The risk of leukemia in Seascale from radiation exposure.
An excess of leukemias in children has been observed between 1950 and 1980 in the village of Seascale (population about 3,000) which is situated approximately 3 km to the south of Sellafield nuclear fuel reprocessing plant in West Cumbria, England. Radiation doses from all the main sources of radiation exposure of the population and risks of radiation-induced leukemia have been calculated for children born and living in Seascale during the period of operation of the plant. For the Seascale study population of 1225 children and young persons, followed to age 20 y, or followed until 1980 for those born after 1960, 0.016 radiation-induced leukemias are predicted from the Sellafield discharges. This corresponds to an average risk to children in the population of about one in 75,000. For the four fatal leukemias observed in the study population (0.5 expected from United Kingdom statistics) to be attributed to the operations at Sellafield, the average risk would have to be increased by a factor of about 250, to one in 300. Although there is some uncertainty about the releases from the plant and concentrations of radionuclides in environmental materials in the Sellafield area, particularly for the early years of its operation, the possibility that the doses calculated and the risk coefficients used for radiation-induced leukemia could be so substantially wrong is very unlikely. The number of radiation-induced leukemias from all radiation sources is calculated to be 0.1, which corresponds to a risk of about one in 12,250 for the average child in the study population. About two-thirds of the risk is from natural radiation, 16% from the Sellafield discharges, and nuclear weapons fallout and medical exposure each contribute about 9%. The models used for calculating radiation doses from intakes of radionuclides were based upon those recommended by the International Commission on Radiological Protection (ICRP). This presented a number of difficulties in the assessment, which included the lack of any generally accepted age-related dosimetric models, particularly for bone-seeking radionuclides; limited information on gut transfer factors for radionuclides incorporated in foodstuffs; and no dosimetric models for the fetus. These and other problems identified in the analysis that require more information are discussed.


Amelioration of dextran sulphate sodium-induced colitis in mice by echinacoside-enriched extract of Cistanche tubulosa.
Echinacoside (ECH) is a major bioactive phenyethanoids in medicinal herba Cistanche and has been reported to have antiinflammatory activity and beneficial effect on wound healing in many experimental studies. This study was to test the efficacy of ECH-enriched extract of Cistanche tubulosa in the treatment of dextran sulphate sodium (DSS)-induced colitis, a preclinical model of ulcerative colitis. Oral administration of ECH extract significantly suppresses the development of acute colitis, indicated by lowering disease activity index (p < 0.0001, n = 8) and preventing colonic damage (p = 0.0336). Histological examinations showed that ECH extract treatment protected intestinal epithelium from inflammatory injury (p = 0.0249) but had less effect on inflammatory cellular infiltration (p = 0.1753). The beneficial effect of ECH extract treatment was associated with upregulation of transforming growth factor (TGF)-β1 as well as with an increase in the number of Ki67(+) proliferating cells in diseased colons (p < 0.0001). In cultured MODE-K cells, the addition of ECH extract enhanced in vitro wound healing that depended on TGF-β1 expression. These data suggest that ECH extract possesses a greater efficacy in preventing DSS-induced colitis in mice, implying the potential of ECH or its derivatives for clinically treating inflammatory bowel disease.


Utility of Maoto in an influenza season where reduced effectiveness of oseltamivir was observed - a clinical, non-randomized study in children.
In an influenza season where reduced effectiveness of oseltamivir was observed, we investigated the effectiveness of Maoto for influenza infection in children. Patients diagnosed with influenza by rapid diagnostic kit underwent treatment in one of the following groups: Maoto-treated group (group 1 (M)); oseltamivir-treated group (group 2 (O)); Maoto+oseltamivir-treated group (group 3 (M+O)); zanamivir-treated group (group 4 (Z)); and Maoto+zanamivir-treated group (group 5 (M+Z)). In influenza A patients who completed the study (n = 150), the mean duration of fever after administration (DFA) was significantly shorter in group 3 (M+O) (31.1 h, p < 0.01) and in group 4 (Z) (35.2 h, p < 0.05), as compared to group 2 (O) (56.0 h). Among these, in patients aged ≤5 years (n = 54), DFA was significantly shorter in group 1 (M) (33.2 h, p < 0.05) and in group 3 (M+O) (34.6 h, p < 0.05), as compared to group 2 (O) (61.4 h). In influenza B patients who completed the study (n = 70), no significant differences in DFA were observed among the groups. Maoto may be useful, particularly in cases of influenza with low sensitivity to oseltamivir and in patients aged ≤5 years for whom the use of zanamivir is difficult.


Intrapartum predictors of uterine rupture.
This case-controlled study reviewed 26 cases of uterine rupture at an academic medical center. Controls were selected in a 2:1 design by reviewing the immediate successful vaginal birth after cesarean delivery (VBAC) before and after each case of uterine rupture. At less than 2 hours before delivery or acute uterine rupture, mild and severe variable decelerations, persistent abdominal pain, and hyperstimulation were more common in cases of uterine rupture as compared to controls and had statistically significant positive likelihood ratios (LR). Mild and severe variable fetal heart rate decelerations, especially in the presence of persistent abdominal pain, may predict uterine rupture in patients attempting VBAC.


Mesenteric lymphatic vessels adapt to mesenteric venous hypertension by becoming weaker pumps.
Lymphangions, the segments of lymphatic vessels between two adjacent lymphatic valves, actively pump lymph. Acute changes in transmural pressure and lymph flow have profound effects on lymphatic pump function in vitro. Chronic changes in pressure and flow in vivo have also been reported to lead to significant changes in lymphangion function. Because changes in pressure and flow are both cause and effect of adaptive processes, characterizing adaptation requires a more fundamental analysis of lymphatic muscle properties. Therefore, the purpose of the present work was to use an intact lymphangion isovolumetric preparation to evaluate changes in mesenteric lymphatic muscle mechanical properties and the intracellular Ca(2+) in response to sustained mesenteric venous hypertension. Bovine mesenteric veins were surgically occluded to create mesenteric venous hypertension. Postnodal mesenteric lymphatic vessels from mesenteric venous hypertension (MVH; n = 6) and sham surgery (Sham; n = 6) animals were isolated and evaluated 3 days after the surgery. Spontaneously contracting MVH vessels generated end-systolic active tension and end-diastolic active tension lower than the Sham vessels. Furthermore, steady-state active tension and intracellular Ca(2+) concentration levels in response to KCl stimulation were also significantly lower in MVH vessels compared with those of the Sham vessels. There was no significant difference in passive tension in lymphatic vessels from the two groups. Taken together, these results suggest that following 3 days of mesenteric venous hypertension, postnodal mesenteric lymphatic vessels adapt to become weaker pumps with decreased cytosolic Ca(2+) concentration.


Revisiting copper reduction in zeolites: the impact of autoreduction and sample synthesis procedure.
At least two distinct processes occur during heating of the copper-exchanged mordenite in oxygen-free environment depending on the sample synthesis procedure. The first process corresponds to the reaction of Cu(ii) sites with the residual traces of carbonaceous impurities left in the sample after the synthesis without calcination in an oxidant-containing environment, yielding Cu(i) and carbon dioxide. The second relates to autoreduction of Cu(ii) into Cu(i) species accompanied with the release of molecular oxygen. The results show that to completely remove all traces of carbonaceous impurities and to avoid the loss of the active Cu(ii) sites during the activation, copper-exchanged zeolite samples should be calcined in oxidative gases at elevated temperature and, preferentially, prior to the experiments to avoid the adsorption of organic compounds from air.


The frequency of involuntary autobiographical memories and future thoughts in relation to daydreaming, emotional distress, and age.
We introduce a new scale, the Involuntary Autobiographical Memory Inventory (IAMI), for measuring the frequency of involuntary autobiographical memories and involuntary future thoughts. Using the scale in relation to other psychometric and demographic measures provided three important, novel findings. First, the frequency of involuntary and voluntary memories and future thoughts are similarly related to general measures of emotional distress. This challenges the idea that the involuntary mode is uniquely associated with emotional distress. Second, the frequency of involuntary autobiographical remembering does not decline with age, whereas measures of daydreaming, suppression of unwanted thoughts and dissociative experiences all do. Thus, involuntary autobiographical remembering relates differently to aging than daydreaming and other forms of spontaneous and uncontrollable thoughts. Third, unlike involuntary autobiographical remembering, the frequency of future thoughts does decrease with age. This finding underscores the need for examining past and future mental time travel in relation to aging and life span development.


Expression of Galectin-3 in renal neoplasms: a diagnostic, possible prognostic marker.
Galectin-3, a member of the lectin family, was shown to be expressed in normal distal tubular cells and in renal cell carcinomas (RCC). However, its diagnostic and prognostic significance in RCC is as yet undefined. To describe the expression of Galectin-3 among different histologic subtypes of renal neoplasms and to determine their diagnostic and prognostic significances. The expression of Galectin-3 was evaluated in 217 renal neoplasms by tissue microarray and immunohistochemistry with semiquantitative analysis. Strong expression of Galectin-3 was observed in 92 of 217 of renal neoplasms (42.4%). Although 22 of 23 oncocytomas (95.7%) and 19 of 21 chromophobe RCCs (90.5%) express Galectin-3, only 4 of 32 papillary RCCs (12.5%) and 47 of 137 clear cell RCCs (34.3%) express Galectin-3, suggesting that it may be used as a potential diagnostic marker. Galectin-3 expression was seen in 55% of high-grade (Fuhrman nuclear grades 3 and 4) versus 21% low-grade (grades 1 and 2) clear cell RCCs (P < .001). This study confirms that Galactin-3 is strongly overexpressed in renal cell neoplasms of distal tubular differentiation, that is, oncocytoma and chromophobe RCCs, suggesting it might be used as a possible differential diagnostic tool for renal cell neoplasm with oncocytic or granular cells. Furthermore, we observed a strong association of overexpression of Galectin-3 and high nuclear grade in clear cell RCC. These results also suggest a possible pivotal role for Galectin-3 in the differentiation and prognosis of clear cell RCC.


Myf5 gene polymorphisms and production performance traits in Songliao white geese.
To explore the relationship between Myf5 gene polymorphisms and production performance traits in Songliao white geese, we used the chicken Myf5 sequence to design primers and amplified part of the exon 1 sequence of the Songliao white goose Myf5 gene. Results of single-strand conformation polymorphism polymerase chain reaction analysis revealed polymorphisms of the amplified fragment, including three genotypes (AA, AB, and BB). Three varieties were dominated by allele A and were mainly expressed in AA genotypes. We also identified that the Myf5 gene has one single nucleotide change (A→G) on exon 1 at locus 1344, and another (G→C) at locus 1410. Analysis of variance showed significant differences between genotypes before slaughter in live weight, carcass weight, eviscerated weight, leg muscle weight, weight of the wings, and slaughter rate. There were no significant differences with respect to other growth and carcass traits evaluated.


[Pathogenesis and significance of gastroduodenal reflux].
For over a century duodenogastric reflux (DGR) has been considered the main cause of the primary or secondary alkaline gastritis. In the first case it occurred in patients who had not been operated earlier, in the latter one in those after surgery of stomach, duodenum, gallbladder and bile ducts. Since first time many reports of clinical and experimental studies have demonstrated destructive effect of pancreatic enzymes, bile acids and their by-products on stomach mucose producing in consequence non-specific histologic lesions. It has been also observed that duodenogastric reflux plays the basic role in the patho-genesis of gastritis and other GI tract diseases (gastric ulcer, reflux oesophagitis, progressing metaplasia or oesophageal and gastric cancer). As far as diagnosing of alkaline gastritis requires histologic confirmation, duodenogastric reflux brings many more problems. However, the progress in medicine and technology allow direct measurement of quality and quantity of this reflux.


Intercellular interaction mechanisms promote diversity in intracellular ATP concentration in Escherichia coli populations.
In fluctuating environments, many microorganisms acquire phenotypic heterogeneity as a survival tactic to increase the likelihood of survival of the overall population. One example of this interindividual heterogeneity is the diversity of ATP concentration among members of Escherichia coli populations under glucose deprivation. Despite the importance of such environmentally driven phenotypic heterogeneity, how the differences in intracellular ATP concentration emerge among individual E. coli organisms is unknown. In this study, we focused on the mechanism through which individual E. coli achieve high intracellular ATP concentrations. First, we measured the ATP retained by E. coli over time when cultured at low (0.1 mM) and control (22.2 mM) concentrations of glucose and obtained the chronological change in ATP concentrations. Then, by comparing these chronological change of ATP concentrations and analyzing whether stochastic state transitions, periodic oscillations, cellular age, and intercellular communication-which have been reported as molecular biological mechanisms for generating interindividual heterogeneity-are involved, we showed that the appearance of high ATP-holding individuals observed among E. coli can be explained only by intercellular transmission. By performing metabolomic analysis of post-culture medium, we revealed a significant increase in the ATP, especially at low glucose, and that the number of E. coli that retain significantly higher ATP can be controlled by adding large amounts of ATP to the medium, even in populations cultured under control glucose concentrations. These results reveal for the first time that ATP-mediated intercellular transmission enables some individuals in E. coli populations grown at low glucose to retain large amounts of ATP.


Evaluation of Maternal and Perinatal Outcomes of Induction in Borderline Oligohydramnios at Term.
Oligohydramnios is described as decreased amniotic fluid volume relative to gestational age. Semiquantitatively it is described using the Amniotic Fluid Index (AFI) which is calculated by adding the depth in centimetres of the largest vertical pocket in each of four equal uterine quadrants. AFI less than or equal to 5 cm is defined as oligohydramnios. A Borderline Oligohydramnios (BO) is defined as AFI 5.1-8 cm. To assess the maternal and perinatal outcome of induction in borderline oligohydramnios cases at term. This is a retrospective observational study done from December 2015 to November 2016 in Mahatma Gandhi Medical College and Research Institute, Puducherry, India. Fifty cases of BO with AFI 5.1 cm - 8 cm taken as case and another 50 cases of Normal Liquor (NL) with AFI 8.1 cm - 18 cm taken as control. Data was collected and analysed by SPSS software version 20.0 For qualitative data, the χ2-test or Fisher's-exact test were used and for continuous variables, the t-test was used. Cases and controls were matched in baseline parameters. More number of cases were found with meconium stained liquor during labour which is statistically significant (p<0.05). Otherwise there were no statistical significant difference between cases and controls in maternal and perinatal outcome. Induction of labour in cases with BO cases compared to those with NL at term did not show very statistically significant difference in terms of induction to delivery interval and neonatal outcome.


One year on.
This month marks the first anniversary of the Department of Health's publication of Reforming Emergency Care; its aim, 'the delivery of fast, responsive, and effective emergency care services' in England.


Preferred shallow-water nursery sites provide acoustic crypsis to southern right whale mother-calf pairs.
Adaptations to sound production behaviour can reduce the detectability of animal signals by eavesdroppers in a phenomenon known as acoustic crypsis. We propose that acoustic crypsis can include selection of locations that affect how sound transmits through the environment: habitats with poor acoustic propagation can minimize the range of detectability of animal signals. We investigated the potential for the preferred habitats of southern right whales to confer acoustic crypsis. We modelled acoustic propagation and range of detection of calls from southern right whales in the shallow, sandy, near shore waters where mothers and calves aggregate during the calving season. At three nursery sites across three continents in the southern hemisphere, results showed that the depth at which right whales are most commonly sighted has the most limited acoustic detection range for their calls. Thus, these habitats allow mother-calf pairs to remain acoustically cryptic from potential eavesdroppers, both predators and conspecifics, when their calves are the most vulnerable. Our results provide preliminary evidence that, in addition to other behavioural strategies, the use of habitats with poor acoustic propagation can contribute to acoustic crypsis. This adaptation may be a widespread and underappreciated mechanism for avoidance of eavesdroppers.


[Fragmentation of the DNA of simian adenovirus type 38 by using restriction endonucleases].
The effect of restricting endonucleases Eco R I, BgI II and Sal I on simian adenovirus type 38 (SV-38) DNA was studied. Bgl II restrictase cleaves the virus DNA into 4 fragments, A, B, G, and D, with molecular weights 9.3 x 10(6), 3.3 x 10(6), and 2.9 x 10(6) daltons, respectively. After restriction with Eco R I and Sal I SV-38 DNA cleaves into 5 and 6 fragments, respectively. The molecular weights of Eco R I fragments are A--8.2 x 10(6), B--6.5 x 10(6), C--4.0 x 10(6), D--1.27 x 10(6), and of Sal I fragments: A--6.5 x 10(6), B--5.4 x 10(6), C--4.2 x 10(6), D--2.8 x 10(6), E--2.5 x 10(6), and F--0.25 x 10(6). By restriction of DNA-protein compex by means of partial DNA hydrolysis, combined Bgl II and Eco R I hydrolysis and secondary restriction of a fragment eluted from the agar gel, the alternation of Eco R I and Bgl II fragments in SV-38 genome was determined.


Education Research: Physician identification and patient satisfaction on an academic neurology inpatient service.
To determine the relationship between neurology inpatient satisfaction and (1) number of physicians involved in the patient's care and (2) patients' ability to identify their physicians. A 10-item questionnaire addressing patient satisfaction and identification of physicians on the care team was administered to patients admitted to an academic, tertiary care, inpatient neurology service from May 1 to October 31, 2012. We hypothesized higher satisfaction among patients having fewer physicians on the care team and among patients able to identify their physicians. A total of 652 patients were enrolled. An average of 3.9 (range 3-8) physicians were involved in each patient's care. Patients were able to correctly identify on average 2.4 (60.7%) physicians involved in their care. Patients who were very satisfied correctly identified a larger percentage of physicians involved in their care (63.8% vs 50.7%, p < 0.001), were more likely to identify a physician who knew them best (94.3% vs 43.6%, p < 0.001) and who was "in charge" of their care (94.1% vs 57.6%, p < 0.001), and were more likely to have private insurance (82.8% vs 70.5%, p < 0.001) and fewer physicians involved in their care (3.84 vs 4.06, p = 0.02). Neurology inpatients' ability to identify physicians involved in their care is associated with patient satisfaction. Strategies to enhance patient satisfaction might target improving physician identification, reducing actual or perceived disparities in care based on payer status, and reducing handoffs or conducting handoffs at the bedside.


Chemopreventive effects of the p53-modulating agents CP-31398 and Prima-1 in tobacco carcinogen-induced lung tumorigenesis in A/J mice.
Lung cancer is the leading cause of cancer deaths worldwide. Expression of the p53 tumor suppressor protein is frequently altered in tobacco-associated lung cancers. We studied chemopreventive effects of p53-modulating agents, namely, CP-31398 and Prima-1, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung adenoma and adenocarcinoma formation in female A/J mice. Seven-week-old mice were treated with a single dose of NNK (10 µmol/mouse) by intraperitoneal injection and, 3 weeks later, were randomized to mice fed a control diet or experimental diets containing 50 or 100 ppm CP-31398 or 150 or 300 ppm Prima-1 for either 17 weeks (10 mice/group) or 34 weeks (15 mice/group) to assess the efficacy against lung adenoma and adenocarcinoma. Dietary feeding of 50 or 100 ppm CP-31398 significantly suppressed (P < .0001) lung adenocarcinoma by 64% and 73%, respectively, after 17 weeks and by 47% and 56%, respectively, after 34 weeks. Similarly, 150 or 300 ppm Prima-1 significantly suppressed (P < .0001) lung adenocarcinoma formation by 56% and 62%, respectively, after 17 weeks and 39% and 56%, respectively, after 34 weeks. Importantly, these results suggest that both p53 modulators cause a delay in the progression of adenoma to adenocarcinoma. Immunohistochemical analysis of lung tumors from mice exposed to p53-modulating agents showed a significantly reduced tumor cell proliferation and increased accumulation of wild-type p53 in the nucleus. An increase in p21- and apoptotic-positive cells was also observed in lung tumors of mice exposed to p53-modulating agents. These results support a chemopreventive role of p53-modulating agents in tobacco carcinogen-induced lung adenocarcinoma formation.


Identification of sSIGLEC5 and sLAG3 as New Relapse Predictors in Lung Cancer.
Lung cancer (LC) continues to be the leading cause of cancer-related deaths in both men and women worldwide. After complete tumour resection, around half of the patients suffer from disease relapse, emphasising the critical need for robust relapse predictors in this disease. In search of such biomarkers, 83 patients with non-microcytic lung cancer and 67 healthy volunteers were studied. Pre-operative levels of sSIGLEC5 along with other soluble immune-checkpoints were measured and correlated with their clinical outcome. Soluble SIGLEC5 (sSIGLEC5) levels were higher in plasma from patients with LC compared with healthy volunteers. Looking into those patients who suffered relapse, sSIGLEC5 and sLAG3 were found to be strong relapse predictors. Following a binary logistic regression model, a sSIGLEC5 + sLAG3 score was established for disease relapse prediction (area under the curve 0.8803, 95% confidence intervals 0.7955−0.9652, cut-off > 2.782) in these patients. Based on score cut-off, a Kaplan−Meier analysis showed that patients with high sSIGLEC5 + sLAG3 score had significantly shorter relapse-free survival (p ≤ 0.0001) than those with low sSIGLEC5 + sLAG3 score.Our study suggests that pre-operative sSIGLEC5 + sLAG3 score is a robust relapse predictor in LC patients.


Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors.
Critically ill patients may be at high risk of venous thromboembolism. The objective was to determine the prevalence, incidence, and risk factors for proximal lower extremity deep venous thrombosis among critically ill medical-surgical patients. Prospective cohort. Closed university-affiliated intensive care unit. We enrolled consecutive patients > or =18 yrs of age expected to be in intensive care unit for > or =72 hrs. Exclusion criteria were an admitting diagnosis of trauma, orthopedic surgery, pregnancy, and life support withdrawal. Interventions included bilateral lower extremity compression ultrasound within 48 hrs of intensive care unit admission, twice weekly, and if venous thromboembolism was clinically suspected. Thromboprophylaxis was protocol directed and universal. We recorded deep venous thrombosis risk factors at baseline and daily, using multivariate regression analysis to determine independent predictors. Patients were followed to hospital discharge. Among 261 patients with a mean Acute Physiology and Chronic Health Evaluation II score of 25.5 (+/-8.4), the prevalence of deep venous thrombosis was 2.7% (95% confidence interval 1.1-5.5) on intensive care unit admission, and the incidence was 9.6% (95% confidence interval 6.3-13.8) over the intensive care unit stay. We identified four independent risk factors for intensive care unit-acquired deep venous thrombosis: personal or family history of venous thromboembolism (hazard ratio 4.0, 95% confidence interval 1.5-10.3), end-stage renal failure (hazard ratio 3.7, 95% confidence interval 1.2-11.1), platelet transfusion (hazard ratio 3.2, 95% confidence interval 1.2-8.4), and vasopressor use (hazard ratio 2.8, 95% confidence interval 1.1-7.2). Patients with deep venous thrombosis had a longer duration of mechanical ventilation (p = .03), intensive care unit stay (p = .005), and hospitalization (p < .001) than patients without deep venous thrombosis. Despite universal thromboprophylaxis, medical-surgical critically ill patients remain at risk for lower extremity deep venous thrombosis. Further research is needed to evaluate the risks and benefits of more intense venous thromboembolism prophylaxis.


Phylogenetic relationships between some members of the genera Neisseria, Acinetobacter, Moraxella, and Kingella based on partial 16S ribosomal DNA sequence analysis.
We obtained 16S ribosomal DNA (rDNA) sequence data for strains belonging to 11 species of Proteobacteria, including the type strains of Kingella kingae, Neisseria lactamica, Neisseria meningitidis, Moraxella lacunata subsp. lacunata, [Neisseria] ovis, Moraxella catarrhalis, Moraxella osloensis, [Moraxella] phenylpyruvica, and Acinetobacter lwoffii, as well as strains of Neisseria subflava and Acinetobacter calcoaceticus. The data in a distance matrix constructed by comparing the sequences supported the proposal that the genera Acinetobacter and Moraxella and [N.] ovis should be excluded from the family Neisseriaceae. Our results are consistent with hybridization data which suggest that these excluded taxa should be part of a new family, the Moraxellaceae. The strains that we studied can be divided into the following five groups: (i) M. lacunata subsp. lacunata, [N.] ovis, and M. catarrhalis; (ii) M. osloensis; (iii) [M.] phenylpyruvica; (iv) A. calcoaceticus and A. lwoffii; and (v) N. meningitidis, N. subflava, N. lactamica, and K. kingae. We agree with the previous proposal that [N.] ovis should be renamed Moraxella ovis, as this organism is closely related to Moraxella species and not to Neisseria species. The generically misnamed taxon [M.] phenylpyruvica belongs to the proposed family Moraxellaceae, but it is sufficiently different to warrant exclusion from the genus Moraxella. Further work needs to be done to investigate genetically similar species, such as Psychrobacter immobilis, before the true generic position of this organism can be determined. Automated 16S rDNA sequencing with the PCR allows workers to accurately determine phylogenetic relationships between groups of organisms.(ABSTRACT TRUNCATED AT 250 WORDS)


Production of triploid transgenic zebrafish, Brachydanio rerio (Hamilton).
Eggs of zebrafish Brachydanio rerio were heat-shocked just after fertilisation to induce triploidy and subsequently subjected to microinjection with the linear recombinant plasmid containing the Rous Sarcoma Virus-Long Terminal Repeat (RSV-LTR) promoter linked to the rainbow trout (Oncorhynchus mykiss) growth hormone (GH)cDNA(pRSVrtGH). Slot and Southern analyses showed the extra chromosomal transfer of pRSVrtGH. Expression of pRSVrtGH was detected in the triploid transformants by RNA slot, Northern and Western analyses.


[Ultrasonographic and x-ray diagnosis of nephrolithiasis].
Neither the ultrasonic, not the x-ray method alone cannot provide the correct diagnosis in nephrolithiasis. Ultrasonic scanning of the kidneys is indicated at the first stage of the diagnosis. In case of a concrement detection without dilatation of the pelvic calyceal system and the presence of a typical pattern of a calcified papilla or coral-like concrement on the picture the diagnosis can be considered made. If ultrasonic scanning detects, besides the concrement shade, a dilatation of the pelvic calyceal system, excretory urography and x-ray television pyeloscopy are necessary to specify the urodynamic state, that is important to predict the concrement of its fragments elimination under the effect of conservative therapy or long-distance lithotripsy.


Knowledge of Heat-Related Illness First Aid and Self-Reported Hydration and Heat-Related Illness Symptoms in Migrant Farmworkers.
Background: Outdoor workers are exposed to hot work environments and are at risk of heat-related morbidity and mortality. The purpose of this study was to evaluate the knowledge of migrant farmworkers about first aid for heat-related illness (HRI) symptoms. Methods: The authors recruited 60 migrant farmworkers out of 66 who were approached from vegetable farms in Georgia. They were workers who participated in the 2018 Farmworker Family Health Program (FWFHP). The authors surveyed the workers to assess demographics, prevalence of HRI symptoms, hydration practices, and knowledge of HRI first aid. Descriptive statistics for worker demographics, HRI symptoms, and hydration data were calculated, as were the percentages of correctly answered pilot questions. Findings: Of the 60 workers who chose to participate in this study, more than 50% incorrectly answered pilot questions related to their knowledge of HRI first aid. The two most common HRI symptoms reported were heavy sweating and muscle cramps. More than two thirds reported experiencing at least one HRI symptom during the workday. Mean liquid consumption within this sample was 72.95 oz per day, which is much less than the recommended 32 oz per hour. Conclusion/Application to Practice: Until larger structural change can occur to protect farmworkers, farm owners can prevent morbidity and mortality from inadequate hydration practices and working in high-heat conditions by providing migrant farmworkers with training in heat-related first aid. Appropriate heat-illness interventions should focus on first aid measures to reduce morbidity and mortality related to heat illness in farmworkers.


Framework for designing sampling programs.
A general framework for designing sampling programs is described. As part of the sampling program the problem of concern, or reason for sampling, needs to be clearly stated and objectives specified. The development of a conceptual model will assist the clarification of objectives and the choice of indicators to be sampled.Objectives can then be stated as testable hypotheses and decisions made about the samallest difference/changes that are to be detected/observed by the sampling.To allow the collection of representative samples, and the statistical analysis of data to be collected, the potential sources of variability in the data must be considered. Site, selection, frequency and replication must account for the expected variability.Before field collection of samples occurs, the sample collection device needs to be tested as to its efficiency to collect a representative sample. It also will usually be necessary to consider how samples are to be preserved to inhibit biological and chemical change. All sample programs require a quality assurance program to identify, measure and control errors.As well as the above the cost-effectiveness of the program should be evaluated in terms of maximizing the information obtained/cost.


Acute lumbosacral plexopathy from gluteal compartment syndrome after drug abuse: a case report.
Acute lumbosacral plexus injury from gluteal compartment syndrome is extremely rare. Physicians should be aware of this diagnosis when examining patients with altered mental status, prolonged immobilization, and gluteal muscle compression. This case report presents a patient with acute complete left lumbosacral plexus paralysis and acute renal failure after gluteal compartment syndrome secondary to prolonged immobilization from drug abuse. Clinical examination, imaging of the pelvis, renal function, creatine phosphokinase, and urine myoglobin were indicative of gluteal compartment syndrome and rhabdomyolysis. Electrodiagnostic studies showed complete limb paralysis. Medical treatment and rehabilitation was administered. Renal function recovered within the 1st week; function at the proximal muscles of the left lower limb improved within 6 months, with mild discomfort on sitting at the buttock, foot drop, and sensory deficits at the leg and dorsum of foot.


[Remote changes in the course of mitosis in synchronized cultures of Chinese hamster cells following inhibition of RNA and protein synthesis].
The effect of inhibition of the synthesis of some types of RNA and proteins was determined in the synchronized culture of Chinese hamster cells at various stages of the interphase on the course of remote mitosis. Analysis of MI and some forms of pathological cell division showed that the action of different doses of AMD and pyromycin during the first part of the interphase provoked an identical effect--C-mitosis at the immediate and remote waves of cell division. Suppression of the synthesis of whole cell RNA and proteins during the second half of the interphase was accompanied by a metaphase cell delay with scattering chromosomes, this indicating derangement of the synthesis of the division spindle component. It is suggested that proteins (tubulins) and RNA participate in the organization of the division spindle during remote mitosis as a "reserve pool".


The prevalence and molecular basis of beta-thalassemia in Isparta province and region.
The prevalence and molecular basis of beta-thalassemia in the district of Isparta were determined in a total of 6,054 healthy high school students who were recruited from 21 randomly selected high schools in the Isparta province and region. In 182 subjects, naked eye single tube red cell osmotic fragility test (NESTROFT test) was positive HbA2 was measured by high-performance liquid chromatography (HPLC) in these subjects and was found to be high in 149 subjects. The incidence of beta-thalassemia was 149 in 6,054 (25%). The beta-thalassemia frequency was lower in the city center than in neighboring towns, 1.7% vs. 2.2%, respectively The most prevalent mutation of beta-thalassemia in this region was IVS 1-110 (G-A), followed by Codon 39 (C-T) and IVSII-745 (C-G).


A DNA real-time quantitative PCR method suitable for routine monitoring of low levels of minimal residual disease in chronic myeloid leukemia.
The BCR-ABL1 sequence has advantages over the BCR-ABL1 transcript as a molecular marker in chronic myeloid leukemia and has been used in research studies. We developed a DNA real-time quantitative PCR (qPCR) method for quantification of BCR-ABL1 sequences, which is also potentially suitable for routine use. The BCR-ABL1 breakpoint was sequenced after isolation by nested short-range PCR of DNA from blood, marrow, and cells on slides, obtained either at diagnosis or during treatment, or from artificial mixtures. PCR primers were chosen from a library of presynthesized and pretested BCR (n = 19) and ABL1 (n = 568) primers. BCR-ABL1 sequences were quantified relative to BCR sequences in 521 assays on 266 samples from 92 patients. For minimal residual disease detectable by DNA qPCR and RT-qPCR, DNA qPCR gave similar minimal residual disease results as RT-qPCR but had better precision at low minimal residual disease levels. The limit of detection of DNA qPCR depended on the amount of DNA assayed, being 10(-5.8) when 5 μg was assayed and 10(-7.0) when 80 μg was assayed. DNA qPCR may be useful and practical for monitoring the increasing number of patients with minimal residual disease around or below the limit of detection of RT-qPCR as the assay itself is simple and the up-front costs will be amortized if sequential assays are performed.


Dynamics of cortical domains in early Drosophila development.
Underlying the plasma membrane of eukaryotic cells is an actin cortex that includes actin filaments and associated proteins. A special feature of all polarized and epithelial cells are cortical domains, each of which is characterized by specific sets of proteins. Typically, an epithelial cell contains apical, subapical, lateral and basal domains. The domain-specific protein sets contain evolutionarily conserved proteins, as well as cell-type-specific factors. Among the conserved proteins are, the Par proteins, Crumbs complex and the lateral proteins Scribbled and Discs large 1. Organization of the plasma membrane into cortical domains is dynamic and depends on cell type, differentiation and developmental stage. The dynamics of cortical organization is strikingly visible in early Drosophila embryos, which increase the number of distinct cortical domains from one, during the pre-blastoderm stage, to two in syncytial blastoderm embryos, before finally acquiring the four domains that are typical for epithelial cells during cellularization. In this Review, we will describe the dynamics of cortical organization in early Drosophila embryos and discuss the processes and mechanisms underlying cortical remodeling.


Transformation of social networks in the late pre-Hispanic US Southwest.
The late pre-Hispanic period in the US Southwest (A.D. 1200-1450) was characterized by large-scale demographic changes, including long-distance migration and population aggregation. To reconstruct how these processes reshaped social networks, we compiled a comprehensive artifact database from major sites dating to this interval in the western Southwest. We combine social network analysis with geographic information systems approaches to reconstruct network dynamics over 250 y. We show how social networks were transformed across the region at previously undocumented spatial, temporal, and social scales. Using well-dated decorated ceramics, we track changes in network topology at 50-y intervals to show a dramatic shift in network density and settlement centrality from the northern to the southern Southwest after A.D. 1300. Both obsidian sourcing and ceramic data demonstrate that long-distance network relationships also shifted from north to south after migration. Surprisingly, social distance does not always correlate with spatial distance because of the presence of network relationships spanning long geographic distances. Our research shows how a large network in the southern Southwest grew and then collapsed, whereas networks became more fragmented in the northern Southwest but persisted. The study also illustrates how formal social network analysis may be applied to large-scale databases of material culture to illustrate multigenerational changes in network structure.


Significance of anti-Ro/SSA antibodies in the response and retention of abatacept in patients with rheumatoid arthritis: a multicentre cohort study.
Objective: To determine whether the positivity of baseline anti-Ro/Sjögren's syndrome antigen A (SSA) antibodies influences the response to abatacept, we compared therapeutic responses between anti-Ro/SSA antibody-negative and -positive patients with rheumatoid arthritis (RA) using a multicentre RA ultrasonography prospective cohort. Method: We reviewed Japanese patients with RA who started abatacept as the first biological disease-modifying anti-rheumatic drug between June 2013 and April 2018. We assessed 28-joint Disease Activity Score-erythrocyte sedimentation rate (DAS28-ESR) change between baseline and 6 or 12 months after treatment in RA patients treated with abatacept, and European League Against Rheumatism (EULAR) response at 6 and 12 months. The Global OMERACT-EULAR Synovitis Score (GLOESS) was calculated at baseline and at 6 and 12 months. Results: Overall, 51 patients were enrolled and divided into anti-Ro/SSA antibody-negative and -positive groups of 35 and 16, respectively. Median age at baseline was significantly higher in the anti-Ro/SSA antibody-negative group (p = 0.04). The retention rate and percentage of EULAR good responders at 12 months were significantly higher in the anti-Ro/SSA antibody-negative group (both p = 0.02). Anti-Ro/SSA antibody-negative patients exhibited larger decreases in both DAS28-ESR and DAS28-C-reactive protein at 12 months than anti-Ro/SSA antibody-positive patients (p = 0.02 and 0.04, respectively). GLOESS decreased significantly at 6 months in anti-Ro/SSA antibody-negative patients (p = 0.03). Multivariate analyses showed that anti-Ro/SSA antibody positivity was an independent factor associated with change in the DAS28-ESR at 6 months (p < 0.05). Conclusion: Anti-Ro/SSA antibody positivity predicts a poor response to abatacept and low retention rate.


Freezing skeletal muscle tissue does not affect its decomposition in soil: evidence from temporal changes in tissue mass, microbial activity and soil chemistry based on excised samples.
The study of decaying organisms and death assemblages is referred to as forensic taphonomy, or more simply the study of graves. This field is dominated by the fields of entomology, anthropology and archaeology. Forensic taphonomy also includes the study of the ecology and chemistry of the burial environment. Studies in forensic taphonomy often require the use of analogues for human cadavers or their component parts. These might include animal cadavers or skeletal muscle tissue. However, sufficient supplies of cadavers or analogues may require periodic freezing of test material prior to experimental inhumation in the soil. This study was carried out to ascertain the effect of freezing on skeletal muscle tissue prior to inhumation and decomposition in a soil environment under controlled laboratory conditions. Changes in soil chemistry were also measured. In order to test the impact of freezing, skeletal muscle tissue (Sus scrofa) was frozen (-20 degrees C) or refrigerated (4 degrees C). Portions of skeletal muscle tissue (approximately 1.5 g) were interred in microcosms (72 mm diameter x 120 mm height) containing sieved (2mm) soil (sand) adjusted to 50% water holding capacity. The experiment had three treatments: control with no skeletal muscle tissue, microcosms containing frozen skeletal muscle tissue and those containing refrigerated tissue. The microcosms were destructively harvested at sequential periods of 2, 4, 6, 8, 12, 16, 23, 30 and 37 days after interment of skeletal muscle tissue. These harvests were replicated 6 times for each treatment. Microbial activity (carbon dioxide respiration) was monitored throughout the experiment. At harvest the skeletal muscle tissue was removed and the detritosphere soil was sampled for chemical analysis. Freezing was found to have no significant impact on decomposition or soil chemistry compared to unfrozen samples in the current study using skeletal muscle tissue. However, the interment of skeletal muscle tissue had a significant impact on the microbial activity (carbon dioxide respiration) and chemistry of the surrounding soil including: pH, electroconductivity, ammonium, nitrate, phosphate and potassium. This is the first laboratory controlled study to measure changes in inorganic chemistry in soil associated with the decomposition of skeletal muscle tissue in combination with microbial activity.


First Report of Diaporthe pseudomangiferae Causing Inflorescence Rot, Rachis Canker, and Flower Abortion of Mango.
Although mango (Mangifera indica L.) is a very important tropical fruit crop, limited studies have been conducted on fungal pathogens affecting the inflorescences. During a disease survey conducted from 2008 to 2010, 50% of the inflorescences were affected with inflorescence rot, rachis canker, and flower abortion characterized by blackening of plant tissue with soft rot lesions and suken lesions on the rachis, respectively. Symptoms were observed at the Mango Germplasm Collection of the University of Puerto Rico's Experiment Station in Juana Diaz, Puerto Rico. Five diseased pieces of 350 inflorescences from cvs. Haden and Irwin were disinfested with 70% ethanol, followed by 0.5% sodium hypochlorite, rinsed with sterile water, and transferred to acidified potato dextrose agar (APDA). Among several typical or common fungi, three isolates of Diaporthe pseudomangiferae (Dp) R.R. Gomes, C. Glienke & Crous were obtained from symptomatic tissue and identified morphologically using taxonomic keys and DNA sequence comparisons (1,2). On APDA, colonies of Dp initially had white-gray moderate aerial mycelia. Pycnidia were black and superficial on cultures with a central ostiole that exuded beige to light orange conidial droplets. Alpha conidia (n = 50) were aseptate, hyaline, smooth, fusiform, apex rounded and base truncate, averaged 7.34 μm long by 2.60 μm wide. Beta conidia (n = 50) were spindle-shaped, aseptate, hyaline and smooth, averaged 22.03 μm long by 1.53 μm wide. DNA analysis of the ITS1-5.8S-ITS2 region using primers ITS5 and ITS4, and fragments of both β-tubulin and translation elongation factor 1 alpha (EF1-α) genes using primers T1 and Bt2b, and EF1-728F and EF1-986R, respectively, were sequenced and compared using BLASTn with sequences available in the GenBank. Accession numbers of gene sequences of Dp submitted to GenBank were KF616498 to KF616500 for ITS region, KF616501 to KF616503 for β-tubulin, and KF616504 to KF616506 for EF1-α. For all genes used, sequences were 99 to 100% identical to reference isolate CBS 388.89 of Dp in GenBank. For each fungal isolate, pathogenicity tests were conducted on six random healthy non-detached mango inflorescences for both cvs. Haden and Irwin. Inflorescences were inoculated with 5-mm mycelial disks from 8-day-old pure cultures grown on APDA and kept in a humid chamber using plastic bags for 8 days under field conditions. Untreated controls were inoculated with APDA disks only. The test was repeated twice. On cv. Haden, isolates of Dp caused rachis canker (sunken lesion on the rachis) at 8 days post inoculation (dpi). On cv. Irwin, isolates of Dp caused inflorescence rot. Initially, white mycelia was observed on inflorescences but eventually inflorescences turned brown and flower abortion was observed at 8 dpi. Untreated controls did not show any of the above symptoms and no fungi were re-isolated from tissue. From diseased inflorescences, Dp was re-isolated, thus fulfilling Koch's postulates. Diaporthe spp. have been associated with fruit rots, stem cankers, decay, and wilt on a wide range of plant hosts (3,4). Recently, Dp was associated with fruit peel of mango in Mexico and the Dominican Republic (2). To our knowledge, this is the first report of Dp causing inflorescence rot, rachis canker, and flower abortion in mango. References: (1) H. L. Barnett and B. B. Hunter. Illustrated Genera of Imperfect Fungi. APS Press. St. Paul, MN, 1998. (2) R. R. Gomes et al. Persoonia. 31:1, 2013. (3) J. M. Santos et al. Persoonia 27:9, 2011. (4) S. M. Thompson et al. Persoonia 27:80, 2011.


The membrane-anchoring domain of epidermal growth factor receptor ligands dictates their ability to operate in juxtacrine mode.
All ligands of the epidermal growth factor (EGF) receptor (EGFR) are synthesized as membrane-anchored precursors. Previous work has suggested that some ligands, such as EGF, must be proteolytically released to be active, whereas others, such as heparin-binding EGF-like growth factor (HB-EGF) can function while still anchored to the membrane (i.e., juxtacrine signaling). To explore the structural basis for these differences in ligand activity, we engineered a series of membrane-anchored ligands in which the core, receptor-binding domain of EGF was combined with different domains of both EGF and HB-EGF. We found that ligands having the N-terminal extension of EGF could not bind to the EGFR, even when released from the membrane. Ligands lacking an N-terminal extension, but possessing the membrane-anchoring domain of EGF, still required proteolytic release for activity, whereas ligands with the membrane-anchoring domain of HB-EGF could elicit full biological activity while still membrane anchored. Ligands containing the HB-EGF membrane anchor, but lacking an N-terminal extension, activated EGFR during their transit through the Golgi apparatus. However, cell-mixing experiments and fluorescence resonance energy transfer studies showed that juxtacrine signaling typically occurred in trans at the cell surface, at points of cell-cell contact. Our data suggest that the membrane-anchoring domain of ligands selectively controls their ability to participate in juxtacrine signaling and thus, only a subclass of EGFR ligands can act in a juxtacrine mode.


Efficacy and Safety of Tetrahydrocurcuminoids for the Treatment of Canker Sore and Gingivitis.
Tetrahydrocurcuminoids (THCs) are among the major metabolites of curcuminoids with a higher bioavailability and physiological stability and exhibit a broad spectrum of therapeutic activities. The objective of this study was to evaluate the efficacy of THCs in patients suffering from canker sore and gingivitis designed as an exploratory clinical trial. This is an open label prospective pilot clinical trial carried out at two clinical centers: Noble Hospital, Pune, Maharashtra, and Sri Venkateshwara Hospital, Bangalore, Karnataka in India. Participants were assigned to 21 days of treatment with chewable oral THCs supplement. Patients were instructed to self-administer one chewable tablet containing 100 mg of THCs twice daily for up to 21 days. This clinical trial was registered at a public Clinical Trial Registry in India (http://www.ctri.nic.in). Thirty-one canker sore and twenty-nine gingivitis patients participated in this study. Body mass index, throat numbness/relief, Visual Analog Scale (VAS) pain score, canker sore lesions, gingival appearance, inflammation and bleeding were assessed before and after treatment, at 14 and 21 days. Vital signs and laboratory parameters were assessed for safety. THCs treatment significantly reduced the reddening at the site, difficulty in chewing, swallowing, and VAS pain score in the canker sore patients. Further, both single and multiple lesions were completely healed. In gingivitis patients, gingival appearance, bleeding, and inflammation were significantly reduced. No adverse effects were observed during the study. Overall, the findings of this study show that supplementation of THCs for 21 days reduced the pain and prevented the progression of the disease in patients suffering from canker sore and gingivitis without adverse side effects.


Risk of new onset diabetes mellitus in patients with asthma or COPD taking inhaled corticosteroids.
A recent case-controlled study reported an increased risk of diabetes mellitus in patients treated with inhaled corticosteroids for asthma or COPD, versus age-matched controls. The purpose of the current study was to evaluate whether there was an increased risk of new onset diabetes mellitus or hyperglycaemia among patients with asthma or COPD treated with inhaled corticosteroids. A retrospective analysis evaluated all double-blind, placebo-controlled, trials in patients ≥4 years of age involving budesonide or budesonide/formoterol in asthma (26 trials; budesonide: n = 9067; placebo: n = 5926), and in COPD (8 trials; budesonide: n = 4616; non-ICS: n = 3643). A secondary dataset evaluated all double-blind, controlled trials in asthma involving the use of inhaled corticosteroids (60 trials; budesonide: n = 33,496; fluticasone: n = 2773). In the primary asthma dataset, the occurrence of diabetes mellitus/hyperglycaemia adverse events (AEs) was 0.13% for budesonide and 0.13% for placebo (HR 0.98 [95% CI: 0.38-2.50], p = 0.96) and serious adverse events (SAEs) was 0% for budesonide and 0.05% for placebo. In the secondary dataset, the occurrence of diabetes/hyperglycaemia as AE and SAE was 0.19% and 0.03%, respectively. In the COPD dataset, the occurrence of diabetes mellitus/hyperglycaemia AEs was 1.3% for budesonide and 1.2% for non-ICS (HR 0.99 [95% CI: 0.67-1.46], p = 0.96) and SAEs was 0.1% for budesonide and 0.03% for non-ICS. Treatment with inhaled corticosteroids in patients with asthma or COPD was not associated with increased risk of new onset diabetes mellitus or hyperglycaemia.


Comparative Study between Intrathecal 0.5% Isobaric Levobupivacaine, 0.5% Isobaric Ropivacaine, and 0.5% Hyperbaric Bupivacaine in Elective Lower Segment Cesarean Section: A Randomized Clinical Study.
Neuraxial anesthesia in obstetrics began with the spinal block by Oskar Kreis in 1900. The technique of subarachnoid blockade has been refined since then and various drugs have been used to provide analgesia and anesthesia for infraumbilical surgeries. This study was conducted because of newer options available, such as an intrathecal drug with appropriate sensory and motor blockade and minimal haemodynamic changes that can be used in the lower segment cesarean section safely. Ninety patients were randomly divided into three groups including 30 patients in each group. Group B, Group L, and Group R, each receiving 2.2 mL of 0.5% hyperbaric bupivacaine, 0.5% isobaric levobupivacaine, and 0.5% isobaric ropivacaine, respectively. All groups were compared concerning sensory block, motor block, hemodynamic stability, and complications if any. The onset of sensory block at T8, two-segment regression time from the highest block, time of regression to L1, total duration of analgesia, onset and total duration of motor block were comparable between Group B and L (P > 0.05), but both these groups were statistically significant with Group R (P < 0.05). Hypotension was observed among all the groups; however, the incidence was minimum in Group R. 12 mg of isobaric ropivacaine and 12 mg of isobaric levobupivacaine, compared to 12 mg hyperbaric bupivacaine (2.2 mL of 0.5% each), when administered intrathecally provides adequate anesthesia for cesarean section. The lesser duration of motor block in ropivacaine compared to the other two drugs could be beneficial for early ambulation, also the incidence of hypotension was lower in Group R.


Oral antiplatelet therapy in cerebrovascular disease, coronary artery disease, and peripheral arterial disease.
Atherothrombosis is a pathophysiologic process that results in clinical ischemic events affecting the cerebral, coronary, and peripheral arterial circulation. Antiplatelet agents, used alone or in combination, are effective in preventing recurrent vascular events among individuals with established vascular disease. To summarize the current state of evidence regarding oral antiplatelet treatment in patients with cerebrovascular disease, coronary artery disease (CAD), and peripheral arterial disease. Using the key terms acute coronary syndrome, atherothrombosis, ischemic stroke, myocardial infarction, MI, peripheral arterial disease, TIA, transient ischemic attack, unstable angina,aspirin,ticlopidine,dipyridamole, and clopidogrel, we searched the MEDLINE database as well as the trial register of the Cochrane Groups to identify studies published from 1960 to August 2004. We manually searched journals and abstract booklets; scrutinized reference lists of trials and review articles; and reviewed meta-analyses, scientific statements, and guidelines from official societies. Appropriate oral first-line antiplatelet therapy is aspirin for individuals with ST-segment elevation myocardial infarction; aspirin or clopidogrel for those with TIA or stroke, chronic stable angina, or peripheral arterial disease; and aspirin combined with clopidogrel for those with non-ST-segment elevation acute coronary syndrome. Aspirin combined with dipyridamole is a possible alternative for patients who experience a first episode of TIA or stroke in the absence of clinically apparent CAD. Although ticlopidine has been shown to be of benefit in various vascular conditions, its adverse-effect profile has limited its use. Aspirin, ticlopidine, clopidogrel, aspirin combined with clopidogrel, and aspirin combined with dipyridamole are effective in preventing recurrent vascular events among various subgroups of patients with vascular disease. Current clinical trial evidence favors the use of aspirin or clopidogrel as first-line agents for the majority of patients with vascular disease. Clinical trials evaluating combination antiplatelet therapies will direct future practice.


Cooling of the epileptic focus suppresses seizures with minimal influence on neurologic functions.
Focal brain cooling is effective for suppression of epileptic seizures, but it is unclear if seizures can be suppressed without a substantial influence on normal neurologic function. To address the issue, a thermoelectrically driven cooling system was developed and applied in free-moving rat models of focal seizure and epilepsy. Focal seizures limited to the unilateral forelimb were induced by local application of a penicillin G solution or cobalt powder to the unilateral sensorimotor cortex. A proportional integration and differentiation (PID)-controlled, thermoelectrically driven cooling device (weight of 11 g) and bipolar electrodes were chronically implanted on the eloquent area (on the epileptic focus) and the effects of cooling (20, 15, and 10°C) on electrocorticography, seizure frequency, and neurologic changes were investigated. Cooling was associated with a distinct reduction of the epileptic discharges. In both models, cooling of epileptic foci significantly improved both seizure frequency and neurologic functions from 20°C down to 15°C. Cooling to 10°C also suppressed seizures, but with no further improvement in neurologic function. Subsequent investigation of sensorimotor function revealed significant deterioration in foot-fault tests and the receptive field size at 15°C. Despite the beneficial effects in ictal rats, sensorimotor functions deteriorated at 15°C, thereby suggesting a lower limit for the therapeutic temperature. These results provide important evidence of a therapeutic effect of temperatures from 20 to 15°C using an implantable, hypothermal device for focal epilepsy.


Cracking the DNA Code for V(D)J Recombination.
To initiate V(D)J recombination for generating the adaptive immune response of vertebrates, RAG1/2 recombinase cleaves DNA at a pair of recombination signal sequences, the 12- and 23-RSS. We have determined crystal and cryo-EM structures of RAG1/2 with DNA in the pre-reaction and hairpin-forming complexes up to 2.75 Å resolution. Both protein and DNA exhibit structural plasticity and undergo dramatic conformational changes. Coding-flank DNAs extensively rotate, shift, and deform for nicking and hairpin formation. Two intertwined RAG1 subunits crisscross four times between the asymmetric pair of severely bent 12/23-RSS DNAs. Location-sensitive bending of 60° and 150° in 12- and 23-RSS spacers, respectively, must occur for RAG1/2 to capture the nonamers and pair the heptamers for symmetric double-strand breakage. DNA pairing is thus sequence-context dependent and structure specific, which partly explains the "beyond 12/23" restriction. Finally, catalysis in crystallo reveals the process of DNA hairpin formation and its stabilization by interleaved base stacking.


A practical method for measuring deoxynivalenol, nivalenol, and T-2 + HT-2 toxin in foods by an enzyme-linked immunosorbent assay using monoclonal antibodies.
We have developed and tested an enzyme-linked immunosorbent assay system for individual measurement of deoxynivalenol, nivalenol, and T-2 + HT-2 toxin using monoclonal antibodies for 3,4,15-triacetyl-nivalenol, for both 3,4,15-triacetyl-nivalenol and 3,15-diacetyl-deoxynivalenol, and for acetyl-T-2 toxin. The assay system comprised three kits (desinated the DON + NIV kit, the NIV kit, and the T-2 + HT-2 kit). The practical performance of the enzyme-linked immunosorbent assay system was assessed by assaying trichothecene mycotoxins in wheat kernels. The enzyme-linked immunosorbent assay system meets all the requirements for use in a routine assay in terms of sensitivity (detection limit: deoxynivalenol 80 ng/g, nivalenol 80 ng/g, T-2 toxin 30 ng/g), reproducibility (total coefficient of variation: 1.9-6.2%), accuracy (recovery: 93.8-112.0%), simplicity and rapidity (time required: <2 h), mass handling (>42 samples/assay), and a good correlation with gas chromatography-mass spectrometry (r=0.9146-0.9991). Components derived from the wheat extract did not interfere with the assay kits. The enzyme-linked immunosorbent assay system is a useful alternative method to gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, or liquid chromatography-ultraviolet absorption for screening cereals and foods for trichothecene mycotoxin contamination.


Axons take a dive: Specialized contacts of serotonergic axons with cells in the walls of the lateral ventricles in mice and humans.
In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular-subventricular zone (V-SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the function of supraependymal axons in the regulation of E1 cells.


Random responses inflate statistical estimates in heavily skewed addictions data.
Some respondents may respond at random to self-report surveys, rather than responding conscientiously (Meade and Craig, 2012), and this has only recently come to the attention of researchers in the addictions field (Godinho et al., 2016). Almost no research in the published addictions literature has reported screening for random responses. We illustrate how random responses can bias statistical estimates using simulated and real data, and how this is especially problematic in skewed data, as is common with substance use outcomes. We first tested the effects of varying amounts and types of random responses on covariance-based statistical estimates in distributions with varying amounts of skew. We replicated these findings in correlations from a real dataset (Add Health) by replacing varying amounts of real data with simulated random responses. Skew and the proportion of random responses influenced the amount and direction of bias. When the data were not skewed, uniformly random responses deflated estimates, while long-string random responses inflated estimates. As the distributions became more skewed, all types of random responses began to inflate estimates, even at very small proportions. We observed similar effects in the Add Health data. Failing to screen for random responses in survey data produces biased statistical estimates, and data with only 2.5% random responses can inflate covariance-based estimates (i.e., correlations, Cronbach's alpha, regression coefficients, factor loadings, etc.) when data are heavily skewed. Screening for random responses can substantially improve data quality, reliability and validity.


Immunoadsorption therapy for myasthenia gravis.
The results of a multicentre trial were analysed to evaluate the efficacy of immunoadsorption therapy for severe generalised myasthenia gravis. Twenty patients with myasthenia gravis who were concurrently receiving high dose prednisolone and azathioprine therapy were treated with an affinity-type adsorbent, using tryptophan-linked polyvinyl alcohol gel (IM-TR), according to a standardised treatment protocol. The 20 patients received five adsorption treatments within a period of 10 days. In 11, pronounced improvement of myasthenic weakness was seen and long-term remission was maintained. The treatment was especially effective in patients with thymic hyperplasia. Circulating acetylcholine receptor (AChR) antibodies were reduced by about 60% by treating one plasma volume. There was no difference in the rate of removal of the AChR antibodies between patients with thymic hyperplasia and patients with thymoma. No serious complications occurred during 100 procedures. It was concluded that the immunoadsorption therapy with IM-TR is useful in controlling symptoms in patients with severe myasthenia gravis who are otherwise unresponsive.


Saving teeth: Revisited. Esthetic improvement and long-term periodontal stability of a pathologic tooth migration case: An 84-month follow-up.
Advances in implant dentistry, often influence our clinical treatment planning and steer us as periodontists from our fundamental values of preserving teeth. Pathologic tooth migration (PTM) of maxillary anterior teeth is a common sequela of periodontitis in patients and results in significant esthetic and functional problems. Patients' growing concern about the esthetics of their teeth and their fears of losing teeth are often reasons for them to seek treatment. We commonly assign a hopeless prognosis to these pathologically migrated teeth because of the significant loss of periodontal support and go with the "safer" choice of replacing them with implants. The purpose of this case report is to present the long-term (7-year) periodontal stability of compromised teeth and to emphasize the successful outcomes achieved when orthodontics, non-surgical periodontal, and restorative treatments are combined. A 38-year-old, otherwise healthy male with compromised function and esthetics, PTM, periodontal disease, and missing teeth presented to our clinic. Primary treatment objectives were to 1) eliminate the periodontal inflammation and 2) restore and stabilize the occlusion by employing non-surgical periodontal treatment, adult orthodontics, and prosthodontics. Following interdisciplinary treatment, clinical and radiographic re-evaluation revealed significant clinical attachment gain, reduction in tooth mobility, favorable esthetics, and better overall prognosis. At an 84-month follow-up, the patient was periodontally healthy and retained his natural dentition. Interdisciplinary collaboration along with patient compliance may increase the longevity of periodontally compromised teeth and improve esthetics for periodontitis patients who suffer from PTM. Such long-term favorable outcomes reaffirm the value of classic periodontal treatment and the success of multidisciplinary treatment to save teeth as a viable alternative to the extraction of teeth and the placement of implant retained restorations.


Assessment of fetal cardiac function in mild preeclampsia.
This study investigated cardiac function in 65 fetuses of mildly preeclamptic mothers and 55 fetuses of healthy mothers at 26-40 weeks of gestation. Fetuses with intrauterine growth restriction were excluded. Cardiac functions were evaluated by M-mode, pulsed-wave, and tissue Doppler echocardiography. The two groups were similar in terms of maternal age, gravidity, parity, and gestational age. Peak systolic aortic and pulmonary artery velocities were significantly lower in the fetuses of the preeclamptic mothers than in the fetuses of the healthy mothers. The two groups did not differ significantly in terms of shortening fraction or with regard to mitral or tricuspid annular plane systolic excursion. Pulsed-wave Doppler-derived E/A ratios in the mitral and tricuspid valves were similar in the two groups. The deceleration time of early mitral inflow was prolonged in the fetuses of the preeclamptic mothers. The Ea, Aa, and Ea/Aa ratios in the interventricular septum, left ventricle posterior wall, and right ventricle free wall were lower in the preeclampsia group than in the control group. The E/Ea ratio was higher in the preeclampsia group than in the control group. The isovolumic relaxation time and the right and left myocardial performance indices were higher in the fetuses of the preeclamptic mothers than in the fetuses of the healthy mothers. An increased ductus venosus pulsatility index (PI) and a decreased middle cerebral artery (MCA) PI were found in the fetuses of the preeclamptic mothers. All the fetuses were asymptomatic. The results suggest that the increase in fetal cardiac afterload in mild preeclampsia may have caused early subclinical changes in fetal systolic and diastolic cardiac function. In addition, the decrease in MCA-PI may have been caused by redistribution of fetal cardiac output in favor of the left ventricle, secondary to increased placental vascular resistance.


Application of peptidyl radicals into a new radical cascade leading to unsaturated gamma-lactams.
Radical cyclization of dipeptides 1a-h proceeds smoothly to give five- and seven-membered rings in good to moderate total yields using Stork's catalytic tin hydride method. A radical is generated on a protecting group and translocated to the peptide moiety. Following a cyclization reaction, the vinyl radical can abstract hydrogen from a benzyl group on an amine, which results in elimination of the protected amine group. Encouraging results have notably been obtained with amino acids other than glycine.


[Thrombolytic therapy with streptodekase in ischemic strokes].
Thrombolytic agents previously employed in the treatment of ischemic stroke were associated with adverse side-effects and hemorrhagic complications. The use of streptodekase (S), a Soviet trombolytic drug, which is a long-acting immobilized ensyme proved to be highly effective. The efficacy of S in ischemic stroke was not investigated. The authors report the use of S within the first 6-8 hours after an ischemic stroke in thrombosis of the main stem of the middle meningeal artery in one case and of the vertebral and main arteries with the development of the locked-in syndrome in the other. In both cases the administration of S led to thrombolysis and restoration of the blood flow. The authors discuss the results of the use of S and indicate the necessity of the earliest possible administration of the drug with regard to a high sensitivity of the brain to ischemic lesions.


Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages.
Macrophage-derived foam cells express apolipoprotein E (apoE) abundantly in atherosclerotic lesions. To examine the physiologic role of apoE secretion by the macrophage in atherogenesis, bone marrow transplantation was used to reconstitute C57BL/6 mice with macrophages that were either null or wild type for the apoE gene. After 13 weeks on an atherogenic diet, C57BL/6 mice reconstituted with apoE null marrow developed 10-fold more atherosclerosis than controls in the absence of significant differences in serum cholesterol levels or lipoprotein profiles. ApoE expression was absent in the macrophage-derived foam cells of C57BL/6 mice reconstituted with apoE null marrow. Thus, lack of apoE expression by the macrophage promotes foam cell formation. These data support a protective role for apoE expression by the macrophage in early atherogenesis.


Multi-Modal Co-Learning for Liver Lesion Segmentation on PET-CT Images.
Liver lesion segmentation is an essential process to assist doctors in hepatocellular carcinoma diagnosis and treatment planning. Multi-modal positron emission tomography and computed tomography (PET-CT) scans are widely utilized due to their complementary feature information for this purpose. However, current methods ignore the interaction of information across the two modalities during feature extraction, omit the co-learning of the feature maps of different resolutions, and do not ensure that shallow and deep features complement each others sufficiently. In this paper, our proposed model can achieve feature interaction across multi-modal channels by sharing the down-sampling blocks between two encoding branches to eliminate misleading features. Furthermore, we combine feature maps of different resolutions to derive spatially varying fusion maps and enhance the lesions information. In addition, we introduce a similarity loss function for consistency constraint in case that predictions of separated refactoring branches for the same regions vary a lot. We evaluate our model for liver tumor segmentation using a PET-CT scans dataset, compare our method with the baseline techniques for multi-modal (multi-branches, multi-channels and cascaded networks) and then demonstrate that our method has a significantly higher accuracy ( ) than the baseline models.


Xenometabolite signatures in the UC Davis type 2 diabetes mellitus rat model revealed using a metabolomics platform enriched with microbe-derived metabolites.
The gut microbiome has the potential to create or modify xenometabolites (i.e., nonhost-derived metabolites) through de novo synthesis or modification of exogenous and endogenous compounds. While there are isolated examples of xenometabolites influencing host health and disease, wide-scale characterization of these metabolites remains limited. We developed a metabolomics platform ("XenoScan") using liquid chromatography-mass spectrometry to characterize a range of known and suspected xenometabolites and their derivatives. This assay currently applies authentic standards for 190 molecules, enriched for metabolites of microbial origin. As a proof-of-principle, we characterized the cecal content xenometabolomics profile in adult male lean Sprague-Dawley (LSD) and University of California, Davis type 2 diabetes mellitus (UCD-T2DM) rats at different stages of diabetes. These results were correlated to specific bacterial species generated via shotgun metagenomic sequencing. UCD-T2DM rats had a unique xenometabolite profile compared with LSD rats, regardless of diabetes status, suggesting that at least some of the variation is associated with host genetics. Furthermore, modeling approaches revealed that several xenometabolites discriminated UCD-T2DM rats at early stages of diabetes versus those at 3 mo postdiabetes onset. Several xenometabolite hubs correlated with specific bacterial species in both LSD and UCD-T2DM rats. For example, indole-3-propionic acid negatively correlated with species within the Oscillibacter genus in UCD-T2DM rats considered to be prediabetic or recently diagnosed diabetic, in contrast to gluconic acid and trimethylamine, which were positively correlated with Oscillibacter species. The application of a xenometabolite-enriched metabolomics assay in relevant milieus will enable rapid identification of a wide variety of gut-derived metabolites, their derivatives, and their potential biochemical origins of xenometabolites in relationship to host gastrointestinal microbial ecology.NEW & NOTEWORTHY We debut a liquid chromatography-mass spectrometry (LC/MS) platform called the XenoScan, which is a metabolomics platform for xenometabolites (nonself-originating metabolites). This assay has 190 in-house standards with the majority enriched for microbe-derived metabolites. As a proof-of-principle, we used the XenoScan to discriminate genetic differences from cecal samples associated with different rat lineages, in addition to characterizing diabetes progression in rat model of type 2 diabetes. Complementing microbial sequencing data with xenometabolites uncovered novel microbial metabolism in targeted organisms.


Non-invasive survey technology for estimating the distribution of oxidant solution: A pilot injection study.
In-situ chemical oxidation (ISCO) can remove pollutants efficiently. However, the most important key to successfully conducting ISCO on site is to place the oxidant in close contact with the contaminant. Therefore, monitoring tools that provide for enhanced tracking of the injectate offer considerable benefit to guide subsequent ISCO injections. In this study, we applied the MagnetoMetric Resistivity (MMR) method to survey the distribution of an injected oxidant. A pilot test was conducted on a 10 m × 10 m site, and the sodium persulfate injection involved four pulse injections from one injection well. A magnetic field survey coupled with conventional monitoring was performed before the initial injection and after each pulse injection. The results of this study showed that groundwater samples from six observation wells and seven direct-push EC loggings did not provide sufficient data to quantify the distribution and flow behavior of the injected oxidant. However, the magnetic field survey visually showed the dynamic distribution of the injected oxidant, and the flow pathways and flow behavior were assessed accordingly. Although the flow behavior of injected solution was changeable in the aquifer, but the magnetic field survey combined with the monitoring of the well samples helped to explain the abnormal changes in the electrical conductivity of the observation wells and supports the use of the magnetic field survey technology as a method of monitoring ISCO injections.


Thermodynamic parameters of helix-random coil transitions in polypeptide chains. IV. Random copolymers of L-alanine with L-glutamic acid.
pH-Induced helix-random coil transitions in random copolymers of Ala with Glu have been investigated in order to determine the effect of Ala on the stability of the helical state of polyglutamic acid. The free energies for the transfer of one uncharged Glu residue from a random coil to a helix (deltaGo) have been determined from potentiometric titration curves by the method of Zimm and Rice. It has been shown that the introduction of Ala hampers the transfer of a Glu residue from a random coil to a helix (reduces -deltaGo), although Ala itself is a helix-forming residue, i.e., its free energy decreases during helix formation. This has suggested that its introduction weakens the helix-stabilizing interactions between the uncharged Glu residues (apparently hydrogen bonds). The evaluation of the intrinsic helix-random coil equilibrium constant s for uncharged Glu residues with consideration of this situation yields a value which is smaller than the value of s for (Glu)n and in good agreement with the theoretical values.


Dendritic cell vaccination combined with a conventional chemotherapy for patients with relapsed or advanced pancreatic ductal adenocarcinoma: a single-center phase I/II trial.
The prognosis of patients with advanced pancreatic cancer is poor. In the present phase I/II study, we have evaluated the safety and the feasibility of Wilms' tumor 1 (WT1) and/or mucin1 (MUC1) peptide-pulsed dendritic cell (DC) vaccination in combination with chemotherapy in patients with advanced or relapsed pancreatic ductal adenocarcinoma (PDAC). Sixty-five eligible patients were enrolled. No severe adverse events related to the vaccinations were observed. Objective response rate and disease control rate was 12.3% and 50.8%, respectively. Median progression-free survival and overall survival were 4.9 and 9.6 months, respectively. DC vaccinations augmented WT1- and MUC1-specific immunity which might be related to clinical outcome. These results indicate that DC-based immunotherapy combined with a conventional chemotherapy is safe and feasible for patients in advanced stage of PDAC.


Epstein-Barr viral loads do not predict post-transplant lymphoproliferative disorder in pediatric lung transplant recipients: A multicenter prospective cohort study.
Prediction of PTLD after pediatric lung transplant remains difficult. Use of EBV VL in WB has been poorly predictive, while measurement of VL in BAL fluid has been suggested to have enhanced utility. The NIH-sponsored Clinical Trials in Organ Transplantation in Children (CTOTC-03) prospectively obtained serial quantitative measurements of EBV PCR in both WB and BAL fluid after pediatric lung transplantation. Descriptive statistics, contingency analyses, and Kaplan-Meier analyses evaluated possible association between EBV and PTLD. Of 61 patients, 34 (56%) had an EBV+PCR (at least once in WB or BAL). EBV donor (D)+patients more often had a positive PCR (D+/recipient (R)-: 13/18; D+/R+: 14/23) compared to EBV D- patients (6/17). Several D-/R- (5/12) patients developed EBV, but none developed PTLD. All four PTLD patients were D+/R- with EBV+PCR. Neither the time to first EBV+PCR nor the CT for PCR positivity in BAL or WB was statistically different between those with and without PTLD. Having an EBV-seropositive donor was associated with increased risk of EBV+PCR in WB. EBV load in BAL was not predictive of PTLD.


Hemisphere lateralization of inductive and deductive processes.
Experiments were performed on 453 Wistar rats. Motion-food and electrodefensive behavioral techniques were applied. The following models were used: a conditioned reflex formation, generalization and specialization of a conditioned reflex, the dynamic stereotype, visual image synthesizing, a conditioned reflex to a stimulus complex. Primary and secondary analysis and synthesis of stimuli were discriminated. Induction and deduction were considered as a certain sequence of analysis and synthesis in time. Primary analysis and secondary synthesis were shown to be mainly lateralized in the left hemisphere and primary synthesis and secondary analysis in the right one. The conclusion was drawn that, in animals, the left hemisphere processes information mainly according to the principle of induction (from the particular to the general) and the right one does so according to the principle of deduction (from the general to the particular).


Reconstructions of shear modulus, Poisson's ratio, and density using approximate mean normal stress lambda epsilon alpha alpha as unknown.
As a differential diagnosis technique for living soft tissues, we are developing ultrasonic-strain-measurement-based shear modulus reconstruction methods. Previously, we reported three-dimensional (3-D) and 2-D reconstruction methods utilizing a typical Poisson's ratio very close to 0.5 (nearly-incompressible). However, because a decrease in the accuracy of the reconstructed value was confirmed to be due to the difference between the original value and the set value, we proposed 3-D and 2-D methods of reconstructing Poisson's ratio as well. Furthermore, we proposed methods of reconstructing density and dealing with dynamic deformation. However, due to tissue incompressibility, the reconstructions of shear modulus, Poisson's ratio, and density became unstable. In this report, to obtain stable, unique reconstructions, we describe a new reconstruction method using mean normal stress approximated by the product of one of Lame's constants X and volume strain epsilon alpha alpha as an unknown. Regularization is simultaneously applied to the respective distributions to decrease the instability of the reconstructions due to measurement errors of the deformation. This method also enables stable, unique reconstructions of shear modulus and density under the condition that the mean normal stress remains unknown. We also verify the effectiveness of this method through 3-D simulations, while showing erroneous artifacts occurring when 2-D and 1-D reconstructions are performed.


Life-event stress induced by the Great East Japan Earthquake was associated with relapse in ulcerative colitis but not Crohn's disease: a retrospective cohort study.
Stress is thought to be one of the triggers of relapses in patients with inflammatory bowel disease (IBD). We examined the rate of relapse in IBD patients before and after the Great East Japan Earthquake. A retrospective cohort study. 13 hospitals in Japan. 546 ulcerative colitis (UC) and 357 Crohn's disease (CD) patients who received outpatient and inpatient care at 13 hospitals located in the area that were seriously damaged by the earthquake. Data on patient's clinical characteristics, disease activity and deleterious effects of the earthquake were obtained from questionnaires and hospital records. We evaluated the relapse rate (from inactive to active) across two consecutive months before and two consecutive months after the earthquake. In this study, we defined 'active' as conditions with a partial Mayo score=2 or more (UC) or a Harvey-Bradshaw index=6 or more (CD). Among the UC patients, disease was active in 167 patients and inactive in 379 patients before the earthquake. After the earthquake, the activity scores increased significantly (p<0.0001). A total of 86 patients relapsed (relapse rate=15.8%). The relapse rate was about twice that of the corresponding period in the previous year. Among the CD patients, 86 patients had active disease and 271 had inactive disease before the earthquake. After the earthquake, the activity indices changed little. A total of 25 patients experienced a relapse (relapse rate=7%). The relapse rate did not differ from that of the corresponding period in the previous year. Multivariate analyses revealed that UC, changes in dietary oral intake and anxiety about family finances were associated with the relapse. Life-event stress induced by the Great East Japan Earthquake was associated with relapse in UC but not CD.


Evaluation of SPECT quantification of radiopharmaceutical distribution in canine myocardium.
This study evaluates the quantitative accuracy of SPECT for in vivo distributions of 99mTc radiopharmaceuticals using fanbeam (FB) and parallel-beam (PB) collimators and compares uniform and nonuniform attenuation correction methods in terms of quantitative accuracy. SPECT quantification of canine myocardial radioactivity was performed followed by well counter measurements of extracted myocardial tissue samples. Transmission scans using a line source and an FB collimator were performed to generate nonuniform attenuation maps of the canine thorax. Emission scans with two energy windows were acquired. Images were reconstructed using a filtered backprojection algorithm, with a dual-window scatter subtraction combined with either no attenuation compensation or single iteration Chang attenuation compensation based on an uniform attenuation map (mu = 0.152 cm-1) or the nonuniform transmission map. The measured mean counts from the SPECT images were converted to radionuclide concentrations (MBq/g) using a standard source calibration and were compared with those obtained using the well counter. The experimental results demonstrate that, compared with well counter values, the in vivo distributions of 99mTc were most accurately determined in FB and PB SPECT reconstructions with nonuniform attenuation compensation, under-estimated without attenuation compensation and overestimated with uniform attenuation compensation.


Polyphosphate dynamics in mycorrhizal roots during colonization of an arbuscular mycorrhizal fungus.
Inorganic polyphosphate (poly P) has been considered to be a translocatable form of phosphate (Pi) in arbuscular mycorrhizal fungi (AMF). Here we examined time-course changes in poly P content during the AMF colonization process. Onion (Allium cepa) plants were cultured with or without inoculation with Gigaspora margarita for 2-8 wk with periodic sampling. Poly P in the extracts, purified through gel filtration, was quantified by the reverse reaction of polyphosphate kinase. The length of poly P in mycorrhizal roots appeared to be shorter than in extraradical hyphae or in spores of the AMF, indicating that AMF depolymerize poly P before providing Pi to the host. The poly P content increased as colonization proceeded, and was highly correlated with the weight of the colonized roots. These results support the model that AMF supply Pi to the host through the poly P pool, and that the poly P content of a mycorrhizal root can be a good indicator of the Pi-supplying activity of AMF.


Degarelix for treating advanced hormone-sensitive prostate cancer.
Degarelix is a gonadotropin-releasing hormone antagonist that leads to medical castration used to treat men with advanced or metastatic prostate cancer, or both. It is unclear how its effects compare to standard androgen suppression therapy. To assess the effects of degree compared with standard androgen suppression therapy for men with advanced hormone-sensitive prostate cancer. We searched multiple databases (CENTRAL, MEDLINE, Embase, Scopus, Web of Science, LILACS until September 2020), trial registries (until October 2020), and conference proceedings (until December 2020). We identified other potentially eligible trials by reference checking, citation searching, and contacting study authors. We included randomized controlled trials comparing degarelix with standard androgen suppression therapy for men with advanced prostate cancer. Three review authors independently classified studies and abstracted data from the included studies. The primary outcomes were overall survival and serious adverse events. Secondary outcomes were quality of life, cancer-specific survival, clinical progression, other adverse events, and biochemical progression. We used a random-effects model for meta-analyses and assessed the certainty of evidence for the main outcomes according to GRADE. We included 11 studies with a follow-up of between three and 14 months. We also identified five ongoing trials. Primary outcomes Data to evaluate overall survival were not available. Degarelix may result in little to no difference in serious adverse events compared to standard androgen suppression therapy (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.62 to 1.05; low-certainty evidence; 2750 participants). Based on 114 serious adverse events in the standard androgen suppression group, this corresponds to 23 fewer serious adverse events per 1000 participants (43 fewer to 6 more). We downgraded the certainty of evidence for study limitations and imprecision. Secondary outcomes Degarelix likely results in little to no difference in quality of life assessed with a variety of validated questionnaires (standardized mean difference 0.06 higher, 95% CI 0.05 lower to 0.18 higher; moderate-certainty evidence; 2887 participants), with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. Data to evaluate cancer-specific survival were not available. The effects of degarelix on cardiovascular events are very uncertain (RR 0.15, 95% CI 0.04 to 0.61; very low-certainty evidence; 80 participants). We downgraded the certainty of evidence for study limitations, imprecision, and indirectness as this trial was conducted in a unique group of high-risk participants with pre-existing cardiovascular morbidities. Degarelix likely results in an increase in injection site pain (RR 15.68, 95% CI 7.41 to 33.17; moderate-certainty evidence; 2670 participants). Based on 30 participants per 1000 with injection site pain with standard androgen suppression therapy, this corresponds to 440 more injection site pains per 1000 participants (192 more to 965 more). We downgraded the certainty of evidence for study limitations. We did not identify any relevant subgroup differences for different degarelix maintenance doses. We did not find trial evidence for overall survival or cancer-specific survival comparing degarelix to standard androgen suppression, but serious adverse events and quality of life may be similar between groups. The effects of degarelix on cardiovascular events are very uncertain as the only eligible study had limitations, was small with few events, and was conducted in a high-risk population. Degarelix likely results in an increase in injection site pain compared to standard androgen suppression therapy. Maximum follow-up of included studies was 14 months, which is short. There is a need for methodologically better designed and executed studies with long-term follow-up evaluating men with metastatic prostate cancer.


Modulation of spontaneous transmitter release during depression and posttetanic potentiation of Aplysia sensory-motor neuron synapses isolated in culture.
An Aplysia motor neuron cocultured with a single presynaptic sensory neuron exhibits spontaneous miniature EPSPs or EPSCs ("minis") that can be used to assay the release process directly, independent of the presynaptic action potential. Sensory-motor synapses in culture undergo homosynaptic depression with low frequency stimulation (< 1 Hz) and posttetanic potentiation (PTP) with high-frequency stimulation (20 Hz) much as they do in intact ganglia, except that PTP does not occur in culture when sensory neurons are impaled. We measured spontaneous release during each of these two forms of homosynaptic plasticity as a way of testing whether they involve depletion or mobilization of synaptic vesicles (Gingrich and Byrne, 1985). We find that PTP is accompanied by an increase in mini frequency that decays with a time course parallel to the decay of evoked EPSP facilitation. In contrast, depression is not paralleled by a reduction of mini frequency, although extensive stimulation reduces mini frequency for a brief period immediately following stimulation. Neither form of plasticity altered miniature EPSP or miniature EPSC amplitude, corroborating previous evidence that both are presynaptically mediated. These findings suggest that PTP is mediated by a presynaptic mechanism independent of the action potential, such as vesicle mobilization. This presumably Ca(2+)-dependent mechanism does not involve protein kinase C, since we found that the inhibitor H7 does not specifically block PTP. In contrast to PTP, depression appears to involve changes unique to excitation-secretion coupling, such as reduced Ca2+ influx during the action potential (Klein et al., 1980).


Supercontinuum generation by femtosecond single and dual wavelength pumping in photonic crystal fibers with two zero dispersion wavelengths.
We investigate supercontinuum generation in photonic crystal fibers under femtosecond single and dual wavelength pumping experimentally and by numerical simulations. Details about the expansion of the blue but also the red side of the continuum due to cross-phase modulation (XPM) and transfer of energy to dispersive waves are revealed and experimentally confirmed. Additionally, simple guidelines are given to predicte the maximum bandwidth of supercontinuum generation only by the use of the dispersion curve of the fiber.


A case study of cost-benefit analysis in occupational radiological protection within the healthcare system of Sweden.
The aim of the present study was to demonstrate cases of cost-benefit analysis within healthcare, of how economic factors can be considered in occupational radiological protection, in agreement with the as low as reasonably achievable principle and present Swedish legislations. In the first part of the present study, a comparison of examples within health economics used by authorities and institutes in Sweden was made. The comparison focused on value of a statistical life, quality-adjusted life year, and monetary cost assigned to a unit of collective dose for radiation protection purposes (α-value). By this comparison, an α-value was determined as an interval between $45 and $450 per man-mSv, for the Swedish society in 2021. The α-value interval can be interpreted as following: Less than $45 per man-mSv is a good investment. From $45 to $450 per man-mSv, other factors than costs and collective dose are important to consider. More than $450 per man-mSv is too expensive. In the second part of the present study, seven cases of cost-benefit analyses in occupational radiological protection were provided. The present study focused specifically on cases where the relevant factors were costs and collective dose. The present case study shows a large variation in costs per collective dose from different types of occupational radiological protection, used at Skaraborg Hospital in Sweden.


Retrospective evaluation of two-year results with a filtering trabeculotomy in comparison to conventional trabeculectomy by exact matching.
Background: To compare two-year results of a filtering trabeculotomy (FTO) to conventional trabeculectomy (TE) in open-angle glaucoma by exact matching. Methods: 110 patients received an FTO and 86 a TE. FTO avoided the need for an iridectomy due to a preserved trabeculo-descemet window anterior to the scleral flap. TE employed a trabecular block excision and iridectomy. Mitomycin C was used in both. FTO and TE were exact matched by baseline intraocular pressure (IOP) and the number of glaucoma medications. Complete and qualified success (IOP ≤18 mmHg and IOP reduction ≥ 30%, with or without medication) were primary endpoints. IOP, visual acuity (BCVA), complications and intervention were secondary endpoints. Results: 44 FTO were exact matched to 44 TE. The IOP baseline in both groups was 22.5±4.7 mmHg on 3±0.9 medications. At 24 months, complete success was reached by 59% in FTO and 66% in TE, and qualified success by 59% in FTO and 71% in TE. In FTO, IOP was reduced to 12.4±4.3 mmHg at 12 months and 13.1±4.1 mmHg at 24 months. In TE, IOP was 11.3±2.2 mmHg at 12 months and 12.0±3.5 mmHg at 24 months. Medications could be reduced at 24 months to 0.6±1.3 in FTO and 0.2±0.5 in TE. There were no significant differences between the two groups in IOP, medications, complications or interventions at any point. Conclusion: Modifying aqueous flow through a limited trabeculotomy in FTO yielded clinical outcomes similar to traditional TE but allowed to avoid an iridectomy.