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Ticks are ectoparasites that cause dermatologic disease directly by their bite and indirectly as vectors of bacterial, rickettsial, protozoal, and viral diseases. In North America, where ticks are the leading cause of vector-borne infection, dermatologists should recognize several tick species. Basic tick biology and identification will be reviewed. Tick bites cause a variety of acute and chronic skin lesions. The tick-borne diseases include Lyme disease, tick-borne relapsing fever, tularemia, babesiosis, Rocky Mountain spotted fever, other spotted fevers, ehrlichiosis, Colorado tick fever, and others. The epidemiology, clinical features, diagnosis, and treatment of these diseases are reviewed with an emphasis on cutaneous manifestations. Finally, the prevention of diseases caused by ticks is reviewed. | Vector Borne Diseases |
A method for cobalt-catalyzed, aminoquinoline- and picolinamide-directed C(sp(2))-H bond alkenylation by alkynes was developed. The method shows excellent functional-group tolerance and both internal and terminal alkynes are competent substrates for the coupling. The reaction employs a Co(OAc)2âÂÂ
4 H2O catalyst, Mn(OAc)2 co-catalyst, and oxygen (from air) as a terminal oxidant. | Picolinic Acids |
BACKGROUND: The differences in the clinical and functional outcomes of closed reduction and percutaneous pin fixation and open reduction with internal fixation (ORIF) using plate and screws have been systematically synthesized by one meta-analysis. With newer studies being published, an effort to update the earlier meta-analysis is necessary. METHODS: Comprehensive searches were done systematically through PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), and Google scholar databases. Randomized controlled trials, quasi-experimental studies, prospective comparative non-randomized studies, and even studies reporting findings from retrospective chart review were eligible to be included. Statistical analysis was done using STATA version 13.0. GRADE assessment was done to assess the quality of pooled evidence. RESULTS: A total of 9 studies were included. The pooled estimates did not suggest any significant differences in the disabilities of the arm, shoulder, and hand (DASH) score [WMD - 0.77; 95% CI, - 3.55, 2.00; I(2) = 75.5%], range of movement (ROM) of the metacarpophalangeal joint ((o)) [WMD 4.44; 95% CI, - 4.19, 13.07; I(2) = 86.0%], and grip strength [WMD - 4.63; 95% CI, - 14.52, 5.26; I(2) = 86.9%] among the two intervention modalities. No difference was seen in the risk of complications between the two interventions (RR 0.93; 95% CI, 0.57, 1.53; I(2) = 31.2%). For all the outcomes, the quality of pooled evidence was judged as low to very low. CONCLUSION: No significant long-term differences were noted in the functional outcomes suggesting that both these techniques are comparable. The choice of modality should be made based on the skills and preference of the surgeon and availability of resources. | Metacarpal Bones |
This study aims to review the global mortality secondary to laryngeal edema in patients diagnosed with hereditary angioedema and their relatives over the years, as well as to describe epidemiological and clinical findings associated with this outcome. An extensive search of the literature was made in PubMed, Scopus, and Embase to identify mortality rates secondary to laryngeal edema in patients with hereditary angioedema. The search was carried out in September of 2020 and in April of 2021, and keywords based on the MeSH terms were searched in three databases. The filter of language was used for finding only articles in English, and there was no limit to the year of publication. A total of twenty-three articles fulfilled the inclusion criteria for review and data extraction. The analyzed studies included 3292 patients and 411 deaths from asphyxia due to laryngeal edema. One hundred and three deaths in close relatives were described as secondary to the same cause. The main findings were summarized in tables: year and place of publication, the number of patients and deaths from laryngeal edema, patients previously diagnosed, and death age. Death rates from laryngeal edema had an average of one death for every 20 patients. Eight studies reported deaths in relatives. For every 7.4 patients in these studies, one relative died. The percentage among deaths in general associated with laryngeal edema was evaluated in three studies (32.7%, 44.4%, and 56%). The high frequency of this outcome suggests that deaths still occur, and improvement of hereditary angioedema treatment still needs to be met." | Hereditary Complement Deficiency Diseases |
INTRODUCTION: Intramuscular Immune Serum Globulin (IM ISG) is recommended as post-measles exposure prophylaxis (PEP) when administered within 6days of initial exposure, with variable effectiveness in preventing measles disease. Effectiveness of IM ISG PEP in preventing clinical measles was assessed during a 2014 measles outbreak among a religious-affiliated community in British Columbia, Canada. MATERIAL AND METHODS: Fifty-five self-reporting measles susceptible contacts were offered exclusively IM ISG PEP within an eligibility period best surmised to be within 6days of initial measles case exposure. Clinical outcome of IM ISG PEP recipients was determined by selective active surveillance and case self-reporting. IM ISG PEP failure was defined as onset of a measles-like rash 8-21days post-IM ISG PEP. Post-IM ISG PEP measles IgG antibody level was tested in 8 recipients. Factors associated with measles disease were analyzed. RESULTS: Seventeen of 55 IM ISG PEP recipients developed clinically consistent measles in the following 8-21days, corresponding to an estimated crude protective effectiveness of 69%. In school aged children 5-18years, among whom potential exposure intensity and immune status confounders were considered less likely, estimated IM ISG PEP protective effectiveness was 50%. Age <25years was significantly associated with breakthrough clinical measles in bivariate analysis (p=0.0217). Among 8 tested contacts of 17 considered IM ISG PEP failures, post-IM ISG PEP measles IgG antibody levels (mean 16.3days (range 16-17days) post-PEP) were all <150mIU/ml. CONCLUSIONS: The estimated crude IM ISG PEP protective effectiveness against measles disease within 8-21days post-ISG administration was 69%. Accuracy of this estimated protective effectiveness is vulnerable to assumptions and uncertainties in ascertaining exposure details and pre-exposure immune status. Increasing the Canadian recommended measles IM ISG PEP dose from 0.25 to 0.5ml/kg (up to 15ml maximum volume) may increase protective effectiveness. | Post-Exposure Prophylaxis |
Continuous infusion of chemotherapy is one of the developments to try to improve the treatment of metastatic cancer. There is a sound theoretical rationale to deliver cytotoxic drugs as a continuous infusion. Furthermore, the development of reliable venous access devices and portable infusion pumps enables patients to be treated in an ambulatory setting. This review focuses on the continuous infusion of the most frequently used drugs: 5-fluorouracil (5-FU) and fluorodeoxyuridine (FUDR). An overview is given of both preclinical studies and studies in humans. Continuous infusion of 5-FU and FUDR has proven to be feasible in all studies. However, the results (response rate and especially survival) are rather disappointing. So far, continuous infusion of cytostatic drugs can still be considered as an experimental procedure. Whether protracted, intermittent of circadian modulated continuous infusion is the optimal treatment schedule has still to be proven in future studies. Furthermore, studies are needed to demonstrate whether dose intensity for most tumours is important for treatment outcome. Also, studies are needed to investigate quality of life and economic issues. | Floxuridine |
OBJECTIVES: This paper aims at covering a literature gap on the effects of copayments, prescription quotas and therapeutic reference pricing on public and private expenditures and volumes (1) When these policies are implemented in different areas at different times, (2) estimating their impact in the short and long run, (3) assessing the extent to which these impacts are interdependent, (4) scrutinising the extent to which the effects are mediated by prescribers' and patients' behaviours. METHODS: Monthly regional data on pharmaceutical expenditures, volumes and policies in Italy from 2000 to 2014 are analysed using a difference-in-differences model enriched to capture short- versus long-term effects and simultaneous and interactive effects. Sobel-Goodman test and bootstrap analyses were used to test for mediation. RESULTS: The three policies have different short- and long-run effects. Interactions support the hypothesis of reinforcing effects. Behavioural reactions to policies such as reducing the demand or total per capita expenditures mediate the impact of policies, thus explaining the different effects between the short and long term. CONCLUSIONS: Evidence on the impact over time of regional policies diversely introduced in different times have important policy implications. First, pharmaceutical policies interact with each other, and the combined effect may be different from what we would expect from the sum of each single policy. Hence, policymakers should be very careful in designing mixed policies for their unexpected combined effects. Second, the impact of policies tends to reduce over time. If longer-term impact is desired, it would be appropriate to introduce some adjustments over time. Third, policies have multiple effects, and this should be considered when they are designed. Finally, pharmaceutical policies may have an unintended impact on health and health care. | Deductibles and Coinsurance |
Basigin may be involved in cardiovascular disease. In our previous study, suppression subtractive hybridization results indicated that basigin may be associated with the early phase of acute myocardial ischemia (AMI) within 1 h. However, little is known regarding the expression of basigin in the early phase of AMI. The aim of the present study was to evaluate the temporal and spatial expression patterns of basigin mRNA and protein levels in AMI in rats. We constructed an AMI model in rats that received left anterior descending coronary artery ligation for 0, 15, 30, 60, 120 or 240 min. RealâÂÂtime quantitative PCR and in situ hybridization (ISH) were conducted to reveal the basigin mRNA levels in the early ischemic myocardium (EIM) and nonâÂÂischemic myocardium (NIM). The expression levels of basigin protein were detected using western blot analysis and immunohistochemistry. The expression levels of basigin mRNA and protein significantly changed in the EIM as early as 30 min from ischemia, and the changes continued to be present throughout the ischemic period (P<0.05). The expression levels of basigin mRNA were significantly reduced, whilst those of the protein underwent a significant ~2-fold increase in the EIM. However, there were no significant differences in the basigin mRNA or protein expression levels from 0âÂÂ240 min in the NIM (P>0.05). We failed to detect a signal for basigin mRNA in the myocardium by ISH. Our findings indicated that basigin may be involved in acute myocardial ischemia following continual ischemia for >30 min. | Basigin |
(R)- as well as (S)-cyanohydrins are now easily available as a result of the excellent accessibility, the relatively high stability and the easy handling of hydroxynitrile lyases (HNLs). The optimization of reaction conditions (solvent, temperature, and using site-directed mutagenesis, etc.) has enabled HNL-catalyzed preparations of optically active cyanohydrins on a technical scale. The enantioselectivity of chiral metal-complex-catalyzed additions of trimethylsilyl cyanide to aldehydes has been improved, but is, by far, not yet competitive with the HNL-catalyzed reactions. | Aldehyde-Lyases |
Bone being a hierarchical composite material has a structure varying from macro- to nanoscale. The arrangement of the components of bone material and the bonding between fibers and matrix gives rise to its unique material properties. In this study, the micromechanisms of cortical bone failure were examined under different loading conditions using scanning electron microscopy. The experimental tests were conducted in longitudinal and transverse directions of bone diaphysis under tensile as well as compressive loading. The results show that bone material has maximum stiffness under longitudinal tensile loading, while the strength is higher under transverse compressive loading. A reverse trend of compressive mechanical properties of bone is observed for longitudinal and transverse loading as compared to trends reported in the previous studies. Therefore, micromechanisms of cortical bone failure were analyzed for different loading conditions to reveal such type of behavior of cortical bone and to correlate bone microstructure with mechanical response of bone. | Mechanical Phenomena |
During the last half of the 19th century dentistry in the Netherlands met little social appreciation. The charismatic leader of Dutch dentistry, Dr. Theodore Dentz, dentist and physician, took the initiative to found the first Dutch dental organisation in 1880. His goals were to improve the image of his profession, to strive for better education and to strengthen the bond between the best dentists in the country. After about 1910 changes in society and dentistry forced 'het Genootschap' to delegate their work in the field of social and professional representation to the newly founded Dutch Dental Association. After that time 'het Genootschap' converted itself into a scientific invitation society. | Societies, Dental |
Using a whole-cell voltage-clamp technique, we identified two time- and voltage-dependent K+ currents: an early outward rectifier and a delayed outward rectifier in single vascular smooth muscle cells of rabbit aorta in culture. About 90% of the single cells tested showed a predominant delayed outward K+ current type. Both K+ currents were decreased by tetraethylammonium. In contrast, bethanidine sulphate (10(-4)M), a pharmacological analog of the cardiac antifibrillatory drug, bretylium tosylate, decreased the early outward K+ current, increased the delayed rectifier K+ current type, and hyperpolarized the resting membrane potential. Bethanidine was found to relax vascular smooth muscle. The vasodilatory effect of bethanidine is associated with the activation of a K+ current that is probably involved in keeping the membrane potential at the resting state, thereby depressing the excitability of the aortic vascular smooth muscle. | Bethanidine |
Post-translational modifications of proteins control many biological processes through the activation, inactivation, or gain-of-function of the proteins. Recent developments in mass spectrometry have enabled detailed structural analyses of covalent modifications of proteins and also have shed light on the post-translational modification of superoxide dismutase. In this review, we introduce some covalent modifications of superoxide dismutase, nitration, phosphorylation, glutathionylaion, and glycation. Nitration has been the most extensively analyzed modification both in vitro and in vivo. Reaction of human Cu,Zn superoxide dismutase (SOD) with reactive nitrogen species resulted in nitration of a single tryptophan residue to 6-nitrotryptophan, which could be a new biomarker of a formation of reactive nitrogen species. On the other hand, tyrosine 34 of human MnSOD was exclusively nitrated to 3-nitrotyrosine and almost completely inactivated by the reaction with peroxynitrite. The nitrated MnSOD has been found in many diseases caused by ischemia/reperfusion, inflammation, and others and may have a pivotal role in the pathology of the diseases. Most of the post-translational modifications have given rise to a reduced activity of SOD. Since phosphorylation and nitration of SOD have been shown to have a possible reversible process, these modifications may be related to a redox signaling process in cells. Finally we briefly introduce a metal insertion system of SOD, focusing particularly on the iron misincorporation of nSOD, as a part of post-translational modifications. | Superoxide Dismutase |
Constraints on phenotypic variation limit the capacity of organisms to adapt to the multiple selection pressures encountered in natural environments. To better understand evolutionary dynamics in this context, we select Escherichia coli for faster migration through a porous environment, a process which depends on both motility and growth. We find that a trade-off between swimming speed and growth rate constrains the evolution of faster migration. Evolving faster migration in rich medium results in slow growth and fast swimming, while evolution in minimal medium results in fast growth and slow swimming. In each condition parallel genomic evolution drives adaptation through different mutations. We show that the trade-off is mediated by antagonistic pleiotropy through mutations that affect negative regulation. A model of the evolutionary process shows that the genetic capacity of an organism to vary traits can qualitatively depend on its environment, which in turn alters its evolutionary trajectory. | Escherichia coli |
A historical review is presented of the elucidation of the mechanisms of oxidation of inorganic sulphur compounds and of electron transport in the thiobacilli. A unitary mechanism, consistent with current knowledge, is proposed. The significance of polythionates is discussed. The relations between oxidation mechanisms, substrate-level and electron transport-dependent phosphorylation, energy-dependent NAD+ reduction and efficiency of growth are assessed in order to evaluate the efficiency of energy conservation in different species. The unresolved problems are identified for the benefit of those planning further assaults on the last redoubts of the thiobacilli." | Gram-Negative Chemolithotrophic Bacteria |
We developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion neurons using a retrograde fluorescence-tracing method, to record ATP-activated current in freshly isolated fluorescence-labeled neurons and to conduct single cell immunohistochemical staining for P2X1 and P2X3 subunits in the same neuron. Three types of ATP-activated current in these neurons (F, I and S) were recorded. The cells exhibiting the type F current mainly showed positive staining for P2X3, but negative staining for P2X1. The results provide direct and convincing evidence at the level of single native nociceptive neurons for correlation of the characteristics of ATP-activated currents with their composition of P2X1 and P2X3 subunits and cell size. The results also suggest that the P2X3, but not P2X1, is the main subunit that mediates the fast ATP-activated current in nociceptive neurons. | Receptors, Purinergic P2X3 |
Midkine is a heparin-binding growth factor highly expressed in various human malignant tumors. However, its role in the growth of oral squamous cell carcinoma is not well understood. In this study, we analyzed the antitumor effect of a novel midkine inhibitor (iMDK) against oral squamous cell carcinoma. Administration of iMDK induced a robust antitumor response and suppressed cluster of differentiation 31 (CD31) expression in oral squamous cell carcinoma HSC-2 cells and SAS cells xenograft models. iMDK inhibited the proliferation of these cells dose-dependently, as well as the expression of midkine and phospho-extracellular signal-regulated kinase in HSC-2 and SAS cells. Moreover, iMDK significantly inhibited vascular endothelial growth factor and induced tube growth of human umbilical vein endothelial cells in a dose-dependent fashion. These findings suggest that midkine is critically involved in oral squamous cell carcinoma and iMDK can be effectively used for the treatment of oral squamous cell carcinoma. | Midkine |
IMPORTANCE: Small cell lung cancer (SCLC) is an aggressive disease that is characterized by rapid growth and the early development of metastases. Patients typically respond to initial chemotherapy but quickly experience relapse, resulting in a poor long-term outcome. Therapeutic innovations that substantially improve survival have historically been limited, and reliable, predictive biomarkers are lacking. OBSERVATIONS: This review examines the biologic characteristics of SCLC, the current treatment landscape, and ongoing efforts to identify novel therapeutic targets. Ongoing research has advanced the understanding of molecular categories and the immunologic microenvironment of SCLC, which in turn has helped improve disease classification and staging. Recently, immunotherapy-based regimens have become available for the management of SCLC, with 2 programmed cell death 1 ligand 1 inhibitors approved in combination with chemotherapy for first-line treatment of extensive-stage disease. For second-line treatment, a novel alkylating agent, lurbinectedin, which inhibits oncogenic transcription, has been approved for use in patients with metastatic SCLC. Furthermore, a wide variety of therapies and innovative combination regimens are being continuously evaluated. Potential therapeutic strategies, including aurora kinase A inhibitors, polyadenosine diphosphate-ribose polymerase inhibitors, ataxia telangiectasia and Rad3-related inhibitors, cyclin-dependent kinase 7 inhibitors, delta-like protein 3 agents, antiganglioside agents, CD47 inhibitors, and lysine-specific histone demethylase 1a inhibitors, are also being examined. CONCLUSIONS AND RELEVANCE: Therapeutic optimization of SCLC remains a challenge, but recent trial results and drug approvals are encouraging. Advances in research have revealed critical information regarding biologic characteristics of the disease, which may lead to the identification of vulnerabilities and the development of new therapies. Further research focused on identifying biomarkers and evaluating innovative therapies will be paramount to improving treatment outcomes for patients with SCLC. | Small Cell Lung Carcinoma |
Malignant ascites is relatively common in patients with certain types of end-stage cancer. Traditional treatments based on fluid and salt restriction and diuretic therapy often are not able to contain neoplastic ascites. These patients consequently undergo repeated abdominal paracentesis, with further plasma protein loss and risk of injury to abdominal viscera. The aim of this study was to evaluate our experience with Denver peritoneovenous shunt and the outcome of patients with malignant ascites and suggest some modifications to improve device patency. From February 1997 to December 1999, 44 Denver peritoneovenous shunts were placed in 42 patients, 17 women and 25 men, aged between 38 and 77 years (mean, 62.3), affected with malignant ascites due to advanced abdominal cancer. At the time of admission, 72% of patients had pain, 88% dysphagia, 66% nausea and/or vomiting, and 83% dyspnea. Eleven patients underwent local anesthesia with lidocaine and 33 general anesthesia with rapidly metabolized drugs. In 27 cases we used the peritoneal-internal jugular right vein surgical approach and in 3 cases the peritoneal-femoral vein surgical access, joining the saphena vein to the cross. In 10 cases, a radiological positioning of the Denver peritoneovenous shunt was effected by a trans-subclavian access. Relief of ascites symptoms was obtained in 87.5% of cases, with reduction of dyspnea, an increased appetite and improved ambulation. Denver peritoneovenous shunt is a good device to relieve malignant ascites, thereby reducing the risk of complications and the number of hospital admissions due to repeated paracentesis and consequently improving the quality of life. A careful patient selection, an accurate follow-up and some device modifications could improve the shunt performance, allowing a wider application of the Denver peritoneovenous shunt. | Peritoneovenous Shunt |
In this paper, we examined the distribution pattern of D-aspartic acid (D-Asp), as well as D-aspartate oxidase (D-AspO), D-amino acid oxidase (D-AAO), and L-amino acid oxidase (L-AAO) activities in different tissues of frog, Rana esculenta. High concentrations of free D-Asp were found in the testes (0.21+/-0.02 micromol/g b.w), in the liver (0.20+/-0.03 micromol/g b.w), and in the Harderian gland (HG) (0.19+/-0.03 micromol/g b.w). A higher activity of both D-AspO and D-AAO with respect to L-AAO was endogenously present in all examined frog tissues, particularly within the kidney, liver, and brain. Our in vivo experiments, consisting of i.p. injections of 2.0 micromol/g b.w. D-Asp in frogs, revealed that all examined tissues can take up and accumulate D-Asp and that this amino acid specifically triggers D-AspO activity. Indeed, no increase in both D-AAO and L-AAO was found in all frog tissues after D-Asp treatment. The optimum pH for D-AspO activity was around 8.2 and the optimum temperature was about 37 degrees C. Furthermore, its activity linearly increased with increasing D-Asp incubation times. In vitro experiments assaying the substrate specificity of D-AspO indicated that the enzyme had greater affinity for N-methyl-D-aspartate than for D-Asp and D-glutamate. This study provides evidence of the presence of free D-Asp in frog R. esculenta tissues, along with its role in triggering D-AspO activity. These findings suggest that D-AspO could play an essential role in decreasing excessive amounts of D-Asp in frog tissues, a phenomenon that, if left unchecked, could have detrimental physiological effects on the animal. | D-Aspartate Oxidase |
The management of pain and morbidity due to the spreading and growth of cancer within bone remains to be a paramount problem in clinical care. Cancer cells actively transform bone, however, the molecular requirements and mechanisms of this process remain unclear. This study shows that functional modulation of the alphavbeta3 integrin receptor in prostate cancer cells is required for progression within bone and determines tumor-induced bone tissue transformation. Using histology and quantitative microCT analysis, we show that alphavbeta3 integrin is required not only for tumor growth within the bone but for tumor-induced bone gain, a response resembling bone lesions in prostate cancer patients. Expression of normal, fully functional alphavbeta3 enabled tumor growth in bone (incidence: 4/4), whereas alphavbeta3 (-), inactive or constitutively active mutants of alphavbeta3 did not (incidence: 0/4, 0/6 and 1/7, respectively) within a 35-day-period. This response appeared to be bone-specific in comparison to the subcutis where tumor incidence was greater than 60% for all groups. Interestingly, bone residing prostate cancer cells expressing normal or dis-regulated alphavbeta3 (either inactive of constitutively active), but not those lacking beta3 promoted bone gain or afforded protection from bone loss in the presence or absence of histologically detectable tumor 35 days following implantation. As bone is replete with ligands for beta3 integrin, we next demonstrated that alphavbeta3 integrin activation on tumor cells is essential for the recognition of key bone-specific matrix proteins. As a result, prostate cancer cells expressing fully functional but not dis-regulated alphavbeta3 integrin are able to control their own adherence and migration to bone matrix, functions that facilitate tumor growth and control bone lesion development. | Integrin alphaVbeta3 |
Phenylselenide substituted BOPHY probes (BOPHY-SePh and PhSe-BOPHY-SePh) were synthesized and characterized by NMR spectroscopy and single-crystal XRD. Both the probes selectively detect HOCl in water with high sensitivity over other reactive oxygen species. A fluorescence turn-on" event was attained due to cease of the PET process through transformation of selenide to selenoxide. Both the probes react with HOCl in less than 1 s. PhSe-BOPHY-SePh probe depicted low background fluorescence due to presence of two phenylselenide groups at BOPHY. PhSe-BOPHY-SePh probe has a low detection limit (0.63 muM) than BOPHY-SePh probe (1.08 muM). The bioimaging studies of both the probes were carried out in MCF 7 cells. Both the probes exhibited a good fluorescence response for HOCl in vitro and in mammalian cells. In addition, the probes showed reversibility with all bio-thiols, which was validated in MCF 7 cells using GSH." | Selenium Oxides |
RATIONALE: Endoplasmic reticulum (ER) stress dysregulates ER proteostasis, which activates the transcription factor, ATF6 (activating transcription factor 6alpha), an inducer of genes that enhance protein folding and restore ER proteostasis. Because of increased protein synthesis, it is possible that protein folding and ER proteostasis are challenged during cardiac myocyte growth. However, it is not known whether ATF6 is activated, and if so, what its function is during hypertrophic growth of cardiac myocytes. OBJECTIVE: To examine the activity and function of ATF6 during cardiac hypertrophy. METHODS AND RESULTS: We found that ER stress and ATF6 were activated and ATF6 target genes were induced in mice subjected to an acute model of transverse aortic constriction, or to free-wheel exercise, both of which promote adaptive cardiac myocyte hypertrophy with preserved cardiac function. Cardiac myocyte-specific deletion of Atf6 (ATF6 cKO [conditional knockout]) blunted transverse aortic constriction and exercise-induced cardiac myocyte hypertrophy and impaired cardiac function, demonstrating a role for ATF6 in compensatory myocyte growth. Transcript profiling and chromatin immunoprecipitation identified RHEB (Ras homologue enriched in brain) as an ATF6 target gene in the heart. RHEB is an activator of mTORC1 (mammalian/mechanistic target of rapamycin complex 1), a major inducer of protein synthesis and subsequent cell growth. Both transverse aortic constriction and exercise upregulated RHEB, activated mTORC1, and induced cardiac hypertrophy in wild type mouse hearts but not in ATF6 cKO hearts. Mechanistically, knockdown of ATF6 in neonatal rat ventricular myocytes blocked phenylephrine- and IGF1 (insulin-like growth factor 1)-mediated RHEB induction, mTORC1 activation, and myocyte growth, all of which were restored by ectopic RHEB expression. Moreover, adeno-associated virus 9- RHEB restored cardiac growth to ATF6 cKO mice subjected to transverse aortic constriction. Finally, ATF6 induced RHEB in response to growth factors, but not in response to other activators of ATF6 that do not induce growth, indicating that ATF6 target gene induction is stress specific. CONCLUSIONS: Compensatory cardiac hypertrophy activates ER stress and ATF6, which induces RHEB and activates mTORC1. Thus, ATF6 is a previously unrecognized link between growth stimuli and mTORC1-mediated cardiac growth." | Activating Transcription Factor 6 |
The genetic dissection of learning and memory in Drosophila is two decades old. Recently, a great deal of progress has been made towards isolating new mutants as well as towards a better understanding of the originally isolated ones. This paper reviews the recent developments in the understanding of the structure and function of the gene identified by the first and best-characterized of these mutants, the Drosophila dunce mutant." | 3',5'-Cyclic-AMP Phosphodiesterases |
The synthesis and processing of structural proteins of human immunodeficiency virus type 1 (HIV-1) were studied in infected cells treated with monensin and cerulenin. In MOLT-3 cells chronically infected with HTLV-IIIB, monensin inhibited the proteolytic cleavage of the env-coded polyprotein gp160 to gp120, leading to the accumulation of the precursor gp160. The formation of syncytia normally observed when CEM cells are cocultivated with HIV-1-infected MOLT-3 cells was significantly inhibited in the presence of monensin. The effect of the ionophore on the culture was reversible, as withdrawal of monensin from the medium restored the ability of the cells to form syncytia with CEM cells and led to the resumption of the processing of gp160 to gp120. Monensin did not affect the synthesis and processing of gag-coded proteins and regulatory proteins. Cerulenin, an inhibitor of de novo fatty acid biosynthesis, inhibited the myristoylation and the proteolytic cleavage of the gag-coded polyprotein Pr53gag to p24 but did not affect the processing of gp160. However, use for monensin and cerulenin as antiviral agents for treatment of HIV-1 infection cannot be foreseen because of the pronounced in vitro toxicity observed. | Cerulenin |
Evidence is accumulating for seven and less fractions in localised prostate cancer, including one large randomised trial. However, there is much more evidence yet to come and changing practice in advance of this may be premature. We review the reasons to persist with moderate hypofractionation for prostate cancer radiotherapy, until the results of further phase III studies are known." | Radiation Dose Hypofractionation |
Microbes inhabit diverse environmental locations, and many species need to shift their physiology between different niches. To do this effectively requires the accurate sensing of and response to the environment. For pathogens, exposure to light is one major change between a free-living saprophyte lifestyle and causation of disease within the host. However, how light may act as a signal to influence pathogenesis, on the side of either the host or the pathogen, is poorly understood. Research during the last 2 decades has uncovered aspects about the machinery for light sensing in a small number of fungi. Now, Fuller et al. have initiated studies into the role that light and two photosensor homologs play in the behavior of the ubiquitous fungal pathogen Aspergillus fumigatus [K. K. Fuller, C. S. Ringelberg, J. J. Loros, and J. C. Dunlap, mBio 4(2):e00142-13, 2013, doi:10.1128/mBio.00142-13]. Light represses the germination of A. fumigatus spores and enhances resistance to ultraviolet light, oxidative stresses, and cell wall perturbations. The phenotypes of the strains with mutations in the LreA and FphA homologs revealed that these sensors control some, but not all, responses to light. Furthermore, interactions occur between blue and red light signaling pathways, as has been described for a related saprophytic species, Aspergillus nidulans. Genome-wide transcript analyses found that about 2.6% of genes increase or decrease their transcript levels in response to light. This use of A. fumigatus establishes common elements between model filamentous species and pathogenic species, underscoring the benefits of extending photobiology to new species of fungi. | Aspergillus fumigatus |
The NIH has recently highlighted the importance of sexual dimorphisms and has mandated inclusion of both sexes in clinical trials and basic research. In this review we highlight new and novel ways sex hormones influence body adiposity and the metabolic syndrome. Understanding how and why metabolic processes differ by sex will enable clinicians to target and personalize therapies based on gender. Adipose tissue function and deposition differ by sex. Females differ with respect to distribution of adipose tissues, males tend to accrue more visceral fat, leading to the classic android body shape which has been highly correlated to increased cardiovascular risk; whereas females accrue more fat in the subcutaneous depot prior to menopause, a feature which affords protection from the negative consequences associated with obesity and the metabolic syndrome. After menopause, fat deposition and accrual shift to favor the visceral depot. This shift is accompanied by a parallel increase in metabolic risk reminiscent to that seen in men. A full understanding of the physiology behind why, and by what mechanisms, adipose tissues accumulate in specific depots and how these depots differ metabolically by sex is important in efforts of prevention of obesity and chronic disease. Estrogens, directly or through activation of their receptors on adipocytes and in adipose tissues, facilitate adipose tissue deposition and function. Evidence suggests that estrogens augment the sympathetic tone differentially to the adipose tissue depots favoring lipid accumulation in the subcutaneous depot in women and visceral fat deposition in men. At the level of adipocyte function, estrogens and their receptors influence the expandability of fat cells enhancing the expandability in the subcutaneous depot and inhibiting it in the visceral depot. Sex hormones clearly influence adipose tissue function and deposition, determining how to capture and utilize their function in a time of caloric surfeit, requires more information. The key will be harnessing the beneficial effects of sex hormones in such a way as to provide 'healthy' adiposity. | Intra-Abdominal Fat |
PURPOSE: To evaluate morphological changes of the gastric stump and not resected stomach mucosa after the completion of truncal vagotomy. METHODS: Eighty male Wistar rats were divided into four groups: CT, TV, RY and RYTV. In CT group, abdominal viscera were manipulated and the abdominal cavity was closed, in TV vagal trunks were isolated and sectioned, in RY a partial Roux-en-Y gastrectomy was performed and in RYTV the vagal trunks were sectioned and a partial Roux-en-Y gastrectomy was performed. At the 54th week after surgery, the rats were euthanized. The findings were submitted to histological analyses. RESULTS: None macroscopic or histological alterations in groups TV and CT was observed. Specimens from RY and RYTV groups did not show alterations in the gastric stump mucosa. At the jejunal side of the gastroenterostomy we found shallow ulcerative lesions always single, well-defined and with variable diameter 3 to 6 mm, six times in the RY group and none in the RYTV group (RY>RYTV, p=0.008). Neoplastic or preneoplastic lesions were not diagnosed in all groups. CONCLUSION: Truncal vagotomy is a safe and non-carcinogenic method in not resected and partially resected stomach. | Vagotomy, Truncal |
The authors demonstrate the case of a female patient with a prolonged mucosal form of candidosis caused by different biotypes of Candida albicans. Despite the fact the long-term and repeated treatment with Nizoral and transfer factor was applied, relapses of the disease developed. Marked improvement of clinical manifestations occurred only after a change of the dietary habits and long-term administration of immunomodulating agents. The authors discuss therapeutic and diagnostic aspects of the disease. | Candidiasis |
The natural occurrence of six major ergot alkaloids, ergometrine, ergosine, ergotamine, ergocornine, ergokryptine and ergocristine, as well as their corresponding epimers, were investigated in 60 cereal samples (barley and wheat) from Algeria. Ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) and a QuEChERS extraction method were used for sample analysis. The results revealed that 12 out of 60 samples (20%) were contaminated with ergot alkaloids. Wheat was the most contaminated matrix, with an incidence of 26.7% (8 out of 30 samples). The concentration of total ergot alkaloids ranged from 17.8 to 53.9 microg/kg for barley and from 3.66 to 76.0 mug/kg for wheat samples. Ergosine, ergokryptine and ergocristine showed the highest incidences in wheat, while ergometrine was the most common ergot in barley. | Ergotamines |
Sand and Dust storms are common phenomena in arid and semi-arid areas. West Asia Region, especially Tigris-Euphrates alluvial plain, has been recognized as one of the most important dust source areas in the world. In this paper, a method is applied to extract SDS (Sand and Dust Storms) sources in West Asia region using thematic maps, climate and geography, HYSPLIT model and satellite images. Out of 50 dust storms happened during 2000-2013 and collected in form of MODIS images, 27 events were incorporated as demonstrations of the simulated trajectories by HYSPLIT model. Besides, a dataset of the newly released Landsat images was used as base-map for the interpretation of SDS source regions. As a result, six main clusters were recognized as dust source areas. Of which, 3 clusters situated in Tigris-Euphrates plain were identified as severe SDS sources (including 70% dust storms in this research). Another cluster in Sistan plain is also a potential source area. This approach also confirmed six main paths causing dust storms. These paths are driven by the climate system including Siberian and Polar anticyclones, monsoon from Indian Subcontinent and depression from north of Africa. The identification of SDS source areas and paths will improve our understandings on the mechanisms and impacts of dust storms on socio-economy and environment of the region. | Meteorology |
School bullying is a widespread public health issue that negatively impacts the mental health of children and adolescents. This study aimed to investigate associations between school bullying involvement and anxiety of children and adolescents. A survey covering all types of pre-college schools (primary, middle, high, and vocational school) was conducted in an ethnic autonomous county in China. 1,943 students participated in this study. Being a victim of verbal (OR=3.08, 95%CI = [2.43,3.91]), physical (OR=3.24, 95%CI = [2.46,4.27]), relational (OR=3.72, 95%CI = [2.90,4.76]), or cyberbullying (OR=3.47, 95%CI = [2.61,4.61]) were associated with increased symptoms of generalized anxiety. Similarly, being a perpetrator of verbal (OR=2.12, 95%CI = [1.45,3.10]), physical (OR=1.85, 95%CI = [1.22,2.79]), relational (OR=1.78, 95%CI = [1.15,2.74]), or cyber-bullying (OR=1.59, 95%CI = [1.08,2.33]) were related to a higher degree of anxiety. Moreover, in both victims and perpetrators higher levels of anxiety were associated with a greater number of types of bullying they were involved in, suggesting a dose-response relation between school bullying involvement and anxiety. Therefore, both bullying victims and perpetrators need mental health support and anti-bullying strategies should address different forms of bullying evenhandedly. | Harassment, Non-Sexual |
AKR1C3 is a promising drug target for castration-resistant prostate cancer (CRPC). Here, 3D-QSAR analysis were performed on 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids to correlate their chemical structures with their observed AKR1C3 inhibitory activity. Three structural alignment methods employing various conformers were used to scrutinize the effect of conformation selection on the predictive accuracy of QSAR models. Using docked conformation, the best CoMFA and CoMSIA models were developed and validated with a training set of 61 molecules and a test set of 7 molecules. Detailed analysis of contour maps provided helpful structural insights to rational design of AKR1C3 inhibitors with enhanced potency." | Hydroxyprostaglandin Dehydrogenases |
Double-balloon endoscopy (DBE) is very useful for the diagnosis and treatment of non-steroidal anti-inflammatory drugs (NSAIDs)-associated enteritis. In cases of long-term NSAIDs administration, aphtha, specific diaphragm-like strictures and circular ulcers are pointed out into details by DBE. Even if on-demand use of NSAIDs, some patients have small bowel injuries when NSAIDs are administered for over several years. Moreover, there are variations for the type and indication of NSAIDs among patients. The cytolysis image and the apoptosis in the base of mucosa were reported as the characteristic histological findings of NSAIDs-associated enteritis. In consideration of widespread use of NSAIDs, a strategy for the management of NSAID-associated enteritis should be discussed and established. | Enteritis |
In tropical and subtropical areas, tuber and root crops are staple foods and a key source of energy. Sweet potato (SP) is currently regarded as one of the world's top ten foods because of its diverse sizes, shapes, color, and health benefits. The resistant starch (RS) content of SP is substantial. It is predicted to become the cheapest item in the food industry due to its extensive variety, food stability, emulsifier and fat substitution capabilities, and as filler. As a result, interest in SP-sourced RS has recently increased. Due to their unique nutritional and functional qualities, novelty has become a popular research focus in recent years. This review will summarize the current understanding of SP starch components and their impact on the technological and physicochemical properties of produced starch for commercial viability. The importance of sweet potato RS in addressing future RS demand sustainability is emphasized. SPs are a viable alternative to tubers as a sustainable raw material for RS production. It has an advantage over tubers because of its intrinsic nutritional value and climatic endurance. Thermal, chemical, and enzymatic treatments are effective RS manufacturing procedures. The adaptability of sweet potato RS allows for a wide range of food applications. | Ipomoea batatas |
Two hundred seventy-seven Salmonella (27 serotypes) were isolated from Kansas swine over a 5-year period (1979 to 1983). Salmonella cholerae-suis was the predominant isolant from all tissues and made up 94.4% of the Salmonella isolants from the lungs. The percentage of Salmonella isolants susceptible to various antimicrobial agents was determined. The percentage of Salmonella susceptible to carbadox decreased from 1980 to 1983. | Carbadox |
Spray-induced gene silencing (SIGS) is an innovative and eco-friendly technology where topical application of pathogen gene-targeting RNAs to plant material can enable disease control. SIGS applications remain limited because of the instability of RNA, which can be rapidly degraded when exposed to various environmental conditions. Inspired by the natural mechanism of cross-kingdom RNAi through extracellular vesicle trafficking, we describe herein the use of artificial nanovesicles (AVs) for RNA encapsulation and control against the fungal pathogen, Botrytis cinerea. AVs were synthesized using three different cationic lipid formulations, DOTAP + PEG, DOTAP and DODMA, and examined for their ability to protect and deliver double stranded RNA (dsRNA). All three formulations enabled dsRNA delivery and uptake by B. cinerea. Further, encapsulating dsRNA in AVs provided strong protection from nuclease degradation and from removal by leaf washing. This improved stability led to prolonged RNAi-mediated protection against B. cinerea both on pre- and post-harvest plant material using AVs. Specifically, the AVs extended the protection duration conferred by dsRNA to 10 days on tomato and grape fruits and to 21 days on grape leaves. The results of this work demonstrate how AVs can be used as a new nanocarrier to overcome RNA instability in SIGS for crop protection. | Gene Silencing |
BACKGROUND: Aneurysm of the main pulmonary artery trunk (PAA) is a rare but severe complicating factor in patients suffering from pulmonary arterial hypertension (PAH). Many centers consider PAA an indication for a heart-lung transplantation. We aimed to summarize our institutional experience with a lung-only strategy in this complex group of patients. METHODS: We performed a retrospective single-center analysis of patients with PAH and a severe PAA who underwent lung transplantation between January 1996 and November 2018. RESULTS: A total of 127 patients with PAH underwent lung transplantation during the study period. Seven patients presented with severe PAA (mean diameter, 70.4 mm). Donor lungs were procured together with the main pulmonary artery (PA). In the recipient, cardiopulmonary bypass with bicaval cannulation was established, and bilateral pneumonectomy together with resection of the entire PA trunk was performed. The right donor lung was implanted, and the attached PA trunk was pulled through behind the superior vena cava and ascending aorta. Anastomosis was performed just above the level of the pulmonary valve. Thereafter, the left lung was implanted by reconnecting the left PA to the main PA trunk. All but 1 patient, who died from sepsis on postoperative day 13, were successfully discharged. CONCLUSIONS: To the best of our knowledge, this is the largest published experience of patients with PAH and severe PAA who underwent lung transplantation. We show that these patients are eligible for double lung transplantation and do not require heart-lung transplantation." | Pulmonary Arterial Hypertension |
Oxidative stress induced by selenium deficiency has been shown to be associated with cardiovascular diseases. Nevertheless, the mechanism associated with oxidative stress induced by selenium deficiency is poorly understood. In the present study, 36 weaning C57BL/6 mice were randomly divided into 4 groups as follows: control (n =9), 4-week selenium deficiency (n =9), 8-week selenium deficiency (n = 9), and 12-week selenium deficiency (n =9). The levels of myocardial glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by Western blotting or commercial kits. Real-time PCR was performed to detect the mRNA expression of dishevelled-1 (Dvl-1) protein. Western blotting was conducted to evaluate the protein expression levels of Dvl-1 and beta-catenin. Our results demonstrated that the levels of GPx and SOD were significantly reduced, along with an increase in MDA in selenium-deficient mice. Importantly, Dvl-1 and beta-catenin were clearly upregulated under oxidative stress. Collectively, our findings indicate that Dvl-1 may be an underlying participant of oxidative stress induced by selenium deficiency. | Dishevelled Proteins |
beta-Catenin and plakoglobin are two related armadillo proteins necessary for the establishment of adhesion junctions and desmosomes. Moreover, beta-catenin can also act as a transcriptional co-activator through its interaction with the members of Tcf/LEF-1 transcriptional factor family. We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. The binding sites of Tcf-4 for these two proteins were compared; whereas beta-catenin requires the N-terminal first 50 amino acids, plakoglobin interacts mainly with residues 51-80. Tcf-4-(51-80) binds plakoglobin in the region of armadillo repeats 1-6. Ternary complexes composed by beta-catenin/Tcf-4/plakoglobin could be detected in vitro, demonstrating that simultaneous binding of the two armadillo proteins to Tcf-4 is possible. Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4. These results indicate that Tcf-4 contains two different sites for binding of beta-catenin and plakoglobin, and the interaction of the latter hinders the transcriptional activity of the complex. | Desmoplakins |
Animal experiments are widely accepted in arteriosclerosis research. The aim of the present study was to establish an organ culture model (rings of rabbit aortic vessels) to investigate inhibitory estrogen effects on post injury neointima formation in the vessel wall and to examine whether these effects are cytotoxic. Estrogens are used for secondary prevention of atherosclerosis in postmenopausal women (estrogen replacement therapy/ERT). Phytoestrogens as well as the ovarian 17 beta-estradiol have been demonstrated to inhibit proliferation and migration of vascular smooth muscle cells which are key events in atherogenesis and restenosis after coronary angioplasty. In situ endothelial denudation of the thoracic and abdominal aorta was performed in female rabbits by a 3F Fogarty catheter. Segments of 5 mm were randomized in groups of n = 12 and held in culture. 17 beta-estradiol, Genistein and Daidzein were applied in concentrations of 20 microM, 30 microM, and 40 microM. Groups without estrogen treatment served as controls. The segments were investigated after 21 days. Afterwards, 3 further groups (n = 12) were held with the lowest concentrations of 17 beta-estradiol or the two phytoestrogens having been evaluated to inhibit the neointima formation significantly. After 21 days of treatment these sections were held in medium only for another 7 days to proof whether these segments were still able to proliferate. A denuded control group was held in medium only over 28 days. Compared to controls, 30 microM 17 beta-estradiol, 20 microM Genistein, and 40 microM Daidzein inhibited neointima formation significantly over 21 days. After another 7 days of cultivation in medium only the amount of neointima formation was comparable to that of non-estrogen-treated controls after 21 days. We therefore suggest that the demonstrated inhibitory effect is not explained by toxicity. In conclusion, by the use of this organ culture model it was possible to demonstrate non-toxic post injury effects of different estrogens in the vasculature. Because 24 aortic segments could be taken from one aortic vessel, the number of animals that would have been necessary for an experiment (8 to 10 per group for statistical reasons) could be markedly reduced. The results are of clinical interest because phytoestrogens and 17 beta-estradiol may offer therapeutic options for patients after coronary angioplasty regarding the process of restenosis. Because phytoestrogens do not affect the reproductive system they can also be used in men. | Tunica Intima |
AIM OF STUDY: Securidaca longepedunculata is used in the treatment of erectile dysfunction in South Africa. The aim of the study was to isolate and identify the active constituents and to determine their activity in the relaxation of corpus cavernosal smooth muscle. MATERIALS AND METHODS: Bioassay guided isolation of the bioactive compounds using a smooth muscle relaxation bioassay and structural elucidation was carried out using different spectroscopic techniques including 2D NMR. RESULTS: Two new xanthones were isolated; one of them showed potent activity to relax the corpus cavernosal smooth muscle by 97 % in comparison to sildenafil (Viagra) at 1.8 x 10(-5) mg/ml. CONCLUSIONS: S. longepedunculata's xanthones stimulate the relaxation of corpus cavenosum smooth muscle, which supports the traditional use of its root bark. | Securidaca |
During the period April 1962 to April 1963, 28 newborn infants, 7 stillborns, and 21 children from 4 to 15 years of age were examined for emission of gamma activity in a low-background, high-sensitivity, total-body counting facility. The 21 children contained traces of combined Zr(95) and Nb(95), Ru(103), (106), and Cs(137) in addition to the normal K(40). The greatest concentration of Cs(137) observed was 80 picocuries per kilogram of body weight, or about 4 percent of the natural K(40) radioactivity. Four of the seven stillborns, each counted for 10 hours, shoWed K(40) and traces of Zr(95), Nb(95), and Ru(103), (106). The ratios of Zr(95) to Nb(95) were lower in the stillborns than in their placentas which suggested placental discrimination against Zr(95). The ratios of Cs(137) to K(40) were lower in infants than in children or adults. Thyroid glands obtained atautopsy from 24 infants during April to September 1962 contained no detectable radioiodine ( less than 30 pc). | Nobelium |
Studies of the secretomes of microbes grown on insoluble substrates are important for the discovery of novel proteins involved in biomass conversion. However, data in literature and this study indicate that secretome samples tend to be contaminated with cytoplasmic proteins. We have examined the secretome of the Gram-negative soil bacterium Cellvibrio japonicus using a simple plate-based culturing technique that yields samples with high fractions (60-75%) of proteins that are predicted to be secreted. By combining this approach with label-free quantification using the MaxLFQ algorithm, we have mapped and quantified proteins secreted by C. japonicus during growth on alpha- and beta-chitin. Hierarchical clustering of the detected protein quantities revealed groups of up-regulated proteins that include all five putative C. japonicus chitinases as well as a chitin-specific lytic polysaccharide monooxygenase (CjLPMO10A). A small set of secreted proteins were co-regulated with known chitin-specific enzymes, including several with unknown catalytic functions. These proteins provide interesting targets for further studies aimed at unraveling the enzymatic machineries used by C. japonicus for recalcitrant polysaccharide degradation. Studies of chitin degradation indicated that C. japonicus indeed produces an efficient chitinolytic enzyme cocktail. All MS data have been deposited in the ProteomeXchange with the dataset identifier PXD002843 (http://proteomecentral.proteomexchange.org/dataset/PXD002843). | Cellvibrio |
How size is controlled is a fundamental question in biology. In this review, we discuss the use of scaling relationships-for example, power-laws of the form y proportional, variantx(alpha)-to provide a framework for comparison and interpretation of size measurements. Such analysis can illustrate the biological and physical principles underlying observed trends, as has been proposed for the allometric dependence of metabolic rate or limb structure on organism mass. Techniques for measuring size at smaller length-scales continue to improve, leading to more data on the control of size in cells and organelles. Size scaling of these structures is expected to influence growth patterns, functional capacity and intracellular transport. Furthermore, organelles such as the nucleus, mitochondria and endoplasmic reticulum show widely varying morphologies that affect their scaling properties. We provide brief summaries of these issues for individual organelles, and conclude with a discussion on how to apply this concept to better understand the mechanisms of size control in the cellular environment. | Cell Size |
Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is a natural herbal drug that has been widely used to treat many diseases. The antitumor effects of G. pentaphyllum were first described in the illustrated catalog of plants. Gypenosides are the major active components of G. pentaphyllum, and they have been widely reported to possess antitumor effects in prostate cancer, gastric cancer, hepatocellular carcinoma, colon cancer, lung cancer, and breast cancer. However, research on the use of gypenoside in the treatment of bladder cancer has not been conducted. In this study, we explored the potential molecular mechanisms of gypenosides in the treatment of bladder cancer using network pharmacology and experimental validation. First, we used a network pharmacology-based method to identify both the effective components of gypenosides and the molecular mechanism underlying their antibladder cancer effects. The results were further confirmed by molecular docking, CCK8 and colony formation assays, and cell cycle and cell apoptosis analyses. Additionally, a mouse xenograft model of bladder cancer was used to investigate the antitumor effect of gypenosides in vivo. We identified 10 bioactive ingredients and 163 gene targets of gypenosides. Network exploration suggested that VEGFA, STAT3, and PI3KCA may be candidate agents for the antibladder cancer effect of gypenosides. In addition, analysis of the Kyoto Encyclopedia of Genes and Genomes pathway revealed that the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway may play a crucial role in the mechanism of action of gypenosides against bladder cancer. Molecular docking revealed that gypenosides combine well with PI3K, AKT, and mTOR. As expected, gypenosides displayed apoptosis-inducing properties in bladder cancer cells by inactivating the PI3K/AKT/mTOR signaling pathway in vitro. Furthermore, gypenosides significantly (P < 0.05) inhibited the growth of bladder cancer cells in vivo. Mechanistically, gypenosides induced the apoptosis of bladder cancer cells via inactivation of the PI3K/AKT/mTOR signaling pathway. | Gynostemma |
This paper reports on the variability of structural polypeptides of 32 strains of Herpes simplex virus 2 (HSV-2) isolated from various locations in the United States and Italy. Most strains were passaged a limited number of times at low multiplicity outside the human host; a few strains were characterized by numerous passages at variable multiplicities in cell culture. The acrylamide gel electrophoresis of polypeptides from purified virions revealed very few differences. Considering these differences the HSV-2 strains analysed can be classified into 3 groups according to the variability of three polypeptides. The study of polypeptides in HSV-2 infected cells revealed more differences than those seen in the structural proteins. Comparisons of the structural proteins specified by HSV-2 and HSV-1 virions, revealed clear variant features of the electrophoretic profiles, especially when pH of main gel was 8.9. | Simplexvirus |
Advances in cancer research have led to the development of new therapeutics with significant and durable responses such as immune checkpoint inhibitors. More recent therapies aim to stimulate anti-tumor immune responses by targeting the tumor necrosis factor (TNF) receptors, however this approach has been shown to require clustering of receptors in order to achieve a significant response. Here we present a perspective on using transthyretin, a naturally occurring serum protein, as a drug delivery platform to enable cross-linking independent clustering of targets. TTR forms a stable homo-tetramer with exposed termini that make TTR a highly versatile platform for generating multimeric antibody fusions to enable enhanced target clustering. Fusions with antibodies or Fabs targeting TRAILR2 were shown to have robust cytotoxic activity in vitro and in vivo in colorectal xenograft models demonstrating that TTR is a highly versatile, stable, therapeutic fusion platform that can be used with antibodies, Fabs and other bioactive fusion partners and has broad applications in oncology and infectious disease research. | Prealbumin |
OBJECTIVE: The aim of the study was to assess the correlation between the cellulite severity and the thickness of the fat fold. MATERIAL AND METHODS: The study comprised 62 women aged 22 to 26 years. A palpation and visual evaluation of cellulite severity was performed on the basis of the Nurnberger and Muller classification, and the thickness of adipose tissue (fatty tissue) was measured with the use of a skinfold caliper. RESULTS: The H0 hypothesis was rejected in favor of the H1 hypothesis (p < 0.001) in the chi-square independence test; therefore, a relationship between the thickness of the adipose tissue fold and the severity of cellulite was confirmed. Moreover, on the basis of obtained results, the hypothesis of the independence of the studied variables (p < 0.0000001) was also rejected. It can be concluded that there is an association between the thickness of adipose tissue and the degree of cellulite. Moreover, the values of the obtained coefficients are greater than zero (the correlation is positive), and the obtained Spearman's R (0.89) and Kendall's tau (0.79) values indicate a very strong correlation between the studied variables. CONCLUSIONS: On the basis of obtained results and their statistical analysis, we can state that there is a relationship between the degree of cellulite and the thickness of the fat fold-the degree of cellulite increases with the increase in the thickness of the measured fat fold. | Cellulite |
An anisotropic plasmonic sheet-core-satellite (PSCS) superstructure can be controlled via competitive binding between aptamer/MC-LR conjugation and aptamer-ssDNA hybridization. SERS nanotags can be incorporated into anisotropic plasmonic sheet-cores, e.g., pGO/nanorods, or pGO/hollow AgCl : Au nanoplates so as to fabricate an aptasensor for ON-OFF" detection of MC-LR toxin. Preparing a PSCS superstructure and detection of toxin can be simultaneously completed so as to simplify the detection procedure of MC-LR toxin. Detection sensitivity of MC-LR toxin can be optimized by controlling aspect ratios or hollow interiors of plasmonic core nanoparticles. Herein, a limit of detection (0.635 pM) with a wide linear range from 1 pM to 10 nM can be obtained via optimized PSCS of pGO/nanorod/dotnanotags. When the aptasensor was tested in real samples, the PSCS shows excellent recoveries from 96.6% to 104.5% with relative standard deviation (RSD) lower than 2.89% in spiked reservoir samples. It can be predicted that a one-step facile nanofabrication/aptasensing approach would be extensively applied for rapid detection of some other environmental contaminants." | Limit of Detection |
In recent years, increasing numbers of small proteins have moved into the focus of science. Small proteins have been identified and characterized in all three domains of life, but the majority remains functionally uncharacterized, lack secondary structure, and exhibit limited evolutionary conservation. While quite a few have already been described for bacteria and eukaryotic organisms, the amount of known and functionally analyzed archaeal small proteins is still very limited. In this review, we compile the current state of research, show strategies for systematic approaches for global identification of small archaeal proteins, and address selected functionally characterized examples. Besides, we document exemplarily for one archaeon the tool development and optimization to identify small proteins using genome-wide approaches. | Archaeal Proteins |
Whether ultra-processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population-based cohort of 98 265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow-up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra-processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HR(quartile 4 vs 1) :1.49; 95% confidence interval [CI]: 1.07-2.07; P(trend) = .021) in a linear dose-response manner (P(nonlinearity) = .075). Subgroup analysis further found that the positive association of ultra-processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HR(quartile 4 vs 1) :2.17; 95% CI: 1.14-4.15) than in those aged >/=65 years (HR(quartile 4 vs 1) :1.32; 95% CI: 0.88-1.94), though the interaction test failed to achieve the statistical significance (P(interaction) = .061). These findings suggest that reducing ultra-processed food consumption may be beneficial in decreasing pancreatic cancer incidence. | Food, Processed |
An earlier model for the study of rib cage mechanics was modified so that rib deformity in scoliosis could be better represented. The rigid ribs of that model were replaced by five-segment deformable ribs. Literature data on cadaver rib mechanical behavior were used to assign stiffnesses to the new individual model ribs so that experimental and model rib deflections agreed. Shear and tension/compression stiffnesses had little effect on individual rib deformation, but bending stiffnesses had a major effect. Level-to-level differences in mechanical behavior could be explained almost exclusively by level to level differences in the rib shape. The model ribs were then assembled into a whole rib cage. Computer simulations of whole rib cage behaviors, both in vivo and in vitro, showed a reasonable agreement with the measured behaviors. The model was used to study rib cage mechanics in two scolioses, one with a 43 degrees and the other with a 70 degrees Cobb angle. Scoliotic rib cage deformities were quantified by parameters measuring the rib cage lateral offset, rib cage axial rotation, rib cage volume and rib distortion. Rib distortion was quantified both in best-fit and simulated computer tomography (CT) scan planes. Model rib distortion was much smaller in best-fit planes than in CT planes. The total rib cage volume changed little in the presence of the scolioses, but it became asymmetrically distributed. | Xiphoid Bone |
Aeromonas species are rarely an identified cause of folliculitis. Here, we describe the case of a patient who had purulent folliculitis of the breast caused by an Aeromonas species and review 4 other cases presented in the literature, highlighting the commonalities observed. Aeromonas infection should be considered in patients who present with purulent folliculitis, particularly those with exposure to nonchlorinated pools or baths. | Folliculitis |
Statistical analysis of psychiatric research requires the translation of qualitative data into quantitative form. This can be achieved using rating scales. However, the reliability and the validity, i.e. the validation of these scales, presents significant problems; these shall be outlined in this article. | Epidemiologic Research Design |
Current therapy of chronic hepatitis C is based on the combination of pegylated interferon-alpha and ribavirin. In spite of 50% sustained virological response, therapy is still limited by unsatisfying success rates with genotype 1 infections and adverse side effects. One attempt to increase success rates is triple combination therapy of interferon and ribavirin with amantadine, a drug assumed to interfere with HCV p7 ion channel function. However, results from clinical trials indicate limited efficacy and the antiviral activity is unclear. In contrast, NS3 protease inhibitors have shown potent antiviral effects in clinical trials but rapid selection for drug resistance may limit their benefit. Targeting cellular factors required for HCV is therefore an attractive alternative. In this study, employing a system for production of infectious HCV particles in cell culture, we determined the antiviral effects of amantadine and iminosugar derivatives; the second of which primarily target host cell glucosidases required for folding and maturation of HCV envelope glycoproteins. We found that across a spectrum of HCV isolates and genotypes, amantadine affected neither RNA replication nor the release or infectivity of HCV particles. In agreement, p7 ion channel activity was not affected by amantadine, demonstrating that amantadine is not an HCV-selective antiviral. In contrast, a dose-dependent reduction of virus titers was achieved with iminosugars. Furthermore, HCV was rapidly eliminated from cell culture upon passage in the presence of a long alkyl chain deoxynojirimycin (DNJ). CONCLUSION: Iminosugar derivatives are potential drugs for treatment of HCV infections. | Hepacivirus |
OBJECTIVE: The present study examined the relationship between the intensity of home-based telework and work engagement. METHODS: This cross-sectional study using a self-administrated questionnaire survey was conducted from December 22 to 25, 2020, in Japan. The subjects were asked single-item questions about the intensity of telework and three-item questions about work engagement using the Utrecht Work Engagement Scale. Coefficients were estimated using a multilevel regression model nested by the prefecture of residence and adjusted for covariates. RESULTS: High-intensity (4 or more days per week) telework was not associated with high work engagement for men or women. In contrast, low and moderate intensity (3 days per week to once per month) were associated with high work engagement. The results were consistent when stratified by sex. CONCLUSIONS: Reasonable-intensity telework may have beneficial effects on work engagement. | Work Engagement |
The Arabidopsis ER-alpha-mannosidase I (MNS3) generates an oligomannosidic N-glycan structure that is characteristically found on ER-resident glycoproteins. The enzyme itself has so far not been detected in the ER. Here, we provide evidence that in plants MNS3 exclusively resides in the Golgi apparatus at steady-state. Notably, MNS3 remains on dispersed punctate structures when subjected to different approaches that commonly result in the relocation of Golgi enzymes to the ER. Responsible for this rare behavior is an amino acid signal motif (LPYS) within the cytoplasmic tail of MNS3 that acts as a specific Golgi retention signal. This retention is a means to spatially separate MNS3 from ER-localized mannose trimming steps that generate the glycan signal required for flagging terminally misfolded glycoproteins for ERAD. The physiological importance of the very specific MNS3 localization is demonstrated here by means of a structurally impaired variant of the brassinosteroid receptor BRASSINOSTEROID INSENSITIVE 1. | alpha-Mannosidase |
As a novel class of dynamic and non-covalent polymers, supramolecular polymers not only display specific structural and physicochemical properties, but also have the ability to undergo reversible changes of structure, shape, and function in response to diverse external stimuli, making them promising candidates for widespread applications ranging from academic research to industrial fields. By an elegant combination of dynamic/reversible structures with exceptional functions, functional supramolecular polymers are attracting increasing attention in various fields. In particular, functional supramolecular polymers offer several unique advantages, including inherent degradable polymer backbones, smart responsiveness to various biological stimuli, and the ease for the incorporation of multiple biofunctionalities (e.g., targeting and bioactivity), thereby showing great potential for a wide range of applications in the biomedical field. In this Review, the trends and representative achievements in the design and synthesis of supramolecular polymers with specific functions are summarized, as well as their wide-ranging biomedical applications such as drug delivery, gene transfection, protein delivery, bio-imaging and diagnosis, tissue engineering, and biomimetic chemistry. These achievements further inspire persistent efforts in an emerging interdisciplin-ary research area of supramolecular chemistry, polymer science, material science, biomedical engineering, and nanotechnology. | Polymers |
The effects of ethanol/broth proportions and the number of steps at varying pH in the presence or absence of sodium chloride (NaCl) were studied as precipitation strategies for the recovery and purification of high molar mass bio-hyaluronic acid (Bio-HA). Bio-HA was synthesized by Streptococcus zooepidemicus in a culture medium containing glucose and soy peptones. A single-step precipitation was more attractive than multistep precipitation in terms of recovery and purity as well as decreased use of ethanol. The best conditions in the absence and presence of salt were 2:1 ethanol/broth (v/v) at pH 4 (55.0 +/- 0.2% purity and 85.0 +/- 0.7% recovery) and 2:1 ethanol/broth (v/v) at pH 7 + 2 mol L(-1) NaCl (59.0 +/- 0.9% purity and 82.0 +/- 4.3% recovery). Dynamic light scattering (DLS) spectra showed different particle sizes as a consequence of the changes in the molecular structure of HA, mainly with changes in pH. Although slight changes in distribution were observed, the average HA molar mass was not affected by the precipitation strategy, remaining on the order of 10(5) Da. Therefore, pH and NaCl modulated the precipitation performance of HA. These findings are relevant to further optimizing the precipitation step, thus minimizing costs in the later stages of HA purification. | Streptococcus equi |
A new rasp for rhinoplasty is presented. It can be dismantled and has a renewable blade that looks like the one you find in a plane. The main advantage of this rasp is that it rasps the cartilaginous septum as well as the bony part of the hump. | Rhinoplasty |
Sunlight is vital for several biochemical processes of the skin organ. However, acute or chronic exposure to ultraviolet radiation (UVR) has several harmful effects on the skin structure and function, especially in the case of the failing function of antioxidative enzymes, which may lead to substantial tissue damage due to the increased presence of reactive oxygen species (ROS). The aim of this work was to investigate the combined effect of ultraviolet B (UVB) irradiation and oxidative stress on the skin barrier integrity. For this, we employed electrical impedance spectroscopy (EIS) to characterize changes of the electrical properties of excised pig skin membranes after various exposure conditions of UVB irradiation, oxidative stress, and the inhibition of antioxidative enzymatic processes. The oxidative stress was regulated by adding hydrogen peroxide (H(2)O(2)) as a source of ROS, while sodium azide (NaN(3)) was used as an inhibitor of the antioxidative enzyme catalase, which is naturally present throughout the epidermis. By screening for the combined effect of UVB and oxidative stress on the skin membrane electrical properties, we developed a new protocol for evaluating these parameters in a simple in vitro setup. Strikingly, the results show that exposure to extreme UVB irradiation does not affect the skin membrane resistance, implying that the skin barrier remains macroscopically intact. Likewise, exposure to only oxidative stress conditions, without UVB irradiation, does not affect the skin membrane resistance. In contrast to these observations, the combination of UVB irradiation and oxidative stress conditions results in a drastic decrease of the skin membrane resistance, indicating that the integrity of the skin barrier is compromised. Further, the skin membrane effective capacitance remained more or less unaffected by UVB exposure, irrespective of simultaneous exposure of oxidative stress. The EIS results were concluded to be associated with clear signs of macroscopic tissue damage of the epidermis as visualized with microscopy after exposure to UVB irradiation under oxidative stress conditions. Finally, the novel methodology was tested by performing an assessment of cosmetic sunscreen formulations with varying sun protection factor (SPF), with an overall successful outcome, showing good correlation between SPF value and protection capacity in terms of skin resistance change. The results from this study allow for the development of new skin sensors based on EIS for the detection of skin tissue damage from exposure to UVB irradiation and oxidative stress and provide a new, more comprehensive methodology, taking into account both the influence of UVB irradiation and oxidative stress, for in vitro determination of SPF in cosmetic formulations. | Sun Protection Factor |
OBJECTIVES: Undoubted fossil Cebidae have so far been primarily documented from the late middle Miocene of Colombia, the late Miocene of Brazilian Amazonia, the early Miocene of Peruvian Amazonia, and very recently from the earliest Miocene of Panama. The evolutionary history of cebids is far from being well-documented, with notably a complete blank in the record of callitrichine stem lineages until and after the late middle Miocene (Laventan SALMA). Further documenting their evolutionary history is therefore of primary importance. MATERIAL: Recent field efforts in Peruvian Amazonia (Contamana area, Loreto Department) have allowed for the discovery of an early late Miocene (ca. 11 Ma; Mayoan SALMA) fossil primate-bearing locality (CTA-43; Pebas Formation). In this study, we analyze the primate material, which consists of five isolated teeth documenting two distinct Cebidae: Cebus sp., a medium-sized capuchin (Cebinae), and Cebuella sp., a tiny marmoset (Callitrichinae). RESULTS: Although limited, this new fossil material of platyrrhines contributes to documenting the post-Laventan evolutionary history of cebids, and besides testifies to the earliest occurrences of the modern Cebuella and Cebus/Sapajus lineages in the Neotropics. Regarding the evolutionary history of callitrichine marmosets, the discovery of an 11 Ma-old fossil representative of the modern Cebuella pushes back by at least 6 Ma the age of the Mico/Cebuella divergence currently proposed by molecular biologists (i.e., ca. 4.5 Ma). This also extends back to > 11 Ma BP the divergence between Callithrix and the common ancestor (CA) of Mico/Cebuella, as well as the divergence between the CA of marmosets and Callimico (Goeldi's callitrichine). DISCUSSION: This discovery from Peruvian Amazonia implies a deep evolutionary root of the Cebuella lineage in the northwestern part of South America (the modern western Amazon basin), slightly before the recession of the Pebas mega-wetland system (PMWS), ca. 10.5 Ma, and well-before the subsequent establishment of the Amazon drainage system (ca. 9-7 Ma). During the late middle/early late Miocene interval, the PMWS was seemingly not a limiting factor for dispersals and widespread distribution of terrestrial mammals, but it was also likely a source of diversification via a complex patchwork of submerged/emerged lands varying through time. | Cebidae |
Normal cellular processes give rise to toxic metabolites that cells must mitigate. Formaldehyde is a universal stressor and potent metabolic toxin that is generated in organisms from bacteria to humans. Methylotrophic bacteria such as Methylorubrum extorquens face an acute challenge due to their production of formaldehyde as an obligate central intermediate of single-carbon metabolism. Mechanisms to sense and respond to formaldehyde were speculated to exist in methylotrophs for decades but had never been discovered. Here, we identify a member of the DUF336 domain family, named efgA for enhanced formaldehyde growth, that plays an important role in endogenous formaldehyde stress response in M. extorquens PA1 and is found almost exclusively in methylotrophic taxa. Our experimental analyses reveal that EfgA is a formaldehyde sensor that rapidly arrests growth in response to elevated levels of formaldehyde. Heterologous expression of EfgA in Escherichia coli increases formaldehyde resistance, indicating that its interaction partners are widespread and conserved. EfgA represents the first example of a formaldehyde stress response system that does not involve enzymatic detoxification. Thus, EfgA comprises a unique stress response mechanism in bacteria, whereby a single protein directly senses elevated levels of a toxic intracellular metabolite and safeguards cells from potential damage. | Methylobacterium extorquens |
We diagram and discuss theories of gender identity development espoused by the clinical groups represented in this special issue. We contend that theories of origin relate importantly to clinical practice, and argue that the existing clinical theories are under-developed. Therefore, we develop a dynamic systems framework for gender identity development. Specifically, we suggest that critical aspects of presymbolic gender embodiment occur during infancy as part of the synchronous interplay of caregiver-infant dyads. By 18 months, a transition to symbolic representation and the beginning of an internalization of a sense of gender can be detected and consolidation is quite evident by 3 years of age. We conclude by suggesting empirical studies that could expand and test this framework. With the belief that better, more explicit developmental theory can improve clinical practice, we urge that clinicians take a dynamic developmental view of gender identity formation into account. | Transsexualism |
BACKGROUND: The hygiene hypothesis suggests that a reduction in microbial exposure contributes to an impaired immune response later in life and increases the incidence of immune-mediated diseases such as inflammatory bowel diseases (IBD). Thumb sucking and nail biting are two early habits that modulate the oral microbiota composition and antigen load. OBJECTIVE: We hypothesized a lower risk of Crohn's disease (CD) and ulcerative colitis (UC) in adults with prior thumb sucking and nail biting. METHODS: 918 IBD cases and their 918 siblings without IBD were asked to fill out a survey containing 32 questions on environmental factors in childhood and early adulthood. Prevalence of thumb sucking and/or nail biting at the usually well-remembered time of (1) school enrollment and (2) coming-of-age ceremonies was the predefined combined risk factor of this study. RESULTS: 65% of the patients were female and 57% suffered from CD. About 49% of IBD patients but only 44% of their siblings reported thumb sucking/nail biting at the time of school enrollment or coming-of-age (p = .007). Sensitivity analysis revealed that this difference was observed in patients with CD (50% versus 41%; RR= 1.22; 95% CI 1.09-1.37, p = .001) but not in patients with UC (49% versus 48%; RR= 1.02; 95% CI 0.90-1.17; p = .83). CONCLUSION: Contrary to our expectation and challenging the hygiene hypothesis, we found that common oral habits are not protective against IBD. Instead, nail biting at the time of school enrollment and coming-of-age was a statistically significant risk factor for CD in our cohort. Key summary Evidence available before this study: The hygiene hypothesis suggests that a reduction in microbial exposure due to improved health activities has contributed to an immunological imbalance in the intestine and an increased incidence of allergic and autoimmune diseases. A population-based birth cohort study has demonstrated that thumb-sucking and nail biting in children lead to a reduction of the risk of atopic sensitization, asthma, and hay fever. Added value of this study: Contrary to the hypothesis, thumb sucking and nail biting were not associated with a reduced risk of IBD. Instead, thumb sucking and/or nail biting at the usually well-remembered points in time of school enrollment and of religious or secular coming-of-age ceremonies was associated with a higher risk of Crohn's disease but not of ulcerative colitis. Our data did not support the hygiene hypothesis, one pathogenic concept in the context of IBD. | Nail Biting |
Two interconvertible forms of glycogen synthase and glycogen phosphorylase, one active (a) or the other less active (b), were predominantly present in a thermosensitive adenylate-cyclase-deficient mutant that had been preincubated at the restrictive temperature of 35 degrees C, either in the presence or in the absence of glucose. Glycogen phosphorylase was at least 20-fold less active after incubation of the cells in the presence of glucose, but this residual activity had kinetic properties identical to those of the active form of enzyme, obtained after incubation in the absence of glucose; this suggests that the b form might be completely inactive and that the low activity measured after glucose treatment must be attributed to a residual amount of phosphorylase a. By contrast, the kinetic properties of the two forms of glycogen synthase were very different. When measured in the absence of glucose 6-phosphate, the two forms of enzyme had a similar affinity for UDP-Glc but differed essentially by their Vmax. Glucose 6-phosphate had no effect on synthase a, but increased both Vmax and Km of synthase b; these effects, however, were in great part counteracted by sulfate and by inorganic phosphate, the latter also having the property of increasing the Km of the a form, without affecting Vmax. It was estimated that at physiological concentrations of substrates and effectors, synthase a was about 20-fold more active than synthase b. When an extract of cells that had been preincubated in the absence of glucose was gel-filtered and then incubated at 30 degrees C, phosphorylase was progressively fully inactivated and synthase was partially activated; these reactions were severalfold faster and, in the case of glycogen synthase, more complete in the presence of 10 mM glucose 6-phosphate. When a gel-filtered extract of cells that had been preincubated in the presence of glucose was incubated at 30 degrees C in the presence of ATP-Mg and EGTA, phosphorylase became activated and synthase was inactivated; the first of these two reactions was severalfold stimulated by micromolar concentrations of Ca2+, whereas both reactions were completely inhibited by 10 mM glucose 6-phosphate and only slightly and irregularly stimulated by cyclic AMP. | Glycogen Synthase |
Physiological processes are mainly controlled by intermolecular recognition mechanisms involving protein-protein and protein-ligand (low molecular weight molecules) interactions. One of the most important tools for probing these interactions is high-field solution nuclear magnetic resonance (NMR) through protein-observed and ligand-observed experiments, where the protein receptor or the organic compounds are selectively detected. NMR binding experiments rely on comparison of NMR parameters of the free and bound states of the molecules. Ligand-observed methods are not limited by the protein molecular size and therefore have great applicability for analysing protein-ligand interactions. The use of these NMR techniques has considerably expanded in recent years, both in chemical biology and in drug discovery. We review here three major ligand-observed NMR methods that depend on the nuclear Overhauser effect-transferred nuclear Overhauser effect spectroscopy, saturation transfer difference spectroscopy and water-ligand interactions observed via gradient spectroscopy experiments-with the aim of reporting recent developments and applications for the characterization of protein-ligand complexes, including affinity measurements and structural determination. | Receptors, Cell Surface |
Oral health surveys are undertaken to provide estimates of the dental health and behaviors of populations or population subgroups. However, the integrity of the data from sample surveys may be compromised by one or more sources of sampling and nonsampling error. An important source of nonsampling error is the failure to collect data from some of the individuals comprising the sample. Consequently, the response to a sample survey, and the direction and magnitude of bias induced by nonresponse, need to be taken into account when using estimates derived from sample surveys. Although the response rate to a survey is usually used as an indicator of the quality of the data it provides, nonresponse error is a function of nonresponse and the extent of differences in the characteristics of responders and nonresponders. Nonresponse may be managed in two ways. The first is to reduce nonresponse to a minimum using response-enhancement strategies. The second is the post-survey adjustment of data using weighting or imputation techniques to produce estimates that correct for nonresponse. This paper discusses issues concerning response and nonresponse bias in oral health surveys and provides guidelines on the management and reporting of nonresponse. It describes response-enhancement strategies to reduce noncontacts and refusals, sources of data to facilitate the comparison of responders and nonresponders, methods of assessing the degree of bias induced by nonresponse, techniques for producing adjusted survey estimates, and the assumptions on which these procedures and processes are based. | Quality of Health Care |
Three statistical models are introduced as explanations of erythrocyte senescence. For the sake of simplicity, we prefer the multievent model, in which one of the parameters represents the number of events (between 7 and 12) needed to signal likely senescence. Proteolysis of a dimeric protein, such as protein 3, accounts for four events in the model, if little of the protein is degraded by senescence. Although each model we propose accommodates the possibility of random destruction, this alternative does not fit well with available experimental data. | Erythrocyte Aging |
Two forms of succinic-semialdehyde dehydrogenase have been isolated in Pseudomonas putida. The two enzymes could be separated by filtration on Sephacryl S-300 and their apparent molecular weights were approx. 200,000 and 100,000. The smaller enzyme, which is induced by growth on 4-hydroxyphenylacetate, has been purified to 88% homogeneity by anion-exchange and affinity chromatography. Electrophoresis in sodium dodecyl sulphate gave rise to a molecular weight of 53,000, indicating that the native enzyme is dimeric. Under standard assay conditions this enzyme acts preferentially with NAD but reduces NADP at 9% of the rate observed for NAD. The large enzyme, which is dependent on NADP, is induced by growth on putrescine and its induction is highly coordinated with putrescine: 2-oxoglutarate transaminase, gamma-amino-butyraldehyde dehydrogenase and gamma-aminobutyrate: 2-oxoglutarate transaminase activities. Activity and stability conditions and true Km values for substrate and cosubstrates of the two enzymes were determined. | Hydroxybutyrate Dehydrogenase |
Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about abstract causal constraints? Recent empirical studies have revealed that experience with one set of causal cues can dramatically alter subsequent learning and performance with entirely different cues, suggesting that learning involves abstract transfer, and such transfer effects involve sequential presentation of distinct sets of causal cues. It has been demonstrated that pre-training (or even post-training) can modulate classic causal learning phenomena such as forward and backward blocking. To account for these effects, we propose a Bayesian theory of sequential causal learning. The theory assumes that humans are able to consider and use several alternative causal generative models, each instantiating a different causal integration rule. Model selection is used to decide which integration rule to use in a given learning environment in order to infer causal knowledge from sequential data. Detailed computer simulations demonstrate that humans rely on the abstract characteristics of outcome variables (e.g., binary vs. continuous) to select a causal integration rule, which in turn alters causal learning in a variety of blocking and overshadowing paradigms. When the nature of the outcome variable is ambiguous, humans select the model that yields the best fit with the recent environment, and then apply it to subsequent learning tasks. Based on sequential patterns of cue-outcome co-occurrence, the theory can account for a range of phenomena in sequential causal learning, including various blocking effects, primacy effects in some experimental conditions, and apparently abstract transfer of causal knowledge. | Transfer, Psychology |
New Delhi metallo-beta-lactamase 1 (NDM-1) is a key enzyme that the pathogen Klebsiella pneumonia uses to hydrolyze almost all beta-lactam antibiotics. It is currently unclear why NDM-1 has a broad spectrum of activity. Docking of the representatives of the beta-lactam families into the active site of NDM-1 is reported here. All the beta-lactams naturally fit the NDM-1 pocket, implying that NDM-1 can accommodate the substrates without dramatic conformation changes. The docking reveals two major binding modes of the beta-lactams, which we tentatively name the S (substrate) and I (inhibitor) conformers. In the S conformers of all the beta-lactams, the amide oxygen and the carboxylic group conservatively interact with two zinc ions, while the substitutions on the fused rings show dramatic differences in their conformations and positions. Since the bridging hydroxide ion/water in the S conformer is at the position for the nucleophilic attack, the S conformation may simulate the true binding of a substrate to NDM-1. The I conformer either blocks or displaces the bridging hydroxide ion/water, such as in the case of aztreonam, and is thus inhibitory. The docking also suggests that substitutions on the beta-lactam ring are required for beta-lactams to bind in the S conformation, and therefore, small beta-lactams such as clavulanic acid would be inhibitors of NDM-1. Finally, our docking shows that moxalactam uses its tyrosyl-carboxylic group to compete with the S conformer and would thus be a poor substrate of NDM-1. | Moxalactam |
PURPOSE: The purpose of this study was to evaluate caries experience, oral hygiene, plaque deposition, and gingival health status of a group of Saudi children with obstructive sleep apnea and snoring (OSA). METHODS: The sample consisted of 30 OSA and snoring patients (three to eight years old) and 30 age- and gender-matched controls. Dental caries, oral hygiene, plaque deposition, and gingival health status were assessed. RESULTS: The prevalence of dental caries was 83 percent for the control group and 47 percent for the study group. More than one-third (37 percent) of the study group had good oral hygiene compared to only one case (three percent) in the control group. The mean plaque accumulation for the study group was (0.78+/-0.57) and (1.09+/-0.3) for the control group, while the mean gingival index score was (0.05+/-0.13) for the study group and (0.17+/-0.29) for the control group. CONCLUSIONS: Young children suffering from obstructive sleep apnea and snoring have different oral health status compared with nonobstructed control children. OSA subjects had less dental caries, plaque deposition, and gingival inflammation and better oral hygiene. | Dental Health Surveys |
BACKGROUND: The use of creams is considered to be generally safe. However, systemic side effects can occur. CASE DESCRIPTION: A 22-year-old woman came to the emergency department with dyspnea, confusion and 'blue' skin after laser treatment of the upper legs for excessive hair. She had used three tubes of a eutectic mixture of local anaesthetics (EMLA) cream containing lidocaine/prilocaine for analgesia. Her oxygen saturation was 87%, measured with pulse oximetry. Blood gas analysis showed a concentration of oxy-Hb of 79% and a met-Hb of 19%. Our working diagnosis was methaemoglobinaemia as a result of using excessive amounts of EMLA cream. Because the met-Hb concentration decreased spontaneously and the oxy-Hb concentration consequently normalised, we did not administer methylene blue. The patient was discharged symptom-free after several hours of observation. CONCLUSION: An overdose of EMLA cream, whether or not in combination with laser-induced skin damage, can produce a high systemic o-toluidine concentration. This can lead to methaemoglobinaemia. In such cases, the pulse oximeter is not reliable for measuring the oxygen saturation; therefore, blood gas analysis is necessary for making a diagnosis. | Anesthetics, Combined |
The application of boron neutron capture therapy (BNCT) mediated by liposomes containing (10)B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 +/- 16 ppm whereas the precancerous tissue contained 11 +/- 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70-88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70-88%. | Boron Neutron Capture Therapy |
Since 2013/2014, an Information Literacy Advocates (ILA) scheme has been running at the University of Nottingham as an extracurricular module on the Nottingham Advantage Award programme. The Information Literacy Advocates scheme, which recruits medicine and health sciences students in their second year or above, aims to facilitate development of information literacy skills and confidence, as well as communication, organisation and teamwork, through the provision of peer support. Previous research indicates peer assistance effectively enhances such skills and is valued by fellow students who welcome the opportunity to approach more experienced students for help. This article, written by guest writer Ruth Curtis from the University of Nottingham, provides an overview of administering the ILA scheme and explores its impact on the Information Literacy Advocates, peers and librarians, and discusses future developments for taking the scheme forward. H. S. | Consumer Advocacy |
Reliable measurements using modern techniques and consensus in experimental design have enabled the assessment of novel data sets for normal maternal and foetal respiratory physiology at term. These data sets include (a) principal factors affecting placental gas transfer, e.g., maternal blood flow through the intervillous space (IVS) (500 mL/min) and foeto-placental blood flow (480 mL/min), and (b) O(2), CO(2) and pH levels in the materno-placental and foeto-placental circulation. According to these data, the foetus is adapted to hypoxaemic hypoxia. Despite flat oxygen partial pressure (pO(2)) gradients between the blood of the IVS and the umbilical arteries of the foetus, adequate O(2) delivery to the foetus is maintained by the higher O(2) affinity of the foetal blood, high foetal haemoglobin (HbF) concentrations, the Bohr effect, the double-Bohr effect, and high foeto-placental (=umbilical) blood flow. Again, despite flat gradients, adequate CO(2) removal from the foetus is maintained by a high diffusion capacity, high foeto-placental blood flow, the Haldane effect, and the double-Haldane effect. Placental respiratory gas exchange is perfusion-limited, rather than diffusion-limited, i.e., O(2) uptake depends on O(2) delivery. | Placental Circulation |
A nonenzymatic reaction between reducing sugars and amino groups of proteins results in the formation of advanced glycation end products, which are linked to a number of chronic progressive diseases with macro- and microvascular complications. In this research, we sought to ascertain the immunological response to d-ibose-glycated fibrinogen. New Zealand White female rabbits were immunized with native and d-ribose-glycated (Rb-gly-Fb) fibrinogen and used for studying the immunological response. Serum from these rabbits analyzed using direct binding and competitive inhibition ELISA was found to contain a high titer of antibodies against Rb-gly-Fb; Rb-gly-Fb was much more immunogenic than its native form. The IgG against Rb-gly-Fb (Rb-gly-Fb-IgG) was highly specific against the immunogenic protein. Moreover, histopathology and immunofluorescence studies revealed the deposition of the Rb-gly-Fb-IgG immune complex in the glomerular basement membrane of the kidneys of immunized rabbits. Furthermore, immunization with Rb-gly-Fb increased the expression of genes encoding proinflammatory cytokines, tumour necrosis factor alpha, interleukin-6, interleukin-1beta, and interferon-gamma, which is indicative of increased inflammation and the antigenic role of Rb-gly-Fb in provoking an immune response. | Biological Factors |
BACKGROUND AND AIMS: The role of bacterial infection in the pathogenesis of ulcerative colitis (UC) is under investigation. This study aims to (i) determine the prevalence of Campylobacter spp. and Arcobacter spp. in patients with UC, (ii) identify the antibiotic susceptibility of isolated agents, and (iii) investigate the role of these microorganisms in the pathogenesis and/or activation of UC. PATIENTS AND METHODS: Eighty patients with UC and 40 healthy individuals were included in the study. Stool samples were used for cultural examination. Direct plating, membrane filtration, and enrichment methods were used for isolation. 16s rRNA sequence analysis was used for definitive identification of isolates that were identified phenotypically. RESULTS: In the UC group, 20 (25%) patients had proctitis, 40 (50%) patients had left-type involvement, and 20 (25%) patients had extensive involvement. Campylobacter spp. were isolated from four (5%) patients in the UC group and isolates were identified as C. curvus, C. concisus, C. sputorum, and C. jejuni. C. concisus and C. jejuni were found to be resistant to ciprofloxacin, levofloxacin, and trimethoprim-sulfamethoxazole. C. jejuni was also resistant to tetracycline. All samples were negative for Arcobacter spp. The samples from the control group neither showed the presence of Campylobacter spp. nor Arcobacter spp. CONCLUSION: Given the clinical, endoscopic, and bacteriological examination results, it is believed that Campylobacter spp. are agents that cause flare-up clinically by being superimposed on the primary disease, rather than agents that initiate the disease in patients with UC. Arcobacter spp., which are known to cause acute gastroenteritis, were not found to be associated with UC. | Arcobacter |
The data reported here summarize a series of results which reveal new functions for nuclear calmodulin (CaM). The addition of CaM inhibitors to cultures of proliferating NRK cells blocked the activity of the cyclin-dependent protein kinases 4 (cdk4) and 2 (cdk2), which are enzymes implicated in the progression of G1 and in the onset of DNA replication, respectively. CaM modulates the activity of cdk4 by regulating the nuclear location of both cdk4 and cyclin D, its associated regulatory subunit. By using CaM-affinity chromatography, we have recently identified two new nuclear CaM-binding proteins: (i) the protein La/SSB, which is an autoantigen implicated in several autoimmune diseases such as lupus erythematosus and Sjogren's syndrome (since La/SSB participates in the process of transcription mediated by RNA polymerase III, CaM could be involved in the regulation of this process); and (ii) the protein SAP145, a member of the spliceosome-associated proteins (SAPs) which is a subunit of the splicing factor SF3(b). This finding suggests the involvement of CaM in pre-mRNA splicing. Finally, a screening for new CaM-binding proteins in the fission yeast performed by using the phage display analysis, revealed that several nucleolar-ribosomal proteins associate to CaM, suggesting that CaM modulates ribosomal assembly and/or function. | Calmodulin-Binding Proteins |
In this article the guiding questions concern the objectives and effectiveness of introducing mediation into an existing school culture of dominance, competition and selection. In addition the necessity will be shown of combining conflict resolution with organisational development and the introduction of a consensual ethics and behaviour code to attain sustainable results in creating a constructive and healthy school environment. Given scarce resources and little time the decisive role of artistic methods will be looked at in providing young people with flexible methods of expressing and negotiating their interests in a changing environment of values and power structures. Some aspects of the development of nonviolent communication, conflict resolution and mediation methods in schools in Germany will be focused on with special emphasis on the type of intervention used and its long term sustainable effects. | Negotiating |
PURPOSE: Expert consensus recommends that all ventral hernias be repaired prior to, or concomitantly with, peritoneal dialysis (PD) catheter insertion. We examined the clinical outcomes of patients undergoing initial PD catheter insertion, with asymptomatic ventral hernias that were not repaired and rather managed using a watchful waiting approach. METHODS: A single-center, retrospective review of patients undergoing PD catheter insertion from 2005-2019 was performed. Patients who did not undergo repair of a pre-existing ventral hernia at the time of their initial PD catheter insertion were included. The primary endpoint was ventral hernia repair following PD catheter insertion. RESULTS: Forty-one patients were included. Most patients presented with an umbilical hernia (78%). Six patients (15%) underwent ventral hernia repair at a median postoperative interval of 12 months [IQR 8-16], due to abdominal discomfort and hernia enlargement (n = 2) and incarceration (n = 2). Two patients remained asymptomatic, yet underwent ventral hernia repair at the time of renal transplantation. The cumulative incidence of ventral hernia repair within 12 and 24 months of PD catheter insertion was 13% and 21%, respectively. CONCLUSION: Watchful waiting may be an acceptable option for select patients with asymptomatic ventral hernias at the time of initial PD catheter placement. These findings highlight the need to better identify factors associated with asymptomatic ventral hernias that do not warrant concomitant repair to aid surgeons in the decision-making process. | Watchful Waiting |
BACKGROUND & AIMS: Frequent repression of the Socs1 (suppressor of cytokine signaling 1) gene in hepatocellular carcinoma (HCC) and increased susceptibility of SOCS1-deficient mice to hepatocarcinogens suggest a tumor suppressor role for SOCS1 in the liver, but the underlying mechanisms remain unclear. Here we investigated the role of SOCS1 in regulating hepatocyte proliferation following partial hepatectomy and HGF stimulation. METHODS: Because Socs1(-/-) mice die prematurely due to deregulated IFNgamma signaling, we used Socs1(-/-)Ifng(-/-) mice to study the role of SOCS1 in liver regeneration following partial hepatectomy. We examined the activation of signaling molecules downstream of IL-6 and hepatocyte growth factor (HGF) receptors in the regenerating liver, primary hepatocytes, and in human hepatoma cells. We examined the interaction between SOCS1 and the HGF receptor c-Met by reciprocal immunoprecipitation. RESULTS: Socs1(-/-)Ifng(-/-) mice displayed accelerated liver regeneration with increased DNA synthesis compared to Ifng(-/-) and wild type mice. The regenerating liver of Socs1(-/-)Ifng(-/-) mice did not show increased IL-6 signaling, but displayed earlier phosphorylation of Gab1, a signaling adaptor downstream of c-Met. Following HGF stimulation, hepatocytes from Socs1(-/-)Ifng(-/-) mice displayed increased phosphorylation of c-Met and Gab1, cell migration and proliferation. Accordingly, SOCS1 overexpression attenuated HGF-induced phosphorylation of c-Met, Gab1, and ERK1/2 in hepatoma cells, and decreased their proliferation and migration. SOCS1 interacted with the Tpr-Met, an oncogenic form of the Met receptor. CONCLUSIONS: SOCS1 attenuates c-Met signaling and thus negative regulation of HGF signaling could be an important mechanism underlying the anti-tumor role of SOCS1 in the liver. | Oncogene Protein tpr-met |
The world economy depends heavily on crude oil. With a conventional oil recovery process, only one-third of crude oil is extracted. Various technologies have been developed to maximize the recovery of oil resources from natural reservoirs. Polymer technology has been used in many oil fields around the world. The biopolymer pullulan, produced by some Aureobasidium species, has been used in many industrial applications, but no research has been conducted regarding its use in the microbial enhancement of oil recovery (MEOR). Here, we investigate the potential of pullulan produced by newly isolated species Aureobasidium mangrovei SARA-138H for enhancement of oil recovery. Our results indicate that under optimized conditions, that is, sucrose as the carbon source in the medium, a pH of 9, incubation at 25 degrees C, and 250 rpm agitation, the fungus was able to produce 10 g/L of pullulan. The maximum viscosity achieved under these conditions was 318 cP after 15 days of incubation. Pullulan solution (10 g/L) showed the ability to recover 36.7% of heavy crude oil after 34.2% of secondary oil recovery. However, diluted pullulan in brine at the ratio (1:1) resulted in the recovery of 20.23% of oil from the residual oil in the core after 22.6% of secondary oil recovery. A 20-day injectivity test revealed that pullulan passed smoothly through the core, causing no blockage. It was concluded that pullulan from A. mangrovei SARA-138H was able to increase oil recovery to a degree comparable to that achieved with many polymers used in oil fields around the world. KEY POINTS: * First report of biopolymer pullulan" from A. mangrovie. * Optimum conditions for pullulan production were obtained. * Pullulan recovered 36.7% of heavy oil from residual oil in place, with good injectivity." | Aureobasidium |
Jugulotympanic paragangliomas were first described approximately 75 years ago. Since that time, there has been considerable evolution in knowledge of tumor biology, methods of classification, and appropriate management strategies. This paper attempts to summarize these gains in information. | Paraganglioma, Extra-Adrenal |
Small and rural hospitals that have financed capital projects successfully have built a strong base of public support among the local community and regulators, and they have been willing to risk failure to achieve their goals. An open mind, community involvement, and participation of experienced professionals are essential to a successful financing." | Hospital Bed Capacity, under 100 |
We tested the in vitro activity of oritavancin against 60 vancomycin-susceptible enterococci (VSE) and 27 vancomycin-resistant enterococci (VRE). The oritavancin MIC ranged from </=0.002 to 0.5mug/mL; the minimum biofilm bactericidal concentration ranged from </=0.002 to 2mug/mL. Oritavancin has promising in vitro activity against VSE and VRE in both planktonic and biofilm states. | Lipoglycopeptides |
Rubia cordifolia Linn (Rubiaceae) is a climbing perennial herbal plant, which is widely distributed in China and India. Its root and rhizome, Rubiae Radix et Rhizoma (called Qiancao in China and Indian madder in India), is a well known phytomedicine used for hematemesis, epistaxis, flooding, spotting, traumatic bleeding, amenorrhea caused by obstruction, joint impediment pain, swelling and pain caused by injuries from falls. In addition, it is a kind of pigment utilized as a food additive and a dye for wool or fiber. This review mainly concentrates on studies of the botany, phytochemistry, pharmacology and toxicology of this Traditional Chinese Medicine. The phytochemical evidences indicated that over a hundred chemical components have been found and isolated from the medicine, such as anthraquinones, naphthoquinones, triterpenoids, cyclic hexapeptides and others. These components are considered responsible for the various bioactivities of the herbal drug, including anti-oxidation, anti-inflammation, immunomodulation, antitumor, effects on coagulation-fibrinolysis system, neuroprotection and other effects. Additionally, based on these existing results, we also propose some interesting future research directions. Consequently, this review should help us to more comprehensively understand and to more fully utilize the herbal medicine Rubiae Radix et Rhizoma. | Rubia |
Cause and effect relationships between sleep disordered breathing (SDB) and illness, poorer quality of life, and public health have been largely overlooked and undertreated by healthcare providers. Obstructive sleep apnea (OSA), central sleep apnea, upper airway resistance syndrome, and obesity hypoventilation are the primary syndromes that fall under the rubric of SDB. Each of these syndromes is defined; however, OSA is the most common form of SDB, and is the focus of this article. Epidemiology, pathophysiology, behavioral manifestations, cardiovascular comorbidity, clinical evaluation, and treatment for OSA are the main topics covered. The article concludes with the role of the nurse in SDB. | Dyssomnias |
A longitudinal study of employment patterns and turnover of clinical laboratory personnel in the Minneapolis-St. Paul area was conducted for the years 1970, 1980, and 1990. Laboratory staffing patterns for the years studied showed a general plateau in numbers and categories of personnel between 1980 and 1990, following a doubling in those numbers between 1970 and 1980. In 1990, for a geographic area of 2.2 million people, a total of 2,500 laboratory personnel were employed in 31 major laboratories. Fifty-six percent were medical technologists (clinical laboratory scientists), 6% cytotechnologists and histologic technicians, 23% laboratory technicians, 9% phlebotomists, and 7% in other" categories. The ratio of full- to part-time employees was approximately 3 to 1. Between 1970 and 1990, annual turnover rates for all laboratory personnel declined from 20% to 15%. In 1990, the personnel group experiencing the lowest turnover was in cytotechnology (4%) and the rate for medical technologists was 9%. The turnover for laboratory technicians was 17%, and the rate for histologic technicians was 19%. Highest turnover occurred among phlebotomists (36%) and "others" (39%). While the numbers of laboratory personnel employed leveled off between 1980 and 1990, numbers of new graduate technologists and technicians decreased by approximately one-half. Personnel shortages in laboratory science can therefore be expected to continue." | Medical Laboratory Personnel |
Uroporphyrinogen decarboxylase (URO-D) catalyzes the fifth step in the heme biosynthetic pathway, converting uroporphyrinogen to coproporphyrinogen by decarboxylating the four acetate side chains of the substrate. This activity is essential in all organisms, and subnormal activity of URO-D leads to the most common form of porphyria in humans, porphyria cutanea tarda (PCT). We have determined the crystal structure of recombinant human URO-D at 1.60 A resolution. The 40.8 kDa protein is comprised of a single domain containing a (beta/alpha)8-barrel with a deep active site cleft formed by loops at the C-terminal ends of the barrel strands. Many conserved residues cluster at this cleft, including the invariant side chains of Arg37, Arg41 and His339, which probably function in substrate binding, and Asp86, Tyr164 and Ser219, which may function in either binding or catalysis. URO-D is a dimer in solution (Kd = 0.1 microM), and this dimer also appears to be formed in the crystal. Assembly of the dimer juxtaposes the active site clefts of the monomers, suggesting a functionally important interaction between the catalytic centers." | Uroporphyrinogen Decarboxylase |
Since their emergence a few years ago, artificial intelligence (AI)-synthesized media-so-called deep fakes-have dramatically increased in quality, sophistication, and ease of generation. Deep fakes have been weaponized for use in nonconsensual pornography, large-scale fraud, and disinformation campaigns. Of particular concern is how deep fakes will be weaponized against world leaders during election cycles or times of armed conflict. We describe an identity-based approach for protecting world leaders from deep-fake imposters. Trained on several hours of authentic video, this approach captures distinct facial, gestural, and vocal mannerisms that we show can distinguish a world leader from an impersonator or deep-fake imposter. | Kinesics |
The purpose of this paper was to present the case of a 15-year-old female diagnosed with infantile Refsum disease (IRD) that presented with generalized enamel defects in the primary and permanent dentition. IRD is an inherited autosomal recessive disorder characterized by aberrant peroxisome function. IRD patients present with multiple clinical manifestations, including: retinitis pigmentosa; nystagmus; sensorineural hearing loss; mental and developmental delays; neuromotor defects; and cerebral ataxia. Craniofacial abnormalities reported include: high forehead; hypoplastic supraorbital ridges; epicanthal folds; midface hypoplasia; and large anterior fontanelle. At present, there is only one known report of dental anomaly associated with this syndrome. This represents the first known reported case in the pediatric dental literature. | Refsum Disease, Infantile |
The rationale, content, and teaching techniques used for a psychiatry residency psychodynamic therapy course based on Psychodynamic Therapy: A Guide to Evidence-Based Practice (Summers & Barber, 2009) are presented in the context of their evolution over the last two decades and the challenges of teaching this topic in the current environment. The central elements of an exciting and engaging psychotherapy teaching program-feelings, framework, and freedom-are explained. Specific topics such as psychodynamic formulation, using videos, self-disclosure, and resistance are discussed. | Psychotherapy, Psychodynamic |
INTRODUCTION: Whether anesthesia depth affects postoperative mortality remains uncertain. MEASUREMENTS: Several databases were systematically searched to identify all articles studying the relationship between depth of anesthesia and postoperative mortality. Post hoc subgroup analyses were conducted for follow-up period (30â¯days vs. longer than 90â¯days) and type of surgery. MAIN RESULTS: The analysis included 38,722 patients from nine studies. We observed a significant relationship between low bispectral index (BIS) and mortality (pooled aHR, 1.22;95% CI, 1.08 to 1.38; Pâ¯=â¯0.001; I(2)â¯=â¯85.4%). Post hoc subgroup analyses indicated low BIS to be linked with significantly elevated mortality risk in patients with >/=90â¯days follow-up (pooled adjusted hazard ratio [aHR], 1.09; 95% CI, 1.00-1.19; Pâ¯=â¯0.01; I(2)â¯=â¯79.4%), but this association did not achieve significance in those with a 30â¯day follow-up duration (pooled aHR, 1.52; 95% CI, 0.97-2.38; Pâ¯=â¯0.28; I(2)â¯=â¯79.0%). In addition, this link between postoperative mortality and low BIS was significant in those who had undergone cardiac surgery (pooled aHR, 1.30; 95% CI, 1.14 to 1.49; Pâ¯<â¯0.001; I(2)â¯=â¯0.0%), but not in patients that had received other forms of surgery (pooled aHR, 1.06; 95% CI, 0.98 to 1.14; Pâ¯=â¯0.14; I(2)â¯=â¯73.2%). CONCLUSIONS: We observed a significant relationship between deep anesthesia and long-term mortality, though this was not significant 30â¯days following surgery. In patients who had received cardiac surgery, deep anesthesia may increase mortality. However, this trend was not observed in patients who had undergone other forms of surgery. | Consciousness Monitors |
OBJECTIVE: To find out an ideal method used in identification of Streptococcus sanguis group (SSG) strains by arbitrary primed polymerase chain reaction (AP-PCR). METHODS: AP-PCR was used to distinguish SSG strains by designing 25 bp arbitrary primer 5' AAG AGA GGA GCT AGC TCT TCT TGG A 3'. RESULTS: There were great differences in the main band of DNA polymorphism among SSG species. The similar band can be obtained from the different DNA extractions in the same species. CONCLUSION: AP-PCR may be useful in the identification and classification of SSG species. | Viridans Streptococci |
Snakebites are estimated to cause approximately 100,000 deaths each year worldwide and disproportionately affect rural populations in resource-poor settings. Snake venoms may produce local tissue damage and/or distinct clinical syndromes, including neurotoxicity, coagulopathy, hypotension, rhabdomyolysis, and renal failure. Field management is aimed at delaying systemic absorption of toxins, minimizing local damage and infection, and expediting transport to medical facilities. The use of the pressure-immobilization method remains controversial. The use of antivenom, administered in a timely fashion and in adequate doses, is the mainstay of hospital treatment of significant envenomation. The availability, efficacy, and safety of antivenoms vary throughout the world, with a current crisis in antivenom supplies. | Antivenins |
Transient cardiac dysfunction, or Takotsubo cardiomyopathy, is a well-known complication among patients presenting with neurologic insult, who are described as having takotsubo syndrome. This condition is commonly associated with aneurysmal subarachnoid hemorrhage but has also been described in patients after cerebral surgery or in those with ischemic stroke, seizure, and traumatic brain injury. Current evidence suggests that cardiac dysfunction in these patients is a result of increases in catecholamines that are induced by supraphysiologic levels of sympathetic activity. The cardiac injury is typically reversible and carries a good prognosis, but secondary complications may arise if the diagnosis is not recognized early. | Takotsubo Cardiomyopathy |
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