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Abstract: Aim: To study whether plasma fibroblast growth factor 21 independently predicts the risk of end‐stage renal disease in Asian people with Type 2 diabetes. Methods: In this prospective cohort study, 1700 Asian people with Type 2 diabetes were followed for a mean of 6.3 years in a regional hospital in Singapore. Incident end‐stage renal disease was identified by linkage with a national renal registry. The association of baseline fibroblast growth factor 21 levels with risk of progression to end‐stage renal disease was studied using survival analyses. Results: Participants were aged 60 ± 10 years, with an average diabetes duration of 12 years. Their estimated GFR was 73 ± 28 ml/min/1.73 m2 and 62% had albuminuria at baseline. A total of 179 incident end‐stage renal disease cases were identified. Plasma fibroblast growth factor 21 interacted with sex in its association with end‐stage renal disease (Pinteraction = 0.003). A 1‐ sd increment in fibroblast growth factor 21 (natural log‐transformed) was associated with a 1.32‐fold (95% CI 1.05–1.66, P = 0.02) increased hazard for end‐stage renal disease in women, after adjustment for traditional risk factors including estimated GFR and albuminuria. Taking death as a competing risk did not materially change the outcome [sub‐distribution hazard ratio 1.35 (95% CI 1.11–1.66, P = 0.003)]. Fibroblast growth factor 21 did not predict end‐stage renal disease risk in men after adjustment for baseline estimated GFR and albuminuria [hazard ratio 1.07 (95% CI 0.89–1.28, P = 0.49)]. Conclusions: Plasma fibroblast growth factor 21 level independently predicted risk of progression to end‐stage renal disease in women with Type 2 diabetes. The pathophysiological relationships among FGF21, sex and renal progression warrant further study. [ABSTRACT FROM AUTHOR]

The Artocarpus fruit fly, Bactrocera umbrosa (Fabricius) (Diptera: Tephritidae), is an oligophagous fruit pest infesting Moraceae fruits, including jackfruit (Artocarpus heterophyllus Lamarck), a fruit commodity of high value in Malaysia. The scarcity of fundamental biological, physiological and ecological information on this pest, particularly in relation to behavioural response to phytochemical lures, which are instrumental to the success of many area-wide fruit fly control and management programmes, underpins the need for studies on this much-underrated pest. The positive response of B. umbrosa males to methyl eugenol (ME), a highly potent phytochemical lure, which attracts mainly males of many Bactrocera species, was shown to increase with increasing age. As early as 7 days after emergence (DAE), ca. 22% of males had responded toME and over 50% by 10 DAE, despite no occurrence of matings (i.e. the males were still sexually immature). Male attraction toMEpeaked from 10 to 27 DAE, which corresponded with the flies' attainment of sexual maturity. In wind-tunnel assays during the dusk courtship period, ME-fed males exhibited earlier calling activity and attracted a significantly higher percentage of virgin females compared with MEdeprived males. ME-fed males enjoyed a higher mating success than ME-deprived males at 1-day post ME feeding in semi-field assays. ME consumption also promotes aggregation behaviour in B. umbrosa males, as demonstrated in wind-tunnel and semi-field assays. We suggest that ME plays a prominent role in promoting sexual communication and enhancing mating performance of the Artocarpus fruit fly, a finding that is congruent with previous reports on the consequences of ME acquisition by other economically important Bactrocera species. [ABSTRACT FROM AUTHOR]

The dung beetle assemblages in the core (CZ), buffer (BZ) and transition (TZ) zones at Tasik Chini Biosphere Reserve (TCBR) was studied for the first time with different types of modified pitfall trap. A total of 2387 individuals belonging to 7 tribes, 12 genera and 36 species was successfully collected using, baited pitfall trap (B), baited pitfall trap with light sources (BL), baited pitfall trap with 1 m fencing at each sided of the container (BF) and baited pitfall trap with 1 m fencing at each sided of the container and light sources (BLF). Significant differences in species richness (F = 19.36; df = 2, 35; P < 0.05) and abundance (F = 27.59; df = 2, 35; P < 0.05) were found between the three different zones. This indicates that the land use intensity in TCBR had a negative effect and requires further research on focal taxon such as dung beetles to detect habitat changes for biodiversity conservation. Considering preference of method, no significant differences were found for both species richness and abundance. However, the catches of some species were affected by different trap designs. Three nocturnal species only collected in BL (Copris haroldi and Onthophagus sp. 1) and in BL and BLF (Aphodius sp.1). While smaller dung beetles Ochicanthon peninsularis and Onthophagus karenensis obtained only in BF and BLF. Therefore, the use of light and fences had a stronger effect on diversity and abundance of particular species of dung beetles in evaluating the status of a forest health. [ABSTRACT FROM AUTHOR]

The effects of sub sterilizing doses of gamma radiation on the longevity and level of inherited sterility in the Australian moth Teia anartoides Walker were determined. Six day-old male pupae were treated with 0,100, and 160 Gy of gamma radiation by using a 1.25 MeV Cobalt60 irradiation source. Laboratory studies of male longevity showed that radiation had little impact in adult moths of the P1, F1, and F2 generations. Inherited deleterious effects resulting from irradiation were observed in the progeny of F1 and F2 generations. Outcrosses between substerile parental males or their highly sterile male progeny to wild-type females did not affect female fecundity. However, adverse effects were observed for these crosses in the rates of successful egg hatch and postembryonic development. Fertility was always greater in out-crosses involving a P1 male than in any of the F1 out-crosses. F1 males were always more sterile than F1 females, and the level of sterility for the F1 and F2 generations was higher than that of the controls. The incidence of larval and pupal mortality was higher in the F2 than the F1 generation. A dose of 100 Gy had the highest success in inducing deleterious effects that were inherited through to the F2 generation. Our results indicated that the use of partially sterilizing doses of radiation has good potential as a selective strategy for management or eradication of T. anartoides. [ABSTRACT FROM AUTHOR]

We have previously reported the isolation of 2 human allospecific cytotoxic T-lymphocyte (CTL) clones that can undergo a reversible functional change from a highly lytic phase to a nonlytic quiescent phase and again to a lytic phase. The entire process was found to be regulated by recombinant interleukin 2 (rIL-2). We have now extended these studies in 3 ways. First, we show that specific alloantigens can also function as a signal to reactivate lytic function in the reverted CTL. However, in contrast to CTL reactivated with rIL-2, the antigen-reactivated CTL apparently fail to undergo subsequent cell division. Second, we have also found that this reversion phenomenon is not the same for all CTL tested, as 2 other CTL clones were found that did not revert to the non-lytie phase when cultured for up to 60 h in rIL-2-free medium. Third, the expression of Tac (IL-2 receptor) was also studied throughout the process of reversion and reactivation. RIL-2 added to the cell that had reverted to a non-lytic phase induced, an increase in the expression of Tac receptors during the reactivation phase, to levels greater than those expressed on cells continuously cultured in rIL-2-supplemented medium. [ABSTRACT FROM AUTHOR]

Cells surface molecules of T-rosette-positive human peripheral blood lymphocytes were labeled by lactoperoxidase and examined on 5% polyacrylamide gels. Several bands, ranging in molecular weight from 220,000 to 170,000 daltons, were seen. Analysis of the tryptic and chymotryptic digests of the 187K, 200K, 210K and 220K proteins indicated that they are of similar peptide composition. Study of clones derived from this population indicated that individual cells within a population differed in expression of these proteins. [ABSTRACT FROM AUTHOR]

Background: Singapore is the most rapidly ageing country in South East Asia, and the number of residents aged 60 and older is expected to be 20% of the national population by 2030[1]. It is therefore crucial that we identify the determinants of requirements for health and social services among the elderly. Objectives:The study was conducted to understand how health, financial status and family support affect the elderlys requirements of such services in a residential area of Singapore reflective of the nations population in 2030. Methodology: Our study was conducted using population based survey in Marine Parade in 2011 for residents aged above 60 years. A multiple logistic regression model was employed to analyse the association between the elderlys health, financial and family support status and their service requirements. Results: Among 2558 respondents, 18% requested one or more services. Respondents living with chronic diseases, depression, pain, the need for ADL assistance, the lack of a caregiver and poor socio-economic status were found to be significantly associated with an increased need for such services. Conclusion: Findings in our study may help to estimate future elderly service requirements and hence assist in policy making. [ABSTRACT FROM AUTHOR]

Objectives: To determine the overlapping prevalence of malnutrition and sarcopenia and the association between parameters of malnutrition with muscle mass and strength in a community-dwelling Singaporean adult population., Design: This was a cross-sectional study., Setting: Large north-eastern residential town of Yishun in Singapore., Participants: Random sampling of community-dwelling Singaporeans aged 21-90 years old (n=541)., Measurements: Anthropometry, body composition and handgrip strength (muscle strength) were measured. Sarcopenia was identified using dual-energy x-ray absorptiometry scan (muscle mass). Nutritional status was measured using Mini Nutritional Assessment (MNA-SF). Other questionnaires collected included physical activity and cognition. Associations between nutritional status with sarcopenia as well as with muscle mass and strength were analysed using multinomial logistics and linear regressions., Results: The overall population-adjusted prevalence of those at nutritional risk and malnourished were 18.5% and 0.1% respectively. More than a third of participants (35%) who were at nutritional risk were sarcopenic. Malnourished participants were all sarcopenic (100%, N=2) whereas those who were sarcopenic, 27.0% (N=37) were at nutritional risk/malnourished. Being at nutritional risk/malnourished was significantly associated with 2 to 3 times increased odds of sarcopenia in multivariate analyses adjusting for age, gender, physical activity level and cognition, and fat mass index. Favourable MNA parameter scores on food intake and BMI were positively associated with greater muscle mass and handgrip strength (p<0.05)., Conclusion: Given the overlapping clinical presentation of malnutrition and sarcopenia, community screening protocols should include combination screening of nutritional status and sarcopenia with appropriate interventions to mitigate risk of adverse health outcomes., Competing Interests: The authors declare that they have no conflict of interest.

Objectives: Due to the lack of a uniform obesity definition, there is marked variability in reported sarcopenic obesity (SO) prevalence and associated health outcomes. We compare the association of SO with physical function using current Asian Working Group for Sarcopenia (AWGS) guidelines and different obesity measures to propose the most optimal SO diagnostic formulation according to functional impairment, and describe SO prevalence among community-dwelling young and old adults., Design: Obesity was defined according to waist circumference (WC), percentage body fat (PBF), fat mass index (FMI), fat mass/fat-free mass ratio (FM/FFM), or body mass index (BMI). SO was defined as the presence of both obesity and AWGS sarcopenia. Muscle function was compared among phenotypes and obesity definitions using ANOVA. Differences across obesity measures were further ascertained using multiple linear regressions to determine their associations with the Short Physical Performance Battery (SPPB)., Setting: Community-dwelling adults 21 years old and above were recruited from a large urban residential town in Singapore., Participants: 535 community-dwelling Singaporeans were recruited (21-90 years old, 57.9% women), filling quotas of 20-40 participants in each sex- and age-group., Measurements: We took measurements of height, weight, BMI, waist and hip circumferences, body fat, muscle mass, muscle strength, and functional assessments. Questionnaire-based physical and cognitive factors were also assessed., Results: Overall prevalence of SO was 7.6% (WC-based), 5.1% (PBF-based), 2.7% (FMI-based), 1.5% (FM/FFM-based), and 0.4% (BMI-based). SO was significantly associated with SPPB only in the FMI model (p<0.05), and total variance explained by the different regression models was highest for the FMI model., Conclusions: Our findings suggest FMI as the most preferred measure for obesity and support its use as a diagnostic criteria for SO., Competing Interests: The authors declare no conflict of interest. The research work conducted for this study comply with the current laws of the country in which they were performed.

Introduction: The motor weakness in sporadic hemiplegic migraine (SHM) is a poorly understood aura manifestation. Cortical spreading depression affecting motor excitability and alterations of neurovascular coupling may be integral to the development of migraine aura., Methods: We studied 10 right-handed SHM patients and 17 healthy controls with functional near-infrared spectroscopy (fNIRS) in the interictal period. Subjects performed a finger opposition task and had real time determination of oxyhemoglobin (OxyHb) and deoxyhemoglobin (deOxyHb) changes. Recordings were completed with 10 left and 10 right sided cortical channels., Results: Mean baseline to peak changes were significantly reduced in SHM patients as compared to controls bilaterally only for OxyHb measurements in the anteromedial channels. Mean time to peak changes were significant delayed in SHM patients compared to controls bilaterally largely for OxyHb measurements in the posterolateral channels, with the exception of 2 recording channels., Conclusions: Our findings suggest presence of abnormal interictal hemodynamic responses to increased metabolic demands during motor activation in SHM. These bilateral cerebrovascular changes involve OxyHb to a much larger degree than deOxyHb. Baseline to peak changes were evident more in the anteromedial channels, whereas time to peak changes were more evident in the posterolateral channels. These findings suggest that oxygen inflow into specific brain regions may be defective in SHM as opposed to oxygen utilization. Our findings suggest that in SHM, enduring hemodynamic deficits in response to an impending motor task are evident, which can be further explored in future studies, and possibly therapeutic trials., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Unlabelled: Development of mixed chimerism by donor bone marrow transplantation (DBMT) has led to long-term tolerance of solid organ allografts in nonhuman primates. As an initial attempt to extend this approach to cellular transplant, islet transplant from the same donor was attempted in the recipient previously made tolerant to a kidney allograft., Methods: After the conditioning with ATG, total body irradiation, thymic irradiation, and splenectomy, DBMT was performed followed by 4 weeks of cyclosporine. Kidney transplantation and native nephrectomies were subsequently performed on day 89. After 2.8 years of DBMT, diabetes was induced by streptozocin (STZ) and islets from bone marrow and kidney donor were transplanted without immunosuppression., Results: After DBMT, the recipient developed chimerism and no evidence of kidney rejection for more than 1000 days. STZ induced diabetes was reversed after the islet transplantation. Islet biopsies demonstrated insulin staining without rejection. Although the recipient became diabetic 300 days after islet transplantation, viable transplanted islets were found in the liver and under the kidney capsule without any evidence of rejection., Conclusion: Tolerance with a nonmyeloablative conditioning can allow successful pancreatic islet transplantation without immunosuppression. Because no histological evidence of rejection was identified, recurrent diabetes is presumed to be inadequate islet mass.

Methyl eugenol (ME), is converted into two major phenylpropanoids, 2-allyl-4,5-dimethoxyphenol and trans-coniferyl alcohol, following consumption by the male fruit fly Bactrocera papayae. Chemical analysis of wild male B. papayae rectal glands, where the compounds are sequestered, revealed the presence of ME metabolites in varying quantities. These phenylpropanoids are shown to be involved in the fruit fly defense both in no-choice and choice feeding tests against the Malayan spiny gecko, Gekko monarchus. After being acclimatized to feeding on fruit flies, geckos consumed significantly fewer ME-fed male flies than controls that consumed all the ME-deprived male flies offered throughout a two-week period. Diagnosis of dissected livers from geckos that consumed ME-fed male flies revealed various abnormalities. These included discoloration and hardening of liver tissue, whitening of the gallbladder, or presence of tumor-like growths in all geckos that consumed ME-fed male flies. Control geckos fed on ME-deprived male flies had healthy livers. When given an alternative prey, geckos preferred to eat untreated house flies, Musca domestica to avoid preying on ME-fed fruit flies.

Background: Nonmyeloablative T cell depletion followed by donor bone marrow infusion has proved to be an effective approach to induction of mixed chimerism and tolerance of organ allografts in non-human primates. To help define the mechanisms involved we have compared T cell depletion with ATG versus anti-CD2 monoclonal antibody with respect to establishment of mixed chimerism and induction of tolerance., Method: Both nonmyeloablative regimens included low dose total body irradiation (1.5 Gy x 2), thymic irradiation (7 Gy), splenectomy and kidney plus donor bone marrow transplantation, followed by a 4-week posttransplant course of cyclosporine. In addition, the ATG group (13 recipients) received antithymocyte globulin, although the LOCD2b group (10 recipients) were treated with an anti-CD2 monoclonal antibody (LOCD2b)., Results: In the ATG group, 11 of 13 monkeys developed multilineage chimerism and 9 survived for more than 100 days without kidney allograft rejection. In contrast, 0/10 monkeys in the LOCD2b group developed chimerism, 5 died of infection and 5 suffered progressive rejection; only 1 recipient survived beyond 100 days. Sequential monitoring of peripheral blood mononuclear cells revealed greater T cell (CD3+) depletion in the LOCD2b-treated animals compared to those receiving ATG. However, NK cells (CD16+CD8+) were significantly more depleted in the ATG group and NK function remained abrogated longer after ATG than LOCD2b treatment (3 weeks vs. <5 days)., Conclusion: Despite excellent T cell depletion by LoCD2b, ATG was more effective in inducing chimerism and tolerance. This difference correlated with anti-NK activity of the two reagents. These data suggest that NK cells may also resist engraftment of allogeneic bone marrow cells in this model.

Background: Multilineage chimerism and long-term acceptance of renal allografts has been produced in non-human primates conditioned with a nonmyeloablative regimen. Our study was undertaken to evaluate the immunological and pathological status of long-term survivors and to define the role of splenectomy and of the primarily vascularized kidney in the regimen., Method: Monkeys were treated with the basic regimen, including: total body irradiation, thymic irradiation, antithymocyte globulin, donor bone marrow transplantation, and a 4-week course of cyclosporine after which no further immunosuppression was given. They were divided into four groups according to the timing of kidney transplantation (KTx) and splenectomy as follows; group A (n=13): KTx and splenectomy on the day of donor bone marrow transplantation (day 0); group B (n=3): KTx on day 0 without splenectomy; group C (n=7): splenectomy on day 0 but delayed KTx until 3 to 16 weeks post-donor bone marrow transplantation; group D (n=3): both splenectomy and KTx delayed until day 120 post-donor bone marrow transplantation., Results: In group A, 11 of 13 monkeys developed chimerism and 9 monkeys achieved long-term survival of 4 to 70 months without evidence of chronic vascular rejection. Alloantibodies were detected in only one long-term survivor. In contrast, all three monkeys in group B developed alloantibodies and rejected their allografts. In group C, long-term survival without alloantibody production was observed in two of three monkeys that had developed chimerism. In group D, all three recipients were sensitized and rejected the kidney allografts rapidly after transplantation., Conclusions: 1) Production of anti-donor antibody was prevented in most recipients that developed mixed chimerism in the regimens with splenectomy at the time of donor bone marrow transplantation. 2) If splenectomy is not included in the initial conditioning regimen, induction of B cell tolerance is less likely and the result is late onset of alloantibody production and allograft rejection. 3) Immediate transplantation of the kidney at the time of recipient conditioning is not essential for induction of donor specific hyporesponsiveness by bone marrow transplantation.

Background: We have previously demonstrated that induction of mixed lymphohematopoietic chimerism resulted in donor specific renal allograft tolerance without the need for chronic immunosuppression in nonhuman primates. Here we have tested whether tolerance can be similarly induced for baboon to cynomolgus renal xenografts., Methods: After preconditioning with anti-thymocyte globulin (ATG), nonlethal total body irradiation, and thymic irradiation, cynomolgus monkeys underwent splenectomy, native nephrectomies, and baboon marrow and renal transplants. Postoperative cyclosporine was given for 28 days., Results: In Group 1 (n=2, survival= 13, 14 days), both animals developed anti-donor immunoglobulin G, had biopsy findings consistent with humoral rejection, and showed rapidly progressive xenograft failure. In Group 2 (n=5, survival=1, 16, 33, 112, 190 days), 15-deoxyspergualine was added to the regimen (Day 0-13). In one long-term survivor, donor specific hyporesponsiveness was first observed (mixed lymphocyte culture [(MLR]) on Day 48. MLR reactivity returned on Day 64 together with the development of anti-donor antibody and subsequent xenograft failure on Day 112. Donor specific T-cell hyporesponsiveness was detected in the other long-term survivor for the first 133 days, after which a donor-specific skin xenograft was placed, (survival 24 days). Following the skin graft rejection, a rise in the MLR, development of anti-donor antibody and progressive rejection of the renal xenograft were observed., Conclusions: Antibody-mediated rejection seems to constitute the major difference between concordant xenografts and allografts. Addition of 15-deoxyspergualine for 2 weeks posttransplant extended concordant primate xenograft survival to 6 months without chronic immunosuppression. In contrast to the allogeneic model, renal transplant acceptance in this xenogeneic system was interrupted by placement of a donor-specific skin graft.

Purpose: The purpose of this study was to examine the effect of high and low glycemic index (GI) carbohydrate (CHO) pre-exercise meals on endurance running capacity., Methods: Eight active subjects (five male and three female) ran on a treadmill at approximately 70% VO2max to exhaustion on two occasions separated by 7 d. Three hours before the run after an overnight fast, each subject was given in a single-blind, random order, isoenergetic meal of 850+/-21 kcal (mean+/-SEM; 67% carbohydrate, 30% protein, and 3% fat) containing either high (HGI) or low (LGI) GI carbohydrate foods providing 2.0 g CHO.kg(-1) body weight., Results: Ingestion of the HGI meal resulted in a 580% and 330% greater incremental area under the 3-h blood glucose and serum insulin response curves, respectively. Performance times were not different between the HGI and LGI trials (113+/-4 min and 111+/-5 min, respectively). During the first 80 min of exercise in the LGI trial, CHO oxidation was 12% lower and fat oxidation was 118% higher than in the HGI trial. Although serum insulin concentrations did not differ between trials, blood glucose at 20 min into exercise in the HGI trial was lower than that during the LGI trial at the same time (3.6+/-0.3 mmol.L(-1) vs 4.3+/-0.3 mmol.L(-1); P < 0.05). During exercise, plasma glycerol and serum free fatty acid concentrations were lower in the HGI trial than in the LGI trial., Conclusions: This results demonstrate that although there is a relative shift in substrate utilization from CHO to fat when a low GI meal is ingested before exercise compared with that for a high GI meal, there is no difference in endurance running capacity.

Prior studies from our laboratory have demonstrated that a nonmyeloablative conditioning regimen can induce transient mixed chimerism and renal allograft tolerance between MHC disparate cynomolgus monkeys. We have also shown that this preparative regimen can be extended to a concordant baboon to cynomolgus xenograft model by adding, to the post transplant protocol, therapy designed to prevent antibody production. Here we examine the use of brequinar (BQR) for this purpose and the efficacy of two new reagents developed to demonstrate the establishment of chimerism in the xenograft recipients. The cynomolgus recipients were conditioned with WBI (300 cGy), TI (700 cGy), ATG, cyclosporine, and brequinar sodium. To detect engraftment of the donor marrow, we prepared a polyclonal cynomolgus anti-baboon antibody (CABA) and a monoclonal antibody (215.1), which distinguish baboon and cynomolgus lymphocytes and granulocytes. We employed flow cytometry analysis to detect multilineage chimerism in the xenograft recipients. Five of the six recipients monitored using our new reagents (CABA and 215.1) developed detectable chimerism and only one of these animals lost its kidney to rejection. However, other complications have not permitted assessment of long-term outcome. The features of the multilineage chimerism included the detection of donor granulocytes (1.8-77.4%) and lymphocytes (2.4-22.2%) for 9 to 37 days. Our new reagents permit the detection of multilineage mixed chimerism, which may be a predictor of xenograft tolerance. We also conclude that brequinar may be effective in preventing antibody formation, but because of its toxicity, it is probably not the drug of choice for extension of the mixed chimerism protocol to concordant xenografts.

Antibody-mediated rejection appears to constitute the major difference between concordant xenografts and allografts in nonhuman primates. Consistent with its known effect on antibody responses, 5-7 addition of DSG to the conditioning regimen has extended concordant primate xenograft survival for up to 6 months after discontinuation of conventional immunosuppression. In contrast to our observations in recipients of renal allografts, donor-specific skin graft rejection can occur and even in long-term recipients may induce rejection of a previously accepted renal xenograft.