Detection of organic matter in interstellar grains.
Star formation and the subsequent evolution of planetary systems occurs in dense molecular clouds, which are comprised, in part, of interstellar dust grains gathered from the diffuse interstellar medium (DISM). Radio observations of the interstellar medium reveal the presence of organic molecules in the gas phase and infrared observational studies provide details concerning the solid-state features in dust grains. In particular, a series of absorption bands have been observed near 3.4 microns (approximately 2940 cm-1) towards bright infrared objects which are seen through large column densities of interstellar dust. Comparisons of organic residues, produced under a variety of laboratory conditions, to the diffuse interstellar medium observations have shown that aliphatic hydrocarbon grains are responsible for the spectral absorption features observed near 3.4 microns (approximately 2940 cm-1). These hydrocarbons appear to carry the -CH2- and -CH3 functional groups in the abundance ratio CH2/CH3 approximately 2.5, and the amount of carbon tied up in this component is greater than 4% of the cosmic carbon available. On a galactic scale, the strength of the 3.4 microns band does not scale linearly with visual extinction, but instead increases more rapidly for objects near the Galactic Center. A similar trend is noted in the strength of the Si-O absorption band near 9.7 microns. The similar behavior of the C-H and Si-O stretching bands suggests that these two components may be coupled, perhaps in the form of grains with silicate cores and refractory organic mantles. The ubiquity of the hydrocarbon features seen in the near infrared near 3.4 microns throughout out Galaxy and in other galaxies demonstrates the widespread availability of such material for incorporation into the many newly forming planetary systems. The similarity of the 3.4 microns features in any organic material with aliphatic hydrocarbons underscores the need for complete astronomical observational coverage in the 2-30 microns region, of lines of sight which sample dust in both dense and diffuse interstellar clouds, in order to uniquely specify the composition of interstellar organics. This paper reviews the information available from ground-based observations, although currently the Infrared Satellite Observatory is adding to our body of knowledge on this subject by providing more extensive wavelength coverage. The Murchison carbonaceous meteorite has also been used as an analog to the interstellar observations and has revealed a striking similarity between the light hydrocarbons in the meteorite and the ISM; therefore this review includes comparisons with the meteoritic analog as well as with relevant laboratory residues. Fundamental to the evolution of the biogenic molecules, to the process of planetary system formation, and perhaps to the origin of life, is the connection between the organic material found in the interstellar medium and that incorporated in the most primitive solar system bodies.


Putting Guidelines Into Practice: Is Frailty Measurement at the Time of Kidney Transplant Eligibility Assessment Valid, Feasible, and Acceptable to Patients?
Clinical Practice Guidelines suggest that frailty be measured during kidney transplant eligibility assessments. Yet it is not known how frailty is best assessed in this setting or whether its assessment is acceptable to patients. We aimed to examine the construct validity and feasibility of Frailty Index (FI) assessment among patients attending a kidney transplant assessment clinic and to explore patients' perspectives on frailty and the acceptability of its routine assessment. A 58-item FI was calculated for 147 clinic patients. Semistructured interviews were conducted with a subgroup of 29 patients. The FI was validated against normative FI characteristics (mean, distribution, limit), age, and the Estimated Post-Transplant Survival Score. Feasibility was assessed using descriptive statistics. Qualitative data were analyzed using reflexive thematic analysis. The mean FI was 0.23 (±0.10, normal distribution, limit 0.53). FI increased with age and Estimated Post-Transplant Survival score. The FI was completed for 62.8% of eligible patients (147/234). The median completion time was 10 min, and completion rate (with no missing data) was 100%. Four themes were identified: perceptions of frailty, acceptability, perceived benefits, and risks of frailty measurement. Patients linked frailty with age and adverse outcomes, and most did not consider themselves frail. Patients reported that the FI was quick, simple, and efficient. They felt that frailty assessment is relevant to transplant eligibility and should be used to address potentially reversible factors. The FI demonstrated construct validity and was feasible and acceptable in this clinic setting. The challenge is ensuring that routine assessments lead to better care.


Peritoneal resting with heparinized lavage reverses peritoneal type I membrane failure. A comparative study of the resting effects on normal membranes.
Ultrafiltration failure (UFF) is a serious complication of long-term peritoneal dialysis (PD). Peritoneal rest (PR) has been demonstrated as a valid treatment to reverse the functional changes that occur in UFF. The effects of PR on a normally functioning human peritoneum are unknown but are expected to be neutral. Our hypothesis was that PR positively modifies peritoneal function in patients with UFF, in contrast to the absence of effects when PR is applied under normal conditions. We studied 84 PR periods, comparing 35 patients with UFF and 49 controls (resting for abdominal surgery with temporary discontinuation of PD). We analyzed peritoneal transport pre-PR and post-PR by calculating the mass transfer coefficients of creatinine (Cr-MTAC), the dialysate/plasma creatinine ratio (D/P Cr) and the ultrafiltration (UF). Baseline data was similar for the 2 groups, although the UFF group had a longer median time in PD (39 [18 - 60] vs 10 [5 - 23] months; p = 0.00001). Peritoneal rest induced a decrease in D/P Cr, Cr-MTAC and an increase in UF capacity in the UFF group (p = 0.0001, p = 0.004 and p = 0.001, respectively), without causing changes in the control group. Peritoneal rest in patients with more than 6 months of UFF was not able to reduce peritoneal solute transport or improve UF capacity. Response to PR did not differ among UFF patients with or without a previous history of peritonitis. Peritoneal rest enabled patients with UFF to continue on PD for a median time of 23 months (range, 13 - 46 months). Peritoneal rest induces functional changes in patients with UFF but not in those with no functional abnormalities. This demonstrates that PR works only when abnormal but reversible functional conditions are present. However, the effect is highly dependent on how early PR is applied.


Do the Costs of AUD-Related Health and Social Care Services Vary Across Patient Profiles?
Alcohol use disorders (AUDs) are associated with high social and health care costs. We compare the direct social and health care costs of patients with AUDs, according to four service use profiles: (a) AUD treatment, (b) mental health (MH) treatment, (c) AUD + MH treatment, (d) no treatment. A separate analysis of the costliest 10% is included. Furthermore, the association between the service user profile and the risk of death is examined. Direct unit service costs were retrieved from the electronic health record system and supplemented with patient grouping-based costs for primary and secondary care services, to examine the yearly mean cost per patient in the AUD cohort (N = 5,136; 71.1% male). We used data collected in the North Karelia region of Finland between 2014 and 2018. Total costs of care for the cohort during the 5-year follow-up were 126 million Euros, and the percentage of the costliest 10% (n = 521) was 51.7% (65 million Euros). Total costs were 12,778 Euros lower if the person received AUD treatment only, compared with those not in treatment. For those receiving MH treatment only, the total costs were 1,819 Euros higher, and costs were 1,523 Euros higher for those receiving AUD + MH treatment. Receiving any treatment was associated with a diminished risk of death (AUD: odds ratio [OR] = 0.56; MH: OR = 0.63; AUD + MH: OR = 0.41). Receiving only AUD treatment was associated with the lowest cost of care. Our results support the early identification of AUDs and provision of treatment in specialized addiction services to lower the costs of care and improve care outcomes.


Basal Endogenous Steroid Hormones, Sex Hormone-Binding Globulin, Physical Fitness, and Health Risk Factors in Young Adult Men.
Purpose: Few large-scale population-based studies have adequately examined the relationships between steroid hormones, health status and physical fitness. The purpose of the study was to describe the relationship of serum basal endogenous steroid hormones (testosterone, TES; empirical free testosterone, EFT; cortisol, COR) and sex hormone-binding globulin (SHBG) to body composition, cardiovascular risk factors, and physical fitness in young healthy men. Methods: Male reservists (25 ± 4 years, N = 846) participated in the study. Basal TES, EFT, COR, and SHBG were measured in morning fasted blood. Stepwise regression analyses were used to examine associations between individual hormones to four separate categories: (1) body composition; (2) cardiovascular risk factors; (3) relative, and (4) absolute physical fitness. Results: Higher TES, EFT, and SHBG were associated with lower waist circumference (TES: β = -0.239, p < 0.001; EFT: β = -0.385, p < 0.001), % body fat (TES: β = -0.163, p = 0.003), and body mass index (SHBG: β = -0.435, p < 0.001). Lower cardiovascular risk factors were associated with higher TES, EFT and SHBG concentrations, especially between SHBG and triglycerides (β = -0.277, p < 0.001) and HDL (β = 0.154, p < 0.001). Greater maximal relative aerobic capacity was concurrent with higher TES, EFT, and SHBG (β = 0.171, 0.113, 0.263, p < 0.001, =0.005, <0.001, respectively). Conclusion: Higher basal concentrations of TES, EFT, and SHBG were weakly associated with healthier body composition, fewer cardiovascular risk factors and greater relative aerobic capacity in healthy young men. It would be interesting to investigate whether these relationships are still evident after a few decades, and how different training modes (endurance, strength or their combination) positively affect physical fitness, body composition and their regulatory mechanisms over the decades.


Ethics and Governance of Stem Cell Banks.
This chapter examines the ethical principles and governance frameworks for stem cell banks. Good governance of stem cell banks should balance facilitation of the clinical use of stem cells with the proper respect and protection of stem cell sample providers and stem cell recipients and ensure compliance with national regulatory requirements to foster public trust in the use of stem cell technology. Stem cell banks must develop with regard to the science, the needs of scientists, and the requirements of the public, which will benefit from this science. Given the international reach of this promising research and its clinical application, it is necessary for stem cell bank governance frameworks to be harmonized across jurisdictions.


Initial Validation of the Diabetes and Breastfeeding Management Questionnaire (DBM-Q).
Women with pre-gestational diabetes face additional challenges after birth as they struggle with breastfeeding and managing unpredictable blood glucose levels. The aim of this study is to validate the Diabetes and Breastfeeding Management Questionnaire (DBM-Q). In total, 142 mothers with type 1 diabetes mellitus answered the questionnaire, which initially consisted of 11 items. The response rate was 82.5% (n = 128) at two months, and 88.4% (n = 137) at six months postpartum. The measurement properties of the Diabetes and Breastfeeding Management Questionnaire were tested according to the Rasch measurement theory (RMT). One item showed both disordered thresholds and several model misfits and was removed. Two items showed disordered thresholds which were resolved by collapsing response categories. This resulted in a 10-item questionnaire with all the fit residuals within the range of +2.5, minor significant differential item functioning, well-targeted items and a person separation index of 0.73. Evaluating the DBM-Q according to the RMT is a strength, as it evaluates data against strict measurement criteria. This study provides an initial validation of the questionnaire. The DBM-Q shows good measurement properties for measuring diabetes and breastfeeding management postpartum in women with pre-gestational diabetes. Further studies are needed to identify cutoffs for when professional support is needed.


Infragranular barrel cortex activity is enhanced with learning.
The barrel cortex (BC) is essential for the acquisition of whisker-signaled trace eyeblink conditioning and shows learning-related expansion of the trained barrels after the acquisition of a whisker-signaled task. Most previous research examining the role of the BC in learning has focused on anatomic changes in the layer IV representation of the cortical barrels. We studied single-unit extracellular recordings from individual neurons in layers V and VI of the BC as rabbits acquired the whisker-signaled trace eyeblink conditioning task. Neurons in layers V and VI in both conditioned and pseudoconditioned animals robustly responded to whisker stimulation, but neurons in conditioned animals showed a significant enhancement in responsiveness in concert with learning. Learning-related changes in firing rate occurred as early as the day of learning criterion within the infragranular layers of the primary sensory cortex.


LIFE-HISTORY ADAPTATION AND REPRODUCTIVE ISOLATION IN A GRASSHOPPER HYBRID ZONE.
Patterns of life-history adaptation and reproductive isolation were investigated in the acridid grasshoppers Melanoplus sanguinipes and M. devastator, which hybridize along an altitudinal gradient in the Sierra Nevada of California. Melanoplus sanguinipes females crossed with M. devastator males produced eggs that were approximately half as viable as eggs from other crosses. Diminished viability was not attributable either to infection by Wolbachia pipientis or to failure of sperm transfer. When offered an opportunity to choose a mate, females from all populations discriminated against males of the other species, whereas in no-choice tests measuring copulation duration only females from the tails of the clines showed preferences. Melanoplus sanguinipes, found at high elevations where the growing season is short, exhibited faster egg hatch, faster larval development, smaller adult body sizes, and smaller clutch sizes than M. devastator. Melanoplus devastator, from California's Central Valley, endured a hot and dry summer in a reproductive diapause that was absent in M. sanguinipes. Clines in reproductive diapause and clutch size coincided with the region of reproductive incompatibility. Development time, body size, and hatch time also changed across the hybrid zone, but the regions of largest transitions in these traits were either difficult to locate using the limited populations studied here or were not coincident with the zone's center. A method is described for combining ecological and phylogenetic analyses to address the unknown issue of whether life-history divergence has conributed to reproductive isolation in this system.


Gut and liver: the organs responsible for increased nitric oxide production after trauma-hemorrhage and resuscitation.
To determine which organs produce the increased levels of nitric oxide (NO) seen after hemorrhage and resuscitation. Adult male rats underwent laparotomy (ie, trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum bleedout volume was returned in the form of Ringer lactate. The rats were then resuscitated with Ringer lactate, 4 times the maximum bleedout volume for 1 hour. Sham-operated animals underwent only the surgical procedure. Plasma levels of nitrate/nitrite (NO3-/NO2-, stable products of NO) were measured by colorimetric assay at the maximum bleedout volume; at the end of hemorrhage; at the end of resuscitation; and 1.5, 4, 8, and 24 hours after resuscitation. In additional rats, the heart, liver, small intestine, kidneys, and spleen were harvested 4 hours after resuscitation for the measurement of NO3-/NO2- levels. Moreover, tissue perfusion was determined in the above-mentioned organs by radioactive microspheres 4 hours after resuscitation in other groups of animals. Plasma levels of NO3-/NO2- were similar to those of sham-operated animals during hemorrhage and at the end of resuscitation. One and a half hours after the end of resuscitation, however, NO production increased significantly. The peak levels of plasma NO3-/NO2- occurred at 4 hours, and the levels remained elevated even 24 hours after resuscitation. Tissue NO3-/NO2- levels were significantly increased in the liver, small intestine, and spleen 4 hours after resuscitation. In contrast, the levels of NO3-/NO2- were similar to those of sham-operated animals in the heart and kidneys at all times. Blood flow in the heart was maintained after hemorrhage, whereas hepatic, intestinal, splenic, and renal perfusion decreased significantly. The gut and liver seem to be the sites responsible for the increased NO production seen after trauma and hemorrhage. The overproduction of NO is most likely caused by up-regulation of inducible NO synthase. Thus, attempts to reduce NO production using specific inhibitors for inducible NO synthase might be helpful for improving hepatic and intestinal functions after trauma and hemorrhagic shock.


Management of post traumatic stress disorder using combat stress treatment principles--a case report.
Combat stress casualties are only generated by war. However, military psychiatrists need to acquire the experience and skills that they would need before they are ever faced with their first combat stress casualty. Non-combat post traumatic stress disorder patients present the best approximation to combat stress casualties. This case study demonstrates how combat stress treatment principles can be successfully applied to a case of non-combat post traumatic stress disorder patient. It is not the intention of this paper to demonstrate whether the combat stress management protocol is superior to other methods or protocols. Recommendations are made on methods to identify post traumatic stress disorder patients and how to seize every available opportunity to practise combat stress treatment principles.


Modern advances in cardiovascular imaging: cardiac computed tomography and cardiovascular MRI in pericardial disease.
The pericardium is characterized by a two-layer sac that surrounds the heart and provides an enclosed, lubricated space. Diseases of the pericardium may occur due to active inflammation, scar, calcification or effusion. While clinical, ECG and hemodynamic evaluation have been the established methods for the diagnosis of pericardial disease, advances in cardiac computed tomography and cardiovascular MRI provide complementary tools for diagnostic, prognostic and therapeutic assessment.


Developmental delays and psychiatric diagnoses are elevated in offspring staying in prisons with their mothers.
The aim of the study was to describe the sociodemographic and clinical features of the mothers and their offspring staying with them in prison. The study was planned as a cross-sectional, single-center study of mothers residing in Tarsus Closed Women's Prison of Turkish Ministry of Justice along with their 0 to 6 years old offspring. Mothers were evaluated via Structured Clinical Interview for DSM-IV Axis I Disorders. A psychologist blind to maternal evaluations applied the Denver Developmental Screening Test II (DII-DST). Children/mothers were also evaluated by a child and adolescent psychiatrist via K-SADS-PL. Twenty-four mothers with a mean age of 29.3 years were included. Most common diagnoses in mothers were nicotine abuse (n = 17, 70.8%), specific phobia (n = 8, 33.3%), alcohol abuse (n = 7, 29.2%) and substance abuse (n = 5, 20.8%). Twenty-six children (53.9% female) were living with their mothers in prison, and the mean age of those was 26.3 months. Results of the D-II-DST were abnormal in 33.3% of the children. Most common diagnoses in children were adjustment disorder (n = 7, 26.9%) separation anxiety disorder (n = 3, 11.5%) and conduct disorder (n = 2, 7.7%). A multi-center study is necessary to reach that neglected/under-served population and address the inter-generational transmission of abuse, neglect, and psychopathology.


Pharmacoeconomics Education in the Middle East and North Africa Region: A Web-Based Research Project.
Pharmacoeconomics (PE) is a relatively new science that is gaining special attention in many countries of the Middle East and North Africa (MENA) region that have limited healthcare resources. Therefore, education is crucial for capacity building in PE in the region. This study aimed to assess the current status of PE education in schools of pharmacy in the MENA region and shed some light on the role played by ISPOR chapters in PE education. A survey containing 5 questions about PE education in 14 MENA countries was self-answered by 2 investigators after screening information available on college or school of pharmacy official websites. Of 176 schools of pharmacy in the MENA region, only 80 offer PE educational courses. Egypt and Jordan have the highest number of schools offering PE teaching, especially on the professional level for undergraduates. The graduate level of PE education was offered mostly in Iran and Egypt. The fundamentals of PE was the topic most taught, whereas decision analysis and modeling topics were the least taught topics. Different ISPOR chapters were found to play a crucial role in developing focused health economics education for better healthcare decision making. There has been an increase in the number of schools of pharmacy offering PE education in the MENA region; however, PE education and research need improvement. Providing structured PE education should be encouraged to establish the infrastructure needed for allocation of limited healthcare resources. Furthermore, updating websites of schools of pharmacy is essential to obtain a complete picture of the PE education in the MENA region.


Sleep-apnea risk and subclinical atherosclerosis in early-middle-aged retired National Football League players.
Limited data from former National Football League (NFL) players suggest that obstructive sleep apnea (OSA) may be highly prevalent after retirement. It remains unclear whether the high prevalence of OSA in retired players is comparable to nonathletes. This retrospective analysis compared sleep apnea (SA) risk in retired NFL players to a community cohort (CARDIA Sleep study), and examined associations between SA risk and cardiovascular risk factors, including subclinical atherosclerosis. Retired NFL players (n=122) were matched to CARDIA Sleep participants by age ±2 years (range 37-55 years), body mass index ±2 kg/m2, race, and male sex. Participants underwent electron-beam computed tomography to measure coronary artery calcium (CAC) and completed the Berlin Questionnaire to determine SA risk. The presence of CAC was defined as an Agatston score >0. Retired NFL players had a greater prevalence of high SA risk than the matched CARDIA Sleep participants (27% vs 11.5%, P=0.002). Compared to the CARDIA Sleep participants, retired players were less likely to smoke, and had higher blood pressure, lower fasting glucose levels, and higher cholesterol levels. However, there was no difference in the prevalence of detectable CAC (30% vs 30%, P=1). In both players and the community cohort, SA risk was not significantly associated with CAC after controlling for age, race, and body mass index. Retired NFL players have a greater prevalence of high SA risk but similar prevalence of CAC compared with a well-matched community cohort.


Common features of the metabolic syndrome and nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic liver disease; including simple steatosis, steatohepatitis, fibrosis, or cirrhosis. The metabolic syndrome (MS) is the existence of metabolic alterations that confer an increased risk for developing cardiovascular disease and diabetes. NAFLD and MS frequently coexist and 90% of NAFLD patients have more than one manifestation of the MS. In addition, both entities are related to other comorbid conditions. Scientific advances in the understanding of the association between NAFLD and the MS have identified insulin resistance as a key aspect in the pathophysiology of both diseases. Knowledge gained from these advances can be applied clinically in the management and prevention of NAFLD, the MS, and associated metabolic alterations. Cardiovascular disease is the leading cause of death in patients with NAFLD and the MS, therefore adequate diagnosis and effective treatment are critical. This review analyzes current evidence of the association between NAFLD and the MS. The growing prevalence of both entities is highlighted. Next, the common mechanisms leading to insulin resistance are discussed. Manifestations and diagnosis of the MS and NAFLD are reviewed, pointing out the associated comorbid conditions shared by both diseases. Finally, a brief overview regarding NAFLD treatment is presented.


Adaptive segmentation and mask-specific Sobolev inpainting of specular highlights for endoscopic images.
Minimally invasive surgical and diagnostic systems rely on endoscopic images of internal organs to assist medical tasks. Specular highlights are common on those images due to the strong reflectivity of the mucus layer on the organs and the relatively high intensity of the light source. This is a significant source of error that can affect the systems' performance. In this paper, we propose a segmentation method of the specular regions based on an automatic color-adaptive threshold and a gradient-based edge detector. The segmented regions are then recovered using a robust mask-specific Sobolev inpainting approach. Experimental results demonstrate the precision and efficiency of the proposed method. In contrast to the existing approaches, the proposed solution does not require manual threshold selection or complex computations to achieve accurate results. Moreover, our method has a real-time performance and can be generalized to various applications.


Use of exhaled air as an improved biomonitoring method to assess perchloroethylene short-term exposure.
This paper shows the use of exhaled air as a biomonitoring method to assess perchloroethylene (PERC) environmental and occupational exposure. A sensitive, fast, and solvent free analytical method was developed to determine PERC in ambient and exhaled air of individuals occupationally exposed. The developed method used cold fiber solid phase microextraction (CF-SPME) as the sampling technique, and a standard permeation method to simulation of air matrix. The analysis were conducted by gas chromatography coupled to mass spectrometry (GC/MS). The methods were validated and were found to be precise, linear and sensitive for environmental and biological monitoring. The developed methods were applied to twenty-seven sampling points spread across Belo Horizonte city, Brazil, twenty four dry cleaners, an electroplating industry, a research laboratory, and an automotive paint preparation shop. The results of ambient air analyses ranging from 14.0 to 3205.0µgm-3 with median concentration of 599.0µgm-3. Furthermore, sampling of exhaled air of individuals occupationally exposed presented results ranging from 6.0 to 2635.0µgm-3 with median concentration of 325.0µgm-3. The strong correlation observed between ambient and exhaled air (r =0.930) demonstrates that exhaled air is a suitable biomarker for evaluating occupational exposure to PERC.


Should aspirin be continued in patients started on warfarin?
Clinicians frequently face the decision of whether to continue aspirin when starting patients on warfarin. We performed a meta-analysis to characterize the tradeoffs involved in this common clinical dilemma. Multiple computerized databases (1966 to 2003), reference lists of relevant articles, conference proceedings, and queries of primary authors. Randomized trials comparing warfarin plus aspirin versus warfarin alone. Studies with target international normalized ratios (INRs) <2 were excluded. Two reviewers independently extracted baseline data and major outcomes: rates of thromboembolism, hemorrhage, and all-cause mortality. Nine studies met the inclusion criteria. Of the five that enrolled patients with mechanical heart valves, four used the same target INR in both groups, while one used a reduced target INR for the warfarin plus aspirin group. Pooling the results of the first four studies demonstrated that combination of warfarin plus aspirin significantly decreased thromboembolic events (relative risk [RR], 0.33; 95% confidence interval [CI], 0.19 to 0.58), increased major bleeding (RR, 1.58; 95% CI, 1.02 to 2.44), and decreased all-cause mortality (RR, 0.43; 95% CI, 0.23 to 0.81) compared to warfarin alone. The one valve trial using a reduced INR in the warfarin plus aspirin group reported no difference in thromboembolic outcomes but found decreased major bleeding and a significant mortality benefit with combination therapy. Of the remaining trials, three evaluated a warfarin indication not routinely used in the United States (post-myocardial infarction), and the only trial that considered atrial fibrillation was terminated early due to inadequate enrollment. For mechanical heart valve patients, the benefits of continuing aspirin when starting warfarin therapy are clear. For other routine warfarin indications, there are not adequate data to guide this common clinical decision.


Development of key-pecking, pause, and ambulation during extended exposure to a fixed-interval schedule of reinforcement.
Six pigeons key-pecked under a fixed-interval (FI) 3-min schedule of food presentation. Each pigeon was studied for 200 daily sessions with 15 intervals per session (3,000 total food presentations). Analyses included the examination of latency to first peck (pause), mean rate of key pecking, and ambulation. Characterizations of stable performance were assessed across measures of behavior and evaluated using commonly employed stability criteria. Stability of response rate and pause was identified better by assessments that evaluated variability and trend, rather than just variability. Between-subject differences in rate of acquisition and terminal values of steady-state performance of pause were observed, and stable pause durations took longer to develop than did stable key-pecking rates. Relative variability in response rate and pause duration decreased as the means increased. A temporally organized pattern of key-pecking (the so-called FI scallop) developed within 50 sessions of exposure to the schedule. Overall ambulation decreased during the early sessions of exposure and further analyses showed greater rates of ambulation during the pause than after it for 4 of the 6 pigeons. Performance under the FI 3-min schedule developed relatively slowly, and key-pecking, pause, and ambulation developed at different rates.


Isolation of monomeric human V(H)s by a phage selection.
Human V(H) domains are promising molecules in applications involving antibodies, in particular, immunotherapy because of their human origin. However, they are, in general, prone to aggregation. Therefore, various strategies have been employed to acquire monomeric human V(H)s. We had previously discovered that filamentous phages displaying engineered monomeric V(H) domains gave rise to significantly larger plaques on bacterial lawns than phages displaying wild type V(H)s with aggregation tendencies. Using plaque size as the selection criterion and a phage-displayed naïve human V(H) library we identified 15 V(H)s that were monomeric. Additionally, the V(H)s demonstrated good expression yields, good refolding properties following thermal denaturation, resistance to aggregation during long incubation at 37 degrees C, and to trypsin at 37 degrees C. These 15 V(H)s should serve as good scaffolds for developing immunotherapeutics, and the selection method employed here should have general utility for isolating proteins with desirable biophysical properties.


Pharmacokinetics of glutathione and its metabolites in normal subjects.
To determine the loading and maintenance dosage of glutathione (GSH) for patients suffering from reactive oxygen species (ROS) injury such as acute paraquat intoxication, a kinetic study of reduced GSH was performed in synchrony with that of cysteine (Cys), cystine (Cys2), and methionine (Met). Human subject's porticipitation was voluntary. The effective dose of Cys, Cys2, and Met against ROS in fibroblast cells generated by paraquat was assessed using laser scanning confocal microscopy. Both Cys and Met suppressed ROS in a dose-dependent manner at concentrations of 1-1,000 microM; the concentration required to suppress ROS by 50% was 10 microM for Cys and 50 microM for Met. Using metabolite kinetics with the assumption that Cys and Met are the metabolites of GSH, expected concentrations of Cys and Met of above 20 and 50 microM were estimated when GSH was administered at 50 mg/kg body weights every 205.4 min for Cys and 427.4 min for Met.


Ground state cooling of a nanomechanical resonator in the nonresolved regime via quantum interference.
Ground state cooling of a nanomechanical resonator coupled to a superconducting flux qubit is discussed. By inducing quantum interference to cancel unwanted heating excitations, ground state cooling becomes possible in the nonresolved regime. The qubit is modeled as a three-level system in Lambda configuration, and the driving fluxes are applied such that the qubit absorption spectrum exhibits electromagnetically induced transparency, thereby canceling the unwanted excitations. As our scheme allows the application of strong cooling fields, fast and efficient cooling can be achieved.


Thin-Film Ferroelectrics.
Over the last 30 years, the study of ferroelectric oxides has been revolutionized by the implementation of epitaxial-thin-film-based studies, which have driven many advances in the understanding of ferroelectric physics and the realization of novel polar structures and functionalities. New questions have motivated the development of advanced synthesis, characterization, and simulations of epitaxial thin films and, in turn, have provided new insights and applications across the micro-, meso-, and macroscopic length scales. This review traces the evolution of ferroelectric thin-film research through the early days developing understanding of the roles of size and strain on ferroelectrics to the present day, where such understanding is used to create complex hierarchical domain structures, novel polar topologies, and controlled chemical and defect profiles. The extension of epitaxial techniques, coupled with advances in high-throughput simulations, now stands to accelerate the discovery and study of new ferroelectric materials. Coming hand-in-hand with these new materials is new understanding and control of ferroelectric functionalities. Today, researchers are actively working to apply these lessons in a number of applications, including novel memory and logic architectures, as well as a host of energy conversion devices.


Photoreactive Hydrogel Stiffness Influences Volumetric Muscle Loss Repair.
Volumetric muscle loss (VML) injuries are characterized by permanent loss of muscle mass, structure, and function. Hydrogel biomaterials provide an attractive platform for skeletal muscle tissue engineering due to the ability to easily modulate their biophysical and biochemical properties to match a range of tissue characteristics. In this work, we successfully developed a mechanically tunable hyaluronic acid (HA) hydrogel system to investigate the influence of hydrogel stiffness on VML repair. HA was functionalized with photoreactive norbornene groups to create hydrogel networks that rapidly crosslink through thiol-ene click chemistry with tailored mechanics. Mechanical properties were controlled by modulating the amount of matrix metalloproteinase-degradable peptide crosslinker to produce hydrogels with increasing elastic moduli of 1.1 ± 0.002, 3.0 ± 0.002, and 10.6 ± 0.006 kPa, mimicking a relevant range of developing and mature muscle stiffnesses. Functional muscle recovery was assessed following implantation of the HA hydrogels by in situ photopolymerization into rat latissimus dorsi (LD) VML defects at 12 and 24 weeks postinjury. After 12 weeks, muscles treated with medium stiffness (3.0 kPa) hydrogels produced maximum isometric forces most similar to contralateral healthy LD muscles. This trend persisted at 24 weeks postinjury, suggestive of sustained functional recovery. Histological analysis revealed a significantly larger zone of regeneration with more de novo muscle fibers following implantation of medium stiffness hydrogels in VML-injured muscles compared to other experimental groups. Lower (low and medium) stiffness hydrogels also appeared to attenuate the chronic inflammatory response characteristic of VML injuries, displaying similar levels of macrophage infiltration and polarization to healthy muscle. Together these findings illustrate the importance of hydrogel mechanical properties in supporting functional repair of VML injuries. Impact statement This report defines the role hydrogel mechanical properties play in the repair of volumetric muscle loss (VML) injuries. We show that an intermediate hydrogel stiffness (3 kPa) more compliant than adult muscle tissue facilitated improved and sustained regenerative outcomes up to 24 weeks postinjury in a rat latissimus dorsi model of VML. Muscles treated with 3 kPa hydrogels showed enhanced myogenesis and attenuation of the chronic inflammatory response characteristic of VML injuries. These results should help guide the future design of hydrogels for skeletal muscle tissue engineering and regeneration.


Cellular migration, transition and interaction during regeneration of the sponge Hymeniacidon heliophila.
Sponges have a high capacity for regeneration and this process improves biomass production in some species, thus contributing to a solution for the biomass supply problem for biotechnological applications. The aim of this work is to characterize the dynamics of cell behavior during the initial stages of sponge regeneration, using bright-field microscopy, confocal microscopy and SEM. We focused on the first 20 h of regeneration, during which blastema formation and epithelium initialization occur. An innovative sponge organotypic culture of the regenerating internal region is described and investigated by confocal microscopy, cell transplantation and vital staining. Cell-cell interaction and cell density are shown to affect events in morphogenesis such as epithelial/mesenchymal and mesenchymal/epithelial transitions as well as distinct cell movements required for regeneration. Extracellular matrix was organized according to the morphogenetic process observed, with evidence for cell-signaling instructions and remodeling. These data and the method of organotypic culture described here provide support for the development of viable sponge biomass production.


The presence of calcaneal fibular remodeling associated with middle facet talocalcaneal coalition: a retrospective CT review of 35 feet. Investigations involving middle facet coalitions--Part II.
Middle facet talocalcaneal coalition is often associated with a rigid pes planovalgus. In the presence of calcaneal valgus, the fibula may come into contact with the lateral calcaneal wall during weight bearing, and develop a pseudoarticulation. Spurring, bone cysts, and other morphologic changes may concomitantly occur at the calcaneus and fibula, suggesting a pathological degenerative process. This association has not been previously studied in middle facet tarsal coalition and we term the condition calcaneal fibular remodeling, the focus of this investigation. To our knowledge, no study has specifically looked at the abutment of the calcaneus and fibula as an additional area of pathology in patients treated operatively for tarsal coalition. Computerized axial tomography was retrospectively reviewed in 21 patients (35 feet) with symptomatic middle facet talocalcaneal coalition who were surgically treated for the coalition on at least 1 foot over a 12-year period. In 19 (54%) of the 35 feet, calcaneal fibular remodeling was identified and associated with concomitant coalition and pes planovalgus deformity. Fifteen (79%) of the 19 feet with calcaneal fibular remodeling were managed surgically at the time of manuscript submission for middle facet talocalcaneal coalition. This new finding suggests that simple resection of the coalition may not fully address the entire deformity and other combined surgical approaches may be more appropriate in the face of middle facet talocalcaneal coalition with heel valgus and calcaneal fibular remodeling.


Tailoring strategies for the management of depression in midlife years.
Depression affects one in every five adults in North America. Women are more affected than men, possibly because of genetics, coping strategies, and hormone variations. The concept of a menopause-associated depression, however, remains a complex and controversial topic. Although hormone therapy is not recommended as first-line therapy for depression in midlife women, estrogen-based hormone therapy may minimize the need for or enhance the response to antidepressant or behavior-based therapies in select perimenopausal women.


The Associations of Complicated Grief, Depression, Posttraumatic Growth, and Hope Among Bereaved Youth.
Research on the association between complicated grief (CG), hope, and posttraumatic growth (PTG) among bereaved youth is limited. Measures of CG, depression, hope, and PTG were completed by 85 youth (aged 7-18 years). Results indicated a strong positive relationship between CG and depressive symptoms, an inverse relationship between hope and depressive symptoms, and a moderate positive relationship between hope and PTG. There was no significant association between CG and hope or between CG and PTG. Higher levels of CG and lower levels of hope independently predicted greater depressive symptoms, but PTG did not. Results have implications for assessing positive outcomes in bereaved youth.


EOSINOPHILIC ANGIOCENTRIC FIBROSIS AS A CAUSE OF NASAL OBSTRUCTION. A CASE REPORT.
Eosinophilic angiocentric fibrosis (EAF) is a rare benign lesion of unknown aetiology, found predominantly in the upper respiratory tract. The fibrosis must be confirmed by considering other lesions in the differential diagnosis. The typical histological characteristics are the basis for establishing the diagnosis. We present a patient with long-term nasal obstruction caused by EAF. The patient had repeated resections of the lesion for its recurrences. As follows from the literature, radical resection is crucial for the treatment of EAF. This procedure may be difficult at times given the extent and localization of the disease..


Modulation of colony stimulating factor-(CSF) dependent growth of acute myeloid leukemia by tumor necrosis factor.
In this study we demonstrate that tumor necrosis factors (TNF alpha and TNF beta) are potent modulators of the in vitro proliferation of human AML cells. Blast cells from 11 cases of acute myeloblastic leukemia (AML) were incubated with recombinant TNF alpha or TNF beta in serum-free 3H-TdR uptake and colony culture systems in the presence or absence of recombinant interleukin-3 (IL-3), granulocyte macrophage colony-stimulating factor (GM-CSF), G-CSF, or M-CSF. Depending on the supplemented CSF, TNF could upregulate or suppress AML blast proliferation. Enhancement of AML growth by TNF was observed in the presence of IL-3 (in 9 of 11 cases in 3H-TdR assay; 6 of 9 cases in colony assay) and GM-CSF (in 8 of 11 cases in 3H-TdR assay; 4 of 9 cases in colony assay). In certain cases in which IL-3 or GM-CSF alone was unable to induce proliferative responses of AML cells, the simultaneous addition of TNF elicited colony growth and DNA synthesis suggesting a synergistic action between TNF and IL-3 or GM-CSF. In contrast, TNF suppressed G-CSF-induced growth (9 of 10 cases in 3H-TdR assay; 5 of 6 cases in colony assay). TNF could also stimulate DNA synthesis (in 2 of 11 cases) or colony formation (in 2 of 9 cases) in AML cultures without the addition of other growth factors. Experiments with neutralizing antibodies and specific radioimmunoassays for individual CSFs showed that the synergistic and antagonistic effects of TNF on AML growth could not be attributed to a release of one of these CSFs by the AML cells. The opposing consequence of exposure of AML blasts to TNF are of interest in view of our understanding of the pathophysiology of AML growth and the in vivo application of recombinant cytokines in AML patients.


Dietary disproportions of amino acids in the rat: effects on food intake, plasma and brain amino acids and brain serotonin.
Food intake, growth, plasma and brain amino acid, and brain serotonin and 5-hydroxyindole-3-acetic acid (5-HIAA) concentrations were measured in rats fed low protein diets containing disproportionate amounts of large neutral amino acids (LNAA) devoid of tryptophan or histidine (tryptophan or histidine imbalance). Five-day food intakes and weight gains of rats fed the imbalanced diets were depressed. The concentration of the limiting amino acid was low in brains of rats fed diets containing LNAA that compete with either tryptophan or histidine for entry into brain. Correlations were observed between the brain concentrations of most individual LNAA and either the ratios of the plasma concentration of that LNAA to the sum of the other LNAA, or the predicted rates of influx of that LNAA. Cumulative food intakes were correlated with brain concentrations of the limiting amino acid, tryptophan or histidine. Food intakes were not consistently correlated with concentrations of serotonin and 5-HIAA because these compounds were altered only in brains of rats in the tryptophan study. Competition among amino acids for uptake into brain appears to be involved in the feeding response of the rat to dietary disproportions of amino acids, but this response is not directly related to changes in brain concentrations of serotonin and 5-HIAA.


Gravitropism interferes with hydrotropism via counteracting auxin dynamics in cucumber roots: clinorotation and spaceflight experiments.
Roots of land plants show gravitropism and hydrotropism in response to gravity and moisture gradients, respectively, for controlling their growth orientation. Gravitropism interferes with hydrotropism, although the mechanistic aspects are poorly understood. Here, we differentiated hydrotropism from gravitropism in cucumber roots by conducting clinorotation and spaceflight experiments. We also compared mechanisms regulating hydrotropism and auxin-regulated gravitropism. Clinorotated or microgravity (μG)-grown cucumber seedling roots hydrotropically bent toward wet substrate in the presence of moisture gradients, but they grew straight in the direction of normal gravitational force at the Earth's surface (1G) on the ground or centrifuge-generated 1G in space. The roots appeared to become hydrotropically more sensitive to moisture gradients under μG conditions in space. Auxin transport inhibitors significantly reduced the hydrotropic response of clinorotated seedling roots. The auxin efflux protein CsPIN5 was differentially expressed in roots of both clinorotated and μG-grown seedlings; with higher expression in the high-humidity (concave) side than the low-humidity (convex) side of hydrotropically responding roots. Our results suggest that roots become hydrotropically sensitive in μG, and CsPIN5-mediated auxin transport has an important role in inducing root hydrotropism. Thus, hydrotropic and gravitropic responses in cucumber roots may compete via differential auxin dynamics established in response to moisture gradients and gravity.


Down-regulation of glucocorticoid and beta-adrenergic receptors on lectin-stimulated splenocytes.
Activation of porcine splenocytes with the mitogen, concanavalin A, increases the number of glucocorticoid and beta-adrenergic receptors with no change in the apparent dissociation constant. Incubation of splenocytes with concanavalin A in the presence of hydrocortisone 21-sodium succinate prevented this mitogen-induced increase in glucocorticoid receptors. Isoproterenol also prevented the concanavalin A-induced increase in beta-adrenoceptors at 24 hr and reduced the binding affinity of these receptors at 48 hr. Neither agonist had any significant effect on the receptor number of binding affinity of nonstimulated cells. These data demonstrate that the increase in the number of glucocorticoid and beta-adrenergic receptors that occur on lymphoid cells after activation by a T-cell mitogen can be prevented by appropriate hormone agonists. Down-regulation of receptor number by appropriate agonists appears to be a common regulatory system that is shared by both the neuroendocrine and the immune systems.


Networked-cage microcrystals for evaluation of host-guest interactions.
We have developed a new synthetic protocol for the preparation of a microcrystalline powder (median size: X50 = 25 μm) of networked M6L4 cages 1a for the stationary phase of an affinity column on a greater than 50 g scale. Analogously to large single crystals 1b (X50 ≈ 0.5 mm), microcrystals 1a accommodate guest molecules tetrathiafulvalene (TTF) and fullerene (C60) at up to 32 and 35 wt %, respectively. Importantly, the host-guest interactions within networked cages could be evaluated in terms of the retention time from HPLC analysis by using microcrystals 1a as the stationary phase. In this way, favorable guests for networked cages 1 and even solution M6L4 cage 2 could easily be assessed by HPLC.


Molecular regulation of human interleukin 2 and T-cell function by interleukin 4.
Distinct functional T-cell subsets, differing in the patterns of lymphokines produced, regulate cell-mediated and humoral immune responses. The two major types and their principal products, interleukin 4 and interferon gamma (IL-4 and IFN-gamma), are reciprocally negatively interactive. To analyze the molecular mechanism of IL-4-mediated suppression of cell-mediated immunity we studied its effects on expression of interleukin 2 (IL-2) and IFN-gamma. IL-4 pretreatment of Jurkat cells prior to stimulation resulted in a decrease in transcription of the IL2 gene. IL-4 suppressed IL-2 and IFN-gamma mRNA levels in primary human T cells, and addition of anti-CD28 antibodies relieved this suppression. Using enhancer-reporter constructs, IL-4 specifically down-regulated the NFIL-2B element. Electrophoretic mobility shift assays using a DNA oligomer containing the NFIL-2B binding site indicated that IL-4 inhibited the NFIL-2B complex and that the NFIL-2B DNA binding factor is distinct from AP-1. These results suggest that IL-4 may regulate development and function of T-cell subsets involved in cell-mediated immunity in part by inhibiting factors required for transcription of the IL2 gene.


The relevance of left ventricular bands.
Left ventricular bands (LVBs) were first described almost a century ago but were largely ignored until their 'rediscovery' by echocardiography. Renewed interest in LVBs and the demonstration of their association with clinical abnormalities have resulted in attempts to establish their causal relationship with various phenomena, especially the vibratory systolic murmur and premature ventricular contractions. Published articles on LVBs are reviewed with specific reference to nomenclature, embryological development, histological features, prevalence, demonstration in vivo and at autopsy, and alleged clinical importance. Current views on LVBs are evaluated and future research directions are suggested.


Primary Sulfonamide Functionalization via Sulfonyl Pyrroles: Seeing the N-Ts Bond in a Different Light.
Despite common occurrence in molecules of value, methods for transforming sulfonamides are distinctly lacking. Here we introduce easy-to-access sulfonyl pyrroles as synthetic linchpins for sulfonamide functionalization. The versatility of the sulfonyl pyrrole unit is shown by generating a variety of products through chemical, electrochemical and photochemical pathways. Preliminary results on the direct functionalization of primary sulfonamides are also provided, which may lead to new modes of activation.


In Vivo Degradation of Forged-Unsintered Hydroxyapatite and Poly-L-lactide Mesh Used for Orbital Reconstruction.
The aim of this study was to assess compositional changes in a forged-unsintered hydroxyapatite and poly-L-lactide (uHA/PLLA) mesh at 651 days after insertion into human body.A 35-year-old female patient had left tripod fracture, orbital medial wall and floor fracture, and superficial lateral palpebral ligament rupture. On the 9th posttrauma day, the tripod fracture was reduced and fixed with plates, and the orbital wall and floor were reconstructed with a resorbable mesh. The floor and medial wall were reconstructed with a trimmed mesh made of uHA/PLLA (Osterotrans-MX; Takiron Co, Umeda, Japan). On postoperative day 620, she complained of enophthalmos of left eye (right eye, 18 mm; left eye, 16 mm). Secondary reconstruction of the orbital floor was performed with an iliac bone graft 651 days after insertion. During the secondary operation, the uHA/PLLA mesh that had been previously inserted was removed. The mesh was removed and analyzed using gel permeation chromatography (GPC) and Fourier transform infrared spectroscopy (FTIR).The GPC revealed that the weight average molecular weight (Mw) decreased from 542,000 to 83,300 Da and the number average molecular weight (Mn) decreased from 124,000 to 20,200 Da in the specimen from the operation. In the postinsertion FTIR spectrum, weak 1648.6 and 1656.1/cm peaks newly appeared. The strong 1038/cm peak of the initial specimen changed slightly into a less strong 1041.8/cm peak.In conclusion, the reduced Mw and Mn in the postinsertion specimen suggest that uHA/PLLA has one of the favorable degradation properties. The newly appeared bands are thought to be carbon-carbon double bonds of alkenes.


High CO2 Downregulates Skeletal Muscle Protein Anabolism via AMP-activated Protein Kinase α2-mediated Depressed Ribosomal Biogenesis.
High CO2 retention, or hypercapnia, is associated with worse outcomes in patients with chronic pulmonary diseases. Skeletal muscle wasting is also an independent predictor of poor outcomes in patients with acute and chronic pulmonary diseases. Although previous evidence indicates that high CO2 accelerates skeletal muscle catabolism via AMPK (AMP-activated protein kinase)-FoxO3a-MuRF1 (E3-ubiquitin ligase muscle RING finger protein 1), little is known about the role of high CO2 in regulating skeletal muscle anabolism. In the present study, we investigated the potential role of high CO2 in attenuating skeletal muscle protein synthesis. We found that locomotor muscles from patients with chronic CO2 retention demonstrated depressed ribosomal gene expression in comparison with locomotor muscles from non-CO2-retaining individuals, and analysis of the muscle proteome of normo- and hypercapnic mice indicates reduction of important components of ribosomal structure and function. Indeed, mice chronically kept under a high-CO2 environment show evidence of skeletal muscle downregulation of ribosomal biogenesis and decreased protein synthesis as measured by the incorporation of puromycin into skeletal muscle. Hypercapnia did not regulate the mTOR pathway, and rapamycin-induced deactivation of mTOR did not cause a decrease in ribosomal gene expression. Loss-of-function studies in cultured myotubes showed that AMPKα2 regulates CO2-mediated reductions in ribosomal gene expression and protein synthesis. Although previous evidence has implicated TIF1A (transcription initiation factor-1α) and KDM2A (lysine-specific demethylase 2A) in AMPK-driven regulation of ribosomal gene expression, we found that these mediators were not required in the high CO2-induced depressed protein anabolism. Our research supports future studies targeting ribosomal biogenesis and protein synthesis to alleviate the effects of high CO2 on skeletal muscle turnover.


The gastrointestinal tract. The "undrained abscess" of multiple organ failure.
This study determined the association between proximal gastrointestinal (GI) colonization and the development of intensive care unit (ICU)-acquired infection and multiple organ failure (MOF) in a population of critically ill surgical patients. ICU-acquired infection in association with progressive organ system dysfunction is an important cause of morbidity and mortality in critical surgical illness. Oropharyngeal and gastric colonization with the characteristic infecting species is common, but its association with ICU morbidity is poorly defined. A prospective cohort study of 41 surgical ICU patients was undertaken. Specimens of gastric and upper small bowel fluid were obtained for quantitative culture; the severity of organ dysfunction was quantitated by a numeric score. One or more episodes of ICU-acquired infection developed in 33 patients and involved at least one organism concomitantly cultured from the upper GI tract in all but 3. The most common organisms causing ICU-acquired infection--Candida, Streptococcus faecalis, Pseudomonas, and coagulase-negative Staphylococci--were also the most common species colonizing the proximal GI tract. Gut colonization correlated with the development of invasive infection within 1 week of culture for Pseudomonas (90% vs. 13% in noncolonized patients, p < 0.0001) or Staphylococcus epidermidis (80% vs. 6%, p < 0.0001); a weaker association was seen for colonization with Candida. Infections associated with GI colonization included pneumonia (16 patients), wound infection (12 patients), urinary tract infection (11 patients), recurrent (tertiary) peritonitis (11 patients), and bacteremia (10 patients). ICU mortality was greater for patients colonized with Pseudomonas (70% vs. 26%, p = 0.03); organ dysfunction was most marked in patients colonized with one or more of the following: Candida, Pseudomonas, or S. epidermidis. The upper GI tract is an important reservoir of the organisms causing ICU-acquired infection. Pathologic GI colonization is associated with the development of MOF in the critically ill surgical patient.


5'-substituted-6-carboxylic-2,2'-bipyridine acid: a pivotal architecton for building preorganized ligands.
A set of ligands bearing 6-bromo-2,2'-bipyridine pendant arms attached in the 5'-position are described. Transformation of the bromo to an ester was performed by a carboethoxylation reaction promoted by low-valent Pd(0), while saponification followed by acidification gave the acids. The introduction of an appended function 3-nitrobenzyl, benzamidomethyl, and tert-butylacetyl opens the way to further functionalize these scaffolds for potential labeling of biological material. The synthetic protocols represent a valuable approach to the rational design of ligands bearing oxophilic and anionic sidearms.


Basic approach to inflammatory ulcers.
Cutaneous ulcers are a difficult problem. A multidisciplinary approach is often adapted in caring for patients with nonhealing wounds. Internists, surgeons, dermatologists, and nurses must work together to provide a patient with the most comprehensive care possible. Dermatologists are consulted for a number of reasons, particularly if the ulcers are secondary to an inflammatory process. In this discussion, we describe a basic and useful approach to the diagnosis and management of inflammatory ulcers. The spectrum of these conditions is wide, ranging from vasculitis, to pyoderma gangrenosum, to ulcers resulting from the antiphospholipid syndrome and cryoprecipitates. The present authors will emphasize that the approach needs to be all-encompassing, and not focused on the ulceration alone. Certain clues are critical to diagnosis. The management, whereas often difficult, can be very rewarding.


Treatment of acne scarring.
Acne scarring is common but surprisingly difficult to treat. Scars can involve textural change in the superficial and deep dermis, and can also be associated with erythema, and less often, pigmentary change. In general, treatment of acne scarring is a multistep procedure. First, examination of the patient is necessary to classify the subtypes of scarring that are present. Then, the patient's primary concerns are elicited, and the patient is offered a menu of procedures that may address the various components of the scarring process. It is important to emphasize to the patient that acne scarring can be improved but never entirely reversed.


5-N-Arylaminothiazoles as Highly Twisted Fluorescent Monocyclic Heterocycles: Synthesis and Characterization.
A series of 5-N-arylaminothiazoles was prepared by reacting thioamide dianions derived from secondary thioamides with thioformamides, followed by sequential oxidation with iodine. X-ray analyses demonstrated that they adopt structures that are highly twisted from planar conformations. Their orientations were tuned by the steric and/or electronic interactions of the substituents at their 2-, 4-, and 5-positions. The 5-aminothiazoles exhibited a range of fluorescent emissions, from blue to orange. Although the absorption spectra were independent of the polarity of the solvent, fluorescent emissions were influenced by the polarity of the solvent: in more polar solvents, the emissions were red-shifted. These phenomena were examined in terms of Lippert-Mataga plots and the change in the dipole moment between the ground and excited states. They also exhibited emissions in the solid state, again from blue to orange. Cyclic voltammetry of the 5-aminothiazoles showed reversible waves of one-electron oxidation. The half-potential of the oxidation was reduced by the introduction of electron-donating groups to the phenyl groups on the nitrogen atom at the 5-position. DFT calculations were carried out to determine the energy levels of the HOMO and LUMO. Finally, the results of TG-DTA showed that they are thermally stable.


The influence of gender on colorectal cancer stage: the state of Ohio, 1996-2001.
The authors sought to determine if colorectal cancer stage at diagnosis varies by gender in the state of Ohio. We conducted a retrospective cohort study. Included in the cohort were patients diagnosed with colorectal cancer from 1996 to 2001 who had their data reported to the State of Ohio Tumor Registry. We collected data on gender, stage of cancer, and three potential confounding variables: age, location of colon cancer, and race. The colorectal cancer was determined to be at one of four stages: (1) carcinoma in situ, (2) local disease, (3) regional disease, and (4) distant disease. In addition, we combined stages 1 and 2 to create a good prognosis category, and we combined stages 3 and 4 to create a bad prognosis category. Our cohort consisted of 27,041 patients [13,807 women (51%) and 13,234 men]. The women with colon cancer were significantly older and had more right-sided colon cancer, (p < 0.05). With the use of logistic regression, the women were significantly less likely to have carcinoma in situ compared with the men (OR = 0.82, 95% CI 0.75-0.89). The women also had a significant decrease in local disease (OR = 0.94, 95% CI 0.89-0.99). In contrast, the women showed significantly more regional disease than men (OR = 1.11, 95% CI 1.05-1.16). The women were less likely to have a good prognostic stage (OR = 0.89, 95% CI 0.85-0.94) and more likely to have a bad prognostic stage (OR = 1.12, 95% CI 1.07-1.18). In the State of Ohio from 1996 to 2001, women had more advanced colon cancer at diagnosis than men.


An Automatic Detection System of Lung Nodule Based on Multigroup Patch-Based Deep Learning Network.
High-efficiency lung nodule detection dramatically contributes to the risk assessment of lung cancer. It is a significant and challenging task to quickly locate the exact positions of lung nodules. Extensive work has been done by researchers around this domain for approximately two decades. However, previous computer-aided detection (CADe) schemes are mostly intricate and time-consuming since they may require more image processing modules, such as the computed tomography image transformation, the lung nodule segmentation, and the feature extraction, to construct a whole CADe system. It is difficult for these schemes to process and analyze enormous data when the medical images continue to increase. Besides, some state of the art deep learning schemes may be strict in the standard of database. This study proposes an effective lung nodule detection scheme based on multigroup patches cut out from the lung images, which are enhanced by the Frangi filter. Through combining two groups of images, a four-channel convolution neural networks model is designed to learn the knowledge of radiologists for detecting nodules of four levels. This CADe scheme can acquire the sensitivity of 80.06% with 4.7 false positives per scan and the sensitivity of 94% with 15.1 false positives per scan. The results demonstrate that the multigroup patch-based learning system is efficient to improve the performance of lung nodule detection and greatly reduce the false positives under a huge amount of image data.


Evaluation of two Plasmodium vivax sexual stage antigens as transmission-blocking vaccine candidates.
Plasmodium vivax transmission-blocking vaccines (TBVs) are receiving increasing attention. Based on excellent transmission-blocking activities of the PbPH (PBANKA_0417200) and PbSOP26 (PBANKA_1457700) antigens in Plasmodium berghei, their orthologs in P. vivax, PVX_098655 (PvPH) and PVX_101120 (PvSOP26), were selected for the evaluation of their potential as TBVs. Fragments of PvPH (amino acids 22-304) and PvSOP26 (amino acids 30-272) were expressed in the yeast expression system. The recombinant proteins were used to immunize mice to obtain antisera. The transmission-reducing activities of these antisera were evaluated using the direct membrane feeding assay (DMFA) using Anopheles dirus mosquitoes and P. vivax clinical isolates. The recombinant proteins PvPH and PvSOP26 induced robust antibody responses in mice. The DMFA showed that the anti-PvSOP26 sera significantly reduced oocyst densities by 92.0 and 84.1% in two parasite isolates, respectively, whereas the anti-PvPH sera did not show evident transmission-reducing activity. The variation in the DMFA results was unlikely due to the genetic polymorphisms of the two genes since their respective sequences were identical in the clinical P. vivax isolates. PvSOP26 could be a promising TBV candidate for P. vivax, which warrants further evaluation.


Apple pollen as a supplemental food source for the control of western flower thrips by two predatory mites, Amblyseius swirskii and Neoseiulus cucumeris (Acari: Phytoseiidae), on potted chrysanthemum.
It has been shown that pollen as a dietary supplement may increase the establishment (development and reproduction) and survival of phytoseiid predatory mites, and therefore the pest control these mites can provide. In this study, the role of apple pollen as a supplemental food source was assessed as a means to increase the efficiency of two predatory mite species, Neoseiulus cucumeris and Amblyseius swirskii, for control of western flower thrips, Frankliniella occidentalis, under greenhouse conditions. The impact of apple pollen on thrips populations and predator establishment on a greenhouse chrysanthemum crop was determined over a 4-week period. The two mite species were released separately and in combination with and without pollen with two control treatments (thrips only and thrips + pollen). The introduction of A. swirskii together with pollen application provided the best control of thrips (adults and immatures). The establishment of N. cucumeris was very low in the crop during the greenhouse trial. This could be attributable, in part, to their response to extreme temperature ranges that were encountered during the greenhouse cage trials. The use of A. swirskii alone and the mixed population of the two predatory mite species without pollen resulted in the lowest frequencies of plants with heavy damage, followed by the same treatments with the addition of apple pollen.


[Spontaneous intracranial hypotension: an unrecognized diagnosis].
We report an observation of spontaneous intracranial hypotension occurring in a 32-year-old man. The diagnosis of intracranial hypotension is easy in a suggestive context: after a lumbar puncture or a diversion of CSF. Clinical and CSF cytological features can mimic chronic meningitis leading to false diagnosis and erroneous therapeutic. Magnetic resonance imaging allows diagnosis. This uncommon and benign pathology must be better known.


Bronchial hyperresponsiveness can improve while spirometry plateaus two to three years after repeated exposure to chlorine causing respiratory symptoms.
Repeated exposure to chlorine in pulp mills and paper can induce persistent asthma-like symptoms such as bronchial hyperresponsiveness and variable changes in airway caliber. The long-term time course of bronchial hyperresponsiveness has not been examined. We studied 20 of 29 subjects (69% participation rate) who demonstrated bronchial hyperresponsiveness to methacholine when they were first assessed, 18 to 24 mo after repeatedly inhaling "puffs" of high concentrations of chlorine in a paper mill over a 3-mo period. Each subject answered a respiratory questionnaire and underwent spirometry and a methacholine inhalation test 12 mo after the initial survey, 30 to 36 mo after the chlorine inhalations. Three subjects required inhaled steroids at the time of the initial survey and three at the time of the second, including two who carried on using these preparations. Only one subject changed smoking habits. There were no significant overall changes in FEV1 on the two occasions, nine subjects having a FEV1 < 80% on the first occasion and eight on the second. Six of the 18 subjects (33%) who underwent a methacholine inhalation test on both occasions had significantly improved PC20 results, including five for whom the PC20 value was within the normal range. All six subjects had normal FEV1 values on both assessments. Although changes in spirometry induced by repeated exposure to chlorine seem to persist, bronchial hyperresponsiveness can improve significantly in those with normal airway caliber. This suggests that less pronounced bronchial alterations induced by repeated exposures to chlorine may be reversible.


Suicide prevention: is more demographic information the answer?
Suicide is an important health issue and its prevention is prioritized in government targets. PCTs in England and Wales are also required to carry out audits of suicide deaths by the Healthcare Commission (HCC). We present findings of a 6-year analysis of suicide deaths between 2002 and 2008 in Birmingham and Solihull, the second largest urban conurbation in the UK. After extensive analysis, no demographic group was shown to have a significantly greater risk of suicide and no geographical area had significantly higher rates than another. Despite the large population examined (c.1.3 million), these findings are likely to be due to the rarity of suicides as an outcome. We discuss the practical implications of these findings for local health organizations charged with reducing suicide rates, the value to local suicide audits and the use of a new suicide audit tool developed for use by PCTs. We conclude that ever increasing collection of information surrounding suicide deaths is unlikely to result in the discovery of local groups amenable to targeted suicide prevention interventions and that the HCC may want to reconsider its performance indicator around suicide audits to allow valuable resources to be used more effectively elsewhere.


The impact of automated writing evaluation on second language writing skills of Chinese EFL learners: a randomized controlled trial.
In the context of the burgeoning field of second language (L2) education, where proficient writing plays an integral role in effective language acquisition and communication, the ever-increasing technology development has influenced the trajectory of L2 writing development. To address the need for enhanced writing skills among English as a Foreign Language (EFL) learners, this study investigates the efficacy of Automated Writing Evaluation (AWE) training. A randomized controlled trial employing repeated measures was conducted, involving a participant pool of 190 Chinese EFL students. The study comprehensively assessed the effects of AWE training, utilizing the Grammarly platform-an AI-driven program-on various dimensions of writing skills, encompassing task achievement, coherence and cohesion, lexicon, and grammatical accuracy. Control variables included writing self-efficacy and global English proficiency. Writing skills were evaluated through the administration of an International English Language Testing System (IELTS) writing sample test. The results unequivocally demonstrate that the experimental group consistently exhibited superior performance across all facets of writing skills compared to the control group. Furthermore, the predictive influence of pre-test scores was pronounced in task achievement, coherence and cohesion, and lexicon, highlighting the pivotal role of learners' initial proficiency levels in shaping subsequent writing outcomes. Notably, the emergence of writing self-efficacy as a significant predictor of task achievement and coherence and cohesion underscores the role of learners' beliefs and confidence in shaping their writing abilities. These findings conclusively suggest that Artificial Intelligence-based instructional programs, specifically AWE, hold the potential to effectively enhance second language writing skills, especially among learners with lower proficiency levels. This study carries crucial implications for EFL educators and researchers, advocating for the seamless integration of AWE into pedagogical strategies to foster a marked improvement in writing competence.


A population study of renal disease in patients with tuberous sclerosis.
To establish the prevalence of renal disease, asymptomatic renal lesions and possible renal symptoms in a geographically defined population of individuals with tuberous sclerosis. The study involved 131 patients (64 men, 67 women) with tuberous sclerosis who were resident in nine of the districts within the Wessex Region and three Bristol Health Districts and who had been identified by a prevalence study [1]. The patients' mean age was 22 years (range 6 months-74 years). Established renal disease was identified by history. Where possible individuals were seen and were examined. Specific enquiry was made for flank pain and macroscopic haematuria. Renal ultrasound, blood pressure measurement and urine analysis was offered to all individuals with tuberous sclerosis who were resident in the Bath Health District. Eight patients (6%) had a history of either renal polycystic kidney disease (two patients) or haemorrhage from renal angiomyolipomas (five female patients, one male patient). A further 21% of female and 3% of male patients had a history of severe flank pain or haematuria. Renal ultrasound screening revealed abnormalities in 10 of 21 individuals; angiomyolipomas > 1 cm were found in seven and were twice as common in female patients. Regular clinical review of individuals with tuberous sclerosis should include enquiry for renal symptoms and abdominal examination. Lesions > 4 cm are most likely to be symptomatic but longitudinal studies are needed before renal ultrasound screening of adolescents or adults can be recommended.


Transport and elastic scattering times as probes of the nature of impurity scattering in single-layer and bilayer graphene.
Transport and elastic scattering times, tau{tr} and tau{e}, are experimentally determined from the carrier density dependence of the magnetoconductance of monolayer and bilayer graphene. Both times and their dependences on carrier density are found to be very different in the monolayer and the bilayer. However, their ratio tau{tr}/tau{e} is found to be close to 1.8 in the two systems and nearly independent of the carrier density. These measurements give insight on the nature (neutral or charged) and range of the scatterers. Comparison with theoretical predictions suggests that the main scattering mechanism in our samples is due to strong (resonant) scatterers of a range shorter than the Fermi wavelength, likely candidates being vacancies, voids, adatoms or short-range ripples.


Periostin serves an important role in the pathogenesis of oral squamous cell carcinoma.
The mechanism underlying OSCC tumorigenesis remains unclear. Periostin is considered to be a prominent oncogene in various solid tumors, although its precise role in OSCC progression remains unknown. In the present study, periostin expression was examined in surgical specimens of OSCC cases, and the results were analyzed for possible correlations with clinical characteristics. In addition, the proliferation and invasiveness of OSCC cells were evaluated following transfection with a Periostin small interfering RNA or an overexpression plasmid. The results revealed that periostin levels were significantly higher in patients with OSCC as compared with those in the controls (P<0.05). In addition, periostin levels in patients with OSCC were significantly associated with permeation classification. Furthermore, periostin expression was observed to promote the proliferation and invasiveness of OSCC cells. The present results suggest that periostin is significantly involved in the pathogenesis of OSCC.


Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging.
Successful development of ultra-sensitive molecular imaging nanoprobes for the detection of targeted biological objects is a challenging task. Although magnetic nanoprobes have the potential to perform such a role, the results from probes that are currently available have been far from optimal. Here we used artificial engineering approaches to develop innovative magnetic nanoprobes, through a process that involved the systematic evaluation of the magnetic spin, size and type of spinel metal ferrites. These magnetism-engineered iron oxide (MEIO) nanoprobes, when conjugated with antibodies, showed enhanced magnetic resonance imaging (MRI) sensitivity for the detection of cancer markers compared with probes currently available. Also, we successfully visualized small tumors implanted in a mouse. Such high-performance, nanotechnology-based molecular probes could enhance the ability to visualize other biological events critical to diagnostics and therapeutics.


A validation of the spectral power clustering technique (SPCT) by using a Rogowski coil in partial discharge measurements.
Both in industrial as in controlled environments, such as high-voltage laboratories, pulses from multiple sources, including partial discharges (PD) and electrical noise can be superimposed. These circumstances can modify and alter the results of PD measurements and, what is more, they can lead to misinterpretation. The spectral power clustering technique (SPCT) allows separating PD sources and electrical noise through the two-dimensional representation (power ratio map or PR map) of the relative spectral power in two intervals, high and low frequency, calculated for each pulse captured with broadband sensors. This method allows to clearly distinguishing each of the effects of noise and PD, making it easy discrimination of all sources. In this paper, the separation ability of the SPCT clustering technique when using a Rogowski coil for PD measurements is evaluated. Different parameters were studied in order to establish which of them could help for improving the manual selection of the separation intervals, thus enabling a better separation of clusters. The signal processing can be performed during the measurements or in a further analysis.


Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans.
The human DARC (Duffy antigen receptor for chemokines) gene encodes a membrane-bound chemokine receptor crucial for the infection of red blood cells by Plasmodium vivax, a major causative agent of malaria. Of the three major allelic classes segregating in human populations, the FY*O allele has been shown to protect against P. vivax infection and is at near fixation in sub-Saharan Africa, while FY*B and FY*A are common in Europe and Asia, respectively. Due to the combination of strong geographic differentiation and association with malaria resistance, DARC is considered a canonical example of positive selection in humans. Despite this, details of the timing and mode of selection at DARC remain poorly understood. Here, we use sequencing data from over 1,000 individuals in twenty-one human populations, as well as ancient human genomes, to perform a fine-scale investigation of the evolutionary history of DARC. We estimate the time to most recent common ancestor (TMRCA) of the most common FY*O haplotype to be 42 kya (95% CI: 34-49 kya). We infer the FY*O null mutation swept to fixation in Africa from standing variation with very low initial frequency (0.1%) and a selection coefficient of 0.043 (95% CI:0.011-0.18), which is among the strongest estimated in the human genome. We estimate the TMRCA of the FY*A mutation in non-Africans to be 57 kya (95% CI: 48-65 kya) and infer that, prior to the sweep of FY*O, all three alleles were segregating in Africa, as highly diverged populations from Asia and ≠Khomani San hunter-gatherers share the same FY*A haplotypes. We test multiple models of admixture that may account for this observation and reject recent Asian or European admixture as the cause.


Hypertension in the elderly is associated with impaired glucose metabolism independently of obesity and glucose intolerance.
We evaluated insulin secretion, insulin sensitivity and blood pressure changes after oral administration of glucose in hypertensive and normotensive elderly subjects. The hypertensive group consisted of 12 subjects (aged 72.5 +/- 1.9 years, mean +/- s.e.m.) who had a history of hypertension lasting 10-25 years and were not more than 20% above ideal body weight. The normotensive group consisted of 12 subjects matched to the hypertensive group for age, sex and weight. All subjects underwent an oral glucose tolerance test (75 g glucose dissolved in 300 ml water), an intravenous glucose tolerance test (0.33 g/kg of a 50% glucose solution) and a euglycaemic, moderately hyperinsulinaemic glucose clamp. In both groups, oral glucose tolerance was normal according to the criteria of the National Diabetes Data Group; the hypertensive group showed significantly higher plasma glucose and insulin responses to oral glucose than the normotensive group, suggesting insulin resistance. The results of the euglycaemic clamp confirmed the state of reduced insulin sensitivity. Our data demonstrate that oral but not intravenous glucose produces a fall in blood pressure in hypertensive but not in normotensive patients, probably because activation of the sympathetic nervous system is impaired in hypertensive subjects; moreover, hypertension in the elderly seems associated with a state of reduced sensitivity to insulin.


Biosynthesis of vicinal dihydroxy fatty acids in the red alga Gracilariopsis lemaneiformis: identification of a sodium-dependent 12-lipoxygenase and a hydroperoxide isomerase.
Biosynthesis of the vicinal diol fatty acid (12R,13S)-dihydroxy-(5Z,8Z,10E,14Z)-eicosatetrae noic acid from arachidonic acid was studied in preparations of the red alga Gracilariopsis lemaneiformis. The transformation consisted of initial 12-lipoxygenase-catalyzed oxygenation of arachidonic acid into (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraeno ic acid followed by hydroperoxide isomerase-catalyzed conversion of the hydroperoxide into (12R,13S)-dihydroxyeicosatetraenoic acid. Short time incubations and trapping experiments with glutathione peroxidase revealed that (12S)-hydroperoxyeicosatetraenoic acid existed as a free intermediate in the overall conversion. The 12-lipoxygenase was mainly present in the soluble fraction of homogenate of G. lemaneiformis. Further, gel filtration experiments showed that the soluble 12-lipoxygenase was a protein having a molecular weight of 84,000-89,000. The enzymatic activity of 12-lipoxygenase isolated by gel filtration was weak; however, addition of 0.8-1 M sodium chloride to such desalted enzyme increased the activity 20-fold. Experiments with different salts revealed that sodium ion was specifically responsible for the stimulatory effect. Hydroperoxide isomerase was about equally distributed between the high speed supernatant and particulate fractions. Gel filtration of hydroperoxide isomerase present in the soluble fraction showed two peaks of activity corresponding to proteins having molecular weights of 220,000 or greater, and 40,000-45,000. The stereochemical course of the biosynthesis of vicinal diol fatty acids was determined using stereospecifically deuterated 6,9,12-octadecatrienoic acids. The 12-lipoxygenase-catalyzed reaction consisted of antarafacial hydrogen removal and oxygen insertion, whereas the hydroperoxide isomerase catalyzed an intramolecular oxygenation which occurred with retention of the configuration of the carbon atom hydroxylated.


Assessing the functionality of temporary isolation rooms.
Challenges with limited single rooms and isolation facilities in hospitals have created an opportunity for temporary, portable isolation technology. This article describes the process used to evaluate the prototype of a new isolation room (RediRoom; CareStrategic Ltd, Brisbane, Queensland, Australia) that can be installed in existing hospital ward areas. Our aim is to assess the functionality of this new room, and in so doing, to evaluate the methods used. We employed a mixed-methods approach involving video recording, interviews, and objective temperature and humidity measurements within a crossover interventional study. Participants completed a range of clinical activities in the RediRoom and a control. The setting for the study was a clinical ward environment at an Australian higher education institution. There were similarities between the RediRoom and the control using a range of measures. The time taken to complete a range of clinical activities in both rooms was broadly consistent. Network analysis also suggested broad similarities in the movement of nurses undertaking activities in both rooms. Our study attempted to simulate a clinical environment and clinical activities and provide the best possible comparison by completing activities sequentially, with immediate feedback to researchers. Video recording added significant value to the process because it provided some objectivity. A form of reflexive ethnography with participants could be of value in similar studies in the future.


Factors associated with Paracoccidiodes brasiliensis infection among permanent residents of three endemic areas in Colombia.
The natural habitat of Paracoccidioides brasiliensis, the aetiologic agent of paracoccidioidomycosis, has not been determined. Consequently, the events leading to the acquisition of infection remain controversial. To identify factors associated with infection in endemic areas we conducted a survey in three rural communities in Colombia where we had previously diagnosed paracoccidioidomycosis in children. Permanent residents were surveyed taking into consideration environmental and occupational variables. Skin tests were used to classify subjects as infected or non-infected. Variables found associated with infection were: (i) community A: previous residence around Porce river and agriculture in vegetable gardens; (ii) community C: frequent use of specific water sources; (iii) community V: housekeeping activities, and (iv) total group: age > 25 years and contact with bats. Residents in communities with higher prevalence of infection were older, had more complex residence history, and referred more contact with armadillos than residents of communities with lower infection.


A theoretical investigation on reciprocity-inspired wide-angle spectrally-selective THz absorbers augmented by anisotropic metamaterials.
In this paper, a theoretical framework relying on the reciprocity theorem is proposed to accurately design a spectrally-selective THz superstrate-loaded metamaterial absorber (SLMA) exhibiting wide-angle feature. By leveraging high-order Floquet harmonics in a generalized transmission line model characterizing the conventional metamaterial absorbers (MAs), it is demonstrated that MAs suffer from impedance mismatch, especially at near grazing angles. From an impedance matching viewpoint, this major challenge is tackled in this paper via two different designs, exploiting a magneto-electric anisotropic Huygens' metamaterial and a multilayer dielectric structure at a certain distance over the MA plane. The numerical results corroborate well the theoretical predictions, elucidating that the proposed SLMA significantly broadens the angular performance of the MA up to near grazing angles (about 80°), where high absorptivity is still achieved in both principal planes. The deteriorating effect of diffraction modes has been comprehensively analyzed. In comparison to the previous wide-angle MA reports based on intricate particle geometries and brute-force optimizations, the proposed design features a straightforward semi-analytical algorithm, which can also be re-developed for microwave, mid-infrared, and optical frequency bands and for any type of MA element. The proposed SLMA would be very promising for various wavelength-selective applications such as sensors and imaging.


Asymmetric postural tremor preceding DOPA-responsive Parkinsonism - the transition disease.
Tremulous Parkinson's disease (PD) and essential tremor are well known to be associated, but characteristics of progression of pure tremor state to PD remain unclear. In this prospective study a cohort of 16 patients suffering from a suggested new disease entity was clinically, pharmacologically, and sonographically analyzed to evaluate whether characteristics giving rise to a new entity in this field can be detected. All patients had a history of asymmetric postural tremor (aPT) who either already had developed surplus Parkinsonism (PARK group), or were still in the state of a pure asymmetric postural tremor syndrome (APT group). Asymmetry of aPT was assessed by tremor scores including an asymmetry index. DOPA-responsivity was analyzed by tremor scores and the score of the motor part of the Unified Parkinson's disease rating scale. Transcranial brain sonography was performed to evaluate echogenicity of the substantia nigra. Mean age at onset of asymmetric postural tremor was 57 ± 8.5 years without significant differences between both groups. Family history was compatible with an autosomal-dominant inheritance pattern in the majority of patients of both the APT and PARK group. All patients in the PARK group and 3 out of 8 patients in the APT group (38%) with respect to their asymmetric postural tremor were DOPA-responsive. All patients of both groups eligible to transcranial brain sonography showed hyperechogenicity of substantia nigra. In both groups, there was no correlation between tremor severity and duration of asymmetric postural tremor. Our data indicate that patients with an initial asymmetric and sometimes DOPA-responsive postural tremor syndrome and PARK patients are at various stages within the transition from aPT to a later developed DOPA-responsive Parkinsonian syndrome. It is postulated that the described group of patients may represent a separate disease entity with a hereditary background.


Antifungal activity of clinical Lactobacillus strains against Candida albicans biofilms: identification of potential probiotic candidates to prevent oral candidiasis.
This study isolated Lactobacillus strains from caries-free subjects and evaluated the inhibitory effects directly on three strains of C. albicans, two clinical strains and one reference strain. Thirty Lactobacillus strains were isolated and evaluated for antimicrobial activity against in vitro C. albicans biofilms. L. paracasei 28.4, L. rhamnosus 5.2 and L. fermentum 20.4 isolates exhibited the most significant inhibitory activity against C. albicans. Co-incubation between these microorganisms resulted in deterrence of biofilm development and retardation of hyphal formation. The hindrance of biofilm development was characterized by the downregulated expression of C. albicans biofilm-specific genes (ALS3, HWP1, EFG1 and CPH1). L. paracasei 28.4, L. rhamnosus 5.2 and L. fermentum 20.4 demonstrated the ability to exert antifungal activity through the inhibition of C. albicans biofilms.


Analysis of severe fever with thrombocytopenia syndrome cluster in east China.
Severe fever with thrombocytopenia syndrome (SFTS) is a common tick-borne, natural focal disease. SFTS virus (SFTSV) transmission can occur between family members through close contact with an infected patient. In this study, we explored the possible transmission route of an outbreak cluster in east China. A case-control study was carried out to analyze the potential risk factors for person-to-person transmission. Bunia virus was detected by IgM antibody, enzyme-linked immunosorbent assay, and reverse transcription polymerase chain reaction. Chi-square, univariate, and multivariate analyses were performed to calculate the association of possible risk factors for SFTSV transmission. Two patients had a clear history of blood and aerosols contact, and one may be exposed to aerosols in a closed environment. Five close contacts of the Index patient were IgM-positive and three were IgM and SFTSV RNA positive. Exposure to a poorly ventilated space where the corpse was stored (χ2 = 5.49, P = 0.019) and contact with the Index patient's contaminated items (χ2 = 15.77, P < 0.001) significantly associated with SFTSV infection. We suspect that the cluster outbreak was possibly a person-to-person transmission of SFTSV, which may have been transmitted by directly contacting with blood of SFTS patient. The propagation of aerosols in closed environments is also an undeniable transmission.


[New Developments in CKD-MBD. Why is phosphate overload harmful?].
Phosphate restriction has been shown to improve clinical outcomes in patients with chronic kidney disease (CKD) . However, the molecular mechanism underlying the harm in phosphate overload remains unclear. Recent studies suggest that the true culprit of phosphate toxicity may not be phosphate per se but calciprotein particles (CPPs) , colloidal nanoparticles composed of calcium phosphate crystals and mineral binding proteins such as Fetuin-A. CPPs are highly bioactive ligands that induce cell damage and innate immune responses. Serum levels of CPPs are increased in CKD patients and independently associated with vascular calcification and chronic inflammation. CPPs may be viewed as a "pathogen" that plays an important role in the pathophysiology of CKD.


Understanding the Activation of Platelets in Diabetes and Its Modulation by Allyl Methyl Sulfide, an Active Metabolite of Garlic.
Diabetes mellitus (DM) is a chronic metabolic disorder associated with higher risk of having cardiovascular disease. Platelets play a promising role in the pathogenesis of cardiovascular complications in diabetes. Since last several decades, garlic and its bioactive components are extensively studied in diabetes and its complications. Our aim was to explore the antiplatelet property of allyl methyl sulfide (AMS) focusing on ameliorating platelet activation in diabetes. We used streptozotocin- (STZ-) induced diabetic rats as model for type 1 diabetes. We have evaluated the effect of allyl methyl sulfide on platelet activation by administrating AMS to diabetic rats for 10 weeks. Flow cytometry-based analysis was used to evaluate the platelet activation, platelet aggregation, platelet macrophage interaction, and endogenous ROS generation in the platelets obtained from control, diabetes, and AMS- and aspirin-treated diabetic rats. AMS treatment for 10 weeks effectively reduced the blood glucose levels in diabetic rats. Three weeks of AMS (50 mg/kg/day) treatment did not reduce the activation of platelets but a significant (p < 0.05) decrease was observed after 10 weeks of treatment. Oral administration of AMS significantly (p < 0.05) reduced the baseline and also reduced ADP-induced aggregation of platelets after 3 and 10 weeks of treatment. Furthermore, 10 weeks of AMS treatment in diabetic rats attenuated the endogenous ROS content (p < 0.05) of platelets and platelet macrophage interactions. The inhibition of platelet activation in diabetic rats after AMS treatment was comparable with aspirin treatment (30 mg/kg/day). We observed an inhibitory effect of allyl methyl sulfide on platelet aggregation, platelet activation, platelet macrophage interaction, and increased ROS levels in type 1 diabetes. Our data suggests that AMS can be useful to control cardiovascular complication in diabetes via inhibition of platelet activation.


Dental education and early careers of Canadian dentists: changes in attitudes, aspirations, and behavior.
Longitudinal data on two cohorts of Canadian dental students are examined in order to determine the nature of the changes in attitudes and aspirations which students experience during their undergraduate dental training and the extent to which attitudes and aspirations which students hold on graduation are consistent with subsequent attitudes and behavior in practice. Data are presented on three dimensions of career-related attitudes and behavior: (1) aspirations toward and actual involvement in alternative practice settings, (2) attitudes and behavior related to selected professional and community activities, and (3) attitudes toward specific issues in dentistry. The results indicate that the dental school has little influence on students for the dimensions considered and suggest that analysis of both student backgrounds and the early practice experience of dental graduates may be the key to understanding the career behavior of dental graduates.