Single-sideband W-band photonic vector millimeter-wave signal generation by one single I/Q modulator.
We propose a new scheme to generate single-sideband (SSB) photonic vector millimeter-wave (mm-wave) signal adopting asymmetrical SSB modulation enabled by a single in-phase/quadrature (I/Q) modulator. The driving signal for the I/Q modulator is generated by software-based digital signal processing (DSP) instead of a complicated transmitter electrical circuit, which significantly simplifies the system architecture and increases system stability. One vector-modulated optical sideband and one unmodulated optical sideband, with different sideband frequencies, located at two sides of a significantly suppressed central optical carrier, are generated by the I/Q modulator and used for heterodyne beating to generate the electrical vector mm-wave signal. The two optical sidebands are robust to fiber dispersion and can be transmitted over relatively long-haul fiber. We experimentally demonstrate the generation and transmission of 4-Gbaud 80-GHz quadrature-phase-shift-keying-modulated (QPSK-modulated) SSB vector mm-wave signal over 240-km single-mode fiber-28 without optical dispersion compensation.


Potassium Citrate is Better in Reducing Salt and Increasing Urine pH than Oral Intake of Lemonade: A Cross-Over Study.
BACKGROUND Urine solute supersaturation leads to the formation of urinary tract caliceal stones. Many parameters can be involved in the supersaturation of solutes in urine, such as pH. Uric acid has pKa ≤5.5, and it is solubilized at pH ≥5.5. The objective of the study was to evaluate the effects of potassium citrate and lemonade supplementation in pediatric patients with urolithiasis. MATERIAL AND METHODS A total of 126 children who had lower ureteral stones calculi and fragments with severe colic pain participated in this cross-over study. Children drank lemonade (2 mEq/kg/day citrate) in 3 divided doses for 5 days. After a 15-day washout period, children drank 2 mEq/kg/day of potassium citrate in 3 divided doses for 5 days. On the sixth of the day of individual intervention, a 24-h urine sample was collected and evaluated for pH, urine volume, citrate level, uric acid level, magnesium, phosphorus, potassium, and sodium. Urinary parameters for 1-day urine collection measurements after each supplementation were compared with baseline using the Mann-Whitney test following Tukey post hoc test at 95% confidence level. RESULTS Potassium citrate supplementation resulted in reduction of sodium concentration (p=0.0337; q=3.76) and increased pH of urine (p=0.0118; q=4.389). However, urine volume, citrate level, and uric acid level, as well as elemental magnesium, phosphorus, and potassium, remained unchanged after 5 days of supplementation with potassium citrate or lemonade. CONCLUSIONS Potassium citrate supplementation is an effective therapy for preventing pediatric urolithiasis, with acceptable adverse effects.


Crosstalk between C/EBPbeta phosphorylation, arginine methylation, and SWI/SNF/Mediator implies an indexing transcription factor code.
Cellular signalling cascades regulate the activity of transcription factors that convert extracellular information into gene regulation. C/EBPbeta is a ras/MAPkinase signal-sensitive transcription factor that regulates genes involved in metabolism, proliferation, differentiation, immunity, senescence, and tumourigenesis. The protein arginine methyltransferase 4 PRMT4/CARM1 interacts with C/EBPbeta and dimethylates a conserved arginine residue (R3) in the C/EBPbeta N-terminal transactivation domain, as identified by mass spectrometry of cell-derived C/EBPbeta. Phosphorylation of the C/EBPbeta regulatory domain by ras/MAPkinase signalling abrogates the interaction between C/EBPbeta and PRMT4/CARM1. Differential proteomic screening, protein interaction studies, and mutational analysis revealed that methylation of R3 constraines interaction with SWI/SNF and Mediator complexes. Mutation of the R3 methylation site alters endogenous myeloid gene expression and adipogenic differentiation. Thus, phosphorylation of the transcription factor C/EBPbeta couples ras signalling to arginine methylation and regulates the interaction of C/EBPbeta with epigenetic gene regulatory protein complexes during cell differentiation.


Exercise autonomous motivation predicts 3-yr weight loss in women.
This study evaluated exercise-related predictors of successful long-term weight control in women by analyzing the extent to which sustained exercise participation and self-determination theory (SDT)-based exercise motivation variables mediated the impact of a behavioral weight control intervention on 3-yr weight change. Longitudinal randomized controlled trial consisting of a 1-yr SDT-based intervention and a 2-yr follow-up with 221 female participants (means ± SD: age = 37.6 ± 7 yr, body mass index = 31.6 ± 4.1 kg·m(-2)). The tested model incorporated experimentally manipulated perceived need support, motivational regulations, and 2-yr exercise adherence as mediators of the intervention's impact on 3-yr weight change. Paths were tested using partial least squares analysis. Where there were significant intervening paths, tests of mediation were conducted. Treatment had significant effects on 1- and 2-yr autonomous regulations, 2-yr physical activity, and 3-yr weight change, fully mediated by the tested paths (effect ratio = 0.10-0.61). Moderate and vigorous exercise at 2 yr had a significant effect (P < 0.001) on weight loss success at 3 yr and partially mediated the effect of treatment on weight change. The 2-yr autonomous regulation effects on follow-up weight change were only partially mediated by physical activity (effect ratio = 0.42). This application of SDT to physical activity and weight management showed that not all types of motivation predict long-term behavioral outcomes and that sustained moderate and vigorous exercise mediated long-term weight change. It provides strong evidence for a link between experimentally increased autonomous motivation and exercise and long-term weight loss maintenance. Results highlight the importance of interventions targeting the internalization of exercise behavioral regulation and making exercise and physical activity positive and meaningful experiences rather than simply focusing on immediate behavior change in overweight/obese women.


Pathogenetic role of the stromal cells in endometriosis and adenomyosis.
Ten cases of endometriosis of bowel, ovaries, uterine serosa and 10 cases of adenomyosis were studied. Blocks of tissue with areas of interest were submitted for serial sectioning of the entire block. Some sections were immunostained for oestrogen receptor, vimentin, Ber-EP-4 and cytokeratins. The common finding was the presence of type 1 nodules, consisting of isolated nodules of endometrial stromal cells without endometrial glands, along blood or lymphatic vessels. The stromal cells showed positive immunoreactivities for oestrogen receptor and vimentin, and negative reactivities for cytokeratins. Due to the absence of connection with adjacent endometriosis or adenomyosis, it is likely that these endometrial stromal nodules arise from the multipotential pericytes. In addition, in serosa of all cases of endometriosis, type 2 nodules, having adjacent mesothelium (Ber-EP4-) changing into epithelium (Ber-EP4+) and type 3 nodules, with non-endometrial epithelium (oestrogen receptor-) changing into endometrial gland (oestrogen receptor+) were identified. We believe that the formation of type 1 nodules from the pericytes and the transformation of the mesothelium into endometrial glands in type 2 and 3 nodules are accomplished through the process of induction by the endometrial stroma, and the proliferation is controlled by genetic, hormonal and immunological factors. Type 1, 2 and 3 nodules are likely to represent a histological continuum in the development of early endometriosis. Subsequent to the formation of endometriosis in the serosa, the pathway of development of endometriosis and adenomyosis is similar. Through the processes of induction and proliferation there is an increase in size of the stroma of type 1 nodules and that of endometrial tissue with subsequent fusion of the stroma of type 1 nodules and that of foci of adenomyosis or endometriosis. Consequently, there is enlargement of the stroma of the foci of adenomyosis or endometriosis. The 'newly enlarged stroma' serves as 'new soil' for further growth of the endometrial glands in the endometrial tissue.


Pathology of the pulmonary vasculature. Correlation with clinical and haemodynamic data.
In dealing with pulmonary vascular disease, essential for the clinician are its correlation with pulmonary arterial pressure and resistance, its potential reversibility and its prognosis for the patient. These relations, however, are far from simple. Medial hypertrophy as well as intimal fibrosis have a fairly good correlation with pressure and resistance in plexogenic arteriopathy but not in pulmonary venous hypertension. Reversibility of intimal fibrosis, and thereby its prognosis for the patient, depends not only on its severity but particularly on its type. The concentric-laminar form of intimal fibrosis for instance has an ominous prognosis when severe in contrast to other types. Not only the various forms of vascular changes and their severity but also the type of pulmonary hypertensive disease have to be taken into account for an accurate evaluation of a lung biopsy.


Self-assembling peptide haemostatic gel reduces incidence of pelvic collection after total mesorectal excision: Prospective cohort study.
Pelvic surgery has the potential to leave behind a large raw surface, which can bleed and ooze postoperatively. The adoption of precision surgical approach for rectal cancers has led to reduction in blood loss. We aimed to assess 1) the feasibility and 2) the safety of using a self-assembling peptide (SAP) haemostatic agent (PuraStat®) after rectal cancer surgery to reduce the incidence of pelvic collections. This prospective cohort pilot study compared the results of 25 consecutive cases of total mesorectal excision (TME) with use of 5-10 ml of SAP, and 25 consecutive cases without PuraStat® application (CON, control group). The groups were compared for complications (Clavien-Dindo grade III and IV classification), postoperative drain output and length of hospital stay (LOS). Statistical analysis was carried out using paired samples T test and Fisher's exact test. Fifty patients (SAP = 25, CON = 25) were enrolled into this study. Mean drain outputs (ml) on day 1, day 2 and day 3 were 60 ± 18, 89 ± 42 and 64 ± 45 in SAP group, and 102 ± 31, 95 ± 52, 66 ± 37 in CON group. This was significantly better for SAP group in day one after surgery. The mean LOS was shorter in SAP group (5.7 versus 7.4 days in CON, p 0.04). Clavien-Dindo III & IV complications were seen in two and five cases respectively (p 0.18). R0 resection rate (p 0.32) and lymph node harvest (p 0.13) were similar in both groups. There were no complications seen in relation to the application of the SAP. These initial data suggest that SAP is a safe product, and feasible to apply in the pelvis after TME surgery. It appears to shorten the LOS and reduce the postoperative drain output and may reduce the incidence of Clavien-Dindo grade III & IV complications.


Safe and successful endoscopic initial treatment and long-term eradication of gastric varices by endoscopic ultrasound-guided Histoacryl (N-butyl-2-cyanoacrylate) injection.
Optimal endoscopic treatment of gastric varices is still not standardized nowadays. Actively bleeding varices may prohibit a successful endoscopic injection therapy of Histoacryl® (N-butyl-2-cyanoacrylate). Since 2006, we have treated gastric varices by standardized endoscopic ultrasound (EUS) guided Histoacryl injection therapy without severe adverse events. We present a large single-center cohort over 7 years with a standardized EUS-guided sclerotherapy of all patients with gastric varices. Application was controlled by fluoroscopy to immediately detect any glue embolization. Only perforating veins located within the gastric wall were treated. In the follow up, we repeated this treatment until varices were eradicated. Utmost patients (36 of 40) were treated during or within 24 h of active bleeding. About 32.5% of patients were treated while visible bleeding. Histoacryl injection was always technically successful and only two patients suffered a minor complication. Acute bleeding was stopped in all patients. About 15% (6 of 40) of patients needed an alternative rescue treatment in the longer course. Three patients got a transjugular portosystemic shunt and another three underwent an orthotopic liver transplantation. Mean long-term survival of 60 months was excellent. Active bleeding of gastric varices can be treated successfully without the necessity of gastric rinsing with EUS-guided injection of Histoacryl.


Site-saturation mutagenesis of the PALTAVETG motif in coxsackievirus A9 capsid protein VP1 reveals evidence of conservation of a periodic hydrophobicity profile.
Enteroviruses possess a highly conserved 9 amino acid stretch of mainly hydrophobic character in the capsid protein VP1. A novel strategy, combining site-saturation mutagenesis and a single-tube cloning and transfection procedure, has been developed for the analysis of this motif in coxsackievirus A9 (CAV-9). Four individual amino acids were separately mutated. Mutagenesis of three of the four positions in CAV-9 resulted in a number of viable but impaired mutant strains, each containing a single amino acid substitution. In contrast, no mutants with amino acid substitutions at leucine 31 were isolated, although three different leucine codons were found among the viruses recovered. Small plaque size was regularly associated with reduced yields of infectious virus and an amino acid substitution at the target site in the viruses isolated from the site-saturated virus pools. From the range of amino acids observed in viable mutants, it was possible to estimate the characteristics that are required at individual amino acid positions. It seems that in the motif studied here, a periodic hydrophobicity profile needs to be conserved. The constraints observed on the ranges of acceptable amino acids presumably reflect the structural-functional requirements that have resulted in the conservation of the motif.


Non-staphylococcal Gram-positive bacteraemia without a known source.
This paper reviews bacteraemia without a known source caused by Gram-positive cocci, excluding staphylococci. These organisms include streptococci of groups A, B, C and G. Bacteraemia caused by nutritionally variant streptococci is also discussed.


Vestibular and cochlear toxicity of aminoglycosides--a review.
Recently, there have been many reports describing the efficacy of intratympanic aminoglycoside injection for the treatment of intractable vertigo in patients with Ménière's disease. However, the number of injections and the amount of drug injected varies, with concomitant variation in the side-effect of hearing deterioration. To identify drugs that are more selectively vestibulotoxic, we have reviewed the ototoxicity of aminoglycosides, focusing on differences between vestibulo- and cochleotoxicity. At present, the basis for the different effects of each drug is unknown. The mechanisms of vestibulo- and cochleotoxicity are deemed worthy of further study.


A pragmatic approach to the diagnosis of inborn errors of metabolism in developing countries.
Inborn errors of metabolism (IEM) are a group of genetically derived diseases that are individually rare but collectively common and can be very severe. While high-income countries usually employ modern scientific technologies like tandem mass spectrometry for IEM investigation, these disorders are, in contrast, only rarely screened for in developing countries due to misconceptions that the required facilities are beyond the reach of these countries. This paper attempts to educate scientists and clinicians in developing countries on low-technology IEM screening methods that only require moderate facilities. Although a definitive diagnosis of IEM may require specialised laboratory investigations and attendant interpretation, in most cases, the basic facilities available in the average clinical chemistry laboratory in developing countries can allow the early detection of IEM. This early detection would facilitate critical early decision making, thus leading to better management, optimised treatment, and reduced morbidity and or mortality of IEM in these resource-limited countries. With this approach, a few referral centres for confirmatory investigation, comparable to those existing in developed countries, could be established. This can be integrated into creative health education for healthcare professionals and families who have individuals with IEM. IEMs are important enough that every country, developed or developing, should have screening plans and basic laboratory facilities that are adequate for initial IEM diagnosis. No country should therefore give up on testing for IEMs on the excuse of a paucity of advanced facilities.


Safety and Acceptability of Community-Based Distribution of Injectable Contraceptives: A Pilot Project in Mozambique.
Mozambique has witnessed a climbing total fertility rate in the last 20 years. Nearly one-third of married women have an unmet need for family planning, but the supply of family planning services is not meeting the demand. This study aimed to explore the safety and effectiveness of training 2 cadres of community health workers-traditional birth attendants (TBAs) and agentes polivalentes elementares (APEs) (polyvalent elementary health workers)-to administer the injectable contraceptive depot-medroxyprogesterone acetate (DMPA), and to provide evidence to policy makers on the feasibility of expanding community-based distribution of DMPA in areas where TBAs and APEs are present. A total of 1,432 women enrolled in the study between February 2014 and April 2015. The majority (63% to 66%) of women in the study started using contraception for the first time during the study period, and most women (over 66%) did not report side effects at the 3-month and 6-month follow-up visits. Very few (less than 0.5%) experienced morbidities at the injection site on the arm. Satisfaction with the performance of TBAs and APEs was high and improved over the study period. Overall, the project showed a high continuation rate (81.1%) after 3 injections, with TBA clients having significantly higher continuation rates than APE clients after 3 months and after 6 months. Clients' reported willingness to pay for DMPA (64%) highlights the latent demand for modern contraceptives. Given Mozambique's largely rural population and critical health care workforce shortage, community-based provision of family planning in general and of injectable contraceptives in particular, which has been shown to be safe, effective, and acceptable, is of crucial importance. This study demonstrates that community-based distribution of injectable contraceptives can provide access to family planning to a large group of women that previously had little or no access.


Effect of mazEF, higBA and relBE toxin-antitoxin systems on antibiotic resistance in Pseudomonas aeruginosa and Staphylococcus isolates.
A toxin-antitoxin (TA) system is a set of two or more closely linked genes that are encoded as a poison and a corresponding antidote on a protein. In typical bacterial physiology, an antitoxin binds to a toxin and neutralizes it, which prevents the bacterium from killing itself. We aimed to determine whether P.aeruginosa and Staphylococcus isolates have TA genes and to investigate whether there is a relationship between the expression levels of TA genes and resistance to antibiotics. This study included 92 P. aeruginosa and 148 Staphylococcus isolates. RelBE, higBA genes were investigated in P.aeruginosa by multiplex polymerase chain reaction (PCR). The mazEF gene and the all TA genes expression were detected by real time PCR. RelBE and higBA genes were detected in 100% of P. aeruginosa. It was found that the level of relBE TA gene expression is increased in isolates sensitive to aztreonam compared to resistant isolates (p<0.05). The mazEF gene was detected in 89.1% of Staphylococcus isolates. In terms of MazEF gene expression level there was no significant difference between methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates (p>0.05) whereas there was a significant difference between MSSA and coagulase-negative Staphylococcus (CNS) isolates, MRSA and CNS isolates (p<0.05). The levels of mazEF gene expression were found to be higher in isolates sensitive to gentamicin, ciprofloxacin, levofloxacin, clindamycin, phosphomycine, nitrofurantoin, fusidic acid, cefoxitin compared to resistant isolates (p<0.05). Studies on the prevalence and functionality of TA systems emphasize that it may be possible to have new sensitive regions in bacteria by activating TA systems. The results of this study lead to the idea that resistance to antibiotics can be reduced by increasing TA gene expression levels. But there is need for further studies to support and develop this issue.


Expression of ecotropic murine leukaemia virus in haemopoietic cells of AKR mice during the embryonic and neonatal period.
Cells which produce ecotropic murine leukaemia virus have been detected in the bone marrow and the spleen of weanling AKR mice, using an infectious centre technique based on the XC test. There is a noticeable increase in the number of virus-producing cells between day 3 and day 12 after birth, in both of these organs. Some of the virus-producing cells that appear after day 3 have been identified as haemopoietic precursor cells of the granulocyte-macrophage blood lineage. Such precursor cells do not produce virus during the embryonic period and they progressively become involved in virus production after day 3. By day 12, all of them are active virus producers. Thus, the ecotropic virus is expressed in precursor cells of the haemopoietic system, and the latter represent at least one-third of the virus-producing cells in the bone marrow of young AKR mice.


Adrenocorticotropin, and corticosterone secretion in Brattleboro rats.
Brattleboro rats which lack endogenous vasopressin have been used to study the role of vasopressin as a corticotropin-releasing factor. Plasma ACTH, beta-endorphin, and corticosterone were measured by RIA in male and female Long-Evans and Brattleboro rats under the following conditions: unstressed, after ether stress, after nicotine injection, and after adrenalectomy. A significant reduction in the ACTH, beta-endorphin, and corticosterone responses to the different experimental procedures was observed in the Brattleboro rats. However, in this strain of rats, a significant increase in the release of all three hormones was obtained, suggesting that vasopressin has only a synergistic role in the regulation of their secretion.


Different expression of renin-angiotensin system components in hearts of normotensive and hypertensive rats.
Tissue renin-angiotensin systems are known to behave differently from the circulating renin-angiotensin system (RAS). It has already been proposed that not only the circulating RAS, but also RAS localized in the cardiac tissue plays an important role in the heart failure. The objective of this study was to compare the gene expression of individual components of the renin-angiotensin system in hearts of normotensive and hypertensive rats. Two genetically hypertensive rat strains--spontaneously hypertensive rats (SHR) and hereditary hypertriglyceridemic rats (HTG)--were compared with Wistar-Kyoto (WKY) and Lewis (LEW) normotensive controls. In addition, developmental changes in gene expression of individual components of cardiac RAS were studied in 20-day-old fetuses, 2-day-old newborns and 3-month-old HTG and LEW rats. In our study, the angiotensinogen gene expression did not differ either among adult normotensive and hypertensive strains, or during development. In contrast, the renin gene expression was significantly increased in hearts of hypertensive compared to normotensive rats. Moreover, a 5-fold increase of renin mRNA was observed in hearts of HTG rats between day 2 and the third month of age. There was also an age-dependent increase of ACE gene expression in both HTG and LEW rats which was substantially delayed in HTG hearts. In conclusion, the results of our study suggest that overexpression of the cardiac renin gene in hypertensive strains could participate in the structural and functional changes of the heart during the development of hypertension.


Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels.
Potassium channels embedded in cell membranes employ gates to regulate K+ current. While a specific constriction in the permeation pathway has historically been implicated in gating, recent reports suggest that the signature ion selectivity filter located in the outer membrane leaflet may be equally important. Inwardly rectifying K+ channels also control the directionality of flow, using intracellular polyamines to stem ion efflux by a valve-like action. This study presents crystallographic evidence of interdependent gates in the conduction pathway and reveals the mechanism of polyamine block. Reorientation of the intracellular domains, concomitant with activation, instigates polyamine release from intracellular binding sites to block the permeation pathway. Conformational adjustments of the slide helices, achieved by rotation of the cytoplasmic assembly relative to the pore, are directly correlated to the ion configuration in the selectivity filter. Ion redistribution occurs irrespective of the constriction, suggesting a more expansive role of the selectivity filter in gating than previously appreciated.


Injuries among Korean Female Professional Golfers: A Prospective Study.
This study aims to analyze the incidence, location, type, and mechanisms of injuries and possible injury risk factors among all levels of Korean female professional golfers. This was a prospective study with a follow-up period of 24 months. A total of 363 members of the Korean Ladies Professional Golf Association (KLPGA), who competed in tournaments during the 2015 and 2016 seasons, took part in the study. The incidence of injury varied by tournament level and was significantly higher in Division II (11.1/1000AEs) and Division III (13.4/1000AEs) than in Division I (5.6/1000AEs) (p < 0.05). The most common location and type of injury were the shoulder/clavicle (Division I: 14.1%, Division II: 15.7%, Division III: 17.3%) and the tendinosis or tendinopathy (21.2%) (Division I: 23.7%, Division II: 21.2%, Division III: 18.5%), respectively. The most common mechanism of injury was the golf swing (47.9%-51.6% for the three divisions), and the most frequent specific phase of injury was upon ball impact (23.5%-30.9%). Multivariate analysis revealed that body mass index and the number of previous season competitions were significantly associated with injury risk in female golfers. The other factors examined did not have a significant association with golf-related injuries. In conclusion, KLPGA golfers were commonly exposed to injuries and showed a higher rate of injuries in competitions than practices, with significantly higher in Division II, III than Division I. However, overall, there was no significant difference in the location, type, mechanism and risk factors for injuries among the division level of KLPGA.


Analysis of SEMA3B methylation and expression patterns in gastric cancer tissue and cell lines.
The family of semaphorins has been demonstrated to possess tumor suppressor activity, in which semaphorin 3B (SEMA3B) is differentially expressed in several types of tumors. The relationship between SEMA3B expression and its clinical significance in gastric cancer (GC) is currently unclear. In the present study, the expression and methylation status of the SEMA3B gene were detected by quantitative PCR and bisulfite sequencing PCR (BSP). Data indicated that the levels of SEMA3B mRNA decreased in gastric tumor tissues and the methylation status of SEMA3B in the tumor group was higher than the paired normal tissues. By BSP, the SEMA3B gene showed high methylated status which was detected in all 4 cell lines (AGS, BGC-823, MGC-803 and SGC-7901). Treatment of the cells with 5-Aza-2'-deoxycytidine revealed clearly elevated mRNA levels of SEMA3B. These results were further confirmed by western blot analysis of Sema3b protein expression. At the same time, increased expression of p53 mRNA in BGC-823, MGC-803 was detected and indicated that p53 may be involved in the regulation of SEMA3B expression in specific genetic background. Downregulation of SEMA3B was negatively correlated with tumor size and N staging in GC (p<0.05). In conclusion, CpG methylation of SEMA3B epigenetically regulates SEMA3B expression during development of GC. Furthermore, 5-Aza-2'-deoxycytidine could reverse the hypermethylation status of SEMA3B, which may benefit future studies exploring the application of demethylating agents in clinical usage of GC.


A field expansions method for scattering by periodic multilayered media.
The interaction of acoustic and electromagnetic waves with periodic structures plays an important role in a wide range of problems of scientific and technological interest. This contribution focuses upon the robust and high-order numerical simulation of a model for the interaction of pressure waves generated within the earth incident upon layers of sediment near the surface. Herein described is a boundary perturbation method for the numerical simulation of scattering returns from irregularly shaped periodic layered media. The method requires only the discretization of the layer interfaces (so that the number of unknowns is an order of magnitude smaller than finite difference and finite element simulations), while it avoids not only the need for specialized quadrature rules but also the dense linear systems characteristic of boundary integral/element methods. The approach is a generalization to multiple layers of Bruno and Reitich's "Method of Field Expansions" for dielectric structures with two layers. By simply considering the entire structure simultaneously, rather than solving in individual layers separately, the full field can be recovered in time proportional to the number of interfaces. As with the original field expansions method, this approach is extremely efficient and spectrally accurate.


Group B streptococcus endocarditis following second-trimester abortion.
An 18-year-old woman who underwent an elective second-trimester abortion developed Streptococcus agalactiae (group B streptococcus) endocarditis characterized by a large, pedunculated vegetation involving a previously normal tricuspid valve. Polyarthritic symptoms, as well as multiple pulmonary emboli, were experienced, and cure followed a course of treatment using intravenous penicillin G potassium combined with gentamicin sulfate. Endocarditis caused by this pathogen usually occurs among individuals compromised by underlying chronic disorders and, today, is a rare sequela of pregnancy and abortion. When planning therapy, consideration should be given to the possibility of tolerance among clinical isolates and the need for operative intervention in selected patients.


Preferential adhesion of fetal liver derived primitive haemopoietic progenitor cells to bone marrow stroma.
The orderly transfer of haemopoiesis from the fetal liver to the medullary cavities during the ontogeny may result from a decrease in the capacity of the fetal liver to support haemopoiesis. Alternatively it could be facilitated by the preferential migration of primitive haemopoietic cells to the marrow. In this study we have compared the ability of high proliferative potential colony forming cells (HPP-CFC) derived from murine fetal liver (FL) on the 15th day of gestation and from murine adult bone marrow (BM) to adhere to either FL or BM derived stromal layers. Adhesion of FL HPP-CFC to bone marrow stromal layers was significantly greater than all other combinations tested. The remarkable affinity of HPP-CFC derived from FL for BM stromal layers is consistent with the preferential migration of haemopoietic cells from the fetal liver to the medullary cavities.


Growth Rate of Giant Clam Tridacna gigas at Bikini Atoll as Revealed by Radioautography.
At Bikini Atoll, radioactivity from strontium-90 deposited in the growing shell of a giant clam, presumably during the testing of nuclear weapons in 1956 and 1958, produced unmistakable lines on radioautographs made from transverse sections of the shell. The regular banding seen in the sections is interpreted as annular in nature. One annulus precedes the 1956 layer of radioactivity, two intervene in 1958, and six follow to the time of collection, so that this clam (length, 52 centimeters) was in its 9th year of life.


Inhibition of Listeria monocytogenes by food antimicrobials applied singly and in combination.
Combining food antimicrobials can enhance inhibition of Listeria monocytogenes in ready-to-eat (RTE) meats. A broth dilution assay was used to compare the inhibition of L. monocytogenes resulting from exposure to nisin, acidic calcium sulfate, ε-poly-L-lysine, and lauric arginate ester applied singly and in combination. Minimum inhibitory concentrations (MICs) were the lowest concentrations of single antimicrobials producing inhibition following 24 h incubation at 35 °C. Minimum bactericidal concentrations (MBCs) were the lowest concentrations that decreased populations by ≥3.0 log(10) CFU/mL. Combinations of nisin with acidic calcium sulfate, nisin with lauric arginate ester, and ɛ-poly-L-lysine with acidic calcium sulfate were prepared using a checkerboard assay to determine optimal inhibitory combinations (OICs). Fractional inhibitory concentrations (FICs) were calculated from OICs and were used to create FIC indices (FIC(I)s) and isobolograms to classify combinations as synergistic (FIC(I) < 1.00), additive/indifferent (FIC(I)= 1.00), or antagonistic (FIC(I) > 1.00). MIC values for nisin ranged from 3.13 to 6.25 μg/g with MBC values at 6.25 μg/g for all strains except for Natl. Animal Disease Center (NADC) 2045. MIC values for ε-poly-L-lysine ranged from 6.25 to 12.50 μg/g with MBCs from 12.50 to 25.00 μg/g. Lauric arginate ester at 12.50 μg/g was the MIC and MBC for all strains; 12.50 mL/L was the MIC and MBC for acidic calcium sulfate. Combining nisin with acidic calcium sulfate synergistically inhibited L. monocytogenes; nisin with lauric arginate ester produced additive-type inhibition, while ε-poly-L-lysine with acidic calcium sulfate produced antagonistic-type inhibition. Applying nisin along with acidic calcium sulfate should be further investigated for efficacy on RTE meat surfaces.


Stress erythropoiesis: new signals and new stress progenitor cells.
Acute anemic stress induces a physiological response that includes the rapid development of new erythrocytes. This process is referred to as stress erythropoiesis, which is distinct from steady state erythropoiesis. Much of what we know about stress erythropoiesis comes from the analysis of murine models. In this review, we will discuss our current understanding of the mechanisms that regulate stress erythropoiesis in mice and discuss outstanding questions in the field. Stress erythropoiesis occurs in the murine spleen, fetal liver and adult liver. The signals that regulate this process are Hedgehog, bone morphogenetic protein 4 (BMP4), stem cell factor and hypoxia. Recent findings show that stress erythropoiesis utilizes a population of erythroid-restricted self-renewing stress progenitors. Although the BMP4-dependent stress erythropoiesis pathway was first characterized during the recovery from acute anemia, analysis of a mouse model of chronic anemia demonstrated that activation of the BMP4-dependent stress erythropoiesis pathway provides compensatory erythropoiesis in response to chronic anemia as well. The BMP4-dependent stress erythropoiesis pathway plays a key role in the recovery from acute anemia and new data show that this pathway compensates for ineffective steady state erythropoiesis in a murine model of chronic anemia. The identification of a self-renewing population of stress erythroid progenitors in mice suggests that therapeutic manipulation of this pathway may be useful for the treatment of human anemia. However, the development of new therapies will await the characterization of an analogous pathway in humans.


Deconstructing childhood conduct and adult antisocial criteria for the diagnosis of antisocial personality disorder.
Antisocial personality disorder (ASPD) is a serious psychiatric disorder that can be incapacitating and costly to individuals and society. The ASPD diagnosis has 2 main components, childhood conduct problems and adult antisocial behaviors, with specific age requirements. The nosological effects of these criteria on population subgroups defined by these aspects of the criteria have not been fully explored. Data for ASPD were analyzed for 3,498 individuals in the St Louis, Missouri, site of the Epidemiologic Catchment Area study of general population psychiatric disorders collected in the early 1980s using structured diagnostic interviews for DSM-III criteria. Effects of the criteria on population subgroups defined by various combinations of the criteria were examined. Earlier-onset conduct disorder was more severe than later-onset childhood conduct disorder, with more total childhood and adult symptoms and negative psychosocial adult outcomes (substance use disorders, criminality, and homelessness). Three subgroups with adult antisocial behaviors (differentiated by no conduct disorder, later-onset conduct disorder, and earlier-onset conduct disorder meeting ASPD criteria) were similar in numbers of adult antisocial symptoms, but the ASPD subgroup had more negative psychosocial adult outcomes. These findings provide evidence for and against reconsideration of the 15-year age-of-onset requirement for conduct symptoms in ASPD criteria.


Availability of hospital dental care services under sedation or general anesthesia for individuals with special needs in the Unified Health System for the State of Minas Gerais (SUS-MG), Brazil.
This study identified the demographic characteristics of individuals and dental treatment care under sedation/general anesthesia in a hospital environment in the Unified Health System in the State of Minas Gerais (SUS-MG). All Hospitalization Authorizations (AIHs) for Dental Treatment for Patients with Special Needs procedures were evaluated between July 2011 and June 2012. Demographic and health care variables for treatment were also assessed. Hospitalization rates per 10,000 inhabitants, and health care coverage provided in the state of Minas Gerais and in each of the Broader Health Regions were calculated. Descriptive analysis of data was carried out by calculating the central trend and variability frequency and measurements. All 1,063 AIHs paid during the study period were evaluated, which is equivalent to a rate of 0.54 hospitalizations per 10,000 individuals. The majority of the patients were adult, male, diagnosed with mental or behavioral disorders and resident in 27.7% of the municipalities in Minas Gerais. The procedures were performed in 39 municipalities and the care coverage was equal to 1.58%. The study reveals a classic demographic and clinical profile of patient attendance. Difficulties in establishing a network of dental care were identified.


Aspects of tail muscle ultrastructure and its degeneration in Rana temporaria.
1. Tail muscles of larval Rana temporaria and to a lesser extent Xenopus laevis, at prometamorphosis, were investigated by light and electron microscopy. In the case of Rana their degeneration is described at metamorphic climax. 2. The non-degenerate tail muscles of both genera are generally similar in their ultrastructure and likewise similar to those striated muscles of other adult vertebrates including amphibians. 3. At climax tail muscles of Rana degenerate by autolysis. It seems likely that lysosomal enzymes are directly involved in sarcoplasmic degeneration. The relationship between lysosomes and myofibrillar degradation is difficult to establish. The subject is discussed in the light of relevant information (mainly mammalian) on muscle dystrophies. 4. Anuran tail muscle is highly degraded before its probable phagocytosis by mesenchymal macrophages.


When success breeds failure: history, hysteresis, and delayed exit decisions.
The effects of feedback equivocality, information availability, and prior decision-making history on escalation and persistence were investigated. Replicating the findings of J.L. Bragger, D.H. Bragger, D.A. Hantula, and J.P. Kirnan (1998), this study found that participants receiving equivocal feedback on their decisions invested more money and invested across more opportunities; those who could purchase information invested fewer resources than did participants who did not have the opportunity to purchase information. There was an inverse linear relationship between the percentage of opportunities in which participants purchased information and the delay to exit decisions and total resources invested. Six weeks earlier, some participants took part in a more profitable investment scenario, and prior experience led to later increased investing when participants were faced with failure, even above that invested in a preceding, succeeding scenario. These results are consistent with an equivocality theory account of escalation.


Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNΔ7 mouse model of SMA.
Spinal muscular atrophy (SMA) is a severe motor neuron (MN) disease caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene, which results in reduced levels of the SMN protein and the selective degeneration of lower MNs. The best-known function of SMN is the biogenesis of spliceosomal snRNPs, the major components of the pre-mRNA splicing machinery. Therefore, SMN deficiency in SMA leads to widespread splicing abnormalities. We used the SMN∆7 mouse model of SMA to investigate the cellular reorganization of polyadenylated mRNAs associated with the splicing dysfunction in MNs. We demonstrate that SMN deficiency induced the abnormal nuclear accumulation in euchromatin domains of poly(A) RNA granules (PARGs) enriched in the splicing regulator Sam68. However, these granules lacked other RNA-binding proteins, such as TDP43, PABPN1, hnRNPA12B, REF and Y14, which are essential for mRNA processing and nuclear export. These effects were accompanied by changes in the alternative splicing of the Sam68-dependent Bcl-x and Nrnx1 genes, as well as changes in the relative accumulation of the intron-containing Chat, Chodl, Myh9 and Myh14 mRNAs, which are all important for MN functions. PARG-containing MNs were observed at presymptomatic SMA stage, increasing their number during the symptomatic stage. Moreover, the massive accumulations of poly(A) RNA granules in MNs was accompanied by the cytoplasmic depletion of polyadenylated mRNAs for their translation. We suggest that the SMN-dependent abnormal accumulation of polyadenylated mRNAs and Sam68 in PARGs reflects a severe dysfunction of both mRNA processing and translation, which could contribute to SMA pathogenesis.


Damage control surgery: 6 years of experience at a level I trauma center.
Damage control surgery (DCS) has been a well-established practice in the management of trauma victims for more than 2 decades now. The primary aim of this study was to review and analyze the presentation and outcome of patients with torso trauma who underwent DCS at Level I trauma center. Retrospective study was conducted using database records prospectively maintained over period of 6 years from 2008 through 2013 at an urban Level I trauma center. Data available from hospital medical records were analyzed to study presentation, mechanism of injury, organs injured, associated injuries, and outcome in patients who underwent DCS following torso trauma. Primary outcome measure was survival. Total of 61 patients were identified who had undergone DCS during the study period. Majority of these patients were males (n=59), had sustained blunt trauma as result of road traffic injury, and had presented with shock (n=49). The 30-day mortality rate was 54%. Mortality was significantly associated with shock (63% cases died; p=0.008), and with Glasgow Coma scale ≤8 (85% died; p=0.001). Injuries significantly associated with high mortality were hepatic injury (n=15; 11 died), major vascular injury (n=10; 3 died), cardiac injury (n=5; 3 died), and pelvic fracture (n=17; 10 died). Re-exploration was required in 28 cases with 13 deaths. Mesh laparostomy was performed in 24 cases, with mortality in 58%. In the absence of more effective alternative, especially at facilities with limited resources, DCS may be appropriate in critically injured patients; however, it continues to be associated with significant morbidity and high mortality, even at tertiary care centers.


Vascular effects of combined enriched Korean Red ginseng (Panax Ginseng) and American ginseng (Panax Quinquefolius) administration in individuals with hypertension and type 2 diabetes: A randomized controlled trial.
Type 2 diabetes is known to abrogate the vascular response. Combination of two commonly consumed ginseng species, American ginseng (AG) and a Korean Red ginseng (KRG), enriched with ginsensoide Rg3, was shown to concomitantly improve glucemic control and blood pressure. We evaluated the hypothesis that improvements in central hemodynamics, vascular function and stiffness markers are involved in observed benefits of co-administration. In this randomized, placebo controlled, two-center trial, patients with type 2 diabetes and hypertension were assigned to either 2.25 g ginsenoside Rg3-enriched KRG&AG co-administration or a control 3 times daily for 12-weeks, treated by standard of care. The effects on central hemodynamics, pulse wave velocity (PWV) and endothelial function over the 12-week administration were analyzed. In intent-to-treat analysis of 80 individuals, a reduction in central systolic BP (-4.69 ± 2.24 mmHg, p = 0.04) was observed with co-administration of Rg3-KRG + AG relative to control at 12-weeks, which was characterized by a decrease in end-systolic pressure (-6.60 ± 2.5 mmHg, p = 0.01) and area under the systolic/diastolic BP curve (-132.80 ± 65.1, p = 0.04, 220.90 ± 91.1, p = 0.02, respectively). There was no significant change in reactive hyperemia index (0.09 ± 0.11, p = 0.44), PWV (-0.40 ± 0.28 %, p = 0.17), and other related pulse wave analysis components. Co-administration of complementary ginseng species improved central systolic BP and components of pulse waveform without a direct effect on endothelial function, when added to background pharmacotherapy in individuals with diabetes. These data support potential utility of ginseng for modest blood pressure benefit to broaden its role in diabetes management.


Federally Qualified Health Centers Can Expand Rural Access to Buprenorphine for Opioid Use Disorder in Arizona.
Medication for Opioid Use Disorder (MOUD) is recommended, but not always accessible to those who desire treatment. This study assessed the impact of expanding access to buprenorphine through federally qualified health centers (FQHCs) in Arizona. We calculated mean drive-times to Arizona opioid treatment (OTP) locations, office-based opioid treatment (OBOT) locations, and FQHCs clinics using January 2020 location data. FQHCs were designated as OBOT or non-OBOT clinics to explore opportunities to expand treatment access to non-OBOT clinics (potential OBOTs) to further reduce drive-times for rural and underserved populations. We found that OTPs had the largest mean drive times (16.4 minutes), followed by OBOTs (7.1 minutes) and potential OBOTs (6.1 minutes). Drive times were shortest in urban block groups for all treatment types and the largest differences existed between OTPs and OBOTs (50.6 minutes) in small rural and in isolated rural areas. OBOTs are essential points of care for opioid use disorder treatment. They reduce drive times by over 50% across all urban and rural areas. Expanding buprenorphine through rural potential OBOT sites may further reduce drive times to treatment and address a critical need among underserved populations.


Transcription of glnA in E. coli is stimulated by activator bound to sites far from the promoter.
Transcription of the Escherichia coli glnALG operon, whose products are glutamine synthetase and the regulatory proteins NRII and NRI, is activated by nitrogen deprivation. Initiation of transcription at the nitrogen-regulated promoter glnAp2 requires sigma 60, the product of rpoN (glnF, ntrA), and NRI, the product of glnG (ntrC). We have now shown that the ability of this promoter to be activated by a low intracellular concentration of NRI depends on two binding sites for NRI located approximately 110 and 140 bp, respectively, upstream of the start of transcription. Moving these binding sites more than 1000 bp does not diminish the ability of NRI to stimulate transcription at glnAp2. Thus, the NRI binding sites resemble enhancers in eukaryotic cells.


Duplication of a truncated paralog of the family B DNA polymerase gene Aa-polB in the Agrocybe aegerita mitochondrial genome.
The Agrocybe aegerita mitochondrial genome contains a truncated family B DNA polymerase gene (Aa-polB P1) whose nucleotide sequence is 86% identical to the previously described and potentially functional Aa-polB gene. A tRNA(Met) gene occurs at the 3' end of the Aa-polB P1 gene. The Aa-polB P1 gene could result from reverse transcription of an Aa-polB mRNA primed by a tRNA(Met) followed by the integration of the cDNA after recombination at the mitochondrial tRNA locus. Two naturally occurring alleles of Aa-polB P1 carry one or two copies of the disrupted sequence. In strains with two copies of Aa-polB P1, these copies are inverted relative to one another and separated by a short sequence carrying the tRNA(Met) gene. Both A. aegerita mitochondrial family B DNA polymerases were found to be related to other family B DNA polymerases (36 to 53% amino acid similarity), including the three enzymes of the archaebacterium Sulfolobus solfataricus. If mitochondria originated from a fusion between a Clostridium-like eubacterium and a Sulfolobus-like archaebacterium, then the A. aegerita family B DNA polymerase genes could be remnants of the archaebacterial genes.


Biophysical evolution of the receptor-binding domains of SARS-CoVs.
With hundreds of coronaviruses (CoVs) identified in bats that can infect humans, it is essential to understand how CoVs that affected the human population have evolved. Seven known CoVs have infected humans, of which three CoVs caused severe disease with high mortalities: severe acute respiratory syndrome (SARS)-CoV emerged in 2002, Middle East respiratory syndrome-CoV in 2012, and SARS-CoV-2 in 2019. SARS-CoV and SARS-CoV-2 belong to the same family, follow the same receptor pathway, and use their receptor-binding domain (RBD) of spike protein to bind to the angiotensin-converting enzyme 2 (ACE2) receptor on the human epithelial cell surface. The sequence of the two RBDs is divergent, especially in the receptor-binding motif that directly interacts with ACE2. We probed the biophysical differences between the two RBDs in terms of their structure, stability, aggregation, and function. Since RBD is being explored as an antigen in protein subunit vaccines against CoVs, determining these biophysical properties will also aid in developing stable protein subunit vaccines. Our results show that, despite RBDs having a similar three-dimensional structure, they differ in their thermodynamic stability. RBD of SARS-CoV-2 is significantly less stable than that of SARS-CoV. Correspondingly, SARS-CoV-2 RBD shows a higher aggregation propensity. Regarding binding to ACE2, less stable SARS-CoV-2 RBD binds with a higher affinity than more stable SARS-CoV RBD. In addition, SARS-CoV-2 RBD is more homogenous in terms of its binding stoichiometry toward ACE2 compared to SARS-CoV RBD. These results indicate that SARS-CoV-2 RBD differs from SARS-CoV RBD in terms of its stability, aggregation, and function, possibly originating from the diverse receptor-binding motifs. Higher aggregation propensity and decreased stability of SARS-CoV-2 RBD warrant further optimization of protein subunit vaccines that use RBD as an antigen by inserting stabilizing mutations or formulation screening.


Mass drug administration: the importance of synchrony.
Mass drug administration, a strategy in which all individuals in a population are subject to treatment without individual diagnosis, has been recommended by the World Health Organization for controlling and eliminating several neglected tropical diseases, including trachoma and soil-transmitted helminths. In this article, we derive effective reproduction numbers and average post-treatment disease prevalences of a simple susceptible-infectious-susceptible epidemic model with constant, impulsive synchronized and non-synchronized drug administration strategies. In the non-synchronized model, the individuals in the population are treated at most once per period and their treatment times are uniformly distributed. Mathematically, the set of pulses for the non-synchronized model has the cardinality of the continuum. We show that synchronized and constant strategies are, respectively, the most and least effective treatments in disease control. Elimination through synchronized treatment is always possible when adequate drug efficacy and coverage are fulfilled and sustained. For a strategy with multiple rounds of synchronized treatment per period, the average post-treatment prevalence is irrelevant what the time differences between treatments are, as long as there are the same number of treatments per period.


Evidence for corneal endothelial cell hypertrophy during postnatal growth of the cat cornea.
Endothelial cell counts made from specular micrographs of 1-month-old kitten and adult cat corneas demonstrate that a progressive increase in endothelial cell size and a reduced endothelial cell density occurs during the postnatal development of the cat cornea. In addition to confirming the difference in cell size, scanning electron micrographs show that kitten endothelial cells are much more pleomorphic than those of the adult. When the number of corneal endothelial cells/mm2 and the size of the whole cornea are calculated for the kitten and adult, hypertrophy rather than mitosis appears to be the principal mechanism responsible for maintaining a confluent endothelial cell monolayer during the postnatal development of the feline cornea. Hypertrophy also appears to play a role in establishing the adult corneal endothelial cell population of the rabbit when the previously published data of others are treated in a similar manner to those of the kitten and adult cat. Thus, endothelial cell hypertrophy plays a role in establishing an "adult" endothelial cell monolayer in species that have a widely divergent corneal endothelial cell mitotic capacity.


A field strain of minute virus of mice (MVMm) exhibits age- and strain-specific pathogenesis.
The influence of mouse strain, immune competence and age on the pathogenesis of a field strain of minute virus of mice (MVMm) was examined in BALB/c, C3H, C57BL/6 and SCID mice experimentally infected as neonates, weanlings and adults. Sera, bodily excretions and tissues were harvested at 7, 14, 28 and 56 days after inoculation and evaluated by serology, quantitative PCR and histopathology. Seroconversion to recombinant viral capsid protein 2 was consistently observed in all immunocompetent strains of mice, regardless of the age at which they were inoculated, while seroconversion to the viral nonstructural protein 1 was only consistently detected in neonate inoculates. Viral DNA was detected by quantitative PCR in multiple tissues of immunocompetent mice at each time point after inoculation, with the highest levels being observed in neonate inoculates at 7 days after inoculation. In contrast, viral DNA levels in tissues and bodily excretions increased consistently over time in immunodeficient SCID mice, regardless of the age at which they were inoculated, with mortality being observed in neonatal inoculates between 28 and 56 days after inoculation. Overall, productive infection was observed more frequently in immunocompetent mice inoculated as neonates as compared to those inoculated as weanlings or adults, and immunodeficient SCID mice developed persistent, progressive infection, with mortality being observed in mice inoculated as neonates. Importantly, the clinical syndrome observed in experimentally infected SCID neonatal mice recapitulates the clinical presentation reported for the naturally infected immunodeficient NOD µ-chain knockout mice from which MVMm was initially isolated.


Classification and Outcome Measures for Psoriatic Arthritis.
Psoriatic arthritis (PsA) is an inflammatory arthritis with multiple manifestations: peripheral/axial arthritis, enthesitis, dactylitis, psoriasis, and nail involvement. From having an agreed upon classification criteria in 2006, the assessment of PsA has advanced from uncertainties to development and validation of numerous specific outcome measures. The Group for Research and Assessment of Psoriasis and Psoriatic arthritis (GRAPPA) has spearheaded the development of a core domain set and is now working on a core outcome measurement set to standardize outcome measures for PsA, that will provide guidance for use of instruments in randomized controlled trials (RCTs) and longitudinal observational studies (LOS). This article summarizes and updates these work processes to improve assessment of this multisystem complex rheumatologic disease.


Ventricular parasystole: a chronobiologic study.
Previous works have reported circadian rhythms for several cardiovascular parameters. A chronobiologic rhythm is characterized by: mesor (a rhythm-determined average), amplitude (half difference between the highest and lowest values), and acrophase (timing of high point in degrees and/or in hours) along with 95% confidence limits. We performed 24-hour ECG Holter monitoring in seven patients (mean age, 50.6 years) with ventricular parasystole (VP) in order to determine whether the chronotropic activity of parasystolic foci has a circadian rhythm similar to that of the sinus node. For each Holter recording parasystolic rates (PRs) and heart rates (HRs) were calculated every hour. Furthermore, a mean hourly PR and a mean hourly HR were calculated from the hourly PRs and HRs of the patients. The statistic chronobiologic analysis was done by single and mean cosinor methods. Correlation between mean hourly PR and HR was evaluated by Pearson's 'r' coefficient. A statistically significant rhythm (P less than 0.05) was found for the single and mean rhythms both of HR and PR. In our patients, HR had acrophase at 1.27 P.M., mesor at 73.28 beats/min, and amplitude at 9.53 beats/min, whereas PR had acrophase at 1.42 P.M., mesor at 38.31 beats/min, and amplitude at 3.64 beats/min. Chronobiological data and the high direct correlation between mean hourly HRs and mean hourly PRs (r = 0.96, P less than 0.001) indicate a similar circadian variability of the chronotropic activity of sinus nodes and parasystolic foci. Although several hypotheses can be made, responsiveness of parasystolic foci to circadian variations of the autonomic nervous system tone (sympathetic and/or vagal) and/or circulating substances (particularly catecholamines) seems the more probable one for explaining our findings.


Quercetin alleviates lipopolysaccharide‑induced acute lung injury by inhibiting ferroptosis via the Sirt1/Nrf2/Gpx4 pathway.
Acute lung injury (ALI) causes high morbidity and mortality rates in critically ill patients, and there are currently no effective therapeutic drugs. Ferroptosis is a newly discovered mode of regulated cell death that contributes to the progression of ALI. Quercetin possesses anti‑inflammatory and antioxidant properties. However, whether quercetin can protect against lipopolysaccharide (LPS)‑induced ALI by inhibiting ferroptosis and its underlying mechanisms remains unclear. The present study evaluated the protective effects of quercetin and underlying molecular mechanisms in LPS‑induced ALI by establishing an ALI mouse model and an alveolar epithelial cell injury model via treatment of the mice or alveolar epithelial cells with LPS. Mouse lung injury was assessed by evaluating the histological lung injury score, bronchoalveolar lavage fluid cell count and inflammatory cytokine levels; alveolar epithelial cell injury was assessed by Cell counting kit‑8, lactate dehydrogenase and EDU assays; and ferroptosis was assessed by detecting the changes in the levels of malondialdehyde, glutathione, iron, glutathione peroxidase 4 (Gpx4) and 4‑hydroxynonenal in vivo and vitro. The present study indicated that quercetin effectively ameliorated LPS‑induced ALI in the mouse model by reducing histopathological changes, proinflammatory cytokine release and reactive oxygen species generation and inhibiting ferroptosis. Quercetin significantly decreased ferroptosis and improved the proliferative ability of LPS‑treated alveolar epithelial cells. Additionally, it was demonstrated that quercetin markedly enhanced the alveolar epithelial barrier, as evidenced by the upregulation of tight junction protein expression both in vivo and in vitro. Mechanistically, quercetin effectively activated the sirtuin 1 (Sirt1)/nuclear factor erythroid 2‑related factor 2 (Nrf2)/Gpx4 signaling pathway, and targeted in vivo inhibition or in vitro knockdown of Sirt1 significantly reduced the anti‑ferroptotic functions of quercetin. In conclusion, the results demonstrated that quercetin exerts its therapeutic effects against LPS‑induced ALI by inhibiting ferroptosis via the activation of the Sirt1/Nrf2/Gpx4 signaling pathway.


Effects of tetracycline on water quality, soil and gases in aerated and unaerated leachfield mesocosms.
We examined the effects of tetracycline (TET) addition on the function of mesocosms representing aerated and unaerated septic system leachfields. Replicate mesocosms (n = 3) were filled with soil and either vented to a leachfield (LEACH) or aerated intermittently to maintain an O(2) level of approximately 0.21 mol mol(-1) (AIR). All mesocosms were dosed every 6 h for 10 d with 3 cm of domestic wastewater amended with 5 mg TET L(-1). Water quality parameters, headspace gas composition, and soil properties were measured prior to and during the dosing period, and for 42 days after the last antibiotic dose. No significant effect of TET was observed on the pH, level of dissolved O(2) or dissolved organic carbon (DOC) in drainage water from either treatment. In contrast, levels of Fe(2+) and SO(4) in drainage water from LEACH mesocosms decreased in response to TET dosing, with lower levels persisting until Day 52. Persistent increases were observed in the level of NO(3) in drainage water from AIR lysimeters and in NH(4) in LEACH mesocosms in response to TET additions. Removal of total P and DOC were unaffected by TET dosing in either treatment. Nitrogen removal in AIR mesocosms decreased during the TET dosing period, returning to pre-dosing values by Day 52. In contrast, TN removal in LEACH mesocosms increased during TET dosing, returning to pre-dosing values by Day 52. The composition of headspace gases in AIR mesocosms was not affected by tetracycline dosing. TET dosing resulted in significant increases in soil NH(4) concentration in LEACH mesocosms, whereas significant decreases were apparent in AIR mesocosms. Elevated levels of H(2)S and CH(4) in the headspace of LEACH mesocosms coincided with TET dosing and returned to pre-dosing levels when antibiotic dosing ceased. The effects of tetracycline on leachfield mesocosms differed as a function of aeration. Although most effects were transient, with values returning to pre-dosing levels after a 6-week recovery period in both treatments, persistent effects were observed in LEACH mesocosms.


Plants used in traditional medicine in eastern Tanzania. II. Angiosperms (Capparidaceae to Ebenaceae).
Sixty-nine plants are listed, which are used by traditional healers in five regions of Eastern Tanzania, Coast, Dar es Salaam, Kilimanjaro, Morogoro and Tanga. For each species the botanical name, vernacular name, collection number, locality, habit, distribution and medicinal uses are given. Results of a literature survey on medicinal uses, isolated constituents, and pharmacological effects are also provided.


Efficient enzymatic cyclization of an inhibitory cystine knot-containing peptide.
Disulfide-rich peptides isolated from cone snails are of great interest as drug leads due to their high specificity and potency toward therapeutically relevant ion channels and receptors. They commonly contain the inhibitor cystine knot (ICK) motif comprising three disulfide bonds forming a knotted core. Here we report the successful enzymatic backbone cyclization of an ICK-containing peptide κ-PVIIA, a 27-amino acid conopeptide from Conus purpurascens, using a mutated version of the bacterial transpeptidase, sortase A. Although a slight loss of activity was observed compared to native κ-PVIIA, cyclic κ-PVIIA is a functional peptide that inhibits the Shaker voltage-gated potassium (Kv) channel. Molecular modeling suggests that the decrease in potency may be related to the loss of crucial, but previously unidentified electrostatic interactions between the N-terminus of the peptide and the Shaker channel. This hypothesis was confirmed by testing an N-terminally acetylated κ-PVIIA, which shows a similar decrease in activity. We also investigated the conformational dynamics and hydrogen bond network of cyc-PVIIA, both of which are important factors to be considered for successful cyclization of peptides. We found that cyc-PVIIA has the same conformational dynamics, but different hydrogen bond network compared to those of κ-PVIIA. The ability to efficiently cyclize ICK peptides using sortase A will enable future protein engineering for this class of peptides and may help in the development of novel therapeutic molecules. Biotechnol. Bioeng. 2016;113: 2202-2212. © 2016 Wiley Periodicals, Inc.


Wheelchair service provision education in academia.
An estimated 70 million people with disabilities need wheelchairs. To address this global crisis, the World Health Organization (WHO) proposed an eight-step wheelchair service provision model to ensure service quality regardless of resource setting. The International Society of Wheelchair Professionals (ISWP) aims to facilitate the integration of the WHO eight-step model into professional rehabilitation programmes. To develop an enhanced understanding of the current wheelchair service provision education provided in professional rehabilitation programmes worldwide. In a cross-sectional design, an online survey was distributed to ISWP contacts of educational institutions. Quantitative responses were analysed through summary statistics and qualitative answers were analysed by content analyses. When relevant, educational institutions were stratified into resource settings. Seventy-two representatives of educational institutions in 21 countries completed the survey. Wheelchair content was taught in 79% of represented institutions, of which 75% of respondents reported using original course material, 10% of respondents used WHO Wheelchair Service Training Packages and 15% of respondents used other available resources. The majority of educational institutions teaching with their own wheelchair-related course material taught ≤ 20 hours. Fourteen of the 15 respondents without wheelchair education, expressed an interest in integrating wheelchair education into their academic curricula. The majority of the educational institutions teach wheelchair education; however, there is great variability in what and how it is taught and evaluated. The results demonstrate the need for more in-depth investigation regarding the integration process of wheelchair education in educational institutions, with the ultimate goal of improving wheelchair service provision worldwide.


Reversed phase chromatography of isoaccepting tRNA's from healthy and crown gall tissues from Nicotiana tabacum.
RPC 5 (Reversed Phase Chromatography) of aminoacyl-tRNA's from healthy and crown gall (induced by Agrobacterium tume-faciens strain B6) tobacco tissues were compared for eleven amino acids. For ten amino acids: alanine, arginine, glutamic acid, glycine, isoleucine, leucine, lysine, methionine, tyrosine, and valine, no qualitative or quantitative differences could be detected between aminoacyl-tRNA's from both sources. Phenylalanyl-tRNA's from crown gall tissues gave two peaks on RPC 5; the minor early eluting species (peak 1) was always absent in elution profiles of phenylalanyl-tRNA's from healthy tissues or from tobacco leaves. After the "Y" base was removed by pH 2.9 treatment, peak 2 of phenylalanine tRNA was shifted to the position of peak 1.


[Breath tests in the diagnosis of gastrointestinal diseases].
Determination of carbon or hydrogen markers in breath has allowed closer investigation of the pathogenic mechanisms of several gastrointestinal diseases. Thus, the 13C-urea breath test is a nonaggressive, simple and safe test with excellent accuracy both in the initial diagnosis of Helicobacter pylori infection and in confirmation of its eradication following treatment. Moreover, because of the simplicity, reproducibility and safety of these types of procedure, they have tended to substitute more uncomfortable and expensive techniques that were traditionally used in gastroenterology. Several breath tests have been developed that allow reliable evaluation of liver or exocrine pancreatic function, gastrointestinal motility, as related to gastric emptying or orocecal transit time, and a diagnostic approach to clinical problems that could be due to bacterial overgrowth or malabsorption of various sugars.


Adhesion molecules expression in noncrescentic acute post-streptococcal glomerulonephritis.
Clinicomorphological features of 11 cases of non-crescentic acute post-streptococcal glomerulonephritis (APSGN) were reviewed. Intraglomerular and interstitial leukocytes and their possible correlation with the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-leukocyte adhesion molecule-1 (ELAM-1/E-selectin) were investigated by an immunohistochemical method. Intraglomerular leukocytes were primarily granulocytes (11.4 +/- 10 cells/glomerular cross-section) and monocytes-macrophages (13.4 +/- 19.4 cells/glomerular cross-section). The granulocytes outnumbered monocytes-macrophages in 7 of 11 specimens. The number of intraglomerular leukocytes correlated with proteinuria at the time of renal biopsy. Intraglomerular ICAM-1 staining was strongly positive in all biopsies, especially when intraglomerular monocytes-macrophages prevailed. Expression of intraglomerular VCAM-1 and E-selectin in diseased kidneys did not differ from that in normal kidneys. Interstitial leukocytes were primarily monocytes-macrophages (158.9 +/- 96.8 cells/mm2) and T lymphocytes (102.2 +/- 63.9 cells/mm2). The number of interstitial leukocytes, especially monocytes-macrophages, correlated with serum creatinine level at the time of biopsy. Interstitial ICAM-1 staining was strongly positive on tubules, peritubular capillaries, and small vessels. The tubular positivity for ICAM-1 correlated with the number of interstitial monocytes-macrophages. Interstitial VCAM-1 and E-selectin were expressed as in normal kidney tissues. The data from this study demonstrate that APSGN is characterized by the presence of both intraglomerular and interstitial leukocyte infiltration, correlating respectively with proteinuria and serum creatinine at the time of renal biopsy. Among the adhesion molecules studied, ICAM-1 seems the most involved in leukocyte recruitment, especially in that of monocytes-macrophages.


Foundations for literacy: emergent literacy competencies of grade R learners on the Cape Flats.
International research has demonstrated that a considerable amount of children's literacy development occurs prior to formal schooling and that emergent literacy skills at school entry are strong predictors of later literacy and general academic achievement. These findings have prompted vigorous early intervention programmes aimed at promoting emergent literacy development to optimise the development of conventional literacy. While there is considerable research conducted in developed countries, there is limited research on the emergent literacy skills of children in South African contexts. In the light of increasing evidence of poor literacy performance of South African children in the foundation phase of schooling it is imperative that appropriate and timely intervention be undertaken. However it is important that intervention be informed by baseline assessments of the children's literacy competencies in the full spectrum of socio-cultural contexts in this diverse country. This study documents the emergent literacy competencies of 101 grade R (the year prior to grade 1, equivalent to kindergarten in the United States) learners attending schools in historically disadvantaged coloured communities on the Cape Flats in the Western Cape. An Emergent Literacy and Language Assessment protocol was developed for use with this population. The children's performance on the assessment tool indicated that in general they possessed a reasonable repertoire of emergent literacy skills. Although they displayed adequate skills to support acquisition of print decoding skills necessary for fluent reading, weaknesses in the decontextualised language skills that have been found to support later reading comprehension, were evident.


Engagement of CD28 outside of the immunological synapse results in up-regulation of IL-2 mRNA stability but not IL-2 transcription.
During T cell activation by APC, CD28 is colocalized with TCR in the central supramolecular activation cluster (cSMAC) region of the immunological synapse. CD28 signaling through PI3K results in the recruitment of protein kinase C (PKC)theta to the cSMAC, activation of NF-kappaB, and induction of IL-2 transcription. These results suggest that localized engagement of CD28 within the cSMAC may be required for CD28 activation and/or signal integration with TCR signals. To test this model we have examined the mechanism of CD28-mediated induction of IL-2 secretion when CD28 is engaged outside of the immunological synapse. CD4 T cells were stimulated with Ag presented by B7-negative APC and CD28 costimulation was provided in trans by anti-CD28-coated beads or by class II-negative, B7-positive cells. We show that induction of IL-2 secretion under these conditions did not require expression of PKCtheta and did not induce NF-kappaB activation or IL-2 transcription. In contrast, CD28 costimulation in trans did induce IL-2 mRNA stability, accounting for the up-regulation of IL-2 secretion. These data indicate that the ability of CD28 to up-regulate IL-2 transcription requires colocalization of TCR and CD28 at the plasma membrane, possibly within the cSMAC of the immunological synapse. In contrast, the ability of CD28 to promote IL-2 mRNA stability can be transduced from a distal site from the TCR, suggesting that signal integration occurs downstream from the plasma membrane. These data support the potential role of trans costimulation in tumor and allograft rejection, but limit the potential functional impact that trans costimulation may have on T cell activation.


Screening by VDRL test to detect hidden cases of syphilis.
A total of 59,450 sera from January 1996 to December 2000 were subjected to VDRL testing. Overall VDRL positivity rate was 3.2% and downward trend was observed in the recent years, 1999 and 2000. Majority of the samples were from Gynaecology department, out of which 1.57% were VDRL positive. Out of 30,045 samples from antenatal females, 517(1.47%) were positive, while 304(1.8%) were positive out of 16,980 samples obtained from couples. Out of 304 samples from couples found positive, 17.4% wives had titre >R16; 27.9% wives had titre R1 to R8, out of which 15.3% husbands had titre of >R16. Also, 166 wives with nonreactive VDRL had 19.3% husbands with titre > R16. Thus, couple VDRL test plays an important role in detection of hidden cases of syphilis in the community and early detection and treatment of such cases will further reduce the perinatal morbidity and mortality.


Human papillomavirus-type predict the clinical outcome of imiquimod therapy for women with vulvar condylomata acuminata.
To investigate the effect of determination of human papillomavirus (HPV) subtype on the success of imiquimod therapy in women with vulvar condylomata acuminata. A total of 132 women with biopsy-proven vulvar condylomata acuminata were enrolled in this prospective study. HPV DNA detection and determination of genotype were made through polymerase chain reaction (PCR) technique. The women were treated with imiquimod cream 5% in the area of the visible lesions, three times a week at night for 16 weeks. Twelve of the 132 women (9.1%) failed to detect any improvement with this therapy during the 16-week period. However, 80 women (60.6%) experienced total clearance of the lesions, and 20 women (15.2%) observed a partial response. The complete response rates were 76.2% for HPV-6, 66.7% for HPV-11, 35% for HPV-6 plus 11, and 6.3% for unclassified HPV subtypes (other HPV subtypes than HPV 6 and -11). Topical imiquimod 5% cream is an appropriate treatment modality for HPV-6 or -11 positive vulvar warts.


[Endoscopic adenoidectomy; use or abuse of the technology?].
To evaluate efficacy of the conventional technique of adenoidectomy by means of transoperative endoscopic revision of the nasopharynx and to evaluate the need for including telescopes as part of usual instruments used in adenoidectomy. Prospective, open, comparative, and transversal study. We included the first 150 patients with absolute indication for adenoidectomy. We did 150 adenoidectomy procedures by conventional technique using Beckman adenotomes, and La Force adenotomes, using a laryngeal mirror to observe condition of nasopharynx once the surgeon thought the procedure was completed, we did a revision of adenoid area with Hopkins telescopes of 0 and 30; if we founded residues of adenoids, these were eliminated with Guggenheim forceps, adenotomes, or curved 40 degrees microdebrider tip, all after endoscopic viewing, which also helped in control of area bleeding. MEASURED PARAMETERS: Presence or absence of adenoids residue location, and presence or absence of active bleeding. Total removal of adenoids was carried in 43 patients, our finding adenoid residues in 107 of cases. Of these, 45.3% were occluding pharyngeal part of Eustachian tubes. Conventional technique for adenoidectomy was effective in < 30%; therefore, it is imperative to use endoscopic revision in each case.


[The concept of health].
Objections to the present WHO (World Health Organization) definition of HEALTH, as "the state of perfect physical, mental and social well-being", are expressed. It is considered to be anachronistic, first because it aims at perfection which is unaltainelle because of district personality characteristics. As the main support for this idea, the necessary renunciation of part of man's drive to liberty in exchange for the lesser insecurity provided by social life (Freud, Castoriadis and McDougall), is groted. The validity of distinguishing between "soma", "psyche" and "society" is questioned and the concept of the "integrated man", alluding to Pierre Marty and to Freud himself is adapted, and situations are recalled in which the interaction of the three aspects mentioned above is actually evident. Finally, the notion of the quality of life, in accordance with an antipositivistic taken from Bion, point of view, is discussed, and the concept that reality is that of each human being, is adapted. This priority and the proposal to rescue subjectivism which was also observed by Foucault when he studied mental disease, leads to a last criticism of the present definition of health, based exclusively on external, objective evaluations.


BMI1 is recruited to DNA breaks and contributes to DNA damage-induced H2A ubiquitination and repair.
DNA damage activates signaling pathways that lead to modification of local chromatin and recruitment of DNA repair proteins. Multiple DNA repair proteins having ubiquitin ligase activity are recruited to sites of DNA damage, where they ubiquitinate histones and other substrates. This DNA damage-induced histone ubiquitination is thought to play a critical role in mediating the DNA damage response. We now report that the polycomb protein BMI1 is rapidly recruited to sites of DNA damage, where it persists for more than 8 h. The sustained localization of BMI1 to damage sites is dependent on intact ATM and ATR and requires H2AX phosphorylation and recruitment of RNF8. BMI1 is required for DNA damage-induced ubiquitination of histone H2A at lysine 119. Loss of BMI1 leads to impaired repair of DNA double-strand breaks by homologous recombination and the accumulation of cells in G(2)/M. These data support a crucial role for BMI1 in the cellular response to DNA damage.


Gaze direction biases emotion categorisation in schizophrenia.
The successful integration of eye gaze direction and emotion cues from faces is important not only for co-ordinated interactions, but also for the detection of social signals alerting us to threat posed by a conspecific, or elsewhere in our immediate environment. It is now well-established that people with schizophrenia experience aberrant eye gaze and facial emotion processing. These social-cognitive differences might contribute to the maintenance of socially-themed delusions which are characterised by the hyper-attribution of threatening intentions to others. However, no study has directly examined whether the mechanisms which govern the integration of eye gaze and emotion information diverge in schizophrenia, and more importantly, whether this reflects a fundamental 'bottom-up' perceptual deficit or a 'top-down' cognitive bias. Fifteen outpatients diagnosed with schizophrenia and 21 healthy age- and IQ-matched controls performed an emotion categorisation task (anger/fear) on morphed facial expressions of anger or fear, displaying either direct or averted gaze. Results in both controls and patients replicated the previous finding that combinations of anger with direct gaze, and fear with averted gaze - which signal a relevant threat to the observer - benefited from more accurate emotion recognition than alternate gaze-emotion combinations. Bayesian model selection revealed that for patients this effect was mediated by a shift in decision bias towards emotions which signal self-relevant threat, rather than a change in sensitivity as observed in controls. These results critically highlight a different cognitive mechanism governing gaze and face-cued emotion integration in schizophrenia, which has a top-down influence on the evaluation of perceptual input.


Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections.
Intravenous cefiderocol (Fetroja®; Fetcroja®) is the first siderophore cephalosporin approved for the treatment of adults with serious Gram-negative bacterial infections. Cefiderocol is stable against all four Ambler classes of β-lactamases (including metallo-β-lactamases) and exhibits excellent in vitro activity against many clinically relevant Gram-negative pathogens, including multidrug resistant strains. In randomized, double-blind clinical trials, cefiderocol was noninferior to imipenem/cilastatin for the treatment of complicated urinary tract infections (cUTI) and to meropenem for nosocomial pneumonia. Furthermore, in a pathogen-focused clinical trial in patients with carbapenem-resistant (CR) infections, cefiderocol showed comparable efficacy to best available therapy (BAT), albeit all-cause mortality rate was higher in the cefiderocol arm, the cause of which has not been established. Cefiderocol had a good tolerability and safety profile in clinical trials. Thus cefiderocol is a novel, emerging, useful addition to the current treatment options for adults with susceptible Gram-negative bacterial infections (including cUTI and nosocomial pneumonia) for whom there are limited treatment options.


Utility of red blood cell acetylcholinesterase measurement in mechanically ventilated subjects after organophosphate poisoning.
Many patients with organophosphate poisoning require mechanical ventilation. Muscle acetylcholinesterase (AChE) activity determines the impairment of muscle force generation, and red blood cell (RBC) AChE has been regarded as a surrogate for muscle AChE in organophosphate poisoning. Therefore, this study was conducted to investigate whether RBC AChE at presentation can predict the duration of mechanical ventilatory support and whether RBC AChE at weaning can predict weaning trial outcomes in patients on mechanical ventilation for organophosphate poisoning. This retrospective observational case series identified 74 patients with a history of mechanical ventilation secondary to organophosphate poisoning and whose RBC AChE levels were available at presentation to the emergency department, at 24 h of presentation, or at weaning. Data were collected for plasma cholinesterase assay results, weaning outcome, duration of mechanical ventilation, and details of patient management (including ICU stay and amount of atropine and pralidoxime administered). RBC AChE activity levels at presentation and at 24 h of presentation had a negative correlation with duration of mechanical ventilation in subjects who ingested dimethyl organophosphate, but this correlation was not observed for those who had ingested diethyl or unclassified organophosphate. The optimal cutoff value of RBC AChE activity at presentation for predicting mechanical ventilation for < 7 d was 1,330 U/L in subjects intoxicated with dimethyl organophosphate. However, there was no difference in RBC AChE activity at the time of weaning trial between successful and failed weaning events, regardless of the chemical formulation of organophosphate. We conclude that RBC AChE activity within 24 h of presentation can help predict the duration of mechanical ventilation for dimethyl organophosphate intoxication; however, RBC AChE activity at the time of weaning trial may not be a suitable parameter for predicting a patient's ability to be weaned from mechanical ventilation.


The attitudes of healthy children and researchers towards the challenges of involving children in research: an exploratory study.
A growing trend in research is to involve co-researchers. It is referred to as Patient and Public Involvement (PPI) and comprises three groups: the patients, the public, and the researchers. Like in adult public involvement, healthy children can also be considered as 'the public'. Paediatric patients and researchers experienced in conducting child-inclusive research are often asked about their attitudes towards the challenges they encounter. This is not the case for healthy children and researchers without such experience. Our aim was to investigate the attitudes of these children and researchers towards the challenges encountered during child-inclusive research. This was an exploratory study. We interviewed healthy children and adult researchers without prior experience in child-inclusive research. We recruited the children through a foundation for young researchers and the adult researchers from two hospitals, both in Groningen, the Netherlands. We audio recorded the interviews, and they were transcribed verbatim. We analysed the data using qualitative content analysis. We interviewed five adult researchers and seven healthy children, aged 9 to 14 years. Both groups thought that it was best to involve children in paediatric research from as early a stage as possible. The children assumed that no prior training would be needed because they had already been trained at school. The researchers' attitudes varied regarding training children beforehand. Both groups thought that researchers did not need prior training on how to involve children if they worked with children on a daily basis. The children felt that recognition and a modest financial reward was appropriate. Adult researchers were cautious about rewarding the children. They feared it might render the children less intrinsically motivated. Our study indicated that young and adult researchers have clear attitudes towards the challenges encountered during child-inclusive research. Young researchers could help adult researchers to find solutions to these challenges, even if they have no prior experience in child-inclusive research. Adult researchers who acknowledge the importance of child-inclusive research represent a significant step towards meaningful involvement of children. Our results imply that children could be involved in the decision-making process concerning the challenges encountered in child-inclusive research.


More Than Just a Removal Service: Scavenger Receptors in Leukocyte Trafficking.
Scavenger receptors are a highly diverse superfamily of proteins which are grouped by their inherent ability to bind and internalize a wide array of structurally diverse ligands which can be either endogenous or exogenous in nature. Consequently, scavenger receptors are known to play important roles in host homeostasis, with common endogenous ligands including apoptotic cells, and modified low density lipoproteins (LDLs); additionally, scavenger receptors are key regulators of inflammatory diseases, such as atherosclerosis. Also, as a consequence of their affinity for a wide range of microbial products, their role in innate immunity is also being increasingly studied. However, in this review, a secondary function of a number of endothelial-expressed scavenger receptors is discussed. There is increasing evidence that some endothelial-expressed scavenger receptors are able to directly bind leukocyte-expressed ligands and subsequently act as adhesion molecules in the trafficking of leukocytes in lymphatic and vascular tissues. Here, we cover the current literature on this alternative role for endothelial-expressed scavenger receptors and also speculate on their therapeutic potential.


Rate of perceived exertion as a tool to monitor cycling exercise intensity in older adults.
The purpose of this study was to determine the efficacy of rate of perceived exertion (RPE) to monitor exercise intensity in older adults. Middle-aged (46.9 +/- 7.0 years, n = 24) and older women (75.5 +/- 3.8 years, n = 29) performed a graded maximal exercise test on a cycle ergometer while RPE, oxygen uptake, heart rate, and blood lactate levels were measured. The Pearson's product moment correlation coefficient between RPE and oxygen uptake for each stage of the graded exercise test was calculated for each participant. The mean coefficient for the older group (r =.954) was similar to that of middle-aged group (r =.963). The autocorrelation coefficient was much lower (r =.411) in the older group than in the middle-aged group (r =.871). Variability in RPE through the graded exercise test was similar between the two groups. In conclusion, RPE was strongly associated with oxygen uptake in the older group. These results indicate that RPE is effective in monitoring exercise intensity in older adults.


Discovery of antimicrobial agent targeting tryptophan synthase.
Antibiotic resistance is a continually growing challenge in the treatment of various bacterial infections worldwide. New drugs and new drug targets are necessary to curb the threat of infectious diseases caused by multidrug-resistant pathogens. The tryptophan biosynthesis pathway is essential for bacterial growth but is absent in higher animals and humans. Drugs that can inhibit the bacterial biosynthesis of tryptophan offer a new class of antibiotics. In this work, we combined a structure-based strategy using in silico docking screening and molecular dynamics (MD) simulations to identify compounds targeting the α subunit of tryptophan synthase with experimental methods involving the whole-cell minimum inhibitory concentration (MIC) test, solution state NMR, and crystallography to confirm the inhibition of L-tryptophan biosynthesis. Screening 1,800 compounds from the National Cancer Institute Diversity Set I against α subunit revealed 28 compounds for experimental validation; four of the 28 hit compounds showed promising activity in MIC testing. We performed solution state NMR experiments to demonstrate that a one successful inhibitor, 3-amino-3-imino-2-phenyldiazenylpropanamide (Compound 1) binds to the α subunit. We also report a crystal structure of Salmonella enterica serotype Typhimurium tryptophan synthase in complex with Compound 1 which revealed a binding site at the αβ interface of the dimeric enzyme. MD simulations were carried out to examine two binding sites for the compound. Our results show that this small molecule inhibitor could be a promising lead for future drug development.


Phylogenomic support for evolutionary relationships of New World direct-developing frogs (Anura: Terraranae).
Phylogenomic approaches have proven able to resolve difficult branches in the tree of life. New World direct-developing frogs (Terraranae) represent a large evolutionary radiation in which interrelationships at key points in the phylogeny have not been adequately determined, affecting evolutionary, biogeographic, and taxonomic interpretations. We employed anchored hybrid enrichment to generate a data set containing 389 loci and >600,000 nucleotide positions for 30 terraranan and several outgroup frog species encompassing all major lineages in the clade. Concatenated maximum likelihood and coalescent species-tree approaches recover nearly identical topologies with strong support for nearly all relationships in the tree. These results are similar to previous phylogenetic results but provide additional resolution at short internodes. Among taxa whose placement varied in previous analyses, Ceuthomantis is shown to be the sister taxon to all other terraranans, rather than deeply embedded within the radiation, and Strabomantidae is monophyletic rather than paraphyletic with respect to Craugastoridae. We present an updated taxonomy to reflect these results, and describe a new subfamily for the genus Hypodactylus.


Impact of surgical trauma on human skeletal muscle protein synthesis.
Muscle protein catabolism is a considerable clinical problem following surgery. However, the impact of surgical trauma on muscle protein synthesis is not well characterized. In this pilot study, we therefore investigated whether the severity of surgical trauma is related to a decrease in muscle protein synthesis rate in humans. Metabolically healthy patients (n=28) were included in the study. Eight of the patients were day-care patients undergoing minor breast surgery (defined as minor surgery). The other 20 patients were subjected to major abdominal surgery and were therefore scheduled to stay overnight in the recovery room during the first postoperative night (defined as major surgery). Protein FSRs (fractional synthesis rates) in skeletal muscle were determined during a measurement period of 90 min before surgery and immediately after termination of surgery. FSR in skeletal muscle of the minor surgery patients was 1.72+/-0.25%/24 h before surgery and 1.67+/-0.29%/24 h after surgery (P=0.68). In the major surgery group, FSR was 1.62+/-0.30%/24 h before surgery and 1.57+/-0.40%/24 h (P=0.59) immediately following surgery. The observations made in this pilot study could not confirm a size-related decrease in muscle protein synthesis immediately following minor and major surgery. This finding is discussed in relation to confounders, postoperative course and to muscle protein degradation. The shortage of knowledge in this field is emphasized.


Fumigant toxicity of citrus oils against cowpea seed beetle Callosobruchus maculatus (F.) (Coleoptera: Bruchidae).
In the present study, the effects of volatile components of Citrus paradisi, C. aurantium, C. limonium and C. sinensis peel essential oils were investigated on the cowpea adult bruchid, Callosobruchus maculatus (F.). The oils were extracted from the fruit peels using hydrodistillation. The results indicated that the citrus oils had high fumigant activity against adult beetles. The mortality of 1-2 day-old adults increased with concentration and exposure time from 3 to 24 h. The oil of C. paradisi was more effective than those of C. aurantium and C. limonium (The LC50 values were 125, 145 and 235 microl L(-1) at 24 h exposure, respectively). The oil of C. sinensis proved to be least toxic (LC50 = 269 microl L(-1). The results suggested that citrus peel oils can be used as potential control measure against cowpea beetles.


Thermoresponsive oligo(ethylene glycol)-based polymer brushes on polymer monoliths for all-aqueous chromatography.
Porous polymer monoliths onto which were grafted a thermoresponsive copolymer, poly(2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA)-co-oligo(ethylene glycol) methacrylate (OEGMA)), were synthesized by the two-step atom transfer radical polymerization (ATRP) method. The copolymer-grafted monoliths were characterized by elemental analysis, scanning electron microscopy, and mercury intrusion porosimetry. They were further used as the thermoresponsive stationary phase for all-aqueous high-performance liquid chromatography (HPLC). The chromatograms of three steroids demonstrated that the chain length of the grafted copolymer, which was regulated by varying the grafting time, could affect the separation by providing different amounts of hydrophobic interaction sites with analytes. Additionally, the elution profiles of steroids on the stationary phase could also be tuned by the comonomer composition. The results showed that the porous polymer monoliths enabled separation of the test mixture in pure aqueous mobile phase under isocratic conditions. Furthermore, the proposed method provides a simple and promising tool in the design and construction of responsive surfaces for chromatography applications.