Paraneoplastic hypoglycaemia secondary to IGF-2 secretion from a metastatic gastrointestinal stromal tumour

We report the case of a 79-year-old male with previous history of non-Hodgkin's lymphoma in remission, who presented acutely to the Accident and Emergency department with recurrent episodes of hypoglycaemia. At the time of presentation, a random glucose was low at 1.4 mmol/l, which upon correction resolved his symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 2 months to which he did not give much notice. While hospitalized, he continued having episodes of symptomatic hypoglycaemia, requiring treatment with intravenous dextrose and per os steroids. Once stable, he was discharged on oral prednisolone and dietary advice. A computed tomography scan performed during inpatient stay showed multiple deposits in the abdomen. An ultrasound guided biopsy of one of the liver deposits was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. The diagnosis of non-islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=105.9 nmol/l; IGF2:IGF1 ratio 23, Upper Level of Normal (ULN) <10). Targeted cytoreductive treatment with Imatinib mesylate following assessment of the tumour's mutational status was successful in preventing hypoglycaemia over a 21-month follow-up observation period

Analysis of squat shear wall with different dimensions and position of opening under different type of static loads

Shear walls are usually used in high-rise building or building on high frequency of wind area as the structural element to restrain lateral forces. Openings are created on the shear wall for the architecture, ventilation or mechanical and electrical purposes. With the existence of the opening, the strength of the wall is reduced by the reduction in concrete area and the discontinuity of the reinforcement due to opening which may lead to structural failure. The main objective is to study the effect of size and position of the opening towards the structural behavior of the shear wall under different type of static loads. The analysis is done using the software ANSYS12.0. The samples are SW1, SW2, SW3, SW4, SW5, SW6, SW7 and SW8 where SW1 is solid shear wall while SW2, SW3, SW4, SW5, SW6, SW7 and SW8 are shear walls with different size and position of opening. They are analyzed by using 2 different types of loads which are uniformly distributed axial load and uniformly lateral load. From the same magnitude of loads applied towards the shear walls, they are compared by the cracking pattern and the stress distribution. Under both axial and lateral loads, it shows a significance results that the shear wall with greater opening size shows less efficiency. The position of opening further from the support shows a more significance effect towards the strength of the wall from axial load but opposite from the lateral load. Besides, the closer the position of the shear wall to the load, the less efficient it is. As a conclusion from the results, the most suitable position of the opening on the shear wall is further from the support and the loads and it shows that there is a significance effect even from a smallest opening

High-Throughput Sequence Analyses of Bacterial Communities and Multi-Mycotoxin Profiling During Processing of Different Formulations of Kunu, a Traditional Fermented Beverage

Kunu is a traditional fermented single or mixed cereals-based beverage popularly consumed in many parts of West Africa. Presently, the bacterial community and mycotoxin contamination profiles during processing of various kunu formulations have never been comprehensively studied. This study, therefore, investigated the bacterial community and multi-mycotoxin dynamics during the processing of three kunu formulations using high-throughput sequence analysis of partial 16S rRNA gene (hypervariable V3-V4 region) and liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. A total of 2,303 operational taxonomic units (OTUs) were obtained across six processing stages in all three kunu formulations. Principal coordinate analysis biplots of the Bray-Curtis dissimilarity between bacterial communities revealed the combined influences of formulations and processing steps. Taxonomically, OTUs spanned 13 phyla and 486 genera. Firmicutes (phylum) dominated (relative abundance) most of the processing stages, while Proteobacteria dominated the rest of the stages. Lactobacillus (genus taxa level) dominated most processing stages and the final product (kunu) of two formulations, whereas Clostridium sensu stricto (cluster 1) dominated kunu of one formulation, constituting a novel observation. We further identified Acetobacter, Propionibacterium, Gluconacetobacter, and Gluconobacter previously not associated with kunu processing. Shared phylotypes between all communities were dominated by lactic acid bacteria including species of Lactobacillus, Lactococcus, Leuconostoc, Pediococcus, and Weissella. Other shared phylotypes included notable acetic acid bacteria and potential human enteric pathogens. Ten mycotoxins [3-Nitropropionic acid, aflatoxicol, aflatoxin B1 (AFB1), AFB2, AFM1, alternariol (AOH), alternariolmethylether (AME), beauvericin (BEAU), citrinin, and moniliformin] were quantified at varying concentrations in ingredients for kunu processing. Except for AOH, AME, and BEAU that were retained at minimal levels of &lt; 2 μg/kg in the final product, most mycotoxins in the ingredients were not detectable after processing. In particular, mycotoxin levels were substantially reduced by fermentation, although simple dilution and sieving also contributed to mycotoxin reduction. This study reinforces the perception of kunu as a rich source of bacteria with beneficial attributes to consumer health, and provides in-depth understanding of the microbiology of kunu processing, as well as information on mycotoxin contamination and reduction during this process. These findings may aid the development of starter culture technology for safe and quality kunu production

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

Corticosteroid Replacement Therapy

The advent of synthetic corticosteroids in the 20th century provided a vital breakthrough in the management of adrenal insufficiency. In this chapter we review the main indications and guidance for appropriate hormone replacement and also look into the management of therapy during special circumstances. For decades hydrocortisone has remained the cornerstone for glucocorticoid replacement but we explore the alternatives including recently introduced modified-release drug preparations and the future treatment considerations currently undergoing research and pre-clinical trials

Glucocorticoid induced hypocalcemia in a patient with established hypoparathyroidism

Glucocorticoids are known to affect calcium balance but are not thought to cause clinically significant hypocalcemia. This case adds to a list of isolated reports noting significant hypocalcemia developing post administration of glucocorticoids in a patient with known hypoparathyroidism, postulating PTH deficiency as a risk factor of decompensated calcium homeostasis

Endocrine abnormality in paraneoplastic syndrome

Paraneoplastic syndromes denote rare but notable phenomena caused by the tumour mediated release of bioactive substances. Peptide and non-peptide hormone causes are explored with a particular focus on pathogenesis, symptoms, diagnosis and treatment. Early detection and management of paraneoplastic syndromes can improve morbidly and mortality; definitive treatment remains effective surgical or anti-tumour therapies. Pituitary autoimmunity may provide a novel presentation of paraneoplastic syndromes for which further research is warranted

A Novel Methicillin-Resistant Staphylococcus aureus t11469 and a Poultry Endemic Strain t002 (ST5) Are Present in Chicken in Ebonyi State, Nigeria

Background. The changing epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) from a hospital-associated pathogen to an organism commonly found in the community and in livestock reflects an organism well-equipped to survive in diverse environments and adjust to different environmental conditions including antimicrobial use. Methods. We investigated the molecular epidemiology of S. aureus and MRSA in poultry in Ebonyi State, Nigeria. Samples were collected from 1800 birds on 9 different farms within the state. Positive isolates were tested for antibiotic susceptibility and molecular typing. Results. Prevalence in birds was 13.7% (247/1800). MRSA prevalence in poultry was 0.8%. The prevalence of MRSA in broilers and layers was 1.2% and 0.4%, respectively. All tested isolates were susceptible to vancomycin. Molecular analysis of the isolates revealed 3 spa types: t002, t084, and a novel spa type, t11469. The novel spa type t11469 belonged to sequence type ST5. Conclusion. The detection of t002 in chicken suggests the presence of livestock-associated MRSA in poultry in Ebonyi State. The detection of the new spa type t11469 in poultry that has not been characterised to ascertain its pathogenic potential remains a cause for concern, especially as some were found to carry PVL genes, a putative virulence factor in staphylococcal infection