Interprofessional working in hospice day care and the patients' experience of the service.
This in-depth study of hospice day care considers professional team working and patient experience of the service. It includes an analysis of how patients' time is spent. The qualitative single case study design involved patient and staff interviews, observations and document analysis. A theoretical framework of interprofessional working informed the study. Analysis of the data revealed a range of goals, variable communication patterns and the existence of core and extended teams. The results challenge the theoretical literature by suggesting that the presence of a team structure alone did not promote interprofessional working. Patients were also seen as integral members of the team. Their experience of day care was a social one, with a wide range of patients identified unmet needs, day care was largely seen as positive. This was despite interprofessional working not clearly being identified in the results. Suggestions for future research are made and implications for practice discussed.


Grapefruit juice and licorice increase cortisol availability in patients with Addison's disease.
Failure to mirror the diurnal cortisol profile could contribute to the impaired subjective health status in Addison's disease (AD). Some patients report benefit from the use of various nutritional compounds. The objective of this study was to investigate the impact of licorice and grapefruit juice (GFJ) on the absorption and metabolism of cortisone acetate (CA). Patients (n=17) with AD on stable CA replacement therapy were recruited from the outpatient clinic at Haukeland University Hospital, Norway. They were assessed on their ordinary CA medication and following two 3-day periods of co-administration of licorice or GFJ. Time series of glucocorticoids (GCs) in serum and saliva were obtained, and GCs in 24 h urine samples were determined. The main outcome measure was the area under the curve (AUC) for serum cortisol in the first 2.6 h after orally administered CA. Compared with the ordinary treatment, the median AUC for serum cortisol increased with licorice (53 783 vs 50 882, P<0.05) and GFJ (60 661 vs 50 882, P<0.05). Median cortisol levels in serum were also elevated 2.6 h after tablet ingestion (licorice 223 vs 186 nmol/l, P<0.05; GFJ 337 vs 186 nmol/l, P<0.01). Licorice increased the median urinary cortisol/cortisone ratio (0.43 vs 0.21, P<0.00001), whereas GFJ increased the (allo-tetrahydrocortisol+tetrahydrocortisol)/tetrahydrocortisone ratio (0.55 vs 0.43, P<0.05). Licorice and in particular GFJ increased cortisol available to tissues in the hours following oral CA administration. Both patients and physicians should be aware of these interactions.


Posttraumatic Stress Disorder Treatment Dropout Among Military and Veteran Populations: A Systematic Review and Meta-Analysis.
High treatment dropout rates reported in recent literature have brought into question the effectiveness of trauma-focused posttraumatic stress disorder (PTSD) treatments among military populations. The aim of the current systematic review was to evaluate PTSD treatment dropout rates among military populations by treatment type and other study-level variables. We searched four databases as well as gray literature for randomized controlled trials that evaluated evidence-based PTSD treatments in samples of active duty personnel and/or veterans. In total, 26 studies were included in this review, with a total of 2,984 participants. We analyzed dropout rates across treatment types using multivariate meta-analysis. Across all forms of treatment, the aggregated dropout rate was 24.2%. Dropout percentages based on treatment type were 27.1% for trauma-focused treatments, 16.1% for non-trauma-focused treatments, and 6.8% for waitlist groups. We found substantial heterogeneity between studies that was not explained by military status or other study-level covariates. Summary risk ratios (RRs) comparing relative dropout between treatment groups indicated that trauma-focused treatment groups had a higher risk of dropout compared to non-trauma-focused treatments, RR = 1.60. The statistical heterogeneity of within-treatment dropout risk ratios was negligible. Dropout rates among military patients receiving trauma-focused therapies were only slightly higher than those reported in the literature among civilian populations and were not explained by study-level covariates.


[A clinicopathologic study of thymomas: a review of 52 cases, with particular reference to results of treatment].
Clinicopathologic aspects of 52 thymomas were reviewed. Masaoka staging revealed stage I in 32, stage II in 2, stage III in 12, stage IV a in 3, and stage IV b in 3. Eleven patients (21%) had associated myasthenia gravis (MG), and three (6%) had pure red cell aplasia (PRCA). Operation was complete resection in 39 patients (stage I 32, stage II 2, stage III 2, and stage IV b 3), subtotal resection in 4 patients (stage III 2, stage IV a 2), partial resection or simple biopsy in 7 patients (stage III 6, stage IV a 1). Survival rates at 5 years and 10 years were 88%, 88% in noninvasive thymomas, and 65%, 45% in invasive thymomas, respectively. Statistical analysis indicated that patients with noninvasive thymomas had significantly longer survival than those with invasive thymomas. Significant difference was not found in survival on the basis of tumor cell type according to lymphocyte/epithelial cell ratio. Associated MG had no influence on the survival of thymoma patients, however, the presence of PRCA was an adverse factor in survival. In cases of invasive thymomas, there was statistically significant difference in the survival rates between the group of patients undergoing complete or subtotal resection and the group undergoing partial resection or only biopsy. Irradiation was of value in local control of thymoma, but lymphogeneous or hematogeneous recurrence occurred in 21% of patients with invasive thymomas from 3 months to 12 years postoperatively. Lifelong follow-up should be necessary in thymoma patients since late recurrence is not so rare.


Sensitivity of cell lines to mitomycin C.
To determine the effect of pH on the cytotoxicity of mitomycin C on a wide range of established cell lines. Cultures of three human tumour cell lines, including two bladder carcinomas and one renal adenocarcinoma, and two mouse cell lines were treated with mitomycin C (concentration range 320 pM-50 microM) at a range of pH (5.8-7.8) for 2 h. The cytotoxicity of mitomycin C over this range was determined using a tetrazolium-dye-based microtitration assay. The cytotoxicity of mitomycin C was significantly greater (confidence level > or = 95%) in acidic conditions (pH 5.8-6.0) than in neutral to alkaline pH (7.2-7.8) for three of the five cell lines. The same trend, although less marked, also occurred in the other two cell lines. The cytotoxicity of mitomycin C was greater under acidic conditions for all these cell lines confirming that the activity of mitomycin C depends on pH and suggesting that the pH of the vehicle used for intravesical chemotherapy may be an important factor in the successful treatment of bladder carcinomas. The modification of pH by urine may explain some of the variation in success rates among patients treated intravesically with mitomycin C.


Effect of Collagen Tripeptide and Adjusting for Climate Change on Skin Hydration in Middle-Aged Women: A Randomized, Double-Blind, Placebo-Controlled Trial.
Introduction: Although collagen is widely used in various forms as a functional ingredient in skin care products, the effect of oral supplementation of collagen tripeptides (CTPs) on human skin is unclear. Moreover, the majority of the positive outcomes of CTP reported so far have not considered the effect of weather conditions. Therefore, we tested the effect of CTP and adjusting for climate change on skin properties in middle-aged women. Materials and Methods: A randomized controlled trial was conducted with 84 women between 40 and 60 years of age. Participants were randomized to receive placebo or 1,000 mg CTP daily for 12 weeks. CTP was prepared from the skin of Nile Tilapia by the digestion method using collagenase from non-pathogenic bacteria of the genus Bacillus. Skin hydration, wrinkling, and elasticity were assessed at baseline and after 6 and 12 weeks with adjustments for temperature, humidity, and ultraviolet A exposure during the evaluation time using weather data from the regional meteorological office. Results: Of the 82 participants, 74 completed the trial without adverse effects. Compared with the control group, trans-epidermal water loss was reduced more in the CTP group after 12 weeks (P < 0.05). At 12 weeks, even after adjustment for humidity, temperature, and UVA in the region, the difference of the two groups in TEWL remained statistically significant (adjusted for humidity and temperature, P = 0.024; adjusted for UVA, P = 0.032; adjusted for temperature, high temperature, and ultraviolet A, P = 0.031). In terms of skin hydration, more improvement was evident in the CTP group than in the control group. In the subgroup analysis, subjects under 50 years of age showed a significant improvement in total score and moisture in the subjective skin improvement questionnaire after taking CTP for 12 weeks. Application of CTP was well-tolerated, and no notable adverse effect was reported from both groups. Discussion: Our findings suggest that oral ingestion of CTP from the Skin of Nile Tilapia (Oreochromis niloticus) is well-tolerated and helps reduce water loss in in middle-aged women. Clinical Trial Registration: www.clinicaltrials.gov/, Identifier: NCT03505684.


Statistical neuroanatomy of the human inferior frontal gyrus and probabilistic atlas in a standard stereotaxic space.
We manually defined the inferior frontal gyrus (IFG) on high-resolution MRIs in native space in 30 healthy subjects (15 female, median age 31 years; 15 male, median age 30 years), resulting in 30 individual atlases. Using standard software (SPM99), these were spatially transformed to a widely used stereotaxic space (MNI/ICBM 152) to create probabilistic maps. In native space, the total IFG volume was on average 5%, and the gray matter (GM) portion 12% larger in women (not significant). Expressed as a percentage of ipsilateral frontal lobe volume (i.e., correcting for brain size), the IFG was an average of 20%, and the GM portion of the IFG 27%, larger in women (P < 0.005). Correcting for total lobar volume yielded the same result. No asymmetry was found in IFG volumes. There were significant positional differences between the right and left IFGs, with the right IFG being further lateral in both native and stereotaxic space. Variability was similar on the left and right, but more pronounced anteriorly and superiorly. We show differences in IFG volume, composition, and position between sexes and between hemispheres. Applications include probabilistic determination of location in group studies, automatic labeling of new scans, and detection of anatomical abnormalities in patients.


Presynaptic antisympathetic action of amiodarone and its metabolite desethylamiodarone.
Amiodarone has a "reserpine-like" sympatholytic action in the heart. The aims of this study were to test whether desethylamiodarone (DEA), the in vivo bioactive metabolite of amiodarone, has this action and whether this action could be demonstrated in a neuronal preparation. Experiments were performed in intact rats, perfused hearts, or brain synaptosomes treated with DEA and amiodarone, and concentrations of norepinephrine (NE) and dihydroxyphenylglycol (DHPG), the intraneuronal metabolite of NE, were assayed in plasma, coronary effluent, and synaptosomes. In perfused hearts, DEA at 1, 3, and 10 microM increased DHPG overflow by threefold, sixfold, and ninefold, respectively (all p < 0.01 vs. control). DEA at 1 microM was more potent than amiodarone in increasing DHPG overflow. DEA at 1 and 3 microM also inhibited NE release evoked by sympathetic nerve stimulation (p < 0.05). In intact rats, intravenous DEA at 15 mg/kg elicited onefold increase in plasma DHPG level, and oral pretreatment with amiodarone did not interfere with the sympatholytic action of intravenous amiodarone. In synaptosomes, 40-min incubation with amiodarone, DEA (both 10 microM), and reserpine reduced synaptosomal NE content by 42, 45, and 60%, respectively. Thus similar to its parent drug, DEA exerts a presynaptic sympatholytic action in rat hearts in vivo and in vitro. This action of amiodarone and DEA also was observed in synaptosomes.


Acute nonlymphoblastic leukemia in children treated for acute lymphoblastic leukemia with an intensive regimen including teniposide.
Some cases of conversion from acute lymphoblastic leukemia (ALL) to acute nonlymphoblastic leukemia (ANLL) at relapse have been reported recently. We report three cases initially diagnosed as having ALL and showing morphological, cytochemical, and immunophenotypic features of ANLL at relapse (lineage switch). Conversion was observed among 14 patients who developed bone marrow relapse while undergoing intensive treatment with our ALL protocol, which includes teniposide, and that had been administered to 62 patients. The three cases converted at first relapse, with a mean time of 20 months (13-29 months). Clinical and immunologic characteristics of T-cell leukemia were present in one patient. Changes documented in cytogenetic studies are discussed. The underlying mechanisms for the lineage switch remain unclear as does its relation with mixed lineage leukemias, but we believe that drugs employed in our therapy protocol could have had an influence on this conversion.


Measurement of ascorbic acid kinetics in man using stable isotopes and gas chromatography/mass spectrometry.
The feasibility of studying ascorbic acid kinetics in man using stable isotope-labelled tracers and gas chromatographic (GC) separation followed by mass spectrometric (MS) quantitation was assessed. Preliminary studies with 13C-labelled material showed that although better precision at low levels could be achieved using the GC/combustion/MS technique, consideration of likely enrichments in a human study made the simpler GC/MS method just as suitable. On this basis, a small pilot study of the kinetics in man was carried out. The enrichment of the ascorbic acid in plasma was measured for a 24 h period after oral administration of 13C-labelled material. The results were fitted to a simple three-compartment model and rate constants and pool sizes were deduced. The results obtained are comparable to those obtained in other published studies, from which we conclude that the technique may be useful as a non-invasive method for the assessment of nutritional status in a variety of populations.


A permutation method for network assembly.
We present a method for assembling directed networks given a prescribed bi-degree (in- and out-degree) sequence. This method utilises permutations of initial adjacency matrix assemblies that conform to the prescribed in-degree sequence, yet violate the given out-degree sequence. It combines directed edge-swapping and constrained Monte-Carlo edge-mixing for improving approximations to the given out-degree sequence until it is exactly matched. Our method permits inclusion or exclusion of 'multi-edges', allowing assembly of weighted or binary networks. It further allows prescribing the overall percentage of such multiple connections-permitting exploration of a weighted synthetic network space unlike any other method currently available for comparison of real-world networks with controlled multi-edge proportion null spaces. The graph space is sampled by the method non-uniformly, yet the algorithm provides weightings for the sample space across all possible realisations allowing computation of statistical averages of network metrics as if they were sampled uniformly. Given a sequence of in- and out- degrees, the method can also produce simple graphs for sequences that satisfy conditions of graphicality. Our method successfully builds networks with order O(107) edges on the scale of minutes with a laptop running Matlab. We provide our implementation of the method on the GitHub repository for immediate use by the research community, and demonstrate its application to three real-world networks for null-space comparisons as well as the study of dynamics of neuronal networks.


Broussoflavonol B restricts growth of ER-negative breast cancer stem-like cells.
Accumulating experimental and clinical evidence has indicated that tumor-initiating or cancer stem-like cells are a sub-population of tumor cells capable of initiating and driving tumor growth, and cancer stem-like cells are resistant to most current cancer therapies, including chemo- and radiation therapy. More effective targeted-therapeutic approaches are urgently needed to eliminate cancer stem-like cells. Here, we report that broussoflavonol B, a chemical purified from the bark of the Paper Mulberry tree (broussonetia papyrifera), exhibited potent growth inhibitory activity towards estrogen receptor (ER)-negative breast cancer SK-BR-3 cells at sub-micromolar concentrations. Broussoflavonol B more potently inhibited growth and induced differentiation of stem-like SK-BR-3 cells-compared to the anti-estrogen tamoxifen. In addition, broussoflavonol B treatment also reduced the steady, state levels of the Human epidermal growth factor receptor-2 (HER2) and ER-α36, a variant of ER-α. Our results, thus, indicate that broussoflavonol B is a potent growth inhibitor of ER-negative breast cancer stem-like cells and provide a rationale for pre-clinical and clinical evaluation of broussoflavonol B for breast cancer therapy.


Trends and health impacts of major urban air pollutants in Kazakhstan.
The air quality in cities in Kazakhstan has been poorly investigated despite the worsening conditions. This study evaluates national air pollution monitoring network data (Total Suspended Particle-TSP, NO2, SO2, and O3) from Kazakhstan cities and provides estimates of excess mortality rates associated with PM2.5 exposure using the Global Exposure Mortality Model (GEMM) concentration-response function. Morbidity rates associated with PM10 exposure were also estimated. Annual average (2015-2017) population-weighted concentrations were Kazakhstan cities was 157, 51, 29, and 41 μg m-3 for TSP, NO2, SO2, and O3 respectively. We estimated a total of 8134 adult deaths per year attributable to PM2.5 (average over 2015-2017) in the selected 21 cities of Kazakhstan. The leading causes of death were ischemic heart disease (4080), stroke (1613), lower respiratory infections (662), chronic obstructive pulmonary disease (434), lung cancer (332). The per capita mortality rate attributable to ambient air pollution (per 105 adults per year) was less than 150 in nine cities, between 150 and 204 in nine cities, and between 276 and 373 in three industrial cities (Zhezkazgan, Temirtau, and Balkhash). Implications: Quantitative information on the health impacts of air pollution can be useful for decision-makers in Kazakhstan to justify environmental policies and identify policy and funding priorities for addressing air pollution issues. This information can also be useful for policymakers by improving the quality of government-funded environmental reports and strategic documents, as they have many shortcomings in terms of the selection of air quality indicators, identification of priority pollutants, and identification of sources of pollution. This study has high significance due to the lack of data and knowledge in Central Asia, especially Kazakhstan.


Convergent and Divergent Structural Connectivity of Brain White Matter Network Between Patients With Erectile Dysfunction and Premature Ejaculation: A Graph Theory Analysis Study.
Sexual dysfunction, namely, erectile dysfunction (ED) and premature ejaculation (PE), has been found to be associated with abnormal structural connectivity in the brain. Previous studies have mainly focused on a single disorder, however, convergent and divergent structural connectivity patterns of the brain network between ED and PE remain poorly understood. T1-weighted structural data and diffusion tensor imaging data of 28 patients with psychological ED, 28 patients with lifelong PE (LPE), and 28 healthy controls (HCs) were obtained to map the white matter (WM) brain networks. Then, the graph-theoretical method was applied to investigate the differences of network properties (small-world measures) of the WM network between patients with ED and LPE. Furthermore, nodal segregative and integrative parameters (nodal clustering coefficient and characteristic path length) were also explored between these patients. Small-world architecture of the brain networks were identified for both psychological ED and LPE groups. However, patients with ED exhibited increased average characteristic path length of the brain network when compared with patients with LPE and HCs. No significant difference was found in the average characteristic path length between patients with LPE and HCs. Moreover, increased nodal characteristic path length was found in the right middle frontal gyrus (orbital part) of patients with ED and LPE when compared with HCs. In addition, patients with ED had increased nodal characteristic path length in the right middle frontal gyrus (orbital part) when compared with patients with LPE. Together, our results demonstrated that decreased integration of the right middle frontal gyrus (orbital part) might be a convergent neuropathological basis for both psychological ED and LPE. In addition, patients with ED also exhibited decreased integration in the whole WM brain network, which was not found in patients with LPE. Therefore, altered integration of the whole brain network might be the divergent structural connectivity patterns for psychological ED and LPE.


Evidence that locustatachykinin I is involved in release of adipokinetic hormone from locust corpora cardiaca.
The glandular cells of the corpus cardiacum of the locust Locusta migratoria, known to synthesize and release adipokinetic hormones (AKH), are contacted by axons immunoreactive to an antiserum raised against the locust neuropeptide locustatachykinin I (LomTK I). Electron-microscopical immunocytochemistry reveals LomTK immunoreactive axon terminals, containing granular vesicles, in close contact with the glandular cells cells. Release of AKH I from isolated corpora cardiaca of the locust has been monitored in an in vitro system where the amount of AKH I released into the incubation saline is determined by reversed phase high performance liquid chromatography with fluorometric detection. We could show that LomTK I induces release of AKH from corpora cardiaca in a dose-dependent manner when tested in a range of 10-200 microM. This is thus the first clear demonstration of a substance inducing release of AKH, correlated with the presence of the substance in fibers innervating the AKH-synthesizing glandular cells, in the insect corpora cardiaca.


Integrative Strategy with Ayurveda and Electro-Acupuncture in Hemifacial Spasm: a Case Report.
We report a primary hemifacial spasm that started four years ago with sudden twitching of the face towards the right side. It was diagnosed as a hemifacial spasm by a neurologist and prescribed with Zeptol 100 mg 0.5 tablet BID for two weeks, followed by two sittings of Botox injection in a gap of 1 year. A year later, it reappeared more severely, driving her towards an integrative treatment modality. Ayurveda treatments including Nasya, Ksheera dhooma, internal medications, and Rasona navaneetha prayoga were administered. GV20, GB14, EX-HN5, ST3, ST4, ST6, TE17, LI4, and GB34 were selected for electro-acupuncture. The scores of hemifacial spasm grading and quality of life scale were 9 and 20 (before), 6 and 16 (after treatment), and 4 and 10 (follow-up after six months), respectively. This integrative approach was safe and has shown an improvement in hemifacial spasm.


Metal and Microelement Biomarkers of Neurodegeneration in Early Life Permethrin-Treated Rats.
Hair is a non-invasive biological material useful in the biomonitoring of trace elements because it is a vehicle for substance excretion from the body, and it permits evaluating long-term metal exposure. Here, hair from an animal model of neurodegeneration, induced by early life permethrin treatment from the sixth to 21th day of life, has been analyzed with the aim to assess if metal and microelement content could be used as biomarkers. A hair trace element assay was performed by the ICP-MS technique in six- and 12-month-old rats. A significant increase of As, Mg, S and Zn was measured in the permethrin-treated group at 12 months compared to six months, while Si and Cu/Zn were decreased. K, Cu/Zn and S were increased in the treated group compared to age-matched controls at six and 12 months, respectively. Cr significantly decreased in the treated group at 12 months. PCA analysis showed both a best difference between treated and age-matched control groups at six months. The present findings support the evidence that the Cu/Zn ratio and K, measured at six months, are the best biomarkers for neurodegeneration. This study supports the use of hair analysis to identify biomarkers of neurodegeneration induced by early life permethrin pesticide exposure.


Dry-compression packing of hydroxyapatite nanoparticles within a flat cuboid chromatography device and its use for fast protein separation.
We describe and discuss a simple dry-compression technique for preparing a flat cuboid chromatography device containing a shallow packed-bed of crystalline hydroxyapatite nanoparticles. We then discuss the use of this device for fast protein separation in the bind-and-elute mode. Such separation could be carried out at quite low pressures, making it possible to use inexpensive low pressure chromatography systems. In the flow rate range examined in this study, the pressure-drop across the device increased linearly with flow rate, indicating negligible media compaction during use. Using this device, binary protein mixtures could be separated in about a minute. Contrary to that observed in most packed-bed chromatographic separations, the width of the flow through and eluted peaks decreased with increase in flow rate. Therefore, both productivity and purity could be simultaneously increased by increasing flow rate. The suitability of this device for preparative protein separations was demonstrated by carrying out purification of a monoclonal antibody (Trastuzumab) from mammalian cell culture supernatant. This study opens up the possibility of developing dry-compression based flat cuboid packed-bed chromatography devices for fast preparative protein separation.


Phenotypic and functional characterization of the hematopoietic stem cell.
The purpose of this report is to demonstrate the phenotypic and functional characteristics of a primitive hematopoietic stem cell (HSC). We present evidence that an isolated murine HSC can repopulate the hematopoietic tissues of lethally irradiated recipient animals long term. By limiting dilution, as few as ten isolated stem cells can reconstitute mice for their lifetime. The stem cell which we have isolated does not copurify with colony forming unit-spleen or radioprotect recipients from lethal radiation. The phenotypic characterization of this rare cell, which represents 0.005% of total bone marrow, includes either the absence or very low expression of markers associated with long-term repopulating cells described by other groups. We believe this stem cell represents a very early self-renewing stem cell in the mouse.


Computer-aided design and finite-element modelling of biomaterial scaffolds for bone tissue engineering.
Scaffold biomaterials for tissue engineering can be produced in many different ways depending on the applications and the materials used. Most research into new biomaterials is based on an experimental trial-and-error approach that limits the possibility of making many variations to a single material and studying its interaction with its surroundings. Instead, computer simulation applied to tissue engineering can offer a more exhaustive approach to test and screen out biomaterials. In this paper, a review of the current approach in biomaterials designed through computer-aided design (CAD) and through finite-element modelling is given. First we review the approach used in tissue engineering in the development of scaffolds and the interactions existing between biomaterials, cells and mechanical stimuli. Then, scaffold fabrication through CAD is presented and characterization of existing scaffolds through computed images is reviewed. Several case studies of finite-element studies in tissue engineering show the usefulness of computer simulations in determining the mechanical environment of cells when seeded into a scaffold and the proper design of the geometry and stiffness of the scaffold. This creates a need for more advanced studies that include aspects of mechanobiology in tissue engineering in order to be able to predict over time the growth and differentiation of tissues within scaffolds. Finally, current perspectives indicate that more efforts need to be put into the development of such advanced studies, with the removal of technical limitations such as computer power and the inclusion of more accurate biological and genetic processes into the developed algorithms.


Proximal paraparesis following spinal anesthesia.
A 70-year-old man with prostatic cancer extending to the urinary bladder underwent transurethral resection of the bladder neck under spinal anesthesia and developed weakness of the proximal lower limbs a few hours after the procedure. The weakness persisted for several months. Because there were no local surgical complications (hematoma, infectious epiduritis, abscess) or bone metastases responsible for nerve root or spinal cord compression, a causal relation between the neurologic deficit and the spinal anesthesia was considered likely. Neurologic deficits are uncommon after spinal anesthesia and can be produced by complications of the surgical procedure (direct nerve injury, hematoma, abscess), arachnoiditis, neurotoxicity of disinfectants or of preservatives added to solutions of anesthetic drugs, or spinal cord ischemia. Precipitating factors for spinal cord ischemia include faulty patient position during the procedure, intraoperative arterial hypotension and injection of vasoconstricting agents.


Considerations for sustainable influenza vaccine production in developing countries.
Through its Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) in collaboration with the United States Department of Health and Human Services has produced a checklist to support policy-makers and influenza vaccine manufacturers in identifying key technological, political, financial, and logistical issues affecting the sustainability of influenza vaccine production. This checklist highlights actions in five key areas that are beneficial for establishing successful local vaccine manufacturing. These five areas comprise: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination. Incorporating the checklist into national vaccine production programmes has identified the policy gaps and next steps for countries involved in GAP's Technology Transfer Initiative. Lessons learnt from country experiences provide context and insight that complement the checklist's goal of simplifying the complexities of influenza prevention, preparedness, and vaccine manufacturing.


Late caliceal fistula after kidney transplantation.
Caliceal fistula is a rare urological complication that can occur usually shortly after kidney transplantation (KTx). The occlusion of the renal accessory artery with subsequent necrosis of the kidney pole is the most common cause of the fistula development. We report a case of a 57-year-old man with reconstruction of two accessory renal arteries by anastomosis to the side of the main artery during graft placement complicated by late caliceal fistula, managed surgically. Directly after KTx good kidney graft function (serum creatinine concentration 151 micromol/L) was observed. The patient noticed protuberance and pain in the kidney graft area 5 months later. Diagnostic imaging revealed moderate urostasis and liquid collection in the region of the lower graft pole. Administration of a contrast medium through the inserted drain visualized a fistula of a lower renal calyx and ureteric stenosis. Percutaneous drainage was applied with subsequent stop of diuresis through the urethral catheter. During the surgery, the resection of a lower kidney graft pole necrosis was performed, with the closure of caliceal fistula. Simultaneously double pigtail ureteric stent was inserted. After the next two months the pigtail catheter was removed, and neither urostasis in the kidney graft nor liquid collection in the perigraft area were observed. The exceptionality of the case is the late caliceal fistula occurrence. We may only speculate, why it happened 5 months after KTx. The thrombosis of stenosed accessory artery is the most probable cause.


Evaluation of the effectiveness of alginate-based hydrogels in preventing peritoneal adhesions.
Infertility and intestinal blockage are just two examples of the postoperative consequences that can arise from peritoneal damage, which can also result in severe peritoneal fibrosis and peritoneal adhesions. Peritoneal adhesions are still not effectively treated, and both pharmaceutical therapy and biomaterial barriers have only had modest preventative effects. In this work, we looked into the effectiveness of in-place injectable sodium alginate hydrogel for peritoneal adhesion prevention. The findings demonstrated that sodium alginate hydrogel promoted human peritoneal mesothelial cell proliferation and migration, prevented peritoneal fibrosis by suppressing the production of transforming growth factor-β1, and, most importantly, promoted mesothelium self-repair. These findings imply that this brand-new sodium alginate hydrogel is a good candidate material for peritoneal adhesion prevention.


Shining light on rhodopsin selectivity: How do proteins decide whether to transport H+ or Cl-?
The versatile microbial rhodopsin family performs a variety of biological tasks using a highly conserved architecture, making it difficult to understand the mechanistic basis for different functions. Besaw et al. now report structures of a recently discovered cyanobacterial Cl--pumping rhodopsin and its functionally divergent mutant that reveal how these transmembrane proteins create a gradient of activity with subtle changes. These insights are paralleled by a second recent report, which in combination answers long-standing questions about rhodopsin selectivity and will facilitate future engineering efforts.


Antioxidative properties of pyrrolidinium and piperidinium salts.
Two series of pyrrolidinium (PYA-n) and piperidinium (PPPA-n) bromides with incorporated antioxidant function were synthesized. Both have hydrocarbon chains with odd number of the carbon atoms (n) ranging between 7 and 15. Pig erythrocytes (RBC) were used to study antioxidant activity of these compounds. They were incorporated into RBC membranes in sublytic (micromolar) concentrations and RBC were then subjected to UV radiation. It was found that all the salts used protected erythrocyte membranes against oxidation of membrane lipids. This protection increased with hydrocarbon chain length. Such effect may be the result of an incorporation of particular compounds to different depths into the lipid phase of RBC membrane depending on their chain length. Such possibility was checked by studies on fluidity changes induced by the compounds studied in ghost membranes by fluorimetric measurements. The measurements showed that pyrrolidinium bromides were slightly more effective in a protection of erythrocytes than the corresponding piperidinium ones. The possible reason of such behaviour may be the difference in lipophilicity between piperidine and pyrrolidine rings.


The effect of insulin on the liver cells of newborn rats. An electron microscopic study.
The liver of newborn rats contains neither glycogen nor lipid droplets. These latter, sometimes in fusion, still could be found in the cytoplasm and the nucleus as well, following a five-minute action of insulin at a dose of 0.2 IU/animal. The lipid droplets were in close relationship with the mitochondria. This time the glycogen, either in fields or rosettes, was missing. Thirty minutes after treatment the fields of glycogen could be well seen. The experiments demonstrated an exclusive sequence of events starting with the receptor and its signal insulin on neonatal liver cells and resulting in a morphological picture (involving first lipid droplets, then glycogen), similar to that of the adult liver cells.


Subnanometer Topological Tuning of the Liquid Intrusion/Extrusion Characteristics of Hydrophobic Micropores.
Intrusion (wetting)/extrusion (drying) of liquids in/from lyophobic nanoporous systems is key in many fields, including chromatography, nanofluidics, biology, and energy materials. Here we demonstrate that secondary topological features decorating main channels of porous systems dramatically affect the intrusion/extrusion cycle. These secondary features, allowing an unexpected bridging with liquid in the surrounding domains, stabilize the water stream intruding a micropore. This reduces the intrusion/extrusion barrier and the corresponding pressures without altering other properties of the system. Tuning the intrusion/extrusion pressures via subnanometric topological features represents a yet unexplored strategy for designing hydrophobic micropores. Though energy is not the only field of application, here we show that the proposed tuning approach may bring 20-75 MPa of intrusion/extrusion pressure increase, expanding the applicability of hydrophobic microporous materials.


An approach for leukemia classification based on cooperative game theory.
Hematological malignancies are the types of cancer that affect blood, bone marrow and lymph nodes. As these tissues are naturally connected through the immune system, a disease affecting one of them will often affect the others as well. The hematological malignancies include; Leukemia, Lymphoma, Multiple myeloma. Among them, leukemia is a serious malignancy that starts in blood tissues especially the bone marrow, where the blood is made. Researches show, leukemia is one of the common cancers in the world. So, the emphasis on diagnostic techniques and best treatments would be able to provide better prognosis and survival for patients. In this paper, an automatic diagnosis recommender system for classifying leukemia based on cooperative game is presented. Through out this research, we analyze the flow cytometry data toward the classification of leukemia into eight classes. We work on real data set from different types of leukemia that have been collected at Iran Blood Transfusion Organization (IBTO). Generally, the data set contains 400 samples taken from human leukemic bone marrow. This study deals with cooperative game used for classification according to different weights assigned to the markers. The proposed method is versatile as there are no constraints to what the input or output represent. This means that it can be used to classify a population according to their contributions. In other words, it applies equally to other groups of data. The experimental results show the accuracy rate of 93.12%, for classification and compared to decision tree (C4.5) with (90.16%) in accuracy. The result demonstrates that cooperative game is very promising to be used directly for classification of leukemia as a part of Active Medical decision support system for interpretation of flow cytometry readout. This system could assist clinical hematologists to properly recognize different kinds of leukemia by preparing suggestions and this could improve the treatment of leukemic patients.


Contractile Characteristics of Mimosa pudica L.
The force-velocity characteristics of the primary pulvinus of Mimosa pudica have been determined using a new polytonic measurement technique. The contractile characteristics were determined from a modified form of Hill's equation (Hill, A. V. 1938. Proc. Roy. Soc. London B126: 136-195) describing the physiological contractile behavior of animal muscle. The values of the resulting Hill's constants were found to be remarkably similar to those of intact animal muscle and reconstituted contractile collagen.


Deliveries After Malignant Disease Before Pregnancy: Maternal Characteristics, Pregnancy, and Delivery Complications.
Survival after cancer has increased, and the question of risks in later pregnancies has become important. A previous malignancy may affect pregnancy outcome. Comparison of women with malignant disease before pregnancy with all other women giving birth during 1994-2011. Data were obtained by linkage between Swedish national health registers. Subfertility, evaluated as time to pregnancy, and in vitro fertilization (IVF) before the relevant delivery were studied. The following delivery diagnoses were studied: gestational diabetes, preeclampsia, placenta previa, placenta abruption, placenta retention, bleeding around delivery, and premature rupture of membranes. The rates of cesarean section and vacuum extraction or forceps delivery were also studied. We identified 3931 women with 7176 deliveries and with a malignancy diagnosed at least 1 year before the delivery. The total number of deliveries in Sweden in these years was 1,746,870. Overall, an increased risk of subfertility (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.07-1.28), use of IVF (OR = 1.36, CI 1.21-1.53), delivery complications (OR = 1.17, 95% CI 1.10-1.24), and rate of caesarean sections (OR = 1.27, 95% CI 1.20-1.34) was observed among women with a history of malignancy compared with other women. We found an increased risk of subfertility, pregnancy, and delivery complications in women with a history of malignant disease. Further studies are needed to evaluate the risks of specific treatments and to provide these women with reliable information that could affect their family planning.


Vasectomy complications minimal.
Vasectomy has 1 of the lowest incidences of side effects when compared with other contraceptive methods. No deaths have been attributed to the procedure in developed countries. Selected largescale studies in Great Britain, Korea, and the US between 1973-74, show that the overall incidence of complications is less than 5/100 vasectomies performed. Minor side effects immediately following vasectomy include discomfort, swelling and bruising of the scrotal skin, all of which usually disappear without treatment. Complications, such as hemorrhage and infection, can occur after any surgery. Other possible complications include epididymitis and sperm granuloma. Epididymitis is an infection of the epididymis frequently associated with a previous history of infection. Sperm granuloma, a chronic inflammatory reaction, may develop as a result of leakage of sperm from the cut ends of the vas. Occasionally the body fails to resorb the granuloma casuing it to become troublesome and require further treatment. Although considered virtually 100% effective, vasectomy can fail because, among other reasons, the cut ends of the vas may reconnect (spontaneous reanastomosis). This occurs, however, in less than 1% of cases. The overall incidence of either hematoma, epididmyitis or infection is less than 2%; sperm for granuloma, less than 1%. Vasectomy provides a means of permanent birth control with a minimum percentage of complications and a maxium percentage of effectiveness and safety.


Confining Sn nanoparticles in interconnected N-doped hollow carbon spheres as hierarchical zincophilic fibers for dendrite-free Zn metal anodes.
We developed a three-dimensional hybrid fiber host consisting of interconnected N-doped hollow carbon spheres embedded with Sn nanoparticles (denoted as Sn@NHCF) for Zn metal anodes in high-performance Zn metal batteries. Experimental observations and density functional theory calculation reveal that the zincophilic Sn nanoparticles and N-doped carbons enable the homogeneous Zn deposition on the interior and exterior surfaces of the hollow fibers. Moreover, the hierarchical hollow fiber network effectively reduces the structural stress during the plating/stripping process. As a result, the developed Sn@NHCF host exhibits remarkable electrochemical properties in terms of high Coulombic efficiency, low voltage hysteresis, and prolonged cycling stability without dendrite formation. Moreover, a full cell based on the designed Sn@NHCF-Zn composite anode and a V2O5 cathode demonstrates superior rate capability and stable cycle life. This work provides a new strategy for the design of dendrite-free Zn anodes for practical applications.


Future directions--toxicology studies of 1,3-butadiene and isoprene.
Examination of a profile of data already existing on 1,3-butadiene shows adequate knowledge in many areas of toxicology that are conventionally required in hazard identification. However, while much progress has been made in areas of metabolism and pharmacokinetics, further studies would be worthwhile to improve mechanistic understanding such as the examination of alternate metabolic pathways, the generation of interspecies scaling factors, and an assessment of the relevance of various tumor sites. In this respect, data pertaining to repeated and pulse exposures of rodents and primates would be helpful. Another important aspect is the need to understand any human health implications of the observed 1,3-butadiene-induction of the murine leukemia virus. In this respect, studies have been pursued that include the comparison of leukemogenesis in congenetic strains, the leukemogenicity of viral isolates in rodent carcinogenicity and human cell culture studies, and the mechanisms of activation of ecotropic proviral sequences. Molecular epidemiological and toxicological research is ongoing in rodents and primates to evaluate hemoglobin adduct formation as an index of 1,3-butadiene exposure. Challenges of specificity, sensitivity, and simplification of current procedures need to be overcome. Recent mutagenicity and metabolism data suggest that structurally-related isoprene may have carcinogenic potential. The use of interstrain comparative studies and data in a second species is discussed, as well as proposed metabolism studies.


Colour correspondence effects between controlled objects and targets.
It is increasingly popular to use movement trajectories as a measure of mental processes related to task performance. Often this is accomplished by moving a cursor to a target on a computer screen. However, the relation between features of the cursor and the targets is rarely, if at all, considered. In five experiments, we examined whether moving a cursor to a target was affected by the relation between their colours, even when this relation was task irrelevant. In Experiments 1-3, a mouse-controlled cursor was moved to one of two coloured targets. Results showed colour correspondence effects in latency to initiate a response, duration of movement times, and movement trajectories when the relationship between cursor and target colours was task relevant (Experiment 1) and when only the cursor colour was task relevant (Experiment 2), but not when only the target was task relevant (Experiment 3). Follow-up experiments using single targets showed that colour correspondence effects occurred as long as attention was dedicated to the colour of the cursor, even when neither the cursor nor the target colour was relevant to selecting the correct movement (Experiments 4 and 5). Furthermore, when the relation between cursor and target colours is task irrelevant, colour correspondence effects for response initiation times are uncorrelated with those for movement times and movement trajectories. We interpret the observed correspondence effect in terms of response coding, although attention cueing may also play a role, and suggest that greater consideration of cursor features is needed when examining movement trajectories in choice reaction tasks.


Synthesis of the C1-C21 domain of azaspiracids-1 and -3.
An efficient synthesis of the C1-C21 fragment of azaspiracids-1 and -3 is described. This features a Nozaki-Hiyama-Kishi reaction to couple the AB and CD ring precursors and formation of the THF-fused ABCD trioxadispiroketal system under thermodynamic conditions.


Transrectal ultrasound-guided interstitial radiation therapy for localized prostate cancer.
The use of interstitial implants for the treatment of low-stage prostate cancer using transrectal ultrasound guidance is evaluated in 80 patients. This outpatient procedure involves the placement of needles through a template and into the prostate. Ultrasound guidance is used to place the needles into a preselected location. The needles are loaded with a radioactive source. In this study Palladium-103 was utilized. This technique allows accurate and complete seeding of the prostate. There was a 50 percent or greater decrease in prostate size in all of the patients who were implanted. Prostate-specific antigen (PSA) levels became normal or decreased by more than 50 percent in 97 percent of the patients. Most patients experienced urethral irritative symptoms which lasted up to five months, but none of the patients experienced rectal symptoms lasting longer than a month. The mean follow-up is 11.8 months which is too brief to ascertain the effectiveness of this therapy. The method appears to be safe and may represent an alternative to external beam irradiation.


The Herpes Simplex Virus Virion Host Shutoff Protein Enhances Translation of Viral True Late mRNAs Independently of Suppressing Protein Kinase R and Stress Granule Formation.
The herpes simplex virus (HSV) virion host shutoff (vhs) RNase destabilizes cellular and viral mRNAs, suppresses host protein synthesis, dampens antiviral responses, and stimulates translation of viral mRNAs. vhs mutants display a host range phenotype: translation of viral true late mRNAs is severely impaired and stress granules accumulate in HeLa cells, while translation proceeds normally in Vero cells. We found that vhs-deficient virus activates the double-stranded RNA-activated protein kinase R (PKR) much more strongly than the wild-type virus does in HeLa cells, while PKR is not activated in Vero cells, raising the possibility that PKR might play roles in stress granule induction and/or inhibiting translation in restrictive cells. We tested this possibility by evaluating the effects of inactivating PKR. Eliminating PKR in HeLa cells abolished stress granule formation but had only minor effects on viral true late protein levels. These results document an essential role for PKR in stress granule formation by a nuclear DNA virus, indicate that induction of stress granules is the consequence rather than the cause of the translational defect, and are consistent with our previous suggestion that vhs promotes translation of viral true late mRNAs by preventing mRNA overload rather than by suppressing eIF2α phosphorylation. The herpes simplex virus vhs RNase plays multiple roles during infection, including suppressing PKR activation, inhibiting the formation of stress granules, and promoting translation of viral late mRNAs. A key question is the extent to which these activities are mechanistically connected. Our results demonstrate that PKR is essential for stress granule formation in the absence of vhs, but at best, it plays a secondary role in suppressing translation of viral mRNAs. Thus, the ability of vhs to promote translation of viral mRNAs can be largely uncoupled from PKR suppression, demonstrating that this viral RNase modulates at least two distinct aspects of RNA metabolism.


[Percutaneous nephrolithotomy through the upper pole calix access for complicated renal calculi: report of 581 cases].
To discuss the optimal approach of percutaneous nephrolithotomy (PCNL) for treatment of complicated renal calculi. A total of 581 patients with complicated renal calculus were treated by PCNL through the upper pole calix access. Of the 581 patients, 55 had multiple upper pole calculi, 136 had staghorn stones, 145 had partial staghorn stones, and 245 had multiple renal calculi. PCNL through the upper pole calix access was completed successfully in all the cases. Of these patients, 90.3% (525/581) were stone-free after a single access, with a total stone-free rate of 94.6% (550/581). Thirty-five patients needed two accesses, 10 needed 3 accesses, 2 required 4 accesses, and 1 patients had 5 accesses. The operative time ranged from 30 to 150 min (mean 45 min). The successful rate of puncture was 100% without occurrence of severe injury of the pleura, intestine, peritoneum or other adjacent organs. Percutaneous nephrolithotomy through the upper pole calix access allows greater stone clearance rate due to its easy access into the intrarenal collecting system and can be an ideal approach for PCNL for complicated renal calculi.


Tissue transfer techniques in reconstructive urology.
Tissue transfer techniques are an essential part of the reconstructive urologist's armamentarium. Flaps and graft techniques are widely used in genital and urethral reconstruction. A graft is tissue that is moved from a donor site to a recipient site without its native blood supply. The main types of grafts used in urology are full thickness grafts, split thickness skin grafts and buccal mucosa grafts. Flaps are transferred from the donor site to the recipient site on a pedicle containing its native blood supply. Flaps can be classified based on blood supply, elevation methods or the method of transfer. The most used flaps in urology include penile, preputial, and scrotal skin. We review the various techniques used in reconstructive urology and the outcomes of these techniques.


Tubomanometry Measurement Success Rate in Clinical Practice.
Tubomanometry (TMM) is an objective method for investigating Eustachian tube (ET) function, but difficulties in technique and interpretation may reduce its usability. The objective of our study was to investigate common difficulties with TMM in different ET dysfunction (ETD) patient groups and at different pressures (30, 40, and 50 mbars) when first introducing TMM to otologic practice. Furthermore, we wanted to investigate whether it would be possible to perform TMM at only one pressure and obtain a representative result. A retrospective chart review of a 2-year cohort of 114 patients with a history of ETD treated at a tertiary referral center. Primary outcome was the success rate of TMM, secondary the reasons for unsuccessful measurements. Tertiary outcome was the correlation of TMM results at adjacent pressures. TMM success rate was 91%, varying 81 to 94% in different ETD patient groups and 87 to 94% at different pressures. Unsuccessful measurements resulted from air-leaks from the external ear canal, abnormal ear canal pressure curves (R < 0) and at 50 mbar, difficulties in reaching sufficient nasopharyngeal pressure. TMM results were similar in 88% of cases at 30 and 40 mbars and in 86% of cases at 40 and 50 mbars. TMM success rate seems sufficiently high for clinical diagnostics, and most difficulties may be overcome with proper interpretation during the TMM measurement session, and thus repeating the measurements when necessary. Considering the diagnostic information that would be lost if using only a single, predefined pressure, we suggest using all three pressures.


Circulating cytokine levels in the treatment of comorbid anxiety disorders.
Psychotherapy research aims to investigate predictors and moderators of treatment outcome, but there are few consistent findings. This study aimed to investigate cytokines in patients undergoing treatment for anxiety disorders and whether the level of cytokines moderated the treatment outcome. Thirty-seven patients with comorbid and treatment-resistant anxiety disorders were investigated using multilevel modelling. Serum cytokine levels were measured three times: pretreatment, in the middle of treatment, and at the end of treatment. Anxiety and metacognitions were measured weekly throughout treatment by self-report. The levels of monocyte chemoattractant protein-1, tumour necrosis factor-alpha, and interleukin-1 receptor antagonist did not change during therapy or were not related to the level of anxiety. Metacognitive beliefs predicted anxiety, but the relationship between metacognitions and anxiety was not moderated by cytokines. Limitations of the study include that the patients were not fasting at blood sampling, and we did not assess body mass index, which may affect cytokine levels. The lack of significance for cytokines as a predictor or moderator may be due to a lack of power for testing moderation hypotheses, a problem associated with many psychotherapy studies. Cytokines did not predict the outcome in the treatment of comorbid anxiety disorders in our sample. Furthermore, cytokines did not moderate the relationship between metacognitions and anxiety.


Biological Evaluation of Aegle marmelos Fruit Extract and Isolated Aegeline in Alleviating Pain-Depression Dyad: In Silico Analysis of Aegeline on MAO-A and iNOS.
Pain and depression have been assessed to co-occur in up to 80% of patients, and this comorbidity is more debilitating and pricier for the patients as compared to either of these disorders alone. Aegle marmelos is a well-known medicinal plant with a broad spectrum of pharmacological activities. Aegeline is a relatively unexplored molecule present in Aegle marmelos. Therefore, the current investigation aims to explore the potential of Aegle marmelos fruit extract (AMFE) and isolated aegeline against the reserpine-induced pain-depression dyad. In the current investigation, aegeline was isolated from AMFE, followed by spectroscopic characterization, i.e., using NMR and mass analyses. AMFE (200 mg kg-1 p.o) and aegeline (10 mg kg-1 p.o.) were administered to reserpinized (0.5 mg kg-1 s.c.) mice, and clorgyline (3 mg kg-1 i.p.) was taken as the standard drug. AMFE and aegeline significantly alleviated the reserpine-induced reduction in a pain threshold and an increase in immobility as observed in behavioral tests of pain and depression, respectively. In silico molecular docking studies of aegeline showed a good binding interaction at the active sites of MAO-A and iNOS. The in vivo analysis showed that AMFE and aegeline treatment significantly decreased the monoamine oxidase-A (MAO-A) activity, serum interleukin-6 (IL-6) level, and lipid peroxidation, along with an increase in the reduced glutathione level in comparison to the reserpine-treated group. Immunofluorescence studies also showed that AMFE and aegeline abrogated the reserpine-induced increase in iNOS expression. Conclusively, the results delineate that AMFE and aegeline might exert a protective effect via downregulating the MAO-A hyperactivity, IL-6 level, oxidative and nitrosative stress.


Growth measurements: estimation of cell division and cell expansion.
The main parameters for the estimation of growth within in vitro cultures are reviewed. Procedures to measure these parameters are described, emphasizing in each case their convenience of use, depending on the features of the culture to evaluate.


Effect of localized nitrate application on isoflavonoid concentration and nodulation in split-root systems of wild-type and nodulation-mutant soybean plants.
Although isoflavonoids are known to be inducers of nod genes in Bradyrhizobium japonicum, it was recently proposed that internal root levels of isoflavonoids may be important in nodule development on soybean (Glycine max [L.] Merr.). The hypernodulating soybean mutants were shown to accumulate higher root concentrations of isoflavonoid compounds (daidzein, genistein, and coumestrol) and to be more extensively nodulated than was the Williams parent when inoculated with B. japonicum. The hypernodulating mutants and the parent line, Williams, also showed decreased isoflavonoid concentrations and decreased nodule development if N was applied. The current study evaluated the effect of localized NO(3) (-) application on root isoflavonoid concentration and on nodulation in split-root systems of the Williams wild type and a hypernodulating mutant (NOD1-3). Nitrate application markedly decreased isoflavonoid concentrations in non-inoculated soybean roots. When roots were inoculated, nodule number, weight, and nitrogenase activity were markedly suppressed on the root-half receiving 5 millimolar NO(3) (-) compared with the other root-half receiving 0 millimolar NO(3) (-). High performance liquid chromatographic analyses of root extracts showed that the root-half receiving 5 millimolar NO(3) (-) was markedly lower in isoflavonoid concentrations in both soybean lines. This was partially due to the localized stimulatory effect of NO(3) (-) on root growth. The inoculated NOD1-3 mutant had higher isoflavonoid concentrations than did the Williams control in both the presence and absence of NO(3) (-). These results provide evidence that the site of N application primarily controls the site of nodulation inhibition, possibly through decreasing isoflavonoid levels. Although the effect of NO(3) (-) on nodule development and root isoflavonoid concentration was strongly localized, there was evidence that NO(3) (-) also resulted in a systemic effect on root isoflavonoids. The results are consistent with previous speculation that internal levels of root isoflavonoids may affect nodule development.


Anaerobic aquifer transformations of 2,4-dinitrophenol under different terminal electron accepting conditions.
We evaluated the susceptibility of 2,4-dinitrophenol (2,4-DNP) and 2,4-diaminophenol to anaerobic biodegradation in aquifer slurries. Aquifer microorganisms depleted 2,4-DNP at rates of 25, 9 and 0.4 microM/day under methanogenic, sulfate-reducing and nitrate-reducing conditions, respectively. Rates of abiotic, 2,4-DNP loss in autoclaved control incubations were 7.2, 6.2 and 0.95 microM/day respectively. Abiotic, 2,4-DNP reduction was especially important as the first step in its transformation. 2-Amino-4-nitrophenol was produced by this process, but this compound was further metabolized in methanogenic and sulfate-reducing aquifer slurries. This partially reduced compound persisted in autoclaved controls and in the nitrate-reducing aquifer slurries. Aquifer slurries incubated with either 2,4-DNP or 2,4-diaminophenol produced methane when incubated with no other electron acceptor suggesting that mineralization had occurred under these conditions. In parallel experiments, aquifer slurries amended with 2,6-dinitrophenol or picric acid did not produce methane at levels above the substrate unamended controls.


Identification of Six Thiolases and Their Effects on Fatty Acid and Ergosterol Biosynthesis in Aspergillus oryzae.
Thiolase plays important roles in lipid metabolism. It can be divided into degradative thiolases (thioase I) and biosynthetic thiolases (thiolases II), which are involved in fatty acid β-oxidation and acetoacetyl-CoA biosynthesis, respectively. The Saccharomyces cerevisiae genome harbors only one gene each for thioase I and thiolase II, namely, Pot1 and Erg10, respectively. In this study, six thiolases (named AoErg10A to AoErg10F) were identified in Aspergillus oryzae genome using bioinformatics analysis. Quantitative reverse transcription-PCR (qRT-PCR) indicated that the expression of these six thiolases varied at different growth times and under different forms of abiotic stress. Subcellular localization analysis showed that AoErg10A was located in the cytoplasm, AoErg10B and AoErg10C were in the mitochondria, and AoErg10D, AoErg10E, and AoErg10F were in the peroxisome. Yeast heterologous complementation assays revealed that AoErg10A, AoErg10D, AoErg10E, AoErg10F, and cytoplasmic AoErg10B (AoErg10BΔMTS) recovered the phenotypes of S. cerevisiae erg10 weak and lethal mutants and that only AoErg10D, AoErg10E, and AoErg10F recovered the phenotype of the pot1 mutant that cannot use oleic acid as the carbon source. Overexpression of AoErg10s affected either the growth speed or the sporulation of the transgenic strains. In addition, the fatty acid and ergosterol content changed in all the AoErg10-overexpressing strains. This study revealed the function of six thiolases in A. oryzae and their effect on growth and fatty acid and ergosterol biosynthesis, which may lay the foundation for genetic engineering for lipid metabolism in A. oryzae or other fungi. IMPORTANCE Thiolases, including thioase I and thiolase II, play important roles in lipid metabolism. Aspergillus oryzae, one of the most industrially important filamentous fungi, has been widely used for manufacturing oriental fermented food such as sauce, miso, and sake for a long time. In addition, A. oryzae has a high capability in production of high lipid content and has been used for lipid production. Thus, it is very important to investigate the function of thiolases in A. oryzae. In this study, six thiolase (named AoErg10A to AoErg10F) were identified by bioinformatics analysis. Unlike other reported thiolases in fungi, three of the six thiolases showed dual functions of thioase I and thiolase II in S. cerevisiae, indicating that the lipid metabolism is more complex in A. oryzae. The reveal of function of these thiolases in A. oryzae can lay the foundation for genetic engineering for lipid metabolism in A. oryzae or other fungi.


The use of technology to find sexual health information online among men who have sex with men in Hanoi, Vietnam, 2016.
In an era where mobile phones and computers are ubiquitous, technology-based interventions to reduce HIV and other sexually transmitted infections (STIs) have great potential to reach high-risk groups, including men who have sex with men (MSM). This study aimed to examine technology usage to find sexual health information online among MSM in Hanoi, Vietnam. A cross-sectional study of 205 MSM in Hanoi was conducted from February to May 2016. Overall, 50.7% of participants reported having used a smartphone, computer, or tablet to find HIV/STI testing locations in the past year, and 75.1% reported having used such devices to find other HIV/STI information online. Unemployment (adjusted prevalence ratio [aPR]: 1.13, 95%CI: 1.00-1.28) and having been tested for HIV (aPR: 1.27, 95%CI: 1.07-1.51) were significantly associated with using technology to find online sexual health information. MSM who had ever exchanged sex for money or drugs (aPR: 0.80; 95%CI: 0.68-0.94) were less likely to use technology to find sexual health information online. Technology is a promising platform for HIV/STI prevention programs among MSM, with the potential to reach different subgroups. Further efforts to develop technology-based interventions tailored to the needs of the MSM communities in Hanoi and to encourage MSM who were not currently seeking sexual health information and testing services online to do so are necessary.


Effect of hippurate on glucose utilization in rat kidney cortex slices.
Hippurate action on glucose utilization was evaluated in rat kidney cortex slices. Studies have shown the following. (1) Hippurate inhibits markedly basal as well as insulin-stimulated glucose utilization and basal gluconeogenesis. (2) Ca deficiency and specific Ca channel blockers diltiazem and isradipine abolish the hippurate inhibition of glucose utilization. (3) K+ channel blockers, i.e. the increased K+ concentration in incubation medium, procaine and sulfonylurea drugs also abolish the hippurate inhibition of glucose utilization. It is concluded that hippurate and benzoate operate through the ATP-dependent K+ channel.


QTL Mapping for Seed Germination Response to Drought Stress in Brassica napus.
Drought stress is one of the most environmental abiotic stresses affecting seed germination and crop growth. In the present study, the genetic characteristics of seed germination under drought stress in a Brassica napus double haploid population were analyzed. Five germination-related indexes, including germination percentage (GP), root length (RL), shoot length (SL), fresh weight (FW), and root-to-shoot length ratio (R/S) under control and drought stress, were calculated, and the drought stress index (DSI), including DSI-GP, DSI-RL, DSI-SL, DSI-FW, and DSI-R/S, was determined using the quantitative trait loci (QTLs) analysis based on high-density genetic linkage map. The phenotypic analysis indicated that the R/S is an effective morphological trait in the determination of drought tolerance in the seedling stage. Thirty-nine identified QTLs were observed for these traits and then integrated into 36 consensus QTLs, in which 18 QTLs were found to affect the DSI of four traits (GP, RL, SL, and R/S). Based on the co-linearity between genetic and physical maps of B. napus, 256 candidate genes were detected, and 128 genes have single-nucleotidepolymorphisms/insertion-deletion (SNP/InDel) variations between two parents, some of which were associated with the drought stress tolerance (for example, BnaC03g32780D, BnaC03g37030D, and BnaC09g27300D). The present results laid insights into drought tolerance and its genetic bases in B. napus.


Repeatability and reproducibility for intraocular pressure measurement by dynamic contour, ocular response analyzer, and goldmann applanation tonometry.
To evaluate and compare the intraocular pressure measurement variability between Goldmann applanation tonometry (GAT), Pascal dynamic contour tonometry (DCT), and ocular response analyzer (ORA) tonometry. Subjects were prospectively recruited from consecutive Albuquerque VA Medical Center eye clinic patients that were previously diagnosed with ocular hypertension, glaucoma suspect, primary open-angle, or normal pressure glaucoma. Two sets of intraocular pressure measurements (3-4 ORA, 2 DCT, and 2 GAT) were obtained approximately 15 minutes apart. Each set was obtained by 1 of 2 examiners using random examiner sequences. ORA was measured first in both eyes, followed by either DCT or GAT, which were obtained in random order. Repeatability was assessed by examining variability of consecutive measurements by the same examiner, and reproducibility was examined by assessing variability between the first and second measurement sets. One hundred and twenty eyes of 60 subjects were included. Mean age was 64.1+/-9.6 years and 58/60 (97%) were male. Intraobserver repeatability was highest for GAT, followed closely by DCT, and then ORA. Intersession reproducibility was similar for all methods, although a tonographic effect may have corrupted GAT and DCT reproducibility results. We found no repeatability or reproducibility differences between eyes, between examiners, or between measurement sets. Although some intermethod variability differences were identified, all 3 methods in this study demonstrated clinically acceptable measurement repeatability and reproducibility. This result, in conjunction with the finding that variability was not different between eyes, examiners, or measurement sets, suggests that DCT and ORA are reliable enough to be clinically useful.


Ultrastructural immunogold localization of vimentin and S-100 protein in guinea pig pars tuberalis.
Ultrastructural features of vimentin- and S-100 protein-positive cells in guinea pig pars tuberalis were examined by immunoelectron microscopy with the postembedding immunogold method. Interstitial cells that exhibited elongated cytoplasm and partly surrounded the specific secretory cells were filled with intermediate filament bundles on which immunogold particles for vimentin were densely located. Small colloid-containing follicles were occasionally distributed in the cranial region surrounding the median eminence. The follicular cells lining the luminal cavities contained considerable amounts of intermediate filaments immunoreactive for vimentin. Some specific secretory cells displayed various amounts of intermediate filaments immunoreactive for vimentin, which were scattered throughout the cytoplasm or concentrated around the nucleus. The specific secretory cells in which many parallel profiles of rough endoplasmic reticulum (RER) or a large number of mitochondria were dispersed throughout cytoplasm, i.e., being highly metabolically active, were devoid of intermediate filaments. The ventrocaudal region in continuity with the pars distalis was occupied by cells that were packed with vesicular inclusions, considered to be dilated cisternae of RER, and frequently formed colloid-containing follicles. Immunoreactivity for S-100 protein was located exclusively in this novel cell type. Immunogold particles for S-100 protein were distributed in the cytoplasmic matrix and were also associated with the membrane of vesicular inclusions. Gold particles were also detected on the tight junctions, desmosomes, and fibril materials at the apical cell regions of the colloid-containing follicles. The finding of two separate populations of cells containing vimentin and S-100 protein, respectively, supports the idea of functional separation in the pars tuberalis.


Analysis of fibroblast growth factor 2 (FGF2) gene transcription and protein distribution in the bovine testis.
Several fibroblast growth factors (FGFs) are implicated in proliferation and differentiation of both somatic and germ cells during testicular development, as well as in spermatogenesis of adult testis. The expression of FGF2 was studied in the adult bovine testis using quantitative RT-PCR, RNA in situ hybridization, and immunohistochemistry. Quantitative RT-PCR revealed consistent levels of FGF2 mRNA in parenchymal samples of the bovine testis. In situ hybridization localized FGF2 transcripts only in a constant fraction of Leydig and Sertoli cells as well as in modified Sertoli cells of the terminal segments. Immunohistochemistry revealed (a) no FGF2 protein in Sertoli cells (b) moderate cytoplasmic staining in Leydig cells and spermatogonia and (c) strong nuclear and faint cytoplasmic staining in myofibroblasts, in epithelial cells of straight tubules and rete testis and in blood vessels. These observations indicate a pleiotropic effect of FGF2 on the control of spermatogenesis in a paracrine and/or autocrine manner.


Consolidation of common parameters from multiple fits in dynamic PET data analysis.
In dynamic positron emission tomography (PET) data analysis, regions of interest (ROI's) are analyzed by fitting a parametric model to the time-activity curve acquired after a radio-labeled tracer has been introduced into the patient's bloodstream. This procedure can be carried out for multiple ROI's and/or multiple injections of the same or a different radiopharmaceutical. The approach presented here takes advantage of prior knowledge that some of the parameters of those multiple fits are the same. Reduction of the total number of parameters to be estimated results in smaller statistical uncertainty for all parameter estimates, especially those common to multiple fits.


Temperature-induced reversals of rotation in phycomyces.
The steady state extension and rotation rates of the Phycomyces sporangiophore were measured as a function of temperature. Maximum growth occurred at 27 degrees C; maximum rotation at 28 degrees C. The rotation to extension ratio, a qualitative parameter of cell wall structure, is affected differently by high and low temperatures. Steady state counterclockwise rotation, as opposed to the normal clockwise rotation, was found at both high and low temperatures. The extensional and rotational responses to step changes in temperature were also measured. The conclusions are drawn that a relative decrease in the lysis rate of wall polymer is responsible for the decrease in growth rate at low temperatures, and that a relative increase in the rate of wall synthesis and cross-linking is responsible for the decrease in growth rate at high temperatures. It is suggested that reversals in rotation result from changes in the handedness of the wall's helical structure.


Functional outcome for patients with hemiparesis, hemihypesthesia, and hemianopsia. Does lesion location matter?
Patients with hemiparesis, hemisensory loss, and hemianopsia ("HHH" deficits) due to stroke may have large cortical lesions caused by middle cerebral trunk vessel occlusion or smaller subcortical lesions due to lenticulostriate involvement. We studied the usefulness of lesion location in predicting functional recovery within this syndrome. We reviewed our records and found 41 patients who had a single ischemic hemispheric stroke, HHH deficits, and an available CT scan performed more than 24 hours after the onset of symptoms. CT scans were read independently and blindly by the authors. Lesions were initially categorized by arterial distribution on the basis of CT templates published by Kinkel. The numerous combinations of arterial branch vessel occlusions observed did not allow for statistical analyses because of the small number of subjects within each subgroup. Lesions were therefore classified as cortical (C), subcortical (S), or mixed (M). There were no significant differences among the three anatomic groups for age, sex, interval after stroke, Mini-Mental Status Examination score, or admission Barthel Index score. Functional outcome measures did not differ significantly for the three groups: mean +/- SD discharge Barthel score (C, 64 +/- 31; S, 47 +/- 20; M, 57 +/- 21), length of stay ([days] C, 64 +/- 25; S, 77 +/- 24; M, 73 +/- 28), and frequency of nursing home placement (C, 4/8; S, 3/6; M, 2/16). For patients with HHH deficits, the anatomic location of the lesion (C versus S versus M) does not affect functional outcome.


[Sudden cardiac death in athletes].
Sudden cardiac death in an athlete is rare and tragic event. An athlete's death draws high public attention given that athletes are considered the healthiest category of society. The vast majority of sudden cardiac death in young athletes is due to congenital cardiac malformations such as hypertrophic cardiomyopathy and various coronary artery anomalies. In athletes over age 35, the usual cause of sudden cardiac death is coronary artery disease. With each tragic death of a young athlete, there is a question why this tragedy has not been prevented. The American College of Sports Medicine and the American Heart Association recommend that a pre-participation exam should include a complete cardiovascular history and physical examination.


Effects of an auditory model on the learning of relative and absolute timing.
The effects of an auditory model on the learning of relative and absolute timing were examined. In 2 experiments, participants attempted to learn to produce a 1,000- or 1,600-ms sequence of 5 key presses with a specific relative-timing pattern. In each experiment, participants were, or were not, provided an auditory model that consisted of a series of tones that were temporally spaced according to the criterion relative-timing pattern. In Experiment 1, participants (n = 14) given the auditory template exhibited better relative- and absolute-timing performance than participants (n = 14) not given the auditory template. In Experiment 2, auditory and no-auditory template groups again were tested, but in that experiment each physical practice participant (n = 16) was paired during acquisition with an observer (n = 16). The observer was privy to all instructions as well as auditory and visual information that was provided the physical practice participant. The results replicated the results of Experiment 1: Relative-timing information was enhanced by the auditory template for both the physical and observation practice participants. Absolute timing was improved only when the auditory model was coupled with physical practice. Consistent with the proposal of D. M. Scully and K. M. Newell (1985), modeled timing information in physical and observational practice benefited the learning of the relative-timing features of the task, but physical practice was required to enhance absolute timing.


An investigation into the causes of abnormal waste of Ortho-K lenses.
To investigate the reasons for wasting orthokeratology (OK) lenses due to breakage or loss, provide more comprehensive guidelines for the clinical care of lenses and minimize time and costs for patients due to excessive broken and lost lenses. A survey was administered to clinic outpatients who had broken or lost their OK lenses before the regularly scheduled replacement cycle (1-1.5 years). The association between the frequency of OK lens breakage and daily care was assessed using Fisher's exact test and multivariable ordered logistic regression analysis. A total of 306 valid questionnaires were collected. Among the subjects, 141 were male, and 165 were female, with a mean age of 10.57 ± 2.00 years (range: 6-18 years). In the investigation of the causes of OK lens waste, 81.4% of the patients reported lens breakage, 13.1% lost their lenses, and 5.6% of patients experienced both fragmentation and lens loss. More than half of the patients (52.90%) used incorrect lens cleaning techniques. In further analysis of the relationship between the frequency of OK lens fragmentation within a year and daily care habits, a significant difference was observed between the caregiver (P = 0.03) and whether the lenses were cleaned promptly after removal (P < 0.001). Mothers as daily caregivers of OK lenses had a lower frequency of fragmentation in a year compared to nanny or grandparents (P = 0.014, OR = 0.33, 95% CI = 0.13, 0.80). The failure to clean the lenses according to eye care practitioners' guidance was a risk factor for the frequent breakage of OK lenses (P < 0.001. OR = 5.29, 95% CI = 3.15, 8.89). The causes of OK lens waste were mainly attributed to caregivers, care practices and some unexpected situations that can be avoided through optometrists' reminders. Regardless of the reasons for noncompliant behavior leading to breakage or loss of OK lenses, all of the complications can probably be addressed by better and more frequent reinforcement of care procedures by practitioners. Better clinical guidance measures and more frequent reminders could prevent a large proportion of abnormal waste of OK lenses.


Red-shifting the optical response of firefly oxyluciferin with group 15/16 substitutions.
Time-dependent density functional theory has been used to investigate the effects of group 15/16 element substitution on the optical response of firefly oxyluciferin. A range of analogues containing symmetrical substitutions at the N and S atom positions of the naturally-occurring oxyluciferin have been found to have red-shifted electronic excitation energies with the heaviest derivative investigated (As/Se) displaying a shift of -0.69 eV. Fluorescence emission wavelengths for all P- and As-containing derivatives in DMSO are estimated to lie in the 710-930 nm region making them interesting for bio-imaging applications.


Molecular dynamics simulation for ligand-receptor studies. Carbohydrates interactions in aqueous solutions.
The review deals with the problem of the study of ligand-receptor interactions and the use of Molecular Dynamics (MD) simulation to approach such a problem. After a short review of the fundamentals of MD we describe the medium in which all biology takes place, water. Emphasis is put on the water models appropriate for simulation of macromolecular systems explicitly including the water molecules. We consider the quality of the water model both in terms of simplicity and performance to describe the liquid water properties. Heavy water, although not a biologically viable medium, is considered since many experiments make use of it as a solvent. Sweetness of carbohydrates is considered as an example of the procedure suitable to characterize active sites on the ligands. Consideration is given to the computation of the binding constants through molecular dynamics. The computation of the Free Energy is described and illustrated. The potentiality of MD for studies of ligand-receptor interactions is limited by the computer resources, for even with large computing facilities the need of relatively long simulation times severely restricts the study of large systems. A method is described in which several shells are treated at different levels of approximation, form mechanical response and mean electrical field to quantum mechanics, through stochastic dynamics and atomic classical MD. The review closes with a brief account of the perspectives of the method.


Increased susceptibility of mice obtained from in vitro fertilization to global cerebral ischemia-reperfusion injury: possible role of hydrogen sulphide and its biosynthetic enzymes.
Aim of the Study: This study was designed to explore the relative susceptibility of in vitro fertilization (IVF)-conceived mice to global cerebral ischemic injury with the possible role of hydrogen sulphide and enzymes responsible for its production.Materials and Methods: IVF was carried to obtain pups, which were allowed to grow to the age of eight weeks. Thereafter, male mice were subjected to 20 min of global ischemia and 24 h of reperfusion. The mice obtained from other groups including normal mating, superovulation but normal mating and normal mating but embryo implantation were also subjected to global ischemia-reperfusion (I/R) injury.Results: IVF-derived mice exhibited significant more injury in response to I/R injury in comparison to other groups assessed in terms of impairment in locomotor activity, development of motor in coordination, neurological severity score, cerebral infarction and apoptosis markers (caspase-3 activity and Bcl-2 expression). Moreover, there was a relative decrease in the brain levels of hydrogen sulphide (H2S) and its biosynthetic enzymes viz. cystathionine-β-synthase and cystathionine-γ-lyase. Interestingly, the levels of H2S and cystathionine-γ-lyase were significantly low in IVF-derived mice in basal conditions also, i.e. before subjecting to I/R injury and these biochemical alterations were associated with the behavioural deficits in mice, even before subjecting to I/R injury.Conclusion: It is concluded that in vitro fertilization-derived mice are more susceptible to global cerebral I/R injury, which may be possibly due to decreased levels of hydrogen sulphide and its biosynthetic enzymes viz., cystathionine-β-synthase and cystathionine-γ-lyase.


Inadequate Zinc Intake in India: Past, Present, and Future.
India has made important strides in reducing nutritional deficiencies over the past several decades. However, for micronutrients such as zinc, previous studies have suggested a worsening situation, contrary to most other dietary indicators. Adding to this burden, higher carbon dioxide (CO2) levels of 550 ppm, projected to potentially occur within decades, could reduce the zinc content of many staple crops. To assess the historical prevalence of inadequate zinc intake, as well as to estimate the future prevalence attributable to rising CO2. Seven household food consumption surveys between 1983 and 2012 were used to calculate total dietary zinc, phytate, and absorbable zinc intakes and to assess the prevalence of historic inadequacy in zinc intake. The added nutritional effect of elevated CO2 on zinc intake is then modeled. Prevalence of inadequate absorbable zinc intake has increased from 17.1% (15.3%-19.0%) in 1983 to 24.6% (22.3%-27.1%) in 2011-12, corresponding to an additional 82 million people consuming inadequate zinc than would have otherwise if 1983 rates had persisted. These increases in inadequacy have been driven by a relatively constant zinc intake being increasingly insufficient to meet a 5% growth in zinc requirements due to the aging of the population. Reaching 550 ppm CO2 by 2050 could potentially increase the prevalence of inadequate zinc intake by another 3.9 percentage points (2.1-5.8), corresponding to 65 million additional people having inadequate zinc intake. The persistently worsening trend for zinc-opposite most other measures of human nutrition-shows that it may pose an ongoing risk unless addressed.


Comparison of end-of-life vehicles management in 31 European countries: A LMDI analysis.
In 2018, a total of 6,083,000 end-of-life vehicles (EVLs) with a total weight of 6,732,000 tonnes (including waste parts) were generated in the European Union. These vehicles are a subject of particular attention because of their bulky mass, the hazardous components they contain, and the valuable materials present. This article analyses the quantities of ELVs and parts of ELVs that have been recycled, energy recovered, disposed, and reused to assess the impact of the changes in these management options on the total quantities managed. The analysis covered the statistical data on EVLs in 31 European countries for the period 2006-2018, using a new extended version of the logarithmic mean divisia index (LMDI) analysis model, which allows analysts to compare and analyse different waste management options simultaneously. The results show that the changes in the waste intensities and household final consumption expenditure were the greatest drivers of changes in the total quantities managed, while changes in the quantities recycled, energy recovered, disposed of, and reused had the least impact. All countries met or were close to meeting the targets during the period analysed. Changes in the total quantities of waste managed depended on the economic activity, which influenced the quantities of ELVs generated and their subsequent management.


Extracellular matrix-derived products modulate endothelial and progenitor cell migration and proliferation in vitro and stimulate regenerative healing in vivo.
Most adult mammals heal without restorative replacement of lost tissue and instead form scar tissue at an injury site. One exception is the adult MRL/MpJ mouse that can regenerate ear and cardiac tissue after wounding with little evidence of scar tissue formation. Following production of a MRL mouse ear hole, 2mm in diameter, a structure rapidly forms at the injury site that resembles the amphibian blastema at a limb amputation site during limb regeneration. We have isolated MRL blastemal cells (MRL-B) from this structure and adapted them to culture. We demonstrate by RT-PCR that even after continuous culturing of these cells they maintain expression of several progenitor cell markers, including DLK (Pref-1), and Msx-1. We have isolated the underlying extracellular matrix (ECM) produced by these MRL-B cells using a new non-proteolytic method and studied the biological activities of this cell-free ECM. Multiplex microELISA analysis of MRL-B cell-free ECM vs. cells revealed selective enrichment of growth factors such as bFGF, HGF and KGF in the matrix compartment. The cell-free ECM, degraded by mild enzyme treatment, was active in promoting migration and proliferation of progenitor cells in vitro and accelerating wound closure in a mouse full thickness cutaneous wound assay in vivo. In vivo, a single application of MRL-B cell matrix-derived products to full thickness cutaneous wounds in non-regenerative mice, B6, induced re-growth of pigmented hair, dermis and epidermis at the wound site whereas scar tissue replaced these tissues at wound sites in mice treated with vehicle alone. These studies suggest that matrix-derived products can stimulate regenerative healing and avert scar tissue formation in adult mammals.


Attitudes and Intentions toward COVID-19 Vaccination among Health Professions Students and Faculty in Qatar.
A population's desire to take the COVID-19 vaccine is an important predictor of a country's future pandemic management. This cross-sectional study examines the impact of psychological and sociodemographic factors on attitudes toward and intentions to take the COVID-19 vaccine among students and faculty at four colleges of health professions and sciences at Qatar University. The data were collected through an online survey using Google Forms. The survey was distributed through various online platforms. Data analysis was conducted using Stata 16. Of the 364 participants, 9.89% expressed a high mistrust of vaccine safety, and 21.7% were uncertain about their levels of trust; 28% expressed strong worries about unforeseen side effects, whereas 54.95% expressed moderate worries. Furthermore, 7.69% expressed strong concerns and 39.84% showed moderate concerns about commercial profiteering. Approximately 13% of the participants expressed a strong preference towards natural immunity, whilst 45.33% appeared to believe that natural immunity might be better than a vaccine. Importantly, 68.13% of the participants intended to receive the COVID-19 vaccine once it became available, compared to 17.03% who were uncertain and 14.83% who were unwilling to be vaccinated. Our findings differ from the data on vaccine hesitancy among the general population of Qatar. We argue that this gap is due to scientific knowledge and domain of education. Furthermore, although knowledge and awareness may affect vaccine attitudes, mental health and sociodemographic factors play a role in shaping attitudes towards vaccines.


Efficacy of intense screening and treatment for synchronous second primary cancers in patients with esophageal cancer.
The optimum management of esophageal cancers with synchronous second primary cancer (SPC) has not been determined. The aim of this study was to evaluate the efficacy of intense screening and treatment for esophageal cancers with synchronous SPC. Between 1981 and 1997, 1479 patients with esophageal cancers were screened for synchronous SPC during the process of initial staging. Radical treatment was recommended for esophageal cancer and synchronous SPC in cases for whom both cancers were curable. Treatment results for esophageal cancer patients with or without synchronous SPC were compared. Among 1479 patients, 155 (10.5%) were found to have 166 synchronous SPC. Primary sites included the stomach in 65, the head and neck in 44, the colon/rectum in 27, the lung in 14 and other sites in 16 patients. Clinical stages of synchronous SPC were stage I in 41%, stage II in 20%, stage III in 25% and stage IV in 14%. The 5-year overall survival rates by clinical stages of esophageal cancers (stage 0, I, II, III, IV) in patients with synchronous SPC were 51% (95% CI, 23-78%), 43% (95% CI, 18-68%), 11% (95% CI, 0-22%), 14% (95% CI, 0-28%) and 12% (95% CI, 1-22%), respectively. The 5-year overall survival rate for patients with or without synchronous SPC were 20% (95% CI, 13-28%) and 32% (95% CI, 29-35%), respectively. No significant difference was observed between both groups (p = 0.2562). Intense screening and treatment may be justifiable in the light of the high detection rate of curable SPC and the reasonable survival of patients with synchronous SPC. However, a prospective study including cost-benefit analysis is needed to provide the evidence to justify the intense screening and treatment.


Cefiderocol for the Treatment of Infections Due to Metallo-B-lactamase-Producing Pathogens in the CREDIBLE-CR and APEKS-NP Phase 3 Randomized Studies.
In the CREDIBLE-CR and APEKS-NP studies, cefiderocol treatment was effective against gram-negative bacteria producing metallo-B-lactamases; rates of clinical cure (70.8% [17/24]), microbiological eradication (58.3% [14/24]), and day 28 all-cause mortality (12.5% [3/24]) compared favorably with comparators of best-available therapy and high-dose meropenem (40.0% [4/10], 30.0% [3/10], and 50.0% [5/10], respectively).


Mitomycin C, with or without surgery, for the treatment of ocular squamous cell carcinoma in horses.
Ocular lesions in horses, confirmed as squamous cell carcinoma, were treated topically with mitomycin C. Fourteen horses with confirmed ocular squamous cell carcinoma, three of which were affected bilaterally, were included in the study. Eight of the affected eyes were treated topically with mitomycin C alone; in the other nine eyes, the tumours were surgically removed and topical treatment with mitomycin C was then applied. The treatment protocol consisted of 0.2 ml of 0.04 per cent mitomycin C instilled into the conjunctival sac of the affected eye, every six hours, in rounds of seven days of treatment followed by seven days without treatment. This was repeated until full regression of the tumour occurred (up to four rounds of treatment with mitomycin C). Of the eight eyes treated with mitomycin C alone (without surgery), clinical resolution occurred in six cases. Of the nine eyes treated with a combination of surgery and topical mitomycin C, clinical resolution occurred in seven cases. No complications were observed.


Thermoelectricity in fullerene-metal heterojunctions.
Thermoelectricty in heterojunctions, where a single-molecule is trapped between metal electrodes, has been used to understand transport properties at organic-inorganic interfaces. (1) The transport in these systems is highly dependent on the energy level alignment between the molecular orbitals and the Fermi level (or work function) of the metal contacts. To date, the majority of single-molecule measurements have focused on simple small molecules where transport is dominated through the highest occupied molecular orbital. (2, 3) In these systems, energy level alignment is limited by the absence of electrode materials with low Fermi levels (i.e., large work functions). Alternatively, more controllable alignment between molecular orbitals and the Fermi level can be achieved with molecules whose transport is dominated by the lowest unoccupied molecular orbital (LUMO) because of readily available metals with lower work functions. Herein, we report molecular junction thermoelectric measurements of fullerene molecules (i.e., C(60), PCBM, and C(70)) trapped between metallic electrodes (i.e., Pt, Au, Ag). Fullerene junctions demonstrate the first strongly n-type molecular thermopower corresponding to transport through the LUMO, and the highest measured magnitude of molecular thermopower to date. While the electronic conductance of fullerenes is highly variable, due to fullerene's variable bonding geometries with the electrodes, the thermopower shows predictable trends based on the alignment of the LUMO with the work function of the electrodes. Both the magnitude and trend of the thermopower suggest that heterostructuring organic and inorganic materials at the nanoscale can further enhance thermoelectric performance, therein providing a new pathway for designing thermoelectric materials.