Factors associated with awareness, treatment and control of hypertension in a disadvantaged rural Indian population.

The aim of this study was to identify factors associated with awareness, treatment and control of hypertension in a rural setting in India. Following screening of the population, all individuals with hypertension (blood pressure (BP) ⩾140/90 mm Hg or taking antihypertensive medications) were invited to participate in this study. We measured BP, height, weight, skinfolds, waist and hip circumference, and administered a questionnaire to obtain information regarding socioeconomic and behavioural characteristics. Multivariable logistic regression was used to determine factors associated with awareness, treatment and control of hypertension. We recruited 277 individuals with hypertension. Awareness (43%), treatment (33%) and control (27%) of hypertension were poor. Greater distance to health services (odds ratio (OR) 0.56 (95% confidence interval (CI)) 0.32-0.98) was associated with poor awareness of hypertension while having had BP measured within the previous year (OR 4.72, 95% CI 2.71-8.22), older age and greater per cent body fat were associated with better awareness. Factors associated with treatment of hypertension were having had BP measured within the previous year (OR 6.18, 95% CI 3.23-11.82), age ⩾65 years, physical inactivity and greater per cent body fat. The only factor associated with control of hypertension was greater per cent body fat (OR 1.05, 95% CI 1.01-1.11). Improving geographic access and utilisation of health services should improve awareness and treatment of hypertension in this rural population. Further research is necessary to determine drivers of control.

Cardiovascular risk outcome and program evaluation of a cluster randomised controlled trial of a community-based, lay peer led program for people with diabetes.

BACKGROUND: The 2013 Global Burden of Disease Study demonstrated the increasing burden of diabetes and the challenge it poses to the health systems of all countries. The chronic and complex nature of diabetes requires active self-management by patients in addition to clinical management in order to achieve optimal glycaemic control and appropriate use of available clinical services. This study is an evaluation of a "real world" peer support program aimed at improving the control and management of type 2 diabetes (T2DM) in Australia. METHODS: The trial used a randomised cluster design with a peer support intervention and routine care control arms and 12-month follow up. Participants in both arms received a standardised session of self-management education at baseline. The intervention program comprised monthly community-based group meetings over 12 months led by trained peer supporters and active encouragement to use primary health care and other community resources and supports related to diabetes. Clinical, behavioural and other measures were collected at baseline, 6 and 12 months. The primary outcome was the predicted 5 year cardiovascular disease risk using the United Kingdom Prospective Diabetes Study (UKPDS) Risk Equation at 12 months. Secondary outcomes included clinical measures, quality of life, measures of support, psychosocial functioning and lifestyle measures. RESULTS: Eleven of 12 planned groups were successfully implemented in the intervention arm. Both the usual care and the intervention arms demonstrated a small reduction in 5 year UKPDS risk and the mean values for biochemical and anthropometric outcomes were close to target at 12 months. There were some small positive changes in self-management behaviours. CONCLUSIONS: The positive changes in self-management behaviours among intervention participants were not sufficient to reduce cardiovascular risk, possibly because approximately half of the study participants already had quite well controlled T2DM at baseline. Future research needs to address how to enhance community based programs so that they reach and benefit those most in need of resources and supports to improve metabolic control and associated clinical outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000469213 . Registered 16 June 2009.

Quantification of polyhydroxyalkanoates in mixed and pure cultures biomass by Fourier transform infrared spectroscopy: comparison of different approaches.

UNLABELLED: Fourier transform infrared (FTIR) spectroscopy was used in this study for the rapid quantification of polyhydroxyalkanoates (PHA) in mixed and pure culture bacterial biomass. Three different statistical analysis methods (regression, partial least squares (PLS) and nonlinear) were applied to the FTIR data and the results were plotted against the PHA values measured with the reference gas chromatography technique. All methods predicted PHA content in mixed culture biomass with comparable efficiency, indicated by similar residuals values. The PHA in these cultures ranged from low to medium concentration (0-44 wt% of dried biomass content). However, for the analysis of the combined mixed and pure culture biomass with PHA concentration ranging from low to high (0-93% of dried biomass content), the PLS method was most efficient. This paper reports, for the first time, the use of a single calibration model constructed with a combination of mixed and pure cultures covering a wide PHA range, for predicting PHA content in biomass. SIGNIFICANCE AND IMPACT OF THE STUDY: Currently no one universal method exists for processing FTIR data for polyhydroxyalkanoates (PHA) quantification. This study compares three different methods of analysing FTIR data for quantification of PHAs in biomass. A new data-processing approach was proposed and the results were compared against existing literature methods. Most publications report PHA quantification of medium range in pure culture. However, in our study we encompassed both mixed and pure culture biomass containing a broader range of PHA in the calibration curve. The resulting prediction model is useful for rapid quantification of a wider range of PHA content in biomass.

Effects of acute caffeine supplementation on reducing exercise-associated hypoglycaemia in individuals with Type 1 diabetes mellitus.

AIM: To determine the effects of acute caffeine ingestion on glycaemia during moderate to vigorous intensity aerobic exercise and in recovery in individuals with Type 1 diabetes. METHODS: A total of 13 patients with Type 1 diabetes [eight women, five men: mean ± sd age 25.9 ± 8.8 years, BMI 71.9 ± 11.0 kg, maximal oxygen consumption 46.6 ± 12.7 ml/kg/min, body fat 19.9 ± 7.2%, duration of diabetes 14.4 ± 10.1 years and HbA1c 55 ± 8 mmol/mol (7.4 ± 0.8%)] were recruited. Participants ingested capsules that contained gelatin or pure caffeine (6.0 mg/kg body mass) and performed afternoon exercise for 45 min at 60% maximal oxygen consumption on two separate visits with only circulating basal insulin levels. RESULTS: The main finding was that a single caffeine dose attenuates the drop in glycaemia by 1.8 ± 2.8 mmol/l compared with placebo intake during exercise (P=0.056). Continuous glucose monitoring data, however, showed that caffeine was associated with elevated glycaemia at bedtime after exercise, compared with placebo, but lower glucose concentrations in the early morning the next day. CONCLUSIONS: Caffeine intake should be considered as another strategy that may modestly attenuate hypoglycaemia in individuals with Type 1 diabetes during exercise, but should be taken with precautionary measures as it may increase the risk of late-onset hypoglycaemia.

Diabetes, trekking and high altitude: recognizing and preparing for the risks.

Although regular physical activity is encouraged for individuals with diabetes, exercise at high altitude increases risk for a number of potential complications. This review highlights our current understanding of the key physiological and clinical issues that accompany high-altitude travel and proposes basic clinical strategies to help overcome obstacles faced by trekkers with Type 1 or Type 2 diabetes. Although individuals with diabetes have adaptations to the hypoxia of high altitude (increased ventilation, heart rate, blood pressure and hormonal responses), elevated counter-regulatory hormones can impair glycaemic control, particularly if mountain sickness occurs. Moreover, high-altitude-induced anorexia and increased energy expenditure can predispose individuals to dysglycaemia unless careful adjustments in medication are performed. Frequent blood glucose monitoring is imperative, and results must be interpreted with caution because capillary blood glucose meter results may be less accurate at high elevations and low temperatures. It is also important to undergo pre-travel screening to rule out possible contraindications owing to chronic diabetes complications and make well-informed decisions about risks. Despite the risks, healthy, physically fit and well-prepared individuals with Type 1 or Type 2 diabetes who are capable of advanced self-management can be encouraged to participate in these activities and attain their summit goals. Moreover, trekking at high altitude can serve as an effective means to engage in physical activity and to increase confidence with fundamental diabetes self-management skills.

The effect of puberty on fat oxidation rates during exercise in overweight and normal-weight girls.

Excess weight is often associated with insulin resistance (IR) and may disrupt fat oxidation during exercise. This effect is further modified by puberty. While studies have shown that maximal fat oxidation rates (FOR) during exercise decrease with puberty in normal-weight (NW) and overweight (OW) boys, the effect of puberty in NW and OW girls is unclear. Thirty-three NW and OW girls ages 8-18 yr old completed a peak aerobic capacity test on a cycle ergometer. FOR were calculated during progressive submaximal exercise. Body composition and Tanner stage were determined. For each participant, a best-fit polynomial curve was constructed using fat oxidation vs. exercise intensity to estimate max FOR. In a subset of the girls, IR derived from an oral glucose tolerance test (n = 20), and leptin and adiponectin levels (n = 11) were assessed in relation to FOR. NW pre-early pubertal girls had higher max FOR [6.9 ± 1.4 mg·kg fat free mass (FFM)(-1)·min(-1)] than NW mid-late pubertal girls (2.2 ± 0.9 mg·kg FFM(-1)·min(-1)) (P = 0.002), OW pre-early pubertal girls (3.8 ± 2.1 mg·kg FFM(-1)·min(-1)), and OW mid-late pubertal girls (3.3 ± 0.9 mg·kg FFM(-1)·min(-1)) (P < 0.05). Bivariable analyses showed positive associations between FOR with homeostatic model assessment of IR (P = 0.001), leptin (P < 0.001), and leptin-to-adiponectin ratio (P = 0.001), independent of percent body fat. Max FOR decreased in NW girls during mid-late puberty; however, this decrease associated with puberty was blunted in OW girls due to lower FOR in pre-early puberty. The presence of IR due to obesity potentially masks the effect of puberty on FOR during exercise in girls.

Acute high-intensity interval exercise reduces the postprandial glucose response and prevalence of hyperglycaemia in patients with type 2 diabetes.

High-volume endurance exercise (END) improves glycaemic control in type 2 diabetes (T2D) but many individuals cite 'lack of time' as a barrier to regular participation. High-intensity interval training (HIT) is a time-efficient method to induce physiological adaptations similar to END, but little is known regarding the effect of HIT in T2D. Using continuous glucose monitoring (CGM), we examined the 24-h blood glucose response to one session of HIT consisting of 10 × 60 s cycling efforts at ~90% maximal heart rate, interspersed with 60 s rest. Seven adults with T2D underwent CGM for 24-h on two occasions under standard dietary conditions: following acute HIT and on a non-exercise control day (CTL). HIT reduced hyperglycaemia measured as proportion of time spent above 10 mmol/l (HIT: 4.5 ± 4.4 vs. CTL: 15.2 ± 12.3%, p = 0.04). Postprandial hyperglycaemia, measured as the sum of post-meal areas under the glucose curve, was also lower after HIT vs. CTL (728 ± 331 vs. 1142 ± 556 mmol/l·9 h, p = 0.01). These findings highlight the potential for HIT to improve glycaemic control in T2D.

The characterization of fibrocyte-like cells: a novel fibroblastic cell of the placenta.

The placenta is a highly vascularized organ thus angiogenesis is a key process in placental development. The contribution that different cells in the villous stroma play in placental angiogenesis is largely unknown. In this study we identified a novel stromal cell type in sections of term placenta which is morphologically fibroblastic and expressing the fibroblast marker TE-7 but also positive for the monocytic markers CD115 and CD14 and designated these cells as fibrocyte-like cells. Populations of fibrocyte-like cells from the placenta were isolated by two methods: culture of adherence-selected placental cells and, for higher purity, by CD45 fluorescence activated cell sorting (FACS). Fibrocyte-like cell conditioned medium increased endothelial tubule-like structure formation 2-fold versus control medium. Both pro-angiogenic growth factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) and the anti-angiogenic factor soluble-Flt were found in the conditioned medium. Neutralizing antibodies against VEGF and b-FGF reduced endothelial cell tubule-like structures to control levels. These data suggests that fibrocyte-like cells, a previously unidentified cell of the villous stroma, may play an important role in the regulation of placental angiogenesis.

The contribution of apoptosis-inducing factor (AIF) to villous trophoblast differentiation.

Apoptosis is postulated to be a delayed but important part of the differentiation of placental villous cytotrophoblasts (CT) into functional syncytiotrophoblast (ST). This hypothesis is based on the observation that the externalization of phosphatidylserine and the activation of caspase 8 are required for trophoblast differentiation. In contradiction to this hypothesis we have previously found that differentiation occurs in the presence of both broad spectrum and caspase 8 specific inhibitors. Apoptosis-inducing factor (AIF) is a mitochondria-associated protein which is known to translocate to the nucleus and induce caspase-independent nuclear condensation, phosphatidylserine externalization and cell death. Thus AIF nuclear translocation may result in the apoptotic-like features associated with trophoblast differentiation and may be an obligatory event for differentiation to proceed. AIF translocation was assessed in isolated primary trophoblasts by optical section microscopy of antibody stained cells. We found AIF to be strongly expressed in the villous trophoblast and that small amounts of AIF were localized to the nucleus of the cells. Significantly, inhibitors of AIF translocation (calpeptin and zFA-fmk) blocked translocation but not differentiation of the cells. We conclude that AIF translocation is not involved in CT differentiation in isolated cell culture.

The joint association of physical activity and glycaemic control in predicting cardiovascular death and all-cause mortality in the US population.

AIMS/HYPOTHESIS: The aim of this study was to examine the joint association of physical activity and glycaemic control as measured by HbA(1c) on all-cause and cardiovascular disease (CVD) mortality risk. METHODS: The sample included 10,352 adults from the Third National Health and Nutrition Examination Survey (NHANES III) Linked Mortality Public-use File (follow-up 13.4 ± 3.9 years; 2,463 deaths). Physical activity was assessed by questionnaire and classified into inactive and active categories based on self-reported frequency of leisure-time activity. HbA(1c) was categorised to reflect the American Diabetes Association diagnostic and treatment guidelines. RESULTS: Being physically active was associated with a decreased risk of all-cause (HR 0.74 [95% CI 0.67, 0.81]) and CVD (HR 0.71 [95% CI 0.62, 0.82]) mortality, whereas higher levels of HbA(1c) were associated with an increased mortality risk. HbA(1c) ≥ 7% (53 mmol/mol) was associated with the highest risk for all-cause (HR 1.54 [95% CI 1.30, 1.82]) and CVD (HR 1.93 [95% CI 1.52, 2.45]) mortality. Across all categories of HbA(1c), active individuals were not at increased risk for all-cause mortality compared with inactive individuals with normal glycaemic control. Similar findings were observed for CVD mortality, except that active individuals with HbA(1c) ≥ 7% (53 mmol/mol) were still at increased risk for CVD mortality. However, their risk for CVD death was substantially lower than the risk for their inactive counterparts (HR 1.38 [95% CI 1.03, 1.84] vs HR 1.98 [95% CI 1.34, 2.92]). CONCLUSIONS/INTERPRETATION: Physical activity is associated with lower all-cause and CVD mortality risk for individuals across all levels of glycaemic control. Therefore, engaging in a physically active lifestyle and achieving normal levels of glycaemic control may both be important for the prevention of early mortality.

Voluntary physical activity and leucine correct impairments in muscle protein synthesis in partially pancreatectomised rats.

AIMS/HYPOTHESIS: Poorly controlled type 1 diabetes mellitus can cause reduced skeletal muscle mass and weakness during adolescence, which may affect long-term management of the disease. The aim of this study was to determine whether regular voluntary physical activity and leucine feeding restore rates of protein synthesis and deficits in skeletal muscle mass in a young, hypoinsulinaemic/hyperglycaemic rat model of diabetes. METHODS: Four-week-old male Sprague-Dawley rats were partially pancreatectomised (Px) to induce hypoinsulinaemia/hyperglycaemia and housed with/without access to running wheels for 3 weeks (n = 12-14/group). Sham surgery rats (shams) served as sedentary controls (n = 18). Protein synthesis and markers of protein anabolism were assessed in the fasted state and following leucine gavage. Fibre type and cross-sectional areas of the gastrocnemius muscle were measured using a metachromatic ATPase stain. RESULTS: Compared with sedentary behaviour, regular activity lowered fasting glycaemia and reduced fed hyperglycaemia in Px rats. Active-Px rats, which ran 2.2 ± 0.71 km/night, displayed greater muscle mass and fibre areas similar to shams, while sedentary-Px rats displayed a 20-30% loss in muscle fibre areas. Muscle protein synthesis (basal and in response to leucine gavage) was impaired in sedentary-Px (by ~65%), but not in active-Px rats, when compared with shams. Following leucine gavage, the phosphorylation status of eIF4E binding protein 1 (4E-BP1) and ribosomal S6 kinase 1 (S6K1), markers of mammalian target of rapamycin complex 1 (mTORC1) signalling, increased in shams (by two- and ninefold, respectively) and in active-Px (1.5- and fourfold, respectively) rats, but not in sedentary-Px rats. CONCLUSION/INTERPRETATION: Moderate physical activity in young Px rats normalises impairments in skeletal muscle growth and protein synthesis. These findings illustrate the critical compensatory role that modest physical activity and targeted nutrition can have on skeletal muscle growth during periods of hypoinsulinaemia in adolescent diabetes.

Continuous moderate-intensity exercise with or without intermittent high-intensity work: effects on acute and late glycaemia in athletes with Type 1 diabetes mellitus.

AIMS: Individuals with Type 1 diabetes mellitus are susceptible to hypoglycaemia during and after continuous moderate-intensity exercise, but hyperglycaemia during intermittent high-intensity exercise. The combination of both forms of exercise may have a moderating effect on glycaemia in recovery. The aims of this study were to compare the physiological responses and associated glycaemic changes to continuous moderate-intensity exercise vs. continuous moderate-intensity exercise + intermittent high-intensity exercise in athletes with Type 1 diabetes. METHODS: Interstitial glucose levels were measured in a blinded fashion in 11 trained athletes with Type 1 diabetes during two sedentary days and during 2 days in which 45 min of afternoon continuous moderate-intensity exercise occurred either with or without intermittent high-intensity exercise. The total amount of work performed and the duration of exercise was identical between sessions. RESULTS: During exercise, heart rate, respiratory exchange ratio, oxygen utilization, ventilation and blood lactate levels were higher during continuous moderate-intensity + intermittent high-intensity exercise vs. continuous moderate-intensity exercise (all P < 0.05). Despite these marked cardiorespiratory differences between trials, there was no difference in the reduction of interstitial glucose or plasma glucose levels between the exercise trials. Nocturnal glucose levels were higher in continuous moderate-intensity + intermittent high-intensity exercise and in sedentary vs. continuous moderate-intensity exercise (P < 0.05). Compared with continuous moderate-intensity exercise alone, continuous moderate-intensity + intermittent high-intensity exercise was associated with less post-exercise hypoglycaemia (5.2 vs. 1.5% of the time spent with glucose < 4.0 mmol/l) and more post-exercise hyperglycaemia (33.8 vs. 20.4% of time > 11.0 mmol/l). CONCLUSIONS: Although the decreases in glucose level during continuous moderate-intensity exercise and continuous moderate-intensity + intermittent high-intensity exercise are similar, the latter form of exercise protects against nocturnal hypoglycaemia in athletes with Type 1 diabetes.

Exercise and diabetes.

Diet and exercise form the foundation of a healthy lifestyle. These are especially important for people living with diabetes mellitus, as they are the most practical non-pharmacological means by which patients may significantly improve their blood glucose levels. Exercise increases insulin sensitivity (both short and long term), lowers blood sugar levels, reduces body fat and improves cardiovascular (CV) function. Because of this, exercise offers enormous benefit to patients with diabetes. Blood glucose levels can significantly drop during and after physical activities, due to the increased utilisation of glucose as a fuel during exercise and the up-regulation of glucose transport into working muscles. Therefore, patients (especially those with type 1 diabetes) must account for the effects of exercise and adjust their medications and nutrition accordingly. Improvements in real-time continuous glucose monitoring and optimisation of basal insulin dosing may offer significant benefit to preventing hypoglycaemia in patients with type 1 diabetes who regularly exercise. Diverse exercise programmes and devices can also assist patients in monitoring their activities as well as motivating them to achieve their exercise goals. For patients with type 1 diabetes, questions such as how much, how long, how strenuous and what kind of exercise must be addressed in order for healthcare professionals to offer maximum benefit to their patients. Additionally, since patients with type 2 diabetes often have other significant co-morbidities such as obesity and CV disease, care providers must evaluate each patient's risk factors before designing an exercise programme. Several publications in the last year have addressed these issues and may serve as a valuable resource to provide safe and effective recommendations to patients and their healthcare providers. To be included in the Exercise and Diabetes chapter for the 2010 YEARBOOK, we reviewed leading peer-reviewed manuscripts that were published in the period July 2009 to June 2010. PubMed was used in the initial screening of articles.

Pharmacokinetics of ketamine in plasma and milk of mature Holstein cows.

The purpose of this study was to evaluate the pharmacokinetics of ketamine in mature Holstein cows following administration of a single intravenous (i.v.) dose. Plasma and milk concentrations were determined using a high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following i.v. administration, plasma T(max) was 0.083 h and plasma C(max) was 18,135 ± 22,720 ng/mL. Plasma AUC was 4484 ± 1,398 ng·h/mL. Plasma t(½ß) was 1.80 ± 0.50 h and mean residence time was 0.794 ± 0.318 h with total body clearance of 1.29 ± 0.70 L/h/kg. The mean plasma steady-state volume of distribution was calculated as 0.990 ± 0.530 L/kg and volume of distribution based on area was calculated as 3.23 ± 1.51 L/kg. The last measurable time for ketamine detection in plasma was 8.0 h with a mean concentration of 24.9 ± 11.8 ng/mL. Milk T(max) was detected at 0.67 ± 0.26 h with C(max) of 2495 ± 904 ng/mL. Milk AUC till the last time was 6593 ± 2617 ng·h/mL with mean AUC milk to AUC plasma ratio of 1.99 ± 2.15. The last measurable time that ketamine was detected in milk was 44 ± 10.0 h with a mean concentration of 16.0 ± 9.0 ng/mL.

Caspase activation is not required for villous cytotrophoblast fusion into syncytiotrophoblasts.

The villous trophoblast renews itself by fusion of individual stem cells (cytotrophoblasts, CT) with a functional syncytium (syncytiotrophoblast, ST). The literature indicates that fusion occurs with limited activation (proteolytic cleavage) of caspase-8 in CT and is inhibited either by blocking caspase-8 synthesis or inhibiting activation with a caspase-8-specific inhibitor, zIETD. We challenge part of this evidence: inhibition of differentiation with caspase-8 inhibitors. Br-cAMP-stimulated differentiation of isolated CT into multinucleated syncytia in culture is not blocked with three different low molecular weight inhibitors of caspase-8: broad caspase inhibitors zVAD-fmk and qVD-OPh and the caspase-8-specific inhibitor zIETD-fmk. Syncytialization was determined by desmoplakin staining of intracellular boundaries surrounding >2 nuclei and by diffusion within fused cells of long-lived cytoplasmic staining from half of original CT to the unstained half. Differentiation of isolated CT into hCGß-secreting syncytiotrophoblast was also not blocked by the inhibitors nor was upregulation of hCGß secretion blocked in ST-stripped and regenerated 5 day explant cultures. The ratio of CT to ST nuclei present was also not changed in explant cultures by caspase inhibitors. The effectiveness of caspase inhibitors was demonstrated by their ability to completely block TNFα-induced apoptosis. We conclude that activation of caspases in general, and caspase-8 in particular, is not required for villous CT differentiation into ST. However, another role of intact caspase-8 (proform) in CT differentiation remains possible.

The aetiology, clinical presentations and outcome of febrile encephalopathy in children in Papua New Guinea.

BACKGROUND: Febrile encephalopathy, defined as fever, seizures and/or altered consciousness, is a common presentation in children in tropical developing countries. Outcomes range from complete recovery through varying degrees of neurological disability which slowly resolve or remain permanent to death from either the acute illness or complications. Whilst bacterial meningitis accounts for a proportion of children affected, the aetiology in many remains unclear but includes malaria and probably viral encephalitis. AIM: To understand the aetiology, presentation and outcome of febrile encephalopathy in children in Papua New Guinea. METHODS: Children aged between 1 month and 12 years presenting to Port Moresby General Hospital with febrile encephalopathy were studied prospectively. A detailed history and examination and the following laboratory investigations were undertaken as appropriate: cerebrospinal fluid (CSF) microscopy and bacterial culture, gram stain, measurement of protein and glucose and latex agglutination testing for Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitides; Ziehl-Neelsen staining and india ink examination on selected samples; IgM for Japanese encephalitis, dengue, rubella and measles; PCR testing and mycobacterial culture for Mycobacterium tuberculosis. Blood was tested for flavivirus, measles and rubella IgM and IgG. RESULTS: 149 children were enrolled in the study. 129 had a lumbar puncture and CSF examination; 66 had a normal CSF white cell count. A clinical or laboratory-based diagnosis was possible for 140 children, but a definite pathogen was identifiable for only 55 (37%). The diagnoses included bacterial meningitis in 33 (S. pneumonia 16, H. influenza 13 and N. meningitides 4), tuberculous meningitis (5), probable tuberculous meningitis (18), malaria (10), cryptococcal meningitis (1), flavivirus encephalitis (5), rubella encephalitis (1), hepatic encephalopathy (1) and HIV encephalopathy (1). There were 28 cases of meningitis of unspecified aetiology. Of the five children with IgM-confirmed flavivirus encephalitis, one had dengue serotype 1 and two had Japanese encephalitis. Twenty-five children (including three of the five children with CSF flavivirus IgM) had serological IgG evidence of previous flavivirus infection. A history of multiple convulsions, the presence of neck stiffness and use of the Glasgow coma score (GCS) and TB score chart helped to identify children with bacterial meningitis and an adverse outcome and those with febrile convulsions. CONCLUSION: The study confirms the importance of S. pneumonia and H. influenza as major causes of febrile encephalopathy in children in Papua New Guinea. Flaviviruses including Japanese encephalitis are a cause of the febrile encephalopathy syndrome, as is Mycobacterium tuberculosis. All children with febrile encephalopathy should have their GCS and TB scores recorded and should be examined for neck stiffness, and a history of the frequency of convulsions should be recorded. These basic clinical data can help to discriminate aetiology, to guide treatment and monitoring and to identify the children at highest risk of adverse outcome.

Exercise equipment and diabetes.

Regular exercise is one of the most powerful treatments for the prevention and treatment of insulin resistance and type 2 diabetes mellitus. Exercise is also beneficial for those living with type 1 diabetes although challenges exist with its prescription as it can promote both hyperglycaemia and hypoglycaemia and motivating patients is always a challenge. Nonetheless, promoting regular exercise should be the cornerstone of all healthcare professionals working with these patients. In this year's review on exercise and exercise equipment, we highlight 10 publications that focus on topics ranging from exercise adherence to fuel metabolism. We also highlight some new innovative tools that facilitate exercise participation and evaluation.

Human cytomegalovirus interacts with toll-like receptor 2 and CD14 on syncytiotrophoblasts to stimulate expression of TNFalpha mRNA and apoptosis.

Placentae from newborns with congenital human cytomegalovirus (HCMV) infection often display shallow implantation, chronic villitis and disruptions of the syncytiotrophoblast. Little is known about how HCMV infection induces inflammation in the placenta and loss of the trophoblast. We propose that the inflammation is initiated with innate defense responses of mature syncytiotrophoblast (ST) to virus. Previously we have shown that ultraviolet irradiation-inactivated (UV-) HCMV interacts with toll-like receptor 2 (TLR2) on primary placental cytotrophoblasts (CT) differentiated into ST-like cells thereby stimulating the release of tumor necrosis factor alpha (TNFalpha) and inducing apoptosis of neighboring cells (Chan et al, J. Pathol. 210: 111, 2006). We now determine whether known co-factors of the interaction of HCMV and TLR2 (TLR1 and CD14) bind to UV-HCMV to stimulate expression of TNFalpha and apoptosis in ST-like cells but not CT. We show that CT both fail to express detectable TLR1 and express much less CD14 than ST and that ST express CD14 but not TLR1 both in vivo and in cultured cells. The interaction of UV-HCMV and HCMV with CD14 on the surface of ST-like cells increases TNFalpha expression and induces apoptosis in the population. Antibody to CD14 also inhibits infectious HCMV induction of HCMV immediate early (HCMV IE) expressing ST-like cells. We conclude that primary villous CT express low levels of CD14 and no TLR1 but that ST strongly expresses CD14 which acts upstream of TLR2 to collect even transcriptionally inactive virus particles to stimulate TNFalpha expression and villous trophoblast damage.

Pharmacokinetics of lidocaine in serum and milk of mature Holstein cows.

The purpose of this study was to evaluate the pharmacokinetics of lidocaine in mature Holstein cows following an inverted L and caudal epidural nerve block. Plasma and milk concentrations were determined using high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following administration via inverted L nerve block, serum T(max) was 0.521 +/- 0.226 h and serum C(max) was 572 +/- 207 ng/mL. Serum AUC was 1348 +/- 335 ng.h/mL. Apparent serum t((1/2)beta) was 4.19 +/- 1.69 h and MRT was 5.13 +/- 2.33 h with clearance uncorrected for the extent of absorption of 2.75 +/- 0.68 L/kg/h. The last measurable time of lidocaine detection in serum was 8.5 +/- 1.4 h with a mean concentration of 51 +/- 30 ng/mL. Milk T(max) was detected at 1.75 +/- 0.46 h with C(max) of 300 +/- 139 ng/mL. Milk AUC till the last time was 1869 +/- 450 ng.h/mL with the mean AUC milk to AUC serum ratio of 1.439 +/- 0.374. The last measurable time of lidocaine detection in milk was 32.5 +/- 16.2 h with a mean concentration of 46 +/- 30 ng/mL. There was no detectable lidocaine concentration in any samples following caudal epidural administration.