Assessing the contamination level, sources and risk of potentially toxic elements in urban soil and dust of Iranian cities using secondary data of published literature.
Research in urban geochemistry has been expanding globally in recent years, following the trend of the ever-increasing human population living in cities. Environmental problems caused by non-degradable pollutants such as metals and metalloids are of particular interest considering the potential to affect the health of current and future urban residents. In comparison with the extensive global research on urban geochemistry, Iranian cities have not received sufficient study. However, rapid and often uncontrolled urban expansion in Iran over recent years has contributed to an increasing number of studies concerning contamination of urban soil and dust. The present work is based on a comprehensive nationwide evaluation and intercomparison of published quantitative datasets to determine the contamination levels of Iranian cities with respect to potentially toxic elements (PTEs) and assess health risks for urban population. Calculation of geoaccumulation, pollution, and integrated pollution indices facilitated the identification of the elements of most concern in the cities, while both carcinogenic and non-carcinogenic risks have been assessed using a widely accepted health-risk model. The analysis of secondary, literature data revealed a trend of contamination, particularly in old and industrial cities with some alarming levels of health risks. Among the elements of concern, As, Cd, Cu, and Pb were found to be most enriched in soils and dusts of the studied cities based on the calculated geochemical indices. The necessity of designing strategic plans to mitigate possible adverse effects of elevated PTE concentrations in urban environments is emphasized considering the role of long-term exposure in the occurrence of chronic carcinogenic and non-carcinogenic health problems.


[Dissection in an adult with dilatation of the ascendent aorta diagnosed in childhood].
Dilatation of the ascending aorta is relatively infrequent during childhood. Besides the Marfan syndrome, the congenital origin should be considered. We report a patient with dilatation of the ascending aorta diagnosed at the age of 10 who presented acute aortic dissection and rupture after a 13-year period of follow-up. Several aspects of the proper diagnosis are discussed.


[Hereditary bone tumors].
Hereditary bone tumors are rare and result from mutations affecting cell cycle regulation (e.g. retinoblastoma syndrome/RB1 and Li-Fraumeni syndrome/TP53, Gardner syndrome/APC), energy metabolism (enchondromatosis/IDH1/2), complex signaling cascades (multiple hereditary exostoses/EXT1/2) and DNA integrity (Rothmund-Thomson/RECQL4, Werner/WRN and Bloom syndromes/BLM). The majority of syndromes are incompletely understood and can lead to multiple benign tumors, of which some might undergo secondary malignant transformation over time (enchondromatosis: enchondromas, multiple hereditary exostoses: osteochondromas, Gardner syndrome: osteomas) or bone sarcomas, primarily osteosarcomas as primary (Li-Fraumeni, Rothmund-Thomson, Werner and Bloom syndromes) or secondary manifestation (retinoblastoma syndrome) of the disease. Some syndromes additionally predispose to the development of a variety of other malignant tumors during life. Compared to sporadically occurring tumors, syndrome-related neoplasms can differ in the time of manifestation, site and histology, which can help in recognizing a specific tumor predisposition syndrome.


Neuron-Specific Markers and their Correlation with Neurological Scales in Patients with Acute Neuropathologies.
In predicting outcomes in patients with acute brain injury, current practice focuses special attention on neuron-specific proteins that reliably reflect the severity of the lesion. Further studies of molecular markers and their specificity and sensitivity could contribute to broadening the understanding of pathophysiological, diagnostic, and prognostic methods, which is vital to reducing the mortality and disability associated with these critical conditions. The purpose of this study was to assess the biomarkers of brain lesions and their correlative relations with the integral Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) in predicting severity and treatment outcomes in patients with acute neuropathologies. Ninety patients were examined, including those with traumatic brain lesions (16.6%, n = 15), hemorrhagic stroke (52.2%, n = 47), and ischemic stroke (31.1%, n = 28). Patients were classified into two groups according to the outcome of the disease: those who survived (group I, 57.8%, n = 52) and those who died (group II, 42.2%, n = 38). In comparison with the survivors, the group of patients who died demonstrated an initial increase in neuron-specific enolase (NSE) by 1.23 and S100 by 6.45 times, and in dynamics by 1.5 and 7.4 times. A significant correlation with NIHSS and GCS was determined for NSE (r = 0.1149; P = 0.3073 and r = -0.0758; P = 0.5011) and for S100 (r = 0.3243; P = 0.0031 and r = -0.2661; P = 0.0163). The receiver operating characteristic (ROC) curves were 0.828 for S100 and 0.712 for NSE. The degree of sensitivity and specificity of the markers was studied. Increased levels of S100 and NSE correlated with NIHSS and GCS, with sensitivity of 80.77 and 63.46% and specificity of 42.11 and 73.68%, respectively, and were predictive of adverse disease outcome. The survival analysis showed that early detection of these biomarkers enables the timely prognostication of the progression of secondary brain injury and aids in implementing treatment.


Induction of A:T to G:C transition mutations by 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), an antiviral pyrimidine nucleoside analogue, in the bone marrow of Muta Mouse.
5-(2-chloroethyl)-2'-deoxyuridine (CEDU) is a pyrimidine nucleoside analogue formerly in development for the treatment of herpes simplex virus infections. The compound proved clearly mutagenic in the mouse spot test and exhibited weak activity in the Salmonella reverse mutation test, which led to the termination of the compound's development. In another study, CEDU, administered orally to beta-galactosidase (lacZ) transgenic mice (Muta Mouse) for five days, induced a clear increase in lacZ mutant frequencies in spleen, lung, and bone marrow. In the present follow-up study, we analyzed 32 of those lacZ mutants isolated from the bone marrow of the Muta Mouse animals of the experiments mentioned above, in order to obtain further information on the type of mutations induced by CEDU. CEDU induced a pronounced increase in A:T to G:C transitions. The distribution of A:T to G:C transitions was clearly non-random, showing a bias towards T to C substitutions in the coding DNA strand and a preference to occur in the sequence motif 5'-(G or C)-T-G-3'. Our data support the hypothesis that CEDU, after being phosphorylated, is incorporated into cellular DNA in place of thymidine, which leads to mispairing with guanosine during subsequent DNA replication. As a result, the compound is thought to exert its mutagenicity by inducing mismatches leading to T to C transitions. Our findings point towards a mode of mutagenic action of CEDU that differs fundamentally from that of other antiviral antinucleosides whose clastogenic and recombinogenic activities prevail.


Serum 25-hydroxyvitamin D and depressive symptoms in older women and men.
Hypovitaminosis D and depressive symptoms are common conditions in older adults. We examined the relationship between 25-hydroxyvitamin D [25(OH)D] and depressive symptoms over a 6-yr follow-up in a sample of older adults. This research is part of a population-based cohort study (InCHIANTI Study) in Tuscany, Italy. A total of 531 women and 423 men aged 65 yr and older participated. Serum 25(OH)D was measured at baseline. Depressive symptoms were assessed at baseline and at 3- and 6-yr follow-ups using the Center for Epidemiological Studies-Depression Scale (CES-D). Depressed mood was defined as CES-D of 16 or higher. Analyses were stratified by sex and adjusted for relevant biomarkers and variables related to sociodemographics, somatic health, and functional status. Women with 25(OH)D less than 50 nmol/liter compared with those with higher levels experienced increases in CES-D scores of 2.1 (P = 0.02) and 2.2 (P = 0.04) points higher at, respectively, 3- and 6-yr follow-up. Women with low vitamin D (Vit-D) had also significantly higher risk of developing depressive mood over the follow-up (hazard ratio = 2.0; 95% confidence interval = 1.2-3.2; P = 0.005). In parallel models, men with 25(OH)D less than 50 nmol/liter compared with those with higher levels experienced increases in CES-D scores of 1.9 (P = 0.01) and 1.1 (P = 0.20) points higher at 3- and 6-yr follow-up. Men with low Vit- D tended to have higher risk of developing depressed mood (hazard ratio = 1.6; 95% confidence interval = 0.9-2.8; P = 0.1). Our findings suggest that hypovitaminosis D is a risk factor for the development of depressive symptoms in older persons. The strength of the prospective association is higher in women than in men. Understanding the potential causal pathway between Vit- D deficiency and depression requires further research.


Development of a new near-infrared, spectrophotometric, and colorimetric probe based on phthalocyanine containing mercaptoquinoline unit for discriminative and highly sensitive detection of Ag+, Cu2+, and Hg2+ ions.
A new near-infrared, spectrophotometric, and colorimetric probe based on a phthalocyanine-containing mercaptoquinoline unit (MQZnPc) has been constructed and utilized for discriminative and highly selective/sensitive detection of Ag+, Cu2+, and Hg2+ ions by using proper masking agents like EDTA, KI, and NaCl. The probe only responds to Ag+, Cu2+, and Hg2+ among the tested ions without any interference. The probe performs quite well (the limit of detection: 160 ppb, 148 ppb, and 276 ppb of Ag+, Cu2+, and Hg2+ions for UV-Vis, and 15 ppb, 37 ppb, and 467 ppb of Ag+, Cu2+, and Hg2+ ions for fluorescence, respectively), and has a fast response time (150 sec, 90 sec, and 90 sec of Ag+, Cu2+, and Hg2+ions for UV-Vis, and 300 sec, 240 sec, and 90 sec Ag+, Cu2+, and Hg2+ions for fluorescence, respectively). The probe also displays a colorimetric feature for UV-Vis and smartphone applications. Based on a single probe, Ag+, Cu2+, and Hg2+ ions which are the main toxic water contaminants could be recognized very quickly and colorimetrically with high recovery values in tap water samples. This study stands out with its unique properties compared to the related studies in the literature.


Tandem diaza-Cope rearrangement polymerization: turning intramolecular reaction into powerful polymerization to give enantiopure materials for Zn2+ sensors.
[3,3]-Sigmatropic rearrangement is a powerful reaction to form C-C bonds stereospecifically; however, owing to intrinsic simultaneous bond formation and breakage, this versatile method has not been utilized in polymerization. Herein, we report a new tandem diaza-Cope rearrangement polymerization (DCRP) that can synthesize polymers with defect-free C-C bond formation from easy and efficient imine formation. A mechanistic investigation by in situ 1H NMR experiments suggests that this polymerization proceeds by a rapid DCR process, forming an enantiospecific C-C bond that occurs almost simultaneously with imine formation. This polymerization produces not only highly stable polymers against hydrolysis due to resonance-assisted hydrogen bonds (RAHBs) but also chiral polymers containing enantiopure salen moieties, which lead to high-performance Zn2+-selective turn-on chemosensors with up to 73-fold amplification. We also found that their optical activities and sensing performances are heavily dependent on the reaction temperature, which significantly affects the stereoselectivity of DCR.


LncRNA WT1-AS over-expression inhibits non-small cell lung cancer cell stemness by down-regulating TGF-β1.
LncRNA WT1-AS is a recently identified potential tumor suppressor in gastric cancer. This study mainly explored the role of WT1-AS in non-small cell lung cancer (NSCLC). WT1-AS and TGF-β1 mRNA in two types of tissues of 74 NSCLC patients were detected by performing RT-qPCR experiments. WT1-AS and TGF-β1 expression vectors were established using the pcDNA3.1 vector. Protein concentration was measured by BCA assay. Mean values in this study were calculated using the data of three biological replicates of each experiment. We found that WT1-AS was down-regulated, while TGF-β1 was upregulated in NSCLC tissues. Survival analysis showed that low levels of WT1-AS expression predicted poor survival of NSCLC patients. WT1-AS and TGF-β1 were inversely correlated in NSCLC tissues. Over-expression experiments revealed down-regulated TGF-β1 after WT1-AS over-expression, while TGF-β1 over-expression failed to affect WT1-AS. WT1-AS over-expression resulted in inhibited cancer cell stemness. TGF-β1 over-expression played an opposite role and attenuated the effects of TGF-β1 over-expression. Therefore, WT1-AS over-expression may inhibit non-small cell lung cancer cell stemness by down-regulating TGF-β1. The First Affiliated Hospital of Anhui Medical University Ethics committee approved this study (AHMU20101009).


Ten-year change in disability prevalence and related factors in two generations of French elderly community dwellers: data from the PAQUID study.
Some studies have reported a decline in disability prevalence in older people, but few data were available for Europe, especially for France. Our aim was to study the 10-year evolution of disability prevalence in elderly community dwellers and related factors. Two generations of subjects aged 75 to 84, participants in the PAQUID (Personnes Agées QUID) cohort were compared. The first generation included 1496 subjects (born between 1903 and 1912) and the second 910 subjects (born between 1913 and 1922). Three domains of disability were assessed: mobility, Activities of Daily Living (ADL) and Instrumental ADL (IADL). Logistic regressions were used to explain the effect of generation on disability, controlling for sociodemographic characteristics, impairment, life-style, medical care, and social support. The percentage of subjects fully independent increased from 13.5 to 23.3% (p < 0.001). A large decline in disability prevalence independent of the controlled factors was observed for mobility in both genders [Odds Ratio for the second generation (OR(G2)) = 0.48, 95% CI 0.38-0.60]. When adjusting for age and education, the risk of IADL disability was significantly lower in women in the second generation (ORG2 0.61, 95% CI 0.49-0.77), and the generation effect was strengthened when adjusting for the other covariates, but unchanged in men (ORG2 1.09, 95% CI 0.81-1.48). There was no significant change for ADL. A significant decline in disability prevalence was observed over 10 years, which was not explained by the selected covariates. These aggregate changes differed by gender, education, and the domain of disability considered.


Critical analysis of current methods for assessing the in vitro antioxidant and antibacterial activity of plant extracts.
Natural product research is an active branch of science, driven by the increased value placed on individual health and well-being. Many naturally-occurring phytochemicals in plants, fruits and vegetables have been reported to exhibit antioxidant and antibacterial activity; often touted as being beneficial for human health. In vitro screening is a common practice in many research laboratories as a means of rapidly assessing these properties. However, the methods used by many are not necessarily optimal; a result of poor standardization, redundant assays and/or outdated methodology. This review primarily aims to give a better understanding in the selection of in vitro assays, with emphasis placed on some common assays such as the total phenolic content assay, free radical scavenging activity, disc-diffusion and broth microdilution. This includes a discussion on the reasons for choosing a particular assay, its strengths and weaknesses, ways to improve the accuracy of results and alternative assays.


Characterization of the gene family encoding a host-protective antigen of the tapeworm Taenia ovis.
Genomic structure has been determined for a gene encoding a host-protective antigen of the parasitic platyhelminth Taenia ovis. An incomplete cDNA, known as 45W, encodes the protective antigen. Southern hybridisation experiments using 45W cDNA as a probe, revealed that the 45W gene was a member of a multigene family. Differential Southern hybridisation and rapid amplification of cDNA end (RACE) experiments were used to characterise the related genes, allowing the full-length coding region of the 45W encoded antigen to be determined. The gene family comprises a minimum of four members per haploid genome with each member showing varying degrees of 5' and 3' homology with respect to the 45W cDNA. A close homologue of the 45W gene, designated 45S, differed from 45W at 11 of 985 nt comprising the full-length mRNA. Sequencing of several independent RACE products for both 45W and 45S identified a cDNA which may be a product of homologous recombination between these genes, suggesting that the two genes may be alleles. Homologous recombination in genes which encode a host protective antigen such as 45W would provide a mechanism by which antigenic variants could arise.


Interdependence of ICD rates in paired quantum dots on geometry.
Using state-of-the-art antisymmetrized multiconfiguration time-dependent Hartree (MCTDH) electron dynamics calculations we study the interdependence of the intermolecular Coulombic decay (ICD) process on the geometric parameters of a doubly-charged paired quantum dot (PQD) model system in the framework of the effective mass approximation (EMA). We find that ICD displays a maximum rate for a certain geometry of the electron-emitting quantum dot, which is simultaneously dependent on both the distance between the quantum dots as well as the photon-absorbing quantum dot's geometry. The rate maximum is shown to be caused by the competing effects of polarization of electron density and Coulomb repulsion. The ICD rate-maximized PQD geometry in GaAs QDs yields a decay time of 102.39 ps. It is given by two vertically-aligned cylindrical QDs with radii of 14.42 nm separated by 86.62 nm. The photon absorbing QD then has a height of 46.59 nm and the electron emitting QD a height of 16.33 nm. © 2017 Wiley Periodicals, Inc.


The evaluation of isolated third nerve palsy revisited: an update on the evolving role of magnetic resonance, computed tomography, and catheter angiography.
The evaluation and management of the neurologically isolated third nerve palsy continues to evolve. The major concern for the clinician confronted with a patient with a third nerve palsy has been the exclusion of an intracranial aneurysm. The evolution of new imaging techniques, such as computed tomography angiography and magnetic resonance angiography, have provided new imaging options for clinicians. This article reviews the pertinent recent literature on the use of these imaging studies in evaluating the patient with a third nerve palsy.


SpeB of Streptococcus pyogenes differentially modulates antibacterial and receptor activating properties of human chemokines.
CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11, are antibacterial for Streptococcus pyogenes. SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/CXCL11, PF4/CXCL4, GROalpha/CXCL1, GRObeta/CXCL2, GROgamma/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3alpha/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3alpha/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity. SpeB destroys most of the signaling and antibacterial properties of chemokines expressed by an inflamed epithelium. The exception is CXCL9 that preserves its antibacterial activity after hydrolysis, emphasizing its role as a major antimicrobial on inflamed epithelium.


Induction potential of antifungals containing an imidazole or triazole moiety. Miconazole and ketoconazole, but not itraconazole are able to induce hepatic drug metabolizing enzymes of male rats at high doses.
Male Wistar rats were dosed with miconazole, ketoconazole and itraconazole by gastric intubation once daily for up to 7 days. A dose- and time-dependent induction of the hepatic drug metabolizing enzyme system was observed for miconazole and ketoconazole, while itraconazole proved to be devoid of inductive properties even at the highest dose studied (160 mg/kg). No effect on drug metabolizing enzymes could be demonstrated for either drug at a dose level of 10 mg/kg, which is just above the antifungally active dose. At a dose of 40 mg/kg, miconazole, but not ketoconazole, significantly increased cytochrome P-450 content. At the highest dose of 160 mg/kg, both miconazole and ketoconazole increased the relative liver weight, the cytochrome P-450- and b5-content and NADPH-cyt c-reductase. Furthermore, miconazole, but not ketoconazole, increased specific microsomal aminopyrine and N,N-dimethylaniline N-demethylase activity, p-nitroanisole O-demethylase activity and UDP-glucuronyltransferase activity towards 4-nitrophenol while the specific aniline hydroxylase activity was unaffected. Ketoconazole at 160 mg/kg only induced O-demethylase activity and UDP-glucuronyltransferase activity, while it lowered the specific activities towards the other substrates. Miconazole was a relatively more potent inducer when compared to ketoconazole. Both drugs displayed biphasic effects on the mixed-function oxidase activities, which were lowered after acute administration (160 mg/kg, 1 hr before death) and were induced when determined after 23 hr had elapsed or after multiple dosage. Both drugs bound strongly to their respective induced cytochromes, giving rise to type II difference spectra, and inhibited the O-demethylase activity of the induced microsomes with an I50 of 5.2 microM for miconazole and 15.1 microM for ketoconazole. On the basis of a comparison of the enzymatic activities induced by both antimycotics with those induced by PB or 3-MC, it was concluded that miconazole behaved as a PB-type inducer, whereas ketoconazole did not belong to either category of inducers. A comparison of electrophoretograms of microsomes from different origins on SDS-PAGE revealed that miconazole increased the concentration of several proteins, whereas ketoconazole selectively induced a protein with Mr of 47,800. The protein pattern in the 50 kDa region of miconazole-induced microsomes resembled that of PB-microsomes qualitatively.


Submandibular gland mucocele: report of two cases.
Submandibular gland mucocele should be remembered in the differential diagnosis of swelling at the submandibular triangle. In the cystic lesion of the submandibular area, the biochemical analysis of aspirated material for amylase should be performed. The cases with submandibular gland mucocele should be treated by removing the lesion with both the submandibular and the sublingual glands.


Local heat effect on sympathetic skin responses after pain of electrical stimulus.
To investigate the analgesic effort of local superficial heating by studying sympathetic skin responses. Randomized trial. Electromyography laboratory in the department of physical therapy and rehabilitation of a university hospital. Twenty healthy volunteers participated with informed consent. Sympathetic skin response (SSR) amplitudes following electrical stimulation of the right peroneal nerve and skin temperatures in both hands were recorded simultaneously. All of the recordings were repeated at 5-minute intervals during local heat application over the right palm and within 15 minutes after heat application was stopped. SSR amplitudes in both hands decreased significantly during local heating (p < .05) and did not return to their initial levels within 15 minutes of the recovery period; the reductions remained statistically significant (p < .05). Amplitude reductions were statistically more significant on the heated hand compared with those on the contralateral hand (p < .05). Therapeutic local heat application reduces the sudomotor response to a painful stimulus. This analgesic effect may be due to suppression of cortical pain sensation resulting from increased levels of endorphins, and may also be a result of local inhibition of both afferent and efferent C fibres.


A biological and a mathematical model of SLE treated by mesenchymal stem cells covering all the stages of the disease.
In this study, we proposed a biological model explaining the progress of autoimmune activation along different stages of systemic lupus erythematosus (SLE). For any upcoming stage of SLE, any new component is introduced, when it is added to the model. Particularly, the interaction of mesenchymal stem cells, with the components of the model, is specified in a way that both the inflammatory and anti-inflammatory functions of these cells would be covered. The biological model is then recapitulated to a model with less complexity that explains the main features of the problem. Later, a 7th-order mathematical model for SLE is proposed, based on this simplified model. Finally, the range of validity of the proposed mathematical model was assessed. For this purpose, we simulated the model and analyzed the simulation results in case of some known behaviors of the disease, such as tolerance breach, the appearance of systemic inflammation, development of clinical signs, and occurrence of flares and improvements. The model was able to reproduce these events, qualitatively.


A cationic detergent, cetyltrimethylammonium bromide (CTAB), selectively dissociates the intermediate filament of the fibroblast.
We investigated conditions for selective solubilization of the intermediate filament (IF) of BHK-21 cells, and found that a cationic detergent, cetyltrimethylammonium bromide (CTAB), was effective for rapid dissociation of IF into the monomeric form. More selective dissociation was performed with a combination of CTAB and Tween 40. The CTAB-dissociated vimentins were unstable, but the breakdown of them was successfully blocked by leupeptin. Thus, with our extraction buffer, composed of 1% CTAB, 1% Tween 40, 10 mM Tris-HCl (pH 7.4) and 25 micrograms/ml leupeptin, almost all of the vimentin as well as the desmin were solubilized, while two thirds or more of actins were retained in the CTAB/Tween-insoluble fraction.


Macroorganisms fouled in marine anthropogenic litter (rafting) arround a tropical bay in the Southwest Atlantic.
The presence of floating marine anthropogenic litter in marine environments increase the possibility of transportation of fouling organisms using these substrates as a vector, mainly for those species with close affinities to artificial substrates. The objectives were to qualitatively and quantitatively report anthropogenic litter and its associated fouling groups arround Ilha Grande Bay (IGB). Litter was collected, classified and examined for the presence of fouling organisms on beaches located at two different levels of wave exposure during rainy and dry seasons. The types of litter do not differ among beaches, and the highest density and cover of fouling were reported on exposed beaches due the currents, winds, and storm waves. Bryozoans, barnacles, polychaetes, and mollusks were the most frequent fouling groups observed in litter and represents a potential vector for the dispersion of species in the IGB and adjacent coastal areas.


Fetal dose evaluation for body CT examinations of pregnant patients during all stages of pregnancy.
CTDIvol-to-fetal-dose coefficients from Monte Carlo simulations are useful for fetal dose evaluations, but the available data is limited to the fetus being completely inside the abdominopelvic scan range. Whereas in a chest examination, the fetus is completely outside the scan range. In an abdominal examination, the fetus after 16 gestational weeks is partly in the scan region, and an earlier fetus is completely outside of it. This work proposes a practical approach to evaluate fetal dose for pregnant patients undergoing body CT examinations, without using Monte Carlo simulation. The proposed method was based on the z-axis dose profile computed for a CT examination, considering CTDIvol, scan range, mA, and maternal WED (water equivalent diameter) at the fetus centroid. Fetal average dose was calculated over the fetus z-axis coverage. For validation, we considered a reference dataset of 24 pregnant patients, each underwent two abdominopelvic examinations (fixed mA, tube current modulation). WED was 30.1 ± 3.3 (25.3-35.6) cm [mean(range)]. Gestational age was <5 weeks for one patient, and 20.3 ± 9.1 (5-35.9) weeks for the others. Fetal depth (from the anterior skin surface to the most anterior part of fetus) was 6.1 ± 2.1 (2.5-10.9) cm. We further considered three whole-body models of a pregnant patient (gestational age, 3, 6, 9 months; weight, 62-73 kg) undergoing chest, abdominal, and abdominopelvic examinations (fixed mA). For the patients and models, profile-based fetal dose calculations were compared with the results of Monte Carlo simulations. Statistical software (R, version 3.5.1) was used to determine the mean and 95th percentile. The fetal dose difference between profile-based evaluations and Monte Carlo simulations was (5.9 ± 3.8)% for 24 fixed-mA examinations, (5.8 ± 4.6)% for 24 tube current modulated examinations, and (8.8 ± 5.9)% for the whole-body models in three scan ranges. Profile-based fetal dose calculations can be performed for patients in body CT, considering maternal size, fetus size and location, and whether fetus is completely inside, partly inside, or outside scan ranges.


Structural basis for client recognition and activity of Hsp40 chaperones.
Hsp70 and Hsp40 chaperones work synergistically in a wide range of biological processes including protein synthesis, membrane translocation, and folding. We used nuclear magnetic resonance spectroscopy to determine the solution structure and dynamic features of an Hsp40 in complex with an unfolded client protein. Atomic structures of the various binding sites in the client complexed to the binding domains of the Hsp40 reveal the recognition pattern. Hsp40 engages the client in a highly dynamic fashion using a multivalent binding mechanism that alters the folding properties of the client. Different Hsp40 family members have different numbers of client-binding sites with distinct sequence selectivity, providing additional mechanisms for activity regulation and function modification. Hsp70 binding to Hsp40 displaces the unfolded client. The activity of Hsp40 is altered in its complex with Hsp70, further regulating client binding and release.


BAALC and ERG expression levels at diagnosis have no prognosis impact on acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.
Brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) expression levels are independent prognostic factors for acute myeloid leukemia (AML); however, their prognostic impacts on AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) require further investigation. We studied 71 de novo AML patients treated with allo-HSCT and defined low and high expressers according to the median expression levels of BAALC and ERG at diagnosis respectively. High BAALC expression was associated with wild-type NPM1 (P = 0.000) and RUNX1 mutations (P = 0.027). High ERG expression was associated with FLT3-ITD absence (P = 0.003) and wild-type NPM1 (P = 0.001). BAALC and ERG expression levels were significantly correlated with each other (P = 0.001). Survival analyses including Kaplan-Meier curves and univariate and multivariate analysis consistently reported that there were no significant differences for both event-free survival (EFS) and overall survival (OS) (all P > 0.1), between high versus low BAALC and ERG expressers. Our study suggested that despite of their well-known adverse role in prognosis of AML, neither BAALC nor ERG expression levels at diagnosis had effect on survival of AML patients who underwent allo-HSCT.


Efficacy of cryotherapy in retinoblastoma.
Five cases of retinoblastoma treated be freezing are reported. From these cases it appears that a single freeze-thaw cycle will destroy all tumour and that with suitable instruments it is possible to destroy tumours involving up to 30% of the volume of the globe without causing blindness.


New species and distribution notes of Cerambycidae (Coleoptera) for the state of Acre and the Amazon basin, Brazil.
A new species, Unachlorus rafaeli sp. nov., is described from Brazil, state of Acre. Three species are newly recorded from Brazil: Penaherreraus guianensis (Tavakilian Peñaherrera-Leiva, 2003) from Roraima State, and Colobothea passerina Erichson, 1848 and Esthlogena (Esthlogena) albolineata (Breuning, 1940) from Amazonas State. Thirty-two species are new state records, 19 from Roraima, 10 from Amazonas and three from Acre.


SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor-independent mechanism.
Dopamine (DA) profoundly modulates excitatory synaptic transmission and synaptic plasticity in the brain. In the present study the effects of SKF83959, the selective agonist of phosphatidylinositol (PI)-linked D(1) -like receptor, on the excitatory synaptic transmission were investigated in rat hippocampus. SKF83959 (10-100 μM) reversibly suppressed the field excitatory postsynaptic potential (fEPSP) elicited by stimulating the Schaffer's collateral-commissural fibers in CA1 area of hippocampal slices. However, the inhibition was not blocked by the D(1) receptor antagonist SCH23390, the D(2) receptor antagonist raclopride, the 5-HT(2A/2C) receptor antagonist mesulergine, or the α(1) -adrenoceptor antagonist prazosin. In addition, SKF83959 inhibited the afferent volley and significantly reduced the paired-pulse facilitation ratios. In dissociated hippocampal CA1 pyramidal neurons, SKF83959 had no detectable effect on glutamate-induced currents but potently inhibited voltage-activated Na(+) current (IC50 value = 26.9 ± 1.0 μM), which was not blocked by SCH23390 or by intracellular dialysis of GDP-β-S. These results demonstrate that SKF83959 suppressed the excitatory synaptic transmission in hippocampal CA1 area, which was independent of D(1) -like receptor. The mechanism underlying the effect could be mainly inhibition of Na(+) channel in the afferent fibers. The suppression of excitatory synaptic transmission and the Na(+) channel by SKF83959 may contribute to its therapeutic benefits in Parkinson's disease.


Applications of hydrogen-bond-acceptor templates to direct 'in-phase' reactivity of a diene diacid in the solid state.
The hydrogen-bond-acceptor (HBA) templates 2,3-bis(4-methylenethiopyridyl)naphthalene (2,3-nap) and 1,8-bis(4-pyridyl)naphthalene (1,8-dpn) are used to assemble (E,E)-2,5-dimethylmuconic acid (dmma) in the solid state for an intermolecular [2 + 2] photocycloaddition. Co-crystallisation of 2,3-nap with dmma affords an 1D hydrogen-bonded polymer that is photostable while 1,8-nap affords a 0D hydrogen-bonded assembly that is photoactive. The diene stacks in-phase and reacts to give a syn monocyclobutane in up to 55% yield.


Doublet regimen of cisplatin plus docetaxel for second-line chemotherapy after prior therapy with cisplatin plus irinotecan for non-small cell lung cancer: a phase II study.
To evaluate the safety and efficacy of second-line chemotherapy with docetaxel and cisplatin for non-small cell lung cancer (NSCLC), we performed a phase II study. The subjects were 25 patients with NSCLC, 75 years or younger, without organ dysfunction (performance status [PS], 0 to 2) in whom treatment with cisplatin and irinotecan had been ineffective or had been followed by recurrence or relapse. Four weeks or more after the end of the previous therapy, 60 mg/m2 of cisplatin and 60 mg/m2 of docetaxel were administered at intervals of 3 weeks. Observed toxicities of grade 3 or 4 included anemia (24% of patients), leukocytopenia (48%), neutropenia (76%), thrombocytopenia (4%), hepatic dysfunction (8%), and electrolyte abnormalities (4%). However, no severe nonhematologic adverse reactions occurred. The overall response rate was 32% (95% confidence interval, 13.7-50.3). The median time to disease progression was 98 days, and the median survival time was 257 days. Our results suggest that cisplatin and docetaxel can be used as second-line chemotherapy against NSCLC. But further, comparative, study of this combination should be performed in patients with good PS and organ function who have responded to prior platinum-based chemotherapy.


Comparisons of diatoms and fishes as toxic metal bioindicator: a case study of an A-class wetland in northwest Turkey under effect of an intensive paddy cultivation stress.
In this research, diatoms as the first step and fishes as the last step of the food chain were compared as toxic metal accumulation bioindicator in an A-class wetland in Turkey. Bioaccumulations of potentially toxic elements (PTEs) were determined in liver, gill and muscle tissues of two commercially consumed fish species Carassius gibelio and Cyprinus carpio and in frustules of epiphytic diatom communities living on submerged macrophytes. Samples were collected seasonally from the Gala Lake, which is among the best stopover habitats of birds migrating between Europe and Africa, considering the paddy harvest period that is a major stress factor for the ecosystem. Also, potential human health risks associated with the consumption of fishes and consumption - dermal contact of diatoms were evaluated both for summer - before paddy harvest (BPH) and autumn - after paddy harvest (APH) periods. As a result of this research, the investigated toxic metal concentrations were increased significantly in diatoms in the APH period, while less significant exchanges were recorded in fishes. The bioaccumulations of PTEs were ranked as follows: Zn > Mn > Se > Cu > B > Cr > Ni > As > Pb > Cd for C. gibelio; Zn > Mn > Se > Cu > B > Cr > As > Ni > Pb > Cd for C. carpio; and Mn > Zn > Se > Pb > B > Ni > Cr > Cu > As > Cd for diatom frustules. Although the HI values in diatoms detected in the APH period were statistically significantly higher (about 1000 times; p < 0.05) than detected in the BPH period, they were less than the limit of 1 in both seasons. However, the HI coefficients of fishes were quite higher than the limit (an average of 23.59 for C. gibelio and 19.18 for C. carpio), which means quite high probable non-carcinogenic health risks for humans. Furthermore, the CR coefficients of Cr, Ni and As in muscle tissues of fishes were considerably higher than the limit of 10-4, which reflects a significant carcinogenic health risk for consumers. The data showed that although the fishes at the top of the food chain bioaccumulate the PTEs in their tissues much higher than the diatoms at the bottom of the food chain, the diatoms are much more sensitive to changes in the environmental conditions than the fishes and they are more effective biological tools as toxic metal accumulation bioindicators.


NH4 + Pre-Intercalation and Mo Doping VS2 to Regulate Nanostructure and Electronic Properties for High Efficiency Sodium Storage.
Sodium-ion hybrid capacitors (SIHCs) have attracted much attention due to integrating the high energy density of battery and high out power of supercapacitors. However, rapid Na+ diffusion kinetics in cathode is counterbalanced with sluggish anode, hindering the further advancement and commercialization of SIHCs. Here, aiming at conversion-type metal sulfide anode, taking typical VS2 as an example, a comprehensive regulation of nanostructure and electronic properties through NH4 + pre-intercalation and Mo-doping VS2 (Mo-NVS2 ) is reported. It is demonstrated that NH4 + pre-intercalation can enlarge the interplanar spacing and Mo-doping can induce interlayer defects and sulfur vacancies that are favorable to construct new ion transport channels, thus resulting in significantly enhanced Na+ diffusion kinetics and pseudocapacitance. Density functional theory calculations further reveal that the introduction of NH4 + and Mo-doping enhances the electronic conductivity, lowers the diffusion energy barrier of Na+ , and produces stronger d-p hybridization to promote conversion kinetics of Na+ intercalation intermediates. Consequently, Mo-NVS2 delivers a record-high reversible capacity of 453 mAh g-1 at 3 A g-1 and an ultra-stable cycle life of over 20 000 cycles. The assembled SIHCs achieve impressive energy density/power density of 98 Wh kg-1 /11.84 kW kg-1 , ultralong cycling life of over 15000 cycles, and very low self-discharge rate (0.84 mV h-1 ).


Description of the response of a fiber optic velocity sensor applied to capillary gas chromatography.
This paper explores the response of a novel fiber optics sensor allowing real-time determination of the migration rate of vapor zones in capillary gas chromatography. The sensitivity is related to the gradient of the vapor zone distribution in the capillary and it is highest when vapor zones show steep variations in concentration. The expected linearity between the height of the velocity peaks and the response of a thermal conductivity detector is demonstrated experimentally. The sensor can be used to infer an approximate value of the analyte diffusion coefficient from the time response. Finally, the time evolution of the envelope of the optical signal is explained with experimental evidences.


Nitric oxide as a target for the hypotensive and vasorelaxing effects induced by (Z)-ethyl 12-nitrooxy-octadec-9-enoate in rats.
The cardiovascular effects induced by a new organic nitrate were investigated in rats. The (Z)-ethyl 12-nitrooxy-octadec-9-enoate (NCOE) was synthesized from ricinoleic acid, the major compound of the castor oil. NCOE induced significant and dose-dependent hypotension and bradycardia in normotensive rats. In rats pretreated with NCOE (60 mg/kg, i.v., once a day) for 4 consecutive days, hypotension induced by the nitrate was similar to that observed in rats that were not pretreated with the compound. The vasorelaxation induced by the compound was concentration-dependent (10(-10)-10(-3) M) in rat mesenteric artery rings, pre-contracted with phenylephrine (1 μM), with or without endothelium. Pre-incubation with PTIO (300 μM), a free radical form of NO (NO) scavenger, attenuated the NCOE vasorelaxation potency. However, in the presence of L-cysteine (3 mM), a reduced form of NO (NO-) scavenger, NCOE response was potentiated. NCOE effect was not changed in the presence of an inhibitor of cytochrome P450, proadifen (10 μM). On the other hand, the vasodilation was reduced in the presence of mitochondrial aldehyde dehydrogenase inhibitor (mtALDH), cyanamide (1 mM); soluble guanylyl cyclase inhibitor (sGC), ODQ (10 μM); and non-selective K+ channels blocker, TEA (3 mM). In addition the NCOE-induced vasorelaxation was reduced by BKCa (iberiotoxin, 100 nM) and KATP selective (glibenclamide, 10 μM) blockers, however the effect was not modified by a KV blocker (4-aminopyridine, 1 mM). Furthermore, NCOE increased NO levels in rat aortic smooth muscle cultured cells, detected by NO-sensitive probe DAF-2DA, by flow cytometry. These results together suggest that NCOE induces short-lasting hypotension and bradycardia, and promotes vasorelaxation due to NO release through the compound metabolism via mtALDH and consequent sGC, KATP and BKCa activation. Furthermore, the compound was not able to induce tolerance.


Production and characterization of murine monoclonal anti-human DNase II antibodies, and their use for immunoaffinity purification of DNase II from human liver and urine.
Four murine monoclonal anti-human deoxyribonuclease II (DNase II) antibodies were obtained from BALB/c mice immunized with human DNase II purified from human liver. Both single radial enzyme diffusion (SRED) and DNA-cast polyacrylamide gel electrophoresis (DNA-cast PAGE) were very useful for obtaining the DNase II-specific antibodies. All of the antibodies showed specific inhibition of human DNase II enzyme activity and specific immunostaining of the 32-kDa enzyme band, which is one of the three non-identical subunits of human DNase II molecule separated by sodium dodecyl sulfate (SDS)-PAGE followed by blotting on a transfer membrane. A formyl-cellulofine resin conjugated with each antibody specifically adsorbed and efficiently desorbed the active DNase II enzyme. Insertion of the immunoaffinity step in our purification procedure made the purification of human DNase II easier, faster and more effective than the conventional procedure.


Screening for infectious diseases in the dental setting.
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are 2 systemic infectious diseases that dental health care professionals can help identify with the goal of improving health outcomes, addressing health disparities, and improving the quality and quantity of life. Whether by identifying suspect oral lesions, as is the case with HIV infection, or offering rapid screening tests in the dental setting for both HIV and HCV, the dental team can play an important role in linkage to confirmatory diagnosis and care.


Gregarine single-cell transcriptomics reveals differential mitochondrial remodeling and adaptation in apicomplexans.
Apicomplexa is a diverse phylum comprising unicellular endobiotic animal parasites and contains some of the most well-studied microbial eukaryotes including the devastating human pathogens Plasmodium falciparum and Cryptosporidium hominis. In contrast, data on the invertebrate-infecting gregarines remains sparse and their evolutionary relationship to other apicomplexans remains obscure. Most apicomplexans retain a highly modified plastid, while their mitochondria remain metabolically conserved. Cryptosporidium spp. inhabit an anaerobic host-gut environment and represent the known exception, having completely lost their plastid while retaining an extremely reduced mitochondrion that has lost its genome. Recent advances in single-cell sequencing have enabled the first broad genome-scale explorations of gregarines, providing evidence of differential plastid retention throughout the group. However, little is known about the retention and metabolic capacity of gregarine mitochondria. Here, we sequenced transcriptomes from five species of gregarines isolated from cockroaches. We combined these data with those from other apicomplexans, performed detailed phylogenomic analyses, and characterized their mitochondrial metabolism. Our results support the placement of Cryptosporidium as the earliest diverging lineage of apicomplexans, which impacts our interpretation of evolutionary events within the phylum. By mapping in silico predictions of core mitochondrial pathways onto our phylogeny, we identified convergently reduced mitochondria. These data show that the electron transport chain has been independently lost three times across the phylum, twice within gregarines. Apicomplexan lineages show variable functional restructuring of mitochondrial metabolism that appears to have been driven by adaptations to parasitism and anaerobiosis. Our findings indicate that apicomplexans are rife with convergent adaptations, with shared features including morphology, energy metabolism, and intracellularity.


Bacterial degradation of distillery wastewater pollutants and their metabolites characterization and its toxicity evaluation by using Caenorhabditis elegans as terrestrial test models.
Distillery wastewater has significant amount of coloring compounds and organic substances even after the secondary treatment process, which poses many severe environmental and health threats. However, the recalcitrant coloured compounds have not yet been clearly identified. In this study, two bacterial strains DS3 and DS5 capable to decolorize distillery wastewater (DWW) pollutants were isolated and characterized as Staphylococcus saprophyticus (MF182113) and Alcaligenaceae sp. (MF182114), respectively. Results showed that mixed bacterial culture was found more effective decolorizing 71.83% DWW compared to axenic culture DS3 and DS5 resulting only 47.94% and 50.67% decolorization, respectively. The FT-IR and LC-MS/MS analysis of untreated DWW showed the presence of many recalcitrant compounds having different functional groups, but after bacterial treatment, most of compounds get diminished and the toxicity of DWW was reduced significantly. Further, the Nile red staining of Caenorhabditis elegans exposed to untreated and bacteria treated DWW for evaluation of toxicity assay and results revealed that the worms exposed to untreated DWW showed sharp reduction in total fat content having more profound effects, suggesting the diminished nAchR signaling as compare to bacterial treated DWW. Hence, this study revealed that inadequate disposal of untreated DWW may cause transfer of toxic substances into the environment and receiving water bodies.


Sex-related substance use and the externalizing spectrum.
Substance use before and during sexual activity is associated with many negative health outcomes. Estimates suggest that at least 4.3 million American adults annually engage in regular sex-related alcohol consumption, indicating that the intersection of substance use and sexual behavior is of public health concern. However, it is likely that when considering broader sex-related substance use, estimates would be notably higher. While substance use disorders and antisocial personality disorder have been associated with sex-related alcohol consumption, no study has investigated how regular sex-related substance use is associated with the broader transdiagnostic externalizing spectrum. Further, no studies have assessed whether or not sexual risk-taking behaviors can be integrated into the externalizing spectrum. In a large internet sample (N=936), we used confirmatory factor analysis, item response theory, and logistic regression to link sex-related alcohol and drug use to an externalizing latent variable; identified psychometric characteristics of these behaviors; and determined the extent to which one's externalizing level was associated with changes in odds of regular sex-related substance use. We then replicated these findings in a nationally representative sample (N=34,653). Results highlighted the close association between sex-related substance use and externalizing, with externalizing increases being associated with significantly increased odds of regular sex-related substance use. These findings bear notable implications for conceptualization and treatment of sex-related substance use. Transdiagnostic intervention can be an efficient means of addressing this problematic behavior as well as other comorbid presentations. Results expand the current conceptualization of the externalizing spectrum.


The embryo rescue derived intergeneric hybrid between chrysanthemum and Ajania przewalskii shows enhanced cold tolerance.
Five intergeneric hybrids between the chrysanthemum cultivar 'Zhongshanjingui' (as female) and Ajania przewalskii (as male) were obtained with the help of embryo culture. While 'Zhongshanjingui' bears a standard anemone type flower and A. przewalskii a non-anemone type one, the inflorescence type of the hybrids varied. The diameter of the hybrids' flowers was intermediate between those of the parents. The chromosome number of the hybrids was 2n = 45, of which GISH analysis was able to establish that 27 were inherited from 'Zhongshanjingui' and the other 18 from A. przewalskii. A combination of various assays was used to show that the cold tolerance of the hybrids was equivalent to that of the highly tolerant A. przewalskii parent. Enhanced cold tolerance was correlated with an increase in free proline and a decrease in malondialdehyde content.


Effect of prenatal care quality on the risk of low birth weight, preterm birth and vertical transmission of HIV, syphilis, and hepatitis.
Averse birth-outcomes still affect newborns worldwide. Although high-quality prenatal care is the main strategy to prevent these outcomes, the effect of prenatal care based on Kotelchuck index combined with consultation contents is still unclear. Thus, this article to evaluate the effect of the quality of prenatal care (PC) process on birth indicators in a cohort of puerperaes who attended maternity hospitals in Brazilian western Amazon, city of Rio Branco, in the state of Acre, Brazil, in 2015. This research was a hospital-based cohort study. The sample consisted of 1,030 women who gave birth in maternity hospitals in the city between April 6 and June 30, 2015. This research was a hospital-based cohort study. The sample consisted of 1,030 women who gave birth in maternity hospitals in Rio Branco between April 6th. and June 30th., 2015. Prenatal care was classified as fully adequate when started ≤4th month; ≥80.0-109% expected consultations for GA according to the Kotelchuck Index; ≥5 records of blood pressure, weight, GA, fundal height, ≥4 records of fetal heart rate, fetal movements or equivalent to 75% of the number of consultations; in addition to recording ABO/RH, hemoglobin, VDRL, urine, glucose, anti-HIV and anti-toxoplamosis during the 1st trimester. The evaluated outcomes were low birth weight (LBW), preterm birth and vertical transmission of human immunodeficiency virus (HIV)/hepatitis/syphilis. Differences between proportions were assessed using the X² test, and the crude and adjusted odds ratios (OR) (95% CI) were estimated using unconditional logistic regression. Overall cohort, the outcomes incidences were 8.8% for LBW, 9.2% for preterm birth, and 1.1% for vertical transmission (syphilis/HIV/hepatitis). Crude and adjusted OR showed that inadequate PC increased the risk statistically significant of LBW (ORcrude: 1.84; 95%CI: 0.99-3.44; ORadjusted: 1.87; 95%CI: 1.00-3.52), and preterm birth (ORcrude: 1.79; 95%CI: 1.00-3.29; ORadjusted: 3.98; 95%CI: 1.40-11.29). The results draw attention to the importance of quality PC in reducing the risks of LBW, preterm birth, and vertical transmission of syphilis/HIV/hepatitis. Moreover, using this proposed quality prenatal care indicator based on Kotelchuck index combined with consultations contents adjusted by GA may accurately predict unfavorable outcomes.


A feasibility study of "plan transformation": A novel workaround enabling patient transfer between different Varian machines.
The objective of this work is to explore a methodology to enable plan transfers from Standard MLC (STD) to High Definition MLC (HD) Varian units without replanning. Using "Plan Transformation", we aim to utilize full departmental capacity to disperse patients from STD Varian units to HD units, when the former goes down for repair. Our centre is equipped with four STD and two HD MLC Varian Truebeam units. Plan transformation is used to transfer patients from STD to HD units when needed. Static or manually segmented fields with Y jaws ≤ 21.6 cm are eligible for plan transformation. The MLC pattern for each field is exported out of Eclipse. An in-house program based on C# is used to convert those patterns from STD to HD. STD and HD MLCs are different in design but dosimetrically comparable for these type of plans. Still to avoid extra uncertainty, transformed plans are recalculated in Eclipse to enable the user to assess the quality of the process. On a given day, more than 25% of appointments on STD units were eligible for transformation. The majority of eligible plans were breast tangent and boost. The delivery and safety of plan transformation was examined directly on a Varian Truebeam linac. A gamma analysis comparison between measured and calculated transformed plans yields a pass-rate of 100% for 3%/3mm, identical to non-transformed plans. Plan transformation is feasible and saves time for planners as it takes less than a quarter the time required for a replan.


Higher order multipole moments for molecular dynamics simulations.
In conventional force fields, the electrostatic potential is represented by atom-centred point charges. This choice is in principle arbitrary, but technically convenient. Point charges can be understood as the first term of multipole expansions, which converge with an increasing number of terms towards the accurate representation of the molecular potential given by the electron density distribution. The use of multipole expansions can therefore improve the force field accuracy. Technically, the implementation of atomic multipoles is more involved than the use of point charges. Important points to consider are the orientation of the multipole moments during the trajectory, conformational dependence of the atomic moments and stability of the simulations which are discussed here.


Radical resection of a pleomorphic carcinoma after relieving airway obstruction by the endobronchial snare method.
A 69-year-old man was hospitalized for fever and cough. He was diagnosed with and treated for an abscess in the left lower jaw and pneumonia by an otolaryngologist, but the pneumonia persisted with no improvement. Chest computed tomography revealed the presence of a heterogeneous torose lesion in the inlet of the left upper bronchus, and bronchoscopy revealed an endobronchial tumor with a smooth surface. An episode of sudden dyspnea occurred and was resolved after the patient changed his sitting position. We concluded that this symptom occurred because the tumor was incarcerated in the left lower lobe bronchus. The tumor was excised by bronchofi berscopic snare resection under tracheal intubation. It was found to be a pleomorphic carcinoma, and left upper lobectomy was performed. There has been no recurrence during the 3 years since the operation.


Campylobacter control in poultry by current intervention measures ineffective: urgent need for intensified fundamental research.
Campylobacter-contaminated poultry meat is an important source of foodborne gastroenteritis and poses a serious health burden in industrialized countries. Broiler chickens are commonly regarded as a natural host for this pathogen and infected birds carry a very high Campylobacter load in their gastrointestinal tract, especially the ceca. This results in contaminated carcasses during processing. While hygienic measures at the farm and control measures during carcass processing can have some effect on the reduction of Campylobacter numbers on the retail product, intervention at the farm level by reducing colonization of the ceca should be taken into account in the overall control policy. This review gives an up-to-date overview of suggested on-farm control measures to reduce the prevalence and colonization of Campylobacter in poultry.


The relationship between health care and nonhealth care norovirus outbreak settings and norovirus genotype in Victoria, Australia, 2002-2005.
There is evidence that norovirus genotype is an important factor in determining norovirus epidemiology, but detailed information is lacking. This report examined this question by studying whether the mix of norovirus genotypes associated with norovirus outbreaks in health care settings was different to that in nonhealth care settings. Norovirus outbreaks tested in Victoria, Australia, 2002-2005 were classified as either health care or nonhealth care. Open reading frame 1 nucleotide sequencing analysis was then used to determine the mix of norovirus genotypes in health care and nonhealth care norovirus outbreaks. For the three most common genotypes detected (GI.2, GII.4, and GIIb), the differences between health care and nonhealth care settings were significant. GII.4 was significantly more common in health care settings than in nonhealth care settings, whereas the genotypes GI.2 and GIIb were significantly more common in nonhealth care settings than in health care settings. Norovirus genotype was found to be an important factor associated with norovirus outbreak setting.


The effects of low intensity focused ultrasound on neuronal activity in pain processing regions in a rodent model of common peroneal nerve injury.
Non-invasive, external low intensity focused ultrasound (liFUS) offers promise for treating neuropathic pain when applied to the dorsal root ganglion (DRG). We examine how external liFUS treatment applied to the L5 DRG affects neuronal changes in single-unit activity from the primary somatosensory cortex (SI) and anterior cingulate cortex (ACC) in a common peroneal nerve injury (CPNI) rodent model. Male Sprague Dawley rats were divided into two cohorts: CPNI liFUS and CPNI sham liFUS. Baseline single-unit activity (SUA) recordings were taken 20 min prior to treatment and for 4 h post treatment in 20 min intervals, then analyzed for frequency and compared to baseline. Recordings from the SI and ACC were separated into pyramidal and interneurons based on waveform and principal component analysis. Following CPNI surgery, all rats (n = 30) displayed a significant increase in mechanical sensitivity. In CPNI liFUS rats, there was a significant increase in pyramidal neuron spike frequency in the SI region compared to the CPNI sham liFUS animals beginning at 120 min following liFUS treatment (p < 0.05). In the ACC, liFUS significantly attenuated interneuron firing beginning at 80 min after liFUS treatment (p < 0.05). We demonstrate that liFUS changed neuronal spiking in the SI and ACC regions 80 and 120 min after treatment, respectively, which may in part correlate with improved sensory thresholds. This may represent a mechanism of action how liFUS attenuates neuropathic pain. Understanding the impact of liFUS on pain circuits will help advance the use of liFUS as a non-invasive neuromodulation option.


Dynamics of an epidemic model with spatial diffusion.
Mathematical models are very useful in analyzing the spread and control of infectious diseases which can be used to predict the developing tendency of the infectious disease, determine the key factors and to seek the optimum strategies of disease control. As a result, we investigated the pattern dynamics of a spatial epidemic model with logistic growth. By using amplitude equation, we found that there were different types of stationary patterns including spotted, mixed, and stripe patterns, which mean that spatial motion of individuals can form high density of diseases. The obtained results can be extended in other related fields, such as vegetation patterns in ecosystems.


Myositis of the superior oblique muscle in a patient with suspected superior oblique muscle palsy.
Orbital myositis comprises a subtype of idiopathic orbital inflammation. Symptoms and clinical signs include orbital pain, eyelid swelling, ptosis, and conjunctival chemosis, sometimes concurrent with diplopia. Orbital myositis typically occurs in an idiopathic acute form and affects one or more extraocular muscles. It mainly involves the rectus muscles; cases involving the superior oblique muscle have been rarely reported. We report the case of a 57-year-old man with sudden-onset diplopia. Initial examination was suggestive of right superior oblique muscle palsy; however, myositis of the right superior oblique muscle was confirmed on magnetic resonance imaging (MRI). The patient was started on intravenous steroid pulse treatment. The steroid was tapered for 4 months. Diplopia, exotropia, and excyclotorsion of the right eye disappeared after 3 weeks of treatment. Cranial MRI obtained 2 months after starting treatment showed a normal superior oblique muscle. There has been no recurrence with 8 months of follow-up after completing the steroid taper.


Interactive associations of the INAFM2 rs67839313 variant and egg consumption with type 2 diabetes mellitus and fasting blood glucose in a Chinese population: A family-based study.
INAFM2 rs67839313 was associated with type 2 diabetes (T2DM) in Japanese populations but not in other populations. We aimed to validate the association of rs67839313 with T2DM and explore interactive associations of INAFM2 rs67839313 and egg consumption with T2DM and fasting blood glucose (FBG) in a Chinese population. In total, 7175 participants (4202 T2DM cases) from 3980 families were included and categorized into two groups (<4 and ≥4 eggs/week) according to the median egg consumption. Multilevel logistic regression and linear regression models were performed to estimate the genetic associations of rs67839313 with T2DM and FBG, respectively. The crossproduct term between the variant and egg was included in the models for interaction analysis. We found that rs67839313_T was associated with an increased risk of T2DM (1.22 [95% CI: 1.17-1.27], P < 0.001). Among individuals with the rs67839313_T genotype, those with egg consumption <4/week (1.37 [1.25-1.51]) had a higher T2DM risk than those with egg consumption ≥4/week (1.17 [1.11-1.23]). A significant interactive effect between rs67839313_T and egg consumption on T2DM risk was identified (P = 0.008). Moreover, among participants without T2DM, rs67839313_T was associated with FBG, with a 0.188 mmol/l increase and a 0.152 mmol/l decrease among those consuming <4 eggs/week and ≥4 eggs/week, respectively. The interaction between rs67839313_T and egg consumption was observed to be significantly associated with FBG (P = 0.003). INAFM2 rs67839313_T was associated with increased T2DM risk and FBG levels in Chinese individuals, and consuming more eggs may eliminate the associated genetic risk. This finding has important implications for understanding the genetic pathogenesis of T2DM and for the precision nutrition management of T2DM.


Evaluation of palate-related factors of the effectiveness of microimplant-assisted rapid palatal expansion in late adolescents and adults.
This study investigated the factors of the effectiveness of microimplant-assisted rapid palatal expansion (MARPE) in late adolescents and adults, such as age, midpalatal suture maturation (MPSM) stage, palate length (PL), palatal index (PI), and midpalatal bone thickness (MBT), and at each microimplant position, the palate bone thickness (PBT), the nasal cortical bone thickness (CoTN), the cancellous bone thickness (CaT), and the palate cortical bone thickness (CoTP) were evaluated. Cone-beam computed tomography (CBCT) images of 50 patients (mean, 23.30 ± 7.03 years; range, 16-51 years) treated with MARPE were evaluated. Maxillary expansion ratio (MER) was used to assess the MARPE effectiveness and grouped patients into low and high MER groups according to the mean of MER. MER was the ratio of maxillary expansion width to MARPE screw expansion measured in CBCT images. The t-test was used to analyze the differences between the low and high MER groups. The Pearson correlation test was performed to investigate the correlation between MER and age, MPSM stage, PL, PI, MBT, PBT, CoTN, CaT, and CoTP. Age, MPSM stage, and MBT in regions 18 mm and 21 mm behind the incisor foramen correlated negatively with MER ([Formula: see text], - 0.390, - 0.386, and - 0.335, respectively, all [Formula: see text]), whereas PBT and CoTN of anterior microimplant positions correlated positively with MER ([Formula: see text] and 0.418, respectively, all [Formula: see text]). No correlation was observed between other variables and MER. MARPE effectiveness decreased as age and midpalatal suture maturation stage increased, respectively. Thinner midpalatal suture bone in regions 18 mm and 21 mm behind the incisor foramen, thicker palate bone, and nasal cortical bone of anterior microimplant positions were related to more effective MARPE. In patients with older chronological age and later MPSM stages, MARPE effectiveness might be unsatisfactory. Clinicians should carefully evaluate the palate bone thickness before MARPE treatment.


Prevalence and incidence of chemotherapy-induced taste alterations in adult cancer patients: a systematic review protocol.
This study will synthesize the available evidence on the prevalence and incidence of chemotherapy-induced taste alterations in adult cancer patients. Taste and smell alterations in cancer patients due to chemotherapy affect patients' quality of life and can cause malnutrition. Recent knowledge about the incidence and prevalence of chemotherapy-induced taste alterations may enable tailored food interventions for this specific population. Describing variations in taste changes in subgroups of chemotherapy is important to inform taste steering interventions. The review will consider studies that include adult cancer patients who are receiving or have received chemotherapy as a treatment for an oncologic issue. It will include studies that investigate the prevalence and incidence of chemotherapy-induced taste alterations that have been assessed objectively or subjectively by patient-reported outcomes. A systematic search will be performed of the following databases: MEDLINE (PubMed), CINAHL (Ovid), Embase, and OpenSIGLE. Analytical, observational, and cross-sectional studies will be considered. All studies will undergo critical appraisal, data extraction, and synthesis. Data will be extracted using the JBI standardized data extraction tool for prevalence and incidence. Type and frequency of treatment and cytostatic agent will be extracted. The population will be described by age and gender. In addition, study methods and proportions of interest to the review question will be extracted. Pooled prevalence estimates will be calculated using a random effects model. PROSPERO CRD42020136706.


GFAP expression withdraws--a trend of glial evolution?
This study is a summary of investigations in the last decade with several collaborators on representatives of different vertebrate stocks. The results suggest that in the main vertebrate stocks (Agnathi, Chondrichthyes, Actinopterygii, Sarcopterygii-Amniotes), which had their parallel brain evolutions from the laminar brains to the elaborated ones, the astroglia also developed in parallel, and had a common trend of evolution. With growing brain complexity, free astrocytes arose and tended to predominate, and the spontaneous glial fibrillary acidic protein (GFAP)-expression regressed, in several areas. In the mammalian, avian, teleost, and batoid brains, therefore, large areas display a paucity, almost a lack of GFAP-immunoreactivity. The GFAP-expression in the GFAP-free areas seems to be inducible only in the presence of free astrocytes.


Performance characteristics of the boson rapid SARS-cov-2 antigen test card vs RT-PCR: Cross-reactivity and emerging variants.
SARS-CoV-2 virus has undergone several mutations on its genome, since the onset of the pandemic. Multiple variants of concern (VOC) have emerged including Alpha, Beta, Gamma, and Delta with the more recent one being the Omicron (B.1.1.529). Specific rapid antigen tests (RADs) have been used for the detection of SARS-CoV-2. However, since the emergence of new VOCs, the performance characteristics of these RADs needs to be re-evaluated. The main purposes of this clinical study were to determine the diagnostic sensitivity and specificity of the BOSON Rapid Antigen Test compared to the gold standard real time RT-PCR and to determine the ability of the RAD to accurately depict different VOC. Additionally, the cross reactivity to other viruses and pathogen, as well as, the possible interference of non Covid-19 hospitalized patients for various causes, were investigated. A total of 623 individuals (symptomatic) were tested. The sensitivity, specificity and accuracy of the BOSON RAD was 95.27%, 100% and 98.45% (n = 448), meeting the WHO recommended standards. Additionally, the Delta (83.33%, Ct < 34) and Omicron (100%, Ct < 26) VOC were determined with high sensitivity. Also, there was no interference from hospitalized, non-Covid 19 patients, and no cross-reactivity was detected. The study showed that this RAD could rapidly identify individuals with SARS-CoV-2, including those with the new dominant Omicron VOC, with no cross reactivity from other pathogens.


Age related changes in the characteristics of the near pupil response.
Static and dynamic aspects of the near pupil response were studied in human subjects in the age range when accommodative amplitude steadily declines. Dynamic accommodative and pupillary responses to step stimuli were recorded in 66 subjects (ages: 14-45 years). Exponential fits to data provided amplitude, peak velocity and time constants. Accommodative amplitude decreased linearly with age (p < 0.05). Pupil constriction per diopter of accommodative response increased exponentially with age (p < 0.05). The amplitude of pupil constriction for a 2D stimulus decreased linearly with age (p < 0.05) and for a 5D stimulus did not change with age (p = 0.90). The latency of pupil constriction did not change with age (p = 0.65), while the mean peak velocity decreased linearly with age (p < 0.05). An increase in the amount of pupil constriction per diopter of accommodative response, but not per diopter of stimulus amplitude, suggests that the near effort per se does not increase with age. There is a slight reduction in the speed of near pupil response with age.


Effect of photobiomodulation therapy on trunk flexor performance after incisional hernia repair: a randomized controlled trial.
To investigate the effect of two photobiomodulation approaches on trunk flexor performance after incisional hernia repair and to compare the effects of both wavelengths. Forty-five patients were randomly distributed after isokinetic trunk flexor assessments into infrared laser, red laser, and placebo groups. Each patient received laser treatment followed by a traditional physical therapy program. In laser treatment, 24 points in both recti were irradiated by infrared or red laser light with the following parameters; 0.6 J per point, 214.28 J/cm2 as energy density, and 17.85 W/cm2 as intensity, while the control group received a placebo approach. All groups received clinical treatments at a rate of 3 sessions per week for 4 weeks; in addition, the physical therapy program was continued on other days for all groups. Isokinetic trunk flexor strength was measured before treatment and 4 weeks after treatment as in each measurement, fatigue protocol was designed, and the trunk flexor strength was measured before fatigue test while the trunk flexor resistance to fatigue was measured after fatigue test. After 4 weeks, pre-and post-fatigue trunk flexor strengths in both laser groups were significantly increased compared to pre-and post-fatigue trunk flexor strength in the placebo group, respectively, and there was no significant difference between the two laser groups. Photobiomodulation approaches enhance trunk flexor response to exercise after incisional hernia repair. This enhancement leads to greater strength and more fatigue resistance for the trunk flexors in photobiomodulation groups compared to the placebo group and no difference between the two photobiomodulation effects.


The Projected Impact of Population-Wide Achievement of LDL Cholesterol <70 mg/dL on the Number of Recurrent Events Among US Adults with ASCVD.
Adults with atherosclerotic cardiovascular disease (ASCVD) are recommended high-intensity statins, with those at very high risk for recurrent events recommended adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor if their low-density lipoprotein cholesterol (LDL-C) is ≥70 mg/dL. We estimated the number of recurrent ASCVD events potentially averted if all adults in the United States (US) ≥45 years of age with ASCVD achieved an LDL-C <70 mg/dL. The number of US adults with ASCVD and LDL-C ≥70 mg/dL was estimated from the National Health and Nutrition Examination Survey 2009-2016 (n = 596). The 10-year cumulative incidence of recurrent ASCVD events was estimated from the REasons for Geographic And Racial Differences in Stroke study (n = 5390), weighted to the US population by age, race, and sex. The ASCVD risk reduction by achieving an LDL-C <70 mg/dL was estimated from meta-analyses of lipid-lowering treatment trials. Overall, 14.7 (95% CI, 13.7-15.8) million US adults had ASCVD, of whom 11.6 (95% CI, 10.6-12.5) million had LDL-C ≥70 mg/dL. The 10-year cumulative incidence of ASCVD events was 24.3% (95% CI, 23.2-25.6%). We projected that 2.823 (95% CI, 2.543-3.091) million ASCVD events would occur over 10 years among US adults with ASCVD and LDL-C ≥70 mg/dL. Overall, 0.634 (95% CI, 0.542-0.737) million ASCVD events could potentially be averted if all US adults with ASCVD achieved and maintained LDL-C <70 mg/dL. A substantial number of recurrent ASCVD events could be averted over 10 years if all US adults with ASCVD achieved, and maintained, an LDL-C <70 mg/dL.


Changes in neutral amino acid transport activity in myeloid leukemia cells differentiated by lipopolysaccharide.
M1 cells derived from mouse myeloid leukemia have been reported to differentiate to macrophage-like cells upon treatment with substances such as lipopolysaccharide. Previously we found that in mouse peritoneal macrophages most of the neutral amino acids were taken up through a unique Na+-independent system. In this paper we have investigated the neutral amino acid transport in M1 cells and in those treated with lipopolysaccharide. In M1 cells serine, alanine and proline were taken up mainly by Na+-dependent transport systems, and leucine was largely transported by a Na+-independent system. By treating the cells with lipopolysaccharide, the activities of the Na+-dependent systems markedly decreased, whereas the activity of the Na+-independent system was little affected. The amino acid concentrations in the cells and the culture medium were measured. As a whole, the intracellular to extracellular distribution ratios for neutral amino acids that are preferred substrates for Na+-dependent systems were decreased on lipopolysaccharide treatment, whereas those for amino acids that are mainly transported by a Na+-independent system were slightly increased. From these results we conclude that M1 cells treated with lipopolysaccharide tend to differentiate to macrophage-like cells with respect to the neutral amino acid transport.


How Skin Tone Influences Relationships Between Discrimination, Psychological Distress, and Self-Rated Mental Health Among Older African Americans.
As within-group differences have emerged as a key area of inquiry for health disparities among African Americans, skin tone has been identified as an important factor. This study aims to examine: (a) the moderating role of skin tone in the relationship between discrimination, self-rated mental health, and serious psychological distress (SPD) and (b) whether this moderating effect differs across genders in a nationally representative sample of older African Americans. Analyses were conducted on a subsample of African Americans aged 55+ (N = 837) from the National Survey of American Life. The mental health outcomes were SPD and self-rated mental health. Discrimination was assessed with the Everyday Discrimination Scale. Skin tone was self-reported. Multiple linear regressions tested the study aims. Discrimination was associated with worse self-rated mental health and SPD in the total sample and among women. Skin tone moderated the association between discrimination and SPD in the total sample and among men and women. The associations between discrimination and mental health outcomes were stronger among darker-skinned respondents than lighter respondents. Gender-stratified analyses indicated skin tone moderated the association between discrimination and self-rated mental health for men but not women. This study contributes to the emerging body of literature on skin tone, discrimination, and mental health. Uncovering mechanisms behind the "why" is an important next step in understanding how skin tone influences the relationship between discrimination and mental health. The negative psychological effects associated with darker complexion provide several areas to be examined.


Surgery-related gastrointestinal symptoms in a prospective study of bariatric surgery patients: 3-year follow-up.
Having accurate information on bariatric surgery-related gastrointestinal (GI) symptoms is critical for patient care. To report on surgery-related GI symptoms over the first 3 years following Roux-en-Y gastric bypass and laparoscopic adjustable gastric band. Three academic medical centers in the United States. As a substudy of the Longitudinal Assessment of Bariatric Surgery Consortium, 183 participants (pre-surgery median body mass index = 45.1 kg/m2; median age = 46 yr; 83.1% female). completed the Eating Disorder Examination-Bariatric Surgery Version interview at≥1 annual assessment. Patients self-reported frequency of dysphagia, dumping syndrome, and spontaneous vomiting. Prevalence of dysphagia at least once weekly decreased post-laparoscopic adjustable gastric band surgery from 43.9% (95% confidence interval [CI], 32.2-55.6) in year 1 to 27.5% (95% CI, 15.2-39.9) in year 3 (P = .02). Dysphagia and dumping at least once weekly also appeared to decrease in years 1-3 post-Roux-en-Y gastric bypass (i.e., from 16.7% [95% CI, 9.4-24.1] to 10.9% [95% CI, 4.0-17.8] and from 9.9% [95% CI, 4.3-15.5] to 6.3% [95% CI, 1.7-10.9], respectively), but power was limited to evaluate trends. Vomiting at least once weekly was rare (<6%) in years 1-3 following both procedures. Controlling for potential confounders and surgical procedure, loss of control eating at least once weekly was associated with higher risk of at least once weekly dysphagia (relative risk = 2.01, 95% CI, 1.36-2.99, P = .001). The prevalence of bariatric surgery-related GI symptoms appears to decrease across follow-up. Symptoms were associated with loss of control eating, suggesting a target for clinical intervention.


Structural basis for the association of PLEKHA7 with membrane-embedded phosphatidylinositol lipids.
PLEKHA7 (pleckstrin homology domain containing family A member 7) plays key roles in intracellular signaling, cytoskeletal organization, and cell adhesion, and is associated with multiple human cancers. The interactions of its pleckstrin homology (PH) domain with membrane phosphatidyl-inositol-phosphate (PIP) lipids are critical for proper cellular localization and function, but little is known about how PLEKHA7 and other PH domains interact with membrane-embedded PIPs. Here we describe the structural basis for recognition of membrane-bound PIPs by PLEHA7. Using X-ray crystallography, nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration calorimetry, we show that the interaction of PLEKHA7 with PIPs is multivalent, distinct from a discrete one-to-one interaction, and induces PIP clustering. Our findings reveal a central role of the membrane assembly in mediating protein-PIP association and provide a roadmap for understanding how the PH domain contributes to the signaling, adhesion, and nanoclustering functions of PLEKHA7.


Effect of ketoconazole on steroidogenic human granulosa-luteal cells in culture.
Ketoconazole (KCZ), a widely used antifungal drug, has been reported in humans to inhibit adrenal and testicular steroidogenesis by interfering with the cytochrome P-450-dependent enzymes. The purpose of this study was to investigate the drug effect on steroidogenic human granulosa-luteal cells, obtained by follicular aspiration from mature follicles of gonadotropin-treated women. Cells were cultured in long-term monolayers, and the steroid production was assayed by radioimmunoassay. A profound inhibition of ovarian cell secretion of progesterone (P), testosterone (T) and estradiol was found. At a low concentration (5 micrograms/ml), KCZ failed to inhibit the conversion of pregnenolone to P, mediated by the non-cytochrome 3 beta-hydroxysteroid dehydrogenase-isomerase enzyme (3 beta-HSDH). At a similar concentration, P secretion by human chorionic gonadotropin (hCG; 100 mIU/ml) -treated cells was decreased by 68% (P less than 0.001) and therefore, an inhibitory effect of KCZ on the cholesterol side-chain cleavage enzyme (P-450SCC) was assumed. A similar marked inhibitory effect (81%) (P less than 0.001) on T secretion was observed for hCG-stimulated cells given pregnenolone as substrate. The P-450 aromatase was profoundly inhibited (86%) (P less than 0.001) in a reversible manner, by a similar concentration (5 micrograms/ml) of KCZ. These findings suggest that KCZ has the capability to suppress human ovarian steroidogenesis similarly as in testis and adrenal.


HPLC-PDA identification and resolution of rufinamide forced degradation impurities: A congregated chemometric expedite optimization coupled with factorials and desirability.
Rufinamide is used presently to treat Lenaux-Gastaut syndrome. A full factorial design and desirability approach was investigated for the optimization of hydrolytic stress via response surface curves (RSCs). The degradation impurities were identified and resolved using reversed-phase high-performance liquid chromatography (RP-HPLC) on the Qualisil® BDS C8 column. Acetonitrile-water (29:71, v/v) was optimized for the mobile phase and used at a flow rate of 1.0 ml/min with detection at a wavelength of 230 nm. Rufinamide showed appreciable susceptibility to hydrolysis under acidic and alkaline stress, and substantial degradation in the neutral condition. It degraded much less under oxidative stress. Exposure towards thermal and photolytic stress conditions indicated appreciable stability. The developed method was subjected to validation as per the recommendations of the International Conference on Harmonization. The proposed method showed no influence from the excipients and the degradation products. As well as good precision and accuracy in determination, the method showed a linear response between 2 and 12 μg ml-1 . The method was extended for determination in a human plasma sample, which resulted in excellent recovery without interference from matrix effects. The combined use of desirability and design for the optimization of acidic and alkaline hydrolytic stress led to simple and rapid analysis.


Activation of protein kinase C by phorbol esters induces DNA synthesis and protein phosphorylations in glomerular mesangial cells.
The tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) is shown to be mitogenic for quiescent glomerular mesangial cells cultured in serum-free conditions. TPA induces DNA synthesis measured by [3H]thymidine incorporation in a dose-dependent manner with an ED50 of 7 ng/ml and an optimal response for 50 ng/ml. The phorbol ester action is potentiated by insulin with an increase of the maximal effect from 232 +/- 15% for TPA alone to 393 +/- 96% for TPA plus insulin. Down-regulation of protein kinase C by prolonged exposure to TPA completely abolishes the mitogenic effect of the phorbol ester. Using a highly resolutive 2D electrophoresis, we have shown that TPA is able to stimulate the phosphorylation of 2 major proteins of Mr 80,000, pl 4.5 (termed 80K) and Mr 28,000, pI 5.7-5.9 (termed 28K). The 80K protein phosphorylation is time- and dose-dependent with an ED50 of 8 ng/ml TPA. Exposure of mesangial cells to heat-shock induces synthesis of a 28K protein among a set of other proteins suggesting that the 28K protein kinase C substrate belongs to the family of low molecular mass stress proteins. Mitogenic concentrations of TPA and phorbol 12,13-dibutyrate inhibit [125 I]epidermal growth factor binding and stimulate the 80K protein phosphorylation with the same order of potency. The inactive tumor-promoter 4 alpha-phorbol was found to be ineffective both on these 2 parameters and on DNA synthesis. These results suggest a positive role for protein kinase C on mesangial cell proliferation and indicate the existence in this cell line of 2 major protein kinase C substrates.


A volunteer-populated online database provides evidence for a geographic pattern in symptoms of black spot infections.
Infections of parasitic digenean trematode metacercariae may lead to a visually observable syndrome in fish commonly called black spot disease. While black spot has been noted from various locations throughout North America, patterns in prevalence across the continent remain unknown. Funding to investigate continental-wide prevalence of low-mortality parasitic infections represents a barrier to such studies. I utilize iNaturalist.org's photograph database to examine fish for signs of black spot infections across North America. Fish targeted include blacknose dace, creek chub, chubs (Nocomis spp.), and stonerollers (Campostoma spp.). Photos were visually examined for symptomatic black spots indicative of infection by trematode species linked to black spot disease. Regardless of fish species group, symptoms of black spot pathogens were highly prevalent (27.1% of 314 fish) in watersheds of southern Ontario Canada, whereas mean prevalence was comparatively low elsewhere (7.8%). In one instance, a user uploaded a higher number of photos, with a higher percentage exhibiting signs of infection than other users in the watershed. However, it is difficult to tease apart if that user fished in waterbodies with high infection rates, uploaded more photos of symptomatic fishes, or some other explanation for the differences in user-reported fish with symptoms. Beyond this exception, geographic patterns in the frequency of black spot symptoms do not appear to be related to solely the users, suggesting the observed pattern is biological or ecological. While causative explanations remain conjectures, the data reported herein provides evidence that across four groups of fish, signs of black spot infections are more common in southern Ontario than other areas studied in North America. This work also represents an initial and unexpected utility of volunteer-population databases such as iNaturalist. Further data contributions could lead to better understanding of the causative agents to variation in black spot pathogens' occurrences.


Exploratory adaptation in large random networks.
The capacity of cells and organisms to respond to challenging conditions in a repeatable manner is limited by a finite repertoire of pre-evolved adaptive responses. Beyond this capacity, cells can use exploratory dynamics to cope with a much broader array of conditions. However, the process of adaptation by exploratory dynamics within the lifetime of a cell is not well understood. Here we demonstrate the feasibility of exploratory adaptation in a high-dimensional network model of gene regulation. Exploration is initiated by failure to comply with a constraint and is implemented by random sampling of network configurations. It ceases if and when the network reaches a stable state satisfying the constraint. We find that successful convergence (adaptation) in high dimensions requires outgoing network hubs and is enhanced by their auto-regulation. The ability of these empirically validated features of gene regulatory networks to support exploratory adaptation without fine-tuning, makes it plausible for biological implementation.


The glutathione-dependent glyoxalase pathway in the yeast Saccharomyces cerevisiae.
Glyoxalase I (EC 184.108.40.206), which catalyzes the reaction methylglyoxal + GSH leads to S-lactoylglutathione, is a ubiquitous enzyme for which no clear physiological function has been shown. In the yeast Saccharomyces cerevisiae, methylglyoxal may derive from the spontaneous decay of intracellular glyceraldehyde-3-P, which may accumulate during growth on glycerol as the carbon source. The half-life time for the triose phosphate was found to be 4.6 h under physiological conditions (pH 6.2, 0.05 M phosphate at 30 degrees C). Glyoxalase I is induced by growth on glycerol or by the addition of methylglyoxal to the growth medium. The enzyme is also subject to carbon catabolite repression. A mutant strain, fully defective in glyoxalase I and bearing only one nuclear mutation, was obtained. The strain, which is killed by exposure to glycerol, excretes methylglyoxal into the medium. Growth of the mutant on glucose as carbon source appears to be similar to that of the wild type strain. This investigation has clearly demonstrated a physiological role of glyoxalase I in a eucaryotic cell.


Update on the epidemiology of work-related traumatic brain injury: a systematic review and meta-analysis.
Traumatic brain injury (TBI) is a public health concern that can occur in a range of contexts. Work-related TBI (wrTBI) is particularly concerning. Despite overall work-related injury claims decreasing, the proportion of claims that are wrTBI have increased, suggesting prevention and support of wrTBI requires ongoing attention. This review aimed to provide updated information on the burden and risk factors of wrTBI among the working adult population. Medline, Embase, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched using a combination of TBI, work, and epidemiology text words and medical subject headings. Two reviewers independently assessed articles for inclusion. Meta-analyses were conducted to estimate prevalence and mortality of wrTBI and a narrative synthesis was conducted to provide additional context. Pooled proportions meta-analyses estimate that 17.9% of TBIs were work-related and 6.3% of work-related injuries resulted in TBI, with 3.6% of wrTBI resulting in death. Populations of wrTBI were predominantly male (76.2%) and were 40.4 years of age, on average. The most commonly reported industries for wrTBI were education and training, healthcare and social assistance, construction, manufacturing, and transportation. Falls, being struck by an object or person, motor vehicle collisions, and assaults were the most commonly reported mechanisms of wrTBI. A better understanding of the epidemiology of wrTBI can inform prevention and management strategies. This review highlights existing gaps, including a notable lack of sex or gender stratified data, to direct future investigation. CRD42020169642.


Identification of conjugated linoleic acid elongation and beta-oxidation products by coupled silver-ion HPLC APPI-MS.
Atmospheric pressure photoionisation (APPI) was used in combination with silver-ion (Ag(+))-HPLC for detection of (conjugated) fatty acid methyl esters (FAME) by tandem-mass spectrometry. APPI-MS of methyl esters of conjugated linoleic acid showed an increase in signal-to-noise ratio by a factor of 40 compared to atmospheric pressure chemical ionization in the positive mode. It was possible to identify double bond position, configuration and chain length of FAME based on chromatographic separation and mass detection. The developed LC-MS method is useful for the analysis of CLA elongation and beta-oxidation products, especially with trans,trans-configuration, which are difficult to analyze by conventional GC-MS techniques.


Asymmetric synthesis of polyfunctionalized pyrrolidines from sulfinimine-derived pyrrolidine 2-phosphonates. Synthesis of pyrrolidine 225C.
[reaction: see text] The Horner-Wadsworth-Emmons reaction of aldehydes with sulfinimine-derived 3-oxo pyrrolidine phosphonates represents a new method for the asymmetric synthesis of ring-functionalized cis-2,5-disubstituted 3-oxo pyrrolidines.


Safety and feasibility of same-day discharge after esophageal endoscopic submucosal dissection.
Endoscopic submucosal dissection (ESD) is used for treating early luminal GI cancers. ESD is the standard of care in Asia, where it results in multiday admissions for observation. The goal of our study was to evaluate the safety and feasibility of same-day discharge (SDD) after ESD. This is a retrospective cohort study of adults who underwent similar esophageal ESD with a Clutch Cutter device (DP2618DT; Fujifilm) at the Mayo Clinic (Rochester, Minn, USA) from 2017 to 2019 with a single endoscopist. The primary end point was postprocedural adverse events within 7 days of ESD. Of 96 patients (75% male, mean age, 70 ± 10.3 years) undergoing a total of 140 ESDs, 85 were SDD versus 55 admissions. Of the 55 admits, 53 were discharged within 24 hours, whereas 2 were admitted for 2 to 3 days for reasons unrelated to the ESD procedure. Admissions were more likely to have a history of antiplatelet/anticoagulant use (56.4% vs 34.1%; P = .01) and higher mean American Society of Anesthesiologists (ASA) score (3.2 vs 2.9; P = .007). Admissions had larger resections (28.6 vs 20.1 mm; P < .0001) with longer procedural durations (103.4 vs 62 minutes; P < .0001). Among SDDs, no intraprocedural or postprocedural adverse events were seen. Among admissions, 1 (1.8% vs 0%; P = .39) experienced intraprocedural bleeding requiring endoscopic intervention, 1 required transfusion before discharge within 24 hours of ESD (1.8% vs 0%; P = .39), and 1 required rehospitalization and endoscopic intervention within 7 days to address an active bleed along the resection margin (1.8% vs 0%; P = .39). SDD after esophageal ESD is safe and feasible. An experienced endoscopist can determine if SDD can be considered in patients with ASA physical classification status ≤2 who undergo resections off antiplatelet/anticoagulant therapy and do not experience intraprocedural adverse events.