Development of active tuberculosis in patients treated with biological disease-modifying antirheumatic drugs.

BACKGROUND: Biological disease-modifying antirheumatic drugs (bDMARDs) have been shown to be highly effective in the treatment of rheumatic conditions, but may increase the risk of infections. Development of tuberculosis (TB) while on bDMARD therapy is of particular concern in high TB burden settings such as Western Cape Province, South Africa. OBJECTIVES: To describe the diagnosis, management and outcome of patients who developed active TB while receiving a bDMARD. RESULTS: Ten patients who screened negative for TB prior to initiation of a bDMARD subsequently developed active TB. TB was diagnosed between 10 months and 9 years from bDMARD initiation, suggesting new infection, and included 6 cases of extrapulmonary TB. All patients required multiple tests to confirm the diagnosis of TB, and all were successfully treated. CONCLUSIONS: TB can occur in patients on bDMARD therapy despite initial screening, and may have unusual, extrapulmonary manifestations that pose a diagnostic challenge.

The impact of weather on the incidence of dark cutting in Australian feedlot cattle.

This study conducted a retrospective analysis of historical Meat Standard Australia (MSA) carcass data in combination with Bureau of Meteorology (BOM) weather data, to evaluate the relationship between climatic conditions prior to feedlot departure on the incidence of dark cutting grain-fed beef. Data records for 2,795,754 carcasses from 17 commercial feedlots over a 6-year period were evaluated within this study. Carcasses were consigned to 16 abattoirs. Weather data from BOM were recorded at 30-min intervals and were obtained from weather stations with the closest proximity to each feedlot. These data were used to calculate the Temperature Humidity Index (THI). Climatic data were amalgamated into daily observations and a series of predictors including ambient temperature (TA, °C), relative humidity (RH, %), wind speed (WS, m/s), rainfall (mm) and THI. In addition, lag interactions from 24 h out to 28 days prior to exiting the feedlot were generated. The incidence of dark cutting was determined as percentage per cohort with an ultimate pH > 5.7. Data were analysed using three models: model 1 included feedlot, abattoir, hormone growth promotant status and sex as fixed effects. Model 2 incorporated the fixed effects within model 1 and minimum, maximum and standard deviation (SD) of TA and RH, daily range in TA, average WS and rainfall as random effects. Model 3 incorporated minimum, maximum, range and SD of THI, average WS and rainfall as random effects in addition to the fixed effects of model 1. The incidence of dark cutting within feedlot had a 10.1% range in estimated means with the lowest incidence was observed at feedlot 17 (0%) and highest incidence at feedlot 10 (10.1%). The inclusion of the climatic variables in model 2 and model 3 accounted for an additional 0.1 to 0.2% of the incidence of dark cutting carcasses. Higher maximum TA, RH and THI in the 3 to 28 days prior to consignment were all associated with an increased incidence of dark cutting (P < 0.05), but not in the 48 h preceding consignment (P > 0.05). Low minimum TA and low THI were also associated with an increase the incidence of dark cutting across all lag periods (P < 0.05). Increased variation in THI and TA in the 48 h prior to consignment increased dark cutting (P < 0.05) while increased standard deviation (SD) of temperature and THI range also increased dark cutting in the 14 and 28 day prior to feedlot exit (P < 0.05). Smaller minimum ranges in TA in the 28 days prior to consignment also reduced dark cutting (P < 0.05). Climatic conditions accounted for a further 0.1 to 0.2% of the incidence of dark cutting, whereas animal management factors, feedlot and abattoir were able to account for 21% of dark cutting. These data suggest that climatic conditions appear to have an inherent role in the incidence of dark cutting, albeit a small impact. Regardless, understanding the influence of climatic conditions on dark cutting allows for the implementation of management strategies within the supply chain to further reduce the impact of climatic conditions on grain-fed cattle.

Short term magnesium supplementation to reduce dark cutting in pasture finished beef cattle.

This study assessed the capacity of magnesium supplementation to reduce muscle glycogen loss, ultimate pH and increase plasma magnesium in pasture fed slaughter cattle. Beef cattle (n = 1075) from 14 farms were supplemented with or without magnesium pellets for 7-14 days prior to slaughter. Magnesium was allocated at 9.83 g of elemental magnesium per head per day, while the control diet was balanced to be isoenergetic and isonitrogenous, but contained no added magnesium. Groups of cattle (n = 44) were slaughtered at the same processing plant over two consecutive seasons, from August - September 2016 to May - July 2017. Magnesium supplementation increased muscle glycogen (P < 0.01) in cattle supplied from 2 of 14 farms, and increased plasma magnesium in 4 of 14 farms (P < 0.01). Magnesium supplementation had no effect on overall incidence of ultimate pH between the magnesium and control supplementation groups. The benefits of short term magnesium supplementation prior to slaughter was inconsistent for protecting muscle glycogen.

Abattoir Factors Influencing the Incidence of Dark Cutting in Australian Grain-Fed Beef.

The aim of this study was to evaluate the effect of carcass traits, lairage time and weather conditions during lairage and abattoir factors that impact the incidence of dark cutting in 142,228 grain-fed carcasses, as defined by Meat Standards Australia (MSA) guidelines. This study was conducted over a 12-month period analysing data from cattle that were supplied from seven feedlots and processed at three abattoirs. Abattoir data indicated that the average incidence of dark cutting within the study was 2.8%. Increased wind speeds (WSs) and rain during lairage at the abattoir was associated with an increased risk of dark cutting, whereas variation in ambient temperature and/or relative humidity did not influence dark cutting. Heavier carcasses with whiter fat, larger hump heights, more rib fat, higher marble scores and lower ossification had lower incidences of dark cutting. The factors abattoir, time in lairage, time to grading and grader within Abattoir had significant effects on the incidence of dark cutting. The results from this study suggest that reducing the time in lairage and increasing the time between slaughter and grading are the two major ways to reduce dark cutting in MSA carcasses.

Prediction of consumer palatability in beef using visual marbling scores and chemical intramuscular fat percentage.

With development of objective technologies that can predict chemical intramuscular fat percentage (IMF%), there is a need to understand the relationships between existing marbling traits, IMF% and eating quality. This study utilised historical carcass data (n = 9641 observations) from the Meat Standards Australia (MSA) industry research dataset and included MSA grading data, chemical IMF% data and weighted composite eating quality scores (MQ4). Several analyses were performed to assess the prediction of MQ4 by MSA marbling, M. longissimus thoracis et lumborum (striploin) IMF% and cut specific IMF%. Results demonstrated that there was similar precision between chemical IMF% (R2 = 0.32, RSE = 11.8) and MSA marbling (R2 = 0.28, RSE = 11.9) in the prediction of grilled 14 day aged striploin MQ4, with similar results across other cut by cook by days aged combinations. These results support the development of objective technologies that predict chemical IMF% in parallel with MSA marbling for carcass grading and the prediction of eating quality.

Importance of case age in the purported association between phylogenetics and hemolytic uremic syndrome in Escherichia coli O157:H7 infections.

Escherichia coli O157:H7 is the largest cause of hemolytic uremic syndrome (HUS). Previous studies proposed that HUS risk varies across the E. coli O157:H7 phylogenetic tree (hypervirulent clade 8), but the role of age in the association is unknown. We determined phylogenetic lineage of E. coli O157:H7 isolates from 1160 culture-confirmed E. coli O157:H7 cases reported in Washington State, 2004-2015. Using generalised estimating equations, we tested the association between phylogenetic lineage and HUS. Age was evaluated as an effect modifier. Among 1082 E. coli O157:H7 cases with both phylogenetic lineage and HUS status (HUS n = 76), stratified analysis suggested effect modification by age. Lineages IIa and IIb, relative to Ib, did not appear associated with HUS in children 0-9-years-old. For cases 10-59-years-old, lineages IIa and IIb appeared to confer increased risk of HUS, relative to lineage Ib. The association reversed in ⩾60-year-olds. Results were similar for clade 8. Phylogenetic lineage appears to be associated with HUS risk only among those ⩾10-years-old. Among children <10, the age group most frequently affected, lineage does not explain progression to HUS. However, lineage frequency varied across age groups, suggesting differences in exposure and/or early disease manifestation.

The effect of packaging on consumer eating quality of beef.

This experiment examined 3 packaging systems: overwrap packaging using oxygen permeable film (OWP); vacuum skin packaging (VSP) and modified atmosphere packaging (MAP, 80%O2 and 20%CO2) on consumer sensory. Three primals from 48 carcasses were aged in vacuum packs for 5, 12 or 40 days. Steaks from longissimus lumborum, gluteus medius and psoas major muscles were packed in OWP, VSP and MAP for 9 days. Untrained consumers scored grilled steaks for tenderness, juiciness, liking of flavour and overall acceptability. Steaks in MAP had 10-12 points lower sensory scores (on a 100 point scale) compared to the OWP, or VSP systems (P < 0.001). The packaging effect was independent of days aging and muscle. It was concluded that high oxygen MAP has the potential to be included as an input variable in the Meat Standards Australia beef grading model. This would be contingent upon research into when the MAP effect occurred and the effect of using different gas mixtures on eating quality.

Superheroes in autoimmune warfare: biologic therapies in current South African practice.

Biologic drugs targeting immune cells or cytokines underlying systemic inflammation have dramatically improved outcomes in patients with rheumatological and autoimmune diseases. Nine biologic drugs are currently available in South Africa (SA)--all showing good efficacy and safety profiles. Their high cost and potential adverse events preclude them from being used as first-line agents. They are therefore indicated for severe disease refractory to standard therapies, and their use must be initiated by a specialist. The most important adverse effect of this class of drugs is infection and, in SA, tuberculosis is of particular concern. As new targets in the immune system are identified, new biologics will be developed. The current challenges are to optimise standard care for all patients with autoimmune diseases, and to offer the appropriate biologic to patients with refractory disease.

Erythromelalgia? A clinical study of people who experience red, hot, painful feet in the community.

We recruited a population of people who clinically suffer from the symptoms of erythromelalgia, red, hot, painful feet made worse by heat and improved by cooling, to better characterise this population and measure their quality of life (QOL). Ninety-two individuals completed the QOL surveys, and 56 individuals were clinically assessed. There was a 3 : 1 ratio of females to males with an average age of 61 years. The estimated prevalence of people who had clinical symptoms of erythromelalgia in the Dunedin community was 15/100,000. Only 27% of people had received a diagnosis for their symptoms despite seeking medical attention. People in the study population had worse quality of life than the general New Zealand population (P < 0.001). In the majority of participants symptoms had a mild-moderate effect on their quality of life. The results of this study indicate that the number of people who have clinical symptoms of erythromelalgia is much greater than is commonly accepted and that the majority of these individuals go unrecognised by the medical profession despite seeking help. They have significantly diminished QOL with the majority of people having mild-to-moderate symptoms.

Intra-individual changes of active matrix metalloproteinase-9 are associated with clinical in-stent restenosis of bare metal stents.

OBJECTIVES: Increased chronic postprocedural levels of active matrix metalloproteinase-9 (MMP-9) have been associated retrospectively with a history of in-stent restenosis (ISR). This study aimed to determine whether index or post-percutaneous coronary intervention (PCI) plasma levels of active MMP-9 are a predictor of subsequent clinical ISR, in a standard population of patients treated with bare metal coronary stents. METHODS: Four hundred thirty-two patients were prospectively recruited and sampled at index and 3 and 6 months after PCI. Those who developed symptomatic angiographically confirmed ISR were compared to randomly selected, asymptomatic controls, stratified by index presentation in a nested case-control design. Plasma samples were analyzed for the active form of MMP-9. RESULTS: In all, 35 patients (8.1%) developed ISR, and these were compared to 98 controls. The increase in active MMP-9 over 3 months was significantly greater in the ISR group (p = 0.030) and independent of the established risk factors. Index clinical presentation was not associated with acute changes in active MMP-9; however, patients with ST-elevation myocardial infarction had greater increases in active MMP-9 at 3 months. CONCLUSIONS: The change in active MMP-9 over 3 months after bare metal coronary stent placement appears to be independently associated with the development of ISR in a standard PCI population.

Cervical squamous intraepithelial lesions and associated cervical infections in an HIV-positive population in Rural Mpumalanga, South Africa.

BACKGROUND: The incidences of genital human papillomavirus (HPV) infection, associated squamous intraepithelial lesions and cervical squamous cell carcinoma are significantly increased in HIV-positive women. The role of other cervicovaginal infections in the acquisition of the HPV infection, cervical carcinogenesis and genital HIV infection remains largely speculative. METHODS: A retrospective study was conducted including 1087 HIV-positive women in rural Mpumalanga province, South Africa, for the period 1 May 2009 to 31 August 2010. For each patient, the age at first presentation, cervical cytological diagnosis, subsequent follow-up cytology and histology, and microscopically visible infections (including endemic Bilharzia) were tabulated and statistically analysed. RESULTS: The prevalence of low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot exclude HSIL (ASC-H) in the study population were 22.1%, 30.9%, 0.6%, 13.5% and 4.0%, respectively. LSIL, HSIL and squamous cell carcinoma were diagnosed, respectively, at the average ages of 35.7, 37.9 and 37.2 years. Four patients with cervical intraepithelial neoplasia grade 1 (CIN1), 32 with CIN2/CIN3 and two with cervical squamous cell carcinoma were also diagnosed with Bilharzia. Of the other infections only bacterial vaginosis had a positive statistical correlation with HPV-induced cervical abnormalities (LSIL, HSIL or squamous cell carcinoma). CONCLUSION: This study confirms the high prevalence of progressive HPV-associated cervical disease in a rural Southern African HIV-positive population, which is at least equal to or worse than in other African HIV-positive studies. The high incidence of Bilharzia infection in those cases that underwent cervical cone excision suggests a possible relationship with progressive HPV disease and cervical carcinogenesis. Bacterial vaginosis (perhaps in combination with Bilharzia) may compromise the normal barriers against HPV and HIV infection.

Pro-MMP-9/TIMP-1 ratio correlates poorly with a direct assessment of MMP-9 activity.

OBJECTIVE: To determine if the pro-MMP-9/TIMP-1 ratio is an accurate surrogate for endogenously active MMP-9 levels. METHODS: Plasma active MMP-9, pro-MMP-9 and TIMP-1 were measured in 295 patients. RESULTS: There was a weak negative correlation between the pro-MMP-9/TIMP-1 ratio and active MMP-9. TIMP-1 was more closely correlated with active MMP-9 than pro-MMP-9. CONCLUSION: Pro-MMP-9/TIMP-1 ratio measured with ELISA is not a good surrogate measure for active MMP-9, and direct measurements of active MMP-9 are therefore recommended.

Seasonal variation and stability of matrix metalloproteinase-9 activity and tissue inhibitor of matrix metalloproteinase-1 with storage at -80°C.

OBJECTIVE: To determine whether active matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 displayed seasonal variation and were stable in storage. METHODS: Plasma active MMP-9 and TIMP-1 were measured at three time-points in 163 individuals. RESULT: There was no evidence for seasonal variation or declining levels for up to three years of storage at -80°C. CONCLUSION: Active MMP-9 and TIMP-1 appear to be stable seasonally, and in storage for at least three years.

Active matrix metalloproteinases 3 and 9 are independently associated with coronary artery in-stent restenosis.

OBJECTIVE: This study aimed to determine whether plasma levels of active matrix metalloproteinases (MMP) are predictors of in-stent restenosis (ISR) in New Zealand patients treated with bare-metal coronary stents. METHODS: A group of 152 patients with a history of ISR were compared with 151 symptom free 1-year post-stenting patients (non-ISR). Demographic and angiographic characteristics were collected. Plasma samples were analyzed for the active forms of MMP-1, -2, -3 and -9 as well as tissue inhibitor of metalloproteinases (TIMP-1) using ELISA-based isoform sensitive assays. RESULTS: Both active MMP-9 and active MMP-3 were independently associated with history of ISR. Elevated levels of both active MMP-3 and -9 had an adjusted odds ratio of 11.8 (95% CI: 4-35, p<0.0001) for association with ISR, with 37% of ISR patients having such levels versus 11% on non-ISR. The addition of both of the MMP biomarkers significantly increased the area under the curve (AUC) of a receiver operator characteristic (ROC) analysis incorporating the significant demographic and angiographic variables (AUC 0.85 versus 0.78, p<0.005). CONCLUSION: Measures of plasma active MMP isoforms appear to be independently associated with ISR, and assessment of multiple MMP markers yields cumulative utility.

Modified early warning score predicts the need for hospital admission and inhospital mortality.

BACKGROUND: The modified early warning score (MEWS) is a useful tool for identifying hospitalised patients in need of a higher level of care and those at risk of inhospital death. Use of the MEWS as a triage tool to identify patients needing hospital admission and those at increased risk of inhospital death has been evaluated only to a limited extent. AIM: To evaluate the use of the MEWS as a triage tool to identify medical patients presenting to the emergency department who require admission to hospital and are at increased risk of inhospital death. METHODS: Physiological parameters were collected from 790 medical patients presenting to the emergency department of a public hospital in Cape Town, South Africa. MEW scores were calculated from the data and multivariate regression analysis was performed to identify independent predictors of hospital admission and inhospital mortality. RESULTS: The proportion of patients admitted and those who died in hospital increased significantly as the MEW score increased (p<0.001). Multivariate regression analysis identified five independent predictors of hospital admission: systolic blood pressure < or =100 mm Hg, pulse rate > or =130 beats per minute, respiratory rate > or =30 breaths per minute, temperature > or =38.5 degrees C and an impaired level of consciousness. Independent predictors of inhospital death were: abnormal systolic blood pressure (< or =100 or > or =200 mm Hg), respiratory rate > or =30 breaths per minute and an impaired level of consciousness. CONCLUSION: The MEWS, specifically five selected parameters, may be used as a rapid, simple triage method to identify medical patients in need of hospital admission and those at increased risk of inhospital death.

Rethinking the role of phosducin: light-regulated binding of phosducin to 14-3-3 in rod inner segments.

Phosducin (Pd), a small protein found abundantly in photoreceptors, is widely assumed to regulate light sensitivity in the rod outer segment through interaction with the heterotrimeric G protein transducin. But, based on histochemistry and Western blot analysis, Pd is found almost entirely in the inner segment in both light and dark, most abundantly near the rod synapse. We report a second small protein, 14-3-3, in the rod with a similar distribution. By immunoprecipitation, phospho-Pd is found to interact with 14-3-3 in material from dark-adapted retina, and this interaction is markedly diminished by light, which dephosphorylates Pd. Conversely, unphosphorylated Pd binds to inner segment G protein(s) in the light. From these results and reported functions of 14-3-3, we have constructed a hypothesis for the regulation of light sensitivity at the level of rod synapse. By dissociating the Pd/14-3-3 complex, light enables both proteins to function in this role.

Physiologically motivated image fusion for object detection using a pulse coupled neural network.

This paper presents the first physiologically motivated pulse coupled neural network (PCNN)-based image fusion network for object detection. Primate vision processing principles, such as expectation driven filtering, state dependent modulation, temporal synchronization, and multiple processing paths are applied to create a physiologically motivated image fusion network. PCNN's are used to fuse the results of several object detection techniques to improve object detection accuracy. Image processing techniques (wavelets, morphological, etc.) are used to extract target features and PCNN's are used to focus attention by segmenting and fusing the information. The object detection property of the resulting image fusion network is demonstrated on mammograms and Forward Looking Infrared Radar (FLIR) images. The network removed 94% of the false detections without removing any true detections in the FLIR images and removed 46% of the false detections while removing only 7% of the true detections in the mammograms. The model exceeded the accuracy obtained by any individual filtering methods or by logical ANDing the individual object detection technique results.