Expression of cDNA encoding the Sendai virus hemagglutinin-neuraminidase gene: characterization of wild-type and mutant gene products.
Cloned cDNA encoding the Sendai virus (SV) hemagglutinin-neuraminidase (HN) envelope glycoprotein was expressed in cultured cells in two ways: (I) infection with HN-expressing recombinant vaccinia virus, or (II) transfection with a plasmid with T7 promoter and termination sequences flanking the HN gene, with intracellular T7 RNA polymerase supplied by coinfection with recombinant vaccinia virus that expresses the enzyme. The HN expressed was indistinguishable from the authentic SV protein in antigenicity, cell surface location, and formation of oligomeric structures. In addition, HN expressed from cDNA functioned normally in both hemadsorption and neuraminidase activities. The usefulness of cDNA expression for analyzing HN structure and function was evaluated by mutating the HN cDNA and observing the consequences for HN protein activity. Since previous work indicated that the lysine residue at position 461 is important for the neuraminidase activity of HN, we used site-directed mutation to produce HN protein with this lysine residue changed to glutamic acid. The mutated HN had neuraminidase activity with significantly increased thermal stability, indicating that residue 461 may be essential to the protein's conformation.


Pelobacter seleniigenes sp. nov., a selenate-respiring bacterium.
Strain KM(T) is a novel bacterium with the unique metabolic abilities of being able to respire selenate as the electron acceptor using acetate as the carbon substrate and possessing the ability to grow fermentatively on short-chain organic acids such as lactate, citrate and pyruvate. Strain KM(T) was isolated from a sediment enrichment culture of a highly impacted wetland system in New Jersey, USA. Strain KM(T) is able to reduce selenate as well as selenite to elemental selenium. The unique metabolic capabilities of strain KM(T) include the respiration of nitrate, poorly crystalline Fe(III) and anthraquinone disulfonate. Phylogenetic analysis of the 16S rRNA gene of the novel isolate indicates that strain KM(T) groups within the family Geobacteraceae in the class Deltaproteobacteria with approximately 96-97 % 16S rRNA gene sequence similarity to the closest known organisms Malonomonas rubra Gra Mal 1(T), Pelobacter acidigallici Ma Gal 2(T) and species of the genus Desulfuromusa. Recognized species of the genera Malonomonas and Pelobacter cannot use any inorganic electron acceptors, while strains of the genus Desulfuromusa do not ferment organic substrates. This contrasts with the ability of strain KM(T) to ferment organic compounds as well as to couple selenate reduction to acetate utilization. Based on 16S rRNA gene phylogeny and metabolic properties, strain KM(T) represents a novel species for which the name Pelobacter seleniigenes sp. nov. (type strain KM(T)=DSM 18267(T)=ATCC BAA-1388(T)) is proposed. Based on the phylogenetic grouping of species of the genus Pelobacter within the Desulfuromusa cluster, it is suggested that Malonomonas rubra Gra Mal 1(T) should also be included in this group.


Endoscopic-assisted disruption of urinary calculi using a holmium:YAG laser in standing horses.
To describe a technique for endoscope-assisted disruption and removal of urinary calculi using a holmium:YAG laser in sedated, standing horses. Retrospective study. Six horses with urinary calculi. A holmium:YAG laser was used to disrupt naturally occurring urinary calculi in horses (4 geldings, 1 stallion, 1 mare). Ischial urethrotomy was performed in male horses to provide a portal for the endoscope and laser fiber. Calculus fragments were removed by a combination of lavage, transendoscopic basket snare removal, forceps, and digital manipulation. Ischial urethrotomies healed by second intention. Follow-up was obtained by recheck examination and telephone interview of owners. No major operative or postoperative complications occurred. Two calculi (1 stallion and 1 mare) were fragmented by a combination of laser ablation and manual disruption with a lithotrite. Postoperative dysuria occurred in the mare, but resolved after 1 month. Mean (+/- SD) follow-up was 306 +/- 149 days; no other complications were reported. Calcium carbonate urinary calculi (up to 15 cm in diameter) in horses can be effectively fragmented with a holmium:YAG laser. It is not known if this technique would be completely effective for larger calculi or extremely dense calculi. Calculus disruption by an endoscopically assisted holmium:YAG laser offers a minimally invasive method that can be performed in standing horses and that minimizes patient risk.


Biosynthesis of vitamin C by yeast leads to increased stress resistance.
In industrial large scale bio-reactions micro-organisms are generally exposed to a variety of environmental stresses, which might be detrimental for growth and productivity. Reactive oxygen species (ROS) play a key role among the common stress factors--directly--through incomplete reduction of O(2) during respiration, or indirectly--caused by other stressing factors. Vitamin C or L-ascorbic acid acts as a scavenger of ROS, thereby potentially protecting cells from harmful oxidative products. While most eukaryotes synthesize ascorbic acid, yeast cells produce erythro-ascorbic acid instead. The actual importance of this antioxidant substance for the yeast is still a subject of scientific debate. We set out to enable Saccharomyces cerevisiae cells to produce ascorbic acid intracellularly to protect the cells from detrimental effects of environmental stresses. We report for the first time the biosynthesis of L-ascorbic acid from D-glucose by metabolically engineered yeast cells. The amount of L-ascorbic acid produced leads to an improved robustness of the recombinant cells when they are subjected to stress conditions as often met during industrial fermentations. Not only resistance against oxidative agents as H(2)O(2) is increased, but also the tolerance to low pH and weak organic acids at low pH is increased. This platform provides a new tool whose commercial applications may have a substantial impact on bio-industrial production of Vitamin C. Furthermore, we propose S. cerevisiae cells endogenously producing vitamin C as a cellular model to study the genesis/protection of ROS as well as genotoxicity.


Multi-family therapy for bulimia nervosa in adolescence: a pilot study in a community eating disorder service.
Multi-family therapy for Bulimia Nervosa (MFT-BN) was developed in response to the modest outcomes following both Family Therapy and Cognitive Behavior Therapy for adolescents with BN. BN impacts individuals and their family members with high levels of carer stress. MFT-BN targets barriers to treatment including low motivation to change, hostility and criticism, negative affect alongside emotion dysregulation and common comorbidities. MFT-BN enhances treatment, providing a community of support and acquisition of emotional regulation and interpersonal skills. The study describes the clinical characteristics of the group of participants to whom MFT-BN is offered and presents the outcomes of families who have participated in it. Prior to MFT-BN, adolescents who received it were more likely to have self-harmed and had elevated levels of eating disordered cognitions than those who did not receive MFT-BN. Following MFT-BN, parents report decreases in the negative experiences of caregiving and in their own symptoms of anxiety. Adolescents report reductions in anxiety and depression alongside improvement in emotion regulation. Improvements in symptoms of eating disorders include reductions in eating disorder cognitions and modest reductions in binge and purge symptoms after 14 weeks of treatment. Adolescents who participated in MFT-BN were less likely to drop out of outpatient treatment.


Photocatalytic reduction and scavenging of Hg(ii) over templated-dewetted Au on TiO2 nanotubes.
Gold-decorated TiO2 nanotubes were used for the photocatalytic abatement of Hg(ii) in aqueous solutions. The presence of dewetted Au nanoparticles induces a strong enhancement of photocatalytic reduction and scavenging performances, with respect to naked TiO2. In the presence of chlorides, a massive formation of Hg2Cl2 nanowires, produced from Au nanoparticles, was observed using highly Au loaded photocatalysts to treat a 10 ppm Hg(ii) solution. EDS and XPS confirmed the nature of the photo-produced nanowires. In the absence of chlorides and/or at lower Hg(ii) starting concentrations, the scavenging of mercury proceeds through the formation of Hg-Au amalgams. Solar light driven Hg(ii) abatements up to 90% were observed after 24 h. ICP-MS analysis revealed that the removed Hg(ii) is accumulated on the photocatalyst surface. Regeneration of Hg-loaded exhaust photocatalysts was easily performed by anodic stripping of Hg(0) and Hg(i) to Hg(ii). After four catalytic-regeneration cycles, only a 10% decrease of activity was observed.


Police killings of Black people and rates of sexually transmitted infections: a cross-sectional analysis of 75 large US metropolitan areas, 2016.
Emerging literature shows that racialised police brutality, a form of structural racism, significantly affects health and well-being of racial/ethnic minorities in the USA. While public health research suggests that structural racism is a distal determinant of sexually transmitted infections (STIs) among Black people, no studies have empirically linked police violence to STIs. To address this gap, our study measures associations between police killings and rates of STIs among Black residents of US metropolitan statistical areas (MSAs). This cross-sectional ecological analysis assessed associations between the number of Black people killed by police in 2015 and rates of primary and secondary syphilis, gonorrhoea and chlamydia per 100 000 Black residents of all ages in 2016 in 75 large MSAs. Multivariable models controlled for MSA-level demographic and socioeconomic characteristics, police expenditures, violent crime, arrest and incarceration rates, insurance rates and healthcare funding. In 2015, the median number of Black people killed by police per MSA was 1.0. In multivariable models, police killings were positively and significantly associated with syphilis and gonorrhoea rates among Black residents. Each additional police killing in 2015 was associated with syphilis rates that were 7.5% higher and gonorrhoea rates that were 4.0% higher in 2016. Police killings of Black people may increase MSA-level risk of STI infections among Black residents. If future longitudinal analyses support these findings, efforts to reduce STIs among Black people should include reducing police brutality and addressing mechanisms linking this violence to STIs.


Recent Developments of Flexible and Stretchable Electrochemical Biosensors.
The skyrocketing popularity of health monitoring has spurred increasing interest in wearable electrochemical biosensors. Compared with the traditionally rigid and bulky electrochemical biosensors, flexible and stretchable devices render a unique capability to conform to the complex, hierarchically textured surfaces of the human body. With a recognition element (e.g., enzymes, antibodies, nucleic acids, ions) to selectively react with the target analyte, wearable electrochemical biosensors can convert the types and concentrations of chemical changes in the body into electrical signals for easy readout. Initial exploration of wearable electrochemical biosensors integrates electrodes on textile and flexible thin-film substrate materials. A stretchable property is needed for the thin-film device to form an intimate contact with the textured skin surface and to deform with various natural skin motions. Thus, stretchable materials and structures have been exploited to ensure the effective function of a wearable electrochemical biosensor. In this mini-review, we summarize the recent development of flexible and stretchable electrochemical biosensors, including their principles, representative application scenarios (e.g., saliva, tear, sweat, and interstitial fluid), and materials and structures. While great strides have been made in the wearable electrochemical biosensors, challenges still exist, which represents a small fraction of opportunities for the future development of this burgeoning field.


Changes in Empathy in Patients With Chronic Low Back Pain: A Structural-Functional Magnetic Resonance Imaging Study.
Objective: Many pieces of research have focused on pain within individuals, but little attention has been paid to whether pain can change an individual's empathic ability and affect social relationships. The purpose of this study is to explore how chronic low back pain changes empathy. Methods: Twenty-four chronic low back pain patients and 22 healthy controls were recruited. We set up an experimental pain-exposed model for each healthy subject. All subjects received a painful-empathic magnetic resonance scan. After the scan, all subjects rated the pain intensity and multiple empathy-related indicators. The clinical assessment scale was the 20-item Basic Empathy Scale in Adults. Result: The chronic low back pain patients reported lower scores on the total scores of BES-A, the subscale scores of emotional disconnection and cognitive empathy, and the discomfort rating. The fMRI results in the chronic low back pain patients showed that there were multiple abnormal brain pathways centered on the anterior insula. The DTI results in the chronic low back pain patients showed that there were reduced fractional anisotropy values in the corpus callosum, bilateral anterior thalamic radiation (ATR), right posterior thalamic radiation (PTR), right superior longitudinal fasciculus (SLF), and left anterior corona radiate (ACR). Conclusion: Our study found that patients with chronic low back pain have impaired empathy ability. The abnormal functional connectivity of multiple brain networks, multiple damaged white matter tracts, and the lower behavioral scores in chronic low back pain patients supported our findings.


Bacterial community richness shifts the balance between volatile organic compound-mediated microbe-pathogen and microbe-plant interactions.
Even though bacteria are important in determining plant growth and health via volatile organic compounds (VOCs), it is unclear how these beneficial effects emerge in multi-species microbiomes. Here we studied this using a model plant-bacteria system, where we manipulated bacterial community richness and composition and determined the subsequent effects on VOC production and VOC-mediated pathogen suppression and plant growth-promotion. We assembled VOC-producing bacterial communities in different richness levels ranging from one to 12 strains using three soil-dwelling bacterial genera (Bacillus, Paenibacillus and Pseudomonas) and investigated how the composition and richness of bacterial community affect the production and functioning of VOCs. We found that VOC production correlated positively with pathogen suppression and plant growth promotion and that all bacteria produced a diverse set of VOCs. However, while pathogen suppression was maximized at intermediate community richness levels when the relative amount and the number of VOCs were the highest, plant growth promotion was maximized at low richness levels and was only affected by the relative amount of plant growth-promoting VOCs. The contrasting effects of richness could be explained by differences in the amount and number of produced VOCs and by opposing effects of community productivity and evenness on pathogen suppression and plant-growth promotion along the richness gradient. Together, these results suggest that the number of interacting bacterial species and the structure of the rhizosphere microbiome drive the balance between VOC-mediated microbe-pathogen and microbe-plant interactions potentially affecting plant disease outcomes in natural and agricultural ecosystems.


Two nations: racial disparities in bloodstream infections recorded at Alice Springs Hospital, central Australia, 2001-2005.
To compare bloodstream infection (BSI) rates, pathogens and mortality among Indigenous and non-Indigenous adults in central Australia. Retrospective study of adult patients (aged > or = 15 years) admitted to Alice Springs Hospital (ASH) between 1 January 2001 and 31 December 2005. Patients were followed up until 30 June 2008. Admission-based and population-based BSI rates and mortality rates for Indigenous and non-Indigenous adults. During the study period, there were 824 BSI episodes (Indigenous, 753; non-Indigenous, 71). The admission-based BSI rate for Indigenous patients was 26.5 (95% CI, 26.4-26.6) per 1000 adult admissions, compared with 5.2 (95% CI, 5.1-5.2) per 1000 adult admissions for non-Indigenous patients (infection rate ratio [IRR], 5.13 [95% CI, 5.10-5.18]). The population-based BSI rate was 1354.7 (95% CI, 1256.3-1460.8) per 100 000 persons per year among Indigenous patients and 69.9 (95% CI, 55.1-88.6) per 100 000 persons per year among non-Indigenous patients (IRR, 19.4 [95% CI, 15.1-24.9]). These differences were not explained by higher comorbidity levels among Indigenous patients. Human T-cell lymphotropic virus type 1 and Strongyloides stercoralis infected 43% and 35%, respectively, of Indigenous patients tested. The risk of death during the follow-up period was 32.1% for Indigenous and 13.4% for non-Indigenous patients (hazard ratio [HR], 2.69 [95% CI, 1.38-5.25]; P = 0.004). Mortality rates were higher among Indigenous patients who had more than a single BSI (HR, 1.86 [95% CI, 1.32-2.62]; P < 0.001). The mean age at death was 48.5 years (SD, 16.2 years) for Indigenous patients and 75.1 years (SD, 18.7 years) for non-Indigenous patients (P < 0.001). Indigenous adults living in central Australia experience BSI rates that are among the highest reported in the world. These are associated with a high risk of death, and are a likely consequence of the poor socioeconomic circumstances of Indigenous people.


Use of cutting balloons in coronary interventions.
To study the efficacy and safety of cutting balloons in coronary interventions. Twenty-two patients with 23 narrowed coronary arteries and 25 lesions enrolled the study, 17 of whom had 18 diseased coronary arteries and 18 lesions were in-stent restenosis. The average time from previous stenting was 7.60 +/- 3.53 months. The lesions were dilated with cutting balloons. All of the lesions were dilated successfully by 5.16 +/- 2.30 inflations of a cutting balloon. The mean total duration of balloon inflation was 233.96 +/- 94.83 seconds at pressures up to 9.40 +/- 1.96 bars. The severity of vascular stenosis was lessened substantially (89.64 +/- 8.65% vs 17.60 +/- 17.15%, P = 0.000) without severe complications. Three restenotic lesions were further dilated with conventional balloons, another one was stented again because of a dissection distal to the previous stent. Three primary lesions were stented for dissection or residual stenosis. Angina pectoris reoccurred in two patients in a mean follow-up period of 7.42 +/- 6.87 (range 0.5-20) months. Cutting balloon dilation is an effective and safe choice in interventions for coronary disease especially for in-stent restenosis.


Hyperthyroidism and atrial myxoma--an intriguing cardio-endocrine association.
A 65-year-old woman presented with dyspnea and bilateral leg edema for 1 week, worsening fatigue for 1 month, and a 7-lb weight loss over the last summer. She was clinically and biochemically hyperthyroid. Echocardiography revealed a left atrial myxoma measuring 6.2 x 3.3 cm protruding into the mitral orifice and left ventricle during diastole. She was treated for Graves' disease with Iodine-131. Six weeks later, her left atrial myxoma measuring 10.1 x 6.2 x 2.4 cm was resected. She became euthyroid before surgery and then biochemically hypothyroid 6 weeks after radioiodine treatment, for which she subsequently required thyroxine replacement. Atrial myxomas are the most common primary cardiac neoplasms. At least 5% to 10% can be attributed to Carney's complex. More than two-thirds of patients with Carney's complex develop one or more cardiac myxomas. Although atrial myxomas in Carney's complex are histologically indistinguishable from the sporadic form, their clinical presentation and course is distinct. This is the first case of newly diagnosed Graves' disease that has been reported in association with an atrial myxoma. The features discussed in this article help differentiate between syndromic and sporadic atrial myxomas.


Substantial genetic influence on mild mental impairment in early childhood.
We report the first major genetic study of mild mental impairment. From a representative sample of 3886 twins (1314 monozygotic, 1296 dizygotic same-sex, and 1276 dizygotic opposite-sex), the lowest 5% were selected on a composite measure of verbal and nonverbal abilities assessed by parents when the twins were 2, 3, and 4 years of age. Twin concordances for mild mental impairment were 74% for monozygotic twins, 45% for same-sex, and 36% for opposite-sex dizygotic twins, indicating substantial genetic influence. Model-fitting analyses estimated group heritability as.49, which is significantly greater than heritability for the rest of the population in early childhood. These results suggest that mild mental impairment is a good target for neuroscience research on global brain function and dysfunction.


Evaluating measures of redundancy in clinical texts.
Although information redundancy has been reported as an important problem for clinicians when using electronic health records and clinical reports, measuring redundancy in clinical text has not been extensively investigated. We evaluated several automated techniques to quantify the redundancy in clinical documents using an expert-derived reference standard consisting of outpatient clinical documents. The technique that resulted in the best correlation (82%) with human ratings consisted a modified dynamic programming alignment algorithm over a sliding window augmented with a) lexical normalization and b) stopword removal. When this method was applied to the overall outpatient record, we found that overall information redundancy in clinical notes increased over time and that mean document redundancy scores for individual patient documents appear to have cyclical patterns corresponding to clinical events. These results show that outpatient documents have large amounts of redundant information and that development of effective redundancy measures warrants additional investigation.


Challenging case of deficient mismatch repair right-sided locally advanced adenocarcinoma of the ascending colon with duodenal involvement: A case report including step-by-step video of operation.
Irresectable colon cancer presents a complex clinical challenge. Neoadjuvant immunotherapy has shown potential in improving resectability. Additionally, advancements in surgical techniques, including complete mesocolic excision (CME) with central vascular ligation (CVL), have contributed to better outcomes for right-sided colon cancer. This case report aims to demonstrate the successful laparoscopic resection of initial appearing irresectable colon cancer with suspected duodenal involvement. A 70-year-old female presented with an irresectable mismatch repair deficient (dMMR) adenocarcinoma of the ascending colon with suspected duodenal ingrowth. Neoadjuvant treatment with pembrolizumab and ataluren resulted in a significant response, allowing for surgical resection. A laparoscopic right hemicolectomy with CME, including CVL, intracorporeal anastomosis and extraction through a Pfannenstiel incision, was performed. Additionally, the serosal layer of the duodenum was shaved after observing the absence of intraluminal invasion. Postoperatively, transient gastroparesis occurred, but overall outcomes were favourable. This case emphasizes the potential of immunotherapy in improving resectability for irresectable dMMR colon cancer with suspected involvement of surrounding organs. The combination of neoadjuvant therapy and advanced surgical techniques, such as CME with CVL, shows promise in achieving favourable clinical outcomes. However, further studies are needed to validate the effectiveness and safety of this combined approach in a larger cohort of patients. The successful laparoscopic resection of initially irresectable dMMR colon cancer with duodenal involvement, following neoadjuvant immunotherapy, demonstrated promising outcomes. This case advocates for further exploration of neoadjuvant treatments' efficacy, coupled with advanced surgical techniques, in managing locally advanced right-sided colon cancer.


Modulation of desmin intermediate filament assembly by a monoclonal antibody.
We have used a monoclonal antibody against desmin to examine the assembly of intermediate filaments (IF) from their building blocks, the tetrameric protofilaments. The antibody, designated D76, does not cross react with any other IF proteins (Danto, S.I., and D.A. Fischman. 1984. J. Cell Biol. 98:2179-2191). It binds to a region amino-terminal to cys-324 of avian desmin that is resistant to chymotrypsin and trypsin digestion, and in the electron microscope appears to bind to the ends of tetrameric protofilaments. In combination, these findings suggest that the epitope of the antibody resides at the amino-terminal end of the alpha-helical rod domain. Preincubation of desmin protofilaments with an excess of D76 antibodies blocks their subsequent assembly into IF. In the presence of sub-stoichiometric amounts of antibodies, IF are assembled from protofilaments but they are morphologically aberrant in that (a) they are capped by IgG molecules at one or both ends; (b) they are unraveled to varying degree, revealing a characteristic right-handed helical arrangement of sub-filamentous strands of different diameters. The antibody binds only to the ends but not along the length of desmin IF. The most straightforward explanation for this is that the epitope resides in a part of the desmin molecule that becomes buried within the core of the filament upon polymerization and is therefore inaccessible to the antibody.


2014 focused update of the Canadian Cardiovascular Society Guidelines for the management of atrial fibrillation.
Atrial fibrillation (AF) is an extremely common clinical problem with an important population morbidity and mortality burden. The management of AF is complex and fraught with many uncertain and contentious issues, which are being addressed by extensive ongoing basic and clinical research. The Canadian Cardiovascular Society AF Guidelines Committee produced an extensive set of evidence-based AF management guidelines in 2010 and updated them in the areas of anticoagulation and rate/rhythm control in 2012. In late 2013, the committee judged that sufficient new information regarding AF management had become available since 2012 to warrant an update to the Canadian Cardiovascular Society AF Guidelines. After extensive evaluation of the new evidence, the committee has updated the guidelines for: (1) stroke prevention principles; (2) anticoagulation of AF patients with chronic kidney disease; (3) detection of AF in patients with stroke; (4) investigation and management of subclinical AF; (5) left atrial appendage closure in stroke prevention; (6) emergency department management of AF; (7) periprocedural anticoagulation management; and (8) rate and rhythm control including catheter ablation. This report presents the details of the updated recommendations, along with their background and rationale. In addition, a complete set of presently applicable recommendations, those that have been updated and those that remain in force from previous guideline versions, is provided in the Supplementary Material.


3D quantitative evaluation of atherosclerotic plaque based on rotational angiography.
Atherosclerosis is a systemic disease that has been shown to cause various cardiovascular diseases and stroke. However, technologies to evaluate the volume of atherosclerotic plaque are limited. We present a method for determination of 3D plaque volume based on RA. 3DRA images obtained from patients were used to evaluate the plaque. Six patients who were diagnosed with atherosclerotic lesions were included. The PR model developed for 3DRA was applied to analyze the geometry of the vessel and calculate the plaque volume. To validate the present method, we tested computer-generated phantoms with different degrees of stenosis. Application of PR to clinical cases allowed the estimation of plaque morphology and quantification of plaque volume. Technique validation showed that on average, PR can rebuild 92% of the plaque and provide satisfactory determination of plaque volume. A new approach to obtain plaque volume based on 3DRA is presented. The initial tests in 6 clinical cases and validation with different phantoms showed that this method is feasible. Further validation in a larger clinical series is required to assess the ultimate value of the present technique.


Surgical treatment of paravalvular leak: Long-term results in a single-center experience (up to 14 years).
The aim of this study is to report the long-term outcomes (median follow-up time, 7 years; range, 1 month to 14 years) of patients who underwent surgery for paravalvular leak in our single-center experience. From October 2000 to November 2007, 122 consecutive patients underwent surgery for symptomatic paravalvular leak (40 patients with aortic paravalvular leak; 82 with mitral paravalvular leak). In 7 patients (5.7%, all mitral), surgery was performed on the beating heart through a right thoracotomy. In 35% of patients, multiple paravalvular leaks were present. The mean age of patients was 62 ± 11 years, and European System for Cardiac Operative Risk Evaluation II was 7.2% ± 6%. Most of the patients were in New York Heart Association functional class III or IV (60%). Symptomatic hemolysis was present in 31% of the patients, and 41% of the patients had more than 1 previous cardiac operation. Paravalvular leak repair was feasible in 79 patients (65%), whereas in 43 patients (35%) prosthesis re-replacement was required. Thirty-day mortality was 10.7% (13/122 patients; 5% for aortic paravalvular leak and 13% for mitral paravalvular leak; P = .1); 2 patients (1.6%) with residual severe mitral paravalvular leak underwent successful redo surgery before discharge. Median length of stay was 7 days. Overall actuarial survival was 39% ± 6% at 12 years; freedom from cardiac death was 54% ± 7% at 12 years. Only 1 patient underwent redo surgery during follow-up. Multivariable analysis identified preoperative chronic renal failure (hazard ratio, 2.6; 95% confidence interval, 1.4-4.9; P = .03) and more than 1 previous cardiac reoperation (hazard ratio, 2.3; 95% confidence interval, 1.3-4; P = .03) as independent predictors of death at follow-up. The operative mortality of surgical treatment of paravalvular leak is still high. Long-term outcomes remain suboptimal in these challenging patients, especially in the presence of multiple previous cardiac operations and associated co-pathologies. These results support the importance of alternative therapeutic options.


High-Intensity Interval Training and Moderate-Intensity Continuous Training in Ambulatory Chronic Stroke: Feasibility Study.
Poststroke guidelines recommend moderate-intensity, continuous aerobic training (MCT) to improve aerobic capacity and mobility after stroke. High-intensity interval training (HIT) has been shown to be more effective than MCT among healthy adults and people with heart disease. However, HIT and MCT have not been compared previously among people with stroke. The purpose of this study was to assess the feasibility and justification for a definitive randomized controlled trial (RCT) comparing HIT and MCT in people with chronic stroke. A preliminary RCT was conducted. The study was conducted in a cardiovascular stress laboratory and a rehabilitation research laboratory. Ambulatory people at least 6 months poststroke participated. Both groups trained 25 minutes, 3 times per week, for 4 weeks. The HIT strategy involved 30-second bursts at maximum-tolerated treadmill speed alternated with 30- to 60-second rest periods. The MCT strategy involved continuous treadmill walking at 45% to 50% of heart rate reserve. Measurements included recruitment and attendance statistics, qualitative HIT acceptability, adverse events, and the following blinded outcome variables: peak oxygen uptake, ventilatory threshold, metabolic cost of gait, fractional utilization, fastest treadmill speed, 10-Meter Walk Test, and Six-Minute Walk Test. During the 8-month recruitment period, 26 participants consented to participate. Eighteen participants were enrolled and randomly assigned to either the HIT group (n=13) or the MCT group (n=5). Eleven out of the 13 HIT group participants attended all sessions. Participants reported that HIT was acceptable and no serious adverse events occurred. Standardized effect size estimates between groups were moderate to very large for most outcome measures. Only 30% of treadmill speed gains in the HIT group translated into overground gait speed improvement. The study was not designed to definitively test safety or efficacy. Although further protocol optimization is needed to improve overground translation of treadmill gains, a definitive RCT comparing HIT and MCT appears to be feasible and warranted.


Controlled Orientations of Neighboring Tetracene Units by Mixed Self-Assembled Monolayers on Gold Nanoclusters for High-Yield and Long-Lived Triplet Excited States through Singlet Fission.
Although tetracene (Tc) is well-known as a good candidate for singlet fission (SF), the number of high-yield and long-lived triplet excited states through SF is extremely limited because of the relative acceleration of the reverse triplet-triplet annihilation (TTA) considering the energy matching between a singlet and two triplet states. Systematic control of electronic interactions between two neighboring units using conventional covalent linkages and molecular assembly methods to optimize these kinetic processes is quite difficult because of the complicated synthesis and random orientations. In this study, we propose a novel supramolecular strategy utilizing mixed self-assembled monolayers (SAMs) with two different chain lengths. Specifically, mixed Tc-SAMs on gold nanoclusters, which are prepared using Tc-modified heterodisulfides with two different chain lengths, attain high-yield SF (ΦSF ≈ 90%) and individual triplet yields (ΦΤ ≈ 160%). The obtained ΦSF is the highest value among Tc derivatives in homogeneous solution to the best of our knowledge.


CYP2D6-guided opioid therapy for adults with cancer pain: A randomized implementation clinical trial.
The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer-related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6-guided opioid prescribing for patients with cancer and reported pilot outcome data. Adult patients from two cancer centers were prospectively enrolled into a hybrid implementation-effectiveness clinical trial and randomized to CYP2D6-genotype-guided opioid selection, with clinical recommendations, or usual care. Implementation metrics, including provider response, medication changes consistent with recommendations, and patient-reported pain and symptom scores at baseline and up to 8 weeks, were assessed. Most (87/114, 76%) patients approached for the study agreed to participate. Of 85 patients randomized, 71% were prescribed oxycodone at baseline. The median (range) time to receive CYP2D6 test results was 10 (3-37) days; 24% of patients had physicians acknowledge genotype results in a clinic note. Among patients with CYP2D6-genotype-guided recommendations to change therapy (n = 11), 18% had a change congruent with recommendations. Among patients who completed baseline and follow-up questionnaires (n = 48), there was no difference in change in mean composite pain score (-1.01 ± 2.1 vs. -0.41 ± 2.5; p = 0.19) or symptom severity at last follow-up (3.96 ± 2.18 vs. 3.47 ± 1.78; p = 0.63) between the usual care arm (n = 26) and genotype-guided arm (n = 22), respectively. Our study revealed high acceptance of pharmacogenetic testing as part of a clinical trial among patients with cancer pain. However, provider response to genotype-guided recommendations was low, impacting assessment of pain-related outcomes. Addressing barriers to utility of pharmacogenetics results and clinical recommendations will be critical for implementation success.


Measurement variability and sincerity of effort: clinical utility of isokinetic strength coefficient of variation scores.
Although the use of measures of strength variability as a means of judging sincerity of effort is becoming common practice, the accuracy of doing so has been questioned. Coefficient of variation (CV) cut-off points, indicating the upper limit of variability for repeated maximal efforts, are routinely used to identify workers providing submaximal efforts during various strength tests. However, the stability of the CV itself has not been considered when comparing an individual's observed CV score to these cut-off points. The purpose of the present study was to examine the day-to-day variability of the CV calculated from maximal isokinetic knee extension efforts, and to describe how this measurement error affects the accuracy of the CV as a distinguishing criterion between maximal and submaximal efforts. Thirty-one healthy males (mean age 25 +/- 4.5 years) completed three maximal and three submaximal isokinetic knee extension efforts on two separate occasions. Although submaximal CVs were significantly greater than maximal CVs (15.6 versus 3.7%; p < 0.01), there was considerable overlap between submaximal and maximal CV frequency distributions. More importantly, an individual observed CV could vary +/- 3.1% as a result of day-to-day variation or measurement error. This range in possible CV scores should be considered when comparing an individual's score to proposed cut-off points. Since individual CVs vary considerably from day-to-day, and since precise cut-off values distinguishing between maximal and submaximal conditions cannot be identified, CV scores must be interpreted cautiously, and the potential errors in relying extensively on this approach to identifying insincere efforts should be recognised.


Identification and characterization of proteins involved in nuclear organization using Drosophila GFP protein trap lines.
Strains from a collection of Drosophila GFP protein trap lines express GFP in the normal tissues where the endogenous protein is present. This collection can be used to screen for proteins distributed in the nucleus in a non-uniform pattern. We analyzed four lines that show peripheral or punctate nuclear staining. One of these lines affects an uncharacterized gene named CG11138. The CG11138 protein shows a punctate distribution in the nuclear periphery similar to that of Drosophila insulator proteins but does not co-localize with known insulators. Interestingly, mutations in Lamin proteins result in alterations in CG11138 localization, suggesting that this protein may be a novel component of the nuclear lamina. A second line affects the Decondensation factor 31 (Df31) gene, which encodes a protein with a unique nuclear distribution that appears to segment the nucleus into four different compartments. The X-chromosome of males is confined to one of these compartments. We also find that Drosophila Nucleoplasmin (dNlp) is present in regions of active transcription. Heat shock leads to loss of dNlp from previously transcribed regions of polytene chromosome without redistribution to the heat shock genes. Analysis of Stonewall (Stwl), a protein previously found to be necessary for the maintenance of germline stem cells, shows that Stwl is present in a punctate pattern in the nucleus that partially overlaps with that of known insulator proteins. Finally we show that Stwl, dNlp, and Df31 form part of a highly interactive network. The properties of other components of this network may help understand the role of these proteins in nuclear biology. These results establish screening of GFP protein trap alleles as a strategy to identify factors with novel cellular functions. Information gained from the analysis of CG11138 Stwl, dNlp, and Df31 sets the stage for future studies of these proteins.


Levels and Associations of Weight Misperception with Healthy Lifestyle among Adults in Saudi Arabia.
Obesity affects more than one-quarter of adults in Saudi Arabia and is on the rise. A significant proportion of overweight and obese individuals misperceive their weight, and this misperception can affect their likelihood to exercise, consume healthy foods, or change unhealthy dietary habits. This study examines the prevalence of weight misperceptions in a national sample of Saudi adults and explores weight misperception association with sociodemographic factors, behavioral factors, and health status. This study was a nationwide cross-sectional survey conducted via phone interviews. A proportional quota sampling technique was used to obtain equal distributions of participants, stratified by age and gender, across the 13 regions of Saudi Arabia. Weight and height were self-reported, and obesity was determined as a BMI ≥30. Participants were asked to describe their current weight as ideal, underweight, overweight, or obese. Misclassification was then compared across groups according to a range of sociodemographic factors, behavioral risk factors, and health indicators. Of the 6,239 participants contacted, 4,709 (75.5%) responded and completed the interview. Of them, 50.1% were female, and the mean age was 36.4 (SD ± 13.55) years. The majority (70.1%) of participants indicated having weighed themselves within the past 30 days. The prevalence of weight misperception in general was 42.0%, and in obese participants, it was 67.6%. In addition, a significant association was observed between weight misperception and obesity, age-group, educational level, diagnosed chronic condition, self-rated health, and sedentary lifestyle. There was no significant association between weight misperception and gender, physical activity, or a nutritional knowledge. Weight misperception could be used as an indicator of a poor health routine that may lead to negative health outcomes.


Kleine-Levin syndrome is associated with LMOD3 variants.
Kleine-Levin syndrome (KLS) is a rare periodic hypersomnia with associated behavioural abnormalities but with often favourable prognosis. There is excess risk of KLS in first-degree relatives, suggesting a strong genetic contribution. So far, no mutation is identified in KLS and comprehensive genetic analysis of affected individuals is lacking. Here we performed whole genome single-nucleotide polymorphism (SNP) genotyping and exome sequencing in a large family with seven affected members. The identified gene with a mutation was resequenced in 38 sporadic KLS patients and the expression of the gene product was mapped in the mouse brain. Linkage analysis mapped the disease locus to chromosome 3 and exome analysis identified a heterozygous missense variant in LMOD3 (p.E142D) in the linkage interval. The variant was found to segregate in all affected and one presumably unaffected member of the family. Resequencing LMOD3 in 38 other KLS patients and their families revealed three other low frequency or rare missense variants in seven cases that were inherited with incomplete penetrance. LMOD3 is expressed in the brain and colocalized with major structures involved in the regulation of vigilance states. LMOD proteins are structural proteins and seem to be developmentally regulated. Our findings suggest that KLS might be a structural/neurodevelopmental brain disease.


The role of mandibular condylar cartilage in articular cartilage repair.
The articular hyaline cartilage of synovial joints has a very limited capacity for repair after injury. In contrast, the mandibular condylar cartilage of the temporomandibular joint possesses as intrinsic potential for regeneration. This study aimed to test the hypothesis that cultured allografts of mandibular condylar cartilage could be used to promote biological repair of injured orthotopic joint surfaces. Using a primate animal model, cultures of mandibular condylar cartilage cells were grafted into surgically created defects in a recipient hyaline cartilage joint surface. Articular wound healing was assessed macroscopically and histologically over a postoperative period of 52 weeks. Mandibular condylar cartilage cells scheduled for allogenous transplantation were initially characterised in vitro. Expansion of primary colonies in organ culture provided the allogenic cellular material for in vivo grafting. Grafting of osteochondral articular wounds with 5-week cultures of mandibular cartilage cells led to wound regeneration with complete reconstitution of articular surface continuity by 52 weeks. There was novel synthesis of cartilage collagens and sulphated glycosaminoglycans within the repair tissue and no evidence of immunological rejection. Healing of grafted defects was thought to occur by a combination of donor cell proliferation and ingress of host mesenchymal cells. In contrast, grafted control wounds underwent largely fibrous repair with incomplete articular regeneration. In conclusion, transplanted allografts of cultured mandibular condylar cartilage appeared to have the ability, in this primate model, to promote cartilaginous repair and regeneration of orthotopic articular wounds.


Amplification of the effects of drug resistance mutations by background polymorphisms in HIV-1 protease from African subtypes.
The vast majority of HIV-1 infections worldwide are caused by the C and A viral subtypes rather than the B subtype prevalent in the United States and Western Europe. Genomic differences between subtypes give rise to sequence variations in the encoded proteins, including those identified as targets for antiretroviral therapies. In the case of the HIV-1 protease, we reported earlier [Velazquez-Campoy et al. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 6062-6067] that proteases from the C and A subtypes exhibit a higher biochemical fitness in the presence of widely prescribed protease inhibitors. In this paper we present a complete thermodynamic dissection of the differences between proteases from different subtypes and the effects of the V82F/I84V drug-resistant mutation within the framework of the B, C, and A subtypes. These studies involved four inhibitors in clinical use (indinavir, saquinavir, ritonavir, and nelfinavir) and a second-generation protease inhibitor (KNI-764). Naturally occurring amino acid polymorphisms found in proteases from the C and A subtypes lower the binding affinities of existing clinical inhibitors by factors ranging between 2 and 7.5 which by themselves are not enough to cause drug resistance. The preexisting lower affinity in the C and A subtypes, however, significantly amplifies the effects of the drug-resistant mutation. Relative to the wild-type B subtype protease, the V82F/I84V drug-resistant mutation within the C and A subtypes lowers the binding affinity of inhibitors by factors ranging between 40 and 3000. When the enzyme kinetic properties (k(cat) and K(m)) are included in the analysis, the biochemical fitness of the C and A subtype drug-resistant mutants can be up to 1000-fold higher than that of the wild-type B subtype protease in the presence of the studied inhibitors. From a thermodynamic standpoint, the combined effects of the drug-resistant mutations and the natural amino acid polymorphisms on the Gibbs energy are additive and involve significant alterations in the enthalpy and entropy changes associated with inhibitor binding. At the biochemical level, the combined effects of naturally existing polymorphisms and drug-resistant mutations might have important consequences on the long-term viability of current HIV-1 protease inhibitors.


National Economic Burden Associated with Management of Periodontitis in Malaysia.
Objectives. The aim of this study is to estimate the economic burden associated with the management of periodontitis in Malaysia from the societal perspective. Methods. We estimated the economic burden of periodontitis by combining the disease prevalence with its treatment costs. We estimated treatment costs (with 2012 value of Malaysian Ringgit) using the cost-of-illness approach and included both direct and indirect costs. We used the National Oral Health Survey for Adults (2010) data to estimate the prevalence of periodontitis and 2010 national census data to estimate the adult population at risk for periodontitis. Results. The economic burden of managing all cases of periodontitis at the national level from the societal perspective was approximately MYR 32.5 billion, accounting for 3.83% of the 2012 Gross Domestic Product of the country. It would cost the nation MYR 18.3 billion to treat patients with moderate periodontitis and MYR 13.7 billion to treat patients with severe periodontitis. Conclusion. The economic burden of periodontitis in Malaysia is substantial and comparable with that of other chronic diseases in the country. This is attributable to its high prevalence and high cost of treatment. Judicious application of promotive, preventive, and curative approaches to periodontitis management is decidedly warranted.


Association of Transoral Robotic Surgery With Short-term and Long-term Outcomes and Costs of Care in Oropharyngeal Cancer Surgery.
The treatment of oropharyngeal cancer has undergone a paradigm shift in the past 2 decades, with an increase in the use of nonoperative treatment owing to poor functional outcomes associated with traditional surgical approaches. Transoral robotic surgery (TORS) allows surgical resection of oropharyngeal cancer (OPC) with less morbidity through a minimally invasive approach. To investigate the relationship among TORS and short- and long-term outcomes and costs in surgically treated patients with OPC. Retrospective cross-sectional analysis of 3573 patients who underwent an ablative procedure for OPC in 2010 to 2012 using the MarketScan Commercial Claim and Encounters database. The association between TORS and short- and long-term outcomes, length of hospitalization, and treatment-related costs was analyzed using descriptive statistics and multivariate regression modeling. Transoral robotic surgery was performed in 304 surgical cases (8.5%); 94.7% of patients were 40 to 64 years old, and 70.7% were male. The use of TORS increased from 4.1% of surgical cases in 2010 to 13.2% of surgical cases in 2012. Patients who underwent TORS had a lower rate of tracheotomy during treatment (3.9% vs 11.4%), and posttreatment gastrostomy tube use (21.9% vs 34.2%), compared with patients undergoing non-TORS procedures. On multivariate analysis, TORS was not associated with significant differences in postoperative complications or length of hospitalization. There was no significant difference in the odds of receiving postoperative radiation therapy between patients who underwent TORS and those who did not; however, among patients receiving radiation therapy, chemoradiation was significantly less likely following TORS (odds ratio [OR], 0.52; 95% CI, 0.29-0.90). TORS was associated with significantly decreased odds of posttreatment gastrostomy (OR, 0.54; 95% CI. 0.30-0.95) and tracheostomy during treatment (OR, 0.17; 95% CI, 0.06-0.55) at 1 year, and was associated with significantly decreased overall treatment-related costs of care (mean incremental cost, -$22 724). The use of TORS for surgical resection of OPC is increasing in the United States and is associated with significantly lower use of adjuvant chemoradiation, late gastrostomy and tracheostomy dependence, and lower overall treatment-related costs of care. These data have implications for discussions of value in OPC care at a time of health care reform.


Closed Shop or Collaborative Hub? An Analysis of the Partners' Importance in CANZUK Countries' Research Collaborations.
Collaborative partners are important in international research collaboration. The research collaborations between four CANZUK countries (Canada, Australia, New Zealand and the United Kingdom) are examined to see whether their research connections are different from the research relationships with other countries. This paper measures the affinity index values and analyses the development of research collaborations among CANZUK countries with those between the CANZUK and other countries. The whole counting method and the fractional counting method are applied in this study to compare the differences in the results. The findings show that although the affinity index values of CANZUK countries were decreasing over time, the importance of CANZUK partners to CANZUK countries has likely increased over time at the expense of the other partners' importance. The study also shows the minor differences in results obtained by applying two different counting methods. These differences can be explained by the nature of the counting methods, and the choice to use either one of these two counting methods should be considered in other international research collaboration studies.


Blastocyst environment and its influence on offspring cardiovascular health: the heart of the matter.
The development of adult-onset diseases such as type II diabetes, obesity and cardiovascular disease is traditionally attributed to adult lifestyle characteristics such as a lack of physical exercise, poor diet and smoking. However, evidence from both human and animal model studies has demonstrated that environmental factors such as an imbalance or reduction in maternal nutrition during gestation can have adverse effects on offspring metabolism and cardiovascular health. The severity and nature of the phenotypic changes induced in offspring is influenced by the period of gestation manipulated. In particular, the mammalian preimplantation embryo in different animal models displays particular sensitivity to environmental factors, either in vivo (maternal diet) or in vitro (embryo culture) that is associated with the onset of cardiovascular dysfunction in adult life. The detailed mechanisms by which environmental conditions can alter postnatal cardiovascular physiology are poorly understood. However, various factors including endothelial function, vascular responsiveness, the renin-angiotensin system, kidney structure and early postnatal growth dynamics have all been recognize as potential contributors. Here, we review the relationship between preimplantation embryo environment and postnatal cardiovascular disease risk, and consider biochemical, molecular, genetic and physiological pathways implicated in this association.


The impact of NCCN-compliant multidisciplinary conference on the uptake of active surveillance among eligible patients with localized prostate cancer.
We sought to investigate the impact of National Comprehensive Cancer Network (NCCN)-compliant multidisciplinary conference on the uptake of active surveillance (AS) among eligible patients with prostate cancer. Retrospective review of our AS database was performed. Patients who are eligible for AS who sought a second opinion at a comprehensive cancer center (2010-2021) were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Cochrane Armitage test was used to examine trends over time. Multivariable regression models were fit to evaluate variables associated with the receipt of AS. Seven hundred twelve patients were identified (19% NCCN very low risk, 32% low risk, and 49% intermediate favorable risk). 43% were recommended AS as the preferred option by the community compared to 68% by LPCC, and 65% elected AS. Recommending AS significantly increased between 2010 and 2021 by the community (from 26% to 57%) and by LPCC (from 52% to 82%), while the proportion of men who received AS increased from 47% to 80% during the same period (P < 0.0001 for all). More recent LPCC era 2017 to 2021 (OR 12.31, 95% CI, 5.60-27.03, P < 0.0001), African American race (OR 0.42, 95% CI, 0.18-0.96, P = 0.04), positive cores at biopsy (OR 0.96, 95% CI, 0.94-0.97, P < 0.0001), age (OR 1.14, 95% CI, 1.10-1.18, P < 0.0001), NCCN low risk (OR 0.25, 95% CI, 0.08-0.81, P = 0.02) and NCCN intermediate favorable risk (OR 0.03, 95% CI, 0.01-0.09, P < 0.0001) were associated with receipt of AS. AS recommendation increased significantly over time by community urologists and to a higher extent by NCCN-compliant multidisciplinary conference. The Uptake of AS significantly increased within the same period. More recent LPCC era 2017 to 2021, African American race, the proportion of positive cores at biopsy, age, and NCCN risk were the main determinants of receipt of AS.


Trauma, stress and multiple sclerosis.
It has been suggested that physical trauma, involving the cervical spinal cord or the brain, and psychological stress may precede MS onset or may influence the disease course, although this hypothesis has mainly come from anecdotal case reports or small uncontrolled or controlled studies. So far there are no studies providing a clear causative relationship between physical trauma (especially head trauma) and MS onset, exacerbation or progression of the disease. On the other hand, recent MRI and experimental studies, supporting the important role of nervous and immune system interactions, particularly by the hypothalamic-pituitary-adrenal axis and by the sympathetic nervous pathways, seem to demonstrate a significant correlation between stress and MS exacerbations. Further frequent MRI and immunological evaluations should be warranted to objectively document the temporal association between stress and clinical and/or sub-clinical disease activity.


Color Stability of CAD/CAM Ceramics Prepared with Different Surface Finishing Procedures.
To investigate the color stability of zirconia-reinforced lithium silicate glass-ceramic and lithium disilicate reinforced glass-ceramic, which were prepared with various surface finishing procedures, following 1-week, 2-week, 1-month, and 2-month storage in various beverages, and after the application of polishing paste. Lithium disilicate glass-ceramic (IPS e.max CAD HT) and zirconia-reinforced lithium silicate ceramic (Vita Suprinity HT) CAD/CAM blocks were sectioned with a diamond saw (Metkon) under water cooling into 1.5 × 7 × 12 mm dimensions (N = 120). All specimens were polished with silicon carbide paper (600-, 800-, and 1200-grit) under water for 120 seconds. The specimens were prepared using 3 surface finishing procedures: glaze, mechanical polishing, and external staining and glaze in accordance with manufacturers' instructions. Then, each group was divided into 2 storage subgroups, black tea and coffee (n = 10/group). Color values were measured in CIELAB color space with dental spectrophotometer (VITA Easyshade) at the initial stage, and following 1-week, 2-week, 1-month, 2-month storage, and after fine-grit polishing paste application (Proxyt). Color changes (ΔE) were calculated and statistically analyzed using ANOVA followed by Bonferroni corrected post-hoc tests using Number Cruncher Statistical System 2007 (α < 0.05). For lithium disilicate glass-ceramic, glaze procedure showed statistically lower color change values than mechanical polishing and external staining and glaze surface finishing groups (p < 0.05) following storage in both beverages, whereas for zirconia-reinforced lithium silicate ceramic, glaze procedure showed statistically lower color change values than mechanical polishing, but statistically insignificant values with respect to external staining and glaze group, following storage in both beverages. Lithium disilicate glass-ceramic groups showed statistically lower or statistically insignificant color change values with respect to zirconia-reinforced lithium silicate ceramic groups, except for the external staining and glaze surface finishing group in coffee. Significantly lower discoloration values were obtained following polishing paste application, with respect to 2-month storage in beverages (p < 0.05). Glazing alone led to more color stability with respect to mechanical polishing and external staining and glaze for zirconia-reinforced lithium silicate and lithium disilicate glass-ceramic. Lithium disilicate glass-ceramic showed higher color stability compared to zirconia-reinforced lithium silicate ceramic. Polishing paste resulted in a decrease in discoloration to clinically acceptable values.


Oxidative stress enhances rotavirus oncolysis in breast cancer and leukemia, except in melanoma with abundant matrix.
This study aimed to explore the impact of oxidative stress and extracellular matrix integrity on rotavirus infection in various cancer cells, including breast cancer, acute lymphoblastic leukemia, and melanoma. We induced oxidative stress using ROS-inducing drugs (cisplatin, metronidazole, melatonin, valproic acid, doxorubicin, losartan, nitrofurantoin, and DHA) and investigated the effects on viral infection in MCF-7, Reh, A375, B16-F1, and SK-MEL-28 cells and the generation of virions from infected cells by harvesting the supernatants every two hours, reinfecting other cells, and analyzing cell viability and DNA fragmentation. In MCF-7 and Reh cells, rotavirus Wt1-5 infection led to increased ROS generation, virion production, membrane permeability, mitochondrial dysfunction, DNA damage, and cell death. These effects were amplified by ROS-inducing drugs. Conversely, melanoma cells (SK-MEL-28 and A375) with a robust extracellular matrix network showed limited sensitivity to the drugs. Notably, losartan, which modulates the extracellular matrix, enhanced viral infection in melanoma cells (99 %). Oxidative stress promotes oncolytic rotavirus infection in breast cancer and acute lymphoblastic leukemia cells, suggesting potential utility in combination with radiotherapy or chemotherapy due to their shared induction of intracellular oxidative stress.


Gene expression analysis to identify mechanisms underlying improvement of myocardial fibrosis by finerenone in SHR.
Both spironolactone and finerenone treatments significantly reduced SBP and there was no statistical difference in their antihypertensive effects. The differences in body weight (at the end of 1/2/3/4 week) to pre-dose body weight ratio and heart rate (at the end of 1/2/3/4 week) to pre-dose heart rate ratio were not statistically significant in the vehicle, spironolactone, finerenone, and control groups.There was no statistically significant difference in mortality among the vehicle, spironolactone, and finerenone groups. The relative heart mass, ANP, BNP, CVF, Col I, TGF-β, and Casp-3 were gradually decreased in vehicle group, spironolactone group, and finerenone group. Among them, BNP, CVF, TGF-β, and Casp-3 were significantly decreased in the finerenone group compared with the vehicle group. HE and Masson staining showed that the cardiomyocytes of rats in the vehicle group and spironolactone group were disorganized, with cell hypertrophy, significantly enlarged cell gaps and a large amount of collagen deposition, whereas the cardiomyocytes of rats in the finerenone group and the control group were more neatly arranged, with smaller cell gaps and a small amount of collagen tissue deposition. RNA sequencing (RNA-seq) showed that there was a total of 119 differentially expressed genes (DEGs) between finerenone treatment and vehicle treatment. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that the signaling pathways involved were mainly in drug metabolism-cytochrome P450, chemical carcinogenesis, IL-17 signaling pathway, axon guidance, and hematopoietic cell lineage. Protein-protein interaction (PPI) analysis showed that the core genes were Oaslf, Nos2, LOC687780, Rhobtb1, Ephb3, and Rps27a.


Trunk muscle balance and muscular force.
An investigation of the absolute strength of the human muscle was carried out on the in vivo erector spinae muscle using magnetic resonance tomography coupled with dynamic muscular testing. The absolute strength of the erector spinae was calculated to be 48 N/cm2. The area of the rectus abdominis was 15.1 cm2, and the area of the erector spinae was 54.5 cm2. The internal moment arm for the rectus abdominis and erector spinae muscles was 7.04 and 5.64 cm, respectively. The static force measures showed the trunk extensor moment to be only 30% greater than the flexor moment. The difference is discussed in terms of the absolute strength of muscle, and other anatomic factors.


Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening.
Adaptive immune function is implicated in the pathogenesis of vascular disease. Inhibition of T-lymphocyte function has been shown to reduce hypertension, target-organ damage, and vascular stiffness. To study the role of immune inhibitory cells, CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), on vascular stiffness, we stimulated the proliferation of Treg lymphocytes in vivo using a novel cytokine immune complex of Interleukin-2 (IL-2) and anti-IL-2 monoclonal antibody clone JES6-1 (mAbCD25). Three-month-old male C57BL/6J mice were treated with IL-2/mAbCD25 concomitantly with continuous infusion of angiotensin type 1 receptor agonist, [Val(5)]angiotensin II. Our results indicate that the IL-2/mAbCD25 complex effectively induced Treg phenotype expansion by 5-fold in the spleens with minimal effects on total CD4(+) and CD8(+) T-lymphocyte numbers. The IL-2/mAbCD25 complex inhibited angiotensin II-mediated aortic collagen remodeling and the resulting stiffening, analyzed with in vivo pulse wave velocity and effective Young's modulus. Furthermore, the IL-2/mAbCD25 complex suppressed angiotensin II-mediated Th17 responses in the lymphoid organs and reduced gene expression of IL-17 as well as T cell and macrophage infiltrates in the aortic tissue. This study provides data that support the protective roles of Tregs in vascular stiffening and highlights the use of the IL-2/mAbCD25 complex as a new potential therapy in angiotensin II-related vascular diseases.


Cerebellar LTD vs. motor learning-lessons learned from studying GluD2.
Synaptic plasticity, such as long-term potentiation and long-term depression (LTD), is believed to underlie learning and memory processes in vivo. The cerebellum is an ideal brain region to obtain definitive proof for this hypothesis. The current belief is that the acquisition of motor learning is stored by LTD at the parallel fiber (PF)-Purkinje cell synapse in the cerebellar cortex. Recently, however, several lines of mutant mice that display normal motor learning in the absence of cerebellar LTD have been reported. A similar dichotomy between synaptic plasticity at the circuitry level and learning at the behavioral level has also been reported in the hippocampus. One possible explanation for this dichotomy is that compensatory pathways at the molecular and circuitry levels play an important role in mice that have been genetically modified for their entire lives. Mice that are genetically modified to be deficient in or to express mutant versions of the δ2 glutamate receptor (GluD2) serve as an interesting model due to the predominant expression of GluD2 at PF-Purkinje cell synapses. Furthermore, two major functions of GluD2-PF synapse formation and LTD induction-can be mechanistically dissociated so that the role of LTD in motor learning can be investigated in the absence of morphological abnormalities caused by altered synapse formation. Therefore, genetic manipulations of GluD2 will help to clarify the relationship between LTD and motor learning in the cerebellum.


Functional adaptive sequential testing.
The study of cognition, perception, and behavior often requires the estimation of thresholds as a function of continuous independent variables (e.g., contrast threshold as a function of spatial frequency, subjective value as a function of reward delay, tracking speed as a function of the number of objects tracked). Unidimensional adaptive testing methods make estimation of single threshold values faster and more efficient, but substantial efficiency can be further gained by taking into account the relationship between thresholds at different values of an independent variable. Here we present a generic method--1functional adaptive sequential testing (FAST)--for estimating thresholds as a function of another variable. This method allows efficient estimation of parameters relating an independent variable (e.g., stimulus spatial frequency; or reward delay) to the measured threshold along a stimulus strength dimension (e.g., contrast; or present monetary value). We formally describe the FAST algorithm and introduce a Matlab toolbox implementation thereof; we then evaluate several possible sampling and estimation algorithms for such two-dimensional functions. Our results demonstrate that efficiency can be substantially increased by considering the functional relationship between thresholds at different values of the independent variable of interest.


Metabolomics and fluxomics approaches.
Systems biology is based on the understanding that the behaviour of the whole is greater than would be expected from the sum of its parts. Thus the ultimate goal of systems biology is to predict the behaviour of the whole system on the basis of the list of components involved. Recent advances in '-omics' technologies and the development of new computational techniques and algorithms have greatly contributed to progress in this field of biology. Among the main '-omics' technologies, metabolomics is expected to play a significant role in bridging the phenotype-genotype gap, since it amplifies changes in the proteome and provides a better representation of the phenotype of an organism than other methods. However, knowledge of the complete set of metabolites is not enough to predict the phenotype, especially for higher cells in which the distinct metabolic processes involved in their production and degradation are finely regulated and interconnected. In these cases, quantitative knowledge of intracellular fluxes is required for a comprehensive characterization of metabolic networks and their functional operation. These intracellular fluxes cannot be detected directly, but can be estimated through interpretation of stable isotope patterns in metabolites. Moreover, analysis of these fluxes by means of metabolic control theories offers a potentially unifying, holistic paradigm to explain the regulation of cell metabolism. In this chapter, we provide an overview of metabolomics and fluxomics, highlighting stable isotope strategies for fluxome characterization. We also discuss some of the tools used to quantitatively analyse the control exerted by components of the network over both the metabolome and the fluxome. Finally, we outline the role and future of metabolomics and fluxomics in drug discovery.


The Accuracy of Classification Systems in Nonsyndromic Sagittal Craniosynostosis.
Numerous classification systems of nonsyndromic sagittal craniosynostosis (NSC) are applied but none has gained a wide acceptance, since each classification is focused on distinct aspects. The aim of the study was to assess the accuracy of 4 classifications of NSC discussed in the literature by defining the associations among the classifications, individual features (sex, age, cranial index), and objective morphologic criteria (frontal bossing, retrocoronal constriction, sagittal ridge, and occipital bulleting). The study was conducted on anonymized thin-cut CT scans of 133 children with NSC 1 to 12 months old (mean age 5.42 mo). The type of cranial dysmorphology was assessed using 4 classification systems, focusing on skull shape, pattern of sagittal suture closure (Heuzé classification), deformation of skull vault (Sakamoto classification), and a single-dominant feature (David classification). Each patient was also independently investigated for the presence of morphologic criteria. A multivariate analysis was performed to explore the relations among the classifications and assess their accuracy. In the analyzed cohort sphenocephaly (38.3%), CFF type by Heuzé (30.8%), type I by Sakamoto (72.9%), and a central type by David (42.9%) were dominant findings. Regarding the morphologic criteria, frontal bossing was observed the most frequently (91.7%). The age of patients and cranial index differed significantly among the shapes of skull and David classifications (P<0.001). The shape-based system showed the strongest correlation with other classifications and with measurable variables. Other classifications have much in common and some overlap, but none of them constitutes a standalone system to define all aspects of cranial dysmorphology in NSC.


Association studies of common variants in 10 hypogonadotropic hypogonadism genes with age at menarche.
Although the timing of puberty is a highly heritable trait, little is known about the genes that regulate pubertal timing in the general population. Several genes have been identified that, when mutated, cause disorders of delayed or absent puberty such as hypogonadotropic hypogonadism (HH). Because severe variants in HH-related genes cause a severe puberty phenotype, we hypothesized that common subtle variation in these genes could contribute to the population variation in pubertal timing. We assessed common genetic variation in 10 HH-related genes in 1801 women from the Hawaii and Los Angeles Multiethnic Cohort with either early (age<11 yr) or late (age>14 yr) menarche and in other replication samples. In addition to these common variants, we also studied the most frequently reported HH mutations to assess their role in the population variation in pubertal timing. SETTING AND PATIENTS/OTHER PARTICIPANTS: Within the general community, 1801 women from the Hawaii and Los Angeles Multiethnic Cohort participated. We assessed the association of genetic variation with age at menarche. We found no significant association between any of the variants tested and age at menarche, although we cannot rule out modest effects of these variants or of other variants at long distances from the coding region. In several self-reported racial/ethnic groups represented in our study, we observed an association between estimated genetic ancestry and age at menarche. Our results suggest that common variants near 10 HH-related loci do not play a substantial role in the regulation of age at menarche in the general population.


Post-9/11 veterans' heart disease knowledge, self-perceived risk, and prevention beliefs and behaviors.
Veterans, including the growing number of women veterans, have a greater risk of heart disease than nonveterans, and the incidence of heart disease is increasing among the most recent veterans who participated in post-9/11 military conflicts. Investigating heart disease-related knowledge, self-perceived risk, and prevention beliefs and behavior among these veterans, and identifying potential differences in knowledge, risk, beliefs and behavior between men and women, may guide prevention strategies. Cross-sectional data from a nationwide survey of 1,141 (53% women) post-9/11 veterans were used to examine heart disease awareness and information-seeking, perceived risk and importance of heart disease risk factors, beliefs about traditional (e.g., weight, blood pressure) and nontraditional (e.g., stress, sleep) factors, and engagement in prevention behaviors. Differences between men and women were also tested, using t-tests, chi-square, and Fisher's exact tests. Only one-third reported they felt very informed or sought information about heart disease, or that their providers had discussed heart disease with them. Although veterans generally believe that addressing traditional and nontraditional factors can reduce their risk of heart disease, far fewer endorsed the value of mental health treatment in prevention. Overall, women were slightly more knowledgeable about heart disease risk, and of behaviors that can lower this risk, but for both men and women, this knowledge did not translate to engaging in equivalent prevention behaviors. Post-9/11 veterans, and potentially their providers, may each benefit from improved education regarding their risk of heart disease. Veterans may also require better, more personalized approaches to prevention. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Association Between Episodic Memory and Genetic Risk Factors for Alzheimer's Disease in South Asians from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD).
Genetic factors play an important role in Alzheimer's disease (AD) and cognitive aging. However, it is unclear whether risk loci identified in European ancestry (EA) populations have similar effects in other groups, such as South Asians. We investigated the allelic distribution and cognitive associations of 56 known AD risk single-nucleotide polymorphisms (SNPs) identified from three EA genome-wide association studies (EA-GWASs) in a South Asian population. Single SNP and genetic risk score (GRS) associations with measures of episodic memory were assessed. The Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). A total of 906 LASI-DAD participants from diverse states in India. Participants were genotyped using the Illumina Global Screening Array and imputed with 1000G Phase 3v5. Cognitive measures included total learning and delayed word recall. Although only a few SNPs were significantly associated with memory scores (P < .05), effect estimates from the EA-GWAS and the LASI-DAD showed moderate correlation (0.35-0.88) in the expected direction. GRSs were also associated with memory scores, although percentage variation explained was small (0.1%-0.6%). Discrepancies in allele frequencies and cognitive association results suggest that genetic factors found predominantly through EA-GWASs may play a limited role in South Asians. However, the extent of differences in the genetic architecture of AD and cognition in EA and South Asians remains uncertain. There is also a critical need to perform a more comprehensive assessment of the mutational spectrum of South Asia to identify novel genetic variants associated with AD and cognition in this population. J Am Geriatr Soc 68:S45-S53, 2020.


Metabolic responses of rice source and sink organs during recovery from combined drought and heat stress in the field.
Drought and heat stress effects on rice have been extensively studied, in particular during the sensitive flowering and grain-filling stages. However, in the field these stresses usually occur together because reduced transpirational cooling under drought conditions results in increased plant tissue temperature. In addition, environmental stresses are usually transient and the ability to efficiently recover from stress may be at least as important for overall stress tolerance as the direct stress response itself. Nevertheless, nothing is known about recovery mechanisms after drought and heat stress in rice under field conditions. We have used gas chromatography-mass spectrometry-based metabolomics to elucidate the metabolic responses of flag leaves, flowering spikelets, and developing seeds from 3 rice cultivars differing in their drought and heat tolerance to rewatering after stress in the field. Within 60 hours after rewatering, many stress-responsive metabolites returned to their control levels, although recovery was not complete. In addition, control plants showed developmental differences that were revealed by metabolite profiles during 60 hours of post-stress sampling, in particular in developing seeds. Correlation analysis identified several metabolites as marker candidates for the stability of grain yield or quality under conditions of combined drought and heat stress. The rewatering responses of stressed plants seemed to be a combination of the reversal of stress effects and reinitiation of development after stress relief. The identified potential markers can be useful in efforts to breed stress-tolerant rice germplasm to ensure food availability under changing climate conditions.


[Some characteristics and opinions of graduates from the master's course on epidemiology. Havana 1984--1999].
Data from the Teaching Department records on, age, gender origin and basic profession of foreign and Cuban students were analyzed, including the opinions of a sample of the Cuban graduates up to 1999, who were administered a survey designed to evaluate the impact of the course. "Pedro Kouri" Tropical medicine Institute is giving the Master's course on Epidemiology since 1984. Out of the 254 graduates up to 1999, 97 were foreigners (75 from Spain); 54.8% of the Cubans came from Havana City and Havana provinces. The mean age was 31 years for foreigners and 36.9 years for Cubans. Most of the students expressed their great satisfaction with the surveillance and research knowledge and skills acquired, stating that they had met their expectations in a good quality course, but others pointed out that they were not satisfied with the time allocated to Quantitative Techniques for Epidemiological Research, Statistics and Computer science modules. It was concluded that the differences in origins and age of the Cuban students makes it necessary to reformulate academic formation policies and strategies so as to increase the educational efficiency according to individual needs. No gender differences were found in the Cuban group where physicians prevailed. Generally speaking, opinions about the course were very positive.


Short sampling intervals reveal very rapid root turnover in a temperate grassland.
Although root growth and mortality play critical regulatory roles in terrestrial ecosystems, little is known about the temporal scale of these dynamics. In temperate grasslands, root dynamics may be particularly rapid because of the high proportion of production allocated to very fine root biomass. In this study, we used minirhizotron tubes to estimate root growth and mortality in an upland grassland in Yellowstone National Park that was grazed by migratory herds of ungulates. Monthly rates of root growth and mortality were estimated from May to September 2005, by measuring the elongation (growth) and disappearance (mortality) of roots at 3-day intervals. Average daily growth (millimeters of root length) was approximately 5 times greater in May and June than in July, August, and September. Average daily mortality (millimeters of root length) did not differ among months. A comparison of the June-September rates of root growth and mortality derived from sampling at short (3-day) and long (1-month) time intervals indicated that the long sampling intervals underestimated both growth and mortality by approximately 60% relative to the short intervals. These results suggest that estimates of grassland root dynamics from minirhizotrons are influenced significantly by sampling interval length, and that rapid root turnover may play a more critical role in regulating energy and nutrient fluxes in temperate grasslands than has previously been recognized.


Head and neck cancers manifested as deep neck infection.
The incidence of head and neck cancers in patients with an initial presentation of deep neck infection is unclear and may be underestimated. Thus, the aim of this study was to assess the incidence of head and neck cancers initially manifested as deep neck infection. Also, the possible risk factors and pathophysiology are discussed. This study was a retrospective medical chart review in a tertiary referral center. A total of 81 consecutive patients admitted with a diagnosis of deep neck infection over a 46-month period were analyzed. The demographic data, physical examinations, laboratory findings, radiographic studies, and pathology report were analyzed. Among the 81 deep neck infection patients, head and neck cancers were histologically demonstrated in four patients (4.9%) with the initial symptom of a painful neck mass. The incidence of head and neck cancer initially manifested as deep neck infection was found to increase in patients aged over 40 years (6.7%; 3/45 vs. 2.8%; 1/36). A detailed history of all patients with deep neck infection should be taken. Furthermore, endoscopic examination, thyroid examination and routine pathological examination should be performed, especially in those aged over 40. Also, careful explanation to the patient and his/her family about the possibility of underlying head and neck cancer (incidence 1-5%) may be needed. If the neck swelling diminishes, but does not disappear completely after full course of antibiotics, repeated fine needle aspiration, endoscopy, or image study should be considered.


Formation of Fe-Ni Nanoparticle Strands in Macroscopic Polymer Composites: Experiment and Simulation.
Magnetic-field-induced strand formation of ferromagnetic Fe-Ni nanoparticles in a PMMA-matrix is correlated with the intrinsic material parameters, such as magnetization, particle size, composition, and extrinsic parameters, including magnetic field strength and viscosity. Since various factors can influence strand formation, understanding the composite fabrication process that maintains the strand lengths of Fe-Ni in the generated structures is a fundamental step in predicting the resulting structures. Hence, the critical dimensions of the strands (length, width, spacing, and aspect ratio) are investigated in the experiments and simulated via different intrinsic and extrinsic parameters. Optimal parameters were found by optical microscopy measurements and finite-element simulations using COMSOL for strand formation of Fe50Ni50 nanoparticles. The anisotropic behavior of the aligned strands was successfully characterized through magnetometry measurements. Compared to the unaligned samples, the magnetically aligned strands exhibit enhanced conductivity, increasing the current by a factor of 1000.


Global plagues and the Global Fund: Challenges in the fight against HIV, TB and malaria.
BACKGROUND: Although a grossly disproportionate burden of disease from HIV/AIDS, TB and malaria remains in the Global South, these infectious diseases have finally risen to the top of the international agenda in recent years. Ideal strategies for combating these diseases must balance the advantages and disadvantages of 'vertical' disease control programs and 'horizontal' capacity-building approaches. DISCUSSION: The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) represents an important step forward in the struggle against these pathogens. While its goals are laudable, significant barriers persist. Most significant is the pitiful lack of funds committed by world governments, particularly those of the very G8 countries whose discussions gave rise to the Fund. A drastic scaling up of resources is the first clear requirement for the GFATM to live up to the international community's lofty intentions. A directly related issue is that of maintaining a strong commitment to the treatment of the three diseases along with traditional prevention approaches, with the ensuing debates over providing affordable access to medications in the face of the pharmaceutical industry's vigorous protection of patent rights. SUMMARY: At this early point in the Fund's history, it remains to be seen how these issues will be resolved at the programming level. Nevertheless, it is clear that significant structural changes are required in such domains as global spending priorities, debt relief, trade policy, and corporate responsibility. HIV/AIDS, tuberculosis and malaria are global problems borne of gross socioeconomic inequality, and their solutions require correspondingly geopolitical solutions.


Distance distributions and electron-density characteristics of protein models.
The analytical expression for the distribution of an interatomic distance resulting from a known error-free distance and a Gaussian perturbation of the atomic coordinates is presented. This is used to estimate the coordinate error on the basis of known geometric features of protein models via the nearest-neighbour or the radial distance distribution. A simple relation is presented that describes the dependence of the map correlation on the positional error of the protein model, the resolution of the X-ray data and the overall atomic displacement parameter. The distribution of geometrical features and the relation between the map correlation and the positional error can be used in assisting the decision-making process during automated model-building procedures.


Clinical efficacy of lumbar and lumbosacral fusion using the Boucher facet screw fixation technique.
The clinical outcome of posterolateral lumbar and lumbosacral fusions with facet screw fixation using the Boucher technique is reviewed retrospectively. The Boucher technique uses AO cortical screws that traverse the facet joint at an angle from the superior lamina, in a medial to lateral direction, to enter the respective inferior pedicle. The procedure was performed on 57 consecutive patients who had a degenerative disk disease. The pre-operative diagnosis was based on a physical examination and radiographs with myelography performed when deemed necessary. Surgery had been indicated and performed on patients with unresolved pain after 6 months of conservative therapy; radiographic signs of disk space narrowing, facet arthrosis, degenerative spondylolisthesis or instability on flexion and extension views. No prior history of spinal surgery, no involvement in any litigation or Workers Compensation process, and no detected psychiatric disturbances were also inclusion criteria for this study. Eighteen consecutive male and 39 consecutive female patients were included in the study. The average age at the time of surgery was 41.8 years. The mean active clinical follow-up (office visits) time was 5.06 months with the minimum follow-up time of 3 months. Two years after their surgery, all the patients were asked to fill out a questionnaire from which their progress was evaluated. All questionnaires were completed and returned. Postoperatively, patients were placed in either a lumbosacral corset, short rigid lumbosacral molded polypropylene brace or body cast. Overall clinical results for single level fusions showed that 91.2% of patients (31 of 34) had excellent results and 8.8% (3 of 34) had poor results. Of the multiple level fusions, 86.4% of patients (19 of 22) had excellent or good results and 9.1% (2 of 22) had poor results. Post-operative complications included only three wound infections at the iliac crest donor site. This study demonstrates that facet screw fixation using the Boucher technique has advantages. The technique not only is easy to implement by placing a small screw through a facet joint and it's respective pedicle, but produces excellent clinical results that are comparable to the other more bulky spinal instrumentation systems.


Mitochondrial DNA depletion reduces PARP-1 levels and promotes progression of the neoplastic phenotype in prostate carcinoma.
Mitochondrial dysfunction resulting from mitochondrial DNA (mtDNA) mutations and/or depletion has been correlated with cancer progression and drug resistance. To investigate the role of mtDNA in prostate cancer progression, we used LNCaP and PC-3 prostate carcinoma cells as experimental model. Compared to minimally invasive androgen-dependent LNCaP cells, highly invasive androgen-independent PC-3 cells, as well as androgen-independent DU145 and C4-2 cells, exhibited significantly reduced mtDNA content. In PC-3 cells, reduction of mtDNA was accompanied by decreased mitochondrial membrane potential (DeltaPsi(m)), increased migration onto the basement membrane protein laminin-1, reduced chemosensitivity to paclitaxel (IC(50)=110 nM vs. 22 nM) and decreased expression of poly(ADP-ribose) polymerase (PARP)-1. To investigate the relationship between mtDNA depletion and these phenotypic characteristics, we established mtDNA-depleted LNCaP cells [Rho(-)] by long-term exposure to ethidium bromide or treated wild-type LNCaP cells with a mitochondrial ionophore, carbonyl cyanide m-chlorophenylhydrazone. Both manipulations resulted in DeltaPsi(m) loss, acquisition of invasive cytology, increased motility onto laminin-1, reduced sensitivity to paclitaxel (IC(50)= approximately 100 nM) and approximately 75% reduction in PARP-1 protein levels, resembling PC-3 cells. Overall, these results provide novel evidence demonstrating that mtDNA depletion in early prostate carcinoma may contribute to the acquisition of a more invasive phenotype that is less sensitive to paclitaxel-induced apoptosis.


Trustable Environmental Monitoring by Means of Sensors Networks on Swarming Autonomous Marine Vessels and Distributed Ledger Technology.
The article describes a highly trustable environmental monitoring system employing a small scalable swarm of small-sized marine vessels equipped with compact sensors and intended for the monitoring of water resources and infrastructures. The technological foundation of the process which guarantees that any third party can not alter the samples taken by the robot swarm is based on the Robonomics platform. This platform provides encrypted decentralized technologies based on distributed ledger tools, and market mechanisms for organizing the work of heterogeneous multi-vendor cyber-physical systems when automated economical transactions are needed. A small swarm of robots follows the autonomous ship, which is in charge of maintaining the secure transactions. The swarm implements a version of Reynolds' Boids model based on the Belief Space Planning approach. The main contributions of our work consist of: (1) the deployment of a secure sample certification and logging platform based on the blockchain with a small-sized swarm of autonomous vessels performing maneuvers to measure chemical parameters of water in automatic mode; (2) the coordination of a leader-follower framework for the small platoon of robots by means of a Reynolds' Boids model based on a Belief Space Planning approach. In addition, the article describes the process of measuring the chemical parameters of water by using sensors located on the vessels. Both technology testing on experimental vessel and environmental measurements are detailed. The results have been obtained through real world experiments of an autonomous vessel, which was integrated as the "leader" into a mixed reality simulation of a swarm of simulated smaller vessels.The design of the experimental vessel physically deployed in the Volga river to demonstrate the practical viability of the proposed methods is shortly described.


Force-induced structural transitions in cross-linked DNA films.
We report on the preparation and characterization of wet-spun films of sodium DNA in which intermolecular cross-links were introduced following formaldehyde treatment. Raman scattering shows that the DNA in moderately cross-linked films is mainly in the B conformation. Stretching experiments show a transition from plastic to elastomeric behavior with increasing exposure to the cross-linking agent. Elastomeric DNA films are strongly disordered. X-ray diffraction shows that stretching of moderately cross-linked films under controlled high humidity conditions results in increased molecular orientation as well as the appearance of meridional reflections at 7.4-7.8 and 8.2 angstroms. These reflections are not observed for any of the classical conformations associated with mixed sequence DNA, and may arise from extended base-pair stacking in a stretched DNA structure.


Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments.
While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. Of particular importance are positional isomers, for which analytical standards are difficult to obtain. We combine ultrahigh-resolution ion-mobility spectrometry with collision-induced dissociation and cryogenic infrared spectroscopy to determine the structure of N-glycan positional isomers. This approach is based on first separating the parent molecules by SLIM-based IMS, producing diagnostic fragments specific to each positional isomer, separating the fragments by IMS, and identifying them by comparing their IR fingerprints to a previously recorded spectral database. We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. Starting with just a few analytical standards, this fragment-based spectroscopy method allows us to develop a database which we can use to identify positional isomers. The generalization of this approach would greatly facilitate glycan analysis.


Candida Infection Associated with Salivary Gland-A Narrative Review.
Candida species are common global opportunistic pathogens that could repeatedly and chronically cause oral mucosa infection and create an inflammatory environment, leading to organ dysfunction. Oral Candida infections may cause temporary or permanent damage to salivary glands, resulting in the destruction of acinar cells and the formation of scar tissue. Restricted function of the salivary glands leads to discomfort and diseases of the oral mucosa, such as dry mouth and associated infection. This narrative review attempts to summarize the anatomy and function of salivary glands, the associations between Candida and saliva, the effects of Candida infection on salivary glands, and the treatment strategies. Overall, clinicians should proactively manage Candida infections by educating patients on oral hygiene management for vulnerable populations, conducting frequent checks for a timely diagnosis, and providing an effective treatment plan.