Bioactive lipids as modulators of immune check point inhibitors.
It is proposed that arachidonic acid (AA, 20:4 n-6) and other polyunsaturated fatty acids (PUFAs) in combination with immune check point inhibitors and tumor infiltrating lymphocytes (TILs) enhances the activity of T and NK cells and macrophages and thus, aids in the elimination of tumor cells and suppresses inflammatory side effects due to immune check point inhibitors.


A novel electrochemiluminescence strategy for ultrasensitive DNA assay using luminol functionalized gold nanoparticles multi-labeling and amplification of gold nanoparticles and biotin-streptavidin system.
Luminol functionalized gold nanoparticles were used as labels for electrochemiluminescence signal amplification and an ultrasensitive, highly selective, convenient, low cost DNA detection strategy was developed.


Presence of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 24-hydroxylase in vitamin D target cells of rat yolk sac.
In the pregnant rat, the yolk sac, which possesses true placental functions, is a vitamin D target organ. We tested its ability to hydroxylate 25-hydroxy- and 1,25-dihydroxyvitamin D3 (25-OHD3 and 1,25-(OH)2D3). 24,25-Dihydroxy- and 1,24,25-trihydroxyvitamin D3 were produced by rat yolk sac homogenates incubated with tritiated 25-OHD3 and 1,25-(OH)2D3. Rat yolk sac homogenates also formed small amounts of 25,26-dihydroxyvitamin D3. These newly synthesized metabolites were isolated and identified by Sephadex LH-20 chromatography, high performance liquid chromatography, and periodate cleavage. Yolk sac 25-OHD3- and 1,25-(OH)2D3-24-hydroxylases were present in mitochondria and were of a mixed function oxidase nature. They were detected in the yolk sac as early as day 12 in the embryonic period and until the end of gestation. No hydroxylation occurred in maternal liver, amnion, fetal brain, or skin homogenates. Both 24-hydroxylases were detected in pure isolated rat yolk sac endodermal cells. This may be of physiological importance, since they are the 1,25-(OH)2D3 target cells in the yolk sac. Injection of 1,25-(OH)2[3H]D3 into rat yolk sac vitelline veins strongly suggested that the yolk sac vitelline veins strongly suggested that the yolk sac produced 1,24,25-(OH)3D3 in vivo. We conclude that the yolk sac and more precisely its endodermal cells may help to control vitamin D metabolism within the fetoplacental unit.


Establishment and characterization of a new human first trimester Trophoblast cell line, AL07.
The limited cell number of primary trophoblasts and contamination of trophoblast cell lines promote us to develop a novel stable trophoblast cell line. Primary trophoblast cells were isolated from first-trimester placenta and telomerase-induced immortalization was used to immortalize these cells. Subsets of cells were then evaluated by flow cytometry using CK7, HLA-G, CD45 and CD14, specific markers for trophoblast cells, extra-villous trophoblast, pan leucocyte and monocyte/macrophage, respectively. Immunofluorescence staining and immunocytochemistry were used to detect CK7 expression in trophoblast cells. The level of secreted human Chorionic Gonadotropin (hCG) was measured by electrochemiluminescence (ECL). The Bio-Plex MAGPIX System was used to analyze the cytokines and chemokines produced by AL07 cell line. We were able to isolate primary trophoblast cells from several first-trimester placentas. One clone, AL07 trophoblast cells, isolated from a week 7 placenta, was morphologically stable and positive for the expression of CK7 by immunofluorescence and immunocytochemistry staining. Characterization of AL07 cells reveled that they are CD45 or CD14 negative and had constitutive secretion of hCG and low HLA-G expression. Furthermore, clone AL07 secret high levels of several cytokines and chemokines, including IL-6, IL-8 and VEGF, and moderately secreted MCP-1 IP-10 and RANTES. We report the successful isolation, immortalization and characterization of AL07 cells, a novel cell clone isolated from first trimester human placenta. The clone is free of contamination of immune cells, and exhibits similar cytokine profile as other trophoblast cell lines. This new cytotrophoblast-like AL07 cell, can be a valuable tool for in-vitro trophoblast studies in the future.


Esterase D phenotypes in North-eastern Japan.
Esterase D (EsD) was typed in 2,367 unrelated healthy blood donors from Yamagata and Miyagi districts, north-eastern area of Japan. The gene frequencies observed were: EsD1 = 0.642, EsD2 = 0.358. In these blood donors two rare EsD phenotypes, EsD 3-2 and a new variant, were found. As for this new variant, the mode of hereditary transmission was discussed by family study.


Purification, properties, and characterization of recombinant Streptomyces sp. strain C5 DoxA, a cytochrome P-450 catalyzing multiple steps in doxorubicin biosynthesis.
DoxA is a cytochrome P-450 monooxygenase involved in the late stages of daunorubicin and doxorubicin biosynthesis that has a broad substrate specificity for anthracycline glycone substrates. Recombinant DoxA was purified to homogeneity from Streptomyces lividans transformed with a plasmid containing the Streptomyces sp. strain C5 doxA gene under the control of the strong SnpR-activated snpA promoter. The purified enzyme was a monomeric, soluble protein with an apparent Mr of 47,000. Purified DoxA catalyzed the 13-hydroxylation of 13-deoxydaunorubicin, the 13-oxidation of 13-dihydrocarminomycin and 13-dihydrodaunorubicin, and the 14-hydroxylation of daunorubicin. The pH optimum for heme activation was pH 7.5, and the temperature optimum was 30 degreesC. The kcat/Km values for the oxidation of anthracycline substrates by purified DoxA, incubated with appropriate electron-donating components, were as follows: for 13-deoxydaunorubicin, 22,000 M-1 x s-1; for 13-dihydrodaunorubicin, 14,000 M-1 x s-1; for 13-dihydrocarminomycin, 280 M-1 x s-1; and for daunorubicin, 130 M-1 x s-1. Our results indicate that the conversion of daunorubicin to doxorubicin by this enzyme is not a favored reaction and that the main anthracycline flux through the late steps of the daunorubicin biosynthetic pathway catalyzed by DoxA is likely directed through the 4-O-methyl series of anthracyclines.


Ozone and other air pollutants and the risk of oral clefts.
Air pollution influences the development of oral clefts in animals. There are few epidemiologic data on the relation of prenatal air pollution exposure and the risk of oral clefts. Our goal in this study was to assess the relations between exposure to ambient air pollution and the risk of cleft lip with or without cleft palate (CL/P). We conducted a population-based case-control study of all 653 cases of CL/P and a random sample of 6,530 control subjects from 721,289 Taiwanese newborns in 2001-2003. We used geographic information systems to form exposure parameters for sulfur dioxide, nitrogen oxides, ozone, carbon monoxide, and particulate matter with an aerodynamic diameter <or= 10 microm (PM10) during the first 3 months of pregnancy using inverse distance weighting method. We present the effect estimates as odds ratios (ORs) per 10-ppb change for SO2, NO(x), and O3, 100-ppb change for CO, and 10-microg/m3 change for PM10. The risk of CL/P was increased in relation to O3 levels in the first gestational month [adjusted OR = 1.20; 95% confidence interval (CI), 1.02-1.39] and second gestational month (adjusted OR = 1.25; 95% CI, 1.03-1.52) in the range from 16.7 ppb to 45.1 ppb, but was not related to CO, NO(x), SO2, or PM10. The study provides new evidence that exposure to outdoor air O3 during the first and second month of pregnancy may increase the risk of CL/P. Similar levels of O3 are encountered globally by large numbers of pregnant women.


Post-partum evaluation of maternal cardiac function after severe preeclampsia.
To evaluate the post-partum maternal cardiac function in patients with history of severe preeclampsia. A series of women with previous singleton pregnancy complicated by severe preeclampsia underwent transthoracic echocardiography at 6-12 months from delivery. A group of women with previous uncomplicated pregnancy was selected as controls. Sixteen women with history of severe preeclampsia were enrolled in the study group whereas 18 patients were selected as controls. In the study group systolic (p=0.002) and diastolic blood pressure (p=0.044) were significantly higher. Significant differences were observed in systolic left ventricular (LV) parameters, such as cardiac output (p=0.034), LV mass indexed to BSA (p=0.024) and longitudinal contraction, expressed by tissue Doppler (TD) S1 wave, which resulted relatively impaired in former preeclamptic women (p=0.049). As regards as diastolic parameters, pulsed Doppler A-wave velocity was increased (p=0.036). TD E-wave velocity was significantly lower in study group (p<0.001) and E/E1 ratio (E=peak early diastole transmitral wave velocity/E1=peak early diastolic velocity at mitral valve annulus at TD) was higher respect to controls (p<0.001). LV contractility and diastolic function, although within normal reference ranges, show slight but significant impairment among women who experienced a severe preeclampsia. TD seems to be a sensible tool to identify these precocious signs of potential LV dysfunction.


Validation of the pain sensitivity questionnaire in chronic pain patients.
Recently, a self-rating measure for pain perception based on imagined painful daily life situations, the Pain Sensitivity Questionnaire (PSQ), has been developed and shown to correlate with experimentally obtained pain intensity ratings in healthy subjects. Here, we assessed the validity of the PSQ for investigation of general pain perception (ie, pain perception outside the site of clinical pain) in chronic pain patients. PSQ scores were obtained in 134 chronic pain patients and compared to those of 185 healthy control subjects. In a subgroup of 46 chronic pain patients, we performed experimental pain testing outside the clinical pain site, including different modalities (heat, cold, pressure, and pinprick) and different measures (pain thresholds, pain intensity ratings). Results show that PSQ scores were significantly correlated with both experimental pain intensity ratings (Pearson's r=0.71, P<.001) and experimental pain thresholds (r=-0.52, P<.001). In addition, chronic pain patients exhibited significantly elevated PSQ scores as compared to healthy controls, consistent with the generalized increase of experimentally determined pain perception that has repeatedly been reported in chronic pain patients. These results demonstrate that the PSQ constitutes a valid self-rating measure of pain perception outside the clinical pain site in chronic pain patients and might serve as an alternative to experimental assessment of pain perception outside the clinical pain site in situations where experimental pain testing is not feasible.


A comparison of two different T-grain films in rare-earth screens with a standard film-screen combination for intravenous pyelography and bone examinations.
T-grain film is claimed to give significantly improved image quality, allowing the use of faster screens without loss of quality and thus reducing radiation dose. We tested this claim for two systems. In each case comparison was made with our usual screen-film combination, Agfa Curix RP1 film with Kodak Xomatic Regular screens (a nominally 200 speed system). The systems tested were Kodak TMatG in Kodak Lanex Medium screens (300 speed) and Agfa STG in Kodak Lanex Regular screens (400 speed). The Agfa STG-Lanex Regular system performed less well than the standard system for intravenous pyelograms (IVPs), bones and soft-tissue detail. Its speed advantage was not apparent below 70 kV. The Kodak TMatG-Lanex Medium system was better than the standard system for IVPs but not as good for bones. It gave virtually no speed advantage below 90 kV. Kodak T-grain film in a medium-speed, rare-earth screen was found to be better than the standard system for IVPs. Agfa T-grain film in a fast rare-earth screen was unsatisfactory for IVPs. Neither combination was as good as the standard system for bones.


The Effect of CDK6 Expression on DNA Methylation and DNMT3B Regulation.
CDK6 is frequently overexpressed in various cancer types and functions as a positive regulator of the cell cycle and as a coregulator of gene transcription. We provide evidence that CDK6 is involved in the process of DNA methylation, at least in ALL. We observe a positive correlation of CDK6 and DNMT expression in a large number of ALL samples. ChIP-seq analysis reveals CDK6 binding to genomic regions associated with DNA methyltransferases (DNMTs). ATAC-seq shows a strong reduction in chromatin accessibility for DNMT3B in CDK6-deficient BCR-ABL + Cdk6-/- cells, accompanied by lower levels of DNMT3B mRNA and less chromatin-bound DNMT3B, as shown by RNA-seq and chromatome analysis. Motif analysis suggests that ETS family members interact with CDK6 to regulate DNMT3B. Reduced representation bisulfite sequencing analysis uncovers reversible and cell line-specific changes in DNA methylation patterns upon CDK6 loss. The results reveal a function of CDK6 as a regulator of DNA methylation in transformed cells.


A Bonferroni mean considering Shapley fuzzy measure under hesitant bipolar-valued neutrosophic set environment for an investment decision.
Bonferroni mean (BM) operators have been established as a powerful tool for handling the interrelationship between the input arguments under various decision-making information. However, the existing BM operators do not take into account the overall interaction among decision makers or criteria. To overcome this limitation, this study considers the Shapley fuzzy measure (SFM) with the normalized weighted BM (NWBM) operator under a neutrosophic environment. In addition, the current research ignores the bipolarity and hesitancy during decision elicitations, resulting in the imprecise decision results. In this paper, the hesitant bipolar-valued neutrosophic set (HBNS) which is the extension of hesitant fuzzy set and bipolar neutrosophic set is employed. The main focus of this paper is in the development of an aggregation operator for HBNS. Based on the literature review, we would like to fill in the gaps by developing a hesitant bipolar-valued neutrosophic Shapley NWBM (HBN-SNWBM) operator where the overall interaction among decision makers can be considered. Besides that, a three-phase decision making framework is also proposed to show the applicability of the proposed aggregation operator to the real-world decision problems. The HBN-SNWBM operator and the decision making framework are applied to two examples of investment selection where evaluations are implemented using the proposed aggregations that based upon hesitant bipolar-valued neutrosophic sets. In the first example, it is found that a weapon company is the best alternative for investment followed by a food company. Sensitivity of parameters of the aggregation operator is also analysed and it is found that the ranking results are consistent despite of different parameter values used. This verifies the insensitivity of p,q parameters in the developed aggregation operator. The proposed decision making framework and hesitant bipolar-valued neutrosophic sets would be a great significance for the practical implementation of the aggregation operators.


Health information seeking and the World Wide Web: an uncertainty management perspective.
Uncertainty management theory was applied in the present study to offer one theoretical explanation for how individuals use the World Wide Web to acquire health information and to help better understand the implications of the Web for information seeking. The diversity of information sources available on the Web and potential to exert some control over the depth and breadth of one's information-acquisition effort is argued to facilitate uncertainty management. A total of 538 respondents completed a questionnaire about their uncertainty related to cancer prevention and information-seeking behavior. Consistent with study predictions, use of the Web for information seeking interacted with respondents' desired level of uncertainty to predict their actual level of uncertainty about cancer prevention. The results offer evidence that respondents who used the Web to search for cancer information were better able than were respondents who did not seek information to achieve a level of uncertainty commensurate with the level of uncertainty they desired.


Effects of axial compression and rotation angle on torsional mechanical properties of bovine caudal discs.
The intervertebral disc is a complex joint that acts to support and transfer large multidirectional loads, including combinations of compression, tension, bending, and torsion. Direct comparison of disc torsion mechanics across studies has been difficult, due to differences in loading protocols. In particular, the lack of information on the combined effect of multiple parameters, including axial compressive preload and rotation angle, makes it difficult to discern whether disc torsion mechanics are sensitive to the variables used in the test protocol. Thus, the objective of this study was to evaluate compression-torsion mechanical behavior of healthy discs under a wide range of rotation angles. Bovine caudal discs were tested under a range of compressive preloads (150, 300, 600, and 900N) and rotation angles (± 1, 2, 3, 4, or 5°) applied at a rate of 0.5°/s. Torque-rotation data were used to characterize shape changes in the hysteresis loop and to calculate disc torsion mechanics. Torsional mechanical properties were described using multivariate regression models. The rate of change in torsional mechanical properties with compression depended on the maximum rotation angle applied, indicating a strong interaction between compressive stress and maximum rotation angle. The regression models reported here can be used to predict disc torsion mechanics under axial compression for a given disc geometry, compressive preload, and rotation angle.


[Personal care and its taboos in nurse training manuals].
At first, not easy to name, the body and its different dimensions gradually found their place in nurse training manuals in the 20th century, conveying a radical change with regard to the place of the body in the nurse-patient relationship. This article looks back at the historical evolution of a key aspect of care.


In vitro culturing of porcine tracheal mucosa as an ideal model for investigating the influence of drugs on human respiratory mucosa.
It has been previously shown that fresh mucosa from different mammals could serve as raw material for in vitro culturing with the differentiation of cilia, which are the most important morphological structures for the function of the mucociliary system. Increasing legal restrictions on the removal of human tissue and changing surgical techniques have led to a lack of fresh human mucosa for culturing. Most of the animals that have been used as donors up to now are genetically not very close to human beings and must all be sacrificed for such studies. We, therefore, established a modified system of culturing mucosa cells from the trachea of pigs, which is available as a regular by-product after slaughtering. With respect to the possibility of developing "beating" cilia, it could be shown that the speed of cell proliferation until adhesion to the coated culture dishes, the formation of conjunctions of cell clusters and the proliferation of cilia were comparable for porcine and human mucosa. Moreover, it could be demonstrated that the porcine cilia beat frequency of 7.57 +/- 1.39 Hz was comparable to the human mucosa cells beat frequency of 7.3 +/- 1.4 Hz and that this beat frequency was absolutely constant over the investigation time of 360 min. In order to prove whether the reaction to different drugs is comparable between the porcine and human cilia, we initially tested benzalkonium chloride, which is known to be toxic for human cells, followed by naphazoline, which we found in previous studies on human mucosa to be non-toxic. The results clearly showed that the functional and morphological reactions of the porcine ciliated cells to these substances were similar to the reaction we found in the in vitro cultured human mucosa.


Sex difference in the repolarization currents of rabbit ventricular cells.
The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, Ito, IK,tail, IK1 and ICa,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD90 was longer in female rabbits (560.4+/-26.5 ms, n=15) than in male ones (489.0+/-20.7 ms, n = 14), P<0. 05. In female rabbit myocytes, IKtail, Ito, IK1 and ICa,L were 0.71+/-0.05 pA/pF (n=17), 8.28+/-1.03 pA/pF (n=18), 24.5+/-3.6 pA/pF (n=12) and 9.0+/-2.3 pA/pF (n=15) respectively. In male rabbit myocytes, they were 0.84+/-0.07 pA/pF (n=18), 8.60+/-1.20 pA/pF (n=18), 25.9+/-4.5 pA/pF (n=14) and 9.3+2.6 pA/pF (n=16) respectively. IK,tail in female rabbits was significantly lower than that of male rabbits (P<0.05), but there was no difference in Ito,IK1 and ICa.L between male rabbits and female rabbits (P>0.05). The lower IK.tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.


Suppression of basal and Corynebacterium parvum-augmented NK activity during chemically induced tumor development.
C3H mice were injected subcutaneously (s.c.) with a tumorigenic dose (150 micrograms/mouse) of 3-methylcholanthrene (MC), followed by a 24-h injection and subsequent weekly injections of Corynebacterium parvum (CP) i.p. for a total of 100 days. Basal and CP-augmented NK cell activities were measured in controls and treatment groups during pre-tumor and tumor development stages. Basal NK activity in spleen, peripheral blood and lung tissue was enhanced by CP, but was suppressed by MC. A resulting transient MC induced suppression of splenic NK activity at 10 days was partially restored and sustained by CP treatment and immunosuppression was again observed in tumor-bearing compared to control mice. Mice treated with MC alone showed a higher tumor incidence than animals treated with MC + CP at 45-60 days, while there was no difference in tumor incidence in these two treatment groups at 100 days post injection. The mechanism of the observed transient immunosuppression induced by MC appears to be related to an early toxic effect on large granular lymphocytes (LGL) which was decreased at 10 days and again at 100 days in tumor-bearing mice. Although MC did not appear to exert an effect on effector:target cell conjugate formation, an early suppression in the lytic activity of LGL, may have predisposed the animal to malignant transformation of susceptible cells at the site of MC injection.


Pilot study of focused ultrasound for drug-resistant epilepsy.
The neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal epilepsy models; however, the safety and efficacy of FUS in humans with epilepsy have not been well established. Patients with drug-resistant epilepsy (DRE) undergoing stereo-electroencephalography (SEEG) provide an opportunity to investigate the neuromodulatory effects of FUS in humans. Patients with DRE undergoing SEEG for localization of the seizure onset zone (SOZ) were prospectively enrolled. FUS was delivered to the SOZ using a neuronavigation-guided FUS system (ceiling spatial-peak temporal-average intensity level = 2.8 W/cm2 , duty cycle = 30%, modulating duration = 10 min). Simultaneous SEEG recordings were obtained during sonication and for 3 days after treatment. Seizures, interictal epileptiform discharges, and adverse events after FUS were monitored. Six patients met the eligibility criteria and completed FUS treatment. A decrease in seizure frequency was observed in two patients within the 3-day follow-up; however, one patient presented an increase in the frequency of subclinical seizures. Posttreatment magnetic resonance imaging revealed neither lesion nor brain edema. Significant changes in spectral power of SEEG were noted at the targeted electrodes during FUS treatment. One patient reported subjective scalp heating during FUS, and one patient developed transient naming and memory impairment that resolved within 3 weeks after FUS. FUS can be safely delivered to the SOZ of patients with DRE, resulting in significant changes in spectral power of SEEG. A larger sample cohort and pursuing optimal sonication parameters will be required to elucidate the neuromodulatory effects of FUS when used for seizure control.


Surgical therapy for dilated cardiomyopathy.
As the next millennium approaches, excitement and promise characterize the future of dilated cardiomyopathy. Until recently, dilated cardiomyopathy was considered an incurable, uniformly fatal chronic disease. Epidemiologic studies have demonstrated that at least a quarter of patients with recent onset of symptoms with cardiomyopathy manifest spontaneous improvement and a sustained favorable prognosis. It is imperative that patients who present with new-onset cardiomyopathy be managed medically and closely followed. Medical treatment remains the foundation of therapy, and certainly the advent of beta-blocker use may herald further benefit beyond that observed with conventional therapy (ACE inhibitors and digoxin). Unless mechanical support is required for hemodynamic instability and end organ failure, patients should be treated medically and observed. As discussed earlier, transient mechanical support as a bridge to recovery should be considered in the appropriate clinical scenario before committing to cardiac transplantation. Patients with established disease who have been followed for extended periods (> 6 months) that have progressive symptoms despite optimal medical therapy should be considered for surgical therapies. Cardiac transplantation is available to only a minority of the diseased population. All newer modalities of surgical unloading therapy theoretically reduce wall stress. Clearly in dilated cardiomyopathy, ventricular performance is reduced; however, individual myocyte contractile function may be intact. Studies of isolated myocytes (which are unloaded) have yielded conflicting data; however, if contractile function is intact and performance is reduced primarily secondary to abnormal loading conditions, surgical unloading therapies should yield benefit. Hence the thesis of Batista that geometric alteration will improve performance assumes intrinsic integrity of the myocyte contractile function. The implication of intrinsic myocyte contractile dysfunction is that surgical remodeling does not yield improved ventricular performance. Although clinicians have learned that selection criteria appear to play a role in predicting beneficial outcomes with cardiomyoplasty and the Batista procedure, clinical techniques to assess the integrity of myocyte function are unsophisticated. Quantifying interstitial fibrosis, assays for the degree of apoptosis, and various immunologic measures currently do not provide the insight necessary to predict outcomes reliably. The future assessment of dilated cardiomyopathy and the decision to consider alternative surgical procedures versus cardiac transplantation will likely be determined by biomolecular studies. At present, these new surgical procedures are promising therapies and potential alternatives to cardiac transplantation. Controlled studies to determine the clinical and survival benefit compared with medical therapy will ultimately be required, after the surgical techniques and patient selection criteria are refined. Randomized, prospective controlled studies assessing LVAD therapy and cardiomyoplasty are in progress.


Hippocampal serotonin-1A receptor function in a mouse model of anxiety induced by long-term voluntary wheel running.
We have recently demonstrated that, in C57/Bl6 mice, long-term voluntary wheel running is anxiogenic, and focal hippocampal irradiation prevents the increase in anxiety-like behaviors and neurobiological changes in the hippocampus induced by wheel running. Evidence supports a role of hippocampal 5-HT1A receptors in anxiety. Therefore, we investigated hippocampal binding and function of 5-HT1A receptors in this mouse model of anxiety. Four weeks of voluntary wheel running resulted in hippocampal subregion-specific changes in 5-HT1A receptor binding sites and function, as measured by autoradiography of [(3) H] 8-hydroxy-2-(di-n-propylamino)tetralin binding and agonist-stimulated binding of [(35) S]GTPγS to G proteins, respectively. In the dorsal CA1 region, 5-HT1A receptor binding and function were not altered by wheel running or irradiation. In the dorsal dentate gyrus and CA2/3 region, 5-HT1A receptor function was decreased by not only running but also irradiation. In the ventral pyramidal layer, wheel running resulted in a decrease of 5-HT1A receptor function, which was prevented by irradiation. Neither irradiation nor wheel running affected 5-HT1A receptors in medial prefrontal cortex or in the dorsal or median raphe nuclei. Our data indicate that downregulation of 5-HT1A receptor function in ventral pyramidal layer may play a role in anxiety-like behavior induced by wheel running.


Characterization of plasma cholinesterase from the White stork (Ciconia ciconia) and its in vitro inhibition by anticholinesterase pesticides.
Blood plasma cholinesterase (ChE) activity is a sensitive biomarker of exposure to organophosphorus (OP) and carbamate (CB) insecticides in vertebrates. Several studies indicate that more than one ChE form may be present in blood of birds. In this study the predominant ChE activity (acetylcholinesterase - AChE- or butyrylcholinesterase - BChE-), the range of ChE activity as well as ChE age-dependent changes in non-exposed individuals of White stork (Ciconia ciconia) have been established. The in vitro sensitivity of ChE to OP and CB insecticides such as paraoxon-methyl, carbofuran and carbaryl was also investigated. Plasma ChE was characterised using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three ChE inhibitors (eserine sulphate, BW284C51 and iso-OMPA). The results indicated that propionylthiocholine was the preferred substrate by plasma cholinesterase followed by acetylcholine and butyrylcholine and the predominant enzymatic activity in plasma of White storks was BChE. Normal plasma BChE activity in White stork was 0.32±0.01μmol/min/ml for adults and 0.28±0.03μmol/min/ml for juveniles. So, the age had no significant effect on the range of BChE activity. The study on the in vitro inhibitory potential of tested anticholinesterase pesticides on plasma ChE activity revealed that paraoxon-methyl is the most potent inhibitor followed by carbofuran and finally by carbaryl. The percentage of in vitro plasma ChE inhibition was observed to be similar between adults and juveniles.


Serum malondialdehyde: possible use for the clinical management of chronic hepatitis C patients.
Serum lipid peroxidation products are increased in inflammatory liver disease and, as we previously reported, also in chronic hepatitis C. We have performed a specific assay of malondialdehyde, the reported most abundant product of lipid peroxidation, in serum of twenty four chronic hepatitis C patients, before, during, and after interferon treatment. Liver biopsies were performed in each patient before and after interferon treatment. The results show higher serum malondialdehyde values in chronic hepatitis C patients than healthy subjects (n = 68) before interferon treatment (p < .001). Mean value of serum malondialdehyde levels after interferon treatment was significantly lower than before it (p < .002). Associating the histopathological findings in each of the 48 biopsies performed, with serum malondialdehyde and alanine aminotransferase activity levels, of the sample obtained the same day of biopsy, a much better correspondence with the histopathological severity was observed for malondialdehyde concentration than for alanine aminotransferase activity. These levels decreased significantly after interferon treatment. However, when the patients were grouped in responding (group I; n = 9) and non-responding (group II; n = 15) to interferon treatment, according to the histopathological findings before and after interferon, the values of group I before interferon treatment were significantly higher than group II (p < .03). Thus, a potential predictive value could be ascribed to the serum malondialdehyde levels before interferon treatment in these patients. We propose the utility of the specific assay of malondialdehyde for the clinical management of chronic hepatitis C patients.


Whole-lesion apparent diffusion coefficient histogram analysis: significance in T and N staging of gastric cancers.
Whole-lesion apparent diffusion coefficient (ADC) histogram analysis has been introduced and proved effective in assessment of multiple tumors. However, the application of whole-volume ADC histogram analysis in gastrointestinal tumors has just started and never been reported in T and N staging of gastric cancers. Eighty patients with pathologically confirmed gastric carcinomas underwent diffusion weighted (DW) magnetic resonance imaging before surgery prospectively. Whole-lesion ADC histogram analysis was performed by two radiologists independently. The differences of ADC histogram parameters among different T and N stages were compared with independent-samples Kruskal-Wallis test. Receiver operating characteristic (ROC) analysis was performed to evaluate the performance of ADC histogram parameters in differentiating particular T or N stages of gastric cancers. There were significant differences of all the ADC histogram parameters for gastric cancers at different T (except ADCmin and ADCmax) and N (except ADCmax) stages. Most ADC histogram parameters differed significantly between T1 vs T3, T1 vs T4, T2 vs T4, N0 vs N1, N0 vs N3, and some parameters (ADC5%, ADC10%, ADCmin) differed significantly between N0 vs N2, N2 vs N3 (all P < 0.05). Most parameters except ADCmax performed well in differentiating different T and N stages of gastric cancers. Especially for identifying patients with and without lymph node metastasis, the ADC10% yielded the largest area under the ROC curve of 0.794 (95% confidence interval, 0.677-0.911). All the parameters except ADCmax showed excellent inter-observer agreement with intra-class correlation coefficients higher than 0.800. Whole-volume ADC histogram parameters held great potential in differentiating different T and N stages of gastric cancers preoperatively.


Use of positive oral contrast agents in abdominopelvic computed tomography for blunt abdominal injury: meta-analysis and systematic review.
To determine whether positive oral contrast agents improve accuracy of abdominopelvic CT compared with no, neutral or negative oral contrast agent. Literature was searched for studies evaluating the diagnostic performance of abdominopelvic CT with positive oral contrast agents against imaging with no, neutral or negative oral contrast agent. Meta-analysis reviewed studies correlating CT findings of blunt abdominal injury with positive and without oral contrast agents against surgical, autopsy or clinical outcome allowing derivation of pooled sensitivity and specificity. Systematic review was performed on studies with common design and reference standard. Thirty-two studies were divided into two groups. Group 1 comprised 15 studies comparing CT with positive and without oral contrast agents. Meta-analysis of five studies from group 1 provided no difference in sensitivity or specificity between CT with positive or without oral contrast agents. Group 2 comprised 17 studies comparing CT with positive and neutral or negative oral contrast agents. Systematic review of 12 studies from group 2 indicated that neutral or negative oral contrasts were as effective as positive oral contrast agents for bowel visualisation. There is no difference in accuracy between CT performed with positive oral contrast agents or with no, neutral or negative oral contrast agent. • There is no difference in the accuracy of CT with or without oral contrast agent. • There is no difference in the accuracy of CT with Gastrografin or water. • Omission of oral contrast, utilising neutral or negative oral contrast agent saves time, costs and decreases risk of aspiration.


A novel histone deacetylase inhibitor reduces abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice.
Aberrant expression of components of the matrix metalloproteinase (MMP) enzyme system is implicated in abdominal aortic aneurysm (AAA) formation. We aimed to investigate the influence of a novel histone deacetylase (HDAC) inhibitor (HDACi) metacept-1 (MCT-1), previously documented to reduce MMP expression, on HDAC activity and MMP expression in aortic smooth muscle cells and the in vivo incidence of AAAs. Western blot and gelatin zymography were used to determine HDAC activity and MMP-2 expression and activity in rat (rVSMCs) and human aortic vascular smooth muscle cells (hVSMCs) in vitro. In vivo AAAs were generated using apolipoprotein E-deficient mice infused with angiotensin (Ang) II. Immunohistochemistry detected MMP-2 and -9 expression in AAA tissue samples. In vitro, MCT-1 inhibited HDAC activity in rVSMCs, and MMP-2 expression and proteolytic activity in hVSMCs. In vivo, Ang II treatment alone exhibited an AAA incidence of 84%. Doxycycline decreased the incidence of AAAs to 50%. Importantly, MCT-1 reduced AAA incidence to approximately 44%. MMP-2 and -9 immunoreactivity was reduced in MCT-1-treated aortic tissue. The novel HDACi MCT-1 inhibits MMP expression and AAA incidence suggesting this compound may warrant further investigation in the context of AAA biology.


Is predicted body-composition and relative fat mass an alternative to body-mass index and waist circumference for disease risk estimation?
New methods to estimate body-composition have recently been proposed, but their relation to diseases, such as diabetes and coronary heart disease, needs further investigation. The purpose of this study was to investigate the association between proposed prediction of body-composition (PBC); Relative Fat Mass (RFM), Body Mass Index (BMI), Waist Circumference (WC) and disease. In a cross-sectional cohort (NHANES) the association between the four body measures and diabetes, high blood pressure, coronary heart disease, cancer, arthritis, and hospitalization were assessed. A total of 13,348 people was included in this study. Receiver operating characteristic (ROC), Area Under Curve (AUC) and statistical testing were used to evaluate the differences. PBC/RFM had significant higher AUC than BMI or WC for diabetes, high blood pressure, hospitalization, and arthritis. PBC had a significant higher AUC than RFM, BMI, WC for Cancer and coronary heart disease. RFM and PBC could be a better indicator to distinguish amongst people with a risk of diseases compared to traditional measures such as BMI and WC. However, future studies need to investigate the longitudinal association between RFM, PBC and the risk of disease development to assess if these measures are better suited for risk-stratification.


Study UNICO: Perception of Urologists and Andrologists, in Spain, about the Use of Sildenafil Oral Suspension in Patients with Erectile Dysfunction.
To describe the profile of patients with erectile dysfunction (ED), attending to consultation and satisfaction using sildenafil oral suspension, from the specialist's perception. This is a nationwide multicenter, epidemiological, descriptive and observational study, with the studied population as the unit of study. Thirty urologists and/or andrologists completed a questionnaire with questions about ED patients' profile attending to their practice, sildenafil oral suspension perception of effectiveness and safeness, and their opinion about patients' satisfaction after sildenafil oral suspension treatment. Aggregate data were collected for the last 6 patients treated or on treatment with sildenafil oral suspension. Overall, 40.9% and 24.9% of patients had moderate or severe ED, respectively. Among the patients, 73.6% were older than 50 years. The disease progression was approximately one year (11.8 months). ED etiology was mostly organic (38.1%) and mixed (31.8%). Cardiovascular comorbidities were present in 57.4%, mental health problems in 16.4% and hormonal disorders in 10.2% of the patients. The main reason for choosing sildenafil oral suspension was the ease of dose adjustment. The specialists considered that 73.4% of the patients responded satisfactorily to treatment. They also rated the perceived effectiveness and safeness of the product as very good or good. Urologists and andrologists consider that most patients with ED achieve a high degree of satisfaction with sildenafil oral suspension. The main advantage of the treatment is the possibility of adjusting the dose according to patient's needs and circumstances.


Retracted: Construction of Teaching Supervision System of Applied Undergraduate Colleges and Universities under the Perspective of "Internet+".
[This retracts the article DOI: 10.1155/2022/9277583.].


The quality of root canal treatment and periapical status of permanent teeth in Turkish children and teens: a retrospective CBCT study.
This study aimed to assess the quality of root canal fillings and the prevalence of periapical radiolucencies in the permanent teeth of 6-18 year-old Turkish children. CBCT images of 150 patients' 235 teeth with a mean age of 16.0 ± 2.06 years were included. Root development stage, quality of root canal filling, the presence and severity of periapical radiolucencies, and their relationship with anatomical structures were recorded. Correlations between the quality of root canal filling, periapical lesion, and lesion size were assessed using regression analyses. A total of 235 teeth (528 root canals) were evaluated. 65.5% of root canals had periapical lesions. Immature roots and mandibular teeth had the highest prevalence and the largest size of periapical radiolucencies (p < 0.05). Overfilling (n = 52), underfilling (n = 93), unfilled (n = 46), inhomogeneously filled (n = 113) root canals and poor coronal restoration (n = 85 teeth) were observed in terms of technical failures of endodontic treatment. The quality of endodontic treatment was associated with the presence of periapical lesion and lesion size (p < 0.05). Teeth with under-filled, overfilled or inhomogeneously filled root canals and poor coronal restoration had a periapical lesion larger than 5 mm (p < 0.05). Immature teeth were most associated with the presence of lesion (OR = 4.07) and the lesion size > 5 mm (OR = 3.71). The prevalence of periapical radiolucencies in young permanent teeth showed an increase when the tooth was an incisor, had incomplete root development, or the root filling had technical errors.


Accelerated healing of pyoderma gangrenosum in Behçet patient treated with cyclosporine and split thickness skin graft.
Pyoderma gangrenosum is a dermatologic manifestation of systemic disease such as inflammatory bowel disease, monoclonal gammopathy, arthritis, malignancies, and Behçet's disease. Pyoderma gangrenosum can be stabilized with oral cyclosporine administration. After stabilization, it can be managed with debridement and skin graft.


Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis.
The Huntington's disease (HD) protein, huntingtin (HTT), is essential for early development. Because suppressing the expression of mutant HTT is an important approach to treat the disease, we must first understand the normal function of Htt in adults versus younger animals. Using inducible Htt knockout mice, we found that Htt depletion does not lead to adult neurodegeneration or animal death at >4 mo of age, which was also verified by selectively depleting Htt in neurons. On the other hand, young Htt KO mice die at 2 mo of age of acute pancreatitis due to the degeneration of pancreatic acinar cells. Importantly, Htt interacts with the trypsin inhibitor, serine protease inhibitor Kazal-type 3 (Spink3), to inhibit activation of digestive enzymes in acinar cells in young mice, and transgenic HTT can rescue the early death of Htt KO mice. These findings point out age- and cell type-dependent vital functions of Htt and the safety of knocking down neuronal Htt expression in adult brains as a treatment.


Multiomics and blood-based biomarkers of electroconvulsive therapy in severe and treatment-resistant depression: study protocol of the DetECT study.
Electroconvulsive therapy (ECT) is commonly used to treat treatment-resistant depression (TRD). However, our knowledge of the ECT-induced molecular mechanisms causing clinical improvement is limited. To address this issue, we developed the single-center, prospective observational DetECT study ("Multimodal Biomarkers of ECT in TRD"; registered 18/07/2022, www.clinicalTrials.gov , NCT05463562). Its objective is to identify molecular, psychological, socioeconomic, and clinical biomarkers of ECT response in TRD. We aim to recruit n = 134 patients in 3 years. Over the course of 12 biweekly ECT sessions (± 7 weeks), participant blood is collected before and 1 h after the first and seventh ECT and within 1 week after the twelfth session. In pilot subjects (first n = 10), additional blood draws are performed 3 and 6 h after the first ECT session to determine the optimal post-ECT blood draw interval. In blood samples, multiomic analyses are performed focusing on genotyping, epigenetics, RNA sequencing, neuron-derived exosomes, purines, and immunometabolics. To determine clinical response and side effects, participants are asked weekly to complete four standardized self-rating questionnaires on depressive and somatic symptoms. Additionally, clinician ratings are obtained three times (weeks 1, 4, and 7) within structured clinical interviews. Medical and sociodemographic data are extracted from patient records. The multimodal data collected are used to perform the conventional statistics as well as mixed linear modeling to identify clusters that link biobehavioural measures to ECT response. The DetECT study can provide important insight into the complex mechanisms of ECT in TRD and a step toward biologically informed and data-driven-based ECT biomarkers.


Solid state structure of p-bromo phenyl 4,5,7-tri-O-benzyl-β-D-glycero-D-talo-septanoside and an analysis of non-covalent interactions.
The solid state structure of a new seven-membered sugar oxepane derivative, namely, p-bromo phenyl 4,5,7-tri-O-benzyl-β-D-glycero-D-talo-septanoside is discussed, as determined through single crystal X-ray structural determination and in relation to their conformational features. The molecule adopts twist-chair as the preferred conformation, with conformational descriptor (O,1)TC(2,3). The solid state packing of molecules is governed by a rich network of non-covalent bonding originating from O-H⋯O, C-H⋯π, C-H⋯Br and aromatic π⋯π interactions that stabilize the packing of molecules in the crystal.


Dorsal Arthroscopic Approach and Intra-Articular Anatomy of the Bovine Antebrachiocarpal and Middle Carpal Joints.
To determine arthroscopic approaches to the dorsal synovial compartments of the antebrachiocarpal and middle carpal joints in adult cattle, and to describe the arthroscopic intra-articular anatomy from each approach. Ex vivo study. Six fresh adult bovine cadavers. Two carpi were injected with latex and dissected to determine the ideal location for arthroscopic portals. Arthroscopy of the antebrachiocarpal and middle carpal joints of 10 carpi was then performed. The dorsolateral approach was made between the extensor carpi radialis and common digital extensor tendons. The dorsomedial approach was made medial to the extensor carpi radialis tendon, midway between the distal radius and proximal row of carpal bones (antebrachiocarpal joint) and midway between the two rows of carpal bones (middle carpal joint), with the joint in flexion. Arthroscopy of the antebrachiocarpal joint allowed visualization of the distal radius, proximal aspect of the radial, intermediate and ulnar carpal bones, and a palmar ligament located between the radius and the intermediate carpal bone. The approach to the middle carpal joint allowed visualization of the distal aspect of the radial, intermediate, and ulnar carpal bones, the proximal aspect of the fourth and fused second and third carpal bones and an interosseous ligament. The most lateral articular structures (lateral glenoid cavity of the distal radius, ulnar carpal and fourth carpal bones) were difficult to assess. Dorsal approaches to the antebrachiocarpal and middle carpal joints allowed visualization of most intra-articular dorsal structures in adult cattle.


[Bone mass in patients with cystic fibrosis of the pancreas. Relationship with anthropometric parameters and genotype].
Cross-sectional study of bone mineral density (BMD) in children and adolescents with cystic fibrosis of the pancreas. The relationship of BMD values with nutritional status, respiratory function and the cystic transmembrane regulator genotype was also evaluated. BMD expressed as grams of hydroxyapatite/cm2 was measured by dual-energy X-ray absorptiometry in the lumbar spine (L2-L4) in 41 patients (21 males and 20 women; age range: 4-21 years) with cystic fibrosis of the pancreas and compared with that of 471 normal controls (256 males and 215 women; age range: 1-20 years). Twenty patients were prepubertal, 9 pubertal and 12 young adults. Clinical repercussion of the disease evaluated by clinical and anthropometric data (weight, height and body mass index) and respiratory function was considered moderate. Height z score (mean [MSE]) was -0.53 (0.28), weight -0.81 (0.21) and body mass index -0.82 (0.12) BMD z score values (mean [MSE]) were -1.14 (0.17) and differed significantly (p < 0.001) from those of normal age- and sex-matched controls. No significant differences were observed between males and women or among prepubertal, pubertal and young adult patients. BMD z score values less than-1 z score were found in 53% and under -2 z score in 8%. Cystic transmembrane regulator genotype was studied in 36 patients (17 were F508/-, 10 F508/F508, 5 G542X/- and 4 diverse) and did not predict bone mineral status. A statistically significant correlation was found between BMD z score values and height z score, weight z score, body mass index z score and clinical assessment according to Shwachman criteria. A negative and statistically significant correlation was observed between BMD z score and functional score. The decrease in BMD values in CF patients begins early in life and appears to be related to the degree of clinical expression of the disease.


The effect of video training and intraoperative progress report on the anxiety of family caregivers waiting for relatives undergoing surgery.
This study aimed to examine the effect of video training and intraoperative progress report on the anxiety of family caregivers awaiting relatives undergoing surgery. A three-armed randomized controlled design was used. One hundred and two participants were enrolled and randomly assigned to three groups: the video training group (n = 34), the intraoperative progress report group (n = 34), and the control group (n = 34). Interventions were performed when the relatives of the participants were undergoing surgery. The participants in the video training group received video training containing images of the operating room environment and animations related to the patient's surgical procedure, postoperative care, and possible complications from the surgery. In the intraoperative progress report group, information regarding the patient's general condition, the percentage of surgical progress, and the approximate time of the patient's transfer from the operating room were provided. The control group received routine care. A demographic data questionnaire and the Spielberger State-Trait Anxiety Inventory (STAI) was used for data collection. It was found a statistically significant decrease in the state anxiety in the video training (p < 0.001) and intraoperative progress report (p < 0.001) group after the intervention when compared to before the intervention. It was found no significant difference among the study groups in terms of the level of state and trait anxiety after the intervention (p > 0.05). This study found that both video training and intraoperative progress report are effective in reducing the state anxiety of family caregivers awaiting relatives undergoing surgery.


Effect of a two-phase tobacco control regulation on incidence from ischemic stroke and hemorrhagic stroke, Shenzhen, China, 2007-2016.
The Shenzhen government is widely considered to be most efficiently implementing smoke-free legislation in China. We evaluated and compared the impact of Shenzhen's two-phase smoke-free regulation on the incidence rates for ischemic and hemorrhagic stroke. An interrupted time series design was used to capture immediate and annual incidence changes from 2007 to 2016 for both ischemic and hemorrhagic stroke due to two-phase smoke-free regulation in Shenzhen, China, by using a generalized additive model. The first phase, implemented on 9 March 2010, required five main public places to be smoke-free. In the second phase, the comprehensive law was expanded to the whole city on 1 March 2014. The regulation implementation during phase I was associated with a strong immediate decline in the incidence rate of ischemic stroke (-14.2%, 95% CI: -19.6 - -8.4) and hemorrhagic stroke (-10.1%, 95% CI: -18.2 - -1.2), but without showing the annual changes (p>0.05). Following the implementation of the comprehensive law, the gradual annual effect showed a significant change in ischemic stroke, with a 6.3% (95% CI: 8.9 - -3.6) reduction. Neither the immediate nor gradual decreases in hemorrhagic stroke incidences associated with the comprehensive regulation were statistically significant during phase II (p>0.05). Subgroup analyses indicate that a much larger health effect of the regulation during phase I was greater among those aged ≥65 years than among those aged 35-64 years. Shenzhen's two-phase smoke-free regulation was well implemented. Even though the regulation did not extend to the whole city, the immediate health benefits on the incidence rates of ischemic stroke and hemorrhagic stroke could be seen. However, the health benefits brought by the implementation of comprehensive smoke-free legislation were attenuated by previous smoke-free regulations in five main public places, which were more evident in hemorrhagic stroke.


Taste-masked nanoparticles containing Saquinavir for pediatric oral administration.
This research has aimed to improve the stability and taste-masking properties by developing nanostructured dosage forms containing Saquinavir. Liquid formulations were developed using Eudragit RS100® and Pullulan as polymers. The physicochemical characteristics, stability, in vitro drug release, morphology, mucoadhesion and taste masking capacity were evaluated. The Saquinavir-nanoparticles had average diameters between 136 and 158 nm, with a Span below 1.4. These formulations presented a drug content above 80%, a high encapsulation efficiency (>97%), slightly acidic pH levels, low dynamic viscosity and controlled drug release. Electron microscopy revealed irregular spherical nanoparticles. The formulations prepared with higher amounts of Eudragit RS100® had greater mucoadhesion. Both polymers were able to improve drug stabilization, taste-masking properties and protection against drug cytotoxicity. The Saquinavir-nanoparticles exhibited stability and control releasing properties, thus making it a promising liquid dosage form with taste-masking properties intended for application in pediatric treatment.


Surface-modified and sulfide electrolyte-infiltrated LiNi0.6Co0.2Mn0.2O2 cathode for all-solid-state lithium batteries.
Sulfide-based all-solid-state lithium batteries (ASSLBs) with high-voltage Ni-rich layered cathodes have shown great potential in energy storage systems. However, the application of ASSLBs is hindered by severe interface issues and poor solid-solid contact between cathodes and sulfide electrolytes. In this work, a suitably thin Li1.5Al0.5Ge1.5(PO4)3 (LAGP) coating (0.41 mS cm-1) is introduced onto the surface of single-crystal LiNi0.6Co0.2Mn0.2O2 particles to mitigate interface side reactions. Subsequently, sheet-type electrodes are fabricated by the infiltration of Li10GeP2S12 to fill the voids and achieve highly dense solid-solid contact, thus preventing contact loss. The Li10GeP2S12-infiltrated ASSLBs with a LAGP buffer layer display a high initial discharge capacity of 141.5 mAh g-1 at 0.05 C and ultrastable cycling for 100 cycles at 0.1 C. An effective fabrication method for highly dense electrodes is proposed in this work, which provides a new direction for scalable industrial production.


A GIS and remote sensing aided assessment of land use/cover changes in resettlement areas; a case of ward 32 of Mazowe district, Zimbabwe.
The research assessed land use/cover changes and their socio-economic impacts on local resident farmers in ward 32 of Mazowe District. A mixed method research design that combines both qualitative and quantitative approaches was adopted. Questionnaires, interviews and observations were employed to gather data from the field. GIS and Remote sensing techniques were used for land use/cover change detection and calculations. Data collected from the field was analyzed using Statistical Package for Social Sciences (SPSS) version 25.0 and Microsoft excel. Arc map 10.5 was used to analyze Remote sensing data. Four major land use/covers namely forest, grassland, water and cultivated were identified as baseline land covers of Mazowe ward 32 in 2000. The research revealed that there has been significant loss in forest, grassland and wetland/water cover and gain in cultivated and bare land cover between 2000 and 2018 in ward 32 of Mazowe District. Scarcity of high energy tree species, fruit trees, construction poles and extinction of wild animals are some of the observed impacts of forest cover loss. The study recommends that Mazowe EMA, RDC and Forestry Commission should cooperate in monitoring natural resources in Mazowe District to ensure sustainable utilization.


Cleft hand, syndactyly and hypoplastic thumb.
The clinical features of 58 patients with typical cleft hand were examined and compared with 86 patients with syndactyly between the long and ring fingers, 27 patients with syndactyly between the ring, little and other fingers, 53 patients with hypoplastic thumb and 100 patients with symbrachydactyly. The clinical findings of the typical cleft hand resembled those of syndactyly. There were two unusual cases of typical cleft hand associated with hypoplastic thumb, congenital heart anomalies and absence of the axial triradius. One of these also had cleft lip and palate. The critical embryonic period of the heart anomaly is early, while that of the cleft lip and palate is late. These findings suggest that an embryo with typical cleft hand and hypoplastic thumb results from impairments at two different times in the early embryonic period.


The impact of neoadjuvant systemic treatment on postoperative complications in breast cancer surgery.
The aim of the study was to analyze the impact of neoadjuvant systemic treatment (NST) on postoperative complications and the beginning of adjuvant treatment. This study includes data from a prospectively maintained database including patients with breast cancer (BC) stage I-IV with or without NST undergoing breast cancer surgery between January 2010 and September 2021. Out of 517 enrolled patients, 77 received NST, 440 had primary breast surgery. After NST patients underwent surgery after a meantime of 34 days (26.5-40 days). No statistical significance could be found comparing the complication grading according to the Clavien Dindo classification. The complications were most frequently rated as grade 3b. There were no complications with grade 4 or higher. When differentiating into short and long-term, the overall rate of short-term complications was 20.3% with no significant difference between the two groups (20.8% vs. 20.2%). Regarding long-term complications, there was more impairment of shoulder mobility (26.0% vs. 9.5%, p ≤ 0.001) and chronic pain (42.9% vs. 28.6%, p ≤ 0.016) for patients with NST. The beginning of the administration of the adjuvant treatment was comparable in both groups (46.3 days vs. 50.5 days). In our cohort, complications between both groups were comparable according to Clavien Dindo. This study shows that NST has no negative impact on postoperative short-term complications and most importantly did not lead to a delay of the beginning of adjuvant treatment. Therefore, NST can be safely admitted, even when followed by extensive breast reconstruction surgery.


Effects of ongoing smoking on the development of radiation-induced pneumonitis in breast cancer and oesophagus cancer patients.
To investigate the influence of smoking on the development of radiation-induced pneumonitis in patients treated for breast and oesophagus cancer. This is a retrospective study on 405 females diagnosed with primary unilateral breast cancer stages 1 and 2 and 201 oesophagus carcinoma patients. The possibilities in Sweden to obtain detailed information from different medical records were used to collect data on smoking habits, radiation treatment and spontaneously reported pneumonitis. Radiation-induced pneumonitis was defined as a combination of roentgenographic infiltrate in the lung field involving an irradiated area on the chest X-ray and clinical symptoms such as non-productive cough and dyspnoea. Six breast cancer patients had spontaneously reported pneumonitis. Five of them were non-smokers (P = 0.182) and the other was a former smoker. Eight of the oesophagus cancer patients had spontaneously reported radiation-induced clinical pneumonitis and they were all non-smokers (P = 0.022), except one, who was a pipe smoker. None of the patients who were cigarette smokers were recorded as developing clinical pneumonitis after irradiation. These data could support the previous clinical observations and experimental studies that smoking depresses the frequency of radiation-induced pneumonitis. The present study as well as earlier observations could justify further studies concerning the possibility of an interaction of smoking with cancer treatment, both from the view of therapeutic failures and reduced adverse effects.


Analysis of glucosyltransferase gene expression of clinical isolates of Streptococcus mutans obtained from dental plaques in response to sub-lethal doses of photoactivated disinfection.
Dental caries is a disease caused by a group of oral streptococcal microorganisms, primarily Strptococcus mutans. Photoactivated disinfection (PAD) has been proposed as a conservative method for treatment of carious lesions. Therefore, the aim of this study was to assess the effectiveness of indocyanine green (ICG)- and toluidine blue O (TBO)-PAD as supplementary tools in reducing the bacterial load and expression profiling of the gene associated with the biofilm formation in S. mutans. S. mutans strains were isolated from dental plaque samples collected from 212 patients through conventional biochemical tests and molecular methods. After identification, S. mutans strains were photosensitized in vitro with TBO and ICG, which were excited at a specific light wavelength based on the photosensitizer. After evaluating doses of TBO- and ICG-PAD contributing to sub-significant reduction of CFU/mL, ROS levels were measured with DCFH-DA fluorescent probe. Eventually, TBO- and ICG-PAD effects on the gtfB gene expression were assessed using real-time quantitative reverse transcription polymerase chain reaction. S. mutans strains were isolated from 50 (23.5%) patients. In this study, maximum doses of TBO- and ICG-PAD contributing to sub-significant reduction of CFU/mL against S. mutans strains were 23.12 μM/mL TBO at fluence of 68.75 J/cm2 and 20.15 μM/mL ICG at fluence of 31.2 J/cm2. According to the results, 3.8- and 6.1-fold increases in the fluorescence were observed in ICG and TBO treated cells compared to the control, respectively. The expression of gtfB was down regulated to approximately 3.9- and 8.25-fold following treatment with TBO- and ICG-PAD, respectively. The gtfB gene expression profiling decreased in the bacterial cells, with ICG-PAD causing a greater reduction. PAD may be a promising therapy for dentinal carious lesions.


Use of the 5-Factor Modified Frailty Index to Predict Hospital-Acquired Infections and Length of Stay Among Neurotrauma Patients Undergoing Emergent Craniotomy/Craniectomy.
Traumatic brain injury is a significant public health concern often complicated by hospital-acquired infections (HAIs); however, previous evaluations of factors predictive of risk for HAI have generally been single-center analyses or limited to surgical site infections. Frailty assessment has been shown to provide effective risk stratification in neurosurgery. We evaluated whether frailty status or age is more predictive of HAIs and length of stay among neurotrauma patients requiring craniectomy/craniotomy. In this cross-sectional analysis, the American College of Surgeons National Surgical Quality Improvement Program 2015-2019 dataset was queried to identify neurotrauma patients who underwent craniectomies/craniotomies. The effects of frailty status (using the 5-factor modified frailty index [mFI-5]) and age on occurrence of HAIs and other 30-day adverse events were compared using univariate analysis. The discriminative ability of each measure was defined by multivariate modeling. Of 3284 patients identified, 1172 (35.7%) contracted an HAI postoperatively. Increasing frailty score predicted increased HAI risk (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.05-1.77, P = 0.022 for mFI-5 = 1 and OR = 2.01, 95% CI = 1.30-3.11, P = 0.002 for mFI-5≥3), whereas increasing age did not (OR = 0.996, 95% CI = 0.989-1.002, P = 0.009). Median length of stay was significantly longer in patients with HAI (16 days [IQR = 9-23]) versus no HAI (7 days [IQR = 4-13]) (P < 0.001). Median daily costs on the ward and neuro-intensive care unit were higher with HAI than with no HAI (neuro-ICU: $111,818.08 [IQR = 46,418.05-189,947.34] vs. $48,920.41 [IQR = 20,185.20-107,712.54], P < 0.001). Increasing mFI-5 correlated with increased HAI risk. Neurotrauma patients who developed an HAI after craniectomy/craniotomy had longer hospitalizations and higher care costs. Frailty scoring improves risk stratification among these patients and may assist in reducing total hospital length of stay and total accrued costs to patients.


Microinjection and expression of a mouse metallothionein human growth hormone fusion gene in fertilized salmonid eggs.
Using a microinjection method (Rokkones et al. 1985) deoxyribonucleic acid was introduced into fertilized salmonid eggs. The survival rate after a 28 day period was 91% for injected eggs in comparison to non-injected controls. A gene construct containing the mouse metallothionein promoter fused to the human growth hormone structural gene was microinjected either as a supercoiled plasmid or as a linear sequence. In Southern blot analysis of both 5 and 73 day old dissected rainbow trout embryos, as well as in 1 year old Atlantic salmon, the mouse metallothionein human growth hormone gene sequence was detected together with the chromosomal DNA when micro-injected as plasmid or as linear DNA. After digestion with Bam HI restriction endonuclease, the human growth hormone gene was excised from the high molecular weight DNA fraction. Transcription into human growth hormone specific RNA, as well as translation and release of human growth hormone immunoreactive protein, could be demonstrated in early embryonic stages.


Maternal Gestational Diabetes Mellitus increases placental and foetal lipoprotein-associated Phospholipase A2 which might exert protective functions against oxidative stress.
Increased Lipoprotein associated phospholipase A2 (LpPLA2) has been associated with inflammatory pathologies, including Type 2 Diabetes. Studies on LpPLA2 and Gestational Diabetes Mellitus (GDM) are rare, and have focused mostly on maternal outcome. In the present study, we investigated whether LpPLA2 activity on foetal lipoproteins is altered by maternal GDM and/or obesity (a major risk factor for GDM), thereby contributing to changes in lipoprotein functionality. We identified HDL as the major carrier of LpPLA2 activity in the foetus, which is in contrast to adults. We observed marked expression of LpPLA2 in placental macrophages (Hofbauer cells; HBCs) and found that LpPLA2 activity in these cells was increased by insulin, leptin, and pro-inflammatory cytokines. These regulators were also increased in plasma of children born from GDM pregnancies. Our results suggest that insulin, leptin, and pro-inflammatory cytokines are positive regulators of LpPLA2 activity in the foeto-placental unit. Of particular interest, functional assays using a specific LpPLA2 inhibitor suggest that high-density lipoprotein (HDL)-associated LpPLA2 exerts anti-oxidative, athero-protective functions on placental endothelium and foetus. Our results therefore raise the possibility that foetal HDL-associated LpPLA2 might act as an anti-inflammatory enzyme improving vascular barrier function.


SHR-1701, a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, for Recurrent or Metastatic Cervical Cancer: A Clinical Expansion Cohort of a Phase I Study.
Patients with recurrent or metastatic cervical cancer have limited treatment options after platinum-containing treatment. We initiated a phase I study to assess SHR-1701, a novel bifunctional fusion protein composed of a mAb against programmed death ligand 1 (PD-L1) fused with the extracellular domain of TGFβ receptor II, in solid tumors (NCT03774979). Here, results from the cervical cancer cohort are presented. Patients with recurrent or metastatic cervical cancer who progressed during or after platinum-based therapy were enrolled to receive SHR-1701 at 30 mg/kg every 3 weeks. Primary endpoint was objective response rate (ORR) per RECIST v1.1. In total, 32 patients were recruited. ORR was 15.6% [95% confidence interval (CI), 5.3-32.8], and disease control rate was 50.0% (95% CI, 31.9-68.1). Responses were still ongoing in 80.0% of the responders; 6-month duration of response rate was 80.0% (95% CI, 20.4-96.9). Median progression-free survival (PFS) was 2.7 months (95% CI, 1.4-4.1). Of note, as assessed by immune-modified RECIST, median PFS was 4.1 months (95% CI, 1.6-4.3). Overall survival rate at 12 months was 54.6% (95% CI, 31.8-72.7). Treatment-related adverse events of grade 3 or 4 were reported in 11 (34.4%) patients. No treatment-related deaths occurred. No difference in ORR was found between patients with PD-L1 combined positive score ≥1 or <1; patients with high phosphorylated SMAD2 level in immune cells or tumor cells had numerically higher ORR. SHR-1701 exhibits encouraging antitumor activity and controllable safety in patients with recurrent or metastatic cervical cancer after platinum-based regimens, and therefore might provide another treatment option for this population. See related commentary by Miller and Friedman, p. 5238.


First trimester abortions associated with a translocation t(1;20)(p36;p11).
A large family with a high rate of spontaneous abortions was found also to have a high incidence of a reciprocal translocation.


Pain management after lumbar spinal fusion surgery using continuous subcutaneous infusion of buprenorphine.
The continuous subcutaneous infusion (CSI) technique is a simple, inexpensive method for managing postoperative pain. We examined the analgesic effects of CSI of buprenorphine in patients undergoing lumbar spinal fusion surgery. The patients were randomly assigned to one of three groups for postoperative pain management: control group (n = 17), high-dose buprenorphine group (BH group, n = 17), and low-dose buprenorphine group (BL group, n = 16). Infusion solutions containing buprenorphine at concentrations of 25.0 and 16.7 microg x ml(-1) combined with droperidol at a concentration of 52.0 microg x ml(-1) were used in the BH and BL groups, respectively; and an infusion solution containing droperidol at a concentration 52.0 microg x ml(-1) was used in the control group. CSI of each solution was started at a rate of 1 ml x h(-1) and was continued for 48 h. The BH and BL groups showed significantly lower scores than the control group on the Visual Analogue Scale. There were significantly fewer administrations of flurbiprofen as a supplemental analgesic in the BL and BH groups than in the control group. The incidences of sedation and nausea were comparable in the three groups. The median number of administrations of flurbiprofen was significantly less in the BH group than in the control group on the day of the operation and on the first postoperative day, whereas the number in the BL group was less than that in the C group only on the day of the operation. CSI of buprenorphine effectively reduces pain after lumbar spinal fusion surgery without apparent side effects. This technique is simple and useful for postoperative pain management.


Synthesis and photoluminescence characteristics of Dy incorporated MoO3 phosphor: Suppression concentration quenching.
A series of MoO3:Dy3+ phosphors have been synthesized via the gel-combustion method. The X-ray and photoluminescence (PL) emission spectra were employed to characterize the obtained phosphors. The prepared samples were characterized through XRD measurements and exhibited that Dy3+ ions can be successfully incorporated into the host material. The PL emission bands of Dy3+ doped MoO3 were observed at 486 nm, 574 nm and 666 nm which are assigned to the transitions of 4F9/2 → 6H15/2, 4F9/2 → 6H13/2 and 4F9/2 → 6H11/2, respectively. Concentration quenching were largely taken into consideration as one of the crucial aspects limiting the application range of phosphors in today's modern world. An abnormal thermal quenching dependence was reported when Dy3+ ions were incorporated into MoO3 host matrix. In order to understand the origin of this beneficial behaviour, energy transfer processes occurring via radiative and nonradiative mechanisms were investigated to elucidate this suppression of the concentration quenching.


Tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene in mouse skin and rat mammary gland.
Studies of the tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene (BP) can provide evidence about the role of the 6 position in the carcinogenic activation of BP. Female Swiss and A-strain mice were treated on the skin with BP, 6-fluorobenzo[a]pyrene (6-FBP), 6-chlorobenzo[a]pyrene (6-C1BP), 6-bromobenzo[a]pyrene (6-BrBP) and 6-iodobenzo[a]pyrene (6-IBP) by repeated application, and in some cases by initiation-promotion. While BP was more potent than 6-FBP, only these two compounds exhibits tumor-initiating and carcinogenic activity in mouse skin. Female Sprague-Dawley rats were treated with BP, 6-FBP, 6-ClBP, and 6-BrBP by intramammillary injection. BP and 6-FBP induced high levels of mammary epithelial tumors and fibrosarcomas. 6-ClBP elicited only a high percentage of fibrosarcomas, whereas 6-BrBP induced a few adenocarcinomas. These results indicate that chloro or bromo substitution at C-6 in BP reduces or eliminates carcinogenic activity. Conversely, 6-FBP, from which the fluoro substituent has been chemically and metabolically removed by one-electron oxidation, displays a moderate carcinogenic activity which is consistent with activation by either one-electron oxidation or monooxygenation.


Management of Intra-orbital Wooden Foreign Bodies at a Resource-limited Setting in Sub-Saharan Africa.
Wooden intra-orbital foreign bodies (IOrbFBs) have a high risk of microbial contamination needing timely diagnosis and treatment. We describe management of three cases of wooden IOrbFB at a resource-limited setting in Liberia. This is a retrospective case series of three patients with IOrbFB managed at the Liberia Eye Center, Monrovia, Liberia. Demographic details, mode of injury, ocular examination findings, neuroimaging, surgical treatment, and clinical findings on post-operative follow-up visits were noted for each patient. All the three patients were young, male, and were involved in traumatic incidents (fall in two cases and road traffic accident in one case). Two patients with visible wooden FB presented within 48 h of injury and one patient with occult FB presented after 2 weeks. All patients underwent orbital imaging followed by surgical exploration for the removal of FB. One patient also had coexisting orbital cellulitis, which was successfully treated medically. One of these patients had best corrected visual acuity of 20/20, and the other two had no perception of light in the affected eyes. History of injury with a wooden material should raise a high index of suspicion for an occult IOrbFB. Timely diagnosis and treatment of wooden IOrbFB can be challenging in a resource-limited setting, but with a systematic approach they can be treated satisfactorily.


Fixed full-arch maxillary prostheses supported by four versus six implants with a titanium CAD/CAM milled framework: 3-year multicentre RCT.
This RCT compares marginal bone level (MBL) change and the clinical parameters after a 3-year function in maxillary implant-supported fixed complete dentures (FCDs) treated with four-implants (4-I) or six-implants (6-I). Three centres treated 56 patients with 280 implants allocated to the 4-I or 6-I group. Radiographic and clinical examinations were performed. The primary outcome was to investigate MBL change between the groups. Implant survival rates were 100% and 99% in the 4-I and 6-I groups, respectively. Considering the clustering effects, the MBL change was not significantly different between the groups over the 3-year follow-up. The MBL in the 4-I group was 0.30 ± 0.50 mm at baseline, 0.24 ± 0.31 mm at 1 year and 0.24 ± 0.38 mm at 3 years. In the 6-I group, MBL was 0.14 ± 0.32 mm at baseline, 0.16 ± 0.35 mm at 1 year and 0.12 ± 0.26 mm at 3 years. There was a statistically significant difference between the groups at BL and 3Y. No significant differences between the groups were reported for clinical parameters at each time point as well as in between the visits. The technical and biological complications rates were 1.6% and 6.0%, respectively. Prosthetic complications affected 25 FCDs (47.2%). Marginal bone level change revealed a stable condition in the 3-year period in the two groups. Few technical and biological complications occurred apart from the chipping/fracture of the prosthetic teeth. Four-implant is a feasible solution if the rehabilitation is oriented towards the most cost-effective treatment and towards avoiding bone augmentation procedures. Clinicians have to consider the potential required visits for prosthetic maintenance.


5-(3-Chloro-phen-ylsulfan-yl)-1-methyl-3-trifluoro-methyl-1H-pyrazole-4-carbaldehyde O-[(2-chloro-1,3-thia-zol-5-yl)meth-yl]oxime.
In the title compound, C(16)H(11)Cl(2)F(3)N(4)OS(2), the benzene ring and the thia-zole ring make dihedral angles of 83.2 (3) and 78.3 (3)°, respectively, with the pyrazole ring. The crystal packing shows S⋯N contacts of 3.309 (2) Å.


An analysis of the biomechanics of interference screw fixation and sheathed devices for biceps tenodesis.
This study aimed to evaluate the differences in biomechanical properties of biceps tenodesis when performed with sheathed versus unsheathed screws and also to investigate the effect of altering the pre-tension. Tenodesis was performed in an in vitro model using biomechanical test blocks and ovine tendons. Blocks were allocated to 1 of 5 groups which varied by method of tenodesis and cyclical loading protocol: Group A, Biosure PK screw (10-100 N), Group B: 7-8 mm Biosure Sync and Biosure PK screw (10-100 N), Group C: Biosure PK screw (10-70 N), Group D: Biosure PK (20-100 N), and Group E: custom sheath and Biosure PK screw (10-100 N). If tenodeses remained intact after 500 cycles maximum load to failure testing was performed. 30% of tenodeses in Group A failed prior to 500 cycles whereas none failed in the sheathed device groups (P=0.02). Using a sheathed device prevented mal-rotation. However, tenodeses in Group B were more likely to fail immediately distal to the tenodesis at a load below the anticipated maximum load to failure suggesting tendon damage during fixation. Using the custom sheath, which did not have sharp edges, resulted in a statistically significant increased maximum load to failure in Group E (348 N) when compared to Group A (228 N, mean difference 120 N, P=0.01) and Group B (253N, mean difference 95 N, P=0.0007). Sheathed devices prevent mal-rotation and increase stiffness and maximum load to failure. This is further improved by reducing tendon damage at the time of tenodesis.


Analysis of Survival Prognosis for Children with Symptomatic Optic Pathway Gliomas Who Received Surgery.
The feasibility and prognosis of surgical treatment for children with optic pathway gliomas (OPGs) is controversial. Therefore this study attempted to evaluate the effects of surgery and discuss prognostic factors related to the survival of children with symptomatic OPGs. One-hundred twenty-five children diagnosed with OPGs underwent surgery in the Department of Neurosurgery, Beijing Tiantan Hospital from 2003-2016. In this retrospective study, their demographics, clinical characteristics, treatments, and survival outcomes were investigated and summarized. Among the 125 patients, the 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 84.1% and 70.6%, respectively. In the univariate analysis, patients who received postoperative radiotherapy (RT) after surgery had significantly better 5-year OS and PFS rates than patients who did not receive RT (P < 0.001 for both comparisons), patients who were 3 years old had better PFS rates than younger patients (P < 0.001), and patients with endocrinology symptoms had significantly worse PFS rates than patients with other symptoms (P = 0.049). In the multiple regression analysis, postoperative treatment with RT and tumors with a lower pathologic grade were better predictors of OS. An age older than 3 years and postoperative treatment with RT were better predictors of PFS. Surgery is safe and feasible for children with large volumes of OPGs and symptoms of functional impairment and obstructive hydrocephalus. Furthermore, adjuvant RT after surgery may significantly improve OS and PFS. The pathologic grade is an independent prognostic factor for OS, and the age at diagnosis is an independent prognostic factor for PFS.


[Eosinophilic pleuritic: An unusual complication of treatment with an angiotensin converting enzyme inhibitor].
Eosinophilic pleural effusions are defined by an eosinophil count ≥10% in pleural fluid and represent approximately 10% of exudative pleural effusions. We report the first case of eosinophilic pleural effusion occurring due to lisinopril treatment. Improvement after drug discontinuation and recurrence after reintroduction indicated that lisinopril was responsible for the effusion. The main causes of eosinophilic pleural effusions are infections including tuberculosis, and malignancies. Drug-induced eosinophilic pleural effusions have only rarely been described, mainly caused by cardiovascular or neuropsychiatric medicines.


Water-resistant hybrid cellulose nanofibril films prepared by charge reversal on gibbsite nanoclays.
A novel method is reported for the preparation of a hybrid gibbsite-cellulose nanofibril (CNF) nanocomposite film with improved wet and dry mechanical properties and barrier properties. A gibbsite and cationic CNF dispersion was dewatered at pH 7 to prepare well-ordered films. Thereafter, the charge on gibbsite was reversed by dipping the film in pH 12 water to induce an ionic interaction between CNFs and gibbsite, enhancing the film properties; modulus improved from 9 GPa to 12 GPa, with a maintained strain-at-break of 6 % and tensile strength of 190 MPa. Additionally, the charge-reversed film swelled a factor of 24 less than a film without any gibbsite. At 23 °C and 80 % RH, the oxygen barrier properties were improved by a factor of 28, to a value of 18 ml·μm·m-2·kPa-1·24 h-1 and the water vapour barrier properties were improved by a factor of 12, to a value of 105 g·μm·m-2·kPa-1·24 h-1.


Clinical, genetic, and electrophysiologic characteristics of a new PAS-domain HERG mutation (M124R) causing Long QT syndrome.
To describe the clinical, genetic, and electrophysiologic characteristics of a new PAS-domain HERG mutation (M124R) that has been identified in a single large Jewish family with Long QT syndrome (LQTS). Many previously reported HERG mutations causing LQTS are located either in the C-terminus, or in the pore region. Relatively fewer clinical data are available on N-terminus (PAS-domain) mutation carriers. Clinical data were available in 76 family members (aged 1-93 years, 69 alive) over 18 years of follow-up, while electrocardiographic data were available in 57, and genetic data in 45 family members. Cellular electrophysiology was assessed in transfected Chinese Hamster Ovary (CHO) cells using the whole-cell patch-clamp technique. Thirty-six family members were phenotypically categorized as nonaffected, 3 as equivocal, and 20 as affected. Mean QTc was 410+/-23, 440+/-10, and 498+/-41 ms, respectively, in these three subgroups. Eight out of 20 affected family members were symptomatic: five had only syncope, two had aborted cardiac arrest, and one sudden death. Genetic analyses identified the M124R point mutation in all affected members tested (n=16), while all those tested with nonaffected (n=26) and equivocal (n=3) phenotype did not carry the mutation. The M124R mutation reduced the HERG tail-current density by 65%, significantly accelerated the deactivation kinetics, and caused a negative shift in the voltage dependence of activation. A new PAS-domain HERG mutation (M124R) was identified as causing LQTS in a large Jewish family, with high penetrance and frequent disease-related symptoms. This mutation markedly decreased the tail-current density and accelerated the deactivation kinetics of the HERG channel in transfected CHO cells.


Giardia duodenalis cyst survival in cattle slurry.
Giardia duodenalis is a protozoan parasite known to infect animals and humans. Zoonotic transmission of G. duodenalis can occur by the consumption of drinking water produced from surface water that is contaminated by runoff from manure-laden fields or pastures. Although it was previously reported that storing solid cattle manure decreases G. duodenalis cyst viability, no data are available on cyst survival in slurry waste from cattle. In this study the number and the viability of G. duodenalis cysts was determined in cattle slurry for up to 90 days. G. duodenalis cysts were counted in 30 slurry samples with a quantitative direct immunofluorescence assay. The geometric mean number of cysts was reduced by 77% after 90 days (P<0.0014), although there was substantial variability between samples. A fluorogenic dye staining using 4',6'-di-amino-2-phenylindole and propidium iodide showed a decreased viability from 45 days onwards, and after 90 days incubation, only 3% of the cysts were viable. Gerbils and lambs were artificially infected with 50 day-old and 90 day-old cysts and faecal excretion of G. duodenalis was monitored between 5 and 7 days after infection. Seven days after infection the gerbils were euthanized for Giardia trophozoite counts. Although one cyst was found in the faeces of one of the gerbils after infection with 50 day-old cysts, no trophozoites were recovered from the intestines of any gerbil (n=8). Experimental infection of lambs with 10(5)50 day-old and 90 day-old slurry cysts caused low cyst excretion in one out of two and one out of three lambs, respectively. Together, these data show that storage of cattle slurry for 90 days greatly reduces the number and viability of G. duodenalis cysts.


Similarities of antisera to casein and epithelial membrane antigen.
Antisera raised against human milk fat globule membranes and against the casein fraction of human milk have been compared. Using an immunohistochemical stain of tissue sections it has been shown that many of the antigenic determinants detected by the different antisera are identical. A radioimmunoassay for epithelial membrane antigen (EMA) showed that casein preparations are associated with small quantities of EMA. Antisera to casein frequently contained appreciable concentrations of antibodies to EMA and this accounts for the immunohistochemical staining of non-mammary tissues.


Cyanamide hepatotoxicity. Incidence and clinico-pathological features.
Ground-glass hepatocytes resembling those seen in HBsAg carriers on hematoxylin and eosin and on trichrome stained sections, but giving a negative reaction to orcein and a positive one to PAS, were found in liver biopsy specimens from nine asymptomatic former alcoholics who were on treatment with cyanamide, in one of four who had been treated with cyanamide several months before the liver biopsy procedure, in none of 15 treated with disulfiram, and in one of eight who had apparently not received aversive drugs. Portal and periportal inflammatory changes and fibrosis were more frequently observed in biopsy specimens containing PAS-positive ground-glass hepatocytes than in those without, but cirrhosis was found with a similar frequency. It is concluded that periportal PAS-positive ground-glass hepatocytes are a histological marker of cyanamide treatment.


Comparing static and dynamic predictors of risk for hostility in serious mental illness: Preliminary findings.
This study compared static predictors of hostility (e.g. demographics, clinician ratings) to subjective (i.e., self-reported affect on slider scales in response to written questions) and objective (i.e., vocal indicators of arousal from speech samples in a story-retelling task) dynamic predictors using ambulatory assessment over five days in a sample of 25 stable outpatients with diagnoses of a serious mental illness. Multilevel modeling showed that both subjective and objective dynamic predictors were significant, but none of the static predictors were. These results suggest that, in predicting hostility, it is more important to account for state variation than static traits.


Promutagen activation by Vicia faba: an assay based on the induction of sister-chromatid exchanges in Chinese hamster ovary cells.
Plant activation of promutagens was studied using Vicia faba S10 (in vitro activation) and the extracts prepared from promutagen-treated roots of Vicia faba (in vivo activation). The induction of sister-chromatid exchanges in Chinese hamster ovary cells was used as an endpoint to evaluate the cytogenetic effects of promutagens activated by Vicia faba. Cyclophosphamide and ethyl alcohol were activated both by Vicia S10 and by the Vicia extracts, and their activation resulted in an increase in SCEs. Benzo[a]pyrene, 2-aminofluorene, and maleic hydrazide were not activated. Aniline was activated, but without effect on the induction of SCEs. The activation capacity in vitro and in vivo of Vicia faba was not very pronounced, except for the activation of ethyl alcohol, when compared with that of rat-liver S9, and showed differences in activation for the 6 chemical agents tested.


Exposure to 4,4'-methylene bis (2-chloroaniline) (MbOCA) in New South Wales, Australia.
This study was conducted to determine the level of exposure of 4,4'-methylene bis (2-chloroaniline) (MbOCA) in New South Wales (NSW), Australia. An integrated occupational hygiene and biological monitoring program were used to assess the workers' exposure to MbOCA via inhalation, ingestion and dermal contact. This was conducted by personal air monitoring, static air monitoring and surface contamination monitoring of the work environment and biological monitoring of the workers' exposure to MbOCA at nine workplaces in NSW. The air monitoring results for MbOCA gave a geometric mean (GM) of 0.06 μg/m3 and a geometric standard deviation (GSD) of 2.70 and a 95% confidence interval of 0.29 μg/m3. The surface contamination in the main work area showed the highest contamination with a GM of 74 ng/cm2 and a GSD of 17 and a 95% confidence interval of 7,751 ng/cm2. Biological monitoring showed a GM of 0.89 μmol/mol cr and a GSD of 11.9 and a 95% confidence interval of 52 μmol/mol cr. This indicated that 13% of the workers were over the SafeWork NSW Biological Occupational Exposure Limit of 15 μmol/mol cr. Workers' exposure through inhalation was minimal; however, evidence from biological monitoring of MbOCA suggested that the main contributing factor to exposure was skin absorption. This was attributed to poor housekeeping and inadequate personal protection. Improvements in these areas were recommended, and it was also recommended to improve the awareness of the workers to the adverse effects to their health of exposure to this carcinogen.


Magnesium as an effective adjunct therapy for drug resistant seizures.
To explore the use of magnesium (Mg), an endogenous ion and enzymatic co-factor used in a variety of medical applications, for the treatment of epileptic seizures resistant to traditional medical therapy. For almost a century, Mg has been used as prophylaxis and treatment of seizures associated with eclampsia. Mg is a CNS depressant, with numerous functions intracellularly and extracellularly. However, because of the availability of well studied anticonvulsant drugs, Mg has not been tested widely in the treatment of epileptic seizures. A retrospective chart review of 22 cases of drug resistant epilepsy, where a trial of empiric oral Mg supplementation (mainly in the form of Mg-oxide) was conducted. Oral Mg supplementation was associated with a significant decrease in the number of seizure days per month, from 15.3 ± 13.2 (mean ± SD) to 10.2 ± 12.6 at first follow up (3-6 months, p=0.021), and to 7.8 ± 10.0 seizure days/month at second follow up (6-12 months, p=0.004). Thirty-six percent had a response rate of 75% or greater at second follow-up. Two patients reported seizure freedom. Most patients were well maintained on MgO 420 mg twice a day, or in 2 cases, Mg Lactate, without significant adverse effects, the most frequent being diarrhea (4/22). These results suggest that oral Mg supplementation may prove to be a worthwhile adjunctive medication in treating drug intractable epilepsy. A prospective, double-blinded, placebo controlled study is warranted to evaluate the potential of Mg for the treatment of drug-resistant seizures.


Experimental reconsideration of the utility of serum starvation as a method for synchronizing mammalian cells.
Accurate cell-size determinations support the prediction that serum starvation and related whole-culture methods cannot synchronize cells. Theoretical considerations predict that whole-culture methods of synchronization cannot synchronize cells. Upon serum starvation, the fraction of cells with a G1-phase amount of DNA increased, but the cell-size distribution is not narrowed. In true synchronization, the cell-size distribution should be narrower than the cell-size distribution of the original culture. In contrast, cells produced by a selective (i.e. non-whole-culture) method have a specific DNA content, a narrow size distribution, and divide synchronously. The general theory leading to the conclusion that whole-culture methods for synchronization do not work implies that one can generalize these serum-starvation results to other cell lines and other whole-culture methods, to conclude that these methods do not synchronize cells.


The effects of sevelamer and calcium acetate on proxies of atherosclerotic and arteriosclerotic vascular disease in hemodialysis patients.
We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated. To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year. The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate -2.5 +/- 1.8 mg/dl vs. sevelamer -2.8 +/- 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium > or =10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 +/- 2.1 g/day - equivalent to 1.2 +/- 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 +/- 350, median change +20, p = 0.002) and aorta (mean change 181 +/- 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects. Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients.