Archetypal clustering reveals physiological mechanisms linking milk yield and fertility in dairy cattle.

Fertility in dairy cattle has declined as an unintended consequence of single-trait selection for high milk yield. The unfavorable genetic correlation between milk yield and fertility is now well documented; however, the underlying physiological mechanisms are still uncertain. To understand the relationship between these traits, we developed a method that clusters variants with similar patterns of effects and, after the integration of gene expression data, identifies the genes through which they are likely to act. Biological processes that are enriched in the genes of each cluster were then identified. We identified several clusters with unique patterns of effects. One of the clusters included variants associated with increased milk yield and decreased fertility, where the "archetypal" variant (i.e., the one with the largest effect) was associated with the GC gene, whereas others were associated with TRIM32, LRRK2, and U6-associated snRNA. These genes have been linked to transcription and alternative splicing, suggesting that these processes are likely contributors to the unfavorable relationship between the 2 traits. Another cluster, with archetypal variant near DGAT1 and including variants associated with CDH2, BTRC, SFRP2, ZFHX3, and SLITRK5, appeared to affect milk yield but have little effect on fertility. These genes have been linked to insulin, adipose tissue, and energy metabolism. A third cluster with archetypal variant near ZNF613 and including variants associated with ROBO1, EFNA5, PALLD, GPC6, and PTPRT were associated with fertility but not milk yield. These genes have been linked to GnRH neuronal migration, embryonic development, or ovarian function. The use of archetypal clustering to group variants with similar patterns of effects may assist in identifying the biological processes underlying correlated traits. The method is hypothesis generating and requires experimental confirmation. However, we have uncovered several novel mechanisms potentially affecting milk production and fertility such as GnRH neuronal migration. We anticipate our method to be a starting point for experimental research into novel pathways, which have been previously unexplored within the context of dairy production.

Validating the female fertility estimated breeding value in Australian commercial dairy herds.

We conducted a retrospective cohort study to validate the efficacy of the Australian multitrait fertility estimated breeding value (EBV). We did this by determining its associations with phenotypic measures of reproductive performance (i.e., submission rate, first service conception rate, and early calving). Our secondary aim was to report the associations between these reproductive outcomes and management and climate-related factors hypothesized to affect fertility. Our study population included 38 pasture-based dairy herds from the northern Victorian irrigation region in Australia. We collected records for 86,974 cows with 219,156 lactations and 438,578 mating events from the date on which managers started herd recording until December 2016, comprising both fertility-related data such as insemination records, calving dates, and pregnancy test results, and systems-related data such as production, herd size, and calving pattern. We also collected hourly data from 2004 to 2017 from the closest available weather station to account for climate-related factors (i.e., temperature humidity index; THI). Multilevel Cox proportional hazard models were used to analyze time-to-event outcomes (days to first service, days to cow calving following the planned herd calving start date), and multilevel logistic regression models for binomial outcomes (conception to first service) in the Holstein-Friesian and Jersey breeds. A 1-unit increase in daughter fertility EBV was associated with a 5.4 and 8.2% increase in the daily hazard of calving in the Holstein-Friesian and Jersey breeds respectively. These are relative increases (i.e., a Holstein-Friesian herd with a 60% 6-wk in-calf rate would see an improvement to 63.2% with a 1-unit increase in herd fertility EBV). Similar results were obtained for submission and conception rate. Associations between 120-d milk yield and reproductive outcome were complicated by interactions with 120-d protein percentage and calving age, depending on the breed and outcome. In general, we found that the reproductive performance of high milk-yielding animals deteriorated faster with age than low milk-yielding animals, and high protein percentage exacerbated the differences between low and high milk-yielding animals. Climate-related factors were also associated with fertility, with a 1-unit increase in maximum THI decreasing first service conception rate by 1.2% for Holstein-Friesians but having no statistically significant association in the Jersey breed. However, THI had a negative association in both breeds on the daily hazard of calving. Our study validates the efficacy of the daughter fertility EBV for improving herd reproductive performance and identifies significant associations between 120-d milk and protein yields and THI on the fertility of Australian dairy cows.

Herd manager attitudes and intentions regarding the selection of high-fertility EBV sires in Australia.

Reproductive performance in dairy cattle has declined over the last 50 years as an unintended consequence of selection for high milk yield. Since the early 2000s, dairy geneticists have released successive versions of fertility estimated breeding values (EBV) to assist in reversing this trend. At the herd level, fertility EBV can help managers accelerate improvements in reproductive performance by acting as a second selection criteria when used in tandem with a breeding index. However, use of the fertility EBV in sire selection currently varies between herd managers. The aim of this study was to better understand the reasons why herd managers choose or do not choose to select high-fertility EBV sires, using the Theory of Planned Behavior (TPB) as a social research framework. Thirty-five Victorian dairy herd managers were recruited as part of a larger study investigating the daughter fertility Australian Breeding Value and interviewed using a series of questions examining TPB constructs. The interviews were recorded and transcribed using template analysis. A wide range of herd manager types were enrolled into the study, with representation from diverse systems. Out of the 35 herd managers, 27 included fertility in their list of high-priority breeding objectives. A wide variation in results was consistent with previous studies that have demonstrated marked heterogeneity in herd manager attitudes toward bull selection. Herd manager-perceived barriers to selection of sires with high daughter fertility EBV included a lack of high daughter fertility bulls with other desirable traits, a lack of trust in the fertility EBV or in the Australian EBV system, difficulty in interpreting international proofs, information overload, semen prices, low bull reliability, and difficulty in understanding bull catalogs. Not all herd managers found the process problematic, however, particularly if a breeding consultant was employed to select all or most of the sires. Herd manager-perceived barriers for choosing to select daughter fertility as a breeding objective include a lack of awareness of the EBV, a lack of interest in genetics in general, low confidence in the impact of genetic selection for fertility, and a feeling that fertility was not important for their production system. The results of this study suggest that animal geneticists and on-farm service providers need to work together to allow the opportunities arising from appropriate use of fertility EBV to be realized more broadly across the dairy industry.

Cross validated serum small extracellular vesicle microRNAs for the detection of oropharyngeal squamous cell carcinoma.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is often diagnosed at an advanced stage because the disease often causes minimal symptoms other than metastasis to neck lymph nodes. Better tools are required to assist with the early detection of OPSCC. MicroRNAs (miRNAs, miRs) are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers. This could be due to variations in the collection, storage, pre-processing, and isolation of RNA, but several reports have indicated that the selection and reproducibility of biomarkers has been widely affected by the methods used for data analysis. The primary analysis issues appear to be model overfitting and the incorrect application of statistical techniques. The purpose of this study was to develop a robust statistical approach to identify a miRNA signature that can distinguish controls and patients with inflammatory disease from patients with human papilloma virus positive (HPV +) OPSCC. METHODS: Small extracellular vesicles were harvested from the serum of 20 control patients, 20 patients with gastroesophageal reflux disease (GORD), and 40 patients with locally advanced HPV + OPSCC. MicroRNAs were purified, and expression profiled on OpenArray™. A novel cross validation method, using lasso regression, was developed to stabilise selection of miRNAs for inclusion in a prediction model. The method, named StaVarSel (for Stable Variable Selection), was used to derive a diagnostic biomarker signature. RESULTS: A standard cross validation approach was unable to produce a biomarker signature with good cross validated predictive capacity. In contrast, StaVarSel produced a regression model containing 11 miRNA ratios with potential clinical utility. Sample permutations indicated that the estimated cross validated prediction accuracy of the 11-miR-ratio model was not due to chance alone. CONCLUSIONS: We developed a novel method, StaVarSel, that was able to identify a panel of miRNAs, present in small extracellular vesicles derived from blood serum, that robustly cross validated as a biomarker for the detection of HPV + OPSCC. This approach could be used to derive diagnostic biomarkers of other head and neck cancers.

Rapid sperm capture: high-throughput flagellar waveform analysis.

STUDY QUESTION: Can flagellar analyses be scaled up to provide automated tracking of motile sperm, and does knowledge of the flagellar waveform provide new insight not provided by routine head tracking? SUMMARY ANSWER: High-throughput flagellar waveform tracking and analysis enable measurement of experimentally intractable quantities such as energy dissipation, disturbance of the surrounding medium and viscous stresses, which are not possible by tracking the sperm head alone. WHAT IS KNOWN ALREADY: The clinical gold standard for sperm motility analysis comprises a manual analysis by a trained professional, with existing automated sperm diagnostics [computer-aided sperm analysis (CASA)] relying on tracking the sperm head and extrapolating measures. It is not currently possible with either of these approaches to track the sperm flagellar waveform for large numbers of cells in order to unlock the potential wealth of information enclosed within. STUDY DESIGN, SIZE, DURATION: The software tool in this manuscript has been developed to enable high-throughput, repeatable, accurate and verifiable analysis of the sperm flagellar beat. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the software tool [Flagellar Analysis and Sperm Tracking (FAST)] described in this manuscript, we have analysed 176 experimental microscopy videos and have tracked the head and flagellum of 205 progressive cells in diluted semen (DSM), 119 progressive cells in a high-viscosity medium (HVM) and 42 stuck cells in a low-viscosity medium. Unscreened donors were recruited at Birmingham Women's and Children's NHS Foundation Trust after giving informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: We describe fully automated tracking and analysis of flagellar movement for large cell numbers. The analysis is demonstrated on freely motile cells in low- and high-viscosity fluids and validated on published data of tethered cells undergoing pharmacological hyperactivation. Direct analysis of the flagellar beat reveals that the CASA measure 'beat cross frequency' does not measure beat frequency; attempting to fit a straight line between the two measures gives ${\mathrm{R}}^2$ values of 0.042 and 0.00054 for cells in DSM and HVM, respectively. A new measurement, track centroid speed, is validated as an accurate differentiator of progressive motility. Coupled with fluid mechanics codes, waveform data enable extraction of experimentally intractable quantities such as energy dissipation, disturbance of the surrounding medium and viscous stresses. We provide a powerful and accessible research tool, enabling connection of the mechanical activity of the sperm to its motility and effect on its environment. LARGE SCALE DATA: The FAST software package and all documentation can be downloaded from www.flagellarCapture.com. LIMITATIONS, REASONS FOR CAUTION: The FAST software package has only been tested for use with negative phase contrast microscopy. Other imaging modalities, with bright cells on a dark background, have not been tested but may work. FAST is not designed to analyse raw semen; it is specifically for precise analysis of flagellar kinematics, as that is the promising area for computer use. Flagellar capture will always require that cells are at a dilution where their paths do not frequently cross. WIDER IMPLICATIONS OF THE FINDINGS: Combining tracked flagella with mathematical modelling has the potential to reveal new mechanistic insight. By providing the capability as a free-to-use software package, we hope that this ability to accurately quantify the flagellar waveform in large populations of motile cells will enable an abundant array of diagnostic, toxicological and therapeutic possibilities, as well as creating new opportunities for assessing and treating male subfertility. STUDY FUNDING/COMPETING INTEREST(S): M.T.G., G.C., J.C.K-B. and D.J.S. gratefully acknowledge funding from the Engineering and Physical Sciences Research Council, Healthcare Technologies Challenge Award (Rapid Sperm Capture EP/N021096/1). J.C.K-B. is funded by a National Institute of Health Research (NIHR) and Health Education England, Senior Clinical Lectureship Grant: The role of the human sperm in healthy live birth (NIHRDH-HCS SCL-2014-05-001). This article presents independent research funded in part by the NIHR and Health Education England. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The data for experimental set (2) were funded through a Wellcome Trust-University of Birmingham Value in People Fellowship Bridging Award (E.H.O.).The authors declare no competing interests.

A systematic review of validated sinus surgery simulators.

BACKGROUND: Simulation provides a safe and effective opportunity to develop surgical skills. A variety of endoscopic sinus surgery (ESS) simulators has been described in the literature. Validation of these simulators allows for effective utilisation in training. OBJECTIVE OF REVIEW: To conduct a systematic review of the published literature to analyse the evidence for validated ESS simulation. SEARCH STRATEGY: Pubmed, Embase, Cochrane and Cinahl were searched from inception of the databases to 11 January 2017. EVALUATION METHOD: Twelve thousand five hundred and sixteen articles were retrieved of which 10 112 were screened following the removal of duplicates. Thirty-eight full-text articles were reviewed after meeting search criteria. Evidence of face, content, construct, discriminant and predictive validity was extracted. RESULTS: Twenty articles were included in the analysis describing 12 ESS simulators. Eleven of these simulators had undergone validation: 3 virtual reality, 7 physical bench models and 1 cadaveric simulator. Seven of the simulators were shown to have face validity, 7 had construct validity and 1 had predictive validity. None of the simulators demonstrated discriminate validity. CONCLUSION: This systematic review demonstrates that a number of ESS simulators have been comprehensively validated. Many of the validation processes, however, lack standardisation in outcome reporting, thus limiting a meta-analysis comparison between simulators.

Consumption of a whey protein-enriched diet may prevent hepatic steatosis associated with weight gain in elderly women.

BACKGROUND AND AIMS: Protein consumption has been associated with cardio-metabolic benefits, including weight loss and improved insulin sensitivity, and may have potential benefits for individuals with fatty liver disease (FLD). We investigated the effect of increasing dietary protein intake from whey relative to carbohydrate on hepatic steatosis. METHODS AND RESULTS: A two-year randomized, double-blind, placebo-controlled trial of 30 g/day whey protein-supplemented beverage (protein) or an energy-matched low-protein high-carbohydrate beverage (control) for cardio-metabolic and bone health in 219 healthy elderly women, recruited from the Western Australian general population. Hepatic steatosis was quantified using computed tomographic liver-to-spleen (L/S) ratio. FLD was defined as liver-to-spleen difference <10 Hounsfield units. At baseline, FLD prevalence was 11.4%. Control and protein groups were similar in body mass index (BMI), insulin resistance, L/S ratio and FLD prevalence at baseline. At two-years, dietary protein increased by 20 g in the protein, but not the control, group. Total energy intake and physical activity remained similar between groups. At two-years, BMI and FLD prevalence increased in both groups, with no between group differences. L/S ratio increased in control, but not protein, group at two-years, with no between group differences. In a within group comparison, change in BMI correlated with changes in L/S ratio in control (r = 0.37, P = 0.0007), but not with protein group (r = 0.04, P = 0.73). CONCLUSION: Increasing dietary protein intake from whey relative to carbohydrate does not reduce weight, hepatic steatosis or the prevalence of FLD in elderly women. However, it may prevent worsening of hepatic steatosis associated with weight gain. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry (Registration no. ACTRN012607000163404).

Validation of virtual-reality-based simulations for endoscopic sinus surgery.

BACKGROUND: Virtual reality (VR) simulators provide an alternative to real patients for practicing surgical skills but require validation to ensure accuracy. Here, we validate the use of a virtual reality sinus surgery simulator with haptic feedback for training in Otorhinolaryngology - Head & Neck Surgery (OHNS). METHODS: Participants were recruited from final-year medical students, interns, resident medical officers (RMOs), OHNS registrars and consultants. All participants completed an online questionnaire after performing four separate simulation tasks. These were then used to assess face, content and construct validity. anova with post hoc correlation was used for statistical analysis. RESULTS: The following groups were compared: (i) medical students/interns, (ii) RMOs, (iii) registrars and (iv) consultants. Face validity results had a statistically significant (P < 0.05) difference between the consultant group and others, while there was no significant difference between medical student/intern and RMOs. Variability within groups was not significant. Content validity results based on consultant scoring and comments indicated that the simulations need further development in several areas to be effective for registrar-level teaching. However, students, interns and RMOs indicated that the simulations provide a useful tool for learning OHNS-related anatomy and as an introduction to ENT-specific procedures. CONCLUSIONS: The VR simulations have been validated for teaching sinus anatomy and nasendoscopy to medical students, interns and RMOs. However, they require further development before they can be regarded as a valid tool for more advanced surgical training.

Atorvastatin plus omega-3 fatty acid ethyl ester decreases very-low-density lipoprotein triglyceride production in insulin resistant obese men.

AIM: To test the effect of atorvastatin (ATV) and ATV plus ω-3 FAEEs on VLDL-TG metabolism in obese, insulin resistant men. METHODS: We carried out a 6-week randomized, placebo-controlled study to examine the effect of ATV (40 mg/day) and ATV plus ω-3 FAEEs (4 g/day) on VLDL-TG metabolism in 36 insulin resistant obese men. VLDL-TG kinetics were determined using d5 -glycerol, gas chromatography-mass spectrometry and compartmental modelling. RESULTS: Compared with the placebo, ATV significantly decreased VLDL-TG concentration (-40%, p < 0.001) by increasing VLDL-TG fractional catabolic rate (FCR) (+47%, p < 0.01). ATV plus ω-3 FAEEs lowered VLDL-TG concentration to a greater degree compared with placebo (-46%, p < 0.001) or ATV monotherapy (-13%, p = 0.04). This was achieved by a reduction in VLDL-TG production rate (PR) compared with placebo (-32%, p = 0.008) or ATV (-20%, p = 0.03) as well as a reciprocal increase in VLDL-TG FCR (+42%, p < 0.05) compared with placebo. CONCLUSION: In insulin resistant, dyslipidaemic, obese men, ATV improves VLDL-TG metabolism by increasing VLDL-TG FCR. The addition of 4 g/day ω-3 FAEE to statin therapy provides further TG-lowering by lowering VLDL-TG PR.

A systematic review and meta-analysis of the role of doxycycline in chronic rhinosinusitis.

OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the role of doxycycline in the management of chronic rhinosinusitis. METHOD: This was a systematic review using Ovid Medline, Cinahl, Scopus and Cochrane and was limited to meta-analyses, systematic reviews and randomised, clinical trials. A combination of the following search terms was used: 'sinusitis', 'nasal polyps', 'doxycycline' and 'tetracycline'. Raw means and standard deviations were extracted from the included studies. The meta-analysis was performed using mean differences of pre- versus post-doxycycline treatment. RESULTS: A total of 279 studies were screened, of which 5 studies met the criteria (all randomised, controlled trials published between 2010 and 2021). The interventions, endpoints and measured outcomes varied across all studies. Meta-analysis performed on pre- versus post-doxycycline treatment for Sino-Nasal Outcome Test-22, nasal polyp scores and symptom scores did not yield statistically significant results. CONCLUSION: This review identified a small number of high-quality studies on the use of doxycycline in chronic rhinosinusitis. There does not seem to be convincing evidence for the routine use of doxycycline in patients with chronic rhinosinusitis. Further research may try to identify certain phenotypes of chronic rhinosinusitis that may better respond to doxycycline.

The south-east Scotland dermatology workload study: 30 years' analysis.

BACKGROUND: Dermatological activity data have been collected for the same region of south-east Scotland (population 1·24 million), approximately every 5 years, since 1981. This has allowed assessment of trends in demand from primary and secondary care, and activity within secondary care dermatology services, assisting planning of dermatological services. OBJECTIVES: To quantify dermatology outpatient workload across the same population to allow comparison with previous studies for trends in practice. METHODS: During November 2010, a standardized proforma was completed for all National Health Service and private practice dermatology outpatient consultations. Demographic data, source and reason for referral, diagnoses, investigations, treatments and disposal were recorded, and comparisons made with five previous studies. RESULTS: A total of 5470 consultations were recorded: 2882 new and 2588 review patients (new to review ratio 1 : 0·9, male to female 1 : 1·3, mean age 49 years, range 1 month to 101 years). Ninety-one per cent of referrals came from primary care and 9% from secondary care. Fifty-eight per cent of referrals were for diagnosis and 32% for hospital management. Diagnostic concordance between referrer and dermatologist ranged from 94% for acne to 14% for melanoma. Benign tumours accounted for 30% of referrals, malignant tumours 13%, dermatitis 13·3%, psoriasis 6·2% and acne/rosacea 5%. The referral rate rose to 23·2/1000 population per annum, with the increase coming mainly from primary care. CONCLUSIONS: Demand for dermatology continues to increase: new referrals have risen by 134% in 30 years, with a 36% increase in the last 5 years, despite corresponding population increases of 5·3% and 3%, respectively.

Acinetobacter calcoaceticus-Acinetobacter baumannii complex species in clinical specimens in Singapore.

This study was performed to determine the prevalence, distribution of specimen sources, and antimicrobial susceptibility of the Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) species complex in Singapore. One hundred and ninety-three non-replicate Acb species complex clinical isolates were collected from six hospitals over a 1-month period in 2006. Of these, 152 (78·7%) were identified as A. baumannii, 18 (9·3%) as 'Acinetobacter pittii' [genomic species (gen. sp.) 3], and 23 (11·9%) as 'Acinetobacter nosocomialis' (gen. sp. 13TU). Carbapenem resistance was highest in A. baumannii (72·4%), followed by A. pittii (38·9%), and A. nosocomialis (34·8%). Most carbapenem-resistant A. baumannii and A. nosocomialis possessed the bla(OXA-23-like) gene whereas carbapenem-resistant A. pittii possessed the bla(OXA-58-like) gene. Two imipenem-resistant strains (A. baumannii and A. pittii) had the bla(IMP-like) gene. Representatives of carbapenem-resistant A. baumannii were related to European clones I and II.

Lysozyme expression is increased in the sinus mucosa of patients with chronic rhinosinusitis.

BACKGROUND: The presence of fungi and bacteria in the paranasal sinuses may contribute to ongoing inflammation. Lysozyme is an innate immune peptide with bactericidal and fungicidal activity. The expression of lysozyme in chronic rhinosinusitis (CRS) is poorly understood and deficiencies in lysozyme expression may contribute to the ongoing inflammation in CRS patients. OBJECTIVE: Determine lysozyme expression in sinus mucosa of normal and CRS patients with (CRSwNP) and without (CRSsNP) nasal polyps. METHODOLOGY: Sinus mucosa specimens (n = 82) were processed for standard histology, immunohistochemical localisation of lysozyme, immunofluorescent localisation of fungi, and qPCR analysis of lysozyme expression. RESULTS: CRS specimens displayed high-levels of lysozyme immunoreactivity in many of the abundant serous cells. Moderate levels were detected in some epithelial cells and inflammatory cells. Low levels were detected in some subepithelial glands of control specimens. No difference in immunoreactivity was detected between CRSwNP and CRSsNP specimens. Fungal elements were not visualised in any sinus specimen. qPCR analysis demonstrated variable lysozyme expression between individuals. CONCLUSIONS: Lysozyme protein expression is increased in patients with CRS, suggesting a defect in lysozyme expression is not responsible for the microbial colonisation often associated with CRS. The functional activity of lysozyme in CRS patients needs to be further investigated.

Lack of association of dengue activity with haze.

Dengue activity depends on fluctuations in Aedes populations which in turn are known to be influenced by climate factors including temperature, humidity and rainfall. It has been hypothesized that haze may reduce dengue transmission. Due to its geographical location Singapore suffers almost every year from hazes caused by wildfires from Indonesia. Such hazes have a significant impact on pollution indexes in Singapore. We set out to study the relationship of dengue activity and haze (measured as pollution standard index) in Singapore, using ARIMA models. We ran different univariate models, each encompassing a different lag period for the effects of haze and temperature (from lag 0 to lag 12 weeks). We analysed the data on a natural logarithmic scale to stabilize the variance and improve the estimation. No association between dengue activity and haze was found. Our findings do not lend support to the hypothesis that haze is associated with reduced dengue activity in Singapore.

Transoral robotic surgery using the Medrobotic Flex® system: the Adelaide experience.

Transoral robotic surgery (TORS) has become an accepted treatment option for a variety of benign and malignant pathologies of the head and neck. The Medrobotics Flex® system is a novel single port platform available as an alternative tool to current multiport robotic technology. We present the Adelaide experience with this system thus far. The Medrobotics Flex® system was introduced in Adelaide in January 2017. Patient demographics, pathology, indication for surgery and complications are prospectively recorded for all cases. The first 20 patients are presented in this case series. 11/20 underwent surgery for malignant disease. Of these nine were diagnosed with oropharyngeal squamous cell carcinoma (OPSCC). Histopathology revealed clear margins of primary tumour excision in 8/9 patients. There were no intraoperative complications. In terms of secondary complications, one patient undergoing tonsillectomy for recurrent tonsillitis experienced a secondary haemorrhage at day 13 following operation and one patient undergoing lateral oropharyngectomy for pT3N2b tonsillar SCC sustained an oro-cervical fistula, which settled with conservative management. We have found the Medrobotic Flex® system to be a safe, reliable tool for managing transoral surgery. The range of pathology managed with this platform, as well as the histologic outcomes presented, demonstrates efficacy in the oropharynx and posterior oral cavity for both benign and malignant disease.

An ABC of apolipoprotein C-III: a clinically useful new cardiovascular risk factor?

BACKGROUND: Hypertriglyceridaemia, commonly found in subjects with obesity and type 2 diabetes mellitus, is associated with increased risk of coronary heart disease (CHD). Apolipoprotein C-III (apoC-III) plays an important role in regulating the metabolism of triglyceride-rich lipoproteins (TRLs) and may provide a new approach to assessing hypertriglyceridaemia. AIMS: We review the role of apoC-III in regulating TRL metabolism and address the potential importance of apoC-III in clinical practice. DISCUSSION: Hypertriglyceridaemia is chiefly a consequence of alterations in the kinetics of TRLs, including overproduction and delayed clearance of very-low density lipoprotein (VLDL). ApoC-III is an inhibitor of lipoprotein lipase and of TRLs remnant uptake by hepatic lipoprotein receptors. Elevated apoC-III, usually resulting from hepatic overproduction of VLDL apoC-III, may cause accumulation of plasma TRLs leading to hypertriglyceridaemia. The results from recent observational studies demonstrate that apoC-III is a strong predictor of risk for CHD, but this chiefly relates to apoC-III in apoB-containing lipoproteins. Lifestyle and pharmacological intervention can correct hypertriglyceridaemia by a mechanism of action that regulates apoC-III transport. CONCLUSIONS: Targeting apoC-III metabolism may therefore be an important, new therapeutic approach to managing dyslipidaemia and CHD risk in obesity, insulin resistance and type 2 diabetes mellitus. However, further work is required to establish the practical aspects of measuring apoC-III in routine laboratory service and the precise therapeutic targets for serum total apoC-III and/or apoC-III in apoB-containing lipoproteins. While showing much promise as a potentially useful cardiovascular risk factor, apoC-III is not yet ready for prime time use in clinical practice.

Gastrointestinal manifestations of dengue infection in adults.

This is a retrospective study of the gastrointestinal symptoms, signs and laboratory parameters in adult dengue patients admitted to Kuala Lumpur Hospital from 1st December 2004 to 31st December 2004. Clinical and laboratory parameters that may predict the need for intensive care were investigated. Six hundred sixty-six patients with clinical and biochemical features consistent with dengue infection were identified. Patients were stratified into those who required intensive care and those who were managed in non high dependency wards. Serum alanine aminotransaminase (ALT) levels were normal in 22.8% of patients and 5.9% of patients had acute fulminant hepatitis. More patients with dengue haemorrhagic fever (DHF) had elevated ALT levels as compared to patients with classic dengue fever (DF) (p = 0.012). Patients with DF had a statistically significant lower mean ALT level as compared to patients with DHF. Abdominal pain (p = 0.01) and tenderness (p<0.001), gastrointestinal bleed (p<0.001), jaundice (p<0.001), hepatomegaly (p<0.001) and ascites (p<0.001) were predictors of need for intensive care. We conclude that gastrointestinal manifestations are very common in dengue patients. Presence of abdominal pain and tenderness, gastrointestinal bleed, jaundice, hepatomegaly and ascites can be used to triage patients requiring intensive care.