Purkinje network and myocardial substrate at the onset of human ventricular fibrillation: implications for catheter ablation.
Mapping data of human ventricular fibrillation (VF) are limited. We performed detailed mapping of the activities underlying the onset of VF and targeted ablation in patients with structural cardiac abnormalities. We evaluated 54 patients (50 ± 16 years) with VF in the setting of ischaemic (n = 15), hypertrophic (n = 8) or dilated cardiomyopathy (n = 12), or Brugada syndrome (n = 19). Ventricular fibrillation was mapped using body-surface mapping to identify driver (reentrant and focal) areas and invasive Purkinje mapping. Purkinje drivers were defined as Purkinje activities faster than the local ventricular rate. Structural substrate was delineated by electrogram criteria and by imaging. Catheter ablation was performed in 41 patients with recurrent VF. Sixty-one episodes of spontaneous (n = 10) or induced (n = 51) VF were mapped. Ventricular fibrillation was organized for the initial 5.0 ± 3.4 s, exhibiting large wavefronts with similar cycle lengths (CLs) across both ventricles (197 ± 23 vs. 196 ± 22 ms, P = 0.9). Most drivers (81%) originated from areas associated with the structural substrate. The Purkinje system was implicated as a trigger or driver in 43% of patients with cardiomyopathy. The transition to disorganized VF was associated with the acceleration of initial reentrant activities (CL shortening from 187 ± 17 to 175 ± 20 ms, P < 0.001), then spatial dissemination of drivers. Purkinje and substrate ablation resulted in the reduction of VF recurrences from a pre-procedural median of seven episodes [interquartile range (IQR) 4-16] to 0 episode (IQR 0-2) (P < 0.001) at 56 ± 30 months. The onset of human VF is sustained by activities originating from Purkinje and structural substrate, before spreading throughout the ventricles to establish disorganized VF. Targeted ablation results in effective reduction of VF burden. The initial phase of human ventricular fibrillation (VF) is critical as it involves the primary activities leading to sustained VF and arrhythmic sudden death. The origin of such activities is unknown. Body-surface mapping shows that most drivers (≈80%) during the initial VF phase originate from electrophysiologically defined structural substrates. Repetitive Purkinje activities can be elicited by programmed stimulation and are implicated as drivers in 37% of cardiomyopathy patients. The onset of human VF is mostly associated with activities from the Purkinje network and structural substrate, before spreading throughout the ventricles to establish sustained VF. Targeted ablation reduces or eliminates VF recurrence.


Differences in Fecal Microbiome and Antimicrobial Resistance between Captive and Free-Range Sika Deer under the Same Exposure of Antibiotic Anthelmintics.
This study aimed to compare the fecal microbiome and antimicrobial resistance between captive and free-range sika deer with the same exposure to antibiotic anthelmintics. The taxonomic differences mainly involved significant changes in the dominant phyla, genera, and species. Linear discriminant analysis effect size (LEfSe) analysis revealed that 22 taxa were significantly different between the two groups. The KEGG analysis showed that the fecal microbiome metabolic function, and all level 2 categories in metabolism had higher abundance in the free-range deer. Based on the carbohydrate-active enzyme (CAZy) database analysis, glycoside hydrolases and carbohydrate-binding modules showed remarkable differences between the two groups. Regarding antibiotic resistance, tetQ and lnuC dominated the antibiotic resistance ontology (ARO) terms, and tetracycline and lincosamide resistance dominated the antimicrobial resistance patterns. Furthermore, the lnuC, ErmF, and tetW/N/W AROs and lincosamide resistance showed higher abundance in the captive deer, suggesting that captivity may yield more serious resistance issues because of the differences in greenfeed diet, breeding density, and/or housing environment. The results also revealed important associations between the phylum Proteobacteria, genus Prevotella, and major antibiotic resistance genes. Although the present study was a pilot study with a limited sample size that was insufficient control for some potential factors, it serves as the metagenomic study on the microbial communities and antimicrobial resistance in sika deer. IMPORTANCE We used a metagenomic approach to investigate whether and how captive and free-range impact the microbial communities and antimicrobial resistance in sika deer. The results provide solid evidence of the significant impacts on the microbial composition and function in captive and free-range sika deer. Interestingly, although the sika deer had the same exposure to antibiotic anthelmintics, the antimicrobial resistances were affected by the breeding environment.


Criteria-based management of an acute multistructure knee injury in a professional football player: a case report.
Case report. Joint stiffness, also called arthrofibrosis, remains the primary complication following any reconstructive knee surgery. Acute anterior cruciate ligament surgery, performed with concomitant multiple ligamentous repair and/or reconstruction, further increases the likelihood of developing impaired knee motion following surgery. The purpose of this case report is to present a criteria-based approach to the postoperative management of a multiligament knee injury. A 25-year-old male professional football player sustained a contact injury to his right knee while making a tackle during a regular season game in 2007. He underwent an acute anterior cruciate ligament reconstruction, with concomitant posterolateral corner repair, biceps femoris/iliotibial band repair, lateral collateral ligament repair, and a medial meniscocapsular junction repair. He completed 17 weeks of a multiphased rehabilitation program that emphasized immediate range of motion, low-load long-duration stretching, therapeutic exercise, neuromuscular reeducation/perturbation training, plyometrics, and sport-specific functional drills. Electrical neurostimulation was implemented during the early stages of rehabilitation to control postoperative pain and to promote a steady progression of therapeutic exercise activity. The patient was cleared to begin sport-specific activity 7 months after major multistructure reconstructive knee surgery. He began the 2008 season on the physically-unable-to-perform list, but was activated midseason and played in every game thereafter. During the 2009 and 2010 seasons, he played all regular season games and all playoff games as a starter, and continues to start as a defensive cornerback in the National Football League. This case report highlights the clinical decision-making process and management involved in an acute multiple ligamentous knee injury/reconstruction. Therapy, level 4.


Underperformance of gallium-67 scan is greater in relapse than in initial staging, compared with FDG PET.
The purpose of this study is to evaluate the performance of gallium-67 scan (GS) and F-18 fluorodeoxyglucose (FDG) PET scan in lymphoma staging and recurrence detection by comparing the 2 imaging studies in the same patient. A total of 42 patients from the period between July 2002 and May 2006 were included in this study. Of the 42 patients, 6 had Hodgkin disease and 36 had non-Hodgkin lymphomas. All of them underwent one or more FDG PET scans and also underwent corresponding GS performed within 7 days of FDG PET, for staging or detection of lymphoma recurrence. Among the non-Hodgkin lymphoma cases, 18 were diffuse large B-cell lymphoma, 10 were follicular center cell lymphoma, and 8 were of other types. Of the total 46 pairs of imaging performed in these 42 patients, 27 were for staging, and 19 for restaging after recurrence. In all these studies, FDG PET detected 230 lesion sites, whereas GS detected 85 lesion sites. All of the lesions detected by GS were noted on FDG PET, whereas GS detected only 37.0% of the lesions detected by FDG PET. Among the 27 studies for staging, FDG PET detected 120 lesions, whereas GS detected 68 lesions (56.7%). In the 19 images taken for relapse, FDG PET detected 110 lesions, whereas GS detected only 17 (15.5%). FDG PET is superior to GS in staging and detecting all types of lymphoma. The difference is notably more significant in recurrence detection.


Context effects in visual length perception: role of ocular, retinal, and spatial location.
In three experiments, we examined the transfer of orientation-contingent context effects between the eyes and across portions of the retina with or without variation in external spatial location. Previous research had shown that vertical lines are judged long, relative to horizontal lines, when the stimulus set comprises relatively long horizontals and short verticals (Contextual Condition B), as compared with the reverse when the stimulus set comprises relatively short horizontals and long verticals (Contextual Condition A). Consequently, the contextual set of stimuli influences the magnitude of the horizontal-vertical illusion (HVI), decreasing its size under Contextual Condition A and increasing its size under Contextual Condition B. Experiment 1 showed that exposing one eye to different stimulus contexts modulated the size of the HVI at the exposed eye but had little or no effect at the other eye. Experiments 2 and 3 showed that the effect of the contextual sets generalized poorly across adjacent portions of the retina but transferred almost perfectly across different locations in external space when retinal location was constant. Thus, orientation-contingent context effects in visual length perception appear to be specific to the eye and to the region of the retina stimulated, suggesting that these effects reflect relatively early and local changes in sensitivity, rather than relatively late and general shifts in response criteria.


(Z)-7-Chloro-3-[(3-chlorophenyl)-methylidene]-4-p-tosyl-3,4-dihydro-2H-1,4-benzoxazine.
In the title compound, C22H17Cl2NO3S, the molecule is a substituted 3,4-dihydro-2H-1,4-benzoxazine compound which has three phenyl rings which are essentially planar. The 3,4-dihydro-2H-oxazine part of the molecule is fused to the benzo ring and has a half-boat conformation; the dihedral angle between the planar part of the oxazine ring and the benzo ring is 10.2 (2) degrees. The (3-chlorophenyl)methylidene substituent has a Z configuration in relation to the ring N atom of the oxazine moiety. Interestingly, the p-toluenesulfonyl (p-tosyl) substituent on the ring N atom protrudes away from the 3-chlorophenyl substituent thus avoiding any steric interaction.


Research Progress and Prospects of Autophagy in the Mechanism of Multidrug Resistance in Tumors.
Although the treatment of cancer has made great strides in clinical practice, its high morbidity and fatality rates remain a major threat to human health. Multidrug resistance (MDR) often appears in the process of tumor treatment, leading to tumor refractory and aggravating the risk of tumor recurrence. Therefore, antitumor MDR plays a key role in tumor chemotherapy. Autophagy is an important process for the turnover of intracellular materials, which is commonly seen in the treatment of sensitive and multidrug-resistant tumors, and it can play different roles in various types of MDR tumor cells and tissues. Autophagy plays a dual regulatory role in MDR tumors. On the one hand, autophagy can promote the formation of MDR in tumor cells, weaken the killing effect of chemotherapy drugs on tumor cells, and play a protective role in tumor survival. On the other hand, autophagy production in the cellular environment can kill MDR tumor cells, reverse tumor resistance and enhance the efficiency of chemotherapy drugs. Therefore, the regulation of autophagy to overcome MDR has become increasingly significant in tumor chemotherapy. In this article, we discussed and summarized the research progress of autophagy in MDR tumors, mainly involving the different characteristics of autophagy in MDR cancer cells.


Gastric artery apoplexy presenting as an acute abdomen in an adolescent.
Nontraumatic abdominal apoplexy, which is the occurrence of hemorrhage into the peritoneal cavity, is uncommon in the pediatric literature. Adult case reports of nontraumatic abdominal apoplexy include visceral artery aneurysms from the aorta, splenic, celiac, hepatic, gastric, and gastroepiploic arteries as well as gynecologic pathology. We identified 2 case reports of spontaneous abdominal apoplexy due to injury of the short gastric arteries in adult patients with histories of vomiting after alcohol consumption. This is the first reported case of nontraumatic abdominal apoplexy due to injury to the short gastric arteries in a pediatric patient.


Interior structure and seasonal mass redistribution of Mars from radio tracking of Mars Pathfinder.
Doppler and range measurements to the Mars Pathfinder lander made using its radio communications system have been combined with similar measurements from the Viking landers to estimate improved values of the precession of Mars' pole of rotation and the variation in Mars' rotation rate. The observed precession of -7576 +/- 35 milliarc seconds of angle per year implies a dense core and constrains possible models of interior composition. The estimated annual variation in rotation is in good agreement with a model of seasonal mass exchange of carbon dioxide between the atmosphere and ice caps.


Modeling shifts in microbial populations associated with health or disease.
Stable microbial communities associated with health can be disrupted by altered environmental conditions. Periodontal diseases are associated with changes in the resident oral microflora. For example, as gingivitis develops, a key change in the microbial composition of dental plaque is the ascendancy of Actinomyces spp. and gram-negative rods at the expense of Streptococcus spp. We describe the use of an in vitro model to replicate this population shift, first with a dual-species model (Actinomyces naeslundii and Streptococcus sobrinus) and then using a microcosm model of dental plaque. The population shift was induced by environmental changes associated with gingivitis, first by the addition of artificial gingival crevicular fluid and then by a switch to a microaerophilic atmosphere. In addition to the observed population shifts, confocal laser scanning microscopy also revealed structural changes and differences in the distribution of viable and nonviable bacteria associated with the change in environmental conditions. This model provides an appropriate system for the further understanding of microbial population shifts associated with gingivitis and for the testing of, for example, antimicrobial agents.


Galectin-3 and sST2 as Prognosticators for Heart Failure Requiring Extracorporeal Life Support: Jack n' Jill.
Extracorporeal life support provides perfusion for patients with heart failure to allow time for recovery, function as a bridge for patients to heart transplantation, or serve as destination therapy for long term mechanical device support. Several biomarkers have been employed in attempt to predict these outcomes, but it remains to be determined which are suitable to guide clinical practice relevant to extracorporeal life support. Galectin-3 and soluble suppression of tumorigenicity-2 (sST2) are two of the more promising candidates with the greatest supporting evidence. In this review, we address the similarities and differences between galectin-3 and sST2 for prognostic prediction in adults and children with heart failure requiring extracorporeal life support and highlight the significant lack of progress in pediatric biomarker discovery and utilization.


Regeneration Profiles of Olfactory Epithelium after SARS-CoV-2 Infection in Golden Syrian Hamsters.
Olfactory dysfunction is one of the most frequent and specific symptoms of coronavirus disease 2019 (COVID-19). Information on the damage and repair of the neuroepithelium and its impact on olfactory function after COVID-19 is still incomplete. While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the ongoing worldwide outbreak of COVID-19, little is known about the changes triggered by SARS-CoV-2 in the olfactory epithelium (OE) at the cellular level. Here, we report profiles of the OE after SARS-CoV-2 infection in golden Syrian hamsters, which is a reliable animal model of COVID-19. We observed severe damage in the OE as early as 3 days postinoculation and regionally specific damage and regeneration of the OE within the nasal cavity; the nasal septal region demonstrated the fastest recovery compared to other regions in the nasal turbinates. These findings suggest that anosmia related to SARS-CoV-2 infection may be fully reversible.


Metabolic correlates to pacemaker activity in the smooth muscle of guinea-pig mesotubarium.
Oxygen consumption (FO2) and lactate production (Flac) were measured during spontaneous activity in the guinea-pig mesotubarium. During spontaneous contractions FO2 increased to maximally 0.270 +/- 0.025 mumol min-1g-1 (n = 23), followed by a rapid fall immediately upon relaxation. In the relaxed period (5-15 min) between spontaneous contractions FO2 continued to slowly decrease by about 25% towards a final value of 0.150 +/- 0.01 mumol min-1g-1. Flac showed no consistent variation during the relaxed period. Ouabain (10(-6)M) produced a contracture, which was abolished by the Ca2(+)-antagonist felodipine (10(-6)M). In the presence of felodipine, addition of ouabain caused depolarization and a decrease of oxygen consumption by 21% and of lactate production by 31%. Exchange of glucose in the physiological Krebs solution for beta-hydroxybutyrate did not influence spontaneous activity, while subsequent addition of cyanide (2 mM) abolished contractions and caused a hyperpolarization of 15 mV. Blockade of ATP-dependent K+ channels by addition of glibenclamide (10(-7)M) to the relaxed muscle in this situation caused spontaneous contractile activity to reappear. In glucose-containing Krebs solution glibenclamide had no effect on the spontaneous contractile and electrical activity and contractions persisted after addition of cyanide. The relaxing and hyperpolarizing effect of pinacidil could be counteracted by addition of glibenclamide. The results suggest that a decrease in electrogenic Na+/K(+)-pump activity in the course of the relaxed period between contractions could contribute to the pacemaker behaviour. ATP-dependent K+ channels, while having little influence on the spontaneous contractile activity under normal metabolic conditions, could be activated during blockade of aerobic and anaerobic metabolism, leading to inhibition of pacemaker activity.


Use of a text of psychomotor ability in an expanded role.
To examine the use of a test of psychomotor ability of disabled persons, a group of 118 persons with permanent impairment of one hand were given the disability rating together with the O'Connor Finger Dexterity Test. Scores showed a substantial correlation of .69 between these two instruments. Scores on the Finger Dexterity Test were strongly correlated to the activities of daily living subscale of the Hand Disability Rating Scale (.88), while rating of disability was not. Age appeared unrelated to either test or disability scores.


Allosuppressor T lymphocytes abolish migration inhibition factor production in autoimmune thyroid disease: evidence from radiosensitivity experiments.
The ability of normal T lymphocytes to abolish the production of migration inhibition factor by antigen-sensitized T lymphocytes of Graves' disease (GD) and Hashimoto's thyroiditis (HT) in response to thyroid antigen has been studied by a modified migration inhibition factor test using isolated T lymphocytes alone. The production of migration inhibition factor was consistently abolished when normal T lymphocytes were mixed with GD or HT T lymphocytes in various ratios (1:9, 2:8, 5:5) as reported previously (Okita et al. 1980b). However, prior in-vitro irradiation (1000 rad) of the normal T lymphocytes resulted in loss of their ability to abolish migration inhibition factor production by the antigen-sensitized T lymphocytes of GD and HT. The effect is consistent with the radiosensitivity of suppressor T lymphocytes and indicates that the effect of normal T lymphocytes on GD and HT T lymphocytes is one of allosuppression. The results support the view that there is a defect in suppressor T cell function in GD and HT.


Development of a framework to derive effect-based trigger values to interpret CALUX data for drinking water quality.
Bioassays are increasingly being implemented for water quality monitoring as targeted chemical analyses are not always sufficient for the detection of all emerging chemicals or transformation products. However, the interpretation of bioassay results remains challenging, in particular because a positive response does not necessarily indicate that there may be an increased risk. For this purpose, effect-based trigger (EBT) values have been introduced as thresholds above which action needs to be undertaken to determine the cause of the response. The goals of this study were to (i) evaluate various approaches used to determine EBT values and (ii) based on the findings, derive human health EBT values for Chemical Activated LUciferase gene eXpression (CALUX) in vitro bioassays used for routine monitoring of water quality in the Netherlands. Finally, (iii) an uncertainty analysis was carried out to determine the protective power of the derived EBT values and the chance that potentially harmful substances might not be detected. EBT values that can be implemented in routine monitoring could be determined for four of eight selected bioassays. These EBT were compared to bioassay results from routine water quality monitoring carried out in the Netherlands. Furthermore, a framework for the calculation and evaluation of derived EBT values for routine application to monitor drinking water and its sources is proposed.


Clinico-prognostic implications of simultaneous increased serum levels of soluble CD23 and beta2-microglobulin in B-cell chronic lymphocytic leukemia.
Soluble CD23 (sCD23) and beta-2 microglobulin (beta2-m) are reliable prognostic parameters in B-cell chronic lymphocytic leukemia (CLL); however, their merit over well-established clinical variables such as clinical stages, bone marrow (BM) histology and lymphocyte doubling time (LDT) remains to be defined. Furthermore, information dealing with the impact on overall survival of the simultaneous increase of either beta2-m or sCD23 are lacking. In this prospective study based on 106 B-cell CLL patients, we propose a combination of beta2-m and sCD23 as a strong prognostic system whose statistical significance was mainly due to an excess of deaths in the subgroup displaying increased serum levels of either beta2-m or sCD23. Multivariate survival analysis confirmed the important dominant role of such a finding, thus excluding features with a high degree of codependence (i.e. clinical stages, LDT) and including variables with low association (i.e. BM histology) in the final regression model. The presence of increased serum levels of beta2-m/sCD23 and diffuse BM histology signified high-risk disease, whereas the absence of any adverse variable was associated with prolonged survival; in between there was a subgroup with only 1 characteristic which displayed an intermediate pattern of survival. Finally, on the basis combined increased serum levels of beta2-m and sCD23, a better stratification of low- and intermediate-risk patients could be obtained, thus allowing the formulation of a clinico-biological staging for CLL.


Development of fetal sheep pancreas after transplantation into athymic mice.
The capacity of the fetal sheep pancreas to grow and function when transplanted into athymic mice was examined to determine whether this source of tissue might be of potential use in reversing diabetes. For this purpose fetal sheep pancreases were obtained in the period between 50 days of gestation and fullterm (148 days). Explants (1 mm3) in organ culture secreted insulin for at least 7 days, but in steadily diminishing amounts. Acute exposure to arginine (10 mM) and theophylline (10 mM), but not glucose (20 mM), calcium chloride (10 mM), and sodium butyrate (10 mM), caused acute secretion of insulin. Explants survived for many months when grafted beneath the renal capsule of athymic mice, but their growth was less, the epithelial-like component smaller, and the percentage of endocrine cells (31 +/- 5%) fewer than the case of transplanted fetal human pancreas. The beta cell was the predominant endocrine cell in the ungrafted fetal sheep pancreas. In the transplanted fetal sheep pancreas this was not so, the alpha and PP cells being dominant--beta:alpha:delta:PP = 3:14:3:11. This pattern was unchanged when the recipient mice were hyperglycaemic--beta:alpha:delta:PP = 4:13:4:28, with no reduction of blood glucose levels being observed for up to 4 mo after transplantation. Altering the site of transplantation to the spleen or liver did not improve survival of the endocrine cells. Fetal sheep pancreatic explants when transplanted into athymic rats failed to survive. Thus, although the unusual pattern of endocrine differentiation in fetal sheep pancreas transplanted into athymic mice makes it an interesting model for further studies of fetal development, it is not of benefit in normalizing the blood glucose levels of the recipients.


Anaesthetic considerations for endoscopic retrograde cholangio-pancreatography procedures.
The purpose of this review is to evaluate the current literature on the use of general anaesthesia and propofol deep sedation for patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) procedures. Propofol is primarily an anaesthetic agent, but its use in a sedative capacity has resulted in the extensive off-label administration of this drug by gastroenterologists and other nonanaesthesia personnel. This has created controversy and enabled the gastroenterology community to gather evidence and campaign for US Food and Drug Administration approval to administer propofol to patients undergoing ERCP and other endoscopic procedures. General anaesthesia appears to be a well tolerated technique for patients undergoing ERCP procedures, although there is a scarcity of publications in this field. The available evidence from prospective and retrospective cohort studies suggests a low incidence of serious outcomes (from sedation-related incidents) in patients undergoing ERCP procedures under propofol deep sedation. However, data from the American Society of Anesthesiologists closed claims analysis report suggests that endoscopy procedures performed under monitored anaesthetic care using propofol as a sedative agent can result in serious patient harm. Deep sedation with propofol, administered by anaesthesia personnel, can be used as an alternative to general anaesthesia for a select group of patients undergoing ERCP procedures. Further research is necessary to clarify the nature and parameters of deep sedation.


Chronic cough: a respiratory viewpoint.
This article reviews the common causes and investigation of chronic cough and explores unexplained cough and its relationship to cough hypersensitivity. Cough plays a critical role in airway protection and clearance of secretions. Chronic cough, however, is a debilitating symptom that can significantly interfere with quality of life. Despite their limitations cough guidelines have raised the awareness of chronic cough as an important problem and provided a framework for a logical care pathway. The use of a systematic approach to diagnosis and management in a specialist clinic can result in successful identification as to the cause, with subsequent relief of symptoms. In a proportion of patients no diagnosis is reached or treatment fails. A common finding among these patients is cough reflex hypersensitivity and this is an important feature irrespective of the underlying diagnosis. The majority of patients referred to tertiary cough clinics are females. Women appear to have an intrinsically heightened cough response with augmented cough challenge and a high frequency of ACE-inhibitor cough. The way in which we review cough has undergone radical change in the last decade. A distinct population of patients with chronic idiopathic cough is emerging in whom cough reflex hypersensitivity is a feature. Extended co-operation between clinicians, scientists and the pharmaceutical industry is required to better understand the pathophysiology of the enhanced cough reflex and the development of more effective antitussive therapies.


Effects of soluble mediators generated during growth of the Landschütz ascites carcinoma on the chemotaxis of normal and Corynebacterium parvum-stimulated peritoneal leucocytes.
The influence of ascites fluid on the chemokinetic and chemotactic responses of mouse peritoneal leucocytes was investigated using modified Boyden chambers and the 'leading front' technique. The migration of normal cells towards endotoxin-activated mouse serum was significantly enhanced at high concentrations of fluid (40 and 20%) but was inhibited at lower concentrations (5 and 1%). By comparison, the chemotactic responsiveness of cells harvested 3 days after Corynebacterium parvum (C. parvum) injection was uniformly and more markedly increased over a wide range of fluid concentrations (0.1-50%). These effects were attributed to the presence of strong chemokinetic and chemotactic material in ascites fluid, which was not inactivated by heating. The activity was also demonstrated in the serum of tumour-bearing animals, was present to a much lesser extent in inflammatory exudate fluid and was absent from normal mouse serum. Detailed morphological studies of migrating cells revealed that although the ascites fluid contained a potent chemo-attractant for neutrophils, it inhibited the migration of mononuclear cells.


Auxin transport: a new synthetic inhibitor.
The new synthetic plant growth regulator DPX1840 (3,3a-dihydro-2-(p-methoxyphenyl)-8H-pyrazolo [5,1-a] isoindol-8-one) was examined for its effects on auxin transport. At a concentration of 0.5 mm in the receiver agar cylinders DPX1840 significantly inhibited the basipetal transport of naphthaleneacetic acid-1-(14)C in stem sections of Vigna sinensis Endl., Pisum sativum L., Phaseolus vulgaris L., Glycine max L., Helianthus annuus L., Gossypium hirsutum L., and Zea mays L. without significantly reducing total auxin uptake or recovery. The time sequence of the effect varied with the plant species. A similar inhibition of the basipetal movement of indoleacetic acid-1-(14)C was observed in intact seedlings of Phaseolus vulgaris L. In contrast to basipetal auxin transport DPX1840 had no significant effect on the acropetal movement of indoleacetic acid-1-(14)C in stem sections of Gossypium hirsutum L. Qualitatively the effect of DPX1840 on basipetal auxin transport was similar to that of other known auxin transport inhibitors. Quantitative differences, however, suggested the following order of activity: Naptalam>morphactin[unk]DPX1840>2,3,5-triiodobenzoic acid.DPX1840 also inhibited the lateral displacement of auxin. In horizontally placed stem sections of Helianthus annuus L. pretreated with DPX1840, the ratio of radioactivity from indoleacetic acid-1-(14)C in the upper versus the lower halves of the sections following basipetal indoleacetic acid-1-(14)C transport was approximately 50:50, whereas in the corresponding controls it was approximately 40:60.The data indicate that many of the characteristic effects of DPX1840 on plants, especially those which are known to involve auxin (e.g., epinasty, abscission, apical dominance, tropism), are due, at least in part, to its effects on auxin transport.


In vivo antioxidant and biochemical evaluation of Sphenocentrum jollyanum leaf extract in P. berghei infected mice.
Recent approach in treatment and drug development suggested that the control of oxidative stress in malarial infected patients may be an added advantage. In this study, effect of methanolic leaf extract of Sphenocentrum jollyanum pier (S. jollyanum) on liver damage, markers of oxidative stress and alteration in lipid profile in P. berghei infected mice was assessed. Oxidative stress was induced by intravenously inoculation of mice with 1 × 10⁷ sporozoites P. berghei. Treatment of parasitized mice with leaf extract of S. jollyanum had a significant (p<0.05) reductions in elevated levels of total protein, globulin, AST, ALT, ALP, GGT and total bilirubin, serum, kidney and liver malondialdehyde (MDA) concentrations, but caused a significant (p<0.05) increased in the activities of serum and liver catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) level when compared with parasitized non-treated group (PNT). The extract treated group also showed significant (p<0.05) improvement in the levels of HDLc, total cholesterol, LDL and reduction in triglyceride compared with parasitized non treated group. Our results revealed that the protective capacity and antioxidant activity of the extract is dose dependant. The findings suggest that antioxidant property of Sphenocentrum jollyanum leave extract might be an added advantage to it anti-malarial activity.


Electronegative LDL from Rabbits Fed with Atherogenic Diet Is Highly Proinflammatory.
Electronegative low-density lipoprotein (LDL(-)) has been found in the plasma of familial hypercholesterolemia and acute myocardial infarction and has been implicated in atherosclerosis and cardiovascular disease. However, less is known about the involvement of LDL(-) in atherosclerosis-related inflammation. This study aims at investigating the inducibility of LDL(-) by atherogenic diet in rabbits and at exploring the proinflammatory potential of the diet-induced LDL(-) in macrophages. Rabbits were fed with an atherogenic diet; LDL was isolated from plasma by NaBr density gradient ultracentrifugation and was then resolved into nLDL and LDL(-) by anion-exchange chromatography. Isolated nLDL and LDL(-) were directly used or incubated with 10 μM CuSO4 for 24 h to produce copper- (Cu-) ox-nLDL and Cu-ox-LDL(-). The effects of these LDLs on inflammation were evaluated in THP-1-derived macrophages. Macrophages were treated with nLDL, LDL(-), and extensively oxidized LDL (ox-LDL), then the levels of interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α in a culture medium were determined by ELISA, and the levels of total and phosphorylated IκB, p65, p38, JNK, and ERK in cell lysates were determined by Western blotting. The LDL(-) induced significantly higher levels of IL-1β, IL-6, and TNF-α in the medium. The levels of phosphorylated/total IκB, p65, p38, JNK, and ERK were also upregulated by LDL(-). In contrast, nLDL, Cu-ox-nLDL, and Cu-ox-LDL(-) exhibited much less effect. Knockdown of lectin-type oxidized LDL receptor- (LOX-) 1 resulted in significant reduction in LDL(-)-induced IL-1β, IL-6, and TNF-α. In addition, these LDL(-) effects were also markedly attenuated by inhibition of NF-κB and ERK1/2. The data suggested that LDL(-) induced inflammation through LOX-1-, NF-κB-, and ERK1/2-dependent pathways. Taken together, our results show that rabbits fed with atherogenic diet produce a highly proinflammatory LDL(-) that is more potent in inducing inflammation than nLDL and extensively oxidize LDL in macrophages. The results thus provide a novel link between diet-induced hypercholesterolemia and inflammation.


Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice.
Augmenting endothelial specific transport of the nitric oxide precursor L-arginine via cationic amino acid transporter-1 (CAT1) can prevent obesity related hypertension. We tested the hypotheses that CAT1 overexpression prevents obesity-induced hypertension by buffering the influence of the sympathetic nervous system (SNS) on the maintenance of arterial pressure and by buffering pressor responses to stress. Wild type (WT; n=13) and CAT1 overexpressing mice (CAT+; n=13) were fed a normal or a high fat diet for 20 weeks. Mice fed a high fat diet were returned to the control diet before experiments commenced. Baseline mean arterial pressure (MAP) and effects of restraint-, shaker- and almond feeding-stress and ganglionic blockade (pentolinium; 5 mg/kg; i.p.) on MAP were determined in conscious mice. Fat feeding increased body weight to a similar extent in WT and CAT+ but MAP was greater only in WT compared to appropriate controls (by 29%). The depressor response to pentolinium was 65% greater in obese WT than lean WT (P < 0.001), but was similar in obese and lean CAT+ (P = 0.65). In lean WT and CAT+, pressor responses to shaker and feeding stress, but not restraint stress, were less in the latter genotype compared to the former (P ≤ 0.001). Pressor responses to shaker and feeding stress were less in obese WT than lean WT (P ≤ 0.001), but similar in obese and lean CAT+. The increase in MAP in response to restraint stress was less in obese WT (22 ± 2%), but greater in obese CAT+ (37 ± 2%), when compared to respective lean WT (31 ± 3%) and lean CAT+ controls (27 ± 2%; P ≤ 0.02). We conclude that CAT1 overexpression prevents obesity-induced hypertension by reducing the influence of the SNS on the maintenance of arterial pressure but not by buffering pressor responses to stress.


Fabrication of Bi4O5Br2 photocatalyst for carbamazepine degradation under visible-light irradiation.
Bi4O5Br2 with irregular flake shape was synthesized by a facile and energy-saving hydrolysis method. Its band gap energy (Eg) was 2.1 eV. The formation mechanism was proposed. The Bi4O5Br2 exhibited superb visible-light-induced photocatalytic activity (>90%) toward the oxidation of carbamazepine. The kinetics rate constant (k) attained 0.0196 min-1. The effect of Bi4O5Br2 dosage, initial solution pH value, and inorganic anions on carbamazepine degradation was investigated. During the oxidation process, photogenerated holes (h+) and superoxide radical anions (•O2-) were the main active species. Based on the reaction intermediates results determined through a combined system of liquid chromatography and mass spectrometry, a possible reaction mechanism was speculated. The degree of contamination of carbamazepine solution after treatment was evaluated through the teratogenic effect experiment. After 120 min of visible light exposure, the carbamazepine solution is free of pollution. Also, the as-synthesized Bi4O5Br2 maintains good chemical stability and could be reused in the photodegradation process, indicating its potential in practical applications.


Cell Surfaces in Plant-Microorganism Interactions : VI. Elicitors of Ethylene from Colletotrichum lagenarium Trigger Chitinase Activity in Melon Plants.
Treatment of melon leaves or seedlings with elicitors of Colletotrichum lagenarium, a fungal pathogen of melon, increases chitinase activity. In treated leaves, chitinase is enhanced within the first 6 hours and becomes 2 to 10 times higher than in control leaves after 24 hours. Ethylene is increased simultaneously and is correlated with chitinase elicitation. In the presence of aminoethoxyvinylglycine, an inhibitor of ethylene synthesis, both elicitor-induced ethylene and elicitor-induced chitinase are inhibited. This inhibition is overcome by added exogenous ethylene. On the other hand, 1-aminocyclopropane-1-carboxylic acid the direct precursor of ethylene, triggers chitinase activity. Chitinase elicitation is thought to be a protein synthesis dependent process, as it does not occur in the presence of cycloheximide.


Locus of control and subjective well-being: Panel evidence from Australia.
This paper's aim is to propose a mediation framework and test whether lifestyle choices and social capital are pathways through which locus of control (LoC) affects subjective well-being. Using longitudinal data for Australia, we find that life satisfaction and mental health are explained by direct and indirect effects of LoC. The direct effect is positive, indicating that individuals with an internal LoC have higher levels of life satisfaction and mental health. We also show that physical activity and social interaction are two pathways linking an internal LoC to higher levels of well-being. Our findings provide new insights into the relationship between LoC and subjective well-being and suggest that, if the aim of policy is to improve well-being, the focus should be on enabling people to develop an internal LoC. This may lead to higher well-being both through the identified channels and, more importantly, through the direct channel of LoC.


Controllable one-step synthesis of spirocycles, polycycles, and di- and tetrahydronaphthalenes from aryl-substituted propargylic alcohols.
A novel, convenient, and efficient method has been developed for selective synthesis of spirocycle, polycycle, and di- and tetrahydronaphthalene systems from aryl-substituted propargylic alcohols by FeCl3- or TsOH-catalyzed multiple activations of unsaturated C-C bonds and C-H bonds.


High Carbapenem Resistance in Clinical Gram-Negative Pathogens Isolated in Egypt.
The emergence and spread of carbapenem-resistant gram-negative bacteria poses a serious threat to human health worldwide. Currently, little is known about the molecular mechanisms underlying carbapenem resistance and their prevalence among gram-negative bacteria in Egypt. In this study, we analyzed carbapenemase production in gram-negative bacteria isolated from hospitalized patients in Egypt in 2014. All isolates were subjected to phenotypic and genotypic susceptibility testing for carbapenem resistance. Our results indicated a high level of carbapenem-resistant gram-negative bacteria in Egypt, with 50.8% of the isolates harboring at least one carbapenem resistance gene. OXA-48-like and NDM-1 were the most prevalent carbapenemases, being detected in 49.2%, and 47.7% of carbapenemase-positive isolates, respectively, whereas Verona integron-encoded metallo-β-lactamase (VIM) was detected in only 26.2% of carbapenemase-positive isolates. This study reports for the first time carbapenemase-producing Serratia marcescens, Morganella morganii, and blaVIM-1-like-producing Pseudomonas aeruginosa in Egypt. It is also the first demonstration of the coexistence of different carbapenemases, being detected in 21.5% of carbapenemase-positive isolates. Effective antibiotic supervision, regional surveillance, and early detection of carbapenemase producers are imperative to prevent their future spread to epidemic levels.


Conventional ventilation modes with small pressure amplitudes and high positive end-expiratory pressure levels optimize surfactant therapy.
High-frequency oscillation studies have shown that ventilation at high end-expiratory lung volumes combined with small volume cycles at high rates best preserves exogenous surfactant and gas exchange in lavaged lungs. We investigated whether surfactant composition and gas exchange can also be preserved by conventional modes of mechanical ventilation, which combine high levels of positive end-expiratory pressure (PEEP) with small pressure amplitudes. Prospective, randomized, nonblinded, controlled study. Research laboratory. Thirty male Sprague-Dawley rats. Rats were lung-lavaged and treated with exogenous surfactant (100 mg/kg). After 5 mins, four different ventilator settings (F(IO)2 = 1.0) were applied for 3 hrs in four groups of rats [peak inspiratory pressure (cm H2O); static PEEP (cm H2O); inspiratory/expiratory ratio; frequency], as follows: 26/2/1:2/30 (group 26/2), 26/6/1:2/30 (group 26/6), 20/10/1:2/30 (group 20/ 10-static), and 20/6/7:3/130, creating an auto PEEP of 4 cm H2O (group 20/10-auto). In all groups, Pao2 increased immediately to prelavage values after surfactant therapy. In group 26/2, Pao2 deteriorated to postlavage values within 30 mins when PEEP was decreased to 2 cm H2O, whereas Pao2 remained stable for 3 hrs in the other groups. The Paco2 increased in groups 26/2 and 20/10-static; Paco2 could not be reduced by increasing ventilation frequency to 130 in group 20/10-static. Groups 26/6 and 20/10-auto remained normocapnic. Bronchoalveolar lavage protein concentration was higher in groups 26/2 and 26/6 compared with groups 20/10-static and 20/10-auto. There was significantly more conversion of surface active large aggregates into nonactive small aggregates in group 26/2 compared with groups 20/10-static and 20/10-auto. We conclude that exogenous surfactant composition is preserved by conventional modes of mechanical ventilation that use small pressure amplitudes, and adequate oxygenation is maintained by high end-expiratory pressure levels. Effective carbon dioxide removal can be achieved by applying a ventilation mode that creates auto PEEP and not by a mode that applies the same level of PEEP by static PEEP only.


Lipid-lowering and LDL-oxidation inhibitory effects of aqueous extract of freshwater clam (Corbicula fluminea)--using tilapia as an animal model.
A previous study has demonstrated that tilapia able to exhibit hyperlipidemia and hypercholesterolemia is a good model for the evaluation of beneficial effects of nutraceuticals. In this study, tilapia were used to evaluate the in vitro and in vivo effects of a hot water extract (FC-HW) of freshwater clam (Corbicula fluminea). FC-HW prolonged the lag phase of Cu(2+)-induced human and tilapia LDL oxidation. The prolongation of the lag phase was concentration-dependent in human (r(2)= 0.94) and tilapia LDL (r(2)= 0.98). The antioxidative potential of FC-HW was 0.33% (on a weight basis) of Trolox, a positive control. Male tilapia (n= 24) were randomly divided into 2 groups and separately fed for 60 d with an isocaloric also isoprotein diet containing 2% (w/w) FC-HW or a control diet. Body length and body mass were significantly higher in fish fed FC-HW than those of the control group (P < 0.05). Total triacylglycerol, cholesterol, and LDL-C in plasma of the FC-HW group were significantly lower (-89.9%, -61.8%, and -54.5%, respectively), while plasma total antioxidant capacity of the FC-HW group was higher and the lag phase in Cu(2+)-induced LDL oxidation was longer than those of the control group (P < 0.05). FC-HW demonstrated hypolipidemia and hypocholesterolemia effects and inhibited human LDL oxidation in vitro and tilapia LDL both in vitro and ex vivo, indicative that FC-HW can be a potential nutraceutical to reduce the risk factors of atherosclerosis.


A prospective trial of transjugular intrahepatic portasystemic stent shunts versus small-diameter prosthetic H-graft portacaval shunts in the treatment of bleeding varices.
The authors compare transjugular intrahepatic portasystemic stent shunts (TIPS) to small-diameter prosthetic H-graft portacaval shunts (HGPCS). Transjugular intrahepatic portasystemic stent shunts have been embraced as a first-line therapy in the treatment of bleeding varices due to portal hypertension, although they have not been compared to operatively placed shunts in a prospective trial. In 1993, the authors began a prospective, randomized trial to compare TIPS with HGPCSs. All patients had bleeding varices and had failed nonoperative management. Shunting was undertaken as definitive therapy in all. Failure of shunting was defined as an inability to accomplish shunting despite repeated attempts, unexpected liver failure leading to transplantation, irreversible shunt occlusion, major variceal rehemorrhage, or death. Mortality and failure rates were analyzed at 30 days (early) and after 30 days (late) using Fischer's exact test. There were 35 patients in each group, with no difference in age, gender, Child's class, etiology of cirrhosis, urgency of shunting, or incidence of ascites or encephalopathy between groups. In two patients, TIPS could not be placed despite repeated attempts. Transjugular intrahepatic portasystemic stent shunts reduced portal pressures from 32 +/- 7.5 mmHg (standard deviation) to 25 +/- 7.5 mmHg (p < 0.01), whereas HGPCS reduced them from 30 +/- 4.6 mmHg to 19 +/- 5.3 mmHg (p < 0.01; paired Student's test). Irreversible occlusion occurred in three patients after placement of TIPS. Total failure rate after TIPS placement was 57%; after HGPCS placement, it was 26% (p < 0.02). Both TIPS and HGPCS reduced portal pressure. Placement of TIPS resulted in more deaths, more rebleeding, and more than twice the treatment failures. Mortality and failure rates promote the application of HGPCS over TIPS.


Positive regulation of cdc2 gene activity by protein phosphatase type 2A.
Several lines of evidence indicate that serine/threonine protein phosphatases may act as negative regulators of cellular growth. For example, treatment of cells with the tumor-promoter okadaic acid, an inhibitor of certain types of these phosphatases, resulted in the increased expression of several proto-oncogenes, indicating a negative role of the respective phosphatases in gene regulation. However, it was puzzling to find that okadaic acid-treated cells, even in the presence of highly expressed proto-oncogenes, did not proliferate, but were arrested at certain points of the cell cycle. To further analyze this discrepancy, we investigated the involvement of protein phosphatases in the control of other cell cycle regulatory genes, such as cdc2 which encodes an essential cell cycle regulatory kinase. We found that cdc2 gene expression was blocked by okadaic acid, but stimulated by protein phosphatase 2A. Protein phosphatase 2A is shown to be a positive regulator of cdc2 gene activity and to be required for cdc2 expression. Thus, our findings identify protein phosphatase 2A as a positive regulator of a major cell cycle regulatory gene and therefore suggest a stimulatory role of this enzyme in this aspect of cellular growth control.


The reform of specialist training for general practice in the Czech Republic.
The aim of this paper is to describe the reform of General Practitioners' (GP) training in the Czech Republic (CR) and compare it with the recommendations of European institutions of General Practitioners and European Union (EU) legislation. The structures of the new Czech GP training (2007) were compared with the recommendations of The European Union of General Practitioners (UEMO), European Academy of Teachers in General Practice and the requirements set by the EU legislation. The comparison with other countries was based on data from the UEMO questionnaire distributed to its members. Data from representatives of institutions responsible for specialist training in the CR and from statistical offices in the CR were also used. The GP specialist training in the Czech Republic does not differ significantly when compared to the other UEMO countries, however, not all the recommendations of the European GP associations have been fulfilled. The reform of GP specialist training brought about positive changes but further developments are still needed. In our opinion, the next necessary step is the setting up of quality criteria for the assessment of GP specialist training and of the primary care as a whole.


[Prenatal diagnosis of meconium ileus and meconium peritonitis: indications for cystic fibrosis testing].
More recently, the regions of increased abdominal echogenicity such as echogenic bowel, meconium ileus and meconium peritonitis have been associated with an increased prevalence of a variety of unfavourable outcomes including chromosomal abnormalities, cytomegalovirus infection, intestinal obstruction, anorectal malformations and cystic fibrosis. Earlier prenatal examinations of these severe autosomal recessive diseases had been suggested only to families with history of cystic fibrosis. Recently, systemic examination has been introduced by ultrasound with bowel hyperechogenicity where the fetus is the index case for genetic disease. Risk for cystic fibrosis with this ultrasonography findings ranges from 0-33%. Two patients are presented, aged 24 and 29 years, both primigravide. The first one had ultrasonography finding of meconium peritonitis revealed at the 37th week of gestation and the other meconium ileus revealed on ultrasonography at the 29th week of gestation. Both patients had prenatal testing of foetal blood obtained by cordocenthesis, both had normal kariotype and were negative for cytomegalovirus infection. Parental DNA testing for the 2nd patient showed that parents were not carriers for the 29 most frequent mutations. Both neonates had intestinal obstruction, underwent surgery and early postoperative course was normal. Hystopathological finding suggested a possibility of cystic fibrosis for the 1st patient, but parents did not want to be tested and for the 2nd one congenital bowel stenosis as a cause of intestinal obstruction. Ultrasonographic echogenic bowel is an indication for invasive procedures for foetal blood testing for chromosomal abnormalities, congenital infections and parental testing for cystic fibrosis. Only if parental heterozygosity is proven foetus should be tested.


Direct compression behavior of low- and high-methoxylated pectins.
The objective of this study was to evaluate possible usefulness of pectins for direct compression of tablets. The deformation behavior of pectin grades of different degree of methoxylation (DM), namely, 5%, 10%, 25%, 35%, 40%, 50%, and 60% were, examined in terms of yield pressures (YP) derived from Heckel profiles for both compression and decompression and measurements of elastic recovery after ejection. All pectin grades showed a high degree of elastic recovery. DM 60% exhibited most plastic deformation (YP 70.4 MPa) whereas DM 5% (104.6 MPa) and DM 10% (114.7 MPa) least. However, DM 60% gave no coherent tablets, whereas tablet tensile strengths for DM 5% and DM 10% were comparable to Starch 1500. Also, Heckel profiles were similar to Starch 1500. For sieved fractions (180-250 and 90-125 mum) of DM 25% and DM 40% originating from the very same batch, YPs were alike, indicating minor effects of particle size. These facts indicate that DM is important for the compaction behavior, and batch-to-batch variability should also be considered. Therefore, pectins of low degree of methoxylation may have a potential as direct compression excipients.


R. v. Bernard, 15 December 1988.
The Supreme Court of Canada held that the offense of sexual assault causing bodily harm is a general intent offense; thus, the only intent that needs to be shown for conviction is that the accused intended to perform the act, and the defense of self-induced intoxication may not be considered.


Food and Beverage Availability in Small Food Stores Located in Healthy Food Financing Initiative Eligible Communities.
Food deserts are a major public health concern. This study aimed to assess food and beverage availability in four underserved communities eligible to receive funding from the Healthy Food Financing Initiative (HFFI). Data analyzed are part of a quasi-experimental study evaluating the impact of the HFFI on the retail food environment in selected Illinois communities. In 2015, 127 small grocery and limited service stores located in the four selected communities were audited. All communities had a large percentage of low-income and African-American residents. Differences in food and beverage item availability (e.g., produce, milk, bread, snack foods) were examined by store type and community location. Food stores had, on average, 1.8 fresh fruit and 2.9 fresh vegetable options. About 12% of stores sold low-fat milk while 86% sold whole milk. Only 12% of stores offered 100% whole wheat bread compared to 84% of stores offering white bread. Almost all (97%) stores offered soda and/or fruit juice. In summary, we found limited availability of healthier food and beverage items in the communities identified for HFFI support. Follow up findings will address how the introduction of new HFFI-supported supermarkets will affect food and beverage availability in these communities over time.


Fat-mobilizing action of amphetamine.
The effects of amphetamine and methamphetamine on plasma free fatty acid (FFA), blood glucose, serum total fat, and triglyceride concentrations were investigated in 21 subjects; the effect of epinephrine were studied in an identical manner in 14 subjects. The administration of amphetamine and methamphetamine led to an increase in the plasma FFA concentration. No significant changes were found in the blood glucose, serum total fat, and triglyceride concentrations. Kinetic studies of FFA were also made in some of the subjects receiving amphetamine, methamphetamine, and epinephrine. It was shown that amphetamine and methamphetamine lead to an augmentation of plasma FFA pool due to a primary increase of FFA production rate. Catecholamine depletion, by prolonged parenteral adminstration of reserpine, nearly completely abolished the adipokinetic action of amphetamine whereas the effect of epinephrine was greatly potentiated. This was interpreted as evidence for the dependence of the adipokinetic action of amphetamine on endogenous catecholamines. ESTIMATED FROM A DOSE RATIO (AMPHETAMINE: epinephrine) of 352:1, the relative adipokinetic potency of amphetamine, expressed as peak DeltaFFA rise, +DeltaFFA area, and DeltaFFA production rate, respectively, was found to be 55, 84, and 39% in comparison with the same effects of epinephrine. The more pronounced changes in +DeltaFFA area reflect the longer duration of action of amphetamine viz. epinephrine. This study demonstrates that amphetamine is an adipokinetic agent causing an increase in the plasma FFA pool of a lesser extent but of longer duration than equipressor doses of epinephrine. The mechanism of fat-mobilizing action of amphetamine is indirect i.e., dependent on endogenous catecholamine release.


Prognostic features of long-term survivors after surgical management of malignant pleural mesothelioma.
The primary aim of this study was to evaluate prognostic features of long-term survivors with pleural mesothelioma. Overall survival outcome was analyzed in 456 patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP), pleurectomy/decortications, or pleurodesis/biopsy with at least 18 months of follow-up. Prospectively collected clinicopathologic and treatment data were assessed for their correlations with actual 18-month survivors in both univariate and multivariate analyses. The actual 18-month survival was 28%. Epithelial subtype was present in 185 patients (41%) and nonepithelial subtype in 183 (40%). Procedures were EPP in 59 patients (13%), pleurectomy/decortication in 250 (55%), and pleurodesis/biopsy in 147 (32%). Forty-two patients (9%) underwent positron emission tomography (PET) scanning. Forty patients (9%) received adjuvant radiotherapy and 45 (10%) received postoperative pemetrexed combination chemotherapy. In univariate analysis, age 65 years or younger (p < 0.001), malignant pleural effusion (p = 0.041), epithelial subtype (p < 0.001), EPP (p < 0.001), PET scan (p = 0.012), adjuvant radiotherapy (p = 0.042), and postoperative pemetrexed combination chemotherapy (p = 0.035) were strongly associated with 18-month survivors. In multivariate analysis, epithelial histopathologic subtype (p < 0.001) and EPP (p < 0.001) were independently associated with 18-month survivors. The actual 18-month survival was 28% in 456 pleural mesothelioma patients who underwent operation. Epithelial histologic subtype and EPP were identified as independent predictors for 18-month survivors.


Effects of tamoxifen on striatal dopamine and 5-hydroxytryptamine release in freely moving male rats: an in-vivo microdialysis investigation.
Recent studies indicating interaction of oestrogens with central cholinergic, dopaminergic and 5-HTergic systems have led to the assumption of a protective role of oestrogens in certain neurodegenerative disorders. The non-steroidal drug tamoxifen, a mixed oestrogen agonist-antagonist, has been shown to modulate central nervous system functions in the corpus striatum. In this study we used a microdialysis technique to examine the effects of tamoxifen upon the striatal dopaminergic and 5-HTergic systems in intact freely moving male rats. The extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid were measured after intraperitoneal administration of either the control or tamoxifen, and were compared with their corresponding baseline levels. Significant 25-35% increases in the baseline levels of dopamine and 3,4-dihydroxyphenylacetic acid were observed after the highest doses of tamoxifen (1.5 mg kg(-1) and 30 mg kg(-1), respectively), whereas the lowest dose of tamoxifen (0.3 mg kg(-1)) elevated dopamine and 3,4-dihydroxyphenylacetic acid levels by a detectable 15% of the basal. In addition, the ratio of 3,4-dihydroxyphenylacetic acid-to-dopamine remained unchanged in comparison with that of the pretreatment levels. Whereas no change in the striatal 5-hydroxyindoleacetic acid concentrations was seen with the lowest and highest dose regimen, the intermediate dose elicited a moderate increase (20%) in basal 5-hydroxyindoleacetic acid levels. The pharmacological relevance of the effects of tamoxifen on the dopaminergic and 5-HTergic systems, as a prelude to the development of non-steroidal oestrogenic compounds in reducing the risk of neurodegenerative disorders such as Alzheimer's disease, is discussed.


Aluminates with Fluorinated Schiff Bases: Influence of the Alkali Metal⁻Fluorine Interactions in Structure Stabilization.
New heterometallic aluminium-alkali metal compounds have been prepared using Schiff bases with electron withdrawing substituents as ligands. The synthesis of these new species was achieved via the reaction of AlMe₃ with the freshly prepared alkali-metallated ligand. The derivatives formed were characterized by NMR in solution and by single crystal X-ray diffraction in the solid state. Aluminate derivatives with lithium and sodium were prepared and a clear influence of the alkali metal in the final outcome is observed. The presence of a Na···F interaction in the solid state has a stabilization effect and the species [NaAlMe₃L]₂ can de isolated for the first time, which was not possible when using Schiff bases without electron withdrawing substituents as ligands.


Genome Sequence of Striga asiatica Provides Insight into the Evolution of Plant Parasitism.
Parasitic plants in the genus Striga, commonly known as witchweeds, cause major crop losses in sub-Saharan Africa and pose a threat to agriculture worldwide. An understanding of Striga parasite biology, which could lead to agricultural solutions, has been hampered by the lack of genome information. Here, we report the draft genome sequence of Striga asiatica with 34,577 predicted protein-coding genes, which reflects gene family contractions and expansions that are consistent with a three-phase model of parasitic plant genome evolution. Striga seeds germinate in response to host-derived strigolactones (SLs) and then develop a specialized penetration structure, the haustorium, to invade the host root. A family of SL receptors has undergone a striking expansion, suggesting a molecular basis for the evolution of broad host range among Striga spp. We found that genes involved in lateral root development in non-parasitic model species are coordinately induced during haustorium development in Striga, suggesting a pathway that was partly co-opted during the evolution of the haustorium. In addition, we found evidence for horizontal transfer of host genes as well as retrotransposons, indicating gene flow to S. asiatica from hosts. Our results provide valuable insights into the evolution of parasitism and a key resource for the future development of Striga control strategies.


Studies on the biosynthesis of phenols in fungi. Biosynthesis of 3,4-dimethoxy-6-methyltoluquinol and gliorosein in Gliocladium roseum I.M.I. 93 065.
1. Gliorosein was obtained in excellent yield (150mg./200ml. of Raulin-Thom medium) from surface cultures of Gliocladium roseum. Its nuclear-magnetic-resonance spectrum showed conclusively that it is 1,6-dihydro-3,4-dimethoxy-6-methyltoluquinone. 2. Sodium [2-(14)C]acetate was incorporated into gliorosein and the related products (3.3% conversion). The specific activities of these substances increased in the order gliorosein, 3,4-dimethoxy-6-methyltoluquinol, the related quinhydrone and quinone, indicating that gliorosein was the actual metabolite that was secreted and that the other compounds were derived from it in the medium. 3. 6-Methylsalicylic acid was not taken up by the mycelium and could be recovered unchanged. Orsellinic acid was decarboxylated by G. roseum and an equivalent amount of orcinol was secreted into the medium. The methyl esters of 6-methylsalicylic acid and orsellinic acid were both hydrolysed by an esterase present in the mycelium. Some of the 6-methylsalicylic acid thus produced was secreted into the medium and the orsellinic acid was decarboxylated. 4. Washed mycelium of G. roseum converted aurantiogliocladin and 3,4-dimethoxy-6-methyltoluquinol quantitatively into gliorosein within 18hr. More critical experiments with (14)C-labelled substrates demonstrated that 3-hydroxy-4-methoxy-6-methyltoluquinol and 3,4-dimethoxy-6-methyltoluquinol, and their respective quinones, were effectively incorporated into gliorosein and related products (49, 68, 30 and 57% respectively). 5. The following sequence of reactions is proposed for the biosynthesis of gliorosein: acetyl-CoA+3 malonyl-CoA+S-adenosyl-methionine --> 5-methylorsellinic acid --> 3-hydroxy-4-methoxy-6-methyltoluquinol --> 3,4-dimethoxy-6-methyltoluquinol --> gliorosein. 6. Since gliorosein is optically active (dextrorotatory), the final tautomerization reaction leading to its formation must be enzyme-catalysed.


[Own clinical observations of toxocara infections].
Toxocarosis clinical forms wers diagnosed according to Kraus et. al. (1995). There were three forms: 1) asymptomatic - marked by hypereosynophilia and ELISA positive serologic reaction, 2) minor - with cutaneous, pulmomary and pseudorheumatic lesions, 3) major - with hepatosplenomegaly and multifocal inflammatory lesions of organ of sight. Over the years of 1994-1997 in Infectious, Parasitic and Tropical Diseases clinic of the Voivodship Specialist Hospital of Lódź we found and treated 137 Toxocara canis cases. Among them 63 (46:0%) asymptomatic, 57 (42.6%) minor and 17 (12.4%) major forms were diagnosed. The disease was detected in 80 (58.4%) adults and 57 (41.6%) children. Seventy six patients lived in towns and 61 in country. Minor form patients had the symptoms as follows: skin allergy, large joints lesions, augmentation in lymph nodes. Radiology examinations revealed pulmonary lesions. Using ultrasonography there was found hepatosplenomegaly and changes echogenity in patients with major form. Biochemical tests showed elevation in hepatic enzymes activity. Lesions of organ of sight were multifocal and usually included uveitis, retinitis, inflammation of anterior chamber and inflammation of vitreous body.


Adaptive noise.
In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise and that noise may be adaptive. For example, gene networks can generate bistable states resulting in phenotypic diversity and switching among individual cells of a genotype, which may be a bet hedging strategy. Here, we review the sources of noise in gene expression, the extent to which noise in biological systems may be adaptive and suggest that applying evolutionary rigour to the study of noise is necessary to fully understand organismal phenotypes.


Antiproliferative and apoptosis inducing effects of citral via p53 and ROS-induced mitochondrial-mediated apoptosis in human colorectal HCT116 and HT29 cell lines.
Despite various anticancer reports, antiproliferative and apoptosis inducing activity of citral in HCT116 and HT29 cells have never been reported. This study aimed to evaluate the cytotoxic and apoptosis inducing effects of citral in colorectal cancer cell lines. The citral-treated cells were subjected to MTT assay followed by flow cytometric Annexin V-FITC/PI, mitochondrial membrane potential and intracellular reactive oxygen species (ROS) determination. The apoptotic proteins expression was investigated by Western blot analysis. Citral inhibited the growth of HCT116 and HT29 cells by dose- and time-dependent manner without inducing cytotoxicity in CCD841-CoN normal colon cells. Flow cytometric analysis showed that citral (50-200μM; 24-48h) induced the externalization of phoshpotidylserine and reduced the mitochondrial membrane potential in HCT116 and HT29 cells. Citral elevated intracellular ROS level while attenuating GSH levels in HCT116 and HT29 cells which were reversed with N-acetycysteine (2mM) pre-treatment indicating that citral induced mitochondrial-mediated apoptosis via augmentation of intracellular ROS. Citral induced the phosphorylation of p53 protein and the expression of Bax while decreasing Bc-2 and Bcl-xL expression which promoted the cleavage of caspase-3. Collectively, our data suggest that citral induced p53 and ROS-mediated mitochondrial-mediated apoptosis in human colorectal cancer HCT116 and HT29 cells.


Cytoskeletal gene expression in normal and neoplastic human odontogenic epithelia.
In situ and Northern hybridization was carried out to study cytokeratin (Ck) 1, 4, 8, 18, and 19 and vimentin (Vim) gene expression in 13- to 24-week-old human fetal tooth germs, including overlying oral epithelium and odontogenic tumors (N = 6) of epithelial (ameloblastoma) and epithelial-ectomesenchymal (ameloblastic fibroma) origin. The results were compared with immunocytochemistry using monoclonal antibodies. A relatively strong expression of simple epithelial Ck 19 mRNA, together with low, but significant expression of Ck 8 and 18 mRNAs, was demonstrated in all normal and neoplastic odontogenic epithelia studied. Transcripts for squamous differentiation marker, Ck 4, and for terminal differentiation marker, Ck 1, were detected suprabasally in the fetal oral epithelium, focally in the dental lamina but not in the enamel organ. Ck 4 mRNA was expressed variably in most odontogenic tumors studied, whereas Ck 1 mRNA was detected in one ameloblastoma only. Vim mRNA was not found in the fetal oral epithelia, dental lamina or the enamel organ, but a distinct immunoreactivity with monoclonal antibodies to Vim was seen in the stellate reticulum cells of the enamel organ. The epithelium of most ameloblastomas showed a focal Vim mRNA and polypeptide expression. In addition to Vim, the neoplastic ectomesenchymal cells of ameloblastic fibroma coexpressed low amounts of simple epithelial Cks 8, 18, and 19. The results indicate that the differentiation and cytoskeletal gene expression programs of odontogenic epithelia upon neoplastic transformation are not fully retained. Most ameloblastomas and ameloblastic fibromas show differentiation parameters reminiscent of dental lamina. Ameloblastomas seem to form a heterogenous group of tumors, which may originate from odontogenic epithelial cells at various differentiation levels. The origin of ameloblastic fibroma is more closely related to the tooth germ proper.


Is there a place for nebulised magnesium sulphate in the management of asthma?
Intravenous magnesium sulphate (MgSO4) is an accepted part of the pharmacological management of patients with asthma. There is conflicting information, however, on whether its nebulised form is beneficial. This article describes a case study in which a patient was given intravenous MgSO4. It was suggested by a medical consultant that she could have been given nebulised MgSO4, so a literature review was undertaken to examine its efficacy. The results suggest there is no evidence to support the use of nebulised MgSO4 in the management of patients with asthma.


Smart multifunctional nanostructure for targeted cancer chemotherapy and magnetic resonance imaging.
Targeted chemotherapy and magnetic resonance imaging of cancer cells in vitro has been achieved using a smart multifunctional nanostructure (SMN) constructed from a porous hollow magnetite nanoparticle (PHMNP), a heterobifunctional PEG ligand, and an aptamer. The PHMNPs were prepared through a three-step reaction and loaded with the anticancer drug doxorubicin while being functionalized with PEG ligands. Targeting aptamers were then introduced by reaction with the PEG ligands. The pores of the PHMNPs are stable at physiological pH, but they are subject to acid etching. Specific binding and uptake of the SMN to the target cancer cells induced by aptamers was observed. In addition, multiple aptamers on the surface of one single SMN led to enhanced binding and uptake to target cancer cells due to the multivalent effect. Upon reaching the lysosomes of target cancer cells through receptor-mediated endocytosis, the relatively low lysosomal pH level resulted in corrosion of the PHMNP pores, facilitating the release of doxorubicin to kill the target cancer cells. In addition, the potential of using SMN for magnetic resonance imaging was also investigated.


The ins and outs of serine and glycine metabolism in cancer.
Cancer cells reprogramme their metabolism to support unrestrained proliferation and survival in nutrient-poor conditions. Whereas non-transformed cells often have lower demands for serine and glycine, several cancer subtypes hyperactivate intracellular serine and glycine synthesis and become addicted to de novo production. Copy-number amplifications of serine- and glycine-synthesis genes and genetic alterations in common oncogenes and tumour-suppressor genes enhance serine and glycine synthesis, resulting in high production and secretion of these oncogenesis-supportive metabolites. In this Review, we discuss the contribution of serine and glycine synthesis to cancer progression. By relying on de novo synthesis pathways, cancer cells are able to enhance macromolecule synthesis, neutralize high levels of oxidative stress and regulate methylation and tRNA formylation. Furthermore, we discuss the immunosuppressive potential of serine and glycine, and the essentiality of both amino acids to promoting survival of non-transformed neighbouring cells. Finally, we point to the emerging data proposing moonlighting functions of serine- and glycine-synthesis enzymes and examine promising small molecules targeting serine and glycine synthesis.


AnoXcel: an Anopheles gambiae protein database.
The proteome of the mosquito Anopheles gambiae was organized on a hyperlinked spreadsheet format containing one protein per row and several pieces of information in each column. The information for each protein ranges from the presence or absence of signal peptide indicative of secretion, presence of transmembrane domains, similarities to several databases, chromosomal location, and relatedness to other An. gambiae proteins, etc. Hosted by AnoBase (http://www.anobase.org/), the whole spreadsheet or segments of it can be downloaded or searched from http://www.anobase.org/AnoBase/Genes/Ano-Xcel by the scientist dealing with the annotation of proteome subsets such as those deriving from transcriptomes, nucleotide microarrays or high throughput mass spectrometry data.


Manual Closed Reduction of Incarcerated Hernia: Is It Safe in the Emergency Department?
Emergency surgical repair is the standard approach to the management of an incarcerated abdominal wall hernia (IAWH). In cases of very high-risk patients, manual closed reduction (MCR) of IAWH may prevent the need for emergency surgery. To evaluate the safety, success rate, and complications of MCR in the management of IAWH conducted in an emergency department. The data of all patients who underwent MCR between 2012 and 2018 were retrospectively collected. Patient demographics, presenting symptoms, clinical parameters, and management during the hospitalization were retrieved from the medical charts. Overall, 548 patients underwent MCR during the study period. The success rate was 25.4% (139 patients). One patient had a complication that required a laparotomy 2 days after his discharge. A recurrent incarceration occurred in 23%, 60% of them underwent successful repeated MCR and the others underwent emergency surgery. Six patients (1.4%) had a bowel perforation after a failed MCR. MCR can be performed safely in the emergency department and should be consider as an option to treat IAWH, especially in high operative risk patients.


Contingencies of UTX/KDM6A Action in Urothelial Carcinoma.
The histone demethylase Ubiquitously Transcribed Tetratricopeptide Repeat Protein X-Linked (UTX/KDM6A) demethylates H3K27me2/3 at genes and enhancers and is often inactivated by mutations in urothelial carcinoma (UC). The consequences of its inactivation are however poorly understood. We have investigated the consequences of moderate UTX overexpression across a range of UC cell lines with or without mutations in KDM6A or its interaction partners and in a normal control cell line. Effects on cell proliferation, especially long-term, varied dramatically between the cell lines, ranging from deleterious to beneficial. Similarly, effects on global gene expression determined by RNA-Seq were variable with few overlapping up- or downregulated genes between the cell lines. Our data indicate that UTX does not act in a uniform fashion in UC. Rather, its effect depends on several contingencies including, prominently, the status of KMT2C and KMT2D which interact with UTX in the COMPASS complex. In particular, we provide evidence that these factors determine the amount of nuclear UTX.


Extraskeletal Mesenchymal Chondrosarcoma of Central Nervous System - A Rare but Aggressive Tumor: Analysis of Five Cases.
Extraskeletal mesenchymal chondrosarcoma (MCS) of the central nervous system (CNS) is extremely rare. Herein, we present the clinicopathological features of five CNS extraskeletal MCS. Over the past 10 years, five cases of CNS MCS have been retrieved from in the archives of histopathology department. All biopsies were stained with vimentin, S-100, CD99, desmin, GFAP, INI1, WT1, STAT6, and EMA. There were four males and one female patient in the age group of 1.5-35 years. The clinical and radiological impression was meningioma in three cases, glomus jugulare and primitive neuroectodermal tumor in one case each. All showed classic biphasic morphology, areas of undifferentiated small blue round cells sharply demarcated from the island of cartilage. Three patients experienced multiple recurrences and died subsequently. Extraskeletal MCS of CNS is rare and favors children and young adults. They show aggressive behavior and tend to recur despite surgery and radiotherapy.


Rapid, Cheap, and Effective COVID-19 Diagnostics for Africa.
Although comprehensive public health measures such as mass quarantine have been taken internationally, this has generally been ineffective, leading to a high infection and mortality rate. Despite the fact that the COVID-19 pandemic has been downgraded to epidemic status in many countries, the real number of infections is unknown, particularly in low-income countries. However, precision shielding is used in COVID-19 management, and requires estimates of mass infection in key groups. As a result, rapid tests for the virus could be a useful screening tool for asymptomatic virus shedders who are about to come into contact with sensitive groups. In Africa and other low- and middle-income countries there is high rate of COVID-19 under-diagnosis, due to the high cost of molecular assays. Exploring alternate assays to the reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19 diagnosis is highly warranted. This review explored the feasibility of using alternate molecular, rapid antigen, and serological diagnostic assays to accurately and precisely diagnose COVID-19 in African populations, and to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR diagnostic challenges in Africa. We reviewed publications from internet sources and searched for appropriate documents available in English. This included Medline, Google Scholar, and Ajol. We included primary literature and some review articles that presented knowledge on the current trends on SARS-CoV-2 diagnostics in Africa and globally. Based on our analysis, we highlight the utility of four different alternatives to RT-PCR. These include two isothermal nucleic acid amplification assays (loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA)), rapid antigen testing, and antibody testing for tackling difficulties posed by SARS-CoV-2 RT-PCR testing in Africa. The economic burden associated COVID-19 mass testing by RT-PCR will be difficult for low-income nations to meet. We provide evidence for the utility and deployment of these alternate testing methods in Africa and other LMICs.


Birth and death processes with random environments in continuous time.
"A generalization to continuous time is given for a discrete-time model of a birth and death process in a random environment. Some important properties of this process in the continuous-time setting are stated and proved including instability and extinction conditions, and when suitable absorbing barriers have been defined, methods are given for the calculation of extinction probabilities and the expected duration of the process."


High-dose barbiturates for intracranial pressure control.
Approximately 10% of severely head-injured patients will manifest elevated intracranial pressure uncontrollable by any currently known medical or surgical treatments, with a resulting mortality of > 90%. High-dose barbiturate therapy used in this setting has been shown to control intracranial pressure and reduce mortality in a small but definite number of patients. The pharmacologic, physiologic, and systemic effects of high-dose barbiturates must be fully appreciated, and appropriate clinical safeguards must be established when this therapy is implemented after severe head injury.


Evaluation of a clinical guideline for the diagnoses of physical and chronic urticaria and angioedema.
In this retrospective study, the feasibility and implementation of a clinical guideline was evaluated in 130 consecutive patients with chronic urticaria. We analysed how often a questionnaire was used, how often routine laboratory tests were performed and on what information (history-taking, detailed questionnaire, laboratory or provocation tests) the diagnosis was made. In this validation sample, the number of identified diagnoses was compared with the number of identified diagnoses of a prospective study previously performed in the same hospital. A cause was identified in 58 patients (45%): 43 of these had physical urticaria and 15 had chronic urticaria. In 50 of the 58 patients (86%) the cause was identified by history-taking and in 8 patients by additional use of the questionnaire. In 38 patients the questionnaire was not in the patient's file. In 89 of 130 patients (68%), laboratory tests were performed without a reason suggested by the patients' history. This did not reveal a cause in any patient. In general, the diagnostic guideline was followed reasonably well. In identifying a cause of urticaria, careful history-taking was important; routine laboratory tests were not helpful. A detailed questionnaire is presented in an appendix.


[Chemotherapy of testicular cancer].
The incidence of testicular tumours is low. It is the most frequent tumour among men between the age of 15 and 44. A risk factor for a testicular tumour is abnormal development of a testicle, for example cryptorchidism. In case of doubt about the diagnosis a scrotal sonography is nearly 100% accurate. The treatment and final prognosis are determined by the histological type and presence or absence of retroperitoneal and/or lung metastasis. Two-thirds of the patients have a chance of cure of over 90%. Standard treatment for a patient with a metastasized non-seminoma and the more extensive forms of metastasized seminoma is chemotherapy with 4 courses of bleomycin, etoposide and cisplatin. Long-term side effects are limited to polyneuropathy in hands and feet in some of the patients. Reduction in fertility appears to be temporarily, the risk for offspring seems nil. In good prognosis patients toxicity can be decreased by reduction of the number of chemotherapy cycles or of the dose of bleomycin. In the poor prognosis subset new drugs may improve the prognosis but to date clear results are lacking. Second-line chemotherapy is only possible with attention for the cumulative bone marrow toxicity; autologous bone marrow rescue or growth factors can diminish this.


Method development for the determination of arsenic by sequential injection/anodic stripping voltammetry using long-lasting gold-modified screen-printed carbon electrode.
An automated method has been developed for determining the concentration of inorganic arsenic. The technique uses sequential injection/anodic stripping voltammetry with a long-lasting gold-modified screen-printed carbon electrode. The long-lasting gold electrode was electrochemically deposited onto a screen-printed carbon electrode at a potential of -0.5 V vs. Ag/AgCl in a supporting electrolyte solution of 1M hydrochloric acid. Under optimal conditions and the applied potentials, the electrode demonstrated that it can be used for a long time without a renewal process. The linear range for the determination of arsenic(III) was 1-100 μg L(-1), and the limit of detection (LOD) in standard solutions was as low as 0.03 μg L(-1) for a deposition time of 120 s and sample volume of 1 mL. This method was used to determine the concentration of arsenic(III) in water samples with satisfactory results. The LOD in real samples was found to be 0.5 μg L(-1). In addition, speciation between arsenic(III) and arsenic(V) has been achieved with the proposed method using deposition potentials of -0.5 V and -1.5 V for the determination of the arsenic(III) concentration and the total arsenic concentration, respectively; the results were acceptable. The proposed method is an automated system that offers a less expensive alternative for determining trace amounts of inorganic arsenic.


Unraveling the Mystery of Erythropoietin-Stimulating Agents in Cancer Promotion.
Erythropoietin-stimulating agents (ESA) are approved for use in treating chemotherapy-induced anemia in patients with nonmyeloid malignancies. However, recent clinical trials have shown evidence of inferior overall survival and/or locoregional control of tumors in patients receiving ESAs. Given these concerning data, current studies are focused on elucidating the biological mechanisms by which ESAs may contribute to cancer promotion. Evidence suggests that ESAs activate several signaling pathways that are important in altering tumor behavior and response to treatment. Although further research is needed to more precisely elucidate these mechanisms, caution should be exercised in the use of ESAs beyond their approved indication in cancer patients. [Cancer Res 2008;68(11):4013-7].


Aroma Acupoint Therapy for Symptom Management with Adolescent Patients: Early Experiences from School-Based Health Centers.
Objectives: The American Academy of Pediatrics has long recognized a need for more resources for integrative medicine for health care providers and for patients. The aim of this study was to introduce Aroma Acupoint Therapy (AAT)-a relatively new integrative medicine modality using essential oils to activate acupoints-and to describe the early experiences of providers using AAT for adolescents at school-based health centers (SBHCs). Materials and Methods: This was a case series of 15 adolescents treated with 1 of 2 AAT specific protocols plus standard medical therapy between April 2018 and February 2019 at SBHCs. Of these 15 patients, ages 12-19, 14 were female. Clinical characteristics and treatment courses were abstracted by retrospective review of the patients' electronic medical records. The main outcomes and measures for this research were clinical characteristics, treatment courses and pre- and post-treatment pain scores for adolescents treated with AAT. Results: All 15 patients had nonspecific symptoms, including headaches, menstrual cramps, nausea, shortness of breath, chest pain, back pain, or dizziness. Pain scores were recorded in 8 of 15 encounters, and suggested improvements in most patients. Subjective documentation by the providers also suggested that most of these patients had reduced symptoms. Conclusions: With the call for nonopiate and integrative approaches to pain management, there is an urgent need to study the effectiveness of such modalities, such as AAT. It is safe, inexpensive, easy to learn, and is well-received by both health care providers and patients.


Somatosensory interactions reveal feature-dependent computations.
Our ability to perceive and discriminate textures is based on the processing of high-frequency vibrations generated on the fingertip as it scans across a surface. Although much is known about the processing of vibration amplitude and frequency information when cutaneous stimulation is experienced at a single location on the body, how these stimulus features are processed when touch occurs at multiple locations is poorly understood. We evaluated participants' ability to discriminate tactile cues (100-300 Hz) on one hand while they ignored distractor cues experienced on their other hand. We manipulated the relative positions of the hands to characterize how limb position influenced cutaneous touch interactions. In separate experiments, participants judged either the frequency or intensity of mechanical vibrations. We found that vibrations experienced on one hand always systematically modulated the perception of vibrations on the other hand. Notably, bimanual interaction patterns and their sensitivity to hand locations differed according to stimulus feature. Somatosensory interactions in intensity perception were only marked by attenuation that was invariant to hand position manipulations. In contrast, interactions in frequency perception consisted of both bias and sensitivity changes that were more pronounced when the hands were held in close proximity. We implemented models to infer the neural computations that mediate somatosensory interactions in the intensity and frequency dimensions. Our findings reveal obligatory and feature-dependent somatosensory interactions that may be supported by both feature-specific and feature-general operations. NEW & NOTEWORTHY Little is known about the neural computations mediating feature-specific sensory interactions between the hands. We show that vibrations experienced on one hand systematically modulate the perception of vibrations felt on the other hand. Critically, interaction patterns and their dependence on the relative positions of the hands differed depending on whether participants judged vibration intensity or frequency. These results, which we recapitulate with models, imply that somatosensory interactions are mediated by feature-dependent neural computations.


One «Both» Sex«es»: Observations, suppositions, and airy speculations on fetal sex anatomy in British scientific literature, 1794-1871.
The hegemony of the two-sex paradigm in the European scientific imagination and wider culture did not automatically equate to the hegemony of two discrete genders. In fact, two sexes facilitated a variety of gender choices: two singular and a number of double or otherwise intersexed (most commonly referred to as "hermaphrodite" or "bisexual" in its anatomical sense). This article explores some key British medical and allied scientific texts, with reference to associated Continental literature, as a means of illustrating the complexity of the two-sex paradigm and the unexpected transformation of gender possibilities that it helped produce through the early and middle decades of the nineteenth century. Discourses surrounding the first direct observations of the earliest development of fetal urinogenital anatomy were pivotal. The prevailing view that the incipient embryo was sexually undifferentiated (a paragon of the one-sex paradigm) was challenged by the Edinburgh anatomist Robert Knox, initially as he sought to bolster his professional reputation at the height of the Burke and Hare "body-snatching" scandal. Knox suggested that every embryo began life in an essentially dual-sexed state, an individual's sex anatomy depending on the greater or lesser development of component female and male structures. Greater clarification on the contested status of the homology-hermaphrodite distinction was achieved with the discovery of the early co-existence of the excretory duct of the Wolffian body (mesonephric duct) and the Müllerian duct (paramesonephric duct), an observation that made anatomical bisexuality difficult to ignore. The nineteenth-century's greatest champion of primordial hermaphroditism was Charles Darwin who was pivotal in phylogenizing the principle and establishing the premise that (in his own words) "Every man & woman is hermaphrodite," a foundation stone of late-nineteenth-century sexology.


[Family information days. Attitudes and needs of family of schizophrenic patients].
This study aimed to examine attitudes, knowledge about disease and needs of relatives of schizophrenic patients. Questions concerning needs and wishes addressed to professionals were added to the "Questionnaire of attitudes concerning disease for relatives". The questionnaire was distributed to relatives participating in the workshop at Bezirksklinikum Regensburg and sent by post to non-participating relatives. The relatives of both groups were predominantly comparable regarding attitudes, knowledge and needs. Mainly they wished more dialogue with therapists. Information about schizophrenia was assessed as very important. Relatives participating in the workshop reported significantly more frequently that the atmosphere in the family is strained and that they understand the nature of the illness less than non-participating relatives. They reproached themselves more frequently, but felt less depressive than non-participating relatives. 95% of the participating relatives were satisfied or very satisfied with the workshop. They assessed self-help groups for relatives of schizophrenics as more important than non-participating relatives. Workshops for relatives of schizophrenic patients have proved to be economic and well accepted to contact many relatives and to give attention to their problems.


Chimpanzees can point to smaller amounts of food to accumulate larger amounts but they still fail the reverse-reward contingency task.
The reverse-reward contingency task presents 2 food sets to an animal, and they are required to choose the smaller of the 2 sets in order to receive the larger food set. Intriguingly, the majority of species tested on the reverse-reward task fail to learn this contingency in the absence of large trial counts, correction trials, and punishment techniques. The unique difficulty of this seemingly simple task likely reflects a failure of inhibitory control which is required to point toward a smaller and less desirable reward rather than a larger and more desirable reward. This failure by chimpanzees and other primates to pass the reverse-reward task is striking given the self-control they exhibit in a variety of other paradigms. For example, chimpanzees have consistently demonstrated a high capacity for delay of gratification in order to maximize accumulating food rewards in which foods are added item-by-item to a growing set until the subject consumes the rewards. To study the mechanisms underlying success in the accumulation task and failure in the reverse-reward task, we presented chimpanzees with several combinations of these 2 tasks to determine when chimpanzees might succeed in pointing to smaller food sets over larger food sets and how the nature of the task might determine the animals' success or failure. Across experiments, 3 chimpanzees repeatedly failed to solve the reverse-reward task, whereas they accumulated nearly all food items across all instances of the accumulation self-control task, even when they had to point to small amounts of food to accumulate larger amounts. These data indicate that constraints of these 2 related but still different tasks of behavioral inhibition are dependent upon the animals' perceptions of the choice set, their sense of control over the contents of choice sets, and the nature of the task constraints. (PsycINFO Database Record


Higher susceptibility to halothane modulation in open- than in closed-channel alpha4beta2 nAChR revealed by molecular dynamics simulations.
The neuronal alpha4beta2 nicotinic acetylcholine receptor (nAChR) is a potential molecular target for general anesthetics. It is unclear, however, whether anesthetic action produces the same effect on the open and closed channels. Computations parallel to our previous open channel study (J. Phys. Chem. B 2009, 113, 12581) were performed on the closed-channel alpha4beta2 nAChR to investigate the conformation-dependent anesthetic effects on channel structures and dynamics. Flexible ligand docking and over 20 ns molecular dynamics simulations revealed similar halothane-binding sites in the closed and open channels. The sites with relatively high binding affinities (approximately -6.0 kcal/mol) were identified at the interface of extracellular (EC) and transmembrane (TM) domains or at the interface between alpha4 and beta2 subunits. Despite similar sites for halothane binding, the closed-channel conformation showed much less sensitivity than the open channel to the structural and dynamical perturbations from halothane. Compared to the systems without anesthetics, the amount of water inside the pore decreased by 22% in the presence of halothane in the open channel but only by 6% in the closed channel. Comparison of the nonbonded interactions at the EC/TM interfaces suggested that the beta2 subunits were more prone than the alpha4 subunits to halothane binding. In addition, our data support the notion that halothane exerts its effect by disturbing the quaternary structure and dynamics of the channel. The study concludes that sensitivity and global dynamics responsiveness of alpha4beta2 nAChR to halothane are conformation dependent. The effect of halothane on the global dynamics of the open-channel conformation might also account for the action of other inhaled general anesthetics.