A clinical review of mpox for the Aotearoa New Zealand clinician.

The World Health Organization declared mpox (formerly monkeypox) a Public Health Emergency of International Concern in July 2022. Aotearoa New Zealand has reported cases of mpox since July, with reports of locally acquired cases since October 2022. The 2022 global mpox outbreak highlights many features of the illness not previously described, including at-risk populations, mode of transmission, atypical clinical features, and complications. It is important that all clinicians are familiar with the variety of clinical manifestations, as patients may present to different healthcare providers, and taking lessons from the HIV pandemic, that all patients are managed without stigma or discrimination. There have been numerous publications since the outbreak began. Our narrative clinical review attempts to bring together the current clinical evidence for the New Zealand clinician.

Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators.

Different types of memory are thought to rely on different types of synaptic plasticity, many of which depend on the activation of the N-Methyl-D Aspartate (NMDA) subtype of glutamate receptors. Accordingly, there is considerable interest in the possibility of using positive allosteric modulators (PAMs) of NMDA receptors (NMDARs) as cognitive enhancers. Here we firstly review the evidence that NMDA receptor-dependent forms of synaptic plasticity: short-term potentiation (STP), long-term potentiation (LTP) and long-term depression (LTD) can be pharmacologically differentiated by using NMDAR ligands. These observations suggest that PAMs of NMDAR function, depending on their subtype selectivity, might differentially regulate STP, LTP and LTD. To test this hypothesis, we secondly performed experiments in rodent hippocampal slices with UBP714 (a GluN2A/2B preferring PAM), CIQ (a GluN2C/D selective PAM) and UBP709 (a pan-PAM that potentiates all GluN2 subunits). We report here, for the first time, that: (i) UBP714 potentiates sub-maximal LTP and reduces LTD; (ii) CIQ potentiates STP without affecting LTP; (iii) UBP709 enhances LTD and decreases LTP. We conclude that PAMs can differentially regulate distinct forms of NMDAR-dependent synaptic plasticity due to their subtype selectivity.

Epidemiology of Exobasidium Leaf and Fruit Spot of Rabbiteye Blueberry: Pathogen Overwintering, Primary Infection, and Disease Progression on Leaves and Fruit.

Epidemiological field studies utilizing disease monitoring, spore trapping, and trap plants were conducted on rabbiteye blueberry (Vaccinium virgatum) between 2014 and 2017 to shed light on the epidemiology of Exobasidium leaf and fruit spot, an emerging disease in the southeastern United States caused by the fungus Exobasidium maculosum. Wash plating of field-collected blueberry tissue from the late dormant season through bud expansion showed that the pathogen overwintered epiphytically on blueberry plants in the field, most likely in its yeast-like conidial stage. Agrichemical applications during the dormant season altered epiphytic populations of the pathogen, which correlated directly with leaf spot incidence later in the spring. Disease monitoring of field plants and weekly exposure of potted trap plants revealed that young leaves at the mouse-ear stage were most susceptible to infection, that disease incidence on leaves progressed monocyclically, and that infection periods were associated with rainfall variables such as the number of days per week with ≥1.0 mm of rain or cumulative weekly rainfall. Weekly spore trapping with an Andersen sampler showed that airborne inoculum was detected only after sporulating leaf lesions producing basidiospores were present in the field, suggesting that the primary inoculum is not airborne. The first symptoms on young, green fruit were observed soon after petal fall (requiring removal of the waxy fruit layer to visualize lesions), and visible disease progress on fruit was delayed by 1 to 3 weeks relative to that on leaves. Fruit infection of field plants and trap plants occurred before airborne propagules were detected by spore trapping and before sporulating leaf lesions were present in the field. Hence, this study showed that fruit infections are initiated by the same initial inoculum as leaf infections but it was not possible to conclusively exclude the possibility of a contribution of basidiospore inoculum from leaf lesions to disease progress on later developing fruit. This is one of only a few studies addressing the epidemiology and disease cycle of an Exobasidium sp. in a pathosystem where artificial inoculation has not been possible to date.

Skin and soft tissue infections and current antimicrobial prescribing practices in Australian aged care residents.

To determine the burden of skin and soft tissue infections (SSTI), the nature of antimicrobial prescribing and factors contributing to inappropriate prescribing for SSTIs in Australian aged care facilities, SSTI and antimicrobial prescribing data were collected via a standardised national survey. The proportion of residents prescribed ⩾1 antimicrobial for presumed SSTI and the proportion whose infections met McGeer et al. surveillance definitions were determined. Antimicrobial choice was compared to national prescribing guidelines and prescription duration analysed using a negative binomial mixed-effects regression model. Of 12 319 surveyed residents, 452 (3.7%) were prescribed an antimicrobial for a SSTI and 29% of these residents had confirmed infection. Topical clotrimazole was most frequently prescribed, often for unspecified indications. Where an indication was documented, antimicrobial choice was generally aligned with recommendations. Duration of prescribing (in days) was associated with use of an agent for prophylaxis (rate ratio (RR) 1.63, 95% confidence interval (CI) 1.08-2.52), PRN orders (RR 2.10, 95% CI 1.42-3.11) and prescription of a topical agent (RR 1.47, 95% CI 1.08-2.02), while documentation of a review or stop date was associated with reduced duration of prescribing (RR 0.33, 95% CI 0.25-0.43). Antimicrobial prescribing for SSTI is frequent in aged care facilities in Australia. Methods to enhance appropriate prescribing, including clinician documentation, are required.

Wound dressing following primary total hip arthroplasty: a prospective randomised controlled trial.

OBJECTIVE: This study compared three methods of surgical wound dressing in patients undergoing primary total hip arthroplasty to determine their effect on wound leakage. METHOD: Total hip arthroplasties were randomised to 3 groups: 2-octyl cyanoacrylate (Dermabond-Ethicon Inc, G) with Opsite (Smith & Nephew; O) [G+O], 2-octyl cyanoacrylate with Tegaderm (3M; T) [G+T], and Opsite without 2-octyl cyanoacrylate [O]. Postoperative wound leakage was assessed and graded daily until discharge, the frequency of the dressing changes was also recorded. Patients were clinically reviewed at three months to assess cosmesis of their surgical scar and wound complications. RESULTS: In all 211 total hip arthoplasties were included. A greater proportion of patients' dressings remained dry on day 1 postoperatively in the two groups using 2-octyl cyanoacrylate (G+O and G+T) compared to the no glue group (O; p=0.0001). The G+T group had a significantly lower proportion of patients with increased leakage of wounds on days 2 and 3 postoperatively compared with both G+O and O groups (p=0.0043). The overall rate of dressing change for G+O was 8%, G+T 5%, and O 13%. Overall wound cosmesis was similar in all groups (p=0.690). CONCLUSION: The reduction in frequency of dressing changes coupled with low levels of wound leakage observed using the combination of the glue and nonabsorbent dressings (O+T), makes this combination of wound closing products ideal for facilitating enhanced recovery and early discharge programmes in elective hip arthroplasty.

A secretory leukocyte protease inhibitor variant with improved activity against lung infection.

Secretory leukocyte protease inhibitor (SLPI) is an important respiratory tract host defense protein, which is proteolytically inactivated by excessive neutrophil elastase (NE) during chronic Pseudomonas infection in the cystic fibrosis (CF) lung. We generated two putative NE-resistant variants of SLPI by site-directed mutagenesis, SLPI-A16G and SLPI-S15G-A16G, with a view to improving SLPI's proteolytic stability. Both variants showed enhanced resistance to degradation in the presence of excess NE as well as CF patient sputum compared with SLPI-wild type (SLPI-WT). The ability of both variants to bind bacterial lipopolysaccharides and interact with nuclear factor-κB DNA binding sites was also preserved. Finally, we demonstrate increased anti-inflammatory activity of the SLPI-A16G protein compared with SLPI-WT in a murine model of pulmonary Pseudomonas infection. This study demonstrates the increased stability of these SLPI variants compared with SLPI-WT and their therapeutic potential as a putative anti-inflammatory treatment for CF lung disease.

A chest radiograph scoring system in patients with severe acute respiratory infection: a validation study.

BACKGROUND: The term severe acute respiratory infection (SARI) encompasses a heterogeneous group of respiratory illnesses. Grading the severity of SARI is currently reliant on indirect disease severity measures such as respiratory and heart rate, and the need for oxygen or intensive care. With the lungs being the primary organ system involved in SARI, chest radiographs (CXRs) are potentially useful for describing disease severity. Our objective was to develop and validate a SARI CXR severity scoring system. METHODS: We completed validation within an active SARI surveillance project, with SARI defined using the World Health Organization case definition of an acute respiratory infection with a history of fever, or measured fever of ≥ 38 °C; and cough; and with onset within the last 10 days; and requiring hospital admission. We randomly selected 250 SARI cases. Admission CXR findings were categorized as: 1 = normal; 2 = patchy atelectasis and/or hyperinflation and/or bronchial wall thickening; 3 = focal consolidation; 4 = multifocal consolidation; and 5 = diffuse alveolar changes. Initially, four radiologists scored CXRs independently. Subsequently, a pediatrician, physician, two residents, two medical students, and a research nurse independently scored CXR reports. Inter-observer reliability was determined using a weighted Kappa (κ) for comparisons between radiologists; radiologists and clinicians; and clinicians. Agreement was defined as moderate (κ > 0.4-0.6), good (κ > 0.6-0.8) and very good (κ > 0.8-1.0). RESULTS: Agreement between the two pediatric radiologists was very good (κ = 0.83, 95% CI 0.65-1.00) and between the two adult radiologists was good (κ = 0.75, 95% CI 0.57-0. 93). Agreement of the clinicians with the radiologists was moderate-to-good (pediatrician:κ = 0.65; pediatric resident:κ = 0.69; physician:κ = 0.68; resident:κ = 0.67; research nurse:κ = 0.49, medical students: κ = 0.53 and κ = 0.56). Agreement between clinicians was good-to-very good (pediatrician vs. physician:κ = 0.85; vs. pediatric resident:κ = 0.81; vs. medicine resident:κ = 0.76; vs. research nurse:κ = 0.75; vs. medical students:κ = 0.63 and 0.66). Following review of discrepant CXR report scores by clinician pairs, κ values for radiologist-clinician agreement ranged from 0.59 to 0.70 and for clinician-clinician agreement from 0.97 to 0.99. CONCLUSIONS: This five-point CXR scoring tool, suitable for use in poorly- and well-resourced settings and by clinicians of varying experience levels, reliably describes SARI severity. The resulting numerical data enables epidemiological comparisons of SARI severity between different countries and settings.

Enteric fever in the Pacific: a regional retrospective study from Auckland, New Zealand.

BACKGROUND: There are limited clinical data on enteric fever in the Pacific and New Zealand (NZ) compared with the Indian subcontinent (ISC) and South-East Asia (SEA). Our objective was to describe enteric fever in Auckland - a large Pacific city, focusing on disease acquired in these regions. METHODS: We reviewed enteric fever cases hospitalised in Auckland from January 2005 to December 2010. RESULTS: Microbiologically confirmed EF was identified in 162 patients. Travel regions: Pacific, 40 cases (25%) (Samoa, 38; Fiji, two), ISC, 72 (44%), SEA, seven (4%), other, three (2%), no travel, 40 (25%). Enteric fever rates for Auckland resident travellers were: India 50.3/100 000; Samoa 19.7/100 000.All Pacific cases were Salmonella Typhi. Of local isolates (without travel history), 38 were S. Typhi (36 fully susceptible, one multi-drug resistant (MDR) + nalidixic acid resistant (NAR), one unknown) and two S. Paratyphi (both NAR). Of non-Pacific travel, 56/82 (69%) isolates were S. Typhi, the remainder S. Paratyphi (15 isolates were fully susceptible, only 1% were MDR). Significant associations of serotype and antibiotic resistance with different travel regions and similarity of phage types (local and Pacific) were observed. Headache, vomiting and acute kidney injuries were more frequent with Pacific travel, while abdominal distension and cholecystitis with local disease. Shorter duration of treatment in the Pacific group was seen despite length of stay in hospital not being reduced. Local cases were associated with longer hospital admissions. CONCLUSIONS: One half of cases in Auckland are acquired either from Pacific or locally. Similarities mean that disease acquired locally is likely of Pacific origin.

The clinical and public health problem of relapse despite primaquine therapy: case review of repeated relapses of Plasmodium vivax acquired in Papua New Guinea.

BACKGROUND: Primaquine is the only drug available for preventing relapse following a primary attack by Plasmodium vivax malaria. This drug imposes several important problems: daily dosing over two weeks; toxicity in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency; partner blood schizontocides possibly impacting primaquine safety and efficacy; cytochrome P-450 abnormalities impairing metabolism and therapeutic activity; and some strains of parasite may be tolerant or resistant to primaquine. There are many possible causes of repeated relapses in a patient treated with primaquine. CASE DESCRIPTION: A 56-year-old Caucasian woman from New Zealand traveled to New Ireland, Papua New Guinea for two months in 2012. One month after returning home she stopped daily doxycycline prophylaxis against malaria, and one week later she became acutely ill and hospitalized with a diagnosis of Plasmodium vivax malaria. Over the ensuing year she suffered four more attacks of vivax malaria at approximately two-months intervals despite consuming primaquine daily for 14 days after each of those attacks, except the last. Genotype of the patient's cytochrome P-450 2D6 alleles (*5/*41) corresponded with an intermediate metabolizer phenotype of predicted low activity. DISCUSSION: Multiple relapses in patients taking primaquine as prescribed present a serious clinical problem, and understanding the basis of repeated therapeutic failure is a challenging technical problem. This case highlights these issues in a single traveler, but these problems will also arise as endemic nations approach elimination of malaria transmission.

Sticking to minimum standards: implementing antibiotic stewardship in intensive care.

BACKGROUND: In Australia, antimicrobial stewardship programmes are a compulsory component of hospital accreditation. Good documentation around anti-microbial prescribing aids communication and can improve prescribing practice in environments with multiple decision makers. AIM: This study aims to develop and implement an intervention to improve antimicrobial prescribing practice in a 24-bed intensive care unit in a tertiary referral adult hospital. METHODS: We conducted a four-phase (observation, reflection, implementation, evaluation) prospective collaborative before-after quality improvement study. Baseline audits and surveys of antimicrobial prescribing practices identified barriers to and enablers of good prescribing practice. A customised intervention was then implemented over 6 weeks and included a yellow medication record sticker, quarterly education sessions and intensive care unit-specific empiric antimicrobial prescribing guidelines. Post-implementation, the effects were monitored by serial antimicrobial prescribing audits for 1 year. The primary outcomes were clear documentation of the start date, the planned stop date or review date and the indication for an antibiotic. These were all considered the 'minimum standards' for an antimicrobial prescription on the medication record. RESULTS: Documentation of minimum standards specifically addressed by the sticker improved (start date (72% to 90%, P < 0.001), stop date (16% to 63%, P < 0.001), antimicrobial indication documented on medication chart (58% to 83%, P < 0.01)). Overall, adherence to all three minimum standards (start date, stop date and indication) improved from 41/306 (13%) to 306/492 (63%) (P < 0.001). One-year post-implementation, the yellow sticker had become embedded into daily practice. CONCLUSION: A systematic approach to quality improvement combined with the implementation of a tailored, multi-faceted intervention can improve antimicrobial prescribing practices.

Helicobacter pylori downregulates expression of human ß-defensin 1 in the gastric mucosa in a type IV secretion-dependent fashion.

Helicobacter pylori establishes a chronic lifelong infection in the human gastric mucosa, which may lead to peptic ulcer disease or gastric adenocarcinoma. The human beta-defensins (hßDs) are antimicrobial peptides, hßD1 being constitutively expressed in the human stomach. We hypothesized that H. pylori may persist, in part, by downregulating gastric hßD1 expression. We measured hßD1 and hßD2 expression in vivo in relation to the presence, density and severity of H. pylori infection, investigated differential effects of H. pylori virulence factors, and studied underlying signalling mechanisms in vitro. Significantly lower hßD1 and higher hßD2 mRNA and protein concentrations were present in gastric biopsies from infected patients. Those patients with higher-level bacterial colonization and inflammation had significantly lower hßD1 expression, but there were no differences in hßD2. H. pylori infection of human gastric epithelial cell lines also downregulated hßD1. Using wild-type strains and isogenic mutants, we showed that a functional cag pathogenicity island-encoded type IV secretion system induced this downregulation. Treatment with chemical inhibitors or siRNA revealed that H. pylori usurped NF-κB signalling to modulate hßD1 expression. These data indicate that H. pylori downregulates hßD1 expression via NF-κB signalling, and suggest that this may promote bacterial survival and persistence in the gastric niche.

Exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1.

Anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (PA) with one of three reported cell surface toxin receptors (ANTXR). Receptor binding has been shown to influence host susceptibility to the toxins. Despite this crucial role for ANTXR in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about ANTXR expression on human leucocytes. We characterized the expression levels of ANTXR1 (TEM8) on human leucocytes using flow cytometry. In order to assess the effect of prior toxin exposure on ANTXR1 expression levels, leucocytes from individuals with no known exposure, those exposed to toxin through vaccination and convalescent individuals were analysed. Donors could be defined as either 'low' or 'high' expressers based on the percentage of ANTXR1-positive monocytes detected. Previous exposure to toxins appears to modulate ANTXR1 expression, exposure through active infection being associated with lower receptor expression. A significant correlation between low receptor expression and high anthrax toxin-specific interferon (IFN)-γ responses was observed in previously infected individuals. We propose that there is an attenuation of ANTXR1 expression post-infection which may be a protective mechanism that has evolved to prevent reinfection.

Imported malaria in Auckland, New Zealand.

AIM: To describe the current malaria situation in Auckland, New Zealand. METHOD: We collected data on all cases of malaria diagnosed in Auckland from 1st October 2008 to 30th September 2009. Enhanced surveillance was arranged with all hospital and community haematology laboratories in the region. Laboratories notified us when a diagnosis of malaria was made. After obtaining informed consent the patient was asked about their travel, prophylaxis taken and symptoms. Laboratory results were collected. RESULTS: There were 36 cases of malaria in 34 patients. Consent could not be obtained from two patients so data is from 34 cases in 32 patients. (One patient had P.falciparum then later P.vivax, the other had P.vivax and relapsed.) There were 24 males and 8 females with a median age of 21 years (range 6 months to 75 years). Eleven of the 32 were New Zealand residents. 8 of these 11 had travelled to visit friends or relatives (VFR) while 3 were missionaries. In this group 6 had P.falciparum, 4 P.vivax and one had both. Twenty-one of the 32 were new arrivals to New Zealand: 11 refugees and 10 migrants. CONCLUSION: Malaria in Auckland is seen in new arrivals and VFR travellers, not in tourist travellers.

The impact of stoma for bowel management after spinal cord injury.

STUDY DESIGN: Multi-centre, retrospective self-report postal survey. OBJECTIVES: To characterise spinal cord injured (SCI) individuals with a stoma, their stoma management and outcomes, to identify sources of information and support for decision making and to explore the impact of a stoma on life satisfaction. SETTING: Five UK spinal cord injury centres. METHODS: A study-specific questionnaire accompanied by self-concept, life satisfaction and mood measures, and three simple rating scales for satisfaction, impact and restriction on life were sent to all known ostomates at five participating centres. RESULTS: Respondents were 92 individuals, mean age 56 years, mean duration of injury 26 years, 91% with colostomy. Multiple sources of information were utilised in deciding on surgery; discussion with other SCI ostomates was important. Duration of bowel care, faecal incontinence, bowel-related autonomic dysreflexia, dietary manipulation and laxative use were all significantly reduced following surgery. Rectal mucous discharge was the most common and bothersome post-stoma problem. Satisfaction with stoma was high; provision of sufficient information preoperatively was important, those with ileostomy were more dependent and less satisfied. Life satisfaction and physical self-concept were both lower in this sample than in previously reported samples of SCI individuals without reported bowel difficulties or stoma. CONCLUSION: The findings of this study of self-selected respondents with a stoma for bowel management after SCI emphasised the benefits of stoma in selected individuals and the importance of timely intervention, the complexity of the associated decision-making and of preoperative counselling. The impact of bowel dysfunction on physical self-concept warrants investigation.

Reliability and validity of measuring scapular upward rotation using an electrical inclinometer.

The aim of this study was to assess the reliability and validity of a modified two-dimensional electrical inclinometer to measure scapular upward rotation during static humeral elevation. Numerous techniques have been proposed to qualitatively and quantitatively measure upward rotation of the scapula. These techniques are limited by expense or an inability to be synchronized with other measurements, such as muscle activity and force output. For validity testing, static scapular upward rotation was measured separately with a digital protractor and electrical inclinometer while participants were at rest and 60°, 90° and 120° of humeral elevation in the scapular plane. For reliability testing, either 20 min before or 20 min after validity testing, participants performed the testing positions while measurements were taken with the electrical inclinometer only. Significant correlations existed between the modified electrical inclinometer and digital protractor at all four positions (r>0.996, p<0.001). The electrical inclinometer demonstrated good to excellent intra-rater reliability (ICC(3,1)>0.892, 95%CI: 0.785-0.988 and SEM<1.8°). These results support the use of the electrical inclinometer to measure scapular upward rotation. These findings provide clinicians and researchers with a practical instrument that can accurately measure scapular upward rotation in synchrony with other measurements, such as electromyography and isokinetic data.

Early-onset growth hormone deficiency results in diastolic dysfunction in adult-life and is prevented by growth hormone supplementation.

OBJECTIVE: The primary goal of growth hormone (GH) replacement is to promote linear growth in children with growth hormone deficiency (GHD). GH and insulin-like growth factor-1 (IGF-1) are also known to have roles in cardiac development and as modulators of myocardial structure and function in the adult heart. However, little is known about cardiac diastolic function in young adults with childhood onset GH deficiency in which GH treatment was discontinued following puberty. The aim of the study was to evaluate the effects of long standing GHD and peri-pubertal or continuous GH replacement therapy on diastolic function in the adult dwarf rat. DESIGN: The dwarf rat, which possesses a mutation in a transcription factor necessary for development of the somatotroph, does not exhibit the normal peri-pubertal rise in GH around day 28 and was used to model childhood or early-onset GHD (EOGHD). In another group of male dwarfs, GH replacement therapy was initiated at 4 weeks of age when GH pulsatility normally begins. Ten weeks after initiation of injections, GH-treated dwarf rats were divided into 2 groups; continued treatment with GH for 12 weeks (GH-replete) or treatment with saline for 12 weeks. This latter group models GH supplementation during adolescence with GHD beginning in adulthood (adult-onset GHD; AOGHD). Saline-treated heterozygous (HZ) rats were used as age-matched controls. At 26 weeks of age, cardiac function was assessed using invasive or noninvasive (conventional and tissue Doppler) indices of myocardial contractility and lusitropy. RESULTS: Systolic function, as determined by echocardiography, was similar among groups. Compared with HZ rats and GH-replete dwarfs, the EOGHD group exhibited significant reductions in myocardial relaxation and increases in left ventricular filling pressure, indicative of moderate diastolic dysfunction. This was further associated with a decrease in the cardiac content of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), one of the important cardiac calcium regulatory proteins. Dwarfs supplemented with GH during the peri-adolescence stage, but not beyond (AOGHD), exhibited a subtle prolongation in the deceleration time to early filling. In contrast, continual GH replacement preserved diastolic function such that the cardiac phenotype of the GH-replete dwarfs resembled that of their age-matched HZ counterpart. DISCUSSION: Our data indicate that GHD during adolescence leads to overt diastolic dysfunction in early adulthood and this is prevented by continual GH replacement therapy. Since discontinuation of GH replacement following adolescence only mitigated the lusitropic deficits that were observed in untreated dwarfs, GH treatment into adulthood could be beneficial.

Mercury empirical relationships in sediments from three Ontario lakes.

Total mercury (THg), methyl mercury (MeHg), total organic carbon (TOC), sediment bulk density (SBD), redox potential (Eh) and percent fines measurements were made on sediment cores collected along transects from littoral to profundal depths in Harp, Dickie, and Blue Chalk lake located on the Canadian Shield near Dorset, Ontario, Canada to determine whether empirical relationships exist among these sediment properties. MeHg was positively correlated with THg in all sediments with a MeHg:THg ratio (0.004+/-0.004) comparable to other uncontaminated profundal lakes. MeHg, MeHg:THg and TOC decreased with sediment depth within the core for all lakes, whereas THg only showed a decrease in Harp Lake. MeHg:THg ratio in surficial sediments was positively correlated with Eh and negatively correlated with TOC [MeHg:THg=-0.009 TOC (%)+0.001 Eh (mV)-1.902, p=0.026]; whereas THg was positively correlated with TOC [log THg (ppb)=0.026 TOC (%)+1.400, p<0.0001].

Weight changes following lower limb arthroplasty: a prospective observational study.

The aim of this study was to assess patterns of weight loss/gain following total hip or knee joint replacement. Four hundred and fifty primary lower limb arthroplasty patients, where the current surgery was the last limiting factor to improved mobility, were selected. Over a one year period 212 gained weight (mean 5.03kg), 92 remained static, and 146 lost weight. The median change was a weight gain of 0.50Kg (p = 0.002). All patients had a significant improvement in Oxford outcome scores. Hip arthroplasty patients were statistically more likely to gain weight than knee arthroplasty patients. A successful arthroplasty, restoring a patient's mobility, does not necessarily lead to subsequent weight loss. The majority of patients put on weight with an overall net weight gain. No adverse effect on functional outcome was noted.

Archaeal diversity and a gene for ammonia oxidation are coupled to oceanic circulation.

Evidence of microbial zonation in the open ocean is rapidly accumulating, but while the distribution of communities is often described according to depth, the other physical factors structuring microbial diversity and function remain poorly understood. Here we identify three different water masses in the North Water (eastern Canadian Arctic), defined by distinct temperature and salinity characteristics, and show that they contained distinct archaeal communities. Moreover, we found that one of the water masses contained an increased abundance of the archaeal alpha-subunit of the ammonia monooxygenase gene (amoA) and accounted for 70% of the amoA gene detected overall. This indicates likely differences in putative biogeochemical capacities among different water masses. The ensemble of our results strongly suggest that the widely accepted view of depth stratification did not explain microbial diversity, but rather that parent water masses provide the framework for predicting communities and potential microbial function in an Arctic marine system. Our results emphasize that microbial distributions are strongly influenced by oceanic circulation, implying that shifting currents and water mass boundaries resulting from climate change may well impact patterns of microbial diversity by displacing whole biomes from their historic distributions. This relocation could have the potential to establish a substantially different geography of microbial-driven biogeochemical processes and associated oceanic production.

PAP-LMPCR for improved, allele-specific footprinting and automated chromatin fine structure analysis.

The analysis of chromatin fine structure and transcription factor occupancy of differentially expressed genes by in vivo footprinting and ligation-mediated-PCR (LMPCR) is a powerful tool to understand the impact of chromatin on gene expression. However, as with all PCR-based techniques, the accuracy of the experiments has often been reduced by sequence similarities and the presence of GC-rich or repeat sequences, and some sequences are completely refractory to analysis. Here we describe a novel method, pyrophosphorolysis activated polymerization LMPCR or PAP-LMPCR, which is capable of generating accurate and reproducible footprints specific for individual alleles and can read through sequences previously not accessible for analysis. In addition, we have adapted this technique for automation, thus enabling the simultaneous and rapid analysis of chromatin structure at many different genes.