A predictive factor of insufficient liver regeneration after preoperative portal vein embolization.
Preoperative portal vein embolization (PVE) is performed to enhance the future remnant liver function (FRLF) and volume (FRLV). However, the volume of the nonembolized liver does not increase enough in some patients, which results in an insufficient FRLF. The aim of this study was to evaluate the predictors of insufficient FRLF after PVE for extended hepatectomy. This retrospective study included 172 patients (107 patients with cholangiocarcinoma, 40 patients with metastatic liver cancer and 25 patients with hepatocellular carcinoma) who underwent PVE before extended hepatectomy. The total liver function was evaluated by measuring the indocyanine green plasma clearance rate (KICG). Computed tomography volumetry was conducted to evaluate the total liver volume and FRLV. The KICG of the future remnant liver (remK) was calculated using the following formula: KICG × FRLV/total liver volume. The safety margin for hepatectomy was set at remK after PVE (post-PVE remK) ≥ 0.05. One hundred and twenty-three patients with a post-PVE remK level of >0.05 underwent hepatectomy without postoperative liver failure [sufficient liver regeneration (SLR) group], and 9 patients with a post-PVE remK level of <0.05 did not due to insufficient FRLF [insufficient liver regeneration (ILR) group]. In the SLR group, the KICG values did not change after PVE (median, 0.144-0.146, p = 0.523); however, the %FRLV and remK increased significantly (35.0-44.3%, p < 0.001 and 0.0488-0.0610, p < 0001, respectively). In contrast, in the ILR group, the KICG values decreased significantly (0.128-0.108, p = 0.021) and the %FRLV increased marginally (27.4-32.6%, p = 0.051). As a result, the remK did not increase significantly (0.0351-0.0365, p = 0.213). A receiver operating characteristic curve demonstrated an remK value of 0.04 obtained before PVE (pre-PVE remK) to be the optimal cutoff point for defective liver regeneration. The univariate and multivariate analyses revealed that a pre-PVE remK value of <0.04 was a factor for ILR. It was also correlated with postoperative liver failure in the analysis of the patients who underwent hepatectomy. The patients in the ILR group did not achieve SLR after PVE due to a significant decrease in the KICG and an insufficient increase in %FRLV. A pre-PVE remK value of <0.04 is a useful predictor of insufficient regeneration of the nonembolized liver, even after PVE.


Examining urban brownfields through the public health "macroscope".
Efforts to cope with the legacy of our industrial cities--blight, poverty, environmental degradation, ailing communities--have galvanized action across the public and private sectors to move vacant industrial land, also referred to as brownfields, to productive use; to curb sprawling development outside urban areas; and to reinvigorate urban communities. Such efforts, however, may be proceeding without thorough investigations into the environmental health and safety risks associated with industrial brownfields properties and the needs of affected neighborhoods. We describe an approach to characterize vacant and underused industrial and commercial properties in Southeast Baltimore and the health and well being of communities living near these properties. The screening algorithm developed to score and rank properties in Southeast Baltimore (n= 182) showed that these sites are not benign. The historical data revealed a range of hazardous operations, including metal smelting, oil refining, warehousing, and transportation, as well as paints, plastics, and metals manufacturing. The data also identified hazardous substances linked to these properties, including heavy metals, solvents, polycyclic aromatic hydrocarbons, plasticizers, and insecticides, all of which are suspected or recognized toxicants and many of which are persistent in the environment. The health analysis revealed disparities across Southeast Baltimore communities, including excess deaths from respiratory illness (lung cancer, chronic obstructive pulmonary disease, influenza, and pneumonia), total cancers, and a "leading cause of death" index and a spatial and statistical relationship between environmentally degraded brownfields areas and at-risk communities. Brownfields redevelopment is a key component of our national efforts to address environmental justice and health disparities across urban communities and is critical to urban revitalization. Incorporating public health into brownfields-related cleanup and land-use decisions will increase the odds for successful neighborhood redevelopment and long-term public health benefits.


The immunomodulatory effect of Sambucol on leishmanial and malarial infections.
A nontoxic dose of Sambucol, an immunomodulator commercially sold as an immune stimulator, was examined in murine models of leishmaniasis and malaria. Sambucol causes a shift in the immune response, as demonstrated in human monocyte cultures, to Th1 (inflammation-associated) responses. Treatment of leishmania-infected mice with Sambucol delayed the development of the disease. As there was no direct IN VITRO anti-leishmanial effect, the observed partial protection IN VIVO is most likely related to immune modulation. Although increased Th1 responses are associated with protection from leishmaniasis, they are considered to be the main immunopathological processes leading to cerebral malaria. Administration of Sambucol to mice prior to and following infection with Plasmodium berghei ANKA increased the incidence of cerebral malaria, while administration of Sambucol after infection had no effect on the disease. The results demonstrate how an inflammatory-like response may alleviate or exacerbate clinical symptoms of disease and hint at the importance of administration timing. The overall effect of immunomodulator administration depends on the ongoing immune response and the Th1/Th2 balance determined by both host and parasite defense mechanisms.


The value of 3D high-resolution IR-prepared fast spoiled gradient-recalled MRI in the diagnosis of meningeal carcinomatosis involving the cranial nerves.
The purpose of this study was to investigate the clinical utility of three-dimension (3D) high-resolution inversion recovery (IR)-prepared fast spoiled gradient-recalled (SPGR) magnetic resonance imaging (MRI) in the diagnosis of cranial nerve meningeal carcinomatosis (MC). A total of 114 patients with MC from January 2015 to March 2020 were enrolled and their MRIs were analyzed retrospectively. All patients underwent MRIs before being administered a contrast agent. Both a 2D conventional MRI sequence and a 3D IR-prepared fast SPGR high-resolution T1-weighted (BRAVO) scan sequence were measured after contrast agent administration. The characteristics of MC and the involved cranial nerves were then examined. Among the 114 MC patients, 81 (71.05%) had cranial nerve enhancement on contrast-enhanced 3D-BRAVO imaging, while only 41 (35.96%) had image enhancement on conventional MRI. The contrast-enhanced 3D-BRAVO displayed stronger image contrast enhancement of the cranial nerves than the conventional MRI (P < 0.001). Furthermore, detection rates for the facial and auditory nerves, trigeminal nerve, oculomotor nerve, sublingual nerve, optic nerve, glossopharyngeal/vagal/accessory nerve, and abductor nerve on contrast-enhanced 3D-BRAVO imaging were 58.77%, 47.37%, 9.65%, 8.77%, 5.26%, 3.51%, and 0.88%, respectively. We found a statistically significant difference between the affected facial and auditory nerves, as well as the trigeminal nerve, oculomotor nerve, sublingual nerve, and optic nerve. In MC, contrast-enhanced 3D-BRAVO imaging displayed the cranial nerves more effectively than 2D conventional enhanced MRI. The facial, auditory, and trigeminal nerves are the primary nerves involved in MC, and improved scanning of these nerves would aid in the early detection and treatment of MC.


[Immunological methods for assessing health in exposure to ambient air pollution].
In the article there have been analyzed the materials obtained in the study of human health state on the results of the study of immunological status. It was shown that the In mass hygienic studies the detection of the state of the human immune system has been shown to be the one of the most promising methods for the determination of human health state, as the immune system is the most vulnerable and feels the changes in the environment. At the same time it was pointed out that the non-invasive method for determining the human immunity is the most accessible.


Mucosal Blood Group Antigen Expression Profiles and HIV Infections: A Study among Female Sex Workers in Kenya.
The ABO blood group antigens are carbohydrate moieties expressed on human red blood cells however; these antigens can also be expressed on some other cells particularly the surface of epithelial cells and may be found in mucosal secretions. In many human populations 80% secrete ABO antigens (termed 'secretors') while 20% do not (termed 'non-secretors'). Furthermore, there are disease conditions that are associated with secretor status. To investigate correlations between secretor status and HIV infection among female sex workers in Nairobi, Kenya. This cross-sectional study recruited 280 female sex workers aged 18-65 years from the Pumwani Majengo cohort, Kenya. Blood typing was determined by serological techniques using monoclonal antibodies to the ABO blood group antigens. Secretor phenotyping was determined using anti-H specific lectins specific to salivary, vaginal and cervical blood group H antigen using the agglutination inhibition technique and correlated to individual HIV sero-status. Participants were additionally screened for Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis. Out of the 280 participants, 212 (75.7%) were secretors and 68 (24.3%) were non-secretors. The incidence of all infections: HIV, Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis was higher among secretors compared to non-secretors. However, this difference was only statistically significant for HIV infection incidence rates: HIV infected secretors (83.7%) versus HIV un-infected secretors (71.8%) (p = 0.029) Based on ABO phenotype stratification, the incidence of HIV infection was higher among blood group A secretors (26/52 = 50%), in comparison to B (12/39 = 33.3%: p = 0.066), AB (3/9 = 33.3%: p = 0.355), and O secretors (36/112 = 32.1%: p = 0.028). This is the first report to document the variable expression of the ABH blood group antigens profiling secretor and non-secretor phenotypes in the female genital tract among a high-risk population in a Kenyan population. These findings suggest the non-secretor phenotype may confer a certain degree of protection against HIV infection.


Informatics Approaches for Harmonized Intelligent Integration of Stem Cell Research.
As biomedical data integration and analytics play an increasing role in the field of stem cell research, it becomes important to develop ways to standardize, aggregate, and share data among researchers. For this reason, many databases have been developed in recent years in an attempt to systematically warehouse data from different stem cell projects and experiments at the same time. However, these databases vary widely in their implementation and structure. The aim of this scoping review is to characterize the main features of available stem cell databases in order to identify specifications useful for implementation in future stem cell databases. We conducted a scoping review of peer-reviewed literature and online resources to identify and review available stem cell databases. To identify the relevant databases, we performed a PubMed search using relevant MeSH terms followed by a web search for databases which may not have an associated journal article. In total, we identified 16 databases to include in this review. The data elements reported in these databases represented a broad spectrum of parameters from basic socio-demographic variables to various cells characteristics, cell surface markers expression, and clinical trial results. Three broad sets of functional features that provide utility for future stem cell research and facilitate bioinformatics workflows were identified. These features consisted of the following: common data elements, data visualization and analysis tools, and biomedical ontologies for data integration. Stem cell bioinformatics is a quickly evolving field that generates a growing number of heterogeneous data sets. Further progress in the stem cell research may be greatly facilitated by development of applications for intelligent stem cell data aggregation, sharing and collaboration process.


Post cholecystectomy bile duct injury: early, intermediate or late repair with hepaticojejunostomy - an E-AHPBA multi-center study.
Treatment of bile duct injuries (BDI) during cholecystectomy depends on the severity of injury and the timing of diagnosis. Standard of care for severe BDIs is hepaticojejunostomy. The aim of this retrospective multi-center study was to assess the optimal timing for repair of BDI with hepaticojejunostomy. Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients with hepaticojejunostomy after BDI from January 2000 to June 2016. Patients were stratified according to the timing of biliary reconstruction with hepaticojejunostomy: early (day 0-7), intermediate (1-6 weeks) and late (6 weeks-6 months). Primary endpoint was re-intervention >90 days after the hepaticojejunostomy and secondary endpoints were severe 90-day complications and liver-related mortality. In total 913 patients from 48 centers were included in the analysis. In 401 patients (44%) the bile duct injury was diagnosed intraoperatively, and 126 patients (14%) suffered from concomitant vascular injury. In multivariable analysis the timing of hepaticojejunostomy had no impact on postoperative complications, the need for re-intervention after 90 days nor liver-related mortality. The rate of re-intervention more than 90 days after the hepaticojejunostomy was significantly increased in male patients but decreased in older patients. Severe co-morbidity increased the risk for liver-related mortality (HR 3.439; CI 1.37-8.65; p = 0.009). After BDI occurring during cholecystectomy, the timing of biliary reconstruction with hepaticojejunostomy did not have any impact on severe postoperative complications, the need for re-intervention or liver-related mortality. Individualised treatment after iatrogenic bile duct injury is still advisable.


IQ and the association with myopia in children.
To evaluate the association between intelligence and myopia in children. Cycloplegic refraction and ocular biometry parameters, including axial length, vitreous chamber depth, lens thickness, anterior chamber depth, and corneal curvature were obtained in 1204 Chinese school children aged 10 to 12 years from three schools who were participants in the Singapore Cohort Study Of the Risk Factors for Myopia (SCORM). Intelligence quotient (IQ) was assessed using the nonverbal Raven Standard Progressive Matrix test. After controlling for age, gender, school, parental myopia, father's education, and books read per week, myopia (spherical equivalent [SE]) of at least -0.5 D was associated with high nonverbal IQ (highest quartile) versus low IQ (lowest quartile) (odds ratio = 2.4; 95% confidence interval, 1.7-3.4). Controlling for the same factors, children with higher nonverbal IQ scores had significantly more myopic refractions (-1.86 D for children with nonverbal IQ in the highest quartile compared with -1.24 D for children with nonverbal IQ in the lowest quartile; P = 0.002) and longer axial lengths (24.06 mm versus 23.80 mm; P = 0.022). Nonverbal IQ accounted for a greater proportion of the variance in refraction compared with books read per week. Nonverbal IQ may be an independent risk factor of myopia, and this relationship may not be explained merely by increased reading (books per week) among myopes. An interesting observation is that nonverbal IQ may be a stronger risk factor for myopia compared with books read per week. The complexity of the relationships between nonverbal IQ, reading, and myopia warrant additional studies to clarify any cause-effect relationship.


[Principles of analgesia and sedation].
This lecture outlines the current pharmacological concepts of sedation and analgesia in the critically ill patient requiring intensive care therapy. The primary goal is to sedate such patients so that they tolerate mechanical ventilation, as well as the therapeutic and diagnostic procedures that are routinely performed on an intensive care ward. The pharmacological regimen comprises both anxiolytic and analgesic drugs. So far, no drug combination has been identified as the ideal therapy; the standard deviation of successful analgosedation is large due to an unpredictable individual response. Because the drugs currently used are free of toxic side effects, the selection made is mainly determined by factors relating to pharmacokinetic criteria, such as short half-life of action or a predictable time of elimination. So far, the selection or combination of certain drugs has not been found to influence the patient's outcome in severe disease states such as sepsis, multiple trauma, or neurotrauma. "Good quality" of sedation and analgesia is still judged by its ability to suppress tachycardia, hypertension, hyperventilation or respiratory efforts against mechanical ventilation and the absence of increases in intracranial pressure during therapeutic manoeuvres.


Comparison of frictional resistance between passive self-ligating brackets and slide-type low-friction ligature brackets during the alignment and leveling stage.
To compare the frictional resistance between passive self-ligating brackets and conventional brackets with low-friction ligature under bracket/archwire and root/bone interface during dental alignment and leveling. A tridimensional model of the maxilla and teeth of a patient treated with conventional brackets, and slide ligatures was generated employing the SolidWorks modeling software. SmartClip self-ligating brackets and Logic Line conventional brackets were assembled with slide low-friction ligatures, utilizing archwires with different diameters and alloys used for the alignment and leveling stage. Friction caused during the bracket/archwire interface and stress during the bone/root interface were compared through a finite element model. SmartClip and Logic Line brackets with slide elastomeric low-friction elastomeric ligature showed similar frictional stress values of 0.50 MPa and 0.64 MPa, respectively. Passive self-ligating brackets transmitted a lower load along the periodontal ligament, compared to conventional brackets with a low-friction ligature. Slide low-friction elastomeric ligatures showed frictional forces during the bracket/archwire interface similar to those of the SmartClip brackets, while the distribution of stresses and deformations during the root/bone interface were lower in the passive self-ligating brackets. Key words:Orthodontic friction, finite element analysis, orthodontic brackets, orthodontic wires.


Acceptability and utility of digital well-being and mental health support for university students: A pilot study.
To assess the acceptability and explore the utility of a novel digital platform designed as a student-facing well-being and mental health support. An adapted version of i-spero® was piloted as a student-facing well-being support and as part of routine university-based mental health care. In both pathways, student participants completed baseline demographics and brief validated measures of well-being and mental health. Weekly measures of anxiety (GAD-7) and depression (PHQ-9) and a Week 8 Experience Survey were also scheduled. Integrated mixed methods analysis was used to assess acceptability and explore the utility of these platforms. Students in the well-being (n = 120) and care pathways (n = 121) were mostly female and between 19 and 22 years of age. Baseline screen positive rates for anxiety and depression were high in both the well-being (68%) and care pathways (80%). There was a substantial drop in adherence over Week 1 (50% well-being; 40% care) followed by minor attrition up to Week 8. Anxiety and depressive symptom levels improved from baseline in students who dropped out after Week 1 (p ≤ .06). The student experience was that i-spero® improved their emotional self-awareness, understanding of progress in care, and knowledge about when to seek help. Most students agreed (>75%) that i-spero® should form part of regular university student wellness support. Digital well-being and mental health support seems acceptable to university students; however, engagement and persistence are areas for further development. Such digital tools could make a positive contribution to an evidence-based stepped approach to student well-being and mental health support.


ERRα augments HIF-1 signalling by directly interacting with HIF-1α in normoxic and hypoxic prostate cancer cells.
Adaptation of cancer cells to a hypoxic microenvironment is important for their facilitated malignant growth and advanced development. One major mechanism mediating the hypoxic response involves up-regulation of hypoxia-inducible factor 1 (HIF-1) expression, which controls reprogramming of energy metabolism and angiogenesis. Oestrogen-related receptor-α (ERRα) is a pivotal regulator of cellular energy metabolism and many biosynthetic pathways, and has also been proposed to be an important factor promoting the Warburg effect in advanced cancer. We and others have previously shown that ERRα expression is increased in prostate cancer and is also a prognostic marker. Here we show that ERRα is oncogenic in prostate cancer and also a key hypoxic growth regulator. ERRα-over-expressing prostate cancer cells were more resistant to hypoxia and showed enhanced HIF-1α protein expression and HIF-1 signalling. These effects could also be observed in ERRα-over-expressing cells grown under normoxia, suggesting that ERRα could function to pre-adapt cancer cells to meet hypoxia stress. Immunoprecipitation and FRET assays indicated that ERRα could physically interact with HIF-1α via its AF-2 domain. A ubiquitination assay showed that this ERRα-HIF-1α interaction could inhibit ubiquitination of HIF-1α and thus reduce its degradation. Such ERRα-HIF-1α interaction could be attenuated by XCT790, an ERRα-specific inverse agonist, resulting in reduced HIF-1α levels. In summary, we show that ERRα can promote the hypoxic growth adaptation of prostate cancer cells via a protective interaction with HIF-1α, suggesting ERRα as a potential therapeutic target for cancer treatment.


Dendritic cells at the end of the millennium.
We have recently proposed a dual role for dendritic cells (DC) in the amplification of innate immune responses and in the activation of adaptive immune responses. The DC are localized along the major routes of entry of micro-organisms, where they perform a sentinel function for incoming pathogens. Soon after interaction with appropriate stimuli, DC undergo a coordinated process of maturation and respond to danger signals by re- programming their functions. The DC first regulate leucocyte recruitment at the site of inflammation, through the production of chemokines, inflammatory cytokines and interferons, and then they acquire migratory properties and undergo a rapid switch in chemokine receptor expression. This allows them to leave the inflamed tissue and to reach the lymph node T cell area. During this migration, DC complete their maturation process and acquire the ability to prime T cell responses. Thus, DC bridge innate and adaptive immunity.


New Pipeline Flex device: initial experience and technical nuances.
Flow diverter stents (FDS) have been described as a breakthrough in the treatment of intracranial aneurysms. Of the various flow diverter models, the Pipeline device has been the main approved and used device, with established and good long-term results. To present the first series of patients treated with its new version, the Pipeline Flex device. This has kept the same device design and configuration but redesigned and completely modified the delivery system. In this technical report, we include 10 consecutive patients harboring 12 saccular aneurysms of the anterior circulation. We report the main changes on the system, immediate results, and technical nuances with illustrative cases. We implanted 12 devices, including 11 Pipeline Flex and one Pipeline device. We used the old version in one case that required a second layer with a short length not available in the Pipeline Flex size range. All attempts at treatment were successful and no device was discharged or removed. Recovery was required or used in half of the cases with good or excellent performance, except in one case that presented with multiple proximal loops and tight curves. We had two transitory events without ischemic lesions on MRI that recovered 1 and 4 h after all patients were discharged home asymptomatic. Pipeline Flex represents a major advance in FDS technology. The redesigned system has significantly improved the deployment of the Pipeline stent, by enabling the operator to resheath the device. It has the potential to continue revolutionizing the endovascular approach for intracranial aneurysms.


High resolution NMR spectroscopy of nanocrystalline proteins at ultra-high magnetic field.
Magic-angle spinning (MAS) solid-state NMR (SSNMR) spectroscopy of uniformly-(13)C,(15)N labeled protein samples provides insight into atomic-resolution chemistry and structure. Data collection efficiency has advanced remarkably in the last decade; however, the study of larger proteins is still challenged by relatively low resolution in comparison to solution NMR. In this study, we present a systematic analysis of SSNMR protein spectra acquired at 11.7, 17.6 and 21.1 Tesla ((1)H frequencies of 500, 750, and 900 MHz). For two protein systems--GB1, a 6 kDa nanocrystalline protein and DsbA, a 21 kDa nanocrystalline protein--line narrowing is demonstrated in all spectral regions with increasing field. Resolution enhancement is greatest in the aliphatic region, including methine, methylene and methyl sites. The resolution for GB1 increases markedly as a function of field, and for DsbA, resolution in the C-C region increases by 42%, according to the number of peaks that can be uniquely picked and integrated in the 900 MHz spectra when compared to the 500 MHz spectra. Additionally, chemical exchange is uniquely observed in the highest field spectra for at least two isoleucine C delta 1 sites in DsbA. These results further illustrate the benefits of high-field MAS SSNMR spectroscopy for protein structural studies.


High glucose and insulin enhance uPA expression, ROS formation and invasiveness in breast cancer-derived cells.
Accumulating evidence indicates that type 2 diabetes is associated with an increased risk to develop breast cancer. This risk has been attributed to hyperglycemia, hyperinsulinemia and chronic inflammation. As yet, however, the mechanisms underlying this association are poorly understood. Here, we studied the effect of high glucose and insulin on breast cancer-derived cell proliferation, migration, epithelial-mesenchymal transition (EMT) and invasiveness, as well as its relationship to reactive oxygen species (ROS) production and the plasminogen activation system. MDA-MB-231 cell proliferation, migration and invasion were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), scratch-wound and matrigel transwell assays, respectively. ROS production was determined using 2' 7'-dichlorodihydrofluorescein diacetate. The expression of E-cadherin, vimentin, fibronectin, urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1) were assessed using qRT-PCR and/or Western blotting assays, respectively. uPA activity was determined using gel zymography. We found that high glucose stimulated MDA-MB-231 cell proliferation, migration and invasion, together with an increased expression of mesenchymal markers (i.e., vimentin and fibronectin). These effects were further enhanced by the simultaneous administration of insulin. In both cases, the invasion and growth responses were found to be associated with an increased expression of uPA, uPAR and PAI-1, as well as an increase in active uPA. An osmolality effect of high glucose was excluded by using mannitol at an equimolar concentration. We also found that all changes induced by high glucose and insulin were attenuated by the anti-oxidant N-acetylcysteine (NAC) and, thus, depended on ROS production. From our data we conclude that hyperglycemia and hyperinsulinemia can promote breast cancer cell proliferation, migration and invasion. We found that these features were associated with increased expression of the mesenchymal markers vimentin and fibronectin, as well as increased uPA expression and activation through a mechanism mediated by ROS.


Meningococcal disease in a large urban population (Barcelona, 1987-1992): predictors of dismal prognosis. Barcelona Meningococcal Disease Surveillance Group.
Studies on meningococcal disease in large urban communities have rarely been performed and are usually based on passive epidemiologic surveillance. Active surveillance may provide new insights. To determine epidemiologic, clinical, and bacteriological characteristics and predictors of dismal prognosis (death and sequelae) in meningococcal disease. Prospective, population-based study. All the acute care hospitals (n = 24) in Barcelona, Spain. The 643 patients whose conditions were diagnosed from 1987 through 1992 were detected by 2 active surveillance methods. Incidence and notification to Public Health Service. Clinical and bacteriological features were determined. Dismal prognosis predictors were determined by logistic regression. Average annual incidence was 6.41 per 100,000 inhabitants, with no clear trend of change (P = .08). Sensitivity of the Public Health Service surveillance system was 69.1%. Children younger than 10 years from the inner city were at higher risk than those from the highest income district (relative risk, 3.00; 95% confidence interval [CI], 1.84-5.06). Increasing annual incidence of serogroup C (0.82-1.29/100,000; P = .008) and decreasing incidence of serogroup B (5.11-2.82/100,000; P = .004) was noted. Average annual mortality was 0.40 per 100,000 inhabitants, while the annual average potential years of life lost was 18 per 100,000 inhabitants. Overall case-fatality rate was 6.4%. Independent predictors of death were hemorrhagic diathesis (odds ratio [OR], 63; 95% CI, 21-194), focal neurologic signs (OR, 10; 95% CI, 3-30), and age 60 years or older (OR, 6; 95% CI, 2-17), whereas preadmission antibiotic therapy was associated with favorable outcome (OR, 0.07; 95% CI, 0.02-0.3). Four percent of survivors presented with sequelae. Independent predictors of sequelae were hemorrhagic diathesis (OR, 21; 95% CI, 3-131), focal neurologic signs (OR, 16; 95% CI, 5-53), age 60 years or older (OR, 7; 95% CI, 2-26), and age between 15 and 59 years (OR, 5; 95% CI, 2-14), whereas preadmission antibiotic therapy had a protective effect (OR, 0.2; 95% CI, 0.04-0.5). Active epidemiologic surveillance significantly improved detection of cases and allowed us to observe that meningococcal disease still causes much morbidity and mortality, especially among children living in the inner city. Hemorrhagic diathesis, focal neurologic signs, and age were independent predictors of dismal prognosis, whereas preadmission antibiotic therapy had a protective effect.


Client-centered approach to develop a seating clinic satisfaction questionnaire: a qualitative study.
The purpose of this study was to develop a program evaluation tool through a client-centered approach. Client satisfaction questionnaires previously developed for service recipients of a pediatric seating clinic have reflected the professionals' views on what should be asked. Seven parents and caregivers of recent service recipients of the seating clinic participated in tape-recorded semistructured interviews. They were asked their views on the seating clinic, how the service could be improved, and the quality of the seat received through the clinic. Data were coded into nine themes related to the process and the product. Using these themes and the vocabulary used by the participants, we developed a satisfaction questionnaire. The validity of the questionnaire was evaluated by requesting feedback on clarity, content, and design from all participants and from a panel of five health professionals. A client-centered approach can be used to develop a client satisfaction tool that reflects the needs of the users. Future work will involve testing the tool in the clinical setting.


Developmental heterogeneity of embryonic neuroendocrine chromaffin cells and their maturation dynamics.
During embryonic development, nerve-associated Schwann cell precursors (SCPs) give rise to chromaffin cells of the adrenal gland via the "bridge" transient stage, according to recent functional experiments and single cell data from humans and mice. However, currently existing data do not resolve the finest heterogeneity of developing chromaffin populations. Here we took advantage of deep SmartSeq2 transcriptomic sequencing to expand our collection of individual cells from the developing murine sympatho-adrenal anlage and uncover the microheterogeneity of embryonic chromaffin cells and their corresponding developmental paths. We discovered that SCPs on the splachnic nerve show a high degree of microheterogeneity corresponding to early biases towards either Schwann or chromaffin terminal fates. Furthermore, we found that a post-"bridge" population of developing chromaffin cells gives rise to persisting oxygen-sensing chromaffin cells and the two terminal populations (adrenergic and noradrenergic) via diverging differentiation paths. Taken together, we provide a thorough identification of novel markers of adrenergic and noradrenergic populations in developing adrenal glands and report novel differentiation paths leading to them.


Virtopsy: forensic traumatology of the subcutaneous fatty tissue; multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) as diagnostic tools.
Traumatic lesions of the subcutaneous fatty tissue provide important clues for forensic reconstruction. The interpretation of these patterns requires a precise description and recording of the position and extent of each lesion. During conventional autopsy, this evaluation is performed by dissecting the skin and subcutaneous tissues in successive layers. In this way, depending on the force and type of impact (right angle or tangent), several morphologically distinct stages of fatty tissue damage can be differentiated: perilobular hemorrhage (I), contusion (II), or disintegration (III) of the fat lobuli, and disintegration with development of a subcutaneous cavity (IV). In examples of virtopsy cases showing blunt trauma to the skin and fatty tissue, we analyzed whether these lesions can also be recorded and classified using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI). MSCT has proven to be a valuable screening method to detect the lesions, but MRI is necessary in order to properly differentiate and classify the grade of damage. These noninvasive radiological diagnostic tools can be further developed to play an important role in forensic examinations, in particular when it comes to evaluating living trauma victims.


Metastatic disease of the spine: evaluation and treatment.
Treatment of patients with metastatic disease of the spine continues to be a challenging problem. Advances in imaging studies and surgical techniques have improved patient outcomes with operative intervention. However, the lack of a validated set of criteria to determine spinal instability makes patient selection for surgical intervention difficult. Multiple classification systems that assist surgeons in determining appropriate operative candidates have been proposed. We will review current information on the evaluation and treatment of metastatic disease of the spine and discuss classification systems that assist in determining appropriate operative candidates.


Indomethacin decreases arterial blood pressure and plasma renin activity in rats with aortic ligation.
Severe renovascular hypertension was produced in rats by complete aortic ligation between the origin of the renal arteries. Six days after coarctation, a carotid cannula was implanted and mean arterial blood pressure (MABP) and plasma renin activity (PRA) were determined. Subsequently, indomethacin (5 mg/kg in oil) or vehicle was administered subcutaneously three times in the following 24-hour period. On day 7, MABP and PRA were again determined. Indomethacin reduced MABP from 179.0 +/- 6.7 to 156.5 +/- 8.8 mm Hg (P less than 0.002, n = 11) and PRA from 21.2 +/- 7.3 to 9.3 +/- 2.9 ng AI/ml per hr (P less than 0.045, n = 10), whereas vehicle treatment did not alter either MABP or PRA (n = 6). There was a significant association between the decrease in MABP and the percentage decrease in PRA following indomethacin treatment (r = 0.766, P less than 0.016). A similar study was performed in aortic ligated rats in which the left kidney was removed at the time of ligation. In these animals, 6 days after surgery, MABP and PRA were 128.0 +/- 5.9 mm Hg and 0.11 +/- 0.06 ng AI/ml per hr (n = 6), respectively, and indomethacin had no effect on either MABP or PRA. These data provide evidence that the prostaglandin system is involved in the release of renin and in the pathogenesis of elevated blood pressure in this model of renin-dependent hypertension.


The Role of Dietary Fats in the Development and Prevention of Necrotizing Enterocolitis.
Necrotizing enterocolitis (NEC) is a significant cause of mortality and morbidity in preterm infants. The pathogenesis of NEC is not completely understood; however, intestinal immaturity and excessive immunoreactivity of intestinal mucosa to intraluminal microbes and nutrients appear to have critical roles. Dietary fats are not only the main source of energy for preterm infants, but also exert potent effects on intestinal development, intestinal microbial colonization, immune function, and inflammatory response. Preterm infants have a relatively low capacity to digest and absorb triglyceride fat. Fat may thereby accumulate in the ileum and contribute to the development of NEC by inducing oxidative stress and inflammation. Some fat components, such as long-chain polyunsaturated fatty acids (LC-PUFAs), also exert immunomodulatory roles during the early postnatal period when the immune system is rapidly developing. LC-PUFAs may have the ability to modulate the inflammatory process of NEC, particularly when the balance between n3 and n6 LC-PUFAs derivatives is maintained. Supplementation with n3 LC-PUFAs alone may have limited effect on NEC prevention. In this review, we describe how various fatty acids play different roles in the pathogenesis of NEC in preterm infants.


Assessment of the impact of genetically modified LibertyLink® maize on reproductive function and progeny development of Wistar rats in three generations.
This publication presents the assessment of the impact of genetically modified (GM) LibertyLink® maize on reproductive function, prenatal and postnatal progeny development of Wistar rats over three generations. The animals were divided into two groups, which were fed with rodent diet with inclusion of GM LibertyLink® ('test' group) and non-GM near-isogenic counterpart ('control' group) maize varieties. The maize was included into the diet at maximum possible level (between 32 and 33%) not causing nutritional imbalance or metabolic disturbance for the experimental animals. Data analysis showed no impact of LibertyLink® maize on the animals' fertility: the observed mating efficiency in both groups was within the normal expected range values under the given experiment conditions. The comparison of progeny prenatal development in the generations F0-F2 has not shown any differences between the groups. Analysis of the physical development of the F0-F2 progeny or pups body weight and length progress did not show any abnormalities. The average number of pups per litter in the control and test groups was within the expected range of variations. Therefore, the results should be considered as direct evidence of the lack of any reproductive toxicity of LibertyLink® maize (a.k.a. T25 maize).


Genetic Variants in METTL14 are Associated with the Risk of Acute Lymphoblastic Leukemia in Southern Chinese Children: A Five-Center Case-Control Study.
Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. METTL14, an N6-methyladenosine (m6A) modification protein, plays several roles in cancer development and is involved in the pathogenesis of various types of cancers. However, the role of METTL14 gene single nucleotide polymorphisms (SNPs) in pediatric ALL susceptibility remains to be investigated. A case-control design and multinomial logistic regression were used to develop models to estimate the overall risk for pediatric ALL and three METTL14 gene SNPs (rs298982 G/A, rs298981 A/G and rs1064034 T/A) in 808 cases and 1340 controls, which were genotyped using a TaqMan assay. The associations were estimated by odds ratios (ORs) with their 95% confidence intervals (CIs). Furthermore, stratified analysis was performed to explore associations of rs298982 and rs1064034 with pediatric ALL susceptibility in terms of age, sex, immunophenotype, minimal residual disease (MRD), and other clinical characteristics. Among the three analyzed SNPs, rs298982 G/A and rs1064034 T/A exhibited a significant association with decreased childhood ALL risk, while rs298981 A/G exhibited no difference. In stratified analysis, rs298982 GA/AA and rs1064034 TA/AA had a protective effect in children <120 months of age and males, common B ALL, TEL-AML, non gene fusion, normal diploid, and high WBC. However, the rs1064034 TA/AA genotype was associated with an increased risk of mixed immunophenotyping. Compared with the reference haplotype GAT, haplotypes CAA, CGT and CGA were significantly associated with elevated ALL risk, while haplotype GGT was significantly associated decreased ALL risk. Moreover, subjects carrying rs298982 A or rs1064034 A exhibited less minimal MRD after induced chemotherapy. Functional annotations revealed that METTL14 gene SNPs rs298982 G/A and rs1064034 T/A could be potential functional variants. In conclusion, METTL14 gene polymorphisms influence the risk of ALL in southern Chinese children and might be potential biomarkers for pediatric ALL susceptibility and chemotherapeutics.


Tick infestations of white-tailed deer in Alabama.
Four species of ticks were collected from 537 white-tailed deer (Odocoileus virginianus), examined during the hunting seasons (November to January) of 1988-89 and 1989-90 at selected locations in Alabama (USA). Ixodes scapularis was the most common tick recovered (2,060 specimens) and infested 54% of the deer. Dermacentor albipictus was the second most frequent tick (1,253 specimens) and infested 15% of the deer. Amblyomma americanum was the third most frequent tick (315 specimens) and infested 24% of the deer; this was the only species of tick collected from deer at all sampling locations. Amblyomma maculatum was an infrequent parasite (five specimens) and infested only 1% of the deer; this tick species was only recorded during the 1989-90 season. Year-to-year and geographical differences in tick infestation parameters were noted. The data are compared with those reported for previous surveys of ticks infesting white-tailed deer in Alabama and adjacent states.


Erf Affects Commitment and Differentiation of Osteoprogenitor Cells in Cranial Sutures via the Retinoic Acid Pathway.
ETS2 repressor factor (ERF) haploinsufficiency causes late-onset craniosynostosis (CRS) (OMIM entry 600775; CRS4) in humans, while in mice Erf insufficiency also leads to a similar multisuture synostosis phenotype preceded by mildly reduced calvarium ossification. However, neither the cell types affected nor the effects per se have been identified so far. Here, we establish an ex vivo system for the expansion of suture-derived mesenchymal stem and progenitor cells (sdMSCs) and analyze the role of Erf levels in their differentiation. Cellular data suggest that Erf insufficiency specifically decreases osteogenic differentiation of sdMSCs, resulting in the initially delayed mineralization of the calvarium. Transcriptome analysis indicates that Erf is required for efficient osteogenic lineage commitment of sdMSCs. Elevated retinoic acid catabolism due to increased levels of the cytochrome P450 superfamily member Cyp26b1 as a result of decreased Erf levels appears to be the underlying mechanism leading to defective differentiation. Exogenous addition of retinoic acid can rescue the osteogenic differentiation defect, suggesting that Erf affects cranial bone mineralization during skull development through retinoic acid gradient regulation.


Thrombin induces production of growth factors from aortic smooth muscle cells.
Myointimal hyperplasia is a common complication of arterial recontructive surgery. The serine protease thrombin has a major role in vessel wall healing and eventual myointimal hyperplasia formation. The aim of this study was to determine the effect of thrombin on the production of PDGF AA and bFGF by arterial smooth muscle cells. Bovine smooth muscle cells were stimulated with thrombin in a serum-free culture. The release of PDGF AA and bFGF was assessed by ELISA. The effect of thrombin on the proliferation of confluent monolayers of bovine smooth muscle cells was determined by tritiated thymidine uptake. Smooth muscle cells stimulated with thrombin released more PDGF AA (P < 0.001) and bFGF (P < 0.001) than the control. Addition of anti-PDGF AA and anti-bFGF antibodies to the medium of smooth muscle cell cultures neutralized the mitogenic effect of thrombin (P < 0.001). The findings of our study suggest that thrombin may lead to myointimal hyperplasia formation through induction of PDGF and bFGF production by smooth muscle cells.


A computational account of threat-related attentional bias.
Visual selective attention acts as a filter on perceptual information, facilitating learning and inference about important events in an agent's environment. A role for visual attention in reward-based decisions has previously been demonstrated, but it remains unclear how visual attention is recruited during aversive learning, particularly when learning about multiple stimuli concurrently. This question is of particular importance in psychopathology, where enhanced attention to threat is a putative feature of pathological anxiety. Using an aversive reversal learning task that required subjects to learn, and exploit, predictions about multiple stimuli, we show that the allocation of visual attention is influenced significantly by aversive value but not by uncertainty. Moreover, this relationship is bidirectional in that attention biases value updates for attended stimuli, resulting in heightened value estimates. Our findings have implications for understanding biased attention in psychopathology and support a role for learning in the expression of threat-related attentional biases in anxiety.


Novel Anti-Tuberculosis Nanodelivery Formulation of Ethambutol with Graphene Oxide.
Tuberculosis (TB) is a bacterial disease responsible for millions of infections and preventable deaths each year. Its treatment is complicated by patients' noncompliance due to dosing frequency, lengthy treatment, and adverse side effects associated with current chemotherapy. However, no modifications to the half-a-century old standard chemotherapy have been made based on a nanoformulation strategy to improve pharmacokinetic efficacy. In this study, we have designed a new nanodelivery formulation, using graphene oxide as the nanocarrier, loaded with the anti-TB antibiotic, ethambutol. The designed formulation was characterized using a number of molecular analytical techniques. It was found that sustained release of the drug resulted in better bioavailability. In addition, the designed formulation demonstrated high biocompatibility with mouse fibroblast cells. The anti-TB activity of the nanodelivery formulation was determined using whole-cell resazurin microtiter plate assay, modified-spot culture growth inhibition assay, and biofilm inhibition assay. The nanodelivery formulation showed good anti-mycobacterial activity. The anti-mycobacterial activity of Ethambutol was unaffected by the drug loading and release process. The results of this study demonstrated the potential of this new nanodelivery formulation strategy to be considered for modifying existing chemotherapy to yield more efficacious antibiotic treatment against TB.


The meaning of vaguely quantified frequency response options on a quality of life scale depends on respondents' medical status and age.
Self-report items in quality of life (QoL) scales commonly use vague quantifiers like "sometimes" or "often" to measure the frequency of health-related experiences. This study examined whether the meaning of such vaguely quantified response options differs depending on people's medical status and age, which may undermine the validity of QoL group comparisons. Respondents (n = 600) rated the frequency of positive and negative QoL experiences using vague quantifiers (never, rarely, sometimes, often, always) and provided open-ended numeric frequency counts for the same items. Negative binomial regression analyses examined whether the numeric frequencies associated with each vague quantifier differed between medical status (no vs. one or more medical conditions) and age (18-40 vs. 60+ years) groups. Compared to respondents without a chronic condition, those with a medical condition assigned a higher numeric frequency to the same vague quantifiers for negative QoL experiences; this effect was not evident for positive QoL experiences. Older respondents' numeric frequencies were more extreme (i.e., lower at the low end and somewhat higher at the high end of the response range) than those of younger respondents. After adjusting for these effects, differences in QoL became somewhat more pronounced between medical status groups, but not between age groups. The results suggest that people with different medical backgrounds and age do not interpret vague frequency quantifiers on a QoL scale in the same way. Open-ended numeric frequency reports may be useful to detect and potentially correct for differences in the meaning of vague quantifiers.


Stapled anopexy: postoperative course and functional outcome in 400 patients.
We performed a retrospective analysis of postoperative course and functional outcome after at least six months' follow-up in a series of 400 consecutive patients who underwent stapled anopexy. All patients were evaluated at one week and one month after surgery and then according to symptoms. A clinical or telephone follow-up was obtained for all patients. The last 50 patients were prospectively evaluated with an obstructive defecation syndrome score and Wexner continence and constipation score before operation and six months after anopexy. There were no intraoperative complications. Postoperative bleeding that requires reoperation was observed in 11 patients, most cases (9/11) occurring in the early experience (first 50 patients). After a median follow-up of 6.1 years, four patients required reoperation. After anopexy, we observed an improvement in patients who present disturbance in defecation. The difference between the median obstructive defecation syndrome score before and after operation was statistically significant. Wexner score showed improvement without significant difference. Treatment of hemorrhoids with circular stapler seems to be effective with low morbidity and high satisfaction rate because of reduced postoperative pain and rapid recovery. This technique also allows improvement of obstructive defecation symptoms, which are seldom studied in patients with hemorrhoids.


Telomeres in evolution and evolution of telomeres.
This paper examines telomeres from an evolutionary perspective. In the monocot plant order Asparagales two evolutionary switch-points in telomere sequence are known. The first occurred when the Arabidopsis-type telomere was replaced by a telomere based on a repeat motif more typical of vertebrates. The replacement is associated with telomerase activity, but the telomerase has low fidelity and this may have implications for the binding of telomeric proteins. At the second evolutionary switch-point, the telomere and its mode of synthesis are replaced by an unknown mechanism. Elsewhere in plants (Sessia, Vestia, Cestrum) and in arthropods, the telomere "typical" of the group is lost. Probably many other groups with "unusual" telomeres will be found. We question whether telomerase is indeed the original end-maintenance system and point to other candidate processes involving t-loops, t-circles, rolling circle replication and recombination. Possible evolutionary outcomes arising from the loss of telomerase activity in alternative lengthening of telomere (ALT) systems are discussed. We propose that elongation of minisatellite repeats using recombination/replication processes initially substitutes for the loss of telomerase function. Then in more established ALT groups, subtelomeric satellite repeats may replace the telomeric minisatellite repeat whilst maintaining the recombination/replication mechanisms for telomere elongation. Thereafter a retrotransposition-based end-maintenance system may become established. The influence of changing sequence motifs on the properties of the telomere cap is discussed. The DNA and protein components of telomeres should be regarded--as with any other chromosome elements--as evolving and co-evolving over time and responding to changes in the genome and to environmental stresses. We describe how telomere dysfunction, resulting in end-to-end chromosome fusions, can have a profound effect on chromosome evolution and perhaps even speciation.


Effects of Common Anti-epileptic Drugs on the Serum Levels of Homocysteine and Folic Acid.
Elevated total plasma homocysteine has been established as an independent risk factor for CVD. A strong relationship between plasma homocysteine levels and mortality has been reported in patients with CAD. Interference with folate and homocysteine metabolism by some drugs, may lead to increased plasma homocysteine levels. The object of the study was to examine the effect of AEDs on the serum concentrations of folic acid. A total of 22, older than 18-year-old, epileptic patients, admitted in the Neurology Clinic, who were treated with AED at least for one year were selected. Twenty-two sex- and age-range-matched controls were enrolled in the study. Concentrations of total homocysteine and folic acid in the serum were measured in a fasted status. Demographic and medicine information was collected via a questionnaire. Data were analyzed by spss(16) software. Mean of serum Hcy concentration in the patients was significantly higher compared to that in the controls (p = 0.04). Serum folic acid had a nonsignificant negative correlation with the dose of drug used (p = 0.2). Serum homocysteine was not significantly correlated with the dose and duration of drug consumption (p values were 0.4, 0.24, respectively). Serum homocysteine was not significantly correlated with the kind of drug (p = 0.4), but folic acid concentration was significantly lower in the monotherapy group than in the poly therapy group (p = 0.02). Homocysteine (Hcy) was not different between the epileptic and nonepileptic groups, although the means of the serum folic acid were similar. Possible mechanisms by which AEDs could cause hyper-homocysteinemia might be through the dysfunction of homocysteine metabolism, the acceleration of vitamin metabolism, and the interference in the metabolism of folic acid coenzymes.


Assessment and management of meningitis following cerebellopontine angle surgery.
The development of postoperative meningitis is a known complication of surgery in the cerebellopontine angle. The management of meningitis and suspected meningitis following surgery in the cerebellopontine angle is of particular interest to neurotologists and others operating in this region. Both bacterial and aseptic meningitis are known to occur in the postoperative period. Substantial differences exist between community-acquired meningitis and postoperative meningitis. Mortality from postoperative bacterial meningitis is rare in patients undergoing resection of an acoustic neuroma. In most instances, reliable early differentiation of bacterial versus aseptic meningitis is not currently possible. Guidance in the management of postoperative patients suspected of having meningitis is available in the literature. The evaluation and management of postoperative meningitis following cerebellopontine angle surgery can be complex. The majority of patients suspected of having postoperative meningitis should be treated with intravenous steroids and antibiotics at least until culture results are finalized, though alternative treatment pathways may be suitable for carefully selected patients. The prompt treatment of bacterial meningitis with steroids and antibiotics is imperative. For patients with postoperative aseptic meningitis, we advocate that the clinician give consideration to steroid treatment.


Shared health governance, mutual collective accountability, and transparency in COVAX: A qualitative study triangulating data from document sampling and key informant interviews.
To facilitate global COVID-19 vaccine equity, the World Health Organization, the Coalition for Epidemic Preparedness Innovations, the Global Alliance for Vaccines and Immunizations, and the United Nations Children's Fund supported the COVID-19 Vaccine Global Access (COVAX) partnership. COVAX's goals may have best been pursued through shared health governance - a theory of global health governance based on six premises, in which global health actors collaborate to achieve a shared goal. Shared health governance employs a framework for accountability termed "mutual collective accountability", in which actors hold each other accountable for achieving their goal, thus relying on transparency with one another. We conducted a multi-method qualitative study triangulating document analysis and key informant interviews to address the question: To what extent did COVAX employ shared health governance, mutual collective accountability, and transparency? We thus aimed to explore the governance structures and accountability and transparency mechanisms in COVAX and determine whether these constituted shared health governance and mutual collective accountability. We identified 117 documents and interviewed 20 key informants. Our findings suggest that COVAX's co-convening organisations were governed by their individual formal governance mechanisms, while each was formally accountable to its own leadership team, resulting in challenges when activities and decisions involved collaboration between organisations. Furthermore, COVAX's governance lacked transparency, as there was little public information about their decision-making processes and operations, including information about the algorithm with which they make vaccine allocation decision, possibly contributing to its inability to achieve its goals. The COVAX partnership only achieved four of the six premises of shared health governance. Since actors involved in COVAX did not hold one another accountable for their role in the partnership, it did not employ mutual collective accountability, while also lacking in transparency. Although these results do not entirely explain COVAX's shortcomings, they contribute to evidence about the roles of good governance, transparency, and accountability in large global health initiatives and underscore failures of the current global governance system.


Remote sensing quantifies widespread abundance of permafrost region disturbances across the Arctic and Subarctic.
Local observations indicate that climate change and shifting disturbance regimes are causing permafrost degradation. However, the occurrence and distribution of permafrost region disturbances (PRDs) remain poorly resolved across the Arctic and Subarctic. Here we quantify the abundance and distribution of three primary PRDs using time-series analysis of 30-m resolution Landsat imagery from 1999 to 2014. Our dataset spans four continental-scale transects in North America and Eurasia, covering ~10% of the permafrost region. Lake area loss (-1.45%) dominated the study domain with enhanced losses occurring at the boundary between discontinuous and continuous permafrost regions. Fires were the most extensive PRD across boreal regions (6.59%), but in tundra regions (0.63%) limited to Alaska. Retrogressive thaw slumps were abundant but highly localized (<10-5%). Our analysis synergizes the global-scale importance of PRDs. The findings highlight the need to include PRDs in next-generation land surface models to project the permafrost carbon feedback.


Fatigue and health-related quality of life in patients with immune thrombocytopenia: a longitudinal assessment in China.
There is lacking studies of longitudinally assessment of fatigue and health-related quality of life (HRQoL) among Chinese immune thrombocytopenia (ITP) adults. We aimed to evaluate changes in fatigue and HRQoL and identify the associated factors. Patients' characteristics, Functional Assessment of Chronic Illness Therapy (FACIT-F) and the ITP-specific Patient Assessment Questionnaire (ITP-PAQ) scores at admission (T0), at discharge (T1), and three months after discharge (T2) were collected. Linear mixed effects models were used to examine changes over time. We included 175 patients. The mean score of FACIT-F at T0 was 37.2 and increased at T1 (39.0), while then decreased at T2 (34.7). Patients who were single, retired, had persistent ITP, splenomegaly had more severe fatigue, whereas those who had not received any prior treatment and had a bleeding score of 0 at admission had milder fatigue. The mean score of ITP-PAQ was 57.7 at T0, then gradually increased to 60.3 at T1 and 62.8 at T2. Patients with persistent ITP and those who have never received treatment for ITP have better HRQoL. ITP adults' fatigue and HRQoL were impaired. Patients' fatigue improved at discharge but worsened at three months after discharge, while HRQoL gradually improved over time.


Confirmation of the inhibitory influence of exogenous oxytocin on cortisol and ACTH in man: evidence of reproducibility.
The influence of low-dose oxytocin perfusion (32 mIU/min) on ACTH and cortisol plasma levels was tested in 8 normal male volunteers (age 18-26). The 1-h oxytocin perfusion periods were preceded and followed by two 1-h saline control periods. During the first period, there was a slight ACTH concentration decrease in 4 individuals. Oxytocin perfusion induced a clear-cut plasma ACTH decrease in 7 out of the volunteers, and a slight decrease in the remaining one. During the second saline infusion, there was a marked ACTH increase in 7 out of the volunteers, and a weak increase in one (P less than 0.0001). A similar pattern was observed in the plasma cortisol levels (P less than 0.00001). Furthermore, a control saline perfusion was performed in 4 of the 8 volunteers and compared to the 4 corresponding oxytocin perfusion tests: the differences between the 2 sets of tests was highly significant both for ACTH (P less than 0.003) and for cortisol (P less than 0.007). Lastly, the reproducibility of this inhibitory influence was retested in 4 volunteers: the tests were repeated under the same conditions 7 days later. There were no global differences between the 2 sets of tests either for ACTH (NS) or for cortisol (NS). ACTH and cortisol concentration fluctuations during the period between each set of tests were not significant. The following variations were measured for ACTH (NS) and for cortisol (NS). The present results confirm the inhibitory influence of low-dose oxytocin perfusion on ACTH and cortisol levels in normal males.(ABSTRACT TRUNCATED AT 250 WORDS)


Cyclooxygenase (COX)-2-dependent effects of the inhibitor SC236 when combined with ionizing radiation in mammary tumor cells derived from HER-2/neu mice.
Cyclooxygenase (COX)-2-derived prostaglandins (PGs) are thought to contribute to tumor growth and resistance to radiation therapy. COX-2 protein expression is increased in many tumors including those of the breast. COX-2-derived PGs have been shown to protect cells from radiation damage. This study evaluated the role of COX-2-derived PG in radiation treatment by using the NMF11.2 mammary tumor cell line originally obtained from HER-2/neu mice that overexpress HER-2/neu. We determined whether the effects of the COX-2 inhibitor SC236 on cell growth, radiation-induced PGE2 production and COX expression, cell cycle redistribution, and vascular endothelial growth factor (VEGF) were acting through COX-2-dependent mechanisms. The NMF11.2 cells expressed both COX-1 and COX-2 protein and mRNA. The radiation treatment alone led to a dose-dependent increase in the levels of COX-2 mRNA and COX-2 protein, which was associated with an increase in the production of PGE2 and prostacyclin (PGI2). Treating NMF11.2 cells with high concentrations (20 microM) of SC236 for 48 h reduced the radiation-induced increase in COX-2 activity and also decreased cell growth. SC236 (20 microM) increased the accumulation of the cells in the radiosensitive G2-M phase of the cell cycle. However, a low concentration (5 microM) of SC236 was adequate to reduce COX-2 activity. The lower concentration of SC236 (5 microM) also decreased cell growth after a longer incubation period (96 h) and, in combination with a 2 or 5 Gy dose, led to an accumulation of cells in G2-M phase. Restoring PG to control values in cells treated with 5 microM SC236 prevented the growth inhibition and G2-M cell cycle arrest. Radiation treatment of NMF11.2 cells also increased VEGF protein expression and VEGF secretion in a dose-dependent manner, which was blocked in those cells pretreated with 20 microM SC236 but not in those pretreated with 5 microM SC236. These findings indicate that the COX-2 inhibitor SC236 reduced cell growth and arrested cells in the G2-M phase of the cell cycle by mechanisms that are both dependent and independent of PG production while its effects on VEGF appear to be independent of COX-2.


Monitoring the Response to Tyrosine Kinase Inhibitor (TKI) Treatment in Chronic Myeloid Leukemia (CML).
The aim of oral tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) is to get ideal hematological, cytogenetic, molecular responses at the critical time points. The depth of the response obtained with TKI and the time to achieve this response are both important in predicting the prognosis in patients with CML. The high efficacy of the TKI treatment of CML has prompted the need for accurate methods to monitor response at levels below the landmark of CCyR. Quantification of BCR-ABL transcripts has proven to be the most sensitive method available and has shown prognostic impact with regard to progression-free survival. European LeukemiaNet (ELN) molecular program harmonized the reporting of results according to the IS (International harmonization of Scale) in Europe. The aim of this review is to outline monitoring the response to optimal TKI treatment based on the ELN CML 2013 recommendations from the clinical point of view as a physician. Careful cytogenetic and molecular monitoring could help to select the most convenient TKI drug and to optimize TKI treatment. Excessive monitoring may have an economic cost, but failure to optimize TKI treatment may result in CML disease acceleration and death.


Donor CMV serologic status and outcome of CMV-seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis.
Cytomegalovirus (CMV) has been a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). The importance of the recipient's serologic status is paramount. However, the importance of the donor's serologic status in CMV-seropositive recipients is controversial. We analyzed the influence of the donor's CMV status in a large cohort of patients. A total of 7018 patients seropositive for CMV reported to the European Group for Blood and Marrow Transplantation (EBMT) were included; 5910 patients had undergone HLA-identical sibling SCT and 1108 patients had undergone unrelated donor SCT. Univariate and multivariate proportional hazards models were constructed for survival, event-free survival, transplant-related mortality, and relapse incidence. Patients receiving grafts from CMV-seropositive HLA-identical sibling donors had the same survival as patients grafted from seronegative donors (hazard ratio [HR], 1.04; P =.37; 95% confidence interval [CI], 0.95-1.14). However, unrelated donor stem cell (SC) transplant recipients receiving grafts from CMV-seropositive donors had an improved 5-year survival (35% versus 27%; HR = 0.8; P =.006), an improved event-free survival (30% versus 22%; HR = 0.8; P =.01), and a reduced transplant-related mortality (49% versus 62%; HR = 0.7; P <.001). There was no influence on the relapse incidence. The effects of donor CMV status remained in multivariate analyses. The effect of donor status was different among different disease categories. In patients with chronic myelogenous leukemia (CML), T-cell depletion abrogated the beneficial effect of donor status, suggesting that the effect is mediated through transfer of donor immunity. Our data suggest that donor CMV status influences outcome of unrelated SCT. For a CMV-seropositive patient, a seropositive donor might be preferable.


Ciliate epibionts associated with crustacean zooplankton in german lakes: distribution, motility, and bacterivory.
Ciliate epibionts associated with crustacean zooplankton are widespread in aquatic systems, but their ecological roles are little known. We studied the occurrence of ciliate epibionts on crustacean zooplankton in nine German lakes with different limnological features during the summer of 2011. We also measured the detachment and re-attachment rates of the ciliates, changes in their motility, and the feeding rates of attached vs. detached ciliate epibionts. Epibionts were found in all lakes sampled except an acidic lake with large humic inputs. Epibiont prevalence was as high as 80.96% on the cladoceran Daphnia cucullata, 67.17% on the cladoceran Diaphanosoma brachyurum, and 46.67% on the calanoid copepod Eudiaptomus gracilis. Both cladoceran groups typically had less than 10 epibionts per individual, while the epibiont load on E. gracilis ranged from 1 to >30 epibionts per individual. After the death of the zooplankton host, the peritrich ciliate epibiont Epistylis sp. detached in an exponential fashion with a half-life of 5 min, and 98% detached within 30 min, leaving behind the stalks used for attachment. Immediately after detachment, the ciliates were immotile, but 62% became motile within 60 min. When a new host was present, only 27% reattached after 120 min. The average measured ingestion rate and clearance rate of Epistylis were 11,745 bacteria ciliate(-1) h(-1) and 24.33 μl ciliate(-1) h(-1), respectively. Despite their high feeding rates, relatively low epibiont abundances were observed in the field, which suggests either diversion of energy to stalk formation, high metabolic loss by the epibionts, or high mortality among the epibiont populations.


Anxiety and depression in patients who undergo a cerebrovascular procedure.
Observe the relationship of anxiety and depression on quality of life outcomes after open and endovascular cerebrovascular procedures. We retrospectively analyzed 349 patients who underwent a procedure for aneurysm, arteriovenous malformation, intraparenchymal hemorrhage, carotid stenosis, acute stroke, and conventional catheter angiogram over three years at a community hospital. We correlated pre-procedural anxiety and depression with Global Physical Health, Global Mental Health, and Modified Rankin Scale scores. We performed univariate and multivariate linear and logistic regression analyses adjusting for past medical history and sociodemographic factors. Anxiety or depression occurred in 18 % of patients. Patients with anxiety or depression were more likely to be female (81% vs 60.8%; p = 0.002) and younger (54 vs. 59 years old; p = 0.025). The groups did not differ in type or urgency of procedure, smoking or history of diabetes. Patients with anxiety or depression reported lower mental health scores at 30 days (45.1 vs 48.2; p = 0.002) post-procedure. In multivariate analyses, anxious or depressed patients had worse mental health scores at 30 days (t = - 2.893; p = 0.008) than those who did not have a history of anxiety or depression. There was no difference between groups in length of stay, mortality, physical health t-scores, functionality scores, or six month quality of life outcomes. Patients undergoing cerebrovascular procedures who self-reported anxiety or depression showed a significant difference in mental health outcomes at 30 days, but six month mental health and other medical and functional outcomes measures were similar to patients without these diagnoses.


Contemporary review of rhinoplasty.
We conducted a contemporary review covering advances and trends in primary and functional rhinoplasty as published during the past decade. Specifically, we reviewed studies supporting the evidence for functional rhinoplasty, nasal valve surgery, and septal reconstruction. In addition, key articles discussing cephalic malpositioning of the lower lateral cartilages and tip contouring are reviewed. We also report studies involving lateral osteotomy techniques, computer imaging, and the use of homologous, alloplastic, and absorbable implants. When appropriate, we review outcomes data from key studies because these data are becoming increasingly important for evidence-based medicine, physician grading, and procedure reimbursement. Using evidence-based approaches whenever possible will help to ensure predictable patient outcomes.


The active heroin metabolite 6-acetylmorphine has robust reinforcing effects as assessed by self-administration in the rat.
Previous studies have suggested that at least some of the behavioral effects of heroin might be mediated by its active metabolite 6-acetylmorphine (6-AM). The aim of the present study was to investigate the reinforcing effects of 6-AM and its role in mediating those of heroin. We used an intravenous self-administration procedure in male Sprague-Dawley rats including four phases: acquisition, extinction, reinstatement of drug-seeking, and re-acquisition. Independent groups of rats readily learned to self-administer equimolar doses (0.135 μmol/kg) of either 6-AM (44.3 μg/kg) or heroin (50 μg/kg). Under a fixed ratio 1 (FR1) schedule of reinforcement, the rate of responding was the same for 6-AM and heroin, but it was significantly higher for 6-AM than for heroin under a FR2 schedule. A non-contingent infusion ('priming') of 0.068 μmol/kg of either 6-AM or heroin reinstated non-reinforced drug-seeking (relapse). The rats readily re-acquired self-administration behaviour when given access to one of two doses (0.068 and 0.135 μmol/kg) of 6-AM or heroin. Pretreatment with a specific monoclonal antibody (mAb) against 6-AM blocked the priming effect of 6-AM, and modified the rate of lever-pressing on re-acquisition of 6-AM self-administration in a manner compatible with a shift to the right of the dose-effect curve. The mAb did not affect heroin responding. The present results show that 6-AM possesses reinforcing effects similar to those of heroin. The lack of effect of 6-AM mAb on heroin priming and heroin self-administration calls for further studies to clarify the role of heroin and its metabolites in heroin reward. This article is part of the Special Issue entitled 'Opioid Neuropharmacology: Advances in treating pain and opioid addiction'.


Streptomyces deserti sp. nov., isolated from hyper-arid Atacama Desert soil.
The taxonomic position of a Streptomyces strain isolated from a hyper-arid desert soil was established using a polyphasic approach. The organism had chemical and morphological properties typical of the genus Streptomyces and formed a phyletic line at the periphery of the Streptomyces coeruleorubidus subcluster in the 16S rRNA gene tree. DNA:DNA relatedness values between the isolate and its nearest phylogenetic neighbours, Streptomyces lomondensis NRRL 3252(T) and Streptomyces lusitanus NRRL B-12501(T) were 42.5 (±0.48)% and 25.0 (±1.78)%, respectively. The isolate was readily distinguished from these organisms using a combination of morphological and phenotypic properties. On the basis of these results, it is proposed that isolate C63(T) (CGMCC 4.6997(T), = KACC 15425(T)) be classified as the type strain of Streptomyces deserti sp. nov.


Transcriptome and methylome profiling reveals relics of genome dominance in the mesopolyploid Brassica oleracea.
Brassica oleracea is a valuable vegetable species that has contributed to human health and nutrition for hundreds of years and comprises multiple distinct cultivar groups with diverse morphological and phytochemical attributes. In addition to this phenotypic wealth, B. oleracea offers unique insights into polyploid evolution, as it results from multiple ancestral polyploidy events and a final Brassiceae-specific triplication event. Further, B. oleracea represents one of the diploid genomes that formed the economically important allopolyploid oilseed, Brassica napus. A deeper understanding of B. oleracea genome architecture provides a foundation for crop improvement strategies throughout the Brassica genus. We generate an assembly representing 75% of the predicted B. oleracea genome using a hybrid Illumina/Roche 454 approach. Two dense genetic maps are generated to anchor almost 92% of the assembled scaffolds to nine pseudo-chromosomes. Over 50,000 genes are annotated and 40% of the genome predicted to be repetitive, thus contributing to the increased genome size of B. oleracea compared to its close relative B. rapa. A snapshot of both the leaf transcriptome and methylome allows comparisons to be made across the triplicated sub-genomes, which resulted from the most recent Brassiceae-specific polyploidy event. Differential expression of the triplicated syntelogs and cytosine methylation levels across the sub-genomes suggest residual marks of the genome dominance that led to the current genome architecture. Although cytosine methylation does not correlate with individual gene dominance, the independent methylation patterns of triplicated copies suggest epigenetic mechanisms play a role in the functional diversification of duplicate genes.


Healthy lifestyle practices: Evidence from clinic attending mothers in the northern province, Sri Lanka.
Healthy lifestyles are known to reduce noncommunicable disease-related mortalities and morbidities. Public health initiatives should encourage healthier lifestyles to prevent the risk of noncommunicable diseases. This study aimed to determine healthy lifestyle practices and their associated factors among clinic-attending mothers (mothers attending antenatal clinics, postnatal clinics, well-baby clinics, family planning clinics, well-women clinics, and polyclinics) in the Chavakachcheri Medical Officer of Health (MOH) area. We conducted a clinic-based cross-sectional study in 19 centers covering 28 Public Health Midwives (PHM) areas. Healthy lifestyle practices, such as regular exercise, consumption of recommended servings of fruits and vegetables, measuring their own BMI, and average salt consumption, were poor. In the multivariate analysis, we found only three factors that had higher odds of affecting healthy lifestyle practices that were statistically significant: attributes of higher level of perceptions about healthy lifestyle practices (AOR = 4.36, 1.32-14.39), participating in Mothers' Support Groups (AOR = 7.97, 2.17-29.27) and BMI value of < 23 kg/m2 (AOR = 4.47, 1.35-14.73). Effective targeted healthy lifestyle-related educational programs instead of regular training during clinic visits and promoting participation in peer groups at the community level may benefit clinic-attending mothers.


CaMeRe: A Novel Tool for Inference of Cancer Metabolic Reprogramming.
Metabolic reprogramming is prevalent in cancer, largely due to its altered chemical environments such as the distinct intracellular concentrations of O2, H2O2 and H+, compared to those in normal tissue cells. The reprogrammed metabolisms are believed to play essential roles in cancer formation and progression. However, it is highly challenging to elucidate how individual normal metabolisms are altered in a cancer-promoting environment; hence for many metabolisms, our knowledge about how they are changed is limited. We present a novel method, CaMeRe (CAncer MEtabolic REprogramming), for identifying metabolic pathways in cancer tissues. Based on the specified starting and ending compounds, along with gene expression data of given cancer tissue samples, CaMeRe identifies metabolic pathways connecting the two compounds via collection of compatible enzymes, which are most consistent with the provided gene-expression data. In addition, cancer-specific knowledge, such as the expression level of bottleneck enzymes in the pathways, is incorporated into the search process, to enable accurate inference of cancer-specific metabolic pathways. We have applied this tool to predict the altered sugar-energy metabolism in cancer, referred to as the Warburg effect, and found the prediction result is highly accurate by checking the appearance and ranking of those key pathways in the results of CaMeRe. Computational evaluation indicates that the tool is fast and capable of handling large metabolic network inference in cancer tissues. Hence, we believe that CaMeRe offers a powerful tool to cancer researchers for their discovery of reprogrammed metabolisms in cancer. The URL of CaMeRe is http://csbl.bmb.uga.edu/CaMeRe/.


Resistance to antivascular endothelial growth factor treatment in age-related macular degeneration.
Age-related macular degeneration (AMD) is the main cause of visual impairment and blindness in people aged over 65 years in developed countries. Vascular endothelial growth factor (VEGF) is a positive regulator of angiogenesis and its proven role in the pathological neovascularization in wet AMD has provided evidence for the use of anti-VEGF agents as potential therapies. In this study, we review the literature for the possible causes of failure after treatment with anti-VEGF agents and attempt to propose an algorithm of suggestive actions to increase the chances of successful management of such difficult cases.


Walking program for people with cancer. Getting started.
Having the energy to maintain functional independence and social roles is an important component of quality of life in cancer patients. Unnecessary bedrest and prolonged sedentarism can contribute significantly to the development of fatigue and may result in rapid and potentially irreversible losses in energy and functioning. Walking is an important self-care activity that can counter some of the debilitating effects of disease, treatment, and inactivity. Research on exercise for ambulatory cancer patients has been limited to moderate intensity, interval, supervised exercise programs on cycle ergometers. However, lower intensity walking can be used as a self-care intervention for individuals or groups. Cancer patients often ask questions about what kind, frequency, duration, and intensity of exercise they should perform. By teaching self-care techniques, such as keeping a walking diary and pulse monitoring to regulate activity, nurses can help patients develop safe activity practices. I also present guidelines and precautions related to safe exercising by ambulatory patients during and after treatment for cancer.


Learning the 'SMART' way... results from a pilot study evaluating an interprofessional acute care study day.
A significant number of patients requiring critical care are now being managed outside of critical care facilities. There is evidence that staff looking after these patients lack the necessary knowledge and skills to care for them safely, and that effective pre-registration education can play a significant role in addressing these shortfalls in nurses' knowledge and skills. A team from Sheffield Hallam University, in collaboration with the University of Sheffield, developed a pilot one day interprofessional acute illness programme which was called SMART® (Student Management of Acute illness - Recognition and Treatment). To evaluate the pilot programme, 16 student doctors and 72 student nurses were recruited. A pre- and post-course questionnaire based on the Featherstone et al. (2005) evaluation of ALERT was used to ascertain the students' general level of knowledge of the deteriorating patient, their experiences of and confidence in caring for an acutely unwell patient, and their level of comfort with interprofessional working. The results from the pilot study indicate that the students' levels of knowledge, their levels of confidence and their comfort with interprofessional working all rose after undertaking the programme. The pilot study has a number of implications for the future teaching and learning of acute care clinical skills, within a theoretically based curriculum.


A critical role for iron and zinc homeostatic systems in the evolutionary adaptation of Escherichia coli to metal restriction.
Host nutritional immunity utilizes metal deprivation to help prevent microbial infection. To investigate bacterial adaptation to such restrictive conditions, we conducted experimental evolution with two metal sequestering agents. Ethylenediaminetetraacetic acid (EDTA) and diethylenetriamine pentamethylene phosphonic acid (DTPMP) were selected as ligands because they differentially affect cellular levels of iron, manganese and zinc in Escherichia coli. Mutants of E. coli strain BW25113 were isolated after cultivation at sub-minimum inhibitory concentration (MIC) chelant levels and genetic changes potentially responsible for tolerance were identified by whole-genome sequencing. In EDTA-selected strains, mutations in the promoter region of yeiR resulted in elevated gene expression. The yeiR product, a zinc-specific metallochaperone, was confirmed to be primarily responsible for EDTA resistance. Similarly, in two of the DTPMP-selected strains, a promoter mutation increased expression of the fepA-entD operon, which encodes components of the ferric-enterobactin uptake pathway. However, in this case improved DTPMP tolerance was only detectable following overexpression of FepA or EntD in trans. Additional mutations in the cadC gene product, an acid-response regulator, preserved the neutrality of the growth medium by constitutively activating expression of the cadAB regulon. This study uncovers specific resistance mechanisms for zinc and iron starvation that could emerge by selection against host nutritional immunity or competition with heterologous metallophores. It also provides insight into the specific metals affected by these two widely used chelators critical for their antibacterial mode of action.


How do patients actually experience and use art in hospitals? The significance of interaction: a user-oriented experimental case study.
This article aims to understand patient wellbeing and satisfaction and to qualify the current guidelines for the application of art in hospitals. Employing anthropological methods, we focus on the interactional aspects of art in health interventions. A user-oriented study ranked 20 paintings, followed by an experiment using paintings in the dayroom of five medical wards. Fieldwork was done over a two-week period. During the first week, dayrooms were configured without the presence of art and in the second week were configured with the artworks. Semi-structured interviews, observation, participant observation and informal conversation were carried out and were informed by thermal cameras, which monitored the usage, patient occupation and flow in two of the dayrooms. The study shows that art contributes to creating an environment and atmosphere where patients can feel safe, socialize, maintain a connection to the world outside the hospital and support their identity. We conclude that the presence of visual art in hospitals contributes to health outcomes by improving patient satisfaction as an extended form of health care. The article draws attention to further research perspectives and methods associated with the development of art in hospitals.


Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease.
Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung.


Computational Study of the Effect of Homogeneous and Heterogeneous Bubbly Flows on Bulk Gas-Liquid Heat Transfer.
A numerical investigation is performed on buoyancy-driven homogeneous and heterogeneous bubbly flows to compare the bulk gas-liquid heat transfer effectiveness for Prandtl (Pr) numbers 0.2-20 and void fractions 〈 α g 〉 0.3-0.5. For this purpose, transient two-fluid model simulations of bubbles rising in a stagnant pool of liquid are conducted in a rectangular box by applying periodic boundary conditions to all the sides. The temperature difference ( Δ T ) between gas and liquid phase is averaged over the rectangular box and monitored with respect to time, the heat transfer rate is studied based on the time at which the Δ T tends to zero. The results of numerical study show that at low Pr numbers, faster decay of Δ T is observed for homogeneous flow of bubbles indicating higher heat transfer rate in comparison with the heterogeneous flow of bubbles for the same void fraction. On the contrary, for high Pr numbers, higher heat transfer rate is observed in heterogeneous flow compared to the homogeneous. The comparison of heat transfer behavior between different void fractions for heterogeneous flow show that, for low Pr numbers higher heat transfer rate is achieved for void fraction 0.4 in comparison with void fraction 0.5. And for high Pr numbers, higher heat transfer is observed for void fraction 0.5 in comparison with void fraction 0.4.


Autoimmune haemolytic anaemia in a patient with advanced lung adenocarcinoma and chronic lymphocytic leukaemia receiving nivolumab and intravenous immunoglobulin.
We describe a rare case of severe autoimmune haemolytic anaemia (AIHA) in the setting of underlying chronic lymphocytic leukaemia receiving intravenous immunoglobulin, history of warm IgG autoantibody and treatment with nivolumab for advanced non-small cell lung cancer. In this report, we describe AIHA as a potential serious immune-related adverse event from immune checkpoint inhibitors, discuss other potential contributing factors and review previously described cases of AIHA in patients receiving programmed death 1 (PD-1) inhibitors. In the era of immunotherapy, we hope to add literature to raise awareness of potential immune-related sequelae such as AIHA. We aim to highlight the importance of close monitoring for prompt identification and management of potentially fatal AIHA and immune-related adverse events of PD-1 inhibitors by holding immunotherapy and treating with high-dose steroids, particularly in subgroups which may be at increased risk.


Primary systemic amyloidosis: comparison of melphalan and prednisone versus placebo.
Satisfactory treatment for primary amyloidosis does not exist. Because the amyloid fibrils consist of a portion of a monoclonal light chain, it appears reasonable to treat amyloidosis with alkylating agents that are effective against the plasma cells that synthesize monoclonal light chains. Fifty-five patients with primary systemic amyloidosis were randomized (double blind) to melphalan-prednisone or placebo. In comparison with the placebo group, patients given melphalan-prednisone were able to continue on treatment for a longer time and to receive larger doses before the code was broken. Among this group, the nephrotic syndrome disappeared in two patients and urinary excretion of protein was reduced by more than 50% in eight others. Of 13 patients who received melphalan-prednisone for more than 12 mo, 6 improved, 3 were stable, and 4 had progression of disease. Survival did not differ significantly between the groups.


A mannosyl-carrier lipid of bovine adrenal meddulla and rat parotid.
1. The transfer of mannose from GDP-(U-14-C)mannose into endogenous acceptors of bovine adrenal medullla and rat parotid was studied. The rapidly labelled product, a glycolipid, was partially purified and characterized. 2. It was stable to mild alkaline hydrolysis but yielded (14-C)mannose on mild acid hydrolysis. It co-chromatographed with mannosyl phosphoryl dolichol in four t.l.c. systems and on DEAE-cellulose acetate. Addition of dolichol phosphate or a dolichol phosphate-enriched fraction prepared from pig liver stimulated mannolipid synthesis. 3. The formation of mammolipid appeared reversible, since addition of GDP to a system synthesizing the mannolipid caused a rapid loss of label from the mannolipid. UDP-N-acetylglucosamine did not inhibit mannolipid synthesis except at high concentrations (2 mM), even though in the absence of GDP-mannose, N-acetylglucosamine was incorporated into a lipid having the properties of a glycosylated polyprenyl phosphate. 4. Mannose from GDP-mannose was also incorporated into two other acceptors, (2y being insoluble in chloroform-methanol (2:1, v/v) but soluble in choloroform-methanol-water (10:10:3, by vol.) and (ii) protein. These are formed much more slowly than the mannolipid. 5. Exogenous mannolipid served as a mannose donor for acceptors (i) and (ii), and it is suggested that transfer of mannose from GDP-mannose to mannosylated protein occurs via two intermediates, the mannolipid and acceptor (i).


A fuzzy convolution model for radiobiologically optimized radiotherapy margins.
In this study we investigate the use of a new knowledge-based fuzzy logic technique to derive radiotherapy margins based on radiotherapy uncertainties and their radiobiological effects. The main radiotherapy uncertainties considered and used to build the model were delineation, set-up and organ motion-induced errors. The radiobiological effects of these combined errors, in terms of prostate tumour control probability and rectal normal tissue complication probability, were used to formulate the rule base and membership functions for a Sugeno type fuzzy system linking the error effect to the treatment margin. The defuzzified output was optimized by convolving it with a Gaussian convolution kernel to give a uniformly varying transfer function which was used to calculate the required treatment margins. The margin derived using the fuzzy technique showed good agreement compared to current prostate margins based on the commonly used margin formulation proposed by van Herk et al (2000 Int. J. Radiat. Oncol. Biol. Phys. 47 1121-35), and has nonlinear variation above combined errors of 5 mm standard deviation. The derived margin is on average 0.5 mm bigger than currently used margins in the region of small treatment uncertainties where margin reduction would be applicable. The new margin was applied in an intensity modulated radiotherapy prostate treatment planning example where margin reduction and a dose escalation regime were implemented, and by inducing equivalent treatment uncertainties, the resulting target and organs at risk doses were found to compare well to results obtained using currently recommended margins.