Effectiveness of intermittent preventive treatment with sulphadoxine-pyrimethamine for control of malaria in pregnancy in western Kenya: a hospital-based study.
To monitor the effectiveness of intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) for the control of malaria in pregnancy at delivery in the Provincial Hospital in Kisumu, Kenya, and to assess the effect of IPT in participants in a cohort study. Between June 1999 and June 2000, information on IPT and birth outcome was collected in 2302 consecutive deliveries. A group of 889 women, who were enrolled in a cohort to assess the interaction between malaria and HIV, were analysed separately because of the enrollment criteria and different access to health care. The prevalence of placental malaria was 13.8% and of low birthweight (LBW) was 12.2%. In multivariable analysis, IPT (> or =1 dose of SP) was associated with a reduction in placental malaria and LBW [adjusted odds ratio (OR) 0.56, 95% confidence interval (CI) 0.39-0.83 and OR 0.65, 95% CI 0.45-0.95, respectively]. An adjusted mean increase in birthweight of 61 g was seen (95% CI 22-101 g) for each increment in number of SP doses (> or =2 doses grouped together). IPT was associated with a reduction in placental malaria in HIV-seronegative women (OR 0.49, 95% CI 0.28-0.86) but this was not significant among HIV-seropositive women (OR 0.45, 95% CI 0.20-1.05). A significant effect on birthweight could not be detected among participants in the HIV-cohort. This evaluation confirms that IPT with SP is effective in reducing placental malaria and LBW. It will be important to increase coverage of IPT and to extend IPT to antenatal clinics in peri-urban and rural areas.


Treatment of drug resistant A-V reciprocating tachycardias with multiprogrammable dual demand A-V sequential (DVI,MN) pacemakers.
Programmable dual A-V sequential demand (DVI,MN) pacemakers were implanted in eight patients with recurrent or incessant, drug-refractory, A-V reciprocating tachycardias. This was done after intracardiac studies had identified a variety of electrogenetic mechanisms which include tachycardias involving Kent bundles, (manifest or concealed Wolff-Parkinson-White syndrome), nodoventricular (Mahaim) fibers, enhanced A-V node pathways (Lown-Ganong-Levine syndrome), and dual intranodal pathways. The antitachycardia features of the pacemaker were evaluated during the electrophysiological studies. No immediate postoperative complications occurred after implantation. Furthermore, during the follow-up periods (4 to 20 months), clinical assessment, ambulatory (Holter) monitoring and invasive (as well as noninvasive) evaluations have confirmed continuous effectiveness in recognizing and automatically terminating the tachycardias. Late pacemaker system malfunction has not occurred. The frequency of the tachycardias and the dosage of concomitantly-administered antiarrhythmic medications were significantly reduced. Furthermore, preliminary studies performed in our laboratory suggest that DVI,MN pacemakers may also be useful in certain types of intra-atrial reentry tachycardias coexisting with sinus node dysfunction.


Leucine-rich repeat kinase 2 and lysosomal dyshomeostasis in Parkinson disease.
Over the last two decades, a number of studies have underlined the importance of lysosomal-based degradative pathways in maintaining the homeostasis of post-mitotic cells, and revealed the remarkable contribution of a functional autophagic machinery in the promotion of longevity. In contrast, defects in the clearance of organelles and aberrant protein aggregates have been linked to accelerated neuronal loss and neurological dysfunction. Several neurodegenerative disorders, among which Alzheimer disease (AD), Frontotemporal dementia, and Amyotrophic Lateral Sclerosis to name a few, are associated with alterations of the autophagy and endo-lysosomal pathways. In Parkinson disease (PD), the most prevalent genetic determinant, Leucine-rich repeat kinase 2 (LRRK2), is believed to be involved in the regulation of intracellular vesicle traffic, autophagy and lysosomal function. Here, we review the current understanding of the mechanisms by which LRRK2 regulates lysosomal-based degradative pathways in neuronal and non-neuronal cells and discuss the impact of pathogenic PD mutations in contributing to lysosomal dyshomeostasis.


Radiology-pathology conference: primary peritoneal mesothelioma.
Primary peritoneal mesothelioma is a rare neoplasm which carries a dismal prognosis. These highly aggressive tumors arise from mesothelial cells lining the peritoneum and are rapidly fatal. The neoplasm is typically associated with crocidolite asbestos exposure. We present the case of a 75-year-old man with primary peritoneal mesothelioma, with invasion into the right hepatic lobe.


What are the impacts of setting up new medical schools? A narrative review.
The growth of the UK's population together with an aging society with increasingly complex health and social care needs has placed a greater demand on statutory care services. In view of this emerging landscape, the UK Government has sought to increase its medically trained workforce in order to better respond to the demands placed on the health service. Five universities were announced as homes to new medical schools offering undergraduate places to boost the numbers of doctors training in England. The aim of this narrative review was to explore how new medical schools could improve the health outcomes of the local population and evaluate the potential contribution it may make to the local economy, workforce and to research and innovation. A narrative review was undertaken using a systematic approach for the search literature strategy. The articles were evaluated by undertaking a critical assessment evaluating the fitness of a paper for review according to results, methods used to test the hypothesis, conclusions and impact and limitations. Thematic analysis was employed to organise and summarise the findings across a heterogeneous body of literature included in the review. The analysis was developed in an inductive manner and there were not any predefined themes to guide data extraction and analysis. Thirty-six articles were selected for inclusion for this narrative review. The review identified six key themes: influence of prior rural exposure, medical school environment and rural enrichment programmes, workforce, health outcomes of local populations, social accountability, economic contribution of medical schools to communities and impact on rural research. The studies included found a wealth of information on a wide-range of topics on the expansion of undergraduate education and its implications on the future medical workforce. It was shown that medical schools can have a positive effect on the health, social, economic and research activity of a region, but this literature tended to be heterogeneous in focus without consideration of the inter-connections between the wider societal and economic impacts arising from long-term sustainable change being brought to a region.


Tunable deep-ultraviolet source generated by scattering off adiabatically prepared Raman coherence in hydrogen gas.
We demonstrate a tunable deep-ultraviolet coherent source generated by the beating of a tunable UV laser and strongly driven vibrational Raman coherence in hydrogen. The total energy conversion efficiency reaches a maximum of 50% at the phase side of the Raman coherence. The generated spectrum of Raman sidebands tunes with the input and extends from 435 to 146 nm for an input at 282 nm.


Reduction in morbidity due to diarrhea in nursing beef calves by use of an inactivated oil-adjuvanted rotavirus-Escherichia coli vaccine in the dam.
An outbreak of neonatal diarrhea occurred among beef calves (2000 animals) from one large Argentinian farm in 1985. Rotavirus was detected in 78% (106/136) and enterotoxigenic Escherichia coli in 1.5% of the samples (2/136) obtained from sick calves. In comparison rotavirus was identified in only 1.6% (1/63) of the samples from clinically healthy calves. The rotavirus strain responsible for the outbreak was characterized as serotype 6 belonging to group A. In the following three years the protective capacity of a combined rotavirus-E. coli inactivated vaccine administered to the dams during the last third of the gestation period was evaluated on this farm by comparison of morbidity due to diarrhea in calves from vaccinated vs. placebo cows within the same year. The morbidity due to diarrhea among calves from dams in the vaccinated and placebo groups was 34% and 77%, respectively in 1986; 23% and 47% in 1987, and 15% and 34%, in 1988. In 1987 morbidity of diarrhea in calves born from vaccinated heifers was 54% and 74% in calves from placebo heifers. In 1988 morbidity from diarrhea was 41% and 54%, respectively among calves in these two groups. In all experiments, calves from heifers showed significantly greater morbidity than calves from cows. Differences in diarrhea morbidity between the vaccinated and placebo groups were statistically significant (P less than 0.05). Additional studies showed that the diarrhea had a significant influence (P less than 0.05) on the average live weight of the calves at weaning (5 to 7 months) with an average weight loss of 7.8 kg per calf among the calves affected with diarrhea.


Differential scanning calorimetric study of the binding of the primary water of hydration to nucleosides.
Differential scanning calorimetry was used to study the water of hydration of all of the nucleosides at 59% relative humidity. Hydration was observed in pristine samples of guanosine, (rG), deoxyguanosine, (dG), and deoxyadenosine, (dA). Two inequivalent water sites were observed in dG and one site in rG. Re-hydration was observed in rG and dG, but not in dA. The activation energies for rG were 0.697 +/- 0.051 eV and 0.683 plus minus 0.090 eV for pristine and cycled samples respectively. dG had activation energies of 0.726 +/- 0.026 eV and 0.997 +/- 0.034 eV for the first and second peaks in the pristine samples while the activation energy for cycled dG was 0.671 +/- 0.133 eV.


Quantitative analysis of free sphingoid bases in the brain and spinal cord tissues by high-performance liquid chromatography with a fluorescence detection.
The o-phthaldialdehyde precolumn derivatives of psychosine, sphinganine and sphingosine extracted from brain and spinal cord tissues were determined by high-performance liquid chromatography-fluorescence detection. This method was developed with the purpose of detecting an endogenous amount of psychosine, sphingosine and sphinganine using small aliquots of brain tissues and spinal cord in rats. These sphingolipid bases were extracted in various ratios of chloroform-methanol and several pH values. Recovery of the method is about 81% in 12 ng/tube (final volume, 320 microl), 90-95% in 45 ng/tube of sphingosine and sphinganine within 2-12% relative standard deviation. Detection limits of these sphingoid bases were about 0.05 pmol/mg brain tissue. In the forebrain, brainstem and spinal cord of rats at three different ages of postnatal days (PND) 1, PND 13 and 6 months old, the endogenous concentrations of psychosine, sphingosine and sphinganine were determined. From these results, this method is suitable for the determination of sphingoid bases in small aliquot of brain and spinal cord tissues.


Colchicine overdose: A South African experience, a case report.
Colchicine overdose is uncommon but is associated with a high mortality rate. It has a narrow therapeutic index and has been described to have a 100% mortality with ingestion of >0.8 mg/kg (Finkelstein et al., 2010; Herran-Monge et al., 2013; Aghabiklooei et al., 2014; Erden et al., 2013). This is a case report of a 19-year-old male who ingested 0.4 mg/kg of colchicine in a suicide attempt. He developed multiorgan dysfunction. He was managed supportively, and the dysfunction resolved. The clinical presentation and management should be familiar to all those who work in acute care in order to be able to identify and treat it timeously thus preventing morbidity and mortality. Treatment is largely supportive. To the best of our knowledge this is the first case of colchicine overdose described in Sub-Saharan Africa.


A review of 100 flexor tendon reconstructions with prosthesis.
A series of one hundred cases where silicone rods were used to prepare a bed for flexor tendon grafting is examined, the main indication for this technique being circumstances where one stage tendon grafting was likely to have a poor result. The main complications noted were a synovitis around the silastic rods, infection, and loss of the distal attachment of the silastic rod. The overall results were satisfactory.


Value from the Patients' and Payers' Perspectives.
Health care costs continue to increase, and the approach of countries and insurers is to focus on the value of the care delivered. Value is a function of quality in relation to costs. The perspective of the individual measuring value is important. Calculation of costs may include return to work if the employer's perspective is taken. The patients' perspectives include out-of-pocket expenses and work lost for both patients and potentially caregivers. The authors provide one example in the area of sleep apnea in which the anesthesiologist can provide value uniquely by being part of the team making the diagnosis.


Garcinia mangostana: a source of potential anti-cancer lead compounds against CEM-SS cell line.
Our current interest in searching for natural anti-cancer lead compounds from plants has led us to the discovery that the stem and roots of Garcinia mangostana can be a source of such compounds. The stem furnished 2,8-dihydroxy-6-methoxy-5-(3-methylbut-2-enyl)-xanthone (1), which is a new xanthone. Meanwhile, the root bark of the plant furnished six xanthones, namely alpha-mangostin (2), beta-mangostin (3), gamma-mangostin (4), garcinone D (5), mangostanol (6), and gartanin (7). The hexane and chloroform extracts of the root bark of G. mangostana as well as the hexane extract of the stem bark were found to be active against the CEM-SS cell line. gamma-Mangostin (4) showed good activity with a very low IC(50) value of 4.7 microg/ml, while alpha-mangostin (2), mangostanol (6), and garcinone D (5) showed significant activities with IC(50) values of 5.5, 9.6, and 3.2 microg/ml, respectively. This is the first report on the cytotoxicity of the extracts of the stem and root bark of G. mangostana and of alpha-mangostin, mangostanol, and garcinone D against the CEM-SS cell line.


Growth hormone aggravates renal abnormalities induced by neonatal enalapril treatment.
Lack of neonatal angiotensin II type-1 receptor stimulation produces irreversible abnormalities of renal function and morphology, which can be prevented by simultaneous administration of insulin-like growth factor-I (IGF-I). Given the fact that growth hormone (GH) is the strongest secretagogue for IGF-I, we wanted to explore whether GH could reproduce the effect of IGF-I. Rats were treated from 3 to 13 days of age with the angiotensin-converting enzyme inhibitor enalapril (10 mg/kg/day) and GH (4 mg/kg/day), alone or in combination. Renal gene expression of IGF-I and IGF-binding proteins (IGFBP) was determined during and after treatment. Renal function and morphology were investigated at adult age. In contrast to the beneficial effect of IGF-I, GH treatment in combination with enalapril further deteriorated both renal function and morphology as compared with enalapril treatment alone, demonstrating: reduced glomerular filtration rate, increased tubular dilation and further expansion of the outer medulla. Enalapril decreased medullary expression of IGF-I and increased renal expression of IGFBP-1, changes that were not affected by concomitant GH treatment. These findings indicate that GH and IGF-I have different roles in the renin-angiotensin system-mediated kidney development.


First identification and genotyping of Enterocytozoon bieneusi and Encephalitozoon spp. in pet rabbits in China.
Microsporidia are common opportunistic parasites in humans and animals, including rabbits. However, only limited epidemiology data concern about the prevalence and molecular characterization of Enterocytozoon bieneusi and Encephalitozoon spp. in rabbits. This study is the first detection and genotyping of Microsporidia in pet rabbits in China. A total of 584 faecal specimens were collected from rabbits in pet shops from four cities in Sichuan province, China. The overall prevalence of microsporidia infection was 24.8% by nested PCR targeting the internal transcribed spacer (ITS) region of E. bieneusi and Encephalitozoon spp. respectively. E. bieneusi was the most common species (n = 90, 15.4%), followed by Encephalitozoon cuniculi (n = 34, 5.8%) and Encephalitozoon intestinalis (n = 16, 2.7%). Mixed infections (E. bieneusi and E. cuniculi) were detected in five another rabbits (0.9%). Statistically significant differences in the prevalence of microsporidia were observed among different cities (χ2 = 38.376, df = 3, P < 0.01) and the rabbits older than 1 year were more likely to harbour microsporidia infections (χ2 = 9.018, df = 2, P < 0.05). Eleven distinct genotypes of E. bieneusi were obtained, including five known (SC02, I, N, J, CHY1) and six novel genotypes (SCR01, SCR02, SCR04 to SCR07). SC02 was the most prevalent genotype in all tested cities (43.3%, 39/90). Phylogenetic analysis showed that these genotypes were clustered into group 1-3 and group 10. Meanwhile, two genotypes (I and II) were identified by sequence analysis of the ITS region of E. cuniculi. To the best of our knowledge, this is the first report of microsporidia infection in pet rabbits in China. Genotype SC02 and four novel genotypes were classified into potential zoonotic group 1, suggesting that pet rabbits may cause microsporidiosis in humans through zoonotic transmissions. These findings provide preliminary reference data for monitoring microsporidia infections in pet rabbits and humans.


Adenovirus-E1A gene therapy enhances the in vivo sensitivity of Ewing's sarcoma to VP-16.
This study determined the effect of Ad-E1A gene therapy in vivo. TC71 cells (2 x 10(6)) injected subcutaneously into nude mice resulted in tumor development (1-3 mm) 6 days later. Animals were then treated with Ad-E1A or Ad-beta-gal (5 x 10(9) plaque-forming units) by intratumoral injection twice weekly for 2 weeks. Animals received 8 mg/kg VP-16 given by intraperitoneal injection daily for 5 days following the first week of treatment with Ad-E1A or Ad-beta-gal. Control animals received no therapy or VP-16 only after tumor cells were injected. When tumors exceeded 2 x 2 cm, the mice were sacrificed and the tumors underwent histologic and immunohistochemical analysis. Tumors from mice treated with Ad-E1A plus VP-16 were 9.6-fold smaller than those treated with VP-16 alone and 6.3-fold smaller than those treated with Ad-E1A alone. HER2/neu p185 protein expression decreased in all tumors that received Ad-E1A therapy. TUNEL fluorescence staining revealed more apoptosis in the tumors from animals treated with Ad-E1A plus VP-16 than in those from animals treated with Ad-E1A alone, Ad-beta-gal plus VP-16, or VP-16 alone. These data demonstrated that Ad-E1A gene therapy down-regulated HER2/neu expression, increased tumor cell apoptosis induced by VP-16, and enhanced tumor cell sensitivity to VP-16. Ad-E1A may have potential in the treatment of relapsed drug-resistant Ewing's sarcoma.


Attenuated hypothalamic responses to α-melanocyte stimulating hormone during pregnancy in the rat.
Increased appetite and weight gain occurs during pregnancy, associated with development of leptin resistance, and satiety responses to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) are suppressed. This study investigated hypothalamic responses to α-MSH during pregnancy, using c-fos expression in specific hypothalamic nuclei as a marker of neuronal signalling, and in vivo electrophysiology in supraoptic nucleus (SON) oxytocin neurons, as a representative α-MSH-responsive neuronal population that shows a well-characterised α-MSH-induced inhibition of firing. While icv injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, supraoptic, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, this response was suppressed in pregnant rats. Similarly, SON oxytocin neurons in pregnant rats did not demonstrate characteristic α-MSH-induced inhibition of firing that was observed in non-pregnant animals. Given the known functions of α-MSH in the hypothalamus, the attenuated responses are likely to facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy. During pregnancy, a state of positive energy balance develops to support the growing fetus and to deposit fat in preparation for the subsequent metabolic demands of lactation. As part of this maternal adaptation, the satiety response to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) is suppressed. To investigate whether pregnancy is associated with changes in the response of hypothalamic α-MSH target neurons, non-pregnant and pregnant rats were treated with α-MSH or vehicle and c-fos expression in hypothalamic nuclei was then examined. Furthermore, the firing rate of supraoptic nucleus (SON) oxytocin neurons, a known α-MSH responsive neuronal population, was examined in non-pregnant and pregnant rats following α-MSH treatment. Intracerebroventricular injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, but no significant increase was observed in any of these regions in pregnant rats. In the SON, α-MSH did induce expression of c-fos during pregnancy, but this was significantly reduced compared to that observed in the non-pregnant group. Furthermore, during pregnancy, SON oxytocin neurons did not demonstrate the characteristic α-MSH-induced inhibition of firing rate that was observed in non-pregnant animals. Melanocortin receptor mRNA levels during pregnancy were similar to non-pregnant animals, suggesting that receptor down-regulation is unlikely to be a mechanism underlying the attenuated responses to α-MSH during pregnancy. Given the known functions of α-MSH in the hypothalamus, the attenuated responses will facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy.


[Clinical and biological studies of 14 cases of the Prader-Labhart-Willi syndrome].
Clinical and cytogenetic studies are performed on 14 patients with PWS including endocrinological investigations, as coagulation factor XI activity and pigmentation studies. Recent hypothesis from molecular analysis are discussed.


Social context influences infants' ability to extract statistical information from a sequence of gestures.
Infants' social environment is rich of complex sequences of events and actions. This study investigates whether 12-month-old infants are able to learn statistical regularities from a sequence of human gestures and whether this ability is affected by a social vs non-social context. Using a visual familiarization task, infants were familiarized to a continuous sequence of eight videos in which two women imitated each other performing arm gestures. The sequence of videos in which the two women performed imitative gestures was organized into 4 different gesture units. Videos within a gesture unit had a highly predictable transitional probability, while such transition was less predictable between gesture units. The social context was manipulated varying the mutual gaze of the actors and their body orientation. At test, infants were able to discriminate between the high- and low-predictable gesture units in the social, but not in the non-social condition. Results demonstrate that infants are capable to detect statistical regularities from a sequence of human gestures performed by two different individuals. Moreover, our findings indicate that salient social cues can modulate infants' ability to extract statistical information from a sequence of gestures.


A Randomized, Controlled Trial of Catheter-Related Infectious Event Rates Using Antibiotic-Impregnated Catheters Versus Conventional Catheters in Pediatric Cardiovascular Surgery Patients.
: We conducted a randomized, controlled clinical trial to determine whether a difference in catheter-associated blood stream infection (CABSI) incidence existed between children who underwent cardiac surgery and had a central venous catheter impregnated with minocycline and rifampin versus those who had a conventional, nonimpregnated catheter after cardiac surgery. Due to a lower number of infections than expected, the study was terminated early. Among 288 evaluable patients, the rates of CABSI and line-related complications were similar between the 2 groups.


Intrahepatic peripheral cholangiocarcinoma (IPCC): comparison between perfusion ultrasound and CT imaging.
This study was done to compare the perfusion patterns of intrahepatic peripheral cholangiocarcinoma (IPCC) on contrast-enhanced ultrasound (CEUS) and dynamic computed tomography (CT). We retrospectively reviewed 23 histologically proven cases of IPCC. All lesions were studied by CEUS with sulfur hexafluoride-filled microbubbles coated with a phospholipid capsule, and by dynamic CT. Contrast-enhancement patterns were evaluated in the arterial phase (CEUS 10-20 s after the injection; CT 25-30 s after the injection) and in the delayed phase (CEUS 120 s after the injection; CT>2-3 min after the injection). Lesions were single in 18/23 cases (78%), single with nearby satellite lesions in 1/23 (4%) cases and multifocal with distant secondary lesions in 4/23 (17%) cases. Lesion diameter was 2-5 cm in 7/23 cases (30%), 5-7 cm in 13/23 cases (57%) and >7 cm in 3/23 (13%) cases. On CEUS, lesions were hypervascular in 16/23 cases (70%). On delayed-phase CEUS, 22/23 lesions (96%) were markedly hypoechoic. CT showed that the lesions were hypovascular in the arterial phase in 15/23 cases (66%) and hypervascular in 7/23 (30%) cases; one lesion (1/23; 4%) was isovascular. On delayed-phase CT, lesions were hyperdense in 17/23 cases (74%), hypodense in 5/23 (22%) cases and isodense in 1/23 (43%) cases. Enhancement discrepancy between delayed-phase CEUS (hypoechogenicity) and CT (hyperdensity) is common semiological findings in the study of IPCC.


Inhibition of oxidative stress and advanced glycation end-product formation in purified BSA/glucose glycation system by polyphenol extracts of selected nuts from Pakistan.
Glycation generates advanced glycation end products (AGE) and its intermediates, thus increasing the risk of developing various ailments including diabetes mellitus. Current study was planned to explore the antioxidant and antiglycation potential of selected nuts viz, Juglans regia (Walnut), Prunus dulcis (Almond), Pistacia vera (Pistachio), and Arachis hypogaea (Peanut), locally available and readily consumed in Faisalabad, Pakistan, for their health-promoting properties. The prepared methanolic extracts of selected nuts were tested for biological activities including the antioxidant and antiglycation potential. The effect of these extracts against oxidation and AGE formation was evaluated by in vitro method using bovine serum albumin (BSA)-glucose system. Juglans regia, Pistacia vera, and Arachis hypogaea were found rich in phenolics and flavonoids contents with increased reducing potential and least IC50 due to the DPPH free radical scavenging inhibition. Dose- and time-dependent inhibition of glucose-induced advanced glycation end-product (AGE) was exhibited by fruit extracts through in vitro bovine serum albumin (BSA)-glucose system. Juglans regia and Pistacia vera were predominantly effective in the inhibition of early and intermediary glycation products at different incubation conditions. The study indicated that the extracts of selected nuts possess significant antioxidant capacity and are rich in phenolics and flavonoids, making them useful supplements as an important part of a balanced diet.


Schmallenberg virus: research on viral circulation in Brazil.
Schmallenberg virus (SBV-Orthobunyavirus serogroup Simbu) is an emerging RNA vector-borne virus which has an important impact in animal health within Europe, and some Asian and African countries. It is mainly reported in ruminants, causing congenital malformations and stillbirths. However, there are no studies regarding the occurrence, diagnosis, or surveillance of SBV in Brazil, due to the lack of diagnostic techniques available so far. This study aimed to implement a reliable diagnostic technique able to detect the SBV in Brazil and also to investigate occurrence of the virus in this country. A molecular technique, quantitative reverse transcription polymerase chain reaction (RT-qPCR), was used to analyze 1665 bovine blood samples and 313 aborted fetuses, as well as 596 serum samples were analyzed by serological analysis. None of the blood and fetus samples analyzed was positive for SBV, and neither serum samples were reactive for antibodies anti-SBV. Thus, although Brazil presents suitable conditions for the dissemination of the SBV, results of the present study suggest that SBV did not propagate in the analyzed bovine population.


Prediction of 67Ga production using the Monte Carlo code MCNPX.
The widely used Monte Carlo simulation code Monte Carlo N-Particle System (MCNPX) has been utilized to simulate the production of (67)Gallium via multiple nuclear reaction channels. Based on the MCNPX-generated, energy-dependent proton flux within a Zn target during irradiation, the (67)Ga production yield was determined. Theoretical calculations of the production yield using the stopping power from the SRIM (stopping and range of ions in matter) code were compared to the measurements from the MCNPX code. These results were in good agreement with reported data, thus confirming the usefulness and accuracy of MCNPX as a tool for the design and optimization of targets for the production of other radionuclides.


The maturation of the central auditory conduction in preterm infants until three months post term. V. The auditory cortical response (ACR).
Auditory cortical evoked responses (ACRs) were recorded in 65 preterm infants, at least on 3 occasions in 48 of them. The infants were divided into 5 groups according to their gestational age (GA). The recording sessions were performed at 8 conceptional age (CA) levels, defined as the gestational age added to the chronological age. The last recordings were obtained at 50-52 weeks CA. The ACRs were analyzed for the primary complex containing middle latency components (MLR) and the secondary complex, containing the slow late components. The ACR records first appear at about 25 weeks CA, initiating the premature stage followed by a transitional stage around term date and the gradual development into the mature stage, achieved at 50-52 weeks CA. The detectability rate of the various components generally increased with increasing conceptional age, for some of the components, especially N2p and N2, this rate achieved a value of about 80%. The degree of prematurity did not influence appreciably the development of the ACR. The waveforms, and to a lesser extent the latency and amplitude values, are strongly age dependent. Remarkable topographic differences between the ACR parameter latency and more importantly amplitude values are found between the derivations from the vertex and the central temporal areas, supporting the theory of different generation sites for the ACR components. The premature and mature ACR appeared relatively insensitive to changes in the states of vigilance. The ACR in premature infants are useful in developmental studies with respect to the central audition in premature infants and might contribute in the clinical assessment on the quality of the premature central auditory system.


Visualization of tRNA movements on the Escherichia coli 70S ribosome during the elongation cycle.
Three-dimensional cryomaps have been reconstructed for tRNA-ribosome complexes in pre- and posttranslocational states at 17-A resolution. The positions of tRNAs in the A and P sites in the pretranslocational complexes and in the P and E sites in the posttranslocational complexes have been determined. Of these, the P-site tRNA position is the same as seen earlier in the initiation-like fMet-tRNA(f)(Met)-ribosome complex, where it was visualized with high accuracy. Now, the positions of the A- and E-site tRNAs are determined with similar accuracy. The positions of the CCA end of the tRNAs at the A site are different before and after peptide bond formation. The relative positions of anticodons of P- and E-site tRNAs in the posttranslocational state are such that a codon-anticodon interaction at the E site appears feasible.


Failure patterns and survival in patients with nasopharyngeal carcinoma treated with intensity modulated radiation in Northwest China: a pilot study.
To evaluate the clinical outcomes and patterns of failure in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiotherapy (IMRT) in Northwest China. From January 2006 to December 2009, 138 NPC patients were treated at Xijing Hospital. Of them, 25 cases with stage I-II received IMRT only, 113 cases with stage III-IVb received IMRT plus accomplished platinum-based chemotherapy. The IMRT prescribed dose was PTV 68-74 Gy to gross disease in nasopharynx and 66-72 Gy to positive lymph nodes in 30-33 fractions, and high risk and low risk region PTV was 60-63 Gy and 50.4~56 Gy in 30~33 and 28 fractions respectively. Plasma Epstein Barr virus (EBV) DNA load was measured before treatment. The clinical toxicities, outcomes and patterns of failure were observed. The median follow up time was 23 months (range 2 to 53 months). EBV infection positive was only 15.9%. Overall disease failure developed in 36 patients, 99% belonged to stage III/IV disease. Among these, there were 26 distant metastases, 6 local recurrence, and 4 regional recurrence. The 3-year local control rate(LCR), distant metastasis-free survival (MFS), disease-free survival (DFS) and the overall survival (OS) was 93.9%, 79.5%, 70% and 83.1% respectively. Multivariate analyses revealed that age and anemia pre-radiotherapy were independent predictors for OS. IMRT with or without chemotherapy can improve the long term survival of NPC patients in Northwest China. Distant metastasis becomes the main cause of treatment failure. Age and anemia before radiotherapy were the main prognosis factors of NPC patients.


Modulation of immunoproteasome subunits by liposomal lipid A.
Liposomes are phospholipid vesicles that have been used as carriers of antigens and adjuvants. Lipid A, the endotoxic moiety of Gram-negative bacterial lipopolysaccharide is a potent adjuvant and incorporation into liposomes essentially reduces the endotoxic activity of lipid A. In this study, we analyzed the effect of liposomal lipid A [L(LA)] on the MHC class I antigen processing machinery in murine antigen presenting cells (APCs). L(LA) enhanced the surface expression of MHC class I, class II, CD80, and CD86 molecules, induced the secretion of IFN-gamma, IL-12p40, TNF-alpha and IL-10, and caused a shift in the proteasome profile from constitutive to immunoproteasomes as observed by the induction of beta2i, beta5i, PA28alpha, and PA28beta subunits. L(LA) acts through the production of IFN-gamma as demonstrated with APCs generated from IFN-gamma knockout mice. L(LA) therefore appears to act as an intracellular adjuvant by upregulating the antigen processing machinery, which could result in efficient antigen presentation.


Unusual cutaneous metastatic carcinoma.
Most of metastatic tumors to the skin are from primary tumors of the breast, lung, or from melanoma; metastases to the skin from primary carcinomas at other sites are rare. Cutaneous metastases of visceral carcinomas most often occur in patients with advanced disease, and are associated with a poor prognosis. We report 6 cases of nonmammary, nonpulmonary carcinoma metastatic to the skin. Most patients were elderly with advanced disease at the time of diagnosis of skin metastasis. The primary tumor sites included the thyroid, esophagus, biliary tract, ovary, and prostate. Awareness of these rare cases of metastasis to the skin will help pathologists and clinicians make the correct diagnosis.


Gender and intergenerational transmission of alcohol use patterns: an analysis of adult children in Moscow.
Based on a 1996 sample of adult children and their parents in Moscow, this study investigates the degree to which alcohol use patterns are transmitted from parents to adult children and examines the roles of gender, family status, and family interaction dynamics for transmission. Findings suggest that parents' drinking and family status/interaction patterns indeed influence adult children's alcohol consumption. Frequency and volume of alcohol use is higher among children whose mothers typically drink about 3 or more drinks daily or who drink on a weekly basis. Fathers' frequency and volume of alcohol use positively influences only sons' drinking. Mothers' drinking, however, may undermine fathers' positive effect on sons. Fathers' verbal and physical abuse significantly affects daughters' consumption.


Predictive values of cranial ultrasound and assessment of general movements for neurological development of preterm infants in the Maribor region of Slovenia.
The aim of the study was to assess the predictive values of cranial ultrasound (US) scans and assessment of general movements of fidgety character (GMs) for the later neurological development of preterm infants in the Maribor region of Slovenia. Results of cranial US scans done longitudinally from the day of birth until the end of three months of chronologic age and results of GMs at three months of corrected age were compared with traditional neurological examination and evaluation of psychomotor development of the same children at the corrected age of six years. A total of 112 preterm infants (gestational age 37 weeks and below) were included in the study. The infants were classified as low-risk or high-risk for neurological impairment on the basis of cranial US scans. The scans classified as low-risk were followed by a normal neurological outcome in 74 (89%) of 83 infants; those classified as high-risk for neurological impairment were followed by abnormal neurological outcome in 21 (72%) of 29 infants. Of 77 infants with normal fidgety movements, 73 (95%) had a normal neurological outcome and 4 (5%) had an abnormal neurological outcome; of 35 infants with abnormal or absent fidgety movements, 26 (74%) had an abnormal neurological outcome and 9 (26%) had a normal neurological outcome. Of 30 children with abnormal outcome, cerebral palsy was diagnosed in 16, mental retardation in one, nine children had both of these, and four had complex minor neurological dysfunction. The validity of the scans was 85%, sensitivity 70%, specificity 90%, positive predictive value 72% and negative predictive value 89%; the validity of the GMs was 88%, sensitivity 87%, specificity 89%, positive predictive value 74% and negative predictive value 95%. The sensitivity of the cranial US scans was clearly lower than that of assessment of general movements of a fidgety character. The specificities of the two methods were almost the same.


Characterization of a messenger RNA transport protein.
A cytoplasmic protein which facilitates the energy-dependent transport of mRNA from isolated nuclei to a specified medium has been further characterized, since it could have relevance to the mechanism of mRNA nucleo-cytoplasmic transport in vivo. This protein is now shown, by cDNA hybridization analysis using appropriate recombinant probes, to be obligatory for the transport of alpha 2u-globulin and albumin mRNA from male rat liver nuclei. It is concentrated in the cytoplasm. When isolated under conditions where they retain nuclear proteins, the nuclei contain less than 2% of the total mRNA transport activity. Approx. 20% is recovered in the cytosol, while the rest (80%) copurifies with the messenger ribonucleoproteins in the polyribosome fraction. The protein is eluted from the poly A-messenger ribonucleoproteins between 0.25 and 0.50 M NaCl. The activities of the cytosolic- and messenger ribonucleoprotein-derived transport proteins were mutually additive below saturation of the transport system. Further, the activities of both fractions were increased when they were fortified with the catalytic subunit of the cAMP-dependent protein kinase in the presence of ATP. On the other hand, protein kinase-induced thiophosphorylation of the protein with ATP[S] decreased transport activity. The molecular weight of the transport protein from either cell compartment as judged by molecular sieving is approx. 35,000. It has now been purified 2000-fold and requires manganese ions and serum albumin for stabilization of activity. The highly purified transport factor from the cytosol is tentatively assigned a molecular weight of 32,000 by SDS-polyacrylamide gel electrophoresis.


Electronic devices based on purified carbon nanotubes grown by high-pressure decomposition of carbon monoxide.
The excellent properties of transistors, wires and sensors made from single-walled carbon nanotubes (SWNTs) make them promising candidates for use in advanced nanoelectronic systems. Gas-phase growth procedures such as the high-pressure decomposition of carbon monoxide (HiPCO) method yield large quantities of small-diameter semiconducting SWNTs, which are ideal for use in nanoelectronic circuits. As-grown HiPCO material, however, commonly contains a large fraction of carbonaceous impurities that degrade the properties of SWNT devices. Here we demonstrate a purification, deposition and fabrication process that yields devices consisting of metallic and semiconducting nanotubes with electronic characteristics vastly superior to those of circuits made from raw HiPCO. Source-drain current measurements on the circuits as a function of temperature and backgate voltage are used to quantify the energy gap of semiconducting nanotubes in a field-effect transistor geometry. This work demonstrates significant progress towards the goal of producing complex integrated circuits from bulk-grown SWNT material.


The venous system of the peripheral choroid. I. The venous system of the pars plana.
The venous network of the pars plana was studied by means of arterial and venous injections of India ink and neoprene latex. The vascular lumens were measured under the microscope. The analysis of samples spread on slides allowed us to discover the existence of a venous anastomotic arch in the ora serrata region.


Phylogeography of cultivated and wild ophiopogon japonicus based on chloroplast DNA: exploration of the origin and sustainable cultivation.
Ophiopogon japonicus, mainly planted in Sichuan (CMD) and Zhejiang (ZMD) province in China, has a lengthy cultivation history. During the long period of domestication, the genetic diversity of cultivated O. japonicus has substantially declined, which will affect the population continuity and evolutionary potential of this species. Therefore, it is necessary to clarify the phylogeography of cultivated O. japonicus to establish a theoretical basis for the utilization and conservation of the genetic resources of O. japonicus. The genetic diversity and population structure of 266 O. japonicus individual plants from 23 sampling sites were analyzed based on 4 chloroplast DNA sequences (atpB-rbcL, rpl16, psbA-trnH and rpl20-5'rps12) to identify the effects of domestication on genetic diversity of cultivars and determine their geographic origins. The results showed that cultivated O. japonicus and wild O. japonicus had 4 and 15 haplotypes respectively. The genetic diversity of two cultivars (Hd = 0.35700, π = 0.06667) was much lower than that of the wild populations (Hd = 0.76200, π = 0.20378), and the level of genetic diversity in CMD (Hd = 0.01900, π = 0.00125) was lower than that in ZMD (Hd = 0.06900, π = 0.01096). There was significant difference in genetic differentiation between the cultivated and the wild (FST = 0.82044), especially between the two cultivars (FST = 0.98254). This species showed a pronounced phylogeographical structure (NST > GST, P < 0.05). The phylogenetic tree showed that the genetic difference between CMD and ZMD was not enough to distinguish the cultivars between the two producing areas by using O. amblyphyllus Wang et Dai as an outgroup. In addition, both CMD and ZMD have a closer relationship with wild populations in Sichuan than that in Zhejiang. The results of the TCS network and species distribution model suggested that the wild population TQ located in Sichuan province could serve as the ancestor of cultivated O. japonicus, which was supported by RASP analysis. These results suggest that cultivated O. japonicus has experienced dramatic loss of genetic diversity under anthropogenic influence. The genetic differentiation between CMD and ZMD is likely to be influenced by founder effect and strong artificial selection for plant traits. It appears that wild populations in Sichuan area are involved in the origin of not only CMD but also ZMD. In addition, we also raise some suggestions for planning scientific strategies for resource conservation of O. japonicus based on its genetic diversity and population structure.


Procedural Pain Management: Clinical Practice Recommendations American Society for Pain Management Nursing.
Throughout the life span procedures are common within health care and have the potential to cause pain. Nurses have an ethical responsibility involving the care of people with pain. The American Society for Pain Management Nursing holds the position that all patients undergoing painful procedures have the right to safe and effective pain management throughout the phases of care and that the interprofessional health care team ensures such ethical obligation is fulfilled within a framework of patients or their designees' goals and preferences. It is recommended that nurses, other health care providers, and health care organizations offer the use of integrative intervention for managing pain during procedures.


Cognitive-motor interference during functional mobility after stroke: state of the science and implications for future research.
Cognitive-motor interference (CMI) is evident when simultaneous performance of a cognitive task and a motor task results in deterioration in performance in one or both of the tasks, relative to performance of each task separately. The purpose of this review is to present a framework for categorizing patterns of CMI and to examine the specific patterns of CMI evident in published studies comparing single-task and dual-task performance of cognitive and motor tasks during gait and balance activities after stroke. We also examine the literature for associations between patterns of CMI and a history of falls, as well as evidence for the effects of rehabilitation on CMI after stroke. Overall, this review suggests that during gait activities with an added cognitive task, people with stroke are likely to demonstrate significant decrements in motor performance only (cognitive-related motor interference), or decrements in both motor and cognitive performance (mutual interference). In contrast, patterns of CMI were variable among studies examining balance activities. Comparing people poststroke with and without a history of falls, patterns and magnitude of CMI were similar for fallers and nonfallers. Longitudinal studies suggest that conventional rehabilitation has minimal effects on CMI during gait or balance activities. However, early-phase pilot studies suggest that dual-task interventions may reduce CMI during gait performance in community-dwelling stroke survivors. It is our hope that this innovative and critical examination of the existing literature will highlight the limitations in current experimental designs and inform improvements in the design and reporting of dual-task studies in stroke.


Determination of polyamines in digestive and reproductive tissues of adult Asterias vulgaris (Echinodermata: Asteroidea).
1. The polyamines spermine, spermidine and putrescine were extracted from tissues of Asterias vulgaris and quantitated using thin layer chromatography. 2. In the pyloric caeca, mean (+/- SE) levels of spermine, spermidine and putrescine were 138(15), 86(24) and 415(77) nmol/g wet wt tissue, respectively. In the testes, levels were 95(12), 13(6) and less than 6 nmol/g wet wt. In the ovaries, levels were 105(9), 11(0.8) and 15(8) nmol/g wet wt. 3. High levels of polyamines in the pyloric caeca may be related to secretion or excretion in this tissue. 4. We hypothesize that polyamines will be important in the regulation of cellular activity in these tissues during the annual reproductive cycle.


Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease.
Cerebral small vessel disease is a common condition associated with lacunar stroke, cognitive impairment and significant functional morbidity. White matter hyperintensities and brain atrophy, seen on magnetic resonance imaging, are correlated with increasing disease severity. However, how the two are related remains an open question. To better define the relationship between white matter hyperintensity growth and brain atrophy, we applied a semi-automated magnetic resonance imaging segmentation analysis pipeline to a 3-year longitudinal cohort of 99 subjects with symptomatic small vessel disease, who were followed-up for ≥1 years. Using a novel two-stage warping pipeline with tissue repair step, voxel-by-voxel rate of change maps were calculated for each tissue class (grey matter, white matter, white matter hyperintensities and lacunes) for each individual. These maps capture both the distribution of disease and spatial information showing local rates of growth and atrophy. These were analysed to answer three primary questions: first, is there a relationship between whole brain atrophy and magnetic resonance imaging markers of small vessel disease (white matter hyperintensities or lacune volume)? Second, is there regional variation within the cerebral white matter in the rate of white matter hyperintensity progression? Finally, are there regionally specific relationships between the rates of white matter hyperintensity progression and cortical grey matter atrophy? We demonstrate that the rates of white matter hyperintensity expansion and grey matter atrophy are strongly correlated (Pearson's R = -0.69, P < 1 × 10(-7)), and significant grey matter loss and whole brain atrophy occurs annually (P < 0.05). Additionally, the rate of white matter hyperintensity growth was heterogeneous, occurring more rapidly within long association fasciculi. Using voxel-based quantification (family-wise error corrected P < 0.05), we show the rate of white matter hyperintensity progression is associated with increases in cortical grey matter atrophy rates, in the medial-frontal, orbito-frontal, parietal and occipital regions. Conversely, increased rates of global grey matter atrophy are significantly associated with faster white matter hyperintensity growth in the frontal and parietal regions. Together, these results link the progression of white matter hyperintensities with increasing rates of regional grey matter atrophy, and demonstrate that grey matter atrophy is the major contributor to whole brain atrophy in symptomatic cerebral small vessel disease. These measures provide novel insights into the longitudinal pathogenesis of small vessel disease, and imply that therapies aimed at reducing progression of white matter hyperintensities via end-arteriole damage may protect against secondary brain atrophy and consequent functional morbidity.


Ethanol preservation and pretreatments facilitate quality DNA extractions in recalcitrant plant species.
The preservation of plant tissues in ethanol is conventionally viewed as problematic. Here, we show that leaf preservation in ethanol combined with proteinase digestion can provide high-quality DNA extracts. Additionally, as a pretreatment, ethanol can facilitate DNA extraction for recalcitrant samples. DNA was isolated from leaves preserved with 96% ethanol or from silica-desiccated leaf samples and herbarium fragments that were pretreated with ethanol. DNA was extracted from herbarium tissues using a special ethanol pretreatment protocol, and these extracts were compared with those obtained using the standard cetyltrimethylammonium bromide (CTAB) method. DNA extracted from tissue preserved in, or pretreated with, ethanol was less fragmented than DNA from tissues without pretreatment. Adding proteinase digestion to the lysis step increased the amount of DNA obtained from the ethanol-pretreated tissues. The combination of the ethanol pretreatment with liquid nitrogen freezing and a sorbitol wash prior to cell lysis greatly improved the quality and yield of DNA from the herbarium tissue samples. This study critically reevaluates the consequences of ethanol for plant tissue preservation and expands the utility of pretreatment methods for molecular and phylogenomic studies.


The biological activities of butyrylcholinesterase inhibitors.
Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and unsatisfactory long-term treatment effect. Recent studies have shown that butyrylcholinesterase (BuChE) inhibitors or double acetyl and butyryl cholinesterase inhibitors have better curative effects on AD, and the side effects are lower than those of specific AChE inhibitors. Dual target cholinesterase inhibitors have become a new hotspot in the research of anti-AD drugs. Herein, the synthesis and bioactivities of BuChE inhibitors were reviewed.


Orthopedic management of vertebral and long bone fractures in patients with osteoporosis.
Because of the evolving demographics of the world's population, fracture surgeons must become experts in the treatment of fractures in osteoporotic bone. Toward this end, fracture surgeons are learning to modify the classic techniques of internal fixation to adapt them to the elderly population. Screws should be placed into the best quality of bone available, which, in most cases, is an opposing cortex. Screw fixation can be augmented using acrylic cement. When using plate fixation, stable bone contact at the fracture site is the most important factor in reducing strain in the plate. Shortening of the affected bone is advisable to achieve this contact in comminuted fractures. Plates should not be used to bridge areas of comminution in osteoporotic bone. Plates should generally be as long as is compatible with the affected bone, with screws placed as close to and as far away from the fracture site as possible. When confronted with diaphyseal fractures or fractures with metaphyseal-diaphyseal comminution, locked intramedullary nails can be used. Angled blade plates are applicable to osteoporotic metaphyseal fractures but should be used as tension band plates, which require stable load-sharing contact opposite the plate. Antiglide plating and use of tension band wires are also effective strategies for osteoporotic fractures. Finally, to reduce the morbidity of bone graft harvest and to ensure adequate volumes of graft, the use of bone graft substitutes is particularly applicable in elderly patients. All patients with evidence of osteoporosis should be started on a medical regimen to combat further bone loss that includes calcium supplementation with a prescription for antiresorptive agents, including bisphosphonates, calcitonin, or hormone replacement therapy.


Tracheal sound-based apnea detection using hidden Markov model in sedated volunteers and post anesthesia care unit patients.
The current method of apnea detection based on tracheal sounds is limited in certain situations. In this work, the Hidden Markov Model (HMM) algorithm based on segmentation is used to classify the respiratory and non-respiratory states of tracheal sounds, to achieve the purpose of apnea detection. Three groups of tracheal sounds were used, including two groups of data collected in the laboratory and a group of patient data in the post anesthesia care unit (PACU). One was used for model training, and the others (laboratory test group and clinical test group) were used for testing and apnea detection. The trained HMMs were used to segment the tracheal sounds in laboratory test data and clinical test data. Apnea was detected according to the segmentation results and respiratory flow rate/pressure which was the reference signal in two test groups. The sensitivity, specificity, and accuracy were calculated. For the laboratory test data, apnea detection sensitivity, specificity, and accuracy were 96.9%, 95.5%, and 95.7%, respectively. For the clinical test data, apnea detection sensitivity, specificity, and accuracy were 83.1%, 99.0% and 98.6%. Apnea detection based on tracheal sound using HMM is accurate and reliable for sedated volunteers and patients in PACU.


AP-2alpha and AP-2gamma regulate tumor progression via specific genetic programs.
The events occurring during tumor formation and progression display similarities to some of the steps in embryonic morphogenesis. The family of AP-2 proteins consists of five different transcription factors (alpha, beta, gamma, delta, and epsilon) that play relevant roles in embryonic development, as demonstrated by the phenotypes of the corresponding knockout mice. Here, we show that AP-2alpha and AP-2gamma proteins play an essential role in tumorigenesis. Down-modulation of AP-2 expression in tumor cells by RNA interference (RNAi) led to enhanced tumor growth and reduced chemotherapy-induced cell death, as well as migration and invasion. Most of these biological modulations were rescued by AP-2 overexpression. We observed that increased xenotransplant growth was mostly due to highly enhanced proliferation of the tumor cells together with reduced innate immune cell recruitment. Moreover, we showed that migration impairment was mediated, at least in part, by secreted factors. To identify the genetic programs involved in tumorigenesis, we performed whole genome microarray analysis of AP-2alpha knockdown cells and observed that AP-2alpha regulates specific genes involved in cell cycle, cell death, adhesion, and migration. In particular, we showed that ESDN, EREG, and CXCL2 play a major role in AP-2 controlled migration, as ablation of any of these genes severely altered migration.


Adoptive cell therapy: Living drugs against cancer.
Immunotherapy has made a profound impact in the treatment of cancer in the last decade. Insights from the study of the intricate relationships between immune cells and cancer have led to the clinical development of strategies that redirect the power of the immune system to target and eliminate cancer. Today, immunotherapy represents a rapidly expanding and transformative force comprising multiple modalities.


Malleus to Stapes Bone Cement Rebridging Ossiculoplasty: Why Don't We Perform Frequently?
To evaluate the effectiveness of malleus to stapes bone cement rebridging (MS-BCR) for Austin Kartush group A ossicular defects and compare the audiological results with incus interposition (IP) and incus to stapes bone cement rebridging (IS-BCR). Patients for whom type 2 tympanoplasty had been performed in a tertiary referral center were examined. Revision cases and those with graft failure were excluded. Three treatment groups were IS-BCR, IP, and MS-BCR. Preoperative and postoperative audiological results were compared. A total of 92 patients were enrolled. The IS-BCR was performed in 42 (45.65%), IP in 18 (19.56%), and MS-BCR in 32 (34.78%) patients. Postoperative mean air bone gap was 20.1 ± 9.8 dB HL and did not differ significantly between the groups (P = .271). Postoperative mean air bone gap less than 20 dB HL was achieved in 23 (54.7%) patients in IS-BCR, 10 (55.5%) patients in IP group, and 24 (75%) patients in MS-BCR group (P = .06). Mean closure in air bone gap was 14.0 ± 11.6 dB HL. The changes in mean and frequency-specific air bone gap were not significantly different between treatment groups (P > .05). Malleus to stapes bone cement rebridging may provide hearing results comparable to IS-BCR and IP.


Effects of Institutional Confinement for Delinquency on Levels of Depression and Anxiety among Male Adolescents.
Youth within the juvenile justice system report higher rates of mental illnesses than their peers. This study tested whether institutional confinement increases levels of depression and anxiety among male adolescents. We examined heterogeneous trajectories of depression and anxiety from ages 11 to 14 for 510 male adolescents. Youths who were first placed in custody at age 15 (treatment group) were matched with control boys (no official arrest or reported confinement during adolescence) within each trajectory group using a propensity score matching procedure. Matches were found for 37 pairs for depression and 34 pairs for anxiety. There were no significant differences between the confined and control groups in levels of depression or anxiety at age 16. More research is needed to identify aspects of the juvenile justice system that may positively or negatively affect youth's mental health status.


Relation between Tc-99m sestamibi uptake and biological factors in hyperparathyroidism.
The aim of this study was to evaluate the relation between uptake ratios of Tc-99m sestamibi (MIBI) and tumor volume, serum biochemical values (i-PTH, Ca, P) and oxyphil cell content. The study population consisted of 19 patients (2 M, 17 F; mean +/- SD: 47 +/- 12 y). Anterior planar images of the neck and chest were acquired early (15 min) and triple late phase (1, 2 and 3-4 h) after intravenous injections of 740 MBq MIBI. Each of the surgical materials was reviewed retrospectively. The percentage of cell type (chief, oxyphil and clear cells) in the tumors was calculated by light microscopy. The uptake ratio obtained from L1 (1 hour) phase was found to be higher than the uptake ratio obtained from early phase, and the difference was statistically significant (1.57 +/- 0.34 and 1.43 +/- 0.29, p = 0.004, respectively). There was no significant correlation between uptake ratios that were obtained from 4 different imaging phases and lesion volumes, i-PTH levels and calcium levels (p > 0.05). However, there was a significant adverse correlation between L2 and L3 uptake ratios and serum phosphorus values (r = -0.44, p = 0.04 and r = -0.46, p = 0.04, respectively). Additionally, no significant correlation between MIBI uptake ratios of each imaging phase and the laboratory data, volume of lesion or oxyphil percentage volume was found after the multiple regression analysis (E: p = 0.46, r = 0.49; L1: p = 0.24, r = 0.58; L2: p = 0.27, r = 0.57; L3: p = 0.32, r = 0.55, respectively. There was no correlation between gland oxyphil percentage volume and MIBI uptake ratios (p > 0.05). The results of our study show that the optimal imaging times after intravenous injection of MIBI are 15 minutes and 1 hour because of the shorter examination time without loss of diagnostic ability. In the present study, there was no significant correlation between MIBI uptake ratios and increased gland volume, or serum Ca and i-PTH levels. Besides, we think that oxyphil cell content may not have a main effect on MIBI uptake and retention. The fact of an adverse relation between phosphorus and MIBI retention in our study suggests that phosphorus level should be considered prior to MIBI imaging.


Protein Arrays I: Antibody Arrays.
Antibody arrays represent one of the very early protein array systems where antibodies are used to capture and detect target proteins in a high-throughput platform. The development of high-quality antibodies, nanomaterial-based novel detection probes, as well as innovative imaging technologies and computational tools has tremendously improved the sensitivity, specificity, and robustness of antibody arrays during the past decade. In this protocol we will incorporate the most updated innovations and developments of antibody arrays into the step-by-step experimental procedures. This includes antibody printing, sample preparation, array detection, as well as imaging and data analysis. Antibody array could be used for cytokine profiling or mapping of phosphorylation, glycosylation, or other post-translational modifications of target proteins.


Binding of monoclonal antibodies to the nuclear estrogen receptor in intact nuclei.
A monoclonal antibody to calf uterus cytoplasmic estrogen receptor shows a specifically displaceable and saturable binding to intact nuclei of mouse uterus after estradiol stimulation. The binding is complete after 3 hr at 0 degree C. The binding of the antibody correlates with the exchangeable estradiol binding activity of the nuclei over a 4-hr time course following in vivo injection of 17 beta-estradiol.


Estrogen prevention of lacrimal gland cell death and lymphocytic infiltration.
Previous studies have shown that ovariectomy causes necrosis of lacrimal acinar cells, apoptosis of plasma cells and gland lymphocytic infiltration. Both, lacrimal gland cell death and lymphocytic infiltration were prevented by androgen treatment. Since estrogens are removed by ovariectomy, and the synthetic estrogen diethylstilbestrol has been shown to affect some biochemical correlates of lacrimal secretion, the purpose of this study was to determine the effect of 17-beta-estradiol treatment on ovariectomy-induced cell death and lymphocytic infiltration. Sexually mature female New Zealand white rabbits (4-4.5 kg) were ovariectomized and divided into two groups. One group was treated with 0.5 mg kg(-1) per day 17-beta-estradiol, and the other group with vehicle alone. A third group of sham operated rabbits was used as controls and they also were treated with vehicle alone. Six days after surgery, the animals were euthanized, the lacrimal glands removed and processed for analysis of apoptosis as assessed by DNA fragmentation, and for morphological examination. DNA fragmentation was determined using the TUNEL assay and agarose gel electrophoresis. Sections were also stained for rabbit thymic lymphocyte antigen (RTLA), and rabbit CD18. Labelled nuclei and stained areas were quantified by automated densitometry. Ovariectomized rabbits showed a significant increase in the values for degraded DNA as a percent of total nuclear area (2.90+/-0.40%) compared to sham operated rabbits (0.73+/-0.22%). 17-beta-estradiol treatment in ovariectomized rabbits prevented the increase in DNA degradation. Examination of TUNEL assay at higher magnification (40x) confirmed previous studies showing that ovariectomy caused apoptosis of interstitial cells. Significant numbers of bulging cells of very pale appearance under light microscopy, also confirm previously identified necrotic cells in acinar regions. Treatment with 17-beta-estradiol prevented this necrosis. Increased numbers of RTLA(+) and CD18(+) interstitial cells were also evident after ovariectomy. 17-beta-estradiol treatment prevented the increase in the number of lymphoid cells. We confirmed previous observations that suggest that glandular atrophy observed after ovariectomy is likely to proceed by necrosis of acinar cells rather than apoptosis, and that ovariectomy triggers an inflammatory response in the gland. These results suggest that in addition to androgens, estrogens also seem to play a role to maintain lacrimal gland structure and function. A decrease in available estrogen levels could trigger both lacrimal gland apoptosis and necrosis, as well as lymphocytic infiltration. Although, the effect of estrogens in these experiments seems to be direct and not through androgens, the possibility of the role of an autocrine and/or paracrine factors, promoted by estrogen on lacrimal gland cells still needs to be investigated.


Randomized controlled trial of standardized education and telemonitoring for pain in outpatients with advanced solid tumors.
Previous studies have not defined the role of telemonitoring with educational tools in outpatients with advanced cancers. We tested the effectiveness of standardized education and telemonitoring for improving pain, distress, anxiety, depression, quality of life (QoL), and performance in outpatients with advanced cancers. A total of 108 patients were randomly assigned to receive pain education alone (control arm) or pain education plus telemonitoring (experimental arm). Nursing specialists provided video-assisted educational material in both arms and daily telemonitoring for the first week in the experimental arm. Assessment was performed at baseline and 1 week and included evaluations of pain (Brief Pain Inventory, BPI), distress (Distress Thermometer, DT), anxiety, and depression (Hospital Anxiety and Depression Scale, HADS), QoL (QLQ-C30), and a Karnofsky score. Overall (n = 108), pain intensity was significantly improved at 1 week, including worst pain (7.3 to 5.7, P < 0.01) and average pain (4.6 to 3.8, P < 0.01). Additionally, anxiety (HADS score ≥ 11, 75% to 56%, P < 0.01), depression (HADS score ≥ 11, 73% to 51%, P < 0.01), QoL (fatigue and insomnia), and the Karnofsky score (32 to 66, P < 0.01) were also significantly improved at 1 week. However, the level of distress did not improve. The telemonitoring plus standardized education group showed more significant improvement in portion of pain >4 on VAS scale (35% vs. 19%, P = 0.02). Standardized pain education using nursing specialists is an efficient way to improve not only pain itself but also anxiety, depression, performance, and QoL. The addition of telemonitoring helps to improve pain management in the outpatient setting.


Examination of intensive care unit patients' oral health.
Oral health problems are common complications that most intensive care unit patients experience. There are many factors that affect oral health negatively and nurses have important responsibilities in this regard. The aim of this study was assessment of the intensive care unit patients' oral health and risk factors. This study was planned as a descriptive study and conducted between December 2015 and June 2016, with 202 patients in 20 intensive care units of 6 hospitals in Turkey. Data were collected via Data Collection Form and Bedside Oral Exam guide. Oral health assessment of patients was made using a source of light and a tongue depressor. We observed a significant difference in score of the Bedside Oral Exam guide by age, consciousness, type of respiration and feeding, the frequency of oral health, the total number of drugs, and technique of oral care (P < 0.05). None of the intensive care units were using the oral assessment guide. The result of this study shows that there are various risk factors that adversely affect the oral health of intensive care unit patients. Nurses should undertake assessments on the basis of oral care protocols for patients at risk and carry out evidence-based individualized oral care applications.


Binge drinking impairs vascular function in young adults.
The aim of this study was to assess whether young binge drinkers (BD) have impaired macrovascular and microvascular function and cardiovascular disease risk factors compared with age-matched alcohol abstainers (A). Binge drinking rates are highest on college campuses and among those age 18 to 25 years; however, macrovascular and microvascular endothelial function in young adults with histories of repeated binge drinking (≥ 5 standard drinks in 2 h in men, ≥ 4 standard drinks in 2 h in women) has not been investigated. Cardiovascular profiles, brachial artery endothelial-dependent flow-mediated dilation (FMD), and flow-independent nitroglycerin (NTG)-mediated dilation and vasoreactivity of resistance arteries (isolated from gluteal fat biopsies) were evaluated in A and BD. Men and women (18 to 25 years of age; A, n = 17; BD, n = 19) were enrolled. In the BD group, past-month mean number of binge episodes was 6 ± 1, and the mean duration of binge drinking behavior was 4 ± 0.6 years. FMD and NTG-mediated dilation were significantly lower in the BD group (FMD: 8.4 ± 0.7%, p = 0.022; NTG-mediated dilation: 19.6 ± 2%, p = 0.009) than in the A group (FMD: 11 ± 0.7%; NTG-mediated dilation: 28.6 ± 2%). Acetylcholine-induced and sodium nitroprusside-induced dilation in resistance arteries was not significantly different between the A and BD groups. However, endothelin-1-induced constriction was significantly enhanced in the BD group compared with the A group (p = 0.032). No differences between groups were found in blood pressure, lipoproteins, and C-reactive protein. Alterations in the macrocirculation and microcirculation may represent early clinical manifestations of cardiovascular risk in otherwise healthy young BD. This study has important clinical implications for screening young adults for a repeated history of binge drinking.


Severely impaired gastric accommodation is a hallmark of post-Nissen functional dyspepsia symptoms.
Laparoscopic Nissen fundoplication is a commonly performed antireflux surgery, after which reflux symptoms are well controlled, however, complications such as inability to belch or dyspeptic symptoms (mimicking those of functional dyspepsia [FD]) might occur. The aim of the study was to prospectively evaluate symptom pattern and underlying pathophysiological mechanisms in patients with post-Nissen dyspepsia. Twenty-four patients (12 f, mean age 44.5±2.8 years) with post-Nissen dyspepsia symptoms, five patients (3 f, mean age 38.8±3.2 years) with post-Nissen dysphagia symptoms and 14 pre-fundoplication patients (3 f, mean age 42.1±2.5 years) were evaluated. Patients filled out a Rome II-based dyspepsia symptom severity score, performed a gastric emptying test, and a gastric barostat study was used to evaluate the function of the proximal stomach. Upper abdominal bloating scores were higher in post-Nissen dyspepsia patients (P=.016) and symptoms of postprandial distress syndrome (PDS) were more present in post-Nissen dyspepsia patients compared to the other two groups (P=.07). Weight loss was significantly higher in the post-Nissen groups compared to the pre-fundoplication (P=.02). Gastric emptying rates were similar in the three groups. Gastric accommodation (GA) was significantly impaired in the post-Nissen dyspepsia group (dyspepsia -30[-86-83] vs dysphagia 163[148-203] vs pre-fundoplication 147[75-174] mL, P=.004) and the prevalence of patients with impaired GA was higher in the post-Nissen group (P=.007). Postprandial fullness was more prevalent in patients with impaired GA compared to those with normal GA (P=.01). Patients with post-Nissen dyspepsia show a symptom pattern similar to that in FD patients with PDS, and the main underlying mechanism seems to be impaired gastric accommodation to a meal.


Strategies for enhancing the production of penicillin G acylase from Bacillus badius: influence of phenyl acetic acid dosage.
Bacillus badius isolated from soil has been identified as potential producer of penicillin G acylase (PGA). In the present study, batch experiments performed at optimized inoculum size, temperature, pH, and agitation yielded a maximum PGA of 9.5 U/ml in shake flask. The experiments conducted in bioreactor with different oxygen flow rates revealed that 0.66 vvm oxygen flow rate could be sufficient for the maximum PGA activity of 12.7 U/ml. From a detailed investigation on the strategies of the addition of phenyl acetic acid (PAA) for increasing the production of PGA, it was found that the controlled addition of 10 ml of 0.1 % (w/v) PAA once in every 2 h from 6th hour of growth showed the maximum PGA activity of 32 U/ml. Thus, our studies for the first time showed that at concentration above 0.1 % (w/v) PAA, the PGA production decreased. This selective condition paves the way for less costly bioprocess for the production of PGA.


Annual variation in domoic acid in phytoplankton and shellfish samples from Daya Bay of the South China Sea.
Domoic acid (DA) is a well-known phycotoxin that causes amnesic shellfish poisoning (ASP) and is mainly produced by diatom species belonging to the genus Pseudo-nitzschia. An annual survey was conducted monthly over the period of September 2020 to August 2021 in Daya Bay of the South China Sea to investigate the dynamics of particulate and shellfish DA and their relationships with the abundance of Pseudo-nitzschia spp. and environmental parameters. Pseudo-nitzschia spp. was one of the most dominant phytoplankton taxa, and a Pseudo-nitzschia bloom occurred during the survey with the highest abundance of 1.91 × 106 cells L-1. DA was detected in almost all plankton samples with the highest value of 120.7 ng L-1, and high DA concentrations coincided with the abundant presence of Pseudo-nitzschia. DA is prevalent in Daya Bay throughout the year, with detection rates of 98.3%, 82.6%, and 82.6% in plankton samples, in-situ and purchased shellfish, respectively. Higher DA concentrations were detected in the scallop (Chamys nobilis), with the highest concentration of 5.34 µg g-1. High water temperature and low DSi:DIN ratio promoted the growth of Pseudo-nitzschia and DA production. The results suggest that the increasing nitrogen loading and silicate limitation during Pseudo-nitzschia blooms together with the increase in water temperature may increase the risk of DA contamination in Daya Bay.


Metabolism of lipoprotein acylglycerols by liver parenchymal cells.
We investigated the metabolism by hepatocyte suspensions of the acylglycerols in lipoprotein remnants as well as those associated with albumin and low or high density lipoproteins. Remnants, albumin and plasma lipoproteins, rich in monoacylglycerol were prepared by short-term incubations of radio-labeled chylomicra or very low density lipoproteins with extrahepatic lipoprotein lipase in the presence of albumin and low and high density lipoproteins. We demonstrated that liver parenchymal cells contain an active monoacylglycerol acyltransferase that is located on the extracellular surface of the cell plasma membrane. Further, the enzyme is capable of degrading the monoacylglycerol in all the above forms. Triacylglycerol in intact chylomicra and very low density lipoproteins were not metabolized by the cells to any appreciable degree. The degradation of the remnant triacylglycerol appeared to depend solely on the activity of the lipoprotein lipase bound to the lipoprotein remnants. Little uptake of intact lipoprotein acylglycerols by the hepatocytes was observed; instead, hydrolysis of the substrates in the medium always preceded the uptake of the products. The products were then utilized for the synthesis of triacylglycerol and phospholipid within the cells.


Coronary hemodynamic effects of angiotensin inhibition by captopril and teprotide in patients with congestive heart failure.
The coronary hemodynamic effects of vasodilator therapy with angiotensin-converting enzyme inhibitors (captopril and teprotide) were studied in 11 patients with ischemic heart disease and severe congestive heart failure (CHF). Over 2 hours, systemic vascular resistance was reduced from 2,408 +/- 240 to 1,715 +/- 170 dynes . s . cm-5 (p less than 0.001), and cardiac output improved 18%, resulting in lower arterial pressure (101 +/- 8 to 86 +/- 5 mm Hg, p less than 0.001) and left ventricular filling pressure (30 +/- 2 to 21 +/- 2 mm Hg, p less than 0.001). Coronary sinus thermodilution blood flow paralleled perfusion pressure but did not significantly vary overall (160 +/- 20 to 133 +/- 12 ml/min, difference not significant [NS]). Coronary vascular resistance was unchanged. Although the left ventricular stroke work index rose slightly (37.7 +/- 8.8 to 41.3 +/- 7.9 g l m/m2, p less than 0.05), there was no change in the coronary arteriovenous oxygen content difference (10.8 +/- 1.0 to 10.4 +/- 1.0 ml/10 ml, NS) or calculated myocardial oxygen consumption (16.4 +/- 1.9 to 13.9 /- 1.6 ml/min, NS). The heart rate-systolic blood pressure product declined significantly during this period (8,824 +/- 703 to 7,087 +/- 514 beats . mm Hg, p less than 0.02); this relief of cardiac effort was a function of the pretreatment plasma renin activity. A derived index of external myocardial efficiency improved 37% (19 +/- 3 to 26 +/- 6, p less than 0.05), reflecting greater left ventricular work without increased oxygen demand. Enhancement of myocardial performance after converting enzyme inhibition appears dependent on reduction of angiotensin-mediated ventricular afterload and preload. The lack of coronary vasomotor effects in patients with advanced ischemic cardiomyopathy may reflect limited coronary vascular reserve. Improvement of heart failure in these patients developed without evidence of myocardial ischemia, since balance was maintained between oxygen supply and demand.


Risk assessment and clinical impact of liquid-based cytology, oncogenic human papillomavirus (HPV) DNA and mRNA testing in primary cervical cancer screening (the FASE study).
New commercial HPV RNA assays require further validation studies in population-based cervical cancer screening settings. To assess the performance of (FDA-approved) APTIMA® HPV Assay (AHPV), Hybrid Capture 2 (HC2), in-house PCR genotyping, and ThinPrep LBC in population-based screening, stratified by three histological gold standards. A multi-center trial in 5006 women undergoing routine screening in France was designed to compare the absolute and relative risks of diagnosing CIN3+ and CIN2+ lesions by different diagnostic tests. Reproducibility between the primary and second pathology reading was excellent for CIN3+ and CIN2+ endpoints (Cohen's kappa 0.948 and 0.854). Absolute risks (PPV) of different tests (AHPV, HC2, PCR genotyping, LBC) in diagnosing CIN2+ (15-20%) and CIN3+ (4-6%) were similar for the first, second, and consensus pathology readings. The relative risks of diagnosing these lesions by the four tests were also similar when the first, second or third pathology readings were employed. AHPV had the highest absolute risk of both histological endpoints, and detects 5% to 15% more CIN3+ and CIN2+ lesions, respectively, than LBC. Compared with HC2 assay, the relative risk of AHPV is 24% to 29% higher, with a significant difference in CIN2+ detection. With LBC as reference, AHPV had the best sensitivity/specificity balance measured by AUC (area under ROC curve) comparison test (significant for CIN2+), and the colposcopy referral rate (9.2%) comparable to that of LBC (8.7%). These data corroborate the suitability of AHPV for the primary cervical cancer screening.


A novel gas production bioassay of thiosulfate utilizing denitrifying bacteria (TUDB) for the toxicity assessment of heavy metals contaminated water.
This study reports for the first-time the possibility of deploying gas production by thiosulfate utilizing denitrifying bacteria (TUDB) as a proxy to evaluate water toxicity. The test relies on gas production by TUDB due to inhibited metabolic activity in the presence of toxicants. Gas production was measured using a bubble-type respirometer. Optimization studies indicated that 300 mg NO3--N/L, 0.5 mL acclimated culture, and 2100 mg S2O32-/L were the ideal conditions facilitating the necessary volume of gas production for sensitive data generation. Determined EC50 values of the selected heavy metals were: Cr6+, 0.51 mg/L; Ag+, 2.90 mg/L; Cu2+, 2.90 mg/L; Ni2+, 3.60 mg/L; As3+, 4.10 mg/L; Cd2+, 5.56 mg/L; Hg2+, 8.06 mg/L; and Pb2+, 19.3 mg/L. The advantages of this method include operational simplicity through the elimination of cumbersome preprocessing procedures which are used to eliminate interferences caused by turbidity when the toxicity of turbid samples is determined via spectrophotometry.


The mitral annulus in transposition of the great arteries late after Senning- and Mustard-procedures (Insights from the CSONGRAD Registry and MAGYAR-Path Study).
Dextro-transposition of the great arteries (dTGA) is a rare condition comprising 5-7% of all congenital heart diseases (CHD). Until 1990s, atrial switch operations were the method of choice for the treatment of dTGA. The aim of our present study was to evaluate the abnormalities of the mitral annulus (MA) by three-dimensional speckle-tracking echocardiography (3DSTE). Potential differences in MA dimensions and functional properties late after Senning- and Mustard-procedures were analyzed as well. This retrospective cohort study comprised 19 dTGA patients late after atrial switch operation, from which 7 subjects were not involved due to inferior image quality. The remaining dTGA patient group comprised 12 subjects (age: 30.7±8.6 years, 7 males). For comparisons, 32 age- and gender-matched healthy controls were evaluated (age: 34.4±12.3 years, 18 males). End-systolic and end-diastolic MA diameter (MAD), area and perimeter proved to be increased, while MA functional parameters [MA fractional area change (MAFAC) and fractional shortening (MAFS)] were reduced in all dTGA patients as compared to matched controls regardless of the atrial switch procedure used. However, MA morphological parameters were tendentiously lower, while MA functional parameters were tendentiously favorable in case of Senning-procedure compared to Mustard-procedure. dTGA is accompanied by MA dilation and its functional impairment late after Senning- and Mustard-procedures.


Ethnic differences in hepatocellular carcinoma prevalence and therapeutic outcomes.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The incidence of HCC is affected by genetic and non-genetic factors. Genetically, mutations in the genes, tumor protein P53 (TP53), catenin beta 1 (CTNNB1), AT-rich interaction domain 1A (ARIC1A), cyclin dependent kinase inhibitor 2A (CDKN2A), mannose 6-phosphate (M6P), smooth muscle action against decapentaplegic (SMAD2), retinoblastoma gene (RB1), cyclin D, antigen presenting cells (APC), AXIN1, and E-cadherin, have been shown to contribute to the occurrence of HCC. Non-genetic factors, including alcohol consumption, exposure to aflatoxin, age, gender, presence of hepatitis B (HBV), hepatitis C (HCV), and non-alcoholic fatty liver disease (NAFLD), increase the risk of HCC. The severity of the disease and its occurrence vary based on geographical location. Furthermore, men and minorities have been shown to be disproportionately affected by HCC, compared with women and non-minorities. Ethnicity has been reported to significantly affect tumorigenesis and clinical outcomes in patients diagnosed with HCC. Generally, differences in gene expression and/or the presence of comorbid medical diseases affect or influence the progression of HCC. Non-Caucasian HCC patients are significantly more likely to have poorer survival outcomes, compared to their Caucasian counterparts. Finally, there are a number of factors that contribute to the success rate of treatments for HCC. Assessment and treatment of HCC must be consistent using evidence-based guidelines and standardized outcomes, as well as international clinical practice guidelines for global consensus. Standardizing the assessment approach and method will enable comparison and improvement of liver cancer research through collaboration between researchers, healthcare providers, and advocacy groups. In this review, we will focus on discussing epidemiological factors that result in deviations and changes in treatment approaches for HCC.


Synthesis, biological evaluation and molecular docking of new triphenylamine-linked pyridine, thiazole and pyrazole analogues as anticancer agents.
A new series of pyridine, thiazole, and pyrazole analogues were synthesized. The pyridone analogues 4a-e were synthesized by treating N-aryl-2-cyano-3-(4-(diphenylamino)phenyl)acrylamides 3a-e with malononitrile. Many 4-arylidene-thiazolidin-5-one analogues 6a-d were obtained by Knoevenagel reactions of 4-(diphenylamino)benzaldehyde (1) with their corresponding thiazolidin-5-one derivatives 5a-d. The structural elucidation of the products was proven by the collections of spectroscopic methods such as IR, 1H NMR, 13C NMR, and MS data. Their anti-cancer activity was examined against two cell lines, MDA-MB-231 (mammary carcinomas) and A-549 (lung cancer). Compared with cisplatin as a reference standard drug, 6-amino-4-(4-(diphenylamino)phenyl)-2-oxo-1-(p-tolyl)-1,2-dihydropyridine-3,5-dicarbonitrile (4b) and 6-amino-4-(4-(diphenylamino)phenyl)-1-(4-nitrophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (4e) exhibited better efficiency against the A-549 cell line, with IC50 = 0.00803 and 0.0095 μM, respectively. Also, these compounds 4b and 4e showed the most potency among the examined compounds against MDA-MB-231 with IC50 = 0.0103 and 0.0147 μM, respectively. The newly synthesized compounds were docked inside the active sites of the selected proteins and were found to demonstrate proper binding. 2-Cyano-2-(4,4-(diphenylamino)benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)-N-(p-tolyl)acetamide (6c) offered the highest binding affinity (- 8.1868 kcal/mol) when docked into (PDB ID:2ITO), in addition to 2-cyano-N-(4-(diethylamino)phenyl)-2-(4-(4-(diphenylamino)benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)acetamide (6a) gave the highest energy score (- 9.3507 kcal/mol) with (PDB ID:2A4L).


Effects of cisapride on postcibal jejunal motor activity.
In the jejunum of fasting humans, cisapride induces a phase 2-like, highly propagative motor pattern. This study investigated cisapride's effects on the fed pattern of the jejunum. Starting 5 min after a phase 3 of the migrating motor complex, 18 healthy men received 5 or 10 mg cisapride or placebo orally in random double-blind fashion and ingested meals containing 1000 and 4200 kJ, respectively. Jejunal pressures were recorded pneumohydraulically with five catheter orifices 10-30 cm aboard the ligament of Treitz. After the 4200-kJ meal, total number and number of propagated contractions as well as area under the curve increased significantly more than after 1000 kJ. Following the 1000-kJ but not the 4200-kJ meal, 10 mg cisapride increased total number of contractions, number of propagated contractions, mean amplitude, and area under curve significantly more than placebo. Fed-pattern duration increased with the meal's caloric content but was not influenced systematically by cisapride. In conclusion, cisapride stimulates jejunal motor activity and induces a propagative pattern after a 1000-kJ but not after a 4200-kJ meal, suggesting that it can produce no further stimulation when motor activity is near maximally enhanced already.


3-hydroxy-3-methylglutaric aciduria: a new assay of 3-hydroxy-3-methylglutaryl-coa lyase using high performance liquid chromatography.
A new assay has been developed for 3-hydroxy-3-methylglutaryl-CoA lyase, the final enzyme in the leucine degradative pathway. The assay was performed by incubating lysates of fibroblasts with [glutaryl-3-14C](D,L)-3-hydroxy-3-methyl-glutaryl coenzyme A. The products were analysed by high performance liquid chromatography with continuous liquid scintillation counting. This provided simultaneous identification and quantification of one of the enzymatic products, [3-14C]acetoacetic acid. The mean 3-hydroxy-3-methylglutaryl-CoA lyase activity in fibroblasts from five controls was 732 +/- 81 (SD) pmol/min X mg protein. Using this assay, we have studied skin fibroblasts cultured from a patient with 3-hydroxy-3-methylglutaric aciduria and found 3% of normal 3-hydroxy-3-methylglutaryl-CoA lyase activity. The activities in skin fibroblasts cultured from the parents were 46 and 53% of control activity which is consistent with heterozygocity. Kinetic studies of 3-hydroxy-3-methylglutaryl-CoA lyase in skin fibroblasts cultured from two normal subjects yielded Km values of 14.4 and 18.8 mumol/l for 3-hydroxy-3-methylglutaryl-CoA.


Expression and localization of estrogen receptor alpha in the C2C12 murine skeletal muscle cell line.
The classical model of 17beta-estradiol action has been traditionally described to be mediated by the estrogen receptor (ER) localized exclusively in the nucleus. However, there is increasing functional evidence for extra nuclear localization of ER. We present biochemical, immunological and molecular data supporting mitochondrial-microsomal localization of ER alpha in the C2C12 skeletal muscle cell line. We first established [(3)H]17beta estradiol binding characteristics in whole cells in culture. Specific and saturable [(3)H]17beta estradiol binding sites of high affinity were then detected in mitochondrial fractions (K(d) = 0.43 nM; B(max) = 572 fmol/mg protein). Immunocytological studies revealed that estrogen receptors mainly localize at the mitochondrial and perinuclear level. These results were also confirmed using fluorescent 17beta estradiol-BSA conjugates. The immunoreactivity did not translocate into the nucleus by 17beta-estradiol treatment. Western and Ligand blot approaches corroborated the non-classical localization. Expression and subcellular distribution of ER alpha proteins were confirmed in C2C12 cells transfected with ER alpha siRNA and by RT-PCR employing specific primers. The non-classical distribution of native pools of ER alpha in skeletal muscle cells suggests an alternative mode of ER localization/function.


NF-kappaB p52, RelB and c-Rel are transported into the nucleus via a subset of importin alpha molecules.
In resting cells NF-kappaB transcription factors are retained in the cytoplasm as latent inactive complexes, until they are activated and rapidly transported into the nucleus. We show that all NF-kappaB proteins are imported into the nucleus via a subset of importin alpha isoforms. Our data indicate that the NF-kappaB components of the classical and alternative pathways have somewhat different specifities to importin alpha molecules. Based on the results from binding experiments of in vitro-translated and Sendai virus infection-induced or TNF-alpha-stimulated endogenous NF-kappaB proteins, it can be predicted that the specifity of NF-kappaB proteins to importin alpha molecules is different and changes upon the composition of the imported dimer. p52 protein binds directly to importin alpha3, alpha4, alpha5 and alpha6 and c-Rel binds to importin alpha5, alpha6 and alpha7 via a previously described monopartite nuclear localization signals (NLSs). Here we show that RelB, instead, has a bipartite arginine/lysine-rich NLS that mediates the binding of RelB to importin alpha5 and alpha6 and subsequent nuclear translocation of the protein. Moreover, we show that the nuclear import of p52/RelB heterodimers is mediated exclusively by the NLS of RelB. In addition, we found that the NLS of p52 mediates the nuclear import of p52/p65 heterodimers.


Comparison of bioMérieux API 20NE and Remel RapID NF Plus, identification systems of type strains of Ralstonia pickettii.
A : Comparison of two commercial miniaturized rapid systems for the identification of Ralstonia pickettii strains. Varying identification results were encountered using the bioMérieux API NE system and the Remel IDS RapID NF Plus commercial systems for R. pickettii. To compare these two systems, eight strains of R. pickettii were purchased from different commercial culture collections. Additionally, 32 industrial and eight clinical isolates, initially identified using the Vitek Junior (bioMérieux) were tested. Total number of isolates tested was 48. The API 20NE identified 29 isolates, as R. pickettii but was unsuccessful with 19 isolates. The Remel IDS RapID NF Plus identified 46 isolates as R. pickettii. One clinical and one industrial isolates was identified as non-R. pickettii with both systems. The above results indicate that the use of API 20NE system for examining the identification of R. pickettii strains is inconsistent. This study demonstrated that the RapID NF Plus is more accurate as an inexpensive identification system for the identification of R. pickettii, a potential emerging organism of medically and industrial importance.


Reply to Charrel, R.N.; Depaquit, J. Comment on "Xu et al. Isolation and Identification of a Novel Phlebovirus, Hedi Virus, from Sandflies Collected in China. Viruses 2021, 13, 772".
Dear Professor Remi N. Charrel and Professor Jerome Depaquit, we thank you for your interest in our research and for your kind suggestions [...].


Sulfoxaflor influences the biochemical and histological changes on honeybees (Apis mellifera L.).
Pesticide application can have an adverse effect on pollinator honey bees, Apis mellifera L., ranging from mortality to sublethal effects. Therefore, it is necessary to understand any potential effects of pesticides. The present study reports the acute toxicity and adverse effects of sulfoxaflor insecticide on the biochemical activity and histological changes on A. mellifera. The results showed that after 48 h post-treatment, the LD25 and LD50 values were 0.078 and 0.162 µg/bee, respectively, of sulfoxaflor on A. mellifera. The detoxification enzyme activity shows an increase of glutathione-S-transferase (GST) enzyme on A. mellifera in response to sulfoxaflor at LD50 value. Conversely, no significant differences were found in mixed-function oxidation (MFO) activity. In addition, after 4 h of sulfoxaflor exposure, the brains of treated bees showed nuclear pyknosis and degeneration in some cells, which evolved to mushroom shaped tissue losses, mainly neurons replaced by vacuoles after 48 h. There was a slight effect on secretory vesicles in the hypopharyngeal gland after 4 h of exposure. After 48 h, the vacuolar cytoplasm and basophilic pyknotic nuclei were lost in the atrophied acini. After exposure to sulfoxaflor, the midgut of A. mellifera workers showed histological changes in epithelial cells. These findings of the present study showed that sulfoxaflor could have an adverse effect on A. mellifera.


The effects of a contingent light-flash on stuttering and attention to stuttering.
The hypothesis that a light-flash made contingent on stuttering would reduce stuttering to the extent that it called subjects' attention to their stuttering responses was investigated with two adult female stutterers. Attention to stuttering was measured by asking subjects to depress a switch each time they detected a stuttering in their speech. For one subject, the contingent light produced a marked reduction in stuttering but had no effect on switch-pressing. For the other subject, the light had little effect on stuttering but resulted in an increase in switch-pressing. For both subjects, reductions in stuttering occurred when they were asked to note their stutterings by pressing the switch. The results suggested that the effect of the light on stuttering was not due to its role in calling attention to stuttering.