Human Melioidosis.

The causative agent of melioidosis, Burkholderia pseudomallei, a tier 1 select agent, is endemic in Southeast Asia and northern Australia, with increased incidence associated with high levels of rainfall. Increasing reports of this condition have occurred worldwide, with estimates of up to 165,000 cases and 89,000 deaths per year. The ecological niche of the organism has yet to be clearly defined, although the organism is associated with soil and water. The culture of appropriate clinical material remains the mainstay of laboratory diagnosis. Identification is best done by phenotypic methods, although mass spectrometric methods have been described. Serology has a limited diagnostic role. Direct molecular and antigen detection methods have limited availability and sensitivity. Clinical presentations of melioidosis range from acute bacteremic pneumonia to disseminated visceral abscesses and localized infections. Transmission is by direct inoculation, inhalation, or ingestion. Risk factors for melioidosis include male sex, diabetes mellitus, alcohol abuse, and immunosuppression. The organism is well adapted to intracellular survival, with numerous virulence mechanisms. Immunity likely requires innate and adaptive responses. The principles of management of this condition are drainage and debridement of infected material and appropriate antimicrobial therapy. Global mortality rates vary between 9% and 70%. Research into vaccine development is ongoing.

Antileishmanial activity evaluation of a natural amide and its synthetic analogs against Leishmania (V.) braziliensis: an integrated approach in vitro and in silico.

Leishmaniasis is considered a neglected disease, which makes it an unattractive market for the pharmaceutical industry; hence, efforts in the search for biologically active substances are hampered by this lack of financial motivation. Thus, in the present study, we report the leishmanicidal activity and the possible mechanisms of action of compounds with promising activity against the species Leishmania (V.) braziliensis, the causative agent of the skin disease leishmaniasis. The natural compound 1a (piplartine) and the analog 2a were the most potent against promastigote forms with growth inhibition values for 50% of the parasite population (IC50) = 8.58 and 11.25 µM, respectively. For amastigote forms, the ICa50 values were 1.46 and 16.7 µM, respectively. In the molecular docking study, piplartine showed favorable binding energy (-7.13 kcal/mol) and with 50% inhibition of trypanothione reductase (IC50) = 91.1 µM. Preliminary investigations of the mechanism of action indicate that piplartine increased ROS levels, induced loss of cell membrane integrity, and caused accumulation of lipid bodies after 24 h of incubation at its lowest effective concentration (IC50), which was not observed for the synthetic analog 2a. The mode of action for the leishmanicidal activity of piplartine (1a) was assigned to involve affinity for the trypanothione reductase of Leishmania (V.) braziliensis TR.

Identification of Burkholderia pseudomallei by Use of the Vitek Mass Spectrometer.

Burkholderia pseudomallei is the causative agent of melioidosis. This condition most often presents as pneumonia and bacteremia, with mortality rates of 9% to 70%. Therefore, early identification of this organism may aid in directing appropriate management. This study aimed to use the Vitek matrix-assisted laser desorption ionization-time of flight mass spectrometer to create a spectrum for the rapid identification of B. pseudomallei Spectra from 85 isolate cultures were acquired using the Vitek mass spectrometer research mode. A SuperSpectrum was created using peak matching and subsequently activated for analysis of organism identification. All 85 isolates were correctly identified as B. pseudomallei A total of 899 spectra were analyzed and demonstrated a specificity of 99.8%. Eighty-one clinical isolates were used, of which 10 were neuromelioidosis, and no discernible spectrum difference was appreciated. Spectrum acquisition from a single spot was only successful in 374/899 (41%) of isolates. This increased to 100% when 3 spots of the same extract were analyzed. The Vitek mass spectrometer can be used for the rapid identification of B. pseudomallei with a high level of specificity.

Women's and healthcare providers' perceptions of long-term complications associated with hypertension and diabetes in pregnancy: a qualitative study.

OBJECTIVES: A diagnosis of hypertensive disorders during pregnancy (HDPs) or gestational diabetes mellitus (GDM) is highly predictive of women at increased risk of developing chronic hypertension, Type 2 diabetes, and cardiovascular disease. This study investigates perceptions of women and healthcare providers in rural India regarding these long-term risks. DESIGN: Qualitative study using modified grounded theory. SETTING: Two states in rural India: Haryana and Andhra Pradesh. POPULATION: Pregnant and postpartum women, community health workers (CHWs), primary care physicians, obstetricians, laboratory technicians, and healthcare officials. METHODS: In-depth interviews and focus group discussions explored: (1) priorities for high-risk pregnant women; (2) detection and management of HDPs and GDM; (3) postpartum management, and (4) knowledge of long-term sequelae of high-risk conditions. A thematic analysis was undertaken. RESULTS: Seven focus group discussions and 11 in-depth interviews (n = 71 participants) were performed. The key priority area for high-risk pregnant women was anaemia. Blood pressure measurement was routinely embedded in antenatal care; however, postpartum follow up and knowledge of the long-term complications were limited. GDM was not considered a common problem, although significant variations and challenges to GDM screening were identified. Knowledge of the long-term sequelae of GDM with regard to an increased risk of Type 2 diabetes and cardiovascular disease among doctors was minimal. CONCLUSIONS: There is a need for improved education, standardisation of testing and postpartum follow up of HDPs and GDM in rural Indian settings. FUNDING: SN is supported by an MRC Clinical Research Training Fellowship (MR/R017182/1). The George Institute for Global Health Global Women's Health programme provided financial support for the research assistant and fieldwork costs in India. TWEETABLE ABSTRACT: Improved education and postpartum care of women with hypertension and diabetes in pregnancy in rural India are needed to prevent long-term risks.

Management of hip fractures in older people in Beijing: a retrospective audit and comparison with evidence-based guidelines and practice in the UK.

UNLABELLED: Despite the high burden of hip fracture in China, there is limited information on its management. This study investigated the management of hip fractures in a Beijing tertiary hospital and compared practice with that in 180 hospitals in the UK. The findings show a significant gap exists between the countries. INTRODUCTION: The purpose of this study was to determine if the management of older people with hip fractures in a Beijing tertiary hospital is comparable with the UK best practice guidelines for hip fracture management and the UK National Hip Fracture Database 2012, obtained from 180 hospitals. METHODS: A retrospective audit was undertaken in a large tertiary care hospital in Beijing. Data were compared with the National Hip Fracture Database 2012 collected in 180 hospitals in the UK on the proportion of patients managed according to the UK Blue Book standards. RESULTS: Sixty-six percent of patients were admitted to an orthopaedic ward within 24 h of fracture, while 100 % of patients in the UK were admitted to an orthopaedic ward within 24 h of arrival to an accident and emergency department. Only 8 % of patients received surgery within 48 h of admission compared with 83 % in the UK; 10 % received no surgery compared with 2.5 % in the UK; and 27 % received orthogeriatrician assessment compared with 70 % in the UK. New pressure ulcers developed in 2 % of patients compared with 3.7 % of those in the UK; whereas, 0.3 % of patients were assessed for osteoporosis treatment and 3.8 % received falls assessment, and comparable figures for the UK were 94 and 92 %, respectively. CONCLUSIONS: Significant gaps exist in hip fracture management in the Beijing hospital compared with the best practice achieved in 180 UK hospitals, highlighting the need to implement and evaluate proactive strategies to increase the uptake of best practice hip fracture care in China.

Acute Q fever in northern Queensland: variation in incidence related to rainfall and geographical location.

The aims of this study were to define the basic epidemiology of serologically confirmed acute Q fever in patients tested via the Townsville Hospital laboratory from 2000 to 2010 and to determine the impact of geographical location and seasonality on the incidence of acute cases in the Townsville region. Seven Statistical Local Areas (SLA) were identified as having an incidence higher than the average Queensland incidence over the study period. The SLA with the highest incidence was Woodstock-Ross with 24.9 cases/100,000. A clear seasonal peak was found, with the greatest number of cases observed in May, 3 months following the peak in rainfall in February. We hypothesize that an increase in wildlife numbers and drier conditions seen immediately following the wet season is the reason for the seasonal peak of human acute Q fever cases in Townsville.

Sleep, blood pressure and obesity in 22,389 New Zealanders.

AIM: To determine the relationship of sleep disorders with blood pressure and obesity in a large, relatively healthy, community-based cohort. METHODS: A cross-sectional study was undertaken using data from 22,389 volunteer blood donors in New Zealand aged 16-84 years. Height, weight, neck circumference and blood pressure were measured directly, and data on sleep and other factors were ascertained using a validated self-administered questionnaire. RESULTS: Even in a relatively young, non-clinical cohort, lack of sleep (34%), snoring (33%), high blood pressure (20%) and obesity (19%) are common. After adjusting for relevant confounders, participants at high risk of sleep apnoea had double the odds of having high blood pressure but only in participants over 40 years. Very low and high quantities of sleep are also associated with high blood pressure. Even after controlling for neck circumference, self-reported sleep apnoea, sleep dissatisfaction and low amounts of sleep are associated with a higher body mass index. CONCLUSIONS: Obesity and hypertension have significant associations with a variety of sleep disorders, even in those less than 40 years of age and after adjusting for a wide range of potential confounders.

Coxiella burnetii causing haemophagocytic syndrome: a rare complication of an unusual pathogen.

We describe an unusual presentation of Q fever with associated haemophagocytic syndrome, confirmed by bone marrow aspirate, Q fever polymerase chain reaction (PCR) and serological testing. Clinical recovery was observed after the commencement of doxycycline with normalisation of the patient's full blood count and serum biochemistry. Serial monitoring of the Q fever serology revealed the subsequent development of sustained high phase 1 IgG antibodies, suggestive of chronic Q fever. Although many infectious aetiologies have been associated with haemophagocytosis, Q fever has only rarely been described in this context. The diagnosis of Q fever is often overlooked, especially when the presentation is atypical. We describe how the use of PCR testing significantly shortened the interval to definitive diagnosis and helped elucidate the underlying cause of the patient's haematological disorder.

Automated erythrocytapheresis for severe falciparum malaria.

We describe a case of severe falciparum malaria with hyperparasitaemia. Treatment with automated erythrocytapheresis, in conjunction with parenteral artesunate, produced a rapid and sustained fall in parasite burden. Several poor prognostic features were present at admission. Despite the development of a severe headache with abnormal cerebrospinal fluid parameters and transient pulmonary oedema, a complete recovery was observed. Erythrocytapheresis can be considered in selected cases where facilities exist and has theoretical and practical advantages over traditional methods of red cell exchange transfusion. The paucity of systematic or trial evidence convincingly demonstrating a benefit in terms of morbidity or mortality has limited its application. However, the lack of robust trial data should not in itself invalidate considering this therapeutic option in the appropriate context.

Spatial analysis of melioidosis distribution in a suburban area.

Burkholderia pseudomallei, the causative agent of melioidosis is associated with soil. This study used a geographic information system (GIS) to determine the spatial distribution of clinical cases of melioidosis in the endemic suburban region of Townsville in Australia. A total of 65 cases over the period 1996-2008 were plotted using residential address. Two distinct groupings were found. One was around the base of a hill in the city centre and the other followed the old course of a major waterway in the region. Both groups (accounting for 43 of the 65 cases examined) are in areas expected to have particularly wet topsoils following intense rainfall, due to soil type or landscape position.

Chronic neck pain following car crashes: a population-based study from Auckland, New Zealand.

BACKGROUND: In a setting with a 'no fault' universal government-funded accident compensation system, we undertook a study to (i) estimate the prevalence and predictors of chronic neck pain in car occupants surviving serious injury-producing crashes and (ii) compare the longer-term health-related quality of life of crash survivors with and without neck discomfort. METHODS: A prospective cohort study recruited hospitalized survivors aged ≥16 years and non-hospitalized drivers of cars involved in serious crashes in Auckland over a 10-month period. Participants completed a structured questionnaire at recruitment and 5 and 18 months later. RESULTS: Of the 268 participants, 50 (18.7%) reported neck pain or stiffness at 5 and 18 months following the crash. Of these, 70% noted the discomfort led to limitations in work and recreation. Depressive and post-traumatic stress symptoms at 5 months were associated with an increased risk of moderate to severe neck discomfort at 18 months. Participants with and without neck discomfort had significantly reduced health-related quality of life based on Short Form-36 scores. CONCLUSION: Significant neck discomfort limiting usual function is relatively common up to 18 months following crashes. The reductions in health status among crash survivors with and without neck pain reveal the complexities in attributing longer-term adverse outcomes to a particular condition in the absence of an appropriate comparison group. The findings indicate the need to manage judiciously comorbid conditions while prioritizing efforts to support crash survivors' return to their usual social roles and activities.

Thoracic osteophyte: rare cause of esophageal perforation.

Esophageal perforation is a difficult problem in thoracic surgery. Esophageal perforations can be spontaneous, iatrogenic, or malignant. We report two cases of esophageal perforations caused by thoracic osteophytes and different management strategies leading to successful outcomes. An 80-year-old male presented with chest pain and dysphagia following a fall. On endoscopy, an esophageal perforation and foreign body was noted which was confirmed as a thoracic osteophyte on computed tomography scan. He was managed conservatively as he declined surgery. A 63-year-old male was admitted with dysphagia following a food bolus obstruction. Following esophagoscopy and dilatation, there was clinical and radiological evidence of perforation. During surgery, a thoracic osteophyte was identified as the cause of perforation. The perforation was closed in layers and the osteophyte was trimmed. Both patients recovered well. Thoracic osteophytes are a rare cause of esophageal perforations and a high index of suspicion is required in patients with osteoarthritis who present with esophageal perforations.

Burkholderia pseudomallei multi-centre study to establish EUCAST MIC and zone diameter distributions and epidemiological cut-off values.

OBJECTIVES: Melioidosis, caused by Burkholderia pseudomallei, requires intensive antimicrobial treatment. However, standardized antimicrobial susceptibility testing (AST) methodology based on modern principles for determining breakpoints and ascertaining performance of methods are lacking for B. pseudomallei. This study aimed to establish MIC and zone diameter distributions on which to set epidemiological cut-off (ECOFF) values for B. pseudomallei using standard EUCAST methodology for non-fastidious organisms. METHODS: Non-consecutive, non-duplicate clinical B. pseudomallei isolates (9-70 per centre) were tested at eight study centres against eight antimicrobials by broth microdilution (BMD) and the EUCAST disc diffusion method. Isolates without and with suspected resistance mechanisms were deliberately selected. The EUCAST Development Laboratory ensured the quality of study materials, and provided guidance on performance of the tests and interpretation of results. Aggregated results were analysed according to EUCAST recommendations to determine ECOFFs. RESULTS: MIC and zone diameter distributions were generated using BMD and disc diffusion results obtained for 361 B. pseudomallei isolates. MIC and zone diameter ECOFFs (mg/L; mm) were determined for amoxicillin-clavulanic acid (8; 22), ceftazidime (8; 22), imipenem (2; 29), meropenem (2; 26), doxycycline (2; none), tetracycline (8; 23), chloramphenicol (8; 22) and trimethoprim-sulfamethoxazole (4; 28). CONCLUSIONS: We have validated the use of standard BMD and disc diffusion methodology for AST of B. pseudomallei. The MIC and zone diameter distributions generated in this study allowed us to establish MIC and zone diameter ECOFFs for the antimicrobials studied. These ECOFFs served as background data for EUCAST to set clinical MIC and zone diameter breakpoints for B. pseudomallei.

Engineering a stable and selective peptide blocker of the Kv1.3 channel in T lymphocytes.

Kv1.3 potassium channels maintain the membrane potential of effector memory (T(EM)) T cells that are important mediators of multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. The polypeptide ShK-170 (ShK-L5), containing an N-terminal phosphotyrosine extension of the Stichodactyla helianthus ShK toxin, is a potent and selective blocker of these channels. However, a stability study of ShK-170 showed minor pH-related hydrolysis and oxidation byproducts that were exacerbated by increasing temperatures. We therefore engineered a series of analogs to minimize the formation of these byproducts. The analog with the greatest stability, ShK-192, contains a nonhydrolyzable phosphotyrosine surrogate, a methionine isostere, and a C-terminal amide. ShK-192 shows the same overall fold as ShK, and there is no evidence of any interaction between the N-terminal adduct and the rest of the peptide. The docking configuration of ShK-192 in Kv1.3 shows the N-terminal para-phosphonophenylalanine group lying at the junction of two channel monomers to form a salt bridge with Lys(411) of the channel. ShK-192 blocks Kv1.3 with an IC(50) of 140 pM and exhibits greater than 100-fold selectivity over closely related channels. After a single subcutaneous injection of 100 microg/kg, approximately 100 to 200 pM concentrations of active peptide is detectable in the blood of Lewis rats 24, 48, and 72 h after the injection. ShK-192 effectively inhibits the proliferation of T(EM) cells and suppresses delayed type hypersensitivity when administered at 10 or 100 microg/kg by subcutaneous injection once daily. ShK-192 has potential as a therapeutic for autoimmune diseases mediated by T(EM) cells.

Vitamin D and respiratory health.

Vitamin D is now known to be of physiological importance outside of bone health and calcium homeostasis, and there is mounting evidence that it plays a beneficial role in the prevention and/or treatment of a wide range of diseases. In this brief review the known effects of vitamin D on immune function are described in relation to respiratory health. Vitamin D appears capable of inhibiting pulmonary inflammatory responses while enhancing innate defence mechanisms against respiratory pathogens. Population-based studies showing an association between circulating vitamin D levels and lung function provide strong justification for randomized controlled clinical trials of vitamin D supplementation in patients with respiratory diseases to assess both efficacy and optimal dosage.

Mite-plant associations from the eocene of southern australia.

Acarodomatia or "mite houses" are located on leaves of many present-day angiosperms and are inhabited by mites that may maintain leaf hygiene. Eocene deposits in southern Australia have yielded acarodomatia on fossil leaves of Elaeocarpaceae and Lauraceae and also contain oribatid mites with close affinities to those that inhabit the acarodomatia of the closest living relatives of the fossil plant taxa. The data indicate that mite-plant associations may have been widespread in southern Australia 40 million years ago.

Carbon-13 nuclear magnetic resonance study of osmoregulation in a blue-green alga.

The process of osmoregulation in a unicellular blue-green alga, Synechococcus sp., has been studied by natural-abundance carbon-13 nuclear magnetic resonance spectroscopy of intact cells and cell extracts. 2-O-alpha-D-Glucopyranosylglycerol was identified as the major organic osmoregulatory solute. This demonstrates the presence of a major osmoregulatory solute in a blue-green alga and is also an example of an osmoregulatory role for glucosylglycerol.

Jupiter:observation of deuterated methane in the atmosphere.

A positive identification of singly deuterated methane has been made in the 4- to 5-micron spectrum of Jupiter.

Early land animals in north america: evidence from devonian age arthropods from gilboa, new york.

A new fossil site near Gilboa, New York, is one of only three where fossils of terrestrial arthropods of Devonian age have been found. The new Gilboan fauna is younger than the other two but richer in taxa. Fragmentary remains and nearly whole specimens assigned to Eurypterida, Arachnida (Trigonotarbida, Araneae, Amblypygi, and Acari), Chilopoda [Craterostigmatomorpha(?) and Scuterigeromorpha(?)], and tentatively to Insecta (Archaeognatha) have been found. The centipedes and possible insects may represent the earliest records known for these groups.

Effect of the major histocompatibility complex on the inhibition of induced cellulitis development in a broiler chicken model.

The chicken major histocompatibility complex (MHC) has been implicated in conferring resistance or susceptibility to several bacterial, parasitic, and viral diseases, the most notable of which is Marek's disease. In Marek's disease certain MHC haplotypes have been shown to confer relative resistance (B21), whereas other haplotypes are susceptible (B13). Relatively little work has been performed looking at the association of the MHC with bacterial diseases. One such disease is cellulitis, which is caused by several different bacteria but most notably by Escherichia coli. In this report, a commercial broiler chicken line known to contain standard B13 and B21, as well as the unique MHC types BA9 and BA12, was examined in a challenge model for cellulitis. The MHC-defined birds were challenged with a cellulitis-causing E. coli isolate and the frequency of lesion development and severity was quantified. In conclusion, B21 had the highest incidence of cellulitis development, B13 had the lowest incidence, and BA9 and BA12 had intermediate results. Results concerning the lesion severity showed that it was independent of the birds' MHC type.