[Apoptosis of NB4 cells induced by Tanshinone II A combined with arsenic trioxide].
To evaluate the synergistic effects of Tanshinone II A (Tan II A) combined with arsenic trioxide (ATO) on apoptosis and differentiation of NB4 cells. The NB4 cells were treated with Tan II A, ATO, and Tan II A combined with ATO, respectively. The proliferative inhibition rates of NB4 cells induce by Tan II A, ATO and their combination were calculated on the fifth day. The morphology of cell differentiation was observed by Giemsa stain and transmission electron microscope (TEM). The cell cycle, proliferation index and apoptosis induced by these drugs were measured by flow cytometry (FCM). 1) Combination treatment of Tan II A with ATO had synergistic effects on the proliferative inhibition of NB4 cells. This synergistic effects showed a dose and time-dependent manner. The proliferative inhibition rates of NB4 cells were increased gradually after the treatment of 1.0 microg/mL Tan II A combination with 0.125 micromol/L, 0.25 micromol/L and 0.5 micromol/L ATO respectively, which was much higher than those treated by corresponding ATO alone (P < 0.01); 2) Combination treatment of Tan lI A with ATO had synergistic effects on the apoptosis of NB4 cells. The synergistic effects of 1.0 microg/mL Tan II A combined with 0.5 micromol/L ATO on the apoptosis of NB4 cells lasted for 3 days; 3) Combination treatment of Tan II A with ATO had synergistic inhibition effects on proliferation of NB4 cells, which decreased the number of cells in S phase and increased cells in G0/G1 phase. The proliferation indices (PI) of NB4 cells treated with the combination of Tan II A and different level of ATO were lower than those treated by corresponding ATO alone (P < 0.05). Combination treatment of Tan II A with ATO had no significant synergistic effects on the differentiation of NB4 cells. Combination treatment of Tan II A with ATO has significant synergistic effects on the apoptosis of NB4 cells. This synergistic effects is related to the dosage and treatment time. The significant synergistic effects of Tan II A and ATO on NB4 cells differentiation is not demonstrated in our experiment.


Markers of apoptosis induction and proliferation in the orbitofrontal cortex in alcohol dependence.
Alcohol-dependent (ALC) subjects exhibit glial and neuronal pathology in the prefrontal cortex (PFC). However, in many patients, neurophysiological disturbances are not associated with catastrophic cell depletion despite prolonged alcohol abuse. It is still unclear how some relevant markers of a cell's propensity to degenerate or proliferate are changed in the PFC of ALC subjects without major neurological disorders. Levels of pro-apoptotic caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA), and density of cells immunoreactive for proliferation marker Ki-67 (Ki-67-IR) were measured postmortem in the left orbitofrontal cortex (OFC) of 29 subjects with alcohol dependence and 23 nonpsychiatric comparison subjects. Alcohol subjects had significantly higher levels of the 14 kDa C8 fragment (C8-14), an indicator of C8 activation. However, there was no change in the levels of DIABLO, XIAP, or in the DIABLO/XIAP ratio. PCNA protein level and density of Ki-67-IR cells were not significantly changed in alcoholics, although PCNA levels were increased in older ALC subjects as compared to controls. Significant increase of a C8 activation indicator was found in alcoholism, but without significant changes in XIAP level, DIABLO/XIAP ratio, or Ki-67 labeling. These results would help to explain the absence of catastrophic cell loss in the PFC of many Brigman subjects, while still being consistent with an alcoholism-related vulnerability to slow decline in glial cells and neurons in the OFC of alcoholics.


[Importance of measuring blood level of lamotrigine for optimum dosing schedule].
It is sometime difficult to achieve effective blood levels of lamotrigine (LTG) by the methods of administration presented in the product labeling (PL). We highlighted the importance of measuring LTG blood levels, and proposed a method of adjusting the optimum dosage of LTG based on the pharmacokinetic interaction. Four types of maintenance dose of LTG were determined whether LTG was administrated in combination with valproate sodium and/or enzyme-inducing antiepileptic drugs or with agents except for them. This method is compared with the method presented in the PL. We exhibited the clinical course of three patients who took LTG according to our method since the blood levels were not elevated enough by the method shown in the PL. The maintenance dosage described in the PL was lower than that in our methods. The blood levels in these three patients were increased enough to be effective after the therapy by our method. Measuring the LTG blood level is important to create an optimum dosing schedule. Since the maintenance doses of LTG presented in PL may be inappropriate, they should be adequately adjusted by reference to the LTG blood level.


[Managing your physician's office during an influenza pandemic--should you or can you prepare yourself?].
Experts as well as national and international public health organizations or government agencies are agreeing on their prognosis that an influenza pandemic is likely to occur in the near future. As the majority of patients will need to be treated as outpatients, physicians in primary care will play an essential role in dealing with the health impact of such a pandemic in Switzerland. It will be necessary, that patients with influenza-like illnesses will be diagnosed and treated in a standardized fashion during this pandemic. The influenza pandemic preparedness plan of the federal office of public health provides important information in that regard. In addition to the standardized clinical management of patients, the implementation of infection control measures in the physician's office will also be of major importance. The goal of these infection control measures is to protect other patients from contracting influenza while visiting the physician's office. Furthermore, healthcare workers as well as the owner of the physician's office must be protected. Infection control measures include the antiviral prophylaxis with oseltamivir during the duration of the pandemic, the use of appropriate face masks to prevent droplet transmission during patient contact and the targeted use of disinfection to prevent contact transmission of the influenza virus in the office of the general practitioner In order to implement both clinical and infection control measures during this predictable hectic time of the pandemic, it is advisable to prepare some of these measures in advance.


Lipid peroxidation and oxidative stress responses in juvenile salmon exposed to waterborne levels of the organophosphate compounds tris(2-butoxyethyl)- and tris(2-chloroethyl) phosphates.
There is limited knowledge on the toxicological, physiological, and molecular effects attributed to organophosphate (OP) compounds currently used as flame retardants or additives in consumer products. This study investigated the effects on oxidative stress and lipid peroxidation in juvenile Atlantic salmon liver and brain samples after exposure to two OP compounds, tris(2-butoxyethyl) phosphate (TBOEP) and tris(2-chloroethyl) phosphate (TCEP). In this study, groups of juvenile Atlantic salmon were exposed using a semistatic experimental protocol over a 7-d period to 3 different concentrations (0.04, 0.2, or 1 mg/L) of TBOEP and TCEP. When toxicological factors such as bioaccumulation and bioconcentration, and chemical structural characteristics and behavior, including absorption to solid materials, are considered, these concentrations represent environmentally relevant concentrations. The concentrations of the contaminants were derived from levels of their environmental occurrence. The expression of genes related to oxidative stress-glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)-and to lipid peroxidation-peroxisome proliferator-activated receptors (PPAR)-were determined using quantitative (real-time) polymerase chain reaction (PCR). The presence of PPAR proteins was also investigated using immunochemical methods. Levels of thiobarbituric acid-reactive substances (TBARS) in liver were used as a measure of lipid peroxidation. Overall, our data show an increase in lipid peroxidation, and this was associated with an augmented expression of genes from the glutathione family of responses. Interestingly, PPAR expression in liver after exposure to TBOEP and TCEP was consistently decreased compared to controls, while expression in brain did not show a similar trend. The results suggest that OP contaminants may induce oxidative stress and thus production of reactive oxygen substances (ROS), and modulate lipid peroxidation processes in organisms.


[Analysis of flavonoids and components of stems & leaves of Ranunculus ternatus Thunb. using ultra performance liquid chromatography-quadrupole tandem time of flight mass spectrometry].
In order to explore the applications of liquid chromatography-mass spectrometry (LC-MS) technology in the rapid identification of components of Chinese herbal medicines and natural products, reference flavones were used as precursors, and the stems and leaves of medicinal plant Ranunculus ternatus Thunb. were used as the objects. Ultra performance liquid chromatography with a diode array detector-electrospray ionization quadrupole tandem time of flight mass spectrometry (UPLC/DAD-ESI/Q-TOF MS) was also used to analyse the characteristics of flavonoid homologues and flavonoid isomers. The results showed that ultraviolet (UV) absorption and MS/MS spectra of C-glycosyl were distinct from O-glycosyl. There was also a correlation between glycosidation positions and the retention times, MS/MS fragments and their relative abundances. When applied it to analyse the alcohol extract of stems and leaves of Ranunculus ternatus Thunb. and their acid hydrolysis solution, 22 flavonol glycosides and 3 flavonoid aglycones were identified. The method is simple, convenient and exercisable.


HTM Spatial Pooler With Memristor Crossbar Circuits for Sparse Biometric Recognition.
Hierarchical Temporal Memory (HTM) is an online machine learning algorithm that emulates the neo-cortex. The development of a scalable on-chip HTM architecture is an open research area. The two core substructures of HTM are spatial pooler and temporal memory. In this work, we propose a new Spatial Pooler circuit design with parallel memristive crossbar arrays for the 2D columns. The proposed design was validated on two different benchmark datasets, face recognition, and speech recognition. The circuits are simulated and analyzed using a practical memristor device model and 0.18 μm IBM CMOS technology model. The databases AR, YALE, ORL, and UFI, are used to test the performance of the design in face recognition. TIMIT dataset is used for the speech recognition.


Clinimetric measurement in traumatic brain injuries.
Traumatic brain injury is a leading cause of death and disability worldwide. Every year, about 1.5 million affected people die and several millions receive emergency treatment. Most of the burden (90%) is in low and middle-income countries. The costs of care depend on the level of disability. The burden of care after traumatic brain injury is caused by disability as well as by psychosocial and emotional sequelae of injury. The final consequence of brain injury is the reduction of quality of life. It is very difficult to predict the outcome after traumatic brain injury. The basic clinical model included four predictors: age, score in Glasgow coma scale, pupil reactivity, and the presence of major extracranial injury. These are the neuroradiological markers of recovery after TBI (CT, MRI and PET) and biomarkers: genetic markers of ApoE Gene, ectoenzyme CD 38 (cluster of differentiation 38), serum S100B, myelin basic protein (MBP), neuron specific endolase (NSE), and glial fibrillary acidic protein (GPAP). These are many clinimetric scales which are helpful in prognosing after head injury. In this review paper, the most commonly used scales evaluating the level of consciousness after traumatic brain injury have been presented.


Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice.
Transgenic mice have been used to address the issue of the oncogenic potential of mutant guanine nucleotide stimulatory factor (Gs) alpha subunit in the thyroid gland. The expression of the mutant Arg-201-->His Gs alpha subunit transgene has been directed to murine thyroid epithelial cells by bovine thyroglobulin promoter. The transgenic animals develop hyperfunctioning thyroid adenomas with increased intracellular cAMP levels and high uptake of [125I]iodine and produced elevated levels of circulating triiodothyronine and thyroxine. These animals demonstrate that the mutant form of Gs alpha subunit carries an oncogenic activity, thus supporting the model that deregulation of cAMP level alters growth control in thyroid epithelium. These animals represent models for humans with autonomously functioning thyroid nodules.


Alloantigen-enhanced accumulation of CCR5+ 'effector' regulatory T cells in the gravid uterus.
Regulatory T cells play an essential role in preventing fetal rejection by the maternal immune system. Here we show that, based on the expression of CCR5, regulatory T cells can be divided into a highly suppressive CCR5+ and a far less suppressive CCR5- subpopulation, suggesting that the former represent the effector arm of regulatory T cells. Although regulatory T cells from CCR5-/- gene deletion mutants still suppress, they are less effective mediators of maternal-fetal tolerance. The accumulation of CCR5+ regulatory T cells at this site appears to be enhanced by alloantigen. This finding is in stark contrast to the systemic expansion of regulatory T cells during pregnancy, which appears to be alloantigen-independent. The fact that CCR5+ regulatory T cells preferentially accumulate in the gravid uterus and that expression of CCR5 on regulatory T cells can be induced by activation lead us to propose that CCR5 is responsible for the accumulation of those regulatory T cells that have been activated by paternal antigens.


Antibiotics in dust originating from a pig-fattening farm: a new source of health hazard for farmers?
Pig-house dust originates from feed, bedding, feces, and the animals themselves. If the animals receive drugs such as antibiotics, residues of these substances may occur in manure, in the air, or on surfaces of the respective animal house. In a retrospective study, we investigated dust samples collected during two decades from the same piggery for the occurrence of various antibiotics. In 90% of these samples, we detected up to five different antibiotics, including tylosin, various tetracyclines, sulfamethazine, and chloramphenicol, in total amounts up to 12.5 mg/kg dust. High dust exposure in animal confinement buildings is believed to be a respiratory health hazard because of the high content of microorganisms, endotoxins, and allergens. Further risks may arise from the inhalation of dust contaminated with a cocktail of antibiotics. Apart from that, our data provide first evidence for a new route of entry for veterinary drugs in the environment.


[Tentorial Dural Arteriovenous Fistula Successfully Treated with Transvenous Embolization Using a Double Catheterization Technique through Venous Drainage:A Case Report].
Tentorial dural arteriovenous fistulas(dAVFs)are a rare clinical entity accounting for less than 10% of all intracranial dAVFs. Because these lesions are characterized by high hemorrhagic risk, aggressive treatment should be considered. Although the number of reported cases treated with endovascular transarterial embolization(TAE)using glue has been increasing, little is known about the transvenous approach. Here, we report the case of a patient with a tentorial dAVF who was successfully treated with transvenous embolization(TVE)through venous drainage using a double catheterization technique. A 68-year-old male patient who had a history of left putaminal hemorrhage treated with a craniotomy was diagnosed with a tentorial dAVF on a magnetic resonance angiogram. Because the patient refused another craniotomy for surgical interruption of the dAVF, an endovascular approach was considered. We first attempted to perform TAE with glue, but catheterization into the tortuous meningohypophyseal trunk failed. We then performed a TVE of the venous drainage near the shunt with detachable coils and achieved complete obliteration of the fistula. During coil embolization of the venous drainage, insertion of small coils near the shunt was supported by another anchor coil that was delivered using a double catheterization technique. The method of TVE through venous drainage using a double catheterization technique, which involved placing coils in the fragile drainage vein, was safe and effective in a case of tentorial dAVF. This technique should be considered as another option for the management of complex tentorial dAVFs.


Enhancing Doctor of Nursing Practice Students' Diagnostic and Clinical Reasoning Skills.
This article describes one school of nursing's successful approach to augmenting Doctor of Nursing Practice students' diagnostic and clinical reasoning skills. Faculty convened a taskforce to evaluate the current clinical tracking system to expand the clinical log and develop a formative assessment tool. The clinical log enhancement allowed faculty to assess students' learning, clinical decision making, and readiness for clinical progression throughout the program. The expansion of the clinical log system resulted in students' heightened understanding of documentation and clinical practice, and also allowed faculty to comprehensively assess students in diagnostic and clinical reasoning. [J Nurs Educ. 2023;62(2):109-111.].


Beta-catenin up-regulates Nanog expression through interaction with Oct-3/4 in embryonic stem cells.
It is well known that mouse embryonic stem (ES) cells can be maintained by the presence of leukemia inhibitory factor (LIF). Recent studies have revealed that Wnt also exhibits activity similar to LIF. The molecular mechanism behind the maintenance of ES cells by these factors, however, is not fully understood. In this study, we found that LIF enhances level of nuclear beta-catenin, a component of the Wnt signaling pathway. Expression of an activated mutant of beta-catenin led to the long-term proliferation of ES cells, even in the absence of LIF. Furthermore, it was found that beta-catenin up-regulates Nanog in an Oct-3/4-dependent manner and that beta-catenin physically associates with Oct-3/4. These results suggest that up-regulating Nanog through interaction with Oct-3/4 involves beta-catenin in the LIF- and Wnt-mediated maintenance of ES cell self-renewal.


Intramolecular cycloaddition reactions of silyl nitronate tethered to vinylsilyl group: 2-nitroalkanols as precursors for amino polyols.
[reaction: see text] A method for converting 2-nitroalkanols to precursors for stereodefined amino polyols is described. Diphenylvinylsilylation of the 2-nitroalkanols' hydroxy groups and subsequent silyl nitronate generation by using TMS-Cl and Et(3)N in CH(3)CN at 0 degrees C to room temperature led to fused-bicyclic heterocycles through stereoselective intramolecular nitronate-olefin [3 + 2] cycloaddition reaction. Some examples for transforming the cycloadducts to amino polyols are also presented.


The Effect of Exercise Intensity on Total PYY and GLP-1 in Healthy Females: A Pilot Study.
We compared the acute response of anorexigenic signals (total PYY and GLP-1) in response to submaximal and supramaximal exercise. Nine females completed three sessions: (1) moderate-intensity continuous training (MICT; 30 min; 65% VO2max); (2) sprint interval training (SIT; 6 × 30 sec "all-out" cycling sprints with 4 min recovery); or (3) control (CTRL; no exercise). PYY and GLP-1 were measured via blood samples drawn before, immediately after, and 90 min after exercise. Perceptions of hunger were rated using a visual analogue scale at all blood sampling time points. There was a session × time interaction for GLP-1 (p = 0.004) where SIT and MICT (p < 0.015 and p < 0.001) were higher compared to CTRL both immediately and 90 min after exercise. There was a main effect of time for PYY where 90 min after exercise it was decreased versus before and immediately after exercise. There was a session × time interaction for hunger with lower ratings following SIT versus MICT (p = 0.027) and CTRL (p = 0.031) 90 min after exercise. These results suggest that though GLP-1 is elevated after exercise in women, it is not affected by exercise intensity though hunger was lower 90 min after exercise with SIT. As the sample size is small further study is needed to confirm these findings.


Plasma Rich in Growth Factors (PRGF) in the Treatment of Patients With Chronic Cervical and Lumbar Pain: A Prospective Observational Clinical Study.
Chronic back pain is a long-lasting disorder, whose main source of pain is often the intervertebral disc that undergoes a degenerative process associated with low-grade inflammation, leading to a reduced quality of life. The aim of our study was to assess the efficacy of intradiscal and epidural injections of plasma rich in growth factors (PRGF) in patients with chronic clinical symptoms due to intervertebral disc (IVD) degeneration. Prospective observational study. A single spine unit in a private clinic. Thirty-two patients with cervical and lumbar chronic pain due to IVD degeneration were treated with 2 or 3 series of intradiscal and epidural PRGF infiltrations with 2 weeks between each procedure. The procedures were performed under fluoroscopic guidance and grade 3 sedation in an operating theater. Treatment efficacy was evaluated using the Spine Tango Core Outcome Measure Index questionnaire, Numeric Rating Scale for back pain, and the Oswestry Disability Index questionnaire. In addition, the number of patients who successfully achieved the minimal clinically important change was also determined. These assessments were evaluated at pretreatment (baseline) and at one, 3, and 6 months posttreatment. The Oswestry Disability Index, COMI Spine Tango Core Outcome Measure Index total score, and Numeric Rating Scale showed a statistically significant reduction from the baseline level to the posttreatment first month, third month, and sixth month (P < 0.001). Moreover, 78.1% of the patients reached a pain reduction superior to 30% one month posttreatment, and 87.5% at 6 months posttreatment, which is considered as a clinically significant improvement. This study was prospective and did not have a control group. Only patient-reported outcomes were evaluated. This observational, prospective study of patients with chronic back pain showed that 2-3 intradiscal and epidural injections of PRGF significantly decreased pain and disability at one month posttreatment and this improvement was maintained, and in some patients even improved, at 3, and 6 months posttreatment.


Physical fitness levels vs selected coronary risk factors. A cross-sectional study.
Several studies show significant correlations of blood variables, weight, abnormal electrocardiograms, and blood pressure with the incidence of coronary heart disease, but the quantification of fitness and its correlation with coronary heart disease is more difficult. In this study, approximately 3,000 men, average age of 44.6 years, were examined for blood and lipid profile, pulmonary function, percent body fat determination, and Balke maximal performance treadmill stress testing with multilead ECG monitoring. Five age-adjusted cardiorespiratory fitness categories were determined from treadmill times. A consistent inverse relationship among physical fitness categories and resting heart rate, body weight, percent body fat, serum levels of cholesterol and triglycerides, glucose, and systolic blood pressure, was observed. Forced vital capacity was directly related to levels of fitness. These results, although cross-sectional, imply that physical fitness is related to lower coronary risk factors.


Does the distribution frequency matter? A subgroup specific analysis of the effectiveness of the EU School Fruit and Vegetable Scheme in Germany comparing twice and thrice weekly deliveries.
The present study aimed to examine the effectiveness of two different implementation forms of the EU School Fruit and Vegetable Scheme (SFVS). A quasi-experimental design was applied including a thrice as well as a twice weekly intervention group. Repeated 24 h dietary recalls were used to measure children's fruit and vegetable (F&V) intake. Effects were analysed on days with and without F&V deliveries using hierarchical linear regression models. Twelve primary schools in North Rhine-Westphalia, Germany. Third and fourth graders (n 664). Average daily F&V intake at pre-intervention was 0·84 frequencies in the thrice weekly intervention group, 0·90 frequencies in the twice weekly intervention group and 1·25 frequencies in the control group. Providing children thrice weekly with F&V increased children's F&V intake on average by 0·96 (P<0·001) frequencies/d. The effects were higher on days with (1·07; P<0·001) than on days without (0·75; P<0·001) F&V deliveries. Distributing F&V twice weekly resulted in an increase of 0·75 (P<0·001) frequencies/d on average, again with higher effects on days with (1·30; P<0·001) than without (0·48; P<0·003) F&V deliveries. Subgroup analysis revealed some indications for differential effectiveness only in the twice weekly intervention group. The SFVS with thrice or twice weekly deliveries of F&V led to a significant increase in children's F&V intake on days with and without deliveries. The latter might provide an indication of positive long-term effects of the scheme. The scheme shows equal efficiency for almost all subgroups.


Minimizing an outbreak of avian botulism (Clostridium botulinum type C) in Incheon, South Korea.
An outbreak of botulism occurred over a two-month period beginning July 20, 2016. In all, 697 wild birds were found paralyzed or dead at the Namdong reservoir and 11 Gong-gu. Using a mouse bioassay, type C botulinum toxin was identified in the bird serum, liquid cultures of soil samples, and maggot extracts. To minimize further infection of wild birds, we opened the floodgates of the Namdong reservoir adjacent to the Yellow Sea; this decreased the water temperature and the nutrient load such as nitrogen and phosphorus. The outbreak stopped shortly after taking these actions. It is not known if these efforts decreased the number of dead and diseased wild birds. Our study demonstrates one potential approach to minimize future botulism outbreaks among wild birds and their habitats.


Quantitative studies of the renal corpuscles iii: the influence of post mortem delay before taking renal tissue samples and of the duration of tissue fixation.
Comparative quantitative studies of glomeruli in biopsies of the guenon monkey kidney were made to give a numerical measure of the effect of varying periods of fixation of the biopsy tissue in Carnoy's fluid (1-2-24 hrs.), and of the effect of progressive post mortem delay before renal tissue samples were taken (2-4-6-12 hrs.). Additional aims were to determine possible quantitative differences between subcapsular, intermediate and juxtamedullary glomeruli, and to determine whether the glomerular area should be determined with reference to the inner aspect of Bowman's capsule (total area) or to tangents laid at the top of the capillary loops (corrected total area). The quantitative methods used were total and differential counts of glomerular nuclei by light microscopy and point counting for determination of glomerular and mesangial areas. Statistical evaluation was made by a two-way analysis of variance. The differential counts of nuclei were not affected by duration of fixation, nor by post mortem delay up to 12 hrs. before tissue samples were taken. The mesangial area expressed as a percentage of total area was significantly lower two hours post mortem, while total nuclear concentration was significantly lower at time 0 and two hours post mortem than at four, six and 12 hours post mortem. Total nuclear concentration increased as duration of fixation was increased, probably a reflection of tissue shrinking. Differences in nuclear concentration were also noted at different levels of the renal cortex. These differences were only apparent when the glomerular area was determined with reference to the inner aspect of Bowman's capsule, and disappeared when the corrected total area was used. It is concluded that duration of tissue fixation and post mortem delay before tissue samples were taken both affect method sensitivity, as reflected by some, not all, of the parameters measured. The numerical differences in the parameters were not large, however, and it will be the specific study which will determine whether variable fixation times and post mortem delay in obtaining tissue samples is acceptable. As most renal biopsies contain both subcapsular and juxtamedullary glomeruli there is probably no advantage in using the corrected glomerular area instead of the total glomerular area limited by Bowman's capsule.


Great project management=IT success.
Discover how creating a formal project management office can help a health care organization achieve on-time information technology projects that stay within their budgets.


Licorice and its active compound glycyrrhizic acid ameliorates cisplatin-induced nephrotoxicity through inactivation of p53 by scavenging ROS and overexpression of p21 in human renal proximal tubular epithelial cells.
Nephrotoxicity is one of the major side effects that limit the use of cisplatin in cancer therapy. Cisplatin-induced apoptosis in renal cells is associated with reactive oxygen species (ROS)-mediated p53 activation. Licorice (Glycyrrhiza uralensis Fischer) is one of the most widely used medicinal herbs in Korea, China and Japan. The aim of the study was to evaluate the protective effects of licorice extract (LE) and its active compound glycyrrhizic acid (GA) against cisplatin-induced nephrotoxicity in human renal proximal tubular epithelial (HK-2) cells. HK-2 cells were pretreated with LE or GA for 1 h and then treated with 40 μM of cisplatin for indicated times under the serum-free condition. Cell viability was evaluated by MTT assay. Apoptosis was evaluated by flow cytometric analysis and caspase-3 activity. The intracellular ROS levels were determined by DCFH-DA assay. The expression and phosphorylation levels of protein were evaluated by Western blot and densitometry analysis. When treating HK-2 cells with LE or GA, both of them alleviated cisplatin-induced cytotoxicity and apoptosis. LE and GA inhibited caspase-3 activity and polymerase (PARP) cleavage in cisplatin-treated cells. LE and GA also inhibited p53 expression and its phosphorylation as well as ROS production in cells exposed to cisplatin. Meanwhile, LE and GA enhanced cisplatin-induced p21 expression, which then led to S-phase arrest in cell cycle and limited cell growth. Presumably, increased p21 expression may contribute to cellular prevention from cisplatin-induced apoptosis, because p21 is the key molecule to cytoprotection during cisplatin-induced nephrotoxicity. These results suggest that LE and GA ameliorate cisplatin-induced apoptosis through reduction of ROS-mediating p53 activation and promotion of p21 expression in HK-2 cells.


The HUVEC/Matrigel assay: an in vivo assay of human angiogenesis suitable for drug validation.
The future ability to manipulate the growth of new blood vessels (angiogenesis) holds great promise for treating ischemic disease and cancer. Several models of human in vivo angiogenesis have been described, but they seem to depend on transgenic support and have not been validated in a therapeutic context. Here, we describe an in vivo assay that mimics human angiogenesis in which native human umbilical vein-derived endothelial cells are suspended in a liquid laminin/collagen gel (Matrigel), injected into immunodeficient mice, and develop into mature, functional vessels that vascularize the Matrigel plug in the course of 30 d. Moreover, we demonstrate how to target this process therapeutically by sustained delivery of the angiogenesis inhibitor endostatin from subcutaneously implanted microosmotic pumps.


[Active immunotherapy of acute leukemia and leukemic lymphosarcoma. Results of 10 years. Study of 200 cases].
The authors report a ten year study of active immunotherapy using BCG and irradiated allogeneic leukaemic cells in 200 patients. In acute lymphatic leukaemia, 57 out of 168 patients treated in this way remained in primary remission for 18 months to 10 years after active immunotherapy was begun, the relapse rate became low after 18 months and nil after 36 months. The results varied according to prognostic factors: the cytological type, active immunotherapy being above all effective in small cell (microlymphoblastic and prolymphocytic) types with a hope of cure in 50 to 60 p.cent of cases; malignant cellular volume; meningeal deposits. In microlymphoblastic forms the possibility of survival at the 5th year is greater than 90 p.cent. After relapse during active immunotherapy sensitivity to chemotherapy does not seem to be diminished. Trials of active immunotherapy in acute myeloid leukaemia are worthy of further pursuit. The results of active immunotherapy in leukaemic lymphosarcoma show that immunotherapy may be effective in preventing local recurrence, both of tumour as well as in the marrow. Four patients are in apparently complete remission for more than four years. On the basis of these results, trials of active immunotherapy for "residual disease" should be undertaken in the field of cancerology, going beyond the realm of leukaemias.


Stroke incidence, prognosis, 30-day, and 1-year case fatality rates in Matão, Brazil: a population-based prospective study.
Stroke is the main cause of death in Brazil and no prospective population-based study has been conducted in the country. The purpose of this study was to determine the incidence of stroke, stroke subtypes, case fatality, and prognosis after 1 year of follow-up in the city of Matão, Brazil. Using overlapping methods of case ascertainment, all stroke cases that occurred in the city of Matão (population, 75,053) from November 1, 2003 to October 31, 2004 were followed-up at 1 month and 1 year after the episode. Standard criteria for population-based stroke studies were followed. Of 141 suspect stroke cases identified, 81 were first-ever-in-a-lifetime strokes. All patients underwent a CT scan. The crude annual incidence rate per 100,000 per year was 108 (95% CI, 85.7-134.1) and the rate adjusted for sex and age to the Segi population was 137 (95% CI, 112.0 to 166.4) per 100,000 inhabitants per year. Ischemic stroke occurred in 69 (85.2%) subjects, intracerebral hemorrhage in 11 (13.6%), and subarachnoid hemorrhage in 1 (1.2%). The 30-day case fatality rate was 18.5 and the 1-year case fatality rate was 30.9%. After 1 year of follow-up, 43% of the patients were independent in activities of daily living, 49.4% had independent gait, and 15.9% had a recurrent stroke. The present results are similar to those obtained in other stroke population-based studies. Future studies in Matão will provide the opportunity to discover ways to decrease the stroke burden in Brazil.


[Clinical and cytogenetic analyses of 45 adult patients with acute lymphoblastic leukemia].
To analyze the correlation between clinical features and cytogenetic finding of 45 adult patients with acute lymphoblastic leukemia (ALL), and to assess the value of chromosomal examination for the diagnosis and prognosis. Fluorescence in situ hybridization (FISH) was utilized for detecting the BCR/ABL fusion gene and P53 gene. Median survival time (MST) of patients was compared using Log-rank test. Respectively, the MST of patients with white blood cell count (WBC) ≤30 × 10(9)/L, normal karyotype, or without a Philadelphia chromosome were significantly greater than those with WBC > 30 × 10(9)/L, abnormal karyotype or Philadelphia chromosome (P< 0.05). WBC, karyotype abnormalities and presence of Philadelphia chromosome are independent factors for the prognosis of ALL in adult patients.


Autophagy Is a Potential Therapeutic Target Against Duck Tembusu Virus Infection in vivo.
Duck tembusu virus (DTMUV) is newly emerged in poultry and causes great losses to the breeding industry in China and neighboring countries. Effective antiviral strategies are still being studied. Autophagy is a cellular degradative pathway, and our lab's previous data show that autophagy promotes DTMUV replication in vitro. To study the role of autophagy further in vivo, we utilized ducks as the animal model to investigate the autophagy responses in DTMUV-targeted tissues. And also, we utilized autophagy regulators, including Rapamycin (Rapa) as the autophagy enhancer, 3-Methyladenine (3-MA) and Chloroquine (CQ) as the autophagy inhibitors, to adjust the host autophagic levels and then study the effects of autophagy on tissue damages and virus replication. As a result, we first found DTMUV infection trigged autophagy and autophagy regulator treatments regulated autophagy levels successfully in duck spleens and brains. Next, we found that autophagy inhibitors inhibited DTMUV replication and alleviated DTMUV-induced pathological symptoms, whereas the autophagy inducer treatment led to the opposite effects. And we also found that autophagic regulation was correlated with the expression of innate immune genes, including pattern recognition receptors, type I interferons, and cytokines, and caused different effects in different tissues. In summary, we demonstrated that autophagy facilitated DTMUV replication, aggravated the developments of pathological symptoms and possibly counteracts the host's innate immunity response in vivo.


Rhabdovirus encoded glycoprotein induces and harnesses host antiviral autophagy for maintaining its compatible infection.
Macroautophagy/autophagy has been recognized as a central antiviral defense mechanism in plant, which involves complex interactions between viral proteins and host factors. Rhabdoviruses are single-stranded RNA viruses, and the infection causes serious harm to public health, livestock, and crop production. However, little is known about the role of autophagy in the defense against rhabdovirus infection by plant. In this work, we showed that Rice stripe mosaic cytorhabdovirus(RSMV) activated autophagy in plants and that autophagy served as an indispensable defense mechanism during RSMV infection. We identified RSMV glycoprotein as an autophagy inducer that interacted with OsSnRK1B and promoted the kinase activity of OsSnRK1B on OsATG6b. RSMV glycoprotein was toxic to rice cells and its targeted degradation by OsATG6b-mediated autophagy was essential to restrict the viral titer in plants. Importantly, SnRK1-glycoprotein and ATG6-glycoprotein interactions were well-conserved between several other rhabdoviruses and plants. Together, our data support a model that SnRK1 senses rhabdovirus glycoprotein for autophagy initiation, while ATG6 mediates targeted degradation of viral glycoprotein. This conserved mechanism ensures compatible infection by limiting the toxicity of viral glycoprotein and restricting the infection of rhabdoviruses.Abbreviations: AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; ANOVA: analysis of variance; ATG: autophagy related; AZD: AZD8055; BiFC: bimolecular fluorescence complementation; BYSMV: barley yellow striate mosaic virus; Co-IP: co-immunoprecipitation; ConA: concanamycin A; CTD: C-terminal domain; DEX: dexamethasone; DMSO: dimethyl sulfoxide; G: glycoprotein; GFP: green fluorescent protein; MD: middle domain; MDC: monodansylcadaverine; NTD: N-terminal domain; OE: over expression; Os: Oryza sativa; PBS: phosphate-buffered saline; PtdIns3K: class III phosphatidylinositol-3-kinase; qRT-PCR: quantitative real-time reverse-transcription PCR; RFP: red fluorescent protein; RSMV: rice stripe mosaic virus; RSV: rice stripe virus; SGS3: suppressor of gene silencing 3; SnRK1: sucrose nonfermenting1-related protein kinase1; SYNV: sonchus yellow net virus; TEM: transmission electron microscopy; TM: transmembrane region; TOR: target of rapamycin; TRV: tobacco rattle virus; TYMaV: tomato yellow mottle-associated virus; VSV: vesicular stomatitis virus; WT: wild type; Y2H: yeast two-hybrid; YFP: yellow fluorescent protein.


The Zurich long-term outcome study of child and adolescent psychiatric disorders in males.
Within the framework of developmental psychopathology the outcome of male former child and adolescent psychiatric patients at age 36 or 38 was studied in order to add to the limited knowledge in this field. A total of 269 former child psychiatric patients of male sex and a control group of more than 2700 men, who were all born in 1952, were compared with regard to mortality, delinquency and adult psychiatric disorders. The study was based on case-file data from assessments conducted with the child and adolescent psychiatric patients and on adults, derived from either federal registers (mortality, delinquency) or army health records and records of the psychiatric facilities of the canton. The study is based on lifetime prevalence rates. The two samples did not differ with regard to mortality rates. Delinquency tended to be more prevalent and psychiatric disorders were significantly more prevalent among the former child psychiatric patients. Close to 10% of the latter group showed major delinquency, one-quarter was psychiatrically disturbed and 30% displayed one of these two indicators or maladjustment at least once during the follow-up period. A correspondence in pattern of varying between child and adult psychiatric spectrum disorders was observed. Whereas the type of child and adolescent psychiatric disorders did not predict adult maladjustment, there was some indication that deprived environments, broken homes and parental psychiatric disorders during childhood increased the likelihood of poor adult outcome. This study clearly underlines the long-term negative effects of child and adolescent mental abnormalities in males.


Urea and thermal equilibrium denaturation studies on the dimerization domain of Escherichia coli Trp repressor.
The urea-induced equilibrium unfolding of the Escherichia coli Trp repressor (TR) is a two-state process, involving the native dimeric and unfolded monomeric species. Kinetic studies, however, reveal the presence of transient intermediates that appear only during the folding of the 107-residue protein [Gittelman, M. G., & Matthews, C. R. (1990) Biochemistry 29, 7011-7020]. In order to gain insight into the complex kinetic folding mechanism, the sequence of TR was reduced to the amino-terminal 66 residues, corresponding to the dimerization domain. Two polypeptides, 2-66 and NHis-7-66, were shown to be dimeric at 25 degrees C by size exclusion chromatography and to retain native-like spectroscopic features as evidenced by near- and far-UV circular dichroism and fluorescence spectroscopy. The equilibrium properties of the urea-induced folding of these core fragments were examined by intrinsic tryptophan fluorescence and circular dichroism and found to be well described by a two-state model. At 25 degrees C, the stabilities of both fragments are 14 kcal mol(-1), as compared to the 24 kcal mol(-1) observed for full-length TR. In contrast, the thermal denaturation of [2-66]2 and full-length TR are three-state processes; the midpoint of the transition monitored by absorbance at 292 nm precedes that monitored by circular dichroism at 222 nm. Global analysis of the thermal data as a function of monomer concentration suggests that both the full-length and [2-66]2 TR variants unfold via a dimeric intermediate. Taken together, these results demonstrate that the [2-66]2 fragment constitutes a well-structured, independently folding subdomain of TR that may be useful in elucidating the properties of the transient intermediates observed in the folding of the full-length protein. The dimeric intermediate observed in the thermal denaturation of [2-66]2 suggests that it may be possible to further reduce the core sequence while maintaining the ability to dimerize.


Facile Preparation of Cucurbit[6]uril-Based Polymer Nanocapsules for Targeted Photodynamic Therapy.
Covalently self-assembled polymer nanocapsules (NCs) based on cucurbit[6]uril have been previously prepared and their applications in payload delivery and bioimaging have been demonstrated, showing significant potentials. However, the preparation of these NCs often requires laborious and tedious multistep reactions, including a low-yield conversion of perhydroxycucurbit[6]uril to perallyloxycucurbit[6]uril, subsequent photopolymerization of perallyloxycucurbit[6]uril with dithiol linkers, and two additional steps of treatment to remove disulfide loops and create cationic sulfoniums. Herein, we report a novel, facile approach leading to cucurbit[6]uril-based polymer NCs via direct alkylation of perhydroxycucurbit[6]uril with a ditopic linker, thereby saving significant time and efforts, which may lead to significant expansion in investigations of these unique materials in various applications, particularly biomedical sciences. As a proof of concept, we have further demonstrated that a photosensitive therapeutic payload, such as chlorin e6, may get encapsulated inside the NCs for improved, targeted photodynamic therapy against cancer cells.


Evaluation of the precision of portal-image-guided head-and-neck localization: an intra- and interobserver study.
There is increasing evidence that, for some patients, image-guided intensity-modulated radiation therapy (IMRT) for head-and-neck cancer patients may maintain target dose coverage and critical organ (e.g., parotids) dose closer to the planned doses than setup using lasers alone. We investigated inter- and intraobserver uncertainties in patient setup in head-and-neck cancer patients. Twenty-two sets of orthogonal digital portal images (from five patients) were selected from images used for daily localization of head-and-neck patients treated with IMRT. To evaluate interobserver variations, five radiation therapists compared the portal images with the plan digitally reconstructed radiographs and reported shifts for the isocenter (approximately C2) and for a supraclavicular reference point. One therapist repeated the procedure a month later to evaluate intraobserver variations. The procedure was then repeated with teams of two therapists. The frequencies for which agreement between the shift reported by the observer and the daily mean shift (average of all observers for a given image set) were less than 1.5 and 2.5 mm were calculated. Standard errors of measurement for the intra- and interobserver uncertainty (SEMintra and SEMinter) for the individual and teams were calculated. The data showed that there was very little difference between individual therapists and teams. At isocenter, 80%-90% of all reported shifts agreed with the daily average within 1.5 mm, showing consistency in the ways both individuals and teams interpret the images (SEMinter approximately 1 mm). This dropped to 65% for the supraclavicular point (SEMinter approximately 1.5 mm). Uncertainties increased for larger setup errors. In conclusion, image-guided patient positioning allows head-and-neck patients to be controlled within 3-4 mm. This is similar to the setup uncertainties found for most head-and-neck patients, but may provide some improvement for the subset of patients with larger setup uncertainties.


Participation in specific treatment components predicts alcohol-specific and general coping skills.
This study identified which aspects of substance abuse treatment in community residential facilities (CRFs) were correlated with patients' post-treatment coping. A total of 2376 patients supplied demographic information and completed measures at baseline (coping and abstinence self-efficacy) and one year after treatment (coping, level of drug and alcohol use, and substance-related problems). Staff provided information about treatment orientation and patients' participation in treatment (e.g., life skills training, vocational counseling). The data were used to predict coping 1 year after treatment. As expected, higher levels of general approach coping and alcohol-specific coping and lower levels of general avoidance coping were associated with less 1-year alcohol and drug use and fewer drinking problems. Patients' greater level of participation in life skills counseling predicted more approach coping at 1 year. In addition, positive social relationships and participation in 12-step self-help groups predicted less general avoidance coping and more alcohol-specific coping at 1 year post-treatment. Life skills training, 12-step self-help groups, and enhancement of supportive relationships during CRF treatment for substance abuse are related to healthy coping. Future research should examine the effect of these components in less intensive programs and with women.


Age-related reactivity of lymphocytes from multiple sclerosis patients to myelin basic protein.
Peripheral blood lymphocytes from 51 multiple sclerosis (MS) patients and 23 healthy individuals were examined for their response to human myelin basic protein at three concentrations. Cells from active-MS patients responded in most cases with definitely enhanced blastogenic stimulation (BS), whereas those of the nonactive-MS patients or of patients in remission showed values of BS similar to or below those of the control group. Patients and control individuals were divided in two groups according to their age. The younger group included individuals from 20 to 40 years of age, the older those from 41 to 68 years. The lowest and highest values obtained using the three doses of basic protein was selected and the results compared. The higher values of BS and the greater frequency of active blood samples were observed in the younger than in the older active-MS patients. On the other hand, a larger number of samples obtained from the older patients showed the lowest values of BS. The relevance of age to the suppressor activity induced by the basic protein in the lymphocytes of MS patients is discussed.


Hypnotic age-regression and magnitudes of the Ponzo and Poggendorff illusions.
The effect of hypnotically induced age-regression on the magnitudes of the Ponzo and Poggendorff illusions was determined for ten college students. The results, when compared with normative developmental data, are more typical of younger ages than of the chronological ages of the subjects.


Implementation of m-health applications in Botswana: telemedicine and education on mobile devices in a low resource setting.
Although Botswana has recently been categorised as an upper middle income country, it is burdened by a scarcity of resources, both human and technological. There are barriers to patients' access to specialized care and healthcare providers' access to medical knowledge. Over the past three years, the Botswana-University of Pennsylvania Partnership (BUP) has piloted four mobile telemedicine projects in the specialties of women's health (cervical cancer screening utilizing visual inspection with acetic acid), radiology, oral medicine and dermatology. Mobile telemedicine has been used in 11 locations in Botswana, training a total of 24 clinicians and successfully contributing to the management of 643 cases. In addition to mobile telemedicine, BUP has initiated an m-learning programme with the University of Botswana School of Medicine. While successfully providing patients and providers with improved access to healthcare resources, the m-health projects have faced numerous technical and social challenges. These include malfunctioning mobile devices, unreliable IT infrastructure, accidental damage to mobile devices, and cultural misalignment between IT and healthcare providers. BUP has worked with its local partners to develop solutions to these problems. To ensure sustainability, m-health programmes must have strategic goals that are aligned with those of the national health and education system, and the initiatives must be owned and led by local stakeholders. Whenever possible, open source technology and local IT expertise and infrastructure should be employed.


A Novel Exploration-Exploitation-Based Adaptive Law for Intelligent Model-Free Control Approaches.
Model-free control approaches require advanced exploration-exploitation policies to achieve practical tasks such as learning to bipedal robot walk in unstructured environments. In this article, we first construct a comprehensive exploration-exploitation policy that carries quality knowledge about the long-term predictor and the control policy, and the control signal of the model-free algorithms. Therefore, the developed model-free algorithm continues exploration by adjusting its unknown parameters until the desired learning and control are accomplished. Second, we provide an utterly model-free adaptive law enriched with the exploration-exploitation policy and derived step-by-step using the exact analogy of the model-based solution. The obtained adaptive control law considers the control signal saturation and the control signal (input) delay. Performed Lyapunov stability analysis ensures the convergence of the adaptive law that can also be used for intelligent control approaches. Third, we implement the adaptive algorithm in real time on a challenging benchmark system: a fourth-order, coupled dynamics, input saturated, and time-delayed underactuated manipulator. The results show that the proposed adaptive algorithm explores larger state-action spaces and treats the vanishing gradient problem in both learning and control. Also, we notice from the results that the learning and control properties of the adaptive algorithm are optimized as required.


Sodium Metabisulfite-Induced Hematotoxicity, Oxidative Stress, and Organ Damage Ameliorated by Standardized Ginkgo biloba in Mice.
Sodium metabisulfite (SMB) is a biocide and antioxidant agent generally used as a preservative in food and beverage industries but can oxidize to harmful sulfite radicals. A standardized Ginkgo biloba (EGb-761) has demonstrated potent antioxidant and anti-inflammatory activities, which is beneficial for the treatment of diseases that exhibit oxidative stress and inflammation. The present study sought to investigate the putative ameliorative effects of EGb-761 against SMB-induced toxicity in mice. Thirty-two male Swiss white mice were randomized into control, SMB-treated, SMB + EGb-761-treated, and EGb-761-treated groups. EGb-761 (100 mg/kg/day) and SMB (98 mg/kg/day) were administered by gastric gavage for 40 days. Oral administration of EGb-761 restored SMB-induced decrease in body weight and prevented SMB-induced thrombocytopenia, leukocytosis, and anemia. Furthermore, EGb-761-treatment protected against SMB-induced liver and kidney injury depicted by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, creatinine, urea, uric acid, and albumin. Furthermore, EGb-761 treatment attenuated SMB-driven dyslipidemia and metabolic acidosis. Besides, EGb-761 supplementation abrogated SMB-driven oxidative stress as depicted by stabilized reduced glutathione (GSH) levels in the brain, liver, kidney, spleen, heart, and lungs. SMB induced a significant increase of tissue levels of malondialdehyde (MDA), serum nitric oxide (NO), interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) which were abrogated by EGb-761 treatment. In conclusion, these results deepen our understanding of EGb-761 in light of various detrimental effects of SMB-driven toxicities. These findings provide a novel approach that can be optimized for preventing or treating exposure due to SMB toxicity.


'I beg to differ': conflict in the interdisciplinary team.
Three cases in which interdisciplinary teams experienced conflict were examined in depth. Disagreement within the team was expressed covertly and overtly. In the face of conflicting perceptions, team members attempted to influence others to agree with them, changed their own recommendations, or tried to find an area of compromise. Team members did not fully address differences across disciplines. Interactions during these cases suggest that team members see themselves primarily as representatives of their own discipline rather than as members of a team. Different values and theoretical perspectives seem to influence divergence of opinion. A need for a common value base, language, and conceptual framework was evident.


Regional distribution of cholinergic nerves in rat parietal pericardium.
The innervation pattern of parietal pericardium was studied in normal as well as chemically sympathectomized rats using the cholinesterase histochemical method. The existence of important regional variations in the distribution of cholinergic nerves within various portions of parietal pericardium studied was observed. The atria appear more richly innervated than ventricles, while the innervation of atria is characterized by the existence of thin and thick cholinergic nerve fibers not organized in plexuses and of elbow-shaped acetylcholinesterase cholinergic nerve fibers. Small blood vessels and islands of adipocytes receive a cholinergic innervation as well. The chemical sympathectomy does not alter the pattern of stained cholinergic nerve fibers. A possible afferent significance of the atrial innervation is discussed.


Metabolism of N-nitrosodimethylamine.
NDMA and NDEA are metabolized by a microsomal enzyme system that requires NADPH and oxygen. This metabolism leads to an unstable product which decomposes to yield a reactive alkylating species. This species is too reactive chemically to influence significantly organs other than those in which it was generated. Alkylation of cellular components, particularly DNA, is a critical event in the initiation of tumours by these carcinogens. The greatest capacity to metabolize these nitrosamines to alkylating agents is found in the liver, but other organs, including the oesophagus, lung and kidney, are also capable of activation. These organs may be more susceptible to alkylation than the liver because they have a lesser ability to catalyse the removal of 06-alkylguanine from their DNA. However, orally administered doses of NDMA and the NDMA formed by nitrosation reactions within the gastrointestinal tract are rapidly absorbed from the upper part of the small intestine and carried to the liver in the portal blood supply. When small doses are given in this way, the capacity of the liver to metabolize the carcinogen is sufficient that the nitrosamine is effectively cleared in a 'first-pass' effect, leaving very little to interact with other organs. This has two important consequences: firstly, levels of NDMA found in peripheral blood may be significantly lower than those expected on the basis of total dietary exposure because of the rapid metabolism and effective clearance of the carcinogen by the liver; secondly, physiological factors leading to reduction of the metabolic activation in the liver may result in more of the carcinogen being metabolized other tissues and in a greater risk of cancer developing in those tissues.


Phosphomolybdic and phosphotungstic acids as efficient catalysts for the synthesis of bridged 1,2,4,5-tetraoxanes from β-diketones and hydrogen peroxide.
Phosphomolybdic acid (PMA) and phosphotungstic acid (PTA) efficiently catalyze the addition of H2O2 to β-diketones to form bridged 1,2,4,5-tetraoxanes. These reactions are not accompanied by the formation of monocyclic peroxides containing hydroxy and hydroperoxide groups or polymeric peroxides. The use of these catalysts made it possible to obtain bridged tetraoxanes from easily oxidizable benzoylacetone derivatives and α-unsubstituted β-diketones. The syntheses are scaled up to ten grams. The resulting peroxides can be easily isolated from the reaction mixture by column chromatography. The yield of tetraoxanes depends on the structure of β-diketone and varies from 12 to 83%. NMR monitoring of two bridged 1,2,4,5-tetraoxanes synthesis was carried out.


Antigen-specific immunotherapies in rheumatic diseases.
The main goal of antigen-specific immunotherapy (ASI) in autoimmune and rheumatic diseases is to reprogramme or remove autoreactive cells and/or induce immune tolerance to self-antigens. Current therapies in these diseases either treat symptoms or slow down disease progression but are not yet curative or preventative - disease-specific treatments are urgently needed. In contrast to the nonspecific treatments in current use that induce generalized immune suppression, which is associated with several adverse effects including increased risk of infections, ASIs target a restricted subset of B cells or T cells, and thus do not compromise systemic immunity and host defence. This Review provides a summary of novel approaches for identifying autoepitopes and detecting and targeting autoreactive cells that might help in the development of ASIs. Promising approaches include the use of tolerizing peptides coupled to MHC constructs and/or nanocompounds, tolerizing dendritic cells and antigen-specific vaccines. Following studies in animal models of rheumatoid arthritis and systemic lupus erythematosus, several of these strategies have now entered clinical trials. However, to use these approaches in humans, several important limitations must first be addressed, such as; selecting the proper immunodominant autoantigen; identifying the optimal timing, dosing and route of administration; finding biomarkers for monitoring the therapy; and optimizing methodology.


Auditory cortical onset responses revisited. II. Response strength.
Most neurons of the auditory pathway discharge spikes locked to the onset of an acoustic stimulus, but it is largely unknown in which way the acoustic parameters of sound onsets shape the neuronal responses. In this paper is analyzed the number of spikes discharged by single neurons in primary auditory cortex of barbiturate-anesthetized cats to the onsets of tones of characteristic frequency. The time course of the peak pressure (i.e., the envelope) was altered by parametrically varying sound pressure level (SPL), rise time, and rise function (linear or cosine-squared). For both rise functions, rise time had manifold, and in some cases dramatic, effects on conventional spike count-level functions. In general, threshold SPL, dynamic range, and the lowest SPL at which monotonic spike count functions saturated increased with prolongation of the rise time. In neurons with mostly nonmonotonic spike count-level functions, "best SPL" increased and the descending high-SPL arms flattened, so that functions obtained with long rise times were often monotonic whereas those obtained with shorter rise times were highly nonmonotonic. Consequently, the "tuning" to SPL was less sharp for longer rise time tones, and spike count versus rise time functions changed from "short-pass" to "long-pass" with an increase in SPL. Systematic effects of rise time persisted when spike counts were plotted against the rate of change of peak pressure or against the maximum acceleration of peak pressure. However, when spike counts were plotted as a function of the instantaneous peak pressure at the time of response initiation, the functions obtained with different rise times, and even with different rise functions, were in close register. This suggests that the stimulus-dependent component of first-spike latency can be viewed as an integration window, during which rate of change of peak pressure is integrated. The window commences with tone onset and its duration is inversely related to the maximum acceleration (or, for linear rise functions, the rate of change) of peak pressure and the neuron's transient sensitivity. The present findings seriously question, for onset responses, the usefulness of the spike count-level function and measures derived from it, such as threshold SPL, dynamic range, best SPL, or degree of nonmonotonicity. They further cast doubt onto the validity of current concepts of intensity coding at cortical levels, because most neurons' onset responses are not indicative of a signal's steady-state SPL. However, they suggest a mechanism by which a neuronal population will sample a given transient in an orderly, sensitivity-dependent, temporal sequence. The sampling rate is automatically adjusted to, and adjusted by, the rapidity of the signal's change. And the instantaneous properties of the transient could be represented by the ratios and spatial distribution of responses across the simultaneously active subpopulation. Such a mechanism could provide the basis for the demonstrated capability of discrimination of rapid transients.


Outcomes and Complications of Aggressive Resection Strategy for Pituitary Adenomas in Knosp Grade 4 With Transsphenoidal Endoscopy.
Surgery for pituitary adenomas (PAs) with cavernous sinus (CS) invasion in Knosp grade 4 is a great challenge and whether to adopt a conservative or aggressive surgical strategy is controversial. The aim of this study is to provide the outcomes and complications of an aggressive resection strategy for Knosp grade 4 PAs with transsphenoidal endoscopic surgery. Outcomes and complications were retrospectively analyzed in 102 patients with Knosp grade 4 PAs. Among them, primary PAs were seen in 60 patients and recurrent PAs were seen in 42 cases. Gross total resection (GTR) of the entire tumor was achieved in 72 cases (70.6%), subtotal tumor resection (STR) in 18 cases (17.6%), and partial tumor resection (PTR) in 12 cases (11.8%). Additionally, GTR of the tumor within the CS was achieved in 82 patients (80.4%), STR in 17 patients (16.7%), and PTR in 3 patients (2.9%). Statistical analyses showed that both recurrent tumors and firm consistency tumors were adverse factors for complete resection (P<0.05). Patients with GTR of the entire tumor were more likely to have favorable endocrine and visual outcomes than those with incomplete resection (P<0.05). Overall, the most common surgical complication was new cranial nerve palsy (n=7, 6.8%). The incidence of internal carotid artery (ICA) injury and postoperative cerebrospinal fluid (CSF) leakage was 2.0% (n=2) and 5.9% (n=6), respectively. Six patients (5.9%) experienced tumor recurrence postoperatively. For experienced neuroendoscopists, an aggressive tumor resection strategy via transsphenoidal endoscopic surgery may be an effective and safe option for Knosp grade 4 PAs.


Additive effects of sequential excitatory and inhibitory theta burst stimulation in improving cortical excitability following ischaemic stroke.
To study the effects of sequential excitatory and inhibitory theta burst stimulation (TBS) on cortical excitability in patients with subacute ischaemic stroke. Fifteen patients with first-ever middle cerebral artery ischaemic stroke within last three months were subjected to intermittent TBS over the hand area (M1) of the stroke hemisphere (iTBSSH) followed by continuous TBS over the intact hemisphere M1 (cTBSIH). The study measured motor evoked potential (MEP) amplitude, resting motor threshold (RMT) and contralateral cortical silent period (cCSP) at baseline and after 7 minutes of each TBS session. The mean age of the patients was 62.4 ± 8.0 years. The absolute changes in baseline motor physiological parameters were significantly greater after cTBSIH than after iTBSSH (p = 0.001). Following iTBSSH, there was a significant decrease in mean RMT (7.4%; p < 0.001). Following cTBSIH, there was further 18.3% increase in mean MEP amplitude and decrease in mean RMT (4.7%; p < 0.001) and cCSP (5.6%; p < 0.001) of the stroke hemisphere. Similar changes of smaller magnitude were noted in 12 age-matched controls. The results indicate that combining iTBSSH and cTBSIH can have additive effect in increasing cortical excitability in subacute ischaemic patients with stroke.


Method to assess identifiability in electronic data files.
The authors developed the Record Uniqueness (RU) software program to assess electronic data files for risk of confidentiality breach based on unique combinations of key variables. The underlying methodology utilized by the RU program generates a frequency distribution for every variable selected for analysis and for all combinations of the variables selected. In addition, the program provides the regression coefficient that designates the relative contribution of each variable to the unique records on the data file. The authors used RU to evaluate a North American Association of Central Cancer Registries research data set with 4.67 million cases from 34 population-based cancer registries for 1995-2001. To illustrate the process and utility of RU, they describe the evaluation process of the confidentiality risk of adding a county-based socioeconomic measure to the research file. The RU method enables one to be assured of record confidentiality, provides flexibility to adjust record uniqueness thresholds for different users or purposes of data release, and facilitates good stewardship of confidential data balanced with maximum use and release of information for research. RU is a useful data tool that can quantify the risk of confidentiality breach of electronic health databases, including reidentifiability of cases through triangulation of information or linkage with other electronic databases.


Why it pays to 'grill' your supplier.
When it comes to ensuring that your cold storage operation and maintenance meets MHRA requirements, it pays to ensure that your service supplier knows what it is doing. So says Joe Fudge, instrumentation service manager for ABB's instrumentation business in the U.K., who outlines some of the key factors to consider when selecting a supplier of cold chain mapping services.


Novel beta-lactam antibiotics synthesized by amination of catechols using fungal laccase.
Novel cephalosporins, penicillins, and carbacephems were synthesized by amination of catechols with amino-beta-lactams like cefadroxil, amoxicillin, ampicillin and the structurally related carbacephem loracarbef using laccase from Trametes sp. All isolated monoaminated products inhibited the growth of several Gram positive bacterial strains in the agar diffusion assay, among them methicillin-resistant Staphylococcus aureus strains and vancomycin-resistant Enterococci. Observed differences in the cytotoxicity and in vivo activity in a "Staphylococcus-infected, immune suppressed mouse" model are discussed.


Binder ratio in the two-dimensional q-state clock model.
We study phase transition properties of the two-dimensional q-state clock model by an extensive Monte Carlo simulation. By analyzing the Binder ratio and its temperature derivative, we confirm that the two-dimensional q-state clock model exhibits two distinct Kosterlitz-Thouless phase transitions for q=5,6 but it has one second-order phase transition for q=4. The critical temperatures are estimated quite accurately from the crossing behavior of the Binder ratio (for q<5) and from negative divergent dips of the derivative of the Binder ratio (for q≥5) around these critical points. We also calculate the correlation length, the helicity modulus, and the derivative of the helicity modulus, and analyze their behaviors in different phases in detail.


Rare earth elements and select actinoids in the Canadian House Dust Study.
Nationally representative baseline data are presented for rare earth elements (REE), thorium (Th) and uranium (U) in house dust sampled from 1025 urban homes, in units of concentrations (μg g-1 ), loadings (μg m-2 ), and loading rates (ng m-2 d-1 ). Spearman rank correlations indicate that, in addition to outdoor sources, consumer products and building materials can influence indoor dust concentrations of REE, Th, and U. Correlations (P<.01) with numbers of occupants, dogs, and cats suggest soil track-in. Correlations (P<.01) with hardwood floors suggest release of REE additives used in pigments and coatings during daily wear and tear. Concentrations of light REE are elevated in smokers' homes compared to non-smokers' homes (P<.001), suggesting that a key source is "mischmetal," the REE alloy used in cigarette-lighter flints. Indoor sources include geological impurities in raw materials used in consumer products, such as U and Th impurities in bentonite clay used in cat litter, and REE impurities in phosphates used for a variety of applications including dog food and building materials. Median gastric bioaccessibility (pH 1.5) of most REE in dust ranges from about 20% to 29%. Household vacuum samples correlate with fresh dust samples from the same homes (P<.001 for all investigated elements).


Patterns of Comorbidity in Hepatocellular Carcinoma: A Network Perspective.
Hepatocellular carcinoma (HCC) is a common and fatal cancer. People with HCC report higher odds of comorbidity compared with people without HCC. To explore the association between HCC and medical comorbidity, we used routinely collected clinical data and applied a network perspective. In the network perspective, we used correlation analysis and community detection tests that described direct relationships among comorbidities. We collected 14,891 patients with HCC living in Jilin Province, China, between 2016 and 2018. Cirrhosis was the most common comorbidity of HCC. Hypertension and renal cysts were more common in male patients, while chronic viral hepatitis C, hypersplenism, hypoproteinemia, anemia and coronary heart disease were more common in female patients. The proportion of chronic diseases in comorbidities increased with age. The main comorbidity patterns of HCC were: HCC, cirrhosis, chronic viral hepatitis B, portal hypertension, ascites and other common complications of cirrhosis; HCC, hypertension, diabetes mellitus, coronary heart disease and cerebral infarction; and HCC, hypoproteinemia, electrolyte disorders, gastrointestinal hemorrhage and hemorrhagic anemia. Our findings provide comprehensive information on comorbidity patterns of HCC, which may be used for the prevention and management of liver cancer.


Detection of drug binding to DNA by hydroxyl radical footprinting. Relationship of distamycin binding sites to DNA structure and positioned nucleosomes on 5S RNA genes of Xenopus.
We report the use of hydroxyl radical footprinting to analyze the interaction of distamycin and actinomycin with the 5S ribosomal RNA genes of Xenopus. There is a qualitative difference in the hydroxyl radical footprints of the two drugs. Distamycin gives a conventional (albeit high-resolution) footprint, while actinomycin does not protect DNA from hydroxyl radical attack, but instead induces discrete sites of hyperreactivity. We find concentration-dependent changes in the locations of distamycin binding sites on the somatic 5S gene of Xenopus borealis. A high-affinity site, containing a G.C base pair, is replaced at higher levels of bound drug by a periodic array of different lower affinity sites that coincide with the places where the minor groove of the DNA would face in toward a nucleosome core that is known to bind to the same sequence. These results suggest that distamycin recognizes potential binding sites more by the shape of the DNA than by the specific sequence that is contained in the site and that structures of many sequences are deformable to a shape that allows drug binding. We discuss the utility of hydroxyl radical footprinting of distamycin for investigating the underlying structure of DNA.


Triatominae (Hemiptera: Reduviidae) fauna in bird nests: the case of Morrinhos, Ceará, Brazil.
Triatominae are associated with various Brazilian habitats, including bird nests, animal burrows, and peridomestic structures. Despite extensive studies on triatomines in domiciliary environments in Ceará, Brazil, there has been limited research on their presence in the wild. This study focuses on the municipality of Morrinhos in Ceará, which is characterized by a Caatinga biome and riparian forests along the Acaraú River. During the study, a total of 185 nests of Pseudoseisura cristata were analyzed in rural locations and triatomines were collected in 26 nests from 12 different locations. A total of 117 triatomines was collected, belonging to three species: Psammolestes tertius, Rhodnius nasutus, and Triatoma pseudomaculata. Rhodnius nasutus was the only species found in a nest inhabited by Didelphis albiventris. Nests of P. cristata serve as shelters for various animals, providing an ideal environment for triatomines to establish colonies due to their proximity to food sources and their generalist feeding habits. The incorporation of anthropogenic materials by birds in nest construction can indirectly affect the presence of other animals that may serve as food sources for triatomines. Understanding the interactions between triatomines, birds, and their habitats is essential for assessing the risks associated with triatomine infestation in wild ecosystems.


Rediscovery of Dixa repanda Peters and description of its putative sister species, Dixa falcata sp. nov., from the south-central United States (Diptera: Dixidae).
Dixa repanda Peters, previously known only from the type series of three males, was rediscovered after targeted collections in the southcentral and midwestern United States. These collections also revealed the presence of its undescribed putative sister species, Dixa falcata sp. nov. The two species are sympatric in the Ozark Mountains. Adults of D. repanda are redescribed and those of Dixa falcata are described. Males of both species are distinguished from related, similarly colored species by a falcate gonostylus and extremely reduced cercus. Males of the two species are easily separated from each other by the shape and thickness of the gonostylus. Females are not reliably separable from each other or related species. Biological insights, including known distributions, of both species are provided.


Comparing Revision Total Knee Arthroplasty Stems at a High-Volume Revision Center.
Hybrid fixation and fully cemented fixation are commonly used in revision total knee arthroplasty (rTKA). These two techniques are typically done based on surgeon preference and one has not demonstrated superiority over the other. The purpose of this study was to examine if there was a difference in survivorship between the two different techniques. A retrospective cohort study of all consecutive patients undergoing rTKA (CPT 27487) from January 1, 2011 to January 1, 2018 at a single academic center was performed. Patients were divided into cemented and hybrid rTKA groups with comparison of patient demographic, clinical and radiological outcomes, reoperation, change in post-operative hemoglobin (HgB), and length of stay (LOS). A total of 133 rTKA for 122 patients were identified: 30.1% in the cemented and 69.9% in the hybrid groups. There was no significant difference in age (p = 0.491), sex (p = 0.250), laterality (p = 0.421), or body mass index (BMI) (p = 0.609) between the two groups. Mean LOS (hybrid 4.13 days, cemented 3.65 days; p = 0.356) and change in Hgb (hybrid 2.95 mg/dL, cemented 2.62mg/dL; p = 0.181) were not statistically different between the groups. Mean follow up for the hybrid (25.4 months, range 2-114 months) and cemented (24.6 months, range 3-75.5 months) rTKA was not statistically significant (p = 0.825). Overall survival rates were 80.9% in the hybrid and 84.6% in the cemented groups (p = 0.642). Hybrid and fully cemented rTKA techniques have similar survival rates at a minimum followup of 2 years. Additionally, in our cohort, age, gender, and BMI were not associated with failure in either group. Furthermore, we did not observe differences in LOS or change in hemoglobin suggesting early postoperative complications may not differ between cemented and hybrid stemmed groups. Continued long-term research is required for defining the best rTKA technique.


THE MAINTENANCE OF POLYGENIC VARIATION IN FINITE POPULATIONS.
Models of the maintenance of genetic variance in a polygenic trait have usually assumed that population size is infinite and that selection is weak. Consequently, they will overestimate the amount of variation maintained in finite populations. I derive approximations for the equilibrium genetic variance, V^G in finite populations under weak stabilizing selection for triallelic loci and for an infinite "rare alleles" model. These are compared to results for neutral characters, to the "Gaussian allelic" model, and to Wright's approximation for a biallelic locus under arbitrary selection pressures. For a variety of parameter values, the three-allele, Gaussian, and Wrightian approximations all converge on the neutral model when population size is small. As expected, far less equilibrium genetic variance can be maintained if effective population size, N, is on the order of a few hundred than if N is infinite. All of the models predict that comparisons among populations with N less than about 104 should show substantial differences in V^G. While it is easier to maintain absolute V^G when alleles interact to yield dominance or overdominance for fitness, less additivity also makes V^G more susceptible to differences in N. I argue that experimental data do not seem to reflect the predicted degree of relationship between N and V^G. This calls into question the ability of mutation-selection balance or simple balancing selection to explain observed V^G. The dependence of V^G on N could be used to test the adequacy of mutation-selection balance models.


Hepatic abscesses after liver transplant: 1997-2008.
Infectious complications (such as liver abscesses) remain one of the major causes of posttransplant morbidity and mortality. Management may be problematic and is often based on experience with hepatic abscess in nontransplant patients. We reviewed our experience with hepatic abscess in liver transplant recipients to assess their presentation, clinical features, treatment, and outcome. A retrospective review of all liver transplant in Shiraz transplant center from September 1997 through September 2008 was performed. Hepatic abscess was defined as a parenchymal hepatic lesion consistent with abscess (as described by a radiologist), positive liver or concurrent blood cultures, or both (within 24 hours), and compatible clinical findings. Of 560 liver recipients, we identified 5 patients (23-42 y) who had experienced 7 episodes of hepatic abscess, 30-240 days after transplant. All patients had received liver from deceased donors. Biliary reconstruction was done by duct-to-duct anastomosis in 4 and hepatico-jejunostomy in 1 case. Pretransplant diagnoses included hepatitis B cirrhosis, autoimmune hepatitis (2 cases), Caroli disease, and cryptogenic cirrhosis. Liver aspirates showed E. coli in 4 cases, and Aspergillus in 1 case. The main predisposing factor was bile-to-duct anastomosis stricture in 3, diabetes mellitus in 2, and hepatic artery thrombosis in 1 of the patients. Two patients died owing to liver and multiorgan failure, despite percutaneous and operative drainage with broad spectrum antibiotics and antifungals. Hepatic abscess, a rare complication after liver transplant, was associated with hepatic artery thrombosis, biliary anastomosis stricture, and diabetes mellitus. Mortality was higher than in patients who had not undergone transplant. Prolonged antibiotic therapy and drainage are required to improve the outcome in these patients.


Euclidean metric representations of haptically explored triangles.
This study explored whether people create Euclidean representations of 2-dimensional right triangles from touch and use them to make spatial inferences in accord with Euclidean distance axioms. Blindfolded participants who were instructed to form visual images of triangles felt the vertical and horizontal sides of right triangles, then estimated the lengths (but not the angles) of the 3 triangle sides. In these 3 experiments, length estimates conformed closely to the Euclidean metric when evaluated on application of the Pythagorean theorem. Participants who used a visual imaging strategy were accurate more often than those who used visual imagery less often. In Experiments 2 and 3, a hypotenuse inference was as accurate as a direct haptic judgment of the hypotenuse. These results demonstrated similar accuracy of the hypotenuse judgments when participants made verbal rather than haptic estimates. The findings indicate that participants can form Euclidean representations under certain conditions from felt 2-dimensional right triangles based on visual images.


BNIP3, a cell pro-apoptotic protein, involved in response to viral infection in orange spotted grouper, Epinephelus coioides.
BNIP3 is a kind of BH3-only protein that induces both cell death and autophagy. Here, a BNIP3 gene (EcBNIP3) was identified from orange spotted grouper, Epinephelus coioides. EcBNIP3 possessed 236 amino acids residues, contained a conservative BNIP3 domain and a transmembrane region. Besides, EcBNIP3 expressed at a relative high level in heart and spleen. EcBNIP3 transcript was up-regulated after SGIV infection in vitro. Subcellular localization analysis revealed that EcBNIP3 was predominantly localized in the cytoplasm and co-localized with mitochondria. In addition, overexpression EcBNIP3 accelerated SGIV infection induced cell death but inhibited viral genes transcription. Taken together, these results provided new evidence that fish BNIP3 might involved in response to virus infection.


Suppression of urokinase receptor expression by bikunin is associated with inhibition of upstream targets of extracellular signal-regulated kinase-dependent cascade.
Our laboratory showed that bikunin, a Kunitz-type protease inhibitor, suppresses 4beta-phorbol 12-myristate 13-acetate (PMA)- or tumor necrosis factor-alpha (TNFalpha)-induced urokinase-type plasminogen activator (uPA) expression in different cell types. In addition to its effects on protease inhibition, bikunin could be modulating other cellular events associated with the metastatic cascade. To test this hypothesis, we examined whether bikunin was able to suppress the expression of uPA receptor (uPAR) mRNA and protein in a human chondrosarcoma cell line, HCS-2/8, and two human ovarian cancer cell lines, HOC-I and HRA. The present study showed that (a) bikunin suppresses the expression of constitutive and PMA-induced uPAR mRNA and protein in a variety of cell types; (b) an extracellular signal-regulated kinase (ERK) activation system is necessary for the PMA-induced increase in uPAR expression, as PD098059 and U0126, which prevent the activation of MEK1, reduce the uPAR expression; (c) bikunin markedly suppresses PMA-induced phosphorylation of ERK1/2 at the concentration that prevents uPAR expression, but does not reduce total ERK1/2 antigen level; (d) bikunin has no ability to inhibit overexpression of uPAR in cells treated with sodium vanadate; and (e) we further studied the inhibition of uPAR expression by stable transfection of HRA cells with bikunin gene, demonstrating that bikunin secretion is necessary for inhibition of uPAR expression. We conclude that bikunin downregulates constitutive and PMA-stimulated uPAR mRNA and protein possibly through suppression of upstream targets of the ERK-dependent cascade, independent of whether cells were treated with exogenous bikunin or transfected with bikunin gene.


Acute Fulminant Hepatic Failure Caused by Sevoflurane Linked to Influenza A.
Sevoflurane is a volatile anesthetic agent that does not tend to cause clinically significant hepatotoxicity, but there are some reported hepatotoxicity cases in the literature. In the case presented here, adenotonsillectomy was performed during influenza infection, and sevoflurane was administered, after which acute fulminant hepatitis developed. At hour 24 of hospitalization after fulminant hepatic failure, liver transplant was performed in a 3.5-year-old patient without any known diseases. In such cases, etiology investigations should be planned, life support therapy should be administered, and information should be given to the patient to avoid exposure to sevoflurane in the future.


[Exposure to pesticides among pregnant women working in agriculture].
Pesticides have been used since the early days of modern agriculture. They are biologically active compounds that may pose a grave risk to health during or after their use. The available data, documenting pesticide exposures and related health effects in farmers, especially in pregnant women, are limited. Women were informed that the purpose of the research was to gather information about the exposure to pesticides during pregnancy. They were asked to provide information about their work in the field, spraying or preparatory work (washing clothes after spraying, cleaning, spraying equipment, preparing mixture for spraying). We received information about all spraying in household during woman's pregnancy, trade names of pesticides, names of active ingredients, type of cultivation and its area. The survey of pregnant women working in agriculture provided us with knowledge of potential hazards resulting from their work during pregnancy, especially from their involvement in spraying or preparatory work and working in the field after spraying. Other data obtained informed us what kind of pesticides were used in agriculture. The results indicate the necessity for increasing awareness of potential exposure to pesticides and their harmful effect among workers, especially among pregnant women. There is also a need to estimate real exposure via biological monitoring.


[Surgical Treatment of Prosthetic Valve Endocarditis; Tips of Complete Resection of Infective Tissue and Valve Replacement].
Fifteen consecutive prosthetic valve endocarditis (PVE) patients were operated from March 2009 to September 2014. The average age of patients was 68 years ( range 49 to 82) and 7 patients were male. The interval between initial surgery and reoperation was 62.4 months(range 2.6 to 340.9). Seven of these cases(47%) developed PVE within the 1st year after surgery were defined as early PVE. All microorganisms isolated from blood cultures in early PVE were Staphylococcus species. Generally, the infective prosthetic valve was removed 1st, then all infective tissues were excised from the periannular cavity. A new prosthetic valve was replaced in supra-annular fashion. One patient who had a severe discontinuity between the most part of left ventricle and aorta necessitated a root replacement. One patient in aortic PVE, needed an additional patch-plasty of anterior mitral leaflet. The mean cardiopulmonary bypass and aortic clamping times were 250 minutes( range 132 to 426) and 165 minutes( range 117 to 309), respectively. Four patients needed permanent pacemaker implanted for complete A-V block. Five patients had transient acute renal failure, and 1 required dialysis could be weaned at 40 post operative day. Average postoperative hospital stay was 39 days (range 21 to 108), and the operative mortality was 0%. The postoperative follow up was 3.1 years( range 0.6 to 6.0), all patients were doing well without re-infection and heart failure except 1 patient died by non-cardiac disease.


Interfacing nanocarbons with organic and inorganic semiconductors: from nanocrystals/quantum dots to extended tetrathiafulvalenes.
There is no doubt that the outstanding optical and electronic properties that low-dimensional carbon-based nanomaterials exhibit call for their implementation into optoelectronic devices. However, to harvest the enormous potential of these nanocarbons it is essential to probe them in multifunctional electron donor-acceptor systems, placing particular attention on the interactions between electron donors/electron acceptors and nanocarbons. This feature article outlines challenges and recent breakthroughs in the area of interfacing organic and inorganic semiconductors with low-dimensional nanocarbons that range from fullerenes (0D) and carbon nanotubes (1D) to graphene (2D). In the context of organic semiconductors, we focus on aromatic macrocycles and extended tetrathiafulvalenes, and CdTe nanocrystals/quantum dots represent the inorganic semiconductors. Particular emphasis is placed on designing and probing solar energy conversion nanohybrids.


The influence of intramammary antibiotic treatment, presence of bacteria, stage of lactation and parity in dairy goats as measured by the California Milk Cell Test and somatic cell counts.
The California Milk Cell Test (CMCT) and somatic cell counts (SCC) on their own were not reliable methods in the identification of subclinical mastitis in the dairy goats studied and should be accompanied by microbiological tests. However, CMCT and SCC were indicators of irritation of the udder parenchyma. In healthy goats Spectrazol Milking Cow (Schering-Plough AH) caused the least and Curaclox LC (Norbrook (ARK AH)) the most irritation of parenchyma after intramammary treatment. The effects of Rilexine 200 LC (Logos Agvet (Virbac)) were intermediate. There was a highly significant difference (P < 0.001) in the mean log SCC between treated and control groups for goats treated with Curaclox LC and Rilexine 200 LC but no significant difference was present in the mean log SCC of treatment and control groups for goats treated with Spectrazol Milking Cow at the 07:00 and at 19:00 samplings. The CMCT was an indicator of the level of SCC in goat milk. The CMCT was more useful in confirming the absence of infection, rather than in diagnosing mastitis.


Effects of acoustic stimulation on biochemical parameters in the digestive gland of Mediterranean mussel Mytilus galloprovincialis (Lamarck, 1819).
Underwater sounds generated by anthropogenic activity can cause behavior changes, temporary loss of hearing, damage to parts of the body, or death in a number of marine organisms and can also affect healing and survival. In this study, the authors examined the effects of high-frequency acoustic stimulations on a number of biochemical parameters in the Mediterranean mussel, Mytilus galloprovincialis. During the experiment, animals were placed in a test tank and exposed to acoustic signals [a linear sweep ranging from 100 to 200 kHz and lasting 1 s, with a sound pressure level range of between 145 and 160 dBrms (re 1μParms)] for 3 h. Total haemocyte count was assessed and glucose levels, cytotoxic activity and enzyme activity (alkaline phosphatase, esterase and peroxidase) in the digestive gland were measured. For the first time, this study suggests that high-frequency noise pollution has a negative impact on biochemical parameters in the digestive gland.


Febrile Illness with Skin Rashes.
Skin rashes that appear during febrile illnesses are in fact caused by various infectious diseases. Since infectious exanthematous diseases range from mild infections that disappear naturally to severe infectious diseases, focus on and basic knowledge of these diseases is very important. But, these include non-infectious diseases, so that comprehensive knowledge of these other diseases is required. Usually, early diagnostic testing for a febrile illness with a rash is inefficient. For clinical diagnosis of diseases accompanied by skin rash and fever, a complete history must be taken, including recent travel, contact with animals, medications, and exposure to forests and other natural environments. In addition, time of onset of symptoms and the characteristics of the rash itself (morphology, location, distribution) could be helpful in the clinical diagnosis. It is also critical to understand the patient's history of specific underlying diseases. However, diagnostic basic tests could be helpful in diagnosis if they are repeated and the clinical course is monitored. Generally, skin rashes are nonspecific and self-limited. Therefore, it could be clinically meaningful as a characteristic diagnostic finding in a very small subset of specific diseases.


[Which medication should be used to treat uncomplicated malaria when chloroquine becomes ineffective in Western Côte d'Ivoire?].
Study of children treated for uncomplicated malaria in the sub-prefecture of Zouan Hounien in Western Côte d'Ivoire demonstrated that clinical failure rates (WHO 14-day test) were 43% for chloroquine and 6% for pyrimethamine-sulfadoxine (PS). Two issues raise serious doubts about the use of PS as a replacement for chloroquine. The first is detection of persistent asymptomatic parasitemia at day 7 in children treated with PS. The second is widespread use of one PS component (sulfadoxine) to prevent opportunistic infection in AIDS patients or to treat infection. Further study will be needed to evaluate the therapeutic and parasitological efficacy of amodiaquine in the region.


Mitral annuloplasty ring suture forces: Impact of surgeon, ring, and use conditions.
The study objective was to quantify the effect of ring type, ring-annulus sizing, suture position, and surgeon on the forces required to tie down and constrain a mitral annuloplasty ring to a beating heart. Physio (Edwards Lifesciences, Irvine, Calif) or Profile 3D (Medtronic, Dublin, Ireland) annuloplasty rings were instrumented with suture force transducers and implanted in ovine subjects (N = 23). Tie-down forces and cyclic contractile forces were recorded and analyzed at 10 suture positions and at 3 levels of increasing peak left ventricular pressure. Across all conditions, tie-down force was 2.7 ± 1.4 N and cyclic contractile force was 2.0 ± 1.2 N. Tie-down force was not meaningfully affected by any factor except surgeon. Significant differences in overall and individual tie-down forces were observed between the 2 primary implanting surgeons. No other factors were observed to significantly affect tie-down force. Contractile suture forces were significantly reduced by ring-annulus true sizing. This was driven almost exclusively by Physio cases and by reduction along the anterior aspect, where dehiscence is less common clinically. Contractile suture forces did not differ significantly between ring types. However, when undersizing, Profile 3D forces were significantly more uniform around the annular circumference. A suture's tie-down force did not correlate to its eventual contractile force. Mitral annuloplasty suture loading is influenced by ring type, ring-annulus sizing, suture position, and surgeon, suggesting that reports of dehiscence may not be merely a series of isolated errors. When compared with forces known to cause suture dehiscence, these in vivo suture loading data aid in establishing potential targets for reducing the occurrence of ring dehiscence.