Bioaccumulation of 210Po and 210Pb in cephalopods collected from Kudankulam (Southeastern coast of Gulf of Mannar, India) and assessment of dose in human beings.
Activities of (210)Po and (210)Pb in various tissues of two common species of cephalopod molluscs (cuttlefishes) of Kudankulam coast were studied. Of all the tissues, (210)Po and (210)Pb were found accumulated more in the digestive gland, shell gland and intestine. Urotheuthis duvauceli accumulated more (210)Po and (210)Pb in certain organs when compared with Sepiella inermis. The activity ratio of (210)Po/(210)Pb fell within the range of 0.6-29.3 in the organs. The biological concentration factor for the organs ranged from 1.2×10(3) to 2×10(5) for (210)Po and 3.6×10(2) to 7.6×10(4) for (210)Pb. A significant variation in the accumulation of (210)Po and (210)Pb was noted between species, organs and seasons (p < 0.05). The whole-body internal dose rate due to (210)Po was 1.24 and 0.83 µGy h(-1) and it was 2×10(-3) and 3×10(-3) µGy h(-1) due to (210)Pb for both the species. The effective dose in humans due to (210)Po intake ranged from 96.3 to 376.6 µSv y(-1) and that of (210)Pb ranged from 35.2 to 105.7 µSv y(-1), respectively. The data generated will act as a reference database for these organisms of this coast in which a nuclear power station is under construction.


Glucose kinetics in glucose-infused small for gestational age infants.
To evaluate the maturation of glucose homeostasis in the small for gestational age (SGA) neonate, glucose kinetics were measured with 78% enriched D-[U-13C]glucose by the prime plus constant infusion technique in nine SGA infants and compared with the rate obtained in seven term appropriate for gestational age infants and 13 preterm appropriate for gestational age infants. All of the infants had received glucose intravenously from birth and continued to receive the glucose infusion throughout the study. Fasting plasma glucose and plasma insulin concentrations and plasma [13/12C]ratios were measured during the steady state turnover period. From this data, the glucose production rate was derived. During the turnover period, the SGA and both groups of appropriate for gestational age infants had similar average plasma glucose, plasma insulin, plasma glucagon concentrations, and similar persistent rates of glucose production during glucose infusion. We conclude that under stimulation of glucose infusion, the SGA infant and his AGA counterpart have similar hormonal regulatory responses as well as functional integrity in handling glucose during the second day after birth.


Evaluation of Eazyplex® LAMP test for fast Candida auris direct detection of colonized patients.
Candida auris is a multidrug-resistant pathogen yeast that produces nosocomial outbreaks, due to its ability in colonizing the skin, mucous membranes and surfaces. Rapid diagnosis is essential to control its spread. The aim of this study was to compare the Eazyplex® Candida auris kit (AmplexDiagnostics GmbH) for the rapid identification of patients colonized with C. auris, with the reference method used in our institution (culture and identification by MALDI-TOF). This easy-to-perform test allows obtaining a fast result, in ~30 min. First, we achieved a preliminary study from previously characterized Candida species colonies obtained from 51 clinical samples, with 100% agreement between culture isolation and the Eazyplex® Candida auris LAMP. Second, 152 epidemiological surveillance samples (pharyngeal and axillary-rectal swabs) were tested retrospectively. The sensitivity, specificity, positive and negative predictive values were 91.8%, 98.8%, 98.2% and 94.5%, respectively. Eazyplex® Candida auris showed acceptable results compared with culture in detecting C. auris from surveillance samples with the advantage of single-test and shorter time for handling and result than culture, in addition to its great specificity, positive and negative predictive values.


Laparoscopic Transhiatal Thoracic Duct Ligation for Chylothorax after Esophagectomy.
In esophagectomy for thoracic esophageal cancer, chylothorax may develop at a certain frequency. For chylothorax, conservative treatment is selected first, but if it is not improved, thoracic duct (TD) ligation is considered. In general, transthoracic approach is chosen to reach the TD. However, it is sometimes difficult to identify the TD due to adhesion in the thoracic cavity. Hence, we selected a laparoscopic transhiatal approach to the TD. We introduce the procedure of our laparoscopic transhiatal TD ligation technique.


Lupus cystitis. report of a case.
A 42-year-old female with a history of systemic lupus erythematosus (SLE) visited the Department of Internal Medicine at our hospital complaining of anorexia. Hydronephrosis was diagnosed, and she was referred to our department for further evaluation. Intravenous pyelography (IVP) revealed bilateral hydronephrosis and hydroureters. Computerized tomography (CT) showed retention of ascitic fluid and thickening of the intestinal and bladder walls with contrast effects in the serosa and mucosa. Lasix-loaded renography showed that both kidneys were normal. Examination of a biopsy specimen revealed interstitial edema, fibrosis, and infiltration of inflammatory cells. Cystometry showed normal intravesical pressure. A diagnosis of lupus cystitis was made and administration of 40mg of prednisolone was started. The anemia was ameliorated, and thickening of the bladder and intestinal walls was no longer seen on CT. Hydronephrosis of the left kidney was less prominent. However, aggravation of the right ureteral stenosis was noted, and a stent was inserted in the stenosed ureter. Stenosis was successfully relieved by the stent, and internal drainage was established. The patient is still receiving steroids and is being followed at our department. Twenty-two reported cases of lupus cystitis in Japan are reviewed.


Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study).
Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment. This prospective registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries. Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.


C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions.
To obtain insight into the role of the retinoblastoma susceptibility gene (Rb; also known as Rb1) in apoptosis, we analyzed Caenorhabditis elegans mutants lacking a functional lin-35 RB gene. We found that the loss of lin-35 function results in a decrease in constitutive germ cell apoptosis. We present evidence that lin-35 promotes germ cell apoptosis by repressing the expression of ced-9, an anti-apoptotic C. elegans gene that is orthologous to the human proto-oncogene BCL2. Furthermore, we show that the genes dpl-1 DP, efl-1 E2F and efl-2 E2F also promote constitutive germ cell apoptosis. However, in contrast to lin-35, dpl-1 (and probably also efl-1 and efl-2) promotes germ cell apoptosis by inducing the expression of the pro-apoptotic genes ced-4 and ced-3, which encode an APAF1-like adaptor protein and a pro-caspase, respectively. Based on these results, we propose that C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions in the germ line and that the transcriptional regulation of components of the central apoptosis machinery is a critical determinant of constitutive germ cell apoptosis in C. elegans. Finally, we demonstrate that lin-35, dpl-1 and efl-2, but not efl-1, function either downstream of or in parallel to cep-1 p53 (also known as TP53) and egl-1 BH3-only to cause DNA damage-induced germ cell apoptosis. Our results have implications for the general mechanisms through which RB-like proteins control gene expression, the role of RB-, DP- and E2F-like proteins in apoptosis, and the regulation of apoptosis.


Secondary Effects of Glyphosate Action in Phelipanche aegyptiaca: Inhibition of Solute Transport from the Host Plant to the Parasite.
It is currently held that glyphosate efficiently controls the obligate holoparasite Phelipanche aegyptiaca (Egyptian broomrape) by inhibiting its endogenous shikimate pathway, thereby causing a deficiency in aromatic amino acids (AAA). While there is no argument regarding the shikimate pathway being the primary site of the herbicide's action, the fact that the parasite receives a constant supply of nutrients, including proteins and amino acids, from the host does not fit with an AAA deficiency. This apparent contradiction implies that glyphosate mechanism of action in P. aegyptiaca is probably more complex and does not end with the inhibition of the AAA biosynthetic pathway alone. A possible explanation would lie in a limitation of the translocation of solutes from the host as a secondary effect. We examined the following hypotheses: (a) glyphosate does not affects P. aegyptiaca during its independent phase and (b) glyphosate has a secondary effect on the ability of P. aegyptiaca to attract nutrients, limiting the translocation to the parasite. By using a glyphosate-resistant host plant expressing the "phloem-mobile" green fluorescent protein (GFP), it was shown that glyphosate interacts specifically with P. aegyptiaca, initiating a deceleration of GFP translocation to the parasite within 24 h of treatment. Additionally, changes in the entire sugars profile (together with that of other metabolites) of P. aegyptiaca were induced by glyphosate. In addition, glyphosate did not impair germination or seedling development of P. aegyptiaca but begun to exert its action only after the parasite has established a connection to the host vascular system and became exposed to the herbicide. Our findings thus indicate that glyphosate does indeed have a secondary effect in P. aegyptiaca, probably as a consequence of its primary target inhibition-via inhibition of the translocation of phloem-mobile solutes to the parasite, as was simulated by the mobile GFP. The observed disruption in the metabolism of major sugars that are abundant in P. aegyptiaca within 48 h after glyphosate treatment provides a possible explanation for this inhibition of translocation and might reflect a critical secondary effect of the herbicide's primary action that results in loss of the parasite's superior sink for solutes.


Lentiviral-based reporter constructs for profiling chondrogenic activity in primary equine cell populations.
Successful clinical translation of mesenchymal stem cell (MSC)-based therapies for cartilage repair will likely require the implementation of standardised protocols and broadly applicable tools to facilitate the comparisons among cell types and chondroinduction methods. The present study investigated the utility of recombinant lentiviral reporter vectors as reliable tools for comparing chondrogenic potential among primary cell populations and distinguishing cellular-level variations of chondrogenic activity in widely used three-dimensional (3D) culture systems. Primary equine MSCs and chondrocytes were transduced with vectors containing combinations of fluorescent and luciferase reporter genes under constitutive cytomeglavirus (CMV) or chondrocyte-lineage (Col2) promoters. Reporter activity was measured by fluorescence imaging and luciferase assay. In 3D cultures of MSC aggregates and polyethylene glycol-hyaluronic acid (PEG-HA) hydrogels, transforming growth factor beta 3 (TGF-β3)-mediated chondroinduction increased Col2 reporter activity, demonstrating close correlation with histology and mRNA expression levels of COL2A1 and SOX9. Comparison of chondrogenic activities among MSC populations using a secretable luciferase reporter revealed enhanced chondrogenesis in bone-marrow-derived MSCs relative to MSC populations from synovium and adipose tissues. A dual fluorescence reporter - enabling discrimination of highly chondrogenic (Col2-GFP) cells within an MSC population (CMV-tdTomato) - revealed marked heterogeneity in differentiating aggregate cultures and identified chondrogenic cells in chondrocyte-seeded PEG-HA hydrogels after 6 weeks in a subcutaneous implant model - indicating stable, long-term reporter expression in vivo. These results suggested that lentiviral reporter vectors may be used to address fundamental questions regarding chondrogenic activity in chondroprogenitor cell populations and accelerate clinical translation of cell-based cartilage repair strategies.


Double-ended needle holder for anterior segment surgery.
A newly designed double-ended needle holder provides the surgeon who is operating on the anterior segment with the advantages of both a straight and curved needle holder without having to change instruments.


Parental feeding styles, young children's fruit, vegetable, water and sugar-sweetened beverage consumption, and the moderating role of maternal education and ethnic background.
To examine the associations between parental feeding styles and children's dietary intakes and the modifying effect of maternal education and children's ethnicity on these associations. Cross-sectional study of parental feeding styles, assessed by the Parental Feeding Style Questionnaire, and children's dietary intakes. Multiple regression analyses were carried out to assess the associations between the parental feeding styles studied ('control', 'emotional feeding', 'encouragement to eat' and 'instrumental feeding') and children's dietary intakes (consumption of fruit, vegetables, water and sugar-sweetened beverages (SSB)). The modifying effect of maternal education and children's ethnicity on these associations was explored. North-western part of the Netherlands. Children aged 3-7 years (n 5926). Both 'encouragement' and 'control' were associated with higher consumption of vegetables and lower consumption of SSB, but only 'encouragement' was positively associated with fruit and water intakes. 'Instrumental feeding' showed a positive association with SSB and negative associations with fruit, vegetable and water consumption. No significant associations were found for 'emotional feeding'. Maternal educational level and children's ethnicity moderated some associations; for example, 'control' was beneficial for vegetable intake in all subgroups, whereas the association with SSB was beneficial only in highly educated mothers. The study shows that both encouraging and controlling feeding styles may improve children's dietary behaviour, while 'instrumental feeding' may have a detrimental effect. Furthermore, maternal educational level and children's ethnicity influence these associations. The study's findings could provide a basis for development of interventions to improve parental feeding styles.


[Recurrent autoreactive pericardial effusion. Impact of an aetiological classification of pericarditis].
A 36 year-old man suffered from fever, fatigue, pleurodynia and precordial discomfort. His family physician suspected febrile tracheobronchitis and treated it with ampicillin for 5 days. Because symptoms persisted an ECG was done which suggested acute myocardial infarction. The patient underwent an emergency coronary angiography which excluded coronary artery disease and aortic dissection. Pericarditis was suspected and the patient put on aspirin, 500 mg/d. Because of persisting cardiac symptoms an echocardiography was performed which revealed systolic separation between epi- and pericardium, characteristic of a small pericardial effusion after acute pericarditis. The symptoms improved after one week of treatment with diclofenac and the ECG had become normal. Two months later the patient was seen at our cardiac outpatient clinic. He had night sweats, sporadic precordial pain and severe dyspnoe. Further investigations revealed tachycardia (120/min), hypotension (95/70 mm Hg), pulsus paradoxus and jugular vein sustension. Echocardiography revealed a large pericardial effusion ("swinging heart"), which explained the low voltage and the electrical alternans in the ECG. Pericardiocentesis was carried out the same day to relieve the tamponade. It was followed by pericardioscopy and epi- as well as pericardial biopsy. 485 ml of a serous effusion were drained. Cytology and histology demonstrated a lymphocytic fibrinous pericarditis. Polymerase chain reaction (PCR) on viral and bacterial RNA and DNA of potentially cardiotropic agents remained negative. The pigtail catheter was left in place and 80 mg of gentamycin were given intrapericardially on day 1 and 2, followed by 500 mg of crystalloid triamcinolone acetate after the PCR was found to be negative. Oral treatment with 0.5 mg colchicine three times a day (off-label use) was started and maintained for 6 months. After 9 months no effusion was detected and the patient was free of symptoms. After exclusion of bacterial and viral pericardial infection, a high single dose of intrapericardial triamcinolone combined with long-term oral colchicine has proven to be a highly efficacious treatment of autoreactive pericarditis which will avoid relapses in most cases.


Modified-chitosan nanoparticles: Novel drug delivery systems improve oral bioavailability of doxorubicin.
The efficacy of most anticancer drugs is highly limited in vivo due mainly to poor pharmacokinetics behavior including poor bioavailability after extravascular administration. We have developed novel chitosan-modified polymeric nanoparticles for oral as well as i.v. administration. Nanoparticles were developed utilizing the double emulsion solvent evaporation technique for sustained delivery of various anticancer drugs. Chitosan diacetate (CDA) and chitosan triacetate (CTA) polymers were previously modified in our laboratory and used as novel matrix. Nanoparticles, loaded with various anticancer drugs, were characterized for particle size using dynamic light scattering as well as transmission electron microscopy and net surface charge using dynamic light scattering. Particles size was below 100nm in diameter and zeta potential ranged - (25-30). Encapsulation efficiency of anticancer drugs varied considerably and was dependent on the physicochemical characteristics of the encapsulated drug. However, chitosan triacetate nanoparticles showed relatively higher encapsulation efficiency than chitosan diacetate nanoparticles. In vitro release of encapsulated drugs was sustained over a period of 14days. Nanoparticles enhanced cellular accumulation of encapsulated drugs, compared to the free drugs, in vitro in MCF-7 and Caco-II tumor cell lines. In conclusion, diacetate and triacetate chitosan are novel polymers that can be used to formulate nanoparticles which efficiently encapsulated anticancer drugs, and sustained the release and enhanced tumor cellular uptake of these drugs. Further, chitosan triacetate nanoparticles enhanced oral bioavailability of doxorubicin. CDA and CTA nanoparticles can be used to efficiently deliver anticancer drugs and improve their in vivo profile.


Cascading One-Pot Synthesis of Biodegradable Uronic Acid-Based Surfactants from Oligoalginates, Semi-Refined Alginates, and Crude Brown Seaweeds.
The present article describes a one-pot and cascade mode process using biocompatible/biodegradable reagents, for simply obtaining surfactant compositions comprising mixtures of d-mannuronic acid and l-guluronic acid directly from oligoalginates or semi-refined alginates (mixtures of alginate, cellulose, hemicellulose, laminaran, and fucan). Simple treatments of partial purification of the reaction crudes (elimination of the salts and/or the residual fatty alcohols) or isolation of the surfactant compositions result in sugar-based compounds having performance levels appropriate to applications in detergency. In addition, the challenging extension of this cascading one-pot synthesis technology to crude milled brown seaweeds was successfully carried out to provide promising surface-active compositions made up of alkyl uronate and alkyl glycoside monosaccharides.


[Psychomotor reaction in primates placed in ballistic flight in rockets].
Psychomotor reactions have been studied in Nemestrina Macaques during flights in rockets in which there were periods of weightlessness lasting about 10 minutes. The animals had undergone motor conditioning and responded to a light signal by pressing on a button placed on a panel where there were four other undifferentiated buttons. The lighting of the panel and pressing on the different buttons in reply was recorded with respect to time. Movement was observed by film recording, and electrical activity of the brain was kept under observation by six different recordings of the cortex. Activity of stretching and bending muscles of the legs was recorded, as well as breathing, and heart activity was recorded on an electrocardiogram. These psychological parameters were transmitted to the earth by long-distance measurement during the entire flight. The recordings made it possible to confirm that the absence of the sensation of weight seems to reduce the alertness of the animals. This fact had already been observed in Wistar's rat and cat. The sensor-psychomotor responses undergo important individual variations and depend on the motivation of the subjects. A very well motivated one reacted after a short period of adaption, as it did in the laboratory: one that was much less motivated would not work until after weightlessness has ended, and showed signs of drowsiness. These observations made during the flights in rockets confirm those of Chambers et al., Harris et al., Lilly et al. made in immersion studies; they show the important role of weight in maintaining alertness, but that changes of psychomotor activity are particularly related to motivation.


Antimuscarinic-induced convulsions in fasted mice after food intake: No evidence of spontaneous seizures, behavioral changes or neuronal damage.
Prolonged or repeated seizures have been shown to cause spontaneous recurrent seizures, increased anxiety‑related behavior, locomotor hyperactivity, impaired functions of learning and memory, and neuronal damage in the hippocampus and other brain regions in animals. Mice and rats treated with antimuscarinic drugs after fasting for two days or less develop convulsions after being allowed to eat ad libitum. To address whether such behavioral and neuroanatomic changes occur following these convulsions, mice treated i.p. with saline (control) or 2.4 mg/kg atropine and given food after 24 h of fasting were grouped according to seizure scores for behavioral and histological analysis. Following convulsions, the occurrence of spontaneous recurrent seizures was observed for 30 days. Motor activity and grooming behavior were assessed in the open field, and memory was assessed using the novel object recognition test 4 and 7 days after onset of convulsions, respectively. Animals allocated for the histological analysis were decapitated 7 days after onset of convulsions and hippocampal slices were evaluated for the percentage of degenerating neurons stained with Fluoro‑Jade C. Spontaneous recurrent seizures, locomotor alterations, anxiety‑related behavior, memory impairment, and neuronal loss in the granular layer of the dentate gyrus were not detected in the animals with seizure score 1-2 or 3-5. These results are in accordance with those related to the absence of behavioral changes, cognitive deficits, and hippocampal neuronal damage after single brief seizures in animals and patients with epilepsy.


How much benefit does Intelligent Speed Adaptation deliver: an analysis of its potential contribution to safety and environment.
The UK Intelligent Speed Adaptation (ISA) project produced a rich database with high-resolution data on driver behaviour covering a comprehensive range of road environment. The field trials provided vital information on driver behaviour in the presence of ISA. The purpose of this paper is to exploit the information gathered in the field trials to predict the impacts of various forms of ISA and to assess whether ISA is viable in terms of benefit-to-cost ratio. ISA is predicted to save up to 33% of accidents on urban roads, and to reduce CO(2) emissions by up to 5.8% on 70 mph roads. In order to investigate the long-term impacts of ISA, two hypothetical deployment scenarios were envisaged covering a 60-year appraisal period. The results indicate that ISA could deliver a very healthy benefit-to-cost ratio, ranging from 3.4 to 7.4, depending on the deployment scenarios. Under both deployment scenarios, ISA has recovered its implementation costs in less than 15 years. It can be concluded that implementation of ISA is clearly justified from a social cost and benefit perspective. Of the two deployment scenarios, the Market Driven one is substantially outperformed by the Authority Driven one. The benefits of ISA on fuel saving and emission reduction are real but not substantial, in comparison with the benefits on accident reduction; up to 98% of benefits are attributable to accident savings. Indeed, ISA is predicted to lead to a savings of 30% in fatal crashes and 25% in serious crashes over the 60-year period modelled.


Acute anterior myocardial infarction after chemotherapy for testicular seminoma in a young patient.
Testicular cancer is the most common solid tumor among young men aged 15 to 35 years. Combination chemotherapy with cisplatin, etoposide, and bleomycin remains the mainstay of treatment. We present a 27-year-old man who presented with an acute anterior myocardial infarction during the second course of chemotherapy for seminoma. Because the patient had no significant risk factors for coronary heart disease, the infarction was likely caused by the chemotherapy regimen.


Investigation of the optimal dose for experimental lipopolysaccharide-induced recognition memory impairment: behavioral and histological studies.
Lipopolysaccharide (LPS) administration is one of the most commonly used methods for inducing inflammation in animal models. Several animal studies have investigated the effects of acute and chronic peripheral administration of LPS on cognitive impairment. However, no previous study has compared the effects of different doses of chronically administered LPS on recognition memory performance. Here, we aimed to investigate the optimal dose of chronically administered LPS for the induction of recognition memory impairment in mice. LPS at different doses (0.25, 0.50 and 0.75 mg/kg) was administered to SWR/J mice daily for 7 days. On day 9, the open field, novel object recognition and novel arm discrimination behavioral tests were performed. Additionally, prefrontal cortical histological examination was conducted. Compared with the control group, mice injected with 0.75 mg/kg LPS notably showed no object preference (familiar vs. novel), a reduction in the discrimination index, and spatial recognition impairment. Administration of the 0.25 and 0.50 mg/kg doses of LPS showed a preference for the novel object compared with the familiar object, had no significant impact on the discrimination index, and caused spatial recognition impairment. These behavioral results are in line with the histological examination of the prefrontal cortex, which revealed that the 0.75 mg/kg dose produced the most histological damage. Our findings suggest that for chronic peripheral administration of LPS, 0.75 mg/kg is the optimal dose for inducing neuroinflammation-associated recognition memory deficits.


Chronic kidney disease, plasma lipoproteins, and coronary artery calcium incidence: the Multi-Ethnic Study of Atherosclerosis.
To determine the association of chronic kidney disease and coronary artery calcium (CAC) incidence, and the distribution of lipoproteins across categories of kidney function and their association with CAC risk. We analyzed data from 2795 participants in the Multi-Ethnic Study of Atherosclerosis with no CAC (calcium score=0) at baseline enrolled at the first Multi-Ethnic Study of Atherosclerosis visit between the years 2000 and 2002. During a median follow-up of 2.4 years, incident calcium (calcium score>0 at follow-up) developed in 12%, 19%, and 27% of participants with a cystatin-c estimated glomerular filtration rate (mL/min per 1.73 m)(2) of ≥90, 60 to 89, and 30 to 59 (P for difference <0.001), respectively. Compared with those with normal kidney function (estimated glomerular filtration rate≥90), adjusted CAC incidence risk ratios, and 95% confidence intervals (CIs) were as follows: 1.26 (95% CI, 1.04-1.52), and 1.56 (95% CI, 1.11-2.20; P(trend)=0.014) in those with estimated glomerular filtration rate of 60 to 89 and 30 to 59, respectively. These associations were attenuated after adjusting for a characteristic and strongly interrelated lipid phenotype (principal component 1), which was more common in those with chronic kidney disease and characterized by a predominance of triglyceride-rich lipoproteins: CAC incidence risk ratios=1.21 (95% CI, 1.00-1.46) and 1.44 (95% CI, 1.02-2.04; P(trend)=0.06) in those with estimated glomerular filtration rate 60 to 89 and 30 to 59, respectively, after adjusting for principal component 1. Chronic kidney disease is strongly associated with CAC incidence. Part of this association is mediated through a characteristic lipid phenotype comprising elevations in triglyceride-rich lipoproteins.


Are trust and satisfaction similar in dental care settings?
Trust and satisfaction in dental care settings are salient constructs to operationalize the concept of dentist-patient relationships (DPR). This study aimed to compare the similarity of both constructs with regard to factor structure and revise the scales for better psychometric properties. Data analysed in the study were collected in self-complete questionnaires from a random sample of 4011 adults living in South Australia. Trust and satisfaction were assessed using the Dentist Trust Scale and the Dental Care Satisfaction scale. Items in the scales were initially examined with a split-half sample in exploratory factor analysis and cluster analysis. Factor structures of different model designs were tested on the other half sample in confirmatory factor analysis. The final model was cross-validated on the first half sample for structural invariance. Exploratory factor analysis revealed a three-factor structure consisting of 'trust', 'satisfaction' and 'distrust/dissatisfaction' (60.2% of the variance explained; Cronbach's α = 0.94, 0.81, 0.73, respectively). Cluster analysis supported the factor solution with the same three major clusters except for a single-item independent branch of the 'cost' domain from the satisfaction scale. The final model was designed with two correlated but distinct factors, 'trust' and 'satisfaction', with the modification of one inter-item covariance and deleting the least associated item (GFI = 0.96, CFI = 0.98, RMSEA = 0.06). The stability of the final model was achieved through cross-validation (P = .143, ∆CFI < 0.001). Trust and satisfaction in dental care settings are unidimensionally different yet highly correlated factors concurrently. Demonstrating the discriminant and complementary functions of both constructs can justify the rationale to apply them together in further studies for DPR.


The visibility of organizational culture in a long-term care facility.
Our findings suggest that the perceptions of the staff members and families are not easily discernible by administrators or outsiders such as family members. This inability to judge important changes in the culture of an organization has important consequences for management. If administrators cannot tell which groups perform in the desired direction, they are not in a position to reward and reinforce desired behaviors. If cultural changes are necessary prerequisites to ensure organizational survival, how will an organization be able to create and maintain changes in the culture if there is no prevailing culture that is visible or public to others? More importantly, how will an organization be able to create a visible culture to others if management does not agree on what constitutes successful change? Nursing leaders who understand organizational culture concepts will be in a better position to influence the successful outcome of organizational change.


Microbiologic diagnosis of ventilator-associated pneumonia.
Specific etiologic diagnosis in ventilator-associated pneumonia is critical to optimal patient care, and a wide array of microbiologic procedures are available to aid in diagnosis. In bacterial infection, direct stains, particularly the Gram stain, provide rapid presumptive information, and cultures provide definitive identification. Specimen selection is critical; endotracheal or ordinary bronchoscopic aspirates provide nonspecific information, and quantitative analysis of protected specimen brushes or bronchoalveolar lavage provides more accuracy. Specialized procedures for other groups of organisms, such as Chlamydia, Legionella, mycobacteria, fungi, and viruses, also may be indicated in some cases.


Isolation and nucleotide sequence of cDNA clone for bovine pancreatic anionic trypsinogen. Structural identity within the trypsin family.
A cDNA clone encoding an anionic form of bovine trypsinogen was isolated from a pancreatic cDNA library. The corresponding 855-nucleotide mRNA contains a short 5' noncoding region of 8 nucleotides and a long 3' noncoding region of 56 nucleotides in addition to a poly(A) tail of at least 50 nucleotides. The deduced amino acid sequence for the anionic pretrypsinogen (247 residues) includes the N-terminal 15-amino-acid signal peptide followed by an 8-amino-acid activation peptide. The zymogen (232 residues) contains an additional C-terminal serine, compared with the amino acid sequence of bovine cationic trypsinogen. The identity between the anionic and cationic forms of bovine trypsinogen (65%) is lower than that existing between the anionic protein and other mammalian anionic trypsinogens (73-85%), suggesting that trypsin gene duplication in mammals occurred prior to the evolutionary events responsible for the species divergence. Bovine pancreatic anionic trypsin possesses all the key amino acids characteristic of the serine protease family.


Reducing Door-In to Door-Out Time for Patients Receiving a Mechanical Thrombectomy Using AutoLaunch Protocol.
Door-in to door-out (DIDO) time for large vessel occlusion (LVO) stroke is an emerging stroke performance measure. Initial presentation at a non-Comprehensive Stroke Center (CSC) requires a transfer process that minimizes delays. Our objective was to assess whether DIDO time for stroke patients was reduced after implementation of an AutoLaunch protocol for interfacility transfers. This was a pre-post analysis of an AutoLaunch protocol for all acute stroke patients transferred to a CSC for mechanical thrombectomy. The distribution of DIDO times between patients transferred via the AutoLaunch and traditional dispatch protocols were compared. We evaluated 92 interfacility transfers, with 22 utilizing the AutoLaunch protocol and 70 utilizing traditional dispatch. Among AutoLaunch transfers, the median DIDO time was 85 minutes (IQR: 71, 133), while the median DIDO time among the traditional transfers was 109 minutes (IQR, 84, 144) (p=0.044). Implementation of an AutoLaunch protocol for patients with suspected LVO was associated with a reduction in DIDO time to CSCs. Further studies should evaluate patient outcomes based on transfer strategies.


Radiation-induced epigenetic alterations after low and high LET irradiations.
Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise in the cell without initiating chromosomal instability.


Treatment of gastric outlet and duodenal obstructions with uncovered expandable metal stents.
To investigate and evaluate the technical feasibility and clinical effectiveness of fluoroscopically guided peroral uncovered expandable metal stent placement to treat gastric outlet and duodenal obstructions. Fifteen consecutive patients underwent peroral placement of Wallstent(TM) Enteral Endoprosthesis to treat gastric outlet and duodenal obstructions (14 malignant, 1 benign). All procedures were completed under fluoroscopic guidance without endoscopic assistance. Follow-up was completed until the patients died or were lost, and the clinical outcomes were analyzed. The technique success rate was 100%, and the oral intake was maintained in 12 of 14 patients varying from 7 d to 270 d. Two patients remained unable to resume oral intake, although their stents were proven to be patent with the barium study. One patient with acute necrotizing pancreatitis underwent enteral stenting to treat intestinal obstruction, and nausea and vomiting disappeared. Ten patients died during the follow-up period, and their mean oral intake time was 50 d. No procedure-related complications occurred. Stent migration to the gastric antrum occurred in one patient 1 year after the procedure, a tumor grew at the proximal end of the stent in another patient 38 d post-stent insertion. Fluoroscopically guided peroral metal stent implantation is a safe and effective method to treat malignant gastrointestinal obstructions, and complications can be ignored based on our short-term study. Indications for this procedure should be discreetly considered because a few patients may not benefit from gastrointestinal insertion, but some benign gastrointestinal obstructions can be treated using this procedure.


Parafilm as an efficient transport matrix for corneal scrapings.
Acanthamoeba spp. are free-living parasites increasingly implicated in causing Acanthamoeba keratitis (AK). AK is diagnosed by demonstration of parasites in corneal samples by direct microscopy, culture, and nucleic acid amplification. Most commonly, corneal scrapings are sent to the laboratory smeared between two glass slides. These scrapings are suitable for direct microscopy but less suitable for culture and polymerase chain reaction (PCR) which, in turn, are more sensitive for the diagnosis of AK. The aim of the study was to explore better alternatives for transporting corneal scrapings from the point-of-care eye center to the concerned laboratories. The study used small Parafilm (Bemis Company Inc., USA) squares (PSs) of 1 cm each prepared by cutting Parafilm using a surgical blade under sterile conditions. Each of the four different dilutions of Acanthamoeba suspension (15, 30, 60, and 120 cells) was used in this study. Each dilution was added onto the surface of 36 PSs and kept at room temperature for 24-h, 48-h, and 72-h incubation. The PSs for one particular time point and dilution were used for calcofluor white staining, its inoculation onto the surface of nonnutrient agar having a lawn of Escherichia coli, and Acanthamoeba-specific PCR amplification. In addition, two PSs inoculated with 30 cells and incubated for 24 h and 72 h were used for scanning electron microscopy (SEM). All three diagnostic techniques, i.e. microscopy, culture, and PCR, detected the presence of Acanthamoeba at all the tested concentrations and time points. However, the growth pattern on culture changed directly in proportion to increased incubation periods and increased concentration of inoculum. In addition, the adherence of Acanthamoeba to the Parafilm was confirmed by SEM; these results suggest the use of these PSs as a suitable matrix for the transport of corneal scrapings.


Health care seeking behavior for common childhood illnesses in Birendranagar municipality, Surkhet, Nepal: 2018.
Appropriate and prompt health care seeking by parents or caretakers can reduce morbidity and mortality among under-five year children. Although remarkable progress has been made in the reduction of under-five mortality, still the under-five mortality rate is high in Nepal. There are few studies on health care seeking behavior among caretakers in Nepal. Therefore, this study was conducted to determine the prevailing health care seeking behavior of caretakers on common childhood illness of under five year children and to identify the association of socio demographic, economic, illness related and health system related factors with health care seeking behavior in 2018. A community based descriptive cross-sectional study was conducted from September to November 2018. Data were collected using a pretested semi-structured interview schedule. Both descriptive and inferential statistics were used to present the data. Bivariate and multivariate logistic regression analysis was used to identify the factors associated with health care seeking behavior. A total of 387 caretakers participated in the study. Of these, 84.8% sought any type of care and 15.2% did nothing. Amongst those who sought care 42.4% visited the pharmacy directly, 25.3% visited the health facility. Amongst those who visited a health facility, 37.2% of caretakers sought prompt health care. Common danger sign stated by caretakers was fever in children (92.4%). Secondary education(AOR = 0.357, 95%CI = 0.142-0.896), involvement in service as an occupation(AOR = 3.533, 95%CI = 1.096-11.384), distance to reach nearest health facility(0.957, 95%CI = 0.923-0.993) and perceived severity of illness; moderate severity (7.612, 95%CI = 2.127-27.242), severe severity (AOR = 15.563, 95%CI = 3.495-69.308) were found to be significantly associated with health care seeking behavior. Strong policies and regulations should be formulated and implemented at Birendranagar municipality of Surkhet district to prevent direct purchase of medicines from pharmacies without any consultation. It is essential to conduct the health awareness program at community level on early recognition of danger signs and importance of consulting health facilities.


Spectroscopic study of the reaction mechanism of buspirone interaction with iodine and tetracyanoethylene reagents and its applications.
The reactions between the drug buspirone (busp) in its base form and iodine amphoteric reagent (n-donor and/or sigma-acceptor) and with tetracyanoethylene as a pi-acceptor reagent (TCNE) have been studied spectrophotometrically at different reactant concentrations, time intervals, temperatures, and with different solvents and wavelengths, with the aim of selecting the conditions that give the most suitable molar extinction coefficients. This study aims chiefly to throw light on the nature of these reactions and to select the most proper conditions for spectrophotometric application of these reagents to determine this biologically active drug used in treating different diseases. The reaction mechanism involves the formation of busp-I(2) outer and inner sphere complexes. The separated busp-I(2) solid product obtained was investigated using elemental analyses, FT-IR, thermal analyses (TA) and electron ionization mass spectrometry (EI-MS) and was found to be biologically active. The reaction mechanism of busp-TCNE involves the formation of a charge transfer (CT) complex. The analytical parameters of the proposed spectrophotometric procedures were calculated. These procedures were applied in the analysis of busp in its formulations as a drug used to treat psychiatric illnesses. The values of the Sandell sensitivity, standard deviation (SD), relative standard deviation (RSD) and recovery percentage show the high sensitivity of these procedures. This study also presents a promising new busp-I(2) drug derivative that can be used more efficiently for the same purposes as its parent. It gives a clear idea about the possible metabolites and metabolic pathways of busp and its derivative that may occur in vivo.


Parent and adolescent intentions to disclose and links to positive social behavior.
Children's disclosure to parents as a buffer against antisocial behavior, and its parenting antecedents, have been extensively studied in recent years. The influence of parents' own disclosure on children's disclosure and positive social behavior has received little attention, however. We assessed mothers' (n = 149), fathers' (n= 105), and 12- to 14-year-old early adolescents' (n = 127) intentions to disclose about distress-related events and rule transgressions, their reasons for disclosing, and links to positive social behavior (assessed by mothers' ratings of willing compliance and by teachers' [n = 114] ratings of prosocial behavior). Parents reported that they disclosed to teach lessons or to encourage their children to disclose, whereas adolescents said they disclosed for comfort and advice. Child intention to disclose about distressing events mediated between mother (but not father) intention to disclose about these same issues and children's willing compliance, but not prosocial behavior in the classroom. Parent and child disclosure about rule transgressions were not related.


Role of Melatonin, Galanin, and RFamide Neuropeptides QRFP26 and QRFP43 in the Neuroendocrine Control of Pancreatic β-Cell Function.
Glucose homeostasis is finely regulated by a number of hormones and peptides released mainly from the brain, gastrointestinal tract, and muscle, regulating pancreatic secretion through cellular receptors and their signal transduction cascades. The endocrine function of the pancreas is controlled by islets within the exocrine pancreatic tissue that release hormones like insulin, glucagon, somatostatin, pancreatic polypeptide, and ghrelin. Moreover, both exocrine and endocrine pancreatic functions are regulated by a variety of hormonal and neural mechanisms, such as ghrelin, glucagon-like peptide, glucose-dependent insulinotropic polypeptide, or the inhibitory peptide somatostatin. In this review, we describe the role of neurohormones that have been less characterized compared to others, on the regulation of insulin secretion. In particular, we will focus on melatonin, galanin, and RFamide neuropeptides QRFP26 and QRFP43, which display either insulinotropic or insulinostatic effects. In fact, in addition to other hormones, amino acids, cytokines, and a variety of proteins, brain-derived hormones are now considered as key regulators of glucose homeostasis, representing potential therapeutic targets for the treatment of diabetes and obesity.


Impact of Interface Type on Noninvasive Ventilation Efficacy in Patients With Neuromuscular Disease: A Randomized Cross-Over Trial.
Around 25% of patients with neuro-muscular diseases (NMD) are treated by home noninvasive ventilation (NIV) through an oronasal mask. However, there is growing evidence that nasal masks require lower NIV pressures and result in fewer residual obstructive events. We hypothesized that nasal masks would improve efficacy and reduce side effects compared to oronasal masks in this population. open label, cross-over, randomized, study in 2 tertiary care hospitals. Patients with NMD treated by home NIV were randomized for one-week periods to nasal and oronasal interfaces respectively (cross-over). At the end of each period, nocturnal polygraphy (monitoring mouth opening) under NIV, synchronized with transcutaneous partial pressure in CO2 (tcCO2) was performed. Data were collected from the NIV built-in software and NIV side-effects were collected. Intention-to-treat and per protocol analyses were performed. The primary outcome was mean nocturnal SpO2. The secondary outcomes were: percentage of sleep with SpO2<90%, oxygen desaturation index (ODI), mean tcCO2, mean duration of mouth opening during sleep, level of non-intentional leaks and side-effects. Thirty patients with NMD were included. There were no between-group differences for either the primary or secondary outcomes. Post hoc comparisons showed that changing between interfaces reduced NIV efficacy: mean nocturnal SpO2 (p=0.04), ODI (p=0.01), mean tcCO2 (p=0.048), side-effects (p=0.008). Nasal masks did not improve NIV efficacy or reduce side effects compared to oronasal masks in patients with NMD treated by home NIV. The efficacy of NIV is reduced during the transition to another interface, requiring close monitoring. Registration number: NCT03458507.


Immunohistological study in sarcoidosis: evaluation at different sites of disease activity.
Sarcoidosis is a multisystem disease characterized by enhanced immune responses at sites of involvement. For this reason, an immunohistological study using monoclonal antibodies against T-cell subpopulations was carried out in order to evaluate the topographic distribution of immunocompetent cells in tissue sections obtained from a variety of involved organs, such as parenchymal lung, lymph nodes, eyes, skin, and liver. Biopsy specimens were also stained for detection of immunoglobulins, complement, and fibrinogen deposits. The data demonstrate a redistribution of T cells from the blood to all the sites of disease activity where they account for the large majority of infiltrating cells, both in the early lesions (merely a lymphocytic infiltrate) and in well-organized granulomas. Moreover, these cells express a helper-related phenotype, as demonstrated by the high Leu-3/Leu-2 ratios, at sites of involvement with respect to the blood (blood, 1.8/1; transbronchial lung biopsies, 10.5/1; lymph nodes, 19/1; skin, 28/1; liver, 22/1; eye, 14/1). In line with this helper infiltration is the presence of plasma cells and immunoglobulin deposits, suggesting a local hyperreactivity of the B-cell immune system. Both the hypergammaglobulinemia and the T lymphopenia usually observed in the blood of sarcoid patients could be explained by these observations. Comparative analysis of immunohistological data and bronchoalveolar lavage (BAL) findings provides further evidence that BAL cellularity reflects the changes already occurring in lung histology. The studies emphasize the importance that immunological phenomena play in the pathogenesis of sarcoidosis and provide new insights into the mechanisms leading to the formation and maintenance of the sarcoid granuloma.


Effect of seasonal malaria chemoprevention on the acquisition of antibodies to Plasmodium falciparum antigens in Ouelessebougou, Mali.
Seasonal malaria chemoprevention (SMC) is a new strategy to reduce malaria burden in young children in Sahelian countries. It consists of the administration of full treatment courses of sulfadoxine-pyrimethamine plus amodiaquine to children at monthly intervals during the malaria season. However, it is not clear if there is a cumulative effect of SMC over time on acquisition of antibodies to malaria antigens. A cross-sectional serosurvey was carried out 1 month after the last dose of SMC in 2016. Children aged 3-4 years were randomly selected from areas where SMC was given for 1, 2 or 3 years during the malaria season. Children in the areas where SMC had been implemented for 1 year but who failed to receive SMC were used as comparison group. Antibody extracted from dry blood spots was used to measure IgG levels to CSP, MSP-142 and AMA1. The prevalence of antibodies to AMA-1 were high and similar in children who received SMC for 1, 2 or 3 years and also when compared to those who never received SMC (96.3 vs 97.5%, adjusted OR = 0.99, 95% CI 0.33-2.97, p = 0.99). The prevalence of antibodies to MSP-142 and to CSP were similar in children that received SMC for 1, 2 or 3 years, but were lower in these children compared to those who did not receive SMC (87.1 vs 91.2%, adjusted OR = 0.55, 95% CI 0.29-1.01, p = 0.05 for MSP-142; 79.8 vs 89.2%, adjusted OR = 0.52, 95% CI 0.30-0.90, p = 0.019 for CSP). SMC reduced seropositivity to MSP-142 and CSP, but the duration of SMC did not further reduce seropositivity. Exposure to SMC did not reduce the seropositivity to AMA1.


Ebselen attenuates cyclophosphamide-induced oxidative stress and DNA damage in mice.
The role of selenium, a trace element in the human diet, has been extensively studied against cancer, immunity and infectious/inflammatory diseases. The purpose of the present study was to investigate the beneficial effect of ebselen, an organo-selenium compound, against cyclophosphamide-induced oxidative stress and DNA damage in mice. Malondialdehyde and total glutathione were estimated in the liver to detect the oxidative stress induced by cyclophosphamide. Standard and modified comet assays (the latter incorporated lesion-specific enzymes, formamidopyrimidine-DNA glycosylase and endonuclease-III) were used to detect the normal and oxidative stress-induced DNA damage by cyclophosphamide in the mouse bone marrow and the peripheral blood lymphocytes. In addition, a micronucleus assay capable of detecting DNA damage was also carried out in the mouse bone marrow and the peripheral blood reticulocytes induced by cyclophosphamide. The results confirm that pre-treatment with ebselen (2.5, 5 and 10 mg/kg) for 5 consecutive days decreased the oxidative stress induced by cyclophosphamide (100 mg/kg) based on the restoration in concentration of malondialdehyde and glutathione in the liver and decreased DNA damage and micronuclei count in the bone marrow and the peripheral blood. It is concluded that pre-treatment with ebselen attenuates cyclophosphamide-induced oxidative stress and the resultant DNA damage in mice.


Influence of the Heat Transfer Process on the Electrical and Mechanical Properties of Flexible Silver Conductors on Textiles.
With the increase in the popularity of wearable and integrated electronics, a proper way to manufacture electronics on textiles is needed. This study aims to analyze the effect of different parameters of the heat transfer process on the electrical and mechanical properties of flexible electronics made on textiles, presenting it as a viable method of producing such electronics. Wires made from different composites based on silver microparticles and an insulating layer were screen-printed on a release film. Then, they were transferred onto a polyester cloth using heat transfer with different parameters. Research showed that different heat transfer parameters could influence the electrical properties of screen-printed wires, changing their resistance between -15% and +150%, making it imperative to adjust those properties depending on the materials used. Changes in the settings of heat transfer also influence mechanical properties, increasing adhesion between layers at higher temperatures. This study shows the importance of tailoring heat transfer properties and the differences that these properties make.


Interference of endogenous B endorphin with opiate binding in the anterior pituitary.
Opiates have been shown to affect prolactin secretion directly at the pituitary level. However, opiate binding sites have not been characterized on anterior pituitary tissue. In the present work we show that a soluble factor present in anterior pituitary membrane preparation inhibit opiate binding on striatal membranes. The high concentrations of B-endorphin like immunoreactivity recovered from the supernatant of pituitary membrane preparations seem to account for this effect on striatal binding and to be responsible for a partial masking of pituitary opiate receptors. We thus attempted to improve membrane fractionation procedure in order to decrease B-endorphin contamination and thus to increase binding of opiate ligands on pituitary membranes. 3-H Etorphine binds to pituitary membranes with a constant of association (kon) of 20.8 10(6) M-1 min-1 and a constant of dissociation (hoff) of 33 min-1. Saturation experiments with 3-H Etorphine and 3-H ethylketocyclazocine indicate the presence of a single population of specific binding sites (KD) value of 12.2 +/- 3.9 nM a maximal binding capacity of 55.9 +/- 10.7 fm/mg protein for 3-H Etorphine binding). These results demonstrate the presence of opiate binding sites in the anterior pituitary. However the difficulty of the membrane preparation and the low density of binding sites did not allow a complete pharmacological characterization of these sites.


Short Communication: Natural killer cells and expression of KIR receptors in chronic HIV type 1-infected patients after different strategies of structured therapy interruption.
Few data evaluating the NK cell profile during structured therapy interruption (STI) in chronic HIV-1 infection are available. Changes in NK cell percentages and KIR and NKG2A receptors were analyzed at baseline and after 2 years of follow-up in 121 patients on ART with CD4(+) >450 cells/ml and VL <200 copies/ml randomized in three arms according to the criteria employed to resume ART during STI: virological arm (VA n = 47, VL >30,000 copies/ml or CD4 <350 cells/ml), immunological arm (IA n = 37, CD4< 350 cells/ml), and a control arm (n = 37) in which ART was maintained. After 2 years of follow-up, a decrease in CD3(-)CD56(+) CD16(+) cell percentages in VA and IA patients, but not in CA patients, was observed. Those patients with higher decrease in CD3(-)CD56(+)CD16(+) cells had a higher decrease in CD4(+) cells (r = 0.35, p = 0.001) and higher increase in PVL (r = -0.26, p = 0.02). KIR and NKG2A receptor expression tended to increase in CA and decreased in the other two arms (more in IA than in VA). Patients who displayed a greater decrease in CD4(+) T cells and a greater rise in PVL after 2 years of follow-up had a significantly higher decrease in KIR and NKG2A receptors expressed in CD3(-)CD56(+) cells. Patients who presented the lowest levels of total NK cells and KIR and NKG2A receptor expression after STI showed the poorest virology or immunology outcomes. This finding suggests that STI could decrease the number of NK subsets, which is related to the worst clinical development in these patients.


Environmental stress promotes the persistence of facultative bacterial symbionts in amoebae.
Amoebae are one major group of protists that are widely found in natural and engineered environments. They are a significant threat to human health not only because many of them are pathogenic but also due to their unique role as an environmental shelter for pathogens. However, one unsolved issue in the amoeba-bacteria relationship is why so many bacteria live within amoeba hosts while they can also live independently in the environments. By using a facultative amoeba- Paraburkholderia bacteria system, this study shows that facultative bacteria have higher survival rates within amoebae under various environmental stressors. In addition, bacteria survive longer within the amoeba spore than in free living. This study demonstrates that environmental stress can promote the persistence of facultative bacterial symbionts in amoebae. Furthermore, environmental stress may potentially select and produce more amoeba-resisting bacteria, which may increase the biosafety risk related to amoebae and their intracellular bacteria.


Hypothalamic fatty acid sensing in Senegalese sole (Solea senegalensis): response to long-chain saturated, monounsaturated, and polyunsaturated (n-3) fatty acids.
We assessed the presence of fatty acid (FA)-sensing mechanisms in hypothalamus of Senegalese sole (Solea senegalensis) and investigated their sensitivity to FA chain length and/or level of unsaturation. Stearate (SA, saturated FA), oleate (OA, monounsaturated FA of the same chain length), α-linolenate [ALA, a n-3 polyunsaturated fatty acid (PUFA) of the same chain length], and eicosapentanoate (EPA, a n-3 PUFA of a larger chain length) were injected intraperitoneally. Parameters related to FA sensing and neuropeptide expression in the hypothalamus were assessed after 3 h and changes in accumulated food intake after 4, 24, and 48 h. Three FA sensing systems characterized in rainbow trout were also found in Senegalese sole and were activated by OA in a way similar to that previously characterized in rainbow trout and mammals. These hypothalamic FA sensing systems were also activated by ALA, differing from mammals, where n-3 PUFAs do not seem to activate FA sensors. This might suggest additional roles and highlights the importance of n-3 PUFA in fish diets, especially in marine species. The activation of FA sensing seems to be partially dependent on acyl chain length and degree of saturation, as no major changes were observed after treating fish with SA or EPA. The activation of FA sensing systems by OA and ALA, but not SA or EPA, is further reflected in the expression of hypothalamic neuropeptides involved in the control of food intake. Both OA and ALA enhanced anorexigenic capacity compatible with the activation of FA sensing systems.


Alkali metal ion complexes of functionalised calixarenes--competition between pendent arm and anion bonding to sodium.
Determination of the crystal structure of the acetonitrile inclusate of the complex formed between sodium trifluoromethanesulfonate (triflate, CF3SO3-) and the narrow-rim functionalised calix[4]arene, 5,11,17,23-tetra-tert-butyl-25,27-di(phenylmethoxy)-26,28-di(2'-methoxyethoxy)calix[4]arene, has shown, somewhat unexpectedly, that the diether pendent arms do not chelate the sodium cation, although coordination of all four phenolic oxygen atoms does draw the calixarene into a nearly symmetrical cone form, consistent with conclusions drawn earlier from solution 1H NMR data. Crystals of C64H80O6.NaO3S.CF3.CH3CN obtained from acetonitrile solvent are monoclinic, C2/c, a structure determination at 'low' temperature (153 K) resolving several difficulties encountered in earlier attempts to analyse data acquired at approximately 295 K, and indicative of an interesting temperature dependence of substituent and anion orientations.


The Influence of Variability Sources on SRAM Stability in 90 Å Non-Rectangular Bulk FinFET SRAM Cell.
The temperature dependency of influence of variability sources on SRAM stability were simulated and analyzed in 90 Å non-rectangular Bulk FinFET SRAM cell. RDF is the most dominant variability source. In addition, it is also shown that standard deviation of read static noise margin (σ(RSNM)) by WFV and RDF decreases with increasing temperature, whereas σ-(RSNM) by LER increases with increasing temperature. Finally, the analyses on the simulation results mentioned above were performed.


Photoisomerization and photodissociation of aniline and 4-methylpyridine.
Photoisomerization and photodissociation of aniline and 4-methylpyridine at 193 nm were studied separately using multimass ion imaging techniques. Photofragment translational energy distributions and dissociation rates were measured. Our results demonstrate that more than 23% of the ground electronic state aniline and 10% of 4-methylpyridine produced from the excitation by 193 nm photons after internal conversion isomerize to seven-membered ring isomers, followed by the H atom migration in the seven-membered ring, and then rearomatize to both methylpyridine and aniline prior to dissociation. The significance of this isomerization is that the carbon, nitrogen, and hydrogen atoms belonging to the alkyl or amino groups are involved in the exchange with those atoms in the aromatic ring during the isomerization.


A Review of Human Performance Models for Prediction of Driver Behavior and Interactions With In-Vehicle Technology.
This study investigated the use of human performance modeling (HPM) approach for prediction of driver behavior and interactions with in-vehicle technology. HPM has been applied in numerous human factors domains such as surface transportation as it can quantify and predict human performance; however, there has been no integrated literature review for predicting driver behavior and interactions with in-vehicle technology in terms of the characteristics of methods used and variables explored. A systematic literature review was conducted using Compendex, Web of Science, and Google Scholar. As a result, 100 studies met the inclusion criteria and were reviewed by the authors. Model characteristics and variables were summarized to identify the research gaps and to provide a lookup table to select an appropriate method. The findings provided information on how to select an appropriate HPM based on a combination of independent and dependent variables. The review also summarized the characteristics, limitations, applications, modeling tools, and theoretical bases of the major HPMs. The study provided a summary of state-of-the-art on the use of HPM to model driver behavior and use of in-vehicle technology. We provided a table that can assist researchers to find an appropriate modeling approach based on the study independent and dependent variables. The findings of this study can facilitate the use of HPM in surface transportation and reduce the learning time for researchers especially those with limited modeling background.


[Comparison of chemical constituents in different parts of Gardenia jasminoides based on multiple wavelength HPLC-DAD].
Seven compounds(deacetylasperulasidic acid methyl ester, gardenoside, chlorogenic acid, geniposide, crocin-Ⅰ, crocin-Ⅱ, chikusetsu saponin Ⅳa)were determined simultaneously by multiple wavelength HPLC with diode array detector(DAD) in different parts of Gardenia jasminoides. The results showed that these components in different parts of G. jasminoides had a different distribution, and there was a large difference in content of each component. Geniposide was mainly distributed in fruits and leaves; chikusetsu saponin Ⅳa was mainly distributed in roots and stems; crocus glycosides existed mainly in fruits; chlorogenic acid had a higher distribution in leaves and stems; gardenoside had a higher distribution in leaves and roots, while ceacetylasperulasidic acid methyl ester had a higher distribution in roots and stems. Based on the analysis of the chemical composition and content difference in different parts of G. jasminoides, the basis for the comprehensive utilization and quality evaluation of resources of G. jasminoides was provided.


Relationship Between Types of Exercise and Quality of Life in a Korean Metabolic Syndrome Population: A Cross-Sectional Study.
Metabolic syndrome (MetS) significantly correlates with exercise. MetS also has an independent and inverse correlation to quality of life (QoL). However, few studies have examined the association between exercise and QoL in people with MetS. The aim of this study was to ascertain the relationship between exercise and QoL in a MetS population. This was a cross-sectional study using public data from the Sixth Korean National Health and Nutrition Examination Survey in 2014 (n = 7550). MetS was defined on the basis of the revised National Cholesterol Education Program criteria. Demographic factors, three types of exercise (resistance, flexibility, walking), five subsets of EuroQoL (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), and QoL scores (EQ-VAS), were investigated. Independent associations of each exercise on five subsets of QoL were determined using odds ratios (OR) adjusted for four demographic factors (age group, sex, weight change, and area of residence) using multivariate logistic regression analysis. Prevalence of MetS was 26.4% and the ratio of subjects performing resistance, flexibility, or walking exercise was 17.7%, 45.8%, and 71.5% among this population, respectively. EQ-VAS of exercisers was significantly higher than that of non-exercisers in resistance, flexibility, and walking exercise. Although resistance and flexibility exercise did not correlate with any subsets of QoL, mobility and self-care were significantly associated with walking exercise (OR = 0.635, 95% CI = 0.439-0.919 and OR = 0.577, 95% CI = 0.348-0.958, respectively). All exercisers showed higher QoL scores than non-exercisers. Among QoL subsets, mobility and self-care were independently associated with walking exercise in the MetS population. Regular walking exercise was important to higher QoL in those with MetS. This is the first clinical report to indicate that QoL could be independently influenced by walking exercise.


A CRISPR Resource for Individual, Combinatorial, or Multiplexed Gene Knockout.
We have combined a machine-learning approach with other strategies to optimize knockout efficiency with the CRISPR/Cas9 system. In addition, we have developed a multiplexed sgRNA expression strategy that promotes the functional ablation of single genes and allows for combinatorial targeting. These strategies have been combined to design and construct a genome-wide, sequence-verified, arrayed CRISPR library. This resource allows single-target or combinatorial genetic screens to be carried out at scale in a multiplexed or arrayed format. By conducting parallel loss-of-function screens, we compare our approach to existing sgRNA design and expression strategies.


[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group].
We conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.


Hepcidin level predicts hemoglobin concentration in individuals undergoing repeated phlebotomy.
Dietary iron absorption is regulated by hepcidin, an iron regulatory protein produced by the liver. Hepcidin production is regulated by iron stores, erythropoiesis and inflammation, but its physiology when repeated blood loss occurs has not been characterized. Hepcidin was assayed in plasma samples obtained from 114 first-time/reactivated (no blood donations in preceding 2 years) female donors and 34 frequent (≥3 red blood cell donations in preceding 12 months) male donors as they were phlebotomized ≥4 times over 18-24 months. Hepcidin levels were compared to ferritin and hemoglobin levels using multivariable repeated measures regression models. Hepcidin, ferritin and hemoglobin levels declined with increasing frequency of donation in the first-time/reactivated females. Hepcidin and ferritin levels correlated well with each other (Spearman's correlation of 0.74), but on average hepcidin varied more between donations for a given donor relative to ferritin. In a multivariable repeated measures regression model the predicted inter-donation decline in hemoglobin varied as a function of hepcidin and ferritin; hemoglobin was 0.51 g/dL lower for subjects with low (>45.7 ng/mL) or decreasing hepcidin and low ferritin (>26 ng/mL), and was essentially zero for other subjects including those with high (>45.7 ng/mL) or increasing hepcidin and low ferritin (>26 ng/mL) levels (P<0.001). In conclusion, hepcidin levels change rapidly in response to dietary iron needed for erythropoiesis. The dynamic regulation of hepcidin in the presence of a low levels of ferritin suggests that plasma hepcidin concentration may provide clinically useful information about an individual's iron status (and hence capacity to tolerate repeated blood donations) beyond that of ferritin alone. Clinicaltrials.gov identifier: NCT00097006.


Recent advances in medical dermatology.
Collectively, new developments in the field of medical dermatology will ultimately lead to improved patient care. We review several new findings in the dermatologic literature including the following: new questions regarding the malignant potential of anti-tumor necrosis factor agents, which are widely used for the treatment of moderate to severe psoriasis as well as psoriatic arthritis; anti-interleulin-12, a promising anticytokine for the treatment of psoriasis; diagnostic advances in the detection of latent Mycobacterium tuberculosis; advances in the primary prevention of human papillomavirus and herpes zoster; and new therapeutic options with existing medications for neuropathic pain and pruritus.


Healthcare professional and manager perceptions on drivers, benefits, and challenges of telemedicine: results from a cross-sectional survey in the Italian NHS.
The Covid-19 pandemic provided new challenges and opportunities for patients and healthcare providers while accelerating the trend of digital healthcare transformation. This study explores the perspectives of healthcare professionals and managers on (i) drivers to the implementation of telemedicine services and (ii) perceived benefits and challenges related to the use of telemedicine across the Italian National Health Service. An online cross-sectional survey was distributed to professionals working within 308 healthcare organisations in different Italian regions. Quantitative and qualitative data were collected through a self-administered questionnaire (June-September 2021). Responses were analysed using summary statistics and thematic analysis. Key factors driving the adoption of telemedicine have been grouped into (i) organisational drivers (reduce the virus spread-80%; enhance care quality and efficiency-61%), (ii) technological drivers (ease of use-82%; efficacy and reliability-64%; compliance with data governance regulations-64%) and (iii) regulatory drivers (regulations' semplification-84%). Nearly all respondents perceive telemedicine as useful in improving patient care (96%). The main benefits reported by respondents are shorter waiting lists, reduced Emergency Department attendance, decreased patient and clinician travel, and more frequent patient-doctor interactions. However, only 7% of respondents believe that telemedicine services are more effective than traditional care and 66% of the healthcare professionals believe that telemedicine can't completely substitute in-person visits due to challenges with physical examination and patient-doctor relationships. Other reported challenges include poor quality and interoperability of telemedicine platforms and scarce integration of telemedicine with traditional care services. Moreover, healthcare professionals believe that some groups of patients experience difficulties in accessing and using the technologies due to socio-cultural factors, technological and linguistic challenges and the absence of caregivers. Respondents believe that telemedicine can be useful to complement and augment traditional care. However, many challenges still need to be overcome to fully consider telemedicine a standard of care. Strategies that could help address these challenges include additional regulations on data governance and reimbursements, evidence-based guidelines for the use of telemedicine, greater integration of tools and processes, patient-centred training for clinicians, patient-facing material to assist patients in navigating virtual sessions, different language options, and greater involvement of caregivers in the care process.


Lyophilic but Nonwettable Organosilane-Polymerized Carbon Dots Inverse Opals with Closed-Cell Structure.
This paper presents a unique lyophilic but nonwettable property of organosilane-polymerized carbon dots inverse opals photonic crystals (SiCDPCs) with closed-cell structure. Little stopband shift was observed for the SiCDPCs when being immersed into the solvents such as isopropanol, olive oil, DMSO, hexane, silicone oil, ethanediol, etc. but keeping lyophilic property. This could be attributed to the combined effect of closed-cell structure and the unique chemical composition of SiCDPCs. Furthermore, more than 30 kinds of organic solvents had been investigated, it was found that there were two kinds of factors that affected the stopband shift upon solvent's immersing; one was the polarity of solvent, and the other one was the viscosity of solvent. That is, mainly nonpolar or high viscosity solvents showed lyophilic but nonwettable property. The distinct solvent-responsive behaviors of the SiCDPCs toward polar/nonpolar solvents had been utilized for the fabrication of 2D/3D pattern. Additionally, the as-prepared SiCDPCs showed improved optical limiting property, excellent low-temperature resistance, and abrasion tolerant property. It is of great importance for the development of multifunctional novel coating materials and creation of novel optical devices.


Selection of new HSF1 and HSF2 DNA-binding sites reveals difference in trimer cooperativity.
Multiple heat shock transcription factors (HSFs) have been discovered in several higher eukaryotes, raising questions about their respective functions in the cellular stress response. Previously, we had demonstrated that the two mouse HSFs (mHSF1 and mHSF2) interacted differently with the HSP70 heat shock element (HSE). To further address the issues of cooperativity and the interaction of multiple HSFs with the HSE, we selected new mHSF1 and mHSF2 DNA-binding sites through protein binding and PCR amplification. The selected sequences, isolated from a random population, were composed primarily of alternating inverted arrays of the pentameric consensus 5'-nGAAn-3', and the nucleotides flanking the core GAA motif were nonrandom. The average number of pentamers selected in each binding site was four to five for mHSF1 and two to three for mHSF2, suggesting differences in the potential for cooperative interactions between adjacent trimers. Our comparison of mHSF1 and mHSF2 binding to selected sequences further substantiated these differences in cooperativity as mHSF1, unlike mHSF2, was able to bind to extended HSE sequences, confirming previous observations on the HSP70 HSE. Certain selected sequences that exhibited preferential binding of mHSF1 or mHSF2 were mutagenized, and these studies demonstrated that the affinity of an HSE for a particular HSF and the extent of HSF interaction could be altered by single base substitutions. The domain of mHSF1 utilized for cooperative interactions was transferable, as chimeric mHSF1/mHSF2 proteins demonstrated that sequences within or adjacent to the mHSF1 DNA-binding domain were responsible. We have demonstrated that HSEs can have a greater affinity for a specific HSF and that in mice, mHSF1 utilizes a higher degree of cooperativity in DNA binding. This suggests two ways in which cells have developed to regulate the activity of closely related transcription factors: developing the ability to fully occupy the target binding site and alteration of the target site to favor interaction with a specific factor.


Aurora Kinase A Promotes AR Degradation via the E3 Ligase CHIP.
Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer. Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation. Aurora A kinase is activated by 2-ME in the S-phase as well as during mitosis, and phosphorylates CHIP at S273. Prostate cancer cells expressing an S273A mutant of CHIP have attenuated AR degradation upon 2-ME treatment compared with cells expressing wild-type CHIP, supporting the idea that CHIP phosphorylation by Aurora A activates its E3 ligase activity for the AR. These results reveal a novel 2-ME→Aurora A→CHIP→AR pathway that promotes AR degradation via the proteasome that may offer novel therapeutic opportunities for prostate cancer. Mol Cancer Res; 15(8); 1063-72. ©2017 AACR.


Danshensu, a major water-soluble component of Salvia miltiorrhiza, enhances the radioresponse for Lewis Lung Carcinoma xenografts in mice.
The molecule 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid (danshensu), a herbal preparation used in traditional Chinese medicine, has been found to possess potential antitumor and anti-angiogenesis effects. The aim of the present study was to investigate the efficacy of the combination of radiation therapy (RT) with danshensu in the treatment of Lewis lung carcinoma (LLC) xenografts, whilst exploring and evaluating the mechanism involved. In total, 8-week old female C57BL/6J mice were randomly assigned into 3 groups to receive: RT, RT + cisplatin and RT + danshensu, respectively, when LLC reached 100-150 mm3. Each group was divided into 7 subgroups according to the different irradiation doses that were administered. Tumor growth curves were created and the sensitization enhancement ratios of the drugs were calculated. The experiment was then repeated, and the 4 groups of tumor-bearing mice were treated with natural saline, danshensu, RT + danshensu and RT, respectively. The mice were sacrificed on day 7, and tumor tissue and blood were collected to determine microvessel density, the expression of proangiogenic factors, and the levels of blood thromboxane B2 and 6-keto-prostaglandin-F1α. Tumor hypoxia was also detected using in vivo fluorescence imaging. With respect to LLC xenografts, treatment with danshensu + RT significantly enhanced the effects of tumor growth inhibition (P<0.05). Furthermore, tumor vasculature was remodeled and microcirculation was improved, which significantly reduced tumor hypoxia (P<0.05). The present study demonstrated that danshensu significantly enhanced the radioresponse of LLC xenografts in mice. The mechanism involved may be associated with the alleviation of tumor cell hypoxia following treatment with danshensu + RT, caused by the improvement of tumor microcirculation and the remodeling of tumor vasculature.


Digital transformation and total factor productivity: Empirical evidence from China.
Digital transformation plays a crucial role in improving the quality development of companies in this era of digital economy with ever-changing technologies. This paper empirically investigates the impact of corporate digital transformation on total factor productivity and the mechanism of action, using A-share listed companies in Shanghai and Shenzhen from 2011-2021 as the research sample, and found that the digital transformation of companies significantly improves total factor productivity, with the plausibility of the findings being verified by a series of robustness tests. Based on the heterogeneity study, it is found that such effect is stronger for private companies, non-high-tech companies, and companies with a high degree of industry competition. The mechanism test indicates that digital transformation facilitates total factor productivity through four ways: strengthening company technological innovation, reducing operational costs, increasing resource allocation efficiency, and improving human capital structure. The findings of this paper support a better understanding of the micro effects of digital transformation and provide empirical evidence for policy formulation and adjustment.


Tangible Needs and External Stressors Faced by Chinese American Families with a Member Having Schizophrenia.
This article examines the tangible needs and external stressors experienced by Chinese American families with a member living with schizophrenia, in the context of a six-month pilot study of family psychoeducation. Therapists' notes from 117 family and group sessions were analyzed. The families expressed concerns regarding housing, finance, work, study, and the shortage of bilingual psychosocial services. Interacting with government offices and social services agencies caused anxiety and frustration, partly due to the high stakes involved given their low socioeconomic status, and partly due to the bureaucracy. As immigrants, study participants had needs for language translation, knowledge about resources, and advocacy by case managers. This study also highlights the importance of interventions beyond the micro individual level to the mezzo and macro levels, where changes in organizations and policies are necessary.


Increased levels of serum angiotensin-converting enzyme activity in hyperthyroidism.
Serum angiotensin-converting enzyme activity was significantly elevated in 21 patients with hyperthyroidism (65 +/- 18 U/mL) as compared with levels in healthy control subjects (30 +/- 9 U/mL). In eight patients treated with thionamide drugs, the enzyme activities decreased to a normal range as thyroid hormone concentrations returned to euthyroid levels. When two patients became hyperthyroid due to an insufficient maintenance dose of antithyroid drugs, the increase in the serum thyroid hormone concentration was followed by the re-elevation of serum angiotensin-converting enzyme levels with a time lag of about 2 weeks. Levels of this enzyme are increased reflecting the elevated serum thyroid hormone levels in hyperthyroidism. The hyperthyroid state should be considered when serum angiotensin-converting enzyme levels are high.


Max-Margin Deep Diverse Latent Dirichlet Allocation With Continual Learning.
Deep probabilistic aspect models are widely utilized in document analysis to extract the semantic information and obtain descriptive topics. However, there are two problems that may affect their applications. One is that common words shared among all documents with low representational meaning may reduce the representation ability of learned topics. The other is introducing supervision information to hierarchical topic models to fully utilize the side information of documents that is difficult. To address these problems, in this article, we first propose deep diverse latent Dirichlet allocation (DDLDA), a deep hierarchical topic model that can yield more meaningful semantic topics with less common and meaningless words by introducing shared topics. Moreover, we develop a variational inference network for DDLDA, which helps us to further generalize DDLDA to a supervised deep topic model called max-margin DDLDA (mmDDLDA) by employing max-margin principle as the classification criterion. Compared to DDLDA, mmDDLDA can discover more discriminative topical representations. In addition, a continual hybrid method with stochastic-gradient MCMC and variational inference is put forward for deep latent Dirichlet allocation (DLDA)-based models to make them more practical in real-world applications. The experimental results demonstrate that DDLDA and mmDDLDA are more efficient than existing unsupervised and supervised topic models in discovering highly discriminative topic representations and achieving higher classification accuracy. Meanwhile, DLDA and our proposed models trained by the proposed continual learning approach cannot only show good performance on preventing catastrophic forgetting but also fit the evolving new tasks well.


[Recurrent pain in children and parents--no factual evidence of familial pain clustering].
Recurrent pain in children is a universal phenomenon, which occurs in about 50 percent of all children. The most prevalent pain areas are the stomach, head, back and neck/shoulders. A somatic cause of the symptoms is seldom found, but the pain is often related to other discomforts, problems or lack of family functioning. There has been a common belief that "pain runs in families". In our investigation of 358 mother-father-child trios, where the members reported on their own symptoms, we found little support for this hypothesis. There is a need for further research on these problems, where the study design and measure instruments should be carefully validated.


Proof of cancer causation and expert evidence: bringing science to the law and the law to science.
This article discusses the medico-scientific and the legal views of cancer causation and how these two approaches impact on expert evidence. Cancer cause lends itself well to an exploration of the critical issues which surround its proof and the role of expert evidence in this proof. The article does not seek to identify or to resolve all the controversies or inconsistencies in the area. Rather, it sets up a basic framework for the general presentation and testing of expert medico-scientific evidence in litigation related to cancer causation. Specifically, it seeks to identify the technical questions of law and medical science regarding which medico-scientific disciplines can be relevant to proving cancer causation, and who the relevant expert witnesses to achieve this task would be. Emerging areas of cancer causation are then examined in light of this framework.


[Hyperechogenicity of the renal medulla in children: clinico-echographic correlations].
Increased renal medullary echogenicity by renal ultrasound associated with hypercalciuria and nephrocalcinosis is often present in childhood. 17 children, 9 boys and 8 girls, aged from 8 months to 10 years were classified into three groups based on ultrasound findings according to Patriquin and Robitaille: type A faint hyperechogenic rim around the sides and tip of the medullary pyramid; type B more intense echogenic rim of the pyramids; type C intense echoes throughout the pyramid. Clinic-echographic correlations showed a pattern C in 4 children with distal renal tubular acidosis and in an infant treated with furosemide; pattern B in 3 patients having different types of tubulopathy associated with hypercalciuria; pattern A in 6 children with congenital tubulopathy and in 3 children treated with vitamin D. Abdominal X-rays detected medullary calcinosis in 2 (11.7%) of total 17 patients. Ultrasonography appears to be an important tool in early diagnosis of renal medullary nephrocalcinosis.


A comprehensive review of neuroanatomy of the prostate.
Although oncologic efficacy is the primary goal of radical prostatectomy, preserving potency and continence is also important, given the indolent clinical course of most prostate cancers. In order to preserve and recover postoperative potency and continence after radical prostatectomy, a detailed understanding of the pelvic anatomy is necessary to recognize the optimal nerve-sparing plane and to minimize injury to the neurovascular bundles. Therefore, we reviewed the most recent findings from neuroanatomic studies of the prostate and adjacent tissues, some of which are contrary to the established consensus on pelvic anatomy. We also described the functional outcomes of radical prostatectomies following improved anatomical understanding and development of surgical techniques for preserving the neurovascular bundles.


Development of Dietary Patterns Spanning Infancy and Toddlerhood: Relation to Body Size, Composition and Metabolic Risk Markers at Three Years.
Little is known about the development of dietary patterns during toddlerhood and the relation to growth and health. The study objective was to characterise the development of dietary patterns from 9-36 mo of age and investigate the association to body size, body composition and metabolic risk markers at 36 mo. Food records were filled out at 9, 18 and 36 mo of age (n = 229). Dietary patterns were identified by principal component analysis (PCA). Three dietary patterns were identified: Transition Food, Healthy Food and Traditional Food. The course of development in dietary patterns from 9-36 mo indicated tracking for a relatively large group of participants in the three patterns. Transition Food and Healthy Food were associated with some of the investigated outcomes. Children with lower adherence to the Transition Food pattern than average at 18 and 36 mo irrespectively of intake at 9 mo had higher BMI z-scores at 36 mo. Similar trend was identified for higher fat mass indices. Children with lower adherence to the Healthy Food pattern than average at all three ages compared to children with higher adherence to the Healthy Food pattern at the first two registrations, 9 and 18 mo had higher total cholesterol and LDL. Hence, this could represent undesirable development of dietary patterns in toddlers. In conclusion, development of dietary patterns can be exploratory characterised by PCA and related to potential cardiovascular risk markers in toddlers even within a relatively homogeneous population with a high socioeconomic status. The tracking of dietary patterns from 9 mo of age indicates a need for early and sustained promotion of healthy diets.


Rapid detection of all known ebolavirus species by reverse transcription-loop-mediated isothermal amplification (RT-LAMP).
Ebola virus disease (EVD), a highly virulent infectious disease caused by ebolaviruses, has a fatality rate of 25-90%. Without a licensed chemotherapeutic agent or vaccine for the treatment and prevention of EVD, control of outbreaks requires accurate and rapid diagnosis of cases. In this study, five sets of six oligonucleotide primers targeting the nucleoprotein gene were designed for specific identification of each of the five ebolavirus species using reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay. The detection limits of the ebolavirus species-specific primer sets were evaluated using in vitro transcribed RNAs. The detection limit of species-specific RT-LAMP assays for Zaire ebolavirus, Sudan ebolavirus, Taï Forest ebolavirus, and Bundibugyo ebolavirus was 256 copies/reaction, while the detection limit for Reston ebolavirus was 64 copies/reaction, and the detection time for each of the RT-LAMP assays was 13.3±3.0, 19.8±4.6, 14.3±0.6, 16.1±4.7, and 19.8±2.4min (mean±SD), respectively. The sensitivity of the species-specific RT-LAMP assays were similar to that of the established RT-PCR and quantitative RT-PCR assays for diagnosis of EVD and are suitable for field or point-of-care diagnosis. The RT-LAMP assays were specific for the detection of the respective species of ebolavirus with no cross reaction with other species of ebolavirus and other viral hemorrhagic fever viruses such as Marburg virus, Lassa fever virus, and Dengue virus. The species-specific RT-LAMP assays developed in this study are rapid, sensitive, and specific and could be useful in case of an EVD outbreak.