD, and Cochrane were searched. After conducting the search and evaluation of selected publications, critical appraisal was done and eligible studies were accepted for inclusion in the systematic review. RESULTS AND DISCUSSION: From 2667 identified publications two of the trials were eligible. The effectiveness and complications of Fractional CO(2) laser were comparable with Er:YAG but Fractional CO(2) laser was 14.7% (p = 0.01) more effective than Q-Switched ND:YAG laser. Cost affectivity of this method was the same as other alternative lasers. In conclusion Fractional CO(2) laser is an effective and safe method for curing of several kinds of skin diseases. Nevertheless there was not sufficient evidence to support its advantage. This device has equal or lower price in comparison to competent technologies except for the non- fractional ablative CO(2) laser that has the same or lower price and comparable effects.
Lasers, Gas
Bacterivorous ciliates play important roles in the functioning of activated sludge by reducing dispersed bacteria and enhancing flocculation. There are, however, no data on the resistance of this functional group of microorganisms to predation. Our experiment was conducted with activated sludge subsamples subjected to artificially introduced three predatory ciliates species. The two predator species originating from activated sludge were Oxytricha sp. and Spathidium spathula. Dileptus margaritifer was a foreign" predator species. The latter was introduced to compare its effect with the influence of predators naturally occurring in activated sludge on the ciliates community potentially adapted to certain predation strategies. Results showed that introduction of predatory ciliates into the activated sludge did not significantly change the total abundance of protozoa but rebuilt bacterivorous ciliate communities. Introduced predators significantly affected the most numerous ciliate species from the genera Epistylis and Cyclidium. In the presence of D. margaritifer, the abundance of sessile, colonial ciliates (Epistylis sp.) was significantly lower compared to the control treatment and to the treatments with the other predators. The activated sludge ciliate community was the most affected by the introduction of the "foreign" predator - D. margaritifer, a large ciliate armed with toxicysts."
Sewage
The nucleus basalis of Meynert (nbM) was first described at the end of the 19th century and named after its discoverer, Theodor Meynert. The nbM contains a large population of cholinergic neurons that project their axons to the entire cortical mantle, the olfactory tubercle, and the amygdala. It has been functionally associated with the control of attention and maintenance of arousal, both key functions for appropriate learning and memory formation. This structure is well-conserved across vertebrates, although its degree of organization varies between species. Since early in the investigation of its functional and pathological significance, its degeneration has been linked to various major neuropsychiatric disorders. For instance, Lewy bodies, a hallmark in the diagnosis of Parkinson's disease, were originally described in the nbM. Since then, its involvement in other Lewy body and dementia-related disorders has been recognized. In the context of recent positive outcomes following nbM deep brain stimulation in subjects with dementia-associated disorders, we review the literature from an historical perspective focusing on how the nbM came into focus as a promising therapeutic option for patients with Alzheimer's disease. Moreover, we will discuss what is needed to further develop and widely implement this approach as well as examine novel medical indications for which nbM deep brain stimulation may prove beneficial.
Basal Nucleus of Meynert
We compared DNA, pollen and macrofossil data obtained from Weichselian interstadial (age more than 40 kyr) and Holocene (maximum age 8400 cal yr BP) peat sediments from northern Europe and used them to reconstruct contemporary floristic compositions at two sites. The majority of the samples provided plant DNA sequences of good quality with success amplification rates depending on age. DNA and sequencing analysis provided five plant taxa from the older site and nine taxa from the younger site, corresponding to 7% and 15% of the total number of taxa identified by the three proxies together. At both sites, pollen analysis detected the largest (54) and DNA the lowest (10) number of taxa, but five of the DNA taxa were not detected by pollen and macrofossils. The finding of a larger overlap between DNA and pollen than between DNA and macrofossils proxies seems to go against our previous suggestion based on lacustrine sediments that DNA originates principally from plant tissues and less from pollen. At both sites, we also detected Quercus spp. DNA, but few pollen grains were found in the record, and these are normally interpreted as long-distance dispersal. We confirm that in palaeoecological investigations, sedimentary DNA analysis is less comprehensive than classical morphological analysis, but is a complementary and important tool to obtain a more complete picture of past flora.
DNA, Plant
Cor triatriatum sinister is a very rare cardiac anomaly that may lead to pulmonary hypertension, right ventricular dilation, and eventually right heart failure. We report a case of a toddler who presented with respiratory distress and cardiomegaly and was found to have cor triatriatum sinister with a restrictive communication, decompressing vertical vein, pulmonary hypertension, severe tricuspid regurgitation, and severe right ventricular dysfunction. She underwent a successful surgical repair, with normalisation of right ventricular function and pulmonary artery pressure.
Cor Triatriatum
The spread of antimicrobial resistance calls for chronic wound management devices that can engage with the wound exudate and signal infection by prompt visual effects. Here, the manufacture of a two-layer fibrous device with independently-controlled exudate management capability and visual infection responsivity was investigated by sequential free surface electrospinning of poly(methyl methacrylate-co-methacrylic acid) (PMMA-co-MAA) and poly(acrylic acid) (PAA). By selecting wound pH as infection indicator, PMMA-co-MAA fibres were encapsulated with halochromic bromothymol blue (BTB) to trigger colour changes at infection-induced alkaline pH. Likewise, the exudate management capability was integrated via the synthesis of a thermally-crosslinked network in electrospun PAA layer. PMMA-co-MAA fibres revealed high BTB loading efficiency (>80 wt.%) and demonstrated prompt colour change and selective dye release at infected-like media (pH > 7). The synthesis of the thermally-crosslinked PAA network successfully enabled high water uptake (WU = 1291 +/- 48 - 2369 +/- 34 wt.%) and swelling index (SI = 272 +/- 4 - 285 +/- 3 a.%), in contrast to electrospun PAA controls. This dual device functionality was lost when the same building blocks were configured in a single-layer mesh of core-shell fibres, whereby significant BTB release (~70 wt.%) was measured even at acidic pH. This study therefore demonstrates how the fibrous configuration can be conveniently manipulated to trigger structure-induced functionalities critical to chronic wound management and monitoring.
Bromthymol Blue
To better understand the transcriptional regulation of human T-lymphotropic viruses, expression of the nuclear proto-oncogenes, jun-B and c-jun were examined in cell lines infected with HTLV-I/II. Constitutive high levels of jun-B and c-jun expression were observed in HTLV-I (MT-2, Hut-102, IR, FS, SP) and HTLV-II infected cell lines (Mo-T, PAN). In contrast, the uninfected cell lines (Jurkat, Hut-78) expressed only basal levels of jun. This expression of jun was not dependent upon IL-2, as both IL-2 dependent (IR, FS, SP, and Pan) and IL-2 independent (MT-2, Hut-102, Mo-T) cell lines constitutively expressed transcripts for jun-B and c-jun. These data demonstrate that deregulated expression of nuclear protooncogenes such as jun may lead to cellular proliferation and the protein products of these nuclear oncogenes may potentially serve as transcriptional activators of HTLV-LTR by complexing with other nuclear proteins."
Primate T-lymphotropic virus 2
The epithelial-mesenchymal transition (EMT) process plays pivotal roles in regulatory mechanisms of embryogenesis and wound healing physiologically, and organ fibrosis, cancer progression, and metastasis pathologically. EMT is classified as primary, secondary, and tertiary during embryonic development. EMT contributes to repair of tissue injury and fibrogenesis by re-epithelialization and regeneration of fibroblasts, respectively. The hallmarks of EMT include loss of contact inhibition, remodeling of extracellular matrix, and reorganization of cytoskeleton, along with expression of mesenchymal markers and reduction of epithelial markers. Cancer cells acquire stemness, migration and invasive capability, evade apoptosis, and initiate metastasis to distant organs. Several EMT regulators including Snail, Zeb1, Zeb2, and Twist in solid tumor and Sox4, distal-less homeobox gene 4 (DLX4), Prdm14, Bmi1, and the forkhead box family in hematological malignancy are reviewed with regard to their signaling pathways, regulatory mechanisms, and clinical interactions.
Polycomb Repressive Complex 1
In vitro quantitative receptor autoradiography was performed on frozen sections of rat and human brain to visualize delta opiate receptors using the specific ligand [3H][D-Pen2, D-Pen5]enkephalin. For comparison, rat brain sections were also labelled with [3H]D-Ala2, D-Leu5-enkephalin. Compounds which block mu and kappa binding were included to make the [3H]D-Ala2, D-Leu5-enkephalin binding more specific. The two ligands had similar, but not identical, distributions in rat forebrain sections. Sites labelled with [3H][D-Pen2,D-Pen5]enkephalin were distributed heterogeneously within the layers of the frontal and parietal cerebral cortex, with high densities in the superficial and deep cortical layers. The claustrum and striatum had the most delta sites, whereas the globus pallidus had no delta binding. The distribution of [3H]D-Ala2,D-Leu5-enkephalin binding sites was similar to that of [3H][D-Pen2,D-Pen5]enkephalin, except that there was less heterogeneity in the frontal cortex. In the human brain regions studied, the highest delta binding was in caudate, putamen, temporal cortex and amygdala. There was less heterogeneity in the binding of [D-Pen2,D-Pen5]enkephalin in the human cortex than in the rat. No delta binding was seen in the medial and lateral segments of the globus pallidus. In both species, a discrepancy between the high enkephalin content of the globus pallidus and the absence of delta binding was apparent.
Enkephalin, Leucine
Several advances have been made in our understanding of the control of the growth and patterning of embryonic limbs. Development of the vertebrate limb is dependent on reciprocal interactions between the ectoderm and mesoderm that regulate the structure and function of the apical ectodermal ridge. One key component of this regulatory program appears to be the precise control of signaling by members of the bone morphogenetic protein family via multiple antagonistic interactions.
Formins
Physical symptoms other than pain often contribute to suffering near the end of life. In addition to pain, the most common symptoms in the terminal stages of an illness such as cancer or acquired immunodeficiency syndrome are fatigue, anorexia, cachexia, nausea, vomiting, constipation, delirium and dyspnea. Management involves a diagnostic evaluation for the cause of each symptom when possible, treatment of the identified cause when reasonable, and concomitant treatment of the symptom using nonpharmacologic and adjunctive pharmacologic measures. Part I of this two-part article discusses fatigue, anorexia, cachexia, nausea and vomiting. Fatigue is the most common symptom at the end of life, but little is known about its pathophysiology and specific treatment. Education of the patient and family is the foundation of treatment with the possible use of adjunctive psychostimulants. Anorexia and cachexia caused by wasting syndromes are best managed with patient and family education, as well as a possible trial of appetite stimulants such as megestrol or dexamethasone. For appropriate pharmacologic treatment, it is helpful to identify the pathophysiologic origin of nausea in each patient."
Pathological Conditions, Signs and Symptoms
Anaerobic bacteria have only recently been recognized as a source of antibiotics; yet, the metabolic potential of Negativicutes (Gram-negative staining Firmicutes) such as the oak-associated Dendrosporobacter quercicolus has remained unknown. Genome mining of D. quercicolus and phylogenetic analyses revealed a gene cluster for a type II polyketide synthase (PKS) complex that belongs to the most ancestral enzyme systems of this type. Metabolic profiling, NMR analyses, and stable-isotope labeling led to the discovery of a new family of anthraquinone-type polyphenols, the dendrubins, which are diversified by acylation, methylation, and dimerization. Dendrubin A and B were identified as strong antibiotics against a range of clinically relevant, human-pathogenic mycobacteria.
Polyketide Synthases
Environmental, physiological, and pathological stimuli induce the misfolding of proteins, which results in the formation of aggregates and amyloid fibrils. To cope with proteotoxic stress, cells are equipped with adaptive mechanisms that are accompanied by changes in gene expression. The evolutionarily conserved mechanism called the heat shock response is characterized by the induction of a set of heat shock proteins (HSPs), and is mainly regulated by heat shock transcription factor 1 (HSF1) in mammals. We herein introduce the mechanisms by which HSF1 tightly controls the transcription of HSP genes via the regulation of pre-initiation complex recruitment in their promoters under proteotoxic stress. These mechanisms involve the stress-induced regulation of HSF1-transcription complex formation with a number of coactivators, changes in chromatin states, and the formation of phase-separated condensates through post-translational modifications.
Proteotoxic Stress
BACKGROUND The Jessa Atrial Fibrillation Knowledge Questionnaire (JAKQ) was successfully used to assess knowledge gaps in patients with atrial fibrillation (AF). AIMS To evaluate the regional differences among Polish patients in their awareness of AF diagnosis and oral anticoagulation use. METHODS A total of 1583 patients with AF at a median (IQR) age of 72 (66-79) years completed the JAKQ in 3 cardiology centers (center I, Krakow; center II, Torun; center III, Kielce) from January 2017 to June 2018. The final analysis included 1525 patients, 32.9% were on vitamin K antagonists (VKAs) and 67.1% on non-VKA oral anticoagulants (NOACs), that is, rivaroxaban and dabigatran (28.9% each), and apixaban (9.3%). RESULTS The mean (SD) score on the JAKQ was 55.5% (18.4%) with better results among patients on VKAs compared with NOACs (58% [18.3%] vs 54.3% [18.4%]; P = 0.0002) with time from AF diagnosis more than 12 months (57.4% [17.5%] vs 50% [19.9%]; P <0.0001). There was a significant difference in the knowledge scores between the 3 centers (I, 59.5%; II, 48.5%; III, 54.3%; P <0.0001). In all centers the number of correct answers correlated inversely with patient's age (r = -0.20; P <0.0001). NOACs were more frequently used in center III. The percentage of correct responses was lower in patients on reduced NOAC doses (35.4% of patients on NOACs), compared with the full-dose NOAC groups in center I (56.9% vs 62.5%; P = 0.012) and II (48.1% vs 56.2%; P = 0.003). CONCLUSIONS Patients from a high-volume academic center showed better knowledge than their peers from district hospitals. There are large regional differences in prescription patterns of oral anticoagulants, including the preferred NOAC.
Patient Medication Knowledge
Fishes of the family Pomacentridae present a wide diversity of mating systems, ranging from polygyny to promiscuity and from individual territorial defense to the establishment of reproductive colonies of males. The damselfish species Abudefduf troschelii has a reproductive colony mating system, in which males temporarily aggregate in reproductive areas to court and attract females. Males defend an individual territory where they receive eggs and perform paternal care behaviors for their offspring. The present study evaluated the advantages of the colonial mating system in A. troschelii. During an entire reproductive period, in a breeding colony within a rocky reef, we located, marked, geo-referenced, and measured the distances between the territories of all males. We quantified the variance among males in their patterns of paternal care investment, eggs acquired, hatching success, reproductive success, body size, and changes in body coloration. We found that males spatially distributed their nests in groups or independently (i.e., solitary nests). Nesting groups are formed by larger males that show intense nuptial coloration during the entire receptivity period. They are located centrally to the colony and consist of three to six males whose territories overlap. In contrast, small solitary males that fail to acquire or maintain nuptial coloration during the receptivity period establish their nests peripherally to the colony, away from the territories of other males. Our results highlight that the reproductive benefits of colonial nesting are unequal for males, as the spatial distribution of nests within the colony determines the reproductive success of males. Group nesting confers the highest reproductive benefits to males regarding eggs obtained, hatching success, and relative fitness and also enables males to reduce their parental investment in brood care behaviors. The preference of females for oviposition could be associated with greater intrasexual competitiveness, defense ability, body condition, or experience of group-nesting males located at the center of the colony or because their progeny will have a lower probability of predation than they would in solitary nests males.
Territoriality
Cold atmospheric plasma (CAP) is a partially ionized gas that gains attention as a well-tolerated cancer treatment that can enhance anti-tumor immune responses, which are important for durable therapeutic effects. This review offers a comprehensive and critical summary on the current understanding of mechanisms in which CAP can assist anti-tumor immunity: induction of immunogenic cell death, oxidative post-translational modifications of the tumor and its microenvironment, epigenetic regulation of aberrant gene expression, and enhancement of immune cell functions. This should provide a rationale for the effective and meaningful clinical implementation of CAP. As discussed here, despite its potential, CAP faces different clinical limitations associated with the current CAP treatment modalities: direct exposure of cancerous cells to plasma, and indirect treatment through injection of plasma-treated liquids in the tumor. To this end, a novel modality is proposed: plasma-treated hydrogels (PTHs) that can not only help overcome some of the clinical limitations but also offer a convenient platform for combining CAP with existing drugs to improve therapeutic responses and contribute to the clinical translation of CAP. Finally, by integrating expertise in biomaterials and plasma medicine, practical considerations and prospective for the development of PTHs are offered.
Plasma Gases
A greenhouse study was performed to evaluate the feasibility of using Agropyron elongatum and lime treatment for remediation of a simulated nickel (Ni) contaminated acidic soil. The acid soil was spiked with four levels of Ni, i.e., 0, 15, 50, and 100 mg Ni kg(-1) soil and the soil pH at each Ni level was adjusted to 4, 6 and 8 by liming with CaO. Addition of lime raised the soil pH and resulted in a decrease in concentrations of DTPA-extractable and water-soluble Ni in the soil, with a maximum reduction of 64 and 28 mg kg(-1), respectively at the highest level of Ni treatment as compared to the control without Ni treatment. In general, excessive Ni content in soil, especially at pH 4 inhibited the growth of Agropyron. Liming improved the growth condition and the highest dry weight yield of 12 g pot(-1) was obtained in soil spiked with 15 mg Ni kg(-1) at pH 6; and at the highest level of Ni, the dry weight yield increased from 0.48 to 5.96 g pot(-1) when the pH was increased from 4 to 6. However a further increase in pH to 8 did not improve plant yield because of the unavailability of nutrients at such a high pH. Nickel contents in plant were positively correlated to soil Ni contents at each respective pH level. Most of the Ni taken up by Agropyron was retained in the roots and the highest Ni uptake by plant was 3.9 mg pot(-1) in soil spiked with 100 mg Ni kg(-1) at pH 5.9, which was about 2.6% of total Ni added to the soil. This implies that Agropyron is not a hyperaccumulating species but is highly tolerant. Lime amendment together with the tolerant characteristic of Agropyron could provide a possible means to remediate Ni contaminated soils through phytostabilization.
Agropyron
Many antimicrobial agents have been associated with hypoprothrombinemia. The precise mechanisms are unknown, but alteration in vitamin K status or utilization is involved. The two postulated mechanisms implicate either direct inhibition of biosynthesis of the vitamin K-dependent clotting factors by the N-methylthiotetrazole (NMTT) moiety found in certain antimicrobial agents or eradication of vitamin K-producing intestinal microflora in patients with reduced oral intake of vitamin K. An English-language review of all prospective studies reported between 1966 and 1988 in which serial prothrombin times were monitored in adult patients revealed that the incidence of hypoprothrombinemia varied from 3.7% to 64% with NMTT-containing regimens and from 0% to 24% with non-NMTT-containing regimens. Detailed evaluation of these and other studies suggests that certain risk factors, including malnutrition, hepatic and renal dysfunction, older age, and severity of illness, may be the major determinants of hypoprothrombinemia. The hypothesis that the NMTT side chain is primarily responsible for hypoprothrombinemia may not be justified. We conclude that patients at high risk for coagulopathy should be carefully monitored and that serious consideration should be given to the use of prophylactic vitamin K in such cases.
Hypoprothrombinemias
In the 21st century, existing human societies and biodiversity on the Earth are under threat because human resource consumption is exceeding or projected to exceed some of the physical and chemical boundaries of our planet (Rockstrom et al., 2009). Space research and space exploration are an integral part of a sustainable development that mitigates these threats: Space science and exploration allow us to monitor environmental threats and they open up access to global communication and participation for all human societies. In addition, space exploration also promises to expand the existing limitations and planetary boundaries imposed on human development. On the other hand space exploration can also cause additional environmental problems. The best known example for the latter is the anthropogenic space debris orbiting Earth, but similar problems are likely to occur in other places, for instance on the Moon, due to scientific and commercial space exploration in the near future. Planetary sustainability is a helpful concept to address the promises and challenges posed by space exploration with respect to sustainability. This concept can be understood as a sustainable development that considers the Earth as a planet in its space environment and considers the space environment as an integral part of sustainable development, with scientific, ethical, economic, and legal ramifications. In this article we review the recent advancements in planetary sustainability. This includes the proposal that the space environment of Earth should be added as an independent goal to the existing 17 Sustainable Development Goals defined by the United Nations, considerations of the planned return of humans to the Moon in 2024, and the implications of the increase of commercial satellite networks in low Earth orbit.
Space Research
The wearable neurotechnology market targets consumers with promises of cognitive benefit and personal wellness. Scientific evidence is essential to substantiate claims about utility, safety, and efficacy and for informed choice and public trust."
Transcranial Direct Current Stimulation
The pharmacokinetic properties of SCE-1141, an anti stereoisomer of cefmenoxime, were compared with those of cefmenoxime. SCE-1141 levels in plasma and tissues peaked at 30 min after the intramuscular administration of 20 mg/kg; the plasma level declined with a half-life of about 18 min. The area under the concentration-time curve in plasma and the half-life after intravenous administration were similar to those after intramuscular administration. SCE-1141 was distributed at high concentrations in the liver and kidney of normal rats, and at lower concentrations in the liver of rats with acute liver impairment. SCE-1141 levels in plasma and tissues, except liver, were lower than those of cefmenoxime. The 24-h biliary and urinary excretions of SCE-1141 were 73% and 26% of the dose, respectively; these were significantly different from those of cefmenoxime: 33% in bile and 55% in urine. In rats with acute liver impairment, the biliary excretion of SCE-1141 was decreased, and the urinary excretion increased.
Cefmenoxime
Black-spot poison ivy dermatitis is a rare manifestation of a common condition. It occurs on exposure to the resins of the plants of the Rhus family also known as Toxicodendron. We describe 5 patients with black deposits on their skin and clothing after contact with poison ivy and review the literature reflecting different aspects of this phenomenon including clinical presentation, histologic findings, and historical background.
Dermatitis, Toxicodendron
The discovery and development of methods for isolation, characterisation and taxonomy of viruses represents an important milestone in the study, treatment and control of virus diseases during the 20th century. Indeed, by the late-1950s, it was becoming common belief that most human and veterinary pathogenic viruses had been discovered. However, at that time, knowledge of the impact of improved commercial transportation, urbanisation and deforestation, on disease emergence, was in its infancy. From the late 1960s onwards viruses, such as hepatitis virus (A, B and C) hantavirus, HIV, Marburg virus, Ebola virus and many others began to emerge and it became apparent that the world was changing, at least in terms of virus epidemiology, largely due to the influence of anthropological activities. Subsequently, with the improvement of molecular biotechnologies, for amplification of viral RNA, genome sequencing and proteomic analysis the arsenal of available tools for virus discovery and genetic characterization opened up new and exciting possibilities for virological discovery. Many recently identified but unclassified" viruses are now being allocated to existing genera or families based on whole genome sequencing, bioinformatic and phylogenetic analysis. New species, genera and families are also being created following the guidelines of the International Committee for the Taxonomy of Viruses. Many of these newly discovered viruses are vectored by arthropods (arboviruses) and possess an RNA genome. This brief review will focus largely on the discovery of new arthropod-borne viruses."
RNA Viruses
OBJECTIVE: To compare the outcomes of balloon catheter dilation and nasolacrimal intubation as treatment for congenital nasolacrimal duct obstruction after failed probing in children younger than 4 years. METHODS: We conducted a prospective, nonrandomized, multicenter study that enrolled 159 children aged 6 months to younger than 48 months who had a history of a single failed nasolacrimal duct probing and at least 1 of the following clinical signs of nasolacrimal duct obstruction: epiphora, mucous discharge, or increased tear lake. One hundred ninety-nine eyes underwent either balloon catheter nasolacrimal duct dilation or nasolacrimal duct intubation. Treatment success was defined as absence of epiphora, mucous discharge, or increased tear lake at the outcome visit 6 months after surgery. RESULTS: Treatment success was reported in 65 of 84 eyes (77%; 95% confidence interval, 65%-85%) in the balloon catheter dilation group compared with 72 of 88 eyes (84% after adjustment for intereye correlation; 74%-91%) in the nasolacrimal intubation group (risk ratio for success for intubation vs balloon dilation, 1.08; 0.95-1.22). CONCLUSION: Both balloon catheter dilation and nasolacrimal duct intubation alleviate the clinical signs of persistent nasolacrimal duct obstruction in a similar percentage of patients.
Lacrimal Duct Obstruction
A case of postabortal hemorrhage in a patient with von Willebrand's disease was controlled by arteriographic embolization of the uterine branch of the internal iliac artery. Selective internal iliac artery embolization has been effectively used to control postpartum hemorrhage and hemorrhage resulting from pelvic malignancy. A discussion is presented for expanding the use of selective embolization for controlling uterine hemorrhage to patients suffering from postabortal bleeding as a means of controlling hemorrhage without sacrificing fertility.
Uterine Hemorrhage
BACKGROUND: Computational finite element models of the aortic root have previously used material properties of the ascending aorta to describe both aortic sinuses and ascending aorta. We have previously demonstrated significant material property differences between ascending aorta and sinuses in pigs. However, it is unknown whether these regional material property differences exist in humans. The main objective of this study was to investigate biomechanics of fresh human ascending aorta and aortic sinuses and compare nonlinear material properties of these regions. METHODS: Fresh human aortic root specimens obtained from the California Transplant Donor Network (Oakland, CA) were subjected to displacement-controlled equibiaxial stretch testing within 24 hours of harvest. Stress-strain data recorded were used to derive strain energy functions for each region. Tissue behavior was quantified by tissue stiffness and a direct comparison was made between different regions of aortic root at physiologic stress levels. RESULTS: All regions demonstrated a nonlinear response to strain during stretch testing in both circumferential and longitudinal directions. No significant difference in tissue stiffness was found between anterior and posterior regions of the ascending aorta or among the three sinuses in both directions. However, our results demonstrated that human ascending aorta is significantly more compliant than aortic sinuses in both circumferential and longitudinal directions within the physiologic stress range. CONCLUSIONS: Significant material and structural differences were observed between human ascending aorta and aortic sinuses. Regionally specific material properties should be employed in computational models used to assess treatments of structural aortic root disease.
Sinus of Valsalva
Rat lungworm, Angiostrongylus cantonensis, is one major cause of human eosinophilic meningitis. This helminth is endemic in Southeast Asia, Pacific Islands, and the Caribbean and has recently expanded to South America. The infection is characterized by an elevated eosinophil count in cerebrospinal fluid. Common symptoms and signs include headache, neck stiffness, paresthesia and nausea/vomiting. The unique history of eating freshwater and land snails or slugs within 2 weeks before onset is helpful for diagnosis. Antihelminthic agents have not shown efficacy in human infection; treatment involves supportive care with management of inflammation and intracranial pressure.
Angiostrongylus cantonensis
BACKGROUND: Fanconi anemia is a severe congenital disorder associated with mutations in a cluster of genes responsible for DNA repair. Arriving at an accurate and timely diagnosis can be difficult in cases of Fanconi anemia with atypical clinical features. It is very important to increase the rate of accurate diagnosis for such cases in a clinical setting. The purpose of this study is to explore the clinical diagnosis of Fanconi anemia in children with atypical clinical features. METHODS: Six cases of Fanconi anemia with atypical clinical features were enrolled in the study, and their clinical features were recorded, their FANCA gene transcription was assessed by RT-PCR, and FANCA mutations and the ubiquitination of FANCD2 protein were analyzed using DNA sequencing and western blotting respectively. RESULTS: All six cases showed atypical clinical features including no apparent deformities, lack of response to immune therapy, and progressively increasing bone marrow failure. They also have significantly increased fetal hemoglobin, negative mitomycin-induced fracture test results, and carry a FANCA gene missense mutation. Single protein ubiquitination of FANCD2 was not observed in those patients. CONCLUSION: The combination of clinical features, FANCA pathogenic gene mutation genotype and the absence of FANCD2 protein ubiquitination are helpful in the accurate and timely diagnosis of Fanconi anemia in children.
Fanconi Anemia
The feline oncornavirus-associated cell membrane antigen (FOCMA) is a target for naturally occurring immunity that protects the cat against development of fibrosarcoma and leukemia. Feline sarcoma virus-transformed nonproducer" mink cells express high levels of FOCMA, but not the major viral structural proteins. Transformation of the same cells by murine sarcoma virus, or infection with feline leukemia virus, which is nontransforming for epithelial or fibroblastic cells, did not induce FOCMA. Thus, FOCMA expression in mind lung cells is specifically associated with transformation by feline sarcoma virus."
Sarcoma Viruses, Feline
Neurological manifestations of preeclampsia are serious and very variable. We report the case of a woman at 34 weeks gestation with preeclampsia who developed blindness within hours without alteration of consciousness. The imagery was in favor of posterior reversible encephalopathy. The therapeutic management consisted of emergency fetal extraction, the administration of antihypertensive drugs and magnesium sulfate. The outcome was favorable with complete recovery of visual function. This case reflects the heterogeneity of the clinical presentation of preeclampsia, as the only neurological manifestation was cortical blindness, with no associated consciousness disorder.
Blindness, Cortical
A mathematical model is used to predict relative body burdens of inhaled contaminants in workers who work two jobs or overtime, or who experience off-the-job exposure to air contaminants. Expected "peak" or maximum body burdens from multiple exposures are compared to those expected from the "normal" occupational exposure on which TLVs and Permissible Exposure Limits (PELs) arebased (five 8-hour days per week with zero off-the-job exposure). The model is designed to predict what adjustments to the TLVs and PELs are necessary to avoid accumulation of excess peak body burdens of contaminants from the additional exposures incurred. The general application of models to determine occupational exposure limits is reviewed, and several models are compared."
Maximum Allowable Concentration
On the basis of literary data and original investigations some phylogenetic, ecological and morphological aspects of the origin of parasitism in trombiculid mites are carefully considered for the first time. It is shown that parasitism in this group of trombidiform mites is a relatively young historical phenomenon and was formed after their ontogenesis had differentiated into active and quiescent stages. Therefore, in the life pattern of trombiculid mites the character of individual development, that defines their biotopical restriction, is much more important than the phase parasitism. Primitive organization of the digestive system and extraintestinal digestion, so characteristic of this group, are one of the main reasons of the origin of their parasitism. Under pasture conditions trombiculid mites, that initially were predators-entomophages with bite-sucking mouth parts, pass easily to parasitism on vertebrate animals and become primary lymphophages. They use the vertebrate host's organism exclusively as a source of food and by the extent of polyphagia are very close to free-living blood-sucking insects. Stylostome, that develops during feeding of trombiculid larvae and some other closely related groups of trombidiform mites, is a universal structure for achieving a large amount of food on a wide range of animals during a relatively short period of time and reflects wide host-parasite specificity of these parasitic mites. From the historical view the larvae of trombiculid mites did not pass from one group of hosts to the others, but owing to morphological preadaptation to parasitism passed in a definite historical period, not earlier than Paleogene, to parasitism on all classes of terrestrial vertebrates, especially on mammals, their primary hosts.
Trombiculidae
Ongoing transcription in vitro of Tomato spotted wilt virus (TSWV) has previously been demonstrated to require the presence of reticulocyte lysate. This dependence was further investigated by testing the occurrence of transcription in the presence of two translation inhibitors: edeine, an inhibitor that still allows scanning of nascent mRNAs by the 40S ribosomal subunit, and cycloheximide, an inhibitor that completely blocks translation including ribosome scanning. Neither of these inhibitors blocked TSWV transcription initiation or elongation in vitro, as demonstrated by de novo-synthesized viral mRNAs with globin mRNA-derived leader sequences, suggesting that TSWV transcription in vitro requires the presence of (a component within) reticulocyte lysate, rather than a viral protein resulting from translation.
Edeine
The action of acute administration of oxytocin (OXY), vasopressin (AVP) or its analog 1-deamino-8-D-arginine-vasopressin (dDAVP) on basal and stress induced PRL release in normal male rats and the effect of chronic injection of AVP on PRL stress response in AVP deficient rats were studied. The hormones (OXY, 600 ng min-1 per rat; AVP 6, 12 or 24 ng min-1 per rat and dDAVP 24 ng min-1 per rat) were infused to conscious rats via the jugular vein for 10 min and then the rats were immobilized under continuing the infusion for further 20 min. In parallel experiments arterial blood pressure (BP) was measured. OXY and 24 ng min-1 AVP caused high BP elevation of the same magnitude, yet the effect of 12 ng min-1 AVP was significantly lower. Neither OXY, dDAVP, nor 6 and 12 ng min-1 of AVP affected basal or stress stimulated PRL values when compared with saline treated animals. 24 ng min-1 of AVP highly stimulated nonstressed PRL levels and no additional stress effect was observed. Intramuscular injection of 2 micrograms (1 U) of AVP daily for 7 days did not influence the basal values or stress induced PRL response in Brattleboro homogygous rats as compared with vehicle treated controls or heterozygous rats treated with AVP or vehicle. These results show that the infusion of 24 ng min-1 per rat of AVP stimulated PRL release which cannot be explained by the nonspecific effect of high BP. Repeated AVP administration did not modulate either the basal or IMO stress stimulated PRL secretion in rats with or without genetic vasopressin deficiency.
Pituitary Hormones, Posterior
The characterization of the drug metabolism and pharmacokinetic (DMPK) profiles of stereoisomers is a fundamental aspect of the drug discovery and development processes. Therefore, chiral drug bioassays are very important to pharmaceutical and biomedical researchers. The recent developments in chiral liquid chromatography coupled to atmospheric pressure ionization tandem mass spectrometry (LC-API-MS/MS) for the analysis of pharmaceuticals are reviewed. Various ionization techniques including electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric photoionization (APPI) interfaced with chiral liquid chromatographic methods are described in terms of their ionization efficiencies, matrix effects and limitations. Examples were selected to demonstrate the applicability of these methods for enantioselective bioanalysis.
Mass Spectrometry
Endometrioid carcinoma with histopathologic resemblance to cutaneous pilomatrix carcinoma with mutations in the gene encoding beta-catenin, CTNNB1 are rare. There are minimal numbers of reports of high-grade tumors with this divergent differentiation in the literature. We report the case of a 29-yr-old female with an unusual presentation of endometrial cancer with overall histologic appearance indicative of a recently reported aggressive subtype of Federation of Gynecology and Obstetrics (FIGO) IVB grade 3 endometrioid carcinoma with features resembling cutaneous pilomatrix carcinoma. She was treated with a primary chemotherapy regimen with an initial significant response to treatment before developing symptomatic brain metastasis for which she underwent whole-brain radiotherapy. We discuss the unusual histologic and radiologic presentation as well as her individual management throughout this case report. The apparent association with morular metaplasia and atypical polypoid adenomyoma suggests that this rare carcinoma is within a spectrum of lesions associated with aberrant beta-catenin expression/beta-catenin mutation. Its aggressive nature highlights the importance of early recognition of this rare lesion.
Carcinoma, Endometrioid
The past decade has seen expeditious developments in our ability to grow and maintain a variety of human cells and tissues, with properties closely mimicking those in the human body. Prominent researchers and entrepreneurs from all over the world assembled in Hyderabad, India to discuss developments in this field that have not only aided fundamental understanding of organ development and disease processes but have served as good physiological models for toxicity testing and drug development. The speakers presented ingenious, cutting-edge technology and forward-thinking ideas. This report presents the salient aspects of their discussions, highlights the importance of identifying unmet needs, and discusses setting of standards that will help regulatory approvals as we move into a new era, with nominal animal use in research and effective drug discovery."
Micro-Electrical-Mechanical Systems
OBJECTIVES: To characterize and compare the histological features of conjunctiva obtained during the repair of trabeculectomy and inadvertent blebs and to assess the effects of antifibrotic agents. METHODS: We used routine paraffin processing and light microscopy to examine conjunctival specimens from 28 eyes undergoing late bleb revision: 19 leaking trabeculectomy blebs, 5 nonleaking trabeculectomy blebs, and 4 inadvertent blebs. Quantitative analysis of histological characteristics included conjunctival epithelial thickness, stromal vascularity, squamous metaplasia, stromal inflammatory cell infiltrate, and goblet cell density. The type of surgery, presence of leaks, prior topical medication, and antifibrotic use were correlated with histological findings. RESULTS: Trabeculectomy blebs (leaking and nonleaking) showed decreases in overall epithelial thickness (P<.02), goblet cell density (P<.001), and vascularity (P<.001) compared with inadvertent bleb controls. Conjunctiva exposed to antifibrotics had fewer layers of epithelial cells than those with no prior exposure (P<.05). CONCLUSIONS: Histological analysis of thin blebs excised following trabeculectomy demonstrated decreases in epithelial thickness and goblet cell density compared with inadvertent blebs. Both leaking and nonleaking trabeculectomy blebs exhibited decreases in localized stromal vascularity and increases in surrounding stromal vascularity compared with normal conjunctiva.
Conjunctiva
Approximately 80% of tumors arising in the brain stem are diffuse intrinsic lesions. Patients typically present with a short duration of symptoms and signs with significant neurological impairment. Imaging findings are typical, and biopsy is not usually necessary to make a diagnosis. Standard treatment consists of radiotherapy alone. Although the majority of patients will show a significant improvement in neurological status following such treatment, the prognosis is very poor. The median time to disease progression is of the order of 5-6 months, the median survival time less than 1 year, and survival at 2 years and beyond, less than 10%. Over the last 10-15 years, numerous studies have been undertaken in an attempt to develop more effective treatment for children with diffuse intrinsic brain stem tumors. Using a hyperfractionated (twice-daily) schedule, doses of radiotherapy as high as 78 Gy have been given without success. Other approaches use chemotherapy combined with radiotherapy in a variety of different ways, including up-front, concurrent, and adjuvant chemotherapy, and high-dose chemotherapy with rescue. The results of these studies using chemotherapy, as well as other approaches using other systemic agents, are reviewed in detail.
Brain Stem Neoplasms
The effect of monosodium-L-glutamate (MSG) administration in the neonatal period on habituation of exploratory behavior related to gender differences was investigated. Rats of both sexes were intraperitoneally treated with MSG (4 mg/g) or hypertonic saline (10% NaCl) on postnatal days 2, 4, 6, 8, and 10. On postnatal day 65, the animals were tested in an open-field test during 4 consecutive days, once daily in 6-min sessions. The rapidity of habituation of exploratory behavior during repeated exposure to the open field (interrupted habituation) and over individual sessions (uninterrupted habituation) was evaluated by using the method of linear regression. Compared to intact controls, there were no significant differences found in interrupted habituation, neither in males nor in females. Uninterrupted habituation in neonatally treated males was slowed down in the first 2 days of testing. No differences in adult behavior between treated groups (MSG and hypertonic saline) were observed, i.e., there were no late effects specific for neonatal MSG administration. In females, uninterrupted habituation was not affected. Males proved to be more sensitive to neonatal stress associated with injections of MSG or hypertonic saline than females, and showed feminine-like habituation in the new environment.
Exploratory Behavior
In eukaryotes, a nascent peptide entering the endoplasmic reticulum (ER) is scanned by two Sec61 translocon-associated large membrane machines for protein N-glycosylation and protein O-mannosylation, respectively. While the structure of the eight-protein oligosaccharyltransferase complex has been determined recently, the structures of mannosyltransferases of the PMT family, which are an integral part of ER protein homeostasis, are still unknown. Here we report cryo-EM structures of the Saccharomyces cerevisiae Pmt1-Pmt2 complex bound to a donor and an acceptor peptide at 3.2-A resolution, showing that each subunit contains 11 transmembrane helices and a lumenal beta-trefoil fold termed the MIR domain. The structures reveal the substrate recognition model and confirm an inverting mannosyl-transferring reaction mechanism by the enzyme complex. Furthermore, we found that the transmembrane domains of Pmt1 and Pmt2 share a structural fold with the catalytic subunits of oligosaccharyltransferases, confirming a previously proposed evolutionary relationship between protein O-mannosylation and protein N-glycosylation.
Walker-Warburg Syndrome
Phytochemical analysis of the high quality Chinese agarwood 'Qi-Nan' originating from Aquilaria sinensis (Lour.) Glig led to the isolation of a new 2-(2-phenylethyl)chromone derivative, qinanones G (1), and four known 2-(2-phenylethyl)chromones (2-5). Their structures were elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR) and MS analyses. The NMR data of chromones 1-3 were first reported, and chromones 2 and 3 showed weak inhibitory activity against acetylcholinesterase.
Chromones
OBJECTIVE: The objective of the study was to develop and test standards of practice for handling non-prescription medicines. METHOD: In consultation with pharmacy registering authorities, key professional and consumer groups and selected community pharmacists, standards of practice were developed in the areas of Resource Management; Professional Practice; Pharmacy Design and Environment; and Rights and Needs of Customers. These standards defined and described minimum professional activities required in the provision of non-prescription medicines at a consistent and measurable level of practice. Seven standards were described and further defined by 20 criteria, including practice indicators. The Standards were tested in 40 community pharmacies in two States and after further adaptation, endorsed by all Australian pharmacy registering authorities and major Australian pharmacy and consumer organisations. The consultation process effectively engaged practicing pharmacists in developing standards to enable community pharmacists meet their legislative and professional responsibilities. MAIN OUTCOME MEASURES: Community pharmacies were audited against a set of standards of practice for handling non-prescription medicines developed in this project. Pharmacies were audited on the Standards at baseline, mid-intervention and post-intervention. Behavior of community pharmacists and their staff in relation to these standards was measured by conducting pseudo-patron visits to participating pharmacies. RESULTS: The testing process demonstrated a significant improvement in the quality of service delivered by staff in community pharmacies in the management of requests involving non-prescription medicines. The use of pseudo-patron visits, as a training tool with immediate feedback, was an acceptable and effective method of achieving changes in practice. Feedback from staff in the pharmacies regarding the pseudo-patron visits was very positive. CONCLUSION: Results demonstrated the methodology employed was effective in increasing overall compliance with the Standards from a rate of 47.4% to 70.0% (P < 0.01). This project led to a recommendation for the development and execution of a national implementation strategy.
Community Pharmacy Services
PURPOSE: A number of studies have reported that aprepitant has been used to prevent chemotherapy-induced nausea and vomiting. In this study, we aimed to analyze the efficacy and safety of aprepitant, which can provide evidence for aprepitant administration. MATERIALS AND METHODS: Fifteen trials involving patients who received moderately or highly emetogenic chemotherapy were included in this pooled analysis. Antiemetic drugs in these studies included aprepitant, dexamethasone, and 5-HT3 receptor antagonists. RESULTS: A total of 4,798 cases were investigated in these clinical trials. Compared with placebo or the standard antiemetic therapy, the cumulative incidence of emesis was significantly reduced in the patients treated with aprepitant-based (125 mg/80 mg) therapy on the first day [relative risk (RR) = 1.13, 95% confidence interval (CI) 1.10-1.16], from 2 to 5 days (RR = 1.35, 95% CI 1.22-1.48) and in the overall 5 days (RR = 1.30, 95% CI 1.22-1.39). In terms of drug safety, there was no significant difference between aprepitant-based regimens and non-aprepitant regimens. CONCLUSION: Results from the analysis suggest that aprepitant with 5-HT3 receptor antagonists and dexamethasone is highly effective in preventing nausea and vomiting in the days after administration of moderately or highly emetogenic chemotherapy (MEC or HEC) agents.
Aprepitant
Vinblastine is shown to induce pronuclear fusion failure in conjugating Tetrahymena thermophila. In this alternate conjugational pathway gametic pronuclei are exchanged between conjugants but do not fuse. Each pronucleus undergoes one mitotic division to produce a new macro- and micronucleus. Genetic consequences of pronuclear fusion failure include the following: (1) the progeny are whole genome homozygotes with nuclei derived from single meiotic products, and (2) half of the progeny are heterokaryons with micro- and macronuclei of different genetic origins. These facts make this process extremely useful in strain construction and mutant isolation. The induction of pronuclear fusion failure by vinblastine suggests that microtubules play an essential role in pronuclear fusion.
Hymenostomatida
Angiogenesis, the process of new blood vessel formation, has been a major target for cancer therapy. Antiangiogenic herbal medicines are useful in the treatment of cancer. In this study, we found that a water extract of Cinnamomum cassia (CCWE) was a potent inhibitor of angiogenesis. In cultured human umbilical vein endothelial cells, CCWE suppressed vascular endothelial growth factor (VEGF)-induced proliferation, migration, invasion, tube formation, and intracellular signaling events such as phosphorylation of ERK, p38 and VEGFR2, and activation of matrix metalloproteinase. Furthermore, CCWE inhibited VEGF-induced vessel sprouting of rat aorta ex vivo. These findings might be of particular interest for drug development because VEGF signaling is a potential target for treatment of angiogenesis-associated diseases.
Cinnamomum aromaticum
One of the most widespread coral diseases linked to anthropogenic activities and recorded on reefs worldwide is characterized by anomalous growth formations in stony corals, referred to as coral growth anomalies (GAs). The biological functions of GA tissue include limited reproduction, reduced access to resources, and weakened ability to defend against predators. Transcriptomic analyses have revealed that, in some cases, disease progression can involve host genes related to oncogenesis, suggesting that the GA tissues may be malignant neoplasms such as those developed by vertebrates. The number of studies reporting the presence of GAs in common reef-forming species highlights the urgency of a thorough understanding of the pathology and causative factors of this disease and its parallels to higher organism malignant tissue growth. Here, we review the current state of knowledge on the etiology and holobiont features of GAs in reef-building corals.
Coral Reefs
We aimed to describe the phenotypic spectrum of seizures in Sotos syndrome, a genetic condition involving overgrowth, macrocephaly, dysmorphic features, and learning disability, in which 60%-90% have NSD1 pathogenic variants. Patients were recruited from clinics and referral from support groups. Those with seizures and a clinical diagnosis of Sotos syndrome were included. Phenotyping data were collected via structured clinical interview and chart review. Forty-nine patients were included. Twenty had NSD1 testing results available; of these, 15 (75%) had NSD1 pathogenic variants. Seizure onset age ranged from 3 months to 12 years. Staring spells (absence or focal impaired awareness seizure) were the most frequently reported semiology (33/49; 67%), followed by febrile seizures (25/49; 51%) and afebrile bilateral tonic-clonic seizures (25/49; 51%). Most patients (33/49; 67%) had multiple seizure types. The majority (33/49; 67%) had seizures controlled on a single antiseizure medication or no medication. Nine (18%) had drug-resistant epilepsy. Epilepsy syndromes included febrile seizures plus, Lennox-Gastaut syndrome, childhood absence epilepsy, and generalized tonic-clonic seizures alone. The seizure phenotype in Sotos syndrome most commonly involves staring spells, afebrile tonic-clonic seizures or febrile convulsions; however, other seizure types may occur. Seizures are typically well-controlled with medication, but drug-resistant epilepsy occurs in a minority.
Sotos Syndrome
Fourth branchial anomalies are rare entities. Despite this, they must be considered when presented with a low lateral neck mass, recurrent lower neck abscesses, or recurrent suppurative thyroiditis. The truly unique presentation of this case highlights the importance of including these anomalies in the differential diagnosis for all neck lesions.
Branchioma
Hydrogen production in nature is performed by hydrogenases. Among them, [FeFe]-hydrogenases have a peculiar active site, named H-cluster, that is made of two parts, synthesized in different pathways. The cubane sub-cluster requires the normal iron-sulfur cluster maturation machinery. The [2Fe] sub-cluster instead requires a dedicated set of maturase proteins, HydE, HydF, and HydG that work to assemble the cluster and deliver it to the apo-hydrogenase. In particular, the delivery is performed by HydF. In this review, we will perform an overview of the latest knowledge on the maturation machinery of the H-cluster, focusing in particular on HydF.
Hydrogenase
Medicare's three-year phase-in for its prospective reimbursement DRG system creates a special problem for radiology and hospital managers trying to manage under contradictory methodologies. One innovative way of coping with that problem is the development of a parallel planning process--one plan for cost-based services and another for DRG services. Such an approach provides radiology administrators with a set of familiar managerial tools to enter into the unknown territory of DRGs."
Insurance, Health, Reimbursement
INTRODUCTION: There is limited information on how the tendency to violence in adolescents is affected by internet addiction and insomnia. This study will contribute to the literature in revealing the effect of internet addiction on insomnia and violence tendency in adolescents. METHODS: The data were collected between 26/May/2021 and 06/July/2021. A total of 2,502 adolescents studying in 9th and 12th grades were included in the study. Data were collected with the adolescent information form, Internet Addiction Scale-Short Form, Bergen Insomnia Scale, and Violence Tendency Scale. Descriptive statistics, independent samples t-test, one-way analysis of variance, correlation, and simple linear regression analyzes were used in the analysis of data. RESULTS: Participants were 15.92 +/- 1.19 years old and 70.80% were women. While internet addiction do not change according to gender, and violence tendency mean scores do not change according to having a device to use the internet, the study variable mean score changes according to all the other socio-demographic variables included in our study. There is a positive relationship between internet addiction, violence tendency, and insomnia. Furthermore, while internet addiction explained 22.1% of insomnia scores, 18.8% of the variance changes in the violence tendency scores, insomnia explained 11.8% of violence tendency scores. CONCLUSION: Although the scale scores of the adolescents in our study were below the average, internet addiction is common problem necessitates working on the subject. In our study, there is a significant relationship between internet addiction, insomnia and tendency to violence, and internet addiction predicts other variables.
Technology Addiction
The role for reactive oxygen species (ROS) in cellular (patho)physiology, in particular in signal transduction, is increasingly recognized. The family of NADPH oxidases (NOXes) plays an important role in the production of ROS in response to receptor agonists such as growth factors or inflammatory cytokines that signal through the Rho-like small GTPases Rac1 or Rac2. The phagocyte oxidase (gp91phox/NOX2) is the best characterized family member, and its mode of activation is relatively well understood. Recent work has uncovered novel and increasingly complex modes of control of the NOX2-related proteins. Some of these, including NOX2, have been implicated in various aspects of (cardio)vascular disease, including vascular smooth muscle and endothelial cell hypertrophy and proliferation, inflammation, and atherosclerosis. This review focuses on the role of the Rac1 and Rac2 GTPases in the activation of the various NOX family members.
rac GTP-Binding Proteins
True and false aneurysms of veins are very rare conditions and only few cases have been described in the literature. We present a case of a 56-year-old female with personal history of primary arterial hypertension and connective tissue disease. Ultrasound of the neck showed a saccular, compressible, hypoechoic structure that appeared to have a direct communication with the left external jugular vein lumen. The venous aneurysm was removed and the histopathology of the mass showed a grossly dilated vein, with continuous aspects of the entire 3 layer of the venous wall, classifying it as a venous aneurysm.
Jugular Veins
The study included 41 patients (Uzbeks by nationality) with tuberculosis of the bones and joints. Of them 19 had localized tuberculosis and 22 disseminated process. The condition of T lymphocytes, B-lymphocytes and specific immunity were investigated by standard immunological methods. Typing by antigens HLA-DR was made with the help of standard microlymphocytotoxic test. It was established that patients with tuberculosis of the bones and joints have worse qualitative and quantitative characteristics of T lymphocytes, reduced number of B-lymphocytes, high specific response of lymphocytes to tuberculin compared to healthy subjects. Such patients have low B-cell level when they are free of antigen HLA-DR4. Carriers of HLA-DR2 antigen exhibit inhibited specific cellular immunity compared to those without this antigen.
HLA-DR2 Antigen
OBJECTIVE: Most previous studies have failed to demonstrate any mutations in the type II 3beta hydroxysteroid dehydrogenase (HSD3B2) gene in patients satisfying the hormonal criteria of nonclassic 3beta-hydroxysteroid dehydrogenase deficiency, suggesting that a mutant 3beta-hydroxysteroid dehydrogenase protein is not the cause of this disorder. We screened the HSD3B2 gene for mutations in girls with premature pubarche and a hormonal diagnosis of 3beta-hydroxysteroid dehydrogenase deficiency. DESIGN: From 30 girls with premature pubarche, we selected 9 whose ACTH-stimulated 17-hydroxypregnenolone levels were elevated (> or =6 SD) and screened the HSD3B2 gene for mutations. MEASUREMENTS: All patients were submitted to a standard ACTH stimulation test. Serum steroids were measured and compared to the mean level of pubertal stage matched control subjects. The four exons and exon-intron boundaries of the HSD3B2 gene were amplified by polymerase chain reaction and screened for mutations by denaturing gradient gel electrophoresis. The fragments with abnormal migration on denaturing gradient gel electrophoresis were directly sequenced. RESULTS: A homozygous T259M mutation was identified in one girl and a new compound heterozygous G129R/P222H mutation was identified in two sisters. The highest ACTH-stimulated 17-hydroxypregnenolone levels, 147, 339 and 351 nmol/l, were found in those patients with mutations in the HSD3B2 gene. In the patients without mutations, ACTH-stimulated 17-hydroxypregnenolone ranged from 48 to 111 nmol/l. ACTH-stimulated dehydroepiandrosterone levels had an overlap among the girls with and without mutations and the normal controls. CONCLUSIONS: Premature pubarche can be caused by mutations in the type II 3beta hydroxysteroid dehydrogenase gene.
17-alpha-Hydroxypregnenolone
Acetyl xylan esterase (AXE) catalyzes the hydrolysis of the acetyl bonds present in plant cell wall polysaccharides. Here, we determined the crystal structure of AXE from Aspergillus luchuensis (AlAXEA), providing the three-dimensional structure of an enzyme in the Esterase_phb family. AlAXEA shares its core alpha/beta-hydrolase fold structure with esterases in other families, but it has an extended central beta-sheet at both its ends and an extra loop. Structural comparison with a ferulic acid esterase (FAE) from Aspergillus niger indicated that AlAXEA has a conserved catalytic machinery: a catalytic triad (Ser119, His259, and Asp202) and an oxyanion hole (Cys40 and Ser120). Near the catalytic triad of AlAXEA, two aromatic residues (Tyr39 and Trp160) form small pockets at both sides. Homology models of fungal FAEs in the same Esterase_phb family have wide pockets at the corresponding sites because they have residues with smaller side chains (Pro, Ser, and Gly). Mutants with site-directed mutations at Tyr39 showed a substrate specificity similar to that of the wild-type enzyme, whereas those with mutations at Trp160 acquired an expanded substrate specificity. Interestingly, the Trp160 mutants acquired weak but significant type B-like FAE activity. Moreover, the engineered enzymes exhibited ferulic acid-releasing activity from wheat arabinoxylan.IMPORTANCE Hemicelluloses in the plant cell wall are often decorated by acetyl and ferulic acid groups. Therefore, complete and efficient degradation of plant polysaccharides requires the enzymes for cleaving the side chains of the polymer. Since the Esterase_phb family contains a wide array of fungal FAEs and AXEs from fungi and bacteria, our study will provide a structural basis for the molecular mechanism of these industrially relevant enzymes in biopolymer degradation. The structure of the Esterase_phb family also provides information for bacterial polyhydroxyalkanoate depolymerases that are involved in biodegradation of thermoplastic polymers.
Acetylesterase
OBJECTIVES: In the context of the ongoing overdose crisis, a stark increase in toxic drug deaths from the unregulated street supply accompanied the onset of the COVID-19 pandemic. Injectable opioid agonist treatment (iOAT - hydromorphone or medical-grade heroin), tablet-based iOAT (TiOAT), and safer supply prescribing are emerging interventions used to address this crisis in Canada. Given rapid clinical guidance and policy change to enable their local adoption, our objectives were to describe the state of these interventions before the pandemic, and to document and explain changes in implementation during the early pandemic response (March-May 2020). METHODS: Surveys and interviews with healthcare providers comprised this mixed methods national environmental scan of iOAT, TiOAT, and safer supply across Canada at two time points. Quantitative data were summarized using descriptive statistics; interview data were coded and analyzed thematically. RESULTS: 103 sites in 6 Canadian provinces included 19 iOAT, 3 TiOAT and 21 safer supply sites on March 1, 2020; 60 new safer supply sites by May 1 represented a 285% increase. Most common substances were opioids, available at all sites; most common settings were addiction treatment programs and primary care clinics, and onsite pharmacies models. 79% of safer supply services were unfunded. Diversity in service delivery models demonstrated broad adaptability. Qualitative data reinforced the COVID-19 pandemic as the driving force behind scale-up. DISCUSSION: Data confirmed the capacity for rapid scale-up of flexible, community-based safer supply prescribing during dual public health emergencies. Geographical, client demographic, and funding gaps highlight the need to target barriers to implementation, service delivery and sustainability.
Harm Reduction
The third stage (the infective stage) of both species, Neoheligmonella dossoi and N. tranieri, appears simultaneously in the coprocultures in two different forms: sheathed larvae and exsheathed larvae. The exsheathed larvae show a much higher infection rate than the sheathed ones, but the last ones could exsheathed under some conditions. These larvae are called: larvae exsheathed by aging". The percentage of exsheathed larvae is higher from April to October, this period corresponding to the rainy season on the Ivory Coast. Considering the host biological characteristics (sedentary, isolated, humid burrows) and the fact that the infection lasts 2 to 4 months, the transmission of the two Trichostrongylid species seems particularly well adapted to local conditions. Transmission appears to follow two infestation strategies, depending on the season: --A "rainy season strategy" characterized by an important initial production of larvae of which a great number are exsheathed larvae, with strong infective potential. --A "dry season strategy" characterized by sheathed larvae, produced more regularly, having a weaker infective potential, and able to exsheathe progressively."
Trichostrongyloidea
BACKGROUND: In an automated dose dispensing (ADD) service, medicines are packed in unit-dose bags according to administration times. When the service is initiated, the patient's medication list is reconciled and the medication is reviewed on the basis of this list. OBJECTIVE: The aim of this national study was to investigate how the medication list was reconciled, what type of medication review was conducted, and what changes were made to the patient's medications when the ADD service is initiated. SETTING: Primary care in Finland. METHOD: All patients enrolled in the service during a 3-week period in autumn 2010 were included in the study. All community pharmacies (n = 267) purchasing unit-dose bags from Espoonlahti Pharmacy documented the actions taken in the ADD initiation process using a structured data collection sheet. MAIN OUTCOME MEASURE: Information sources needed in medication reconciliation, the type of medication review conducted and changes made to patients' medications. RESULTS: Documentation was completed for 147 out of 325 new ADD users resulting 45 % as a response rate. More than one source was needed for 63 % of the patients in medication reconciliation. The most common sources used were nursing staff (72 % of the patients) and an existing medication list (71 %). Some type of medication review, most commonly a prescription review, was conducted for the majority of the patients (96 %), usually in multi-professional collaboration. Treatment-related changes were made for 43 % of the patients and technical changes were made for 93 % of the patients. CONCLUSION: The medication list was incomplete for more than half of the patients. Some type of medication review was conducted for most of the patients. Both treatment-related changes and technical changes were made on patients' medications during the initiation process. The start-up process of the ADD service needs further development to ensure a standard procedure and optimum use of resources.
Medication Systems
AIMS: Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesized that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality. METHODS AND RESULTS: Withdrawal of dietary creatine in AGAT-/- mice provided an estimate of myocardial creatine efflux of approximately 2.7%/day; however, in vivo cardiac function was maintained despite low levels of myocardial creatine. Using AGAT-/- mice naive to dietary creatine we confirmed absence of phosphocreatine in the heart, but crucially, ATP levels were unchanged. Potential compensatory adaptations were absent, AMPK was not activated and respiration in isolated mitochondria was normal. AGAT-/- mice had rescuable changes in body water and organ weights suggesting a role for creatine as a compatible osmolyte. Creatine-naive AGAT-/- mice had haemodynamic impairment with low LV systolic pressure and reduced inotropy, lusitropy, and contractile reserve. Creatine supplementation only corrected systolic pressure despite normalization of myocardial creatine. AGAT-/- mice had low plasma HA and supplementation completely rescued all other haemodynamic parameters. Contractile dysfunction in AGAT-/- was confirmed in Langendorff perfused hearts and in creatine-replete isolated cardiomyocytes, indicating that HA is necessary for normal cardiac function. CONCLUSIONS: Our findings argue against low myocardial creatine per se as a major contributor to cardiac dysfunction. Conversely, we show that HA deficiency can impair cardiac function, which may explain why low HA is an independent risk factor for multiple cardiovascular diseases.
Amidinotransferases
AIM: To study liver cell apoptosis caused by the toxicity of selenium and observe the alteration of choline compounds using in vitro 9.4T high resolution magnetic resonance spectroscopy. METHODS: Twenty male Wistar rats were randomly divided into two groups. The rats in the treatment group were intraperitoneally injected with sodium selenite and the control group with distilled water. All rats were sacrificed and the livers were dissected. (1)H-MRS data were collected using in vitro 9.4T high resolution magnetic resonance spectrometer. Spectra were processed using XWINNMR and MestRe-c 4.3. HE and TUNEL staining was employed to detect and confirm the change of liver cells. RESULTS: Good (1)H-MR spectra of perchloric acid extract from liver tissue of rats were obtained. The conventional metabolites were detected and assigned. Concentrations of different ingredient choline compounds in treatment group vs control group were as follows: total choline compounds, 5.08 +/- 0.97 mmol/L vs 3.81 +/- 1.16 mmol/L (P = 0.05); and free choline, 1.07 +/- 0.23 mmol/L vs 0.65 +/- 0.20 mmol/L (P = 0.00). However, there was no statistical significance between the two groups. The hepatic sinus and cellular structure of hepatic cells in treatment group were abnormal. Apoptosis of hepatic cells was confirmed by TUNEL assay. CONCLUSION: High dose selenium compounds can cause the rat liver lesion and induce cell apoptosis in vivo. High resolution (1)H-MRS in vitro can detect diversified metabolism. The changing trend for different ingredient of choline compounds is not completely the same at early period of apoptosis.
Sodium Selenite
Upper authorities have tightly controlled local budgets, especially at the administrative township level. Taiwan has been facing this particular phenomenon for a long period. This article explains how a township, before general elections, sees the choice of an improved environmental administrative work plan as a political advantage and uses simple and easy-to-use collective decision-making to assist. Then, survey residents' perceptions of implementing the new environmental policy. The research results are discussed not only as suggestions to improve the effectiveness of township public environmental policies and to respond to the needs of civilians appropriately but also to lead future research directions.
Policy
The development of novel and increasingly safer vaccines frequently utilizes well-characterized antigens, in particular highly purified proteins or synthetic peptides. In spite of some achievements, this approach is frequently impeded by the fact that such antigens are often poor immunogens when administered alone. This fact has necessitated the development of suitable adjuvants that possess the ability to enhance the immunogenicity of a given antigen, preferably with little or no side effects. This paper discusses one of the successes of vaccinology of the past decade: virosomal vaccines. The principles of the concept, immunoadjuvant action and application of virosomes in two currently licensed vaccines are detailed, with specific reference to the induction of both humoral and cellular immunity.
Virosomes
BACKGROUND: The positive effects of nitrogen fertilization on the performance of phytophagous insects have been reported extensively; the physiological and molecular basis involved, however, is largely unclear. Here, we test experimentally whether enhancement of juvenile hormone (JH) is responsible for the increased weight and fecundity of pea aphid (Acyrthosiphon pisum) under nitrogen fertilization. RESULTS: Aphids fed on Medicago truncatula with nitrogen fertilization have a greater amino acid content, higher weight at the fourth instar and adult stage, and produce more offspring than those without nitrogen fertilization. Furthermore, nitrogen fertilization upregulates the transcripts of JH biosynthesis-related genes and increases JH titre at the fourth instar and adult stage, suggesting that JH is involved in the positive responses of aphids to nitrogen fertilization. Application of 100 ng JH increases adult weight and fecundity in aphids fed on M. truncatula without nitrogen fertilization. Conversely, impairing JH signalling by pharmacologically inhibiting the target of rapamycin pathway or by knocking down JH biosynthetic gene decreases adult weight and fecundity in aphids fed on M. truncatula with nitrogen fertilization, whereas application of JH rescued the phenotype. CONCLUSION: The increased JH titre at the fourth instar and adult stage is required for the increases of weight and fecundity of A. pisum under nitrogen fertilization. (c) 2018 Society of Chemical Industry.
Nymph
The effect of dehydration and (2)H2O/H2O isotope substitution on electron transport reactions and relaxation of proton-containing groups was studied in chromatophore membranes of Ectothiorhodospira shaposhnikovii. During dehydration (including isotope substitution of hydrate water) of preliminarily dehydrated isolated photosynthetic membranes there was a partial correlation between hydration intervals within which activation of electron transport from high-potential cytochrome c to photoactive bacteriochlorophyll dimer P890 of photosynthetic reaction center and variation of spin-lattice and spin-spin proton relaxation time was observed. Partial correlation between hydration intervals can be considered as evidence of correlation between mobility of non-water proton-containing groups with proton relaxation frequency approximately 10(8) sec(-1) with efficiency of electron transfer at the donor side of the chain."
Ectothiorhodospira shaposhnikovii
Even though the absence of the body prevents sure conclusions, the death of Alexander the Great remains a hot topic of retrospective diagnosis. Due to the serious mishandling of ancient sources, the scientific literature had Alexander dying of every possible natural cause. In previous works, the hypothesis that typhoid fever killed Alexander was proposed, based on the presence of the remittent fever typical of this disease in the narrations of Plutarch and Arrian. Here we provide additional evidence for the presence of stupor, the second distinctive symptom of typhoid fever. In fact, based on the authority of Caelius Aurelianus and Galen, we demonstrate that the word ἄphiomeganuomicronvarsigma, used to describe the last moments of Alexander, is a technical word of the lexicon of the pathology of Hippocrates. Used by him, the word defines a group of diseases sharing a serious depression of consciousness and motility. The association of stupor with the remittent fever strengthens the typhoid fever hypothesis.
Stupor
BACKGROUND/OBJECTIVES: Prior research indicates that younger adults overestimate their peers' engagement in risk-taking behaviours, with these estimates being directly associated with engagement in such behaviours. However, the extent to which younger adults perceive their peers' approval of, and engagement in, road traffic violations (such as mobile phone use while driving) is yet to be clearly identified. Further, the influence of such perceptions on subsequent mobile phone use while driving behaviours remains unclear. Accordingly, the aim of this systematic review was to (a) examine young drivers' perceptions regarding their peers' approval of (injunctive norms), and engagement in (descriptive norms) mobile phone use while driving and (b) to identify whether such perceptions increase young drivers own engagement in the behaviour. METHODS: Studies were eligible for review if they measured (a) perceived social norms (descriptive/injunctive) and (b) the relationship between such norms and mobile phone use while driving in younger adults aged 16-25 years. Searches were conducted in December 2021, using Pubmed, Scopus, Web of Science, and TRID. Five articles were included in the review. RESULTS: Overall, the results indicate that young drivers perceive their peers to engage in mobile phone use while driving on a frequent basis, however they typically believe that their peers disapprove of the behaviour. The majority of studies indicated that descriptive norms were significantly associated with increasing engagement in mobile phone use while driving (including distracted driving behaviours). Finally, the few studies that investigated injunctive norms on mobile phone use while driving indicated positive correlations between perceived peer approval and increasing distracted driving behaviour. DISCUSSION: The findings highlight the importance of social norms in influencing behaviour, indicating that both descriptive and injunctive norms warrant further investigation when examining the impact of peer influences on mobile phone use while driving.
Cell Phone Use
INTRODUCTION: Oxalobacter formigenes, as a gram-negative anaerobic bacterium, metabolizes oxalate in the intestine by the enzymes oxalyl-CoA decarboxylase (OXC) and formyl-CoA transferase (FRC). Therefore, not only the presence of the bacterium but also microbial load may affect intestinal absorption and urinary exertion. We evaluated the relationship between Oxalobacter formigenes load and the formation of calcium oxalate urolithiasis using quantitative molecular methods. METHODS: By clinical manifestation and stone analysis, we selected the urine and stool specimens of 73 patients with calcium oxalate urolithiasis. First, the gene regions of the two genes FRC and OXC in Oxalobacter formigenes were selected utilizing bioinformatics and specific primers designed for these regions. Following DNA extraction from stool specimens by specific primers of each gene, PCR was carried out and positive samples were sequenced. Then, qPCR was applied to determine the effective load of Oxalobacter. Also, biochemical tests were performed to measure the excretion rate of oxalate in urine specimens. RESULTS: In addition to oxalobacter identification by PCR, the load of bacteria was quantitatively assessed using qPCR by specific primers for both FRC and OXC gene regions. A significant negative relationship had found between the formation of calcium oxalate urolithiasis and the presence of Oxalobacter formigenes in patients with kidney stone disease. The mean excretion of oxalate and citrate in urolithiasis cases were 22.93 and 552.106 mg/24h, respectively. CONCLUSION: The presence of Oxalobacter formigenes can highly inhibit the generation of calcium oxalate urolithiasis. Furthermore, molecular techniques are more effective than other methods such as culture for the isolation of this bacterium.
Oxalobacter formigenes
Rickettsia are small, obligately intracellular, gram-negative bacilli. They are distributed among a variety of hematophagous arthropod vectors and cause illness throughout the world. Rickettsioses present as an acute undifferentiated febrile illness and are often accompanied by headache, myalgias, and malaise. Cutaneous manifestations include rash and eschar, which both occur at varying incidence depending on the infecting species. Serology is the mainstay of diagnosis, and the indirect immunofluorescence assay is the test of choice. Reactive antibodies are seldom present during early illness, so testing should be performed on both acute-phase and convalescent-phase sera. Doxycycline is the treatment of choice.
Rickettsia Infections
Glycine decarboxylase, a constituent of the glycine cleavage system, in patients with either nonketotic or ketotic hyperglycinemia (NKH and KH) was examined using an anti-chicken glycine decarboxylase antibody. Patients with NKH who have lesion in glycine decarboxylase are differentiated by its expressed level in the liver. One group is cases of the neonatal onset type who have neither activity of the enzyme nor protein reactive to the antibody. The other is a case of the late onset type who shows low but detectable activity of the enzyme and the desirable amount of the immunoreactive material. In the liver of a patient with KH not showing the appreciable activity of H-protein, ubiquitous amount of protein reactive to anti-H-protein IgG is detected and amount of glycine decarboxylase has also been lowered. It is suggested that several mechanisms may be involved in determining the expressed level of glycine decarboxylase in patients with hyperglycinemias.
Glycine Decarboxylase Complex
Derivatives of the nonselective excitatory amino acid antagonist kynurenic acid (4-oxo-1,4-dihydroquinoline-2-carboxylic acid, 1) have been synthesized and evaluated for in vitro antagonist activity at the excitatory amino acid receptors sensitive to N-methyl-D-aspartic acid (NMDA), quisqualic acid (QUIS or AMPA), and kainic acid (KA). Introduction of substituents at the 5-, 7-, and 5,7-positions resulted in analogues having selective NMDA antagonist action, as a result of blockade of the glycine modulatory (or coagonist) site on the NMDA receptor. Regression analysis suggested a requirement for optimally sized, hydrophobic 5- and 7-substituents, with bulk tolerance being greater at the 5-position. Optimization led to the 5-iodo-7-chloro derivative (53), which is the most potent and selective glycine/NMDA antagonist to date (IC50 vs [3H]glycine binding, 32 nM; IC50's for other excitatory amino acid receptor sites, greater than 100 microM). Substitution of 1 at the 6-position resulted in compounds having selective non-NMDA antagonism and 8-substituted compounds were inactive at all receptors. The retention of glycine/NMDA antagonist activity in heterocyclic ring modified analogues, such as the oxanilide 69 and the 2-carboxybenzimidazole 70, suggests that the 4-oxo tautomer of 1 and its derivatives is required for activity. Structurally related quinoxaline-2,3-diones are also glycine/NMDA antagonists, but are not selective and are less potent than the 1 derivatives, and additionally show different structure-activity requirements for aromatic ring substitution. On the basis of these results, a model accounting for glycine receptor binding of the 1 derived antagonists is proposed, comprising (a) size-limited, hydrophobic binding of the benzene ring, (b) hydrogen-bond acceptance by the 4-oxo group, (c) hydrogen-bond donation by the 1-amino group, and (d) a Coulombic attraction of the 2-carboxylate. The model can also account for the binding of quinoxaline-2,3-diones, quinoxalic acids, and 2-carboxybenzimidazoles.
Xanthurenates
In response to a sound stimulus, the inner ear emits sounds called otoacoustic emissions. While the exact mechanism for the production of otoacoustic emissions is not known, active motion of individual hair cells is thought to play a role. Two possible sources for otoacoustic emissions, both localized within individual hair cells, include somatic motility and hair bundle motility. Because physiological models of each of these systems are thought to be poised near a Hopf bifurcation, the dynamics of each can be described by the normal form for a system near a Hopf bifurcation. Here we demonstrate that experimental results from three-frequency suppression experiments can be predicted based on the response of an array of noninteracting Hopf oscillators tuned at different frequencies. This supports the idea that active motion of individual hair cells contributes to active processing of sounds in the ear. Interestingly, the model suggests an explanation for differing results recorded in mammals and nonmammals."
Otoacoustic Emissions, Spontaneous
Clinically, there is strong rationale for developing a method which will provide a scientific basis for comparing the efficacy of one hyperthermia treatment with another. In order to accomplish this goal, methods must first be developed which will allow the clinician to know the three-dimensional temperature distribution in heated tissue. In this paper, examples of how this goal can be achieved are presented. Techniques for compensating for various modifiers of hyperthermia effectiveness are proposed. The limitations and advantages of these approaches are described and directions for future research are discussed.
Neoplasms, Experimental
BACKGROUND: Previous studies demonstrated positive relations between various forms of maltreatment and suicidal ideation in youth; however, mechanisms underlying these relationships are not well understood. We propose that the experience of maltreatment in childhood may lead to high levels of generalized guilt and shame, resulting in an increase of depressive symptoms and suicidal thoughts in adolescents. The aim of the current study was to test our model of relations between these constructs using path analysis. METHODS: 112 inpatient adolescents aged 12-17 years completed the Childhood Trauma Questionnaire to measure various types of maltreatment, the Personal Feelings Questionnaire to evaluate generalized guilt and shame, the Beck Depression Inventory-II to assess depressive symptoms, and the Columbia-Suicide Severity Rating Scale to assess suicidal ideation. RESULTS: Findings partly confirmed the theoretical model. Indirect positive effects of sexual and emotional abuse, as well as emotional and physical neglect on suicidal ideation via generalized self-conscious emotion and/or depression were demonstrated. In contrast to our predictions, indirect negative effects of physical abuse on suicidal thoughts via generalized guilt and shame and depression were found. LIMITATIONS: Sample characterized by predominately Caucasian inpatient adolescents from financially stable and well-educated environments, over-reliance on self-report measures and the lack of a longitudinal design were main limitations of the study. CONCLUSIONS: The study provides novel information on the potential mechanisms underlying the association between childhood maltreatment and suicidal ideation in adolescents. Generalized guilt and/or shame could be possible targets for interventions for victims of some forms of maltreatment to reduce depressive symptoms and suicidal ideation.
Guilt
Reactive arthritis (ReA) is a form of inflammatory arthritis triggered by a remote antecedent infection, usually in the genitourinary or gastrointestinal tract. It is part of the spondyloarthropathy (SpA) spectrum, an umbrella term for a group of distinct conditions with shared clinical features. Typically, it presents with an asymmetric oligoarthritis of the lower limb joints, and patients may also have sacroiliitis, enthesitis and dactylitis. Other features often seen include anterior uveitis, urethritis and skin manifestations such as pustular lesions on the plantar areas. Although ReA was characterised initially as a sterile arthritis, the detection of metabolically active Chlamydia species in the joint fluid of some affected patients has generated further questions on the pathophysiology of this condition. There are no formal diagnostic criteria, and the diagnosis is mainly clinical. HLA-B27 can support the diagnosis in the correct clinical context, and serves as a prognostic indicator. The majority of patients have a self-limiting course, but some develop chronic SpA and require immunomodulatory therapy.
Post-Infectious Disorders
PURPOSE: To evaluate the effects of dietary caffeine intake and withdrawal on cerebral blood flow (CBF), as determined from a randomized, blinded, placebo-controlled study. MATERIALS AND METHODS: Twenty adults (16 men, four women; age range, 24-64 years) categorized as low (mean, 41 mg/d) or high (mean, 648 mg/d) caffeine users underwent quantitative flow-sensitive alternating inversion-recovery perfusion magnetic resonance (MR) imaging twice: 90 minutes after a dose of caffeine (250 mg) on one day and after a dose of placebo on another day (randomized counterbalanced design). Doses were preceded by 30 hours of caffeine abstinence to induce withdrawal in high caffeine users. Quantitative CBF maps were gray matter (GM)-white matter (WM) segmented and subjected to region-of-interest analysis to obtain mean CBF in WM, anterior circulation GM (AGM), and posterior circulation GM (PGM). By using two-way repeated-measures analysis of variance, regional CBF data were tested for within-subject differences between caffeine and placebo and for between-subject differences related to dietary caffeine habits. Linear regression was used to determine whether dietary caffeine use predicts CBF or CBF response to caffeine. RESULTS: Caffeine reduced CBF (P < or =.05) by 23% (AGM, PGM) and 18% (WM) in all subjects. Postplacebo (withdrawal) CBF in high caffeine users exceeded that in low users (P < or =.05) by 31% (AGM) and 32% (WM) (PGM, not significant). Mean postcaffeine CBF reduction in AGM was 26% in high users versus 19% in low users (P < or =.05; PGM and WM, not significant). Increasing caffeine consumption predicted higher CBF (P < or =.05) in all regions: r = 0.79 (AGM), 0.57 (PGM), and 0.76 (WM). Dietary caffeine use did not predict CBF response to caffeine. CONCLUSION: Dietary caffeine consumption and withdrawal are potential confounding variables in cerebral perfusion and functional MR imaging.
Cerebrovascular Circulation
The infralimbic (IL) and prelimbic (PL) cortices of the medial prefrontal cortex (mPFC) have been shown to differentially control context-dependent behavior, with the PL implicated in the expression of contextually conditioned fear and drug-seeking, and the IL in the suppression of these behaviors. However, the roles of these subregions in contextually driven natural reward-seeking remain relatively underexplored. The present study further examined the functional dichotomy within the mPFC in the contextual control over cued reward-seeking, using a contextual biconditional discrimination (CBD) task. Rats were first trained to emit a nose poke response to the presentation of an auditory stimulus (e.g., X) for the delivery of sucrose reward, and to withhold a nose poke response to the presentation of another auditory stimulus (e.g., Y) in a context-specific manner (e.g. Context A: X+, Y-; Context B: X-, Y+). Following acquisition, rats received bilateral microinjections of GABA receptor agonists (muscimol and baclofen), or saline into the IL or PL, prior to a CBD training session and a probe test (under extinction conditions). Both IL and PL inactivation resulted in robust impairment in CBD performance, indicating that both subregions are involved in the processing of appetitively motivated contextual memories in reward-seeking.
Drug-Seeking Behavior
The construction of novel efficient catalysts for the treatment of organic pollutants in the aqueous environment is essential. The lamellar-like Cu-Al layered double hydroxides (CuAl-LDHs) with various mole ratios were synthesized by a simple route of co-precipitation, and the corresponding degradation characteristic was tested for the removal of tetracycline (TC) using PMS activation. The degradation efficiency of TC over CuAl-LDHs increased up to 93% within 10 min for the Cu/Al mole ratio of 3:1 and almost not changed at a higher mole ratio. For further calcining the optimal catalyst at 300 ℃, the degradation efficiency of TC was found to be increased to 96%. Sulfuric radicals and singlet oxygen were analyzed to be the main reason for the change in degradation characteristics, which was proved by radical quenching experiments and electron paramagnetic resonance technique. The parameters including PMS concentration, catalyst dosage, and reaction temperature on the TC degradation as well as the degradation mechanism for PMS activation were elaborated. The best proportion of CuAl-LDHs owned splendid stability and catalytic activity after reusing, which showed enormous potential in practical application.
Anions