Impact of formulation on the quality and stability of freeze-dried nanoparticles.
Freeze-drying is an effective approach to improve the long-term stability of nanomedicines. Lyoprotectants are generally considered as requisite excipients to ensure that the quality of nanoparticles is maintained throughout the freeze-drying process. However, depending on the type of nanoparticles, the needs for lyoprotectants or the challenges they face during freeze-drying may be different. In this study, we compared and identified the impact of freeze-drying on key characteristics of three types of nanoparticles: solid lipid nanoparticles (SLNs), polymeric nanoparticles (PNs), and liposomes. Sucrose, trehalose, and mannitol were added to nanoparticle suspensions before freeze-drying. The same conservative freeze-drying conditions with controlled ice nucleation at -8 °C were employed for all formulations. The collapse temperatures of nanoparticle formulations were found to be the same as those of the lyoprotectant added, except PN formulation. Likely the poly(vinyl alcohol) (PVA) in the formulation induced a higher collapse temperature and retardation of drying of PNs. Freeze-drying of both SLNs and liposomes without lyoprotectants increased particle size and polydispersity, which was resolved by adding amorphous disaccharides. Regardless of the addition of lyoprotectants, freeze-drying did not alter the size of PNs possibly due to the protection from PVA. However, lyoprotectants were still necessary to shorten the reconstitution time and reduce the residual moisture. In conclusion, different types of nanoparticles face distinct challenges for freeze-drying, and lyoprotectants differentially affect various stability and quality attributes of freeze-dried nanoparticles.


Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions.
Invariant natural killer T (iNKT) cells exist in a 'poised effector' state, which enables them to rapidly produce cytokines following activation. Using a nearly monospecific T cell receptor, they recognize self and foreign lipid antigens presented by CD1d in a conserved manner, but their activation can catalyse a spectrum of polarized immune responses. In this Review, we discuss recent advances in our understanding of the innate-like mechanisms underlying iNKT cell activation and describe how lipid antigens, the inflammatory milieu and interactions with other immune cell subsets regulate the functions of iNKT cells in health and disease.


Evaluation of characteristics of Pediococcus spp. to be used as a vaginal probiotic.
The aim of our research was to select, identify and characterize an isolate of lactic acid bacteria to be considered as a vaginal probiotic. Thirty-five isolates of Pediococcus spp. showed bacteriocinogenic activity against Listeria monocytogenes and the ability to survive in simulated vaginal fluid (SVF) at pH 4.2. One isolate of Pediococcus spp. was selected and characterized to evaluate its safety before the use as vaginal probiotic. Pediococcus pentosaceus SB83 did not show the presence of virulence factors such as the production of gelatinase, lipase and DNase, haemolytic activity, nor the presence of virulence genes (genes esp, agg, gelE, efaAfm, efaAfs, cylA, cylB and cylM). Pediococcus pentosaceus SB83 was considered sensitive to chloramphenicol, gentamicin, streptomycin, kanamycin, erythromycin and ampicillin. This strain was considered resistant to tetracycline and vancomycin. Pediococcus pentosaceus SB83 was a biofilm producer at different pH values (4.2, 5.5 and 6.5) in SVF and in de Man, Rogosa and Sharpe medium. The in vitro results provide a basis for the use of P. pentosaceus SB83 as a vaginal probiotic, to prevent colonization by L. monocytogenes in pregnant women. The application of vaginal probiotics could have the potential for preventing vaginal infections and consequently reduce abortion and neonatal infections.


Reassessing Fano Resonance for Broadband, High-Efficiency, and Ultrafast Terahertz Wave Switching.
Miniaturized ultrafast switchable optical components with high efficiency and broadband response are in high demand to the development of optical imaging, sensing, and high-speed communication. Sharp Fano-type resonance switched by active materials is one of the key concepts that underpins the control of light in metaoptics with high sensitivity. However, actuating such metasurfaces exhibits a long-standing trade-off between modulation depth and operational bandwidth. Here, the limitations are circumvented by theoretical analysis, numerical simulation, and experimental realization of an achromatic Fano metasurface so that a high contrast of tunability with ultrafast switching rate over a broad range of frequency is achieved. By developing the physics of inter-mode coupling, the Fano metasurface is designed according to a complete phase diagram derived from coupled mode theory. Unlike conventional Fano metasurfaces, the cross-polarized inter-metaatoms coupling is discovered as a superior ability of high-efficiency broadband achromatic polarization conversion. To prove the ultrasensitive nature, a metadevice is constructed by incorporating a thin amorphous Ge layer with a weak photoconductivity perturbation. Transmission modulation over broadband frequency range from 0.6 to 1.1 THz is thus successfully realized, featuring its merits of modulation depth over 90% and On-Off-On switching cycle less than 10 ps.


Biphenotypic leukemia: immunologic and morphologic evidence for a common lymphoid-myeloid progenitor in humans.
A 5-year-old white girl had a white blood cell count of 80,000/cu mm and 82% lymphoblasts in the peripheral blood. Acute lymphocytic leukemia (ALL) was diagnosed, defined by typical morphology (FAB-L1), a positive reaction for terminal deoxynucleotidyl transferase (TdT) and characteristic surface antigens detected with lymphoid monoclonal antibodies. The patient's peripheral lymphoblast count fell rapidly with ALL therapy, but the WBC count began to rise unexpectedly on the sixth day of treatment, with 84% myeloblasts and monocytoid blasts. Malignant cells in the bone marrow showed FAB-M4 morphology and were no longer reactive with antibodies directed against TdT or common ALL antigen. However, the myeloblasts continued to react with some of the same monoclonal antibodies as the original leukemia cells, and in addition expressed new determinants detected by monoclonal antibody TA-1 and peanut agglutinin. The rapid dynamic evolution of the malignancy during the course of induction chemotherapy favors the existence of a stem cell capable of differentiation into both lymphoid and myeloid clones that are both independently and selectively sensitive to specific chemotherapeutic regimens.


Recurrent deep-vein thrombosis based on homozygous factor V Leiden mutation acquired after liver transplantation.
Several genetic liver diseases can be treated by liver transplantation (LT). However, some genetic defects also may be acquired by this procedure. We describe a patient who developed recurrent deep-vein thromboses after LT for hepatitis C virus-associated hepatocellular carcinoma on the basis of a homozygous Leiden mutation of the factor V gene in the donor liver. Liver donors with a history of venous thrombosis should be screened for the presence of activated protein C (APC) resistance. In addition, we recommend looking for APC resistance in liver recipients who develop venous thromboembolic disease in the post-LT course. Molecular analysis of donor tissue may be necessary to make a definite diagnosis of factor V Leiden mutation in these patients. As a consequence, intensified postoperative thromboprophylaxis or lifelong anticoagulant therapy may be necessary if this thrombophilic gene defect is detected.


Spatial variation in larval concentrations as a cause of spatial variation in settlement for the barnacle, Balanus glandula.
Settlement rates of the high intertidal barnacle, Balanus glandula, were monitored at three sites in the rocky intertidal zone in Central California simultaneously with measurements of larval concentrations in the adjacent water column. In both 1983 and 1984, settlement rates onto vacant substrate differed among the sites by nearly two orders of magnitude. For all sampling dates, this spatial variation in settlement mirrored the spatial distribution of Balanus glandula cyprid concentration in the water column. A perfect rank correlation was found between cyprid concentrations near a site and subsequent settlement. A noteworthy observation was that the sites switched rank in their settlement rates from 1983 to 1984. This change in settlement rankings matched a switch in rankings for cyprid concentrations.Settlement itself appears to be an important cause of the spatial pattern of cyprid concentrations. Comparing the rates of settlement to estimates of the number of cyprids available at a site suggests that settlement causes a large drain on the cyprid population as a water mass passes over successive sites. No consistent spatial patterns were found in the distribution of other major plankton groups (calanoid copepods) that are similar in size to Balanus cyprids but do not settle.The large differences in settlement rates among these sites were previously shown to be a leading cause of large differences in the structure of benthic barnacle populations. The close correspondence shown here between these large differences in settlement and differences in larval concentrations suggests that nearshore oceanic processes affecting larval arrival contribute to the control of benthic community structure.


Shear strength and filler particle characterization of Maryland (acid etch) bridge resin cements.
The shear strengths of Maryland (acid etch) bridge cements were investigated and ranged from 44 to 70 MPa. The bulk shear strength of the resin cements is sufficient; the weak link in the system (other than the technique sensitivity) is the interface at or adjacent to the resin and metal or the resin and enamel. The resin cements were polished and etched, and scanning electron micrographs were taken and digitized to illustrate the filler particle sizes and distribution.


Profile of patients with post-tuberculosis bronchiectasis in a tertiary care hospital in Brazil.
Bronchiectasis are abnormal permanently dilated bronchi which lead to chronic cough and other respiratory symptoms. Though tuberculosis (TB) is a common cause of bronchiectasis, data on this association are scarce. The objective of this study was to describe the profile of patients with post-TB bronchiectasis at a tertiary hospital in the southern region of Brazil. This was a retrospective study with data from patients in follow-up at our hospital from January 2005 to December 2020. We included patients 14 years of age or older who had bronchiectasis on chest computed tomography and a history of pulmonary TB. We excluded patients with bronchiectasis due to other causes or with confirmed non-tuberculous mycobacteria infection. We included 54 of the 204 non-cystic fibrosis bronchiectasis patients seen at our hospital during the study period. Most of the patients were female, older, and non-smokers. Less than a third had chronic bronchial infection by some agent. More than two thirds had some type of ventilatory defect, the most common being obstruction. More than half had upper-lobe impairment. Severity of the disease seemed to be equally distributed from mild to severe. Treatment was varied, including bronchodilators, inhaled corticosteroids, and azithromycin. We found that the profile of patients in our hospital is similar to that described in other studies, with slight differences in regard to microbiology and treatment.


Pneumatized Articular Eminence and Assessment of Its Prevalence and Features on Panoramic Radiographs.
Pneumatized articular eminence or tubercle (PAT) is an air cell cavity in the zygomatic process of the temporal bone. Pneumatization of articular eminence may be seen incidentally on panoramic radiographs (PRs) as a unilocular or multilocular radiolucent defect. The aim of this study was to assess the prevalence and the pattern of PAT on PR in an Iranian population. A total of 3,098 PRs belonging to 1,735 females and 1,363 males were retrospectively investigated for the presence and radiographic features of PAT. All PRs were taken for routine dental examination. Chi-square test, univariate odds ratio (OR) and corresponding 95% confidence interval (95% CI) and binary logistic regression were used for statistical analysis. Overall, PAT was found in 2.1 % of cases including 41 females and 23 males (with a mean age of 33.23±12.43 and 35.64±13.24 years, respectively, range 19-69 years). There were 40 unilateral and 24 bilateral cases (total: 88 PATs) including 49 unilocular and 39 multilocular cases. There was no significant difference in PAT between males and females or different age groups (P>0.05 and all CIs included 1.00). Binary logistic regression indicated that there was no relationship between the presence of PAT and age or sex. Knowledge about this anatomical variation is helpful for clinicians who are planning to perform temporomandibular joint surgery. They should assess the radiographic imaging thoroughly before the surgery. It can also provide valuable information to understand the differential diagnosis of pathological entities in this region.


Enhanced production of high-quality biomass, delta-aminolevulinic acid, bilipigments, and antioxidant capacity of a food alga Nostochopsis lobatus.
The growing interest in natural food has raised the global demand for nutraceuticals. We studied enhanced production of biomass, delta-aminolevulinic acid (delta-ALA), bili pigments and antioxidant capacity of a food alga Nostochopsis lobatus in a full-factorial (three level) design with supplemental Zn, glutamine, and Zn + glutamine in batch culture. Production of biomass, pigments, and antioxidant capacity all were higher under immobilized cell cultures in comparison to free cell cultures. Maximum biomass (2,390 mg dry wt l(-1)), delta-ALA (2.715 microg mg(-1) dry wt h(-1)), phycocyanin (98.50 mg g(-1) dry wt), phycoerythrin (158.0 mg g(-1) dry wt), and antioxidant capacity (140.50 mumoles ascorbic acid equivalent capacity g(-1) fresh wt) were recorded when Zn and glutamine were supplemented together in the growth medium at pH 7.8. These effects were found to be significantly related to the activities of glutamine synthetase (GS(max): 490.2 nmoles mg protein(-1) min(-1)), glutamate synthase (GOGAT(max): 27.0 nmoles mg protein(-1) min(-1)), and glutamate dehydrogenase (GDH(max): 159.9 nmoles mg protein(-1) min(-1)). This study shows that N. lobatus could be a promising bioresource for the production of nutritionally rich biomass, delta-ALA, bili pigments, and antioxidants. Use of immobilized cells in batch culture supplemented with Zn and glutamine could be an effective approach for scaling up production for commercial use.


Three strategies when physicians provide complex information in interactions with patients: How to recognize and measure them.
To define and operationalize three taught strategies for providing information in interactions with patients using videos collected in a randomized controlled trial (RCT). This was a qualitative exploratory study embedded in a randomized controlled design, using microanalysis of face-to-face dialogue as an inductive video analysis method to operationalize physicians' use of three information-provision strategies. Data were 34 video-recorded simulated (but unscripted) interactions between 17 physicians and 34 multiple sclerosis patients collected before and after a brief course on information provision. We operationalized (1) mapping the patient's preferences and (2) checking the patient's understanding, and pauses indicative of (3) portioning information. Results are detailed analytical definitions, criteria, and assessable, quantifiable outcomes for each of the three strategies. Patients responded to portioning pauses as expected: whereas 91% of these pauses elicited an immediate patient response, only 23% of non-portioning pauses did so. Our methods revealed how to define and evaluate information sharing strategies physicians used within the contingencies of clinical interaction. Findings provide applicable methods to teach, analyze, and evaluate information sharing strategies and indications for further training.


A systematic review of the quality of randomized controlled trials in head and neck oncology surgery.
To determine the quality of randomized controlled trials (RCTs) in head and neck surgery in which surgery was a primary intervention. Potential articles were identified in PubMed without publication date restrictions. Articles were scored using the CONSORT checklist and the relationship between the checklist score and whether the first and/or last authors were surgeons was investigated. Differences in the checklist score based on how many surgeons were among the first and last authors of the study were analyzed using the Kruskal-Wallis test. Fisher's exact test was used to examine if there was a significant difference of the reporting of individual items from the checklist between surgeons and nonsurgeons. A nonparametric trend test was used to determine whether there was a difference in the reporting of individual items based on whether there were none, one, or two surgeons among first and last authors. A total of 38 publications satisfied the inclusion criteria. There was a trend toward lower quality for studies in which surgeons were either first, last, or both first and last authors compared to studies that were first-authored and last-authored by nonsurgeons (P = 0.068). Nonsurgeons were more likely to report on critical elements regarding hypothesis, sample size determination, randomization, and eligibility of centers (P = 0.023-0.058). The quality of RCTs in head and neck surgery is poor. Improved training in conducting and reporting clinical research is needed in otolaryngology residencies.


Gastrointestinal hormones as potential adjuvant treatment of exocrine pancreatic adenocarcinoma.
Gastrointestinal hormones and their antagonists can alter the growth of pancreatic adenocarcinoma in vitro and in vivo. The potential clinical benefit of this approach deserves further study. Epithelial cell growth is normally under hormonal control. Hormones also affect the growth of many epithelial cancers, and this fact is used to modify tumor growth. Pancreatic epithelial cell growth is under the influence of gastrointestinal hormones. This article reviews experiments designed to determine the effect of gastrointestinal hormones on the growth of pancreatic adenocarcinoma. Eighty-eight articles were identified from a Medline search using the terms pancreatic adenocarcinoma and the individual names of gastrointestinal hormones. The experimental design and results of these studies are reviewed. In general, somatostatin, vasoactive intestinal polypeptide, pancreatic polypeptide, and pancreastatin inhibit pancreatic adenocarcinoma growth. Cholecystokinin, secretin, bombesin, gastrin, EGF, TGF-alpha, insulin, and IGF-1 have a growth-promoting effect.


The effect of combined application of Streptomyces rubrogriseus HDZ-9-47 with soil biofumigation on soil microbial and nematode communities.
Meloidogyne incognita causes significant damage to many different crops. Previous studies showed that Streptomyces rubrogriseus HDZ-9-47 is a promising biocontrol agent. Combining it with biofumigation improved its efficacy against M. incognita. In the present study, the reason for the improved efficacy of the combination was investigated by analyzing its impact on both the soil microbial and the nematode communities in the field. The results showed that the combined application reduced root galls by 41% and its control efficacy was greater than each treatment alone. Cultivation-based analyses showed that the combination treatment affected the soil microbial community. Actinomycetes and bacterial densities were negatively correlated with the root knot score. In contrast, the fungal densities were positively correlated with the root knot score. Denaturing gradient gel electrophoresis (DGGE) results showed that the combination of S. rubrogriseus HDZ-9-47 and biofumigation enriched beneficial microbes and reduced certain soil-borne fungal phytopathogens, thereby enhancing the efficacies of both S. rubrogriseus HDZ-9-47 and biofumigation against M. incognita. And HDZ-9-47 could colonize in soil. The total abundance of nematode and plant parasites, the ratio of soil fungivore nematode to fungivore plus bacterivore nematode, and the nematode diversity indices all decreased with the combination treatment. Overall, the results of this study demonstrate that combined application of HDZ-9-47 with biofumigation was a useful and effective approach to suppress M. incognita by manipulating soil microbial communities in field.


Fibrosis-4 Index Predicts Long-Term All-Cause, Cardiovascular and Liver-Related Mortality in the Adult Korean Population.
Associations between hepatic fibrosis and mortality remain to be fully elucidated in large population-based studies. This study aimed to evaluate the associations of the fibrosis-4 index (FIB-4) with all-cause, cardiovascular, cancer, and liver-related mortality in the adult Korean population without viral hepatitis. Baseline data were retrieved from the Korea National Health and Nutrition Examination Survey, and mortality data were retrieved from the Korean Cause of Death data registry. Adults (age, ≥19 y) without viral hepatitis B or C, liver cirrhosis, any cancer, stroke, myocardial infarction, angina pectoris, or renal failure at baseline were eligible. Presumed hepatic fibrosis was evaluated with FIB-4. Hazard ratios (HRs) and 95% CIs were calculated using multivariable Cox regression analysis, and Kaplan-Meier estimates of the cumulative mortality were evaluated. There were 46,456 individuals with a median follow-up period of 8.6 years (interquartile range, 6.3-10.6 y). Kaplan-Meier curves for cumulative mortality showed that participants with a FIB-4 of ≥2.67 (vs FIB-4, <2.67) had higher cumulative all-cause, cardiovascular, cancer, and liver-related mortality. In the fully adjusted model, Cox regression analysis revealed that presumed advanced hepatic fibrosis (FIB-4, ≥2.67) remained associated with all-cause mortality (HR, 1.64; 95% CI, 1.23-2.18), cardiovascular mortality (HR, 2.96; 95% CI, 1.60-5.46), and liver-related mortality (HR, 10.50; 95% CI, 4.70-23.44), but not cancer mortality, after adjusting for confounders including central obesity and insulin resistance. Excluding participants with an estimated alcohol intake of 30 grams or more for men and 20 grams or more for women did not affect the results. At the population level, liver fibrosis estimated by FIB-4 was associated with increased cumulative all-cause, cardiovascular, and liver-related mortality.


Carcinoid tumor of the renal pelvis: report of a case with positive urine cytology.
A case of histologically and ultrastructurally confirmed carcinoid tumor of the renal pelvis is reported. The patient's urine sediment showed a few groups and sheets of polygonal malignant cells with scant cytoplasm and oval nuclei displaying chromatin clumping and micronucleoli.


Optimization of maghemite-loaded PLGA nanospheres for biomedical applications.
Magnetic nanoparticles have been proposed as interesting tools for biomedical purposes. One of their promising utilization is the MRI in which magnetic substances like maghemite are used in a nanometric size and encapsulated within locally biodegradable nanoparticles. In this work, maghemite has been obtained by a modified sol-gel method and encapsulated in polymer-based nanospheres. The nanospheres have been prepared by single emulsion evaporation method. The different parameters influencing the size, polydispersity index and zeta potential surface of nanospheres were investigated. The size of nanospheres was found to increase as the concentration of PLGA increases, but lower sizes were obtained for 3 min of sonication time and surfactant concentration of 1%. Zeta potential response of magnetic nanospheres towards pH variation was similar to that of maghemite-free nanospheres confirming the encapsulation of maghemite within PLGA nanospheres. The maghemite entrapment efficiency and maghemite content for nanospheres are 12% and 0.59% w/w respectively.


Early TB case detection by community-based mobile X-ray screening and Xpert testing in Balochistan.
This survey was conducted at 35 sites of 20 cities in 15 districts with low programmatic TB case notifications in the past years in Balochistan. To assess the effectiveness of the systemic community-based screening and diagnosis for early detection of TB; and 2) to describe the characteristics and understand the strengths and weaknesses of the intervention in Balochistan, and sociodemographic factors associated with it. This cross-sectional descriptive study was conducted using a mobile van equipped with a digital X-ray machine with computer-aided detection for TB (CAD4TB) software for screening, followed by confirmatory high sensitivity Xpert® MTB/RIF assay testing. A total of 236 (3.4%) TB cases was detected out of 6,899 screened. About 1,168 (17%) presumptive TB cases were identified and 1,065 (91%) sputum samples were tested on Xpert. Among those diagnosed, 166 (70%) were Mycobacterium tuberculosis-positive and 70 (30%) were with clinical suspicion. Of the sputum samples tested, 87% (923/1065) had a probability score of >70 on CAD4TB. Community-based screening with innovative activities, comprising sensitive screening and diagnostic tools, effectively improves TB case detection, which might suffice to reduce the prevalence of TB and break the chain of infection transmission in the at-risk population.


Better sleep quality in chronic haemodialyzed patients is associated with morning-shift dialysis: a cross-sectional observational study.
The aim of the study was to investigate the association between dialysis shift and subjective sleep quality in chronic haemodialyzed patients. A cross-sectional observational study. A total of 206 haemodialyzed patients aged from 22 to 71 participated in this study. Participants were grouped into the morning-shift and other-shifts groups. Subjective sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). All participants also completed the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Dialysis shift significantly predicted the PSQI score with patients receiving morning-shift haemodialysis having better sleep quality (β=0.15, p=0.01). Other independent predictors of the PSQI score included depression (β=0.42, p<0.001), anxiety (β=0.38, p<0.001), and tea drinking (β=0.20, p0.001). Together these factors explained 48.2% of the variance in the PSQI score. Morning dialysis shift was significantly associated with better subjective sleep quality in chronic haemodialyzed patients after adjusting for other confounders.


A simple microcomputer-controlled device for automated measurement of refractory period of excitable tissue.
A computer-controlled tissue stimulator interface will be described. This device can generate a basic train at a predetermined rate. An extra pulse is introduced after a selected number of pulses. The initial latency of this extra pulse is shorter than the tissue refractory period. The latency is increased, automatically, until the tissue produces a conducted response. This is made possible by the computer checking the tissue response. The device is inexpensive and can be readily controlled by any 8 bit microcomputer, such as the Commodore PET or VIC-20. The use of a signal conditioner has been discussed. Such a circuit facilitates detection of the often slowly occurring action potential of the premature beat riding on the repolarization phase of the normal action potential.


Figural factors and the development of pictorial inferences.
The role of figural characteristics in the development of pictorial inferences was examined. Two versions of 10 three-picture story sequences were presented to kindergarten and third-grade children. One version maximized while the other minimized figural similarity among pictures. After viewing the sequences, the children were asked to discriminate old study pictures and inferentially consistent new pictures from distractors. While the kindergarteners identified significantly fewer inference pictures than the third graders in all conditions, there was less difference between the grades in the figurally similar conditions. Overall, the kindergarteners identified the fewest inference pictures in the presence of distractors that figurally matched the study pictures. These results indicate that although the pictorial inferences drawn by kindergarteners are heavily influenced by figural representations, such figural dependency cannot account for all of the observed developmental differences.


Neurocognitive measures predict voluntary stepping performance in older adults post-hip fracture.
Hip fracture is a debilitating injury, especially in older adults. The purpose of this study was to determine the relationships between Trail-Making test performance and parameters of the choice stepping reaction time test in community-dwelling older adults after hip fracture. Twenty-four older adults post-hip fracture repair participated in an ancillary study for physical therapy interventions. Measures included Trail-Making test (Parts A & B) scores, movement time (time from foot liftoff to touchdown), step speed, reaction time (time from cue to foot liftoff), and total response time (time from step cue to touchdown) in the forward and lateral directions. Paired t-tests and multiple linear regressions were used for analysis. Significant differences were found in movement time, speed and reaction time between limbs in the lateral direction, and in movement and reaction time in the forward direction. Trails A predicted step speed, reaction time and total response time for the fractured limb in the lateral direction, as well as reaction time and total response time in the forward direction. However, Trails A could not predict performance for the non-fractured limb. Trails B predicted stepping performance for both limbs in the forward and lateral directions. Trails A correlated with the fractured limb's ability to perform the choice stepping test, but not in the non-fractured limb. Meanwhile, Trails B correlated with stepping performance in both limbs, suggesting those with poorer executive function have a lower protective stepping capability and may be at a higher risk for future falls and injury.


An examination of the relation between conduct disorder, childhood and adulthood traumatic events, and posttraumatic stress disorder in a nationally representative sample.
Clinical data has indicated that exposure to trauma and meeting diagnostic criteria for posttraumatic stress disorder (PTSD) are common among individuals with a history of conduct disorder. However, these relationships have not been adequately examined in a population-based sample. Data were drawn from Wave 2 of the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) collected in 2004-2005 (n = 34,653, response rate = 86.7%). Multivariate logistic regression analyses were conducted to examine relations between conduct disorder, traumatic life events, and PTSD in the full sample, and separately for males and females. The main findings indicate that childhood maltreatment was associated with conduct disorder (Adjusted Odds Ratio [AOR] ranging from 2.4 to 4.7) after adjustment for sociodemographic variables. Additionally, respondents with a history of conduct disorder compared to respondents without conduct disorder were more likely to report experiencing any traumatic event (AOR = 2.7, 95% CI = 2.0-3.6) and PTSD (AOR = 2.2, 95% CI = 1.8-2.7) after adjusting for sociodemographic variables. Although sex differences were noted, conduct disorder was associated with the greatest odds of assaultive violence for males and females. The majority of individuals (72.9%) diagnosed with both conduct disorder and PTSD developed conduct disorder symptoms before PTSD symptoms. Results of this study provide the first known sex-stratified examination of the relationship between conduct disorder, traumatic events, and PTSD in a large, population-based sample of adults and are consistent with clinical impressions. Policy and clinical implications are discussed.


Aquaporin-3 expression in human fetal airway epithelial progenitor cells.
Airway epithelium stem cells have not yet been prospectively identified, but it is generally assumed that both secretory and basal cells have the capacity to divide and differentiate. Previously, we developed a test for progenitor cells of the human airway epithelium, relying on the transplantation of fetal respiratory tissues into immunodeficient mice. In this study, we hypothesized that airway-repopulating epithelial progenitors can be marked with surface antigens, and we screened an array of such candidate markers, including lectin ligands, the CD44 and CD166 adhesion molecules, and the aquaporin-3 (AQP3) water channel. We observed that AQP3 is selectively expressed on the surface of basal cells, allowing the separation by flow cytometry of AQP3+ basal cells and AQP3- ciliated and secretory cells. Functional evaluation of sorted cells in vivo showed that AQP3+ cells can restore a normal pseudostratified, mucociliary epithelium as well as submucosal glands. AQP3- cells are also endowed with a similar potential, although faster engraftment suggests their inclusion of more committed progenitors. These results show that stem cell candidates in the human tracheo-bronchial mucosa can be positively selected with a novel marker but also, for the first time, that epithelial progenitors exist among both basal and suprabasal cell subsets within the human airway.


Dynamics of expression of antibacterial and antioxidant defence genes in Indian major carp, Labeo rohita in response to Aeromonas hydrophila infection.
Cells produce large number of antioxidant molecules to prevent reactive oxygen species-induced self-damage during microbial assault while generating simultaneously number of antimicrobial molecules to target the pathogen. The present study was aimed at looking into molecules involved in antibacterial and self-protection mechanism of a host Labeo rohita when challenged with a pathogenic bacterium Aeromonas hydrophila. Expression profiles of few of the important host antibacterial genes viz., inducible nitric oxide synthase (iNOS), lysozyme G (LysoG), apolipoprotein A-I (ApoA-I) and hepcidin, and self-defence anti-oxidant genes viz., manganese superoxide dismutase (MnSOD), catalase and glutathione peroxidases (GPx3) were examined in skin and muscle tissues of bacteria challenged fish. Transcription levels of iNOS, LysoG, ApoA-I, hepcidin, catalase, GPx3 and MnSOD were significantly upregulated (P < 0.05) in both tissues at different time points post-bacterial challenge. Increased expression of antibacterial genes in the muscle and skin clearly explains strong defensive mechanism activated in fish tissues in terms of both oxygen-dependent (iNOS) and independent (lysozyme) ways of microbe reduction, and bacterial lysis via production of antimicrobial molecules (ApoA-I and hepcidin) in the host. Simultaneous upregulation of MnSOD, GPx3 and catalase genes explains their involvement in patrolling the cells with regulated production of reactive oxygen species and keeping at a safe level to protect the host's own cells from oxidative damage.


Two-birds with one stone: Improving both cathode and anode electrochemical performances via two-dimensional Te-CoTe2/rGO ultrathin nanosheets as sulfur hosts in lithium-sulfur batteries.
A Te-doped CoTe2 film could be grown in situ on reduced graphene oxide (rGO) to develop a Te-CoTe2/rGO composite with an ultrathin layered structure, which has multiple protective effects on both the sulfur positive electrode and lithium negative electrode in lithium sulfur (Li-S) batteries. The Te-CoTe2/rGO composite as a sulfur host not only shows a strong adsorbing ability for lithium polysulfides (LiPSs) but can also accelerate the conversion reaction of active material sulfur during the charging/discharging process. More importantly, this host can turn the shuttle effect from an unfavorable factor to a favorable factor, which could improve the electrochemical performance of the lithium anode with uniform lithium plating/stripping resulting from the intermediate polytellurosulfide species (Li2TexSy), which could be generated on the cathode surface via Te reacting with soluble Li2Sn (4 ≤ n ≤ 8). As a result, the S@Te-CoTe2/rGO cathode shows a discharge capacity of 970.0 mA h g-1 in the first cycle at 1 C and retains a high capacity of 545.5 mA h g-1 after 1000 cycles, corresponding to a low capacity decay rate of only 0.043% per cycle. In addition, in situ X-ray diffraction (XRD) and in situ Raman were used to explore the sulfur conversion process. This study not only demonstrates that a two-dimensional (2D) ultrathin Te-CoTe2/rGO composite is successfully developed with multiple effects on Li-S batteries but also opens a new pathway for designing unique sulfur hosts to promote the electrochemical performance of Li-S batteries.


Combat related vascular injuries: Dutch experiences from a role 2 MTF in Afghanistan.
In a combat environment, major vascular trauma endures as the leading cause of death. The Dutch role 2 Medical Treatment Facility (MTF), provided supportive care during the mission in Uruzgan, Afghanistan. Aim of this study was to conduct detailed analysis of the admitted major haemorrhages (vascular injuries) and to compare our findings with NATO coalition partners. Retrospective, descriptive study. Participants eligible for this study came from the role 2 MTF admission database, where they fitted the criteria 'Major haemorrhage (class 2 haemorrhage or more according to the ATLS(®) classification) between 2006 and 2010'. Results were contrasted with studies from coalition partners. The query revealed 194 casualties sustaining 208 central (60% abdominal, 40% thoracic/neck), and 99 extremity major haemorrhages leading to 1.6 major haemorrhages per casualty. Survival was significantly better (p<0.05) in the peripheral vascular injuries cohort (96% versus 72%). Primary amputation was needed in 73/84 of lower, and in 8/15 of upper extremity major haemorrhages. Vascular repair or vascular Damage Control Surgery techniques (e.g. shunting) were used in 19/84 cases in the lower, and 7/15 in the upper extremity cohort, with a success rate of 69.2 percent. Amputation rates of coalition partners, using different inclusion and exclusion criteria, ranged from 5 to 60 percent. Only in a few cases genuine peripheral vascular surgery was needed (<1%). This limited number of reconstructions does not demonstrate the need for extensive skills in all areas of vascular surgery. Achieved success rate until discharge was almost 70%. Vascular damage control surgery seems effective as initial limb saving skill in a role 2 MTF. The difference in usage of definitions concerning vascular injuries in current literature warrants further assessment. For optimal analysis there is need for detailed (NATO wide) registration with uniform definitions for vascular injuries. Level IV--Epidemiologic study.


Influence of concomitant methotrexate use on the clinical effectiveness, retention, and safety of abatacept in biologic-naïve patients with rheumatoid arthritis: Post-hoc subgroup analysis of the ORIGAMI study.
We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.


Reversibility of Diffusion-Weighted Imaging Lesions in Patients With Ischemic Stroke in the WAKE-UP Trial.
Reversibility of the diffusion-weighted imaging (DWI) lesion means that not all of the DWI lesion represents permanently injured tissue. We investigated DWI reversibility and the association with thrombolysis, reperfusion and functional outcome in patients from the WAKE-UP trial (Efficacy and Safety of Magnetic Resonance Imaging-Based Thrombolysis in Wake-Up Stroke). In this retrospective analysis of WAKE-UP, a randomized controlled trial (RCT) between September 2012 and June 2017 in Belgium, Denmark, France, Germany, Spain and United Kingdom, a convolutional neural network segmented the DWI lesions (b=1000 s/mm2) at baseline and follow-up (24 hours). We calculated absolute and relative DWI reversibility in 2 ways: first, a volumetric (baseline volume-24-hour volume >0) and second, a voxel-based (part of baseline lesion not overlapping with 24-hour lesion) approach. We additionally defined relative voxel-based DWI-reversibility >50% to account for coregistration inaccuracies. We calculated the odds ratio for reversibility according to treatment arm. We analyzed the association of reversibility with excellent functional outcome (modified Rankin Scale score of 0-1), in a multivariable model. In 363 patients, the median DWI volume was 3 (1-10) mL at baseline and 6 (2-20) mL at follow-up. Volumetric DWI reversibility was present in 19% (69/363) with a median absolute reversible volume of 1 mL (0-2) or 28% (14-50) relatively. Voxel-based DWI reversibility was present in 358/363 (99%) with a median absolute volume of 1 mL (0-2), or 22% (9-38) relatively. In 18% of the patients (67/363), relative voxel-based DWI reversibility >50% was present. Volumetric DWI reversibility and relative voxel-based DWI reversibility >50% was more frequent in patients treated with alteplase versus placebo (OR, 1.86 [95% CI, 1.09-3.17] and OR, 2.03 [95% CI, 1.18-3.50], respectively). Relative voxel-based DWI reversibility >50% was associated with excellent functional outcome (OR, 2.30 [95% CI, 1.17-4.51]). Small absolute volumes of DWI reversibility were present in a large proportion of randomized patients in the WAKE-UP trial. Reversibility was more often present after thrombolysis.


Rapid quantitative analysis of carnitine and acylcarnitines by ultra-high performance-hydrophilic interaction liquid chromatography-tandem mass spectrometry.
l-Carnitine and its acyl esters (acylcarnitines) play an important role in the metabolism of fatty acids. However, most of the present methods for the quantitative analysis of acylcarnitines have restrictions both in sample preparation and in chromatographic separation. Herein we present a validated method for determination of carnitine and eleven acylcarnitines in human serum and rat tissue biopsies by using ultra-high performance-hydrophilic interaction liquid chromatography-tandem mass spectrometry (UHP-HILIC-MS/MS). The procedure uses minimal sample preparation including only addition of organic solvent, labeled internal standard, incubation and centrifugation. The separation is performed without derivatization or addition of ion-pairing reagent within 7min on a hydrophilic interaction liquid chromatographic column with mass spectrometric detection. The method is linear in response over the concentration range from 20 to 600ng/ml for carnitine and acetylcarnitine and 5-200ng/ml for the other acylcarnitines, with correlation coefficients higher than 0.994. Recoveries were higher than 88% for most of the compounds. Limits of detection were 5ng/ml for carnitine and acetylcarnitine and approximately 0.5ng/ml for other acylcarnitines. The method was applied to the analysis of serum and tissue samples.


Phenotype plasticity rather than repopulation from CD90/CK14+ cancer stem cells leads to cisplatin resistance of urothelial carcinoma cell lines.
Tumour heterogeneity and resistance to systemic treatment in urothelial carcinoma (UC) may arise from cancer stem cells (CSC). A recent model describes cellular differentiation states within UC based on corresponding expression of surface markers (CD) and cytokeratins (CK) with CD90 and CK14 positive cells representing the least differentiated and most tumourigenic population. Based on the fact that this population is postulated to constitute CSCs and the origin of cisplatin resistance, we enriched urothelial carcinoma cell lines (UCCs) for CD90 and studied the tumour-initiating potential of these separated cells in vitro. Magnetic- and fluorescence-activated- cell sorting were used for separation of CD90(+) and CD90(-) UCCs. Distribution of cell surface markers CD90, CD44, and CD49f and cytokeratins CK14, CK5, and CK20 as well as the effects of short- and long-term treatment with cisplatin were assessed in vitro and measured by qRT-PCR, immunocytochemistry, reporter assay and flow cytometry in 11 UCCs. We observed cell populations with surface markers according to those reported in tumour xenografts. However, expression of cytokeratins did not concord regularly with that of the surface markers. In particular, expression of CD90 and CK14 diverged during enrichment of CD90(+) cells by immunomagnetic sorting or following cisplatin treatment. Enriched CD90(+) cells did not exhibit CSC-like characteristics like enhanced clonogenicity and cisplatin resistance. Moreover, selection of cisplatin-resistant sublines by long-term drug treatment did not result in enrichment of CD90(+) cells. Rather, these sublines displayed significant phenotypic plasticity expressing EMT markers, an altered pattern of CKs, and WNT-pathway target genes. Our findings indicate that the correspondence between CD surface markers and cytokeratins reported in xenografts is not maintained in commonly used UCCs and that CD90 may not be a stable marker of CSC in UC. Moreover, UCCs cells are capable of substantial phenotypic plasticity that may significantly contribute to the emergence of cisplatin resistance.


Analysis of Risk Factors Related to Acute Subarachnoid Hemorrhage After Spinal Surgery.
Subarachnoid hemorrhage (SAH) is a rare complication secondary to cerebrospinal fluid (CSF) leakage during spinal surgery, but the specific cause of bleeding is still unclear. In this retrospective single-center study, we studied cases of acute SAH after spinal surgery to identify the related risk factors for bleeding. A total of 441 patients with CSF leakage who underwent spinal surgery from 2011 to 2020 were retrospectively analyzed. According to whether postoperative SAH occurred, the patients were divided into the SAH group and the control group. By comparing the demographic data, past history, imaging data, intraoperative findings, perioperative complications, and treatment conditions in the 2 groups to identify the risk factors for SAH, we aimed to provide guidance for the prevention of SAH after spinal surgery. In our study, the incidence of CSF during spinal surgery is 3.04%, and the rate for SAH associated with spine operation is 0.16%. In the SAH group, 17 patients (73.9%) had preoperative hypertension, and 3 patients (13.0%) had diabetes. The intraoperative CSF leakage was approximately 118.4 ± 56.9 mL. The mean postoperative drainage was 15.4 ± 5.8 mL/hour. Compared with the SAH group, the control group had 123 patients (29.4%) with hypertension before the operation and 40 patients (9.6%) with diabetes. The intraoperative CSF leakage was approximately 76.3 ± 23.0 mL, and the mean postoperative continuous drainage was 9.7 ± 2.1 mL/hour. Binary logistic regression analysis showed that hypertension, intraoperative CSF leakage, and postoperative CSF continuous drainage speed were related to SAH. The rapid leakage of CSF caused by rupture of the dural sac during surgery and the rapid drainage of CSF after surgery were closely related to the occurrence of SAH. In addition, hypertension was a factor related to SAH during spinal surgery.


Extraction of nickel from edible oils with a complexing agent prior to determination by FAAS.
In the present work, a new extraction method for separation of nickel from edible oils and determination by FAAS is reported. This method is based on extraction of Ni(II) ions from the oil to aqueous phase with N,N'-bis(4-methoxysalicylidene) ethylenediamine (MSE) and determination by FAAS. Properties of the complex formed between MSE and Ni(II) were investigated spectrophotometrically. Central composite design (CCD) was utilized for optimization of MSE to oil, stirring time and temperature, which were 0.97 mL g(-1), 15.4 min, and 29.7°C, respectively. The developed method was tested with an oil-based metal standard and the recovery was 93.8±3.9%. The proposed method was applied with five different edible oils.


Facilitating learning of community-based rehabilitation through problem-based learning in higher education.
The quality of community-based rehabilitation (CBR) personnel is one of the key factors that contributes to the success of CBR programs. Integrating knowledge and practical skills in various stages of the learning process is essential in community-based rehabilitation. Problem-based learning (PBL) is a pedagogical strategy that uses real-world situations as the basis for developing knowledge and problem-solving skills. Through PBL, learners are guided and facilitated in assuming active problem-solving roles in real-world situations. This study developed and tested a framework and a PBL protocol for use in teaching community-based rehabilitation (CBR) in higher education. Part I of this study focused on the development of a framework and a protocol for PBL. An initial framework for the development of this protocol was formed based on a review of relevant literature. Concrete guidelines were delineated to describe the application, process, and delivery of teaching and learning. PBL was implemented in three CBR related courses. Students were facilitated to learn CBR in passing various stages of PBL through a self-directed learning process. The cumulative efforts of each group were compiled, recorded, and displayed using e-portfolios. In Part II, the processes and outcomes of using this new learning mode were evaluated using a case study approach to examine the protocol's efficacy. Focus group interviews, a questionnaire, and a detailed examination of the e-portfolios were administered for evaluation. One hundred thirty-three students from three CBR related courses were recruited. PBL was regarded as an effective, realistic and practical method that enables critical thinking in CBR. Practicality was addressed by covering context-related materials with the use of real cases or examples. Participants were actively engaged in the learning process and their CBR competence was enhanced. Through the new protocol, the students were equipped with active learning, critical thinking, and problem-solving skills that should facilitate success in CBR.


Phage-choline Kinase Inhibitor Combination to Control Pseudomonas aeruginosa: A Promising Combo.
Pseudomonas aeruginosa is one of the most prevalent opportunistic pathogens in humans that has thrived and proved to be difficult to control in this "post-antibiotic era." Antibiotic alternatives are necessary for fighting against this resilient bacterium. Even though phages might not be "the wonder drug" that solves everything, they still provide a viable option to combat P. aeruginosa and curb the threat it imposes. The combination of antibiotics with phages, however, poses a propitious treatment option for P. aeruginosa. Choline kinase (ChoK) is the enzyme that synthesizes phosphorylcholine subsequently incorporated into lipopolysaccharide located at the outer membrane of gram-negative bacteria. Recently, inhibition of ChoKs has been proposed as a promising antibacterial strategy. Successful docking of Hemicholinium-3, a choline kinase inhibitor, to the model structure of P. aeruginosa ChoK also supports the use of this inhibitor or its derivatives to inhibit the growth of this microorganism. Therefore, the combination of the novel antimicrobial "choline kinase inhibitors (ChoKIs)" with a phage cocktail or synthetic phages as a potential treatment for P. aeruginosa infection has been proposed.


A cleavage map of the TOL plasmid of Pseudomonas putida mt-2.
A cleavage map of the TOL plasmid pWWO has been determined for the restriction endonucleases HindIII and XhoI. A number of techniques were employed including (i) digestion of purified cleavage products with a second enzyme; (ii) hybridisation of purified XhoI fragments to Southern blots of HindIII digest products and (iii) analysis of a number of deletion mutants.


Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia: a case report in acquired von Willebrand syndrome and review of the literature.
Acquired von Willebrand syndrome is a rare bleeding disorder and treatment of the associated gastrointestinal (GI) bleeding due to angiodysplasia is challenging. The aim of this study was to present a new case on the successful use of thalidomide in a patient with acquired von Willebrand syndrome and recurrent angiodysplasia-related GI bleedings, and to conduct a literature review on the use of thalidomide in patients with GI angiodysplasia. A literature review was conducted, searching the electronic databases PubMed, Embase and Cochrane. We present a 75-year-old woman with IgG MGUS-associated acquired von Willebrand syndrome (AVWS) who suffered from recurrent gastrointestinal (GI) bleedings and epistaxis. Treatment with immunoglobulins, desmopressin, Haemate-P and blood transfusions failed to achieve long-term haemostasis. Eventually, after these bleedings relapsed for almost a decade at 1- to 3-month intervals, thalidomide was prescribed. Since then, only one single nose bleed and one single melaena episode had occurred. She currently remains in remission of GI bleeds after 3 years and 3 months follow-up. The literature review revealed a beneficial effect of thalidomide in reducing GI bleeding due to angiodysplasia, including four case reports on inherited von Willebrand disease. In conclusion, thalidomide can be a reasonable option for the treatment of recurrent GI bleeding due to angiodysplasia in AVWS and we report for the first time that refractory or relapsing GI bleeding in patients with AVWS can successfully be controlled with thalidomide.


Covert video surveillance in Munchausen syndrome by proxy. Ethical compromise or essential technique?
It has been suggested that the use of covert video surveillance in suspected cases of Munchausen syndrome by proxy should be curtailed as it represents a breach of trust between health care workers, parents and children. We present a case of asphyxia induced by a mother, which was discovered by videotaping without consent. Two previous sudden infant deaths in the family over the preceding two years, with unexplained apnoeic episodes in the third child, were considered sufficiently suspicious to justify covert surveillance. Incontrovertible evidence of parentally induced asphyxia was obtained within 24 hours of full-time covert surveillance. Despite initial denial, the mother eventually pleaded guilty to manslaughter of the first infant and to causing grievous bodily harm to the third infant. We believe that alternative techniques, such as parent-child separation, or of videotaping only after informed consent has been obtained, could have compromised the investigation and produced unacceptable delays which would have placed the surviving infant at risk of serious morbidity or of death.


Associations of Variation in Retinal Thickness With Visual Acuity and Anatomic Outcomes in Eyes With Neovascular Age-Related Macular Degeneration Lesions Treated With Anti-Vascular Endothelial Growth Factor Agents.
When initiating anti-vascular endothelial growth factor (VEGF) treatment for patients with neovascular age-related macular degeneration (nAMD), knowledge of prognostic factors is important for advising patients and guiding treatment. We hypothesized that eyes with greater fluctuation in retinal thickness over time have worse outcomes than eyes with less variation. To investigate whether visual and anatomic outcomes in eyes with nAMD initiating anti-VEGF treatment are associated with fluctuations in retinal thickness. In this study using data from the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and the Inhibition of VEGF in Age-Related Choroidal Neovascularization (IVAN) randomized clinical trial, people with previously untreated nAMD were included. Data were collected from February 2008 to November 2012, and data were analyzed from April 2017 to April 2020. Foveal center point thicknesses (FCPTs) were extracted from 1165 study eyes from CATT and 566 study eyes from the IVAN trial, excluding those with 3 measurements or less. For each eye, the SD of FCPT was calculated. Eyes were grouped by FCPT SD quartile. Associations of FCPT SD quartile with outcomes were quantified at month 24 or the last available visit by linear or logistic regression, adjusting for baseline best-corrected visual acuity (BCVA) and randomized allocations to drug and treatment regimen, for BCVA, development of fibrosis, and development of macular atrophy. Of the 1731 included patients, 1058 (61.1%) were female, and the mean (SD) age was 78.6 (7.4) years. The median (interquartile range) FCPT SD was 40.2 (27.1-61.2) in the IVAN cohort and 59.0 (38.3-89.4) in the CATT cohort. After adjustment for baseline BCVA and trial allocations, BCVA worsened significantly across the quartiles of FCPT SD; the difference between the first and fourth quartiles was -6.27 Early Treatment Diabetic Retinopathy Study letters (95% CI, -8.45 to -4.09). The risk of developing fibrosis and macular atrophy also increased across FCPT SD quartiles. Odds ratios ranged from 1.40 (95% CI, 1.03 to 1.91) for quartile 2 to 1.95 (95% CI, 1.42 to 2.68) for quartile 4 for fibrosis and from 1.32 (95% CI, 0.90 to 1.92) for quartile 2 to 2.10 (95% CI, 1.45 to 3.05) for quartile 4 for macular atrophy. Greater variation in retinal thickness in eyes with nAMD during treatment with anti-VEGF was associated with worse BCVA and development of fibrosis and macular atrophy in these post hoc analyses, despite protocol-directed treatment frequency. Practitioners may want to consider variation in retinal thickness when advising patients about their prognosis.


Antiestrogen use in breast cancer patients reduces the risk of subsequent lung cancer: A population-based study.
There is accumulating epidemiological and preclinical evidence that estrogen might be a driver of lung cancer. Breast cancer survivors can offer a unique patient cohort to examine the effect of antiestrogen therapy on lung cancer carcinogenesis because many of these women would have received long-term selective estrogen receptor modulators (SERMs) and/or aromatase inhibitors (AIs) as adjuvant treatment. Our hypothesis is that estrogens play a role in lung cancer development, and that antiestrogen therapy would affect the incidence of subsequent lung cancer among breast cancer survivors. Using the Taiwan National Health Insurance (NHI) database, the study included 40,900 survivors of non-metastatic breast cancer after primary surgery, and most antiestrogen users complied well with the medication regimen. We evaluate the effect of antiestrogen therapy on the incidence of subsequent lung cancers. This population-based study revealed that antiestrogen use in breast cancer patients was associated with a reduced risk of subsequent lung cancer in older patients (≥50 years) (HR 0.73, 95%CI 0.54-0.99) when compared with breast cancer survivors who did not use antiestrogens. The study supports the hypothesis that antiestrogen therapy modifies lung cancer carcinogenesis in older women. Further well-designed clinical trials to explore the potential of antiestrogens in lung cancer prevention and treatment would be worthwhile.


Reference ranges for 51Cr-EDTA measurements of glomerular filtration rate in children.
51Cr-Ethylenediaminetetraacetic acid (51Cr-EDTA) is widely used to measure the glomerular filtration rate (GFR) in children and adults. To produce paediatric reference data for use with the British Nuclear Medicine Society (BNMS) GFR guidelines. This was a retrospective study of children and adolescents, aged 0-17 years, undergoing combined 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scintigraphy and GFR examination. GFR was evaluated from Cr-EDTA plasma clearance using blood samples taken at 2, 3 and 4 h according to the methods set out in the BNMS GFR guidelines. 99mTc-DMSA images were reviewed to identify children with normal scans. Of the 45 children having a combined 99mTc-DMSA and GFR investigation, 27 (12 females, 15 males) had a normal scan result. The mean GFR (standard deviation) in the 24 subjects aged 2-17 years was 109.5 (16.8) ml . min(-1) . (1.73 m2)(-1). This compared with a predicted figure of 107.0 (17.0) ml . min(-1) . (1.73 m2)(-1) when the paediatric reference range published by Piepsz et al. was adjusted to be consistent with the BNMS GFR guidelines. When the GFR results in the present study were calculated according to the single-sample and two-sample methods used by Piepsz et al., there was close agreement with the results obtained in the latter study [116.7 (24.2) vs. 114.7 (25.8) ml . min(-1) . (1.73 m2)(-1)]. Children with abnormal 99mTc-DMSA scans had significantly lower GFR than those with normal scans (P=0.003). There is a consistent difference between the GFR results in children with normal 99mTc-DMSA scans obtained in the present study and the unadjusted results of Piepsz et al. that can be explained by the different methods of calculating GFR in the two studies. Given the larger number of children in the latter study, it is proposed that centres evaluating GFR according to the BNMS method should adopt the Piepsz et al. reference range adjusted for consistency with the BNMS guidelines. This gives a mean GFR (SD) in children of 2 years and over of 107 (17) ml . min(-1) . (1.73 m2)(-1).


Prevalence and profile of daily smokers seen at three primary health care units in Pelotas, southern Brazil.
To estimate the prevalence of daily smoking among users of three primary health care units affiliated with a university hospital in the municipality of Pelotas, southern Brazil, and to identify factors associated with daily tobacco consumption. This cross-sectional study included all individuals over 14 years of age who sought treatment at the health care units between June 29, 2009, and February 23, 2010, and lived in the area covered by the unit. Interviews were conducted during home visits to collect data on sociodemographic characteristics and health behaviors; the Mini International Neuropsychiatric Interview (MINI) was used to assess the presence of mood disorders; and a question from the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) on the daily use of tobacco in the past 3 months was used to assess smoking. The total sample comprised 1,848 individuals, mostly female (72.9%), aged between 46 and 60 years (28.5%), and belonging to socioeconomic class C (61%). The prevalence of daily smoking was 23.4% (n = 432), and there was a statistically significant difference between men and women: 27 vs. 22.1% (p < 0.050). Our findings confirm a high prevalence of smoking among users of primary health care units, underscoring the need for a more accurate process of diagnosis and treatment at these facilities.


Collateral Vessel Development in Central and Branch Retinal Vein Occlusions Are Associated With Worse Visual and Anatomic Outcomes.
The purpose of this study was to investigate the effects of the extension of collateral vessels on the outcomes of eyes affected by central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). The study was designed as a cross-sectional case series. Patients affected by CRVO and BRVO were progressively recruited, along with an age- and sex-matched control group of healthy subjects. Structural optical coherence tomography (OCT) and OCT angiography (OCTA; 4.5 × 4.5 mm and 9.0 × 9.0 mm acquisitions) were performed on all participants in order to assess the relationship between the presence of collateral vessels and final anatomical outcomes - central macular thickness (CMT), foveal avascular zone - and functional outcomes - best corrected visual acuity (BCVA). Fifty-six eyes affected by CRVO and 47 eyes affected by BRVO were included. Baseline LogMAR BCVA was 0.41 ± 0.33 LogMAR in CRVO, and 0.39 ± 0.25 LogMAR in BRVO (P < 0.01), improving to 0.20 ± 0.26 LogMAR in CRVO (P < 0.01), and 0.19 ± 0.22 LogMAR in BRVO (P < 0.01). Baseline CMT was 511 ± 214 µm in CRVO and 482 ± 178 µm in BRVO (P > 0.05), decreasing to 328 ± 105 µm (P < 0.01) and 321 ± 78 µm in CRVO and BRVO, respectively (P < 0.01). Collateral vessels were detected in 16 of 56 eyes (29%) in CRVO and in 47 of 47 eyes (100%) in BRVO. Their extension was correlated with worse anatomic and visual outcomes. Remarkably, no correlation was found with peripheral capillary nonperfusion and vessel density impairment. The present study demonstrates that collateral vessel extension is associated with worse anatomic and functional outcomes in patients affected by CRVO and BRVO.


Distribution of pelvic organ support measures in a population-based sample of middle-aged, community-dwelling African American and white women in southeastern Michigan.
The purpose of this study was to report the distribution of pelvic support among a population-based sample of middle-aged community-dwelling women, as defined by pelvic organ prolapse quantification (POP-Q) and study factors that might influence POP-Q measurements. We conducted a secondary analysis of a population-based study of community-dwelling, African American and white women aged 35-64 years from southeastern Michigan. Three hundred ninety-four women consented to physical examination using the POP-Q. Statistical analysis included descriptive statistics and multivariable regression. Estimates were weighted to reflect probability and nonresponse characteristics of the sample to increase generalizability of the findings. The following values were the mean values for POP-Q points: Aa and Ba = -1.2 cm, C = -6.5 cm (intact uterus), C = -6.9 cm (hysterectomy), and Ap and Bp = -1.8 cm. The POP-Q stages were organized in the following manner: stage 0, 8.8%; stage I, 21.4%; stage II, 67.7%; stage III, 2.1%. Increasing vaginal parity was associated with increasing descent of the anterior, apical, and posterior vaginal wall (P < .001). In this population-based study of women from southeastern Michigan, 90% of the women had anterior and posterior vaginal wall support that was above or extended to the hymen. Increasing vaginal parity was associated with increasing descent of the anterior, posterior, and vaginal apex.


Decreased utilization of allocentric coordinates during reaching movement in individuals with autism spectrum disorder.
Despite numerous reports of abnormalities in limb motor controls in spatial orientation in individuals with autism spectrum disorder (ASD), the underlying mechanisms have not been elucidated. We studied the influence of allocentric coordinates on ongoing reaching movements, which has been reported to strongly affect the reaching movements of typically developing (TD) individuals. ASD and TD participants observed a target presented randomly on one of the four corners of a frame on a screen. After it disappeared, another frame was presented slightly shifted leftward/rightward. The participants touched the memorized position of the target relatively congruent with a reference frame (allocentric condition) or ignoring it (egocentric condition). Results suggested that TD individuals were apt to touch the positions in allocentric manner rather than egocentric manner, while ASDs did not show this prioritization. Our findings demonstrate that decreased utilization of visual landmarks in ongoing movement may underlie motor disabilities in autism.


Heat shock at the germinal vesicle breakdown stage induces apoptosis in surrounding cumulus cells and reduces maturation rates of porcine oocytes in vitro.
The objectives were to determine the effects of cumulus cells (CC) on porcine oocyte maturation in vitro (IVM) after heat shock (HS). Treated oocytes were cultured at 39 degrees C for 20h, followed by HS treatment (42 degrees C for 1h), and then matured in vitro for 23h. The CC were removed before maturation (H1), after HS (H2), or after maturation (H3). Control oocytes were continuously cultured under the same conditions and CC were similarly removed before maturation (C1), after 21h of IVM (C2), and after maturation (C3). Maturation rates were affected by HS (P<0.01) and by an interaction between HS and CC (P<0.01). A significant decrease in maturation rate only occurred when CC were not removed from cumulus oocyte complexes during IVM after HS (H3, 39.2+/-5.7% versus C3, 78.2+/-8.2%, P<0.01). Mature oocytes in all treatment groups were electrically activated and cultured for 8 d in NCSU23. Blastocyst rates in group H1 (7.2+/-3.5%) and C1 (6.3+/-3.1%) were lower than in other groups (H2, 21.4+/-4.4%, C2, 20.5+/-7.0%, H3, 23.1+/-2.0%, C3, 24.3+/-3.1%, P<0.05). Damaged DNA was detected in CC by a comet assay at 0h after HS (60.8+/-12.5% compared with 9.2+/-2.2% in control, P<0.05); in HS groups, both DNA damage (comet assay, 74.9+/-6.3% compared with 10.0+/-2.1% in control) and apoptosis (TUNEL assay, 21.6+/-1.6% compared with 5.6+/-0.6% in control) in CC were increased (P<0.05) at 44h of maturation. In conclusion, heat shock (42 degrees C for 1h) during IVM induced DNA damage and apoptosis of porcine CC; furthermore, apoptotic CC may contribute to maturation failure of oocytes in vitro.


Detection of transferrin isoforms in human serum: comparison of UV and ICP-MS detection after CZE and HPLC separations.
Two methods for separation of transferrin (Tf) sialoforms, capillary electrophoresis (CE) and high performance liquid chromatography (HPLC) with conventional UV absorbance detection, have been investigated and compared. First, conditions affecting the separation of the Tf isoforms by capillary zone electrophoresis and HPLC were carefully optimized. The use of 15 mmol L(-1) borate buffer (pH 8.4) containing 3 mmol L(-1) diaminobutane (DAB) as additive enabled good separation of the Tf isoforms by CE (75 cm x 50 microm i.d. fused silica capillary) at 25 kV. In HPLC, a gradient of ammonium acetate (from 0 to 250 mmol L(-1) in 45 min) buffered at pH 6 (Tris-HCl) proved suitable for separation of Tf isoforms on a Mono-Q HR 5/5 anion-exchange column. On-line specific detection of the iron associated with the different Tf isoforms, after Fe saturation, by inductively coupled plasma mass spectrometry (ICP-MS) was studied in detail to compare its analytical performance with UV detection. For both CE and HPLC an octapole reaction system (ORS) ICP-MS instrument was used to minimize polyatomic interferences on the (56)Fe major isotope. Limits of detection of the different isoforms were in the range of 0.02-0.04 micromol L(-1) Tf for HPLC-ICP (ORS)-MS. This hybrid technique proved more selective and reliable detection of transferrin isoforms with 2, 3, 4, 5, and 6 sialic acid residues (S(2), S(3), S(4), S(5), and S(6)) in real serum samples. Interesting results from iron speciation of Tf in serum from healthy individuals and from pregnant women are given.


A significant association between spontaneous abortion and tubal ectopic pregnancy.
A retrospective study of 83 patients with pathologically documented tubal ectopic pregnancy demonstrated a statistically significant association (P less than 0.005) between prior spontaneous abortion and ectopic pregnancy. In this population with a low incidence of chronic salpingitis, it is suggested that delayed (post-midcycle) ovulation, causing preovulatory over-ripeness of the ovum, may be the common underlying etiologic factor. The clinical significance of this finding is also briefly discussed.


Predicting the appropriate uncuffed endotracheal tube size for children: a radiograph-based formula versus two age-based formulas.
To determine whether a radiograph-based formula using the tracheal diameter from a chest radiograph predicted the appropriate endotracheal tube (ETT) size in children, and to compare these results with those produced using age-based formulas. Retrospective, observational study. Medical record review. Data from 537 pediatric patients, aged 3 to 6 years, who underwent orotracheal intubation with an uncuffed ETT, were randomly divided into two datasets: one was used to derive a formula and the other was for validation. A radiograph-based formula was obtained by linear regression modeling between the tracheal diameter at the seventh cervical vertebra (C7) on chest radiography and the appropriate ETT size from the estimation dataset (n=268). The appropriate size was defined as the ETT size when air leak pressure was 10 to 30 cmH2O. The predictive ability of this equation was evaluated using the validation dataset (n=269). The primary outcome was the success rate of the prediction. The following radiograph-based formula was obtained: ID = 3 + 0.3 × (tracheal diameter at C7). The success rate of the radiograph-based formula was 57%, which is higher than the 32% (P < 0.001) of the standard age-based formula (ID = 4 + age/4) or 43% (P = 0.002) of Penlington's formula (ID = 4.5 + age/4). An underestimation of the actual tracheal size occurred in 65% of cases using the age-based formulas, but in only 19% with the radiograph-based formula (P < 0.001). The radiograph-based formula may be useful for predicting the appropriate ETT size in children aged 3 to 6 years.


Using on-line solid phase extraction for determination of amiloride in human urine by sequential injection technique.
This presented paper deals with a new methodology for the direct determination of amiloride in human urine. The methodology described is based on the sequential injection analysis technique (SIA) coupled with solid phase extraction (SPE) microcolumn. SPE microcolumn was used for selective retention of amiloride, while the urine matrix components were eluted with water carrier flow to the waste. Due to the acid-basic and polarity properties of amiloride molecule and principles of ion-exchange chromatography, it was possible to retain amiloride on the ion-exchange sorbent (SPE BAKER WCX-carboxy group). Eluting solution was 0.01 M HNO3+0.1 M KCl, flow rate 20 microl s(-1). The fluorescence detection of amiloride was performed at lambda(em) 385 nm (secondary filter). Recovery was found in the range 96.8-99.4% for 10 times diluted urine, linearity of determination in the range 0.5-100 microg ml(-1) (r=0.998), and 3sigma limit of detection (LOD) was 0.05 microg ml(-1). The whole procedure comprising raw sample pre-treatment, analyte detection and column reconditioning took 8 min. The proposed SIA-SPE method has been applied for direct determination of amiloride in human urine.


Butanol production by bioconversion of cheese whey in a continuous packed bed reactor.
Butanol production by Clostridium acetobutylicum DSM 792 fermentation was investigated. Unsupplemented cheese whey was adopted as renewable feedstock. The conversion was successfully carried out in a biofilm packed bed reactor (PBR) for more than 3 months. The PBR was a 4 cm ID, 16 cm high glass tube with a 8 cm bed of 3mm Tygon rings, as carriers. It was operated at the dilution rate between 0.4h(-1) and 0.94 h(-1). The cheese whey conversion process was characterized in terms of metabolites production (butanol included), lactose conversion and biofilm mass. Under optimized conditions, the performances were: butanol productivity 2.66 g/Lh, butanol concentration 4.93 g/L, butanol yield 0.26 g/g, butanol selectivity of the overall solvents production 82 wt%.


The early wound signals.
Wounding of tissue barriers, such as epithelia, disrupts homeostasis and allows infection. Within minutes, animals detect injury and respond to it by recruitment of phagocytes and barrier breach closure. The signals that activate these first events are scarcely known. Commonly considered are cytoplasmic factors released into the extracellular space by lysing cells (Damage Associated Molecular Patterns, DAMPs). DAMPs activate inflammatory gene transcription through pattern recognition receptors. But the promptness of wound responses is difficult to explain by transcriptional mechanisms alone. This review highlights the emerging role of nonlytic stress signals in the rapid detection of wounds.


Recovery of functional status after stroke in a tri-ethnic population.
To examine recovery of functional status for white, black, and Hispanic patients who have had a stroke from the time of admission to inpatient medical rehabilitation to 12 months after discharge. A longitudinal study that used information from the Stroke Recovery in Underserved Population database, a prospective observational study of persons with stroke who received inpatient medical rehabilitation services during 2005-2006. Eleven inpatient rehabilitation facilities located across diverse regions of the United States, including California, Florida, Iowa, Illinois, Kentucky, New Jersey, New York (2), Texas (2), and Washington, DC. A total of 990 adults aged 55 years or older who had a stroke and were admitted to 1 of 11 inpatient medical rehabilitation facilities in the United States were interviewed at 4 time points, including admission to and discharge from an inpatient medical rehabilitation facility and 3 and 12 months after discharge. Not applicable. Functional status as measured by the Functional Independence Measure (FIM). For the total sample, FIM ratings increased from admission to discharge and from discharge to 3-month follow-up, with little recovery occurring between 3 and 12 months. In random effects mixed models, at 3-month follow-up, both black and Hispanic patients had lower FIM ratings than did white patients. At 12-month follow-up, black and white patients were similar; however, Hispanic patients continued to have lower FIM ratings compare with white patients. Racial/ethnic group, age, length of stay, and medical comorbidities were significant predictors of total FIM ratings over the 4 time points. Persons 55 years and older who have had a stroke, regardless of race/ethnicity, appear to benefit from inpatient medical rehabilitation. Most functional status gains occur during inpatient medical rehabilitation and continue in the first few months after discharge, with little change afterward.


Animal models of COPD: Barriers, successes, and challenges.
Animal models have definite utility in the study of chronic obstructive pulmonary disease. However, choice of model must be determined with the full knowledge of their value, or potential limitations.


Vascular endothelial growth factor-B expression in postischemic rat brain.
Vascular endothelial growth factor-B (VEGF-B) protects against experimental stroke, but the effect of stroke on VEGF-B expression is uncertain. We examined VEGF-B expression by immunohistochemistry in the ischemic border zone 1-7 days after middle cerebral artery occlusion in rats. VEGF-B immunoreactivity in the border zone was increased after middle cerebral artery occlusion and was associated with neurons and macrophages/microglia, but not astrocytes or endothelial cells. These findings provide additional evidence for a role of VEGF-B in the endogenous response to cerebral ischemia.


Digital transformation risk management in forensic science laboratories.
Technological advances are changing how forensic laboratories operate in all forensic disciplines, not only digital. Computers support workflow management, enable evidence analysis (physical and digital), and new technology enables previously unavailable forensic capabilities. Used properly, the integration of digital systems supports greater efficiency and reproducibility, and drives digital transformation of forensic laboratories. However, without the necessary preparations, these digital transformations can undermine the core principles and processes of forensic laboratories. Pertinent examples of problems involving technology that have occurred in laboratories are provided, along with opportunities and risk mitigation strategies, based on the authors' experiences. Forensic preparedness concentrating on digital data reduces the cost and operational disruption of responding to various kinds of problems, including misplaced exhibits, allegations of employee misconduct, disclosure requirements, and information security breaches. This work presents recommendations to help forensic laboratories prepare for and manage these risks, to use technology effectively, and ultimately strengthen forensic science. The importance of involving digital forensic expertise in risk management of digital transformations in laboratories is emphasized. Forensic laboratories that do not adopt forensic digital preparedness will produce results based on digital data and processes that cannot be verified independently, leaving them vulnerable to challenge. The recommendations in this work could enhance international standards such as ISO/IEC 17025 used to assess and accredit laboratories.


Edoxaban for Thromboembolism Prevention in Pediatric Patients With Cardiac Disease.
Standard of care (SOC) anticoagulation for thromboembolism (TE) prevention in children with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exists for alternate use of direct oral anticoagulants in children. The investigators aimed to obtain safety and efficacy data for edoxaban in children. We performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients <18 years of age with cardiac disease (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease] trial). Patients were randomized 2:1 to age- and weight-based oral edoxaban once daily vs SOC for 3 months (main study period), stratified by cardiac diagnosis. Both groups could continue in an open-label edoxaban extension arm through 1 year. The primary endpoint was adjudicated clinically relevant bleeding (CRB). The main secondary endpoint was symptomatic TE or asymptomatic intracardiac thrombosis. The modified intention-to-treat cohort included 167 children. One patient per group experienced a nonmajor CRB in the main period. Treatment-emergent adverse events occurred in 46.8% (51 of 109) with edoxaban and 41.4% (24 of 58) with SOC. One SOC patient experienced 2 TE events (DVT with PE). Among 147 children in the extension, 1 CRB event (0.7%) and 4 TEs occurred (2.8%; 2 strokes and 2 of 33 Kawasaki disease patients with coronary artery thromboses and/or myocardial infarctions). Edoxaban is a potential alternative mode of thromboprophylaxis in children with cardiac disease showing low rates of CRB and TEs with advantages of once daily dosing and infrequent monitoring requirement. (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots] (Thrombotic Events) in Children at Risk Because of Cardiac Disease trial; NCT03395639).


Sevoflurane attenuates brain damage through inhibiting autophagy and apoptosis in cerebral ischemia‑reperfusion rats.
The present study aimed to investigate the effects of sevoflurane post‑conditioning in a rat brain cerebral ischemia‑reperfusion (I/R) model and examine its possible mechanism. Rats were randomly divided into six groups: Sham control group (Sham), I/R group, sevoflurane group (Se), Toll‑like receptor‑4 (TLR4) inhibitor group (Tak‑242), nuclear factor (NF)‑κB inhibitor group (QNZ) and Sevoflurane post‑conditioning combined with TLR4‑NF‑κB signaling pathway inhibitor group (Se + Tak‑242). Morris water maze test and tetrazolium chloride staining were used to investigate the I/R injury. The nerve cell apoptosis and autophagy in cortical tissue were detected by TUNEL and transmission electron microscopy, respectively. The expression of TLR4 protein in cortical tissue was observed by immunohistochemical staining. The expression of autophagy and apoptotic associated proteins in cortical tissues and the activity of TLR4‑NF‑κB signaling pathway were assayed by western blot analysis. Sevoflurane post‑conditioning improved the learning and memory dysfunction caused by cerebral I/R injury. The cerebral infarction area, nerve cell apoptosis and formation of autophagic vacuoles were reduced after sevoflurane administration. The expression of light chain 3II/I, Beclin‑1, Bad and Cleaved‑Caspase‑3 proteins were inhibited and the expression of Bcl‑2 protein was upregulated after sevoflurane administration. Sevoflurane post‑conditioning also inhibited the TLR4 protein and NF‑κB phosphorylation, and increased inhibitor of kBα phosphorylation. The treatment effect of Tak‑242 and QNZ groups were not significantly different compared with the Se group (P>0.05), and the Se + Tak‑242 group had the best results. The present study demonstrated that sevoflurane post‑conditioning could protect middle cerebral artery occlusion‑induced brain injury rats by inhibiting autophagy and apoptosis, and that its mechanism is related to the TLR4‑NF‑κB signaling pathway.


Thioether-Containing Zirconium(Alkoxy)Siloxanes: Synthesis and Study of Dielectric and Mechanical Properties of Silica-Filled Polydimethylsiloxane Compositions Cured by Them.
A number of thioether-containing zirconium siloxanes, differing in their composition and metal atom shielding degree with a siloxy substituent, were synthesized and characterized. Synthesis of such compounds made it possible to evaluate the effect of sulfur atoms' presence in the cured compositions on their dielectric properties, as well as to evaluate their curing ability and influence on mechanical characteristics compared to the sulfur-free analogs obtained earlier. Studying a wide range of compositions differing in their content and ratio of metallosiloxane and silica components revealed that such systems are still typical dielectrics. At the same time, the introduction of thioether groups can provide increased dielectric constant and conductivity in comparison with previously obtained sulfur-free similar compositions in the <102 Hz frequency range (dielectric constant up to ~10-30 at frequency range 1-10 Hz). As before, the dielectric parameters increase is directly determined by the silica component proportion in the cured material. It is also shown that varying sulfur-containing zirconium siloxanes structure and functionality and its combination with previously obtained sulfur-free analogs, along with varying the functionality and rubber chain length, can be an effective tool for changing the dielectric and mechanical material parameters in a wide range (tensile strength 0.5-7 Mpa, elastic deformation 2-300%), which determine the prospects for the use of such cured systems as dielectric elastomers for various purposes.


Catechol-O-methyltransferase association with hemoglobin A1c.
Catecholamines have metabolic effects on blood pressure, insulin sensitivity and blood glucose. Genetic variation in catechol-O-methyltransferase (COMT), an enzyme that degrades catecholamines, is associated with cardiometabolic risk factors and incident cardiovascular disease (CVD). Here we examined COMT effects on glycemic function and type 2 diabetes. We tested whether COMT polymorphisms were associated with baseline HbA1c in the Women's Genome Health Study (WGHS), and Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), and with susceptibility to type 2 diabetes in WGHS, DIAbetes Genetics Replication And Meta-analysis consortium (DIAGRAM), and the Diabetes Prevention Program (DPP). Given evidence that COMT modifies some drug responses, we examined association with type 2 diabetes and randomized metformin and aspirin treatment. COMT rs4680 high-activity G-allele was associated with lower HbA1c in WGHS (β=-0.032% [0.012], p=0.008) and borderline significant in MAGIC (β=-0.006% [0.003], p=0.07). Combined COMT per val allele effects on type 2 diabetes were significant (OR=0.98 [0.96-0.998], p=0.03) in fixed-effects analyses across WGHS, DIAGRAM, and DPP. Similar results were obtained for 2 other COMT SNPs rs4818 and rs4633. In the DPP, the rs4680 val allele was borderline associated with lower diabetes incidence among participants randomized to metformin (HR=0.81 [0.65-1.00], p=0.05). COMT rs4680 high-activity G-allele was associated with lower HbA1c and modest protection from type 2 diabetes. The directionality of COMT associations was concordant with those previously observed for cardiometabolic risk factors and CVD.


A comparison of the perceptions of wearing an ankle foot orthosis by individuals with peripheral artery disease according to their baseline-level of physical activity.
Peripheral artery disease (PAD) is a prevalent cardiovascular disease that limits an individual's ability to walk. One potential way to improve physical activity for patients with PAD is an ankle foot orthosis (AFO). Previous research has found that various factors may influence an individual's willingness to wear AFOs. However, one factor that has been understudied is an individual's baseline physical activity level prior to wearing AFOs. Therefore, the purpose of this study was to compare the perceptions of wearing AFOs for 3 months among individuals with PAD according to their baseline level of physical activity. Accelerometer-derived physical activity prior to AFO prescription was used to classify participants into either a higher or lower activity group. Semi-structured interviews were conducted at 1.5 and 3-months after wearing the AFOs to assess participants' perceptions of using the orthosis. Data were analyzed by a directed content analysis approach, then the percentage of respondents for each theme were calculated and compared between higher and lower activity groups. Several differences were found. Participants in the higher activity group more often reported positive impacts from wearing the AFOs. Additionally, participants who were in the lower activity group more often reported the AFOs caused physical pain while participants in the higher activity group more often reported the device was uncomfortable during daily activities. Baseline physical activity levels may help to better understand barriers to wear and needed support to increase adherence to an AFO wear prescription, especially for patients with PAD with limited activity.


Terrestrial-type nitrogen-fixing symbiosis between seagrass and a marine bacterium.
Symbiotic N2-fixing microorganisms have a crucial role in the assimilation of nitrogen by eukaryotes in nitrogen-limited environments1-3. Particularly among land plants, N2-fixing symbionts occur in a variety of distantly related plant lineages and often involve an intimate association between host and symbiont2,4. Descriptions of such intimate symbioses are lacking for seagrasses, which evolved around 100 million years ago from terrestrial flowering plants that migrated back to the sea5. Here we describe an N2-fixing symbiont, 'Candidatus Celerinatantimonas neptuna', that lives inside seagrass root tissue, where it provides ammonia and amino acids to its host in exchange for sugars. As such, this symbiosis is reminiscent of terrestrial N2-fixing plant symbioses. The symbiosis between Ca. C. neptuna and its host Posidonia oceanica enables highly productive seagrass meadows to thrive in the nitrogen-limited Mediterranean Sea. Relatives of Ca. C. neptuna occur worldwide in coastal ecosystems, in which they may form similar symbioses with other seagrasses and saltmarsh plants. Just like N2-fixing microorganisms might have aided the colonization of nitrogen-poor soils by early land plants6, the ancestors of Ca. C. neptuna and its relatives probably enabled flowering plants to invade nitrogen-poor marine habitats, where they formed extremely efficient blue carbon ecosystems7.


Impact of therapeutic drug monitoring of antibiotics in the management of infective endocarditis.
Treatment of infective endocarditis (IE) is based on high doses of antibiotics with a prolonged duration. Therapeutic drug monitoring (TDM) allows antibiotic prescription optimization and leads to a personalized medicine, but no study evaluates its interest in the management of IE. We conducted a retrospective, bicentric, descriptive study, from January 2007 to December 2019. We included patients cared for IE, defined according to Duke's criteria, for whom a TDM was requested. Clinical and microbiological data were collected after patients' charts review. We considered a trough or steady-state concentration target of 20 to 50 mg/L. We included 322 IE episodes, corresponding to 306 patients, with 78.6% (253/326) were considered definite according to Duke's criteria. Native valves were involved in 60.5% (185/306) with aortic valve in 46.6% (150/322) and mitral in 36.3% (117/322). Echocardiography was positive in 76.7% (247/322) of cases. After TDM, a dosage modification was performed in 51.5% (166/322) (decrease in 84.3% (140/166)). After initial dosage, 46.3% (82/177) and 92.8% (52/56) were considered overdosed, when amoxicillin and cloxacillin were used, respectively. The length of hospital stay was higher for patient overdosed (25 days versus 20 days (p = 0.04)), and altered creatinine clearance was associated with overdosage (p = 0.01). Our study suggests that the use of current guidelines probably leads to unnecessarily high concentrations in most patients. TDM benefits predominate in patients with altered renal function, but probably limit adverse effects related to overdosing in most patients.


Production and characterization of Amanitin toxins from a pure culture of Amanita exitialis.
Amanita exitialis Zhu L. Yang and T.H. Li is a lethal mushroom species recently isolated in Guangdong Province, China. In this report, a pure culture of this species was obtained for the first time. To confirm the identity of the pure culture, the internal transcribed spacer regions of the nuclear ribosomal DNA of the pure culture and of a typical fruiting body of the species were sequenced and compared. Further, amatoxins produced by pure cultures were analyzed and characterized by high-performance liquid chromatography and mass spectrometry analysis. The results showed that the pure cultures produced 728.3 +/- 43.8 microg g(-1) (dry matter) of alpha-Amanitin and 60.0 +/- 20.7 microg g(-1) (dry matter) of beta-Amanitin, respectively, a yield which is about 10% of that produced by fruiting bodies.


Cough. 5: The type 1 vanilloid receptor: a sensory receptor for cough.
Evidence is presented to support the proposal that activation of the type 1 vanilloid receptor (VR1) is an important sensory mechanism in cough.


Analysis of responses to endothelins in isolated porcine blood vessels by using a novel endothelin antagonist, BQ-153.
We examined the effects of a novel ETA-selective endothelin (ET) antagonist, BQ-153, on vascular responses to ET-1 and ET-3 in isolated porcine coronary and pulmonary blood vessels, to clarify the roles of ET receptor subtypes in the regulation of vascular smooth muscle tension. With endothelium-denuded vascular tissues, the concentration-contraction curve (CCC) for ET-1 appeared as a single sigmoidal shape for all types of tissue. The CCC for ET-1 was antagonized by BQ-153 (2 and 10 microM) in all tissues, but part of the contraction was resistant. The CCC for ET-3 usually consisted of two different phases with higher (first phase) and lower (second phase) sensitivities to the peptide. Only the second phase of CCC for ET-3 was completely inhibited by BQ-153 (2 microM) in all tissues, while the first phase was resistant. The BQ-153-resistant contractile phases of ET-1 and ET-3-induced vasoconstriction appeared to have similar sensitivity in all tissues, and the contractile activity varied with each type of tissue. With endothelium-intact materials, the potencies of ET-1 and ET-3 for endothelium-dependent vasorelaxation in pulmonary artery were almost equivalent. BQ-153 (10 microM) did not inhibit ET-induced vasorelaxation. These results indicate that ET-induced vasoconstriction is mediated not only through ETA but also through ETnonA (probably ETB), and that the relative proportions of the ET-receptor subtypes mediating contractions vary in different vascular areas. In addition, results showed that ET-induced endothelium-dependent vasorelaxation is mediated through ETB.