Retrospective, epidemiological cluster analysis of the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic using open source data.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is caused by a novel coronavirus discovered in 2012. Since then, 1806 cases, including 564 deaths, have been reported by the Kingdom of Saudi Arabia (KSA) and affected countries as of 1 June 2016. Previous literature attributed increases in MERS-CoV transmission to camel breeding season as camels are likely the reservoir for the virus. However, this literature review and subsequent analysis indicate a lack of seasonality. A retrospective, epidemiological cluster analysis was conducted to investigate increases in MERS-CoV transmission and reports of household and nosocomial clusters. Cases were verified and associations between cases were substantiated through an extensive literature review and the Armed Forces Health Surveillance Branch's Tiered Source Classification System. A total of 51 clusters were identified, primarily nosocomial (80·4%) and most occurred in KSA (45·1%). Clusters corresponded temporally with the majority of periods of greatest incidence, suggesting a strong correlation between nosocomial transmission and notable increases in cases.

Public understandings of potential policy responses to health inequalities: Evidence from a UK national survey and citizens' juries in three UK cities.

A substantial body of research describes the distribution, causes and potential reduction of health inequalities, yet little scholarship examines public understandings of these inequalities. Existing work is dominated by small-scale, qualitative studies of the experiences of specific communities. As a result, we know very little about what broader publics think about health inequalities; and even less about public views of potential policy responses. This is an important gap since previous research shows many researchers and policymakers believe proposals for 'upstream' policies are unlikely to attract sufficient public support to be viable. This mixed methods study combined a nationally representative survey with three two-day citizens' juries exploring public views of health inequalities and potential policy responses in three UK cities (Glasgow, Manchester and Liverpool) in July 2016. Comparing public opinion elicited via a survey to public reasoning generated through deliberative processes offers insight into the formation of public views. The results challenge perceptions that there is a lack of public support for upstream, macro-level policy proposals and instead demonstrate support for proposals aiming to tackle health inequalities via improvements to living and working conditions, with more limited support for proposals targeting individual behavioural change. At the same time, some macro-economic proposals, notably those involving tax increases, proved controversial among study participants and results varied markedly by data source. Our analysis suggests that this results from three intersecting factors: a resistance to ideas viewed as disempowering (which include, fundamentally, the idea that health inequalities exist); the prevalence of individualising and fatalistic discourses, which inform resistance to diverse policy proposals (but especially those that are more 'upstream', macro-level proposals); and a lack of trust in (local and national) government. This suggests that efforts to enhance public support for evidence-informed policy responses to health inequalities may struggle unless these broader challenges are also addressed.

Oxygen for treatment of severe pneumonia in The Gambia, West Africa: a situational analysis.

SETTING: Health facilities in The Gambia, West Africa. OBJECTIVES: Oxygen treatment is vital in pneumonia, the leading cause of death in children globally. There are shortages of oxygen in developing countries, but little information is available on the extent of the problem. We assessed national oxygen availability and use in The Gambia, a sub-Saharan African country. METHODS: A government-led team visited 12 health facilities in The Gambia. A modified World Health Organization assessment tool was used to determine oxygen requirements, current provision and capacity to support effective oxygen use. RESULTS: Eleven of the 12 facilities managed severe pneumonia. Oxygen was reliable in three facilities. Requirement and supply were often mismatched. Both oxygen concentrators and oxygen cylinders were used. Suboptimal electricity and maintenance made using concentrators difficult, while logistical problems and cost hampered cylinder use. Children were usually triaged by trained nurses who reported lack of training in oxygen use. Oxygen was given typically by nasal prongs; pulse oximetry was available in two facilities. CONCLUSIONS: National data showed that oxygen availability did not meet needs in most Gambian health facilities. Remedial options must be carefully assessed for real costs, reliability and site-by-site usability. Training is needed to support oxygen use and equipment maintenance.

Could mainstream anti-smoking programs increase inequalities in tobacco use? New Zealand data from 1981-96.

OBJECTIVE: To examine changes in the socio-economic and ethnic distribution of smoking in the New Zealand population from 1981 to 1996, and to consider the implication of these data for policies aimed at reducing tobacco consumption. METHODS: Cross-sectional data were taken from 4.7 million respondents to the 1981 and 1996 New Zealand Censuses and 4,619 participants in a 1989 national survey, aged 15 to 79 years. Smoking prevalence rates were calculated by socio-economic position and ethnicity. RESULTS: Smoking prevalence fell in the period 1981-96 in every population group. However, socio-economic and ethnic differences in smoking increased in relative terms. Smoking prevalence ratios comparing the least advantaged with the most advantaged groups increased in men from 1.20 to 1.53 by income, 1.54 to 1.85 by education, and 1.49 to 1.67 by ethnicity. In women, prevalence ratios increased from 1.17 to 1.51 by income, 1.55 to 2.02 by education, and 1.85 to 2.20 by ethnicity. The greatest increase in socio-economic differences may have occurred during the 1980s, the period of greatest overall decline in total population smoking. CONCLUSIONS: Socio-economic and ethnic disparities in New Zealanders' smoking patterns increased during the 1980s and '90s, a period of significant decline in overall smoking prevalence. IMPLICATIONS: Public health programs aimed at reducing tobacco use should pay particular attention to disadvantaged, Indigenous and ethnic minority groups in order to avoid widening relative inequalities in smoking and smoking-related health outcomes.

Is local alcohol outlet density related to alcohol-related morbidity and mortality in Scottish cities?

Alcohol consumption may be influenced by the local alcohol retailing environment. This study is the first to examine neighbourhood alcohol outlet availability (on- and off-sales outlets) and alcohol-related health outcomes in Scotland. Alcohol-related hospitalisations and deaths were significantly higher in neighbourhoods with higher outlet densities, and off-sales outlets were more important than on-sales outlets. The relationships held for most age groups, including those under the legal minimum drinking age, although were not significant for the youngest legal drinkers (18-25 years). Alcohol-related deaths and hospitalisations were higher in more income-deprived neighbourhoods, and the gradient in deaths (but not hospitalisations) was marginally larger in neighbourhoods with higher off-sales outlet densities. Efforts to reduce alcohol-related harm should consider the potentially important role of the alcohol retail environment.

A positive association between agonist-induced cyclic AMP production in vitro and metastatic potential in murine B16 melanoma and hamster fibrosarcoma.

A positive association between agonist-stimulated cyclic AMP production in vitro and both experimentally induced (B16 melanoma) and spontaneous (fibrosarcoma) metastases were found. Five B16 melanoma cell lines producing varying degrees of lung colonization following intravenous injection and three hamster fibrosarcoma cell lines producing a varying number of metastases in lungs and regional lymph nodes after removal of the primary tumour were studied. Agonist-stimulated (forskolin and melanocyte-stimulating hormone), but not basal cyclic AMP accumulation, increased with increasing metastatic potential. This relationship did not extend to other intracellular signalling systems as determined by investigation of basal or foetal-calf stimulated phosphatidylinositol hydrolysis for either tumour type. Intracellular free calcium was also similar in B16 melanoma cell lines of varying metastatic potential.

The regulation of cyclic AMP production and the role of cyclic AMP in B16 melanoma cells of differing metastatic potential.

The nature of the relationship between agonist-stimulated cyclic AMP production and metastatic potential was examined in detail for four B16 melanoma cell lines of varying metastatic potential. Highly metastatic cells (B16 F10C1) appeared to differ from cells of low metastatic potential (B16 F1C29) in the degree to which cyclic AMP production in intact cells was stimulated by protein kinase C activation. No significant difference was found in the adenylate-cyclase enzyme activities of the broken cells, irrespective of the agonist used, or in the distribution of cyclic AMP between the intracellular and extracellular compartment. Although B16F1, F10 and F10C1 cells all produced equally pigmented tumors in vivo, the cells differed in their melanogenic response to cyclic AMP elevating agents in vitro: the least metastatic cells produced least agonist-induced cyclic AMP but this induced greatest tyrosinase activation and melanin production in vitro; conversely, the more metastatic cells produced more cyclic AMP but less tyrosinase activation and melanin production in response to agonist stimulation. Thus, agonist-stimulated cyclic AMP production does not appear to be coupled to the differentiated function of melanogenesis for highly metastatic B16 melanoma cells.

Molecular flexibility profiling using NMR spectroscopy.

Molecular flexibility is a factor that is not extensively studied in most pharmaceutical research efforts. When it is, the level of effort is high involving the preparation of detailed models supported by either molecular dynamics simulations and/or Nuclear Magnetic Resonance data. While these studies are both powerful and illuminating, they cannot be routinely applied in a drug discovery setting as they are time and expertise intensive. Yet there seems to be little doubt that at least in some cases, molecular flexibility plays a key role in complex formation. A simple, rapid and generally applicable flexibility profiling protocol was applied to two model systems and data describing the internal mobility of carbon atoms were obtained. The protocol utilizes the Model Free approach and NMR data to characterize the internal molecular dynamics of these compounds. The first model system consisted of fluorene and diphenylmethane where the anticipated flexibility trends were observed in the data providing a link between chemical intuition and the experimental results. Data on a second model system, which consisted of two Paclitaxel analogs, showed predictable patterns including dynamical phenyl and methyl groups and a relatively immobile taxane core. Subtle differences in the internal dynamics within the taxane core suggest that it cannot be considered as a rigid structure. Key advantages of using this approach are that no prior knowledge or supposition of dynamical features is required, the protocol can be carried out in most medicinal chemistry laboratories and the data obtained provide a common, empirically derived reference point to discuss the effects of molecular flexibility on activity.

Facilitation of sympathetic neurotransmission in the rat anococcygeus muscle by prostaglandins D2 and F2 alpha.

1 Investigations were made into the effects of prostaglandins D2 (PGD2) and F2 alpha (PGF2 alpha) on the responses of the rat anococcygeus muscle to field stimulation of intrinsic motor (sympathetic) and inhibitory nerves, and to exogenous noradrenaline. 2 PGD2 (2.8 X 10(-6) mol/1) substantially increased the motor responses to field stimulation at all frequencies tested (2 to 32 Hz), and caused a smaller increase in the responses to noradrenaline. 3 PGF2 alpha (2.8 X 10(-6) mol/1) strongly potentiated the motor responses to field stimulation (2 to 32 Hz) and also to noradrenaline. This prostaglandin had quantitatively similar effects on the responses to both types of stimulus. 4 PGD2 was without effect on the inhibitory responses evoked by field stimulation in the presence of guanethidine. PGF2 alpha seemed to reduce the inhibitory responses to low frequencies of stimulation (0.5 to 1.5 Hz), but this effect was marginal. 5 The results suggest that PGD2 facilitates sympathetic neurotransmission in this tissue by both pre- and post-junctional actions. The effect of PGF2 alpha seems likely to be mediated predominantly post-junctionally.

Electrolyte metabolism in patients with periodic affective disorders during treatment with rubidium.

Five patients suffering from periodic affective disorders with short mood-cycles were treated with rubidium chloride, producing peak erythrocyte concentrations between 9 and 13 mmol/l. Loading with rubidium was associated with decreased total body potassium, but red-cell potassium was unchanged. Regular mood-cycling was disturbed, together with the associated body-weight changes. There was a slight extracellular "metabolic" acidosis. Electrolyte concentrations fluctuate abnormally in these patients, and two muscle biopsy specimens had very low potassium contents.

Urinary dicarboxylic acids in patients receiving lithium or rubidium salts.

Lithium salts administered in therapeutic doses to four subjects who were kept on controlled diets increased up to fivefold the urinary output of some dicarboxylic acids. Some of the acids affected are intermediates in the tricarboxylic acid cycle, others are chemically similar but not directly related in metabolic terms. This is probably a direct effect on renal transport. Rubidium salts increased urinary 2-oxoglutarate output and blood 2-oxoglutarate levels, probably by some action on intermediary metabolism.

Intraoperative physiologic variables and outcome in cardiac surgery: Part I. In-hospital mortality.

BACKGROUND: Risk stratification schemes have been developed to predict outcome of coronary artery bypass grafting (CABG) procedures, which are predominately based upon unalterable preoperative patient characteristics. The purpose of this study was to determine if minimum intraoperative hematocrit, maximum glucose concentration, mean arterial pressure on cardiopulmonary bypass, or duration of bypass influence risk-adjusted in-hospital mortality after CABG. METHODS: Outcome data from 2,862 CABG patients were merged with intraoperative physiologic data. A preoperative mortality risk index was calculated for each patient. Variables found significant (p<0.05) by univariate logistic regression were tested in a multiple variable model to determine risk-adjusted association with mortality. RESULTS: Overall mortality rate was 1.85%. The preoperative risk index was significantly associated with mortality (p = 0.0001). No significant association was present between mortality and intraoperative variables. Preexisting hypertension was an independent predictor of mortality after controlling for risk index and bypass duration. CONCLUSIONS: Preexisting hypertension proved to be an independent predictor of mortality in our patient population. This study found no evidence to support the hypothesis that mean arterial pressure less than 50 mm Hg, lower hematocrit, or elevated glucose while on bypass increases in-hospital mortality.

Intraoperative physiologic variables and outcome in cardiac surgery: Part II. Neurologic outcome.

BACKGROUND: The impact of alterable physiologic variables on neurologic outcome after coronary artery bypass grafting procedures is unknown. The purpose of this study was to determine whether minimum intraoperative hematocrit, maximum glucose concentration, or mean arterial pressure during cardiopulmonary bypass influences risk-adjusted neurologic outcome after coronary artery bypass grafting. METHODS: Outcome data from 2,862 patients undergoing coronary artery bypass grafting were merged with intraoperative physiologic data. A preoperative stroke risk index was calculated for each patient. Variables found significant by univariate logistic regression were tested in a multivariable model to determine association with outcome. RESULTS: The incidence of stroke or coma in the study population was 1.3%. After controlling for stroke risk and bypass time, only an index of low mean arterial pressure during bypass retained a significant inverse association with outcome (p = 0.0304). CONCLUSIONS: This study found no evidence that glucose concentration or minimum hematocrit are associated with major adverse neurologic outcome. The association between lower pressure during bypass and decreased incidence of stroke or coma persisted in all risk groups. This points to mechanisms other than hypoperfusion as the primary cause of neurologic injury associated with cardiac surgery.

Signal transduction in murine B16 melanoma cells.

The relationship between lung colonization and signal transduction was investigated for six B16 melanoma variants. A range of experimental metastatic potential (as determined by lung colonization), forskolin-stimulated cyclic AMP accumulation and FCS-stimulated protein kinase C activity was found. The major findings were that: (1) cells with the highest agonist-stimulated cyclic AMP production were those with the highest level of membrane-associated protein kinase C activity; (2) clones which differed in protein kinase C levels and distribution did so in the presence but not in the absence of foetal calf serum; and (3) no simple relationship was seen between either signal transduction system and lung colonization for all six variants. Altered ras expression was also excluded as an explanation for the differences in signal transduction and lung colonization potential which were observed. We conclude that differences in signal transduction in vitro between these cells do not relate simply to lung colonization potential in vivo.

Simulated annealing image reconstruction method for a pinhole aperture single photon emission computed tomograph (SPECT).

A series of computer experiments was performed to determine the relative performance of simulated annealing, quenched annealing, and a least-squares iterative technique for image reconstruction for single photon emission computed tomography (SPECT). The simulated SPECT geometry was of the pinhole aperture type, with 32 pinholes and 128 or 512 detectors. To test the robustness of the reconstruction techniques upon arbitrary geometries, a 360-detector geometry with a random pixel-detector-factor matrix was tested. Eight computer-simulated, 10-cm-diameter planar phantoms were used with 1961 2-mm(2) reconstruction bins and a range of 3000 to 50,000,000 detected photon counts. Reconstruction quality was measured by a normalized, squared error picture distance measure. Over a wide range of noise, the simulated annealing method had slightly better reconstruction quality than the iterative method, although requiring greater reconstruction time. Quenched annealing was faster than simulated annealing, with comparable reconstruction quality. Methods of efficiently controlling the simulated annealing algorithm are presented.

Maillard reaction causes suppression of virulence gene expression in Listeria monocytogenes.

Many environmental signals affect the expression of virulence genes of the food borne pathogen Listeria monocytogenes. In addition media composition has been shown to suppress levels of haemolytic activity. Using a Pr(plcA)::luxAB reporter gene fusion it was observed that the heat processing of media also reduces the level of virulence gene expression in L. monocytogenes without affecting its growth. Physicochemical factors that are considered to enhance the Maillard reaction were also found to increase the levels of suppression. The results indicate that heat treatment of a multicomponent matrix gives rise to specific inhibitors of the Listeria virulence gene operon.

Fatal microvascular pulmonary emboli from precipitation of a total nutrient admixture solution.

BACKGROUND: Paroxysmal respiratory failure and death occurred in two young adult females with pelvic infections. Autopsy revealed an amorphous material containing calcium obstructing the pulmonary microvasculature of each patient. Both patients received an identical total nutrient admixture (TNA) solution before their deaths. METHODS: Infusion of TNA into an animal model was undertaken in an effort to reproduce the clinical effect. Laboratory investigation was also performed to isolate a precipitate and identify the factors contributing to precipitation. RESULTS: A nonvisible precipitate containing calcium, phosphorus, and organic material was isolated from the TNA solution. Infusion of the formulation into healthy pigs resulted in sudden death within 4 hours. Alteration of the amino acid component, mix sequence, agitation technique, and mixing container influenced precipitate formation. CONCLUSION: Pulmonary embolization of a precipitate containing calcium phosphate resulted in the death of two patients. The pH of the amino acid component, transient elevation of calcium and phosphorus concentrations during mixing, and the lack of agitation during automated preparation of the formulation were identified as the etiologic factors producing the fatal precipitate.

Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus. III. Structural elucidation.

The structure of the antitumor antibiotic himastatin was determined using a combination of spectroscopic and chemical degradation techniques. Himastatin is a unique dimeric cyclohexadepsipeptide joined through a biphenyl linkage between two oxidized tryptophan units. The gross structure of the dimer was established through degradative ozonolysis. Himastatin consists of D-valine, D-threonine, L-leucine, L-alpha-hydroxyisovaleric acid, (3R,5R)-5-hydroxypiperazic acid, and (2R,3aR,8aR)-3a-hydroxyhexahydropyrrolo[2,3b]indole 2-carboxylic acid subunits.

Organisation of the external region of the starch granule as determined by infrared spectroscopy.

Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) was used to study the external regions of starch granules. Native starches (wheat, potato, maize, waxy maize and amylomaize) were analysed and compared to gelatinised and acid-hydrolysed starches. The IR spectra of potato and amylomaize starches were closer to that of highly ordered acid-hydrolysed starch than the other starches. FTIR was not able to differentiate between A- and B-type crystallinity so the difference observed between starches was not related to this factor. The variation between starch varieties was interpreted in terms of the level of ordered structure present on the edge of starch granules with potato and amylomaize being more ordered on their outer regions. This could explain the high resistance of both these starches to enzyme hydrolysis.