A Field Technique Measuring Virus Decay and Potential Aerosol Hazard from Wastewater Sprinkler Irrigation

The increased use of domestic wastewater for irrigation purposes has stimulated a growing practice of sprinkler irrigating from oxidation ponds and other domestic wastewaters. Aerosols generated from these sprinkler irrigation systems may contain potentially hazardous pathogens. Subsequently, the aerosols can contain infective viruses which can be carried through the air to surrounding populations. Thus, a public health hazard can be created by sprinkler irrigating domestic wastewater. This study is an investigation of a means by which the virus decay rate of viruses in aerosols and the potentials hazard of sprinkler irrigation aerosol clouds may be examined. A means of injection of a human and animal virus stimulant, MS-2 bacteriophage, is described. In addition, the factors which are known to effect the survival of viruses in aerosols are discussed. The ambient air factors that are known to effect virus survival and which are discussed include relative humidity, air temperature, solar radiation, and aerosol age. The suspending fluid factors that are known to effect virus survival and which are discussed include dissolved inorganic salt contact, dissolved organic content, filterable solids and pH. The decay rate of the aerosolized MS-2 was measured with an all-glass impinger (AGI-30) when the wind velocity and distance of the sampler from the sprinkler system, and the initial and final concentrations of aerosolized MS-2 virus were known. The aerosol hazard of a domestic wastewater sprinkler irrigation system is defined in terms of the likelihood of infective aerosol particles to be inhaled and penetrate the human lung. Thus, the aerosol hazard is a function of aerosol particle size. The aerosol particle size distribution of the infective aerosol cloud was measured wit the Andersen sampler. A high and homogeneous concentration of the virus in the wastewater was insured by using pressure differentials in the sprinkler irrigation delivery line. By injecting the MS-2 virus into the line at a constant rate along with a tracer, Bacillus subtilus var niger (Bacillus globigii) spores, the decay rate of the virus during airborne exposure to environmental factors could be determined. The decay rate was determined assuming the environmental factors had no affect on the concentration of the tracer. It was proposed that the environmental engineer, after knowing the virus decay rates under varying environmental conditions, can define buffer zones which would be required around sprinkler irrigation sites. The buffer zone would reduce the possibility of contaminating humans by prohibiting access. The usefulness of the filed technique was demonstrated and the MS-2 was found to undergo a 33.3 percent decay per minute in the dark (no solar radiation) at 33 percent relative humidity, 70.6 percent dissolved organic material, 29.4 percent dissolved inorganic salts, 30.1 mg/1 filterable solids, and 17 degree C air temperature. The aerosol cloud resulting from the spray irrigation process appeared potentially hazardous because the Andersen sampler collected 84.2 percent of the virus infective droplets in the size range that could be inhaled

Failure of functional imaging with gallium-68-DOTA-D-Phe1-Tyr3-octreotide positron emission tomography to localize the site of ectopic adrenocorticotropic hormone secretion: a case report

<p>Abstract</p> <p>Introduction</p> <p>The diagnostic efficacy of biochemical and imaging modalities for investigating the causes of Cushing's syndrome are limited. We report a case demonstrating the limitations of these modalities, especially the inability of functional imaging to help localize the site of ectopic adrenocorticotropic hormone secretion.</p> <p>Case presentation</p> <p>A 37-year-old Arabian woman presented with 12 months of progressive Cushing's syndrome-like symptoms. Biochemical evaluation confirmed adrenocorticotropic hormone -dependent Cushing's syndrome. However, the anatomical site of her excess adrenocorticotropic hormone secretion was not clearly delineated by further investigations. Magnetic resonance imaging of our patient's pituitary gland failed to demonstrate the presence of an adenoma. Spiral computed tomography of her chest only revealed the presence of a non-specific 7 mm lesion in her left inferobasal lung segment. Functional imaging, including a positron emission tomography scan using 18-fluorodeoxyglucose and gallium-68-DOTA-D-Phe1-Tyr3-octreotide, also failed to show increased metabolic activity in the lung lesion or in her pituitary gland. Our patient was commenced on medical treatment with ketoconazole and metyrapone to control the clinical features associated with her excess cortisol secretion. Despite initial normalization of her urinary free cortisol excretion rate, levels began to rise eight months after commencement of medical treatment. Repeated imaging of her pituitary gland, chest and pelvis again failed to clearly localize a source of her excess adrenocorticotropic hormone secretion. The bronchial nodule was stable in size on serial imaging and repeatedly reported as having a nonspecific appearance of a small granuloma or lymph node. We re-explored the treatment options and endorsed our patient's favored choice of resection of the bronchial nodule, especially given that her symptoms of cortisol excess were difficult to control and refractory. Subsequently, our patient had the bronchial nodule resected. The histological appearance of the lesion was consistent with that of a carcinoid tumor and immunohistochemical analysis revealed that the tumor stained strongly positive for adrenocorticotropic hormone. Furthermore, removal of the lung lesion resulted in a normalization of our patient's 24-hour urinary free cortisol excretion rate and resolution of her symptoms and signs of hypercortisolemia.</p> <p>Conclusion</p> <p>This case report demonstrates the complexities and challenges in diagnosing the causes of adrenocorticotropic hormone -dependent Cushing's syndrome. Functional imaging may not always localize the site of ectopic adrenocorticotropic hormone secretion.</p

Can houseplants improve indoor air quality by removing CO2 and increasing relative humidity?

High indoor CO2 concentrations and low relative humidity (RH) create an array of well-documented human health issues. Therefore, assessing houseplants’ potential as a low-cost approach to CO2 removal and increasing RH is important. We investigated how environmental factors such as ’dry’ ( 0.30 m3 m-3) growing substrates, and indoor light levels (‘low’ 10 µmol m-2 s-1, ‘high’ 50 µmol m-2 s-1 and ‘very high’ 300 µmol m-2 s-1), influence the plants’ net CO2 assimilation (‘A’) and water-vapour loss. Seven common houseplant taxa – representing a variety of leaf types, metabolisms and sizes – were studied for their ability to assimilate CO2 across a range of indoor light levels. Additionally, to assess the plants’ potential contribution to RH increase, the plants’ evapo-transpiration (ET) was measured. At typical ‘low’ indoor light levels ‘A’ rates were generally low (< 3.9 mg hr-1). Differences between ‘dry’ and ’wet’ plants at typical indoor light levels were negligible in terms of room-level impact. Light compensation points (i.e. light levels at which plants have positive ‘A’) were in the typical indoor light range (1-50 µmol m-2 s-1) only for two studied Spathiphyllum wallisii cultivars and Hedera helix; these plants would thus provide the best CO2 removal indoors. Additionally, increasing indoor light levels to 300 µmol m-2 s-1 would, in most species, significantly increase their potential to assimilate CO2. Species which assimilated the most CO2 also contributed most to increasing RH

PAM variants in patients with thyrotrophinomas, cyclical Cushing’s disease and prolactinomas

IntroductionGermline loss-of-function variants in PAM, encoding peptidylglycine α-amidating monooxygenase (PAM), were recently discovered to be enriched in conditions of pathological pituitary hypersecretion, specifically: somatotrophinoma, corticotrophinoma, and prolactinoma. PAM is the sole enzyme responsible for C-terminal amidation of peptides, and plays a role in the biosynthesis and regulation of multiple hormones, including proopiomelanocortin (POMC).MethodsWe performed exome sequencing of germline and tumour DNA from 29 individuals with functioning pituitary adenomas (12 prolactinomas, 10 thyrotrophinomas, 7 cyclical Cushing’s disease). An unfiltered analysis was undertaken of all PAM variants with population prevalence &lt;5%.ResultsWe identified five coding, non-synonymous PAM variants of interest amongst seven individuals (six germline, one somatic). The five variants comprised four missense variants and one truncating variant, all heterozygous. Each variant had some evidence of pathogenicity based on population prevalence, conservation scores, in silico predictions and/or prior functional studies. The yield of predicted deleterious PAM variants was thus 7/29 (24%). The variants predominated in individuals with thyrotrophinomas (4/10, 40%) and cyclical Cushing’s disease (2/7, 29%), compared to prolactinomas (1/12, 8%).ConclusionThis is the second study to demonstrate a high yield of suspected loss-of-function, predominantly germline, PAM variants in individuals with pathological pituitary hypersecretion. We have extended the association with corticotrophinoma to include the specific clinical entity of cyclical Cushing’s disease and demonstrated a novel association between PAM variants and thyrotrophinoma. PAM variants might act as risk alleles for pituitary adenoma formation, with a possible genotype-phenotype relationship between truncating variants and altered temporal secretion of cortisol

Genome-wide gene expression profiling identifies overlap with malignant adrenocortical tumours and novel mechanisms of inefficient steroidogenesis in familial ACTH-independent macronodular adrenal hyperplasia.

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of sporadic or familial late-onset Cushing's syndrome. It is a cytologically benign disease, of unknown pathogenesis, and characterised by inefficient steroidogenesis, ascribed to differential cellular localisation of steroidogenic enzymes. The objectives were to determine the molecular mechanisms involved in the pathogenesis of familial AIMAH tumours and the mechanisms of their inefficient steroidogenesis. Using Affymetrix Human GeneChip® HumanGene 1.0 ST arrays, we compared the genome-wide gene expression profile of two AIMAH nodules from each of three affected siblings with normal adrenal cortex and analysed the data for differential expression and using Ingenuity Pathway Analysis, Gene Set Enrichment Analysis and Motif Activity Response Analysis. Expression profiling identified: (i) that amongst the most highly differentially expressed genes were ones known to have involvement in tumorigenesis and metastasis; (ii) enrichment for differentially expressed genes in sporadic AIMAH and other benign and malignant adrenocortical tumours and (iii) reduced activity of key transcriptional regulators (Steroidogenic factor-1, SF-1 and transcription factor Sp1, Sp1) of steroidogenic enzymes. Genome-wide gene expression studies of familial AIMAH nodules have identified overlap with malignant adrenocortical tumours, which is intriguing given the benign biological behaviour of these tumours. This requires further study. Novel mechanisms of inefficient steroidogenesis were also identified

Obesity and immune function relationships.

The immunological processes involved in the collaborative defence of organisms are affected by nutritional status. Thus, a positive chronic imbalance between energy intake and expenditure leads to situations of obesity, which may influence unspecific and specific immune responses mediated by humoral and cell mediated mechanisms. Furthermore, several lines of evidence have supported a link between adipose tissue and immunocompetent cells. This interaction is illustrated in obesity, where excess adiposity and impaired immune function have been described in both humans and genetically obese rodents. However, limited and often controversial information exist comparing immunity in obese and non-obese subjects as well as about the cellular and molecular mechanisms implicated. In general terms, clinical and epidemiological data support the evidence that the incidence and severity of specific types of infectious illnesses are higher in obese persons as compared to lean individuals together with the occurrence of poor antibody responses to antigens in overweight subjects. Leptin might play a key role in linking nutritional status with T-cell function. The complexities and heterogeneity of the host defences concerning the immune response in different nutritional circumstances affecting the energy balance require an integral study of the immunocompetent cells, their subsets and products as well as specific and unspecific inducer/regulator systems. In this context, more research is needed to clarify the clinical implications of the alterations induced by obesity on the immune function

The ethics of psychopharmacological research in legal minors

Research in psychopharmacology for children and adolescents is fraught with ethical problems and tensions. This has practical consequences as it leads to a paucity of the research that is essential to support the treatment of this vulnerable group. In this article, we will discuss some of the ethical issues which are relevant to such research, and explore their implications for both research and standard care. We suggest that finding a way forward requires a willingness to acknowledge and discuss the inherent conflicts between the ethical principles involved. Furthermore, in order to facilitate more, ethically sound psychopharmacology research in children and adolescents, we suggest more ethical analysis, empirical ethics research and ethics input built into psychopharmacological research design

Transforming medical professionalism to fit changing health needs

<p>Abstract</p> <p>Background</p> <p>The professional organization of medical work no longer reflects the changing health needs caused by the growing number of complex and chronically ill patients. Key stakeholders enforce coordination and remove power from the medical professions in order allow for these changes. However, it may also be necessary to initiate basic changes to way in which the medical professionals work in order to adapt to the changing health needs.</p> <p>Discussion</p> <p>Medical leaders, supported by health policy makers, can consciously activate the self-regulatory capacity of medical professionalism in order to transform the medical profession and the related professional processes of care so that it can adapt to the changing health needs. In doing so, they would open up additional routes to the improvement of the health services system and to health improvement. This involves three consecutive steps: (1) defining and categorizing the health needs of the population; (2) reorganizing the specialty domains around the needs of population groups; (3) reorganizing the specialty domains by eliminating work that could be done by less educated personnel or by the patients themselves. We suggest seven strategies that are required in order to achieve this transformation.</p> <p>Summary</p> <p>Changing medical professionalism to fit the changing health needs will not be easy. It will need strong leadership. But, if the medical world does not embark on this endeavour, good doctoring will become merely a bureaucratic and/or marketing exercise that obscures the ultimate goal of medicine which is to optimize the health of both individuals and the entire population.</p