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This present study proposes an integrated model of destination brand gestalt, and its effect on brand attachment and brand loyalty. Specifically, it aims to investigate the aggregate influence of brand gestalt on brand attachment and brand loyalty at the construct level and its four dimensions (i.e., story, sensescape, servicescape, and stakeholder). The proposed model has been tested using a structural equation model on survey-based data with 684 visitors of North Sulawesi, Indonesia. To obtain robust and convergent results, the survey has been done across three destination categories (beach and sea, mountain and nature, festival and culinary). Results have confirmed that brand gestalt is a significant predictor of tourists' attachment and loyalty to the destination. Destination brand attachment and loyalty are influenced by three dimensions of the brand gestalt - story, sensescape, and servicescape. This study also provides empirical evidence on the effect of brand attachment and brand loyalty on tourism destination context. These results can inform tourism practitioners on the critical role that brand gestalt plays in strengthening tourist-destination connection, as well as creating and sustaining brand loyalty among tourists. [ABSTRACT FROM AUTHOR]

Background. Diabetes mellitus has several complications related to mental health, such as stress and depression. Stress may disrupt the self-concept of a person with type 2 diabetes mellitus (T2DM). Objectives. The aim of this study was to analyze the relationship between stress and self-concept among T2DM patients in Medan, Indonesia. Material and methods. This is a cross-sectional study of a total of 100 subjects. The subjects were selected using convenience sampling. The primary data were collected from interviews using questionnaire guidelines. The Perceived Stress Scale-10 was used to determine the stress level, while the Tennesse Self-Concept Scale was used to determine the patient's self-concept. The data were processed using SPSS and analyzed with the chi-squared test. Results. The results showed that 83% of diabetic patients experienced a moderate level of stress, whereas 61% of patients had a fair self-concept. Furthermore, the chi-squared test showed that there was no relationship between stress and self-concept in T2DM patients (p < 0.05). Conclusions. There was no relationship between stress level and self-concept among T2DM patients (p < 0.05). Although stress and self-concept are closely related, especially in T2DM patients, the present study did not find a relationship between the two variables. However, efforts should still be made to prevent mental health disorders and to control the disease. [ABSTRACT FROM AUTHOR]

• We reported dengue and COVID-19 coinfection in Indonesia. • Possible cross-reactivity between SARS-CoV-2 and DENV antibodies in rapid serological tests is presented. • This cross-reactivity will be a significant hurdle to have a simple point-of-care test for COVID-19 in dengue-endemic countries. Similar symptoms and laboratory findings between dengue and coronavirus disease 2019 (COVID-19) pose a diagnostic challenge in some dengue-endemic countries in Asia. In this study, we reported three cases of suspected COVID-19-dengue coinfection in hospitals of Bali, Indonesia. Serological data demonstrated that patients with positive results for dengue virus (DENV) NS1 antigen and anti-dengue IgM were also reactive to COVID-19 rapid antibody tests, suggesting dengue−COVID-19 coinfection. However, two patients were later confirmed negative for SARS−COV-2 by qRT-PCR, implying a plausible cross-reactivity of anti-dengue and anti−COVID-19 antibodies in the serological test. Coinfection of dengue and COVID-19 was evident in one patient, following confirmation of SARS−COV-2 by qRT-PCR and DENV infection using the NS1 antigen serology test. This case was the first case of dengue and COVID-19 coinfection in Indonesia and revealed possible cross-reactivity between SARS−COV-2 and DENV antibodies based on rapid serological tests. Our study indicates a public health concern regarding COVID-19 and dengue detection in Indonesia as well as in other dengue-endemic countries, and it is important for these nations to manage both pathogens concurrently. [ABSTRACT FROM AUTHOR]

Worldwide, silicified woods are found in many geological formations. Significantly, the organic materials of wood are no longer dominant; almost all wood fossils have been mineralized into inorganic silica materials. These unique geological processes must be understood to develop better understanding on organic material fossilization, particularly in the micron scale. Therefore, our aim was to characterize the composition of silicified wood using comprehensive microanalysis. The methods utilized were XRF, ICP-MS, XRD, FTIR, and FE-EPMA. Specimens are from Jasinga, West Java, Indonesia. The results showed that wood silicification was controlled by the infiltration of silica from the host rock into the spaces of the wood structure. In Jasinga, they are controlled by Pliocene tuffaceous sedimentary rocks. The ratio of silica phases revealed a trend in the degree of silicification. Besides silica, the distribution of trace elements also demonstrates the geochemical interaction between the wood fossil and host rock. Wood fossils are affected by the gradual replacement of organic carbon-based materials with silica through silicification. Silica enrichment occurs in the internal of wood, facilitates permineralization and recrystallization. Silica replaces organic material and preserves the wood structures. The microanalytical approach provides comprehensive perspectives on wood petrification, leads to better insights for paleontological studies., (© 2024. The Author(s).)

The effects of Ocean acidification (OA) on the coastal waters of small islands in Indonesia have yet to be extensively studied. This research aims to investigate the process of OA in the coastal waters of small Indonesian islands and examine how land-sea interactions impact carbonate mineral saturation. We collected seawater samples from seven locations on small islands in Indonesia between 2015 and 2021 to analyze the aragonite saturation state. The result shows that most of Indonesia's coastal waters are accompanied by supersaturation of aragonite saturation state (Ωarag>1). Selayar Island's waters had the highest aragonite saturation, averaging 4.96 ± 0.48, while Pari Island's coastal waters had the lowest, averaging 2.49 ± 0.50. Salinity had the greatest effect on Ωarag in all of the sampling sites, ranging from 24.13% to 52.92%, except Aceh Island, where temperature had a greater impact (34.35%) than salinity (26.99%). By the end of this century, Ωarag is predicted to decline based on projections related to climate change. Small island coastal waters are expected to experience a more substantial decline compared to those near the mainland, ranging from 4.71% to 79.58%. The coastal waters of Weh and Selayar Island are probably going to decline the greatest, while the coastal waters of Sorong (mainland) are probably going to decline the least. All seven sampling locations are expected to observe the decrease. This decline will be observed at all seven sampling locations, with Ωarag values ranging from 1.91 to 3.35., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The damage caused by natural disasters in rural areas differs in nature extent, landscape, and structure, from the damage caused in urban environments. Previous and current studies have focused mainly on mapping damaged structures in urban areas after catastrophic events such as earthquakes or tsunamis. However, research focusing on the level of damage or its distribution in rural areas is lacking. This study presents a methodology for mapping, characterizing, and assessing the damage in rural environments following natural disasters, both in built-up and vegetation areas, by combining synthetic-aperture radar (SAR) and optical remote sensing data. As a case study, we applied the methodology to characterize the rural areas affected by the Sulawesi earthquake and the subsequent tsunami event in Indonesia that occurred on 28 September 2018. High-resolution COSMO-SkyMed images obtained pre- and post-event, alongside Sentinel-2 images, were used as inputs. This study's results emphasize that remote sensing data from rural areas must be treated differently from that of urban areas following a disaster. Additionally, the analysis must include the surrounding features, not only the damaged structures. Furthermore, the results highlight the applicability of the methodology for a variety of disaster events, as well as multiple hazards, and can be adapted using a combination of different optical and SAR sensors.

Background: Dinoflagellates of family Symbiodiniaceae are important to coral reef ecosystems because of their contribution to coral health and growth; however, only a few studies have investigated the function and distribution of Symbiodiniaceae in Indonesia. Understanding the distribution of different kinds of Symbiodiniaceae can improve forecasting of future responses of various coral reef systems to climate change. This study aimed to determine the diversity of Symbiodiniaceae around Lombok using environmental DNA (eDNA)., Methods: Seawater and sediment samples were collected from 18 locations and filtered to obtain fractions of 0.4-12 and >12 µm. After extraction, molecular barcoding polymerase chain reaction was conducted to amplify the primary V9-SSU 18S rRNA gene, followed by sequencing (Illumina MiSeq). BLAST, Naïve-fit-Bayes, and maximum likelihood routines were used for classification and phylogenetic reconstruction. We compared results across sampling sites, sample types (seawater/sediment), and filter pore sizes (fraction)., Results: Phylogenetic analyses resolved the amplicon sequence variants into 16 subclades comprising six Symbiodiniaceae genera (or genera-equivalent clades) as follows: Symbiodinium , Breviolum , Cladocopium , Durusdinium , Foraminifera Clade G, and Halluxium . Comparative analyses showed that the three distinct lineages within Cladocopium , Durusdinium , and Foraminifera Clade G were the most common. Most of the recovered sequences appeared to be distinctive of different sampling locations, supporting the possibility that eDNA may resolve regional and local differences among Symbiodiniaceae genera and species., Conclusions: eDNA surveys offer a rapid proxy for evaluating Symbiodiniaceae species on coral reefs and are a potentially useful approach to revealing diversity and relative ecological dominance of certain Symbiodiniaceae organisms. Moreover, Symbiodiniaceae eDNA analysis shows potential in monitoring the local and regional stability of coral-algal mutualisms., Competing Interests: The authors declare there are no competing interests., (©2022 Pratomo et al.)

Objective: Several studies demonstrated that a high body mass index (BMI) might actually benefit patients with cardiovascular disease, including coronary heart disease. However, other studies were unable to confirm this paradoxical phenomenon in all populations. Therefore, this study aims to determine the association between BMI and long-term clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI)., Patients and Methods: This was a retrospective cohort study of 400 STEMI patients undergoing PCI. Clinical outcome evaluation was done by face-to-face or phone interview and collecting objective data. Statistical analysis was performed to compare the outcomes between underweight-normal group with overweight-obese group., Results: The incidence of major adverse cardiovascular events (MACE) was lower in patients with higher BMI group in 2-years evaluation (24.1% vs. 39.9%; p < 0.001). Multivariate analysis showed that BMI was an independent predictor of MACE and the incidence of recurrent infarction (OR 2.322 [CI 95% 1.505-3.584; p < 0.001]). The risk of MACE reduces as the weight increases, with a nadir of risk reduction for MACE at 28 to 29.0 kg/m2, in which the curve rises after, but remained below the risk associated with BMI of 23 kg/m2., Conclusions: In our population, patients with high BMI have a lower incidence of long-term MACE, especially recurrent myocardial infarction, in patients with STEMI undergoing PCI.

The Convention on Biological Diversity's post-2020 Global Biodiversity Framework will probably include a goal to stabilize and restore the status of species. Its delivery would be facilitated by making the actions required to halt and reverse species loss spatially explicit. Here, we develop a species threat abatement and restoration (STAR) metric that is scalable across species, threats and geographies. STAR quantifies the contributions that abating threats and restoring habitats in specific places offer towards reducing extinction risk. While every nation can contribute towards halting biodiversity loss, Indonesia, Colombia, Mexico, Madagascar and Brazil combined have stewardship over 31% of total STAR values for terrestrial amphibians, birds and mammals. Among actions, sustainable crop production and forestry dominate, contributing 41% of total STAR values for these taxonomic groups. Key Biodiversity Areas cover 9% of the terrestrial surface but capture 47% of STAR values. STAR could support governmental and non-state actors in quantifying their contributions to meeting science-based species targets within the framework.

Objective: This study will test the performance of the anal swab PCR test when compared with the nasopharyngeal swab PCR test as a diagnostic tool for COVID-19., Design: An observational descriptive study which included hospitalised suspected, or probable cases of hopitalised COVID-19 patients, conducted in Dr. Cipto Mangunkusumo National Hospital, Ciputra Hospital, Mitra Keluarga Depok Hospital and Mitra Keluarga Kelapa Gading Hospital, Indonesia. Epidemiological, clinical, laboratory and radiology data were obtained. Nasopharyngeal and anal swabs specimens were collected for SARS-CoV-2 RNA detection., Results: We analysed 136 subjects as part of this study. The clinical spectrum of COVID-19 manifesation in this study was typical of hospitalised patients, with 25% classified as mild cases, 14.7% in severe condition and 12.5% of subjects classified as having acute respiratory distress syndrome. When compared with nasopharyngeal swab as the standard specimen for reverse transcription polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 antigen, the sensitivity and specificity of the anal swab was 36.7% and 93.8%, respectively. The positive and negative predictive value were 97.8% and 16.5 %, respectively. The performance of the anal swab remained similar when only the subgroup of patients with gastrointestinal symptoms (n=92, 67.6%) was analysed (sensitivity 40% and specificity 91.7%). Out of all the subjects included in analysis, 67.6% had gastrointestinal symptoms. Similarly, 73.3% of patients in the anal swab-positive group had gastrointestinal symptoms. The two most common gastrointestinal symptoms in the subjects' population were nausea and anorexia., Conclusion: Anal swab specimen has low sensitivity (36.7%) but high specificity (93.8%) for detecting SARS-CoV-2 antigen by RT-PCR. Only one additional positive result was found by anal swab among the nasopharyngeal swab-negative group. Anal swab may not be needed as an additional test at the beginning of a patient's diagnostic investigation and nasopharyngeal swab RT-PCR remains as the standard diagnostic test for COVID-19., Competing Interests: Competing interests: MA reports grants from Indonesian Ministry of Research, Technology and Higher Education during the conduct of the study. DGS has nothing to disclose. VNM has nothing to disclose. JK has nothing to disclose. AR has nothing to disclose. APU has nothing to disclose. RRP has nothing to disclose. MFI has nothing to disclose. YY has nothing to disclose. SM has nothing to disclose. AS has nothing to disclose. HS has nothing to disclose. IR has nothing to disclose. CWP has nothing to disclose. KR has nothing to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The loss of forest is a leading cause of species extinction, and reforestation is 1 of 2 established interventions for reversing this loss. However, the role of reforestation for biodiversity conservation remains debated, and lacking is an assessment of the potential contribution that reforestation could make to biodiversity conservation globally. We conducted a spatial analysis of overlap between 1,550 forest-obligate threatened species' ranges and land that could be reforested after accounting for socioeconomic and ecological constraints. Reforestation on at least 43% (∼369 million ha) of reforestable area was predicted to potentially benefit threatened vertebrates. This is approximately 15% of the total area where threatened vertebrates occur. The greatest opportunities for conserving threatened vertebrate species are in the tropics, particularly Brazil and Indonesia. Although reforestation is not a substitute for forest conservation, and most of the area containing threatened vertebrates remains forested, our results highlight the need for global conservation strategies to recognize the potentially significant contribution that reforestation could make to biodiversity conservation. If implemented, reforestation of ∼369 million ha would also contribute substantially to climate-change mitigation, offering a way to achieve multiple sustainability commitments at once. Countries must now work to overcome key barriers (e.g., unclear revenue streams, high transaction costs) to investment in reforestation., (© 2020 Society for Conservation Biology.)

Background: Recent studies demonstrate that rabies post-exposure prophylaxis (RPEP) in international travelers is suboptimal, with only 5-20% of travelers receiving rabies immune globulin (RIG) in the country of exposure when indicated. We hypothesized that travelers may not be receiving RIG appropriately, and practices may vary between countries. We aim to describe the characteristics of travelers who received RIG and/or RPEP during travel., Methodology/principal Findings: We conducted a multi-center review of international travelers exposed to potentially rabid animals, collecting information on RPEP administration. Travelers who started RPEP before (Group A) and at (Group B) presentation to a GeoSentinel clinic during September 2014-July 2017 were included. We included 920 travelers who started RPEP. About two-thirds of Group A travelers with an indication for rabies immunoglobulin (RIG) did not receive it. Travelers exposed in Indonesia were less likely to receive RIG in the country of exposure (relative risk: 0.30; 95% confidence interval: 0.12-0.73; P = 0.01). Travelers exposed in Thailand [Relative risk (RR) 1.38, 95% Confidence Interval (95% CI): 1.0-1.8; P = 0.02], Sri Lanka (RR 3.99, 95% CI: 3.99-11.9; P = 0.013), and the Philippines (RR 19.95, 95% CI: 2.5-157.2; P = 0.01), were more likely to receive RIG in the country of exposure., Conclusions/significance: This analysis highlights gaps in early delivery of RIG to travelers and identifies specific countries where travelers may be more or less likely to receive RIG. More detailed country-level information helps inform risk education of international travelers regarding appropriate rabies prevention., Competing Interests: The authors have declared that no competing interests exist.

The congrid eel genus Macrocephenchelys in Taiwan is reviewed. Three species are recognized. Macrocephenchelys brachialis was originally described from Indonesia and is also known from Taiwan, Madagascar, and Vanuatu; it is common in Taiwan but known from few specimens elsewhere. Macrocephenchelys brevirostris was described from Taiwan, where it is common; its occurrence outside Taiwan is uncertain. Macrocephenchelys nigriventris sp. nov. is described here from 28 specimens collected in Taiwan. Macrocephenchelys brachialis is distinguished from the other two species by its more elongate body, more posterior dorsal-fin origin (behind tip of pectoral fin), shorter head (less than 10% total length), presence of a supratemporal pore, absence of fleshy papillae dorsally on the head, absence of sensory pits on the abdomen, and more than 170 vertebrae. Macrocephenchelys nigriventris is distinguished from M. brevirostris by the presence of a patch of black pigment around the anus and adjacent abdomen (absent in M. brevirostris), preanal length 24-28% total length (27-34% in M. nigriventris), and 128-135 vertebrae (147-154 in M. brevirostris). The only other species currently recognized is M. soela from Australia; it is distinguished from all the others by the more anterior origin of the dorsal fin, over the middle of the pectoral fin (vs. over or behind the tip of the pectoral fin).

A Gram-stain-positive, endospore-forming, aerobic and thermophilic bacterium, designated strain LC2-13AT, was isolated from Cisolok geyser, West Java, Indonesia, at 50 °C. The isolate was rod-shaped and motile by means of peritrichous flagella. The major cellular fatty acids were iso-C16 : 0, C16 : 0 and anteiso-C15 : 0 and the major quinone was menaquinone 7. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The genomic DNA G+C content was 56.6 mol% and the major diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain LC2-13AT is related most closely to Paenibacillus kobensis DSM 10249T (94.86 % similarity), Paenibacillus tarimensis SA-7-6T (94.77 %) and Paenibacillus barengoltzii SAFN-016T (94.77 %). On the basis of phenotypic, chemotaxonomic and phylogenetic evidence, strain LC2-13AT is affiliated to the genus Paenibacillus, but could be distinguished from recognized species of this genus. A novel species with the name Paenibacillus cisolokensis sp. nov. is thus proposed. The type strain is LC2-13AT (=UICC B-42T=NRRL B-65368T=DSM 101873T).

Total mercury (Hg) concentrations in hair and urine are often used as biomarkers of exposure to fish-derived methylmercury (MeHg) and gaseous elemental Hg, respectively. We used Hg stable isotopes to assess the validity of these biomarkers among small-scale gold mining populations in Ghana and Indonesia. Urine from Ghanaian miners displayed similar Δ(199)Hg values to Hg derived from ore deposits (mean urine Δ(199)Hg=0.01‰, n=6). This suggests that urine total Hg concentrations accurately reflect exposure to inorganic Hg among this population. Hair samples from Ghanaian miners displayed low positive Δ(199)Hg values (0.23-0.55‰, n=6) and low percentages of total Hg as MeHg (7.6-29%, n=7). These data suggest that the majority of the Hg in these miners' hair samples is exogenously adsorbed inorganic Hg and not fish-derived MeHg. Hair samples from Indonesian gold miners who eat fish daily displayed a wider range of positive Δ(199)Hg values (0.21-1.32‰, n=5) and percentages of total Hg as MeHg (32-72%, n=4). This suggests that total Hg in the hair samples from Indonesian gold miners is likely a mixture of ingested fish MeHg and exogenously adsorbed inorganic Hg. Based on data from both populations, we suggest that total Hg concentrations in hair samples from small-scale gold miners likely overestimate exposure to MeHg from fish consumption., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To compare the sensitivity of inspections of cattle herds and adult fly trapping for detection of the Old World screw-worm fly (OWS)., Procedures: The incidence of myiases on animals and the number of OWS trapped with LuciTrap®/Bezzilure were measured concurrently on cattle farms on Sumba Island (Indonesia) and in peninsular Malaysia (two separate periods for the latter). The numbers of animal inspections and traps required to achieve OWS detection at the prevalent fly densities were calculated., Results: On Sumba Island, with low-density OWS populations, the sensitivity of herd inspections and of trapping for OWS detection was 0.30 and 0.85, respectively. For 95% confidence of detecting OWS, either 45 inspections of 74 animals or trapping with 5 sets of 4 LuciTraps for 14 days are required. In Malaysia, at higher OWS density, herd inspections of 600 animals (twice weekly, period 1) or 1600 animals (weekly, period 2) always detected myiases (sensitivity = 1), while trapping had sensitivities of 0.89 and 0.64 during periods 1 and 2, respectively. For OWS detection with 95% confidence, fewer than 600 and 1600 animals or 2 and 6 LuciTraps are required in periods 1 and 2, respectively., Conclusions: Inspections of cattle herds and trapping with LuciTrap and Bezzilure can detect OWS populations. As a preliminary guide for OWS detection in Australia, the numbers of animals and traps derived from the Sumba Island trial should be used because the prevailing conditions better match those of northern Australia., (© The State of Queensland (through the Department of Agriculture, Fisheries and Forestry) 2014. Australian Veterinary Journal © 2014 Australian Veterinary Association.)

Context: Citronellal is a monoterpene present in the oil of many species, including Cymbopogon winterianus Jowitt (Poaceae)., Objective: The present study investigated the effect of citronellal on inflammatory nociception induced by different stimuli and examined the involvement of the NO-cGMP-ATP-sensitive K⁺ channel pathway., Materials and Methods: We used male Swiss mice (n = 6 per group) that were treated intraperitoneally with citronellal (25, 50 or 100 mg/kg) 0.5 h after the subplantar injection of 20 μl of carrageenan (CG; 300 µg/paw), tumor necrosis factor-α (TNF-α; 100 pg/paw), prostaglandin E₂ (PGE₂; 100 ng/paw) or dopamine (DA; 30 μg/paw). The mechanical nociception was evaluated at 0.5, 1, 2 and 3 h after the injection of the agents, using a digital analgesimeter (von Frey). The effects of citronellal were also evaluated in the presence of L-NAME (30 mg/kg) or glibenclamide (5 mg/kg)., Results: At all times, citronellal in all doses inhibited the development of mechanical nociception induced by CG (p < 0.001 and p < 0.01) and TNF-α (p < 0.001, p < 0.01, and p < 0.05). The citronellal was able to increase the pain threshold in the DA test (p < 0.001, p < 0.01, and p < 0.05) and in the PGE₂ test at all times (p < 0.001 and p < 0.05). L-NAME and glibenclamide reversed the antinociceptive effects of the citronellal at higher doses in the PGE₂ test., Discussion and Conclusion: These data suggest that citronellal attenuated mechanical nociception, mediated in part by the NO-cGMP-ATP-sensitive K⁺ channel pathway.

Both phenotypic and genetic evidence for asymmetric hybridization between rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques has been observed in the region of Indochina where both species are sympatric. The large-scale sharing of major histocompatibility complex (MHC) class II alleles between the two species in this region supports the hypothesis that genes, and especially genes involved in immune response, are being transferred across the species boundary. This differential introgression has important implications for the incorporation of cynomolgus macaques of unknown geographic origin in biomedical research protocols. Our study found that for 2,808 single-nucleotide polymorphism (SNP) markers, the minor allele frequencies (MAF) and observed heterozygosity calculated from a sample of Vietnamese cynomolgus macaques was significantly different from those calculated from samples of both Chinese rhesus and Indonesian cynomolgus macaques. SNP alleles from Chinese rhesus macaques were overrepresented in a sample of Vietnamese cynomolgus macaques relative to their Indonesian conspecifics and located in genes functionally related to the primary immune system. These results suggest that Indochinese cynomolgus macaques represent a genetically and immunologically distinct entity from Indonesian cynomolgus macaques., (© 2012 Wiley Periodicals, Inc.)

Over 20,000 lipid extracts of plants and marine organisms were evaluated in a human breast tumor T47D cell-based reporter assay for hypoxia-inducible factor-1 (HIF-1) inhibitory activity. Bioassay-guided isolation and dereplication-based structure elucidation of an active extract from the Bael tree (Aegle marmelos) afforded two protolimonoids, skimmiarepin A (1) and skimmiarepin C (2). In T47D cells, 1 and 2 inhibited hypoxia-induced HIF-1 activation with IC50 values of 0.063 and 0.068 μM, respectively. Compounds 1 and 2 also suppressed hypoxic induction of the HIF-1 target genes GLUT-1 and VEGF. Mechanistic studies revealed that 1 and 2 inhibited HIF-1 activation by blocking the hypoxia-induced accumulation of HIF-1α protein. At the range of concentrations that inhibited HIF-1 activation, 1 and 2 suppressed cellular respiration by selectively inhibiting the mitochondrial electron transport chain at complex I (NADH dehydrogenase). Further investigation indicated that mitochondrial respiration inhibitors such as 1 and rotenone induced the rapid hyperphosphorylation and inhibition of translation initiation factor eIF2α and elongation factor eEF2. The inhibition of protein translation may account for the short-term exposure effects exerted by mitochondrial inhibitors on cellular signaling, while the suppression of cellular ATP production may contribute to the inhibitory effects following extended treatment periods.

Xenobiotic and folate metabolic pathways are important for the maintenance of genetic stability and may influence susceptibility to the development of childhood acute lymphoblastic leukaemia (ALL). In this study, we investigated 10 polymorphisms in 6 genes (GSTM1-present/null, GSTT1-present/null, GSTP1 1578A > G, NQO1 609C > T, MTHFR 677C > T, MTHFR 1298A > C, MTHFD1 1958G > A, 3'-TYMS 1494 6bp-deletion/insertion, 5'-TYMS 28bp-tandem repeats, and SLC19A1 80G > A) in a cohort of 185 Javanese children with ALL and 177 healthy controls. In ALL patients, none of the polymorphisms demonstrated a statistically significant association with ALL after correcting for multiple comparisons. Gender-stratified analysis showed that in girls, GSTT1-null genotype was associated with increased ALL risk (OR = 2.20; p = 0.027), while GSTP1 1578AG genotype was associated with reduced risk (OR = 0.43; p = 0.031). Strong linkage disequilibrium between the MTHFR 677C > T and 1298A > C polymorphisms was observed (D' = 1.0; r(2) = 0.072). The haplotypes 677C-1298C and 677T-1298A were associated with a reduced risk of ALL (OR = 0.68 and 0.64, respectively; gender-adjusted global p = 0.028). Classification and regression tree (CART) analysis was employed to identify potential high-order gene-gene interactions and cluster subjects into susceptibility groups. SLC19A1 80G > A emerged as the predominant polymorphism associated with risk of ALL. Individuals simultaneously carrying MTHFR 1298AA, 3'-TYMS 6bp deletion(s) and SLC19A1 80A-allele(s) were at higher disease risk (OR = 2.21; p < 0.001). On the contrary, simultaneous possession of MTHFR 1298CC, 3'-TYMS 6bp homozygosity and SLC19A1 80A-allele(s) conferred lower risk (OR = 0.25; p = 0.004). Carriage of NQO1 609C-allele amongst SLC19A1 80GG genotype was associated with lower risk (OR = 0.47; p = 0.003). In conclusion, our study has demonstrated the importance of gender and gene-gene interaction within the xenobiotic and folate pathways in modulating childhood ALL susceptibility., (Copyright © 2010 John Wiley & Sons, Ltd.)

Background: Most of Asia, including Indonesia, does not use Haemophilus influenzae type b (Hib) conjugate vaccines. We estimated total vaccine-preventable disease burden and the cost-effectiveness of Hib conjugate vaccine in Indonesia., Methods: Hib pneumonia and meningitis incidences for children with access to health care were derived from a randomized vaccine probe study on Lombok Island, Indonesia during 1998-2002. Incidences were adjusted for limited access to care. Health system and patient out-of-pocket treatment cost data were collected concurrent with the probe study. For Hib vaccine in monovalent and combined (with DTP-HepB) presentations, we used 2007 UNICEF vaccine prices of US$3.30 and $3.75 per dose., Results: For the 2007 Indonesian birth cohort, Hib vaccine would prevent meningitis in 1 of every 179 children, pneumonia in 1 of every 18 children, and 4.9% of mortality among those younger than 5 years. The total incremental societal costs of introducing Hib vaccine in monovalent and pentavalent presentations were, respectively, US$11.74 and $8.93 per child vaccinated. Annual discounted treatment costs averted amounted to 20% of pentavalent vaccine costs. For the pentavalent vaccine, the incremental costs per discounted death and disability adjusted life-year averted amounted to US$3102 and $74, respectively, versus $4438 and $102 for monovalent vaccine., Conclusions: Routine infant Hib vaccination would prevent a large burden of pediatric illness and death in Indonesia. Even without external funding support, Hib vaccine will be a highly cost-effective intervention in either a monovalent or pentavalent presentation based on commonly used benchmarks.

Genetic variations in the polymorphic tandem repeat sequence of the enhancer region of the thymidylate synthase promoter (TSER), as well as in methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, influence methotrexate sensitivity. We studied these polymorphisms in children with acute lymphoblastic leukaemia (ALL) and in subjects without malignancy in Indonesia and Holland. The frequencies of TT and CT genotypes were two-fold higher in Dutch children. The TSER 3R/3R repeat was three-fold more frequent in the Indonesian children, while the 2R/2R repeat was only 1% compared to 21% in the Dutch children. No differences of these polymorphisms were found between ALL cells and normal blood cells, indicating an ethnic rather than leukemic origin. These results may have implications for treatment of Indonesian children with ALL.

This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found. The eight Asian countries involved in this study are home to approximately 80% of the world's typhoid fever cases. These results document the scale of drug resistance across Asia. The Ser83-->Phe substitution in GyrA was the predominant alteration in serovar Typhi strains from Vietnam (117/127 isolates; 92.1%). No mutations in gyrB, parC, or parE were detected in 55 of these strains. In vitro time-kill experiments showed a reduction in the efficacy of ofloxacin against strains harboring a single-amino-acid substitution at codon 83 or 87 of GyrA; this effect was more marked against a strain with a double substitution. The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions.

The lipid extract of an Indonesian Lendenfeldia sp. sponge inhibited hypoxia-induced hypoxia-inducible factor-1 (HIF-1) activation in T47D breast tumor cells. Chromatographic separation yielded the new substituted naphthalene dimer 1, the new furanolipid 2, and three known homoscalarane sesterterpenes, 3-5. Compounds 1 and 3-5 inhibited hypoxia-induced HIF-1 activation (IC50 values: 0.64-6.9 microM), but also reduced the viability of T47D and MDA-MB-231 breast tumor cells. Compound 4 was the most potent and showed a unique tumor cell line selectivity in the NCI 60-cell line panel. The general cytotoxicity of these compounds precluded their further consideration as HIF-1 inhibitors.

In order to define evolutionarily significant and management units (ESUs and MUs) among subpopulations of Sumatran (Pongo pygmaeus abelii) and Bornean (P. p. pygmaeus) orangutans we determined their genetic relationships. We analyzed partial sequences of four mitochondrial genes and nine autosomal microsatellite loci of 70 orangutans to test two hypotheses regarding the population structure within Borneo and the genetic distinction between Bornean and Sumatran orangutans. Our data show Bornean orangutans consist of two genetic clusters-the western and eastern clades. Each taxon exhibits relatively distinct mtDNA and nuclear genetic distributions that are likely attributable to genetic drift. These groups, however, do not warrant designations as separate conservation MUs because they demonstrate no demographic independence and only moderate genetic differentiation. Our findings also indicate relatively high levels of overall genetic diversity within Borneo, suggesting that observed habitat fragmentation and erosion during the last three decades had limited influence on genetic variability. Because the mtDNA of Bornean and Sumatran orangutans are not strictly reciprocally monophyletic, we recommend treating these populations as separate MUs and discontinuing inter-island translocation of animals unless absolutely necessary.

An entomopathogenic fungus (IndGH 96), identified as Paecilomyces reniformis, was isolated from long-horned grasshoppers (Orthoptera: Tettigoniidae) in Sulawesi, Indonesia. The phenotypic and molecular data identified the IndGH 96 as a P. reniformis. We present the first comprehensive characterization of this species using morphological features, sequencing of the ITS1-5.8s-ITS2 region, D1/D2 region of 28S of rDNA, and a portion of the tubulin gene, and laboratory bioassays. Distinguishing features include a hyphal body stage during vegetative growth and the production of distinctly curved, light-green conidia. High dosage bioassays showed that IndGH 96 was infectious to both long-horned and short-horned grasshoppers but not to the house cricket, Acheta domestica, or to the lepidopterans velvetbean caterpillar, Anticarsia gemmatalis or fall armyworm, Spodoptera frugiperda. Phenotypic and genetic analyses suggest that IndGH 96 and other isolates of P. reniformis are more closely related to Nomuraea rileyi than to other species of Paecilomyces.

Phase-III vaccine efficacy trials typically employ individually randomized designs intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects. As a result, decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes, due to the combination of direct plus indirect vaccine protective effects. Vaccine total protection can be better evaluated with cluster randomized trials. Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide (PS) vaccine in Asia by the Diseases of the Most Impoverished (DOMI) typhoid fever programme. The DOMI's programme multi-country study is one of the largest cluster randomized vaccine trials ever mounted in Asia, which includes approximately 200,000 individuals. Its main objective is to determine the effectiveness of a licensed Vi PS vaccine. The rationale and design of this study are discussed. Preliminary results are presented that determined the final planning of the trial before immunization. Important methodological and practical issues regarding vaccine cluster randomized designs are illustrated.

Diarrhea-related dehydration is a leading cause of childhood death in developing countries such as Indonesia, despite being largely preventable and treatable through use of Oral Rehydration Solution (ORS). While the extent to which ORS is used in Indonesia has been explored in earlier studies, the issue of whether it is being used correctly has not been adequately investigated. The purpose of this study was to assess mothers' ORS preparation and administration practices and to determine their source of instruction for these practices. A structured questionnaire was administered orally to 100 mothers of children under the age of 5 years, in a rural village of West Java, Indonesia. Only 23.7% of mothers were found to have correctly prepared ORS, and none exhibited fully correct administration practices. Primary sources of instruction were health workers (62.9%), package instructions (23.7%), and family members or friends (12.4%). Resulting recommendations include education of health care workers, community health education programs, reallocation of health care resources, and revision of ORS packaging guidelines.

Molar crown preparations, as described in the literature, have standard forms dictated by the demands of retention, resistance and the physical properties of materials. Standard designs may not be appropriate for all patients because of ethnic variations in tooth shape, pulp size and dentine thickness. Accurate data on these features could assist clinicians to minimize the risk of accidental pulpal injury. The aim of this study was to compare the first molar crown and pulp dimensions between Asian (Chinese, Korean, Malay) and other ethnic groups, using measurements from the bitewing radiographs of 121 subjects. Comparisons revealed the following significantly different features of Asian first molars: larger total pulp areas in uppers (P < 0.0005); shorter crowns (P < 0.0005); narrower upper teeth at the cervix (P < 0.0005); wider pulps at the cervix of lowers (P < 0.02); more bulbous crowns (P < 0.0005 for uppers; P < 0.01 for lowers), and finally significantly thinner dentine interproximally at the cervix (P=0.001 for uppers; P=0.011 for lowers). Preparations with wide shoulders could pose hazards to the pulps in Asian subjects. This study emphasizes the value of bitewing films in assessing crown and pulp size and shape before making crown preparations. The experienced practitioner may intuitively include tooth and pulp morphology in treatment planning, but this appears not to be taught or documented in textbooks.

Genetic variability among populations of orangutans from Borneo and Sumatra was assessed using seven SSR loci. Most SSR loci were highly polymorphic and their allele frequencies exhibited substantial variation across subpopulations. While significant genetic subdivision was observed among the island populations, genetic distance did not increase with geographic distance and sufficient gene flow persists to prevent marked genetic subdivision. Since it is unlikely that the Bornean Orangutans dispersed naturally among locations separated by such formidable geographic barriers, human assistance might already have altered their genetic structure. Our data suggests that there may be at least two subspecific clades of orangutans within Borneo while Central Kalimantan animals may have become more genetically related to animals in Sumatra due to human intervention.

The partial molecular characterization of a large deletion present in two members of an Indonesian-Malay family with beta-thalassemia trait is described. Polymerase chain reaction and sequencing analyses of the breakpoint identified a sequence which has previously been described in patients with the 45 kb Filipino beta 0-thalassemia deletion, i.e. a 5' breakpoint at position -4279 nucleotides 5' from the Cap site of the beta-globin gene. The 3' breakpoint is located in an L1 family of repetitive sequences at an unknown distance from the beta-globin gene. The hematological and hemoglobin data of the patients with this beta 0-thalassemia deletion further supports the concept that the unusually high Hb A2 levels are unique to deletions removing the 5' beta-globin gene region, and points to the importance of the 3' junction sequences for the regulation of Hb F levels in patients with deletional defects of the beta-globin gene cluster.

Background: Regular exercise is generally considered to reduce the risk of coronary heart disease. Reduced levels of physical activity in Indo-Asians may partly explain why patients from this ethnic group sustain so many heart attacks., Aim: To investigate ethnic differences in pre-admission levels of physical activity amongst patients admitted with myocardial infarction and triggers for the acute cardiac event., Design: Cross-sectional study using standard Baecke questionnaire, which provided a semi-quantitative work score, sport score, leisure score and total activity score of general daily activities, with additional questions on activity at the onset of chest pain., Setting: Coronary Care Unit, City Centre Teaching Hospital., Patients and Results: We studied 100 consecutive patients (76 males, mean age 62.3 years, S.D. 12.5; 74 caucasians, 26 Indo-Asians) admitted with myocardial infarction. Most patients were engaged in sedentary activities, including lying in bed (25%), sitting (19%), watching television (14%) and sleeping (6%), whilst only 21% of patients were engaged in physical activity at chest pain onset; there were, however, no ethnic differences in activity at chest pain onset. There was a diurnal variation in chest pain onset, with the mode between 08:00 and 10:00 h. As the mean age of Indo-Asians was significantly lower than caucasians in the whole group (56.3 vs. 64.4 years; t-test, P < 0.002), the Baecke questionnaire analysis was confined to only male patients aged < 70 years (n = 56). Indo-Asian patients with myocardial infarction were found to have a significantly lower overall physical activity score (3.78 vs. 5.33; P = 0.003), leisure time physical activity (2.43 vs. 2.74; P < 0.05) and sporting score (0.14 vs. 0.82; P < 0.01) when compared to caucasians, despite a similar mean age and body mass index., Conclusion: The majority of myocardial infarction patients were engaged in sedentary activities at chest pain onset. Although there were no differences between caucasians and Indo-Asians in activity at symptom onset, Indo-Asian patients had a significantly lower overall physical activity score, leisure time physical activity and sporting score compared to caucasians. The lower general physical activity amongst Indo-Asians may in part contribute to the high prevalence of ischaemic heart disease amongst this ethnic group.

Oral vaccines offer great promise as public-health measures to prevent disease in less-developed countries. CVD 103-HgR, a genetically engineered, attenuated, Vibrio cholerae O1 strain has proved effective in industrialised countries. We have assessed the safety, immunogenicity, and excretion of this live cholera vaccine in children in north Jakarta, Indonesia. 412 children aged 5-9 years received single doses of 5 x 10(6), 5 x 10(7), 5 x 10(8), 5 x 10(9), or 1 x 10(10) colony forming units (CFU) of CVD 103-HgR or placebo (5 x 10(8) inactivated Escherichia coli K-12) with buffer. All doses were well tolerated. The 5 x 10(8) CFU dose, which is highly immunogenic in subjects in industrialised countries (greater than 90% seroconversion), elicited seroconversions of vibriocidal antibody in only 16% of Indonesian children. By contrast, a single 5 x 10(9) CFU dose of vaccine resulted in high rates (75% and 87%) of seroconversion with two different batches of vaccine. A batch prepared with a centrifugation step gave significantly higher geometric mean titres (16-fold increase over baseline) than did a batch in which there was a filtration step between fermentation and lyophilisation (10-fold increase over baseline). At a 5 x 10(9) CFU dose, CVD 103-HgR is well tolerated and highly immunogenic in Indonesian children and should therefore be further investigated for use as a one-dose live oral cholera vaccine in developing countries.

Conjunctival impression cytology was performed on 236 Indonesian preschool children, half of whom had mild xerophthalmia and half of whom were age-matched controls. We devised an applicator that applies a paper disk of fixed area to the conjunctiva with even pressure. The disk applicator was used to collect impression cytology specimens from the temporal bulbar conjunctiva of one eye while the original strip technique was used on the other eye. Mean (+/- SD) serum retinol values for children with normal and abnormal discs were 22.0 +/- 8.6 micrograms/dL and 18.0 +/- 7.2 micrograms/dL P less than .0001). Mean serum values for normal and abnormal strips were 21.7 +/- 8.6 micrograms/dL and 19.0 +/- 7.7 micrograms/dL (P less than .03). Specimens obtained with the new disk applicator corresponded more closely with serum vitamin A levels and therefore vitamin A status than those obtained with the traditional strip technique.