Differential effects of alpha- and beta-defensin on cytokine production by cultured human bronchial epithelial cells.
Defensins are cysteine-rich cationic antimicrobial peptides that play an important role in innate immunity and are known to contribute to the regulation of host adaptive immunity. In addition to direct antimicrobial activities, it has been recently reported that alpha-defensins, mainly present in neutrophils in the lung, have a cytotoxic effect and induce IL-8 production from airway epithelial cells. Although beta-defensins are expressed in epithelial cells in various tissues, including lung, there are no reports of their effects on cytokine synthesis in airway epithelial cells. The aim of the present study was to determine the effects of both alpha- and beta-defensins on the cytokine production, transcription factor binding activity, and cytotoxicity in primary cultured human bronchial epithelial cells (HBECs). We used human neutrophil peptide-1 (HNP-1; alpha-defensin) and human beta-defensin-2 (HBD-2) to stimulate HBECs. The results showed that treatment of HBECs with HNP-1, but not HBD-2, increased IL-8 and IL-1beta mRNA expression in a dose-dependent manner and also enhanced IL-8 protein secretion and NF-kappaB DNA binding activity. The 24-h treatments with >20 microg/ml of HNP-1 or >50 microg/ml of HBD-2 were cytotoxic to HBECs. These results suggest that alpha- and beta-defensins have different effects on cytokine synthesis by airway epithelial cells, and we speculate that they play different roles in inflammatory lung diseases.


Assessing the Impact of Laparoscopic Cholecystectomy on Satisfaction, Quality of Life, and Cost-Effectiveness in Saudi Patients With Gallstone Disease: A Comprehensive Cross-Sectional Analysis.
Cholelithiasis, or gallstone disease, is a prevalent medical condition with substantial global implications. Laparoscopic cholecystectomy (LC) has become the dominant surgical solution for treating various biliary conditions in affluent countries due to its numerous benefits, such as shorter hospital stays and reduced costs. An assessment of postoperative recovery, patient satisfaction, and quality of life (QoL) is crucial to judge the success of any medical procedure regarding long-term patient well-being. Given the scarcity of research on the satisfaction, QoL, and cost-effectiveness of LC among Saudi patients, this study seeks to fill this gap. To achieve the study's objectives, a cross-sectional research study was conducted from January to December 2023, focusing on Saudi patients who had received LC for gallstone disease. We utilized an extensive questionnaire to determine patient satisfaction, QoL, and the perceived value of LC, which combined closed and open-ended questions to provide a holistic understanding. Additionally, an in-depth literature review was performed to compare our findings with existing research. Our survey received answers from 886 Saudi LC patients. Generally, participants showed satisfaction with LC, though complications were reported in a significant number of cases. However, a minority of participants were dissatisfied. Most respondents indicated a moderate enhancement in their QoL postsurgery. Notably, demographic factors like gender, age, and employment status had profound effects on satisfaction and QoL, with male participants more likely to report higher satisfaction and QoL than females. Our data firmly support the ongoing use of LC as the preferred surgical technique for treating biliary diseases in Saudi Arabia. They emphasize the benefits of personalizing care based on patient demographics to improve the overall experience. Proper communication, thorough preoperative planning, and attentive postoperative care are essential for achieving the best outcomes. Despite these findings, more research is needed, focusing on different patient demographics and comparing LC with other treatment methods to enhance our understanding of gallstone disease management in the Saudi context.


Re-appraisal of the tocopheroxyl radical reaction with beta-carotene: evidence for oxidation of vitamin E by the beta-carotene radical cation.
Photobleached beta-carotene (Car) is regenerated in hexane on a microsecond timescale in the presence of alpha-tocopherol (TOH) but not when alpha-tocopherol is absent, as studied by laser flash photolysis. Beta-carotene radical cations (Car.+) likewise react with (excess) alpha-tocopherol: Car.+ + TOH-->Car + TO. + H+ (second-order rate constant of k = 1.7 +/- 0.1 x 10(7) M(-1) s(-1) in homogeneous di-tert-butylperoxide/benzene at 20 degrees C) rather than alpha-tocopheroxyl radicals (TO.) reacting with beta-carotene. In hexane, hexane radicals formed by pulse radiolysis react considerably faster with beta-carotene (k = 2.1 +/- 0.1 x 10(9) M(-1) s(-1)) than with alpha-tocopherol (k = 4.9 +/- 0.1 x 10(6) M(-1) s(-1)). No evidence was obtained for a slower rate of beta-carotene radical cation formation in beta-carotene/alpha-tocopherol mixtures resulting from alpha-tocopheroxyl radical oxidation of beta-carotene. Steady-state radiolysis experiments confirmed that alpha-tocopherol protects beta-carotene from oxidation by hexane radicals. In both solvent systems, beta-carotene is regenerated from the radical cation by alpha-tocopherol rather than alpha-tocopherol being regenerated by beta-carotene from the alpha-tocopheroxyl radical.


CD200 modulates macrophage cytokine secretion and phagocytosis in response to poly(lactic co-glycolic acid) microparticles and films.
Biocompatibility is a major concern for developing biomaterials used in medical devices, tissue engineering and drug delivery. Poly(lactic-co-glycolic acid) (PLGA) is one of the most widely used biodegradable materials, yet still triggers a significant foreign body response that impairs healing. Immune cells including macrophages respond to the implanted biomaterial and mediate the host response, which can eventually lead to device failure. Previously in our laboratory, we found that CD200, an immunomodulatory protein, suppressed macrophage inflammatory activation in vitro and reduced local immune cell infiltration around a biomaterial implant. While in our initial study we used polystyrene as a model material, here we investigate the effect of CD200 on PLGA, a commonly used biomaterial with many potential clinical applications. We fabricated PLGA with varied geometries, modified their surfaces with CD200, and examined macrophage cytokine secretion and phagocytosis. We found that CD200 suppressed secretion of the pro-inflammatory cytokine TNF-α and enhanced secretion of the anti-inflammatory cytokine IL-10, suggesting a role for CD200 in promoting wound healing and tissue remodeling. In addition, we found that CD200 increased phagocytosis in both murine macrophages and human monocytes. Together, these data suggest that modification with CD200 leads to a response that simultaneously prevents inflammation and enhances phagocytosis. This immunomodulatory feature may be used as a strategy to mitigate inflammation or deliver drugs or anti-inflammatory agents targeting macrophages.


Volumetric behavior of the {CO2 (1) + C2H6 (2)} system in the subcritical (T = 293.15 K), critical, and supercritical (T = 308.15 K) regions.
The volumetric behavior for the {CO2 (1) + C2H6 (2)} system has been studied. Density measurements of {CO2 (1) + C2H6 (2)} binary mixtures at 293.15 and 308.15 K, at several pressures and compositions, and density measurements for infinitely dilute solutions at 304.21 and 308.15 K were carried out using an Anton Paar DMA 512-P vibrating-tube densimeter calibrated with the forced path mechanical calibration model. The mean relative standard deviation of density, s(rho)(r), was estimated to be better than 0.1%, and the uncertainties in temperature and pressure were estimated as +/-0.01 K and +/-0.001 MPa, respectively. In the experimental setup, an uncertainty in the mole fraction of u(x(j)) = +/-0.0015 has been achieved. Other properties related to P-rho-T-x data such as the compressibility factor, Z, excess molar volumes, V(m)(E), and partial molar volumes, V(i) and V(i)(infinity) have been calculated. The volumetric behavior has been compared with literature data and with that obtained from the PC-SAFT EoS rescaled parameters; these parameters have been obtained from our previous experimental values for the critical temperature and pressure of pure compounds. The value for the Krichevskii parameter, A(Kr), was obtained from the experimental density data for infinitely dilute solutions measured in this work, and it has been compared with that obtained from critical properties. Structural properties such as direct and total correlation function integrals and cluster size were calculated using the Krichevskii function concept.


Optical properties of Nd3+ doped ionic liquid immobilized on mesoporous silica support.
The synthesis of a new material based on Nd3+ ions doped into an imidazolium-type ionic liquid with further immobilization on a mesoporous silica support is reported. The material was investigated by DR-UV/VIS, FT-IR, thermogravimetric analysis, N2 adsorption measurements and time-resolved photoluminescence spectroscopy. The intensity of the near-infrared emission of Nd3+ was weak and the lifetime measured at about 910 nm was 7 micros.


Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis.
Noninvasive imaging of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) may identify early stages of inflammation in atherosclerosis. We hypothesized that a novel, second-generation VCAM-1-targeted agent with enhanced affinity had sufficient sensitivity to enable real-time detection of VCAM-1 expression in experimental atherosclerosis in vivo, to quantify pharmacotherapy-induced reductions in VCAM-1 expression, and to identify activated cells in human plaques. In vivo phage display in apolipoprotein E-deficient mice identified a linear peptide affinity ligand, VHPKQHR, homologous to very late antigen-4, a known ligand for VCAM-1. This peptide was developed into a multivalent agent detectable by MRI and optical imaging (denoted VINP-28 for VCAM-1 internalizing nanoparticle 28, with 20 times higher affinity than previously reported for VNP). In vitro, VINP-28 targeted all cell types expressing VCAM-1. In vivo, MRI and optical imaging in apolipoprotein E-deficient mice (n=28) after injection with VINP-28 or saline revealed signal enhancement in the aortic root of mice receiving VINP-28 (P<0.05). VINP-28 colocalized with endothelial cells and other VCAM-1-expressing cells, eg, macrophages, and was spatially distinct compared with untargeted control nanoparticles. Atheromata of atorvastatin-treated mice showed reduced VINP-28 deposition and VCAM-1 expression. VINP-28 enhanced early lesions in juvenile mice and resected human carotid artery plaques. VINP-28 allows noninvasive imaging of VCAM-1-expressing endothelial cells and macrophages in atherosclerosis and spatial monitoring of anti-VCAM-1 pharmacotherapy in vivo and identifies inflammatory cells in human atheromata. This clinically translatable agent could noninvasively detect inflammation in early, subclinical atherosclerosis.


Exploring expert practice through reflection.
This article describes an unusual experience drawn from clinical practice which has been used to enable self-criticism and expansion of personal knowledge. The importance of practice knowledge, knowing the patient and relatives, expanded eclectic knowledge and teamwork are highlighted. This paper, while exploring the complexity of expert practice, identifies the importance of viewing the individual patient holistically.


Wortmannin inhibits spreading and chemotaxis of rat osteoclasts in vitro.
Wortmannin (WT) and 17beta-hydroxywortmannin (HWT), which are inhibitors of phosphatidylinositol-3(OH)-kinase (PI3K), have been shown previously to inhibit bone resorption in vitro and in vivo, possibly by interfering with formation of the osteoclast ruffled border. Since migration of osteoclasts also plays an important role in the process of bone resorption, we investigated the effects of these inhibitors on osteoclast morphology and motility. Both HWT and WT caused a sustained decrease in the planar area of osteoclasts in vitro (half maximal effect at 25 and 165 nM, respectively), with the effect of HWT on cell area more readily reversible than WT. These agents also caused accumulation of intracellular vesicles. Time-lapse video microscopy was used to record the migration of osteoclasts in response to macrophage colony-stimulating factor (M-CSF) or vehicle, flowing passively from a micropipette positioned 200-400 microm from the cell. M-CSF caused directed migration of osteoclasts, indicating chemotaxis (over 3 h osteoclasts migrated 96 +/- 14 microm in response to M-CSF vs. 11 +/- 2 microm in control experiments). Both WT (100 or 500 nM) and LY294002 (100 microM), a specific PI3K inhibitor structurally unrelated to WT, significantly inhibited osteoclast chemotaxis in response to M-CSF. Taken together, these effects of WT, HWT, and LY294002 are consistent with an important role for PI3K in regulating cytoskeletal function in osteoclasts. The inhibitory effects of WT and HWT on bone resorption may be due, in part, to impairment of osteoclast motility.


Long-term effects of exposure to methylnitrosourea on blastocysts following transfer to surrogate female mice.
The effect of in vitro preimplantation exposure of mouse embryos to N-methyl-N-nitrosourea (MNU) on development subsequent to embryo transfer into pseudopregnant surrogate mothers has been investigated. The offspring developed from mouse blastocysts exposed to MNU or to solvent were examined carefully for 1 year after birth and then examined with X-rays and complete autopsies. Metaphase chromosomes were examined in some of these animals. Exposure to MNU at the morula stage did not affect progression to the blastocyst stage in vitro; however, exposure at the blastocyst stage resulted in a profound reduction in the live birth rate. Offspring developed from blastocysts exposed to MNU in vitro were found to have a 3-fold-higher crude mortality rate than offspring developed from blastocysts exposed to solvent. There were no gross dysmorphogenic effects of exposure, nor were any major histological abnormalities associated with MNU exposure. No chromosomal abnormalities were discovered in either surviving group of offspring.


Sensitive assay for laboratory evolution of hydroxylases toward aromatic and heterocyclic compounds.
Powerful directed evolution methods have been developed for tailoring proteins to our needs in industrial applications. Here, the authors report a medium-throughput assay system designed for screening mutant libraries of oxygenases capable of inserting a hydroxyl group into a C-H bond of aromatic or O-heterocyclic compounds and for exploring the substrate profile of oxygenases. The assay system is based on 4-aminoantipyrine (4-AAP), a colorimetric phenol detection reagent. By using 2 detection wavelengths (509 nm and 600 nm), the authors achieved a linear response from 50 to 800 microM phenol and standard deviations below 11% in 96-well plate assays. The monooxygenase P450 BM-3 and its F87A mutant were used as a model system for medium-throughput assay development, identification of novel substrates (e.g., phenoxytoluene, phenylallyether, and coumarone), and discovery of P450 BM-3 F87A mutants with 8-fold improvement in 3-phenoxytoluene hydroxylation activity. This activity increase was achieved by screening a saturation mutagenesis library of amino acid position Y51 using the 4-AAP protocol in the 96-well format.


Treatment of Human Intraosseous Periodontal Defects Using Recombinant Human Bone Morphogenetic Protein-2: A Randomized Controlled Clinical Trial.
Aim The purpose of this research was to assess the clinical and radiographic outcomes of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the treatment of intraosseous abnormalities after periodontal flap surgery. Material and methods Patients aged 35-55 years who had undergone periodontal treatment at Shree Bankey Bihari Dental College and Research Centre, Ghaziabad, and had a total of 14 intraosseous abnormalities were included in the research. Those in the control group had open flap debridement with alloplast, whereas those in the experimental group underwent the same procedure with the addition of rhBMP-2. Clinical indicators, such as plaque index (PI), gingival index, probing pocket depth (PPD), clinical attachment level, and radiographic defect fill, were collected at baseline at three months, six months, and nine months. Results The findings demonstrated that following periodontal treatment, both sets of patients had considerable improvements in their PI, gingival index, and PPD. The degree of relative connection improved significantly in both groups. When comparing the two groups radiographically, we saw that the test group had significantly better defect fill than the control group. Conclusion According to this research, there was a statistically significant decrease in PI, gingival index, PPD, clinical attachment level, and radiographic bone fill in patients who received rhBMP-2. Open flap debridement with rhBMP-2 and alloplastic bone grafts showed better reduction than open flap debridement with alloplastic bone grafts group in the radiographic defect fill.


Exogenous Sequences in Tumors and Immune Cells (Exotic): A Tool for Estimating the Microbe Abundances in Tumor RNA-seq Data.
The microbiome affects cancer, from carcinogenesis to response to treatments. New evidence suggests that microbes are also present in many tumors, though the scope of how they affect tumor biology and clinical outcomes is in its early stages. A broad survey of tumor microbiome samples across several independent datasets is needed to identify robust correlations for follow-up testing. We created a tool called {exotic} for "exogenous sequences in tumors and immune cells" to carefully identify the tumor microbiome within RNA sequencing (RNA-seq) datasets. We applied it to samples collected through the Oncology Research Information Exchange Network (ORIEN) and The Cancer Genome Atlas. We showed how the processing removes contaminants and batch effects to yield microbe abundances consistent with non-high-throughput sequencing-based approaches and DNA-amplicon-based measurements of a subset of the same tumors. We sought to establish clinical relevance by correlating the microbe abundances with various clinical and tumor measurements, such as age and tumor hypoxia. This process leveraged the two datasets and raised up only the concordant (significant and in the same direction) associations. We observed associations with survival and clinical variables that are cancer specific and relatively few associations with immune composition. Finally, we explored potential mechanisms by which microbes and tumors may interact using a network-based approach. Alistipes, a common gut commensal, showed the highest network degree centrality and was associated with genes related to metabolism and inflammation. The {exotic} tool can support the discovery of microbes in tumors in a way that leverages the many existing and growing RNA-seq datasets. The intrinsic tumor microbiome holds great potential for its ability to predict various aspects of cancer biology and as a target for rational manipulation. Here, we describe a tool to quantify microbes from within tumor RNA-seq and apply it to two independent datasets. We show new associations with clinical variables that justify biomarker uses and more experimentation into the mechanisms by which tumor microbiomes affect cancer outcomes.


Oxidative stress and left ventricular remodelling after myocardial infarction.
In acute myocardial infarction (MI), reactive oxygen species (ROS) are generated in the ischaemic myocardium especially after reperfusion. ROS directly injure the cell membrane and cause cell death. However, ROS also stimulate signal transduction to elaborate inflammatory cytokines, e.g. tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and -6, in the ischaemic region and surrounding myocardium as a host reaction. Inflammatory cytokines also regulate cell survival and cell death in the chain reaction with ROS. Both ROS and inflammatory cytokines are cardiodepressant mainly due to impairment of intracellular Ca(2+) homeostasis. Inflammatory cytokines stimulate apoptosis through a TNF-alpha receptor/caspase pathway, whereas Ca(2+) overload induced by extensive ROS generation causes necrosis through enhanced permeability of the mitochondrial membrane (mitochondrial permeability transition). Apoptosis signal-regulating kinase-1 (ASK1) is an ROS-sensitive, mitogen-activated protein kinase kinase kinase that is activated by many stress signals and can activate nuclear factor kappaB and other transcription factors. ASK1-deficient mice demonstrate that the ROS/ASK1 pathway is involved in necrotic as well as apoptotic cell death, indicating that ASK1 may be a therapeutic target to reduce left ventricular (LV) remodelling after MI. ROS and inflammatory cytokines activate matrix metalloproteinases which degrade extracellular matrix, causing a slippage of myofibrils and hence LV dilatation. Consequently, collagen deposition is increased and tissue repair is enhanced with myocardial fibrosis and angiogenesis. Since the extent of LV remodelling is a major predictor of prognosis of the patients with MI, the therapeutic approach to attenuating LV remodelling is critically important.


Partially Reversible Immobilization of Free-Ranging Huemul Deer (Hippocamelus bisulcus) with Medetomidine-Ketamine and Atipamezole.
A combination of intramuscular medetomidine and ketamine was used to immobilize 46 free-ranging huemul deer (Hippocamelus bisulcus) with a remote drug delivery system in Chilean Patagonia for tagging and biological sampling. Captures occurred in May-October of 2005-09 between fall and early spring in the southern hemisphere. An initial dose of 6.6 mg medetomidine and 185 mg ketamine was adjusted after 17 captures to 3 mg and 200 mg, respectively, in the 29 remaining deer. Mean±SD adjusted dose was 0.042±0.012 mg/kg of medetomidine and 2.929±0.427 mg/kg of ketamine. Inductions were calm and the mean±SD time to sternal recumbency was 10.3±10.1 min. Palpebral reflex and jaw tone were present during immobilization. Atipamezole at 5 mg/mg of medetomidine was administered intramuscularly for reversal after 55.3±18.8 min procedure time. Recoveries were smooth and mean±SD time to standing was 10.2±3.3. All immobilized animals were hypoxemic by pulse oximetry (blood oxygen saturation approximately 81%). Three animals that developed apnea were resuscitated through chest compression and atipamezole administration, another regurgitated during capture, and all developed tachypnea. The combination of medetomidine-ketamine and atipamezole can be used for partially reversible immobilization of huemul, but supplemental oxygen should be administered, blood oxygenation should be monitored, and equipment for intubation and manual ventilation should be available.


Fast Regulation of Vertical Squat Jump during Push-Off in Skilled Jumpers.
The height of a maximum Vertical Squat Jump (VSJ) reflects the useful power produced by a jumper during the push-off phase. In turn this partly depends on the coordination of the jumper's segmental rotations at each instant. The physical system constituted by the jumper has been shown to be very sensitive to perturbations and furthermore the movement is realized in a very short time (ca. 300 ms), compared to the timing of known feedback loops. However, the dynamics of the segmental coordination and its efficiency in relation to energetics at each instant of the push-off phase still remained to be clarified. Their study was the main purpose of the present research. Eight young adult volunteers (males) performed maximal VSJ. They were skilled in jumping according to their sport activities (track and field or volleyball). A video analysis on the kinematics of the jump determined the influence of the jumpers' segments rotation on the vertical velocity and acceleration of the body mass center (MC). The efficiency in the production of useful power at the jumpers' MC level, by the rotation of the segments, was measured in consequence. The results showed a great variability in the segmental movements of the eight jumpers, but homogeneity in the overall evolution of these movements with three consecutive types of coordination in the second part of the push-off (lasting roughly 0.16 s). Further analyses gave insights on the regulation of the push-off, suggesting that very fast regulation(s) of the VSJ may be supported by: (a) the adaptation of the motor cerebral programming to the jumper's physical characteristics; (b) the control of the initial posture; and


"Partial duplication of lower lip and hemimandible" A rare case.
Duplication of mandible and lower lip is a very rare congenital entity. We report an extremely uncommon case of Congenital Duplication of Lower lip and Mandible in a 3 year old girl, who was treated surgically in a single stage for correction of both lip and mandible. This was a commissure preserving single staged procedure. The Surgical procedure, the problems related to this anomaly and the embryology are discussed.


Expression of immunoreactive glutathione S-transferases in hepatic neoplasms induced by aflatoxin B1 or 1,2-dimethylbenzanthracene in rainbow trout (Oncorhynchus mykiss).
The expression of immunoreactive glutathione S-transferase (GST) was examined in hepatic neoplasms induced in rainbow trout by aflatoxin B1 (AFB) or 1,2-dimethylbenzanthracene (DMBA). Tumors were induced in adult trout by continuous dietary exposure to 8 p.p.b. AFB1 for 12 months or embryo bath exposure to DMBA (5 p.p.m. for 24 h, 3 times with 12 h intervals between exposures). Polyclonal antiserum specific for the two major trout hepatic GST subunits in trout liver was produced by immunizing rabbits with affinity-purified trout GST. Hepatocellular, cholangiolar and mixed neoplasms as well as foci of hepatocellular alteration were examined for GST immunoreactivity by the PAP technique. The majority of lesions were GST-deficient (AFB treated, 67%; DMBA treated, 54%), whereas GST expression was induced in 21% (AFB treated) and 31% (DMBA treated) of altered hepatic foci. The GST-induced foci were consistently small (AFB treated, 0.07 +/- 0.05 mm2; DMBA treated, 0.02 +/- 0.01 mm2) and none had progressed beyond the altered focus stage. The majority of larger advanced lesions (adenomas and carcinomas) were GST deficient (AFB treated, 2.33 +/- 0.35 mm2; DMBA treated, 2.95 +/- 0.59 mm2). These studies demonstrate that induced GST expression occurs in some small populations of hepatocytes, but not in larger advanced stages of malignant progression of aflatoxin- or PAH-induced hepatic neoplasms in rainbow trout.


Novel fabrication of polyaniline particles wrapped by exfoliated clay sheets and their electrorheology.
Taking into account of unique merits of conducting polymer/inorganic nanocomposites which play a positive effect in enhancing electrorheological (ER) performances, we adopted exfoliated clay sheet as a stabilizer to fabricate novel nano-scaled polyaniline (PANI) granules (PANI/clay) via pickering inverse emulsion polymerization in this study. Successfully synthesized PANI nano-spheres which were initialized by oil-soluble benzoyl peroxide possessed polydispersed size distribution. These armed PANI nanoparticles, of which the surface is compactly wrapped by clay sheets, are observed, as confirmed by SEM and TEM images. Some nano-scaled particles even possess irregular shape with sharp angle because clay plates are difficult to be bended to follow the spherical trace due to the extremely small size of PANI granules. The extent of exfoliation of Clay sheets covered on the surface of PANI particles were characterized by XRD pattern which did not indicate any obvious sharp peak, demonstrating the nearly completely exfoliated clay layers. TGA spectra also gave some additional information on thermal stability and mass composition. At last, an ER fluid was prepared by dispersing PANI/clay nanoparticles in silicone oil and the ER performances were investigated via a rotational test.


Transformed follicular non-Hodgkin lymphoma.
Histologic transformation of follicular lymphoma to an aggressive non-Hodgkin lymphoma is a critical biologic event with profound implications on the natural history of this otherwise indolent disease. Recent insights into the genetic and epigenetic basis of transformation have been described, with the recognition of pivotal events governing the initiation and persistence of tumor evolution. Outcomes of patients with transformed lymphoma have historically been poor; however, several studies in the rituximab era suggest that survival may be more favorable than previously recognized. This review highlights our current understanding of transformed follicular lymphoma biology and pathogenesis, current treatment, and future directions.


[Place of super-selective vagotomy in the treatment of perforated duodenal ulcer].
Thirty-two duodenal ulcer perforations were treated by suture and supraselective vagotomy. Perioperative mortality was nil. The recurrence rate was 6.2% against 17% after elective supraselective vagotomy performed by the same surgeons during the same period. Results of this technique for treatment of perforated duodenal ulcer are compared with those of 28 simple sutures and 32 truncal vagotomies.


Current challenges and potential solutions to the use of digital health technologies in evidence generation: a narrative review.
Digital health is a field that aims to improve patient care through the use of technology, such as telemedicine, mobile health, electronic health records, and artificial intelligence. The aim of this review is to examine the challenges and potential solutions for the implementation and evaluation of digital health technologies. Digital tools are used across the world in different settings. In Australia, the Digital Health Translation and Implementation Program (DHTI) emphasizes the importance of involving stakeholders and addressing infrastructure and training issues for healthcare workers. The WHO's Global Task Force on Digital Health for TB aims to address tuberculosis through digital health innovations. Digital tools are also used in mental health care, but their effectiveness must be evaluated during development. Oncology supportive care uses digital tools for cancer patient intervention and surveillance, but evaluating their effectiveness can be challenging. In the COVID and post-COVID era, digital health solutions must be evaluated based on their technological maturity and size of deployment, as well as the quality of data they provide. To safely and effectively use digital healthcare technology, it is essential to prioritize evaluation using complex systems and evidence-based medical frameworks. To address the challenges of digital health implementation, it is important to prioritize ethical research addressing issues of user consent and addressing socioeconomic disparities in access and effectiveness. It is also important to consider the impact of digital health on health outcomes and the cost-effectiveness of service delivery.


Point of Care Ultrasound: A WFUMB Position Paper.
Over the last decade, the use of portable ultrasound scanners has enhanced the concept of point of care ultrasound (PoC-US), namely, "ultrasound performed at the bedside and interpreted directly by the treating clinician." PoC-US is not a replacement for comprehensive ultrasound, but rather allows physicians immediate access to clinical imaging for rapid and direct solutions. PoC-US has already revolutionized everyday clinical practice, and it is believed that it will dramatically change how ultrasound is applied in daily practice. However, its use and teaching are different from continent to continent and from country to country. This World Federation for Ultrasound in Medicine and Biology position paper discusses the current status and future perspectives of PoC-US. Particular attention is given to the different uses of PoC-US and its clinical significance, including within emergency and critical care medicine, cardiology, anesthesiology, rheumatology, obstetrics, neonatology, gynecology, gastroenterology and many other applications. In the future, PoC-US will be more diverse than ever and be included in medical student training.


Evaluation of female gamete fertility through histological observation by the clearing procedure in Lilium cultivars.
Lilies (Lilium spp.) are one of the most important floricultural crops. As most lily cultivars have originated from interspecific hybridization, they usually have complex genome composition and occasionally fail to develop normal gametes. Further improvement of lily cultivars by sexual crossing requires evaluation of gamete development and subsequent male and female fertility. Although male fertility is easily evaluated through microscopic observation after staining or by pollen culture for germination, evaluation of female fertility is difficult, because gametes develop inside an ovule within an ovary. Lilium species have the Fritillaria type of embryo sac, which, at maturity, consists of a haploid egg apparatus, including one haploid egg cell and two haploid synergids, two polar nuclei (one haploid nucleus and one triploid nucleus) and three triploid antipodal cells. Compared to the Polygonum type of embryo sac, composition of the embryo in the Fritillaria type of embryo sac is complex. We developed an efficient microscopic observation technique for ovules using the clearing procedure, which allowed us to categorize abnormal patterns of female gametes and to elucidate the frequency of abnormal female gamete development. The relationship among normal embryo sac, pollen stainability and seed formation in lily cultivars is discussed.


Listeria monocytogenes serotypes in Italian meat products.
Listeria monocytogenes was isolated and enumerated in Italian fresh ground beef, fresh pork meat and industrial sausages. All the samples contained less than 2000 L. monocytogenes/g of meat. The main serotype isolated was 1/2c (56.9%). Other serotypes isolated included 1/2a, 1/2b, 3c, 4b and 4c. A prevalence of less virulent serotypes over more virulent was thus noted. It seems that the low incidence of listeriosis from these products is related to the low concentration and virulence of L. monocytogenes present.


A photometric high-throughput method for identification of electrochemically active bacteria using a WO3 nanocluster probe.
Electrochemically active bacteria (EAB) are ubiquitous in environment and have important application in the fields of biogeochemistry, environment, microbiology and bioenergy. However, rapid and sensitive methods for EAB identification and evaluation of their extracellular electron transfer ability are still lacking. Herein we report a novel photometric method for visual detection of EAB by using an electrochromic material, WO(3) nanoclusters, as the probe. This method allowed a rapid identification of EAB within 5 min and a quantitative evaluation of their extracellular electron transfer abilities. In addition, it was also successfully applied for isolation of EAB from environmental samples. Attributed to its rapidness, high reliability, easy operation and low cost, this method has high potential for practical implementation of EAB detection and investigations.


Elastography detected solid organ stiffness increased in patients with acromegaly.
Elastography is a method to examine the increase in solid organs stiffness (SOS), and there is no data in the literature regarding to its use in patients with acromegaly. In this study, we aimed to investigate the change of SOS in patients with acromegaly and to determine the parameters closely related to SOS in same patient groups.We included 40 subjects with acromegaly and 40 healthy control subjects. In addition to routine renal, liver and thyroid ultrasonography (USG), SOS for 3 solid organs were measured by elastography. The participants of the study were divided into 3 groups as the control (Group-I), acromegaly patients with remission (Group-II), and acromegaly patients without remission (Group-III).Insulin growth factor-1 (IGF-1) level significantly increased from Group-I to Group-III. Glucose, creatinine, albuminuria, alkaline phosphatase, TSH, and growth factor levels were highest in Group-III and statistically significance was found only between Group-I and Group-III. Liver, kidney and thyroid size and echogenicity were increased from Group-I to Group-III. Liver and renal stiffness and thyroid gland strain ratio significantly increased from Group-I to Group-III and these parameters were statistically different between all groups. In linear regression analysis, IGF-1 levels were independent determinants of SOS.SOS values of acromegaly patients with active disease were significantly increased compared to both the control group and the acromegaly patients in remission phase. Serum IGF-1 levels were independently associated with SOS in these patients. SOS measurement should be part of a routine USG examination in patients with acromegaly, especially in patients during active disease.


Hybridization between Cu-O chain and Cu(110) surface states in the O(2×1)/Cu(110) surface from first principles.
The O(2×1)/Cu(110) surface reconstruction of the Cu(110) surface is induced by 0.5 ML of oxygen adsorption and is formed by Cu-O chains running along the [001] direction. Here, we show that hybridization between surface states of the Cu(110) substrate and one-dimensional states of the Cu-O chains is crucial in understanding the electronic structure of this surface. Specifically, the interaction between one occupied antibonding band of the Cu-O chain with O(p(y)) character (y-axis taken along the Cu-O chain direction) and the partially occupied surface state at the Y point of the clean Cu(110) surface with Cu(p(y)) character causes major changes in the electronic structure close to the Fermi energy (E(F)). This surface state decays very slowly into the bulk and a thick slab is needed to properly describe it, which might explain why the importance of this hybridization has not been recognized so far. In our calculations we obtain two hybrid bands: (i) a fully occupied band that strongly hybridizes with the bulk Cu sp states nearby E(F), becoming a very broad resonance, thus explaining why it is not observed in photoemission experiments; (ii) an empty band that acquires surface state character, including its dispersion close to the zone boundary at the Y point. This splitting induces a partial population of the p(y) antibonding band that is necessary to reconcile the calculated charge transfer from the Cu(110) substrate to the Cu-O chain (~0.5 electrons/f.u.) with the apparently fully occupied band structure of the adsorbed Cu-O chain (consistent with 1 electron transferred per formula unit).


Early Selection Enabled by the Implementation of Genomic Selection in Coffea arabica Breeding.
Genomic Selection (GS) has allowed the maximization of genetic gains per unit time in several annual and perennial plant species. However, no GS studies have addressed Coffea arabica, the most economically important species of the genus Coffea. Therefore, this study aimed (i) to evaluate the applicability and accuracy of GS in the prediction of the genomic estimated breeding value (GEBV); (ii) to estimate the genetic parameters; and (iii) to evaluate the time reduction of the selection cycle by GS in Arabica coffee breeding. A total of 195 Arabica coffee individuals, belonging to 13 families in generation of F2, susceptible backcross and resistant backcross, were phenotyped for 18 agronomic traits, and genotyped with 21,211 SNP molecular markers. Phenotypic data, measured in 2014, 2015, and 2016, were analyzed by mixed models. GS analyses were performed by the G-BLUP method, using the RKHS (Reproducing Kernel Hilbert Spaces) procedure, with a Bayesian algorithm. Heritabilities and selective accuracies were estimated, revealing moderate to high magnitude for most of the traits evaluated. Results of GS analyses showed the possibility of reducing the cycle time by 50%, maximizing selection gains per unit time. The effect of marker density on GS analyses was evaluated. Genomic selection proved to be promising for C. arabica breeding. The agronomic traits presented high complexity for they are controlled by several QTL and showed low genomic heritabilities, evidencing the need to incorporate genomic selection methodologies to the breeding programs of this species.


Phthalocyanine Doped Metal Oxide Nanoparticles on Multiwalled Carbon Nanotubes Platform for the detection of Dopamine.
The electrocatalytic properties of metal oxides (MO = Fe3O4, ZnO) nanoparticles doped phthalocyanine (Pc) and functionalized MWCNTs, decorated on glassy carbon electrode (GCE) was investigated. Successful synthesis of the metal oxide nanoparticles and the MO/Pc/MWCNT composite were confirmed using UV-Vis, EDX, XRD and TEM techniques. Successful modification of GCE with the MO and their composite was also confirmed using cyclic voltammetry (CV) technique. GCE-MWCNT/ZnO/29H,31H-Pc was the best electrode towards DA detection with very low detection limit (0.75 μM) which compared favourably with literature, good sensitivity (1.45 μA/μM), resistance to electrode fouling, and excellent ability to detect DA without interference from AA signal. Electrocatalytic oxidation of DA on GCE-MWCNT/ZnO/29H,31H-Pc electrode was diffusion controlled but characterized with some adsorption of electro-oxidation reaction intermediates products. The fabricated sensors are easy to prepare, cost effective and can be applied for real sample analysis of dopamine in drug composition. The good electrocatalytic properties of 29H,31H-Pc and 2,3-Nc were related to their (quantum chemically derived) frontier molecular orbital energies and global electronegativities. The better performance of 29H,31H-Pc than 2,3-Nc in aiding electrochemical oxidation of DA might be due to its better electron accepting ability, which is inferred from its lower ELUMO and higher χ.


Renal manifestation of tuberous sclerosis complex.
Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. It commonly causes several types of cystic disease and benign tumors (angiomyolipomata) in the kidneys that can both lead to significant premature loss of glomerular filtration rate. The main risks of angiomyolipomata, severe bleeding, loss of renal function, and pulmonary lymphangioleiomyomatosis, can be ameliorated by active surveillance and preemptive therapy with mTOR inhibitors. The cystogenic mechanism may involve primary cilia, but also appears to also involve a majority of normal tubular cells and may be driven by a minority of cells with mutations inactivating both their TSC1 or TSC2 genes. Malignant tumors are rare.


How industries change.
It's fairly obvious: To make intelligent investments within your organization, you need to understand how your whole industry is changing. But such knowledge is not always easy to come by. Companies misread clues and arrive at false conclusions all the time. To truly understand where your industry is headed, you have to take a long-term, high-level look at the context in which you do business, says Boston University professor Anita McGahan. She studied a variety of businesses from a cross section of industries over a ten-year period, examining how industry structure affects business profitability and investor returns. Her research suggests that industries evolve along one of four distinct trajectories--radical, progressive, creative, and intermediating--that set boundaries on what will generate profits in a business. These four trajectories are defined by two types of threats. The first is when new, outside alternatives threaten to weaken or make obsolete core activities that have historically generated profits for an industry. The second is when an industry's core assets--its resources, knowledge, and brand capital--fail to generate value as they once did. Industries undergo radical change when core assets and core activities are both threatened with obsolescence; they experience progressive change when neither are jeopardized. Creative change occurs when core assets are under threat but core activities are stable, and intermediating change happens when core activities are threatened while core assets retain their capacity to create value. If your company's innovation strategy is not aligned with your industry's change trajectory, your plan for achieving returns on invested capital cannot succeed, McGahan says. But if you understand which path you're on, you can determine which strategies will succeed and which will backfire.


Administration time-dependent effects of valsartan on ambulatory blood pressure in elderly hypertensive subjects.
Previous results have indicated that valsartan administration at bed-time, as opposed to upon wakening, improves the diurnal/nocturnal ratio of blood pressure (BP) toward a normal dipping pattern, without loss of 24 h efficacy. This ratio is characterized by a progressive decrease with aging. Accordingly, we investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin blocking agent, in elderly hypertensive patients. We studied 100 elderly patients with grade 1-2 essential hypertension (34 men and 66 women), 68.2+/-4.9 years of age, randomly assigned to receive valsartan (160 mg/d) as a monotherapy either upon awakening or at bed-time. BP was measured for 48 h by ambulatory monitoring, at 20 min intervals between 07:00 to 23:00 h and at 30 min intervals at night, before and after 3 months of therapy. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately determine the duration of sleep and wake spans to enable the accurate calculation of the diurnal and nocturnal means of BP for each subject. There was a highly significant BP reduction after 3 months of valsartan treatment (p < 0.001). The reduction was slightly larger with bed-time dosing (15.3 and 9.2 mm Hg reduction in the 24 h mean of systolic and diastolic BP, respectively) than with morning dosing (12.3 and 6.3 mm Hg reduction in the 24 h mean of systolic and diastolic BP, respectively). The diurnal/nocturnal ratio, measured as the nocturnal decline of BP relative to the diurnal mean, was unchanged in the group ingesting valsartan upon awakening (-1.0 and -0.3 for systolic and diastolic BP; p > 0.195). This ratio was significantly increased (6.6 and 5.4 for systolic and diastolic BP; p < 0.001) when valsartan was ingested at bed-time. The reduction of the nocturnal mean was doubled in the group ingesting valsartan at bed-time, as compared to the group ingesting it in the morning (p < 0.001). In elderly hypertensive patients, mainly characterized by a diminished nocturnal decline in BP, bed-time valsartan dosing is better than morning dosing since it improves efficacy during the nighttime sleep span, with the potential reduction in cardiovascular risk that has been associated with a normalized diurnal/nocturnal BP ratio.


[Value of immediate operation in acute cholecystitis].
Operations were performed on 221 patients for tentative diagnosis of acute cholecystitis at the Surgical Department of Goslar District Hospital, between January 1982 and August 1986. Evaluation was possible of 179 of these cases. This group was compared with 96 patients who had undergone surgery some time after admission to hospital, between January 1980 and December 1981, with 90 patients of these patients being evaluated. Mortality, postoperative complications, length of surgical sessions, and length of hospitalisation of immediate treated patients were lower than those recorded from patients with delayed operations. Mixed germ cultures were recordable from the former group and monocultures from the latter. On balance, the rate of complications following immediate surgery did not deviate from data given for early surgery in the literature, in that it was below the rate following interval operation. Therefore, immediate surgery in the authors' hospital is considered to be the appropriate approach to acute cholecystitis.


Interactions between pectic compounds and procyanidins are influenced by methylation degree and chain length.
The interactions between procyanidins and pectic compounds are of importance in food chemistry. Procyanidins with low (9) and high (30) average degrees of polymerization (DP9 and DP30) were extracted from two cider apple varieties. Commercial apple and citrus pectins, as well as three pectin subfractions (homogalacturonans, partially methylated homogalacturonans with degree of methylation 30 and 70) at 30 mM galacturonic acid equivalent, were titrated with the two procyanidin fractions (at 30 mM (-)-epicatechin equivalent) by isothermal titration calorimetry and UV-vis spectrophotometry. Slightly stronger affinities were recorded between commercial apple or citrus pectins and procyanidins of DP30 (Ka = 1460 and 1225 M(-1) respectively, expressed per monomer units) compared to procyanidins of DP9 (Ka = 1240 and 1085 M(-1), respectively), but stoichiometry and absorbance maxima differed between apple and citrus pectins. It was proposed that methylated homogalacturonans interacted with procyanidins DP30 mainly through hydrophobic interactions. The stronger association was obtained with the longer procyanidin molecules interacting with highly methylated pectins.


Direct Online Determination of Laser-Induced Particle Size Distribution by ICPMS.
The characterization of the aerosol (size, composition, and concentration) generated by Laser Ablation is of great interest due to its impact on the analytical performances when coupled to Inductively Coupled Plasma Mass Spectrometry (ICPMS). The capabilities of High Resolution ICPMS as a direct tool to characterize nanoparticles produced by femtosecond Laser Ablation of pure copper are presented. An analytical protocol, similar to the "single particle ICPMS" technique used to characterize the size distribution of nanoparticles in solution, was developed in order to observe the signals of individual particles produced by a single ablation shot. A Visual Basic for Applications (VBA) data processing was developed to count and sort the particles as a function of their size and thus determine the particle size distribution. To check the reliability of the method, the results were compared to a more conventional technique, namely, Electrical Low Pressure Impaction (ELPI) for 4000 shots. Detection limit for the particles produced by the laser ablation of a copper foil is of a few attograms corresponding to a nanoparticle of 14 nm. The direct online determination of particle size by ICPMS gave similar results than ELPI for copper particles ejected during the ablation shot by shot at a fixed spot, from 1 to 100 shots. Particles larger than 159 nm represented less than 1% of the aerosol whose distribution was centered on 25-51 nm.


Relationship between risk stratification by cardiac troponin level and adherence to guidelines for non-ST-segment elevation acute coronary syndromes.
The threshold of troponin elevation that stimulates changes in clinical decision making for patients with non-ST-segment elevation acute coronary syndromes (NSTE ACSs) has not been previously evaluated. A total of 23 298 patients with NSTE ACSs from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) initiative were separated into categories of maximum troponin ratios (ratio of the highest recorded troponin value in the first 24 hours to the local laboratory troponin assay upper limit of normalization [ULN]). Unadjusted rates of in-hospital mortality increased from the group with troponin levels below the reference limit (maximum troponin ratio 0-1 x ULN; n = 5291) to those with minor (1-2 x ULN; n = 2499), intermediate (2-5 x ULN; n = 3825), and major (>5 x ULN; n = 11 683) elevations (-2.8% vs 4.6% vs 4.7% vs 6.0%). The use of early (<24 hours) aspirin, heparin, glycoprotein IIb/IIIa inhibitors, and beta-blockers was similar for the group with troponin levels below the reference limit compared with those with minor troponin elevations, and greater use of medications was demonstrated in patients with intermediate and major troponin elevations. Use of cardiac catheterization and percutaneous coronary intervention was higher in patients with troponin levels below the reference limit compared with those with minor troponin elevations, and procedures were used most frequently in patients with major troponin elevations. Similar patterns of care were demonstrated after excluding patients with chronic renal insufficiency. Any degree of troponin elevation is associated with a higher risk of mortality for patients with NSTE ACSs, but guideline-recommended medical therapies are used more commonly only in patients with intermediate and major troponin elevations, whereas patients with troponin levels below the reference limit underwent invasive procedures more frequently than those with mild troponin elevations.


Isolation and detection of small RNAs from plant tissues.
In plants, several classes of non-coding small RNA (sRNA) have been shown to be important regulators of gene expression in a wide variety of biological processes. The two main classes of sRNA, the small-interfering RNA (siRNA) and microRNA (miRNA) classes, are well documented and several experimental approaches have been developed to allow for their routine isolation and detection from plant tissues. Here, we describe the current methods used for the isolation of total RNA and the subsequent enrichment of low-molecular-weight (LMW) RNA species, as well as to outline how sRNAs are detected from such nucleic acid preparations.


Public health, science, and policy debate: being right is not enough.
Public health is usually enacted through public policies, necessitating that the public engage in debates that, ideally, are grounded in solid scientific findings. Mistrust in science, however, has compromised the possibility of deriving sound policy from such debates, partially owing to justified concerns regarding undue interference and even outright manipulation by commercial interests. This situation has generated problematic impasses, one of which is the emergence of an anti-vaccination movement that is already affecting public health, with a resurgence in the United States of preventable diseases thought to have been eradicated. Drawing on British sociologist Harry Collins' work on expertise, we propose a theoretical framework in which the paralyzing, undue public distrust of science can be analyzed and, it is hoped, overcome.


Orbital exenteration--a retrospective study over an 11 year period analyzing all cases from a single unit.
A retrospective analysis of all cases of orbital exenteration performed at the National Scottish Ocular Oncology Center over an 11 year period. We sought all exenteration cases (1993-2003) from ocular oncology and oculoplastic databases. Fifteen exenterations were performed. One case record was irretrievable. Clinicopathological features and outcome of 14 patients were analyzed. All operations were performed by the same consultant. The male to female ratio was 1:1 and the average age at surgery was 66 years. There was a left sided predominance of pathology demonstrated (right to left orbit ratio was 1:1.3. The average follow up period postsurgery was 35 months. The most common underlying diagnosis was malignant melanoma (9/14). Ocular/orbital discomfort was the most frequent presenting symptom (7/14); a mass lesion (10/14) was the most common presenting sign. The average duration of symptoms/signs prior to tertiary institution referral was 10.9 months (range: 0.5-60 months). Exenteration was performed on average 39.7 months (range: 0.13-204) after initial tertiary center presentation. This included patients managed from the outset who failed treatment(s) and then required exenteration. The eyelids were sacrificed in ten cases (10/14). Sockets were lined with eyelid skin (4/10), split skin (thigh) (3/10) or healed secondarily (7/10). Thirteen cases (13/14) had clear histological margins. The average post operative stay was 8.3 days. The most common complication was socket fistula formation (7/14). Ethmoid sinuses were always involved. The average time to fistula development was 4.9 months (sockets lined by skin = 2.2 months compared with sockets left to heal secondarily = 6.9 months). The majority of patients wore occlusive shields long term. The most common pathology necessitating exenteration was malignant melanoma. Most patients presented with a mass lesion. Histological tumor free margins were obtained in thirteen of fourteen cases. The most common complication was socket fistula formation.


A fast and powerful eQTL weighted method to detect genes associated with complex trait using GWAS summary data.
Although genomewide association studies (GWASs) have identified many genetic variants underlying complex traits, a large fraction of heritability still remains unexplained. Integrative analysis that incorporates additional information, such as expression quantitativetrait locus (eQTL) data into sequencing studies (denoted as transcriptomewide association study [TWAS]), can aid the discovery of trait-associated genetic variants. However, general TWAS methods only incorporate one eQTL-derived weight (e.g., cis-effect), and thus can suffer a substantial loss of power when the single estimated cis-effect is not predictive for the effect size of a genetic variant or when there are estimation errors in the estimated cis-effect, or if the data are not consistent with the model assumption. In this study, we propose an omnibus test (OT) which utilizes a Cauchy association test to integrate association evidence demonstrated by three different traditional tests (burden test, quadratic test, and adaptive test) using GWAS summary data with multiple eQTL-derived weights. The p value of the proposed test can be calculated analytically, and thus it is fast and efficient. We applied our proposed test to two schizophrenia (SCZ) GWAS summary data sets and two lipids trait (HDL) GWAS summary data sets. Compared with the three traditional tests, our proposed OT can identify more trait-associated genes.


Arabidopsis non-TZF gene AtC3H17 functions as a positive regulator in salt stress response.
Functional studies of CCCH-type zinc finger proteins in abiotic stress responses have largely focused on tandem CCCH-type zinc finger (TZF) genes, whereas the study of functional roles of non-TZF genes in abiotic stress responses has largely been neglected. Here, we investigated the functional roles of AtC3H17, a non-TZF gene of Arabidopsis, in salt stress responses. AtC3H17 expression significantly increased under NaCl, mannitol, and ABA treatments. AtC3H17-overexpressing transgenic plants (OXs) were more tolerant under NaCl and MV treatment conditions than the wild type (WT). atc3h17 mutants were more sensitive under NaCl and MV treatment conditions compared with the WT. The transcription of the salt stress-responsive genes in ABA-dependent pathway, such as RAB18, COR15A, and RD22, was significantly higher in AtC3H17 OXs than in WT both under NaCl-free condition and after NaCl treatment. Our results demonstrate that AtC3H17 functions as a positive regulator in salt stress response, via the up-regulation of ABA-dependent salt stress-response pathway.


Physicians' Perceptions of Their Patients' Attitude and Knowledge of Long-Term Oral Anticoagulant Therapy in Bulgaria.
Background and Objectives: Oral anticoagulation (OAC) is widely used in daily clinical practice worldwide for various indications. We aimed to explore the perception of Bulgarian clinicians about their patients' attitude and knowledge of long-term OAC, prescribed for atrial fibrillation (AF) and/or known deep venous thrombosis (DVT)/pulmonary embolism (PE). Materials and Methods: We performed a cross-sectional study that involved 226 specialists: 187 (82.7%) cardiologists, 23 (10.2%) neurologists, and 16 (7.1%) vascular surgeons. They filled in a questionnaire, specially designed for our study, answering various questions regarding OAC treatment in their daily clinical practice. Results: The mean prescription rate of OACs in AF patients was 80.3% and in DVT/PE-88.6%. One hundred and eighty-seven (82.7%) of the participants stated they see their patients on OAC at least once per month. According to more than one-third of the inquired clinicians, the patients did not understand well enough the provided information concerning net clinical benefit of OAC treatment. About 68% of the clinicians declared that their patients would prefer a "mutual" approach, discussing with the physician the OAC options and taking together the final decision, whereas according to 43 (19.0%), the patients preferred the physician to take a decision for them. Patients' OAC treatment had been interrupted at least once within the last year due to a physician's decision by 178 (78.8%) of the participants and the most common reason was elective surgery. The most influential factors for a patient's choice of OAC were the need of a specific diet to be kept, intake frequency, and possible adverse reactions. Conclusions: Our results suggest that a clinician's continuous medical education, shared decision-making, and appropriate local strategies for improved awareness of AF/DVT/PE patients are key factors for improvement of OAC management.


Serotonin in blood: assessment of its origin by concomitant determination of β-thromboglobulin (platelets) and chromogranin A (enterochromaffin cells).
Serotonin is produced in enterochromaffin (EC) cells, taken up and stored in platelets and released during platelet activation. Measurement of platelet-poor plasma serotonin is difficult, mainly due to platelet activation during blood sampling. We aimed to establish a method to assess the influence of platelet release upon platelet-poor plasma serotonin measurement by concomitant determination of serotonin, β-thromboglobulin (β-TG) and chromogranin A (CgA). Blood samples from patients with thrombocytosis, thrombocytopenia and small intestinal neuroendocrine (EC-cell) tumors (SI-NETs) as well as healthy volunteers were analyzed. We also measured serotonin in venous and arterial samples from patients undergoing coronary angiography to evaluate peripheral serotonin metabolism. Serotonin and CgA were significantly higher in patients with SI-NETs compared to all other groups implying EC cell origin of serotonin in patients with SI-NETs. We found that the serotonin concentration was similar in patients with thrombocytosis and thrombocytopenia, whereas plasma β-TG was higher and lower respectively. A high EDTA concentration in the sampling tubes gave significantly lower serotonin concentrations. Serotonin concentrations did not differ between arterial and venous blood. Our methodology to measure platelet-poor plasma serotonin was appropriate. Blood platelet numbers did not affect the level of serotonin in contrast to β-TG.


Acute thrombocytopenic purpura associated with primary Epstein-Barr virus infection.
Acute idiopathic thrombocytopenic purpura (ITP) often appears to be related to the sensitization by some viral infections. However, the causative viral agents are not identified in most cases. Although the primary infection with Epstein-Barr virus (EBV) occurs during early childhood in Japan, the majority of cases are usually asymptomatic. A minority are associated with acute infectious mononucleosis (IM), which is characterized by fever, tonsillitis, lymphadenopathy, splenomegaly and liver dysfunction. In this report, three cases are described of children with EBV-induced ITP who clinically had atypical findings of IM. Their primary EBV infections were confirmed by serological test and, in addition, were verified by the enhanced expression of activation antigens (HLA-DR and CD45RO) on T cells as well as the inverted ratio of CD4+ to CD8+ subsets. These observations imply that ITP can occur as one of the host responses during primary EBV infections, irrespective of clinical manifestations. Evaluation of lymphocyte subpopulations may be useful for the assessment of primary EBV infection in ITP.


Acute prefrontal cortex TMS in healthy volunteers: effects on brain 11C-alphaMtrp trapping.
High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (LDLPFC) is a technique with purported efficacy as a treatment for major depression. Here, we assessed in vivo, in healthy volunteers, the effect of acute rTMS of the LDLPFC, relative to the stimulation of the left occipital cortex (LOC), on brain regional serotonin synthesis capacity, using the [(11)C]-alpha-methyl-tryptophan ((11)C-alphaMtrp)/PET method. Ten subjects were studied twice, once following rTMS of the LDLPFC and once following rTMS of the LOC in a randomized counterbalanced order. Three blocks of 15 trains of 10 Hz rTMS were delivered 10 min apart. Behavioural and autonomic measures were recorded before and after each rTMS session. Comparisons of TMS-related changes in regional normalized brain uptake and trapping of (11)C-alphaMtrp (K*) values were carried out using SPM99. Statistically significant regional differences were identified on the basis of an extent threshold of 50 voxels, with a peak threshold of p=0.005 uncorrected. Behavioural and autonomic measures were unaffected by rTMS. Relative to LOC stimulation, LDLPFC rTMS was associated with marked changes in normalized K* in limbic areas, with significantly lower values in the left parahippocampal gyrus (BA 28) and the right insula (BA 13), and higher values in the right cingulate gyrus (BA 31) and cuneus (BA 18). These findings indicate that acute rTMS of the LDLPFC in healthy volunteers modulates aspects of tryptophan/5-HT metabolism in limbic areas. Such adaptive changes may contribute to the mechanism of action of prefrontal rTMS in major depression.


Contribution of self-grooming to onset of puberty in male rats.
Self-grooming was observed to increase during the prepubertal period of Long-Evans rats. Males were significantly more likely than females to engage in genital grooming during this period. To determine whether self-grooming contributes to the onset of puberty, males were fitted with collars that either prevented or allowed self-grooming of hindquarters or were left uncollared from 27 to 48 or 55 days of age when autopsied to determine weight of accessory organs. Ventral, dorsal, and lateral prostates and seminal vesicles were significantly lighter in those rats wearing collars that prevented self-grooming. It was concluded that self-grooming, probably of the genitals, contributes to accessory organ growth in males of this species.


[Comparison of two methods for the study of the in vitro susceptibility to sertaconazole of yeast clinical isolates].
We evaluated a commercial method for studying the in vitro susceptibility to sertaconazole based on its diffusion in agar with standardized tablets, with the aim of determining its correlation with the method of microdilution in Shadomy modified liquid medium (YNBg). A total of 110 Candida genus strains (50 C. albicans, 26 C. tropicalis, 15 C. glabrata, 8 C. parapsilosis, 8 C. krusei, 2 C. guilliermondii and 1 C. kefyr) from pathological clinical processes were used. The results of both techniques showed a statistically significant correlation that depended on the type of reading used in the liquid medium microdilution technique, with results being -0. 4199 with IC50; -5135 with IC90: -0.6634 with MIC24 h; and -0.4945 with MIC48 h. These values demonstrate the existence of a correlation for sertaconazole, and that it is bigger when it is compared with the logarithm of the MIC obtained after 24 hours of incubation.


Enantioselective Synthesis of Polycyclic Aromatic Hydrocarbon (PAH)-Based Planar Chiral Bent Cyclophanes by Rhodium-Catalyzed [2+2+2] Cycloaddition.
The enantioselective synthesis of polycyclic aromatic hydrocarbon (PAH)-based planar chiral cyclophanes was achieved for the first time by the rhodium-catalyzed intramolecular regio- and enantioselective [2+2+2] cycloaddition of tethered diyne-benzofulvenes followed by stepwise oxidative transformations. The thus synthesized planar chiral bent cyclophanes, that possess bent p-terphenyl- and 9-fluorenone-cores, were converted to 9-fluorenol-based ones with excellent ee values of >99 % by diastereoselective 1,2-reduction. These 9-fluorenol-based cyclophanes exhibited high fluorescence quantum yields, which were significantly higher than that of an acyclic reference molecule (78-82 % vs. 48 %). The bending effect on the chiroptical property was also examined, which revealed that the anisotropy factors (gabs values) for electronic circular dichroism (ECD) of these 9-fluorenol-based planar chiral bent cyclophanes increase as the tether length becomes shorter.


Discovery of Distinct Immune Phenotypes Using Machine Learning in Pulmonary Arterial Hypertension.
Accumulating evidence implicates inflammation in pulmonary arterial hypertension (PAH) and therapies targeting immunity are under investigation, although it remains unknown if distinct immune phenotypes exist. Identify PAH immune phenotypes based on unsupervised analysis of blood proteomic profiles. In a prospective observational study of group 1 PAH patients evaluated at Stanford University (discovery cohort; n=281) and University of Sheffield (validation cohort; n=104) between 2008 and 2014, we measured a circulating proteomic panel of 48 cytokines, chemokines, and factors using multiplex immunoassay. Unsupervised machine learning (consensus clustering) was applied in both cohorts independently to classify patients into proteomic immune clusters, without guidance from clinical features. To identify central proteins in each cluster, we performed partial correlation network analysis. Clinical characteristics and outcomes were subsequently compared across clusters. Four PAH clusters with distinct proteomic immune profiles were identified in the discovery cohort. Cluster 2 (n=109) had low cytokine levels similar to controls. Other clusters had unique sets of upregulated proteins central to immune networks-cluster 1 (n=58; TRAIL [tumor necrosis factor-related apoptosis-inducing ligand], CCL5 [C-C motif chemokine ligand 5], CCL7, CCL4, MIF [macrophage migration inhibitory factor]), cluster 3 (n=77; IL [interleukin]-12, IL-17, IL-10, IL-7, VEGF [vascular endothelial growth factor]), and cluster 4 (n=37; IL-8, IL-4, PDGF-β [platelet-derived growth factor beta], IL-6, CCL11). Demographics, PAH clinical subtypes, comorbidities, and medications were similar across clusters. Noninvasive and hemodynamic surrogates of clinical risk identified cluster 1 as high-risk and cluster 3 as low-risk groups. Five-year transplant-free survival rates were unfavorable for cluster 1 (47.6%; 95% CI, 35.4%-64.1%) and favorable for cluster 3 (82.4%; 95% CI, 72.0%-94.3%; across-cluster P<0.001). Findings were replicated in the validation cohort, where machine learning classified 4 immune clusters with comparable proteomic, clinical, and prognostic features. Blood cytokine profiles distinguish PAH immune phenotypes with differing clinical risk that are independent of World Health Organization group 1 subtypes. These phenotypes could inform mechanistic studies of disease pathobiology and provide a framework to examine patient responses to emerging therapies targeting immunity.


Epidemiology of chronic obstructive pulmonary disease in the global HIV-infected population: a systematic review and meta-analysis protocol.
Evidence suggests a relationship between human immunodeficiency virus (HIV) infection and chronic obstructive pulmonary disease (COPD). Although the high burden of COPD and the HIV disease is clearly demonstrated, to the best of our knowledge, there is a lack of summary and meta-analysis data on the epidemiology of COPD in the global HIV-infected population to date. The present protocol for a systematic review and meta-analysis intends to summarize existing data on the prevalence, incidence, and risk factors of COPD in the global HIV-infected population. The present review will include cohort, cross-sectional, and case-control studies conducted among HIV infected people, which report prevalence, incidence, and factors associated with COPD or enough data for their estimation. We will consider published and unpublished studies in English and French language, regardless of geographical location. Relevant records will be searched using PubMed/Medline, and Scopus from inception to December 31st, 2016. Reference lists of eligible papers and relevant review articles will be screened. Two investigators will independently screen, select studies, and extract data, with discrepancies resolved by consensus or arbitrarily by a third investigator. Risk of bias and methodological quality of the included studies will be assessed using the Newcastle-Ottawa Scale. Funnel-plots and Egger's test will be used to determine publication bias. The study-specific estimates will be pooled through a random-effects meta-analysis model to obtain an overall summary estimate. To keep the effect of studies with extremely small or extremely large estimates on the overall estimate to a minimum, the variance of the study-specific prevalence/incidence will be stabilized with the Freeman-Tukey single arc-sine transformation. The heterogeneity will be evaluated by the χ2 test on Cochrane's Q statistic. Results will be presented by geographic region and by antiretroviral therapy status. We plan to summarize data on factors associated with COPD in narrative format. This systematic review and meta-analysis will give an overview of the epidemiology of COPD in the global HIV population to inform policy-makers and to provide accurate data that can underpin effective interventions for optimizing their detection and management. PROSPERO CRD42016052639 .


The KrasG12D;Trp53fl/fl murine model of undifferentiated pleomorphic sarcoma is macrophage dense, lymphocyte poor, and resistant to immune checkpoint blockade.
Sarcomas are rare, difficult to treat, mesenchymal lineage tumours that affect children and adults. Immunologically-based therapies have improved outcomes for numerous adult cancers, however, these therapeutic strategies have been minimally effective in sarcoma so far. Clinically relevant, immunologically-competent, and transplantable pre-clinical sarcoma models are essential to advance sarcoma immunology research. Herein we show that Cre-mediated activation of KrasG12D, and deletion of Trp53, in the hindlimb muscles of C57Bl/6 mice results in the highly penetrant, rapid onset undifferentiated pleomorphic sarcomas (UPS), one of the most common human sarcoma subtypes. Cell lines derived from spontaneous UPS tumours can be reproducibly transplanted into the hindlimbs or lungs of naïve, immune competent syngeneic mice. Immunological characterization of both spontaneous and transplanted UPS tumours demonstrates an immunologically-'quiescent' microenvironment, characterized by a paucity of lymphocytes, limited spontaneous adaptive immune pathways, and dense macrophage infiltrates. Macrophages are the dominant immune population in both spontaneous and transplanted UPS tumours, although compared to spontaneous tumours, transplanted tumours demonstrate increased spontaneous lymphocytic infiltrates. The growth of transplanted UPS tumours is unaffected by host lymphocyte deficiency, and despite strong expression of PD-1 on tumour infiltrating lymphocytes, tumours are resistant to immunological checkpoint blockade. This spontaneous and transplantable immune competent UPS model will be an important experimental tool in the pre-clinical development and evaluation of novel immunotherapeutic approaches for immunologically cold soft tissue sarcomas.


Crescentic glomerulonephritis associated with bacterial endocarditis--antibiotics alone may be sufficient. A case report.
Crescentic glomerulonephritis complicating the course of bacterial endocarditis carries a poor prognosis. Ideal treatment strategy is not clearly defined. In addition to antibiotic treatment, plasmapheresis and steroids have been used with variable results. Here we report a case of 40-year old female who was referred because of generalized body swelling and decrease urine output associated with low grade fever on and off for two to three months. She was diagnosed to have acute renal failure secondary to tricuspid valve endocarditis. Staph aureus was isolated from blood culture and renal biopsy showed crescentic glomerulonephritis. She received dialysis support and antibiotics and had complete recovery of renal function 6 weeks after initiation of therapy. Eradication of infection with antibiotics treatment may be sufficient for resolution of crescentic glomerulonephritis associated with infective endocarditis in some cases.


Lack of axial rotation in mobile-bearing knee designs.
It has often been assumed rotational kinematics are improved with mobile-bearing TKA designs as the terms mobile-bearing and rotating platform imply. We tested this assumption by assessing the in vivo axial rotation magnitudes and patterns of 527 knees implanted with 12 different mobile-bearing TKA designs. Implants were grouped and compared by type--posterior stabilized (PS), posterior cruciate retaining (PCR), and posterior cruciate sacrificing (PCS)--and by specific design. We hypothesized all three mobile-bearing types (PS, PCR, and PCS) would achieve greater than 10 degrees average axial rotation and we would find no differences in axial rotation between types. Only 14% of PS knees, 3% of PCS knees, and 17% of PCR knees attained greater than 10 degrees axial rotation when measured from 0 degrees to 90 degrees . The percentage of PCS knees with greater than 10 degrees axial rotation was less compared with the other two groups. Axial rotation averaged 4.3 degrees , 2.5 degrees , and 3.8 degrees for the PS, PCS, and PCR knees, respectively. Incidences of reverse rotation were observed in 17% of PS knees, 32% of PCS knees, and 28% of PCR knees. Compared with the PCS group, the PS group achieved greater average axial rotation and had a lower percentage of knees displaying incidences of reverse rotation. The data refuted the hypotheses.


Clinicoradiographic presentation of a girl with progressive pseudorheumatoid arthropathy.
We report the case of a girl-child who manifested the clinicoradiographic features of pseudorheumatoid arthritis. 3D-CT scan of the craniocervical junction showed distinctive features of dystopic type of os odontoideum. The report highlights the necessity to explore the craniocervical junction in patients with progressive pseudorheumatoid arthropathy.


αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior.
The α-Ca(2+)/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a 'molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice. We found that alcohol drinking was initially diminished in αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice, but could be established at wild-type level after repeated withdrawals. The locomotor activating effects of a low-dose alcohol (2 g/kg) were absent in αCaMKII(T286A) mice, whereas the sedating effects of high-dose (3.5 g/kg) were preserved after acute and subchronic administration. The in vivo microdialysis revealed that αCaMKII(T286A) mice showed no dopamine (DA) response in the nucleus accumbens to acute or subchronic alcohol administration, but enhanced serotonin (5-HT) responses in the prefrontal cortex. The attenuated DA response in αCaMKII(T286A) mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest αCaMKII autophosphorylation as a facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA-5-HT balance as a putative mechanism.


Accurate and quick calibration method for polarization-modulation spectroscopy using an ac-modulated polarizing undulator.
An accurate calibration method in which an ac-modulated polarizing undulator is used for polarization modulation spectroscopy such as circular dichroism (CD) and linear dichroism (LD) has been proposed and successfully applied to vacuum ultraviolet (vuv) CD and LD spectra measured at beamline BL-5B in the electron storage ring, TERAS, at AIST. This calibration method employs an undulator-modulation spectroscopic method with a multireflection polarimeter, and it uses electronic and optical elements identical to those used for the CD and LD measurements. This method regards the polarimeter as a standard sample for the CD and LD measurements in the vuv region in which a standard sample has not yet been established. The calibration factors for the CD and LD spectra are obtained over a wide range of wavelengths, from 120 to 230 nm, at TERAS BL-5B. The calibrated CD and LD spectra measured at TERAS exhibit good agreement with the standard spectra for wavelengths greater than 170 nm; the mean differences between the standard and calibrated CD and LD spectra are approximately 7% and 4%, respectively. This method enables a remarkable reduction in the experimental time, from approximately 1 h to less than 10 min that is sufficient to observe the storage-ring current dependence of the calibration factors. This method can be applied to the calibration of vuv-CD spectra measured using a conventional photoelastic modulator and for performing an accurate analysis of protein secondary structures.


An activity-based functional test for identifying homologous recombination deficiencies across cancer types in real time.
Homologous recombination (HR)-mediated DNA repair is a prerequisite for maintaining genome stability. Cancer cells displaying HR deficiency (HRD) are selectively eliminated by poly(ADP-ribose) polymerase inhibitors (PARPis). To date, sequencing of HR-associated genes and analyzing genome instability have been used as clinical predictions for PARPi therapy. However, these genetic tests cannot reflect dynamic changes in the HR status. Here, we have developed a virus- and activity-based functional assay to quantify real-time HR activity directly. Instead of focusing on a few HR-associated genes, our functional assay detects endpoint HR activity and establishes an activity threshold for identifying HRD across cancer types, validated by PARPi sensitivity and BRCA status. Notably, this fluorescence-based assay can be applied to primary ovarian cancer cells from patients to reflect their level of HRD, which is associated with survival benefits. Thus, our work provides a functional test to predict the response of primary cancer cells to PARPis.


Fabrication of silver nanoparticles dispersed in palm oil using laser ablation.
In this study we used a laser ablation technique for preparation of silver nanoparticles. The fabrication process was carried out by ablation of a silver plate immersed in palm oil. A pulsed Nd:YAG laser at a wavelength of 1064 nm was used for ablation of the plate at different times. The palm coconut oil allowed formation of nanoparticles with very small and uniform particle size, which are dispersed very homogeneously within the solution. The obtained particle sizes for 15 and 30 minute ablation times were 2.5 and 2 nm, respectively. Stability study shows that all of the samples remained stable for a reasonable period of time.


[Attention should be paid to the treatment of traumatic pancreatitis].
Traumatic pancreatitis(TP) is an acute non-infectious inflammation secondary to pancreatic injury.TP can be masked by analgesia or other organ damage after pancreatic injury. So it is difficult to diagnosis in the early stage, easy to missed and misdiagnosis, subsequently prone to infection of pancreatic necrosis (IPN).At present, the treatment of TP is advocated as a step-by-step treatment strategy, which takes minimally invasive surgery as the guidance and takes into account of the principles of multiple injury treatment, inflammation control, infection and necrosis clearance, which runs through the two important links of pancreatic injury and IPN management.


NO-donating tacrine hybrid compounds improve scopolamine-induced cognition impairment and show less hepatotoxicity.
A series of tacrine-NO donor hybrid compounds are synthesized and evaluated for cholinesterase inhibitory activity, cognition improving activity, and hepatotoxicity. The pharmacological results indicate that hybrid compounds 1, 2, and 3a potently inhibit cholinesterase in vitro and significantly improve the scopolamine-induced cognition impairment, whereas an analogue (3h) of 2 without the NO donor moiety does not. Compared to tacrine, 1 and 2 show much less hepatotoxicity. Molecular modeling studies suggest that 2 may interact with the catalytic and the peripheral anionic site of acetylcholinesterase.


Immunohistochemical localization of NALP3 inflammasome in experimental periapical lesions.
To explore the role of NALP3 inflammasome [NALP3, its effector molecule apoptosis associated speck-like protein (ASC), caspase-1, interleukin (IL)-1β and IL-18] in the development of periapical lesions in rats. Periapical lesions were developed within 21 days after mandibular first molar pulp exposure in Sprague-Dawley rats. The animals were randomly sacrificed at 0, 1, 3, 7, 10, 14 and 21 days after pulpal exposure. The bilateral mandibles were extracted for histological processing, then they were haematoxylin-eosin (HE) stained to examine inflammation infiltration in the apical region and immunohistochemically examined for the NALP3 inflammasome signalling pathway. Data were analysed by one-way analysis of variance and the Pearson(') s correlation and linear tendency test. NALP3 was detected in the cytoplasm of fibroblasts, monocytes, neutrophils, macrophages and vascular endothelial cells in the periapical region. From day 1 to day 21, the number of NALP3-positive cells ascended and was significantly correlated with the intensity of inflammatory infiltration (r = 0.776, P < 0.01). ASC, caspase-1, IL-1β and IL-18 were all expressed in the inflammatory periapical tissues. The positive cell counts of IL-1β and IL-18 were significantly correlated with that of NALP3, and r = 0.718, P < 0.01; r = 0.688, P < 0.01, respectively. NALP3 inflammasome is expressed in the inflammatory periapical tissues. This cytokine-signalling pathway may therefore be crucial in the regulatory control of inflammatory responses in periapical tissues and the development of periapical lesions.


Increased plasma nitrites in migraine and cluster headache patients in interictal period: basal hyperactivity of L-arginine-NO pathway?
Nitrite concentrations in plasma were investigated in a population of migraine and cluster headache patients and a group of healthy non-headache controls. A hundred migraine patients and 69 cluster headache patients in the interictal period, and 112 controls, were studied. Significantly higher nitrite concentrations were found in migraine patients, with and without aura, and cluster headache patients, in remission and cluster phase, than in controls. These findings suggest that a basal dysfunction in the L-arginine-NO pathway may be involved in the peripheral mechanisms predisposing subjects with neurovascular headaches to individual attacks.


Quantum information storage for over 180 s using donor spins in a 28Si "semiconductor vacuum".
A quantum computer requires systems that are isolated from their environment, but can be integrated into devices, and whose states can be measured with high accuracy. Nuclear spins in solids promise long coherence lifetimes, but they are difficult to initialize into known states and to detect with high sensitivity. We show how the distinctive optical properties of enriched (28)Si enable the use of hyperfine-resolved optical transitions, as previously applied to great effect for isolated atoms and ions in vacuum. Together with efficient Auger photoionization, these resolved hyperfine transitions permit rapid nuclear hyperpolarization and electrical spin-readout. We combine these techniques to detect nuclear magnetic resonance from dilute (31)P in the purest available sample of (28)Si, at concentrations inaccessible to conventional measurements, measuring a solid-state coherence time of over 180 seconds.


Odour character differences for enantiomers correlate with molecular flexibility.
The olfactory system sensitively discerns scents from many small molecules as the brain analyses signals from nasal receptors. These receptors are selective to some degree, though the mechanism for selectivity is still controversial. Enantiomers, chiral pairs of left- and right-handed structures, are an important class of molecules in assessing proposed mechanisms. We show that there is a correlation between molecular (structural) flexibility and whether or not the left- and right-handed enantiomers smell the same. In particular, for the fairly extensive class of enantiomers with six-membered ring flexibility, enantiomers do not smell the same. There are, of course, significant experimental uncertainties, which we discuss here. We discuss models of receptor selectivity, both those based on shape and those where discrimination is based on other factors, such as electron affinity, proton affinity or vibration frequencies. The differences in scent of these enantiomers appear to be consistent with simple generalizations of a 'swipe card' model in which, while the shape must be good enough, critical information for actuation is a separate factor.


Polyadenylic-polyuridylic acid as adjuvant in the treatment of operable breast cancer: recent results.
A randomized trial of polyadenylic-polyuridylic acid (Poly(A).Poly(U) given as an adjuvant in the treatment of operable breast cancer, has included 300 patients of the Institut Gustave-Roussy from September 1972 to December 1979; 145 patients were allocated to conventional treatment alone and 155 to conventional treatment plus Poly(A).Poly(U). Reviews after mean periods of follow-up of 50 and 87 months were previously published. The present review performed after a mean follow-up period of 111 months confirmed a significant increase in the overall survival of patients with invaded nodes treated with Poly(A).Poly(U). The best results were achieved in the subset of patients with up to three affected nodes who showed a significant increase of both overall and relapse-free survival. The benefit seemed to be greater in postmenopausal women (P = 0.07). Present status of other ongoing trials of adjuvant Poly(A).Poly(U) is presented.


Half-scan cone-beam x-ray microtomography formula.
An x-ray shadow projection microtomographic system using a scannable point source is under development at AMIL-ARTS, SUNY at Buffalo. To overcome the limitations of the commonly used Feldkamp's cone-beam reconstruction formula, we have developed a generalized Feldkamp-type cone-beam reconstruction formula. In the generalized Feldkamp-type cone-beam reconstruction, a scanning locus can be either planar or helix-like, and a transaxial slice is reconstructed using projection data collected from a 360 degrees angular range (full scan). In this paper, the full-scan cone-beam formula is modified to require only projection data of approximate 180 degrees plus two fan-angles (half scan). First, a half-scan derivative-free noncircular fan-beam reconstruction formula is formulated. Then, a half-scan cone-beam reconstruction formula is derived as an extension of the half-scan fan-beam reconstruction formula using Feldkamp's procedure. Typical numerical simulation results are given for both half-scan formulae. Compared with the full-scan cone-beam formula, the half-scan cone-beam formula reduces the involved angular range of projection data and allows better longitudinal/temporal resolution.


The in Vitro and in Vivo Antitumor Activities of Tetracyclic Triterpenoids Compounds Actein and 26-Deoxyactein Isolated from Rhizome of Cimicifuga foetida L.
This work aims to study the in vitro and in vivo antitumor activities of tetracyclic triterpenoids compounds actein and 26-deoxyactein. Further, the mechanism is investigated. In vitro, a modified MTT method was used to assay the cytotoxicities of actein and 26-deoxyactein in 12 human tumor cell lines. In vivo, mouse sarcoma S180 and human lung cancer A549 cells were respectively implanted subcutaneously in ICR mice and nude mice to establish implanted tumor models. Flow cytometry (FCM) was used to assay the cycle distribution of the tumor cells. Immunohistochemistry was used to measure CD31-positive expression in the xenogrft tumor by analyzing microvessel density (MVD). In addition, acute toxicities of actein and 26-deoxyactein were also evaluated. Actein and 26-deoxyactein inhibited the proliferation of the 12 human cancer cell lines tested with the values of 50% inhibitory concentrations (IC50) between 12.29 and 88.39 μg/mL. In vivo, both actein (3-27 mg/kg) and 26-deoxyactein (3-27 mg/kg) significantly inhibited the growth of the implanted sarcoma S180 in a dose-dependent manner. Actein (10, 30 mg/kg) and 26-deoxyactein (10, 30 mg/kg) markedly inhibited the xenograft growth with T/C (%) values of 38%, 55% for actein, and 35%, 49% for 26-deoxyactein. Compared with the vehicle control, actein (10, 30 mg/kg) and 26-deoxyactein (10, 30 mg/kg) significantly reduced the MVD in the xenograft tumor. The FCM result showed that human leukemia HL-60 cells were arrested at G₁ phase after treated with either actein (6.25-25 μg/mL) or 26-deoxyactein (6.25-25 μg/mL) for 48 h. A limited trial in mice showed that both of the minimal lethal doses (MLDs) of actein and 26-deoxyactein were over 5 g/kg. Both actein and 26-deoxyactein have low toxicities. Importantly, both these two tetracyclic triterpenoids compounds isolated from rhizome of Cimicifuga foetida L. have significant antitumor activities in vitro and in vivo, which is associated with cell cycle arrest and angiogenesis inhibition.


The periplasmic, group III catalase of Vibrio fischeri is required for normal symbiotic competence and is induced both by oxidative stress and by approach to stationary phase.
The catalase gene, katA, of the sepiolid squid symbiont Vibrio fischeri has been cloned and sequenced. The predicted amino acid sequence of KatA has a high degree of similarity to the recently defined group III catalases, including those found in Haemophilus influenzae, Bacteroides fragilis, and Proteus mirabilis. Upstream of the predicted start codon of katA is a sequence that closely matches the consensus sequence for promoters regulated in Escherichia coli by the alternative sigma factor encoded by rpoS. Further, the level of expression of the cloned katA gene in an E. coli rpoS mutant is much lower than in wild-type E. coli. Catalase activity is induced three- to fourfold both as growing V. fischeri cells approach stationary phase and upon the addition of a small amount of hydrogen peroxide during logarithmic growth. The catalase activity was localized in the periplasm of wild-type V. fischeri cells, where its role could be to detoxify hydrogen peroxide coming from the external environment. No significant catalase activity could be detected in a katA null mutant strain, demonstrating that KatA is the predominately expressed catalase in V. fischeri and indicating that V. fischeri carries only a single catalase gene. The catalase mutant was defective in its ability to competitively colonize the light organs of juvenile squids in coinoculation experiments with the parent strain, suggesting that the catalase enzyme plays an important role in the symbiosis between V. fischeri and its squid host.


Biomechanical lower limb model to predict patellar position alteration after medial open wedge high tibial osteotomy.
Medial open-wedge high tibial osteotomy is a surgical treatment for patients with a varus deformity and early-stage medial knee osteoarthritis. Observations suggest that this surgery can negatively affect the patellofemoral joint and change the patellofemoral kinematics. However, what causes these effects and how the correction angle can change the surgery's impact on the patellofemoral joint has not been investigated before. The objective of this study was to develop a biomechanical model that can predict the surgery's impact on the patellar position and find the correlation between the opening angles and the patellar position after the surgery. A combined finite element and multibody model of the lower limb was developed. The model's capabilities for predicting the patellofemoral kinematics were evaluated by performing a passive deep flexion simulation of the native knee and comparing the outcomes with magnetic resonance images of the study subject at various flexion angles. The model at a fixed knee flexion angle was then used to simulate the high tibial osteotomy surgery virtually. The results showed a correlation between the wedge opening angles and the patellar position in various degrees of freedom. These results indicate that larger wedge openings result in increased values of patellar distalization, lateral patellar shift, patellar rotation, and patellar internal tilt. The developed model in this study can be used in future studies to monitor the stress distribution on the patellar cartilage and connecting tissues to investigate their relationship with observations of pain and cartilage injury due to post-operative altered patellar kinematics.