Effect of bariatric surgery on heart failure.
Obesity increases the risk of heart failure (HF), which continues to be a significant proportion of all cardiovascular diseases and affects increasingly younger populations. The cross-talk between adipose and the heart involves insulin resistance, adipokine signaling and inflammation, with the capacity of adipose tissue to mediate hemodynamic signals, promoting progressive cardiomyopathy. Areas covered: From a therapeutic perspective, there is not yet a single obesity-related pathway that when addressed, can ameliorate cardiomyopathy in obese patients and this is a matter of ongoing research. There is poor evidence of the beneficial long-term effect of small nonsurgical intentional weight loss on HF outcomes, in contrast to the field of HF accompanying severe obesity where observational studies have shown that bariatric surgery is associated with improved cardiac structure/function in severely obese patients with HF and preserved ejection fraction (HFpEF) as well as with improved cardiac structure/function in those with HF and reduced ejection fraction (HFrEF). Few studies report positive outcomes in subjects with obesity and HF, both severe, who underwent bariatric surgery as a rescue treatment, including bridge to heart transplantation. Expert commentary: The fast growing prevalence of obesity will continue to require the development of appropriate interventions directed at controlling or slowing pathways of cardiac damage in these patients, but at present, bariatric surgery should be considered an option to try to decrease morbidity associated with HF in severely obese adults.


The Sequential Integration of Pharmacotherapy and Psychotherapy in the Treatment of Major Depressive Disorder: A Meta-Analysis of the Sequential Model and a Critical Review of the Literature.
A number of randomized controlled trials in major depressive disorder have employed a sequential model, which consists of the use of pharmacotherapy in the acute phase and of psychotherapy in its residual phase. The aim of this review was to provide an updated meta-analysis of the efficacy of this approach in reducing the risk of relapse in major depressive disorder and to place these findings in the larger context of treatment selection. Keyword searches were conducted in MEDLINE, EMBASE, PsycINFO, and Cochrane Library from inception of each database through October 2014. Randomized controlled trials examining the efficacy of the administration of psychotherapy after successful response to acute-phase pharmacotherapy in the treatment of adults with major depressive disorder were considered for inclusion in the meta-analysis. Thirteen high-quality studies with 728 patients in a sequential treatment arm and 682 in a control treatment arm were included. All studies involved cognitive-behavioral therapy (CBT). The pooled risk ratio for relapse/recurrence was 0.781 (95% confidence interval [CI]=0.671-0.909; number needed to treat=8), according to the random-effects model, suggesting a relative advantage in preventing relapse/recurrence compared with control conditions. A significant effect of CBT during continuation of antidepressant drugs compared with antidepressants alone or treatment as usual (risk ratio: 0.811; 95% CI=0.685-0.961; number needed to treat=10) was found. Patients randomly assigned to CBT who had antidepressants tapered and discontinued were significantly less likely to experience relapse/recurrence compared with those assigned to either clinical management or continuation of antidepressant medication (risk ratio: 0.674; 95% CI=0.482-0.943; number needed to treat=5). The sequential integration of CBT and pharmacotherapy is a viable strategy for preventing relapse in major depressive disorder. The current indications for the application of psychotherapy in major depressive disorder are discussed, with special reference to its integration with pharmacotherapy.


Nanoparticle-Exposure-Triggered Virus Reactivation Induces Lung Emphysema in Mice.
Nanoparticles (NPs) released from engineered materials or combustion processes as well as persistent herpesvirus infection are omnipresent and are associated with chronic lung diseases. Previously, we showed that pulmonary exposure of a single dose of soot-like carbonaceous NPs (CNPs) or fiber-shaped double-walled carbon nanotubes (DWCNTs) induced an increase of lytic virus protein expression in mouse lungs latently infected with murine γ-herpesvirus 68 (MHV-68), with a similar pattern to acute infection suggesting virus reactivation. Here we investigate the effects of a more relevant repeated NP exposure on lung disease development as well as herpesvirus reactivation mechanistically and suggest an avenue for therapeutic prevention. In the MHV-68 mouse model, progressive lung inflammation and emphysema-like injury were detected 1 week after repetitive CNP and DWCNT exposure. NPs reactivated the latent herpesvirus mainly in CD11b+ macrophages in the lungs. In vitro, in persistently MHV-68 infected bone marrow-derived macrophages, ERK1/2, JNK, and p38 MAPK were rapidly activated after CNP and DWCNT exposure, followed by viral gene expression and increased viral titer but without generating a pro-inflammatory signature. Pharmacological inhibition of p38 activation abrogated CNP- but not DWCNT-triggered virus reactivation in vitro, and inhibitor pretreatment of latently infected mice attenuated CNP-exposure-induced pulmonary MHV-68 reactivation. Our findings suggest a crucial contribution of particle-exposure-triggered herpesvirus reactivation for nanomaterial exposure or air pollution related lung emphysema development, and pharmacological p38 inhibition might serve as a protective target to alleviate air pollution related chronic lung disease exacerbations. Because of the required precondition of latent infection described here, the use of single hit models might have severe limitations when assessing the respiratory toxicity of nanoparticle exposure.


Products distribution in the oxidation of thymine with hydroxyl radicals.
In the oxidation of thymine with hydroxyl radical generated from L-ascorbic acid/copper(II) ion/O system, four reaction products, thymine glycol(TG), N-formyl-N'-pyruvylurea(FPU), 5-hydroxymethyluracil(HMU) and 5-hydroxy-5-methyl barbituric acid(HMBA) were obtained. A reaction scheme was proposed to explain the products distribution observed.


Fosaprepitant dimeglumine (MK-0517 or L-785,298), an intravenous neurokinin-1 antagonist for the prevention of chemotherapy induced nausea and vomiting.
This paper reviews the existing literature on fosaprepitant, an intravenous neurokinin-1 anatgonist for the prevention of chemotherapy induced nausea and vomiting. To describe the development of fosaprepitant and to situate the intravenous form of aprepitant in the current market of available antiemetics. Literature was screened and selected in order to compare the intravenous form of the already commonly used NK-1 receptor antagonist aprepitant. Aprepitant is the first and still the only marketed neurokinin-1 (NK-1) antagonist. Interestingly, the first studies were performed with fosaprepitant dimeglumine (MK-0517 or L-785,298), the water-soluble prodrug of aprepitant. Fosaprepitant is converted into aprepitant within 30 min after intravenous administration. Based on equivalence studies, 115 mg fosaprepitant seems to be the substitute for 125 mg orally administrated aprepitant. Tolerability of the prodrug is no different from the active drug. The number of efficacy studies with fosaprepitant is very limited and most data are derived from existing aprepitant results. Fosaprepitant has recently been approved by FDA and EMEA as an intravenous substitute for oral aprepitant on day 1 of the standard 3-day CINV prevention regimen, which also includes dexamethasone and a 5-HT3 antagonist.


Crystallographic rationalization of the reactivity and spectroscopic properties of (2R)-S-(2,5-dihydroxyphenyl)cysteine.
At 150 K, the title compound, C(9)H(11)NO(4)S, crystallizes in the orthorhombic form as a zwitterion and has a low gauche conformation [chi = -46.23 (16) degrees] for an acyclic cysteine derivative. A difference in bond length is observed for the alkyl C-S bond [1.8299 (15) A] and the aryl C-S bond [1.7760 (15) A]. The -NH(3)(+) group is involved in four hydrogen bonds, two of which are intermolecular and two intramolecular. The compound forms an infinite three-dimensional network constructed from four intermolecular hydrogen bonds. Characterization data ((13)C NMR, IR and optical rotation) are reported to supplement the incomplete data disclosed previously in the literature.


Biomarkers of treatment toxicity in combined-modality cancer therapies with radiation and systemic drugs: study design, multiplex methods, molecular networks.
Organ toxicity in cancer therapy is likely caused by an underlying disposition for given pathophysiological mechanisms in the individual patient. Mechanistic data on treatment toxicity at the patient level are scarce; hence, probabilistic and translational linkages among different layers of data information, all the way from cellular targets of the therapeutic exposure to tissues and ultimately the patient's organ systems, are required. Throughout all of these layers, untoward treatment effects may be viewed as perturbations that propagate within a hierarchically structured network from one functional level to the next, at each level causing disturbances that reach a critical threshold, which ultimately are manifested as clinical adverse reactions. Advances in bioinformatics permit compilation of information across the various levels of data organization, presumably enabling integrated systems biology-based prediction of treatment safety. In view of the complexity of biological responses to cancer therapy, this communication reports on a "top-down" strategy, starting with the systematic assessment of adverse effects within a defined therapeutic context and proceeding to transcriptomic and proteomic analysis of relevant patient tissue samples and computational exploration of the resulting data, with the ultimate aim of utilizing information from functional connectivity networks in evaluation of patient safety in multimodal cancer therapy.


[Possibilities of use of digital imaging in forensic medicine].
Based on the daily practice with digital photography and documentation, the authors point out the achievements of the computer technologies implementation to the practice of forensic medicine. The modern methods of imaging, especially the digital photography, offer a wide spectrum of use in forensic medicine--the digital documentation and archivation of autopsy findings, the possibility of immediate consultation of findings with another experts via Internet, and many others. Another possibility is a creation of digital photographic atlas of forensic medicine as a useful aid in pre- and postgradual study. Thus the application of the state-of-the-art computer technologies to the forensic medicine discloses the unknown before possibilities for further development of such a discipline of human medical sciences.


A phase I human trial of mitoguazone and gemcitabine sequential bi-weekly treatment of cancer patients.
Our previous studies have demonstrated the existence of synergism in a combination therapy using mitoguazone and gemcitabine when the mitoguazone is administered 24 hours before gemcitabine. Based on the cell culture and animal experimental results, a phase I clinical trial was performed in order to determine the toxicity of the combined treatment. Mitoguazone and gemcitabine were administered sequentially: mitoguazone on day 1 and gemcitabine on day 2. This cycle was repeated every 2 weeks. The dosages of these two drugs were varied between patients. Ten patients were enrolled in the study. Six patients began treatment at dose level 1 (mitoguazone 500 mg/m2, gemcitabine 1500 mg/m2), three at dose level 2 (mitoguazone 500 mg/m2, gemcitabine 2000 mg/m2), and one at dose level 3 (mitoguazone 600 mg/m2, gemcitabine 2000 mg/m2). Dose-limiting toxicity (DLT) was only observed in two patients treated at dose level 1 and one patient treated at dose level 3, while all the other patients only experienced nonhematologic toxicity, such as asthenia and mucositis. Two melanoma patients showed responses (one partial and one minor) to the treatment. One lymphoma patient also showed a brief partial response. This phase I trial indicated that the combination of mitoguazone and gemcitabine had limited but noticeable activity for treatment of cancer patients. Further study on the toxicity and on the effect of the scheduled mitoguazone-gemcitabine combination is needed.


Cache Valley virus: A scoping review of the global evidence.
Cache Valley virus (CVV) is a mosquito-borne RNA virus detected throughout North America, Central America and parts of South America. A limited number of human case reports have described severe illness. CVV infection has been associated with outbreaks of congenital defects in small ruminants in Canada and the United States. A scoping review was conducted to identify, characterize and summarize research on CVV, and to identify research gaps. A structured search was conducted in eight electronic databases, with additional search verification and grey literature investigation. All captured studies were independently appraised by two reviewers for relevance and data characterization. The review captured 143 relevant studies investigating CVV epidemiology (n = 104), pathogenesis (n = 37), viral characteristics (n = 24), transmission (n = 14), diagnostic test performance (n = 8) and mitigation strategies (n = 2). Evidence of CVV infection was found in mosquito studies (n = 47), and serological evidence of exposure was demonstrated in animals (n = 41), as well as human (n = 20) studies. In sheep, five outbreaks of birth defects following asymptomatic dam CVV infection during the first 50 days of pregnancy were reported. Only six human cases of CVV-associated illness were captured, with case symptoms described as initially non-specific, progressing to more severe clinical signs (e.g., meningitis). No research was identified investigating treatment, societal knowledge and risk perception, economic burden or predictive models related to the impact of climate change on CVV. CVV circulates in mosquito and animal species across a large area of the Americas. Small ruminants are the only animals in which CVV-associated clinical disease has been extensively studied. It is likely that human cases are under-reported or misdiagnosed. Future research should focus on the impact of CVV infection in human and animal populations.


The dynamic evolution and coupling coordination development mechanism of new urbanization and green economy: an empirical study based on various provinces in China.
Under the background that the country is vigorously promoting the construction of new urbanization and seeking green development, this paper takes 31 provinces of China as the research object. It constructs a comprehensive evaluation system that integrates new urbanization and green economy into the same research framework, analyzes the evolution characteristics of new urbanization and green economy from the scale analysis of time and space, and, through the relative development model, coupling coordination model, and the random panel Tobit model, further explores the relative development and coupling coordination relationship between the two, deconstructing the internal driving factors. Research shows that the regional differences in the development level of new urbanization are decreasing year by year, while the efficiency of the green economy is increasing yearly. The relative development types of the two have obvious regional distribution characteristics. The level of coupling coordination gradually increases over time. The impact of economic development and growth, urban construction, regional opening up, urban expansion, government investment, industrialization level, and industrial structure on the coupling coordination degree of new urbanization and green economy is inconsistent.


Whole Body Vibration-Induced Omental Macrophage Polarization and Fecal Microbiome Modification in a Murine Model.
Human nutrient metabolism, developed millions of years ago, is anachronistic. Adaptive features that offered survival advantages are now great liabilities. The current dietary pattern, coupled with massively reduced physical activities, causes an epidemic of obesity and chronic metabolic diseases, such as type 2 diabetes mellitus. Chronic inflammation is a major contributing factor to the initiation and progression of most metabolic and cardiovascular diseases. Among all components of an innate immune system, due to their dual roles as phagocytic as well as antigen-presenting cells, macrophages play an important role in the regulation of inflammatory responses, affecting the body's microenvironment and homeostasis. Earlier studies have established the beneficial, anti-inflammatory effects of whole body vibration (WBV) as a partial exercise mimetic, including reversing the effects of glucose intolerance and hepatic steatosis. Here for the first time, we describe potential mechanisms by which WBV may improve metabolic status and ameliorate the adverse consequences through macrophage polarization and altering the fecal microbiome.


Structural and functional consequences of buserelin-induced enteric neuropathy in rat.
Women treated with gonadotropin-releasing hormone (GnRH) analogs may develop enteric neuropathy and dysmotility. Administration of a GnRH analog to rats leads to similar degenerative neuropathy and ganglioneuritis. The aim of this study on rat was to evaluate the early GnRH-induced enteric neuropathy in terms of distribution of neuronal subpopulations and gastrointestinal (GI) function. Forty rats were given the GnRH analog buserelin (20 μg, 1 mg/ml) or saline subcutaneously, once daily for 5 days, followed by 3 weeks of recovery, representing one treatment session. Two weeks after the fourth treatment session, the animals were tested for GI transit time and galactose absorption, and fecal weight and fat content was analyzed. After sacrifice, enteric neuronal subpopulations were analyzed. Blood samples were analyzed for zonulin and antibodies against GnRH and luteinizing hormone, and their receptors. Buserelin treatment transiently increased the body weight after 5 and 9 weeks (p < 0.001). Increased estradiol in plasma and thickened uterine muscle layers indicate high estrogen activity. The numbers of both submucous and myenteric neurons were reduced by 27%-61% in ileum and colon. The relative numbers of neurons containing calcitonin gene-related peptide (CGRP), cocaine- and amphetamine-related transcript (CART), galanin, gastrin-releasing peptide (GRP), neuropeptide Y (NPY), nitric oxide synthase (NOS), serotonin, substance P (SP), vasoactive intestinal peptide (VIP) or vesicular acetylcholine transporter (VAchT), and their nerve fiber density, were unchanged after buserelin treatment, but the relative number of submucous neurons containing somatostatin tended to be increased (p = 0.062). The feces weight decreased in buserelin-treated rats (p < 0.01), whereas feces fat content increased (p < 0.05), compared to control rats. Total GI transit time, galactose absorption, zonulin levels in plasma, and antibody titers in serum were unaffected by buserelin treatment. A marked enteric neuronal loss with modest effects on GI function is found after buserelin treatment. Increased feces fat content is suggested an early sign of dysfunction.


In vitro effects of islet-activating protein on cultured rat pancreatic islets. Enhancement of insulin secretion, adenosine 3':5'-monophosphate accumulation and 45Ca flux.
Pancreatic islets were maintained in culture with or without islet-activating protein (IAP), which is a new protein purified from culture medium of Bordetella pertussis. These cultured islets (IAP-treated or control) were then incubated for 30 min in IAP-free medium with various insulin secretagogues. During incubation, much more insulin was released from IAP-treated islets than control islets in response to glucose, arginine, glucagon, and sulfonylurea. IAP was effective in this regard when added to cultures at concentrations higher than 0.01 ng/ml; the effect was dependent on concentration up to 100 ng/ml. Enhanced insulin secretion was associated with accumulation of cyclic AMP when breakdown of the nucleotide was prevented by a methylxanthine. Epinephrine caused marked inhibitions, via alpha-adrenergic receptors, of glucose-induced insulin release, cyclic AMP accumulation and 45Ca uptake in control islets but did not in IAP-treated islets during incubation. None of these effects of IAP pretreatment were observed unless the medium for incubation was supplemented with Ca ions. 45Ca ion flux through the islet cell membrane was accelerated by the IAP treatment; conceivably, IAP was effective in causing sustained activation of native calcium ionophores on the membrane, which would be responsible for the enhanced insulin and cyclic AMP responses characteristic of IAP-treated islets.


Biochemical aspects of therapy-resistant depression.
Despite the relatively high incidence of therapy-resistant depression, there is little clinical evidence to suggest that there are significant biochemical differences between therapy-resistant and therapy-responsive patients. A major problem for investigators is the lack of an internationally recognised definition of resistant depression. Also, it is possible that depressed patients with delusional symptoms or rapidly cycling affective disorders from subgroups that are more likely to be resistant to tricyclic antidepressant treatment and are therefore classified as therapy-resistant. Evidence is presented to show that an abnormality in serotonergic function may characterise some therapy-resistant depressed patients.


A lesson for unraveling complex aspects of novel immunodeficiencies from the human equivalent of the nude/SCID phenotype.
The human equivalent form of the severe combined congenital immunodeficiency of the nude/SCID mouse has been recently described in 2 siblings originating from a small community in southern Italy. Similar to the mouse, the human phenotype is characterized by a profound T cell ontogenetic defect associated with congenital alopecia and nail dystrophy. The disease is related in either mice and humans to molecular alterations of the gene encoding a forkhead/winged helix transcription factor, which is selectively expressed in thymic epithelia. Remarkably, due to the selectivity of the tissue expressivity of the gene responsible for the syndrome, this is the first example of SCID not primarily related to an hematopoietic cell abnormality, but rather to thymic aplasia. The opportunity to study immunological reconstitution in the absence of a functioning thymus following a bone marrow transplantation from a related HLA-identical sibling gave us insight into the role of the thymus in in vivo T cell ontogeny and maintenance of T cell functionality. This model led us to address a few general issues that may have clinical implications.


Subepithelial rectal gastrointestinal stromal tumor - the use of endoscopic ultrasound-guided fine needle aspiration to establish a definitive cytological diagnosis: a case report.
Gastrointestinal stromal tumors are the most common mesenchymal neoplasms affecting the gastrointestinal tract. The stomach is the most common location to be affected, and the rectum one of the rarest, but the whole gastrointestinal tract remains susceptible. Gastrointestinal stromal tumors account for only 0.1% of rectal tumors. Currently, endoscopic ultrasound plays an essential role in the diagnostic process of gastrointestinal stromal tumors, especially when the affected sites have a worse outcome and higher morbidity rates. We describe the case of a 68-year-old white Japanese man with a history of long-term mild rectal pain and tenesmus. A digital rectal examination revealed a right palpable solid mass ranging from 3 to 7 cm from his anal verge. A colonoscopy was performed and showed a 5 cm elevated lesion covered by normal mucosa, located 4 cm above the pectineal line. Endoscopic ultrasound confirmed the diagnosis of a homogeneous hypoechoic mass with areas of necrosis as a rectal subepithelial lesion originating at the fourth layer (muscularis propria). He then underwent endoscopic ultrasound-guided fine needle aspiration of the lesion, followed by cytological and immunohistochemistry evaluation. The evaluation showed spindle and epithelioid cells of variable sizes, in fascicles separated by stroma, which reacted firmly and consistently to CD117/c-kit and CD34, and negative to desmin and S-100 protein. There was weak staining for nuclear Ki-67 in the tumor cells. A diagnosis of rectal gastrointestinal stromal tumor was confirmed. After a multidisciplinary meeting, an abdominoperineal resection of his rectum was performed. The pathology of the specimen confirmed the diagnosis of rectal gastrointestinal stromal tumor. He is now asymptomatic after 3 months' follow-up and is on adjuvant therapy with a tyrosine-kinase inhibitor. Gastrointestinal stromal tumors are rare tumors, and among the variety of primary location sites, the rectum is one of the rarest. The localization of this type of tumor has worse outcomes and higher morbidity rates. We report this rare case to emphasize the need for precise diagnosis and the important role of endoscopic ultrasound-guided fine needle aspiration in such situations.


Assessment of Difficulties Associated with Endotracheal Intubation using Modified Mallampati and Upper Lip Bite Test.
This study was aimed at finding the parameters for prediction of difficulty in endotracheal intubation, that are easy to examine and that could better predict difficulty. The current observational prospective, cross sectional study was conducted in the department of Anaesthesia, Analgesia and Intensive Care Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from March 2015 to September 2015 comprising 180 patient of both sexes requiring endotracheal intubation were arranged into two groups, Group A: Modified Mallampati test Group and Group B: Modified Mallampati & upper lip bite test group (combined) Assessment of difficulty in intubation was done by Cormack & Lehane direct Laryngoscopic grading. Outcome was measured as no difficulty or difficulty in intubation. In Group A 33 cases were true positive, 15 false negative, 26 false positive, 16 true negative. In Group B 53 cases were true positive, 1 false positive, 8 false negative, 28 true negative. The validity tests for Group A for evaluation of difficult intubation were indicated by sensitivity 55.9%, Specificity 51.6%, Accuracy 54.41%, Positive predictive value 68.8% and Negative predictive value 38.1%. The values for Group-B were 86.9%, 96.6%, 90.0%, 98.1% and 77.8% respectively. Combined modified Mallampati & Upper Lip Bite Test has definite value in the diagnosis of difficulty in intubation and can be regarded as sensitive & specific test for operative discrimination of the patient.


Rapid testing for the MCAD G583A mutation, by PCR-mediated site directed mutagenesis, in an Australian population of SIDS patients.
Medium Chain Acyl CoA Dehydrogenase (MCAD) deficiency is the most common genetic disorder of fatty acid metabolism and has been reported as a cause of sudden death in infants. We investigated the incidence of a rare MCAD mutation (G583A) in a large population of SIDS patients. A method utilising PCR mediated site directed mutagenesis and restriction enzyme digestion was devised to enable rapid and simple testing of large numbers of samples. The G583A mutation was not detected in 413 SIDS patients tested suggesting the mutation is not an important cause of sudden death in infants. The prevalence of this mutation in the general population was estimated to be between 0 and 0.89%.


Teaching visual thinking in radiology.
We have implemented a tutoring system, Radiology Puzzler, for teaching visual recognition of intracranial lesions on radiological images. The system is designed to support the learning of radiological patterns through graphical case retrieval. Using radiologic feature samplers, the user may define brain lesion characteristics and use visual query when searching for reference cases. A rule-based module generates a hierarchical list of diagnostic hypotheses and provides a feed-back to the user. Relevant cases that match the sampler's index are retrieved from the case library for comparison with the case in question.


Taurocholic acid lowers the inflammatory response of gingival fibroblasts, epithelial cells, and macrophages.
Taurocholic acid (TCA), a conjugation of cholic acid with taurine, is one of the main bile acids that is elevated in liver disease. Considering the epidemiologic linkage of periodontal disease to liver disease, the question arises about the possible effect of elevated TCA levels on periodontal cells. To answer this question, gingival fibroblasts and human oral squamous cell carcinoma cell line (HSC-2) were pretreated with interleukine1β (IL1β) and tumor necrosis factorα (TNFα) in the presence and absence of TCA. Also, mouse macrophages (RAW 264.7) were incubated with sterile-filtered human saliva with and without TCA. Inflammatory cytokines were measured by real time polynucleotide chain reaction (RT-PCR) and an immunoassay. The nuclear translocation of the p65 subunit was visualized by immunostaining. In pretreated gingival fibroblasts and HSC-2 cells, TCA considerably reduced the expression of IL1β, IL6, and IL8. In support of these observations, TCA lowered the saliva-induced expression of IL1α, IL1β and IL6 in RAW 264.7 cells. An immunoassay confirmed the capacity of TCA to diminish inflammation-induced expression of IL6 in gingival fibroblasts, HSC-2 and RAW 264.7 cells. Consistently, TCA blocked the nuclear translocation of p65 in fibroblasts. These findings suggest that TCA has anti-inflammatory activity in gingival fibroblasts, human oral squamous cell carcinoma cells and macrophages in vitro.


[Proton therapy: clinico-methodological aspects, treatment results].
In the period of 1975-1986, 457 patients (81 with breast and prostatic cancer, 24 with endocrine ophthalmopathy, 20 with diabetic angioretinopathy, 206 with pituitary adenomas, 115 with arteriovenous and 6 with arterial brain malformations, and 6 with epilepsy) were given proton beam therapy at the Central Research Roentgenoradiology Institute using the 1000 MeV synchrocyclotron of the Leningrad Institute for Nuclear Physics. A prolonged remission was noted in 75-90% of the patients with pituitary adenomas. Angiography showed complete exclusion of aneurysm from the blood flow 2 yrs. after irradiation almost in 50% of the patients with arteriovenous malformations. A high efficacy and safety of the method was shown.


Ameliorative effects of mulberry (Morus alba L.) leaves on hyperlipidemia in rats fed a high-fat diet: induction of fatty acid oxidation, inhibition of lipogenesis, and suppression of oxidative stress.
To determine the effects of mulberry (Morus alba L.) leaves on hyperlipidemia, we performed gene expression profiling of the liver. Rats were fed a high-fat diet and administered mulberry leaves for 7 weeks. Plasma triglyceride and non-esterified fatty acid levels were significantly lower in the rats treated with mulberry leaves as compared with the untreated rats. DNA microarray analysis revealed that mulberry leaves upregulated expression of the genes involved in α-, β- and ω-oxidation of fatty acids, mainly related to the peroxisome proliferator-activated receptor signaling pathway, and downregulated the genes involved in lipogenesis. Furthermore, treatment with mulberry leaves upregulated expression of the genes involved in the response to oxidative stress. These results indicate that consumption of fatty acids and inhibition of lipogenesis are responsible for the reduction in plasma lipids caused by mulberry administration. In addition, mulberry treatment maintains the body's oxidative state at a low level despite enhancing fatty acid oxidation.


Heavy metal hazards of sachet water in Nigeria.
The authors assessed sachet water samples sold in Eastern Nigeria. Using an atomic absorption spectrophotometer, they analyzed levels of lead, cadmium, copper, and nickel. They also analyzed other parameters, such as nitrates, sulfates, chlorides, salinity, total hardness, biological oxygen demand, total dissolved solids, and pH level. Lead levels ranged from 0.002 to 0.036 mg/L in the samples; 5 samples (12.2%) had lead levels above the maximum contaminant level (MCL; 0.015 mg/L). Lead was not detectable in 20 samples (48.8%). Cadmium levels ranged from 0.002 to 0.036 mg/L and exceeded the MCL of 0.005 mg/L in 8 samples (19.5%); it was not detectable in 23 samples (56.1%). Copper was not detected in 2 (0.05%) of the samples. Its range was between 0.018 and 1.401 mg/L. Two samples (0.05%) had copper levels above the MCL (1.30 mg/L). Nickel levels ranged from 0.003 to 0.050 mg/l. The biological oxygen demand of the samples ranged from 3.20 to 36.80 mg/L. Other parameters were normal. The authors found that some of the sachet waters contain heavy metals, and consumers may be exposed to hazards.


A Yeast-Based Screening System for Differential Identification of Poisons and Suppressors of Human Topoisomerase I.
Inhibition of human topoisomerase I (TOP1) by camptothecin and topotecan has been shown to reduce excessive transcription of PAMP (Pathogen-Associated Molecular Pattern)-induced genes in prior studies, preventing death from sepsis in animal models of bacterial and SARS-CoV-2 infections. The TOP1 catalytic activity likely resolves the topological constraints on DNA that encodes these genes to facilitate the transcription induction that leads to excess inflammation. The increased accumulation of TOP1-DNA covalent complex (TOP1cc) following DNA cleavage is the basis for the anticancer efficacy of the TOP1 poisons developed for anticancer treatment. The potential cytotoxicity and mutagenicity of TOP1 targeting cancer drugs pose serious concerns for employing them as therapies in sepsis prevention. In this study we set up a novel yeast-based screening system that employs yeast strains expressing wild-type or a dominant lethal mutant recombinant human TOP1. The effect of test compounds on growth is monitored with and without overexpression of the recombinant human TOP1. This yeast-based screening system can identify human TOP1 poisons for anticancer efficacy as well as TOP1 suppressors that can inhibit TOP1 DNA binding or cleavage activity in steps prior to the formation of the TOP1cc. This yeast-based screening system can distinguish between TOP1 suppressors and TOP1 poisons. The assay can also identify compounds that are likely to be cytotoxic based on their effect on yeast cell growth that is independent of recombinant human TOP1 overexpression.


Headspace solid phase microextraction applied to the analysis of organophosphorus insecticides in strawberry and cherry juices.
A method based on a headspace solid phase microextraction (HS-SPME) technique followed by gas chromatography with flame thermionic and mass spectrometric detection was developed for the determination of seven organophosphorus (OPs) insecticide residues in strawberry and cherry juice samples. The extraction capacities of four fiber coatings, polyacrylate (PA 85 microm), poly(dimethylsiloxane) (PDMS 100 microm), carbowax-divinylbenzene (CW-DVB 65 microm), and poly(dimethylsiloxane)-divinylbenzene (PDMS-DVB 65 microm), have been studied and compared. The method was developed using spiked strawberry and cherry juices in a concentration range of 0.5-50 microg/L. The PDMS 100 microm fiber showed good extraction efficiency for the target compounds. An increase in the extraction efficiency of OP insecticides was observed when the parameters affecting the HS-SPME process such as temperature, extraction time, salt additives, stirring rate, pH, and effect of dilution were optimized. Good linearity of compounds was observed in the tested concentration range. The relative standard deviations were found to be <20%. The limits of detection were between 0.025 and 0.050 microg/L. The mean relative recoveries ranged from 82 to 102%.


Omicron variant of SARS-CoV-2: a review of existing literature.
On November 24th, 2021 a case of a new viral variant of SARS-CoV-2 was reported by South Africa and Botswana to WHO, which later was designated as the variant of concern on 26th November 2021. It has around 60 mutations (50 non synonymous, 8 synonymous, and 2 non coding) as compared to the original parent strain of Wuhan. Different hypotheses have been put forward as an explanation for the origin like reverse zoonosis i.e. animal to human transmission, origin from an immune compromised patient or use of highly mutagenic drug like molnupiravir as treatment. A huge spike in cases around the globe is suggestive of a high rate of infectivity and transmissivity as compared to the previous known variants. With whatever cases have been documented so far, it is said that omicron causes mostly mild clinical illnesses and there is a less chance of hospitalization according to the clinicians. Among the reported cases, there were already vaccinated patients also. So there is a possibility that omicron might be able to evade the vaccine induced immunity due to a huge number of mutations (especially in the spike protein sequences). Until new vaccines specific to the pathogen are being developed, the coverage of the currently acceptable vaccines should be increased so that none is deprived of the mandatory doses and a third booster dose might help to reduce the chances of serious complications of this new strain beforehand. So an equal focus on the host and environment is required along with the pathogen.


[Discussion on the On-site Inspection Scheme of Using Infant Incubator].
The standard terms of infant incubators with high clinical risk and high incidence of adverse events has been tested through the introduction of YY/T 0841-2011 standard, an on-site inspection scheme for using infant incubators has been proposed, the problems existing in the inspection are analyzed and reasonable suggestions are put forward, this paper provides a certain technical reference for the whole life cycle management of the infant incubator.


A PHYLOGENETIC ANALYSIS OF BODY SIZE EVOLUTION AND BIOGEOGRAPHY IN CHUCKWALLAS (SAUROMALUS) AND OTHER IGUANINES.
The evolution of body size was reconstructed in chuckwallas (genus Sauromalus), large herbivorous lizards of southwest North America, using a phylogeny derived from sequence variation in the mitochondrial cytochrome b gene. The body mass of two endemic island species (S. hispidus and S. varius) is typically fivefold larger than mainland species. We tested the hypothesis that large body size has evolved on these islands in response to local ecological conditions against the alternative hypothesis that large size is simply retained from large iguanine ancestors. The most parsimonious tree topology depicts the insular gigantic Sauromalus as monophyletic, having diverged from a common ancestor on the Baja California peninsula after the radiation of smaller bodied clades. In a robustness analysis of this topology, we found general support for this tree over alternative topologies representing minimum evolution hypotheses that imply large body size is retained from large iguanine ancestors. The most parsimonious reconstruction of body size evolution implies a change from large to small size after the Sauromalus ancestor diverged from Iguana, and one reversal back to large size within Sauromalus. The large size increase in the gigantic clade contrasts with evolutionary stasis of small body size (for an iguanine) in mainland populations. The gigantic species show 3-4% total sequence divergence from S. obesus populations on the nearby Baja California peninsula, and mainland populations of S. obesus obesus show similar levels of divergence from each other. An analysis of character transitions and comparative behavior implicates predation, and its relaxation on isolated islands, as a strong selective force in Sauromalus. Patterns of genetic differentiation in Sauromalus and biogeographic implications are discussed.


Aspects of the stability and bioavailability of carbohydrates and carbohydrate derivatives.
Carbohydrates play a critical role in many biological processes and disease states including cancer, inflammation and infection. The development of carbohydrates as therapeutics continues to gain interest, as the biological roles of these biopolymers are further elucidated and understood. However, many carbohydrates display poor affinity, stability and bioavailability characteristics, which has led to a widely held view that this class of molecules make poor drugs. As there are already a significant number of carbohydrate-based drugs presently being employed by physicians, it is clear that some carbohydrates do make effective drugs. Recent advances in (a) the understanding of carbohydrate specific transport mechanisms, and (b) the development of novel carbohydrate based bioactives which may overcome many of the previous limitations of stability and bioavailability, suggest that carbohydrate-based compounds may provide a rich source of new drug candidates for a variety of diseases.


Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2-mediated Wnt/β-catenin pathway.
Propofol is a commonly used intravenous anesthetic in tumor surgery. Recently, studies have confirmed that propofol has an antitumor effect on hepatocellular carcinoma (HCC); however, the molecular mechanism underlying this effect has not been elucidated until now. The present study aimed to investigate the mechanism of propofol on HepG2 cell proliferation, apoptosis and invasion, focusing on High Mobility Group AT-Hook 2 (HMGA2)-mediated Wnt/β-catenin pathway. The HepG2 cells were treated with various concentrations of propofol for 24 h, the relative protein levels of HMGA2, Wnt3a, β-catenin, Snail Family Zinc Finger 1 and c-myc were determined by western blot analysis. HMGA2-pcDNA3.1 plasmid was transfected into the HepG2 cells to overexpress HMGA2. Cell proliferation, apoptosis and invasion were examined by MTT assays, flow cytometry and Transwell-matrigel invasion assays, respectively. The results showed that propofol suppressed HMGA2 expression and Wnt/β-catenin signaling in a dose-dependent manner. Propofol was able to inhibit cell proliferation and invasion, and induce cell apoptosis of HepG2 cells; however, these effects were attenuated by HMGA2 overexpression. The suppressed Wnt/β-catenin signaling in HepG2 cells by treatment with propofol was also reversed by HMGA2 overexpression. In conclusion, this study provided a novel mechanism underlying the anti-tumor function of propofol on HCC. To the best of our knowledge, the present study is the first to demonstrate that propofol could downregulate the expression of HMGA2, which inhibited the Wnt/β-catenin pathway, thus leading to the inhibition of cell proliferation and invasion, as well as the apoptosis of HepG2 cells.


Monitoring and analysis of the change process in curriculum mapping compared to the National Competency-based Learning Objective Catalogue for Undergraduate Medical Education (NKLM) at four medical faculties. Part II: Key factors for motivating the faculty during the process.
Objective: After adoption of the National Competency-based Learning Objectives Catalogue in Medicine [Nationaler Kompetenzbasierter Lernzielkatalog Medizin, NKLM], the German medical faculties are asked to test the learning obejctives recorded in it and evaluate them critically. The faculties require curricular transparency for competence-oriented transition of present curricula, which is best achieved by systematic curriculum mapping in comparison to the NKLM. Based on this inventory, curricula can be further developed target-oriented. Considerable resistance has to be expected when a complex existing curriculum is to be mapped for the first time and a faculty must be convinced of its usefulness. Headed by Tübingen, the faculties of Freiburg, Heidelberg, Mannheim and Tübingen rose to this task. This two-part article analyses and summarises how NKLM curriculum mapping was successful at the locations despite resistance. Part I presented the resources and structures that supported implementation. Part II focuses on factors that motivate individuals and groups of persons to cooperate in the faculties. Method: Both parts used the same method. In short, the joint project was systematically planned following the steps of project and change management and adjusted in the course of the process. From the beginning of the project, a Grounded-Theory approach was used to systematically collect detailed information on measures and developments at the faculties, to continually analyse them and to draw final conclusions. Results: At all sites, faculties, teachers, students and administrative staff were not per se willing to deal with the NKLM and its contents, and even less to map their present curricula. Analysis of the development reflected a number of factors that had either a negative effect on the willingness to cooperate when missing, or a positive one when present. These were: clear top-down and bottom-up management; continuous information of the faculty; user-oriented support in the mapping process by reduction of the mapping categories, portioning and condensation of the NKLM via student pre-mapping (blueprint) and visibility of growing consent. Apart from that, there were a series of frequent questions, objections and concerns that could be countered strategically and by argumentation. They particularly referred to relevance, benefit, feasibility and effort of curriculum mapping. Conclusion: An overview of beneficial framework conditions, strategies and results from different points of view is achieved and interrelations are made visible. Based on literature results, the motivating factors as well as their implementation and effects in the faculties involved are critically reflected on. Recommendations can be derived that can support other faculties in practice.


Expression profile of circular RNAs in human gastric cancer tissues.
Circular RNAs (circRNAs) represent a newly identified class of non‑coding RNA molecules, which interfere with gene transcription by adsorbing microRNAs (miRNAs). CircRNAs serve important roles in disease development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNAs in the occurrence and development of gastric cancer (GC) remains unclear. In the present study, the expression profiles of circRNAs were compared between GC and adjacent normal tissues using a circRNA microarray, following which quantitative polymerase chain reaction (qPCR) was used to confirm the results of the circRNA microarray. Compared with the adjacent, normal mucosal tissues, 16 circRNAs were upregulated and 84 circRNAs were downregulated in GC. A total of 10 circRNAs were selected for validation in three pairs of GC and adjacent noncancerous tissues. The qPCR results were consistent with the findings of the microarray‑based expression analysis. Of the circRNAs studied, only circRNA‑0026 (hsa_circ_0000026) exhibited significantly different expression in GC (2.8‑fold, P=0.001). Furthermore, online Database for Annotation, Visualization and Integrated Discovery annotation was used to predict circRNA‑targeted miRNA‑gene interactions. The analysis revealed that circRNA‑0026 may regulate RNA transcription, RNA metabolism, gene expression, gene silencing and other biological functions in GC. In conclusion, differential expression of circRNAs may be associated with GC tumorigenesis, and circRNA‑0026 is a promising biomarker for GC diagnosis and targeted therapy.


Ultra-Stable ITO-Free Organic Solar Cells and Modules Processed from Non-Halogenated Solvents under Indoor Illumination.
Organic Photovoltaics (OPV) is a very promising technology to harvest artificial illumination and power smart devices of the Internet of Things (IoT). Efficiencies as high as 30.2% have been reported for OPVs under warm white light-emitting diode (LED) light. This is due to the narrow spectrum of indoor light, which leads to an optimal bandgap of ≈1.9 eV. Under full sunlight, OPV devices often suffer from poor stability compared to the established inorganic PV technologies such as crystalline silicon. This study focuses on a potentially very cost-effective Indium Tin Oxide (ITO) free cell stack with absorber materials processed from non-halogenated solvents. These organic solar cells and modules with efficiencies up to 21% can already achieve remarkable stabilities under typical indoor illumination. Aging under 50,000 lux LED lighting leads to very little degradation after more than 11 000 h. This light dose corresponds to more than 110 years under 500 lux. For modules encapsulated with a flexible barrier, extrapolated lifetimes of more than 41 years are achieved. This shows that OPV is mature for the specific application under indoor illumination. Due to the large number of potential organic semiconducting materials, further efficiency increase can be expected.


Insular hypocretin transmission regulates nicotine reward.
Damage to the insular cortex can profoundly disrupt tobacco addiction in human smokers, reflected in spontaneous cessation of the tobacco habit and persistently decreased urge to smoke. Little is known concerning the neurobiological mechanisms through which the insula may control the maintenance of the tobacco habit. Emerging evidence suggests that hypocretin (orexin) transmission may play an important role in drug reinforcement processes, but its role in the rewarding actions of nicotine, considered the key addictive component of tobacco smoke, remains largely unexplored. Here we show that blockade of hypocretin transmission at hypocretin-1 (Hcrt-1; orexin-1) receptors decreases i.v. nicotine self-administration in rats and the motivation to obtain the drug. Blockade of Hcrt-1 receptors also abolished the stimulatory effects of nicotine on brain reward circuitries, as measured by reversal of nicotine-induced lowering of intracranial self-stimulation thresholds. In addition, we show that hypocretin-containing fibers innervate the insula, Hcrt-1 receptors are located on insular cells, and blockade of Hcrt-1 receptors in the insula but not in the adjacent somatosensory cortex decreases nicotine self-administration. These data demonstrate that insular hypocretin transmission plays a permissive role in the motivational properties of nicotine, and therefore may be a key neurobiological substrate necessary for maintaining tobacco addiction in human smokers.


Treatment and Prevention of Oral Candidiasis in Elderly Patients.
The incidence of oral candidiasis has increased in the elderly in recent years. Although the increase of the elderly population plays a big role in this rise of oral candidiasis, the broader recognition that elderly people have higher infection rates for oral candidiasis is considered to be also an important factor. Oral candidiasis can be categorized into three types. Pseudomembranous oral candidiasis is characterized by the appearance of white moss, erythematous oral candidiasis by the eruption of erythema, and hyperplastic oral candidiasis by mucosal hyperplasia. Miconazole has been commonly used when treating oral candidiasis. Elderly patients, however, have a tendency to develop oral candidiasis repeatedly. It is therefore critical to take measures to prevent recurrence. We recommend the use an oral moisturizer containing hinokitiol, an antifungal substance, on a regular basis, to help prevent recurrence of oral candidiasis.


Safety and efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) in patients with glomerular diseases who received rituximab.
Patients on B-cell-depleting agents may have a suboptimal response to vaccination, placing them at a higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or suffering from a more severe prognosis. Indeed, available data on pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) in subjects with glomerular diseases (GDs) who received rituximab are limited. We conducted a prospective study analysing the safety and efficacy of tixagevimab/cilgavimab for pre-exposure prophylaxis in patients with GDs who received rituximab in the previous 12 months. The rates of symptomatic infections and hospitalizations were compared with those for patients with GD treated with rituximab who refused to receive tixagevimab/cilgavimab. Tixagevimab/cilgavimab was administered to 22 patients (12 females, mean age 58.4 ± 19.6 years) with GD diagnoses including membranous nephropathy, lupus nephritis, anti-neutrophil cytoplasmic antibody-associated vasculitis and focal segmental glomerulosclerosis. No patient treated with tixagevimab/cilgavimab experienced symptomatic infection with SARS-CoV-2 during the follow-up (mean observation time of follow-up was 112 ± 23 days), while 11 of 28 controls (39.3%) reported a symptomatic infection (P = .0001), requiring hospitalization in 2 cases. Reported adverse events were mild, namely self-limiting headache [4], discomfort at the injection site [3], flu-like symptoms/myalgia [3] and fever [1]. No serious adverse events (e.g. cardiac events, anaphylaxis) were reported. Pre-exposure prophylaxis with tixagevimab/cilgavimab seems safe and lowered the risk of symptomatic SARS-CoV-2 infection by ≈40% in vaccinated subjects with GD who received anti-CD20 therapy. Possible applications in the subset of patients who need immunosuppressive therapy, especially with rituximab, in a pandemic setting might be envisaged.


The manufacturing procedure of 3D printed models for endoscopic endonasal transsphenoidal pituitary surgery.
Endoscopic endonasal transsphenoidal pituitary surgery is usually difficult and risky. With limited sources of cadaveric skulls, traditional methods of using virtual images to study the surgery are difficult for neurosurgeons and students because the surgery requires spatial imagination and good understanding of the patient's conditions as well as practical experience. The three-dimensional (3D) printing technique has played an important role in clinical medicine due to its advantages of low cost, high-efficiency and customization. CT images are used as the source data of 3D printing. The data obtained directly from the CT machine has limited accuracy, which cannot be printed without processing. Some commercial platforms can help build an accurate model but the cost and customization are not satisfactory. In this situation, a tactile, precise and low-cost 3D model is highly desirable. Five kinds of computer software are used in the manufacturing of medical 3D models and the processing procedure is easy to understand and operate. This study proposes a practical and cost-effective method to obtain the corrected digital model and produce the 3D printed skull with complete structures of nasal cavity, sellar region and different levels of pituitary tumors. The model is used for the endoscopic endonasal transsphenoidal pituitary surgery preparation. The 3D printed medical model can directly help neurosurgeons and medical students to practice their surgery skills on both general and special cases with customized structures and different levels of tumors.


Inbreeding depression in one of the last DFTD-free wild populations of Tasmanian devils.
Vulnerable species experiencing inbreeding depression are prone to localised extinctions because of their reduced fitness. For Tasmanian devils, the rapid spread of devil facial tumour disease (DFTD) has led to population declines and fragmentation across the species' range. Here we show that one of the few remaining DFTD-free populations of Tasmanian devils is experiencing inbreeding depression. Moreover, this population has experienced a significant reduction in reproductive success over recent years. We used 32 microsatellite loci to examine changes in genetic diversity and inbreeding in the wild population at Woolnorth, alongside field data on breeding success from females to test for inbreeding depression. Wefound that maternal internal relatedness has a negative impact on litter sizes. The results of this study imply that this population may be entering an extinction vortex and that to protect the population genetic rescue should be considered. This study provides conservation managers with useful information for managing wild devils and provides support for the "Wild Devil Recovery Program", which is currently augmenting small, isolated populations.


Limited midline myelotomy for visceral pain.
The traditional commissural myelotomy consists of a sagittal cut in the midline and was originally described by Greenfield and performed by Armour in 1926. Today, myelotomy refers to the selective disruption of the ascending visceral pain pathway. The success of the procedure is incumbent on the correct identification of the midline. Limited midline open myelotomy for the treatment of medically intractable abdominal or pelvic visceral cancer pain, with the aid of somatosensory evoked potentials to identify midline, offers patients superior pain relief over similar percutaneous techniques. Multicenter registries are needed to better elucidate the best surgical technique for this procedure. The video can be found here: https://youtu.be/0unlmwp08po.


Pathobiology of cancer metastasis: a short account.
Cancer-initiating cells display aberrant functional and phenotypic characteristics of normal stem cells from which they evolved by accumulation of multiple cytogenetic and/or epigenetic alterations. Signal transduction pathways which are essential for normal stem cell function are abnormally expressed by cancer cells, with a cancer cell phenotype playing an essential role in cancerization and metastasis.Local tumour progression, metastasis and metastatic tumour growth are mediated by direct cell-to-cell and paracrine reciprocal interactions between cancer cells and various stromal cells including fibroblasts, macrophages, bone marrow derived stem cells and progenitor cells. These interactions mediate breakdown of basement membrane barriers and angiogenesis both locally at the invasive front of the primary tumour and at the distant metastatic site; attract primary tumour cells to the candidate metastatic site; and promote proliferation, survival and growth of primary tumour cells and of metastatic cells at their distant site.It is the purpose of this article to highlight the analogies between some of the genetic programs of normal stem cells, and of cancer cells participating in the process of metastasis.


Aortic balloon occlusion simplifies dissected thoracoabdominal aortic aneurysm repair after frozen elephant trunk.
Here, we report a case of a dissected thoracoabdominal aortic aneurysm repair after frozen elephant trunk implantation, using aortic balloon occlusion technique to simplify the proximal anastomosis and avoid deep hypothermic circulatory arrest.


Rules to follow before advising patients on dietary supplements/alternative medicine: Part I.
Sales and the overall prevalence of dietary supplements/alternative medicine (CAM) use have dramatically increased in the United States and in numerous countries around the world. Thus, health care professionals should be provided with general rules to follow or guidelines on dietary supplements in order to improve communication with patients. In Part I of this series, ten rules that can be generally applied or used in a clinical setting will be described. Rules to follow when patients inquire about CAM will be outlined in Part II.


Evaluating a De-Centralized Regional Delivery System for Breast Cancer Screening and Patient Navigation for the Rural Underserved.
Providing breast cancer screening services in rural areas is challenging due to the fractured nature of healthcare delivery systems and complex reimbursement mechanisms that create barriers to access for the under- and uninsured. Interventions that reduce structural barriers to mammography, like patient navigation programs, are effective and recommended, especially for minority and underserved women. Although the literature on rural healthcare is significant, the field lacks studies of adaptive service delivery models and rigorous evaluation of evidence-based programs that facilitate routine screening and appropriate follow-up across large geographic areas. To better understand how to implement a decentralized regional delivery "hub & spoke" model for rural breast cancer screening and patient navigation, we have designed a rigorous, structured, multi-level and mixed-methods evaluation based on Glasgow's RE-AIM model (Reach, Effectiveness, Adoption, Implementation, and Maintenance). The program is comprised of three core components: 1) Outreach to underserved women by partnering with county organizations; 2) Navigation to guide patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to coordinate funding for screening services through a central contract with Medicaid Breast and Cervical Cancer Services (BCCS). Using Glasgow's RE-AIM model, we will: 1) assess which counties have the resources and capacity to implement outreach and/or navigation components, 2) train partners in each county on how to implement components, and 3) monitor process and outcome measures in each county at regular intervals, providing booster training when needed. This evaluation strategy will elucidate how the heterogeneity of rural county infrastructure impacts decentralized service delivery as a navigation program expands. In addition to increasing breast cancer screening access, our model improves and maintains time to diagnostic resolution and facilitates timely referral to local cancer treatment services. We offer this evaluation approach as an exemplar for scientific methods to evaluate the translation of evidence-based federal policy into sustainable health services delivery in a rural setting.


[New heterocyclic derivatives with germicidal activity. VI. Synthesis and activity of new 2-benzoxazoyl-2'-furanes and -thiophenes variously substituted in 5 and 5' positions].
Seventeen derivatives of 2'-furyl-2-benzoxazole and three derivatives of 2'-thienyl-2-benzoxazole, having different substituents in the benzene moiety (position 5) and in the furanic or thiophenic ring (position 5'), are described, with the aim of studying antibacterial and antimycotic structure-activity relationships. None of the compounds show an important antibacterial and/or antimycotic activity, when tested against nine bacteria and Candida albicans cultures; in any case it was much lower than that previously reported for the corresponding benzimidazoles. It seems that the = NH group of the imidazole ring, which is absent in the benzoxazole derivatives, might be important for the biological activity of this class of compounds.


How do I manage a blood product shortage?
The demand for blood products sometimes exceeds the available inventory. Blood product inventories are dependent upon the availability of donors, supplies and reagents, and collection staff. During prolonged extreme shortages, blood centers and transfusion services must alter practices to meet the needs of patients. The Association for the Advancement of Blood and Biotherapies Donor and Blood Component Management Subsection compiled some strategies from its blood center and hospital transfusion service members that could be implemented during blood product shortages. Some strategies that blood centers could use to increase their available inventories include increasing donor recruitment efforts, using alternate types of collection kits, manufacturing low-yield apheresis-derived platelets and/or whole blood-derived platelets, using cold-stored platelets, transferring inventory internally among centers of the same enterprise, using frozen inventory, decreasing standing order quantities, prioritizing allocation to certain patient populations, filling partial orders, and educating customers and blood center staff. Transfusion service strategies that could be implemented to maximize the use of the limited available inventory include increasing patient blood management efforts, using split units, finding alternate blood suppliers, trading blood products with other hospital transfusion services, developing a patient priority list, assembling a hospital committee to decide on triaging priorities, using expired products in extreme situations, and accepting nonconforming products after performing safety checks. Blood centers and transfusion services must choose the appropriate strategies to implement based on their needs.


[Quality of methodology and reporting of Meta-analyses on acupuncture treating ischemic stroke in China].
To evaluate the quality of methodology and reporting of Meta-analyses on acupuncture treating ischemic stroke in China. The domestic literature of systematic reviews (SRs) on acupuncture treating ischemic stroke was retrieved from CBM, VIP, CNKI and WANFANG databases. The quality of methodology and reporting was measured by A Measurement Tool to Assess Systematic Reviews (AMSTAR) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Seven studies involving 6 papers in Chinese and 1 paper in English were chosen from 402 papers. The deficiencies of methodology mainly contained incomplete retrieval strategy, less attention to the publication bias and the heterogeneity, etc. The shortages of reporting was on retrieval strategy reporting, the studies features and the risk of bias reporting and evidence strength level reporting, etc. At present the quality of methodology and reporting of SRs on acupuncture treating ischemic stroke in China has flaws, which needs improvement.


The Role of Choline in Neurodevelopmental Disorders-A Narrative Review Focusing on ASC, ADHD and Dyslexia.
Neurodevelopmental disorders appear to be rising in prevalence, according to the recent Global Burden of Disease Study. This rise is likely to be multi-factorial, but the role of certain nutrients known to facilitate neurodevelopment should be considered. One possible contributing factor could be attributed to deficits in choline intake, particularly during key stages of neurodevelopment, which includes the first 1000 days of life and childhood. Choline, a key micronutrient, is crucial for optimal neurodevelopment and brain functioning of offspring. The present narrative review discusses the main research, describing the effect of choline in neurodevelopmental disorders, to better understand its role in the etiology and management of these disorders. In terms of findings, low choline intakes and reduced or altered choline status have been reported in relevant population subgroups: pregnancy (in utero), children with autism spectrum disorders, people with attention deficit hyperactivity disorder and those with dyslexia. In conclusion, an optimal choline provision may offer some neuronal protection in early life and help to mitigate some cognitive effects in later life attributed to neurodevelopmental conditions. Research indicates that choline may act as a modifiable risk factor for certain neurodevelopmental conditions. Ongoing research is needed to unravel the mechanisms and explanations.


Use of a noninvasive halo in children.
Retrospective review of clinical experience in children using a new noninvasive halo. To report on the efficacy, complications and indications for use of a noninvasive halo in the pediatric population. A halo vest with pins in the skull is the gold standard for providing maximum immobilization and control of the cervical spine. Inherent complications include scarring, infection, cerebral spinal fluid leakage, loosening of pins, and penetration of the cranial vault. Less invasive orthoses historically provide significantly less immobilization and control of the cervical spine. A Minerva cast has problems with patient tolerance and skin care. The noninvasive halo was used on 30 children (ages 6 months to 16 years) for the following indications: muscular torticollis release, 18 children; cervical fusion immobilization 7 children; closed reduction of C1-C2 rotatory subluxation, 5 children. The noninvasive halo was successful with no complications in 29 of 30 patients. One complication consisted of dislodgment of a C2-C4 anterior strut graft, though fusion ensued without further surgery and the clinical result was successful. Longstanding C1-C2 rotatory subluxations were safely reduced in 5 children with the noninvasive halo. In 18 children following sternocleidomastoid release, the cervical spine was successfully immobilized in an overcorrected position after surgery. A noninvasive halo was used successfully for postoperative immobilization of children with stable cervical spines. This device was particularly useful for the gentle and safe reduction of C1-C2 subluxations, and for postoperative immobilization in an overcorrected position following stenocleidomastoid release for congenital muscular torticollis.


Protein depletion using the arabinose promoter in Xanthomonas citri subsp. citri.
Xanthomonas citri subsp. citri (X. citri) is a plant pathogen and the etiological agent of citrus canker, a severe disease that affects all the commercially important citrus varieties, and has worldwide distribution. Citrus canker cannot be healed, and the best method known to control the spread of X. citri in the orchards is the eradication of symptomatic and asymptomatic plants in the field. However, in the state of São Paulo, Brazil, the main orange producing area in the world, control is evolving to an integrated management system (IMS) in which growers have to use less susceptible plants, windshields to prevent bacterial spread out and sprays of cupric bactericidal formulations. Our group has recently proposed alternative methods to control citrus canker, which are based on the use of chemical compounds able to disrupt vital cellular processes of X. citri. An important step in this approach is the genetic and biochemical characterization of genes/proteins that are the possible targets to be perturbed, a task not always simple when the gene/protein under investigation is essential for the organism. Here, we describe vectors carrying the arabinose promoter that enable controllable protein expression in X. citri. These vectors were used as complementation tools for the clean deletion of parB in X. citri, a widespread and conserved gene involved in the essential process of bacterial chromosome segregation. Overexpression or depletion of ParB led to increased cell size, which is probably a resultant of delayed chromosome segregation with subsequent retard of cell division. However, ParB is not essential in X. citri, and in its absence the bacterium was fully competent to colonize the host citrus and cause disease. The arabinose expression vectors described here are valuable tools for protein expression, and especially, to assist in the deletion of essential genes in X. citri.


Plague from eating raw camel liver.
We investigated a cluster of 5 plague cases; the patients included 4 with severe pharyngitis and submandibular lymphadenitis. These 4 case-patients had eaten raw camel liver. Yersinia pestis was isolated from bone marrow of the camel and from jirds (Meriones libycus) and fleas (Xenopsylla cheopis) captured at the camel corral.


The E. coli Whole-Cell Modeling Project.
The Escherichia coli whole-cell modeling project seeks to create the most detailed computational model of an E. coli cell in order to better understand and predict the behavior of this model organism. Details about the approach, framework, and current version of the model are discussed. Currently, the model includes the functions of 43% of characterized genes, with ongoing efforts to include additional data and mechanisms. As additional information is incorporated in the model, its utility and predictive power will continue to increase, which means that discovery efforts can be accelerated by community involvement in the generation and inclusion of data. This project will be an invaluable resource to the E. coli community that could be used to verify expected physiological behavior, to predict new outcomes and testable hypotheses for more efficient experimental design iterations, and to evaluate heterogeneous data sets in the context of each other through deep curation.


Passive imaging at 250 GHz for detection of face presentation attacks.
Face presentation attacks are becoming more efficient since new 3D facial masks are used. Passive terahertz imaging offers specific physical properties that may improve presentation attack detection capabilities. The non-zero transmission capability through a variety of non-metallic materials may provide necessary information for presentation attack detection. The aim of this paper is to present outcomes of a study on face presentation attack detection using passive imaging at 250 GHz. An analysis of presentation attacks for facial recognition systems using custom displayed and printed photographs, 3D-printed and full-face flexible 3D-latex masks, is provided together with spectral characterization of various presentation attack instruments. A set of experiments with various instruments and various sets of clothing is described and discussed. Finally, two presentation attack detection methods are proposed. The first method is based on a threshold corresponding to a difference between mean intensities of selected regions of interests while the second method uses eight different deep learning classifiers to detect presentation attacks. Results of two validation schemes are presented.


Pilon fracture: a case report of a 45-year-old dental technician.
Pilon fractures are complex and difficult-to-treat fractures of the lower extremity that account for about 1% of all lower extremity fractures and up to 10% of tibial fractures. The injury is caused by high energy axial load either from motor vehicle accidents or a fall from height. The treatment of these fractures has caused controversy among surgeons due to mixed outcomes. Here we report a case of pilon fracture in a 45 year old male patient who has sustained the injury as a result of a fall from a height of approximately 12 feet. We describe why it is absolutely crucial that the patient is treated with external fixation initially and evaluate its merits and drawbacks as well as ways to minimize the complications associated with external fixation of open intra-articular distal tibial fractures.


Naloxone, theophylline, bromocriptine, and obstructive sleep apnea. Negative results.
A total of 28 male patients objectively diagnosed with obstructive sleep apnea syndrome (OSAS) participated in specific drug trials involving naloxone (an opioid antagonist), theophylline and bromocriptine mesylate (a dopamine agonist). All subjects were between 15 and 40% overweight. The group median apnea-hypopnea (A + H) index was 58. None of the drugs had any significant beneficial effects on the number and duration of upper airway apneas and hypopneas or directly related oxygen desaturation. Theophylline increased the diaphragmatic activity during REM sleep-related mixed apnea but had no impact on upper airway apnea in the studied population.


[Observation on effect of pifubing xuedu pill combined with diyin tablet in treatment of psoriasis].
To observe the clinical effect of Pifubing Xuedu Pill (PXDP) combined with Diyin Tablet (DYT) in treating patients with psoriasis. Sixty patients were divided into 2 groups by randomized controlled method. DYT was orally taken by all patients, while XDP was given additionally to patients in the treated group, the medication was continued for 1 month. The therapeutic effect, toxic and adverse reaction were observed. In the treated group, 7 patients were cured, 11 basically cured, 4 markedly effective, 7 improved, and 1 ineffective, with the clinical cured rate of 60.0% and the total effective rate 73.3%. In the control group, 3 were cured, 4 basically cured, 9 markedly effective, 10 improved, and 4 ineffective, with the clinical cured rate of 23.3% and the total effective rate 53.3%. No significant difference was shown in comparison of the total effective rate between the two groups (chi2 = 0.27, P > 0.05), however, significant difference was shown in comparison of the clinical cured rate (chi2 = 6.48, P < 0.05) between them. The toxic and adverse reaction in the treated group was obviously lower than those in the control group (t = 5.27, P <0.05). DYT combined with PXDP in treating psoriasis shows better therapeutic effect, with quicker initiation, lesser toxic and adverse reaction, and higher efficacy than using DYT alone.


Stationary and automated laparoscopically assisted technologies.
The extent that laparoscopy may impact upon the practice of surgery remains to be clarified. One problem with these techniques is the maintenance of an adequate, stationary visual field in morphometrically different abdomens. This requires the attentive, trained, and skillful utilization of someone or something to operate the camera portal. Herein reported are the theory, advantages, disadvantages, and clinical utilization of mechanical and robotic arm systems to replace this second assistant during laparoscopic surgery.


Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1.
Cell death in higher organisms is negatively regulated by Inhibitor of Apoptosis Proteins (IAPs), which contain a ubiquitin ligase motif, but how ubiquitin-mediated protein degradation is regulated during apoptosis is poorly understood. Here, we report that Drosophila melanogaster IAP1 (DIAP1) auto-ubiquitination and degradation is actively regulated by Reaper (Rpr) and UBCD1. We show that Rpr, but not Hid (head involution defective), promotes significant DIAP1 degradation. Rpr-mediated DIAP1 degradation requires an intact DIAP1 RING domain. Among the mutations affecting ubiquitination, we found ubcD1, which suppresses rpr-induced apoptosis. UBCD1 and Rpr specifically bind to DIAP1 and stimulate DIAP1 auto-ubiquitination in vitro. Our results identify a novel function of Rpr in stimulating DIAP1 auto-ubiquitination through UBCD1, thereby promoting its degradation.


Higher Charlson Comorbidity Index Increases 90-Day Readmission Rate with Poorer Functional Outcomes in Surgically Treated Hip Fracture Patients.
The associated mortality and morbidity in hip fracture patients pose a major healthcare burden for ageing populations worldwide. We aim to analyse how an individual's comorbidity profile based on age-adjusted Charlson Comorbidity Index (CCI) may impact on functional outcomes and 90-day readmission rates after hip fracture surgery. Surgically treated hip fracture patients between 2013 and 2016 were followed up for 1-year and assessed using Parker Mobility Score (PMS), EuroQol-5D (EQ-5D) and Physical and Mental Component Scores (PCS and MCS, respectively) of Short Form-36 (SF-36). Statistical analysis was done by categorising 444 patients into three groups based on their CCI: (1) CCI 0-3, (2) CCI 4-5 and (3) CCI ≥ 6. PMS, EQ-5D and SF-36 PCS were significantly different amongst the CCI groups pre-operatively and post-operatively at 3, 6 and 12 months (all P < 0.05), with CCI ≥ 6 predicting for poorer outcomes. In terms of 90-day readmission rates, patients who have been readmitted have poorer outcome scores. Multivariate analysis showed that high CCI scores and 90-day readmission rate both remained independent predictors of worse outcomes for SF-36 PCS, PMS and EQ-5D. CCI scores ≥6 predict for higher 90-day readmission rates, poorer quality of life and show poor potential for functional recovery 1-year post-operation in hip fracture patients. 90-day readmission rates are also independently associated with poorer functional outcomes. Peri-operatively, surgical teams should liaise with medical specialists to optimise patients' comorbidities and ensure their comorbidities remain well managed beyond hospital discharge to reduce readmission rates. With earlier identification of patient groups at risk of poorer functional outcomes, more planning can be directed towards appropriate management and subsequent rehabilitation. Further research should focus on development of a stratified, peri-operative multidisciplinary, hip-fracture care pathway treatment regime based on CCI scores to determine its effectiveness in improving functional outcomes.


Effect of long-term alcohol ingestion on the femoral head of rabbit.
Twenty New Zealand rabbits were chosen for this study (5 for controls and 15 for the alcohol group). In the alcohol group, each rabbit was fed with rice wine (2 g/kg/day alcohol) for 1 year. Bone marrow pressure of the femoral basal neck, erythrocyte sedimentation rate (ESR), liver functions, uric acid, triglyceride, cholesterol, amylase, and blood alcohol level were measured at 0 day, 6 months and 1 year. Finally, the rabbits were sacrificed at the end of the study. The livers and femoral heads were examined for pathology. The bone volume and fat cell size of the femoral head were measured with a computerized "Bone Scanner". The results (1 year comparison) were a significantly higher level of cholesterol in the alcohol group (72 +/- 40 mg% vs 26 +/- 8 mg%, p less than 0.05) and greater bone marrow pressure (27.71 +/- 8.97 mmHg vs 18.20 +/- 4.09 mmHg, p less than 0.05), and no significant difference in triglyceride, uric acid and liver function, ESR, etc., when using Student's 2-tailed t-test. Liver changes (fatty liver) occurred in 3 animals in the alcohol group. The effect of alcohol on the trabecular bone volume was not significant (51.5 +/- 4.6 vol.% vs 50.0 +/- 5.2 vol.%), but the average fat cell size of the femoral head was significantly larger than that for normal controls (2,745 +/- 605 mu2 vs 2,185 +/- 458 mu2, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Conservative management of abnormally invasive placenta: four case reports.
Prenatal diagnosis of placenta increta and percreta is essential to avoid potentially life-threatening hemorrhage by optimizing peripartal management. Invasive placentation presents significant challenges at cesarean section even for highly skilled surgeons. In the four cases of placenta increta/percreta presented here we tried to avoid hysterectomy by leaving the placenta behind and tried to accelerate regression of placental tissue by administering methotrexate. The outcome in each of the four women was different, but no major bleeding occurred in any of the cases. Close follow-up for many weeks is mandatory.


Increased microvascular vasodilation and cardiovascular risk following a pre-eclamptic pregnancy.
Women who develop pre-eclampsia are at high-risk for premature cardiovascular disease and death. The aim of this study was to assess microvascular function and cardiovascular risk in the early postpartum period for women who did/did not have a pregnancy complicated by pre-eclampsia. Peripheral microvascular function was assessed in women in the third trimester of uncomplicated pregnancies, with re-evaluation at 2 and 6 months postpartum. The effect of pre-eclampsia on postpartum microvascular function was assessed 2 and 6 months after delivery. Never-pregnant, naturally cycling women served for comparison. Cutaneous microvascular reactivity to acetylcholine and sodium nitroprusside, delivered locally by iontophoresis, was measured by laser Doppler flowmetry. 30-year and lifetime risk estimates for cardiovascular disease were established. Acetylcholine-mediated vasodilation was enhanced by normotensive pregnancy, and declined to nonpregnant levels by 6 months postpartum. Acetylcholine-mediated vasodilation remained high in pre-eclamptic subjects from 2 to 6 months postpartum compared to normotensive and never-pregnant controls. Pre-eclamptic subjects exhibited elevated 30-year and lifetime risk at 6 months postpartum. This study provides in vivo evidence of microvascular and cardiovascular risk implications of pre-eclampsia as early as 6 months postpartum, and suggests that the development of pre-eclampsia may be used to identify women at risk and eligible for risk screening and intervention.


[A relationship between cyclooxygenase-2 expression and tumor angiogenesis in experimental rat liver carcinogenesis].
To explore the relationship between the expression of cyclooxygenase-2 (COX-2) and angiogenesis in hepatocellular carcinoma. Forty Wistar rats were divided into two groups: a model group (30 rats) and a normal group (10 rats). Hepatocellular carcinoma was induced with 0.01% diethylnitrosamine (DEN) in the model group rats. The rats were sacrificed in batches at the 6th, 12th and 18th week of the experiment. Histological sections of liver tissues were made using routine methods. The expressions of COX-2, VEGF, VEGFR-2/KDR, and MMP-2 protein in the liver tissues were evaluated using immunohistochemical methods. In liver sections from the model group there were marked pathological changes (steatosis, cell infiltration, cirrhosis and liver cancer). The expressions of VEGF, VEGFR-2/KDR, and MMP-2 in those liver tissues were remarkably increased during the hepatocellular carcinogenesis. Microvessel density (MVD) was also obviously raised during the process of the cancer development. There was a direct correlation between the MVD and VEGF/KDR/MMP-2 (r=0.858, 0.788, 0.684, respectively; all P less than 0.01). There was also a direct correlation between the COX-2 and VEGF/KDR/MMP-2/MVD (r=0.771, 0.599, 0.690, 0.788, respectively; all P < 0.01). COX-2 can promote tumor angiogenesis during rat hepatocellular carcinogenesis. This may be one of the mechanisms in which COX-2 promotes carcinomas.


Sebaceous carcinoma in Western Australia: A registry-based study of site-related outcomes.
Sebaceous carcinoma is a rare cutaneous malignancy which is typically regarded as relatively aggressive and has traditionally been subdivided into periorbital or extraorbital tumours. We conducted a retrospective review of all cases of sebaceous carcinoma reported to the Western Australian Cancer Registry between 1987 and May 2019. The incidence of sebaceous carcinoma in Western Australia has increased over the last three decades, with extraorbital tumours being much more common than periorbital tumours. Very few sebaceous carcinomas have led directly to the death of patients; however, adverse outcomes were more likely with periorbital tumours, in particular local recurrence and the need for major surgical intervention.


Can Free Carnitine or Bilirubin in Blood Be Used in Neonatal Screening for Biliary Atresia?
To investigate the efficiency of free carnitine, unconjugated bilirubin (UBIL), bilirubin monoglucuronide (BMG), and bilirubin diglucuronide (BDG) in dry blood spots (DBSs) measured using tandem mass spectrometry (MS/MS) for screening biliary atresia (BA). All the patients with BA, residing in Shanghai, were collected from four different children's hospitals in Shanghai from January 1, 2015, to June 30, 2017. UBILMS, BMG, BDG, and free carnitine were measured in the DBS samples of 48 patients with BA, 10,008 pediatric patients, and 52,862 newborns using MS/MS. Conjugated bilirubin was measured by MS/MS (CBMS) = BMG + BDG, and total bilirubin was measured by MS/MS (TBMS) = UBILMS + CBMS. Four hundred pediatric patients' direct bilirubin (DB) and total bilirubin (TB), measured by the clinical laboratory and MS/MS, were used as a control. The total number of births at the registered permanent residences in Shanghai was 233,000; among them, the occurrence of BA was in 33 patients in 2 years. Therefore, the incidence of BA in Shanghai was 1:7,060. The ratio of DB/TB and CBMS/TBMS of most patients with BA was elevated gradually in the neonatal period and higher than the normal range after 1 month after birth. The area under the receiver operating characteristic curve of DB, DB/TB, CBMS/TBMS, CBMS, and free carnitine for predicting BA was 0.98, 0.95, 0.73, 0.57, and 0.92, respectively. Using the 95% percentile as a cutoff, the sensitivity of DB and free carnitine to predict BA was 100 and 85%, respectively, and the specificity was 52 and 85%, respectively. In free carnitine, DB, and CBMS/TBMS tests, blood concentrations are elevated in all infants with BA. However, they may not be elevated while they are newborns. These tests will result in high false negatives or positives. Thus, they should not be used as newborn screening tests for BA due to their lower sensitivity and specificity.


Case study: ED acts quickly after anthrax.
After last year's anthrax attacks, EDs at Capital Health System in Trenton, NJ, had to address decontamination of large numbers of patients. Patients who didn't require decontamination were sent to the hospital's employee health facility so they could bypass the ED. Clinicians, nursing staff, educators, and paramedics were trained in the decontamination process. Direct communication with first responders was established with a portable scanner.


Structural polarity induced by cooperative hydrogen bonding and lone-pair alignment in the molecular uranyl iodate Na2[UO2(IO3)4(H2O)].
Na2[UO2(IO3)4(H2O)] has been synthesized under mild hydrothermal conditions. Its structure consists of Na+ cations and [UO2(IO3)4(H2O)](2-) anions. The [UO2(IO3)4(H2O)](2-) anions are formed from the coordination of a nearly linear uranyl, UO2(2+), cation by four monodentate IO(3-) anions and a coordinating water molecule to yield a pentagonal bipyramidal environment around the uranium center. The water molecules form intermolecular hydrogen bonds with the terminal oxo atoms of neighboring [UO2(IO3)4(H2O)](2-) anions to yield one-dimensional chains that extend down the b axis. There are two crystallographically unique iodate anions in the structure of Na2[UO2(IO3)4(H2O)]. One of these anions is aligned so that the lone-pair of electrons is also directed along the b axis. The overall structure is therefore polar, owing to the cooperative alignment of both the hydrogen bonds and the lone-pair of electrons on iodate. The polarity of the monoclinic space group C2 (a = 11.3810(12) A, b = 8.0547(8) A, c = 7.6515(8) A, beta = 90.102(2) degrees , Z = 2, T = 193 K) found for this compound is consistent with the structure. Second-harmonic generation of 532 nm light from a 1064 nm laser source yields a response of approximately 16x alpha-SiO2.


Analysis of the repetitive component and retrotransposon population in the genome of a marine angiosperm, Posidonia oceanica (L.) Delile.
Posidonia oceanica is a monocotyledonous marine plant that plays a crucial role in maintaining the Mediterranean environment. Despite its ecological importance, basic knowledge of the functional and structural genomics of this species is still limited, as it is for the other seagrasses. Here, for the first time, we report data on the repetitive component of the genome of this seagrass using a low coverage of Illumina sequences and different assembly approaches. A dataset of 19,760 assembled sequences, mostly belonging to the repetitive fraction of the genome, was produced and annotated. Based on mapping Illumina reads onto this dataset, the genome structure of P. oceanica and its repetitive component was inferred. A very large proportion of the genome is represented by long-terminal-repeat (LTR) retrotransposons of both the Copia and Gypsy superfamilies. Posidonia LTR-retrotransposons were classified and their sequences analysed. Gypsy elements belong to three main lineages, while Copia ones belong to seven lineages. Gypsy elements were more represented than Copia ones in the set of assembled sequences and in the genome. Analysis of sequence variability indicated that Gypsy lineages have experienced amplification in more recent times compared to Copia ones.


The Coulter principle for analysis of subvisible particles in protein formulations.
The Coulter principle can be used for analysis of subvisible particles in protein formulations. The approach has several advantages including: an orthogonal operating principle, high sensitivity, ability to detect very small particles, excellent reproducibility, and high-resolution size information. This minireview discusses some of the important considerations that must be taken into account when utilizing the Coulter principle for subvisible particle analysis in protein formulations.


A comparison between different semiclassical approximations for optical response functions in nonpolar liquid solution. II. The signature of excited state dynamics on two-dimensional spectra.
Optical response functions are known to reflect quantum dynamics in a superposition state and as such, lack a well-defined classical limit. In a previous paper we considered the importance of accounting for the quantum nature of the dynamics by comparing the linear absorption spectrum and homodyne-detected time-integrated two-pulse photon-echo signal as calculated via the semiclassical forward-backward approach, linearized semiclassical approach, and standard approach which is based on equilibrium ground state dynamics [Shi and Geva, J. Chem. Phys. 122, 064506 (2005)]. In the present paper, we extend the comparison to the case of heterodyne-detected and time-resolved nonlinear time-domain rephasing and nonrephasing signals generated in three-pulse experiments and the corresponding frequency-domain two-dimensional spectra. The comparison is performed in the context of a two-state chromophore solvated in a nonpolar liquid. It is shown that the inherent insensitivity of the standard method to the nonequilibrium dynamics on the excited state potential surface gives rise to two-dimensional spectra which are symmetrical relative to the diagonal. In contrast, accounting for the effect of nonequilibrium excited state dynamics, as is the case within the forward-backward and linearized semiclassical methods, is found to give rise to two-dimensional spectra that become increasingly asymmetrical relative to the diagonal as the waiting time between the second and third pulses becomes larger. It is argued that the emergence of the asymmetry provides a useful probe of nonequilibrium solvation on the excited state potential surface.


Mechanistic studies of the flavoenzyme tryptophan 2-monooxygenase: deuterium and 15N kinetic isotope effects on alanine oxidation by an L-amino acid oxidase.
Tryptophan 2-monooxygenase (TMO) from Pseudomonas savastanoi catalyzes the oxidative decarboxylation of l-tryptophan during the biosynthesis of indoleacetic acid. Structurally and mechanistically, the enzyme is a member of the family of l-amino acid oxidases. Deuterium and 15N kinetic isotope effects were used to probe the chemical mechanism of l-alanine oxidation by TMO. The primary deuterium kinetic isotope effect was pH independent over the pH range 6.5-10, with an average value of 6.0 +/- 0.5, consistent with this being the intrinsic value. The deuterium isotope effect on the rate constant for flavin reduction by alanine was 6.3 +/- 0.9; no intermediate flavin species were observed during flavin reduction. The kcat/Kala value was 1.0145 +/- 0.0007 at pH 8. NMR analyses gave an equilibrium 15N isotope effect for deprotonation of the alanine amino group of 1.0233 +/- 0.0004, allowing calculation of the 15N isotope effect on the CH bond cleavage step of 0.9917 +/- 0.0006. The results are consistent with TMO oxidation of alanine occurring through a hydride transfer mechanism.


Cytotoxicity of isoflavones from Millettia dura.
The first phytochemical investigation of the flowers of Millettia dura resulted in the isolation of seven isoflavones, a flavonol and a chalcone. Eleven isoflavones and a flavonol isolated from various plant parts from this plant were tested for cytotoxicity against a panel of cell lines, and six of these showed good activity with IC50 values of 6-14 μM. Durmillone was the most active with IC50 values of 6.6 μM against A549 adenocarcinomic human alveolar basal epithelial cancer cell line with low cytotoxicity against the non-cancerous cell lines BEAS-2B (IC50 = 58.4 μM), LO2 hepatocytes (IC50 78.7 μM) and CCD19Lu fibroblasts (IC50 >100 μM).


Impaired myocardial t-PA release in patients with coronary artery disease.
Myocardial ischemia remains a significant perioperative complication in coronary artery disease (CAD) patients. We hypothesized that noxious stimuli during major surgery are associated with an acute release of tissue-type plasminogen activator (t-PA) into the coronary circulation, and that this response is reduced by CAD. Two patient groups, with (n=14) and without (n=8) CAD, were studied during the initial phase of heart surgery. After retrograde great cardiac vein catheterizations during closed-chest conditions, coronary arterial-venous concentration gradients of t-PA and plasminogen activator inhibitor type-1 (PAI-1) were measured together with coronary blood flow measurements, allowing derivation of coronary net release rates. Pre-surgery atrial pacing, performed to evaluate the influence of increases in heart rate (+ 40 beats/min) and coronary blood flow (+ 80 ml/min), did not significantly alter coronary net release of t-PA or PAI-1 in either patient group. Sternotomy induced a prominent increase in coronary net release of both total and active t-PA in the non-CAD group. This response was considerably reduced in the CAD group. This study provides the first analysis of coronary t-PA release during major surgery and demonstrates a deficient local endothelial t-PA release in patients with CAD. This suggests a reduced local fibrinolytic capacity in CAD patients, which may explain the increased risk for coronary thrombosis in this patient group.


A rapid, sensitive method for the quantitation of specific metabolites of sulfur mustard in human urine using isotope-dilution gas chromatography-tandem mass spectrometry.
Sulfur mustard agent (HD) (2,2'-dichloroethyl sulfide), a Schedule I compound on the Chemical Weapons Convention Schedule of Chemicals, remains a public health concern because it is simple to synthesize and it is in the chemical weapon stockpiles of several countries. A sensitive, rapid, accurate, and precise method was developed to quantitate trace levels of 1,1'-sulfonylbis [2-(methylthio) ethane] (SBMTE) in human urine as a means of assessing exposure to HD. The method used immobilized liquid-liquid extraction with diatomaceous earth, followed by the analysis of the urine extract using isotope-dilution gas chromatography-tandem mass spectrometry. Relative standard deviations were less than 8.6% at 1 ng/mL and 3.6% at 20 ng/mL. The limit of detection for SBMTE was 0.038 ng/mL in 0.5 mL of urine.