G(1) and G(2) cell-cycle arrest following microtubule depolymerization in human breast cancer cells.
Microtubule-depolymerizing agents are widely used to synchronize cells, screen for mitotic checkpoint defects, and treat cancer. The present study evaluated the effects of these agents on normal and malignant human breast cell lines. After treatment with 1 microM nocodazole, seven of ten breast cancer lines (type A cells) arrested in mitosis, whereas the other three (type B cells) did not. Similar effects were observed with 100 nM vincristine or colchicine. Among five normal mammary epithelial isolates, four exhibited type A behavior and one exhibited type B behavior. Further experiments revealed that the type B cells exhibited a biphasic dose-response curve, with mitotic arrest at low drug concentrations (100 nM nocodazole or 6 nM vincristine) that failed to depolymerize microtubules and a p53-independent p21(waf1/cip1)-associated G(1) and G(2) arrest at higher concentrations (1 microM nocodazole or 100 nM vincristine) that depolymerized microtubules. Collectively, these observations provide evidence for coupling of premitotic cell-cycle progression to microtubule integrity in some breast cancer cell lines (representing a possible "microtubule integrity checkpoint") and suggest a potential explanation for the recently reported failure of some cancer cell lines to undergo nocodazole-induced mitotic arrest despite intact mitotic checkpoint proteins.


Solitary fibrous tumor of the orbit: is it rare? Report of a case series and review of the literature.
The real incidence of solitary fibrous tumor (SFT) of the orbit is unknown, but it seems that since it was first described in 1994, orbital SFT has been increasingly recognized. We believe that the orbital SFT is a relatively common tumor and that it should be considered in the differential diagnosis of any orbital tumor. Interventional case series. Four new cases of orbital SFT. Four patients affected by solitary fibrous tumor of the orbit are described. One patient experienced a recurrent SFT shortly after initial surgical excision performed elsewhere. Thirty-eight cases have been reported in the literature in 7 years. The number of orbital SFTs reported has been increasing, reaching an average of more than five tumors reported per year. Since the first orbital SFT was described in 1994, 37 cases have been reported in the literature. We add four new cases in our series, including a recurrent tumor. A total of 42 cases have now been described, eight with recurrences. Malignant transformation occurred in one case. We believe that before 1994, the diagnosis orbital SFT was confused with other benign orbital tumors, such as fibrous histiocytoma and hemangiopericytoma because of a lack of use of immunohistochemical techniques. This entity should now be considered relatively common and should be included in the differential diagnosis of orbital tumors in any age group. Local recurrences of SFT are possible and usually follow an incomplete initial excision. Recurrent tumors in the orbit have shown the tendency to infiltrate the surrounding tissues and the bone, rendering complete secondary excision more difficult. Recurrent orbital SFT also has the potential for malignant transformation. The treatment of choice of orbital SFT is complete surgical excision and careful follow-up. Considering the more aggressive course followed by recurrent tumor, correct diagnosis and management is essential.


Recurrence of duodenal ulceration in patients on maintenance sucralfate. A 12-month follow-up study.
A single-blind, 1-year follow-up study of 70 patients with recently healed duodenal ulcers was undertaken to assess the value of sucralfate (Ulsanic; Continental Ethicals) in preventing recurrence and to establish the lowest dose required to achieve this. Endoscopy was repeated on clinical relapse and routinely at 6 and 12 months. Fifty of the 70 patients were followed up for 12 months or to recurrence proved on endoscopy; the remaining 20 patients were excluded from analysis because of default or protocol violation. Endoscopic evidence of recurrence was found in 6 of 19 patients (32%) given sucralfate 1 g twice a day (group B), in 7 of 15 (47%) on sucralfate 1 g at night (group A), and in 13 of 16 controls (81%). The recurrence rates in groups A and B were significantly lower than in the control group (P less than 0,05 and P less than 0,005 respectively), and there was a significant gradient between the number of patients in remission at 12 months and the amount of medication (P less than 0,05).


Mass Release of Trichogramma evanescens and T. cacoeciae Can Reduce Damage by the Apple Codling Moth Cydia pomonella in Organic Orchards under Pheromone Disruption.
Cydia pomonella is a major pest in apples in Denmark. Trichogramma spp. are known biocontrol agents of C. pomonella eggs and two naturally occurring species in Denmark, which are also both commercially available, were chosen for mass-release trials. Trichogramma evanescens, T. cacoeciae or a mix of the two species were evaluated for mass-release to control C. pomonella in two commercial organic apple orchards, one in 2012 and one in 2013, using a complete randomized block design. Pheromone disruption was used in both orchards, making the study one of the first to evaluate Trichogramma release under a mating disruption regime. Trichogramma activity was assessed using bait cards with Sitotroga cerealella eggs. The percent C. pomonella damaged fruit was recorded and the fruit yield was estimated. In 2012 cool and wet weather conditions resulted in low Trichogramma activity (<16% bait cards parasitized) and only T. evanescens was recovered from bait cards. The conditions in 2013 were warmer but T. evanescens was still >10 times more frequently found in bait cards than T. cacoeciae. There was a significant effect of the treatment and year (p = 0.009) and of the sampling period (p = 0.0008) on Trichogramma activity (proportion bait cards parasitized), with no significant difference between treatments in 2012. In 2013 the highest activity was found in T. evanescens and mixed treatments, in July reaching 69% and 47% bait cards parasitized, respectively. Fruit damage was highest in the control plots (7.1%) compared with Trichogramma treatments (T. evanescens 2.8%, T. cacoeciae 3.8%, mixed 3.3%) (p = 0.028). Yield did not differ significantly between treatments. In conclusion, Trichogramma mass release is a promising biocontrol method for use in the Danish climate, but further studies are needed regarding the performance of the two Trichogramma species (and potential other Trichogramma species) towards C. pomonella eggs in the field to identify the best biocontrol candidate.


[Intestinal endotoxin in induction of type 1 diabetes].
We studied serum level of intestinal flora endotoxin (LPS) in 45 children and adolescents aged 3-17 years old with diabetes mellitus type 1. Levels of endotoxin, were significantly elevated in type 1 diabetic patients (2.89 +/- 0.33 Eu/ml) compared with control (0.4 +/- 0.03 Eu/ml). There was significant difference in serum LPS levels in patients with type 1 diabetes onset (3.93 +/- 0.79 Eu/ml) compared with children and adolescent with old time diabetes (2.37 +/- 0.27 Eu/ml). These results have a major implication on our understanding of the role of gut flora endotoxin in pathogenesis of type 1 diabetes.


Chaos, synchronization, and desynchronization in a liquid-fueled diffusion-flame combustor with an intrinsic hydrodynamic mode.
We experimentally investigate the nonlinear dynamics of a thermoacoustically self-excited aero-engine combustion system featuring a turbulent swirling liquid-fueled diffusion flame in a variable-length combustor. We focus on the steady-state dynamics via simultaneous measurements of the acoustic pressure in the combustor and the heat release rate (HRR) from the flame. When the combustor length is increased following the onset of thermoacoustic instability, we find that the pressure signal transitions from a period-1 limit cycle to chaos, whereas the HRR signal remains chaotic owing to the presence of an intrinsic hydrodynamic mode in the flame. When the hydrodynamic mode is filtered out of the data, we find that the pressure and HRR signals are in generalized synchronization. However, when the hydrodynamic mode is retained in the data, we find that the pressure and HRR signals are either weakly phase synchronized or desynchronized. This study has two main contributions: (i) it shows that a liquid-fueled diffusion-flame combustor can exhibit dynamics as complex as those of its gaseous-fueled premixed-flame counterparts and (ii) it highlights the need to be exceptionally careful when selecting a diagnostic signal from which to calculate nonlinear measures of self-excited thermoacoustic oscillations, because our experiments show that the pressure and HRR signals can be desynchronized by the presence of a hydrodynamic mode in the flame at a frequency different from that of the dominant thermoacoustic mode.


Effects of feed restriction and prolactin-release inhibition at drying off on metabolism and mammary gland involution in cows.
A cow's risk of acquiring a new intramammary infection during the dry period increases with milk production at drying off and decreases as mammary gland involution progresses. A method commonly used to reduce milk production is a drastic reduction in feed supply in the days that precede drying off. Milk production can also be reduced by inhibiting the lactogenic signal driven by prolactin (PRL). This study aimed to compare the effects of these 2drying-off procedures on metabolism, immunity, and mammary gland involution in cows. A total of 24Holstein cows in late lactation were assigned to 1 of 3treatments based on milk yield, somatic cell count, and parity. The cows were fed a lactation diet until drying off (control; n=8), only dry hay during the last 5d before drying off (DH; n=8), or the same lactation diet as the control cows but with twice-daily i.m. injections of 4mg of quinagolide, a specific inhibitor of PRL release, from 5d before drying off until 13d after (QN; n=8). Quinagolide induced a decrease in PRL concentration in blood and in milk and mammary secretions on all the injection days. Interestingly, PRL was also depressed in the blood and milk of the hay-fed cows before drying off. Both the QN and DH treatments induced a decrease in milk production, which averaged 17.9 and 10.1kg/d for the QN and DH cows, respectively, at drying off in comparison with 24.8kg/d for the control cows. Both BSA concentration and Na(+)-to-K(+) ratio increased faster in the mammary secretions of both the DH and QN cows than in those of the control cows, whereas citrate-to-lactoferrin ratio, another indicator of involution rate, decreased faster. The DH treatment decreased blood concentrations of glucose and most amino acids and increased blood concentrations of β-hydroxybutyrate and nonesterified fatty acids. Quinagolide increased blood glucose but did not affect the other metabolites. The serum harvested on d-1 from the hay-fed cows reduced peripheral blood mononuclear cell proliferation and IL-4 production, whereas the serum from the quinagolide-treated cows had no effect. In conclusion, this experiment shows that PRL-release inhibition could be a new alternative for reducing milk production before drying off and for hastening mammary gland involution without disturbing the metabolism of the cow.


[Purely phasic neurons of the medial geniculate body--markers of changes in the signal].
The majority of neurons in the medial geniculate body responded with short bursts of activity to increments of the noise signal, and some of them--to decrements of the signal as well. Responses to changes in the signal envelope were only observed in narrow intensity range different for different neurons. The data suggest that division of neurons into groups acting within local dynamic ranges related to the cochlear nerve level, remains on the medial geniculate body level so as the ability of the organism to detect small changes in the signal envelope is maintained by the convergence of information from local detectors.


Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with (188)Re.
Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of (188)Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all (188)Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The (188)Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of (188)Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental (188)Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of (188)Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.


Child health clincs and inverse care laws: evidence from longitudinal study of 1878 pre-school children.
In a longitudinal study it was intended that 1878 children should receive periodic developmental examinations from the age of 6 weeks to 3 years. The children were divided into those with a high or low risk of developmental problems. Although clinic attendance rate of 85-89% were achieved in the catchment area 100% coverage was difficult because of population mobility and non-attendance at clinics. Children in families who moved away from the area were more difficult to trace and thus more likely to miss developmental examinations. This was a greater problem in the high-risk group. Altogether 683 home developmental examinations were carried out on 269 children who did not attend clinics. Thirty-five per cent of these children were in the high-risk group compared with 22% in the study population, and significantly more had developmental problems. Thus one possible way of reaching and helping such children is though home developmental examinations.


Injury Profiles Associated with Artisanal and Small-Scale Gold Mining in Tarkwa, Ghana.
Artisanal and small-scale gold mining (ASGM) is inherently risky, but little is known about mining-associated hazards and injuries despite the tremendous growth worldwide of ASGM and the benefits it offers. The current study aimed to characterize the physical injuries associated with ASGM in Ghana to guide policy formulation. A cross-sectional survey was carried out in the Tarkwa mining district of the Western Region of Ghana in 2014. A total of 404 small-scale miners were recruited and interviewed regarding their occupational injury experiences over the preceding 10 years using a paper-based structured questionnaire. Nearly one-quarter (23.5%) of the miners interviewed reported getting injured over the previous 10 years, and the overall injury rate was calculated to be 5.39 per 100 person years. The rate was significantly higher for women (11.93 per 100 person years) and those with little mining experience (e.g., 25.31 per 100 person years for those with less than one year of work experience). The most injury-prone mining activities were excavation (58.7%) and crushing (23.1%), and over 70% of the injuries were reported to be due to miners being hit by an object. The majority of the injuries (57%) were lacerations, and nearly 70% of the injuries were to the upper or lower limbs. Approximately one-third (34.7%) of the injuries resulted in miners missing more than two weeks of work. One-quarter of the injured workers believed that abnormal work pressure played a role in their injuries, and nearly two-fifths believed that their injuries could have been prevented, with many citing personal protective equipment as a solution. About one-quarter of the employees reported that their employers never seemed to be interested in the welfare or safety of their employees. These findings greatly advance our understanding of occupational hazards and injuries amongst ASGM workers and help identify several intervention points.


Alteration of Notch signaling in skeletal development and disease.
Notch signaling is an evolutionarily conserved mechanism for specifying and regulating organogenesis and tissue renewal. Human and mouse genetic studies have demonstrated mutations in many components of the Notch signaling pathway that cause skeletal patterning defects. More recently, the in vivo effects of Notch signaling on osteoblast specification, proliferation, and differentiation have been demonstrated in addition to its regulation of osteoclast activity. However, while our understanding of canonical Notch signaling in skeletal biology is rapidly evolving, the role of noncanonical Notch signaling is still poorly understood. In a pathologic context, aberration of Notch signaling is also associated with osteosarcoma. These studies raise the question of how Notch may interact with other signaling pathways, such as Wnt. Finally, manipulation of Notch signaling for bone-related diseases remains complex because of the temporal and context-dependent nature of Notch signaling during mesenchymal stem cell and osteoblast differentiation.


Risk for Major Hemorrhages in Patients Receiving Clopidogrel and Aspirin Compared With Aspirin Alone After Transient Ischemic Attack or Minor Ischemic Stroke: A Secondary Analysis of the POINT Randomized Clinical Trial.
Results show the short-term risk of hemorrhage in treating patients with acute transient ischemic attack (TIA) or minor acute ischemic stroke (AIS) with clopidogrel plus aspirin or aspirin alone. To characterize the frequency and kinds of major hemorrhages in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. This secondary analysis of the POINT randomized, double-blind clinical trial conducted in 10 countries in North America, Europe, and Australasia included patients with high-risk TIA or minor AIS who were randomized within 12 hours of symptom onset and followed up for 90 days. The total enrollment, which occurred from May 28, 2010, through December 17, 2017, was 4881 and constituted the intention-to-treat group; 4819 (98.7%) were included in the as-treated analysis group. The primary safety analyses were as-treated, classifying patients based on study drug actually received. Intention-to-treat analyses were performed as secondary analyses. Data were analyzed in April 2018. Patients were assigned to receive clopidogrel (600 mg loading dose on day 1 followed by 75 mg daily for days 2-90) or placebo; all patients also received open-label aspirin, 50 to 325 mg/d. The primary safety outcome was all major hemorrhages. Other safety outcomes included minor hemorrhages. A total of 269 sites worldwide randomized 4881 patients (median age, 65.0 years [interquartile range, 55-74 years]; 2195 women [45.0%]); the primary results have been published previously. In the as-treated analyses, major hemorrhage occurred in 21 patients (0.9%) receiving clopidogrel plus aspirin and 6 (0.2%) in the aspirin alone group (hazard ratio, 3.57; 95% CI, 1.44-8.85; P = .003; number needed to harm, 159). There were 4 fatal hemorrhages (0.1%; 3 in the clopidogrel plus aspirin group and 1 in the aspirin alone group); 3 of the 4 were intracranial. There were 7 intracranial hemorrhages (0.1%); 5 were in the clopidogrel plus aspirin group and 2 in the aspirin plus placebo group. The most common location of major hemorrhages was in the gastrointestinal tract. The risk for major hemorrhages in patients receiving either clopidogrel plus aspirin or aspirin alone after TIA or minor AIS was low. Nevertheless, treatment with clopidogrel plus aspirin increased the risk of major hemorrhages over aspirin alone from 0.2% to 0.9%. ClinicalTrials.gov identifier: NCT00991029.


Pharmacological therapy of female urinary incontinence.
Although not a life threatening condition, UI is a common problem in women that produces embarrassing and debilitating symptoms, severely affects the quality of life and represents a significant public health problem. The bladder and urethra in women constitute a functional unit that is controlled by a complex interplay between the central and peripheral cholinergic and noradrenergic nervous systems and local regulatory factors. A substantial part of urethral tone in women is also mediated through the effect of estrogen on urethral mucosal function. Theoretically, detrusor instability can be improved by agents that decrease detrusor contractility and genuine stress incontinence by agents that increase outlet resistance. To review the use of various drugs in treatment of female urinary incontinence [UI] and present the current evidence-based recommendations. Systematic review of literature. The strength of evidence for the use of such agents, however, varies from data obtained from pharmacological and physiological experiments to those derived from clinical studies. Hence, the use of some of the currently prescribed drugs for treatment of female UI is founded more on tradition than on evidence based on results from controlled clinical trials. There is also an urgent medical need for a new smooth muscle agent for treating UI in women because current drug therapy of UI is either inadequate or ineffective. Therefore, further clinical experience with drugs that selectively modulate the electrophysiological properties and the intracellular pathways of the smooth muscles of the lower urinary tract in women as therapeutic agents for UI is awaited with interest.


White light-emitting diode coated with ZnSe:Mn/ZnSe nanocrystal films enveloped by SiO2.
Mn-doped nanocrystals (NCs) have attracted much attention for their excellent properties. In our work, colloidal Mn-doped NCs with high quantum yield are synthesized and enveloped with silica hydrosol. The blend of NCs and silica hydrosol is coated on a blue light-emitting diode (LED), and the appropriate thickness of the NC film is found. White light is gained through the mix of the blue emission of the LED and the orange emission from Mn-doped NC films. The chromaticity coordinates and the image of the white LED indicate that Mn-doped NCs can be a good substitute for YAG:Ce phosphor, and the reliability of the white LED can be improved by enveloping NCs with SiO(2).


P450 enzymes of estrogen metabolism.
Endogenous and exogenous estrogens undergo extensive oxidative metabolism by specific cytochrome P450 enzymes. Certain drugs and xenobiotics have been found to be potent inducers of estrogen hydroxylating enzymes with C-2 hydroxylase induction being greater than that of C-16 hydroxylase. Oxygenated estrogen metabolites have different biological activities, with C-2 metabolites having limited or no activity and C-4 and C-16 metabolites having similar potency to estradiol. Pathophysiological roles for some of the oxygenated estrogen metabolites have been proposed, e.g. 16 alpha-hydroxyestrone and 4-hydroxyestrone. These reactive estrogens are capable of damaging cellular proteins and DNA and may be carcinogenic in specific cells.


[Active sites of enzymes: stereochemistry and dynamics].
The concept of an enzyme active site as of an integrated network system, which is substantiated by multipoint contacts between constituents, is presented. The conformational and electronic state of an enzyme active site supposed to be determined by hydrogen bonds network, which connects different subsites and components of the active site. The substrate specificity of an enzyme is achieved by means of hydrogen bonds formation between the protein and nonreacting fragment of the substrate molecule. As a consequence, reacting fragment of a substrate and those of an enzyme are locked in the configuration close to that of the transition state for the reaction. Stereochemical and dynamical aspects of ribonucleases specificity are considered in the framework of the concept. A molecular mechanism for the enzyme-substrate recognition is suggested.


Population structure of the Chagas disease vector, Triatoma infestans, at the urban-rural interface.
The increasing rate of biological invasions resulting from human transport or human-mediated changes to the environment has had devastating ecological and public health consequences. The kissing bug, Triatoma infestans, has dispersed through the Peruvian city of Arequipa. The biological invasion of this insect has resulted in a public health crisis, putting thousands of residents of this city at risk of infection by Trypanosoma cruzi and subsequent development of Chagas disease. Here, we show that populations of Tria. infestans in geographically distinct districts within and around this urban centre share a common recent evolutionary history although current gene flow is restricted even between proximal sites. The population structure among the Tria. infestans in different districts is not correlated with the geographical distance between districts. These data suggest that migration among the districts is mediated by factors beyond the short-range migratory capabilities of Tria. infestans and that human movement has played a significant role in the structuring of the Tria. infestans population in the region. Rapid urbanization across southern South America will continue to create suitable environments for Tria. infestans, and knowledge of its urban dispersal patterns may play a fundamental role in mitigating human disease risk.


Controlled sub-nanometer tuning of photonic crystal resonator by carbonaceous nano-dots.
We propose and demonstrate a scheme that enables spectral tuning of a photonic crystal high-quality resonant mode, in steps finer than 0.2 nm, via electron beam induced deposition of carbonaceous nano-dots. The position and size of a nano-dot with a diameter of <100 nm are controlled to an accuracy on the order of nanometers. The possibility of selective modal tuning is also demonstrated by placing nano-dots at locations pre-determined by theoretical computation. The lasing threshold of a photonic crystal mode tends to increase when a nano-dot is grown at the point of strong electric field, showing the absorptive nature of the nano-dot.


Effects of gluten on schizophrenics.
Previous studies have suggested that a cereal- and milk-free diet may be beneficial to schizophrenics and that the gluten in regular diets is harmful to schizophrenics. In an effort to replicate these findings, with improved control vehicles, patients on a locked ward were placed on a cereal- and milk-free diet. Thirteen schizophrenics were given gluten-free peanut-flour supplementary cookies and 13 were given virtually identical cookies with gluten added. Tests and rating scales before and after the ten-day study period showed no greater improvement for those receiving the gluten-free cookies than for those receiving the gluten-added cookies. Contrary to expectations, the group receiving gluten-added cookies showed significantly greater improvement of Profile on Mood States measures of tension-anxiety and anger-hostility. Previous findings were not supported. Perhaps a longer time on the diet is required for any beneficial effects to appear.


Humoral factors may mediate increased rat hindquarter blood flow in portal hypertension.
Chronic portal hypertension is associated with systemic hypotension and reduced peripheral vascular resistance. Although it is well established that splanchnic and renal vascular resistances are reduced, the contribution of possible alterations in skeletal muscle hemodynamics in portal hypertension is unknown. The present study was designed to determine if skeletal muscle vascular resistance was reduced and blood flow increased in portal hypertensive rats. In portal hypertensive animals, hind-quarter blood flow was significantly increased while vascular resistance was significantly reduced. The fall in resistance in the portal hypertensive animals was associated with an increase in the capillary filtration coefficient, suggesting that an increase in functional exchange vessel surface area occurred. Cross perfusion of control hindquarters with portal hypertensive blood resulted in a 38% reduction in hindquarter vascular resistance. Raising the plasma glucagon concentration to levels reported in portal hypertensive animals resulted in no change in blood flow or vascular resistance in control hindquarters. Skeletal muscle vascular sensitivity to norepinephrine was assessed by constructing dose-response curves in control and portal hypertensive animals. Mean ED50 values were not different. The results of these studies indicate that skeletal muscle vascular resistance is reduced in portal hypertension and humoral factors, but not glucagon, are primarily responsible for the skeletal muscle hyperemia associated with portal hypertension.


[New methodologicalapproaches to establishment the sizes of the sanitary protection zone and roadside clear zones of civil airports].
This circumstance leads to considerable mistakes it creation of SPZ borders of the airports, in some cases it impedes development of the latters and causes objective difficulties for hygienic assessment of projects. In this article the results of studies on the creation and validation of two new domestic methods for the construction of impact zones of aircraft noise and dispersion of the concentrations of pollutants in assessing the negative impact of airports are considered. Both branch methods agreed upon with the Ministry of Transport have been harmonized with ICAO (International Civil Aviation Organization) requirements. The results of full-scale measurements have confirmed the possibilities of developed software for their implementation in the formation of a common SPZ border of an airport.


LOW SERUM CHROMIUM IS RARE IN PATIENTS THAT UNDERWENT ENDOSCOPIC GASTROSTOMY FOR LONG TERM ENTERAL FEEDING.
Patients that underwent Percutaneous Endoscopic Gastrostomy (PEG) present with protein-energy malnutrition. Trace elements are required in small quantities and Chromium (Cr) displays a major role in the metabolism. This study aims to evaluate Cr levels and its relationship with serum proteins, BMI and underlying diseases during the first 3 months of PEG feeding. Prospective observational study during 3-months, when PEG was performed (T0), after 4 (T1), and 12 weeks (T3). Initial evaluation included: age, gender, underlying disease, NRS-2002, BMI, serum albumin, transferrin and Cr concentration. At T1 and T3 a blood sample was collected for Cr, albumin and transferrin. A Graphite Furnace Atomic Absorption Spectroscopy was used to assess Cr. According with the underlying disease, patients were divided into two groups: head and neck cancer (HNC) and neurological dysphagia (ND). All patients were fed with homemade meals. A one hundred and twenty-nine patients (80 males), 26-95 years old were studied: HNC-52; ND-77. The observed data included low mean values of BMI from 71 patients; low Cr-8, low albumin-70, low transferrin-85 and 57 with both proteins low. Albumin was associated with survival time ( P =0.024) and there was a significant correlation between albumin and Cr (r=0.217, P =0.012). A good evolution of Cr and proteins values was observed, with no low Cr levels at T3. Low serum Cr is rare in PEG-patients, with no relationship to other studied parameters. For the minority of patients displaying low Cr before gastrostomy, homemade PEG meals seem to be effective.


Early Transition to Microdiets Improves Growth, Reproductive Performance and Reduces Skeletal Anomalies in Zebrafish (Danio rerio).
Zebrafish is a model species with a high variability of feeding regimes among fish facilities. The use of live feeds for early life stages is a common practice, and few studies have focused early weaning into microdiets. The lack of standardized feeding protocols among research facilities promotes discrepancies in biological performances, and few studies relate dietary regimes to zebrafish development. The objective of this work was to assess the effect of an early transition into microdiets in zebrafish development by evaluating growth, survival, reproductive performance, and skeletal anomalies. These parameters were assessed in one group exclusively fed on Artemia nauplii and two groups fed on microdiets (commercial and experimental). Results showed that an early weaning with the two microdiets significantly improved zebrafish growth and reproductive performance, while a decrease in incidence of vertebral column anomalies was observed. A high survival was also maintained in fish fed microdiets at an early developmental stage when comparing to exclusive Artemia nauplii feeding. In conclusion, early weaning with high quality microdiets is beneficial for zebrafish growth, reproductive performance, and skeletal development, contributing to the standardization of zebrafish husbandry practices.


The IPEMB code of practice for electron dosimetry for radiotherapy beams of initial energy from 2 to 50 MeV based on an air kerma calibration. Institution of Physics and Engineering in Medicine and Biology.
This report contains the recommendations of the Electron Dosimetry Working Party of the UK Institution of Physics and Engineering in Medicine and Biology (IPEMB). The recommendations consist of a code of practice for electron dosimetry for radiotherapy beams of initial energy from 2 to 50 MeV. The code is based on the 2 MV (or 60Co) air kerma calibration of the NE 2561/2611 chamber, which is used as the transfer instrument between national standards laboratory and hospitals in the UK. The code utilizes an ND.air approach. Designated chambers are the NE 2571 (graphite-walled Farmer chamber), to be calibrated against the transfer instrument in a megavoltage photon beam, and three parallel-plate chambers, to be calibrated against the NE 2571 in a higher-energy electron beam. The practical code is supplemented by comprehensive discussion of the theoretical background and the sources and values of included data.


Economic and environmental feasibility of a perennial cow dairy farm.
More efficient and economical production systems are needed to improve the sustainability of dairy farms. One concept to consider is using perennial cows. Perennial cows are those that maintain a relatively high milk production for >or=2 yr without going through the typical dry period followed by calving. Farm records show that some cows have produced over 20 kg/d after 4 yr of continuous lactation. A farm simulation model was used to evaluate the long-term performance, environmental impact, and economics of a conceptual perennial cow production system on a typical dairy farm in Pennsylvania. Compared with a traditional 100-cow farm with replacement heifers produced on the farm, a perennial herd of 100 cows and purchased replacements provided environmental benefit but sustained a substantial economic loss. However, increasing the perennial herd to 128 cows better utilized the feed produced on the farm. Compared with the traditional 100-cow farm, use of the perennial 128-cow herd reduced supplemental protein and mineral feed purchases by 38%, increased annual milk sales by 21%, reduced nitrogen losses by 17%, maintained a phosphorus balance, and increased annual net return to farm management by 3200 dollars. A traditional 120-cow dairy farm with purchased replacements also used a similar amount of farm-produced feed. Compared with this option, the farm with 128 perennial cows reduced protein and mineral feed purchases by 36%, maintained similar annual milk sales, increased manure production by 7%, reduced N losses by 10%, and increased annual net return by 12,700 dollars. The economic feasibility of the perennial-cow dairy farm was very sensitive to the milk production maintained by the perennial herd and market prices for milk and perennial replacement animals. The analysis was relatively insensitive to the assumed useful life of perennial cows as long as they could be maintained in the herd for at least 3 yr. Thus, a perennial cow production system can improve the economic and environmental sustainability of a traditional dairy farm if a similar level in annual milk production per cow can be maintained.


Protection from radiation nephropathy by WR-2721.
The efficacy of WR-2721 pretreatment against radiation injury to the growing kidney was evaluated in the weanling mouse. Immediately following unilateral nephrectomy, animals received intraperitoneal injections of saline or WR-2721 (220 mg/kg). Thirty minutes later both nonprotected (saline-treated) control animals and protected (WR-2721-treated) animals received 1000-rad single-fraction radiation to the remaining kidney. Other animals received WR-2721 immediately following unilateral nephrectomy but no radiation. Animals were sacrificed at 3 and 24 weeks. Nonirradiated animals treated with WR-2721 only showed normal compensatory renal growth, body growth, and renal function at 24 weeks. The nonprotected, irradiated animals exhibited renal growth inhibition without body growth inhibition, and renal functional abnormalities including elevation of serum BUN and reduction of glomerular filtration rate. Pretreatment with WR-2721 prior to 1000 rad prevented the renal growth inhibition and functional abnormalities seen in the nonprotected irradiated animals. Within the observation period there were no differences in renal morphology by light and electron microscopy between protected and nonprotected groups; only mild glomerular and tubular abnormalities compatible with radiation injury were seen. WR-2721 can modulate renal radiation injury; however, the growth and functional protection is not well correlated with specific histologic change. The dose reduction factor for WR-2721 renal growth protection is between 1.16 and 1.2. WR-2721 may have future clinical utility by increasing radiation tolerance of the kidney.


A Metagenomics Study on Hirschsprung's Disease Associated Enterocolitis: Biodiversity and Gut Microbial Homeostasis Depend on Resection Length and Patient's Clinical History.
Objectives: Since 2010, several researches demonstrated that microbiota dynamics correlate and can even predispose to Hirschsprung (HSCR) associated enterocolitis (HAEC). This study aims at assessing the structure of the microbiota of HSCR patients in relation to extent of aganglionosis and HAEC status. Methods: All consecutive HSCR patients admitted to Gaslini Institute (Genova, Italy) between May 2012 and November 2014 were enrolled. Institutional review board (IRB) approval was obtained. Stools were sampled and 16S rDNA V3-V4 regions were sequenced using the Illumina-MiSeq. Taxonomy assignments were performed using QIIME RDP. Alpha diversity indexes were analyzed by Shannon and Simpson Indexes, and Phylogenetic Diversity. Results: We enrolled 20 patients. Male to female ratio was 4:1. Six patients suffered from Total Colonic Aganglionosis (TCSA). Considering sample site (i.e., extent of aganglionosis), we confirmed the known relationship between sample site and both biodiversity and composition of intestinal microbiota. Patients with TCSA showed lower biodiversity and increased Proteobacteria/Bacteroidetes relative abundance ratio. When addressing biodiversity, composition and dynamics of TCSA patients we could not find any significant relationship with regard to HAEC occurrences. Conclusions: The composition of HAEC predisposing microbiota is specific to each patient. We could confirm that total colon resections can change the composition of intestinal microbiota and to dramatically reduce microbial diversity. The subsequent reduction of system robustness could expose TCSA patients to environmental microbes that might not be part of the normal microbiota. Future long-term studies should investigate both patients and their family environment, as well as their disease history.


Amyloidosis and endomyocardial biopsy: Correlation of extent and pattern of deposition with amyloid immunophenotype in 100 cases.
The heart is subject to involvement by primary (AL), senile (AS), and familial (AF) forms of amyloidosis, but the frequency, severity, and therapy of amyloid-related cardiac symptoms differ depending on the type of amyloidosis present. Endomycardial biopsy is a safe and reliable procedure for diagnosing cardiac amyloidosis, and immunohistochemical staining of routinely processed biopsy specimens can be performed to classify the type of amyloid present. However, whether or not the type can be determined from the histologic extent and pattern of amyloid deposition is unclear. Endomyocardial biopsy specimens from 100 patients with cardiac amyloidosis (74 AL, 22 AS, 4 AF) were examined, and the histologic extent and pattern of amyloid deposition were correlated with the amyloid immunophenotype. No difference in the extent of amyloid deposition was identified among the three types. Interstitial nodules of amyloid were more common in AS (82%) than in AL (50%, p = 0.0129), whereas vascular involvement was more frequently observed in AL (88%) than in AS (26%, p < 0.0001). Endocardial and interstitial pericellular deposition occurred with similar frequencies in both groups. Although statistically significant differences existed in the patterns of amyloid deposition, they did not allow reliable distinction between the different types in individual cases. Consequently, in older patients without serum or urinary light chains, immunohistochemical staining is recommended to distinguish AL from AS types of amyloid in cardiac biopsy tissues.


Reduction of infectious morbidity with uterine stapling device.
Due to the recent development of absorbable surgical staples, application of gynecologic stapling methods has expanded to the field of obstetrics. Several studies have been published presenting the results of utilization of a novel hysterotomy and uterine stapling device for cesarean section (Poly CS-57, U.S. Surgical Corp, Norwalk CT). A review of all available data was analyzed to determine the rate of infectious morbidity secondary to the use of the device. Four studies fulfilled several criteria, including use of proper controls. A total of 383 patients were included in these studies with an infection rate of 6.4% (12/187) versus 16.3% (32/196) for the stapled and non-stapled (traditional sutured) group, respectively (p less than 0.001). The individual investigations attributed the decreased infection rate to reductions in blood loss and incisional hematoma formation and decreased reactivity of copolymer absorbable staples.


New targeted molecular therapies for dedifferentiated thyroid cancer.
Dedifferentiated thyroid cancer (DeTC) derived from follicular epithelium is often incurable because it does not respond to radioiodine, radiotherapy, or chemotherapy. In cases, RET/PTC rearrangements are found in 30%-40%, RAS mutations in about 10%, and BRAF mutations in around 40%-50%, with no overlap between these mutations results in papillary thyroid cancer, while a higher prevalence of BRAF mutations (up to 70%) has been observed in DeTC. The identification of these activating mutations in DeTC makes this malignancy an excellent model to examine the effect of tyrosine kinase inhibitors (TKIs). Clinical trials with several TKIs targeting RET, and to a lesser extent BRAF, and other TKRs have shown positive results, with about one-third of DeTC showing a reduction in tumor size up to 50%, with the longest treatment duration of approximately three-four years. Angiogenesis inhibitors have also shown promising activity in DeTC. Progress is being made toward effective targeted DeTC therapy. The possibility of testing the sensitivity of primary DeTC cells from each subject to different TKIs could increase the effectiveness of the treatment.


Quantitative Evaluation of Medial Temporal Lobe Morphology in Children with Febrile Status Epilepticus: Results of the FEBSTAT Study.
The pathogenesis of febrile status epilepticus is poorly understood, but prior studies have suggested an association with temporal lobe abnormalities, including hippocampal malrotation. We used a quantitative morphometric method to assess the association between temporal lobe morphology and febrile status epilepticus. Brain MR imaging was performed in children presenting with febrile status epilepticus and control subjects as part of the Consequences of Prolonged Febrile Seizures in Childhood study. Medial temporal lobe morphologic parameters were measured manually, including the distance of the hippocampus from the midline, hippocampal height:width ratio, hippocampal angle, collateral sulcus angle, and width of the temporal horn. Temporal lobe morphologic parameters were correlated with the presence of visual hippocampal malrotation; the strongest association was with left temporal horn width (P < .001; adjusted OR, 10.59). Multiple morphologic parameters correlated with febrile status epilepticus, encompassing both the right and left sides. This association was statistically strongest in the right temporal lobe, whereas hippocampal malrotation was almost exclusively left-sided in this cohort. The association between temporal lobe measurements and febrile status epilepticus persisted when the analysis was restricted to cases with visually normal imaging findings without hippocampal malrotation or other visually apparent abnormalities. Several component morphologic features of hippocampal malrotation are independently associated with febrile status epilepticus, even when complete hippocampal malrotation is absent. Unexpectedly, this association predominantly involves the right temporal lobe. These findings suggest that a spectrum of bilateral temporal lobe anomalies are associated with febrile status epilepticus in children. Hippocampal malrotation may represent a visually apparent subset of this spectrum.


Racial and Ethnic Disparities in Reproductive Health Services and Outcomes, 2020.
Racial and ethnic disparities in women's health have existed for decades, despite efforts to strengthen women's reproductive health access and utilization. Recent guidance by the American College of Obstetricians and Gynecologists (ACOG) underscores the often unacknowledged and unmeasured role of racial bias and systemic racial injustice in reproductive health disparities and highlights a renewed commitment to eliminating them. Reaching health equity requires an understanding of current racial-ethnic gaps in reproductive health and a concerted effort to develop and implement strategies to close gaps. We summarized national data for several reproductive health measures, such as contraceptive use, Pap tests, mammograms, maternal mortality, and unintended pregnancies, by race-ethnicity to inform health-equity strategies. Studies were retrieved by systematically searching the PubMed (2010-2020) electronic database to identify most recently published national estimates by race-ethnicity (non-Hispanic Black or African American, Hispanic or Latinx, and non-Hispanic White women). Disparities were found in each reproductive health category. We describe relevant components of the Affordable Care Act (ACA) and the Preventing Maternal Deaths Act, which can help to further strengthen reproductive health care, close gaps in services and outcomes, and decrease racial-ethnic reproductive health disparities. Owing to continued diminishment of certain components of the ACA, to optimally reach reproductive health equity, comprehensive health insurance coverage is vital. Strengthening policy-level strategies, along with ACOG's heightened commitment to eliminating racial disparities in women's health by confronting bias and racism, can strengthen actions toward reproductive health equity.


A novel role for P450 eicosanoids in the neurogenic control of cerebral blood flow in the rat.
The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are endogenous lipid mediators produced in the brain by P450 epoxygenases and metabolized through multiple pathways, including soluble epoxide hydrolase (sEH). Epoxyeicosatrienoic acids play important functions in the brain, including regulation of cerebral blood flow and protection from ischaemic brain injury. We previously demonstrated that ischaemic preconditioning induces cytochrome P450 2C11 epoxygenase (CYP2C11) expression in the brain, and that pharmacological inhibition and genetic deletion of sEH increases EETs and protects against stroke-induced brain damage. However, the expression profiles of CYP2C11 and sEH in normal brain remain unknown. In agreement with previous reports in peripheral vessels, we here demonstrate by immunofluorescence double-labelling that within cerebral parenchymal microvessels, sEH-immunoreactivity (IR) is localized to the vascular smooth muscle layer. Unexpectedly, however, analysis of large cerebral conduit arteries such as the middle cerebral artery revealed CYP2C11 and sEH expression in extrinsic perivascular nerves. Double-labelling studies revealed that CYP2C11- and sEH-IR predominantly colocalized with neuronal nitric oxide synthase-IR within perivascular nerve fibres. Significant colocalization for CYP2C11 and sEH was also observed with the parasympathetic markers vasoactive intestinal peptide and choline actetyltransferase, in addition to the sensory fibre markers calcitonin gene-related peptide and substance P. No colocalization was observed for either CYP2C11 or sEH with the sympathetic nerve markers dopamine beta-hydroxylase or neuropeptide Y. The presence of enzymes involved in production and inactivation of EETs within extrinsic parasympathetic and sensory vasodilator fibres suggests a novel role for EETs in the neurogenic control of cerebral arteries.


Disordered eating and its psychosocial correlates among Chinese adolescent females in Hong Kong.
To study the prevalence of disordered eating and its relationship with body dissatisfaction, family dysfunction, and depression among Chinese adolescent females in Hong Kong. Two hundred ninety-four schoolgirls completed a demographic and weight history sheet, Eating Attitudes Test-26, Body Dissatisfaction Scale, cohesion and conflict subscales of the Family Environment Scale, and the Beck Depression Inventory. 6.5% of subjects were EAT-26 high scores. Disordered eating was positively predicted by body dissatisfaction and, to a lesser extent, family cohesion and conflict. Body dissatisfaction was in turn positively predicted by depression, which was negatively predicted by family cohesion. Western patterns of body dissatisfaction and disordered eating attitudes are common among Chinese adolescent females. In the presence of psychosocial vulnerability factors, more weight control behavior and eating disorders may be expected to arise in Hong Kong.


Subtelomeric rearrangements in idiopathic mental retardation.
To estimate the frequency of subtelomeric rearrangements in patients with sporadic and non-syndromic idiopathic mental retardation (IMR). A total of 18 IMR patients were taken for the study. Selection criteria included no known syndromes or chromosomes abnormalities and known causes of IMR. All patients signed an informed consent to participate. Chromosome analysis was carried out on all patients to rule out gross chromosome abnormalities. Lymphocyte cultures were initiated and harvested using standard protocols. For fluorescence in situ hybridization (FISH), Chromoprobe Multiprobe-T system was used. This system consists of 24 embossed areas with each area having one reversibly bound subtelomere probe for a specific chromosome. The subtelomere probes were differentially labeled with green fluorescence for short arm and orange for the long arm. Hybridization, washing and staining are done using standard protocols. A minimum of 5 metaphases were analyzed per chromosome per patient. A total of 2 subtelomeric rearrangements were detected (11.1%). Case 1 involved a 17-year-old with severe MR, profound deafness and dysmorphic features with reciprocal translocation t(3;7)(q26.2; p15.1). The second case involved a 4.6-year-old with mild developmental delay and a terminal deletion of the long arm of chromosome 2, del(2) (q37.3). The frequency of abnormalities detected in our study is in agreement with published reports. Subtelomeric screening with FISH is a useful tool for investigation of IMR, however, it is not cost effective in all cases. Conventional chromosome analysis coupled with targeted FISH testing might be the optimal strategy for investigation of IMR.


Intracellular delivery of a peptide nucleic acid-based hybrid of an autophagy inducing peptide with a cell-penetrating peptide.
Development of an intracellular delivery method for functional peptides via cell-penetrating peptides (CPPs) expands peptide use in basic research and therapeutic applications. Although direct conjugation of a functional peptide with a CPP is the simplest method for delivery, this method has not always been reliable. CPPs usually contain several positively charged amino acids that potentially interact non-specifically with negatively charged molecules in cells and subsequently interfere with conjugated functional peptide function. Here we demonstrate a new intracellular delivery method for peptides in which a functional peptide is released from a positively charged CPP via peptide nucleic acids (PNAs). We prepared an 8-mer PNA conjugated to octa-arginine in tandem (PNA1-CPP) and linked its complementary PNA to an autophagy inducing peptide (PNA2-AIP) by solid-phase peptide synthesis. PNA1-CPP and PNA2-AIP formed a 1 : 1 hybrid via PNA1/PNA2 interaction, thereby indirectly but stably connecting the AIP to the CPP. PNA2-AIP was successfully delivered into cells in a hybrid formation-dependent manner and at least some portion of the PNA1-CPP/PNA2-AIP hybrids dissociated into PNA2-AIP and PNA1-CPP inside the cells. Notably, PNA2-AIP delivered to cells induced more autophagy than AIP directly conjugated to CPP (CPP-AIP). Further, the PNA hybrid did not induce significant cell death. These findings indicate that the PNA1/PNA2 hybrid can function as a molecular glue enabling the delivery of functional peptides into cells.


Prediction value of model for end-stage liver disease scoring system on prognosis in the acute on chronic liver failure patients with plasma exchange treatment.
Hepatitis B virus-related acute-on-chronic liver failure (AoCLF) is associated with a high mortality rate. Plasma exchange (PE) is useful to bridge patients with AoCLF to liver transplantation or recovery. The aim of this study was to analyze the impact of the model for end-stage liver disease (MELD) score on 30-day survival in patients with AoCLF treated with PE or conventional medications and to evaluate the therapeutic effectiveness of PE. In this study, 62 enrolled patients with AoCLF who received PE treatment were compared with 131 patients treated with conventional medications. The MELD scores were calculated according to the original formula, and the 30-day survival in patients was recorded. The 30-day survival rate of the patients who received PE versus controls was 41.9% versus 25.2% (p < 0.05). The 30-day survival rate of patients in the PE group (50.0%) with a MELD score from 20 to 30 was higher than that of the control group (31.7%, p < 0.05); for MELD scores more than 30, there was no significant difference in two groups (8.3% vs. 0%, p > 0.05). PE seems to be efficacious and safe for the treatment of patients with AoCLF and significantly increased the survival rates of patients with a MELD score of 20-30.


Quantitative trait locus analyses and the study of evolutionary process.
The past decade has seen a proliferation of studies that employ quantitative trait locus (QTL) approaches to diagnose the genetic basis of trait evolution. Advances in molecular techniques and analytical methods have suggested that an exact genetic description of the number and distribution of genes affecting a trait can be obtained. Although this possibility has met with some success in model systems such as Drosophila and Arabidopsis, the pursuit of an exact description of QTL effects, i.e. individual gene effect, in most cases has proven problematic. We discuss why QTL methods will have difficulty in identifying individual genes contributing to trait variation, and distinguish between the identification of QTL (or marker intervals) and the identification of individual genes or nucleotide differences within genes (QTN). This review focuses on what ecologists and evolutionary biologists working with natural populations can realistically expect to learn from QTL studies. We highlight representative issues in ecology and evolutionary biology and discuss the range of questions that can be addressed satisfactorily using QTL approaches. We specifically address developing approaches to QTL analysis in outbred populations, and discuss practical considerations of experimental (cross) design and application of different marker types. Throughout this review we attempt to provide a balanced description of the benefits of QTL methodology to studies in ecology and evolution as well as the inherent assumptions and limitations that may constrain its application.


Expression of ADK-S and ADK-L Isoforms and Their Association with CD39/CD73/A2aR in Colorectal Cancer.
The level of mRNA of the long (L) and short (S) isoforms of adenosine kinase (ADK) was analyzed in patients with colorectal cancer (CRC). ADK is required to convert adenosine (ADO) to AMP. It was shown that tumor and normal colon tissues (n=13) do not differ in the level of ADK-S and ADK-L mRNA. At the same time, the level of ADK-S mRNA (tumor: p=0.0214, normal: p=0.005) in the colon tissue was lower than in the blood of CRC patients (n=20), and the level of ADK-L mRNA (tumor: p=0.007, normal: p=0.024), on the contrary, was higher. A negative correlation was found between the level of ADK-S mRNA and the level of A2aR mRNA in both tumor and normal tissues (p=0.018 and p=0.0014, respectively). In the tumor tissue, a positive correlation was shown between ADK-L and CD73 mRNA levels (p=0.017). The obtained data indicate the association ADK with the expression of CD39/CD73/A2aR in CRC patients. In this regard, the effect of recombinant ADK on the expression of CD39 and CD73 ectonucleotidase by T cells in vitro was analyzed. In a culture of peripheral blood mononuclear cells isolated from the blood of 5 healthy donors, ADK did not abolish the inhibitory effect on the expression of CD39 and CD73 by CD8+T cells in the presence of a high concentration of ATP (a source for ADO). Effects on CD39+CD4+, CD73+CD4+T cells and CD39+ Treg cells were also not found.


Cytotoxic and apoptotic effects of boron compounds on leukemia cell line.
In this study we investigated the effects of boric acid and sodium tetraborate on an acute leukemia cell line and healthy human lymphocytes. We evaluated the effects of boric acid and sodium tetraborate on the HL-60 cell line and healthy human lymphocytes by using the methods of MTT, Neutral Red, AO (flow cytometry) and transmission electron microscope. We found that there were dead cells at a concentration of 500 µM boric acid and sodium tetraborate (50 % and 40 %, respectively). An apoptotic effect was found at a concentration of 1,000 µM concentration in normal lymphocytes and HL-60 (acute leukemia cells) cells (2.5 % and 8.8 % respectively). We observed that boric acid at a concentration of 500 µM caused double nucleus and micronucleus formation in both HL-60 cells and lymphocytes. An expansion in mitochondrial dimension and deformation in cristas also appeared. Our findings suggest that boric acid is more effective than sodium tetraborate on the HL-60, and boric acid in particular showed a cytotoxic effect on HL-60 in comparison to healthy lymphocytes and it also affected the mitochondrial pathway.


Response of canine cardiocyte lysosomes to ATP.
The present study was designed to evaluate the relationship of adenosine triphosphate (ATP) to maintenance of cardiac lysosome latency. Highly latent lysosomes were isolated from adult canine ventricular myocytes or cardiocytes and exhibited latency values (based on % free N-acetyl-beta-glucosaminidase, NAGA) of 29.3 +/- 4.7% (SE), minimal cross contamination by mitochondria (less than 2% cardiolipin by weight) and only 1.68% of the total cytochrome c oxidase activity; enzymatic enrichments ranged from 10-fold for NAGA to almost 50-fold for cathepsin B. Incubations of cardiocyte lysosomes at pH 7.0 and 25 degrees C for up to 1 h resulted in changes in the rate of loss in lysosomal latency when ATP levels were adjusted from 0.0 to 5.0 mM; under these conditions as ED50 of 0.62 mM ATP was determined. The protection afforded by ATP was reversed by addition of the H+ ionophore m-chlorocarbonylcyanide phenylhydrazone (CCCP) at 10 microM to the lysosomal suspensions. A significant increase in lysosomal membrane fluidity, measured by fluorescent polarization of diphenylhexatriene, was also seen in the absence of ATP. Adenosine diphosphate (ADP) afforded significant protection only at the very highest concentration (5.0 mM); inorganic pyrophosphate (PPi) did not protect against loss of latency at any concentration. Thus ATP exerts a significant stabilizing effect on cardio(myo)cyte lysosomes in vitro and may be one of the metabolites regulating lysosomal integrity in vivo.


Multimodal treatment of ADHD in the MTA: an alternative outcome analysis.
To conduct a post hoc investigation of the utility of a single composite measure of treatment outcome for the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) at 14 months postbaseline. Examination of multiple measures one at a time in the main MTA intent-to-treat outcome analyses failed to detect a statistically significant advantage of combined treatment (Comb) over medication management (MedMgt). A measure that increases power and precision using a single outcome score may be a useful alternative to multiple outcome measures. Factor analysis of baseline scores yielded two "source factors" (parent and teacher) and one "instrument factor" (parent-child interactions). A composite score was created from the average of standardized parent and teacher measures. The composite was internally consistent (alpha = .83), reliable (test-retest over 3 months = 0.86), and correlated 0.61 with clinician global judgments. In an intent-to-treat analysis, Comb was statistically significantly better than all other treatments, with effect sizes ranging from small (0.28) versus MedMgt, to moderately large (0.70) versus a community comparison group. A composite of ADHD variables may be an important tool in future treatment trials with ADHD and may avoid some of the statistical limitations of multiple measures.


Laparoscopic Nissen fundoplication: two-year comprehensive follow-up of a technique of minimal paraesophageal dissection.
To provide a comprehensive follow-up of 381 patients after laparoscopic Nissen fundoplication (LNF) using a technique of minimal paraesophageal dissection. Patients underwent a 24-hour pH recording, esophageal manometry, and symptom score assessment for six symptoms of gastroesophageal reflux disease preoperatively. To date, 260 patients have undergone repeat studies at 6 months and 108 patients at 2 years. LNF was associated with a significant (p < 0.0001) increase in the lower esophageal sphincter (LES) pressure and a significant (p < 0.0001) drop in duration of acid reflux in 24 hours and symptom score 6 and 24 months after surgery when compared to preoperative values. Twelve patients (3%) have experienced recurrence of reflux symptoms, 8 presenting in the first 6 months and 4 by the second year after surgery, but only 1 has required repeat surgery. The incidence of clinical dysphagia was found to be 1.3% of the patient group. LNF remains an effective antireflux procedure at 2 years. Most recurrences occur early, and there is no significant deterioration in the high-pressure zone at the LES, the percentage reflux in 24 hours, or symptom control between 6 months and 2 years after surgery, suggesting that the long-term results should be satisfactory.


Fibrin-targeted direct factor Xa inhibition: construction and characterization of a recombinant factor Xa inhibitor composed of an anti-fibrin single-chain antibody and tick anticoagulant peptide.
We investigated whether the direct fXa inhibitor tick anticoagulant peptide (TAP) can be N-terminally coupled to a clot-targeting, single-chain antibody specific for fibrin (scFv(59D8)). Due to its unique position at the convergence point of the intrinsic and extrinsic pathways early in the coagulation cascade, factor Xa (fXa) represents an attractive therapeutic target. In contrast to indirect inhibitors, direct fXa inhibitors effectively inhibit clot-bound and prothrombinase-associated fXa. Targeting of direct fXa inhibitors to clots promises to enhance local anticoagulative potency and to reduce systemic anticoagulation which potentially results in less bleeding complications.TAP is a highly potent fXa inhibitor. Since its N-terminus is essential for anti-fXa activity, it was a challenging question, whether TAP will be active as a N-terminally coupled fusion molecule. Two step affinity chromatography with Ni(2+) and beta(15-22)-peptide of human fibrin results in a pure 36 kDa protein, which was tested for its targeting function and anti-fXa activity. The recombinant fusion did not destroy the function of the fusion partners. Antibody binding function was on a par with the parent molecule. TAP activity was partially reduced, arguing that a free N-terminus is not required for anti-fXa activity, but is important for maximal potency. In human whole blood clots, scFv(59D8)-TAP revealed anticoagulative properties at concentrations (200 to 500 nM) where non-targeted TAP did not reveal anticoagulative activity at all. In summary, scFv(59D8)-TAP constitutes a promising new anticoagulant with fibrin-targeted factor Xa inhibition. The production in E. coli and the established purification methods are a solid basis for a modern, large scale production at low cost and reproducible activity.


[Unstable stenocardia: indicators of platelet activity and the effect of verapamil].
Beta-thromboglobin (BTG) and 4 platelet factor (4PF) blood concentration reflecting platelet functional state were determined by radioimmunoassay in 17 patients with unstable angina pectoris, in 18 patients with severe stable angina pectoris (IV functional class) and in 6 healthy subjects. Patients with unstable angina pectoris exhibited signs of platelet activation, i.e significant increase in blood BTG and 4PF concentration, which made qualitative difference from the patients with severe but stable form of the disease. The study of platelet activity at the peak of pain attack has demonstrated further increase in BTG and 4PF concentration in 6 patients having high initial characteristics. In 12 patients with unstable angina pectoris verapamil effect on the platelet functional activity was studied, they exhibited a decrease in BTG and 4PF concentration by intravenous injections as well as by long-term oral administration.


Low Complex CORDIC-based Hand Movement Recognition Design Methodology for Rehabilitation and Prosthetic Applications.
Hand movement recognition using Electromyography (EMG) signals have gained much significance lately and is extensively used for rehabilitation and prosthetic applications including stroke-driven disability and other neuromuscular disorders. Herein, quantitative analysis of EMG signals is very crucial. However, such applications are constrained by power consumption limitations due to the battery backup necessitating low-complex system design and the on-chip area requirement. Existing hand movement recognition methodologies using single-channel EMG signal involve computationally intensive stages, including Ensemble Empirical Mode Decomposition (EEMD), Fast Independent Component Analysis (FastICA), feature extraction, and Linear Discriminant Analysis (LDA) classification, which can not be mapped onto the low-complex architecture directly from the algorithmic level. The high computational complexity of LDA classification makes it difficult to be used for low-complex applications. In this paper, we introduce a low-complex CORDIC-based hand movement recognition design methodology targeting resource-constrained rehabilitation applications. This work explores replacing LDA classification with K-Means clustering due to its reduced complexity and efficient clustering algorithm. CORDIC-based K-Means clustering is used to further reduce the overall computational complexity of the system. The proposed low complex, K-Means clustering-based hand movement recognition for classifying seven hand movements using single-channel EMG data is found to be 99.77 % less complex and 1.28% more accurate than the conventional LDA-based classification.


Insect succession on a decomposing piglet carcass placed in a man-made freshwater pond in Malaysia.
This entomological study was conducted in a man-made freshwater pond in a palm oil plantation in Tanjung Sepat, Selangor from 23 July 2007 by using pig (Sus scrofa) as a carcass model. A 1.5 month old piglet (5 kg), which died of asphyxia after being accidentally crushed by its mother, was thrown into a pond. Observation was made for ten days; one visit per day and climatological data were recorded. On the first two days, the piglet carcass sunk to the bottom of the pond. The carcass floated to the surface on the third day but no fly activities were seen. The blow fly, Chrysomya megacephala and Chrysomya rufifacies started to oviposit on the fourth day. Other than adult flies, a spider (Arachnida) was also observed on the carcass. Bubbles accumulated at the mouthpart, and the abdomen was greenish black. A lot of blow fly eggs were seen on the body surface on the fifth day (floating decay), along with first and second instars C. megacephala crawling under the piglet's skin. On the sixth day, adult blow fly, C. megacephala,and C. rufifacies,and muscid flies, Ophyra spinigera and Musca domestica were observed on to the carcass. High numbers of first and second instars of flies were observed wandering around the body surface with C. megacephala larvae being the predominant species. Two prominent maggot masses occurred on seventh and eighth days. Bloated deterioration stage began on day eighth exposing rib bones, humerus bones and intestines. Carcass was partially sinking and the maggot masses were at the water level. On day ninth, the carcass was partially sinking and three maggot masses were observed on the exposed surface. There were very few adult flies, including a scarab beetle was sighted on the carcass at this stage. The carcass along with the maggots sunk on day tenth, leaving an oily layer on the water surface.


Combining a Candidate Vaccine for Opioid Use Disorders with Extended-Release Naltrexone Increases Protection against Oxycodone-Induced Behavioral Effects and Toxicity.
Opioid use disorders (OUDs) and opioid-related fatal overdoses are a significant public health concern in the United States and worldwide. To offer more effective medical interventions to treat or prevent OUD, antiopioid vaccines are in development that reduce the distribution of the targeted opioids to brain and subsequently reduce the associated behavioral and toxic effects. It is of critical importance that antiopioid vaccines do not interfere with medications that treat OUD. Hence, this study tested the preclinical proof of concept of combining a candidate oxycodone vaccine [oxycodone-keyhole limpet hemocyanin (OXY-KLH)] with an FDA-approved extended-release naltrexone (XR-NTX) depot formulation in rats. The effects of XR-NTX on oxycodone-induced motor activity and antinociception were first assessed in nonvaccinated naïve rats to establish a baseline for subsequent studies. Next, OXY-KLH and XR-NTX were coadministered to determine whether the combination would affect the efficacy of each individual treatment, and it was found that the combination of OXY-KLH and XR-NTX offered greater efficacy in reducing oxycodone-induced motor activity, thigmotaxis, antinociception, and respiratory depression over a range of repeated or escalating oxycodone doses in rats. These data support the feasibility of combining antibody-based therapies with opioid receptor antagonists to provide greater or prolonged protection against opioid-related toxicity or overdose. Combining antiopioid vaccines with XR-NTX may provide prophylactic measures to subjects at risk of relapse and accidental or deliberate exposure. Combination therapy may extend to other biologics (e.g., monoclonal antibodies) and medications against substance use disorders. SIGNIFICANCE STATEMENT: Opioid use disorders (OUDs) remain a major problem worldwide, and new therapies are needed. This study reports on the combination of an oxycodone vaccine [oxycodone-keyhole limpet hemocyanin (OXY-KLH)] with a currently approved OUD therapy, extended-release naltrexone (XR-NTX). Results demonstrated that XR-NTX did not interfere with OXY-KLH efficacy, and combination of low doses of XR-NTX with vaccine was more effective than each individual treatment alone to reduce behavioral and toxic effects of oxycodone, suggesting that combining OXY-KLH with XR-NTX may improve OUD outcomes.


Targeted glycan degradation potentiates the anticancer immune response in vivo.
Currently approved immune checkpoint inhibitor therapies targeting the PD-1 and CTLA-4 receptor pathways are powerful treatment options for certain cancers; however, most patients across cancer types still fail to respond. Consequently, there is interest in discovering and blocking alternative pathways that mediate immune suppression. One such mechanism is an upregulation of sialoglycans in malignancy, which has been recently shown to inhibit immune cell activation through multiple mechanisms and therefore represents a targetable glycoimmune checkpoint. Since these glycans are not canonically druggable, we designed an αHER2 antibody-sialidase conjugate that potently and selectively strips diverse sialoglycans from breast cancer cells. In syngeneic breast cancer models, desialylation enhanced immune cell infiltration and activation and prolonged the survival of mice, an effect that was dependent on expression of the Siglec-E checkpoint receptor found on tumor-infiltrating myeloid cells. Thus, antibody-sialidase conjugates represent a promising modality for glycoimmune checkpoint therapy.


More on the reliability of the microparticle enzyme immunoassay (MEIA) for therapeutic tacrolimus monitoring.
Recently, the validity of determining tacrolimus concentrations in blood samples using Abbott's microparticle enzyme immunoassay (MEIA) has been seriously questioned. This communication presents the results obtained in our laboratory using the MEIA for 31 pooled blood samples from kidney and liver transplant patients (Tacrolimus International Proficiency Testing Scheme). A good correlation was found with regard to the average of the MEIA method (r=0.950) without reaching clinical significance for the difference between the means (9.54 ng/ml vs 9.74 ng/ml), although the standard error of the estimate (Syx=0.66 ng/ml) was clinically significant. With regard to the average values for HPLC-methods, a lower correlation coefficient was found (r=0.819), with a difference between the means (9.54 ng/ml vs 8.91 ng/ml) slightly greater than the clinically acceptable value, and a clinically significant standard error of the estimate (Syx=1.22 ng/ml). In the case of the correlation between the average values for the MEIA and HPLC methods, a higher correlation coefficient was found (r=0.918), with a difference between the means (9.74 ng/ml vs 8.91 ng/ml) and a standard error of the estimate (Syx=0.75 ng/ml) being clinically significant. However, these differences were lesser than 15% of HPLC results in accordance with the American Association of Pharmaceutical Scientists acceptance criteria for analytical methods employed for quantification of drugs and their metabolites.


Mortality in middle-aged smokers and nonsmokers.
We assessed the relation of cigarette smoking to mortality in an 11-year follow-up study of 4004 men and women, 35 to 54 years of age, who responded to urging to have multiphasic health checkups. Accounting for 48 other characteristics, both individually and in combination, failed to eliminate the association of smoking with mortality from all causes or with mortality from coronary heart disease. The smoker-to-nonsmoker mortality ratios, crude and adjusted respectively, were 2.6 and 2.1 for all causes and 4.7 and 3.6 for coronary heart disease. This analysis did not support the counterhypothesis that the association of cigarette smoking with mortality is secondary to some underlying characteristic.


Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA).
The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as 'post-acute COVID-19' may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance.


Converting enzyme inhibition and kidney function in normotensive diabetic patients with persistent microalbuminuria.
The effects of a long term reduction in blood pressure on the kidney function of normotensive diabetic patients who had persistent microalbuminuria (30-300 mg albumin/24 hours) were studied in two groups of 10 such patients before and during six months of treatment with either 20 mg enalapril or placebo daily. Treatments were assigned randomly in a double blind fashion. Before treatment both groups had similar clinical characteristics, weight, diet, total glycosylated haemoglobin, median albumin excretion rate (enalapril group 124 mg/24 h, placebo group 81 mg/24 h), and mean arterial pressure (enalapril group 100 (SD 8) mm Hg, placebo group 99 (6) mm Hg). During treatment weight, urinary urea excretion, and total glycosylated haemoglobin remained unchanged. The mean arterial pressure decreased in the enalapril group but not in the placebo group (enalapril group 90 (10) mm Hg, placebo group 98 (8) mm Hg). The median albumin excretion rate also fell in the enalapril group but not in the placebo group (enalapril group 37 mg/24 h, placebo group 183 mg/24 h.) The glomerular filtration rate rose in the enalapril group from 130 (23) ml/min/1.73 m2 to 141 (24) ml/min/1.73 m2, and total renal resistances and fractional albumin clearance decreased while fractional albumin clearance increased in the placebo group. These results show that in patients who have diabetes but not hypertension a reduction in blood pressure by inhibition of converting enzyme for six months can reduce persistent microalbuminuria, perhaps by decreasing the intraglomerular pressure.


[Chronic osteomyelitis: a new therapeutical idea]
We studied the case of a male patient aged 43 affected by post-traumatic chronic osteomyelitis with frequent relapses. Having supposed an insufficiency of the arterial and venous microcirculation in perilesional bone and soft tissue we decided for a therapy with iloprost and antibacterial drugs. After 15 months of treatment the patient hasn't showed any clinically evident relapsing episodes and we have not reported any side effects related to the therapy.


Comparison of automated candidate gene prediction systems using genes implicated in type 2 diabetes by genome-wide association studies.
Automated candidate gene prediction systems allow geneticists to hone in on disease genes more rapidly by identifying the most probable candidate genes linked to the disease phenotypes under investigation. Here we assessed the ability of eight different candidate gene prediction systems to predict disease genes in intervals previously associated with type 2 diabetes by benchmarking their performance against genes implicated by recent genome-wide association studies. Using a search space of 9556 genes, all but one of the systems pruned the genome in favour of genes associated with moderate to highly significant SNPs. Of the 11 genes associated with highly significant SNPs identified by the genome-wide association studies, eight were flagged as likely candidates by at least one of the prediction systems. A list of candidates produced by a previous consensus approach did not match any of the genes implicated by 706 moderate to highly significant SNPs flagged by the genome-wide association studies. We prioritized genes associated with medium significance SNPs. The study appraises the relative success of several candidate gene prediction systems against independent genetic data. Even when confronted with challengingly large intervals, the candidate gene prediction systems can successfully select likely disease genes. Furthermore, they can be used to filter statistically less-well-supported genetic data to select more likely candidates. We suggest consensus approaches fail because they penalize novel predictions made from independent underlying databases. To realize their full potential further work needs to be done on prioritization and annotation of genes.


Guided growth for the correction of pediatric lower limb angular deformity.
Guided growth is useful in correcting pediatric angular deformities. Although growth manipulation has been applied to various deformities, it is most commonly used to correct coronal plane deformity about the knee. Temporary hemiepiphysiodesis is performed using staples, percutaneous transphyseal screws, or a tension band plate. Permanent hemiepiphysiodesis can be done using either an open Phemister or a percutaneous approach. These techniques function by tethering one side of a growing physis, thereby allowing differential growth. Applied correctly, this can also result in angular deformity correction. Undercorrection and overcorrection are common problems with guided growth. However, careful preoperative planning and appropriate follow-up can minimize complications and allow for excellent deformity correction with minimal morbidity.


Aquatic exercise in a chest-high pool for hormone therapy-induced arthralgia in breast cancer survivors: a pragmatic controlled trial.
To investigate the impact of aquatic exercise on pressure pain threshold in breast cancer survivors with hormone therapy-associated arthralgia. Single-blind, controlled trial. Two major metropolitan hospitals and a Sport and Spa Club in Granada, Spain. Forty women aged 29-71 years with stage I-III breast cancer who reported arthralgia. Patients were allocated alternately to either aquatic exercise in a chest-high pool or usual care while on the waiting list; control patients received treatment later. The two-month hydrotherapy intervention consisted of 24 sessions 3 days per week. Each session included 5 minutes of warm-up, 15-20 minutes of aerobic exercise, 15 minutes of mobility exercise and 20 minutes of recovery techniques. Pressure pain threshold at neck, shoulder, hand and leg were evaluated as primary outcomes. Cancer-related fatigue, as measured by the Piper Fatigue Scale, body mass index and waist circumference were secondary outcomes. A 2 × 2 repeated-measure ANCOVA was used in this study. No adverse events or development of worsening of pain was observed. Almost all the participants in the intervention group (89%) adhered to the hydrotherapy programme. Participants experienced a decrease in pressure pain threshold measured in neck, hand, shoulder and leg, as measured by algometry pressure, and waist circumference; all P < 0.05. Cancer-related fatigue (P = 0.06) and body mass index (P = 0.42) did not show significant improvement. These data suggest that hydrotherapy in a chest-high pool may reduce the pain threshold and waist circumference in breast cancer survivors with hormone therapy-associated arthralgia.


Advancement in magnetic hyperthermia-based targeted therapy for cancer treatment.
Magnetic hyperthermia utilizing magnetic nanoparticles (MNPs) and an alternating magnetic field (AMF) represents a promising approach in the field of cancer treatment. Active targeting has emerged as a valuable strategy to enhance the effectiveness and specificity of drug delivery. Active targeting utilizes specific biomarkers that are predominantly found in abundance on cancer cells while being minimally expressed on healthy cells. Current comprehensive review provides an overview of several cancer-specific biomarkers, including human epidermal growth factor, transferrin, folate, luteinizing hormone-releasing hormone, integrin, cluster of differentiation (CD) receptors such as CD90, CD95, CD133, CD20, and CD44 also CXCR4 and vascular endothelial growth factor, these biomarkers bind to ligands present on the surface of MNPs, enabling precise targeting. Additionally, this review touches various combination therapies employed to combat cancer. Magnetic hyperthermia synergistically enhances the efficacy of conventional cancer treatments such as targeted chemotherapy, radiation therapy, gene therapy, and immunotherapy.


Relative and absolute gender gap in all-cause mortality in Europe and the contribution of smoking.
This paper examined whether international variations in absolute and relative gender differences in mortality are related to the overall mortality rates, and whether the international variation in gender gap in mortality can in part be explained by smoking. I used data on mortality from all causes in 32 European countries published by the World Health Organisation, and indirect estimates of mortality attributable to smoking in the age band 35-69 years by Peto et al. The main analyses were restricted to the age band 35-69 years but results for mortality at all ages were virtually identical. The overall mortality rates (both sexes combined) were strongly related to absolute gender differences (r = 0.91) but only weakly to relative differences (r = 0.35). The gender gap was larger in eastern than in western Europe for rate differences (1005 vs. 530 per 100,000, respectively), but it was similar for rate ratios (2.3 vs. 2.1, respectively). Both absolute and relative gender differences in mortality were strongly related to the difference between men and women in the proportion of all deaths attributed to tobacco (partial correlations, after controlling for the overall death rates, were 0.59 and 0.66, respectively). Excluding tobacco-related deaths attenuated the associations between the overall mortality rates with absolute differences (r = 0.70) and reduced the difference in the absolute gender gap between eastern and western Europe. More importantly, excluding tobacco-related deaths eliminated entirely the association with relative differences (r = -0.15) as well as any suggestion that the relative gender gap is larger in eastern than in western Europe. These results show that tobacco plays an important role in generating international differences in the size of gender gap in mortality. The much discussed association between' the overall life expectancy and the gender gap in life expectancy is a numerical product of absolute death rates (differences in life expectancy are driven by differences in rates). The association of overall mortality with male/female mortality ratios is much weaker.


The association of virulence factors with genomic islands.
It has been noted that many bacterial virulence factor genes are located within genomic islands (GIs; clusters of genes in a prokaryotic genome of probable horizontal origin). However, such studies have been limited to single genera or isolated observations. We have performed the first large-scale analysis of multiple diverse pathogens to examine this association. We additionally identified genes found predominantly in pathogens, but not non-pathogens, across multiple genera using 631 complete bacterial genomes, and we identified common trends in virulence for genes in GIs. Furthermore, we examined the relationship between GIs and clustered regularly interspaced palindromic repeats (CRISPRs) proposed to confer resistance to phage. We show quantitatively that GIs disproportionately contain more virulence factors than the rest of a given genome (p<1E-40 using three GI datasets) and that CRISPRs are also over-represented in GIs. Virulence factors in GIs and pathogen-associated virulence factors are enriched for proteins having more "offensive" functions, e.g. active invasion of the host, and are disproportionately components of type III/IV secretion systems or toxins. Numerous hypothetical pathogen-associated genes were identified, meriting further study. This is the first systematic analysis across diverse genera indicating that virulence factors are disproportionately associated with GIs. "Offensive" virulence factors, as opposed to host-interaction factors, may more often be a recently acquired trait (on an evolutionary time scale detected by GI analysis). Newly identified pathogen-associated genes warrant further study. We discuss the implications of these results, which cement the significant role of GIs in the evolution of many pathogens.


Time-of-flight imaging based on resonant photoelastic modulation.
A time-of-flight imaging system is proposed and its working principle demonstrated. To realize this system, a new device, a free-space optical mixer, is designed and fabricated. A scene is illuminated (flashed) with a megahertz-level amplitude-modulated light source, and the reflected light from the scene is collected by a receiver. The receiver consists of the free-space optical mixer, comprising a photoelastic modulator sandwiched between polarizers, placed in front of a standard complementary metal-oxide-semiconductor (CMOS) image sensor. This free-space optical mixer downconverts the megahertz-level amplitude modulation frequencies into the temporal bandwidth of the image sensor. A full-scale extension of the demonstrated system will be able to measure phases and Doppler shifts for the beat tones and use signal processing techniques to estimate the distance and velocity of each point in the illuminated scene with high accuracy.


Ultra-rapid auxin metabolite profiling for high-throughput mutant screening in Arabidopsis.
Auxin (indole-3-acetic acid, IAA) plays fundamental roles as a signalling molecule during numerous plant growth and development processes. The formation of local auxin gradients and auxin maxima/minima, which is very important for these processes, is regulated by auxin metabolism (biosynthesis, degradation, and conjugation) as well as transport. When studying auxin metabolism pathways it is crucial to combine data obtained from genetic investigations with the identification and quantification of individual metabolites. Thus, to facilitate efforts to elucidate auxin metabolism and its roles in plants, we have developed a high-throughput method for simultaneously quantifying IAA and its key metabolites in minute samples (<10 mg FW) of Arabidopsis thaliana tissues by in-tip micro solid-phase extraction and fast LC-tandem MS. As a proof of concept, we applied the method to a collection of Arabidopsis mutant lines and identified lines with altered IAA metabolite profiles using multivariate data analysis. Finally, we explored the correlation between IAA metabolite profiles and IAA-related phenotypes. The developed rapid analysis of large numbers of samples (>100 samples d-1) is a valuable tool to screen for novel regulators of auxin metabolism and homeostasis among large collections of genotypes.


Absolute calibration up to 20 MeV of an online readout CMOS system suitable to detect high-power lasers accelerated protons.
We present the design and absolute calibration of a charged particle online readout CMOS system tailored for high-power laser experiments. This system equips a Thomson parabola spectrometer, which is used at the Apollon petawatt scale laser facility to measure the spectra of protons produced by high-intensity laser-target interactions. The RadEye1 CMOS matrices array detectors are paired with a custom triggering system for image grabbing. This allows us to register the proton and ion signals remotely. The repetition rate is presently 1 shot/min, but the frame grabbing enables the system to be compatible with modern high-power lasers running, e.g., at 1 Hz. We detail here the implementation, in the harsh electromagnetic environment of such interactions, of the system, and its absolute calibration, which was performed for proton energies from 4 to 20 MeV.


Academic performance in children with rolandic epilepsy.
The aim of this study was to investigate the frequency of reading, writing, and calculation disabilities in children with typical rolandic epilepsy (RE) and healthy control children. We also aimed to define the possible electroclinical markers of specific cognitive dysfunctions in RE. School abilities were evaluated and compared in 20 children (eight males, 12 females; mean age 10y 3mo [SD 1y 7mo]; range 7y 9mo-12y 9mo) consecutively diagnosed with typical RE, and a group of 21 healthy controls (nine males, 12 females; mean age 10y 4mo [SD 1y 8mo]; range 7y 6mo-13y 3mo). All the children received standardized neuropsychological tests. For each patient an exhaustive seizure diary was kept and all the sleep electroencephalogram (EEG) recordings were reviewed. Specific difficulties with reading, writing, and calculation (diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition) were found in nine out of 20 children with RE and two out of 21 healthy controls (chi2=0.01). The specific learning disabilities in the RE group were correlated with a marked increase in epileptiform discharges during sleep (chi2=0.02) and an early onset of epilepsy (chi2=0.02). Our findings suggest that seizure onset before age 8 years and epileptiform discharges (more than 50% of the sleep EEG recording) in several tracings over more than a year are relevant markers for identifying patients at risk of developing academic difficulties.


A ratiometric fluorescence imprinted sensor based on N-CDs and metal-organic frameworks for visual smart detection of malathion.
Sensitive and rapid detection of pesticide residues in food is essential for human safety. A ratiometric imprinted fluorescence sensor N-CDs@Eu-MOF@MIP (BR@MIP) was constructed to sensitively detect malathion (Mal). Europium-based metal organic frameworks (Eu-MOF) were used as supporters to improve the sensitivity of the BR@MIP. N-doped carbon dots (N-CDs) were used as fluorescent source to produce fluorescent signal. A linear relationship between the concentration of Mal and the fluorescence response of the sensor was found in the Mal concentration range of 1-10 μM with a limit of detection (LOD) of 0.05 μM. Furthermore, the sensor was successfully applied for the detection of Mal in lettuce, tap water, and soil samples, with recoveries in the range of 93.0 % - 99.3 %. Additionally, smartphone-based sensors were used to detect Mal in simulated real samples. Thus, the construction of ratiometric imprinted fluorescence sensor has provided a good strategy for the detection of Mal.