Associations of individual, household and environmental characteristics with carbon dioxide emissions from motorised passenger travel.
Carbon dioxide (CO2) emissions from motorised travel are hypothesised to be associated with individual, household, spatial and other environmental factors. Little robust evidence exists on who contributes most (and least) to travel CO2 and, in particular, the factors influencing commuting, business, shopping and social travel CO2. This paper examines whether and how demographic, socio-economic and other personal and environmental characteristics are associated with land-based passenger transport and associated CO2 emissions. Primary data were collected from 3474 adults using a newly developed survey instrument in the iConnect study in the UK. The participants reported their past-week travel activity and vehicle characteristics from which CO2 emissions were derived using an adapted travel emissions profiling method. Multivariable linear and logistic regression analyses were used to examine what characteristics predicted higher CO2 emissions. CO2 emissions from motorised travel were distributed highly unequally, with the top fifth of participants producing more than two fifth of emissions. Car travel dominated overall CO2 emissions, making up 90% of the total. The strongest independent predictors of CO2 emissions were owning at least one car, being in full-time employment and having a home-work distance of more than 10 km. Income, education and tenure were also strong univariable predictors of CO2 emissions, but seemed to be further back on the causal pathway than having a car. Male gender, late-middle age, living in a rural area and having access to a bicycle also showed significant but weaker associations with emissions production. The findings may help inform the development of climate change mitigation policies for the transport sector. Targeting individuals and households with high car ownership, focussing on providing viable alternatives to commuting by car, and supporting planning and other policies that reduce commuting distances may provide an equitable and efficient approach to meeting carbon mitigation targets.


Post-tonsillectomy infiltration with bupivacaine reduces immediate postoperative pain in children.
Pain management after tonsillectomy in children remains a dilemma for the anaesthetist. A previous study demonstrated that the administration of lidocaine 1% topical spray to the peritonsillar fossae before tracheal extubation provided considerable immediate postoperative pain relief in infants and children. However, the pain relief was of short duration. We were hopeful that the use of bupivacaine would offer more prolonged pain relief because of its pharmacological characteristics. Therefore, this study was designed to compare the effects of bupivacaine 0.5% with 1:200,000 epinephrine administered after tonsillectomy either as topical spray or submucosal infiltration on postoperative pain in children. Forty-three patients aged two to ten years were randomized into three groups after tonsillectomy was performed. Group (1) received 0.5 ml.kg-1 normal saline spray; (2) received 2 mg.kg-1 bupivacaine 0.5% with 1:200,000 epinephrine peritonsillar infiltration in a similar volume to Group 1 and; (3) received 2 mg.kg-1 bupivacaine 0.5% with 1:200,000 epinephrine spray to both tonsillar beds. The patients in each group were compared postoperatively with regard to the quality of pain control using the Objective Pain Score, and their analgesic requirements. Peritonsillar infiltration of bupivacaine provided superior immediate postoperative analgesia as reflected by lower recovery room pain scores (P < 0.05) and opioid requirements (P < 0.01). Ward pain scores and analgesic requirements were similar among groups. Peritonsillar infiltration of bupivacaine 0.5% with 1:200,000 epinephrine provides better post-tonsillectomy pain control in the immediate postoperative period than bupivacaine spray or placebo.


Positron emission tomography (PET) in primary prostate cancer staging and risk assessment.
Prostate cancer (PCa) is one of the few neoplasms that are not well served by 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). As a result, a number of PET tracers have been developed to target particular biological features of PCa. Such agents can be used for diagnosis, staging, identification of biochemical recurrence (BCR) and evaluation of metastatic disease. Here, we focus on primary disease and local staging. To date, magnetic resonance imaging (MRI) has proven superior to PET in the imaging of primary PCa. However, some PET agents have shown remarkable promise in staging high-risk PCa (defined as any combination of a clinical T3, a PSA score >20 ng/mL, or a Gleason score of 8-10), as well as biochemical relapse after definitive therapy and metastatic PCa. PET agents can be divided into those that interrogate tumor metabolism (18F-FDG, 11C-Choline, 18F-Choline, 11C-Acetate, 18F-FACBC), hormone receptors (18F-FDHT), and other targets such as prostate specific membrane antigen (PSMA) (68Ga-PSMA, 18F-DCFBC, 18F-DCFPyl) or gastric releasing peptide (18F-GRP or 18F-Bombesin). In this review, we compare the available PCa targeted PET tracers utilized in staging of high risk tumors.


Dietary antioxidant quality score (DAQs) is associated with bone mass assessed by calcaneal quantitative ultrasound in young women
Evidence suggests that intake of antioxidants could positively influence bone mass by preventing bone metabolism against oxidative stress. We aimed to investigate the possible influence of single antioxidant intakes and dietary antioxidant quality score (DAQs) on calcaneal quantitative ultrasound (QUS) in a population of young adults. A total of 605 young Spanish adults participated in this study (median age 20.38 ± 2.67). Bone mass was measured by calcaneal QUS to determine broadband ultrasound attenuation (BUA, dB/MHz) parameter. Body composition was assessed by bioelectrical impedance analysis and dietary intakes were determined using a 72-hour diet recall interview. DAQs was applied to calculate antioxidant nutrients intake. Linear regression analyses were performed to investigate the possible influence of DAQs on calcaneal QUS. Most of young adults showed a low-quality antioxidant intake (only 17.6% of women and 20.3% of men had a score of 4 or 5 in DAQs). A positive correlation between DAQs and BUA was observed in women (r = 0.117; p = 0.024). Linear regression analysis revealed that DAQs was significantly associated with BUA parameter in women after adjusting by body weight, height, calcium intake and physical activity (PA) (p = 0.035). No significant associations between single antioxidant and calcaneus QUS measurement were found. Our findings suggest that high-quality antioxidant intakes could influence bone health in young women. Future studies should further investigate the protective role of antioxidant nutrients against osteoporosis.


Patient recall in advanced education in prosthodontics programs in the United States.
This study surveyed program directors of Advanced Education Programs in Prosthodontics (AEPP) in the United States to determine the extent, type, incidence, and perceived effectiveness of implemented recall systems. Surveys were sent to AEPP directors across the United States to assess their program's recall protocol. This survey first identified whether an active recall program existed. For programs with recall systems, rigor in promoting ongoing oral health was surveyed by focusing on recall frequency, patient tracking protocol, involved personnel, interaction with other university departments, provided clinical procedures, and therapy completion protocol. Whether the directors perceived that their recall system was successful was also investigated. Thirty-three of 46 programs responded, giving a response rate of 72%. Of these 33 programs, only 21 (64%) had an active recall system, although 30 (91%) believed recall to be important. Twelve (57%) directors with recall programs considered their system to be effective. Prosthodontic program directors felt their program's recall effectiveness could be improved. Due to the numerous potential benefits of an active recall system, AEPPs should consider implementing or enhancing their recall programs. Further studies are indicated to determine specific criteria that describe an effective recall system for prosthodontic programs within the context of patient health promotion, program curriculum, and financial ramifications.


The value of transcriptomics in advancing knowledge of the immune response and diagnosis in tuberculosis.
Blood transcriptomics analysis of tuberculosis has revealed an interferon-inducible gene signature that diminishes in expression after successful treatment; this promises improved diagnostics and treatment monitoring, which are essential for the eradication of tuberculosis. Sensitive radiography revealing lung abnormalities and blood transcriptomics have demonstrated heterogeneity in patients with active tuberculosis and exposed asymptomatic people with latent tuberculosis, suggestive of a continuum of infection and immune states. Here we describe the immune response to infection with Mycobacterium tuberculosis revealed through the use of transcriptomics, as well as differences among clinical phenotypes of infection that might provide information on temporal changes in host immunity associated with evolving infection. We also review the diverse blood transcriptional signatures, composed of small sets of genes, that have been proposed for the diagnosis of tuberculosis and the identification of at-risk asymptomatic people and suggest novel approaches for the development of such biomarkers for clinical use.


Dom34 Links Translation to Protein O-mannosylation.
In eukaryotes, Dom34 upregulates translation by securing levels of activatable ribosomal subunits. We found that in the yeast Saccharomyces cerevisiae and the human fungal pathogen Candida albicans, Dom34 interacts genetically with Pmt1, a major isoform of protein O-mannosyltransferase. In C. albicans, lack of Dom34 exacerbated defective phenotypes of pmt1 mutants, while they were ameliorated by Dom34 overproduction that enhanced Pmt1 protein but not PMT1 transcript levels. Translational effects of Dom34 required the 5'-UTR of the PMT1 transcript, which bound recombinant Dom34 directly at a CA/AC-rich sequence and regulated in vitro translation. Polysomal profiling revealed that Dom34 stimulates general translation moderately, but that it is especially required for translation of transcripts encoding Pmt isoforms 1, 4 and 6. Because defective protein N- or O-glycosylation upregulates transcription of PMT genes, it appears that Dom34-mediated specific translational upregulation of the PMT transcripts optimizes cellular responses to glycostress. Its translational function as an RNA binding protein acting at the 5'-UTR of specific transcripts adds another facet to the known ribosome-releasing functions of Dom34 at the 3'-UTR of transcripts.


Exploring Zebrafish Larvae as a COVID-19 Model: Probable Abortive SARS-CoV-2 Replication in the Swim Bladder.
Animal models are essential to understanding COVID-19 pathophysiology and for preclinical assessment of drugs and other therapeutic or prophylactic interventions. We explored the small, cheap, and transparent zebrafish larva as a potential host for SARS-CoV-2. Bath exposure, as well as microinjection in the coelom, pericardium, brain ventricle, or bloodstream, resulted in a rapid decrease of SARS-CoV-2 RNA in wild-type larvae. However, when the virus was inoculated in the swim bladder, viral RNA stabilized after 24 h. By immunohistochemistry, epithelial cells containing SARS-CoV-2 nucleoprotein were observed in the swim bladder wall. Our data suggest an abortive infection of the swim bladder. In some animals, several variants of concern were also tested with no evidence of increased infectivity in our model. Low infectivity of SARS-CoV-2 in zebrafish larvae was not due to the host type I interferon response, as comparable viral loads were detected in type I interferon-deficient animals. A mosaic overexpression of human ACE2 was not sufficient to increase SARS-CoV-2 infectivity in zebrafish embryos or in fish cells in vitro. In conclusion, wild-type zebrafish larvae appear mostly non-permissive to SARS-CoV-2, except in the swim bladder, an aerial organ sharing similarities with the mammalian lung.


'You're never making just one decision': exploring the lived experiences of ambulance Emergency Operations Centre personnel.
The aim of this study was to explore the experiences of ambulance dispatch personnel, identifying key stressors and their impact on staff well-being. Qualitative methodology was used. Nine semistructured interviews were conducted with National Health Service (NHS) ambulance Emergency Operations Centre (EOC) dispatch personnel in the UK between July and August 2014. Participants were asked about their experiences of the role, stress experienced and current strategies they use to deal with stress. Transcripts were analysed using an inductive, bottom-up thematic analysis. Three key themes were identified: (1) 'How dispatch is perceived by others', (2) 'What dispatch really involves' and (3) 'Dealing with the stresses of dispatch'. All participants expressed pride in their work, but felt overloaded by the workload and undervalued by others. Several sources of additional stress, not directly related to the execution of their work, were identified, including the need to mentally unwind from work at the end of a shift. Participants were able to identify a number of ways in which they currently manage work-related stress, but they also suggested changes the organisation could put in place in order to reduce stress in the working environment. Building on existing theory on work stress and postwork recovery, it was concluded that EOC dispatch staff require greater support at work, including skills training to promote postshift recovery, in order to reduce the likelihood of sickness absence, and prevent work-related fatigue.


Position statement. Part two: Maintaining immune health.
The physical training undertaken by athletes is one of a set of lifestyle or behavioural factors that can influence immune function, health and ultimately exercise performance. Others factors including potential exposure to pathogens, health status, lifestyle behaviours, sleep and recovery, nutrition and psychosocial issues, need to be considered alongside the physical demands of an athlete's training programme. The general consensus on managing training to maintain immune health is to start with a programme of low to moderate volume and intensity; employ a gradual and periodised increase in training volumes and loads; add variety to limit training monotony and stress; avoid excessively heavy training loads that could lead to exhaustion, illness or injury; include non-specific cross-training to offset staleness; ensure sufficient rest and recovery; and instigate a testing programme for identifying signs of performance deterioration and manifestations of physical stress. Inter-individual variability in immunocompetence, recovery, exercise capacity, non-training stress factors, and stress tolerance likely explains the different vulnerability of athletes to illness. Most athletes should be able to train with high loads provided their programme includes strategies devised to control the overall strain and stress. Athletes, coaches and medical personnel should be alert to periods of increased risk of illness (e.g. intensive training weeks, the taper period prior to competition, and during competition) and pay particular attention to recovery and nutritional strategies.


Interactions Between Cassava Mosaic Geminiviruses and Their Vector, Bemisia tabaci (Hemiptera: Aleyrodidae).
The sweetpotato whitefly, Bemisia tabaci (Gennadius) is the vector of the cassava mosaic geminiviruses (CMGs) that cause cassava mosaic disease (CMD). Synergistic interactions between B. tabaci and CMGs have been hypothesized as a cause of whitefly "super-abundance," which has been a key factor behind the spread of the severe CMD pandemic through East and Central Africa. The current study investigated this hypothesis by conducting experiments with CMD-susceptible cassava varieties infected with different CMGs in both the north-western Lake Zone region (pandemic affected) and the eastern Coast Zone where CMD is less severe. Male and female pairs of B. tabaci were placed in clip cages for 48 h on plants of three cassava varieties at each of the two locations. There were significantly more eggs laid on CMG-infected than on CMG-free plants in the Lake Zone, whereas in Coast Zone, there were no significant differences. There were no significant differences in proportions, mortality, and development duration of immature stages of B. tabaci among virus states and cassava variety in the two locations. The overall number of eggs was significantly higher with longer development duration of the immature stages in the Lake than in the Coast Zone, whereas mortality was significantly higher in the Coast than in the Lake Zone. Based on these results, it is concluded that there was no net positive synergistic interaction between CMGs and B. tabaci for either lowland coastal or mid-altitude inland populations. Consequently, other factors seem more likely to be the cause of the "super-abundance," and require further investigation.


Pharmacovigilance of antimalarial treatment in Africa: is it possible?
Pharmacovigilance, defined as "the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug related problem", is increasingly being recognized in Africa. Many African countries have simultaneously adopted artemisinin derivative based combination therapy (ACT) as first-line treatment for uncomplicated malaria, offering an opportunity to assess the safety of these drugs when used widely. While ACTs appear to be safe and well-tolerated, there is little experience with these medicines in Africa, outside clinical trials. Pharmacovigilance for ACTs and other combination treatments in Africa is essential. Malaria transmission intensity is high and antimalarial medicines are used frequently. Presumptive treatment of fever with antimalarials is common, often in the absence of a confirmed diagnosis, using drugs obtained without a prescription. Informal use of antimalarial drugs may increase the risk of incorrect dosing, inappropriate treatment, and drug interactions, which may impact negatively on drug safety. Furthermore, the administration of antimalarial treatments in patients with a concomitant illness, including HIV/AIDs, tuberculosis and malnutrition, is a concern. African countries are being encouraged to establish pharmacovigilance systems as ACTs are rolled out. However, pharmacovigilance is difficult, even in countries with a well-developed health care system. The rationale for pharmacovigilance of antimalarial drugs is discussed here, outlining the practical challenges and proposing approaches that could be adopted in Africa.


Acid/base-controllable fluorescent molecular switches based on cryptands and basic N-heteroaromatics.
Two kinds of fluorescent BMP32C10-based cryptands 1 and 2 have been developed. Cryptand 1 contains a binaphthol group, while cryptand 2 bears a coumarin group in their third arms. Based on this design, novel self-assemblies constructed from cryptand 1 or 2 and basic N-heteroaromatic guests 3-6 were successfully obtained. Moreover, the threading/dethreading processes of the host-guest complexes could be well switched by the alternate addition of acid/base, and accompanied by concurrent changes in fluorescence.


Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials.
Randomised controlled trials (RCTs) of vitamin D to prevent COPD exacerbations have yielded conflicting results.Individual participant data meta-analysis could identify factors that explain this variation. PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial. Four eligible RCTs (total 560 participants) were identified; individual participant data were obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75). Vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels. CRD42014013953.


Bilateral additional slips of triceps brachii forming osseo-musculo-fibrous tunnels for ulnar nerves.
Rare additional slips of triceps brachii muscle was found bilaterally in a sixty two year old South Indian male cadaver during routine dissection of upper limb for undergraduate students at Melaka-Manipal Medical College, Manipal University, Manipal, India. On left side, the variant additional muscle slip took origin from the lower part of the medial intermuscular septum about 4 cm proximal to the medial humeral epicondyle. From its origin, the muscle fibres were passing over the ulnar nerve and were joining the triceps muscle to get inserted to the upper surface of olecranon process of ulna. On right side, the additional muscle slip was larger and bulkier and was arising from the lower part of the medial border of the humerus about 4 cm proximal to the medial epicondyle in addition to its attachment to the medial intermuscular septum. On both sides, the additional slips were supplied by twigs from the radial nerve. On both sides, the ulnar nerve was passing between variant additional slip and the lower part of the shaft of the humerus in an osseo-musculo-fibrous tunnel. Such variant additional muscle slips may affect the function of triceps muscle and can lead to snapping of medial head of triceps and ulnar nerve over medial epicondyle and also can dynamically compress the ulnar nerve during the contraction of triceps leading to ulnar neuropathy around the elbow.


Validation of a questionnaire measuring preschool children's reactions to and coping with noise in a repeated measurement design.
The aim of the study was to explore and describe the reliability and validity of an instrument to measure preschool children's reactions to and coping with indoor noise at preschools or day care centres. Data were derived from an acoustical before and after intervention study providing repeated measurements. The study was performed at seven preschools in Mölndal, Sweden. Children were recruited from these preschools and the final sample comprised 61 and 59 preschool children aged 4-5 years, with a response rate of 98% and 48% girls and 52% boys. Two children were excluded from analysis because they fell outside the age range. The instrument was developed based on a qualitative study performed in Swedish preschools. Questions pertained to preschool children's perception of noise when at school, their bodily and emotional reactions to it, non-specific symptoms and the coping strategies used by them to diminish the detrimental effects of the noise. Confirmative factor analysis yielded a three-factor model fitted to 10 items pertaining to angry reactions, symptoms and coping. The model fit was moderate to good (standardised root mean square residual=0.08, 0.12; adjusted goodness of fit=0.97/0.91) in the before and after conditions, respectively. The scales showed moderate to good reliability in terms of internal consistency, with an α ranging between 0.52 and 0.67, and was stronger in the before condition. Concurrent validity was strongest for symptoms by comparing groups based on bodily reaction (general and sound specific). Young children's emotional and bodily reactions to coping with noise can be reliably measured with this instrument. Like adults and older children, young children are able to distinguish between emotional reactions, bodily reactions, coping and unwell-being. Future research on larger groups of preschool children is needed to further refine the questions, in particular the questions pertaining to well-being.


Modulation of endotoxin-induced cardiopulmonary dysfunction by S-nitroso-albumin.
Nitric oxide (NO) is an endogenous vasodilator and modulator of inflammation. During endotoxemia, the beneficial effects of NO are overwhelmed by the inflammatory cascade, resulting in a functional depletion of NO. S-nitroso-albumin (S-NO-alb) exists as a novel and highly stable NO thiol complex that slowly releases NO into the vascular micro-environment. Using a porcine model, we examined the ability of intravenous S-NO-alb to modulate cardiopulmonary dysfunction characteristic of endotoxemia. Pigs were anesthetized, instrumented for standard cardiopulmonary function measurements, and randomly assigned to receive: (i) albumin + saline; (ii) albumin + LPS; or (iii) S-NO-alb + LPS. Cardiopulmonary parameters were evaluated every 30 min and ex vivo phorbol myristate acetate (PMA)-stimulated superoxide release was serially determined as a marker of in vivo neutrophil priming. Lung myeloperoxidase (MPO) activity was measured as a marker of neutrophil migration into the lung. LPS-induced cardiopulmonary dysfunction was characterized by a sustained elevation in mean pulmonary arterial pressure, pulmonary vascular resistance, and peak intratracheal pressure, as well as a reduction in cardiac index, stroke volume index and PaO(2) over 6 h. Pretreatment with S-NO-alb attenuated LPS-induced cardiopulmonary dysfunction without adversely affecting systemic hemodynamics. Moreover, S-NO-alb blunted the LPS-induced hypoxemic response and reduced neutrophil activation. S-NO-alb did not, however, attenuate LPS-induced increases in lung MPO. Our results suggest that S-NO-alb can selectively modulate endotoxin-induced pulmonary dysfunction, attenuate neutrophil priming and block the early mortality (40%) in this model.


Guided-mode analysis by the Lanczos-Fourier expansion.
The Lanczos-Fourier series expansion is employed to analyze the guided-mode field in an asymmetrical slab waveguide, the core of which has an anisotropic and inhomogeneous dielectric permittivity. A system of linear homogeneous equations is derived by the collocation technique with consideration of the wave equation and the appropriate boundary conditions at the interfaces between the core and cladding media. The propagation constants are found from a determinant equation that ensures the existence of a nontrivial solution of the system. Numerical results are presented for several cases of dielectric permittivity, including the constant, parabolic, linear, and anisotropic cases. This approach is found to converge reasonably fast, and Richardson's extrapolation technique is applied to accelerate the convergence further. The approach can be easily generalized from the scalar to the vector equation, and, as an example, we consider the guided modes of a circular fiber.


The epidemiological surveillance of malignant mesothelioma in Italy (1993-2015): methods, findings, and research perspectives.
as a legacy of the large asbestos consumption until the definitive ban in 1992, Italy had to tackle a real epidemic of asbestos related diseases. The Italian National Registry of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with a regional structure. Aims, assignments and territorial network of ReNaM are described, as well as data collection, recording and coding procedures. to describe the Italian epidemiological surveillance system of mesothelioma incidence, to provide updated data about occurrence of malignant mesothelioma in Italy, and to discuss goals, attainments, and expectations of registering occupational cancer. analysis of data by malignant mesothelioma incident cases surveillance system. Italy, network of regional surveillance system, all Italian regions. a Regional Operating Centre (COR) is currently established in all the Italian regions, actively searching incident malignant mesothelioma cases from health care institutions. Occupational history, lifestyle habits, and residential history are obtained using a standardized questionnaire, administered to the subject or to the next of kin by a trained interviewer. The extent of dataset, epidemiological parameters, and occupations involved are reported updated at 31.12.2016, and standardized incidence rates are calculated. at December 2016, ReNaM has collected 27,356 malignant mesothelioma cases, referring to the period of incidence between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of defined cases (14,818). the Italian experience shows that epidemiological systematic surveillance of asbestos related diseases incidence has a key importance for assessing and monitoring the public health impact of occupational and/or environmental hazards, programming preventive interventions, including remediation plans and information campaigns, and supporting the efficiency of insurance and welfare system. Monitoring the incidence of malignant mesothelioma through a specialized cancer registry is essential to follow-up the health effects of changing modalities and extent of occupational exposures over years and of environmental contamination. Such consolidated surveillance system is recommended also for occupational cancers with low aetiological fraction.


Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells.
Treatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant precursor B-lineage leukemic patients. Here, we show that prednisolone resistance is associated with increased glucose consumption and that inhibition of glycolysis sensitizes prednisolone-resistant ALL cell lines to glucocorticoids. Treatment of prednisolone-resistant Jurkat and Molt4 cells with 2-deoxy-D-glucose (2-DG), lonidamine (LND), or 3-bromopyruvate (3-BrPA) increased the in vitro sensitivity to glucocorticoids, while treatment of the prednisolone-sensitive cell lines Tom-1 and RS4; 11 did not influence drug cytotoxicity. This sensitizing effect of the glycolysis inhibitors in glucocorticoid-resistant ALL cells was not found for other classes of antileukemic drugs (ie, vincristine and daunorubicin). Moreover, down-regulation of the expression of GAPDH by RNA interference also sensitized to prednisolone, comparable with treatment with glycolytic inhibitors. Importantly, the ability of 2-DG to reverse glucocorticoid resistance was not limited to cell lines, but was also observed in isolated primary ALL cells from patients. Together, these findings indicate the importance of the glycolytic pathway in glucocorticoid resistance in ALL and suggest that targeting glycolysis is a viable strategy for modulating prednisolone resistance in ALL.


Effect of Tether Conductivity on the Efficiency of Photoisomerization of Azobenzene-Functionalized Molecules on Au{111}.
We establish the role of tether conductivity on the photoisomerization of azobenzene-functionalized molecules assembled as isolated single molecules in well-defined decanethiolate self-assembled monolayer matrices on Au{111}. We designed the molecules so as to tune the conductivity of the tethers that separate the functional moiety from the underlying Au substrate. By employing surface-enhanced Raman spectroscopy, time-course measurements of surfaces assembled with azobenzene functionalized with different tether conductivities were independently studied under constant UV light illumination. The decay constants from the analyses reveal that photoisomerization on the Au{111} surface is reduced when the conductivity of the tether is increased. Experimental results are compared with density functional theory calculations performed on single molecules attached to Au clusters.


Multi-panel drugs detection in human serum for personalized therapy.
This work focuses on P450 biosensors based on multiwalled carbon nanotubes (MWCNT) and different cytochrome isoforms: 3A4, 2B4, 2C9. The proposed biosensors exhibit enhanced sensitivities and decreased detection limits thanks to carbon nanotubes. The MWCNT structuring improves the sensitivity from 5.1 to 20.5 nA/mM mm(2) in case of CYP2B4-mediated Benzphetamine detection, from 0.26 to 0.63 nA/μM mm(2) in case of CYP3A4-mediated Cyclophosphamide detection, and from 0.11 to 0.25 nA/μM mm(2) in case of CYP2C9-mediated Naproxen detection. By using MWCNT, the limit of detection was enhanced from 59 to 12 μM in case of Cyclophosphamide and from to 187 to 82 μM in case of Naproxen. This makes possible the drug detection in human serum within the pharmacological range. In the paper, a new mathematical model is also proposed to succeed in discriminating different drug contributions in a mixture containing both Cyclophosphamide and Dextromethorphan or combining Naproxen and Flurbiprofen. Data analysis shows variations in reduction peaks that are dependent on the drug ratio, and that are consistent with competitive kinetics of substrates. This new approach enables multiple drug detection and opens the way to possible applications in personalized therapy.


Exposure to bisphenol-A during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice.
Bisphenol-A (BPA) is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β-cell function and gene expression in the major peripheral organs that control energy flux: white adipose tissue (WAT), the liver and skeletal muscle, in male offspring 17 and 28 weeks old. Pregnant mice were treated with a subcutaneous injection of 10 µg/kg/day of BPA or a vehicle from day 9 to 16 of pregnancy. One month old offspring were divided into four different groups: vehicle treated mice that ate a normal chow diet (Control group); BPA treated mice that also ate a normal chow diet (BPA); vehicle treated animals that had a high fat diet (HFD) and BPA treated animals that were fed HFD (HFD-BPA). The BPA group started to gain weight at 18 weeks old and caught up to the HFD group before week 28. The BPA group as well as the HFD and HFD-BPA ones presented fasting hyperglycemia, glucose intolerance and high levels of non-esterified fatty acids (NEFA) in plasma compared with the Control one. Glucose stimulated insulin release was disrupted, particularly in the HFD-BPA group. In WAT, the mRNA expression of the genes involved in fatty acid metabolism, Srebpc1, Pparα and Cpt1β was decreased by BPA to the same extent as with the HFD treatment. BPA treatment upregulated Pparγ and Prkaa1 genes in the liver; yet it diminished the expression of Cd36. Hepatic triglyceride levels were increased in all groups compared to control. In conclusion, male offspring from BPA-treated mothers presented symptoms of diabesity. This term refers to a form of diabetes which typically develops in later life and is associated with obesity.


Stimulatory effect of hydrothermally synthesized biodegradable hydroxyapatite granules on osteogenesis and direct association with osteoclasts.
Calcium-deficient hydroxyapatite (HA) granules with a unique spherical shape were prepared using an applied hydrothermal method. Spherical stoichiometric HA granules were also prepared by normal sintering and both granules were used for implantation into rat tibiae to compare the biological responses to each implant. Twelve and 24 weeks after implantation, the volume of calcium-deficient HA granules was significantly less than that of stoichiometric HA granules, and the biodegradability of calcium-deficient HA granules was confirmed. The larger number of osteoclasts, larger osteoblast surface and larger bone volume in the implanted area of calcium-deficient HA than those of stoichiometric HA suggested that osteoclastic resorption of calcium-deficient HA affected osteogenesis in that area. To analyze the direct contribution of osteoclasts to osteogenesis, C2C12 multipotent myoblastic cells, which have the potential to differentiate into osteoblasts in the presence of bone morphogenetic protein 2, were cultured with supernatants of osteoclasts cultured on calcium-deficient HA, stoichiometric HA, beta-tricalcium phosphate disks or plastic dishes, or bone marrow macrophages cultured on plastic dishes. Supernatants of osteoclasts but not bone marrow macrophages stimulated the expression of Runx2 and osteocalcin in C2C12 cells in concert with bone morphogenetic protein 2. The expression of alkaline phosphatase was stimulated with supernatants of osteoclasts cultured on ceramic disks. These results suggested that osteoclasts produced certain soluble factors which stimulated osteoblastic differentiation and they were thought to be associated with the induction of a larger osteoblast surface and bone volume in the animals implanted with calcium-deficient HA granules.


Functional analysis of the Drosophila diaphanous FH protein in early embryonic development.
The Drosophila Formin Homology (FH) protein Diaphanous has an essential role during cytokinesis. To gain insight into the function of Diaphanous during cytokinesis and explore its role in other processes, we generated embryos deficient for Diaphanous and analyzed three cell-cycle-regulated actin-mediated events during embryogenesis: formation of the metaphase furrow, cellularization and formation of the pole cells. In dia embryos, all three processes are defective. Actin filaments do not organize properly to the metaphase and cellularization furrows and the actin ring is absent from the base of the presumptive pole cells. Furthermore, plasma membrane invaginations that initiate formation of the metaphase furrow and pole cells are missing. Immunolocalization studies of wild-type embryos reveal that Diaphanous localizes to the site where the metaphase furrow is anticipated to form, to the growing tip of cellularization furrows, and to contractile rings. In addition, the dia mutant phenotype reveals a role for Diaphanous in recruitment of myosin II, anillin and Peanut to the cortical region between actin caps. Our findings thus indicate that Diaphanous has a role in actin cytoskeleton organization and is essential for many, if not all, actin-mediated events involving membrane invagination. Based on known biochemical functions of FH proteins, we propose that Diaphanous serves as a mediator between signaling molecules and actin organizers at specific phases of the cell cycle.


Biofilm formation by a biotechnologically important tropical marine yeast isolate, Yarrowia lipolytica NCIM 3589.
Biofilm formation by Yarrowia lipolytica, a biotechnologically important fungus in microtitre plates, on glass slide surfaces and in flow cell was investigated. In microtitre plates, there was a short lag phase of adhesion followed by a period of rapid biofilm growth. The fungus formed extensive biofilms on glass slides, whereas in flow-cells a multicellular, three-dimensional microcolony structure was observed. The isolate formed biofilms in seawater and in fresh water media at neutral pH when grown in microtitre plates. The carbon sources differentially affected formation of biofilms in microtitre plates. Lactic acid, erythritol, glycerol, glucose and edible oils supported the formation of biofilms, while alkanes resulted in sub-optimal biofilm development. A variation in the morphology of the fungus was observed with different carbon sources. The results point to the possible existence of highly structured biofilms in varied ecological niches from where the yeast is isolated.


Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications: LAS VEGAS - an observational study in 29 countries.
Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. This was a prospective international 1-week observational study using the 'Assess Respiratory Risk in Surgical Patients in Catalonia risk score' (ARISCAT score) for PPC for risk stratification. Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome. The study was registered at Clinicaltrials.gov, number NCT01601223.


Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study.
IMPORTANCE Modifying levels of factors associated with age-related macular degeneration (AMD) may decrease the risk for visual impairment in older persons. OBJECTIVE To examine the relationships of markers of inflammation, oxidative stress, and endothelial dysfunction to the 20-year cumulative incidence of early AMD. DESIGN, SETTING, AND PARTICIPANTS This longitudinal population-based cohort study involved a random sample of 975 persons in the Beaver Dam Eye Study without signs of AMD who participated in the baseline examination in 1988-1990 and up to 4 follow-up examinations in 1993-1995, 1998-2000, 2003-2005, and 2008-2010. EXPOSURES Serum markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and white blood cell count), oxidative stress (8-isoprostane and total carbonyl content), and endothelial dysfunction (soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1) were measured. Interactions with complement factor H (rs1061170), age-related maculopathy susceptibility 2 (rs10490924), complement component 3 (rs2230199), and complement component 2/complement factor B (rs4151667) were examined using multiplicative models. Age-related macular degeneration was assessed from fundus photographs. MAIN OUTCOMES AND MEASURES Early AMD defined by the presence of any size drusen and the presence of pigmentary abnormalities or by the presence of large-sized drusen (≥125-μm diameter) in the absence of late AMD. RESULTS The 20-year cumulative incidence of early AMD was 23.0%. Adjusting for age, sex, and other risk factors, high-sensitivity C-reactive protein (odds ratio comparing fourth with first quartile, 2.18; P = .005), tumor necrosis factor-α receptor 2 (odds ratio, 1.78; P = .04), and interleukin-6 (odds ratio, 1.78; P = .03) were associated with the incidence of early AMD. Increased incidence of early AMD was associated with soluble vascular cell adhesion molecule-1 (odds ratio per SD on the logarithmic scale, 1.21; P = .04). CONCLUSIONS AND RELEVANCE We found modest evidence of relationships of serum high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and soluble vascular cell adhesion molecule-1 to the 20-year cumulative incidence of early AMD independent of age, smoking status, and other factors. It is not known whether these associations represent a cause and effect relationship or whether other unknown confounders accounted for the findings. Even if inflammatory processes are a cause of early AMD, it is not known whether interventions that reduce systemic inflammatory processes will reduce the incidence of early AMD.


A comparison of the gut microbiome between long-term users and non-users of proton pump inhibitors.
Proton pump inhibitor (PPI) use is associated with an increased risk of Clostridium difficile infection (CDI), though the mechanism is unclear. PPI induced alterations to the gut microbiome may facilitate the emergence of CDI, though the effects of PPIs on gut microbiota are not well characterised. [Correction added on 10 March 2016, after first online publication: microflora has been changed to microbiota throughout the article.] To compare the faecal microbiomes of long-term PPI users to those with no history of PPI use. We used a population-based database to identify individuals with ≥5 years of continuous PPI use along with non-PPI using controls. Stool samples were subjected to microbiological analysis, with hierarchical clustering at genus level, along with alpha and beta diversity measures comparing the two groups. Metadata was accounted for using quantile regression to eliminate potential confounding variables in taxonomic abundance comparisons. Sixty-one subjects (32 PPI, 29 controls) were analysed. While no significant differences in alpha diversity were found between the PPI users and controls, a moderate shift of the PPI users away from the non-PPI user cluster in the beta diversity was observed. After controlling for pertinent confounders, we discovered a decrease in Bacteroidetes and an increase in Firmicutes at the phylum level. We also performed species classifications and found Holdemania filiformis and Pseudoflavonifractor capillosus to be increased and decreased in the PPI cohort, respectively. Long-term PPIs use has an effect on the gut microbiome. The alteration in the ratio of Firmicutes to Bacteroidetes may pre-dispose to the development of CDI.


Major depressive disorder is associated with attenuated cardiovascular reactivity and impaired recovery among those free of cardiovascular disease.
To examine cardiovascular reactivity and recovery to laboratory stress among a naturalistic sample of individuals diagnosed with major depressive disorder (MDD) and healthy control participants. Prospective evidence suggests that MDD confers risk for cardiovascular disease equal to or greater than the risk associated with depressed mood. Enhanced cardiovascular reactivity has been proposed as a mechanism explaining increased risk, but data are inconsistent as to whether depressed individuals exhibit enhanced or attenuated reactivity. Further, few studies have examined appraisal and recovery differences. Participants diagnosed with MDD (N = 25) and healthy control participants (N = 25) engaged in a cardiovascular reactivity protocol including 2 tasks, each followed by a brief recovery period. Blood pressure, heart rate, pre-ejection period, cardiac output and total peripheral resistance were assessed. Appraisals of tasks were assessed prior to each task. Depressed participants exhibited significantly less systolic blood pressure, heart rate, and cardiac output reactivity during speech, less heart rate reactivity during mirror tracing, and less heart rate recovery after speech and mirror tracing than controls. Depressed participants appraised the tasks as more demanding, threatening, and stressful and reported being less able to cope than controls. Appraisals were related to heart rate reactivity, but appraisals did not mediate the relationship between depression group and reactivity. Impaired recovery rather than exaggerated cardiovascular reactivity may partially explain the increased prospective cardiovascular disease risk in depressed individuals.


The guanine nucleotide exchange factor RasGRP is a high -affinity target for diacylglycerol and phorbol esters.
RasGRP is a recently described guanine nucleotide exchange factor (GEF) that possesses a single C1 domain homologous to that of protein kinase C (PKC). The phorbol ester [(3)H]phorbol 12, 13-dibutyrate ([(3)H]PDBu) bound to this C1 domain (C1-RasGRP) with a dissociation constant of 0.58 +/- 0.08 nM, similar to that observed previously for PKC. Likewise, the potent PKC activator bryostatin 1, a compound currently in clinical trials, showed high affinity binding for C1-RasGRP. Structure activity analysis using several phorbol ester analogs showed both similarities and differences in ligand selectivity compared with PKC; the differences were comparable in magnitude to those between different PKC isoforms. Similarly, the potency of the PKC inhibitor calphostin C to inhibit [(3)H]PDBu binding to C1-RasGRP was similar to that observed for PKC. In contrast to the relative similarities in ligand recognition, the lipid cofactor requirements differed between RasGRP and PKC. The C1 domain plus the EF-hand motif of RasGRP (C1EF-RasGRP) was markedly less dependent on acidic phospholipids than was PKCalpha. The differences in lipid requirements were reflected in differential ligand selectivity under conditions of limiting lipid. Despite the presence of twin EF-hand like motifs, calcium did not affect the binding of [(3)H]PDBu to C1EF-RasGRP. We conclude that RasGRP is a high affinity receptor for phorbol esters and diacylglycerol. RasGRP thus provides a direct link between diacylglycerol generation or phorbol ester/bryostatin treatment and Ras activation.


Ovarian cancer screening in asymptomatic postmenopausal women.
From 1987 to 1992, 3220 asymptomatic postmenopausal women underwent screening with transvaginal sonography (TVS) as part of the University of Kentucky Ovarian Cancer Screening Project. Ovarian volume was calculated using the prolate ellipsoid formula (length x height x width x 0.523). An abnormal sonogram was defined by (1) an ovarian volume > 10cm3 or (2) a papillary projection into a cystic ovarian tumor. All women with an abnormal TVS had a repeat sonogram in 4-6 weeks. If the repeat sonogram was abnormal, a morphology index score was assigned to each tumor, and a serum CA-125 was obtained. The patient then had a pelvic examination and an exploratory laparotomy. Forty-four patients (1.4%) with a persisting abnormality on TVS underwent exploratory laparotomy. Twenty-one patients had serous cystadenomas and 3 had primary ovarian cancers. Two patients with primary ovarian cancer had Stage IA disease and one had Stage IIIB disease. All patients with ovarian cancer had normal pelvic examinations and normal serum CA-125 levels, and are presently alive and well 32, 31, and 8 months after conventional therapy. Over 5000 screening years have been accumulated at this institution, and there have been no ovarian cancer deaths in the screened population. TVS screening has produced a decrease in stage at detection and case-specific mortality from ovarian cancer. A multi-institutional trial to test the efficacy of TVS as a screening method for ovarian cancer is indicated.


"The Patient Is Dying, Please Call the Chaplain": The Activities of Chaplains in One Medical Center's Intensive Care Units.
Patients and families commonly experience spiritual stress during an intensive care unit (ICU) admission. Although most patients report that they want spiritual support, little is known about how these issues are addressed by hospital chaplains. To describe the prevalence, timing, and nature of hospital chaplain encounters in ICUs. This was a retrospective cross-sectional study of adult ICUs at an academic medical center. Measures included days from ICU admission to initial chaplain visit, days from chaplain visit to ICU death or discharge, hospital and ICU lengths of stay, severity of illness at ICU admission and chaplain visit, and chart documentation of chaplain communication with the ICU team. Of a total of 4169 ICU admissions over six months, 248 (5.9%) patients were seen by chaplains. Of the 246 patients who died in an ICU, 197 (80%) were seen by a chaplain. There was a median of two days from ICU admission to chaplain encounter and a median of one day from chaplain encounter to ICU discharge or death. Chaplains communicated with nurses after 141 encounters (56.9%) but with physicians after only 14 encounters (5.6%); there was no documented communication in 55 encounters (22%). In the ICUs at this tertiary medical center, chaplain visits are uncommon and generally occur just before death among ICU patients. Communication between chaplains and physicians is rare. Chaplaincy service is primarily reserved for dying patients and their family members rather than providing proactive spiritual support. These observations highlight the need to better understand challenges and barriers to optimal chaplain involvement in ICU patient care.


Alterations in leaf carbohydrate metabolism in response to nitrogen stress.
A series of experiments was conducted to characterize alterations in carbohydrate utilization in leaves of nitrogen stressed plants. Two-week-old, nonnodulated soybean plants (Glycine max [L.] Merrill, ;Ransom'), grown previously on complete nutrient solutions with 1.0 millimolar NO(3) (-), were transferred to solutions without a nitrogen source at the beginning of a dark period. Daily changes in starch and sucrose levels of leaves were monitored over the following 5 to 8 days in three experiments. Starch accumulation increased relative to controls throughout the leaf canopy during the initial two light periods after plant exposure to N-free solutions, but not after that time as photosynthesis declined. The additional increments of carbon incorporated into starch appeared to be quantitatively similar to the amounts of carbon diverted from amino acid synthesis in the same tissues. Since additional accumulated starch was not degraded in darkness, starch levels at the beginning of light periods also were elevated. In contrast to the starch effects, leaf sucrose concentration was markedly higher than controls at the beginning of the first light period after the N-limitation was imposed. In the days which followed, diurnal turnover patterns were similar to controls. In source leaves, the activity of sucrose-P synthase did not decrease until after day 3 of the N-limitation treatment, whereas the concentration of fructose-2,6-bisphosphate was decreased on day 2. Restricted growth of sink leaves was evident with N-limited plants within 2 days, having been preceeded by a sharp decline in levels of fructose-2,6 bisphosphate on the first day of treatment. The results suggest that changes in photosynthate partitioning in source leaves of N-stressed plants resulted largely from a stable but limited capacity for sucrose formation, and that decreased sucrose utilization in sink leaves contributed to the whole-plant diversion of carbohydrate from the shoot to the root.


The dynamics of solvation dictates the conformation of polyethylene oxide in aqueous, isobutyric acid and binary solutions.
Polymers hydrogen-bonding with solvent represent an important broad class of polymers, properties of which depend on solvation. Using atomistic molecular dynamics simulations with the OPLS/AA force field we investigate the effect of hydrogen bonding on PEO conformation and chain mobility by comparing its behavior in isobutyric acid and aqueous solutions. In agreement with experimental data, we found that in isobutyric acid PEO forms a rather rigid extended helical structure, while in water it assumes a highly flexible coil conformation. We show that the difference in PEO conformation and flexibility is the result of the hydrogen bond stability and overall solvent dynamics near PEO. Isobutyric acid forms up to one hydrogen bond per repeat unit of PEO and interacts with PEO for a prolonged period of time, thereby stabilizing the helical structure of the polymer and reducing its segmental mobility. In contrast, water forms on average 1.2 hydrogen bonds per repeat unit of PEO (with 60% of water forming a single hydrogen bond and 40% of water forming two hydrogen bonds) and resides near PEO for a noticeably shorter time than isobutyric acid, leading to the well-documented high segmental mobility of PEO in water. We also analyze PEO conformation, hydrogen bonding and segmental mobility in binary water/isobutyric acid solutions and find that in the phase separated region PEO resides in the isobutyric-rich phase forming about 25% of its hydrogen bonds with isobutyric acid and 75% with water. We show that the dynamics of solvation affects the equilibrium properties of macromolecules, such as conformation, and by mixing of hydrogen bond-donating solvents one can significantly alter both polymer conformation and its local dynamics.


Sphingomyelin is more sensitively detectable as a negative ion than phosphatidylcholine: a matrix-assisted laser desorption/ionization time-of-flight mass spectrometric study using 9-aminoacridine (9-AA) as matrix.
Phospholipids (PLs) are increasingly analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and imaging MS. Different classes of PLs are preferentially detectable either as positive or negative ions depending on the charges of their headgroups. Sphingomyelin (SM) and phosphatidylcholine (PC) occur in virtually all biological samples and both are assumed to be detectable with the same sensitivity (in the positive ion mode) because their headgroups are identical. We will show here that the detectabilities of PC and SM depend on the matrix used. In the presence of 2,5-dihydroxybenzoic acid (DHB) SM is more sensitively detectable in positive ion mode than PC while the use of 9-aminoacridine (9-AA) as matrix inverts the detectabilities. Our explanation is that the preferred generation of negative ions from SM if 9-AA is used as matrix results in a reduced yield of positive ions. It will also be shown that this is not only valid if a simplified model system is investigated, but also if, for instance, extracts from human erythrocytes are investigated. It will also be outlined that this finding is particularly important in the context of imaging studies where no previous separation of the lipids of interest can be performed.


Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model.
To study the effects of geranylgeranylacetone (GGA) on the expression of inducible (HSP72) and constitutive (HSC70) heat shock proteins (HSPs) on retinal ganglion cells (RGCs) in a rat model of glaucoma. Adult Wistar rats were given intraperitoneal injections of GGA at 200 mg/kg daily. Western blot analysis and immunohistochemical staining for HSP72 and HSC70 were performed after 1, 3, and 7 days of treatment with GGA. After 7 days of GGA pretreatment, intraocular pressure (IOP) was elevated unilaterally by repeated trabecular argon laser photocoagulation 5 days after intracameral injection of india ink. After the first laser photocoagulation, GGA was administered twice a week. RGC survival was evaluated after 5 weeks of elevated IOP. Immunohistochemistry and TdT-mediated biotin-dUTP nick end labeling (TUNEL) were performed after 1 week of elevated IOP. Quercetin, an inhibitor of HSP expression, was also administered to a separate group. There was increased expression of HSP72 in RGCs at 3 and 7 days after administration of GGA, but HSC70 was unchanged. After 5 weeks of elevated IOP, there was a 27% +/- 6% loss of RGCs. The administration of GGA significantly reduced the loss of RGCs, lessened optic nerve damage, decreased the number of TUNEL-positive cells in the RGC layer, and increased HSP72. Quercetin abolished these protective effects. These results demonstrate that systemic administration of GGA protects RGCs from glaucomatous damage in a rat model and suggest a novel pathway for neuroprotection in patients with glaucoma.


Tardive dyskinesia associated with metoclopramide.
Eleven cases of tardive dyskinesia associated with metoclopramide have been reported to the Swedish Adverse Drug Reactions Advisory Committee from 1977 to 1981, 10 of which developed during the past three years. All patients were women, with a mean age of 76 years. Median duration of treatment before the onset of symptoms was 14 months. Calculated from total drug sales and prescription statistics the incidence of tardive dyskinesia during treatment with metoclopramide was estimated to be one in 2000-2800 treatment years. Extrapolation of data on long term treatment (more than six months) of patients aged 70 years or more, from a survey based on individual prescriptions yielded an incidence of more than one in a 1000 patients. Long term treatment with metoclopramide is accompanied by a substantial risk of developing tardive dyskinesia especially among elderly people.


View-Tolerant Face Recognition and Hebbian Learning Imply Mirror-Symmetric Neural Tuning to Head Orientation.
The primate brain contains a hierarchy of visual areas, dubbed the ventral stream, which rapidly computes object representations that are both specific for object identity and robust against identity-preserving transformations, like depth rotations [1, 2]. Current computational models of object recognition, including recent deep-learning networks, generate these properties through a hierarchy of alternating selectivity-increasing filtering and tolerance-increasing pooling operations, similar to simple-complex cells operations [3-6]. Here, we prove that a class of hierarchical architectures and a broad set of biologically plausible learning rules generate approximate invariance to identity-preserving transformations at the top level of the processing hierarchy. However, all past models tested failed to reproduce the most salient property of an intermediate representation of a three-level face-processing hierarchy in the brain: mirror-symmetric tuning to head orientation [7]. Here, we demonstrate that one specific biologically plausible Hebb-type learning rule generates mirror-symmetric tuning to bilaterally symmetric stimuli, like faces, at intermediate levels of the architecture and show why it does so. Thus, the tuning properties of individual cells inside the visual stream appear to result from group properties of the stimuli they encode and to reflect the learning rules that sculpted the information-processing system within which they reside.


Colorectal cancer: prognostic values.
After lung cancer colorectal cancer (Cc) is ranked the second, as a cause of cancer-related death. The purpose of this study was to analyze the Cc cases in our material with respect to all prognostic values including histological type and grade, vascular invasion, perineural invasion, and tumor border features. There were investigated 149 cases of resection specimen with colorectal cancer, which were fixed in buffered neutral formalin and embedded in paraffin. Tissue sections (4(mum thick) were cut and stained with H&E. Adenocarcinoma was the most frequent histological type found in 85,90% of cases, in 60,94% of males and 39,06% of females; squamous cell carcinoma in 7,38%, in 63,63% of males and 36,36% of females; mucinous carcinoma in 4,68%, in 57,15% of males and 42,85% of females; while adenosquamous carcinoma, undifferentiated carcinoma and carcinoma in situ in 0,71% of cases each. Dukes' classification was used in order to define the depth of invasion. Dukes B was found in 68,45% of cases, whereas in 31,54% of cases Dukes C was found. As far as histological grading is concerned, Cc was mostly with moderate differentiation (75,16%) with neither vascular nor perineural invasion. Resection margins were in all cases free of tumor. Our data indicate that the pathologic features of the resection specimen constitute the most powerful predictors of postoperative outcome in Cc. Dukes' stage and degree of differentiation provide independent prognostic information in Cc. However, differentiation should be assessed by the worst pattern.


[Characterization of anti human uterine endometrial cancer antibody (MSN-1) and its usefulness in clinical application].
We have produced a monoclonal antibody (MSN-1), by using our endometrial cancer-cultured cell line (SNG-II) as an immunogen. MSN-1 belongs to the IgM immunoglobulin class and mainly recognized the Lewis carbohydrate moiety. It seldom, reacted immunohistochemically with normal endometrium but with about 90% of endometrial cancer cases. So, we evaluated the effectiveness of its use in clinical application. We studied the relationship between the stage of cancer and reactivity to MSN-1, and that between the reactivity of moderately differentiated endometrial cancer to MSN-1 and a 5-year survival rate. Endometrial cancer with a poor prognosis tended to react poorly to MSN-1, suggesting the possibility that the reactivity to MSN-1 is useful as a new prognostic factor. A study of endometrial hyperplasia revealed that the reactivity to MSN-1 was high in the high risk group (individuals diagnosed as endometrial cancer later). This suggested that the analysis of the expression of the antigen recognized by MSN-1 is useful in selecting the high risk group out of patients with endometrial hyperplasia. Furthermore, we indicated that abnormal expression of the antigen recognized by MSN-1 associated with neoplasia of endometrial cells is useful in developing a new diagnostic method for example our endometrial cell enzyme immunoassay (EmC-EIA) and will be helpful in developing diagnostic approaches, such as missile therapy with a complex of MSN-1 and adriamycin for endometrial cancer.


Maternal breastfeeding history and Alzheimer's disease risk.
The effect of early and midlife factors on later-life cognitive function has attracted scientific and public interest in recent years, especially with respect to hormonal risk factors for dementia. There is substantial evidence for reproductive history affecting Alzheimer's disease (AD) etiology. Here, we demonstrate how breastfeeding history affects women's risk of AD. Reproductive history data was collected, and AD diagnostic interviews were performed, for a cohort of elderly British women. Using Cox proportional-hazard models, we find that longer breastfeeding duration corresponded to reduced risk of AD (p < 0.01, n = 81). Women who breastfed had lower AD risk than women who did not breastfeed (p = 0.017, n = 81). Breastfeeding practices are an important modifier of cumulative endogenous hormone exposure for mothers. Ovarian hormone deprivation and/or insulin sensitivity benefits of breastfeeding may be responsible for the observed reduction in AD risk. Future studies concerning hormone effects on AD risk should consider how reproductive history leads to variation in endogenous hormone exposure and how this may influence the relationship between hormones and AD.


Local renin-angiotensin system in the microcirculation of spontaneously hypertensive rats.
We studied the local renin-angiotensin system in the microcirculation of cremaster muscle in spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. We used intravital microscopy in an original preparation of cremaster isolated from its normal blood supply and externally perfused with physiological solution, thus allowing the exclusion of circulating converting enzyme, circulating renin, and circulating angiotensinogen. We classified arterioles studied as second-, third-, and fourth-order, with mean diameters, respectively, of 67 +/- 6, 35 +/- 2, and 17 +/- 1 microns in WKY controls and 61 +/- 5, 34 +/- 2, and 16 +/- 1 microns in SHR. No difference between WKY controls and SHR was found for arteriolar vasoconstrictions in response to topical administration of 0.01 to 1 nmol/mL angiotensin II. Conversely, in response to 0.01 to 1 nmol/mL angiotensin I, significantly more arteriolar vasoconstriction was found in SHR cremaster muscle. In both strains, responses to angiotensin I were significantly inhibited by 10 nmol/mL of the angiotensin-converting enzyme inhibitor lisinopril. When angiotensinogen-rich, renin-free plasma containing 2.3 nmol/mL angiotensinogen was administered, almost no vasoconstriction was found in WKY controls, but significant constrictions were observed in SHR (23 +/- 4%, 30 +/- 5%, and 41 +/- 4% for second-, third-, and fourth-order arterioles, respectively). In SHR, vasoconstriction in response to angiotensinogen-rich, renin-free plasma was dose dependent, was inhibited by lisinopril, and was not found 24 hours after bilateral nephrectomy. Topical administration of 1.2 micrograms/mL renin did not induce arteriolar vasoconstriction in either WKY or SHR cremaster muscle.(ABSTRACT TRUNCATED AT 250 WORDS)


Meeting report: A celebration of the work of Professor Tony Hart, Liverpool, United Kingdom, 7 March 2009.
Over 300 delegates participated in this scientific meeting to celebrate the career of the late Professor Tony Hart, who was Head of Department of Medical Microbiology, University of Liverpool, from 1986 until his death in September 2007. The meeting, which was opened by Professor James Stewart (Head, School of Infection and Host Defence, University of Liverpool) and closed by Professor Bernard Brabin (Head of the Child Health Group, Liverpool School of Tropical Medicine), captured some of the major elements that distinguished Tony Hart's remarkable career. These included: broad research interests spanning both human and veterinary medicine; the ability to conduct both clinical and basic science research with equal skill and vigour; and his phenomenal mentorship of postgraduate students. Each session was chaired by a colleague who had co-supervised students with Tony Hart and 10 former students spoke about the work that they undertook under his supervision. Session themes included herpes viruses (cytomegalovirus and herpes simplex virus), paediatric infections (respiratory syncytial virus, rotavirus, Neisseria meningitidis and Salmonella typhi) and zoonoses (non-typhoidal salmonellae, Cryptosporidium, antibiotic resistance and emerging infections), reflecting the broad range of Tony Hart's contribution to medical microbiology.


Signaling proteins and pathways affected by flavonoids in leukemia cells.
Flavonoids are a class of plant secondary metabolites that are found ubiquitously in plants and in the human diet. Our objective is to investigate the antiproliferative effects of flavonoids (baicalein, luteolin, genistein, apigenin, scutellarin, galangin, chrysin, and naringenin) toward leukemia cells (HL-60, NB4, U937, K562, Jurkat) as well as the relationship between their antileukemic potencies and molecular structures. At the proteomic level, we evaluate the effects of different flavonoids on the expression levels of various proteins using Protein Pathway Array (PPA) technology. Our results showed a dose-dependent cytotoxicity of flavonoids toward various types of leukemia cells. The results of PPA illustrated that flavonoids, such as baicalein, genistein, and scutellarin affected different proteins in different leukemia cell lines. Cell cycle regulatory proteins, such as CDK4, CDK6, Cyclin D1, Cyclin B1, p-CDC2, and p-RB were affected in different leukemia cells. Furthermore, we found that baicalein suppresses CDK4 and activates p-ERK in most leukemia cells; genistein mainly affects CDK4, p-ERK, p-CDC2, while scutellarin dysregulated the proteins, cell division control protein 42, Notch4, and XIAP. Collectively, a wide variety of dysregulation of key signaling proteins related to apoptosis and cell-cycle regulation contributes to the antileukemic properties of these flavonoids.


A randomized control trial examining the effect of acceptance and commitment training on clinician willingness to use evidence-based pharmacotherapy.
This study evaluated the effectiveness of acceptance and commitment training (ACT) for increasing drug and alcohol counselors' willingness to use evidence-based agonist and antagonist pharmacotherapy. Fifty-nine drug and alcohol counselors were randomly assigned to either a 1-day ACT workshop or a 1-day educational control workshop. Both groups then attended a 2-day workshop on empirically supported treatments for substance abuse. Measures were taken at pre- and posttraining and 3-month follow-up on reported use of pharmacotherapy, willingness to use pharmacotherapy, perceived barriers to implementing new treatments, and general acceptance. As compared with those in the education alone condition, participants in the ACT condition showed significantly higher rates of referrals to pharmacotherapy at follow-up, rated barriers to learning new treatments as less believable at posttraining and follow-up, and showed greater psychological flexibility at posttraining and follow-up. Mediational analyses indicated that reduced believability of barriers and greater psychological flexibility mediated the impact of the intervention. Results support the idea that acceptance-based interventions may be helpful in addressing the psychological factors related to poor adoption of evidence-based treatments.


Spinal cord injury after traumatic spine fracture in patients with ankylosing spinal disorders.
OBJECTIVE Spinal cord injury (SCI) is a major complication of spinal fractures in patients with ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH). Due to the uncommon nature of these conditions, existing literature consists of relatively small case series without detailed neurological data. This study aims to investigate the incidence, predictors, and sequelae of SCI in patients with a traumatic fracture of the ankylosed spine. METHODS The study included all patients older than 18 years of age with AS or DISH who presented to two affiliated tertiary care centers between January 1, 1990, and January 1, 2016, and had a traumatic fracture of the spine. Factors associated with SCI after traumatic fracture were compared using Fisher's exact tests. Logistic regression was used for the analysis of predictive factors for SCI. For the comparison of probability of survival between patients with and without SCI, Kaplan-Meier methodology was used. RESULTS One hundred seventy-two patients with a traumatic fracture of an ankylosed spine were included. Fifty-seven patients (34.1%) had an SCI associated with the fracture. The cervical spine was the most fractured region for patients both with (77.2%) and without (51.4%) SCI. A cervical fracture (odds ratio [OR] 2.70, p = 0.024) and a spinal epidural hematoma (SEH) after fracture (OR 2.69, p = 0.013) were predictive of SCI. Eleven patients (19.3%) with SCI had delayed SCI (range 8-230 days). Of 44 patients with SCI and sufficient follow-up, 20 (45.5%) had neurological improvement after treatment. Early and late complication rates were significantly higher (p = 0.001 and p = 0.004) and hospital stay was significantly longer (p = 0.001) in patients with SCI. The probability of survival was significantly lower in the SCI group compared with the non-SCI group (p = 0.006). CONCLUSIONS The incidence of SCI was high after fracture of the spine in patients with AS and DISH. Predictive factors for SCI after fracture were a fracture in the cervical spine and an SEH following fracture. One-fifth of the patients with SCI had delayed SCI. Patients with SCI had more complications, a longer hospital stay, and a lower probability of survival. Less than half of the patients with SCI showed neurological improvement.


Deep vein harvest: predicting need for fasciotomy.
Deep thigh veins, including the superficial femoral, superficial femoropopliteal, and profunda femoris veins, are versatile autogenous conduits for arterial reconstruction. Although late venous complications are unusual, deep vein harvest may induce severe venous hypertension and predispose the limb to acute compartment syndrome. The purpose of this study was to define the frequency of fasciotomy in patients undergoing deep vein harvest and to identify clinical predictors of the need for fasciotomy after deep vein harvest. Over 9 years, 162 patients underwent arterial reconstruction with deep vein harvested from 264 limbs. Indications for deep vein harvest included aortofemoral reconstruction in 127 patients, brachiocephalic arterial reconstruction in 22 patients, and visceral arterial reconstruction in 13 patients. Fasciotomy was performed in 47 of 264 limbs (17.8%) after deep vein harvest. The prevalence of fasciotomy after deep vein harvest was 20.6% for patients requiring aortofemoral reconstruction, whereas no patients underwent fasciotomy after deep vein harvest for mesenteric or brachiocephalic arterial reconstruction (P =.0068). Fasciotomy was performed in 20.7% of limbs after complete deep vein harvest to a level below the adductor hiatus, but no fasciotomies were performed in patients undergoing subtotal deep vein harvest, ending above the adductor hiatus (P =.0023). The mean preoperative ankle-brachial index (ABI) was significantly lower in limbs requiring fasciotomy (ABI, 0.39 +/- 0.05), compared with patients who did not require fasciotomy (ABI, 0.79 +/- 0.02; P <.0001). Fasciotomy was performed in 76.0% of limbs undergoing concurrent ipsilateral greater saphenous vein (GSV) and deep vein harvest, compared with 11.7% of patients undergoing deep vein harvest alone (P <.0001). The mean volume of intraoperative fluid administered to patients requiring fasciotomy was almost 50% higher than the fluid resuscitation received by patients who did not require fasciotomy (9.6 +/- 1.2 L vs 6.5 +/- 0.6 L; P <.0001). Logistic regression analysis determined that lower preoperative ABI (odds ratio [OR], 60.1; 95% confidence interval [CI], 12.5-289.3; P <.0001) and concurrent harvest of the ipsilateral GSV (OR, 9.9; 95% CI, 3.1-31.3; P <.0001) were predictors of the need for fasciotomy. One in four patients undergoing deep vein harvest for aortofemoral reconstruction may be expected to develop acute compartment syndrome and require fasciotomy. The risk appears to be greatest in patients with severe lower extremity ischemia and in patients undergoing simultaneous GSV and deep vein harvest. Prophylactic fasciotomy may be appropriate in patients with both risk factors, but vigilance for the development of compartment syndrome after deep vein harvest is required in all patients undergoing deep vein harvest for aortofemoral reconstruction.


Regulation of intercellular adhesion molecule-1 (ICAM-1) in ischemic and reperfused canine myocardium.
Previous studies in vitro have shown an important role for intercellular adhesion molecule-1 (ICAM-1) in adherence interactions of canine neutrophils with canine jugular vein endothelial cells and in cytotoxicity of canine neutrophils for adult cardiac myocytes. To evaluate the regulation of ICAM-1 in myocardial inflammation and its role in the pathogenesis of myocardial ischemia and reperfusion, a series of in vivo and ex vivo studies were performed in canine animals. Systemic administration of LPS elicited ICAM-1 mRNA in several tissues, including myocardium, which demonstrated increasing ICAM-1 staining on intercalated discs of cardiac myocytes. In ischemia and reperfusion protocols: (a) ICAM-1 mRNA was found in ischemic segments within 1 h of reperfusion and in both ischemic and normally perfused segments by 24 h of reperfusion; (b) expression of ICAM-1 was detected in cardiac myocytes in the ischemic region by 6 h of reperfusion; increased expression was seen thereafter as a function of time; (c) post-ischemic (but not preischemic) cardiac lymph collected at intervals from 1 to 24 h after reperfusion elicited ICAM-1 mRNA, ICAM-1 expression, and ICAM-1-dependent neutrophil adhesion in canine jugular vein endothelial cells and in cardiac myocytes with peak cytokine activity seen by 1 h; (d) extravascular localization of neutrophils was detected in ischemic areas only, and was associated with endothelium bearing high levels of ICAM-1 within 1 h of reperfusion; infiltration increased thereafter in association with increasing levels of ICAM-1 mRNA in myocardial segments and increasing levels of ICAM-1 expression on cardiac myocytes. These findings provide the first direct evidence for inflammatory regulation of ICAM-1 in ischemic and reperfused canine myocardium. They support the hypothesis that ICAM-1 participates in neutrophil-mediated myocardial damage.


Suicide Prevention: A Healer Education and Referral Program for Nurses.
The aim of this study was to describe the pilot expansion of a proactive suicide risk-screening program, initially designed for physicians, to nurses. The Healer Education, Assessment and Referral (HEAR) program detects at-risk physicians and facilitates referral to mental healthcare. Nothing similar has been available for at-risk nurses. Local nurse suicides served as the catalyst to extend the HEAR program to nurses. Education, outreach, and an encrypted, online, anonymous, proactive risk screening were conducted to identify and refer nurses with depression and suicide risk. During the 1st 6 months of the program, 172 of 2475 (7%) nurses completed questionnaires; 74 (43%) were rated as high risk, and another 98 (55%) as moderate risk; 12 (7%) reported current active thoughts or actions of self-harm, and 19 (11%) reported previous suicide attempts. Forty-four (26%) received in-person or verbal counseling, and 17 accepted referral for continued treatment. An encrypted, anonymous, proactive risk screening is effective at identifying nurses at risk and referring them to mental healthcare.


Pancreatic primitive neuroectodermal tumor: Focus on radiological features and differential diagnosis - A case report and literature review.
Primitive neuroectodermal tumor (PNET) is an exceedingly rare type of malignant tumor. The diagnosis of pancreatic PNET is usually challenging for radiologists and surgeons, especially when an accurate preoperative diagnosis is needed. Herein, we report a case of a 36-year-old patient with a mass diagnosed as PNET in the head of the pancreas and present a literature review. Compared to previous literature reports, there were some imaging features observed by computed tomography (CT) in our case that might be helpful for a relatively accurate preoperative diagnosis. PNET should be considered preoperatively for soft-tissue neoplasms of the pancreas when the diagnosis of more common pancreatic tumors is not favored by signs in CT, especially in pediatric and adolescent populations. This case is the 20th case of pancreatic PNET reported in literature.


Synthetic Terrein Inhibits Progression of Head and Neck Cancer by Suppressing Angiogenin Production.
Head and neck cancers are the fifth most common cancer type worldwide, affecting more than half a million patients annually. Development of effective therapeutic drugs is, therefore, required for this type of disease. This study assessed the effects of synthetic terrein on head and neck cancer. Synthetic terrein was prepared by using the modified Altenhach's procedure. The effect of synthetic terrein on cell proliferation of head and neck cancer cells and HUVECs was assessed. Angiogenin secretion and ribosome biogenesis were examined by ELISA and silver staining of the nucleolar organizer region. A mouse xenograft model was prepared by inoculating mice with suspensions of cells of the human head and neck cancer cell line OSC-19 subcutaneously into the dorsal region of each mouse. Ki-67, CD31 and angiogenin expression in xenografted tumors was examined by immunohistochemistry. Synthetic terrein inhibited the growth of various head and neck cancer cells. In addition, an in vivo experiment revealed that synthetic terrein inhibited a xenograft tumor growth in athymic mice. Immunohistochemical analysis revealed that expression of Ki-67, CD31 and ANG was down-regulated in synthetic terrein-treated tumors, compared to controls. Synthetic terrein suppressed the ANG secretion and ribosome biogenesis in cancer cells, and cell proliferation in vascular endothelial cells. The mechanism underlying the anti-tumor effects of synthetic terrein against head and neck cancer consists of the inhibition of both tumor cell proliferation and angiogenesis via the suppression of ANG production.


The elderly patient with acute renal failure.
Structural and functional changes observed in the aging kidney predispose the elderly patient to acute renal failure. Up to 36% of the patients with acute renal failure from this institution were over 70 yr, and the literature is full of similar experiences. The elderly patient with abrupt cessation of adequate renal function requires a special work-up in diagnosis and treatment. Prerenal and obstructive causes are of particular interest. Although the question of whether or not age has an independent prognostic importance during an episode of acute renal failure remains debated; when these and other authors compared the outcome of young and old populations with these disorders, a similar evolution was always observed. Age should not be used as a discriminant factor in therapeutic decisions concerning acute renal failure.


Myocarditis secondary to smallpox vaccination.
The development of vaccines ushered in the most profound advancement in 20th century medicine, and have widely been regarded as the one of the most important scientific discovery in the history of mankind. However, vaccines are not without risk; reactions can range from injection site reactions to life-threatening anaphylaxis. Among the more serious vaccine-related sequela is myocarditis. Although myocarditis has been reported following many different vaccines, the smallpox vaccine has the strongest association. We report a case of a 36-year-old active duty service member presenting with progressive dyspnoea, substernal chest pain and lower extremity swelling 5 weeks after receiving the vaccinia vaccination. The aetiology of his acute decompensated heart failure was determined to be from myocarditis. Although the majority of cases of myocarditis resolve completely, some patients develop chronic heart failure and even death. Vaccine-associated myocarditis should always be on the differential for patients that exhibit cardiopulmonary symptoms after recent vaccinations.


Charge Transport in Zirconium-Based Metal-Organic Frameworks.
Metal-organic frameworks (MOFs) are a class of crystalline porous materials characterized by inorganic nodes and multitopic organic linkers. Because of their molecular-scale porosity and periodic intraframework chemical functionality, MOFs are attractive scaffolds for supporting and/or organizing catalysts, photocatalysts, chemical-sensing elements, small enzymes, and numerous other functional-property-imparting, nanometer-scale objects. Notably, these objects can be installed after the synthesis of the MOF, eliminating the need for chemical and thermal compatibility of the objects with the synthesis milieu. Thus, postsynthetically functionalized MOFs can present three-dimensional arrays of high-density, yet well-separated, active sites. Depending on the application and corresponding morphological requirements, MOF materials can be prepared in thin-film form, pelletized form, isolated single-crystal form, polycrystalline powder form, mixed-matrix membrane form, or other forms. For certain applications, most obviously catalytic hydrolysis and electro- or photocatalytic water splitting, but also many others, an additional requirement is water stability. MOFs featuring hexa-zirconium(IV)-oxy nodes satisfy this requirement. For applications involving electrocatalysis, charge storage, photoelectrochemical energy conversion, and chemiresistive sensing, a further requirement is electrical conductivity, as embodied in electron or hole transport. As most MOFs, under most conditions, are electrically insulating, imparting controllable charge-transport behavior is both a chemically intriguing and chemically compelling challenge.Herein, we describe three strategies to render zirconium-based metal-organic frameworks (MOFs) tunably electrically conductive and, therefore, capable of transporting charge on the few nanometers (i.e., several molecular units) to few micrometers (i.e., typical dimensions for MOF microcrystallites) scale. The first strategy centers on redox-hopping between periodically arranged, chemically equivalent sites, essentially repetitive electron (or hole) self-exchange. Zirconium nodes are electrically insulating, but they can function as grafting sites for (a) redox-active inorganic clusters or (b) molecular redox couples. Alternatively, charge hopping based on linker redox properties can be exploited. Marcus's theory of electron transfer has proven useful for understanding/predicting trends in redox-hopping based conductivity, most notably, in accounting for variations as great as 3000-fold depending on the direction of charge propagation through structurally anisotropic MOFs. In MOF environments, propagation of electronic charge via redox hopping is necessarily accompanied by movement of charge-compensating ions. Consequently, rates of redox hopping can depend on both the identity and concentration of ions permeating the MOF. In the context of electrocatalysis, an important goal is to transport electronic charge fast enough to match or exceed the inherent activity of MOF-based or MOF-immobilized catalysts.Bandlike electronic conductivity is the focus of an alternative strategy: one based on the introduction of molecular guests capable of forming donor-acceptor charge transfer complexes with the host framework. Theory again can be applied predictively to alter conductivity. A third strategy similarly emphasizes electronic conductivity, but it makes use of added bridges in the form of molecular oligomers or inorganic clusters that can then be linked to span the length of a MOF crystallite. For all strategies, retention of molecular-scale porosity is emphasized, as this property is key to many applications. Finally, while our focus is on Zr-MOFs, the described approaches clearly are extendable to other MOF compositions, as has already been demonstrated, in part, in studies by others.


Chemical Composition and Antimicrobial Activities of Iranian Propolis
With considering the importance of natural products for their remedial and therapeutic value, this research was aimed to analyze the chemical compositions and antimicrobial activity of four propolis samples from different areas of Iran (Chenaran, Taleghan, Morad Beyg, and Kalaleh) with various climates and flora. Ethanolic (70% EtOH) and dichlromethane (DCM) extracts of Iranian propolis were analyzed by gas chromatography-mass spectrometry (GC-MS) methods, and antimicrobial activity was evaluated against Candida albicans, Escherichia coli, and Staphylococcus aureus using disk diffusion antimicrobial method. The results of GC-MS analysis showed the presence of fatty acids, flavonoids, terpenes, aromatic-aliphatic acids, and their related esters. The total flavonoids in DCM extract of Chenaran, Taleghan, Morad Beyg, and Kalaleh propolis were pinocembrin and pinostrobin chalcone. The common phenolic and terpene compounds detected in all four tested EtOH extracts were P-cumaric acid and dimethyl -1,3,5,6-tetramethyl-[1,3-(13C2)] bicycloce [5.5.0] dodeca-1,3,5,6,8,10-hexaene-9,10-dicarboxylate, respectively. The highest inhibitory diameter zone of the Iranian propolis against C. albicans, E. coli, and S. aureus was for DCM extract of Kalaleh propolis (13.33 mm), Morad Beyg propolis (12 mm), and Kalaleh (11.67 mm), respectively. Iranian propolis showed antimicrobial activities against C. albicans, E. coli, and S. aurous, perhaps due to the presence of flavonoids, phenolic acids, and terpenes as active components that can be used alone or in combination with the selected antibiotics to synergize antibiotic effect, as well as to prevent microbial resistance to available antimicrobial drugs.


Production of B cell stimulatory factor-2 and interferon gamma in the central nervous system during viral meningitis and encephalitis. Evaluation in a murine model infection and in patients.
Synthesis of B cell-stimulating factor-2 (BSF-2) and IFN-gamma was shown in cerebrospinal fluids (CSF) collected from mice with experimental viral meningitis. In the CSF, the level of BSF-2 started to increase 24 h after intracerebral infection with lymphocytic choriomeningitis virus (LCMV) with rapid increase after day 4. IFN-gamma was not detected in the CSF before day 5 or 6 after infection, but increased sharply thereafter. In athymic nude mice, LCMV infection did not result in meningitis, and both BSF-2 and IFN-gamma levels were only slightly and transiently elevated. These findings suggest that activated mature T cells are required for development of disease and production of both BSF-2 and IFN-gamma. As observed in mice, BSF-2 was also detected in 16 out of 19 CSF samples collected from patients with acute viral infections of the central nervous system (CNS). Intrathecal production of BSF-2 and IFN-gamma may be instrumental in local production of antiviral antibodies by B lymphocytes/plasma cells invading the CNS during viral CNS disease.


Collagen genes and proteins in osteogenesis imperfecta.
Type I collagen is a heteropolymer of alpha 1(I) and alpha 2(I) chains, each of which is a separate product of genes localised to chromosomes 17 and 7 respectively. Molecular defects of type I collagen produce a group of inherited disorders of connective tissue primarily affecting bones, which are easily broken and collagen depleted (osteogenesis imperfecta). Sillence classifies these diseases into four groups, two of which are autosomal dominant and relatively mild, the others being either genetic lethals or responsible for very severe progressive disease. Here we describe two specific molecular abnormalities of type I collagen. One, a cysteine substitution in alpha 1(I) collagen, causes a mild Sillence type I disease, the other, a four base deletion in the C terminal extension of alpha 2(I) collagen, causes progressive Sillence type III disease in the homozygously affected patient and mild premature osteoporosis in his clinically symptomless parents. We have briefly reviewed a variety of other similar mutations causing various OI syndromes, which are tabulated, including various helical and non-helical deletions and a variety of structural protein changes. Several restriction fragment length polymorphisms for alpha 2(I) and alpha 1(II) collagens have also been described, and 5' EcoRI and 3' MspI polymorphisms for alpha 2(I) collagen segregate with Sillence type IV OI.


The evolution of a UK regional tobacco control office in its early years: social contexts and policy dynamics.
The Smoke Free North East Office (SFNEO) is the first dedicated tobacco control office in the UK coordinating a regional tobacco control network, Smoke Free North East (SFNE). On the basis of ethnographic research conducted between 2006 and 2008, this article examines the context for SFNEO's emergence at this time and in this region of England, and the main policy and practice challenges it has faced in its early years. SFNE formed in a favourable political and cultural climate, although regional champions were crucial in setting it up. It has worked well in branding itself and in taking advantage of the opportunity to lobby in support of comprehensive smoke-free legislation, although the success of the legislation presents a risk that people will regard SFNE's work as finished. There is a need for independent sustainable funding, strong partnership working and the 'bringing together' of existing organizations under its leadership for an organization such as SFNE to succeed. SFNE offers a model that is transferable to other places as well as to other public health concerns such as alcohol, and has been taken up by public health planners and policy makers with alacrity. This indicates a general perception that SFNE plays an effective role in public health delivery.


Implantology and Periodontal Disease: The Panacea to Problem Solving?
The specialty of periodontology has changed dramatically in recent years. With the long-standing goal of retaining teeth in a functional and esthetical state, the periodontology has developed a high level of expertise in the regeneration of bone and connective tissues that support the teeth. However, periodontists have also joined maxillofacial surgeons as the primary providers of implant surgery. The tremendous innovations of periodontists induced also by the marketplace resulted in predictable periodontal treatment outcomes for most patients by the implants led to a dramatically different marketplace in which many patients with periodontitis can be treated by the implants rather than the traditional periodontal treatment. The aim of this article is to focus on the innovator's dilemma for periodontists today is that key elements of our rewarding contributions to dentistry in recent decades are unlikely to be part of a strong and rewarding future for the profession. With the intriguing role of the personalized medicine approach that integrates genomic and clinical information to predict a possible predisposition, we do not suggest a reduced role for periodontists in dental implant surgery but rather a more prominent role in complex cases to achieve surgical implant needs and proper reconstruction and long-term maintenance of the patient's health.