The inhibitory effect of Sunset Yellow on thermally induced Human Serum Albumin aggregates: Possible role in naturopathy.
Intensive research in the field of protein aggregation confirmed that the deposition of amyloid fibrils of proteins are the major cause for the development of various neurotoxic and neurodegenerative diseases, which could be controlled by ensuring the efficient inhibition of aggregation using anti aggregation strategies. Herein, we elaborated the anti amyloidogenic potential of Sunset Yellow (SY) dye against Human Serum Albumin (HSA) fibrillogenesis utilising different biophysical, computational and microscopic techniques. The inhibitory effect of sunset yellow was confirmed by Rayleigh Light Scattering (RLS) measurements along with different dye binding assays (ANS, ThT and CR) by showing concentration dependent reduction in scattering intensity and fluorescence intensity respectively. Further, destabilization and anti fibrillation activity of HSA aggregates were characterized through spectroscopic techniques like Circular Dichroism (CD) and other microscopic techniques like Transmission Electron Microscopy (TEM) for elucidating the structural properties. The SDS-PAGE was also carried out that render the disaggregation effect of the dye on the protein. Moreover, Molecular Docking studies revealed the binding parameters justifying the stable protein-dye complex. Simulation studies were also performed accordingly. Thus, this dye which is used as food additive can serve as a potential aggregation inhibiting agent that can aid in the prevention of amyloidogenic diseases.


Sonochemical synthesis of supersaturated Ga-Al liquid-alloy fine particles and Al3+-doped γ-Ga2O3 nanoparticles by direct oxidation at near room temperature.
In this study, we investigated the fabrication of supersaturated gallium (Ga)-aluminum (Al) liquid alloy and Al3+-doped γ-Ga2O3 nanoparticles (NPs) at near room temperature (60 °C) using sonochemical and sonophysical effects. Supersaturated Ga-Al liquid alloy microparticles (Dav = 1.72 µm) were formed and stabilized at 60 °C by the thermal nonequilibrium field provided by sonochemical hot spots. Compared with liquid Ga, supersaturated Ga-Al liquid alloy was rapidly oxidized to a uniform oxide without Al2O3 or Al deposition. Thus, ultrafine Al3+-doped γ-Ga2O3 NPs were obtained after only 1 h of ultrasonic irradiation at 60 °C. The oxidation of liquid Ga was remarkably accelerated by alloying with metallic Al and ultrasonic irradiation, and the time was shortened. The average diameter and surface area of the γ-Ga2O3-based NPs were 59 nm and 181 m2/g, respectively. Compared with γ-Ga2O3, the optical bandgap of the Al3+-doped γ-Ga2O3 NPs was broadened, and the thermal stability improved, indicating Al3+-doping into the γ-Ga2O3 lattice. However, the lattice constant of γ-Ga2O3 was almost unchanged with or without Al3+-doping. Al3+ was introduced into the defect sites of Ga3+, which were massively induced in the defective spinel structure during ultrasonic processing. Therefore, sonochemical processing, which provides nonequilibrium reaction fields, is suitable for the synthesis of supersaturated and metastable materials in metals and ceramics fields.


Erratum.
Volume 34 Issue 3 - July/Aug/Sept 2012. Nutritional and epidemiological aspects of patients with chronic renal failure undergoing hemodialysis from Brazil, 2010. The author's name Advisor Carmen Tzanno-Martins was highlighted in the incorrect place, the correct one is mentioned above.


Dermal and underlying tissue pharmacokinetics of salicylic acid after topical application.
The time course of salicylic acid at a dermal application site and in local underlying tissues below the site in rats was examined using a physiologically based pharmacokinetic model assuming first-order diffusional mass transfer between the dermis and underlying tissues. The concentrations of salicylic acid in tissues below the applied site were measured and compared with plasma concentrations and concentrations in similar tissues on the contralateral side. The direct penetration of salicylic acid was dominant only to a depth of 3-4 mm below the applied site for the first approximately 2 hr after application. The time course of salicylic acid in individual rats was modeled using known tissue blood flows and tissue-tissue clearances by (i) numerical integration and nonlinear regression of a series of differential equations representing events in individual tissues, and (ii) numerical integration and nonlinear regression of a single differential equation representation of the concentration-time course in an individual tissue with a polynomial representation of salicylate concentrations in other input tissues and an exponential representation of the input from the solution. Tissue-tissue clearances were deduced by both nonlinear regression and mass balance analysis (only for underlying dermis) using area-under-the-curves from salicylic acid tissue penetration data in anesthetized rats. The relative importance of direct penetration and blood supply in determining the concentrations of salicylic acid in deeper tissues was assessed by simulations in which either no direct penetration occurred or there was zero input from blood. Simulations confirm that direct penetration is only evident in the superficial tissues for approximately 2 hr. An attempt was also made to examine the dermal pharmacokinetics of salicylic acid using statistical moments.


Toward understanding of the high number of plant aquaporin isoforms and multiple regulation mechanisms.
Since the discovery of the first plant aquaporin (AQP) in 1993, our conception of the way plants control cell water homeostasis as well as their global water balance has been revisited. Plant AQPs constitute a large family of evolutionarily related channels that, in addition to water, can also facilitate the membrane diffusion of a number of small solutes, such as urea, CO2, H2O2, ammonia, metalloids, and even ions, indicating a wide range of cellular functions. At the cellular level, AQPs are subject to various regulation mechanisms leading to active/inactive channels in their target membranes. In this review, we discuss several specific questions that need to be addressed in future research. Why are so many different AQPs simultaneously expressed in specific cellular types? How is their selectivity to different solutes controlled (in particular in the case of multiple permeation properties)? What does the molecular interaction between AQPs and other molecules tell us about their regulation and their involvement in specific cellular and physiological processes? Resolving these questions will definitely help us better understand the physiological advantages that plants have to express and regulate so many AQP isoforms.


Muscle glucose-6-phosphate dehydrogenase deficiency.
Muscle glucose-6-phosphate dehydrogenase (G6PD) deficiency is described in four clinically heterogeneous patients: an athlete who developed myoglobinuria after physical exercise; a 7-year-old, mildly mentally retarded boy, who had episodes of dark urine and high creatine kinase; and two brothers of Sardinian origin, the elder showing moderate exercise intolerance. Histochemical and biochemical studies showed a lack of G6PD activity in muscle biopsy specimens as well as in erythrocytes. G6PD characterization in erythrocytes classified these mutant enzymes as Mediterranean variant in all the patients. The deficiency was confirmed in the patients' myotubes and skin fibroblasts, where residual activity was present. Electrophoretic studies in tissue culture extracts showed that the residual muscle enzyme migrated as a single electrophoretic band like normal human muscle G6PD.


A lymphoblastoid cell line from an adenosine deaminase deficient patient established by Epstein-Barr virus.
Lymphoblastoid cell lines from a patient with adenosine deaminase (ADA) deficiency and his parents were established by Epstein-Barr virus (EBV). ADA activity in the lymphoblastoid cells from the patient was not detectable, while the enzyme activity in the cells from his parents was approximately a half level of the controls'. No inhibitor to ADA could be detected in the lymphoblastoid cells from the patient.


Radiation exposure of ovarian cancer patients: contribution of CT examinations performed on different MDCT (16 and 64 slices) scanners and image quality evaluation: an observational study.
The objective of this study is to compare radiation doses given to ovarian cancer patients by different computed tomographies (CTs) and to evaluate association between doses and subjective and objective image quality.CT examinations included were performed either on a 16-slice CT, equipped with automatic z-axis tube current modulation, or on a 64-slice CT, equipped with z-axis, xy-axis modulation, and adaptive statistical iterative algorithm (ASIR). Evaluation of dose included the following dose descriptors: volumetric CT dose index (CTDIvol), dose length product (DLP), and effective dose (E). Objective image noise was evaluated in abdominal aorta and liver. Subjective image quality was evaluated by assessment of image noise, spatial resolution and diagnostic acceptability.Mean and median CTDIvol, DLP, and E; correlation between CTDIvol and DLP and patients' weight; comparison of objective noise for the 2 scanners; association between dose descriptors and subjective image quality.The 64-slice CT delivered to patients 24.5% lower dose (P < 0.0001) than 16-slice CT. There was a significant correlation between all dose descriptors (CTDIvol, DLP, E) and weight (P < 0.0001). Objective noise was comparable for the 2 CT scanners. There was a significant correlation between dose descriptors and image noise for the 64-slice CT, and between dose descriptors and spatial resolution for the 16-slice CT.Current dose reduction systems may reduce radiation dose without significantly affecting image quality and diagnostic acceptability of CT exams.


Heterogeneous photocatalytic degradation of methyl orange in schwertmannite/oxalate suspension under UV irradiation.
Schwertmannite was synthesized through an oxidation of FeSO(4) by Acidithiobacillus ferrooxidans LX5 cell suspension at an initial pH 2.5 and 28°C for 3 days and characterized using X-ray diffraction spectroscopy and scanning electron microscope. The schwertmannite photocatalytic degradation of methyl orange (MO) by oxalate was investigated at different initial pH values, concentrations of schwertmannite, oxalate, and MO. The results demonstrated that photodegradation of MO in the presence of schwertmannite or oxalate alone was very weak. However, the removal of MO was significantly enhanced when schwertmannite and oxalate coexisted in the reaction system. Low pH (4 or less) was beneficial to the degradation of MO. The optimal doses of schwertmannite and oxalate were 0.2 g L(-1) and 2 mM, respectively. Hydroxyl radicals (·OH) and Fe(II), the intermediate products, were also examined during the reaction to explore their correlation with the degradation of MO. A possible mechanism for the photocatalytic decomposition of MO in the study was proposed. The formation of Fe(III)-oxalate complexes on the surface of schwertmannite was a precursor of H(2)O(2) and Fe(II) production, further leading to the yield of ·OH responsible for the decomposition of MO.


Marrow-derived mesenchymal stem cells restore biochemical markers of acute liver injury in experimental model.
Bone marrow-derived mesenchymal stem cells were investigated as prompters of liver regeneration in an experimental model of acute hepatic injury. A model was created in Wistar rats through intraperitoneal injection of carbon tetrachloride (CCl4). Bone marrow-derived mesenchymal stem cells collected from the long bones of 10 Wistar rats were intravenously infused 24 hours after induction of acute liver failure in 16 rats, group A. In group B, the control group, 16 rats received a peritoneal injection of CCl4, and an intravenous infusion of normal saline solution. All rats were sacrificed at 2, 3, 4, and 7 days post-CCl4 injection to examined biochemical markers and pathological appearances. The platelet counts were higher in group A versus group B on post-CCl4 infusion days 2 (P = .02) and 3 (P = .001), as were the transaminase trends in glutamic oxaloacetic (P = .002), and glutamic-pyruvic transaminases (P < .0001). Pathological examination showed a greater grade of hepatocellular necrosis with neutrophilic infiltration in group B (P = .02). In conclusion, infusion of bone marrow-derived mesenchymal stem cell resulted in a less aggressive picture of hepatic damage.


Ameliorative effects of a non-competitive BACE1 inhibitor TAK-070 on Aβ peptide levels and impaired learning behavior in aged rats.
We examined the effects of TAK-070, a novel non-competitive β-secretase (BACE1) inhibitor, on the levels of Aβ peptides and behavioral deficits in rats. TAK-070 reduced soluble Aβ40 and Aβ42 levels of the cerebral cortex in a time- and dose-dependent manner in young rats. We found that the insoluble Aβ42 content increased significantly with aging from 22 months old without changing Aβ40 content. TAK-070 normalized the Aβ42 levels to those in young rats when they were fed chow containing TAK-070 starting at 19 months old for 6.5 months. Repeated administration of TAK-070 to aged rats for 2 weeks ameliorated the impaired spatial learning in the Morris water maze task and reduced the levels of soluble and insoluble Aβ peptides at doses of 0.3-1mg/kg, (p.o.). Interestingly, TAK-070 significantly recovered the reduced brain synaptophysin levels in aged rats to those in young rats. Our findings support the idea that partial inhibition of BACE1 by TAK-070 exerts symptomatic as well as disease-modifying effects for the treatment of Alzheimer's disease.


Cloning vectors, derived from a naturally occurring plasmid of Pseudomonas savastanoi, specifically tailored for genetic manipulations in Pseudomonas.
A minimal replicon of 1.8 kb isolated from a 10-kb plasmid of Pseudomonas savastanoi, pPS10, has been used to obtain a collection of small vectors specific for Pseudomonas (P. savastanoi, P. aeruginosa and P.putida). In addition, shuttle vectors that can be established both in Pseudomonas and Escherichia coli have been constructed by adding a pMB9 replicon. The vectors permit cloning of DNA fragments generated by a variety of restriction enzymes using different antibiotic resistance markers for selection and offer the possibility to screen recombinants by insertional inactivation. This cloning system can be used to establish recombinant plasmids in Pseudomonas either at low or high copy number. pPS10 derivatives are compatible with other Pseudomonas vectors derived from broad-host-range replicons of the incompatibility groups P1, P4/Q and W. Introduction and expression of the iaaMH operon in a P. savastanoi mutant deficient in the production of indoleacetic acid has been achieved using one of these vectors.


Brain-targeting delivery for RNAi neuroprotection against cerebral ischemia reperfusion injury.
Nanoparticles (NPs) with modification of brain-targeting molecules have been extensively exploited for therapeutic gene delivery across the blood-brain barrier (BBB). As one of the effective RNA interference (RNAi) approaches, short hairpin RNA (shRNA) has been proved to be promising in the field of gene therapy. Apoptosis signal-regulating kinase 1 (Ask1) has been reported to be an important target for gene therapy against cerebral ischemia reperfusion injury. In this study, dendrigraft poly-l-lysine (DGL) was decorated by dermorphin (a μ-opiate receptor agonist) through PEG for efficient brain-targeting, then complexed with anti-Ask1 shRNA plasmid DNA, yielding the DGL-PEG-dermorphin/shRNA NPs. The DGL-PEG-dermorphin/shRNA NPs were characterized and estimated the brain-targeting ability. In vitro, increased cellular uptake and transfection efficiency were explored; in vivo, preferable accumulation and gene transfection in brain were showed in images. The DGL-PEG-dermorphin/shRNA NPs also revealed high efficiency of neuroprotection. As a result of RNAi, corresponding mRNA was distinctly degraded, expression of Ask1 protein was obviously suppressed, apoptotic cell death was apparently decreased and cerebral infarct area was significantly reduced. Above all, DGL-PEG-dermorphin/shRNA NPs were proved to be efficient and safe for brain-targeting RNAi neuroprotection against cerebral ischemia reperfusion injury.


The effect of the chain length of heparin on its interaction with lipoprotein lipase.
The interactions of bovine milk lipoprotein lipase (triacylglycero-protein acylhydrolase, EC 220.127.116.11) with the glycosaminoglycans heparin and heparan sulphate were investigated using the technique of fluorescence polarization spectroscopy. The type of complex formed with the enzyme depends on the chain length of the heparin. In 0.05 M NaCl and when the heparin was in molar excess, one heparin chain of Mr 10000-18400 formed a very stable complex with the dimeric protein molecule (the 1:1 complex). With excess protein, weaker interactions produced complexes with higher molecular weights. These two classes of complex were also detected with shorter heparins (Mr 6600-8000), although in these circumstances the more stable complex possessed a heparin:protein dimer ratio of 2:1. In higher salt (0.2 M NaCl) and lower heparin concentrations (less than 6 . 10(-8) M) the weaker class of compound was undetectable and Kd values of 4 . 10(-8) M and 6 . 10(-9) M were assigned to the 2:1 and 1:1 complexes, respectively. Heparan sulphate of Mr 17000 could only form one class of complex. This had a 1:1 stoichiometry and with Kd values of 3 . 10(-8) M and 1.6 . 10(-7) M at 0.05 and 0.2 M NaCl, respectively. The results could be explained if there is a distinct binding region for glycosaminoglycans on each subunit of the dimeric enzyme and a single heparin chain of Mr greater than 10000 can satisfy both sites to form a 1:1 complex. Smaller heparin chains are unable to span the sites and, in order to occupy them, two chains must interact with each enzyme molecule.


Frequency-dependent enhancement of bone formation in murine tibiae and femora with knee loading.
Knee loading is a relatively new loading modality in which dynamic loads are laterally applied to the knee to induce bone formation in the tibia and the femur. The specific aim of the current study was to evaluate the effects of loading frequencies (in Hz) on bone formation at the site away from the loading site on the knee. The left knee of C57/BL/6 mice was loaded with 0.5 N force at 5, 10, or 15 Hz for 3 min/day for 3 consecutive days, and bone histomorphometry was conducted at the site 75% away from the loading site along the length of tibiae and femora. The results revealed frequency-dependent induction of bone formation, in which the dependence was different in the tibia and the femur. Compared with the sham-loading control, for instance, the cross-sectional cortical area was elevated maximally at 5 Hz in the tibia, whereas the most significant increase was observed at 15 Hz in the femur. Furthermore, mineralizing surface, mineral apposition rate, and bone formation rate were the highest at 5 Hz in the tibia (2.0-, 1.4-, and 2.7 fold, respectively) and 15 Hz in the femur (1.5-, 1.2-, and 1.8 fold, respectively). We observed that the tibia had a lower bone mineral density with more porous microstructures than the femur. Those differences may contribute to the observed differential dependence on loading frequencies.


Exploitation of a cellulose-binding domain from Neurospora crassa.
After eight decades as a purely research organism, Neurospora crassa is becoming a production system for heterologous peptides. The present work exploits the cbh-1 gene, which encodes a class C cellobiohydrolase (EC 22.214.171.124) and has, at its carboxy-terminus, a domain with homology to other fungal cellulose-binding domains. We describe the construction of two translational fusions of the putative cellulose-binding domain with a reporter gene, which is the catalytic domain of the gla-1 glucoamylase gene of the same species, their transformation back into the organism, and expression of the constructs as cellulose-binding glucoamylase activity. This adds to the developing biotechnology of the organism the potential for enzyme/protein immobilisation.


Risk indicators of oral health status among young adults aged 18 years analyzed by negative binomial regression.
Limited information on oral health status for young adults aged 18 year-olds is known, and no available data exists in Hong Kong. The aims of this study were to investigate the oral health status and its risk indicators among young adults in Hong Kong using negative binomial regression. A survey was conducted in a representative sample of Hong Kong young adults aged 18 years. Clinical examinations were taken to assess oral health status using DMFT index and Community Periodontal Index (CPI) according to WHO criteria. Negative binomial regressions for DMFT score and the number of sextants with healthy gums were performed to identify the risk indicators of oral health status. A total of 324 young adults were examined. Prevalence of dental caries experience among the subjects was 59% and the overall mean DMFT score was 1.4. Most subjects (95%) had a score of 2 as their highest CPI score. Negative binomial regression analyses revealed that subjects who had a dental visit within 3 years had significantly higher DMFT scores (IRR = 1.68, p < 0.001). Subjects who brushed their teeth more frequently (IRR = 1.93, p < 0.001) and those with better dental knowledge (IRR = 1.09, p = 0.002) had significantly more sextants with healthy gums. Dental caries experience of the young adults aged 18 years in Hong Kong was not high but their periodontal condition was unsatisfactory. Their oral health status was related to their dental visit behavior, oral hygiene habit, and oral health knowledge.


Toxicological evaluation of the staircase test for assessing fine motor movements.
A variety of tests have been developed to study neurotoxicant-related changes in motor function. However, despite recent advances, there remains a need for simple and specific tests of fine motor movements. Accordingly, we chose to evaluate whether a method developed for measuring changes in skilled movements following motor pathway lesions in rodents would provide a sensitive, specific, and economical approach to assessing fine motor control in the toxicology laboratory. We measured skilled paw reaching using the "staircase test" developed by Montoya et al. [Prog. Brain Res. 82 (1990) 459], in which a rat retrieves food pellets by reaching down from a central platform to a series of descending steps on either side, grasping the pellets in its forepaw, and lifting them to its mouth. Staircase boxes were scaled for the body weights of young adult male (350 g) and female (250 g) Long-Evans rats. Studies were conducted using harmaline, a tremorigen; scopolamine; methyl scopolamine; and 2,4-dithiobiuret (DTB), a compound that causes muscle weakness by interfering with cholinergic transmission at the neuromuscular junction. Harmaline (0, 1.0, 3.0, and 10.0 mg/kg) reduced pellet retrieval only at a dose that also caused visible tremor. Both scopolamine (0, 0.1, 0.3, and 1.0 mg/kg) and methyl scopolamine (0, 0.104, 0.312, and 1.04 mg/kg) impaired pellet retrieval; scopolamine was more effective than methyl scopolamine. DTB (5 daily doses of 0, 0.1, 0.2, and 0.5 mg/kg) had no effect on retrieval, even when causing visible signs of weakness. These data cast doubt on the utility of this method for detecting and quantifying subtle chemical-induced changes in motor function in rats.


Activated partial thromboplastin time is a predictive parameter for further miscarriages in cases of recurrent fetal loss.
To determine whether clinically routine clotting tests such as activated partial thromboplastin time (aPTT), prothrombin time (PT), or fibrinogen can be used to predict further miscarriages. Prospective study. Nagoya City University Hospital, Nagoya, Japan. A total of 261 patients with a history of two consecutive first-trimester spontaneous abortions who had no antiphospholipid antibodies or other autoimmune diseases and no anatomic anomalies were examined for aPTT, PT, and fibrinogen before becoming pregnant again. Blood tests were performed before pregnancy. Patients then were followed up during subsequent pregnancy and their outcomes were compared with their previous blood test results. Activated partial thromboplastin time, PT, and fibrinogen were measured by coagulation time methods. Fifty-eight of 261 patients (22.2%) had a subsequent miscarriage. Mean (+/-SD) values for preconception aPTT in individuals whose subsequent pregnancies ended in success and failure were 88.2%+/-23.4% and 99.3%+/-26.4%, respectively. The difference was statistically significant. Respective values were 106.8%+/-22.8% and 106.3%+/-21.4% for PT and 245+/-61.1 mg/dL and 259.1+/-57 mg/dL for fibrinogen. These findings were not significantly different. A shortened aPTT before conception is associated with further miscarriages in patients with a history of recurrent spontaneous abortions who have no antiphospholipid antibodies.


Derivation of a clinical prediction rule for bloodstream infection mortality of patients visiting the emergency department based on predisposition, infection, response, and organ dysfunction concept.
Bloodstream infection (BSI) is a serious infection with a high mortality. We aimed to construct a predictive scoring system to stratify the severity of patients with BSI visiting the emergency department (ED). We conducted a retrospective cohort study consisting of patients who visited the ED of a tertiary hospital with documented BSI in 2010. The potential predictors of mortality were obtained via chart review. Multivariate logistic regression was utilized to identify predictors of mortality. Penalized maximum likelihood estimation (PMLE) was applied for score development. There were 1063 patients with bacteremia included, with an overall 28-day mortality rate of 13.2% (n = 140). In multiple logistic regression with penalization, the independent predictors of death were "predisposition": malignancy (β-coefficient, 0.65; +2 points); "infection": Staphylococcus aureus (S. aureus) bacteremia (0.69; +2 points), pneumonia (1.32; +4 points), and bacteremia with an unknown focus (0.70; +2 points); "response": body temperature <36 °C (1.17; +3 points), band form >5% (1.00; +3 points), and red blood cell distribution width (RDW) >15% (0.63; +2 points); and "organ dysfunction": pulse oximeter oxygen saturation <90% (0.72; +2 points) and creatinine >2 mg/dL (0.69; +2 points). The area under receiver operating characteristic curve (AUROC) for the model was 0.881 [95% confidence interval (CI), 0.848-0.913], with a better performance than the Pitt bacteremia score (AUROC: 0.750; 95% CI 0.699-0.800, p < 0.001). The patients were stratified into four risk groups: (1) low, 0-3 points, mortality rate: 1.5%; (2) moderate, 4-6 points, mortality rate: 10.5%; (3) high, 7-8 points, mortality rate: 28.6%; and (4) very high, ≥ 9 points, mortality rate: 65.5%. The new scoring system for bacteremia could facilitate the prediction of the risk of 28-day mortality for patients visiting the ED with BSI.


Solid-state nuclear magnetic resonance determination of the physical form of BHA on common pharmaceutical excipients.
The purpose of this study was to evaluate the physical form of 2-tert-butyl-4-methoxy-phenol (BHA) following wet granulation onto common pharmaceutical excipients. A 13C label was incorporated into the methoxy group of BHA, the major isomer in synthetic butylated hydroxyanisole. Solutions of the labeled BHA were used to load the labeled BHA onto common pharmaceutical excipients. After air drying under ambient conditions, the mixtures were examined by 13C MAS and CP/MAS nuclear magnetic resonance (NMR) spectroscopy to evaluate the physical form of the BHA. The data suggested that BHA could exist as either a crystalline or an amorphous component and that amorphous material was either bound to excipients or relatively mobile during the time of the NMR experiment. At 0.1% loading, BHA appeared to be amorphous and mobile in the freshly prepared blends. At 0.5% loading, BHA was shown to be amorphous on microcrystalline cellulose (MCC) and hydroxypropylmethylcellulose (HPMC) while remaining crystalline on lactose, mannitol, calcium phosphate dihydrate, and croscarmellose sodium. Solid-state NMR spectroscopy has been used to probe the physical forms of 13C-labeled BHA granulated onto common pharmaceutical excipients. The techniques described in this paper may be applied to help explain stability changes in formulations containing BHA.


NIDCD's 5-Year Strategic Plan Describes Scientific Priorities and Commitment to Basic Science.
The National Institute on Deafness and Other Communication Disorders (NIDCD) recently issued a new strategic plan that describes the institute's scientific priorities over the next five years. Developed in collaboration with informed stakeholders, the 2023-2027 NIDCD Strategic Plan: Advancing the Science of Communication to Improve Lives creates a unified vision to stimulate discoveries in basic research, model systems, innovative technologies, individualized treatment approaches, scientific data sharing, and translation of research findings into clinical practice. To further accelerate scientific discoveries, the institute encourages collaborations and information sharing among interdisciplinary teams conducting research in these priority areas, and advocates for the utilization of biomedical databases to share scientific findings. NIDCD also welcomes investigator-driven applications that capitalize on advances in basic research to better understand normal and disordered processes; develop or improve model systems to inform research; or facilitate the use of biomedical data utilizing best practices. Through these efforts, NIDCD will continue to conduct and support research that improves the quality of life for the millions of American impacted by conditions affecting hearing, balance, taste, smell, voice, speech, or language.


Haplotypes and Sequence Variation in the Ovine Adiponectin Gene (ADIPOQ).
The adiponectin gene (ADIPOQ) plays an important role in energy homeostasis. In this study five separate regions (regions 1 to 5) of ovine ADIPOQ were analysed using PCR-SSCP. Four different PCR-SSCP patterns (A₁-D₁, A₂-D₂) were detected in region-1 and region-2, respectively, with seven and six SNPs being revealed. In region-3, three different patterns (A₃-C₃) and three SNPs were observed. Two patterns (A₄-B₄, A₅-B₅) and two and one SNPs were observed in region-4 and region-5, respectively. In total, nineteen SNPs were detected, with five of them in the coding region and two (c.46T/C and c.515G/A) putatively resulting in amino acid changes (p.Tyr16His and p.Lys172Arg). In region-1, -2 and -3 of 316 sheep from eight New Zealand breeds, variants A₁, A₂ and A₃ were the most common, although variant frequencies differed in the eight breeds. Across region-1 and region-3, nine haplotypes were identified and haplotypes A₁-A₃, A₁-C₃, B₁-A₃ and B₁-C₃ were most common. These results indicate that the ADIPOQ gene is polymorphic and suggest that further analysis is required to see if the variation in the gene is associated with animal production traits.


DNA-templated electrodeposition of silver nanoparticles for direct and label-free aptasensing of ochratoxin A.
We present in this work, an aptasensing strategy based on the DNA-templated electrodeposition of silver nanoparticles (AgNPs). The homogeneous electro-deposition of AgNPs on screen printed carbon electrode (SPCE) surface was achieved based on a unique aptamer scaffold. This was constructed by immobilizing a DNA aptamer on SPCE by electrochemical oxidation of its amine groups. The electrodeposition of AgNPs was investigated before and after the addition of the aptamer's specific target; the mycotoxin, ochratoxin A (OTA). Electrochemical characterization by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) showed the effect of the scaffold layer on the electrodeposition of AgNPs. The conformational change induced by aptamer after binding its targeted molecule affects AgNPs electrodeposition and the electron transfer thus allowing OTA detection by cyclic voltammetry. The voltammograms showed a good proportionality between the analyte concentration and the current response. The constructed platform allowed the quantitative aptasensing of OTA within the range of (1.56-400 ng/mL) and the detection limit of 0.6 ng/mL. In term of aptasensor applicability, the proposed strategy showed excellent performance in rice samples.


Angle-to-angle and spur-to-spur distance analysis with high-resolution optical coherence tomography.
To measure angle-to-angle (ATA) and spur-to-spur (STS) distances along six meridians using high-resolution swept-source optical coherence tomography (SS-OCT) and to compare those values with horizontal white-to-white (WTW) distance. 68 eyes from 68 patients were quantitatively assessed with the Anterion SS-OCT (Heidelberg Engineering, Heidelberg, Germany). ATA and STS distances were measured with the SS-OCT's B-Scan in six cross-sectional images corresponding to the vertical (6-12 o'clock), 1-7 o'clock, 2-8 o'clock, horizontal (3-9 o'clock), 4-10 o'clock and 5-11 o'clock meridians. WTW was measured horizontally with the device's infrared camera. A Pearson correlation analysis was carried out to compare ATA and STS distances with WTW. The largest values were found for the vertical meridian and the shortest for the 2-8 o'clock meridian, both for ATA and STS distances. No statistically significant differences were found between WTW, ATA and STS along the horizontal meridian (p > 0.1). However, ATA and STS showed statistically significant differences elsewhere, except for the horizontal and the 2-8 o'clock meridians (p > 0.05). Moreover, we found that ATA and STS varied significantly depending on the meridian being assessed, except for ATA at 4-10 versus 3-9 o'clock and for STS at 4-10 versus 3-9 o'clock and at 3-9 versus 2-8 o'clock (p > 0.1). R2 values ranged from 0.49 to 0.75 for ATA and STS at the different meridians, showing the best correlation at 3-9 o'clock meridian (0.64 and 0.75, respectively) and the worst at 6-12 o'clock meridian (R2 = 0.49 for both ATA and STS). ATA and STS distances vary radially, thus showing that the anterior chamber is vertically oval. Therefore, it is advisable to measure these two distances along the meridian to be used.


Optimization of the Erbium:YAG laser for precise incision of ureteral and urethral tissues: in vitro and in vivo results.
Tissue damage during endoscopic treatment of urethral and ureteral strictures may result in stricture recurrence. The Erbium:YAG laser ablates soft tissues with minimal peripheral damage and may be a promising alternative to cold knife and Holmium:YAG laser for precise incision of urological strictures. Optimization of the Er:YAG laser was conducted using ex vivo porcine ureteral and canine urethral tissues. Preliminary in vivo studies were also performed in a laparoscopic porcine ureteral model with exposed ureter. Laser radiation with a wavelength of 2.94 microm, pulse lengths of 8, 70, and 220 microseconds, output energies of 2-35 mJ, fluences of 1-25 J/cm2, and pulse repetition rates of 5-30 Hz, was delivered through 250-microm and 425-microm core germanium oxide optical fibers in direct contact with tissue. Ex vivo perforation thresholds measured 2-4 J/cm2, with ablation rates of 50 microm/pulse at fluences of 6-11 J/cm2. In vivo perforation thresholds were approximately 1.8 J/cm2, with the ureter perforated in less than 20 pulses at fluences greater than 3.6 J/cm2. Peripheral thermal damage in tissue decreased from 30 to 60 microm to 10-20 microm as the laser pulse length decreased from 220 to 8 microseconds. Mechanical tissue damage was observed at the 8 microseconds pulse duration. The Er:YAG laser, operating at a pulse duration of approximately 70 microseconds, a fluence greater than approximately 4 J/cm2, and a repetition rate less than 20 Hz, is capable of rapidly incising urethral and ureteral tissues with minimal thermal and mechanical side-effects.


An eco-friendly corrosion inhibitor Cuscuta reflexa extract and PEG400 for mild steel inhibition in acidic medium: computational and experimental investigations.
Herein, the mechanism of corrosion prevention of mild steel (MS) by extract of Cuscuta reflexa/Amarbel (AME) as green inhibitor is explained by gravitational, electrochemical measurements. The viability of neat extract and after adding an intensifier was investigated as corrosion inhibitor for MS in hydrochloric acid. The presence of electron-rich moieties in AME was characterized through Fourier-transform infrared spectroscopy (FTIR). Furthermore, polarization measurements showed that AME acted as a mixed type inhibitor against corrosion. The formulation of 100 ppm AME with 50 ppm polyethylene glycol 400 (PEG400) as an intensifier showed inhibition efficiency of 97.51% for MS in 0.5 M HCl. The protection of MS in (AME + PEG) formulation was also assessed through the Langmuir, Freundlich, and Flory-Huggins adsorption isotherm model. The surface studies of the MS were examined by atomic force microscopy (AFM) and scanning electron microscopy (SEM) that indicated a smoothened surface of the metal in the presence of the studied compounds. XPS study was executed to analyze the interaction of the inhibitor with the metal surface. In addition, computational quantum study provides the molecular structural relationship with corrosion inhibitive competence of the extract.


In vivo antitumor activity of S 16020-2, a new olivacine derivative.
The antitumor activity of S 16020-2, a new olivacine derivative, was investigated in vivo and compared with that of Adriamycin and elliptinium acetate in a panel of murine (P388 leukemia, M5076 sarcoma, Lewis lung carcinoma, and B16 melanoma) and human (NCI-H460 non-small-cell lung and MCF7 breast carcinomas) tumor models. S 16020-2 given i.v. was active against P388 leukemia implanted i.p., s.c., or intracerebrally. The therapeutic effect of an intermittent schedule (administration on days 1, 5, 9) was superior to that of single-dose treatment, allowing the i.v. administration of high total doses of S 16020-2 and resulting in the cure of 60% of mice in the i.p. P388 model. In this model, S 16020-2 was more active than elliptinium acetate and showed a better therapeutic index than Adriamycin: > or = 8 versus 2. A good therapeutic effect of S 16020-2 was also observed in three P388 leukemia sublines displaying the classic multidrug-resistance phenotype, namely, P388/VCR, P388/VCR-20, and P388/MDRC.04, the latter being totally insensitive to vincristine and Adriamycin. However, S 16020-2 was not active against the P388/ADR leukemia, a model highly resistant to adriamycin in vivo. S 16020-2 was both more active than Adriamycin and curative in the M5076 sarcoma and Lewis lung carcinoma implanted s.c. In the B16 melanoma implanted i.p. or s.c., S 16020-2 was less active than Adriamycin. Against the NCI-H460 human tumor xenograft, S 16020-2 demonstrated activity superior to that of Adriamycin (T/C = 20% versus 43% on day 21). Against the MCF7 breast cancer xenograft, S 16020-2 was active, but less so than Adriamycin (T/C = 23% versus 9% on day 21), whereas elliptinium acetate was marginally active (T/C = 49% on day 24). The hematological toxicity of S 16020-2 given to B6D2F1 mice at pharmacological dose appeared to be less severe than that of Adriamycin, particularly in bone-marrow stem cells. These results demonstrate that S 16020-2 is a highly active antitumor drug in various experimental tumor models and is markedly more efficient than elliptinium acetate. Because of its pharmacological profile, which is globally different from that of Adriamycin, S 16020-2 is considered an interesting candidate for clinical trials.


Hydrogen sulfide suppresses the expression of MMP-8, MMP-13, and TIMP-1 in left ventricles of rats with cardiac volume overload.
To study the effects of hydrogen sulfide (H2S) on the left ventricular expression of MMP-8, MMP-13, and TIMP-1 in a rat model of congenital heart disease. Male SD rats underwent abdominal aorta-inferior vena cava shunt operation. H2S donor NaHS (56 μmol·kg(-1)·d(-1), ip) was injected from the next day for 8 weeks. At 8 weeks, the hemodynamic parameters, including the left ventricular systolic pressure (LVSP), the left ventricular peak rate of contraction and relaxation (LV ± dp/dtmax) and the left ventricular end diastolic pressure (LVEDP) were measured. The left ventricular tissues were dissected out, and hydroxyproline and collagen I contents were detected with ELISA. The expression of MMP-8, MMP-13, and a tissue inhibitor of metalloproteinase-1 (TIMP-1) in the tissues was measured using real-time PCR, Western blotting, and immunohistochemistry, respectively. The shunt operation markedly reduced LVSP and LV ± dp/dtmax, increased LVEDP, hydroxyproline and collagen I contents, as well as the mRNA and protein levels of MMP-8, MMP-13, and TIMP-1 in the left ventricles. Chronic treatment of the shunt operation rats with NaHS effectively prevented the abnormalities in the hemodynamic parameters, hydroxyproline and collagen I contents, and the mRNA and protein levels of MMP-13 and TIMP-1 in the left ventricles. NaHS also prevented the increase of MMP-8 protein expression, but did not affect the increase of mRNA level of MMP-8 in the shunt operation rats. H2S suppresses protein and mRNA expression of MMP-8, MMP-13, and TIMP-1 in rats with cardiac volume overload, which may be contributed to the amelioration of ventricular structural remodeling and cardiac function.


Troponin T amino acid mutation (ΔK210) knock-in mice as a neonatal dilated cardiomyopathy model.
Dilated cardiomyopathy (DCM) in children is often associated with poor morbidity and mortality and exhibits distinct pathological entities from those of adult DCM. Owing to the limited number of patients and the lack of a good animal model, the molecular mechanisms underlying pediatric DCM remain poorly understood. The purpose of this study is to establish an animal model of neonatal DCM and identify early progression factors. Cardiac phenotypes and comprehensive gene expression profiles in homozygous ΔK210 knock-in (TNNT2ΔK210/ΔK210) mice were analyzed and compared to TNNT2+/ΔK210 and wild-type mice at 0 days and 1 week of age. Immediately after birth, the cardiac weight in TNNT2ΔK210/ΔK210 mice was already increased compared to that in TNNT2+/ΔK210 and wild-type mice. Echocardiographic examination of 0-day-old and 1-week-old TNNT2ΔK210/ΔK210 mice revealed similar phenotypes of pediatric DCM. In addition, several genes were significantly upregulated in the ventricular tissues of TNNT2ΔK210/ΔK210 mice, and the KEGG PATHWAY analysis revealed several important pathways such as cancer and focal adhesion that might be associated with the pathogenesis and development of DCM. TNNT2ΔK210/ΔK210 mice have already developed DCM at birth, indicating that they should be an excellent animal model to identify early progression factors of DCM. TNNT2ΔK210/ΔK210 mice are excellent animal model for DCM. TNNT2ΔK210/ΔK210 mice are excellent animal model to identify early progression factors of DCM. KEGG PATHWAY analysis revealed that several important pathways such as cancer and focal adhesion might be associated with the pathogenesis and development of neonatal DCM.


Surface charge modulation of liposomes by enzymatic hydrolysis of macrocyclic 1,2-dotriacontanedioyl-sn-glycero-3-phosphocholine.
1,2-Dotriacontanedioyl-sn-glycero-3-phosphocholine (dTPC) was synthesized, and by a sonication method, dTPC was transformed into liposomes with physical features (charge, size, gel-to-liquid crystalline phase transition constants, etc.) similar to those of liposomes made of acyclic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Quantitative enzymatic assays using phospholipases A2 and C showed that dTPC was comparable with or better than DPPC as a substrate. Remarkably, the liposomes assembled from a mixture of dTPC and 1,2-distearyl-sn-glycero-3-phosphocholine were converted rapidly into anionic liposomes at pH 7 by the action of phospholipase A2, keeping their vesicular structure and exposing CO2H groups of the lysolipids of dTPC on the membrane surface. The use of dTPC is discussed in conjunction with the enzyme-catalyzed modification of the liposomes.


Akt deficiency attenuates muscle size and function but not the response to ActRIIB inhibition.
Akt is a critical mediator of developmental skeletal muscle growth. Treatment with a soluble ActRIIB fusion protein (ActRIIB-mFc) increases skeletal muscle mass and strength by inhibiting myostatin and related peptides. Recent in vitro studies have suggested that Akt signaling is necessary for the ability of ActRIIB inhibition to induce muscle hypertrophy. Thus, we hypothesized that mice deficient in either Akt1 or Akt2 would not respond to in vivo inhibition of ActRIIB with ActRIIB-mFc treatment. We analyzed body composition and muscle parameters in wild-type C57BL/6J and Akt1 and Akt2 knockout mice, and compared the responses to blockade of ActRIIB signaling via ActRIIB-mFc treatment. Mice lacking Akt1 or Akt2 had reduced muscle mass, grip strength and contractile force. However, deficiency of Akt1 or Akt2 did not prevent the ability of ActRIIB-mFc treatment to induce muscle hypertrophy, or increase grip strength and contractile force. Akt1 and Akt2 deficient mice responded similarly as wild type mice to ActRIIB-mFc treatment by increasing fiber size. Akt1 and Akt2 are important for the regulation of skeletal muscle mass and function. However, these Akt isoforms are not essential for the ability of ActRIIB inhibition to regulate muscle size, fiber type, strength or contractile force.


Time-lapse deselection model for human day 3 in vitro fertilization embryos: the combination of qualitative and quantitative measures of embryo growth.
To present a time-lapse deselection model involving both qualitative and quantitative parameters for assessing embryos on day 3. Retrospective cohort study and prospective validation. Private IVF center. A total of 270 embryos with known implantation data (KID) after day 3 transfer from 212 IVF/intracytoplasmic sperm injection (ICSI) cycles were retrospectively analyzed for building the proposed deselection model, followed by prospective validation using an additional 66 KID embryos. None. Morphological score on day 3, embryo morphokinetic parameters, abnormal cleavage patterns, and known implantation results. All included embryos were categorized either retrospectively or prospectively into 7 grades (A+, A, B, C, D, E, F). Qualitative deselection parameters included poor conventional day 3 morphology, abnormal cleavage patterns identified via time-lapse monitoring, and <8 cells at 68 hours postinsemination. Quantitative parameters included time from pronuclear fading (PNF) to 5-cell stage and duration of 3-cell stage. KID implantation rates of embryos graded from A+ to F were 52.9%, 36.1%, 25.0%, 13.8%, 15.6%, 3.1%, and 0 respectively (area under the curve [AUC] = 0.762; 95% confidence interval [CI], 0.701-0.824), and a similar pattern was seen in either IVF (AUC = 0.721; 95% CI, 0.622-0.821) or ICSI embryos (AUC = 0.790; 95% CI, 0.711-0.868). Preliminary prospective validation using 66 KID embryos also showed statistically significant prediction in Medicult (AUC = 0.750; 95% CI, 0.588-0.912) and Vitrolife G-Series (AUC = 0.820; 95% CI, 0.671-0.969) suites of culture media. The proposed model involving both qualitative and quantitative deselection effectively predicts day 3 embryo implantation potential and is applicable to all IVF embryos regardless of insemination method by using PNF as the reference starting time point.


Lymph node mapping in rabbit liver cancer with nanocarbon and methylene blue injecta.
To discuss the value of lymph node mapping in rabbit liver cancer with nanocarbon and methylene blue injecta. Rabbit liver cancer model was established by transplanting VX2 cells with laparotomy in celiac planting method. Twenty Japan white rabbits were divided into two groups randomly. Each group had 10 rabbits. Lymph node mapping in two groups rabbit liver cancer were observed. Two groups rabbit liver cancer and local lymph nodes were removed. The number and location of local lymph nodes were recorded, and then the samples were obtained from both groups. The lymph nodes dyed time was (100.50±29.92) s in nanocarbon group, and (11.20±4.18) s in methylene blue group with statistical significance between two groups (P=0.000). In the comparison of lymph node fading time, nanocarbon group was (2.22±0.74) h, methylene blue group was (1.63±0.54) h, nanocarbon group was longer than the methylene blue group, but without statistical significance (P=0.058). The accuracy was 87.5% (35/40) in methylene blue group, while, the nanocarbon group was 87.2% (34/39), with statistical significance (P=1.000). Experimental results show that application of nanocarbon injection and methylene blue injection during resection of liver cancer and local lymph nodes in rabbit liver cancer model has obvious tracer function in liver cancer and lymphatic drainage. It can reduce the complexity and risk of the operation, and avoid the blindness in the process of traditional lymph node dissection surgery. Besides, they can effectively reduce the number of residual lymph nodes after operation. It can achieve the lymph node dissection more thoroughly, promptly, easily and safely.


Obesity in youth is not an independent predictor of carotid IMT in adulthood. The Cardiovascular Risk in Young Finns Study.
Being obese in childhood may be associated with increased cardiovascular morbidity and mortality in adulthood. We examined the relationship between obesity and overweight identified in youth and carotid artery intima-media thickness assessed in adulthood. As part of the longitudinal Cardiovascular Risk in Young Finns Study, we assessed tracking of body mass index (BMI) from youth (ages 3-18 years) to young adulthood (ages 24-39 years) in a cohort of 2,260 subjects. BMI measured in youth was significantly associated with BMI measured in adulthood. The risk of being obese in adulthood (BMI > 30 kg/m(2)) was increased by three-fold in subjects who had been overweight or obese (BMI > 80th percentile) in childhood (ages 3-9 years) and by four-fold in subjects who had been overweight or obese in adolescence (ages 12-18 years). Age and sex adjusted adult IMT values were comparable in subjects who had been consistently overweight/obese in youth and adulthood and in subjects who became obese in adulthood, 0.642 mm versus 0.634 mm, respectively. IMT values were lower (overall P < 0.0001) and comparable in subjects who had remained consistently non-obese and those who had been obese in youth but had become non-obese in adulthood, 0.610 mm versus 0.627 mm, respectively. We conclude that being obese in youth is associated with increased carotid IMT in adulthood, but this relationship is explained by significant tracking of body mass from youth to adulthood.


Chloramphenicol- and tetracycline-resistant uropathogenic Escherichia coli (UPEC) exhibit reduced virulence potential.
It is well documented that uropathogenic Escherichia coli (UPEC) isolates resistant to nalidixic acid have reduced virulence potential. Our goal was to assess whether UPEC isolates resistant to chloramphenicol, tetracycline and streptomycin also exhibit reduced virulence potential. Among 110 human UPEC isolates, the prevalences of the virulence factors fimH, papC, papGII, papGIII, sfa/focDE, afa, hlyA, cnf1, usp, ibeA, fyuA, iroN, iucD, ireA, and K1 and K5 capsules as well as of pathotypes, phylogenetic groups, O antigens and a pathogenicity island (PAI) marker were compared between chloramphenicol-, tetracycline-, streptomycin- and, as a control, nalidixic acid-resistant and -susceptible strains. Our findings show that among human UPEC isolates, not only nalidixic acid-resistant but also chloramphenicol- and tetracycline-resistant isolates have reduced virulence potential compared with susceptible strains. To our knowledge, this is the first report of a statistically significant reduction in virulence traits among chloramphenicol- and tetracycline-resistant isolates.


Toll-like receptor 2 mediates inflammatory cytokine induction but not sensitization for liver injury by Propioni- bacterium acnes.
Recognition of Gram-positive bacteria by Toll-like receptor 2 (TLR2) induces activation of proinflammatory pathways. In mice, sensitization with the Gram-positive Propionibacterium acnes followed by a challenge with the TLR4 ligand, lipopolysaccharide (LPS), results in fulminant hepatic failure. Here, we investigated the role of TLR2 in liver sensitization to LPS-induced injury. Stimulation of Chinese hamster ovary cells and peritoneal macrophages with heat-killed P. acnes required expression of TLR2 but not of TLR4, suggesting that P. acnes was a TLR2 ligand. Cell activation by P. acnes was myeloid differentiation primary-response protein 88 (MyD88)-dependent, and it was augmented by coexpression of CD14 in mouse peritoneal macrophages. In vitro, P. acnes behaved as a TLR2 ligand and induced TLR4 hetero- and TLR2 homotolerance in peritoneal macrophages. In vivo priming of wild-type mice with P. acnes, but not with the selective TLR2 ligands peptidoglycan and lipotheicoic acid, resulted in hepatocyte necrosis, hyperelevated serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, interferon-gamma (IFN-gamma), and IL-12 (p40/p70), and increased RNA expression of proinflammatory cytokines (IL-12p40, IL-1alpha, IL-6, IL-1beta, IL-18, IFN-gamma) in the liver after a LPS challenge. Furthermore, P. acnes priming sensitized TLR2-deficient (TLR2-/-) but not MyD88-/- mice to LPS-induced injury, evidenced by hepatocyte necrosis, increased levels of serum TNF-alpha, IFN-gamma, IL-6, and liver proinflammatory cytokine mRNA expression. IFN-gamma, a cytokine sensitizing to endotoxin, was induced by P. acnes in splenocytes of TLR2-/- and TLR9-/- but not MyD88-/- mice. These results suggest that although P. acnes triggers TLR2-mediated cell activation, TLR2-independent but MyD88-dependent mechanisms mediate in vivo sensitization by P. acnes for LPS-induced liver injury.


Sintering Pmperature-Dependence on Radiopacity of Bi(2-x) ZrxO(3+x/2) Powders Prepared by Sol-Gel Process.
Bismuth oxide (Bi₂O₃) is an effective additive used to enhance radiography resolution for dental materials. However, there are potential concerns regarding its biocompatibility and connection to tissue discoloration. In the present study, we modified the radiopacity properties of Bi₂O₃ with zirconium oxide (ZrO₂) using a sol-gel process and investigated the composition, as well as the effects of heat treatment temperature using Thermogravimetry analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The harvested Bi2-xZrxO3+x/2 particles showed that the dominant phase transferred from α-Bi₂O₃ to β-Bi7.38Zr0.62O12.31 after a heat treatment of over 750 °C for 2 h. As the x values of Bi2-xZrxO3+x/2 increased from 0.2 to 1.0, more zirconium oxide precipitated onto the particle surface, thus enhancing the surface roughness of particles. For sol-gel Bi1.8Zr0.2O3.1 powders (x = 0.2), the radiopacity values became 4.90 ± 0.23 and 5.83 ± 0.22 mmAl after a heat treatment of 500 °C and 750 °C, respectively.


Augmented chondroprotective effect of coadministration of celecoxib and rebamipide in the monosodium iodoacetate rat model of osteoarthritis.
Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive loss of articular cartilage and chronic pain. Although cyclooxygenase-2 (COX-2) inhibitors such as celecoxib are recommended to patients at high risk of gastrointestinal (GI) adverse events, COX-2 inhibitors do not completely prevent GI adverse events. Rebamipide, a gastroprotective agent, has anti-inflammatory properties and acts as an oxygen radical scavenger. The aim of this study was to investigate the in vivo effects of coadministration of rebamipide and celecoxib in an OA rat model. OA was induced by intra-articular injection of monosodium iodoacetate. Oral administration of rebamipide was initiated on the day of OA induction. In this study, rebamipide showed antinociceptive properties and attenuated cartilage degeneration. Rebamipide reduced the expression of matrix metalloproteinase 13, interleukin-1β, inducible nitric oxide synthase, and nitrotyrosine in OA cartilage. OA rats treated with celecoxib in combination with rebamipide demonstrated a higher pain threshold than those treated with monotherapy. Histological examination also showed that the joints from OA animals treated with combination therapy demonstrated less cartilage damage than those of animals treated with monotherapy. We showed that the potential benefit of combination therapy with celecoxib and rebamipide on pain and cartilage degeneration in OA.


Protein kinase C deficiency increases fatty acid oxidation and reduces fat storage.
Metabolic syndrome is common in the general population, but there is little information available on the underlying signaling mechanisms regulating triglyceride (TG) content in the body. In the current study, we have uncovered a role for protein kinase Cbeta (PKCbeta) in TG homeostasis by studying the consequences of a targeted disruption of this kinase. PKCbeta(-/-) mutant mice were considerably leaner and the size of white fat depots was markedly decreased compared with wild-type littermates. TG content in the liver and skeletal muscle of PKCbeta(-/-) mice was also significantly low. Interestingly, mutant animals were hyperphagic and exhibited higher food intake and reduced feed efficiency versus wild type. The protection from obesity involves elevated oxygen consumption/energy expenditure and increased fatty acid oxidation in adipose tissue with concurrent increased mitochondria genesis, up-regulation of PGC-1alpha and UCP-2, and down-regulation of perilipin. The ability of PKCbeta deficiency to promote fat burning in adipocytes may suggest novel therapeutic strategies for obesity and obesity-related disorders.


Potential therapeutic applications of phosphodiesterase inhibition in prostate cancer.
Phosphodiesterases (PDEs) play a role in controlling cyclic nucleotide action, including cyclic guanosine monophosphate (cGMP). Previous studies have ascribed a protective role of cGMP signaling on hypoxia-mediated cancer progression. Herein, we determine their potential role in hypoxia-mediated chemoresistance and immune escape. Phosphodiesterase assays were used to measure PDE activity in prostate cancer cell lines (DU145, PC3). Immunoblots were performed to determine the presence of PDEs in human prostate tissue samples. The effect of PDE inhibition on hypoxia-induced chemoresistance (compared to normoxic controls, 20% O2) was determined using clonogenic assays. Flow cytometry was used to determine the effects of PDE inhibition on surface MHC class I-related chain A (MICA), a natural killer (NK) cell-activating ligand. A mouse model was used to evaluate the in vivo effects of PDE inhibition on the growth of human prostate cancer cells. PDE5 and PDE11 were the most prominent PDEs in the cell lines, representing between 86 and 95% of the total cGMP-specific PDE activity. Treatment of DU-145 cells with a PDE inhibitor significantly reduced the hypoxia-associated acquisition of resistance to doxorubicin, with a mean 51% reduction in surviving fraction compared to controls (p < 0.001, ANOVA). As well, PDE inhibition completely reversed (p = 0.02, ANOVA) hypoxia-induced shedding of the immune stimulatory molecule, MICA, and attenuated the growth of human prostate tumor xenografts in an NK cell-competent murine model (p = 0.03, Wilcoxon, Mann-Whitney). These results suggest a rationale for future studies on the potential therapeutic applications of PDE inhibitors in men with prostate cancer.


Characteristics of basophil histamine release by neuromuscular blocking drugs in patients with anaphylactoid reactions.
Histamine release from the basophil leucocytes of patients with apparently non-immune, anaphylactiod reactions to neuromuscular blockers ( NMB ) has been studied in vitro. Substantial release was obtained in the majority of patients with clinical reactions, with little or no release in normal subjects. The chemical specificity and selectivity varied in individual patients: each individual reacting to one agent or a particular combination of NMB drugs. The test was of considerable diagnostic and predictive value. We studied some of the characteristics of the histamine release process and the effect of certain modulators. The findings strongly suggest a non-cytotoxic secretory process requiring the presence of two quaternary ammonium groups as suggested by the rarity of release with tubocurarine; inhibition of succinyldicholine (suxamethonium)-induced histamine release by serum cholinesterase treatment, acetylcholine and tubocurarine; and the bell-shaped dose-response curve, particularly with suxamethonium. Histamine release by all NMB was completely inhibited in calcium-free medium, and markedly potentiated by deuterium oxide, a microtubule stabilizer. Both tachyphylaxis (by prior exposure to the specific agent in absence of calcium), and cross-tachyphylaxis with anti-IgE were elicited.


Heterosis in a wild strain of Drosophila polymorpha with a lethal closely linked to the major esterase locus.
A laboratory population derived from a single wild inseminated female has a lethal so closely linked to the major esterase locus that in 3 years of observations no crossover products have been detected. Linkage with a chromosome inversion was excluded by cytological analysis. The heterozygotes are superior to the homozygotes in egg-adult viability, egg-laying rate, and longevity. Electrophoretic analysis of larvae, pupae, and 2-h-old adults shows that the specific phase for the lethal effect in homozygotes is the pupal stage.


Effects of internet-based interventions on improvement of glycemic control and self-management in older adults with diabetes: Systematic review and meta-analysis.
To assess and summarize the effects of internet-based interventions on diabetes control and self-management of older adults with diabetes. PubMed, Web of Science and three Chinese databases were searched to identified articles published in until December 2021. Clinical trials if they covered the effects of internet-based interventions on diabetes control and self-management of older adults with diabetes were included. All data analysis were performed by Review Manager 5.3. Sixteen studies with a total of 5604 participants met the inclusion criteria. Our primary outcomes included HbA1c control and self-management. (1) HbA1c control: results indicated statistically difference and high heterogeneity [Q = 112.9, df = 8, p < 0.001, I2 = 93%], in the subgroup analysis of studies in China, results showed a significant influence of internet-based interventions on HbA1c control [Q = 21.31, df = 5, p = 0.03, I2 = 77%]; (2) self-management: in the subgroup analysis of study duration ≤ 6 months [Q = 84.62, df = 2, p < 0.001, I2 = 98%]. Internet-based interventions are promising on diabetes control and self-management of older adults with diabetes, but still preliminary due to the heterogeneity of intervention components and the limited number of higher methodological quality trials. Applicable.


Electrosurgery in operative arthroscopy.
Electrosurgery is a useful tool in the orthopedic procedures outlined, including lateral release, synovial lesions, and shoulder impingement syndrome. The salient positive characteristic of electrosurgery is the capacity to obtain immediate and thorough hemostasis, thereby allowing the patient to begin a rehabilitative program far sooner than with conventional operative techniques. Less hemarthrosis also lowers the level of postoperative pain and the risk of postoperative infection. By becoming familiar with some of the basics of electrosurgery, including equipment and electrosurgical principles, the surgeon and staff can better utilize electrosurgery and be aware of the potential, yet avoidable, complications. The future appears bright for electrosurgery, with new equipment and procedures being developed, but more research is needed to clarify the long-term effects on tissues involved and the clinical results of patients.


Strain-induced damage reduces echo intensity changes in tendon during loading.
Tendon functionality is related to its mechanical properties. Tendon damage leads to a reduction in mechanical strength and altered biomechanical behavior, and therefore leads to compromised ability to carry out normal functions such as joint movement and stabilization. Damage can also accumulate in the tissue and lead to failure. A noninvasive method with which to measure such damage potentially could quantify structural compromise from tendon injury and track improvement over time. In this study, tendon mechanics are measured before and after damage is induced by "overstretch" (strain exceeding the elastic limit of the tissue) using a traditional mechanical test system while ultrasonic echo intensity (average gray scale brightness in a B-mode image) is recorded using clinical ultrasound. The diffuse damage caused by overstretch lowered the stress at a given strain in the tissue and decreased viscoelastic response. Overstretch also lowered echo intensity changes during stress relaxation and cyclic testing. As the input strain during overstretch increased, stress levels and echo intensity changes decreased. Also, viscoelastic parameters and time-dependent echo intensity changes were reduced.


Analysis and functional relevance of the chaperone TRAP-1 interactome in the metabolic regulation and mitochondrial integrity of cancer cells.
The 90 kDa heat shock protein, Hsp90, functions as a cancer chaperone contributing to tumor proliferation. We have encountered the mitochondrial homolog of Hsp90, the TRAP-1, regulating mitochondrial dynamics, metabolism, and tumor metastasis. Although Hsp90 is associated with a broad network of proteins regulating various cellular processes, TRAP-1-mediated cellular networks are unclear. Therefore, using TRAP-1 knockdown (KD) and overexpression (OE) systems, we compared their quantitative transcriptome (RNA Sequencing) and proteomic (LC-MS/MS) patterns to obtain molecular signatures that are altered in response to TRAP-1 KD or OE. We report TRAP-1 modulating vital metabolic pathways such as the tricarboxylic acid cycle, oxidative phosphorylation, electron transport chain, glycolysis, and gluconeogenesis. In addition, TRAP-1 facilitated the pentose phosphate pathway to shunt carbons back to glycolysis or gluconeogenesis, a much-solicited tumor response. Subsequently, we examined the TRAP-1 interactome using the tandem affinity purification system and identified 255 unique proteins. These diverse proteins appear to regulate several cellular processes, including energy metabolism, suggesting that TRAP-1, in addition to metabolic rewiring, maintains mitochondrial integrity. Our study exposes the unknown functions of TRAP-1 in cancer cells. Systematic evaluation of TRAP-1 interactors may uncover novel regulatory mechanisms in disease aggression. Since metabolic inhibitors are emerging as potential anticancer agents, our study gains importance.


Association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis.
Psoriasis (Ps) is a chronic dermatosis characterized by erythematous-squamous plaques derived from an inflammatory response. The effect of polymorphisms in the genes that encode the members of the IL-17 family and their receptors has been studied to find an association with the susceptibility to Ps. However, the findings have not been conclusive. To describe the association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to Ps. A systematic review was conducted using the PubMed and Scopus databases to identify studies that evaluated the association between IL-17A, IL-17F, and IL-17RA gene polymorphisms and Ps susceptibility. This meta-analysis included reports published until June 2021. Heterogeneity was assessed using Cochran's Q-statistic test and I2 statistics. The associations between polymorphisms and Ps susceptibility were determined by pooled OR with a 95% CI. Fifteen studies were included. The frequency of the T allele of the IL-17F rs763780 polymorphism was significantly lower in patients with vulgar Ps (OR = 0.732, p = 0.026). The TT genotype of the IL-17F rs763780 polymorphism was significantly associated with a decreased frequency in individuals with Ps and psoriatic arthritis (PsA) (TT:TC + CC OR = 0.664, p = 0.046). Regarding IL-17RA polymorphisms, the AG genotype of the rs4819554 polymorphism showed a near-significant decrease in psoriasis risk compared to the GG genotype (AG:GG OR = 0.604, p = 0.050). Other polymorphisms in IL-17A, IL-17F and IL-17RA showed no association with Ps. The T allele and TT genotype of the IL-17F rs763780 polymorphism may be associated with a decreased risk of psoriasis. Therefore, the implications of this variant on psoriasis pathogenesis and treatment require further investigation.


Ocular toxoplasmosis; common and rare symptoms and signs.
The common and rare symptoms and signs of congenital, childhood and adult ocular toxoplasmosis are discussed together with the differential diagnosis of the retinal lesions. A choroidal coloboma in connection with congenital toxoplasmosis is described. The occurrence of an optic pit with congenital macular toxoplasmosis, growth of subretinal new vessels as well as disappearance of arteriolar and venular sheathing is demonstrated.


Quality of life and neuropsychological changes in mild head trauma. Late analysis and correlation with S100B protein and cranial CT scan performed at hospital admission.
mild head trauma (MHT) is defined as a transient neurological deficit after trauma with a history of impairment or loss of consciousness lasting less than 15 min and/or posttraumatic amnesia, and a Glasgow Coma Scale between 13 and 15 on hospital admission. We evaluated 50 MHT patients 18 months after the trauma, addressing signs and symptoms of post-concussion syndrome, quality of life and the presence of anxiety and depression. We correlate those findings with the S100B protein levels and cranial CT scan performed at hospital admission after the trauma. patients were asked to fill out questionnaires to assess quality of life (SF36), anxiety and depression (HADS), and signs and symptoms of post-concussion syndrome. For the control group, we asked the patient's household members, who had no history of head trauma of any type, to answer the same questionnaires for comparison. total quality of life index for patients with MHT was 58.16 (+/-5), lower than the 73.47 (+/-4) presented by the control group. Twenty patients (55.2%) and four (11.1%) controls were depressed. Seventeen patients (47.2%) presented anxiety, whereas only eight (22.2%) controls were considered anxious. Victims of MHT complained more frequently of loss of balance, dry mouth, pain in the arms, loss of memory and dizziness than their respective controls (p<0.05). We found no correlation between the presence of these signs and symptoms, quality of life, presence of anxiety and depression with S100B protein levels or with presence of injury in the cranial CT performed at hospital admission. MHT is associated with a higher incidence of post-concussion syndrome symptoms, lower quality of life and anxiety than their respective controls even 18 months after the trauma.


Biosynthetic studies of marine lipids. 42. Biosynthesis of steroid and triterpenoid metabolites in the sea cucumber Eupentacta fraudatrix.
The saponins, conjugated sterols, and free sterols of the sea cucumber Eupentacta fraudatrix were examined. A total of 85 steroids, twelve of them new, were identified in the free sterol, sulfated sterol, and sterol-xyloside fractions. The free sterol fraction contained 4 alpha,14 alpha-dimethylcholest-9(11)-en-3 beta-ol(6) and 14 alpha-methylcholest-9(11)-en-3 beta-ol(7) together with 18 minor sterols. Examination of the aglycone moieties of the sterol-beta-xyloside fraction afforded 31 different sterols. Cholestan-3 beta-ol (15) and 24-methylcholesta-7,22-dien-3 beta-ol (20) were the major sterols in this group. Cholestanol sulfate (74) and cholesterol sulfate (64) were identified as the major components among the 34 different sterol sulfates present. Finally, cucumariosides G1 (1), C1 (2), C2 (3), H (4), and G2 (5) were isolated from the saponin fraction. Radiolabeling experiments indicated that there are two pathways of sterol biosynthesis in E. fraudratix. The first involves transformation of squalene to produce lanosta-9(11),24-dien-3 beta-ol(parkeol) which is subsequently demethylated to form 4 alpha,14 alpha-dimethylcholest-9(11)-en-3 beta-ol (6) and 14 alpha-methylcholest-9(11)-en-3 beta-ol (7). The second proceeds through squalene to lanosterol which is further metabolized to produce the triterpene saponins, 5 alpha-cholest-7-en-3 beta-ol (19) and its xyloside (49).


COVID-19 vaccination and HIV transmission among persons who inject drugs during the first two years of the COVID-19 pandemic in New York City.
To examine COVID-19 vaccination and HIV transmission among persons who inject drugs (PWID) during the COVID-19 pandemic (2020-2022) in New York City (NYC). Two hundred and seventy five PWID were recruited from October 2021 to September 2022. A structured questionnaire was used to measure demographics, drug use behaviors, overdose experiences, substance use treatment history, COVID-19 infection, vaccination, and attitudes. Serum samples were collected for HIV, HCV, and SARS-CoV-2 (COVID-19) antibody testing. Participants were: 71% male, the mean age was 49 (SD 11), 81% reported at least one COVID-19 immunization, 76% were fully vaccinated and 64% of the unvaccinated had antibodies for COVID-19. Self-reported injection risk behaviors were very low. HIV seroprevalence was 7%. Eighty-nine percent of the HIV seropositive respondents reported knowing they were HIV seropositive and being on antiretroviral therapy prior to the COVID-19 pandemic. There were two likely seroconversions in 518.83 person-years at risk from the March 2020 start of the pandemic to the times of interviews, for an estimated incidence rate of 0.39/100 person-years, 95% Poisson CI 0.05-1.39/100 person-years. There is concern that the COVID-19 pandemic disruptions to HIV prevention services and the psychological stress of the pandemic may lead to increased risk behavior and increased HIV transmission. These data indicate adaptive/resilient behaviors in both obtaining COVID-19 vaccination and maintaining a low rate of HIV transmission among this sample of PWID during the first two years of the COVID-19 pandemic in NYC.


Long-term outcomes in patients with advanced and/or metastatic non-small cell lung cancer who completed 2 years of immune checkpoint inhibitors or achieved a durable response after discontinuation without disease progression: Multicenter, real-world data (KCSG LU20-11).
Immune checkpoint inhibitors (ICIs) have shown significant improvements in patients with advanced non-small cell lung cancer (NSCLC). One of the major issues with ICIs is determining the optimal treatment duration. This multicenter, retrospective study analyzed clinical outcomes in patients with NSCLC who completed 2 years of ICI therapy or were treated for more than 6 months and then discontinued ICIs without disease progression at 11 medical centers in Korea between August 2017 and December 2020. Ninety-six patients who completed 2 years of ICIs were reviewed. The median durations of treatment and follow-up were 24.0 and 33.9 months, respectively. The objective response rate (ORR) was 85.4%. The median progression-free survival (PFS) and overall survival (OS) periods were not reached. After completion, the PFS and OS rates were 81.1% and 96.4%, respectively, at 12 months. Forty-three patients were identified who discontinued ICIs without disease progression: 26 (60.5%) for adverse events and 17 (39.5%) for other causes. The median durations of treatment and follow-up were 10.5 and 21.2 months, respectively. The ORR was 90.7%. The median PFS and OS periods were not reached. After discontinuation, the PFS and OS rates were 71.0% and 90.0%, respectively, at 12 months. A significantly high proportion of patients who completed 2 years of ICI therapy continued to experience long-term PFS. Even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long-term survival. The optimal treatment duration for immune checkpoint inhibitors (ICIs) remains to be determined. This study reports the long-term outcomes of patients with non-small cell lung cancer who completed 2 years of ICI therapy or achieved a durable response after the discontinuation of ICIs without disease progression in real-world practice. A significantly high proportion of patients who completed 2 years of ICIs continued to experience long-term progression-free survival. In addition, even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long-term survival.


Induction of clusterin/apoJ expression by histone deacetylase inhibitors in neural cells.
The regulation of clusterin expression is poorly characterized although some regulatory elements have been identified, such as CpG-rich methylation domain. Environmental stress, aging, diet and diseases regulate DNA methylation and protein acetylation status but interestingly, the same insults increase clusterin expression in vivo. Our purpose was to elucidate whether histone deacetylase inhibitors, such as TSA, SAHA and M344, as well as an inhibitor of DNA methylation, 5'-aza-2'-deoxycytidine, could regulate the expression of clusterin in cultured neural cells. We observed that histone deacetylase inhibitors induced the expression of clusterin mRNA and protein in all neural cells studied. The induction of clusterin mRNA was blocked by actinomycin D which indicates that TSA regulates clusterin expression at the transcriptional level. An inhibitor of DNA methylation, 5'-aza-2'-deoxycytidine, itself did not affect the expression of clusterin mRNA but strongly potentiated the TSA-induced expression of clusterin. Proteasomal stress (MG-132 and PI-1 treatments) and apoptotic stress (okadaic acid treatment) did not affect clusterin expression which indicates that the induction of clusterin expression requires more specific inducers than cellular stress in general. Furthermore, LPS did not affect clusterin expression in N9 microglia although activated NF-kappaB signaling and IL-6 expression. CAPE and helenalin, inhibitors of NF-kappaB signalling, did not affect the clusterin mRNA expression either in non-treated or in TSA-treated N9 microglia. These observations suggest that clusterin induction is NF-kappaB-independent and unrelated to the inflammatory response in N9 microglia.


Rapid repair of UVA-induced oxidized purines and persistence of UVB-induced dipyrimidine lesions determine the mutagenicity of sunlight in mouse cells.
Despite the predominance of ultraviolet A (UVA) relative to UVB in terrestrial sunlight, solar mutagenesis in humans and rodents is characterized by mutations specific for UVB. We have investigated the kinetics of repair of UVA- and UVB-induced DNA lesions in relation to mutagenicity in transgenic mouse fibroblasts irradiated with equilethal doses of UVA and UVB in comparison to simulated-sunlight UV (SSL). We have also analyzed mutagenesis-derived carcinogenesis in sunlight-associated human skin cancers by compiling the published data on mutation types found in crucial genes in nonmelanoma and melanoma skin cancers. Here, we demonstrate a resistance to repair of UVB-induced cis-syn cyclobutane pyrimidine-dimers (CPDs) together with rapid removal of UVA-induced oxidized purines in the genome overall and in the cII transgene of SSL-irradiated cells. The spectra of mutation induced by both UVB and SSL irradiation in this experimental system are characterized by significant increases in relative frequency of C-->T transitions at dipyrimidines, which are the established signature mutation of CPDs. This type of mutation is also the predominant mutation found in human nonmelanoma and melanoma tumor samples in the TP53, CDKN2, PTCH, and protein kinase genes. The prevailing role of UVB over UVA in solar mutagenesis in our test system can be ascribed to different kinetics of repair for lesions induced by the respective UV irradiation.


Adult Refsum disease: a form of tapetoretinal dystrophy accessible to therapy.
Adult Refsum disease is characterized by an elevated plasma phytanic acid level and high concentrations of phytanic acid in a variety of tissues. Besides tapetoretinal degeneration, additional symptoms are anosmia, skeletal malformations, chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, ichthyosis, and cardiac abnormalities. A diet low in phytanic acid ameliorates polyneuropathy and ataxia and slows or even stops the other manifestations. In order to be able to apply dietary therapy, as many patients as possible (even better if all of them are) have to be identified at an early stage. The ophthalmologist plays a crucial role in achieving this goal because of the early manifestation of the tapetoretinal degeneration.


Antiplasmodial and antitrypanosomal activity of Triclisia sacleuxii (Pierre) Diels.
The antiplasmodial and antitrypanosomal activities of Triclisia sacleuxii (Pierre) Diels were investigated on three Plasmodium falciparum strains [FcB1, 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) strains] and on Trypanosoma brucei Tbsf 221. Roots, stems and leaves ethanolic extracts as well as crude tertiary and quaternary alkaloids fractions were considered. Whereas the ethanolic extracts and quaternary crude alkaloids fractions exhibited no significant activity, the roots and stems tertiary alkaloid fractions revealed interesting growth inhibition against the Plasmodium FcB1 and Trypanosoma Tbsf 221 strains. The IC(50) were 1.04 and 0.89 microg/ml for roots, 2.50 and 0.91 microg/ml for stems. The leaves tertiary alkaloids fraction also showed a promising antitrypanosomal activity (IC(50): 1.85 microg/ml). Phytochemical analysis of the roots tertiary alkaloids fraction yielded four major compounds, phaeanthine, N-methylapateline, 1,2-dehydroapateline and 1,2-dehydrotelobine, which were identified on the basis of their spectroscopic data. The four compounds displayed (in vitro) antitrypanosomal activity with IC(50) of 2.68, 1.19, 1.06 and 1.11 microM, respectively. They also demonstrated antiplasmodial activity on Plasmodium falciparum 3D7, with IC(50) of 1.72, 0.93, 1.39 and 12.4 microM respectively and on the chloroquine-resistant W2 with IC(50) of 0.35, 1.10, 1.63 and 1.52 microM.


A bilayered scaffold with segregated hydrophilicity-hydrophobicity enables reconstruction of goat hierarchical temporomandibular joint condyle cartilage.
Temporomandibular joint (TMJ) supports chewing, talking or other daily oral activities. So far, it still remains a great challenge to treat the defected TMJ condyle cartilage through tissue engineering technology. Herein, a bilayered scaffold is designed to fully reconstruct the different cartilage matrices of TMJ condyle under same induction condition. The bilayered scaffold with segregated hydrophobicity-hydrophilicity in top and bottom layer is prepared from a low and high content of polyethylene glycol (PEG) crosslinked poly (L-glutamic acid)-g-polycaprolactone (PLGA-g-PCL). The hydrophobic aggregates in top layer support the adhesion and spread of bone mesenchymal stem cells (BMSCs), thus inducing the differentation towards fibrocartilage; while aggregates (spheroids) are formed on the hydrophlic bottom layer, showing a preferable hyaline differentiation pathway under same chondrogenic induction in vitro. After 14 d in vitro induction, the scaffold/BMSCs construct is implanted in goat TMJ condyle defects. The post-operative outcome after 2 months demonstrates that the defects are fully covered by neo-cartilage. And the regenerated hierarchical TMJ condyle cartilage perfectly consist of ordered fibrocartilage and hyaline cartilage, which is same as natural condyle cartilage. These results corroborate that this bilayered scaffold with segregated hydrophilicity-hydrophobicity carrying induced BMSCs is a promising for treatment of TMJ condyle cartilage defects.


Heart-rate reactivity to cold pressor stress following biofeedback training.
Three previous studies have shown that biofeedback training is useful in modifying heart-rate and pain ratings during ice water stimulation (cold pressor test). Subjects were given an initial cold pressor followed by heart-rate biofeedback training and a final cold pressor test in which they were instructed to control their heart rate in accordance with the prior training. It was assumed that a heart-rate control skill had been learned. In the present study, two groups of subjects (N = 9 each) were given either increase or decrease heart-rate biofeedback training following the same procedures as previously, but subjects were not instructed to control their heart rate during the final cold pressor test. Heart rate, skin conductance, electromyographic activity, and respiration were measured. The biofeedback training effects replicate the previous results. However, no heart-rate or pain rating differences were found between the two groups during the final cold pressor test. Thus, previous findings cannot be accounted for simply by a shift in heart rate and/or pain reactivity following training itself. The findings suggest that a biofeedback strategy may be useful in modifying physiological and subjective responses to painful stimuli but only if it can be used as an active coping skill.


Automated separation process for radioanalytical purposes at nuclear power plants.
Chemical separation processes have been developed to remove the matrix components and thus to determine fission products, especially radioiodine nuclides, in the primary coolant of WWER-type nuclear reactors. Special procedures have been elaborated to enrich long-lived nuclides in waste waters to be released and to separate and enrich caesium isotopes in the environment. All processes are based mainly on ion-exchange separations using amorphous zirconium phosphate. Automated equipment was constructed to meet the demands of the plant personnel for serial analysis.


Occupational exposure to whole-body vibration and neck pain in the Swedish general population.
The primary aim of this study was to determine if occupational exposure to whole-body vibration (WBV) was associated with reporting neck pain. A cross-sectional study was conducted on a sample of the general population living in northern Sweden, aged 24-76 years. Data was retrieved through a digital survey that collected subjectively reported information on exposure to WBV and biomechanical exposures as well as neck pain. The study included 5,017 participants (response rate 44%). Neck pain was reported by 269 men (11.8%) and 536 women (20.2%). There was a statistically significant association between reporting occupational exposure to WBV half the time or more (adjusted OR 1.91; 95% CI 1.22-3.00) and reporting neck pain. In gender-stratified analyses, the same pattern was observed in men, while there were too few women to determine any association. We conclude that occupational exposure to whole-body vibration was associated with neck pain in men.Practitioner summary: This cross-sectional, survey-based study investigated associations between self-reported occupational whole-body vibration and neck pain. It showed significant associations between frequent exposure to whole-body vibration and neck pain among men but not women. In occupational health care settings, whole-body vibration could be considered as a possible risk factor for neck pain.


Comparison of Adenosine Deaminase, Zinc, Magnesium, Lipid Profile, and some Micronutrient Elements and their Relation with CD4 Counts in Human Immunodeficiency Virus Positive and Negative Patients.
There is strong evidence regarding the patterns of alteration in the blood parameters in human immunodeficiency virus (HIV)-positive patients. However, no consensus has been reached in this regard and the results vary from different regions and studies. Our study aims to report these patterns in a population of HIV-infected patients in Iran. We studied two groups of HIV-infected and HIV-negative patients. One hundred and fourteen subjects were enrolled in each group; blood parameters were compared in these two. Variables of HIV-negative patients changed as follows compared to HIV-positive patients: with regard to the hematological variables, CD4+↓; CD8+↓; WBC↓; RBC↓; HCT↓; MCV↑; MCH↑; MCHC↑; PLT↓; EOS↑; and BASO↑; and among the metabloic parameters, TG↓; CH↑; HDL↓; LDL↓, MG↑; ZN↑; P↑; and ADA↓, which showed significnat differences between groups (P < 0.05). We conclude that HIV infection affects hematopoiesis by diminishing the hematological productivity parameters and increasing red blood cell related morphology, along with a different pattern of lipid profile (decreased TG, LDL, HDL, and increased CH) and serum micronutrients (elevated concentration of serum trace elements) in our population of study.


Segmental dynamics of polymers in nanoscopic confinements, as probed by simulations of polymer/layered-silicate nanocomposites.
In this paper we review molecular modeling investigations of polymer/layered-silicate intercalates, as model systems to explore polymers in nanoscopically confined spaces. The atomic-scale picture, as revealed by computer simulations, is presented in the context of salient results from a wide range of experimental techniques. This approach provides insights into how polymeric segmental dynamics are affected by severe geometric constraints. Focusing on intercalated systems, i.e. polystyrene (PS) in 2 nm wide slit-pores and polyethylene-oxide (PEO) in 1 nm wide slit-pores, a very rich picture for the segmental dynamics is unveiled, despite the topological constraints imposed by the confining solid surfaces. On a local scale, intercalated polymers exhibit a very wide distribution of segmental relaxation times (ranging from ultra-fast to ultra-slow, over a wide range of temperatures). In both cases (PS and PEO), the segmental relaxations originate from the confinement-induced local density variations. Additionally, where there exist special interactions between the polymer and the confining surfaces ( e.g., PEO) more molecular mechanisms are identified.


Laparoscopic ultrasound-assisted liposuction for lymph node dissection: a pilot study.
Lymphadenectomy is a surgical technique for staging and treating cancer. Laparoscopic lymphadenectomy for obese patients is challenging. Laparoscopic ultrasound-assisted liposuction (UAL) has been successful in porcine models. The current study aimed to evaluate whether UAL facilitates pelvic laparoscopic lymphadenectomy in obese subjects. The UAL technique was evaluated in two human cadavers and in six obese Ossabaw pigs. Both a standard and a prototype ultrasonic probe with a wider contact surface were tested. Pelvic lymphadenectomy comparing UAL with standard monopolar cautery was performed using obese Ossabaw pigs. The animals were survived for 2 weeks. Descriptive data regarding intra- and postoperative outcomes were recorded, including histologic analysis of dissected tissue after 2 weeks. Cytologic analysis of aspirated fluid coming from UAL also was recorded. The UAL procedure was safely performed for all the cadavers and animals. Lymph node exposure and clean exposure of surrounding structures were dramatic compared with monopolar assisted dissection. One animal was excluded from further analysis due to ultrasonic device malfunction (a broken footswitch cord). In general, UAL notably debulks adipose tissue with dramatic field exposure. Postoperative adhesions were present in all animals undergoing either monopolar or UAL dissection. Histology showed areas of foreign body reaction from mild to severe, with no predominance of either extreme seen with monopolar or UAL dissection. Cytologic analysis of collected pooled oil emulsion did not contain lymph node tissue. The UAL approach permits pelvic lymphadenectomy in the obese animal and cadaver model, with excellent exposure of lymph nodes and surrounding pelvic anatomy. The use of a new ultrasonic prototype probe with a wider contact surface allowed dissection with less mechanical and thermal penetration of tissue. Further studies are needed to assess oncologic safety (cancer cell dissemination), postoperative healing, and adhesion formation.


Chaetogaster limnaei (annelida: oligochaeta) as a parasite of the zebra mussel Dreissena polymorpha, and the quagga mussel Dreissena bugensis (mollusca: bivalvia).
Dreissenid mussels, Dreissena polymorpha and D. bugensis, were found to be infected by the naidid oligochaete Chaetogaster limnaei at four sites in the St. Lawrence River. This is the first report of this species infecting dreissenids anywhere in the world. Most worms inhabited the mantle cavity, where they caused erosion of the mantle and gill epithelia as determined by histopathological examination. Others penetrated various tissues; one had invaded the ovary and was feeding on oocytes and ovarian tissues. Of 606 mussels examined, 166 (27.4%) harbored at least 1 C. limnaei. The prevalence varied between 1% and 80%, depending on the collection site and date. The worms were slightly but significantly more prevalent in D. bugensis than in D. polymorpha. The intensity ranged from 1 to 18 worms per infected host. Variations in prevalence and intensity were not related to the size or sex of the host, but the data did suggest some seasonality.


Compact artificial neuron based on anti-ferroelectric transistor.
Neuromorphic machines are intriguing for building energy-efficient intelligent systems, where spiking neurons are pivotal components. Recently, memristive neurons with promising bio-plausibility have been developed, but with limited reliability, bulky capacitors or additional reset circuits. Here, we propose an anti-ferroelectric field-effect transistor neuron based on the inherent polarization and depolarization of Hf0.2Zr0.8O2 anti-ferroelectric film to meet these challenges. The intrinsic accumulated polarization/spontaneous depolarization of Hf0.2Zr0.8O2 films implements the integration/leaky behavior of neurons, avoiding external capacitors and reset circuits. Moreover, the anti-ferroelectric neuron exhibits low energy consumption (37 fJ/spike), high endurance (>1012), high uniformity and high stability. We further construct a two-layer fully ferroelectric spiking neural networks that combines anti-ferroelectric neurons and ferroelectric synapses, achieving 96.8% recognition accuracy on the Modified National Institute of Standards and Technology dataset. This work opens the way to emulate neurons with anti-ferroelectric materials and provides a promising approach to building high-efficient neuromorphic hardware.


Extractability of water-soluble soil organic matter as monitored by spectroscopic and chromatographic analyses.
Cold and hot water processes have been intensively used to recover soil organic matter, but the effect of extraction conditions on the composition of the extracts were not well investigated. Our objective was to optimize the extraction conditions (time and temperature) to increase the extracted carbon efficiency while minimizing the possible alteration of water extractable organic matter of soil (WEOM). WEOM were extracted at 20°C, 60°C, or 80°C for 24 h, 10-60 min, and 20 min, respectively. The different processes were compared in terms of pH of suspensions, yield of organic carbon, spectroscopic properties (ultraviolet-visible absorption and fluorescence), and by chromatographic analyses. For extraction at 60°C, the time 30 min was optimal in terms of yield of organic carbon extracted and concentration of absorbing and fluorescent species. The comparison of WEOM 20°C, 24 h; 60°C, 30 min; and 80°C, 20 min highlighted significant differences. The content of total organic carbon, the value of specific ultraviolet absorbance (SUVA(254)), the absorbance ratio at 254 and 365 nm (E (2)/E (3)), and the humification index varied in the order: WEOM (20°C, 24 h) < WEOM (80°C, 20 min) < WEOM (60°C, 30 min). The three WEOM contained common fluorophores associated with simple aromatic structures and/or fulvic-like and common peaks of distinct polarity as detected by ultra performance liquid chromatography. For the soil chosen, extraction at 60°C for 30 min is the best procedure for enrichment in organic chemicals and minimal alteration of the organic matter.


Three-Dimensional Sonography of Biliary Tract Disorders.
In this pictorial essay, we review the 3-dimensional sonographic appearance of the normal gallbladder and biliary tree, as well as the appearance of congenital and acquired biliary tract disorders. Using examples, we demonstrate the advantage of 3-dimensional scanning compared with 2-dimensional sonography and, even in certain cases, magnetic resonance cholangiopancreatography.