Gallbladder microbiota in healthy dogs and dogs with mucocele formation.

To date studies have not investigated the culture-independent microbiome of bile from dogs, a species where aseptic collection of bile under ultrasound guidance is somewhat routine. Despite frequent collection of bile for culture-based diagnosis of bacterial cholecystitis, it is unknown whether bile from healthy dogs harbors uncultivable bacteria or a core microbiota. The answer to this question is critical to understanding the pathogenesis of biliary infection and as a baseline to exploration of other biliary diseases in dogs where uncultivable bacteria could play a pathogenic role. A pressing example of such a disease would be gallbladder mucocele formation in dogs. This prevalent and deadly condition is characterized by excessive secretion of abnormal mucus by the gallbladder epithelium that can eventually lead to rupture of the gallbladder or obstruction of bile flow. The cause of mucocele formation is unknown as is whether uncultivable, and therefore unrecognized, bacteria play any systematic role in pathogenesis. In this study we applied next-generation 16S rRNA gene sequencing to identify the culture-negative bacterial community of gallbladder bile from healthy dogs and gallbladder mucus from dogs with mucocele formation. Integral to our study was the use of 2 separate DNA isolations on each sample using different extraction methods and sequencing of negative control samples enabling recognition and curation of contaminating sequences. Microbiota findings were validated by simultaneous culture-based identification, cytological examination of bile, and fluorescence in-situ hybridization (FISH) performed on gallbladder mucosa. Using culture-dependent, cytological, FISH, and 16S rRNA sequencing approaches, results of our study do not support existence of a core microbiome in the bile of healthy dogs or gallbladder mucus from dogs with mucocele formation. Our findings further document how contaminating sequences can significantly contribute to the results of sequencing analysis when performed on samples with low bacterial biomass.

The development of a new accountability measurement framework and tool for global health initiatives.

The Global Strategy for Women's Children's and Adolescents' Health emphasizes accountability as essential to ensure that decision-makers have the information required to meet the health needs of their populations and stresses the importance of tracking resources, results, and rights to see 'what works, what needs improvement and what requires increased attention'. However, results from accountability initiatives are mixed and there is a lack of broadly applicable, validated tools for planning, monitoring and evaluating accountability interventions. This article documents an effort to transform accountability markers-including political will, leadership and the monitor-review-act cycle-into a measurement tool that can be used prospectively or retrospectively to plan, monitor and evaluate accountability initiatives. It describes the development process behind the tool including the literature review, framework development and subsequent building of the measurement tool itself. It also examines feedback on the tool from a panel of global experts and the results of a pilot test conducted in Bauchi and Gombe states in Nigeria. The results demonstrate that the tool is an effective aid for accountability initiatives to reflect on their own progress and provides a useful structure for future planning, monitoring and evaluation. The tool can be applied and adapted to other accountability mechanisms working in global health.

Metallosis mimicking a metabolic disorder: a case report.

Metalic prosthesis or occupational exposure are potential sources of systemic cobalt and chromium ion toxicity. The resultant multisystemic clinical presentation can lead to unnecessary investigations before a final etiologic diagnosis is made; with an average delay of a year or more commonly noted. A 58-year old man presented with cardiomyopathy, pericardial effusion, polycytaemia, polyneuropathy, visual impairment, sudden hearing loss and hypothyroidism over a 2-year period post a metal-on-polyethylene hip replacement surgery. Biochemistry test results showed serum lactate of 3.8 mmol/L (0.5-2.2 mmol/L). Urine organic acid screen showed mild increases in excretion of tricarboxylic acid cycle intermediates and 2-ethylhydracryllate; suggestive of primary or secondary mitochondrial dysfunction. There were also slight increases in excretion of 4-hydroxyphenyllactate and 4-hydroxyphenylpyruvate suggestive of liver dysfunction. Acylcarnitine profile showed slight increase in hydroxybutyrylcarnitine and tetradeceneoylcarnitine that may reflect ketosis. In view of his clinical presentation and abnormal metabolic investigations, the initial working diagnosis was mitochondrial disease. Subsequently, patient presented with hip pain, and radiologic and imaging studies revealed high density collections lateral to the right proximal part of the femur, and medial to the right ilium with signal changes suggestive of metallic content. This prompted toxicology screen which revealed elevated plasma cobalt concentration (903.32 µg/L; reference range: 0.1-0.4) and chromium (71.32 µg/L; <0.5). Six months post right hip prosthesis removal the concentrations have declined and was 61.72 µg/L and chromium 23.97 µg/L. Patient felt some improvement symptomatically, without evident deterioration in his vision or hearing. This case emphasises careful consideration of past medical history, in patients presenting with multisystemic disease suggestive of mitochondrial dysfunction, and potential causality related to exposure to toxic agents. In retrospect, the absence of a family history could be viewed as a pertinent negative finding. Not uncommonly, specialist focus on their favored system and may not search for a unifying diagnosis. It is likely further delays in diagnosis would have occurred had the patient not developed hip pains, and ultimately referred to the orthopedic surgeons more familiar with similar cases.