Dim light at night affects the locomotor activity of nocturnal African pygmy mice (Mus minutoides) in an intensity-dependent manner.

Rodents are integral components of ecosystems as they provide several important ecosystem services. Despite their importance as prey, pollinators and seed distributors, African rodents are largely understudied. The effect of anthropogenic changes such as artificial light at night extends past urban areas to peri-urban and rural habitats, and can have profound effects on entire ecosystems. We investigated the effect of dim light at night (dLAN) on the locomotor activity rhythms of the African pygmy mouse (Mus minutoides). Pygmy mice showed a dramatic, intensity-dependent reduction in their locomotor activity when subjected to dLAN, which was accompanied by a delay in the activity onset. We also considered masking responses with a dark pulse (DP) during the day and a light pulse at night. All animals became inactive in response to a light pulse during the night, whereas approximately half of the animals showed activity during a DP in the day. Our results suggest that the African pygmy mouse is highly sensitive to light and that their activity is strongly masked by light. In their natural environment, vegetation could shield pygmy mice against high light levels; however, other anthropogenic disturbances can alter the behaviour of these animals and could affect their survival.

Gall bladder ejection fractions in dogs investigated for chronic altered appetite: 14 cases (2015-2017).

OBJECTIVES: To determine if gall bladder dysmotility occurs in dogs investigated for chronic altered appetite and to determine if gall bladder dysmotility warrants further investigation as a contributing factor to altered appetite. MATERIALS AND METHODS: Case series of dogs investigated for chronic gastrointestinal disease. Gastrointestinal clinical signs were assessed before and after a 6-week hydrolysed protein diet. Gall bladder ejection fractions were determined at the end of the 6-week hydrolysed protein diet as part of an investigation that included a full blood cell count, biochemistry, abdominal X-rays and ultrasound. The gall bladder ejections fraction results of dogs with normal appetite were compared to dogs with general inappetence and dogs with diurnal inappetence in the morning. RESULTS: In this retrospective case series of 14 dogs, altered appetite was the most frequent and persistent clinical sign associated with chronic gastrointestinal disease. Nine dogs had suboptimal gall bladder function and this occurred in dogs with, and without, gravity-dependent biliary sludge. Gall bladder function and volumes of dogs in this study were comparable to those of dogs with nongravity-dependent gall bladder sludge or gall bladder mucoceles in other studies. There was an observable difference in gall bladder ejection fractions between groups defined by appetite but no statistically significant difference was present. Small sample sizes meant the effect size was large. CLINICAL SIGNIFICANCE: Gall bladder dysmotility and distension can occur in the absence of gall bladder sludge and mucocoeles in younger dogs. Gall bladder dysmotility requires further investigation as a potential contributing factor to altered appetite in dogs.

Exploring the phytochemical variation of non-volatile metabolites within three South African Salvia species using UPLC-MS fingerprinting and chemometric analysis.

The South African Salvia species, Salvia africana-lutea, S. lanceolata and S. chamelaeagnea, are widely used to treat fever and inflammation associated with skin and lung infections. The aim of this study was to explore the non-volatile secondary metabolites and the phytochemical variation within these lesser known species, to support product development and commercialisation. Chemical profiles of the methanol extracts of 81 wild-harvested samples were obtained using ultra performance-quadrupole-Time-of-Flight-mass spectrometry (UPLC-qToF-MS). Forty-one compounds, including caffeic acid, rosmarinic acid, carnosol, carnosic acid and ursolic acid, were detected and confirmed across the three species. Nineteen compounds were tentatively identified of which 14 have not been reported in these species. Principal component analysis revealed distinct clusters corresponding to the three species, confirming chemical differences. Marker compounds for each species were revealed using orthogonal projection to latent structures-discriminant analysis. Further chemometric analysis reflected a degree of intraspecies variation, although the chemistry within populations was mostly conserved. Potential chemotypes for each species were identified through unique compounds associated with each group. The concentrations of medicinally important metabolites, namely, rosmarinic acid, carnosol, carnosic acid and ursolic acid, were determined, using validated UPLC-PDA methods. Ursolic acid was present at levels up to 38.2 mg/g, confirming that these species are a rich source of this compound. No similar studies combining liquid chromatography with chemometric analysis, and utilising a large sample size from various habitats, have been reported for these three Salvia species. The results will guide selection of cultivars with the best attributes for the intended therapeutic application, thereby protecting wild populations from over-exploitation.

Clinical characteristics and histology of cholecystectomised dogs with nongravity-dependent biliary sludge: 16 cases (2014-2019).

OBJECTIVES: To report the available histology, biochemistry and clinical progression of dogs without classic overt biliary tract signs that underwent cholecystectomy for nongravity-dependent biliary sludge. MATERIALS AND METHODS: Case series of client-owned dogs for which a cholecystectomy was performed for nongravity-dependent biliary sludge. In six dogs, for which nongravity-dependent biliary sludge filled less than half of gall bladder volume, gall bladder ejection fractions were measured. Available histology, biochemistry, presenting clinical signs and post-surgical clinical progression were reported. RESULTS: Sixteen dogs were included in this retrospective case series. No dogs met the histological criteria for gall bladder mucocoeles or had histological evidence of primary hepatitis or cholangitis. Biochemistry was normal for 11 dogs. Hypercholesterolaemia was not noted in any dog. Twelve dogs had cholecystitis (11 lymphoplasmacytic, one neutrophilic) and nine dogs had biliary mucosal hyperplasia. Thirteen dogs had enteritis (12 lymphoplasmacytic, one eosinophilic) and nine dogs had reactive hepatitis (eight lymphoplasmacytic, one neutrophilic). All six dogs with nongravity-dependent biliary sludge that filled less than half of gall bladder volume had sub-optimal gall bladder function. Presenting clinical signs, including diurnal inappetence in the morning and exercise intolerance, resolved in 86% (12/14) of dogs after cholecystectomy and clinical improvement was noted in 81% (13/16) of dogs overall. CLINICAL SIGNIFICANCE: Duodenal inflammation could potentially impact gall bladder dysmotility in dogs with nongravity-dependent biliary sludge. Furthermore, diurnal inappetence in the morning and exercise intolerance could indicate symptomatic gall bladder disease in dogs with NDBS and can potentially precede more obvious systemic clinical signs associated with gall bladder mucocoeles.

Access to chloroquine in patients with rheumatic and musculoskeletal diseases attending rheumatology outpatient clinics during the COVID-19 pandemic.

Herbal medicines made from the bark of the Cinchona tree, and later quinine, have been widely used for centuries to treat medical conditions such as tropical malaria. More recently, chloroquine (CQ) and its synthetic derivatives have been used as antimalarials and to treat systemic lupus erythematosus, rheumatoid arthritis, and in the past 14 months or so, COVID-19 pneumonia. Anecdotal evidence and the erratic covering through social media of its potential efficacy in the treatment of COVID-19 pneumonia have resulted in the widespread off-label use of CQ in South Africa and worldwide. This study aimed to show that access to CQ as a chronic medication for rheumatic and musculoskeletal diseases was limited during the COVID-19 pandemic, and that this resulted in an increased incidence of flares in these patients, affecting their morbidity and potentially leading to mortality.

Considerations for the design of nutrition-sensitive production programmes in rural South Africa.

BACKGROUND: Very little has been researched about the efficacy, effectiveness, feasibility, sustainability and impact of food-based approaches on the diets and nutritional status of populations at risk of hunger and food insecurity. This study contributes knowledge about the impact of food-based approaches on the diets of populations at risk of hunger and food insecurity in four of the poorest rural communities in South Africa. The study investigated the consumption and production patterns of rural households (278 in summer and 280 in winter) in four sites in the poorest municipalities in South Africa. METHODS: A multistage stratified random sampling technique was applied to identify the communities and sample households for the quantitative survey and qualitative assessments. Qualitative and quantitative data were collected between 2013 and 2015 through focus group discussions (FGDs), key informant interviews and the two-round panel survey to cover both the summer and winter seasons at each site. RESULTS: Home gardening led to a significant positive increase in the consumption of white roots and tubers, dark green leafy vegetables, orange-coloured fruit and other fruit in the 24 h prior to the survey. Participation in a community garden led to significant increases in the consumption of dark green leafy vegetables and other vegetables. School gardening did not demonstrate any statistical relationships with the consumption of foods from the crop-related food groups. Crop production improved dietary diversity. Selling produce and irrigation showed a stronger improvement in dietary diversity. Seasonality affected the availability of fresh fruit and vegetables for home consumption in winter. CONCLUSIONS: Producing beyond that solely for home consumption has greater benefits for dietary diversity and a consumption-smoothing effect during the post-harvest period. Politicians and the scientific community should recognise the role that household and small-scale crop production plays in supporting household consumption and the provision of essential micronutrients despite constraints and disincentives. Production and education programmes should focus on strengthening existing good consumption patterns and promoting the consumption of foods that can improve dietary diversity.

A chemometric assessment of essential oil variation of three Salvia species indigenous to South Africa.

Indigenous Salvia species from southern Africa are popular traditional medicines for the treatment of a variety of conditions. They produce fragrant volatiles that can be isolated as essential oils. Some of these volatile organic compounds may play a role in the biological activities of the extracts. Three indigenous Salvia species, Salvia africana-lutea, S. lanceolata and S. chamelaeagnea, were selected for this study as they are commonly used in traditional medicine in South Africa, and the essential oils from these species have potential for commercialisation. Although some studies have described the essential oil compositions and some biological activities, only single composite samples were used. The aim of this study was to investigate the intra- and interspecies variation of the essential oils, sampled over a wide geographical area and using a representative sample size, to encourage commercialisation of the essential oil. Essential oils were isolated from individual plants using conventional hydrodistillation of the aerial parts, harvested from several localities. Gas chromatography coupled simultaneously to mass spectrometry/flame ionisation detection (GC-MS/FID) was used to identify and quantify the volatile constituents. The essential oils of S. africana-lutea consisted mainly of terpinene-4-ol + ß-caryophyllene (1.4 - 29.0%), T-cadinol (1.2 - 20.0%), α-eudesmol (trace - 23.0%) and ß-eudesmol (trace - 26.0%), those of S. lanceolata comprised mainly terpinene-4-ol + ß-caryophyllene (4.3 - 31.0%), α-humulene (2.3 - 15.0%), bicyclogermacrene (trace - 37.0%) and spathulenol (trace - 25.0%), while the essential oils of S. chamelaeagnea were characterised by δ-3-carene (trace - 18.0%), limonene (1.6 - 36.0%), viridiflorol (9.8 - 61.0%) and 1,8-cineole (not detected - 11.0%). The compounds identified in the essential oils of the three selected Salvia species have been identified in other Salvia essential oils. To add to the novelty of this study, the superior resolving power of two-dimensional gas chromatography was demonstrated through analysis of selected essential oils. Many additional compounds were identified, and previously co-eluting compounds were clearly separated. Chemometric modelling of the GC-MS data using SIMCA P+ 14 software allowed distinct clustering patterns to be discerned. The unsupervised principal component analysis model revealed separate clusters for the three species, confirming substantial chemical differences between their essential oils. Quantitative, rather than qualitative differences were evident when individual essential oil samples representing the same species, were compared. For each species, two chemically distinct groups were observed and unique marker compounds could be identified. This study has contributed detailed information on the major and minor volatile compounds present in the essential oils of the three Salvia species investigated.

Distribution of Pseudocercospora species causing Sigatoka leaf diseases of banana in Uganda and Tanzania.

Sigatoka leaf diseases are a major constraint to banana production. A survey was conducted in Tanzania and Uganda to assess the distribution of Pseudocercospora species and severity of Sigatoka leaf diseases. Pseudocercospora species were identified using species-specific primers. Sigatoka-like leaf diseases were observed in all farms and on all cultivars, but disease severity varied significantly (P < 0.001) between countries, districts/regions within countries, altitudinal ranges and banana cultivars. In all regions except Kilimanjaro, P. fijiensis, the causal agent of black Sigatoka, was the only pathogen associated with Sigatoka disease. Mycosphaerella musae was associated with Sigatoka-like symptoms in Kilimanjaro region. Black Sigatoka disease was more severe in Uganda, with a mean disease severity index (DSI) of 37.5%, than in Tanzania (DSI = 19.9%). In Uganda, black Sigatoka disease was equally severe in Luwero district (mean DSI = 40.4%) and Mbarara district (mean DSI = 37.9%). In Tanzania, black Sigatoka was most severe in Kagera region (mean DSI = 29.2%) and least in Mbeya region (mean DSI = 11.5%). Pseudocercospora fijiensis, the most devastating sigatoka pathogen, was detected at altitudes of up to 1877 m a.s.l. This range expansion of P. fijiensis, previously confined to altitudes lower than 1350 m a.s.l. in East Africa, is of concern, especially for smallholder banana farmers growing the susceptible East African Highland bananas (EAHB). Among the banana varieties sampled, the EAHB, FHIA hybrids and Mchare were the most susceptible. Here, the loss of resistance in Yangambi KM5, a banana variety previously resistant to P. fijiensis, is reported for the first time.

The new buzz: Investigating the antimicrobial interactions between bioactive compounds found in South African propolis.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis, a resinous substance produced by the Apis mellifera bee, contains a number of flavonoids sourced from plants found in the surrounding region. Whilst bees use this substance to seal off and protect the beehive, humans have used propolis therapeutically for centuries, making use of its antibacterial, antiseptic, antipyretic and wound healing properties, among others. South African propolis is rich in the flavonoids pinocembrin, galangin, and chrysin and very little previous research has been conducted on the antimicrobial effects of these compounds. AIM OF THE STUDY: To obtain an understanding of the antimicrobial activity of the compounds pinocembrin, galangin, and chrysin, both independently and in combination. MATERIALS AND METHODS: The compounds pinocembrin, galangin and chrysin were investigated for interactive antimicrobial activity by determining the minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), anti-quorum sensing activity, biofilm studies, and toxicity studies (brine shrimp lethality assay). RESULTS: Minimum inhibitory concentration results demonstrated that combinations of compounds showed better inhibitory activity than single compounds. When the flavonoids were tested in combination using the MIC assay, synergy was noted for 22% of the 1:1 ratio combinations and for 66% of the triple 1:1:1 ratio combinations. Similarly, MBC results showed bactericidal activity from selected combinations, while the compounds on their own demonstrated no cidal activity. Quorum sensing studies showed that compound combinations are more effective at inhibiting bacterial communication than the individual compounds. Biofilm assays showed that the highest percentage inhibition was observed for the triple combination against E. coli at 24 h. Finally, brine shrimp lethality studies revealed that combinations of the three compounds had reduced cytotoxicity when compared to the individual compounds. CONCLUSION: The results obtained in this study demonstrate that the compounds found in South African propolis work synergistically to achieve an optimal antimicrobial effect, whilst simultaneously minimizing cytotoxicity.

Evaluation of factors and patterns influencing the 30-day readmission rate at a tertiary-level hospital in a resource-constrained setting in Cape Town, South Africa.

BACKGROUND: Factors contributing to and causes of hospital readmissions have been investigated worldwide, but very few studies have been performed in South Africa (SA) and none in the Western Cape Province. OBJECTIVES: To investigate possible preventable and non-preventable factors contributing to readmissions to the Department of Internal Medicine at Tygerberg Hospital (TBH), Cape Town, within 30 days of hospital discharge. The researchers tested a risk-stratification tool (the LACE index) to evaluate the tool's performance in the TBH system. METHODS: A retrospective analysis was conducted of all 30-day readmissions (initial hospitalisation and rehospitalisation within 30 days) to the Department of Internal Medicine at TBH for the period 1 January 2014 - 31 March 2015. Potential risk factors leading to readmission were recorded. RESULTS: A total of 11 826 admissions were recorded. Of these patients, 1 242 were readmitted within 30 days, representing a readmission rate of 10.5%. The majority of patients (66%) were readmitted within 14 days after discharge. The most important risk factor for readmission was the number of comorbidities, assessed using the Charlston score. The study also identified a large burden of potentially avoidable causes (35% of readmissions) due to system-related issues, premature discharge being the most common. Other reasons for 30-day readmission were nosocomial infection, adverse drug reactions, especially warfarin toxicity, inadequate discharge planning and physician error. CONCLUSIONS: Despite TBH being a low-resource, high-turnover system, the 30-day readmission rate was calculated at 10.5%. Global readmission rates vary from 10% to 25%, depending on the reference article/source used. We found that 35% of 30-day readmissions were potentially avoidable. Venous thromboembolism was a minor contributor to readmission but was associated with a very high mortality rate. A secondary outcome evaluated was the utility of the LACE and modified LACE (mLACE) index in the TBH environment. The risk tool performed well in the TBH population, and a high LACE and mLACE score correlated with an increased risk of 30-day readmission (p<0.001).

The in vitro antimicrobial evaluation of commercially essential oils and their combinations against acne.

OBJECTIVE: The study investigated the efficacy of commercial essential oil combinations against the two pathogens responsible for acne with the aim to identify synergy and favourable oils to possibly use in a blend. MATERIALS AND METHODS: Antimicrobial activity was assessed using the minimum inhibitory concentration (MIC) assay against Staphylococcus epidermidis (ATCC 2223) and Propionibacterium acnes (ATCC 11827), and the fractional inhibitory concentration index (ΣFIC) was calculated. Combinations displaying synergistic interactions were further investigated at varied ratios and the results plotted on isobolograms. RESULTS: From the 408 combinations investigated, 167 combinations were identified as displaying noteworthy antimicrobial activity (MIC value ≤1.00 mg mL-1 ). Thirteen synergistic interactions were observed against S. epidermidis, and three synergistic combinations were observed against P. acnes. It was found that not one of the synergistic interactions identified were based on the combinations recommended in the layman's aroma-therapeutic literature. Synergy was evident rather from leads based on antimicrobial activity from previous studies, thus emphasizing the importance of scientific validation. Leptospermum scoparium J.R.Forst. and G.Forst (manuka) was the essential oil mostly involved in synergistic interactions (four) against S. epidermidis. Cananga odorata (Lam.) Hook.f. and Thomson (ylang ylang) essential oil was also frequently involved in synergy where synergistic interactions could be observed against both pathogens. The combination with the lowest MIC value against both acne pathogens was Vetiveria zizanioides Stapf (vetiver) with Cinnamomum verum J.Presl (cinnamon bark) (MIC values 0.19-0.25 mg mL-1 ). Pogostemon patchouli Benth. (patchouli), V. zizanioides, C. verum and Santalum spp. (sandalwood) could be identified as the oils that contributed the most noteworthy antimicrobial activity towards the combinations. The different chemotypes of the essential oils used in the combinations predominantly resulted in similar antimicrobial activity. CONCLUSIONS: The investigated essential oil combinations resulted in at least 50% of the combinations displaying noteworthy antimicrobial activity. Most of the synergistic interactions do not necessarily correspond to the recommended layman's aroma-therapeutic literature, which highlights a need for scientific validation of essential oil antimicrobial activity. No antagonism was observed.

A comparison of the effects of a 4% modified fluid gelatin and a 6% hydroxyethyl starch on haemodilution, colloid osmotic pressure, haemostasis and renal parameters in healthy ponies.

REASONS FOR PERFORMING STUDY: Adverse effects on renal health and haemostasis have been documented in human patients administered hydroxyethyl starches (HESs). Gelatins may represent useful substitutes should similar adverse effects be identified in horses. OBJECTIVES: To compare the effects of a 4% modified fluid gelatin (MFG) with a 6% (130/0.4) HES on haemodilution, colloid osmotic pressure (COP), haemostasis and renal parameters in healthy ponies. STUDY DESIGN: Randomised crossover experiment. METHODS: Three treatments (Treatment A: 10 ml/kg bwt HES; Treatment B: 10 ml/kg bwt MFG; Treatment C: 20 ml/kg bwt MFG) were administered to 6 healthy ponies with a 1 week washout period between treatments. Haematocrit, platelet count, total serum protein, COP, thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen concentration were measured at baseline and at multiple time points up to 24 h post-infusion. Serum creatinine concentration, urine specific gravity (USG), urine protein:creatinine ratio (UPC), urine γ-glutamyltransferase:creatinine ratio (UGC) and urine sediment examination (USE) were performed before and at 24 h after each treatment, as well as at 1 week after the final treatment. RESULTS: All treatments resulted in significant haemodilution and increases in COP. Treatment C had a significantly greater effect on haematocrit than the other treatments. The platelet count decreased with all treatments and was significantly lower following Treatment C compared with Treatment B. No clinically relevant differences were observed in any of the TEG parameters within or between treatments. No significant differences in PT, aPTT or fibrinogen concentration were observed among treatments. Serum creatinine concentration, UPC and UGC did not change significantly between pre- and post-study measurements. USG and USE remained within normal limits. CONCLUSIONS: Modified fluid gelatin could be considered as an alternative to HES for volume expansion and oncotic support. Neither MFG nor HES were associated with clinically significant adverse effects on haemostasis or renal parameters.

Familial Hypercholesterolaemia in the Era of Genetic Testing.

Familial hypercholesterolaemia (FH) is a relatively common autosomal dominant genetic condition leading to premature ischaemic vascular disease and mortality if left untreated. Currently, a universal consensus on the diagnostic criteria of FH does not exist but the diagnosis of FH largely relies on the evaluation of low density lipoprotein-cholesterol (LDL-C) levels, a careful documentation of family history, and the identification of clinical features. Diagnosis based purely on lipid levels remains common but there are several limitations to this method of diagnosis both practically and in the proportion of false-negatives and false-positives detected, resulting in substantial under-diagnosis of FH. In some countries, diagnostic algorithms are supplemented with genetic testing of the index case as well as genetic and lipid testing of relatives of the index case. Such "cascade" screening of families following identification of index cases appears to not only improve the rate of diagnosis but is also cost-effective. Currently, we observe a great variation in the excess mortality among patients with FH, which likely reflects a combination of additional genetic and environmental effects on risk overlaid on the risk associated with FH. Current accepted drug therapies for FH include statins and PSCK9 inhibitors. Further work is required to evaluate the cardiovascular disease risk in patients with genetically diagnosed FH and to determine whether a risk-based approach to the treatment of FH is appropriate.

Multi-environment Evaluation of Maize Inbred Lines for Resistance to Fusarium Ear Rot and Fumonisins.

Fusarium verticillioides causes Fusarium ear rot (FER) of maize and produces fumonisins, which affects grain quality. Host-plant resistance can reduce both FER and fumonisins in maize. In this study, 18 maize inbred lines were evaluated for resistance to F. verticillioides and fumonisin accumulation at five localities in South Africa. Additive main effects and multiplicative interaction analyses revealed significant environment × genotype interactions, with inbred lines CML 390, US 2540W, RO 424W, and VO 617y-2 consistently exhibiting low FER severity (≤5.4%), fungal target DNA (≤0.1 ng µl-1), and fumonisin levels (≤5.6 ppm). Genotype main effect and genotype × environment biplots showed that inbred lines CML 390, US 2540W, and RO 424W were most resistant to FER, fungal colonization, and fumonisin accumulation, respectively, while inbred line RO 424W was most stable in its resistance response over environments. These inbred lines also demonstrated broad adaptability by consistently exhibiting resistance to FER, fungal colonization, and fumonisins across localities. The identified lines could serve as valuable sources of resistance against F. verticillioides and its fumonisins in local breeding programs.

Antimicrobial activity and chemometric modelling of South African propolis.

AIMS: This study reports on the inhibitory and bactericidal properties of 39 South African (SA) propolis samples and three propolis samples from Brazil. METHODS AND RESULTS: Ethanolic extracts of propolis (EEP) were prepared and their antimicrobial activities tested using the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Some samples displayed substantial antimicrobial activity with MIC and MBC values as low as 6 µg ml(-1) against Staphylococcus aureus. The correlation between liquid chromatography-mass spectrometry (LC-MS) chemical data and the antimicrobial activity of propolis extracts was investigated using multivariate data analysis tools. Orthogonal projections to latent structures (OPLS) models were created for the two Gram-positive bacteria (Enterococcus faecalis and S. aureus) and Candida albicans. Using the S-plot function, it was possible to identify the bioactive constituents in propolis as chrysin, pinocembrin, galangin and pinobanksin-3-O-acetate. CONCLUSION: The SA propolis samples tested displayed noteworthy antimicrobial activity, favourably comparable to that of the Brazilian comparator and 'gold standard'. The observed antimicrobial activity of SA propolis can possibly be attributed to its flavonoid content. SIGNIFICANCE AND IMPACT OF THE STUDY: Based on the good antimicrobial activity observed for SA propolis, this natural resource shows promise and should be considered for development which may contribute to growing the bio-economy in the region.

Improving the odds: ezetimibe and cardiovascular disease.

The beauty of science is that well-conducted experiments provide answers to questions which were posed in times of greater ignorance. Cardiovascular disease (CVD) is the leading cause of death worldwide and will be for some time. Cholesterol is a critical player which drives the underlying pathophysiological process of atherosclerosis. Statins are the first line treatment for lipids in CVD given their ability to low-density lipoprotein cholesterol (LDL-C) by up to 50%, and their proven benefits in both primary and secondary intervention . Despite the unprecedented efficacy of statins, additional treatments are sought to potentially reduce the residual risk that remains despite statin treatment such as that associated with reduced high-density lipoprotein cholesterol levels (HDL-C) or triglycerides . In the last 5 years, several trials have reported on their potential additional benefit beyond statin therapy. These include omega-3 fatty acids in patients with prediabetes or diabetes , fibrates in diabetes , nicotinic acid/niacin in cardiovascular disease and cholesterol ester transfer protein inhibitors in cardiovascular disease . Despite their promise, none of these treatments were able to demonstrate benefit beyond baseline statin therapy when compared with placebo . The idea that benefit beyond statin treatment may be an unachievable goal has dogged the medical community working on CVD prevention. The phrase, 'Statins for atherosclerosis - as good as it gets?' was coined in 2005 and has rung true up until now .

The impact of plant volatiles on bacterial quorum sensing.

UNLABELLED: Studies describing the use of essential oil constituents as antimicrobial agents have steadily increased; however, some phyto-constituents are often overlooked due to unfavourable minimum inhibitory concentration (MIC) values. Virulence depends on transcriptional factors which are regulated by cell-to-cell communication called quorum sensing (QS). This study was undertaken to evaluate the antimicrobial and anti-QS properties of 29 compounds commonly found in essential oils using two bioreporter strains. QS-inhibitory activity was assessed qualitatively by agar diffusion and quantitatively by spectrophotometric assays. MICs of all the tested compounds ranged from 0·032 to >5 mg ml(-1). Twenty-two compounds displayed varying levels of QS inhibitory activity with zones of violacein inhibition ranging from 9 to 16 mm. Majority of tested molecules inhibited violacein and pyocyanin production in Chromobacterium violaceum and Pseudomonas aeruginosa, while seven compounds increased violacein and pyocyanin production. Interestingly, it was observed that the (+)-enantiomers of carvone, limonene and borneol increased violacein and pyocyanin production, while their levorotary analogues inhibited this production. α-Terpineol and cis-3-nonen-1-ol exhibited >90% violacein inhibition, suggesting their potential as QS inhibitors. This preliminary study indicates that plant volatiles have the potential to impede or promote bacterial communication and further studies need to be undertaken to explore the contribution of structural analogues and stereochemistry of molecules in this process. SIGNIFICANCE AND IMPACT OF THE STUDY: Antimicrobial and antiquorum sensing (QS) properties of 29 common essential oil compounds were evaluated. Interruption of QS may lead to the development of therapeutic, antivirulence agents to control disease-causing pathogens which are preferable over antimicrobial agents as the latter drives selection pressure on microbial communities to acquire resistance. Twenty-two compounds inhibited QS, while seven promoted the QS to a variable extent in Chromobacterium violaceum and Pseudomonas aeruginosa. Preliminary results suggest that QS-inhibitory compounds of natural origin may inspire the formulation of new generation of antimicrobial agents to control infectious pathogens.

Efficacy of a pectin-lecithin complex for treatment and prevention of gastric ulcers in horses.

The objective of this study was to evaluate the effect of a commercial feed supplement containing pectin-lecithin on squamous mucosa ulceration in horses exposed to an experimental ulceration model. Five mares were treated while five mares were controls for this crossover, blinded study. The mares were fed concentrates and hay and were stabled with a two-hour turn out per day for a period of four weeks. The pectin-lecithin complex was fed for the duration of the study on the treated group. At the end of a four-week period, all mares underwent a seven-day alternating feed deprivation (week 5). The study was repeated again after a four-week washout period. Gastroscopy was performed on days 1, 28 and 35 of the study and was digitally recorded. Independent evaluation of the recordings and scoring of the lesions using the Equine Gastric Ulcer Syndrome (EGUS), severity and number scores were performed by three experienced gastroscopists. The prevalence and severity of squamous ulcers significantly increased after intermittent feed deprivation (P<0.001). No significant effect of the treatment was observed (P>0.05). In this study, the addition of a commercially available pectin-lecithin complex to the feed of horses for five weeks did not prevent or minimise the risk for gastric ulceration of the squamous mucosa.

Coagulation, oncotic and haemodilutional effects of a third-generation hydroxyethyl starch (130/0.4) solution in horses.

REASONS FOR PERFORMING STUDY: Clinical indications for hydroxyethyl starches (HES) in horses include rapid plasma volume expansion and oncotic support during periods of hypoproteinaemia. Side effects such as coagulopathies associated with HES administration pose limitations to their use in veterinary medicine. In man, tetrastarch (130/0.4) has demonstrated less profound effects on coagulation compared with first- and second-generation HES. OBJECTIVES: To evaluate the haemostatic and oncotic effects of tetrastarch (130/0.4) administered at 10, 20 and 40 ml/kg bwt in healthy horses. STUDY DESIGN: Randomised crossover experiment. METHODS: Tetrastarch (130/0.4) was administered to 6 healthy pony mares at 10, 20 and 40 ml/kg bwt with a 2-week washout period. Packed cell volume, plasma total solids, colloid osmotic pressure (COP), platelet count and thromboelastography (TEG) were measured at baseline, immediately after infusion (0 h), and 1, 6, 12, 24, 48 and 96 h after tetrastarch infusion. RESULTS: All TEG variables remained within normal reference ranges in all 3 treatment groups. Administration of tetrastarch at 40 ml/kg bwt resulted in a prolonged K-time (P = 0.049) at 6 h post infusion, and decreased maximum amplitude at 0 (P<0.001), 1 (P = 0.022), 6 (P = 0.006), 24 (P<0.001) and 48 h (P = 0.013) post infusion compared with baseline. Administration of tetrastarch increased mean COP values above baseline in all 3 treatment groups, persisting to 24, 6 and 48 h for the 10, 20 and 40 ml/kg bwt doses, respectively. CONCLUSIONS: Although still within established reference ranges, compared with lower dosages, the administration of 40 ml/kg bwt tetrastarch (130/0.4) is more likely to induce changes in coagulation as measured by TEG. Tetrastarch increased COP at all dosages evaluated in healthy horses. Tetrastarch (130/0.4) at 10 and 20 ml/kg bwt has potential as a synthetic colloid for resuscitation and provision of oncotic support in horses.

Insulin resistance: a risk marker for disease and disability in the older person.

Clinical metabolic studies have demonstrated that insulin action declines progressively with age in humans. In addition to its close association with Type 2 diabetes, which reduces life expectancy in older people, age-related insulin resistance is implicated in pathogenesis of several highly prevalent disorders for which ageing is a major risk factor. These include atherosclerotic cardiovascular disease, dementia, frailty and cancer. Accordingly, insulin resistance may be viewed as biomarker of age-related ill health and reduced lifespan. The rapidly rising number of older people, coupled with a high prevalence of insulin resistance resulting from obesity and sedentary lifestyles, presents unprecedented public health and societal challenges. Studies of centenarians have shown that preserved whole-body sensitivity to insulin is associated with longevity. The mechanisms through which insulin action is associated with age-related diseases remain unclear. Changes in body composition, i.e. sarcopenia and excess adiposity, may be more potent than age per se. Moreover, the impact of insulin resistance has been difficult to disentangle from the clustering of vascular risk factors that co-segregate with the insulin resistance-hyperinsulinaemia complex. Potentially modifiable mediators of age-related changes in insulin sensitivity include alterations in adipocytokines, impaired skeletal myocyte mitochondrial function and brown fat activity. The hypothesis that improving or maintaining insulin sensitivity preserves health and extends lifespan merits further evaluation. Practical non-pharmacological interventions directed against age-related insulin resistance remain underdeveloped. Novel metabolically active pharmacological agents with theoretical implications for some age-related disorders are entering clinical trials. However, recent adverse experiences with the thiazolidinediones suggest the need for a cautious approach to the use of insulin sensitizing drugs in older people. This could be particularly important in the absence of diabetes where the risk to benefit analysis may be less favourable.