Comparison of polymerization shrinkage of pattern resins.
The dimensional stability, in particular polymerization shrinkage, of pattern resins affects the accuracy of implant prosthesis fabrication. Recently introduced photopolymerizing pattern resins are easy to use, but their shrinkage needs to be determined and compared with traditional autopolymerizing pattern resins. The purpose of the study was to compare the polymerization shrinkage of photopolymerizing pattern resins with autopolymerizing pattern resins. Two autopolymerizing (DuraLay, GC Pattern resin) and 2 photopolymerizing (Primopattern LC Gel, Primopattern LC Paste) pattern resins were tested. The sample size was 10 for each group. Polymerization shrinkage was determined by measuring the change in area dimensions with image analysis. The percentage of volumetric shrinkage was calculated, and the results were statistically analyzed with ANOVA, followed by the Student-Newman-Keuls post hoc test (α=.05). The volumetric shrinkage values (%; mean ±standard deviation) for GC Pattern Resin were 5.72 ±0.89; for DuraLay, 5.07 ±1.36; for Primopattern LC Gel, 5.42 ±1.83; and for Primopattern LC Paste, 7.43 ±0.62. The volumetric shrinkage of the Primopattern LC Paste was significantly higher than that of the other 3 materials. The photopolymerizing pattern resin in gel form (Primopattern LC Gel) had a similar shrinkage value to the autopolymerizing pattern resins (DuraLay and GC Pattern Resin). However, the photopolymerizing pattern resin in paste form (Primopattern LC Paste) shrank significantly more than the other 3 materials tested.


Probiotics for the prevention of Hirschsprung-associated enterocolitis: a systematic review and meta-analysis.
Hirschsprung-associated enterocolitis (HAEC) is a life-threatening complication of Hirschsprung's disease. HAEC is reported to occur in 6-50% of patients preoperatively and in 2-35% postoperatively. The exact cause of HAEC is not fully understood, but disturbances of intestinal microbiota have recently been reported in patients with HAEC. In recent years, the administration of probiotics has been proposed to reduce the incidence of HAEC. We conducted a systematic review and meta-analysis to determine the effect of probiotics on postoperative HAEC. A systematic literature search for relevant articles was performed in four databases using the combinations of following terms "probiotics", "microbiota", "enterocolitis", "Lactobacillus", "Bifidobacterium", "Saccharomyces", "Streptococcus", and "Hirschsprung disease/Hirschsprung's disease" for studies published between 2002 and 2017. The relevant cohorts of the effect of probiotics in postoperative patients were systematically searched for clinical outcomes. Odds ratio (OR) or standard mean difference (SMD) with 95% confidence intervals (CI) were calculated using standardized statistical methodology. The search strategy identified 1274 reports. Overall, five studies met defined inclusion criteria, reporting a total of 198 patients. Two studies were prospective multicenter randomized control trials. Lactobacillus, Bifidobacterium, Streptococcus, and Enterococcus were used as probiotics. The incidence of HAEC with/without probiotics was 22.6 and 30.5%, respectively, but this was not statistically different (OR 0.72; 95% CI 0.37-1.39; P = 0.33). This study shows that the administration of probiotics was not associated with a significant reduction in the risk of HAEC. Additional studies are required to understand more fully the role of microbiota and complex interactions that cause HAEC. With increasing knowledge of the role of microbiota in HAEC, we are likely to understand better the potential benefits of probiotics in this disease.


Comparison of the rate and size of HIV-1 viral load blips with Roche COBAS TaqMan HIV-1 versions 1.0 and 2.0 and implications for patient management.
The Roche COBAS TaqMan HIV-1 version 1.0 (v1.0) real-time PCR test detects more low level viral loads (VL) compared to the previous Roche Amplicor version 1.5 assay. Due to under-quantification issues, the Roche TaqMan HIV-1 version 2.0 (v2.0) was introduced in 2009. Controversy remains on differences at the low VL end, where clinical decisions regarding possible viral escape are based. To compare the rate and size of VL blips with v1.0 and v2.0 in virologically suppressed patients and describe the impact of v2.0 on patient management. A cohort study of HIV-positive patients on antiretroviral therapy with a VL <50 copies/ml at the beginning and end of the study period (July 2008-February 2010). VL blips were compared during two consecutive 9-month periods, initially measured by v1.0, then v2.0. Genotypic resistance testing and treatment switches were described. 1037 of 2584 patients (73.1% male) with median age 43 years were included. 2465 VL samples were measured on v1.0 and 2206 on v2.0. 108 (10.4%) patients had blips on v1.0 (4.4% of samples) compared to 99 (9.5%) patients (4.5% of samples) on v2.0. Median log VL was 1.89 (78 copies/ml) for v1.0 and 2.06 (116 copies/ml) for v2.0 (p=0.002). Further characterisation of 11 samples detected no resistance and no treatment modifications were identified. TaqMan v1.0 and v2.0 have similar blip rates, while blips are higher with v2.0. This study supports the strategy to increase the threshold of concern for VL blips on v2.0.


High-Resolution UPLC-MS Profiling of Anthocyanins and Flavonols of Red Cabbage (Brassica oleracea L. var. capitata f. rubra DC.) Cultivated in Egypt and Evaluation of Their Biological Activity.
In this paper, biological investigations and a high-resolution UPLC-PDA-ESI-qTOF-HRMS technique were employed for Brassica oleracea L. var. capitata f. rubra DC. (red cabbage) of the family Brassicaceae (Cruciferae), cultivated in Egypt, for the first time. The positive ionization mode is usually performed to identify anthocyanins. However, this technique cannot differentiate between anthocyanins and corresponding non-anthocyanin polyphenols. Thus, the negative ionization mode was also used, as it provided a series of characteristic ions for the MS analysis of anthocyanins. This helped in identifying five kaempferol derivatives for the first time in red cabbage, as well as nine-previously reported-anthocyanins. For the biological investigations, the acidified methanolic extract of fresh leaves and the methanolic extract of air-dried powdered leaves were examined for their antioxidant, antimicrobial, and anticancer activities. The freshly prepared phenolic extract was proven to be more biologically potent. Statistical significance was determined for its anticancer activity in comparison with standard doxorubicin.


Influence of milk on the bioavailability of doxycycline--new aspects.
This study was conducted to examine the pharmacokinetics of doxycycline in nine healthy volunteers who had fasted overnight. Single-dose cross-over design was used. Each subject received orally 0.2 g doxycycline. The subjects swallowed the antibiotic capsules with 300 ml of water or 300 ml of fresh milk. Simultaneous ingestion of milk diminished the peak plasma concentration by 24% and the absorption by 9-53% (mean 30%). It is concluded that, like the other tetracyclines, doxycycline should not be administered together with milk.


Disparities in insecurity, social support, and family relationships in association with poor mental health among US adults during the COVID-19 pandemic.
The COVID-19 pandemic has had a significant impact on mental health. Identifying risk factors and susceptible subgroups will guide efforts to address mental health concerns during the pandemic and long-term management and monitoring after the pandemic. We aimed to examine associations of insecurity (concerns about food, health insurance, and/or money), social support, and change in family relationships with poor mental health and to explore disparities in these associations. An online survey was collected from 3952 US adults between May and August 2020. Symptoms of anxiety, depression, stress, and trauma-related disorders were assessed by the Generalized Anxiety Disorder 7-item scale, the Patient Health Questionnaire-9, the Perceived Stress Scale-4, and the Primary Care Post-Traumatic Stress Disorder Screen, respectively. Social support was measured by the Oslo Social Support Scale. Logistic regression was used and stratified analyses by age, race/ethnicity, and sex were performed. We found a higher prevalence of poor mental health among those who were younger, female, with lower socioeconomic status, and racial/ethnic minorities. Participants who were worried about money, health insurance, or food had higher odds of symptoms of anxiety (OR = 3.74, 95% CI: 3.06-4.56), depression (OR = 3.20, 95% CI: 2.67-3.84), stress (OR = 3.08, 95% CI: 2.67-3.57), and trauma-related disorders (OR = 2.93, 95% CI: 2.42-3.55) compared to those who were not. Compared to poor social support, moderate and strong social support was associated with lower odds of all four symptoms. Participants who had changes in relationships with parents, children, or significant others had worse mental health. Our findings identified groups at higher risk for poor mental health, which offers insights for implementing targeted interventions.


Simplified quantification of nicotinic receptors with 2[18F]F-A-85380 PET.
Neuronal nicotinic acetylcholine receptors (nAChRs), widely distributed in the human brain, are implicated in various neurophysiological processes as well as being particularly affected in neurodegenerative conditions such as Alzheimer's disease. We sought to evaluate a minimally invasive method for quantification of nAChR distribution in the normal human brain, suitable for routine clinical application, using 2[(18)F]F-A-85380 and positron emission tomography (PET). Ten normal volunteers (four females and six males, aged 63.40+/-9.22 years) underwent a dynamic 120-min PET scan after injection of 226 MBq 2[(18)F]F-A-85380 along with arterial blood sampling. Regional binding was assessed through standardized uptake value (SUV) and distribution volumes (DV) obtained using both compartmental (DV(2CM)) and graphical analysis (DV(Logan)). A simplified approach to the estimation of DV (DV(simplified)), defined as the region-to-plasma ratio at apparent steady state (90-120 min post injection), was compared with the other quantification approaches. DV(Logan) values were higher than DV(2CM). A strong correlation was observed between DV(simplified), DV(Logan) (r=.94) and DV(2CM) (r=.90) in cortical regions, with lower correlations in thalamus (r=.71 and .82, respectively). Standardized uptake value showed low correlation against DV(Logan) and DV(2CM). DV(simplified) determined by the ratio of tissue to metabolite-corrected plasma using a single 90- to 120-min PET acquisition appears acceptable for quantification of cortical nAChR binding with 2[(18)F]F-A-85380 and suitable for clinical application.


New biodegradable dextran-based hydrogels for protein delivery: Synthesis and characterization.
A new derivative of dextran grafted with polyethylene glycol methacrylate through a carbonate bond (DEX-PEG-MA) has been synthesized and characterized. The photo-crosslinking reaction of DEX-PEG-MA allowed the obtainment of biodegradable networks tested for their mechanical and release properties. The new hydrogels were compared with those made of dextran methacrylate (DEX-MA), often employed as drug delivery systems of small molecules. The inclusion of PEG as a spacer created additional interactions among the polymeric chains improving the extreme fragility and lack of hardness typical of gels made of DEX-MA. Moreover, the different behavior in terms of swelling and degradability of the networks was able to affect the release of a model macromolecule over time, making DEX-PEG-MA matrices suitable candidates for the delivery of high molecular weight peptides. Interestingly, the combination of the two dextran derivatives showed intermediate ability to modulate the release of high molecular weight macromolecules.


Investigation of the role of the miR17-92 cluster in BMP9-induced osteoblast lineage commitment.
Bone morphogenetic protein 9 (BMP9) has been identified as a crucial inducer of osteoblastic differentiation in mesenchymal stem cells (MSCs). Although microRNAs (miRNAs) are known to play a role in MSC osteogenesis, the mechanisms of action of miRNAs in BMP9-induced osteoblastic differentiation remain poorly understood. In this study, we investigate the possible role of the miR17-92 cluster in the BMP9-induced osteogenic differentiation of MSCs by using both in vitro and in vivo bone formation assays. The results show that miR-17, a member of the miR17-92 cluster, significantly impairs BMP9-induced osteogenic differentiation. This impairment is effectively rescued by a miR-17 sponge, an antagomiR sequence against miR-17. Using TargetScan and the 3'-untranslated region luciferase reporter assays, we show that the direct target of miR-17 is the retinoblastoma gene (RB1), a gene that is pivotal to osteoblastic differentiation. We also confirm that RB1 is essential for the miR-17 effects on osteogenesis. Our results indicate that miR-17 expression impairs normal osteogenesis by downregulating RB1 expression and significantly inhibiting the function of BMP9.


Release of 6-keto-prostaglandin F1 alpha and thromboxane B2 from mouse peritoneal macrophages during their adhesion and spreading on a glass surface.
The release of 6-keto-prostaglandin F1 alpha (6KF1 alpha) and of thromboxane B2 (TXB2) from cells were investigated using mouse peritoneal exudate cells (PECs) and non-cultured peritoneal macrophages. They were prepared by adhesion to glass dishes and incubated for 1 hr at 37 degrees C in 5% CO2 in air. Both the percentage of spreading macrophages and the release of 6KF1 alpha and TXB2 increased in proportion to the incubation time. 6KF1 alpha and TXB2 were released from the macrophages, not from the non-coated glass dishes, the spreading of macrophages was hardly detected and lower amounts of 6KF1 alpha and TXB2 were released from these cells compared with cells incubated in non-treated glass dishes. These findings suggest that adhesion with the correlated spreading of macrophages on glass dishes serve as a considerable physical factor for the release of 6KF1 alpha and TXB2.


Assessment of the Rate of Adherence to International Guidelines for Androgen Deprivation Therapy with External-beam Radiation Therapy: A Population-based Study.
The National Comprehensive Cancer Network and the European Association of Urology guidelines recommend using radiation therapy (RT) with androgen deprivation therapy (ADT) to treat high-risk and locally advanced prostate cancer patients. To evaluate the degree of adherence to these guidelines. Between 2003 and 2009, in the Surveillance Epidemiology and End Results (SEER)-Medicare database, 14 180 patients were diagnosed with high-risk (T1-T2 with World Health Organization histologic grade 3) or locally advanced (T3-T4 with any histologic grade) prostatic adenocarcinoma. Administration of RT-ADT versus RT alone. We assessed the rate of adherence to guidelines with respect to use of RT-ADT in the overall population and after stratification according to stage-grade groupings (T1-T2 G3 vs T3-T4 any grade), age (66-69, 70-74, 75-79, ≥80 yr), Charlson Comorbidity Index (CCI) (0, 1, ≥2), and preexisting baseline cardiovascular (CV) disease. We depicted the rate of RT-ADT administration graphically over the study period. Multivariable logistic regression analyses were performed to assess the predictors of RT-ADT use. RT-ADT rates and guideline adherence were 58-75%, with the highest rate (75%) in 2003 and the lowest (58%) in 2009. When stratified according to stage-grade groupings, age, CCI, and preexisting baseline CV disease, similar results were obtained. In multivariable analyses, year of diagnosis (p<0.001), patient age (p<0.001), stage-grade groupings (p<0.001), CCI (p=0.036), race (p<0.001), marital status (p<0.001), population density (p<0.001), and US regions (p<0.001) were independent predictors of RT-ADT use. The limitations of our study include age >65 yr and exclusive Medicare coverage. The rate of guideline adherence regarding the use of RT-ADT is suboptimal and decreases with time instead of increasing. This population-based study provides evidence of low adherence to international urologic guidelines regarding the combination of radiation therapy (RT) with androgen deprivation therapy (ADT) for high-risk and locally advanced prostate cancer (PCa) patients. Despite the increasing number of randomized controlled trials over time that showed a survival benefit for patients with high-risk and locally advanced PCa treated with RT-ADT compared with RT alone, the rate of adherence to guidelines decreased with time.


Circulating renin-angiotensin systems mediated feedback controls over the mean-arterial pressure.
The renin-angiotensin systems play pivotal role in cardiovascular physiology through its effects on regulating blood pressure and electrolyte homeostasis. Components of circulating RAS (cRAS) that include precursor angiotensinogen, two critical enzymes (renin and angiotensin-converting enzyme, ACE), their bioactive products, angiotensin- I, II together with its receptors (AT1R and AT2R) essentially determine this homeostasis. Most classical studies, however, showed the deleterious role of cRAS in elevating the blood pressure. Contemporary discovery of non-canonical components of the RAS has challenged this classic hypothesis that it can only exert deleterious effects on the cardiovascular systems. Using the classic cRAS model, we have designed in-silico experiments to test the hypothesis that AT2R-mediated feedback effects play pivotal role for maintaining the normal variation of the mean-arterial pressure (MAP).Beside the AT2R-mediation of downstream singling pathways consisting of several non-canonical RAS components, this study first time illustrated AT2R mediated feedback controls over the blood pressure regulation: one that impedes AT1R activity, and the other that downregulates renin. It has been shown that relatively stronger suppression of renin activity significantly contributes in maintaining the normal MAP and that tight AT2R-mediated regulation is relaxed in hyper-and hypotension. This control mechanism is noted to be robustly maintained with the MAP variations through an established linear steady-state relationship among renin, angiotensin I and angiotensin II. This examination suggests that AT2R-mediated downregulation of renin activities potentially counteracts the AT1R-mediated deleterious actions of Ang II. This study, therefore, provides a solid ground for considering different AT2 receptor adaptor protein and direct agonism at AT2R that can cause greater effects along with contemporary approaches of blocking AT1R mediation to attenuate hypertension or other cardiovascular disorders.


Benign lymphoid infiltrate of the iris simulating a malignant melanoma.
To report a clinicopathologic correlation of an unusual benign lymphocytic iris mass in a patient who had no systemic lymphoproliferative disease. Case report. A 49-year-old man developed a circumscribed, tan lesion in his left iris. The lesion was suspected clinically to be an atypical iris melanoma. Histopathologic studies of the resected mass revealed a solid tumor that was comprised of lymphocytes and histiocytes. Immunohistochemical studies identified that most of the cells were T lymphocytes. The histopathologic diagnosis was atypical lymphoid infiltrate. Workup for systemic lymphoma and Epstein-Barr virus infection was negative. Lymphoid infiltrate can manifest as a solitary mass that can simulate an iris melanoma.


Nematicidal activity of 3,4-dihydroxybenzoic acid purified from Terminalia nigrovenulosa bark against Meloidogyne incognita.
In this study, the 3,4-dihydroxybenzoic acid (3,4-DHBA) from Terminalia nigrovenulosa bark (TNB) was purified and its in vitro nematicidal activity was investigated against Meloidogyne incognita. The purification of 3,4-DHBA used a silica gel column and Sephadex LH-20 chromatography combined with thin-layer chromatography and high performance liquid chromatography. Structural identification of the 3,4-DHBA was conducted using (1)H nuclear magnetic resonance (NMR), (13)C NMR, and liquid chromatography time-of-flight mass spectrometry. Nematicidal activity bioassays revealed that 3,4-DHBA treatment resulted in 33.3, 47.5, 72.5 and 94.2% J2 mortality at 0.125, 0.25, 0.5 and 1.0 mg/ml, respectively after 12 h incubation. J2 mortality was increased significantly (P < 0.0001) with increasing incubation time in the range of 54.2-94.2% from 3 to 9 h after incubation with 3,4-DHBA (1.0 mg/ml), but with no significant difference observed where the incubation time was increased from 9 to 12 h. The 3,4-DHBA treatment resulted in 33.3, 65.0, 76.7 and 85.0% hatch inhibition at 0.125, 0.25, 0.5 and 1.0 mg/ml, respectively, 3 days after incubation. Changes in the shape of the eggs were determined after incubation for 1 day with a 3,4-DHBA concentration of 1.0 mg/ml.


A reaction-advection-diffusion model of cholera epidemics with seasonality and human behavior change.
Cholera is a water- and food-borne infectious disease caused by V. cholerae. To investigate multiple effects of human behavior change, seasonality and spatial heterogeneity on cholera spread, we propose a reaction-advection-diffusion model that incorporates human hosts and aquatic reservoir of V. cholerae. We derive the basic reproduction number [Formula: see text] for this system and then establish a threshold type result on its global dynamics in terms of [Formula: see text]. Further, we show that the bacterial loss at the downstream end of the river due to water flux can reduce the disease risk, and describe the asymptotic behavior of [Formula: see text] for small and large diffusion in a special case (where the diffusion rates of infected human and the pathogen are constant). We also study the transmission dynamics at the early stage of cholera outbreak numerically, and find that human behavior change may lower the infection level and delay the disease peak. Moreover, the relative rate of bacterial loss, together with convection rate, plays an important role in identifying the severely infected areas. Meanwhile spatial heterogeneity may dilute or amplify cholera infection, which in turn would increase the complexity of disease spread.


Fast single-photon detectors and real-time key distillation enable high secret-key-rate quantum key distribution systems.
Quantum key distribution has emerged as the most viable scheme to guarantee information security in the presence of large-scale quantum computers and, thanks to the continuous progress made in the past 20 years, it is now commercially available. However, the secret key rates remain limited to just over 10 Mbps due to several bottlenecks on the receiver side. Here we present a custom multipixel superconducting nanowire single-photon detector that is designed to guarantee high count rates and precise timing discrimination. Leveraging the performance of the detector and coupling it to fast acquisition and real-time key distillation electronics, we remove two major roadblocks and achieve a considerable increase of the secret key rates with respect to the state of the art. In combination with a simple 2.5-GHz clocked time-bin quantum key distribution system, we can generate secret keys at a rate of 64 Mbps over a distance of 10.0 km and at a rate of 3.0 Mbps over a distance of 102.4 km with real-time key distillation.


Analysis of neutrophil bactericidal activity.
The primary function of neutrophils is to engulf and destroy invading pathogens. If the bactericidal capacity of neutrophils is defective, an individual may suffer from enhanced susceptibility to potentially fatal microbial infection. To identify such defects, and to investigate the mechanisms used to kill bacteria, the bactericidal activity of neutrophils must be accurately quantified. This chapter provides details of a comprehensive microbiological technique that quantifies neutrophil bactericidal activity by measuring the loss of viability of ingested bacteria over time. Two variations of this technique are presented: a simple "one-step" protocol providing a composite measure of phagocytosis and killing, and a more advanced "two-step" protocol that allows calculation of separate rate constants for both of these processes.


Self-assembly of microcapsules via colloidal bond hybridization and anisotropy.
Particles with directional interactions are promising building blocks for new functional materials and may serve as models for biological structures. Mutually attractive nanoparticles that are deformable owing to flexible surface groups, for example, may spontaneously order themselves into strings, sheets and large vesicles. Furthermore, anisotropic colloids with attractive patches can self-assemble into open lattices and the colloidal equivalents of molecules and micelles. However, model systems that combine mutual attraction, anisotropy and deformability have not yet been realized. Here we synthesize colloidal particles that combine these three characteristics and obtain self-assembled microcapsules. We propose that mutual attraction and deformability induce directional interactions via colloidal bond hybridization. Our particles contain both mutually attractive and repulsive surface groups that are flexible. Analogously to the simplest chemical bond--in which two isotropic orbitals hybridize into the molecular orbital of H2--these flexible groups redistribute on binding. Via colloidal bond hybridization, isotropic spheres self-assemble into planar monolayers, whereas anisotropic snowman-shaped particles self-assemble into hollow monolayer microcapsules. A modest change in the building blocks thus results in much greater complexity of the self-assembled structures. In other words, these relatively simple building blocks self-assemble into markedly more complex structures than do similar particles that are isotropic or non-deformable.


Structural Perspective of Benzophenones Targeting Tubulin as Anticancer Agents.
Cancer is the leading cause of death and the most significant determinant of life expectancy in almost every country in this twenty-first century. According to the World Health Organization (WHO), cancer is responsible for the leading cause of death globally. Benzophenone derivatives are found in a variety of naturally occurring compounds which are known to be pharmacologically efficacious against a variety of diseases, including cancer. Microtubules are thought to be a good target for cancer chemotherapies. Microtubule polymerization and depolymerization are induced by a variety of natural, synthetic, and semisynthetic chemicals having a benzophenone nucleus, affecting tubulin dynamics. Several medications that affect microtubule dynamics are in various stages of clinical trials, including Combretastatins (phase II), Vincristine (clinically approved), Paclitaxel (in clinical usage), and epothilone (phase III), and only a few have been patented. Benzophenone derivatives target the colchicine binding site of microtubules, damage them and cause cell cycle arrest in the G2-M phase. Belonging to this class of molecules, phenstatin, a potent inhibitor of tubulin polymerization, has shown strongly inhibit cancer cell growth and arrest the G2/M phase of the cell cycle by targeting the colchicine binding site of microtubules. In the present manuscript, we described the benzophenone as tubulin polymerization inhibitors, their Structure-Activity Relationships (SARs) and molecular docking studies that reveal its binding affinity with the colchicine binding site.


Method validation in the bioanalytical laboratory.
Bioanalytical methods, based on a variety of physico-chemical and biological techniques such as chromatography, immunoassay and mass spectrometry, must be validated prior to and during use to engender confidence in the results generated. The fundamental criteria for assessing the reliability and overall performance of a bioanalytical method are: the evaluation of drug and analyte stability, selectivity, limits of quantification and detection, accuracy, precision, linearity and recovery. The extent to which a method is validated is dependent on its prospective use, the number of samples to be assayed and the use to which the data are put. Specific analytical techniques may require additional validation such as antibody-binding characteristics, peak purity determination, evaluation of matrix effects or structural confirmation of the analyte. Ideally each assay should be cross-validated with a method utilizing a highly specific detector such as a mass spectrometer. Once in use, the performance of the method should be monitored using quality control standards. If a method is set up in another laboratory, the performance of that assay should be monitored with quality control standards sent from the originating laboratory.


History of oral contraceptive use and risk of spontaneous abortion.
To examine the association between pregravid oral contraceptive (OC) use and spontaneous abortion (SAB). In an Internet-based preconception cohort study of 4862 Danish pregnancy planners, we used Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals (CIs) for the association between OC use and SAB. We controlled for maternal age, physical activity, parity, education, alcohol and caffeine consumption, body mass index, and smoking. Compared with women who discontinued OCs >1 year before conception, HRs were 0.95 (95% confidence interval (CI) = 0.77-1.17), 0.99 (95% CI = 0.82-1.19), and 0.80 (95% CI = 0.60-1.06) for women who discontinued OCs 7-12, 2-6, and 0-1 months before conception, respectively. Compared with less than 4 years of OC use, HRs for 4-7, 8-11, and 12 years or more of OC use were 1.05 (95% CI = 0.80-1.37), 0.92 (95% CI = 0.71-1.19), and 0.88 (95% CI = 0.65-1.19), respectively. Dose of estrogen and generation of progestin were not materially associated with SAB risk. We found no evidence that pregravid OC use is associated with an increase in SAB. Use within 1 month of conception was associated with a slightly lower risk of SAB, but this may be due to increased reproductive fitness in women who conceive quickly after discontinuation of OCs.


Forecasting cataract surgeries and intraocular lens implantation to 1990 using a model of population dynamics.
Extending the recently observed dramatic growth rates of cataract surgery and intraocular lens implantation into the future is not necessarily valid because of changes in population size, new incidence of cataracts, and rates of treatment for patients diagnosed in current as well as in previous years. Accelerated treatment of the pool of previously diagnosed patients caused a sharp growth in cataract surgery since 1980, but at the same time reduced patients and thus the potential for continued high growth rates. This paper describes a model that produces forecasts through explicit consideration of the many aspects of population dynamics. It provides an opportunity to examine how forecasts might vary under different assumptions about advances in medical technology.


Identification and functional analysis of mutations in FAD-binding domain of mitochondrial glycerophosphate dehydrogenase in caucasian patients with type 2 diabetes mellitus.
Ca2+-responsive mitochondrial FAD-linked glycerophosphate dehydrogenase (mGPDH) is a key component of the pancreatic beta-cell glucose-sensing device. The purpose of this study was to examine the association of mutations in the cDNA coding for the FAD-binding domain of mGPDH and to explore the functional consequences of these mutations in vitro. To investigate this association in type 2 diabetes mellitus, we studied a cohort of 168 patients with type 2 diabetes and 179 glucose-tolerant control subjects of Spanish Caucasian origin by single-stranded conformational polymorphism analysis. In vitro site-directed mutagenesis was performed in the mGPDH cDNA sequence to reproduce those mutations that produce amino acid changes in a patient with type 2 diabetes. We detected mutations in the mGPDH FAD-binding domain in a single patient, resulting in a Gly to Arg amino acid change at positions 77, 78, and 81 and a Thr to Pro at position 90. In vitro expression of the mutated constructs in Xenopus oocytes resulted in a significantly lower enzymatic activity than in cells expressing the wild-type form of the enzyme. Our results indicate that although mutations in the mGPDH gene do not appear to have a major role in type 2 diabetes mellitus, the reduction in mGPDH enzymatic activity associated with the newly described mGPDH mutations suggests that they may contribute to the disease in some patients.


Repetitive transcranial magnetic stimulation regulates L-type Ca(2+) channel activity inhibited by early sevoflurane exposure.
Sevoflurane might be harmful to the developing brain. Therefore, it is essential to reverse sevoflurane-induced brain injury. This study aimed to determine whether low-frequency repetitive transcranial magnetic stimulation (rTMS) can regulate L-type Ca(2+) channel activity, which is inhibited by early sevoflurane exposure. Rats were randomly divided into three groups: control, sevoflurane, and rTMS groups. A Whole-cell patch clamp technique was applied to record L-type Ca(2+) channel currents. The I-V curve, steady-state activation and inactivation curves were studied in rats of each group at different ages (1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks old). In the control group, L-type Ca(2+) channel current density significantly increased from week 2 to week 3. Compared with the control group, L-type Ca(2+) channel currents of rats in the sevoflurane group were significantly inhibited from week 1 to week 3. Activation curves of L-type Ca(2+) channel shifted significantly towards depolarization at week 1 and week 2. Moreover, steady-state inactivation curves shifted towards hyperpolarization from week 1 to week 3. Compared with the sevoflurane group, rTMS significantly increased L-type Ca(2+) channel currents at week 2 and week 3. Activation curves of L-type Ca(2+) channel significantly shifted towards hyperpolarization at week 2. Meanwhile, steady-state inactivation curves significantly shifted towards depolarization at week 2. The period between week 2 and week 3 is critical for the development of L-type Ca(2+) channels. Early sevoflurane exposure inhibits L-type Ca(2+) channel activity and rTMS can regulate L-type Ca(2+) channel activity inhibited by sevoflurane.


Using Icare HOME tonometry for follow-up of patients with open-angle glaucoma before and after selective laser trabeculoplasty.
Monitoring the results of selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) using a home rebound tonometry. To evaluate the role of Icare HOME tonometry in open-angle glaucoma patients being treated with SLT. A clinic-based prospective case study. Fourteen eyes from 14 patients diagnosed with primary open-angle glaucoma were recruited. The trabecular meshwork of each eye was treated 360° with a frequency-doubled Q-switched Nd:YAG laser. IOP was measured four times a day for a week before and after SLT. On the day of SLT, the patients were required to measure the IOP in the evening to record any IOP spikes. The use of Icare HOME in following up patients post-laser trabeculoplasty without the need for clinic attendance. Icare HOME recorded a significant reduction of 5.12 mmHg in the mean IOP post-SLT (95% confidence interval [CI] 3.75-6.50 mmHg, P < .001). The maximum IOP was also reduced by 6.14 mmHg (95% CI 3.07-9.21, P < .001) with no IOP spikes recorded post-SLT. There was a reduction in IOP fluctuation post-SLT by 1.07 mmHg (95% CI 0.24-1.89 mmHg, P = .021). No adverse effects for using the Icare HOME were reported by the study participants. This methodology could be highly useful for facilitating safe follow-up of patients residing in remote and rural areas, thus reducing healthcare cost with better information on IOP.


Microbial safety control of compost material with cow dung by heat treatment.
Various kinds of pathogenic bacteria derived from the intestinal tract of animals exist in compost material like cow dung. In order to sterilize the pathogenic bacteria completely in compost material, the cow dung was put into a heat treatment machine in pilot plan, and harmless condition in short time was examined. The results indicated, pathogenic indicator bacteria such as coliform bacteria, fecal coliform, Escherichia coli and salmonella were all 106 cfu/g dw at the beginning, died rapidly when cow dung temperature rose to above 50 degrees C, and not detected at 54-68 degrees C for 6-24 h heat treatment. Coliform bacteria and salmonella in heated cow dung were not detected by re-growth culture and enrichment culture examination. Moreover, it was hardly influenced on the fermentation ability of composting microbe, organic decomposition bacteria. During heat treatment, the mesophile decreased rapidly and the thermophile stabilized or increased, and the most of composting microbe were bacillus in cow dung by fluorescence microscope, this indicated that bacillus was dominator and composting microbe in composting process.


Carbonic anhydrase activators: synthesis of high affinity isozymes I, II and IV activators, derivatives of 4-(4-tosylureido-amino acyl)ethyl-1H-imidazole (histamine derivatives).
Reaction of histamine (Hst) with tetrabromophthalic anhydride and protection of its imidazole moiety with tritylsulfenyl chloride, followed by hydrazinolysis, afforded N-1-tritylsulfenyl histamine, a key intermediate which was further derivatized at its aminoethyl moiety. Reaction of the key intermediate with 4-tosylureido amino acids/dipeptides (ts-AA) in the presence of carbodiimides, afforded after deprotection of the imidazole moiety, a series of compounds with the general formula ts-AA-Hst (ts=4-MeC(6) H(4) SO(2) NHCO). Some structurally related dipeptide derivatives with the general formula ts-AA1-AA2-Hst, were also prepared, by in a similar way to the amino acyl compounds mentioned above. The new derivatives were examined as activators of three carbonic anhydrase (CA) isozymes, hCA I, hCA II (cytosolic forms) and bCA IV (membrane-bound form). Efficient activation was observed against all three isozymes, but especially against hCA I and bCA IV, with affinities in the 1-10 nanomolar range for the best compounds. hCA II was on the other hand activatable with affinities around 20-50 nM. This new class of CA activators might lead to the development of drugs/diagnostic agents for the CA deficiency syndrome, a genetic disease of bone, brain and kidneys.


[Oxygen supply of middle- and inner ear in experimental tubar occlusion (author's transl)].
1. The mucosa of the middle ear is not only supplied with oxygen from the blood but also from the air space of the middle ear. 2. Under physiological conditions, the perilymph is supplied partially with oxygen from the tympanic cavity. When the PO2 in the middle ear falls below 57 mm Hg, a net diffusion flux of oxygen from the perilymph to the middle ear induces a loss of oxygen from the inner ear. 3. A negative pressure of 25 mm Hg generated in the middle ear, causes a transudate. Subsequently, slight disturbances of microcirculation should occur in the mucosal membrane (pO2-histogram). More pronounced negative pressure lead to very distinct disturbances of microcirculation and local oxygen supply.


Maternal iron nutriture modulates placental development in a rat model of fetal alcohol spectrum disorder.
Prenatal alcohol exposure (PAE) causes developmental abnormalities known as fetal alcohol spectrum disorder (FASD). Maternal iron status modulates the severity of these defects in the offspring. Because the placenta is central in supporting fetal development, we investigated whether maternal iron status similarly modulates alcohol's effects in the placenta. We hypothesized that PAE causes placental insufficiency by decreasing placental weight and efficiency, and we hypothesized that these are worsened by maternal iron deficiency (ID) and alleviated by dietary iron fortification (IF). We also determined whether altered placental iron flux and inflammatory balance contribute to placental insufficiency. Pregnant Long-Evans rats consumed an iron-deficient (ID; 2-6 ppm), iron-sufficient (IS; 100 ppm), or iron-fortified (IF; 500 ppm) diet. Alcohol (5 g/kg body weight) or isocaloric maltodextrin (MD) was gavaged daily from gestational day (GD) 13.5-19.5. Placental outcomes were evaluated on GD20.5. PAE reduced fetal weight (p < 0.0001), placental weight (p = 0.0324), and placental efficiency (p = 0.0043). PAE downregulated placental transferrin receptor (p = 0.0032); it also altered placental Il1b and Tnf expression and the Il6:Il10 ratio (p = 0.0337, 0.0300, and 0.0034, respectively) to generate a response favoring inflammation. ID-PAE further reduced fetal growth and placental efficiency and induced a heightened pro-inflammatory placental profile. IF did not rescue the alcohol-reduced fetal weight, but it normalized placental efficiency and decreased placental inflammation. These placental cytokines correlated with fetal and placental growth, and explained 45% of the variability in fetal weight and 20% of the variability in placental efficiency. In summary, alcohol induces placental insufficiency and is associated with a pro-inflammatory cytokine profile exacerbated by maternal ID and mitigated by maternal IF. Because the placenta is closely linked to intrauterine growth, the placental insufficiency reported here may correlate with the lower birth weights in a subgroup of individuals who experienced PAE.


Imaging of soft tissue abnormalities about the hip.
Soft tissue abnormalities about the hip represent a common clinical problem. Although the signs and symptoms of some of these abnormalities are clinically evident, other entities are frequently overlooked. This article provides an overview and discusses the role of major imaging modalities, especially MR imaging, the primary modality for evaluation of many soft-tissue abnormalities. An introduction to fundamental imaging anatomy and functional roles of soft tissue structures about the hip is provided, recognizing their importance in making the correct diagnosis. Intra-articular and extra-articular soft tissue abnormalities reviewed systematically according to their mechanism of injury and anatomic or functional compartments.


Molecular bases for the asynchronous activation of sodium and potassium channels required for nerve impulse generation.
Most action potentials are produced by the sequential activation of voltage-gated sodium (Nav) and potassium (Kv) channels. This is mainly achieved by the rapid conformational rearrangement of voltage-sensor (VS) modules in Nav channels, with activation kinetics up to 6-fold faster than Shaker-type Kv channels. Here, using mutagenesis and gating current measurements, we show that a 3-fold acceleration of the VS kinetics in Nav versus Shaker Kv channels is produced by the hydrophilicity of two "speed-control" residues located in the S2 and S4 segments in Nav domains I-III. An additional 2-fold acceleration of the Nav VS kinetics is provided by the coexpression of the β1 subunit, ubiquitously found in mammal tissues. This study uncovers the molecular bases responsible for the differential activation of Nav versus Kv channels, a fundamental prerequisite for the genesis of action potentials.


Gestational diabetes. Ensuring optimal outcome for mother and child.
Traditional management recommendations for gestational diabetes are being questioned and are changing. Key components of revised plans of management are that all pregnant women should be screened for gestational diabetes, that stringent goals for blood glucose level are important for better outcome, that self-monitoring of blood glucose levels is essential, and that close attention should be paid to monitoring weight gain during pregnancy. Moreover, maintenance of ideal weight and yearly assessments for diabetes are important follow-up measures for the woman with gestational diabetes.


Peripheral ghrelin reduces food intake and respiratory quotient in chicken.
Ghrelin injection, either centrally or peripherally strongly stimulates feeding in human and rodents. In contrast, centrally injected ghrelin inhibits food intake in neonatal chickens. No information is available about the mechanism and its relationship with energy homeostasis in chicken. Since ghrelin is predominantly produced in the stomach, we investigated the effect of peripherally injected ghrelin (1 nmol/100g body weight) on food intake and energy expenditure as measured in respiratory cells by indirect calorimetry for 24h in one-week-old chickens. Plasma glucose, triglycerides, free fatty acids, total protein and T(3) were measured in a separate experiment until 60 min after injection. Food intake decreased until at least 1h after intravenous ghrelin administration. The respiratory quotient (RQ) in ghrelin-injected chickens was reduced until 14 h after administration whereas plasma glucose and triglycerides concentrations were not altered. Free fatty acids and total protein levels also remained unchanged. Ghrelin did not influence heat production and this was supported by the absence of changes in plasma T(3) levels when compared to the control values. In conclusion, peripheral ghrelin reduces food intake as well as RQ and might influence the type of substrate (macronutrient) that is used as metabolic fuel.


The fatiguing effect of broadband noise: An EEG-based study.
Fatigue continues to be identified as one of the primary contribution factors in aircraft and motor vehicle crashes. The aim of the present study was to examine the fatiguing effect of continuous noise, noise that is present in the cabin of a truck, or an aircraft during flight. In pursuit of this aim, a monotonous driving scenario that has previously been shown to induce fatigue was employed, along with broadband noise set at 75dBA. Changes in participants brain wave activity as measured using an Electroencephalography (EEG), along with subjective measures and driving performance were analysed. Forty-five drivers were randomly assigned to one of three experimental groups (ambient noise group at 40 dBA and broadband noise groups at 55 dBA and 75 dBA) and asked to complete a 90 min monotonous drive. Alpha brain wave activity, subjective fatigue response and deteriorating driving performance all indicate the monotonous drive to be fatiguing. Noise effects were evident with theta brain wave activity where the two noise groups (55 dBA and 75 dBA) had higher levels of theta activity than the ambient noise group. However, no interactions for time by noise were evident in any of the recorded brain activity frequency bands, although trends were evident with alpha activity. These results are discussed from both a theoretical and applied perspective.


Will "personalized medicine" need personalized laboratory approach?
Medicine is evolving on the whole, so laboratory medicine does. Great emphasis is currently presently placed on personalized medicine, particularly by many of the most influential healthcare-linked institutions, communities, organisations and companies. Personalized medicine is an appealing terminology, meaning an individualised approach to patients for either diagnosis or treatment using the most advanced and proper scientific and technological tools, which has its basis on a consolidate literature regarding the main ways for drawing more useful information by laboratory tests. A novel approach tailored around personalized medicine would allow construction of a revolutionary healthcare framework, where a list of laboratory tests adopted for each individual should be descriptive enough of the personal metabolic characteristics, as to be useful in a lifelong perspective, with the needed adjustments due to peculiar genetic variations and/or diseases. By a "personalized" approach, supported by informatics and computer science, each individual would benefit of an "in progress" assessment and the variations from the steady state timely evidenced and acknowledged.


Wide-scope screening of multi-class contaminants in seafood using a novel sample preparation (QuEChUP) procedure coupled with UHPLC-Q-TOF-MS: Application for semi-quantitation of real seafood samples.
A high-resolution mass spectrometry screening method was developed and validated based on EU SANTE/11312/2021 guidelines for the analysis of 850 multi-class contaminants in commercial seafood samples. Samples were extracted using a novel sequential QuEChUP preparation method that combines the QuEChERS and QuPPe procedures. The screening detection limits (SDLs) and limits of identification (LOIs) were equal to or lower than 0.01 mg·kg-1 for 92% and 78% of contaminants, respectively. This screening procedure was ultimately applied for a target screening analysis of 24 seafood samples. The concentrations of identified contaminants were assessed using semi-quantitative approach. Two identified contaminants, diuron and diclofenac, showed the highest estimated average concentrations: 0.076 and 0.068 mg·kg-1 respectively in mussel samples. Suspect screening was also performed. Target and suspect screening led to the identification of mixtures of contaminants (pesticides, veterinary products, industrial chemicals and personal care products) and the assessment of their frequencies of appearance (FoA).


Understanding the determinants of happiness through Gallup World Poll.
The idea of happiness is as old as civilization, but breakthrough is achieved only in 20th century. Happiness can be broadly segmented into biological and behavioural component. The sufferings from illnesses hamper happiness. Happiness correlates negatively with morbidity, mortality, stress and anxiety in contrast to a positive correlation with motivation, healthy behaviours and longevity. In this article, an attempt has been made to understand the relationship between happiness and its important contributory factors. The current study used data from the Gallup World Poll available under license CC0. Data analysis was performed using R studio version 1.0.136. Initially, descriptive analysis in the form of mean (standard deviation), violin plot, correlation matrix, and scatter plots were reported. Subsequently, robust regression estimates along with bootstrap standard errors and confidence intervals were used to report inferential statistics. Norway, with a happiness score of 7.537 ranked first followed by Denmark with a score of 7.522. Burundi with a score of 2.905 is at the bottom of ranking for happiness. Freedom (CI; 0.95-2.22) and Family (CI; 0.92 - 1.57) are the strongest predictors of happiness. The trust variable does not have a significant (CI; -0.27 - 1.94) relationship with happiness. The values and norms in society are changing at a fast pace. Therefore, the measures of happiness require consistent and innovative approaches to measure it.


Effect of preganglionic sympathectomy on the cholinesterase activity in the superior cervical ganglia of rats and hamsters.
By employing biochemical assay and histochemical enzyme techniques the effect of preganglionic sympathectomy on the cholinesterase (ChE) activity in the superior cervical ganglia of rats and hamsters was investigated. Biochemical assays indicate that the ChE activity in the superior cervical ganglia of adult rats and hamsters is 57.19 and 28.63 respectively (expressed in micron moles acetylcholine hydrolyzed per min per g of tissue); two weeks after preganglionic denervation, about 50% and 60% of ChE activity are lost respectively. Histochemical enzyme examination reveals that in the rat superior cervical ganglion, the majority of the neurons are adrenergic with weak to moderate acetylcholinesterase (ACHhE) reaction and the minority of the neurons are cholinergic with strong AChE activity, while only one type of adrenergic neurons exhibits a weak AChE activity in the hamster superior cervical ganglion. The AChE activity is localized in the perinuclear area, in the cisternae of the rough surfaced endoplasmic reticulum, in the Golgi complex and on the plasma membrane of the hamster's neurons; it is mainly locolized in the cisternae of the rough surfaced endoplasmic reticulum of the rat's neurons. AChE reaction product is also detected on the aeolemmal membranes of the preganglionic nerve fibers in the sympathetic ganglia of rats and hamsters. After preganglionic sympathectomy, the AChE activity in the adrenergic neurons and in the preganglionic unmyelinated nerve fibers is markedly reduced, whereas the cholinergic neurons and preganglionic myelinated nerve fibers remain unchanged. On the basis of these results two conclusions have been reached: (1) The fact that strong AChE activity localized in the cholinergic neurons and preganglionic myelinated fibers is not influenced by denervation, suggests that these structures are able to produce AChE. (2) The reduction of AChE activity in the rat and hamster superior cervical ganglia two weeks after preganglionic denervation, observed by histochemical examination, can be correlated with a concomitant measurable reduction determined by biochemical assays.


Unbalanced globin chain synthesis by Hb Lincoln Park (anti-Lepore) reticulocytes.
Hemoglobin synthesis was studied in vitro in reticulocytes from a patient with the anti-Lepore variant Hb Lincoln Park. Incorporation of L-leucine-3H into the alpha and beta delta chains of Hb Lincoln Park was substantially less than the incorporation into the corresponding globin chains of Hb A, with the rate of synthesis of the beta delta chain being similar to that of the delta chain of Hb A2. Synthesis of the alpha and total non-alpha globin components was unbalanced, with a substantial excess of alpha chain synthesis. These findings help to explain the mild hemolytic disease present in individuals with this hemoglobin variant.


Resolution of fused bicyclic ketones by a recombinant biocatalyst expressing the Baeyer-Villiger monooxygenase gene Rv3049c from Mycobacterium tuberculosis H37Rv.
Recombinant Escherichia coli B834 (DE3) pDB5 expressing the Rv3049c gene encoding a Baeyer-Villiger monooxygenase from Mycobacterium tuberculosis H37Rv was used for regioselective oxidations of fused bicyclic ketones. This whole-cell system represents the first recombinant Baeyer-Villiger oxidation biocatalyst that effectively resolves the racemic starting materials in this series. Within biotransformations using this organism one substrate enantiomer remains in high optical purity, while the second enantiomer is oxidized to one type of regioisomeric lactone preferably.


Width as an alternative measurement to length for post-mortem interval estimations using Calliphora augur (Diptera: Calliphoridae) larvae.
The length of fly larvae collected from corpses is often used to help provide an entomological estimate of time since death. However, 'head-curling' by larvae can affect the accuracy of length measurements. To investigate a possible resolution to this problem, larvae of Calliphora augur were grown on sheep's liver at two constant temperatures (20 and 25 degrees C). Replicate samples were collected at set time intervals until pupation. Body length and width were measured for individual larvae and examined as predictors of age. It was found that body width, as measured at the junction of the fifth and sixth abdominal segments, is comparable with body length for age prediction of maggots of C. augur grown at these temperatures. Furthermore, conversion of width to length can be done with 95% accuracy from a simple linear model.


Value of PCR in surgically treated patients with staphylococcal infective endocarditis: a 4-year retrospective study.
The aim of the study was to establish a diagnostic value for broad-range polymerase chain reaction (br-PCR) and staphylococci-specific multiplex PCR (ssm-PCR) performed on surgical material from patients with staphylococcal infective endocarditis (IE). Data were analysed retrospectively from 60 patients with suspected staphylococcal IE and 59 controls who were surgically treated at three cardiosurgery centres over 4 years. Both PCR tests showed high agreement and could be aggregated. In patients with definite and rejected IE, the clinical sensitivity and specificity of PCR reached 89 and 95%, respectively. Tissue culture (TC) and PCR agreed with blood culture (BC) in 29% and 67% of IE cases. TC helped to determine aetiology in five BC negative cases while PCR aided in nine cases. Out of 52 patients with conclusive staphylococcal IE, 40 were diagnosed with S. aureus and 12 with coagulase-negative staphylococci. PCR was shown to be highly superior to TC in confirming preoperative diagnosis of IE. In addition to aid in culture negative patients, PCR helped to establish or refine aetiology in inconclusive cases. We suggest that simultaneous br-PCR and ssm-PCR performed on surgical material together with histopathology could significantly increase the performance of current Duke criteria.


The rates of saxitoxin action and of saxitoxin-tetrodotoxin interaction at the node of Ranvier.
Voltage clamp experiments were done on single nodes of Ranvier of Rana esculenta. Equilibrium effects were obtained from INa-V curves, the rates of action from changes in INa on changing solutions during repetitive depolarizing pulses. 2. Saxitoxin (STX) exclusively and reversibly blocked Na channels, the effect being fully described by a one-to-one reaction between STX and a receptor at the channel with an equilibrium dissociation constant, Ks, of 1.4 nM; the mean offset rate constant k2s, was 1.76 X 10(-2) sec-1 (16 +/- 1 degree C;pH 7.2), 1.7 times the value for tetrodotoxin (TTX). 3. At pH 5.6, K2S WAs increased by a factor of 1.33 while the equilibrium STX effects was decreased in a way suggesting competition between STX and protons. 4. After pretreatment of nodes with 3.1 nM TTX the extra block on adding 9.0 nM STX as well as its relief on taking out STX of the TTX-STX mixture revealed transients in the time course of receptor occupation. 5. These non-monotonic time courses are incompatible with the idea of two independent blocking sites (for STX and TTX) per channel but could be quantitatively fitted by analog-computed curves assuming competition between STX and TTX for the same site.


Modeling Pancreatic Cancer with Patient-Derived Organoids Integrating Cancer-Associated Fibroblasts.
Pancreatic cancer is a devastating disease and is highly resistant to anticancer drugs because of its complex microenvironment. Cancer-associated fibroblasts (CAFs) are an important source of extracellular matrix (ECM) components, which alter the physical and chemical properties of pancreatic tissue, thus impairing effective intratumoral drug delivery and resulting in resistance to conventional chemotherapy. The objective of this study was to develop a new cancer organoid model, including a fibrous tumor microenvironment (TME) using CAFs. The CAF-integrated pancreatic cancer organoid (CIPCO) model developed in this study histologically mimicked human pancreatic cancer and included ECM production by CAFs. The cancer cell-CAF interaction in the CIPCO promoted epithelial-mesenchymal transition of cancer cells, which was reversed by CAF inhibition using all-trans retinoic acid. Deposition of newly synthesized collagen I in the CIPCO disturbed the delivery of gemcitabine to cancer cells, and treatment with collagenase increased the cytotoxic effect of gemcitabine. This model may lead to the development of next-generation cancer organoid models recapitulating the fibrous TME.


Significance of Preoperative Prognostic Nutritional Index in the Perioperative Management of Gastric Cancer.
Malnutrition leads to accelerated tumor progression through the suppression of tumor immunity. The present study examined the significance of the preoperative prognostic nutritional index (PNI) for predicting postoperative survival outcomes in gastric cancer (GC). A total of 447 patients who underwent curative gastrectomy for GC were included in the present study. PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte counts (per mm3). The prognostic impact of preoperative PNI was examined using two multivariate analysis models. The optimal cutoff value of preoperative PNI for predicting overall survival (OS) was 48 based on a receiver operating characteristic curve. The 5-year OS rate was 59.5% in the PNI<48 group and 91.3% in the PNI≥48 group (p<0.001). In the first multivariate survival analysis where all explanatory variables were composed of preoperative factors alone, a PNI<48 (hazard ratio [HR] 3.33; 95% confidence interval [CI] 2.01-5.56, p<0.001), upper-third GC and cT2-T4 were identified as independent indicators of a poor OS. In the second survival analysis where explanatory variables were composed of preoperative, intraoperative, and pathological factors, a PNI<48 (HR 2.80; 95% CI 1.65-4.78, p<0.001), hypertension, open gastrectomy, intraoperative blood loss≥100g, pT2-T4, and pN+ were independent prognostic factors. Preoperative PNI may be a useful predictor of postoperative survival outcomes both before and immediately after surgery in GC. Appropriate perioperative interventions and the meticulous surveillance of GC relapse are necessary for patients with PNI<48.


Fatty acid profiles in erythrocyte membranes following the Mediterranean diet - data from a multicenter lifestyle intervention study in women with hereditary breast cancer (LIBRE).
Evidence-based concepts to prevent breast cancer in women with BRCA1/2 mutations are limited. Adherence to a Mediterranean diet (MedD) has been associated with a lower risk for breast cancer, possibly due to a favorable fatty acid (FA) intake. Here, we studied in an at-risk population the effect of a lifestyle intervention that included the MedD on FA composition in red blood cell membranes (RBCM). Data derived from the German multicenter trial LIBRE, from which 68 women were randomized into an intervention group (IG) trained for MedD and increased physical activity for 12 months, and a usual care control group (CG). Adherence to the diet was assessed after 3 and 12 months using the validated Mediterranean Diet Adherence Screener (MEDAS) and a food frequency questionnaire. RBCM FA were analyzed by gas chromatography with mass spectrometry. The MEDAS was increased in both groups after 3 months (IG: P < 0.001; CG: P = 0.004), and remained increased only in the IG after 12 months (P < 0.001). The food frequency questionnaire revealed an increased intake of omega-3 (n-3) FA at month 3 and month 12 in the IG (both P < 0.01), but not in the CG, in which intake of energy, protein and saturated FA decreased. In both groups n-6 FA in the RBCM decreased (P < 0.001), while n-9 FA increased (P < 0.001) and n-3 FA were unchanged. Women with higher consumption of fish had higher amounts of n-3 fatty acids in the RBCM. The MEDAS was inversely correlated with n-6 fatty acids. The RBCM FA composition was associated with dietetic parameters related to the MedD. Adherence to the MedD resulted in an altered, likely favorable FA composition. Our data suggest selected FA as biomarkers to monitor compliance to a dietetic intervention such as the MedD. The trial is registered at ClinicalTrials.gov (reference: NCT02087592).


Adult vertebrate behavioural aquatic toxicology: Reliability and validity.
Current advances in the ability to assay adult aquatic vertebrate behaviour are potentially very useful to aquatic toxicologists wishing to characterise the effects of pollutants on behaviour, cognition or neurodevelopment. This review considers two specific challenges faced by researchers wishing to exploit these technologies: maximising reliability and validity. It will suggest two behavioural procedures, with the potential for automation and high-throughput implementation, which can be used to measure social cohesion and anxiety, two areas of interest in behavioural aquatic toxicology. In addition, the review will make recommendations about how these procedures (and others) could be carried out to maximise reliability and validity.


Prey analysis of four species of tropical orb-weaving spiders (Araneae: Araneidae) and a comparison with araneids of the temperate zone.
The actual prey in the orb webs of four araneid spiders (Nephila clavipes, Eriophora fuliginea, Argiope argentata, and A. savignyi) and the relative abundance of their potential prey (pitfall traps, yellow traps, and sweep-netting) was investigated over 1 year at different locations in Panama. The relative abundance of insects and spiders depends on seasonal fluctuations (Fig. 2) which are reflected by corresponding variations in the effectiveness of the webs. The main prey groups are Nematocera (50%-68%), winged Formicoidea (6%-15%) and Hymenoptera, Coleoptera, and Brachycera (4%-10% each) (Fig. 4-6). The remaining 10%-17% of the prey comes from up to 26 other groups (Table 2). Differences in prey size and prey composition between the spider species are small (Fig. 7). Most prey items are 1-2 mm long: only a few insects exceed 30 mm body length (Figs. 9-12). Relative to the available prey, some groups (e.g. Nematocera, Aphidoidea, Psocoptera) are caught selectively, while other groups (e.g. Heteroptera, Coleoptera, Brachycera, Orthoptera) are underrepresented in the prey spectrum and obviously avoid orb webs (Table 7). The differences in prey composition between araneids of the tropics and of the temperate zone are discussed (Table 8) and compared to those recorded in other studies (Table 9, 10). Most of these report large numbers of big prey items (Odonata, Lepidoptera, wasps/bees). It is pointed out that those studies do not take into account the total available prey in a spider's web but only that part which the spider selects from the web (mainly according to size). The importance of small prey items even for large spiders is explained and an obvious lack of niche partitioning among coexisting araneids is discussed (Table 11).


Corneal oxygen availability during contact lens wear: a comparison of methodologies.
Three distinct methodologies have been used to assess corneal oxygen supply during contact lens wear--oxygen transmissibility (Dk/L), equivalent oxygen percentage (EOP), and corneal swelling. To examine the interelation among these methodologies, we measured the EOP and the amount of corneal swelling in response to a set of contact lenses of a range of Dk/L values on 10 subjects. We also measured the corneal swelling response after exposure to gas mixtures of 0.00, 1.01, 2.65, 5.13, and 10.3% oxygen concentration (balance nitrogen). Analysis of covariance showed that the relation between corneal swelling and EOP during lens wear was significantly different from the relation between corneal swelling and oxygen concentration after exposure to the gas mixtures, leading to different estimates of the minimum oxygen tension required to avoid corneal swelling (18.0% for the EOP technique vs. 10.9% for the gas mixtures). This discrepancy may be explained in terms of the underlying assumptions of the various techniques and by consideration of the mechanisms of corneal swelling during contact lens wear. The clinical implication of this result is that an EOP of 18% should be used as the basis for the development of a daily wear contact lens that provides an "edemafree" response.


Separation of cells by affinity chromatography on SpA-sepharose 6MB.
A cell separation technique was designed which was based on the reaction of protein A of Staphylococcus aureus (SpA) with the Fc regions of IgG antibodies. SpA covalently linked to Sepharose 6MB is able to fix antibody-bearing cells, while non-fixed cells are removed by washing. The fixed cells can be released by dog IgG or by mechanical treatment. As an example of the use of the technique, Ig-bearing cells were isolated from mouse spleen cells treated with rabbit IgG anti-mouse Ig antibody; the purity of the Ig-bearing lymphocytes so isolated was better than 90%. The viability and the ability of the cells to shed the antibodies from their surface were not significantly impaired by the fractionation method. The technique can be generally applied to cell separation providing IgG antibodies against specific surface markers are available.


Measurement uncertainty arising from sampling and analytical steps of dissolution test of prednisone tablets.
Dissolution is used to determine the rate and extent of drug release from the dosage form into a dissolution medium, which allow to assess the batch-to-batch variability. Considering that the dissolution test is used to predict the vivo performance of the drug as well, it is important to guarantee the quality and reliability of dissolution test results. The aim of this work was to evaluate the measurement uncertainty arising from sampling and analytical steps of dissolution test of prednisone tablets. Dissolution test was performed using 900 mL of purified water as dissolution medium and a dissolution apparatus equipped with paddles rotating at 50 rpm for 30 min. Quantification was performed by UV spectrophotometer. Uncertainty arising from sampling was estimated using the duplicate method (empirical approach), using 17-sampling target, two samples for each sampling target, and three replicas for each sample, totalizing 102 analyses. Uncertainty arising from analytical steps considered the uncertainty from dissolution step (estimated using Monte Carlo method and regression equation obtained using DoE) and uncertainty from quantification step. Overall uncertainty value was found to be 2.2%, which is below the target uncertainty value (ut =2.5%). The contributions of uncertainty sources in this study were as follows: 24% from sampling uncertainty, 29% from the dissolution step uncertainty, and 47% from the quantification step uncertainty. The results of dissolution test should be compared to the specification limits (Q). According to the pharmacopeia requirements, the batch of the medicine should be declared compliant if the dissolved amount of prednisone for six tablets are above the specification limits + 5% (Q+5%=85%). Since the measured values for all six tablets (96.5%, 94.0%, 96,4%, 95.3%, 96.0%, and 96.9%) were above the multivariate acceptance limit (90.2%, calculate as the standard uncertainty multiplied by multivariate coverage factor), the batch of the prednisone tablets was declared complaint, with a reduced total risk of false decision (total risk value below 5%).


Comparative transcriptomics of the nematode gut identifies global shifts in feeding mode and pathogen susceptibility.
The nematode Pristionchus pacificus has been established as a model for comparative studies using the well known Caenorhabditis elegans as a reference. Despite their relatedness, previous studies have revealed highly divergent development and a number of morphological differences including the lack of a pharyngal structure, the grinder, used to physically lyse the ingested bacteria in C. elegans. To complement current knowledge about developmental and ecological differences with a better understanding of their feeding modes, we have sequenced the intestinal transcriptomes of both nematodes. In total, we found 464 intestine-enriched genes in P. pacificus and 724 in C. elegans, of which the majority (66%) has been identified by previous studies. Interestingly, only 15 genes could be identified with shared intestinal enrichment in both species, of which three genes are Hedgehog signaling molecules supporting a highly conserved role of this pathway for intestinal development across all metazoa. At the level of gene families, we find similar divergent trends with only five families displaying significant intestinal enrichment in both species. We compared our data with transcriptomic responses to various pathogens. Strikingly, C. elegans intestine-enriched genes showed highly significant overlaps with pathogen response genes whereas this was not the case for P. pacificus, indicating shifts in pathogen susceptibility that might be explained by altered feeding modes. Our study reveals first insights into the evolution of feeding systems and the associated changes in intestinal gene expression that might have facilitated nematodes of the P. pacificus lineage to colonize new environments. These findings deepen our understanding about how morphological and genomic diversity is created during the course of evolution.


[General surgery following heart valve replacement (author's transl)].
Patients with heart valve replacement regarding further surgical treatment are sub-divided into 3 groups. 1) Patients after open or closed reconstruction of valves with sinus rhythm and no anticoagulation.--2) Arrhythmic patient of the same kind but under anticoagulation.--3) Patients with valve replacement, who are under anticoagulation if there is no vital contraindication.--Group 1 and 2 may be operated on at every general hospital, provided cardiological supervision can be practiced. Until now patients of group 3 should always be treated in a cardiosurgical centre.


Meta-analysis does not support routine traditional nuclear medicine studies for malignant otitis.
The role of traditional nuclear medicine studies in the management of malignant otitis externa (MOE) is unclear and there are ongoing debates regarding their diagnostic value. The authors perform a systematic review and meta-analysis to assess the sensitivity and specificity of traditional nuclear medicine studies in the diagnosis of MOE. In accordance with PRISMA guidelines, a query of the Medline, Embase, Web of Science, and Cochrane databases was undertaken. The primary outcomes of interest were the sensitivity and specificity of traditional nuclear medicine studies to detect MOE. Of the initial 1317 hits from the four databases, 20 articles with a combined 608 patients were ultimately included in the review. The pooled sensitivities for Technetium-99 and Gallium-67 were 85.1% (95% CI, 72.0-98.1%) and 71.2% (95% CI, 55.1-87.3%) respectively. The available evidence suggested poor specificity of these modalities, but was insufficient for meta-analysis. Neither modality was shown to be effective in the assessment of disease resolution. The sensitivities of Technetium-99 and Gallium-67 to detect MOE are less favorable than was initially thought. Given this finding and their poor specificity, lack of anatomic resolution, unproven ability to detect disease resolution and variable availability, this review does not support the routine use of these studies in the management of MOE. N/A Laryngoscope, 130:1812-1816, 2020.


Sleep mediates the relationship between having an autistic child and poor family functioning.
Sleep is an important biological necessity, a lack of which can have many cognitive, psychological, social, and physical impacts. Children with autism are known to present with sleep difficulties more frequently than their typically developing peers but despite this, there is relatively little research looking at the impact of sleep on the family. To investigate the effect of sleep on families of autistic and typically developing (TD) children, we conducted a study of sleep disturbances among children, sleep quality of their parents in association with their family function. In our study, 239 parents of autistic children and 227 parents of TD children participated. These parents completed a survey about their child's sleep disturbances, their own sleep quality, and their family function, along with a series of demographic questions. Analyses indicated that autistic children experience more sleep difficulties than TD peers, that children's sleep disturbances are associated with parental sleep quality and that parents of autistic children report decreased sleep quality compared to parents of TD children. Parental sleep quality, and child sleep quality were both found to partially mediate the relationship between autism diagnosis and family function.


Predictors for occasional and recurrent falls in community-dwelling older people.
Little is known about the prevalence of falls and the related risk factors in the general population of community-living older people in Germany. To assess the prevalence and related predictors of different types of falls in a sample of community-dwelling 65 years and older people in Germany living in a metropolitan area. Study design and setting prospective cohort study in 622 community dwelling people aged > or =65 years. A total of 107 persons (17.2%) reported falling at least once (occasional fallers), while 36 (5.7%) experienced two or more falls (recurrent fallers) in the last 6 months. Main predictors for all fallers were age (OR 1.8; 95% CI 1.1-3.0), being female (OR 1.7; 95% CI 1.1-2.2), living alone (OR 1.9; 95% CI 1.2-2.9), poor health status (OR 3.3; 95% CI 2.1-5.3), varifocals (OR 1.7; 95% CI 1.0-3.1), disturbance of memory (OR 1.7; 95% CI 1.0-3.0), depression (OR 4.8; 95% CI 2.5-9.2), sleep disturbances (OR 2.7; 95% CI 1.7-4.3), incontinence (OR 2.1; 95% CI 1.3-4.9), dizziness (OR 3.0; 95% CI 1.9-5.0), 3 medical conditions or more (OR 3.3; 95% CI 2.1-5.1), lower physical functioning and mobility. Two of the strongest predictors were reported falls (OR 4.9; 95% CI 3.1-7.7) and recurrent falls (OR 10.0; 95% CI 5.0-20.0) in the last 6 months. Older adults living at home should be screened for falls in history and problems in gait and mobility in any anamnesis to identify those who are at risk for falls.


γ-Cyclodextrin encapsulated thymol for citrus preservation and its possible mechanism against Penicillium digitatum.
The volatility of essential oils greatly limits their industrial applications. Here, we successfully prepared γ-cyclodextrin (γ-CD) inclusion compounds (γ-CDTL) containing thymol (TL) for the control of green mold caused by Penicillium digitatum (P. digitatum) in citrus fruit. In vitro experiment showed that the minimum fungicidal concentration (MFC) of γ-CDTL against the hyphae growth of P. digitatum was 2.0 g/L, and 8 × MFC treatment significantly reduced the occurrence of green mold in citrus fruit and had no adverse effect on fruit quality in vivo test compared to prochloraz. Scanning electron microscopy (SEM), x-ray diffraction (XRD), fourier transform-infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), physical properties and sustained release properties were also performed, results indicated that the hydrogen bonds between TL and γ-CD were the basis for the formation of γ-CDTL. We further investigated the inhibition mechanism of γ-CDTL. SEM and TEM experiments showed that γ-CDTL treatment caused severe damage to the hyphal morphology and cells in 30 min and disrupted the permeability of P. digitatum mycelial cell walls by increasing the chitinase activity, thus accelerating the leakage of intracellular lysates. However, the integrity of the cell membrane was obviously damaged only after 60 min of treatment. In conclusion, we prepared a novel inclusion complex γ-CDTL with obvious antifungal effects and preliminarily elucidated its inclusion mechanism and antifungal mechanism. γ-CDTL might be a potent alternative to chemical fungicides for controlling the postharvest decay of citrus.


Recombination of parent and daughter strand DNA after UV-irradiation in mammalian cells.
The mechanism by which mammalian cells replicate DNA containing pyrimidine dimers is poorly understood. When DNA synthesis is initiated after UV-irradiation in bacteria, parental DNA containing pyrimidine dimers has been shown to 'exchange' into the daughter strand DNA by a recA-dependent mechanism. In earlier experiments, when growing mammalian cells were UV-irradiated and then incubated with labelled thymidine, pyrimidine dimers were initially interpreted to be in the newly synthesized DNA, but later were found to be only adjacent to newly synthesized DNA in daughter strand present before UV treatment. A way to avoid these problems of interpretation would be to use cells in G0 or G1 which are not synthesizing DNA at the time of irradiation. UV damage could then be detected in a very sensitive quantitative assay such as that recently described using alkaline elution and an endonuclease preparation from Micrococcus luteus. I have now used this approach and report that up to 3 dimers per 10(9) daltons of daughter strand DNA could be detected 34-45 h after UV-irradiation in human peripheral blood lymphocytes (PBL), normal human fibroblasts, group A xeroderma pigmentosum (XP) fibroblasts and mouse 3T3 cells. This represents approximately 1-3% of the dimers present in the parent strand at this time after UV.


EGFR cooperates with glucose transporter SGLT1 to enable chromatin remodeling in response to ionizing radiation.
EGFR and the sodium-dependent glucose transporter, SGLT1, are found in complex after radiation treatment. The aim of this study was to elucidate the role of EGFR in glucose uptake and chromatin remodeling. Glucose accumulation was quantified with help of (3)H-glucose. Involvement of SGLT was detected by a specific inhibitor. Role of EGFR was proved by EGFR overexpression and siRNA driven knockdown. Functional endpoints were intracellular ATP levels, protein expression, residual DNA-damage and colony formation. EGFR/SGLT1 interactions in response to ionizing radiation were associated with increased glucose uptake. Nevertheless, tumor cells exhibit ATP depletion following irradiation. Recovery from radiation-induced ATP crisis was EGFR/SGLT-dependent and associated with increased cell survival and improved DNA-repair. The blockage of either EGFR or SGLT inhibited ATP level recovery and histone H3 modifications crucial for both chromatin remodeling and DNA repair in response to irradiation. Inhibition of the acetyltransferase TIP60, which is essential for histone H3-K9 acetylation and ATM activation, prevented energy crisis and chromatin remodeling. Radiation-associated interactions between SGLT1 and EGFR resulted in increased glucose uptake, which counteracts the ATP crisis in tumor cells due to chromatin remodeling. The blockage of recovery from ATP crisis led to radio-sensitization in tumor cells.


Misoprostol for induction of labor with a live fetus.
Induction of labor is common in clinical practice. Many different medical and mechanical methods have been used, but the current gold standard is vaginal dinoprostone. Misoprostol has been used for the induction of labor since 1987. In early studies with large misoprostol doses (e.g. 200 microg) there were high rates of uterine hyperstimulation. Cochrane meta-analysis, however, shows that when used in low doses it is as effective as vaginal dinoprostone and with no excess of hyperstimulation. 25 microg vaginal misoprostol 4-hourly, 50 microg oral misoprostol 4-hourly or 20 microg oral misoprostol solution 2-hourly are all safe and effective regimens. Reports of uterine rupture in women with previous cesarean sections mean that it remains contraindicated in this group.


Assessing the contribution of the two protein disulfide isomerases PDIA1 and PDIA3 to cisplatin resistance.
Intracellular binding of cisplatin to non-DNA partners, such as proteins, has received increasing attention as an additional mode of action and as mechanism of resistance. We investigated two cisplatin-interacting isoforms of protein disulfide isomerase regarding their contribution to acquired cisplatin resistance using sensitive and resistant A2780/A2780cis ovarian cancer cells. Cisplatin cytotoxicity was assessed after knockdown of either protein disulfide isomerase family A member 1 (PDIA1) or protein disulfide isomerase family A member 3 (PDIA3). Whereas PDIA1 knockdown led to increased cytotoxicity in resistant A2780cis cells, PDIA3 knockdown showed no influence on cytotoxicity. Coincubation with propynoic acid carbamoyl methyl amide 31 (PACMA31), a PDIA1 inhibitor, resensitized A2780cis cells to cisplatin treatment. Determination of the combination index revealed that the combination of cisplatin and PACMA31 acts synergistically. Our results warrant further evaluation of PDIA1 as promising target for chemotherapy, and its inhibition by PACMA31 as a new therapeutic approach.


Synthesis of recyclable GO/Cu3(BTC)2/Fe3O4 hybrid nanocomposites with enhanced photocatalytic degradation of aflatoxin B1.
This study evaluated the photocatalytic performance of the activated carbon assisted GO/Cu3(BTC)2/Fe3O4 photocatalyst for aflatoxin B1 (AFB1) degradation under ultraviolet light. The nanocomposite was characterized by Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption-desorption. The numerous factors influencing the degradation efficiency of AFB1 including catalyst dose, pH importance, and contact time were also probed. The elevated degradation performance of AFB1 by 99% was due to a larger surface area and improved GO/Cu3(BTC)2/Fe3O4 photocatalyst. The degradation process followed a pseudo-first-order kinetic model. Moreover, it is possible to quickly isolate the catalyst from the solution and retain successful operation. In the degradation of AFB1, the hole(h+) and the hydroxyl radicals(OH) were found to play a significant role. These studies showed that GO/Cu3(BTC)2/Fe3O4 has high capturing capacity and photoactivity synergy, thereby offering a quick effect, and green solution to AFB1 degradation.


Comparison of 2.4 GHz WiFi FTM- and RSSI-Based Indoor Positioning Methods in Realistic Scenarios.
With the addition of the Fine Timing Measurement (FTM) protocol in IEEE 802.11-2016, a promising sensor for smartphone-based indoor positioning systems was introduced. FTM enables a Wi-Fi device to estimate the distance to a second device based on the propagation time of the signal. Recently, FTM has gotten more attention from the scientific community as more compatible devices become available. Due to the claimed robustness and accuracy, FTM is a promising addition to the often used Received Signal Strength Indication (RSSI). In this work, we evaluate FTM on the 2.4 GHz band with 20 MHz channel bandwidth in the context of realistic indoor positioning scenarios. For this purpose, we deploy a least-squares estimation method, a probabilistic positioning approach and a simplistic particle filter implementation. Each method is evaluated using FTM and RSSI separately to show the difference of the techniques. Our results show that, although FTM achieves smaller positioning errors compared to RSSI, its error behavior is similar to RSSI. Furthermore, we demonstrate that an empirically optimized correction value for FTM is required to account for the environment. This correction value can reduce the positioning error significantly.


Obesity in nursing homes: an escalating problem.
To estimate trends in the prevalence of obesity in nursing homes, to characterize the obese nursing home population, and to evaluate the extent to which estimates of the prevalence of obesity varied by facility and geographic location. Cross-sectional. One thousand six hundred twenty-five nursing homes in Kansas, Maine, Mississippi, New York, and South Dakota from 1992 to 2002; 16,110 nursing homes in the United States in 2002. Newly admitted residents between 1992 and 2002 (n=847,601) in selected states and 1,448,046 residents newly admitted to a U.S. nursing home in 2002 with height and weight documented on the Minimum Data Set (MDS) assessment. Data were from the Systematic Assessment of Geriatric Drug Use via Epidemiology database. Residents were classified as having a body mass index of less than 18.5 kg/m2, 18.5 to 24.9 kg/m2, 25.0 to 29.9 kg/m2, 30 to 34.9 kg/m2, or 35.0 kg/m2 or greater. Adjusting for sociodemographics, in Kansas, Maine, Mississippi, New York, and South Dakota, fewer than 15% of newly admitted residents were obese in 1992, rising to more than 25% in 2002. In U.S. nursing homes, the distribution of obese residents is not shared equally across facilities. Nearly 30% of residents with a BMI of 35 kg/m2 or greater are younger than 65, and a disproportionate percentage of obese residents are non-Hispanic black. Residents identified as obese had a higher likelihood of comorbid conditions (e.g., diabetes mellitus, arthritis, hypertension, depression, and allergies). Increasing prevalence of obesity in nursing homes and substantial variation of obesity prevalence within facilities raise concerns about nursing home preparedness and access.


Study on the mechanical properties of unloading damaged sandstone under cyclic loading and unloading.
To reveal the mechanical properties of rocks under stress disturbance and unloading confining pressure, conventional triaxial compression tests, triaxial compression tests on unloading damaged sandstone, and cyclic loading and unloading tests on unloading damaged sandstone were conducted. Then, the evolutionary characteristics of dissipated energy in sandstone under cyclic loading and unloading were explored, and damage variables were proposed. The crack development characteristics were analyzed from a microscopic perspective. The study results reveal that: (1) the sandstone exhibits obvious brittle failure under different stress paths, and the macroscopic failure mode is dominated by shear failure. As the number of cycles increases, the load-bearing capacity, elastic modulus, and deformation modulus of the sandstone will be significantly reduced if it suffers greater unloading damage. (2) The cyclic action in the early stage inhibits the development of the internal fracture. However, the inhibitory effect is significantly reduced for specimens with larger unloading quantities. The damage variable in the cyclic loading and unloading is about 50.00% of that in the unloading, indicating that unloading confining pressure is the dominant factor for specimen failure. (3) The extension of microcracks within the sandstone is dominated by intergranular cracks, and the number of cracks increases with the increase of unloading quantity. After cyclic loading and unloading, the structure becomes looser. The test results deepen the understanding of rock mechanical behavior and fracture evolution under cyclic loading and can provide a basis for structural stability improvement under stress disturbance and unloading confining pressure.


Simultaneous determination of fraxin and its metabolite, fraxetin, in rat plasma by liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study.
For the first time, a rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of fraxin and its metabolite, fraxetin, in rat plasma, using esculin as the internal standard (IS). The plasma samples were precipitated with methanol before separation on an Nova-Pak C18 column (150mm×3.9mm, 3μm) using a mobile phase consisting of 0.1% formic acid and methanol (55:45) at a flow rate of 0.8mL/min. The analytes were detected by multiple reaction monitoring in the negative ion mode with the mass transitions at m/z 368.9→ m/z 191.9 (fraxin), m/z 206.9→ m/z 191.8 (fraxetin) and m/z 339.0→ m/z 176.9 (esculin, IS). The results demonstrated that the calibration curves for both analytes have good linearity (r≥0.995) over a concentration range of 5.00-3000ng/mL. The assay was validated according to the regulatory bioanalytical guidelines and proved acceptable. The intra- and inter-day precisions (R.S.D.%) were within 10.9% for both analytes, whereas the deviation of assay accuracies (R.E.%) ranged from -5.3 to 1.0%. The method was successfully applied to a pharmacokinetic study after a single oral dose of fraxin at 50mg/kg to rats.


CSDB_GT, a curated glycosyltransferase database with close-to-full coverage on three most studied nonanimal species.
We report the accomplishment of the first stage of the development of a novel manually curated database on glycosyltransferase (GT) activities, CSDB_GT. CSDB_GT (http://csdb.glycoscience.ru/gt.html) has been supplemented with GT activities from Saccharomyces cerevisiae. Now it provides the close-to-complete coverage on experimentally confirmed GTs from the three most studied model organisms from the three kingdoms: plantae (Arabidopsis thaliana, ca. 930 activities), bacteria (Escherichia coli, ca. 820 activities) and fungi (S. cerevisiae, ca. 270 activities).


Ultrastructural studies of vasopressin neurons of the paraventricular nucleus of the hypothalamus using a monoclonal antibody to vasopressin: analysis of synaptic input.
The ultrastructure of the vasopressin neurons of the paraventricular nucleus of the hypothalamus was studied by immunocytochemical techniques. Tissue antigen was detected in unembedded tissue sections using a monoclonal antibody that recognizes vasopressin but not oxytocin or vasotocin. At the light-microscopic level, reaction product was seen to fill the cytoplasm of the neuron cell body as well as large portions of the dendrite and axon. Immunoreactive spines were seen on both somatic and dendritic surfaces and their presence was confirmed at the ultrastructural level. In the light-microscope, axonal processes do not have spines and are thinner and more varicose than dendritic processes. At the electron-microscopic level, both axons and dendrites of the vasopressin cells are filled with reactive neurosecretory granules. The presence of large numbers of these organelles made it difficult to distinguish proximal dendrites from Herring bodies (axonal swellings). At the ultrastructural level, reaction product was also observed in the cytoplasm of all segments of the vasopressin cells. The presence of reaction product outside of membranous compartments is undoubtably due to disruption of membranes by detergent treatment or exposure to basic pH. However, the staining procedure used did allow us to examine the synaptic input to the vasopressin cells. All portions of the vasopressin neuron receive a diverse innervation. The somata have synapses on their surfaces and on spines. These axo-somatic terminals are primarily, but not exclusively, symmetrical and the presynaptic elements contain spherical or elongate vesicles. On the dendrites, terminals again were observed on the surface or on spines. these axo-dendritic synapses were usually asymmetrical. The presynaptic elements contained clear spherical, elongate or pleomorphic vesicles. Occasional varicosities with dense-core granules were seen to make en passant contacts with dendrites; these contacts did not have obvious membrane specializations. Input to vasopressin axons was studied both along the paraventricular-neurohypophysial tract and in the median eminence. Vasopressin axons receive a synaptic input (axo-axonic), predominately of the asymmetric variety with clear, spherical vesicles in the presynaptic element. These findings demonstrate that the vasopressin neurons of the paraventricular nucleus receive a diverse innervation.


Prevalence and Risk of Metastatic Thyroid Cancers and Management Outcomes: A National Perspective.
Examine the prevalence and risk of metastasis in thyroid cancers and management outcomes. Retrospective analysis of the National Cancer Database, 2004-2014. The study population included adult (≥ 18 years) patients with thyroid cancer. Analysis included multivariate logistic regression and Cox hazard ratio modeling. A total of 152,979 patients were included. Distant metastasis was reported in 1,867 (1.22%) patients. The distribution of metastatic cases based on pathology and tumor size were as follows in descending order: papillary thyroid carcinoma (PTC) 1 to 4 cm (30.53%), PTC > 4 cm (19.34%), undifferentiated (UTC) > 4 cm (14.14%), PTC < 1 cm (8.46%), follicular thyroid carcinoma (FTC) > 4 cm (7.28%), FTC 1 to 4 cm (5.52%), medullary thyroid cancer (MTC) ≤ 4 cm (3.96%), MTC > 4 cm (3.91%), UTC ≤ 4 cm (3.32%), Hürthle (HCC ) > 4 cm (2.09%), and HCC 1 to 4 cm (1.45%). Significant predictors of distant metastasis, while controlling for tumor pathology and size, included older age, male gender, non-White minorities, presence of multiple comorbidities, minimal, gross extrathyroidal extension (ETE), lymphovascular invasion (LVI), and concomitant central and lateral lymph node metastasis (LNM) (P < .05 each). The risk of distant metastasis in the absence of nodal metastasis, ETE, and LVI was highest for FTC > 4 cm. Although the risk of metastasis in well-differentiated thyroid carcinoma (WDTC) is low, the prevalence of metastatic thyroid cancer is highest in WDTC population because it is the most common type of thyroid cancer. Certain pathological features, including minimal ETE and central LNM, are associated with a higher prevalence of metastatic disease. NA Laryngoscope, 131:237-244, 2021.


Six years' experience in treatment of chromomycosis with 5-fluorocytosine,.
Twenty-three patients with chromomycosis were treated with oral 5-fluorocytosine for periods ranging from 2 to 67 months. Sixteen were considered cured, after 3 consecutive monthly controls showing healing of the lesions and absence of fungi in mycologic and histopathologic examinations of biopsy specimens. Seven, in spite of initial clinical improvement, showed resistance to treatment. Associated treatment with amphotericin B, calciferol or thiabendazole failed to help patients resistant to 5-fluorocytosine. Resistance seems to occur especially in those with long-standing lesions or widespread involvement.