Fruit form Influences Postprandial Glycemic Response in Elderly and Young Adults.

OBJECTIVES: This study compared the effects of consuming different forms (bite size, puree) and two fruit types (guava, papaya) on glycemic response (GR) in elderly and young adults. DESIGN: This study was conducted using a randomized, crossover design. PARTICIPANTS: Nineteen healthy participants (9 elderly, 10 young adults) were recruited from the general public in Singapore. INTERVENTION: Participants consumed glucose (reference food) on three occasions and test fruits (guava bites, guava puree, papaya bites, and papaya puree) on one occasion each. MEASUREMENTS: Blood glucose was analyzed prior to consuming the test food, at 15, 30, 45, 60, 90 and 120 minutes after food consumption. RESULTS: The incremental area under the blood glucose response curve (iAUC) over 120 minutes for all the treatments was significantly lower than glucose (all P < 0.001). All fruit forms and types studied were low glycemic index (GI) (guava bites: 29; papaya bites: 38; papaya puree: 42; guava puree: 47), albeit a significant difference in GI between the treatments was found (P = 0.003). Elderly exhibited significantly greater GR than young participants (P = 0.019). CONCLUSION: Although fruit form influences GR in the elderly and young adults, all fruit types and forms studied were found to be low GI. This study indicates that fruits are a valuable source of nutrient irrespective of the form of delivery in elderly and young adults. This study was registered at www.anzctr.org.au as ACTRN12614000655640.

Central adiposity-induced plasma-free amino acid alterations are associated with increased insulin resistance in healthy Singaporean adults.

BACKGROUND/OBJECTIVES: Recent metabolomics technique reveals a plasma-free amino acid (PFAA)-based metabolite signature that is suggestive of altered PFAAs being an early manifestation of obesity-related insulin resistance. However, the PFAA profiles within non-obese, but more insulin-resistant Asians are not well researched. Compared with Caucasians, Asian populations have more central adiposity, which is generally regarded as metabolically more adverse, but the underlying mechanisms remain unclear. In the present study, we examined whether PFAA profiling was at least one important factor mediating central adiposity and insulin resistance, and aid in cardiovascular risk assessment in healthy Asians with normal body weight. SUBJECT/METHODS: This was a cross-sectional study. A total of 190 healthy men (n=87 with a mean±s.d. body mass index (BMI) of 23.5±3.5 kg/m2) and women (n=103 with a mean±s.d. BMI of 21.4±3.7 kg/m2) residing in Singapore took part in this study. PFAA levels were measured by using an amino acid analyzer. Basic anthropometric measurements, fasting blood glucose, fasting serum insulin and lipid profiles were obtained using standard protocols. RESULTS: Seven out of 18 amino acids were significantly correlated with measures of obesity (for example, waist circumference; waist-to-hip ratio and BMI) in current participants. Among them, the plasma concentrations of five amino acids, including Phe, Tyr, Met, Ala and His were positively associated with waist-to-hip ratio. With the exception of His, which had no association with insulin resistance, Phe, Tyr, Met and Ala were significantly associated with hyperinsulinemia and insulin resistance (P<0.05). In contrast, no associations were observed between circulating BCAAs (that is, Val, Leu, Ile), measures of obesity and insulin resistance. However, significant inverse associations were observed between BCAAs and total cholesterol and high-density lipoprotein. CONCLUSIONS: We found that central adiposity was associated with alterations of specific amino acids. As a result, PFAAs may serve as metabolite predictors of hyperglycemia, hyperinsulinemia and dyslipidemia in healthy participants.

Effects of non-nutritive (artificial vs natural) sweeteners on 24-h glucose profiles.

Replacing nutritive sweetener with non-nutritive sweeteners (NNS) has the potential to improve glycaemic control. The objective of this study was to investigate the effects of consuming artificial NNS (that is, aspartame), natural NNS (that is, monk fruit and stevia), and sucrose-sweetened beverages on 24-h glucose profiles. Ten healthy males took part in this randomised, crossover study with the following four treatments: aspartame-, monk fruit-, stevia-, and sucrose- (65 g) sweetened beverages. Participants were asked to consume the test beverage as a preload mid-morning. Medtronic iPro2 continuous glucose monitoring system was used to measure mean 24-h glucose, incremental area under the curve (iAUC) and total area under the curve (AUC) for glucose, and 24-h glycaemic variability. Overall no significant differences were found in mean 24-h glucose, iAUC and total AUC for glucose, and 24-h glycaemic variability between the four test beverages. Twenty-four-hour glucose profiles did not differ between beverages sweetened with non-nutritive (artificial vs natural) and nutritive sweeteners. The simple exchange of a single serving of sucrose-sweetened beverage with NNS over a day appears to have minimal effect on 24-h glucose profiles in healthy males.

Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake.

BACKGROUND: Substituting sweeteners with non-nutritive sweeteners (NNS) may aid in glycaemic control and body weight management. Limited studies have investigated energy compensation, glycaemic and insulinaemic responses to artificial and natural NNS. OBJECTIVES: This study compared the effects of consuming NNS (artificial versus natural) and sucrose (65 g) on energy intake, blood glucose and insulin responses. METHODS: Thirty healthy male subjects took part in this randomised, crossover study with four treatments: aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages. On each test day, participants were asked to consume a standardised breakfast in the morning, and they were provided with test beverage as a preload in mid-morning and ad libitum lunch was provided an hour after test beverage consumption. Blood glucose and insulin concentrations were measured every 15 min within the first hour of preload consumption and every 30 min for the subsequent 2 h. Participants left the study site 3 h after preload consumption and completed a food diary for the rest of the day. RESULTS: Ad libitum lunch intake was significantly higher for the NNS treatments compared with sucrose (P=0.010). The energy 'saved' from replacing sucrose with NNS was fully compensated for at subsequent meals; hence, no difference in total daily energy intake was found between the treatments (P=0.831). The sucrose-sweetened beverage led to large spikes in blood glucose and insulin responses within the first hour, whereas these responses were higher for all three NNS beverages following the test lunch. Thus, there were no differences in total area under the curve (AUC) for glucose (P=0.960) and insulin (P=0.216) over 3 h between the four test beverages. CONCLUSIONS: The consumption of calorie-free beverages sweetened with artificial and natural NNS have minimal influences on total daily energy intake, postprandial glucose and insulin compared with a sucrose-sweetened beverage.

Mutation analysis of genes within the dynactin complex in a cohort of hereditary peripheral neuropathies.

The cytoplasmic dynein-dynactin genes are attractive candidates for neurodegenerative disorders given their functional role in retrograde transport along neurons. The cytoplasmic dynein heavy chain (DYNC1H1) gene has been implicated in various neurodegenerative disorders, and dynactin 1 (DCTN1) genes have been implicated in a wide spectrum of disorders including motor neuron disease, Parkinson's disease, spinobulbar muscular atrophy and hereditary spastic paraplegia. However, the involvement of other dynactin genes with inherited peripheral neuropathies (IPN) namely, hereditary sensory neuropathy, hereditary motor neuropathy and Charcot-Marie-Tooth disease is under reported. We screened eight genes; DCTN1-6 and ACTR1A and ACTR1B in 136 IPN patients using whole-exome sequencing and high-resolution melt (HRM) analysis. Eight non-synonymous variants (including one novel variant) and three synonymous variants were identified. Four variants have been reported previously in other studies, however segregation analysis within family members excluded them from causing IPN in these families. No variants of disease significance were identified in this study suggesting the dynactin genes are unlikely to be a common cause of IPNs. However, with the ease of querying gene variants from exome data, these genes remain worthwhile candidates to assess unsolved IPN families for variants that may affect the function of the proteins.

Influenza A(H1N1)pdm09 infection in pregnant and non-pregnant women hospitalized in Singapore, May - December 2009.

OBJECTIVES: The aim of this study was to compare the demographic and clinical characteristics of pregnant women and non-pregnant women of childbearing age hospitalized with laboratory-confirmed influenza A(H1N1)pdm09 infection in Singapore, and to assess whether pregnancy was a risk factor associated with the development of influenza-related complications. STUDY DESIGN: Retrospective observational study. METHODS: We retrospectively identified and collected information from available medical records of all women admitted to three tertiary hospitals between 26 May 2009 and 31 December 2009 with laboratory-confirmed influenza A(H1N1)pdm09 infection who were either pregnant or non-pregnant and of childbearing age between 15 and 50 years. RESULTS: A total of 222 women, of whom 81 (36.5%) were pregnant, were hospitalized during the study period. Pregnant women were significantly more likely to be hospitalized with influenza A(H1N1)pdm09 infection than non-pregnant women of childbearing age (relative risk 26.3; 95% confidence interval: 20.1-34.6). Among those hospitalized, the proportion of pregnant women having at least one underlying medical condition that could predispose them to influenza-related complications was significantly lower than that of non-pregnant women (32.1% versus 56.0%, P < 0.001). The median time from onset of symptoms to administration of anti-viral drugs was significantly shorter among pregnant women than among non-pregnant women (three days versus five days, P < 0.001). The median length of stay in hospital was also significantly shorter among pregnant women than that of non-pregnant women (two days versus three days, P = 0.002). About 4.9% of pregnant women developed influenza-related complications, compared with 12.8% among non-pregnant women (P = 0.066). CONCLUSIONS: Pregnant women with influenza A(H1N1)pdm09 infection were at a higher risk of hospitalization. Upon hospitalization, they were not at a higher risk of developing influenza-related complications.

Prevalence of antibodies against measles, mumps and rubella in the childhood population in Singapore, 2008-2010.

We undertook a national paediatric seroprevalence survey of measles, mumps and rubella (MMR) in Singapore to assess the impact of the national childhood immunization programme against these three diseases after introduction of the trivalent MMR vaccine in 1990. The survey involved 1200 residual sera of Singapore residents aged 1-17 years collected from two hospitals between 2008 and 2010. The overall prevalence of antibodies against measles, mumps and rubella was 83∙1% [95% confidence interval (CI) 80∙9-85∙1], 71.8% (95% CI 69∙1-74∙2) and 88∙5% (95% CI 86∙6-90∙2), respectively. For all three diseases, the lowest prevalence was in children aged 1 year (47∙8-62∙3%). The seroprevalence of the vaccinated children declined over time. The national MMR immunization programme is effective in raising the herd immunity of the childhood population, although certain age groups are more susceptible to infection, in particular, those who are not eligible for vaccination at age <15 months.

Comparative seroepidemiology of pertussis, diphtheria and poliovirus antibodies in Singapore: waning pertussis immunity in a highly immunized population and the need for adolescent booster doses.

BACKGROUND: We assessed the seroepidemiology of pertussis, diphtheria and poliovirus antibodies in a cohort of highly immunized children, together with the burden of these diseases in Singapore. METHODS: Hospital residual sera collected between August 2008 and July 2010 from 1200 children aged 1-17 years were tested for the prevalence of IgG antibodies against Bordetella pertussis, diphtheria toxoid, and all three poliovirus types by enzyme-linked immunosorbent assays. RESULTS: We found an overall seroprevalence of 99.4% (95% CI 98.8-99.7%) for diphtheria, and 92.3% (95% CI 90.6-93.6%) for poliomyelitis, along with no indigenous cases of these diseases since 1993. However, the seroprevalence for pertussis was 60.8% (95% CI 58.0-63.5%) only. Among the subjects who had completed three doses of pertussis vaccination by the age of 2 years (n=1092), the pertussis seroprevalence was 85.0% (95% CI 79.7-89.2%) in those who received the last vaccination within a year before the study, and it decreased to 75.0% (95% CI 64.5-83.2%) and 63.1% (95% CI 50.9-73.8%) in those who had the last vaccination 1 year and 2 years before the study, respectively. The seroprevalence remained at about 50% for those whose last pertussis vaccination was administered 4 years and longer before the study. CONCLUSIONS: The high seroprevalence for poliomyelitis and diphtheria confer solid herd immunity to eliminate these diseases in Singapore. In contrast, immunity against pertussis waned considerably over time, and routine boosters should be given to adolescents to ensure sustained immunity against pertussis.

Current guidelines for nut consumption are achievable and sustainable: a hazelnut intervention.

Nuts are known for their hypocholesterolaemic properties; however, to achieve optimal health benefits, nuts must be consumed regularly and in sufficient quantity. It is therefore important to assess the acceptability of regular consumption of nuts. The present study examined the long-term effects of hazelnut consumption in three different forms on 'desire to consume' and 'overall liking'. A total of forty-eight participants took part in this randomised cross-over study with three dietary phases of 4 weeks: 30 g/d of whole, sliced and ground hazelnuts. 'Overall liking' was measured in a three-stage design: a pre- and post-exposure tasting session and daily evaluation over the exposure period. 'Desire to consume' hazelnuts was measured during the exposure period only. Ratings were measured on a 150 mm visual analogue scale. Mean ratings of 'desire to consume' were 92 (SD 35) mm for ground, 108 (SD 33) mm for sliced and 116 (SD 30) mm for whole hazelnuts. For 'overall liking', the mean ratings were 101 (SD 29) mm for ground, 110 (SD 32) mm for sliced and 118 (SD 30) mm for whole hazelnuts. Ground hazelnuts had significantly lower ratings than both sliced (P ≤ 0·034) and whole hazelnuts (P < 0·001), with no difference in ratings between sliced and whole hazelnuts (P ≥ 0·125). For each form of nut, ratings of 'overall liking' and 'desire to consume' were stable over the exposure period, indicating that not only did the participants like the nuts, but also they wished to continue eating them. Therefore, the guideline to consume nuts on a regular basis appears to be a sustainable behaviour to reduce CVD.

Effects of different forms of hazelnuts on blood lipids and α-tocopherol concentrations in mildly hypercholesterolemic individuals.

BACKGROUND/OBJECTIVES: Diets high in nuts reduce cholesterol, probably due to their favorable lipid profile and other bioactive substances. However, the physical form of the nut may be important as the cell wall of intact nuts may limit the hypocholesterolemic effect of nuts by reducing lipid bioavailability. Therefore, we investigated the effects on blood lipids of incorporating three different forms of hazelnuts (ground, sliced and whole) into the usual diet. SUBJECTS/METHODS: In a randomized crossover study with three phases, 48 mildly hypercholesterolemic participants were asked to consume 30 g of ground, sliced or whole hazelnuts for 4 weeks. Body weight, plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triacylglycerol (TAG), apolipoprotein (apo) A1, apo B100 and α-tocopherol were measured at baseline and at the end of each dietary phase. RESULTS: There were no significant differences in any outcome variable between the different forms of nuts (all P ≥ 0.159). However, compared with baseline, mean values at the end of each hazelnut intervention were significantly higher for HDL-C (P = 0.023) and α-tocopherol (P = 0.005), and significantly lower for TC (P < 0.001), LDL-C (P < 0.001), TC:HDL-C ratio (P <0 .001), apo B100 (P = 0.002) and apo B100:apo A1 ratio (P < 0.001), with no significant difference in body weight (P = 0.813). CONCLUSIONS: The ingestion of three different forms of hazelnuts equally improved the lipoprotein profile and α-tocopherol concentrations in mildly hypercholesterolemic individuals. Hazelnuts can therefore be incorporated into the usual diet as a means of reducing cardiovascular disease risk.

High failure rate of the dissolution tests for 500-mg amoxicillin capsules sold in Cambodia: is it because of the product or the test method?

OBJECTIVES: During the survey of substandard medicines in Cambodia in 2007, it was found that more than 90% of 500-mg amoxicillin (AMPC) capsules failed the United States Pharmacopeia (USP) 30 TEST 1 dissolution test. In the USP, several monographs provide multiple methods for performing the dissolution test. By using the 500-mg AMPC capsule as an example, we aimed to identify the problems and implications of the USP methods adopted for the dissolution test as a global standard. METHODS: All AMPC samples were collected from the Cambodian market in 2007. For the quantitative test, we referred to USP 30. We performed the USP 28 and USP 30 TEST 2 dissolution tests and compared these results with those of the USP 30 TEST 1. RESULTS: All 500-mg AMPC capsules used for the comparison passed the quantitative test. Samples that passed the USP 28 and USP 30 TEST 2 dissolution tests were identical, and the pass rate was 97.1% (34/35), whereas the pass rate with the USP 30 TEST 1 was 8.6% (3/35). The difference in the dissolution results between the three methods was significant (P<0.0001). CONCLUSION: This study revealed that many users would select the most stringent method when multiple methods exist in the USP. This may lead to a high failure rate of the tests. Because USP is a global standard, we recommend that it take into consideration the developing countries and create a more detailed user-friendly manual for selection for appropriate methods.

Successful immunotherapy of HCMV disease using virus-specific T cells expanded from an allogeneic stem cell transplant recipient.

Opportunistic infection remains the principal cause of mortality in allogeneic stem cell transplant recipients with active extensive chronic graft-versus-host disease. Human cytomegalovirus (HCMV) represents an important cause of disease in this setting and the toxicity of protracted and recurrent antiviral treatment together with eventual drug resistance represents a significant limitation to therapy. Although the expansion and adoptive transfer of HCMV-specific T cells from the healthy original donor can be an effective strategy to control viral replication, this is not possible when donors are seronegative or are subsequently inaccessible. Here we demonstrate for the first time, the successful expansion of HCMV-specific T cells from a seropositive transplant recipient of a seronegative graft with active HCMV disease and the long-term reconstitution of protective antiviral immunity following their adoptive transfer back into the patient.

A simplified endogenous erythroid colony assay for the investigation of polycythaemia.

The in vitro growth of erythroid colonies in the absence of erythropoietin, known as endogenous erythroid colonies (EEC) forms part of the diagnostic criteria for polycythaemia vera (PV). The availability of EEC culture in routine laboratory setting is limited as culture methods are technically demanding, difficult to standardize, expensive and laborious. In this study, we assessed the performance characteristics of a simplified method using ammonium chloride red cell lysis followed by culture on commercially available, batch-tested, methylcellulose media. Seventy-six patients were included; four were secondarily excluded on the basis of culture failure. Of the 14 patients with PV, 13 (93%) were positive for EEC on at least one occasion: 90% (nine of 10) of bone marrow and 67% (six of nine) of peripheral blood specimens were positive. All 30 patients with secondary polycythaemia (n = 12) or apparent polycythaemia (n = 18) were negative for EEC. The incidence of EEC in idiopathic erythrocytosis was 40% (eight of 28); 50% (five of 10) in those who met one of the minor criteria for PV and 17% (three of 18) in those who did not. We conclude that our EEC assay yield results comparable with that of more elaborate methods.

Percutaneous renal biopsy complicated by renal capsular artery pseudoaneurysm.

We report a case of renal capsular artery pseudoaneurysm caused by percutaneous renal biopsy. The injury was diagnosed and treated with arteriography and transarterial embolization. Because the arterial injury was extraparenchymal, the clinical manifestations of blood loss were flank pain and decreasing hematocrit without hematuria. Injury to renal capsular arteries during percutaneous renal biopsy is a rare possibility because of their small size.