Systematic Review and Consensus Guidelines for Environmental Sampling of Burkholderia pseudomallei

Background

Burkholderia pseudomallei, a Tier 1 Select Agent and the cause of melioidosis, is a Gram-negative bacillus present in the environment in many tropical countries. Defining the global pattern of B. pseudomallei distribution underpins efforts to prevent infection, and is dependent upon robust environmental sampling methodology. Our objective was to review the literature on the detection of environmental B. pseudomallei, update the risk map for melioidosis, and propose international consensus guidelines for soil sampling.

Methods/Principal Findings

An international working party (Detection of Environmental Burkholderia pseudomallei Working Party (DEBWorP)) was formed during the VIth World Melioidosis Congress in 2010. PubMed (January 1912 to December 2011) was searched using the following MeSH terms: pseudomallei or melioidosis. Bibliographies were hand-searched for secondary references. The reported geographical distribution of B. pseudomallei in the environment was mapped and categorized as definite, probable, or possible. The methodology used for detecting environmental B. pseudomallei was extracted and collated. We found that global coverage was patchy, with a lack of studies in many areas where melioidosis is suspected to occur. The sampling strategies and bacterial identification methods used were highly variable, and not all were robust. We developed consensus guidelines with the goals of reducing the probability of false-negative results, and the provision of affordable and ‘low-tech’ methodology that is applicable in both developed and developing countries.

Conclusions/Significance

The proposed consensus guidelines provide the basis for the development of an accurate and comprehensive global map of environmental B. pseudomallei.     

Design and synthesis of functionalized piperazin-1yl-(E)-stilbenes as inhibitors of 17α-hydroxylase-C17,20-lyase (Cyp17)

The synthesis of steroid hormones is critical to human physiology and improper regulation of either the synthesis of these key molecules or activation of the associated receptors can lead to disease states. This has led to intense interest in developing compounds capable of modulating the synthesis of steroid hormones. Compounds capable of inhibiting Cyp19 (Aromatase), a key enzyme in the synthesis of estrogens, have been successfully employed as breast cancer therapies, while inhibitors of Cyp17 (17α-hydroxylase-17,20-lyase), a key enzyme in the synthesis of glucocorticoids, mineralocorticoids and steroidal sex hormones, are a key component of prostate cancer therapy. Inhibition of CYP17 has also been suggested as a possible target for the treatment of Cushing Syndrome and Metabolic Syndrome. We have identified two novel series of stilbene based CYP17 inhibitors and demonstrated that exemplary compounds in these series have pharmacokinetic properties consistent with orally delivered drugs. These findings suggest that compounds in these classes may be useful for the treatment of diseases and conditions associated with improper regulation of glucocorticoids synthesis and glucocorticoids receptor activation.     

Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study

Background:

Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine.

Methods:

To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale).

Results:

We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval [CI] 28.4%–35.2%) and ranged from 10.8% to 44.2% across centres (χ² test for overall difference, p < 0.001). Most deaths (70.2% [160/228], 95% CI 63.9%–75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ² test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care.

Interpretation:

We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury.Traumatic brain injury is the leading cause of death and disability among patients younger than 45 years of age, with mortality rates ranging from 30% to 40%.^1–3 Moreover, the impact of traumatic brain injury on quality of life among survivors is tremendous, with up to 30% of patients acquiring major neurologic sequelae.Although few studies have compared mortality among centres in global trauma populations,^4,5 overall mortality and variation in mortality, specifically for patients with critical illness and traumatic brain injury, are less well described. Because patients with severe traumatic brain injury lack capacity for making medical decisions, relatives and medical teams must frequently estimate patients’ preferences for treatment, including life support. Decisions to withdraw life-sustaining therapies are usually based on perceptions of unfavourable prognosis for meaningful neurologic recovery.^6–8 However, there are relatively few accurate and useful prediction tools to inform such estimates of prognosis. Therefore, prognostication is often based on clinicians’ impressions and past experiences. The subjective nature of neuroprognostication may lead to variability in the incidence of death associated with the withdrawal of life-sustaining therapy. With the recent advent of programs for organ donation following cardiovascular death, potential variability in mortality and withdrawal of life-sustaining therapy among patients with severe traumatic brain injury would be of major importance from a medicolegal perspective. The ethical debate surrounding organ donation following cardiovascular death having recently reached a public hearing⁹ highlights the need to improve our understanding of withdrawal of life-sustaining therapy for this specific population of patients.We hypothesized that hospital mortality varies across centres and that this may be explained, at least in part, by variability in the rate of withdrawal of life-sustaining therapy. We conducted a multicentre cohort study in six Canadian level-one trauma centres to investigate and compare rates of death associated with withdrawal of life-sustaining therapy among patients with severe traumatic brain injury.     

Proteomic profiling of clinical and environmental strains of Pseudomonas aeruginosa

Molecular Biology Reports - Pseudomonas aeruginosa is a ubiquitous bacterium, which is able to change its physiological characteristics in response to different habitats. Environmental strains are...     

Review: “Doctor,will that x-ray harm my unborn child?”

Abstract: Exposure to ionizing radiation can be a source of anxiety for many pregnant women and their health care providers. An awareness of the radiation doses delivered by different techniques and the acceptable exposure thresholds can help both patients and practitioners. We describe exposure to radiodiagnostic procedures during pregnancy and suggest an approach to assess the potential risk.Case 1: A 29-year-old patient underwent an upper gastrointestinal series as part of the diagnosis of prolonged heartburn. She comes to see you 1 week later and is very upset because her period is 1 week late and she was about 4 weeks pregnant at the time of the procedure. The patient asks you to schedule the termination of her pregnancy on the advice of several family members.Case 2: A 40-year-old woman arrives at the emergency department with acute pleuritic chest pain and shortness of breath. The patient is 15 weeks'' pregnant. To rule out a pulmonary embolus, should you perform a ventilation-perfusion scan or computed tomography (CT) angiography?Case 3: A 37-year-old woman who is 20-weeks pregnant reports persistent pain in her right upper thigh that is exacerbated after jogging. The pain is localized and has no radicular properties. A physical examination shows localized tenderness on the right hip joint without any abnormal neurological findings. You suspect hip bursitis but want to order a radiograph to rule out osteoarthritis with degenerative changes. The patient is nervous about the possible effects of the radiation on her baby; how would you counsel her?Many women are exposed to radiation from diagnostic imaging procedures before they know they are pregnant or because it is necessary during a known pregnancy. These patients often question the potential effects of the radiation on the developing fetus, and they may perceive radiation as being very harmful.^1–4 A realistic and informed approach to counselling these patients can minimize the anxiety felt by both patients and health care providers.Humans are exposed to both background and man-made sources of radiation. For the purpose of this review, “radiation” refers to ionizing radiation (e.g., x-rays, γ-rays, radionuclides) and not to other forms of radiation (e.g., long-wavelength electromagnetic waves such as radar, microwaves, diathermy and FM radio waves).Ionizing radiation in the form of x-rays and γ-rays are short-wavelength electromagnetic rays. Low-energy photons in x-rays and high-energy photons in γ-rays can alter the normal structure of a living cell both directly and indirectly. The direct mechanism involves disruption of the atom''s structure to produce an ionized compound and a free electron. The indirect mechanism involves radiolysis of water and generation of free radicals.⁵Ionizing radiation can cause two types of effects.⁵ First, loss of tissue function (deterministic effect) can occur. This type of injury has tissue-specific thresholds and may involve various repair and compensatory mechanisms. If the radiation dose is fractionated, there is greater repair and proliferation, hence there is greater tolerance of the tissue to the radiation. Second, damage can occur from a single random modification in a cell component (e.g., DNA) (stochastic effect). There is no dose threshold for stochastic effects.Since invention of the x-ray in 1895, ionizing radiation has been harnessed for diagnostic and therapeutic purposes. With the atomic bombings in World War II, the world became aware of the serious potential carcinogenic, teratogenic and mutagenic effects of ionizing radiation. Despite the increase in concern about the health effects of ionizing radiation, the medical use of x-rays has continued to grow. In 1980, the number of radiographs performed in the United States was 225 million, including about 80 million fertile men and women.⁵ In 2006, the estimated total number of radiographs in the US was about 330 million.⁶ The fetus is exposed to unavoidable (background) radiation from cosmic rays, terrestrial radiation from ground and building and naturally occurring radioisotopes that are inhaled or ingested. The total fetal dose from background radiation sources is 0.1 rad or less during the entire pregnancy.⁵     

Memories of ethnic violence in Sri Lanka among immigrant Tamils in the UK

This article contributes to recent studies on the relationship between ethnicity and memory in the formation of transnational communities. The focus of the article is migrant Tamils' memories of violence in Sri Lanka in 1958, in the aftermath of an act declaring Sinhala to be the sole language of administration in the country. The ways in which past violence is remembered by this overlooked older generation helps in understanding the particular impetus of the contemporary Tamil diaspora, which continues to play a key role in shaping the image of Sri Lanka abroad. Research on the formation of the diaspora must therefore be situated within a more concrete history of relations between Sinhalese and Tamils in post-independence Sri Lanka.