Netrin-1 role in angiogenesis: to be or not to be a pro-angiogenic factor?
Angiogenesis designates the formation of new vessels from preexisting ones, and occurs mainly during development. Tight control of this process is a prerequisite to avoid excess/defect in angiogenesis that are the underlying causes of several diseases conditions. Growing lines of evidences have indicated that some guidance cues are involved in regulation of vascular system elaboration, in addition to their role during nervous system development. In this way, netrin-1 has been involved in control of angiogenesis. However, a controversy has emerged regarding its action, since it was concluded from different studies that this protein was either a pro or an anti-angiogenic factor. Thus, netrin-1 role is still unclear. The aim of this review is to propose clues to explain previously reported discrepancies, in light of the dependence receptors model. Indeed, netrin-1 could likely favor angiogenesis, notably by blocking apoptosis induced by its unbound UNC5B receptor.


Molecular follow up of donor lymphocyte infusion in CML children after allogeneic bone marrow transplantation.
In this study we present the applicability of fluorescence in situ hybridisation (FISH) and RT-PCR to detect the minimal residual disease (MRD) in relapsed Ph+ children after donor lymphocyte infusion (DLI) post bone marrow transplantation (BMT). In both patients BCR/ABL fusion was detected and its transcript at the moment of relapse. After the DLI treatment in short time intervals a decreasing number of cells with BCR/ABL fusion were noticed and the expression of the hybrid gene disappeared. These results demonstrate that all the methods presented in this study provide a feasible, rapid and accurate way for the detecting of the minimal residual disease after DLI in Ph positive CML patients.


Pristine graphdiyne-hybridized photocatalysts using graphene oxide as a dual-functional coupling reagent.
Advanced functional hybrids based on carbon materials (CMs) represent one of the main achievements of scientific communities. To achieve the hybridization, pristine CMs have to be chemically modified, or surfactants, which are nonfunctional for the performances of the hybrids, have to be employed as a cross-linkage. The construction of pristine CM-based hybrids using dual-functional coupling reagents, which work not only as a glue for hybridization but also as a functional component for enhanced performance, is strongly desired. Here, we report that pristine graphdiyne (GD), a recently synthesized new carbon allotrope, can be facilely hybridized with Ag/AgBr using graphene oxide (GO) as a cross-linkage. We demonstrate that compared to Ag/AgBr, Ag/AgBr/GO, and Ag/AgBr/GD, our Ag/AgBr/GO/GD exhibits an enhanced photocatalytic performance toward the degradation of methyl orange (MO) pollutant under visible light irradiation. In our Ag/AgBr/GO/GD, GO serves not only as a glue for a successful hybridization, but also as a functional component for enhanced catalytic performance. Beyond GD, our work likely paves a new avenue for the fabrication of advanced functional hybrids based on pristine carbon allotropes, wherein desired functions or properties might be achieved by choosing desired CMs and desired hybridized components.


Self-Expandable Electrode Based on Chemically Polished Nickel-Titanium Alloy Wire for Treating Endoluminal Tumors Using Bipolar Irreversible Electroporation.
The application of irreversible electroporation (IRE) to endoluminal organs is being investigated; however, the current preclinical evidence and optimized electrodes are insufficient for clinical translation. Here, a novel self-expandable electrode (SE) made of chemically polished nickel-titanium (Ni-Ti) alloy wire for endoluminal IRE is developed in this study. Chemically polished heat-treated Ni-Ti alloy wires demonstrate increased electrical conductivity, reduced carbon and oxygen levels, and good mechanical and self-expanding properties. Bipolar IRE using chemically polished Ni-Ti wires successfully induces cancer cell death. IRE-treated potato tissue shows irreversibly and reversibly electroporated areas containing dead cells in an electrical strength-dependent manner. In vivo study using an optimized electric field strength demonstrates that endobiliary IRE using the SE evenly induces well-distributed mucosal injuries in the common bile duct (CBD) with the overexpression of the TUNEL, HSP70, and inflammatory cells without ductal perforation or stricture formation. This study demonstrates the basic concept of the endobiliary IRE procedure, which is technically feasible and safe in a porcine CBD as a novel therapeutic strategy for malignant biliary obstruction. The SE is a promising electrical energy delivery platform for effectively treating endoluminal organs.


Transmitter-gated currents of GABAergic amacrine-like cells in chick retinal cultures.
A subpopulation of cells developing in dissociated neuronal cultures prepared from 8-day-old embryonic chick retinae can be identified as putative in vitro counterparts of GABAergic amacrine cells by immunocytochemical and autoradiographic markers and by their electrophysiological responses to transmitter agonists. In the present study, transmitter-gated conductances expressed by these neurons were examined using the whole-cell patch-clamp technique. At negative holding potentials, the excitatory amino acid agonists N-methyl-D-aspartate (NMDA), kainate quisqualate, and glutamate induced inward currents with reversal potentials close to 0 mV in most of the cells selected for recording. NMDA-evoked responses were selectively blocked by the noncompetitive inhibitor MK 801 and by Mg2+ (in a voltage-dependent manner) and were potentiated in the presence of submicromolar concentrations of glycine. Glutamate apparently interacted with both NMDA and non-NMDA type receptors. All cells tested responded to the inhibitory transmitters GABA and glycine. Both inhibitory agonists could be shown to activate chloride conductances. Responses to GABA and glycine were specifically inhibited in the presence of bicuculline and strychnine, respectively. Thus, GABAergic neurons in retinal cultures express at least two different excitatory amino acid receptors--NMDA and non-NMDA--and two different inhibitory amino acid receptors--the GABAA and the glycine receptor. The results demonstrate the ability of the cultured neurons to develop an apparently mature phenotype and contribute to the understanding of the functional properties of GABAergic amacrine cells in the vertebrate retina.


Fasting glucose level is associated with nocturnal hypoglycemia in elderly male patients with type 2 diabetes.
Nocturnal hypoglycemia was a common and serious problem among patients with type 2 diabetes (T2DM), especially in the elderly. This study investigated whether fasting glucose was an indicator of nocturnal hypoglycemia in elderly male patients with T2DM. A total of 291 elderly male type 2 diabetic patients who received continuous glucose monitoring (CGM) between January 2007 and January 2011 were enrolled in the study. The association of fasting glucose and nocturnal hypoglycemia based on CGM data was analyzed, comparing with bedtime glucose. Based on CGM data, patients with nocturnal hypoglycemia had significantly lower fasting glucose (5.88 ± 1.29 versus 6.92 ± 1.32 mmol/L) and bedtime glucose (7.33 ± 1.70 versus 8.01 ± 1.95 mmol/L) than patients without nocturnal hypoglycemia (both p < 0.01). Compared with the highest quartile, the lowest quartile of fasting glucose had a significantly increased risk of nocturnal hypoglycemia after the multiple adjustments (pfor trend < 0.001). However, this association did not appear in bedtime glucose. When the prediction of nocturnal hypoglycemia either by fasting glucose or bedtime glucose using the area under receiver operating characteristic (ROC) curve, fasting glucose but not bedtime glucose, was an indicator of nocturnal hypoglycemia, with an area under the ROC curve (AUC) of 0.714 (95% CI: 0.653 ∼ 0.774, p < 0.001). On the ROC curve, the Youden index was maximal when fasting glucose was 6.1 mmol/L. Fasting glucose may be a convenient and clinically useful indicator of nocturnal hypoglycemia in elderly male patients with T2DM. Risk of nocturnal hypoglycemia significantly increased when fasting glucose was less than 6.1 mmol/L.


The Oral Administration Effect of Drug Mannuronic Acid (M2000) on Gene Expression of Matrix and Tissue Inhibitor of Metalloproteinases in Rheumatoid Arthritis Patients.
Rheumatoid Arthritis (RA) is a complex disease involving an unknown number of genes, and affecting a large number of organs, tissues, and sites across the body. It is affecting approximately 1% of the population worldwide. The safety and therapeutic efficacy of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property has been demonstrated under in vitro, in vivo examinations and clinical trials phase 1/11 in Ankylosing Spondylitis (AS) patients in addition to phase I/11 and 111 in Rheumatoid Arthritis (RA) patients. In this study, our goal is to evaluate the therapeutic efficacy of oral administration of M2000 on gene expression of the matrix metalloproteinase (MMP2, MMP9) and tissue inhibitor of metalloproteinase (TIMP1, TIMP2) as inflammatory molecules in the progression of rheumatoid arthritis. The study has included 15 RA patients who had an insufficient response to the conventional drug. Therefore, mannuronic acid was used as an additive to the conventional regime. The research was a single-blinded study. The dose of M2000 was 500mg orally twice per day for 12 weeks. There were 15 healthy participants considered as control. Blood samples have been collected from both groups once from the healthy control and twice from RA patients before and after treatment with M2000. The Peripheral Blood Mononuclear Cells (PBMCs) were isolated for assessment of the gene expression level of MMP2, MMP9, TIMP1, and TIMP2 using the real-time PCR method. The gene expression level of MMP2 and MMP9 reported a significant reduction in RA patients after treatment with M2000 compared to before treatment. On the other hand, the gene expression level of TIMP2 demonstrated a significant increase in RA patients after treatment with mannuronic acid compared to before treatment, but there was no significant difference between the group of RA patients before treatment and the control group. Vice versa to other molecules, there was no significant difference in the level of TIMP1 in compression with RA patients before and after treatment. our findings proved that the β -D- mannuronic acid) as a novel NSAID with immunosuppressive property has a significant effect on the gene expression level of MMP2, MMP9 and TIMP2 molecules in RA patients.


Prevalence, predictors, and clinical relevance of α-gal sensitization in patients with chronic urticaria.
Little is known about α-gal (galactose-α-1,3-galactose) sensitization in patients with chronic urticaria (CU). The aim of this study was to examine the prevalence, predictors and clinical relevance of α-gal sensitization in patients with CU. Two consecutive cohorts of newly referred patients with CU from a primary care allergology practice and a tertiary hospital dermatology department, plus a control group with allergic disease, but not CU, from the allergology practice, were interviewed and screened for α-gal sensitization (serum specific-IgE ≥0.35 KU/L). Of 733 patients included, 21 (5.6%) and 11 (3.9%) of CU patients from private practice and hospital, respectively, were α-gal sensitized. In total, 8 patients (38.1% of sensitized patients, and 2.1% of all CU patients) from private practice, and 2 patients (18.2% of sensitized patients, and 0.7% of all CU patients) from hospital, had clinically relevant α-gal allergy. In private practice, male sex (47.6 vs. 24.7%), p = 0.020, obesity (33.3 vs. 23.6%), p = 0.302, and frequency of angioedema (61.9 vs. 51.4%), p = 0.350; and in hospital, male sex (72.7 vs. 27.9%), p = 0.003, and high total immunoglobulin E (median 168 vs. 70.5 KU/L), p = 0.022 were associated with α-gal sensitization. α-gal sensitization is observed in a small fraction of CU patients with only few patients experiencing clinically relevant sensitization. Certain patients, particularly from primary care, may constitute a relevant population for aimed testing.


Delayed presentation and management of blunt traumatic inferior gluteal artery pseudoaneurysm with associated arteriovenous fistula.
Disruption of arterial wall integrity as a result of trauma, iatrogeny, inflammation, or infection may result in pseudoaneurysm formation. Gluteal artery aneurysms are rare and represent less than 1% of all arterial aneurysms. Pseudoaneurysms of the inferior gluteal artery (IGA) following blunt trauma are exceptionally rare with only 6 reported cases in the English literature. We describe an 82-year-old female with a remote history of a fall presenting with an enlarging buttock mass. Imaging confirmed an IGA pseudoaneurysm with associated arteriovenous fistula that was successfully treated with endovascular embolization.


Growth hormone regulates the rodent hepatic epidermal growth factor receptor at a pretranslational level.
Recent studies have implicated the involvement of pituitary factor(s) in the regulation of hepatic epidermal growth factor receptor (EGF-R) levels. In the present study the possible role of GH as a regulator of EGF-R has been examined by measuring hepatic EGF-R mRNA and EGF binding in intact and GH-deficient rats and mice before and after administration of GH. Using a human EGF-R probe, 10.5 and 6.0 kb transcripts were detected in mouse and rat liver by Northern gel analysis. EGF-R mRNA was quantified by solution hybridization, and EGF binding determined by incubation of 125I-labelled EGF with a low-density membrane fraction. Levels of hepatic EGF-R mRNA and binding of EGF in female rats were about two-thirds of those in male rats. GH-deficient (lit/lit) male and female mice had approximately 10 and 25% respectively of the levels of EGF-R mRNA and EGF binding of intact male and female mice. Furthermore, hypophysectomized rats exhibited a reduced level of EGF-R mRNA and EGF binding, corresponding to about 20% of the levels detected in intact male rats. When hypophysectomized male and female rats received recombinant human GH (hGH) either as intermittent injections or by continuous infusion using osmotic minipumps, the EGF-R mRNA and EGF binding levels increased to about half those of the intact male animals. No differences between intermittent or continuous administration of hGH on the induction of EGF-R mRNA or EGF binding could be seen.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of human endothelial cell-derived proteoglycans on human smooth muscle cell growth.
Extracellular proteoglycans (PGs) purified from cultured human arterial endothelial cells were tested for their effects on the proliferation of human vascular smooth muscle cells (VSMC). Fractions containing perlecan, the basement membrane heparan sulphate (HS) PG, the large chondrotin sulphate (CS) proteoglycan from connective tissue and other immunoreactive CS did not inhibit the proliferation of human VSMC. Native endothelial extracellular matrix, which was shown to contain the same PGs, demonstrated a pronounced stimulatory effect on the proliferation of human VSMCs. This stimulatory effect was not removed by pre-incubation of the matrix with 1 M NaCl, heparin, platelet extract or plasmin. These experiments demonstrate that PGs produced by human arterial endothelial cells do not inhibit the proliferation of VSMC. These data do not support the hypothesis that human endothelial cells, in vivo, control the activation or proliferation of VSMCs directly by the secretion of a non-proliferative molecule. Instead they support the hypothesis that the endothelial cells counteract intimal hyperplasia of VSMC indirectly by providing a barrier from activating factors in the plasma.


A theory for the coexistence of coiled and stretched configurational phases in the extensional flow of entangled polymer melts.
It has recently been demonstrated via nonequilibrium molecular dynamics (NEMD) simulation [M. H. Nafar Sefiddashti, B. J. Edwards, and B. Khomami, J. Chem. Phys. 148, 141103 (2018); Phys. Rev. Lett. 121, 247802 (2018)] that the extensional flow of entangled polymer melts can engender, within a definite strain-rate regime [expressed in terms of the Deborah number (De) based on the Rouse time], the coexistence of separate domains consisting primarily of either coiled or stretched chain-like macromolecules. This flow-induced phase separation results in bimodal configurational distributions, where transitions of individual molecules between the coiled and stretched states occur very slowly by hopping over an apparent energy activation barrier. We demonstrate that the qualitative aspects of this phenomenon can be described via the single-mode Rolie-Poly model including Convective Constraint Release (CCR) and finite extensibility of the chain-like macromolecules. This analysis reveals the physical mechanism for the configurational coexistence, namely, the nonlinear rate of change of the average entropic restoring force of a given entangled chain with extension. Under conditions of significant flow-induced disentanglement, the rate of change of the effective restoring force initially decreases with extension (effective spring softening) and then increases (hardens) as the maximum chain length is approached. When balanced by flow-induced chain stretching, we find that there can be two configuration states within the same De regime, as covered by the NEMD simulations; therefore, a region of conformational coexistence can indeed exist. However, we demonstrate that this coexistence of configurational microstates is only possible when the magnitude of the CCR parameters is consistent with the rate of flow-induced disentanglement, as observed in the NEMD simulations.


Weakly Supervised Identification and Localization of Drug Fingerprints Based on Label-Free Hyperspectral CARS Microscopy.
Understanding drug fingerprints in complex biological samples is essential for the development of a drug. Hyperspectral coherent anti-Stokes Raman scattering (HS-CARS) microscopy, a label-free nondestructive chemical imaging technique, can profile biological samples based on their endogenous vibrational contrast. Here, we propose a deep learning-assisted HS-CARS imaging approach for the investigation of drug fingerprints and their localization at single-cell resolution. To identify and localize drug fingerprints in complex biological systems, an attention-based deep neural network, hyperspectral attention net (HAN), was developed. By formulating the task to a multiple instance learning problem, HAN highlights informative regions through the attention mechanism when being trained on whole-image labels. Using the proposed technique, we investigated the drug fingerprints of a hepatitis B virus therapy in murine liver tissues. With the increase in drug dosage, higher classification accuracy was observed, with an average area under the curve (AUC) of 0.942 for the high-dose group. Besides, highly informative tissue structures predicted by HAN demonstrated a high degree of similarity with the drug localization shown by the in situ hybridization staining results. These results demonstrate the potential of the proposed deep learning-assisted optical imaging technique for the label-free profiling, identification, and localization of drug fingerprints in biological samples, which can be extended to nonperturbative investigations of complex biological systems under various biological conditions.


18F-FDG imaging: pitfalls and artifacts.
18F-FDG PET is emerging as a useful tool in the staging and restaging of many malignant neoplasms, such as lymphoma, lung cancer, colorectal cancer, head and neck cancer, breast cancer, and melanoma. To accurately interpret 18F-FDG findings one must be familiar with the normal physiologic distribution of the tracer, frequently encountered physiologic variants, and benign pathologic causes of 18F-FDG uptake that can be confused with a malignant neoplasm. The objectives of this article are to (a) describe the mechanism of 18F-FDG uptake, (b) list the patient preparation and pertinent patient history before 18F-FDG imaging, (c) describe the whole-body physiologic distribution of 18F-FDG, (d) list and discuss normal physiologic variants, and (e) list and discuss benign pathologic causes of 18F-FDG uptake.


Pore-bridging poly(dimethylsiloxane) membranes as selective interfaces for vapor-phase chemical sensing.
A new kind of polymer-based sensor is described in which the experimental parameters controlling selectivity and sensitivity are decoupled. The sensor is based on a surface acoustic wave (SAW) gravimetric transducer modified with a high-surface-area, nanoporous alumina coating. A very thin ( approximately 40 nm) poly(dimethylsiloxane) (PDMS) coating resides atop the porous alumina structure. In this configuration, the total surface area of the nanoporous alumina coating controls the sensitivity of the device, while the chemical properties of the PDMS membrane control selectivity. In conventional polymer-based sensors, the polymer plays the dual role of controlling both selectivity (via the chemical composition of the coating) and sensitivity (via the volume of the film). In this paper, we show that PDMS acts as a chemically selective gate that absorbs polar and nonpolar VOCs but does not transport these analytes to the underlying pore volume. In contrast, water vapor is absorbed by the PDMS to a very minor extent but is easily transported through it to the underlying walls of the porous substructure. Specifically, there was little difference in the mass-loading response arising from polar and nonpolar VOCs dosed onto planar and nanoporous SAW devices modified with PDMS. In contrast, SAW devices having nanoporous coatings responded up to 24 times more selectively to water than planar sensors modified identically.


Identification of complement regulatory domains in vaccinia virus complement control protein.
Vaccinia virus encodes a homolog of the human complement regulators named vaccinia virus complement control protein (VCP). It is composed of four contiguous complement control protein (CCP) domains. Previously, VCP has been shown to bind to C3b and C4b and to inactivate the classical and alternative pathway C3 convertases by accelerating the decay of the classical pathway C3 convertase and (to a limited extent) the alternative pathway C3 convertase, as well as by supporting the factor I-mediated inactivation of C3b and C4b (the subunits of C3 convertases). In this study, we have mapped the CCP domains of VCP important for its cofactor activities, decay-accelerating activities, and binding to the target proteins by utilizing a series of deletion mutants. Our data indicate the following. (i) CCPs 1 to 3 are essential for cofactor activity for C3b and C4b; however, CCP 4 also contributes to the optimal activity. (ii) CCPs 1 to 2 are enough to mediate the classical pathway decay-accelerating activity but show very minimal activity, and all the four CCPs are necessary for its efficient activity. (iii) CCPs 2 to 4 mediate the alternative pathway decay-accelerating activity. (iv) CCPs 1 to 3 are required for binding to C3b and C4b, but the presence of CCP 4 enhances the affinity for both the target proteins. These results together demonstrate that the entire length of the protein is required for VCP's various functional activities and suggests why the four-domain structure of viral CCP is conserved in poxviruses.


Acceptability of severe pain among hospitalized adults.
It is unclear why some hospitalized adults experiencing severe pain report that this degree of pain is acceptable to them. A 25% random sample of cognitively intact patients admitted to nine medical/surgical units in a New York City hospital were enrolled. Patients were interviewed daily, Monday to Friday from April 1, 2001 through February 14, 2003, to collect information on the presence of pain, pain intensity, analgesic use, and acceptance of pain. Patients were asked to rate their current level of pain using a four-point scale. Three hundred ninety-two of 1254 patients ( 31%) experiencing severe pain reported that their pain was acceptable to them. Variables significantly associated with an episode of acceptable severe pain in multivariate analyses included resolution of the painful episode (odds ratio = 4.7; 95% confidence interval [CI], 3.54-6.17), recent surgery (odds ratio = 1.5; 95% CI, 1.11-1.99), African American compared to white (odds ratio = 0.7; 95% CI, 0.48-0.955), age (odds ratio = 0.985; 95% CI, 0.977-0.993), and patients taking analgesics (odds ratio = 0.7; 95% CI, 0.46-0.964 for nonsteroidal anti-inflammatory drugs [NSAIDs]/acetaminophen and odds ratio = 0.6; 95% CI, 0.46-0.85 for opioids). Overall, 86 of 252 (34%) reported the pain was acceptable because it had resolved, 47 (19%) believed the pain would eventually go away, and 47 (19%) reported they were able to tolerate the pain. A substantial percentage of patients reporting severe pain report this experience as acceptable. Given recent research linking high intensity pain to adverse outcomes, future studies directed at improving the management of pain need to target both pain intensity and patients' beliefs about the acceptability of severe pain.


Longitudinal changes in mental health professionals' perceived trauma care competencies after participation in a brief online training programme.
Further developments in trauma care training for mental health staff are needed to ensure that trauma survivors are recognised and get the most effective care. The evaluation of the effects of trauma care training programs would enable the untangling of the most efficient ways of building the competence of clinicians who encounter trauma-exposed patients in their routine clinical practice. We aimed to analyse longitudinal changes in mental health professionals' perceived trauma care competencies after a brief online trauma care training, and to examine associations between these changes and specific work-related characteristics. In total, 223 mental health professionals, 96.4% women, 42 years on average, and 51.6% with more than 10 years of clinical practice, participated in a brief online trauma care training programme. The Readiness to Work with Trauma-Exposed Patients Scale (RTEPS) was used to measure perceived trauma care competencies at the pre-training, post-training, and at a 3-month follow-up. Training had a significant effect on all measured perceived trauma care competencies of assessment, treatment and affect tolerance at post-training and 3-month follow-up. We also found that many years of unspecific clinical practice did not contribute to perceived trauma care competencies, and the training was perceived equally beneficial by professionals with more or less clinical practice. Our study indicates that brief training can have lasting effects on clinicians' self-confidence in trauma care. Further investigation of factors associated with the effects of training might help to increase the effectiveness of the training programs.


Clinical utility of ambulatory blood pressure: perspectives for national insurance coverage.
During 2001, the Center for Medicare and Medicaid Services (CMS, formally known as HCFA) independently evaluated the US national insurance coverage policy for ambulatory blood pressure monitoring. Diagnostic uses evaluated included screening for white-coat hypertension, assessment for possible antihypertensive drug resistance, evaluation of hypotensive symptoms, episodic hypertension, and autonomic dysfunction. In their analysis, the committee presented and analyzed the relevant scientific and clinical literature on the use of ABPM in certain patient populations and delineated the reason for a limited national coverage decision for patients with suspected white-coat hypertension.


Brachytherapy: A critical component of primary radiation therapy for cervical cancer: From the Society of Gynecologic Oncology (SGO) and the American Brachytherapy Society (ABS).
Brachytherapy is well-established as an integral component in the standard of care for treatment of patients receiving primary radiotherapy for cervical cancer. A decline in brachytherapy has been associated with negative impacts on survival in the era of modern EBRT techniques. Conformal external beam therapies such intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT) should not be used as alternatives to brachytherapy in patients undergoing primary curative-intent radiation therapy for cervical cancer. Computed tomography or magnetic resonance image-guided adaptive brachytherapy is evolving as the preferred brachytherapy method. With careful care coordination EBRT and brachytherapy can be successfully delivered at different treatment centers without compromising treatment time and outcome in areas where access to brachytherapy maybe limited.


Ultrastructural localization of major basic protein in the human eosinophil lineage in vitro.
We examined the ultrastructural localization of (a) a secondary granule matrix protein--eosinophil peroxidase (EPO)--by cytochemistry, (b) a secondary granule core protein (major basic protein, MBP) by immunogold labeling, and (c) a primary granule protein (the Charcot-Leyden crystal protein, CLC protein) by immunogold labeling in eosinophilic myelocytes (EMs) and mature, activated eosinophils that differentiated from umbilical cord blood progenitors cultured in the presence of recombinant human interleukin-5 (rhIL-5). These studies provide the first substructural localization of MBP to condensing cores of immature secondary granules of EMs, as well as identification of unicompartmental, MBP-rich secondary granules that are devoid of matrix compartments and EPO content and are not primary granules by virtue of their lack of CLC protein. These granules occur in quantity in IL-5-activated mature human eosinophils, which have previously been shown to actively transport EPO from the matrix compartments of their secondary granules to the extracellular milieu in smooth membrane-bound cytoplasmic vesicles, a secretory process termed piecemeal degranulation, whereby eosinophils progressively empty cytoplasmic granules of their contents in the absence of classical granule extrusion.


Tsunami run-up and inundation along the coast of Sabah and Sarawak, Malaysia due to a potential Brunei submarine mass failure.
Submarine landslides, also known as submarine mass failures (SMFs), are major natural marine disasters that could critically damage coastal facilities such as nuclear power plants and oil and gas platforms. It is therefore essential to investigate submarine landslides for potential tsunami hazard assessment. Three-dimensional seismic data from offshore Brunei have revealed a giant seabed mass deposited by a previous SMF. The submarine mass extends over 120 km from the continental slope of the Baram Canyon at 200 m water depth to the deep basin floor of the Northwest Borneo Trough. A suite of in-house two-dimensional depth-averaged tsunami simulation model TUNA (Tsunami-tracking Utilities and Application) is developed to assess the vulnerability of coastal communities in Sabah and Sarawak subject to potential SMF tsunami. The submarine slide is modeled as a rigid body moving along a planar slope with the center of mass motion parallel to the planar slope and subject to external forces due to added mass, gravity, and dissipation. The nonlinear shallow water equations are utilized to simulate tsunami propagation from deepwater up to the shallow offshore areas. A wetting-drying algorithm is used when a tsunami wave reaches the shoreline to compute run up of tsunami along the shoreline. Run-up wave height and inundation maps are provided for seven densely populated locations in Sabah and Sarawak to highlight potential risks at each location, subject to two scenarios of slide slopes: 2° and 4°. The first wave may arrive at Kudat as early as 0.4 h after the SMF, giving local communities little time to evacuate. Over a small area, maximum inundated depths reaching 20.3 m at Kudat, 26.1 m at Kota Kinabalu, and 15.5 m at Miri are projected, while the maximum inundation distance of 4.86 km is expected at Miri due to its low-lying coast. In view of the vulnerability of some locations to the SMF tsunami, it is important to develop and implement community resilience program to reduce the potential damage that could be inflicted by SMF tsunamis.


Proteomic analysis by iTRAQ-MRM of soybean resistance to Lamprosema Indicate.
Lamprosema indicate is a major leaf feeding insect pest to soybean, which has caused serious yield losses in central and southern China. To explore the defense mechanisms of soybean resistance to Lamprosema indicate, a highly resistant line (Gantai-2-2) and a highly susceptible line (Wan 82-178) were exposed to Lamprosema indicate larval feedings for 0 h and 48 h, and the differential proteomic analyses of these two lines were carried out. The results showed that 31 differentially expressed proteins (DEPs) were identified in the Gantai-2-2 when comparing 48 h feeding with 0 h feeding, and 53 DEPs were identified in the Wan 82-178. 28 DEPs were identified when comparing Gantai-2-2 with Wan 82-178 at 0 h feeding. The bioinformatic analysis results showed that most of the DEPs were associated with ribosome, linoleic acid metabolism, flavonoid biosynthesis, phenylpropanoid biosynthesis, peroxisome, stilbenoid, diarylheptanoid and gingerol biosynthesis, glutathione metabolism, pant hormone signal transduction, and flavone and flavonol biosynthesis, as well as other resistance related metabolic pathways. The MRM analysis showed that the iTRAQ results were reliable. According to the analysis of the DEPs results, the soybean defended or resisted the Lamprosema indicate damage by the induction of a synthesis of anti-digestive proteins which inhibit the growth and development of insects, reactive oxygen species scavenging, signaling pathways, secondary metabolites synthesis, and so on.


Recombinant canine coronaviruses related to transmissible gastroenteritis virus of Swine are circulating in dogs.
Four canine coronavirus type II (CCoV-II) strains were identified in the guts and internal organs of pups which had died of acute gastroenteritis. The CCoV-II strains were strictly related to porcine transmissible gastroenteritis virus (TGEV) in the N-terminal domain of the spike protein, whereas in the other parts of the genome, a higher genetic relatedness to recent CCoV-II isolates was observed. Experimental infection of dogs with a TGEV-like isolate induced mild gastroenteritis without any systemic involvement. By virus neutralization tests, antigenic differences between reference and TGEV-like CCoVs were found. Our data support the potential recombinant origin of the TGEV-like CCoVs.


TRINS: a method for gene modification by randomized tandem repeat insertions.
In nature, the evolution of new protein functions is driven not only by side-chain substitutions (point mutations), but also by backbone modifications (insertions and deletions). The current laboratory diversification methods, however, are largely limited to point mutations. Of particular interest are short insertions-by-duplication that are frequent in nature but cannot be introduced in vitro in a library format (i.e. in random locations and lengths). Here, we describe a new procedure that allows the generation of tandem repeats of random fragments of the target gene via rolling-circle amplification, and the concurrent incorporation of these repeats into the target gene. This procedure, dubbed tandem repeat insertion, or TRINS, results in a library of genes carrying insertions-by-duplication of variable lengths (3-150 bp) at random positions. This diversification pattern allows sampling of sequence space regions that are not readily accessible by other protocols. We demonstrate this method by constructing three different gene libraries, and by selecting insertion variants of TEM-1 β-lactamase.


Chronic heart rate reduction remodels ion channel transcripts in the mouse sinoatrial node but not in the ventricle.
We investigated the effects of chronic and moderate heart rate (HR) reduction on ion channel expression in the mouse sinoatrial node (SAN) and ventricle. Ten-week-old male C57BL/6 mice were treated twice daily with either vehicle or ivabradine at 5 mg/kg given orally during 3 wk. The effects of HR reduction on cardiac electrical activity were investigated in anesthetized mice with serial ECGs and in freely moving mice with telemetric recordings. With the use of high-throughput real-time RT-PCR, the expression of 68 ion channel subunits was evaluated in the SAN and ventricle at the end of the treatment period. In conscious mice, ivabradine induced a mean 16% HR reduction over a 24-h period that was sustained over the 3-wk administration. Other ECG parameters were not modified. Two-way hierarchical clustering analysis of gene expression revealed a separation of ventricles from SANs but no discrimination between treated and untreated ventricles, indicating that HR reduction per se induced limited remodeling in this tissue. In contrast, SAN samples clustered in two groups depending on the treatment. In the SAN from ivabradine-treated mice, the expression of nine ion channel subunits, including Navbeta1 (-25%), Cav3.1 (-29%), Kir6.1 (-28%), Kvbeta2 (-41%), and Kvbeta3 (-30%), was significantly decreased. Eight genes were significantly upregulated, including K+ channel alpha-subunits (Kv1.1, +30%; Kir2.1, +29%; Kir3.1, +41%), hyperpolarization-activated cation channels (HCN2, +24%; HCN4, +52%), and connexin 43 (+26%). We conclude that reducing HR induces a complex remodeling of ion channel expression in the SAN but has little impact on ion channel transcripts in the ventricle.


Electrolyte changes and metabolic effects of lisinopril/bendrofluazide treatment. Results from a randomized, double-blind study with parallel groups.
The metabolic effects of lisinopril and bendrofluazide therapy were studied in 61 patients with essential hypertension in a randomized, double-blind study with parallel groups. The insulin sensitivity index, measured by hyperinsulinemic euglycemic clamp test, decreased by 22% (P < .01) during bendrofluazide treatment and by 15% (NS) during lisinopril treatment. The initial insulin response at intravenous glucose tolerance test (IVGTT) increased by 21% (P < .05) during lisinopril treatment but decreased by 13% (P < .05) during treatment with bendrofluazide, and in addition, the glucose disappearance rate decreased by 9% (P < .05) in the latter group. During oral glucose tolerance test (OGTT), the area under the glucose curve (AUCglucose) increased by 17% (P = .05) in the bendrofluazide-treated group but decreased by 19% (P = .05) in the lisinopril group, although there was no difference between the drug effects on AUCinsulin. The LDL/HDL cholesterol ratio increased during bendrofluazide treatment. The serum potassium concentration decreased by 10% (P = .0001) during bendrofluazide treatment but increased by 6% (P = .0001) in the lisinopril-treated group. The change in serum potassium was correlated to the change in initial insulin response and glucose disappearance rate at IVGTT, and inversely correlated to the change in AUCglucose at OGTT. In conclusion, alterations in serum potassium balance may affect the initial insulin release and glucose disposal. Bendrofluazide treatment decreases the serum potassium concentration, reduces the initial insulin release and the glucose disposal, and, in addition, impairs insulin sensitivity. Lisinopril treatment increases serum potassium concentration and the initial insulin response, and decreases AUCglucose, but does not improve insulin sensitivity per se.


[Assessment of worklife areas and stress intensity among Border Guard officers].
Stress is associated with the performance of high-risk occupations. It can be defined as a set of reactions that results from mismatched working conditions and requirements to capabilities of an employee. People who differently assess these areas of work may experience varying degrees of stress. The total of 128 Border Guard officers took part in the test. A subjective assessment of areas of work was made by using the Areas of Worklife Survey. The Perceived Stress Scale (PSS-10) was used to examine the severity of stress. Three groups of examined people, differing significantly in the assessment of all areas of working life, were identified. Affiliation of the examined people to these groups explains 8% of the variability in the severity of stress. The results of the regression analysis allowed to consider the assessments of 3 areas of working life (control, rewards and workload) as important predicators of the severity of stress experienced by officers. The model turned out to be statistically significant, the variables included in the model explain 19% of the variability of the dependent variable. The officers who assess the areas of working life differently, differ in terms of severity of the experienced stress. The severity of stress is significantly related to the ability to make independent decisions and to enjoy rewards. The stress experienced by Border Guard officers is mainly related to the assessment of the following areas of work: sense of control, rewards and workload. Med Pr 2018;69(2):199-210.


Placental Vitamin D-Binding Protein Expression in Human Idiopathic Fetal Growth Restriction.
Vitamin D-binding protein is a multifunctional serum protein with multiple actions related to normal health. Vitamin D-binding protein transports vitamin D and influences the metabolism of this key hormone but it also has additional immunomodulatory and actin-clearing properties. We investigated whether vitamin D-binding protein expression is altered in fetal growth restriction-associated placental dysfunction. Protein was extracted from 35 placentae derived from 17 healthy control subjects and 18 gestation-matched subjects with fetal growth restriction (FGR). FGR subjects were further subdivided as idiopathic (n = 9) and nonidiopathic (n = 9). Vitamin D-binding protein and 25(OH) vitamin D were measured by ELISA and normalized to protein concentration. The results showed significantly reduced levels of placental vitamin D-binding protein (control versus FGR, p < 0.05, Student's t-test) that were strongly associated with idiopathic fetal growth restriction (p < 0.01, Kruskal-Wallis), whereas levels of vitamin D-binding protein were not associated with placental 25(OH) vitamin D stores (p = 0.295, Pearson's correlation). As such, vitamin D-binding protein may be a factor in unexplained placental dysfunction associated with idiopathic fetal growth restriction and may potentially serve as a biomarker of this disease.


Airway and systemic inflammation and decline in lung function in patients with COPD.
Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1. There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1. A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8). At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3). During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr. Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 x 10(6) cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05). Patients with frequent exacerbations (> or = 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr). Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018). Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively. In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function.


Processive enzyme mimic: Kinetics and thermodynamics of the threading and sliding process.
The kinetics and thermodynamics of the threading and dethreading process of polymers through the cavity of a synthetic toroidal host is investigated by studying its complexation with a series of end-functionalized polymers of different lengths containing an end group that is selectively recognized by the host. The system is designed in such a way that complexation is only observed if the host has traveled all of the way across the complete polymer. Detailed kinetic investigations using fluorescence spectroscopy have revealed that the barrier for this process is length dependent and most likely related to the stretching of the polymer. Moreover, the results indicate that our previously reported processive enzyme mimic most likely operates by randomly sliding along its macromolecular substrate.


Effects of feeding corn containing an alpha-amylase gene on the performance and digestibility of growing cattle.
Two growth performance studies and two digestibility trials were conducted to evaluate the effects of feeding Enogen Feed Corn silage and corn grain to growing cattle. In Exp. 1, there were a total of four diets offered for ad libitum intake. The four diets consisted of two varieties of corn (Enogen Feed Corn [EFC] vs. yellow #2 corn [CON]) with two different methods of corn processing (dry-rolled [DR] vs. whole-shelled [WS]) and were formulated to provide 1.13 Mcal NEg/kg dry matter (DM); corn grain was 28.6% of diet DM. Average daily gain (ADG) and ending body weight tended to be greater for calves fed EFC than for those fed CON (P < 0.10). Gain:feed (G:F) was better for calves fed EFC (P < 0.01), improving by 5.5% over calves fed CON. In Exp. 2, a digestibility trial was conducted using seven cannulated Holstein steers fed the same diets from Exp. 1. Ruminal pH was not affected by corn variety (P > 0.82). Liquid passage rate was greater for CON-fed calves and associated with lower digestibility. Total tract DM and organic matter (OM) digestibilities were greater for EFC-fed calves (P < 0.04). In Exp. 3, there were four diets offered for ad libitum intake. Dietary factors were arranged as a 2 × 2 factorial and consisted of two hybrids of corn silage (EFC silage [EFC-S] vs. control silage [CON-S]) and two varieties of corn grain (EFC grain [EFC-G] vs. control [CON-G]; both were dry-rolled). Diets were formulated to provide 1.11 Mcal NEg/kg DM; corn grain was 38.5% of diet DM, and corn silage was 40% of diet DM. ADG was 6.0% greater (P < 0.01) and G:F was numerically (P < 0.14) 3.3% greater for calves fed EFC-S than for those fed CON-S, but substituting EFC-G for CON-G did not affect ADG or G:F. In Exp. 4, a digestibility trial was conducted using eight cannulated beef steers fed the same diets as Exp. 3. Liquid passage rate (P > 0.20), ruminal pH (P > 0.23), and ruminal total volatile fatty acid concentrations (P > 0.27) were unaffected by treatment. Total tract digestibilities of DM and OM were numerically greater by 2.5% and 2.2%, respectively, for calves fed the EFC-S compared with those fed CON-S. Feeding a corn hybrid containing alpha-amylase enzyme improved G:F of growing calves. Feeding EFC can benefit the beef industry by allowing less processing of grain without sacrificing performance.


Evidence-based abstracts: what research summaries should contain to support evidence-based medicine.
The practice of evidence-based medicine involves the integration of individual clinical expertise with the best available external clinical evidence from the systematic retrieval of the most current literature. Clinicians need to conduct a critical appraisal of the medical articles they access. However, clinicians in developing countries usually lack access to the best resources for evidence-based practice (EBP). The abstracts of 100 of the most recently published randomised controlled trials were used in the present study. These abstracts were critically appraised using a new questionnaire. Questions 1 to 8 were answerable by 38%, 26%, 52%, 23%, 12%, 53%, 36% and 12%, respectively, of the examined summaries. EBP requires better access to medical resources. Therefore, the summaries of relevant studies should be complete and self-sufficient to support EBP. This means a research summary should adequately report the findings of a clinical trial without needing to access the full text.


Melatonin-induced phase and dose responses in a diurnal mammal, Funambulus pennantii.
Melatonin, an essential pineal hormone, acts as a marker of the circadian clock that regulates biological rhythms in animals. The effects of exogenous melatonin on the circadian system of nocturnal rodents have been extensively studied; however, there is a paucity of studies on the phase-resetting characteristics of melatonin in diurnal rodents. We studied the phase shifting effects of exogenous melatonin as a single melatonin injection (1 mg/kg) at various phases of the circadian cycle on the circadian locomotor activity rhythm in the palm squirrel, Funambulus pennantii. A phase response curve (PRC) was constructed. Adult male squirrels (N = 10) were entrained to a 12:12 h light-dark cycle (LD) in a climate-controlled chronocubicle with food and water provided ad libitum. After stable entrainment, squirrels were transferred to constant dark condition (DD) for free-running. Following stable free run, animals were administered a single dose of melatonin (1 mg/kg in 2% ethanol-phosphate buffered saline (PBS) solution) or vehicle (2% ethanol-PBS solution) at circadian times (CTs) 3 h apart to evoke phase shifts. The phase shifts elicited at various CTs were plotted to generate the PRC. A dose response curve was generated using four doses (0.5, 1, 2 and 4 mg/kg) administered at the CT of maximum phase advance. Melatonin evoked maximum phase advances at CT0 (1.23 ± 0.28 h) and maximum phase delays at CT15 (0.31 ± 0.09 h). In the dose response experiment, maximal phase shifts were evoked with 1 mg/kg. In contrast, no significant shifts were observed in control groups. Our study demonstrates that the precise timing and appropriate dose of melatonin administration is essential to maximize the amelioration of circadian rhythm-related disorders in a diurnal model.


Direct Coronary Artery Reimplantation of Anomalous Aortic Origin of the Right Coronary Artery: A Case Report.
Anomalous aortic origin of the coronary artery (AAOCA) is a rare congenital cardiac abnormality. Although AAOCA can cause angina, syncope, palpitations, and sudden cardiac death, most patients remain asymptomatic. A 60-year-old woman experienced occasional chest discomfort. A coronary computed tomography (CT) showed that the right coronary artery (RCA) originated from the left sinus of Valsalva, indicating AAORCA. Exercise myocardial scintigraphy revealed ischemia in the inferior wall. Cardiac catheterization showed stenosis in the ostium of the RCA. Therefore, direct reimplantation of the RCA into the right sinus was performed under cardiopulmonary bypass. The patient recovered uneventfully, postoperatively. Postoperative coronary CT showed no evidence of bending or stenosis in the RCA. Moreover, exercise scintigraphy showed no ischemic changes. The patient was discharged on postoperative day 18 after the resolution of chest discomfort and remained healthy for the following one year. AAORCA is a rare congenital abnormality that could lead to sudden cardiac death. Appropriate imaging studies and surgery should be performed in symptomatic patients with AAORCA who have inter-arterial paths between the ascending aorta and pulmonary artery with right coronary ostial stenosis. Reimplantation of the RCA directly into the right coronary sinus with adequate mobilization of the RCA is a simple procedure that can return the anatomic and biophysiologic status of AAORCA patients to normal and resolve most morphologic abnormalities.


[Polymorphonuclear leukocytes decrease the immunostimulatry capacity of human dendritic cells].
The aim of this work was to evaluate the ability of polymorphonuclear leukocytes (PMNL) to modulate the function of dendritic cells (DCs). Human DCs were used to analyze the effect of PMNL on DCs. The allostimulatory proliferation of T cells induced by DCs incubated with PMNL was lower (42 +/- 14%, n:8, p<0.05) compared with untreated DCs. The decreased proliferation correlated with lower IFNgamma production (DCs: 781 +/- 3 pg/ ml; DCs-CS: 343 +/- 178 pg/ml, p<0.05). The same effect was observed in an antigen specific assay. However, the effect was not observed when PMNL where incubated with mature DCs. Indeed, the effect of PMNL was partially reverted with serine proteases inhibitors. Overall, these results suggest that PMNL modulates DCs activity by serine proteases.


Genetic variation and demographic history of Sudan desert sheep reveal two diversified lineages.
More than 400 million sheep are raised on the African continent, the majority of which are indigenous and are primarily reared for sustenance. They have effectively adapted to various climatic and production environments, surviving and flourishing. The genetic relationships among these sheep populations remain understudied. Herein, we sequenced the entire mitochondrial DNA control region of 120 animals from Hamary and Kabashi and their crossbreed (Hamary x Kabashi) of Sudan desert sheep (SDS) to understand their maternal-inherited genetic variation and demographic history profiles and relate those to the history of sheep pastoralism on the African continent. The results show a diversified and predominant D- loop haplogroup B (n = 102, 85%), with all other sequences belonging to haplogroup A. Most of the maternal genetic variation was partitioned between haplogroup (76.3%) while within haplogroup accounted for 23.7% of the variation. However, little genetic differentiation was observed among the two breeds and their crosses, with our results supporting a Hamari maternal origin for the crossbreed. Bayesian coalescent-based analysis reveals distinct demographic history between the two haplogroups, two breeds and their crosses. Comparison of the two haplogroup showed that haplogroup B experienced an earlier expansion than haplogroup A. Unlike the breed-based comparison, the expansion of the two breeds started roughly at the same time, around 6500 years ago, with Kabashi having a slightly greater effective population size. The maternal ancestors of SDS may have diverged before their introduction to the African continent. This study provides novel insights into the early history of these two main breeds of Sudan desert sheep and their crosses.


Violent behavior among adolescents in post-war Lebanon: the role of personal factors and correlation with other problem behaviors.
Adolescent violence is a significant public health problem. The primary objective of this study is to assess the prevalence and correlates of violent behavior among adolescent students in Lebanon. A cross-sectional study was conducted among a representative sample of 827 secondary students enrolled in public and private schools in Beirut. Using a series of multiple logistic regression techniques, socio-demographic variables which significantly associated with violent behavior were included as potential confounders in building the models for risk behavior. Nearly 42 and 17% of adolescents reported being involved in physical fights and weapon carrying, respectively. Boys were significantly more likely to use violence than girls. Whereas associations with physical fights were stronger for socio-economic variables and perceived rank in class, weapon carrying was significantly associated with problem behaviors, such as unintentional injury, substance abuse and sexual activity, with effect measures being stronger than those estimated for physical fighting. Compared with other countries, the rates of violent behavior in Lebanon are relatively high. The results from this study are discussed in light of the political ecology of Lebanon which may contribute to a culture that perpetrates violent behavior and may have influenced the clustering pattern of risk behaviors.


Cold agglutinin disease revisited: a multinational, observational study of 232 patients.
We retrospectively studied 232 patients with cold agglutinin disease (CAD) at 24 centers in 5 countries. In Norway and a northern region of Italy, the study was close to being population-based. For the first time, we demonstrate fourfold differences between cold and warmer climates regarding prevalence (20 vs 5 cases/million) and incidence (1.9 vs 0.48 cases/million per year). Mean baseline hemoglobin level was 9.3 g/dL, but 27% had hemoglobin <8 g/dL. Identification of typical features of CAD-associated lymphoproliferative disorder in the bone marrow was greatly increased by centralized biopsy assessment. CAD seems to be associated with a slightly increased risk of venous thrombosis. This work includes a follow-up study of therapies, focusing on the long-term outcomes of the rituximab plus bendamustine and rituximab plus fludarabine regimens. Rituximab plus bendamustine therapy resulted in responses in 35 (78%) of 45 patients; 24 (53%) achieved complete response. Interestingly, these rates were still higher than observed in the original (2017) prospective trial, and we also found a shift toward deeper responses with time. This is explained by the prolonged time to response seen in many patients, probably related to long-lived plasma cells. In patients responding to rituximab-bendamustine, median response duration was not reached after 88 months, and estimated 5-year sustained remission was 77%. The regimen appeared safe regarding late-occurring malignancies. Rituximab plus fludarabine therapy seems to carry a higher risk of long-term adverse effects.


Does selection on floral odor promote differentiation among populations and species of the sexually deceptive orchid genus Ophrys?
Sexually deceptive orchids from the genus Ophrys attract their pollinators primarily through the chemical mimicry of female hymenopteran sex pheromones, thereby deceiving males into attempted matings with the orchid labellum. Floral odor traits are crucial for the reproductive success of these pollinator-limited orchids, as well as for maintaining reproductive isolation through the attraction of specific pollinators. We tested for the signature of pollinator-mediated selection on floral odor by comparing intra and interspecific differentiation in odor compounds with that found at microsatellite markers among natural populations. Three regions from southern Italy were sampled. We found strong floral odor differentiation among allopatric populations within species, among allopatric species and among sympatric species. Population differences in odor were also reflected in significant variation in the attractivity of floral extracts to the pollinator, Colletes cunicularius. Odor compounds that are electrophysiologically active in C. cunicularius males, especially alkenes, were more strongly differentiated among conspecific populations than nonactive compounds in the floral odor. In marked contrast to these odor patterns, there was limited population or species level differentiation in microsatellites (FST range 0.005 to 0.127, mean FST 0.075). We propose that the strong odor differentiation and lack of genetic differentiation among sympatric taxa indicates selection imposed by the distinct odor preferences of different pollinating species. Within species, low FST values are suggestive of large effective population sizes and indicate that divergent selection rather than genetic drift accounts for the strong population differentiation in odor. The higher differentiation in active versus non-active odor compounds suggests that divergent selection among orchid populations may be driven by local pollinator preferences for those particular compounds critical for pollinator attraction.


[The surgical therapy of periacetabular malignant tumors].
To study the limb salvage methods and treatment outcomes in malignant periacetabular bone tumors. The data of 31 patients of periacetabular malignant tumors who had limb salvage surgery between January 1999 and December 2006 was retrospectively reviewed. There were 14 females and 17 males with a mean age of 53 years (range, 42-75 years). Twenty-four patients had chondrosarcomas, 4 patients had Ewing sarcomas, 1 patient had osteosarcoma, and the remaining 2 patients had metastatic disease. Sixteen patients had Types II pelvic resections, 5 patients had Types I and II pelvic resections, another 5 had Type I and III pelvic resections, and Type I , II and III pelvic resections in the remaining patients. Seventeen patients had reconstructions after tumor resection. The mean follow-up time for all patients was 52 months (range, 12-84 months). Fourteen patients were alive with no evidence of disease, 4 patients were alive with disease at the most recent follow-up, and 13 patients died of disease. The local recurrence rate and mortality rate in 24 patients with chondrosarcomas was 20.8% and 33.3% respectively. Two patients with metastatic disease died at 11 and 34 months postoperatively. One patient with osteosarcoma and 2 patients with Ewing sarcoma died of lung metastases. Enneking scoring system was used to evaluate the functional outcome in 18 alive patients. In 13 patients who had reconstructions, 6 were in excellent, 6 were in good, and 1 was in poor. While in 6 patients who had no reconstructions, 3 were in excellent, 2 were in good, and 1 was in poor. Minor complications occurred in 6 patients. Clear margin tumor resection with decreased local recurrence rate is critical for limb salvage surgery in periacetabular sarcomas. The ranges of tumor invasion and resection, the principle of individual treatment should be considered in functional reconstruction.


Is it Sjögren's syndrome or burning mouth syndrome? Distinct pathoses with similar oral symptoms.
Sjögren's syndrome (SS) and burning mouth syndrome (BMS) typically occur in postmenopausal women. Although these conditions have significantly different etiopathogeneses, patients with SS or BMS often present with analogous oral complaints. The similarities between the two conditions have led to considerable confusion on the part of medical and dental practitioners, and those with BMS or SS often wait years to receive a diagnosis. Therefore, it is imperative for clinicians to understand the characteristic subjective and objective features of each disease and how these can be used to distinguish them. This review will discuss the proposed etiology, clinical manifestations, histopathology, diagnostic criteria, and patient management of SS and BMS. We also identify key differences between the two pathoses that aid in establishing the correct diagnosis. Recognition of the defining features of each condition will lead to reduced time to diagnosis and improved patient management for these poorly understood conditions.


Outcomes of sacrocolpopexy/sacrohysteropexy with mesh placement targeted to affected compartment.
No recommendation regarding the number of meshes to be implanted in laparoscopic genital prolapse surgery exists. Is it necessary to implant a mesh into a compartment that is not affected to prevent its prolapse in the follow-up? Our objective was to compare the long-term outcomes of laparoscopic sacrocolpopexy according to compartments where mesh was implanted. This is a retrospective cohort study of 328 patients after laparoscopic sacrocolpopexy at our centre in 7/2005 - 3/2021. 294 patients with perioperative data and POP-Q and/or prolapse symptoms in mean follow-up of 42.8 months was available for the outcome analysis. Surgical failure was defined as prolapse beyond hymen, subjective recurrence or retreatment. The women were divided into four groups depending on compartments, where the mesh was implanted. Group A - anterior, group P - posterior, Group AP - compound of patients with anterior or posterior single arm mesh placement and (B), with anterior and posterior arm placement. Groups AP and B were compared for feasibility of single compartment mesh implantation. Comparison of groups A and P allowed assessment of non-inferiority of single anterior vs. posterior compartment placement. The data were compared using Wilcoxon Two Sample test, Chi-square test or Fisheŕs Exact test, p-value < 0.05 was considered statistically significant. A single compartment mesh implantation was associated with shorter operating time and hospital stay and comparable incidence of complications. A statistically significant difference in all POP-Q points in favour of group B was observed, however, with comparable rate of prolapse beyond hymen(6.3%AP vs. 7.8%B). Similar frequency of surgical failure (17.5%AP vs. 13.8%B) and incidence of de novo pelvic floor disorders or pain was observed. Comparison of groups A and P showed higher suspension of point C in group P(-2.6 vs. -4.0, p < 0.05) with no difference in points Ba, Bp, surgical failure rate and de novo pelvic floor disorders. Implantation of a single sheet of mesh was not associated with inferior outcome to implantation of mesh to both compartments. Laparoscopic sacrocolpopexy with a single mesh arm placed into the affected compartment along with apical suspension does not induce a de novo prolapse in unoperated compartment.


[Biomechanical study of the Oxford knee prosthesis with mobile meniscus].
Polyethylene meniscal bearing of the Oxford knee produce conforming surfaces and are free to move with knee movements. We studied polyethylene wear of 23 meniscal bearings implanted after a mean time of 38 months. The mean penetration rate of the polyethylene was 0.026 mm per year, statistically correlated with implanted time. The large areas of contact provided by such design are able to reduce polyethylene wear in knee prosthesis at levels smaller to those reported for hip. We also studied bearing movement on six cadaveric specimens fixed in a six degrees of freedom rig. The movements take place in both compartments of the knee in the same direction as for normal menisci during flexion-extension and rotation. Unicompartmental arthroplasty using meniscal bearing knee can restore such movements when the anterior cruciate ligament is present.


Voice Outcomes Following Colon Interposition.
This case highlights the consequences of colon interposition on phonation and swallowing. Findings in this patient included laryngopharyngeal reflux, vocal fold paralysis, poor esophageal peristalsis, failed bolus transfers, and others. The mechanical and functional differences between the colon and the esophagus can impact bolus transfer, reflux, and phonation. Further research is required to identify the mechanisms by which colon interposition can impact voice and swallowing.


Red and Near-Infrared Absorbing DicyanomethyleneSquaraine Cyanine Dyes: PhotophysicochemicalProperties and Anti-Tumor Photosensitizing Effects.
Photodynamic therapy is a medical modality developed for the treatment of several diseases of oncological and non-oncological etiology that requires the presence of a photosensitizer, light and molecular oxygen, which combined will trigger physicochemical reactions responsible for reactive oxygen species production. Given the scarcity of photosensitizers that exhibit desirable characteristics for its potential application in this therapeutic strategy, the main aims of this work were the study of the photophysical and photochemical properties and the photobiological activity of several dicyanomethylene squaraine cyanine dyes. Thus, herein, the study of their aggregation character, photobleaching and singlet oxygen production ability, and the further application of the previously synthesized dyes in Caco-2 and HepG2 cancer cell lines, to evaluate their phototherapeutic effects, are described. Dicyanomethylene squaraine dyes exhibited moderate light-stability and, despite the low singlet oxygen quantum yields, were a core of dyes that exhibited relevant in vitro photodynamic activity, as there was an evident increase in the toxicity of some of the tested dyes exclusive to radiation treatments.


A new approach for bone marrow-derived stem cells intrapancreatic autotransplantation in diabetic rats.
A new technique for stem cells intrapancreatic autotransplantation in rats. Section of a femoral diaphysis and aspirations of the bone marrow in both femoral segments were performed. A Kirschner needle was placed into the femur. Cells were isolated in Ficoll gradients and preserved at 4-6 degrees C. The second day, cells were injected, via aortic celiac trunk, into the pancreas of the same rat. Femoral surgery were well tolerated. Intrapancreatic homing of the injected cells was suggested with methylene blue injection that stained the pancreas, and proved by labeled cells in pancreas sections. Cell counts after Ficoll isolation were 1 x 10(6) +/- 2 x 10(5) ES. A technique is described for stem cell autotransplantation in rats. First we obtain autologous bone marrow-derived stem cells. Second, we inject the cells in the pancreas of the donor rat. This approach can be applied to experimental diabetes and other pancreatic processes.


Propeller vs Quasi-Planar 6-Cantilever Small Molecular Platforms with Extremely Two-Dimensional Conjugated Extension.
Two exotic 6-cantilever small molecular platforms, characteristic of quite different molecular configurations of propeller and quasi-plane, are established by extremely two-dimensional conjugated extension. When applied in small molecular acceptors, the only two cases of CH25 and CH26 that could contain six terminals and such broad conjugated backbones have been afforded thus far, rendering featured absorptions, small reorganization and exciton binding energies. Moreover, their distinctive but completely different molecular geometries result in sharply contrasting nanoscale film morphologies. Finally, CH26 contributes to the best device efficiency of 15.41 % among acceptors with six terminals, demonstrating two pioneered yet highly promising 6-cantilever molecular innovation platforms.


Genetic analysis of an in vitro model system for human papillomavirus type 16-associated tumorigenesis.
We have investigated the genetic basis for malignant progression of an human papillomavirus type 16 immortalized human keratinocyte cell line (HPKIA) by somatic cell fusion. In this cell culture model system for human papillomavirus type 16-associated tumorigenesis, early passage cells (HPKIA-nt) are nontumorigenic, whereas gamma-irradiated late passage cells (HPKIA-t) are tumorigenic when tested in nude mice. Fusion of HPKIA-t cells with normal human keratinocytes or with HPKIA-nt gave rise to hybrid clones in which the tumorigenic phenotype is suppressed. This observation is in line with complementation studies conducted for other tumor cell systems and indicates that, also in the case of HPKIA-t cells, the tumorigenic phenotype is recessive. Hybrid clones derived by fusion of HPKIA-t with cells of the cervical carcinoma cell lines C4-I, HeLa, or C33A were also nontumorigenic. However, the tumorigenic phenotype was retained in all of the HPKIA-t x SiHa and HPKIA-t x MS751 hybrids tested. The cervical carcinoma cell lines SiHa and MS751, therefore, cannot complement the gene defect(s) related to tumor growth of HPKIA-t cells. This may suggest that HPKIA-t, SiHa, and MS751 cells share the same defect(s) in regulatory pathway(s) involved in tumor suppression. Differences in the steady state levels of viral E6-E7 transcripts were noted for most of the hybrid cells. The observations of this study underline the potential use of nontumorigenic and tumorigenic HPKIA cells to define genetic differences that may also correlate with tumor progression in vivo.


Applying task analysis in design specification: current problems and a solution.
This paper addresses the following criticisms of task analysis: its requirement for an existing system; its focus on analysis rather than design; its limited scope within the design cycle; its underspecification of the application domain; and its inadequate documentation of design outputs. Such criticisms constitute problems for the application of task analysis. Solutions to these problems have emerged indirectly from the development of a structured method intended to rectify the typically late involvement of human factors in system development, e.g. only at the evaluation stage. This paper describes how task analysis has been extended and incorporated throughout the design cycle.


Serologic pattern of canine heartworm (Dirofilaria immitis) infection.
A total of 602 dogs at the Louisiana State University Veterinary Teaching Hospital were tested for antibodies to Dirofilaria immitis by enzyme-linked immunosorbent assay (ELISA), using a purified adult dirofilaria-derived antigen. Most dogs also were evaluated for heartworm infection by a complete WBC count and a Knott test for circulating microfilariae. The serologic prevalence of heartworm infection was 34.7%; prevalence increased significantly (P = 0.0003) with age up to 8 years and then decreased. Dogs usually kept indoors were significantly (P = 0.005) less likely to be infected, as were dogs given diethylcarbamazine therapy (P = 0.0004). Coat length, sex, breed, and presence of intestinal parasites were not associated (P greater than 0.05) with a positive heartworm ELISA result. The ELISA titers showed a positive relationship with both eosinophil and basophil counts. A total of 99 dogs evaluated radiographically were grouped according to results of the Knott test and radiographic examination as follows: (i) negative Knott test and negative radiographic examination (14 dogs), (ii) negative Knott test and positive radiographic examination (57 dogs), and (iii) positive Knott test and positive radiographic examination (28 dogs). The serologic prevalences of D immitis infection in each of these groups were 35.7%, 56.1%, and 85.7% for groups (i), (ii), and (iii), respectively. The ELISA, when used in conjunction with the Knott test results, record of exposure, clinical signs, laboratory results, and radiographic changes, was found to be useful for studying serologic patterns and identifying risk factors for canine heartworm infection.


Current trends in managing oral mucositis.
Oral mucositis is an inflammatory and ulcerative process of the oral cavity that results from an assault on the epithelial mucous membrane tissue and most commonly is associated with the administration of radiotherapy and chemotherapy. The incidence of oral mucositis ranges from 15%-40% in patients receiving stomatotoxic chemotherapy or radiotherapy and 70%-90% in bone marrow recipients. Knowledge regarding the pathophysiology of oral mucositis has evolved and now guides practice. Assessment tools to measure the level of mucositis provide valuable data concerning the status of the oral cavity. No single oral assessment tool has been found to be appropriate in all clinical settings. Mucositis has a significant impact on patients' quality of life and treatment plan. Management of oral mucositis is aimed at minimizing this side effect and its subsequent sequelae. The strategies of care are geared toward early intervention and supportive care for patients at risk for developing mucositis and include specific targeted therapies for the management of debilitating side effects. This article provides an overview of the risk factors, pathophysiology, incidence, impact, clinical presentation, oral assessment tools, management strategies, and nursing implications related to oral mucositis.


Perforator-based forearm and hand adipofascial flaps for the coverage of difficult dorsal hand wounds.
The author presents several case studies of alternative therapy for large and small dorsal hand and finger defects. These alternatives avoid the need for a lengthy free flap procedure, avoid the meticulous dissection required by the posterior interosseous flap, and avoid the loss of radial artery required by the reverse radial forearm flap. Distally based hand and forearm adipofascial flaps consist of the subcutaneous fat and fascia of the hand and/or forearm. They are easy to elevate, with operative times typically less than 2 hours, and can cover surfaces ranging from an individual finger to the entire dorsum of the hand. The blood supply is based on the rich profusion of perforators that exist in the hand and wrist. If desired, a skin paddle can be included with these flaps. These techniques are an important addition to the plastic and hand surgeon's armamentarium.


Autophagy is required for dietary restriction-mediated life span extension in C. elegans.
Dietary restriction extends life span in diverse species including Caenorhabditis elegans. However, the downstream cellular targets regulated by dietary restriction are largely unknown. Autophagy, an evolutionary conserved lysosomal degradation pathway, is induced under starvation conditions and regulates life span in insulin signaling C. elegans mutants. We now report that two essential autophagy genes (bec-1 and Ce-atg7) are required for the longevity phenotype of the C. elegans dietary restriction mutant (eat-2(ad1113) animals. Thus, we propose that autophagy mediates the effect, not only of insulin signaling, but also of dietary restriction on the regulation of C. elegans life span. Since autophagy and longevity control are highly conserved from C. elegans to mammals, a similar role for autophagy in dietary restriction-mediated life span extension may also exist in mammals.


Highly defined multiblock copolypeptoids: pushing the limits of living nucleophilic ring-opening polymerization.
Advanced macromolecular engineering requires excellent control over the polymerization reaction. Living polymerization methods are notoriously sensitive to impurities, which makes a practical realization of such control very challenging. Reversible-deactivation radical polymerization methods are typically more robust, but have other limitations. Here, we demonstrate by repeated (≥10 times) chain extension the extraordinary robustness of the living nucleophilic ring-opening polymerization of N-substituted glycine N-carboxyanhydrides, which yields polypeptoids. We observe essentially quantitative end-group fidelity under experimental conditions that are comparatively easily managed. This is employed to synthesize a pentablock quinquiespolymer with high definition.


Uncoupling of longevity and telomere length in C. elegans.
The nematode Caenorhabditis elegans, after completing its developmental stages and a brief reproductive period, spends the remainder of its adult life as an organism consisting exclusively of post-mitotic cells. Here we show that telomere length varies considerably in clonal populations of wild-type worms, and that these length differences are conserved over at least ten generations, suggesting a length regulation mechanism in cis. This observation is strengthened by the finding that the bulk telomere length in different worm strains varies considerably. Despite the close correlation of telomere length and clonal cellular senescence in mammalian cells, nematodes with long telomeres were neither long lived, nor did worm populations with comparably short telomeres exhibit a shorter life span. Conversely, long-lived daf-2 and short-lived daf-16 mutant animals can have either long or short telomeres. Telomere length of post-mitotic cells did not change during the aging process, and the response of animals to stress was found independent of telomere length. Collectively, our data indicate that telomere length and life span can be uncoupled in a post-mitotic setting, suggesting separate pathways for replication-dependent and -independent aging.


Clinical relevance of proteinuria and microalbuminuria.
Proteinuria (protein excretion > 300 mg/d) is an independent risk factor for the development of cardiovascular disease and renal failure. The finding of persistent proteinuria in otherwise asymptomatic patients often precedes the development of arterial hypertension and renal failure. When proteinuria is accompanied by arterial hypertension, blood pressure control can decrease the quantity of protein excretion but not the incidence of proteinuria. In this sense, converting enzyme inhibitors seem to possess a higher capacity to reduce proteinuria. Nevertheless, the effects of reducing proteinuria on renal function and cardiovascular risk remain to be elucidated. Microalbuminuria (urine albumin excretion oscillating between 30 and 300 mg/d) seems to be a predictor of cardiovascular disease in diabetic and nondiabetic subjects and has been established as a predictor for the development of diabetic nephropathy. Blood pressure levels and urinary albumin excretion correlate positively, and antihypertensive therapy of any kind decreases the quantity of albumin present in the urine. The role of increased albumin excretion in essential hypertension and in renal failure remains to be elucidated.


Active surveillance versus treatment in low-risk DCIS: Women's preferences in the LORD-trial.
Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but most DCIS lesions remain indolent. However, guidelines recommend surgery, often supplemented by radiotherapy. This implies overtreatment of indolent DCIS. The non-randomised patient preference LORD-trial tests whether active surveillance (AS) for low-risk DCIS is safe, by giving women with low-risk DCIS a choice between AS and conventional treatment (CT). Here, we aim to describe how participants are distributed among both trial arms, identify their motives for their preference, and assess factors associated with their choice. Data were extracted from baseline questionnaires. Descriptive statistics were used to assess the distribution and characteristics of participants; thematic analyses to extract self-reported reasons for the choice of trial arm, and multivariable logistic regression analyses to investigate associations between patient characteristics and chosen trial arm. Of 377 women included, 76% chose AS and 24% CT. Most frequently cited reasons for AS were "treatment is not (yet) necessary" (59%) and trust in the AS-plan (39%). Reasons for CT were cancer worry (51%) and perceived certainty (29%). Women opting for AS more often had lower educational levels (OR 0.45; 95% confidence interval [CI], 0.22-0.93) and more often reported experiencing shared decision making (OR 2.71; 95% CI, 1.37-5.37) than women choosing CT. The LORD-trial is the first to offer women with low-risk DCIS a choice between CT and AS. Most women opted for AS and reported high levels of trust in the safety of AS. Their preferences highlight the necessity to establish the safety of AS for low-risk DCIS.


Improving patient satisfaction in pediatric ophthalmology.
While there have been few studies of patient satisfaction in pediatric ophthalmology, the general medical and pediatric literature report findings that can be helpful. Interpersonal sensitivity is the most important factor for patient satisfaction. Two patients, the child and the parent, must be considered and treated. A more satisfied child, who despite the drops, enjoyed the office visit because she received direct communication and was praised and rewarded, leads to a more satisfied parent. Parents also need to be encouraged and reassured in their challenging parenting role. Satisfaction does not guarantee compliance with treatment recommendations, but helps considerably.


Chemical Vapor Deposition Growth of Linked Carbon Monolayers with Acetylenic Scaffoldings on Silver Foil.
Graphdiyne analogs, linked carbon monolayers with acetylenic scaffoldings, are fabricated by adopting low-temperature chemical vapor deposition which provides a route for the synthesis of two-dimensional carbon materials via molecular building blocks. The electrical conductivity of the as-grown films can reach up to 6.72 S cm-1 . Moreover, the films show potential as promising substrates for fluorescence suppressing and Raman advancement.


Clinical application of temporal modulation transfer function.
The temporal modulation transfer function (temporal MTF) was measured in normal controls and in patients with retinal diseases, optic neuritis and amblyopia. The temporal MTF of controls showed "band-pass" filter properties, having a peak sensitivity at about 15 Hz at 1,000 trolands of mean retinal illuminance. As the retinal illuminance was reduced, the sensitivity decreased, first at high temporal frequencies, then the peak sensitivity decreased. Finally at low temporal frequencies the sensitivity decreased and the peak shifted toward the lower frequency. In retinal diseases, abnormal temporal MTF was detected, and the curves were very similar to those of normal controls when retinal illuminance was reduced. These patterns were not specific to any retinal diseases, and the severity of the condition seemed to determine the pattern. In optic neuritis, an attenuated sensitivity was detected in all frequency ranges; however, the degree of attenuation was more severe than that found in retinal diseases even when the visual acuity was similar. At the convalescent stage, the low frequency sensitivity was restored first, and high frequency loss was observed even when the visual acuity was recovered to 1.0. Two amblyopic patients showed an attenuated sensitivity in the high and intermediate frequency ranges, and in one case sensitivity was attenuated in all frequencies. Three other patients showed normal sensitivity. By occlusion of the nonamblyopic eye, recovery of the sensitivity was observed in one patient whose visual acuity improved.


Normative Data on Grip Strength in a Population-Based Study with Adjusting Confounding Factors: Sixth Korea National Health and Nutrition Examination Survey (2014-2015).
Background: We investigated population-based data on grip strength, analyzed for demographic factors, and proposed a formula to estimate grip strength that could be generalized to a population with different anthropometric and background characteristics. Methods: This study used a complex, stratified, multistage probability cluster survey with a representative sample of the population. Select household Korean participants (n = 6577) over age 10 who were able to perform daily tasks without issue were included. Grip strength was measured in both hands, alternately, three times using a digital grip strength dynamometer. Results: There was a curvilinear relationship between grip strength and age, and grip strength was higher in males than females (p = 0.001). Hand preference significantly affected grip strength (p = 0.001). Weight and height were positively correlated with strength in both hands (p = 0.001), but waist circumference was negatively correlated with strength in both hands (p = 0.001). The intensity of occupational labor did significantly affect grip strength in both hands (p = 0.001). The formulas for estimating grip strength of each hand are presented as main results. Conclusions: To determine normative data on grip strength, we may consider factors such as occupations with different physical demands, underlying medical conditions, anthropometric characteristics, and unmodifiable factors such as age and sex.


Induction of exocytosis from permeabilized mast cells by the guanosine triphosphatases Rac and Cdc42.
We applied recombinant forms of the Rho-related small guanosine triphosphatases (GTPases) Rac2 and Cdc42/G25K to permeabilized mast cells to test their ability to regulate exocytotic secretion. Mast cells permeabilized with streptolysin-O leak soluble (cytosol) proteins over a period of 5 min and become refractory to stimulation by Ca2+ and guanosine triphosphate (GTP)gammaS over about 20-30 min. This loss of sensitivity is likely to be due to loss of key regulatory proteins that are normally tethered at intracellular locations. Exogenous proteins that retard this loss of sensitivity to stimulation may be similar, if not identical, to those secretory regulators that are lost. Recombinant Rac and Cdc42/G25K, preactivated by binding GTPgammaS, retard the loss of sensitivity (run-down) and, more importantly, enable secretion to be stimulated by Ca2+ alone. Investigation of the concentration dependence of each of these two GTPases applied individually to the permeabilized cells, and of Cdc42/G25K applied in the presence of an optimal concentration of Rac2, has provided evidence for a shared effector pathway and also a second effector pathway activated by Cdc42/G25K alone. Dominant negative mutant (N17) forms of Rac2 and Cdc42/G25K inhibit secretion induced by Ca2+ and GTPgammaS. Our data suggest that Rac2 and Cdc42 should be considered as candidates for GE, GTPases that mediate exocytosis in cells of hematopoeitic origin.


Pump-probe spectroscopy of two-body correlations in ultracold gases.
We suggest pump-probe spectroscopy to study pair correlations that determine the many-body dynamics in weakly interacting, dilute ultracold gases. A suitably chosen, short laser pulse depletes the pair density locally, creating a "hole" in the electronic ground state. The dynamics of this nonstationary pair density is monitored by a time-delayed probe pulse. The resulting transient signal allows us to spectrally decompose the hole and to map out the pair correlation function.


Belching Disorders and Rumination Syndrome: A Literature Review.
Belching disorders and rumination syndrome (RS) are disorders of gut-brain interaction (DGBIs) in Rome IV. Belching disorders are composed of excessive gastric belching (GB) and supragastric belching (SGB). Excessive GB is related to physiological phenomenon whereas excessive SGB and RS are behavioral disorders. A recent large internet survey found that prevalence of belching disorders and RS were 1% and 2.8%, respectively. It has been recognized that not a few patients with two behavioral disorders, excessive SGB and RS, could be misdiagnosed as proton pump inhibitors (PPI)-refractory gastroesophageal reflux disease (GERD). In patients with reflux symptoms, distinguishing these conditions is essential because they need psychological treatment (i.e., cognitive behavioral therapy (CBT) rather than acid suppressants. Clinicians should take a medical history meticulously first to identify possible excessive SGB and/or RS. High-resolution impedance manometry and/or 24-h impedance-pH monitoring can offer an objective diagnosis of the disorders. Several therapeutic options are available for excessive SGB and RS. The first-line therapy should be CBT using diaphragmatic breathing that can stop the behaviors involving complex muscle contraction (e.g., abdominal straining) to generate SGB or rumination. Overlap with eating disorders and/or other DGBIs such as functional dyspepsia can make management of the behavioral disorders challenging since such coexisting conditions often require additional treatments. Excessive SGB and RS are not unusual conditions. It is important to raise awareness of the behavioral disorders for appropriate management.


Foreign body aspiration associated with the use of an aerosol inhaler.
A 51-yr-old asthmatic carpenter aspirated a penny using a hand-held, self-pressurized aerosol device. The penny was extracted using a fiberoptic bronchoscope. Because no similar instances are reported in the medical literature, experimental systems were designed to test the likelihood of this event happening with a variety of nebulizers. Nickels , dimes , and pennies were tested for ejection potential and for aspiration likelihood. All inhalers, excepting that designed for Intal, were capable of accommodating dimes and pennies and ejecting them down simulated airways during inspiration. Nickels were accommodated by several inhalers but were not ejected during conventional inspiratory volumes and pressures.


Role of Wax Ester Synthase/Acyl Coenzyme A:Diacylglycerol Acyltransferase in Oleaginous Streptomyces sp. Strain G25.
Recently, we isolated a novel Streptomyces strain which can accumulate extraordinarily large amounts of triacylglycerol (TAG) and consists of 64% fatty acids (dry weight) when cultivated with glucose and 50% fatty acids (dry weight) when cultivated with cellobiose. To identify putative gene products responsible for lipid storage and cellobiose utilization, we analyzed its draft genome sequence. A single gene encoding a wax ester synthase/acyl coenzyme A (CoA):diacylglycerol acyltransferase (WS/DGAT) was identified and heterologously expressed in Escherichia coli The purified enzyme AtfG25 showed acyltransferase activity with C12- or C16-acyl-CoA, C12 to C18 alcohols, or dipalmitoyl glycerol. This acyltransferase exhibits 24% amino acid identity to the model enzyme AtfA from Acinetobacter baylyi but has high sequence similarities to WS/DGATs from other Streptomyces species. To investigate the impact of AtfG25 on lipid accumulation, the respective gene, atfG25, was inactivated in Streptomyces sp. strain G25. However, cells of the insertion mutant still exhibited DGAT activity and were able to store TAG, albeit in lower quantities and at lower rates than the wild-type strain. These findings clearly indicate that AtfG25 has an important, but not exclusive, role in TAG biosynthesis in the novel Streptomyces isolate and suggest the presence of alternative metabolic pathways for lipid accumulation which are discussed in the present study. A novel Streptomyces strain was isolated from desert soil, which represents an extreme environment with high temperatures, frequent drought, and nutrient scarcity. We believe that these harsh conditions promoted the development of the capacity for this strain to accumulate extraordinarily large amounts of lipids. In this study, we present the analysis of its draft genome sequence with a special focus on enzymes potentially involved in its lipid storage. Furthermore, the activity and importance of the detected acyltransferase were studied. As discussed in this paper, and in contrast to many other bacteria, streptomycetes seem to possess a complex metabolic network to synthesize lipids, whereof crucial steps are still largely unknown. This paper therefore provides insights into a range of topics, including extremophile bacteria, the physiology of lipid accumulation, and the biotechnological production of bacterial lipids.


Dietary calcium and vitamin D intake in an adult Middle Eastern population: food sources and relation to lifestyle and PTH.
Little is known about calcium and vitamin D intakes in Middle Eastern countries, where the prevalence of hypovitaminosis D is high. This study identifies major sources of calcium and vitamin D in the Lebanese diet, examines lifestyle factors that may influence intake of these nutrients and investigates the relationship between nutritional or lifestyle factors and parathyroid hormone (PTH). Three hundred sixteen young healthy volunteers aged 30 to 50 (men, non-veiled and veiled women) were recruited from different rural and urban Lebanese community centers. Food frequency questionnaire was used to evaluate the consumption of vitamin D and calcium-rich foods. We also measured serum PTH levels. Mean daily calcium and vitamin D intake were respectively 683.8 +/- 281.2 mg and 100.6 +/- 71.0 IU. Daily vitamin D sources were divided as follows: 30.4 +/- 46.4 IU from milk and dairy products, 28.2 +/- 26.3 IU from meat and poultry, 25.8 +/- 25 IU from fish, 8.5 +/- 8.6 IU from eggs, and 7.8 +/- 14.3 IU from sweets (respectively 30.2%, 28%, 25.6%, 8.4% and 7.7% of the total vitamin D intake). Mean daily calcium from animal and vegetable sources were respectively 376.3 +/- 233.6 mg and 307.9 +/- 118.5 mg. Animal/total calcium intake ratio was 52% and was only statistically significantly higher in urban people compared to rural ones. Multivariate analysis showed that male sex and urban residence were independent predictors of both vitamin D and calcium intakes (p < 0.01 and p < 0.01 respectively). In addition, veiling was an independent predictor of low vitamin D intake (p < 0.05) and a high body mass index (BMI) was an independent predictor of low calcium intake (p < 0.05). Finally, PTH was inversely correlated with vitamin D intake and the animal/total calcium intake ratio (r = -0.18 and r = -0.22, p < 0.01), while no significant results were achieved for the vegetable calcium. In a multivariate model, urban living, female gender, low vitamin D and calcium intakes, low animal/total calcium intake ratio, and high BMI, are independent predictors of hyperparathyroidism. The deficient nutritional status of vitamin D and calcium in Lebanon justify the implementation of dietary public health measures. People at most risk for secondary hyperparathyroidism should be advised to increase their dietary calcium (mostly animal calcium) and vitamin D, to take supplements, or to increase their sun exposure.


The Montreal Cognitive Assessment as a Screening Tool for Preoperative Cognitive Impairment in Geriatric Patients.
Study the prevalence of cognitive impairment using the Montreal Cognitive Assessment (MoCA), its relationship to physiologic age-related change, and the preoperative drugs used in geriatric patients. At the preoperative visit, the co-researchers invited 322 general/vascular patients (190 male, 132 female) and 260 urological patients (220 male, 40 female) who met the inclusion criteria and were scheduled for elective surgery to join the study. They went for the MoCA interview, and their preoperative drugs used were recorded in a medication reconciliation file. A cut-off score 24 or above was considered normal. Ninety-two general/vascular and 126 urological patients had taken drugs before admission, but those did not show any correlation with the MoCA score. There were 231 and 91 general/vascular patients and 175 and 85 urological patients with formal education of less than six years and equal/more than six years respectively. The 286 and 36 general/vascular patients and 212 and 48 urological patients posted scores of less than 24 and equal/more than 24 respectively. Gender and education correlated positively and significantly with the score; however age proved negatively significant. The prevalence of cognitive impairment featured highly in preoperative geriatric patients. The gender age, and education but not preoperative drugs used affected cognitive function.