Quantitative and qualitative analysis of stability for 16 serum immunoregulators over 50 freeze-thaw cycles.

OBJECTIVES: To evaluate the reliability of data from the assay of bio-archived specimens, a 50-freeze-thaw-cycle (FTC) degradation study of fresh sera was conducted to test the stability of 16 immunoregulators. METHODS: Twenty de-identified serum specimens were obtained from volunteers at United Health Services-Wilson Memorial Hospital. Specimens were stored at -20°C and underwent daily 1 h thawing and subsequent freezing for each FTC over 50 consecutive days. Immunoregulator concentrations were assessed via enzyme-linked immunosorbent assay (ELISA) in participant samples at 2 FTC (baseline), 25 FTC, and 50 FTC. Specific immunoregulators observed in the study were C-reactive protein (CRP), interleukin (IL)-1α, 4, 6, 8, 10, monocyte chemoattractant protein-1 (MCP-1, CCL2), monocyte chemoattractant protein-2 (MCP-2, CCL8), eotaxin-1, thymus-and-activation-regulated chemokine (TARC, CCL17), regulated on activation normal T-cell expressed and secreted (RANTES, CCL5), growth-regulated oncogene-alpha (GRO-α, CXCL1), small inducible cytokine A1 (I-309, CCL1), interferon-gamma (IFN-γ), interferon-gamma inducible protein-10 (IP-10, CXCL10), and tumor necrosis factor-alpha (TNF-α). RESULTS: Quantitative stability of serum immunoregulators: Serum CRP, IL-8, IL-10, IFN-γ, IP-10, and eotaxin-1 levels appear to be statistically equivalent from baseline to 50 FTC (p ≤ .05). Retention of patterns in serum immunoregulators: patterns across FTC were retained for TARC (age) and CRP, IFN-γ, and MCP-2 (sex). CONCLUSIONS: While the effect of multiple FTC on serum immunoregulator levels may not replicate prolonged freezer storage, the results of this study provide valuable information on the robustness of immunoregulators for research using bio-archived sera.

Investigating surface binding effects: antibacterial efficacy of bound 8-hydroxyquinoline against Staphylococcus aureus and Escherichia coli.

AIMS: To investigate the binding of the antimicrobial compound 8-hydroxyquinoline (8HQ) to a material interface and to determine whether immobilization affects the antibacterial efficacy. METHODS AND RESULTS: The 8HQ derivative 5-carboxy-8-hydroxyquinoline (5C8HQ) was attached to silica beads through amide bond coupling at the carboxyl moiety of 5C8HQ. Attachment of 5C8HQ was confirmed using a combination of mass spectrometry, thermogravimetric analysis, colorimetric testing and Soxhlet extraction. Computational modelling results indicated that this substitution did not compromise the active sites on the molecule, whereas other positions on the ring system could potentially inhibit antimicrobial activity. The antibacterial effect of 8HQ and the 5C8HQ-modified silica complex against Escherichia coli 15597 (ATCC® 25922) and Staphylococcus aureus (ATCC 25923) was evaluated. CONCLUSIONS: The test results show that the immobilized 8HQ continues to exhibit antibacterial activity, however, quantifying the efficacy compared to free 8HQ bears further investigation. The expected antibacterial mechanism requires that the metal chelation site of 8HQ be retained and available after attachment to a surface. The retention of antibacterial activity after surface bonding represents a novel mechanism of action not previously reported. SIGNIFICANCE AND IMPACT OF THE STUDY: Recent changes in regulations due to environmental concerns prompted many companies and organizations to explore antimicrobial treatments that are chemically bound to the product. Chemically bonding biocidal compounds to a surface limits environmental release; however, molecular mechanisms that drive antibacterial activity when compounds are immobilized are limited. The results reported here demonstrate that the 8HQ reactive site retains antibacterial efficacy even after covalent attachment to a surface. This approach supersedes other antimicrobial treatments where the active component is gradually released from the material surface in order to elicit antimicrobial effects. This specific antibacterial activity of bound 8HQ represents a novel mechanism of action not previously reported, and a potential conduit to a new class of bound antimicrobial materials.

Using multiple correspondence analysis to identify behaviour patterns associated with overweight and obesity in Vanuatu adults.

OBJECTIVE: The present study evaluates the use of multiple correspondence analysis (MCA), a type of exploratory factor analysis designed to reduce the dimensionality of large categorical data sets, in identifying behaviours associated with measures of overweight/obesity in Vanuatu, a rapidly modernizing Pacific Island country. DESIGN: Starting with seventy-three true/false questions regarding a variety of behaviours, MCA identified twelve most significantly associated with modernization status and transformed the aggregate binary responses of participants to these twelve questions into a linear scale. Using this scale, individuals were separated into three modernization groups (tertiles) among which measures of body fat were compared and OR for overweight/obesity were computed. SETTING: Vanuatu.ParticipantsNi-Vanuatu adults (n 810) aged 20-85 years. RESULTS: Among individuals in the tertile characterized by positive responses to most of or all the twelve modernization questions, weight and measures of body fat and the likelihood that measures of body fat were above the US 75th percentile were significantly greater compared with individuals in the tertiles characterized by mostly or partly negative responses. CONCLUSIONS: The study indicates that MCA can be used to identify individuals or groups at risk for overweight/obesity, based on answers to simply-put questions. MCA therefore may be useful in areas where obtaining detailed information about modernization status is constrained by time, money or manpower.

Changes in verbal and visuospatial working memory from Grade 1 to Grade 3 of primary school: Population longitudinal study.

BACKGROUND: Adaptive working memory training is being implemented without an adequate understanding of developmental trajectories of working memory. We aimed to quantify from Grade 1 to Grade 3 of primary school (1) changes in verbal and visuospatial working memory and (2) whether low verbal and visuospatial working memory in Grade 1 predicts low working memory in Grade 3. METHOD: The study design includes a population-based longitudinal study of 1,802 children (66% uptake from all 2,747 Grade 1 students) at 44 randomly selected primary schools in Melbourne, Australia. Backwards Digit Recall (verbal working memory) and Mister X (visuospatial working memory) screening measures from the Automated Working Memory Assessment (M = 100; SD = 15) were used to assess Grades 1 and 3 (ages 6-7 and 8-9 years) students. Low working memory was defined as ≥1 standard deviation below the standard score mean. Descriptive statistics addressed Aim 1, and predictive parameters addressed Aim 2. RESULTS: One thousand seventy (59%) of 1802 Grade 1 participants were reassessed in Grade 3. As expected for typically developing children, group mean standard scores were similar in Grades 1 and 3 for verbal, visuospatial, and overall working memory, but group mean raw scores increased markedly. Compared to "not low" children, those classified as having low working memory in Grade 1 showed much larger increases in both standard and raw scores across verbal, visuospatial, and overall working memory. Sensitivity was very low for Grade 1 low working memory predicting Grade 3 low classifications. CONCLUSION: Although mean changes in working memory standard scores between Grades 1 and 3 were minimal, we found that individual development varied widely, with marked natural resolution by Grade 3 in children who initially had low working memory. This may render brain-training interventions ineffective in the early school year ages, particularly if (as population-based programmes usually mandate) selection occurs within a screening paradigm.

Ownership of consumer electronics is associated with measures of adiposity during health transition in Vanuatu.

OBJECTIVE: The Republic of Vanuatu, like many developing nations, is undergoing a rapid health transition. Our previous study identified several behavioral risk factors for the rising prevalence of obesity. Unexpectedly, daily time spent using television and radio was revealed as a protective factor for obesity in 2007. In this study, we sought to explore associations between ownership of consumer electronics (CE) and measures of adiposity in Vanuatu in 2011. METHODS: We surveyed 873 adults from five islands varying in level of economic development. Height, weight, and waist circumferences; triceps, subscapular, and suprailiac skinfolds; and percent body fat by bioelectrical impedance were measured. Ownership of eight types of CE, diet through 24-h dietary recall and leisure-time activity patterns were assessed using a questionnaire. RESULTS: Participants from more developed islands owned more types of CE, and revealed higher measures of adiposity on average as well as higher prevalence of obesity/central obesity. When controlling for demographic factors, and dietary and activity patterns, increased measures of adiposity and risk for obesity/central obesity were associated with ownership of cellphones, music players, televisions, video players, microwaves, and/or refrigerators. Positive correlations between CE ownership and measures of adiposity were mainly observed among men on the two most developed islands. CONCLUSIONS: The results of this study indicate a possible role of CE use in the rising prevalence of obesity and the shift to a sedentary lifestyle in Vanuatu and many other modernizing regions, where prevention efforts including education on healthy use of CE are imperative.

Secular change in adult stature associated with modernization in Vanuatu.

OBJECTIVE: To determine whether: (1) there is a secular increase in adult stature in Vanuatu, and (2) whether adult stature is positively associated with modernization in Vanuatu. METHODS: This study reports on stature measurements collected on 650 adult (age > 17 years) men and women from four islands of varying economic development in Vanuatu. Measurements were collected as part of the Vanuatu Health Transitions Research Project in 2007 and 2011. RESULTS: Stature increased significantly in adults born between the 1940s and 1960s in Vanuatu, before leveling off in those born between the 1970s and 1990s. Adults are significantly taller on Efate, the most modernized island in the study sample, than on the less economically developed islands. CONCLUSIONS: Modernization is likely associated with improvements in child growth in Vanuatu, as assessed by gains in adult stature.

A prescription for sustaining community engagement in malaria elimination on Aneityum Island, Vanuatu: an application of Health Empowerment Theory.

BACKGROUND: Community engagement has contributed to disease control and elimination in many countries. Community engagement in malaria elimination (ME) on Aneityum Island has been sustained since its introduction in the early 1990s. Capacity developed within this population has led to a health empowered community response. Health Empowerment Theory (HET) can account for the innovative community actions and capacity development efforts taken to realize and sustain meaningful changes in well-being. This study used the HET framework to investigate participant perceptions of ME efforts on the island focusing on two HET elements, personal and social-contextual resources. The purpose of this study was to explore the role of empowerment as a critical element of community engagement. METHODS: Six focus group discussions, ten key informant interviews and 17 in-depth interviews were conducted in July 2012 on Aneityum. Both deductive and inductive approaches to qualitative content analysis were used to identify themes, which were condensed, coded and classified based on the HET elements above. RESULTS: Awareness and use of personal and social-contextual resources played an important role in ME efforts. Most participants shared their knowledge to prevent malaria reintroduction. Many participants reported their skills needed for behavioral maintenance, problem-solving or leadership. Participants who perceived a threat took preventive actions even in the dry season. Community leaders focused on second generation capacity development. A local health coalition provided ME services. Members of networks were sources of information and assistance. Face-to-face was the preferred method of communication. Barriers to engagement (e.g., financial difficulties, health literacy issues and underdeveloped infrastructure) were minimized through active collaboration and mutual assistance. CONCLUSIONS: In the community engagement continuum, health empowerment develops incrementally overtime as people gain their knowledge and skills, form coalitions and develop collaborative networks (social capital) to make decisions and take action for change. Community engagement, which facilitates local personal and social-contextual resource development, has potential for ME and multilevel empowerment through community-based capacity development processes. These self-empowered communities have written and will continue to write a 'prescription' for sustaining high levels of engagement.

Impact of modernization on adult body composition on five islands of varying economic development in Vanuatu.

OBJECTIVE: The Republic of Vanuatu, similar to other South Pacific island nations, is undergoing a rapid health transition as a consequence of modernization. The pace of modernization is uneven across Vanuatu's 63 inhabited islands, resulting in differential impacts on overall body composition and prevalence of obesity among islands, and between men and women. In this study, we investigated (1) how modernization impacts body composition between adult male and female Melanesians living on four islands of varying economic development in Vanuatu, and (2) how body composition differs between adult Melanesians and Polynesians living on rural islands in Vanuatu. METHODS: Anthropometric measurements were taken on adult male and female Melanesians aged 18 years and older (n = 839) on the islands of Ambae (rural), Aneityum (rural with tourism), Nguna (rural with urban access), and Efate (urban) in Vanuatu, in addition to Polynesian adults on Futuna (rural). RESULTS: Mean measurements of body mass and fatness, and prevalence of obesity, were greatest on the most modernized islands in our sample, particularly among women. Additionally, differences between men and women became more pronounced on islands that were more modernized. Rural Polynesians on Futuna exhibited greater body mass, adiposity, and prevalence of obesity than rural Melanesians on Ambae. CONCLUSIONS: We conclude that Vanuatu is undergoing an uneven and rapid health transition resulting in increased prevalence of obesity, and that women are at greatest risk for developing obesity-related chronic diseases in urbanized areas in Vanuatu.

Complex polymorphisms in the Plasmodium falciparum multidrug resistance protein 2 gene and its contribution to antimalarial response.

Plasmodium falciparum has the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including the Apicomplexa parasites. P. falciparum genome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters: Pfmrp1, previously associated with decreased parasite drug susceptibility, and the poorly studied Pfmrp2. The role of Pfmrp2 polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of the Pfmrp2 genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found that Pfmrp2 harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identified Pfmrp2 polymorphisms with altered in vitro susceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggested Pfmrp2 polymorphisms modulate the parasite's in vitro response to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association with in vivo parasite clearance. In conclusion, our study reveals that the Pfmrp2 gene is the most diverse ABC transporter known in P. falciparum with a potential role in antimalarial drug resistance.

Determinants of the use of insecticide-treated bed nets on islands of pre- and post-malaria elimination: an application of the health belief model in Vanuatu.

BACKGROUND: Insecticide-treated nets (ITNs) are an integral piece of any malaria elimination strategy, but compliance remains a challenge and determinants of use vary by location and context. The Health Belief Model (HBM) is a tool to explore perceptions and beliefs about malaria and ITN use. Insights from the model can be used to increase coverage to control malaria transmission in island contexts. METHODS: A mixed methods study consisting of a questionnaire and interviews was carried out in July 2012 on two islands of Vanuatu: Ambae Island where malaria transmission continues to occur at low levels, and Aneityum Island, where an elimination programme initiated in 1991 has halted transmission for several years. RESULTS: For most HBM constructs, no significant difference was found in the findings between the two islands: the fear of malaria (99%), severity of malaria (55%), malaria-prevention benefits of ITN use (79%) and willingness to use ITNs (93%). ITN use the previous night on Aneityum (73%) was higher than that on Ambae (68%) though not statistically significant. Results from interviews and group discussions showed that participants on Ambae tended to believe that risk was low due to the perceived absence of malaria, while participants on Aneityum believed that they were still at risk despite the long absence of malaria. On both islands, seasonal variation in perceived risk, thermal discomfort, costs of replacing nets, a lack of money, a lack of nets, nets in poor condition and the inconvenience of hanging had negative influences, while free mass distribution with awareness campaigns and the malaria-prevention benefits had positive influences on ITN use. CONCLUSIONS: The results on Ambae highlight the challenges of motivating communities to engage in elimination efforts when transmission continues to occur, while the results from Aneityum suggest the possibility of continued compliance to malaria elimination efforts given the threat of resurgence. Where a high degree of community engagement is possible, malaria elimination programmes may prove successful.

Placing the maxilla in the most aesthetic sagittal position: validation of several reference lines in relation to the forehead shape.

The ideal sagittal position of the maxilla is highly subjective in orthognathic surgical treatment planning. There is no consensus on an analysis to predict the ideal sagittal position of the maxilla. The objective of this study was to determine the preferred maxillary position in relation to the forehead shape, in the Southern Chinese population. The maxilla position of eight patients was simulated based on Steiner's analysis (SA), glabella vertical (GV), Andrews' Element II (AE2), and the Barcelona reference (BR). The simulations were then used in an electronic survey, where respondents ranked the images for each patient from to 1-4 (most to least attractive). A total of 128 responses were collected from dental professionals and laypersons. The most preferred to the least preferred simulation was as follows (mean rank scores for the male and female patients in parenthesis): BR (males 2.06; females 1.98), GV (males 2.11; females 2.21), SA (males 2.59; females 2.40), and AE2 (males 3.24; females 3.41). There was no significant difference in the results according to the sex, age group, or profession of the respondents. The Barcelona reference and glabella vertical are useful in predicting the ideal maxillary position in patients with a flat forehead, and the Barcelona reference is the most preferred in patients with a rounded forehead.

Urine congophilia associated with preeclampsia does not persist 6-months postpartum.

INTRODUCTION: Preeclampsia is a common hypertensive disorder of pregnancy. Several studies have demonstrated that protein aggregates, detected through urine congophilia, is associated with preeclampsia; however, it has yet to be investigated whether urine congophilia remains postpartum in these women. In this study, we aimed to augment prior studies and determine whether urine congophilia is present postpartum. METHODS: Women were recruited from Lyell McEwin Hospital, South Australia. Urine samples were collected during pregnancy and 6-months postpartum from women with non-preeclampsia pregnancies (n = 48) and women with pregnancies complicated by preeclampsia (n = 42). A Congo Red Dot blot test, total protein and creatinine levels from urine, as well as serum Soluble fms-like tyrosine kinase 1 to placental growth factor ratio (sFlt-1:PlGF), were assessed and correlated. RESULTS: Preeclamptic women exhibited increased urine congophilia (P < 0.01), sFlt-1:PlGF ratio (P < 0.0001) and total protein (P < 0.01) during pregnancy; with a positive correlation between urine congophilia and total protein across the entire cohort (P < 0.0001). Although urine congophilia was no longer detected 6-months postpartum in preeclamptic women, total protein remained elevated (P < 0.05). sFlt-1:PlGF ratio during pregnancy was positively correlated with congophilia across the cohort (P = 0.0007). Serum creatinine was also higher in preeclamptic women during pregnancy (P < 0.001). DISCUSSION: These results support that urine congophilia is significantly elevated in pregnancies complicated with preeclampsia and show that it does not continue postpartum, although larger cohort studies are needed to determine its feasibility as a diagnostic marker.

Phase I PIANO trial-PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416). METHODS: Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m2 every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures. RESULTS: In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased. CONCLUSIONS: The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments.

The origins and genetic distinctiveness of the Chamorros of the Marianas Islands: an mtDNA perspective.

BACKGROUND: Archaeological and linguistic evidence suggests the Marianas Islands were settled around 3,600 years before present (ybp) from Island Southeast Asia (ISEA). Around 1,000 ybp latte stone pillars and the first evidence of rice cultivation appear in the Marianas. Both traditions are absent in the rest of prehistoric Oceania. OBJECTIVE: To examine the genetic origins and postsettlement gene flow of Chamorros of the Marianas Islands. METHODS: To infer the origins of the Chamorros we analyzed ∼360 base pairs of the hypervariable-region 1 (HVS1) of mitochondrial DNA from 105 Chamorros from Guam, Rota, and Saipan, and the complete mitochondrial genome of 32 Guamanian Chamorros, and compared them to lineages from ISEA and neighboring Pacific archipelagoes from the database. RESULTS: Results reveal that 92% of Chamorros belong to haplogroup E, also found in ISEA but rare in Oceania. The two most numerous E lineages were identical to lineages currently found in Indonesia, while the remaining E lineages differed by only one or two mutations and all were unique to the Marianas. Seven percent of the lineages belonged to a single Chamorro-specific lineage within haplogroup B4, common to ISEA as well as Micronesia and Polynesia. CONCLUSIONS: These patterns suggest a small founding population had reached and settled the Marianas from ISEA by 4,000 ybp, and developed unique mutations in isolation. A second migration from ISEA may have arrived around 1,000 ybp, introducing the latte pillars, rice agriculture and the homogeneous minority B4 lineage.

Patterns of childhood and adolescent overweight and obesity during health transition in Vanuatu.

OBJECTIVE: Rapid economic development and subsequent changes in lifestyle and disease burdens ('health transition') is associated with increasing prevalence of obesity among both adults and children. However, because of continued infectious diseases and undernutrition during the early stages of transition, monitoring childhood obesity has not been prioritized in many countries and the scope of the problem is unknown. Therefore we sought to characterize patterns of childhood overweight and obesity in an early transitional area, the South Pacific archipelago of Vanuatu. DESIGN: We completed an anthropometric survey among children from three islands with varying levels of economic development, from rural areas (where adult obesity prevalence is low) to urban areas (where adult obesity prevalence is high). SETTING: The islands of Ambae (rural), Aneityum (rural with tourism) and Efate (urban). SUBJECTS: Boys and girls (n 513) aged 6-17 years. RESULTS: Height-, weight- and BMI-for-age did not vary among islands, and prevalence of overweight/obesity based on BMI was low. However, girls from Aneityum - a rural island where the tourism industry increased rapidly after malaria eradication - had increased central adiposity compared with girls from the other islands. This is contrary to adult patterns, which indicate higher obesity prevalence in urban areas. Multiple factors might contribute, including stunting, biological responses after malaria control, sleeping patterns, diet and physical activity levels. CONCLUSIONS: Measures of central adiposity highlight an emerging obesity risk among girls in Vanuatu. The data highlight the synergistic relationship among infectious diseases, undernutrition and obesity during the early stages of health transition.

Profiles of language development in pre-school children: a longitudinal latent class analysis of data from the Early Language in Victoria Study.

BACKGROUND: Pre-school language impairment is common and greatly reduces educational performance. Population attempts to identify children who would benefit from appropriately timed intervention might be improved by greater knowledge about the typical profiles of language development. Specifically, this could be used to help with the early identification of children who will be impaired on school entry. METHODS: This study applied longitudinal latent class analysis to assessments at 8, 12, 24, 36 and 48 months on 1113 children from a population-based study, in order to identify classes exhibiting distinct communicative developmental profiles. RESULTS: Five substantive classes were identified: Typical, i.e. development in the typical range at each age; Precocious (late), i.e. typical development in infancy followed by high probabilities of precocity from 24 months onwards; Impaired (early), i.e. high probabilities of impairment up to 12 months followed by typical language development thereafter; Impaired (late), i.e. typical development in infancy but impairment from 24 months onwards; Precocious (early), i.e. high probabilities of precocity in early life followed by typical language by 48 months. The entropy statistic (0.84) suggested classes were fairly well defined, although there was a non-trivial degree of uncertainty in classification of children. That half of the Impaired (late) class was expected to have typical language at 4 years and 6% of the numerically large Typical class was expected to be impaired at 4 years illustrates this. Characteristics indicative of social advantage were more commonly found in the classes with improving profiles. CONCLUSIONS: Developmental profiles show that some pre-schoolers' language is characterized by periods of accelerated development, slow development and catch-up growth. Given the uncertainty in classifying children into these profiles, use of this knowledge for identifying children who will be impaired on school entry is not straightforward. The findings do, however, indicate greater need for language enrichment programmes among disadvantaged children.

Inherited and somatic mitochondrial DNA mutations in Guam amyotrophic lateral sclerosis and parkinsonism-dementia.

There is increasing evidence for mitochondrial dysfunction in neurodegenerative disorders, although the exact role of mitochondrial DNA (mtDNA) mutations in this process is unresolved. We investigated inherited and somatic mtDNA substitutions and deletions in Guam amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD). Hypervariable segment 1 sequences of Chamorro mtDNA revealed that the odds ratio of a PD or ALS diagnosis was increased for individuals in the E1 haplogroup while individuals in the E2 haplogroup had decreased odds of an ALS or PD diagnosis. Once the disorders were examined separately, it became evident that PD was responsible for these results. When the entire mitochondrial genome was sequenced for a subset of individuals, the nonsynonymous mutation at nucleotide position 9080, shared by all E2 individuals, resulted in a significantly low odds ratio for a diagnosis of ALS or PD. Private polymorphisms found in transfer and ribosomal RNA regions were found only in ALS and PD patients in the E1 haplogroup. Somatic mtDNA deletions in the entire mtDNA genome were not associated with either ALS or PD. We conclude that mtDNA haplogroup effects may result in mitochondrial dysfunction in Guam PD and reflect Guam population history. Thus it is reasonable to consider Guam ALS and PD as complex disorders with both environmental prerequisites and small genetic effects.

Behavioral changes associated with economic development in the South Pacific: health transition in Vanuatu.

UNLABELLED: Health patterns are changing in developing countries; as diet and activity patterns change with economic development, chronic disease prevalence increases, which is a characteristic of health transition. The islands of Vanuatu (South Pacific) have varying rates of economic development and provide a natural experimental model of health transition. OBJECTIVES: To characterize behavioral changes associated with modernization. METHODS: We surveyed 425 children and 559 adults on three islands varying in degree of economic development. We assessed diet (24-h dietary recall), physical activity (mode of transport, work activities, and recreation), substance use, and other behavioral patterns. RESULTS: Spending patterns and access to Western foods followed modernization gradients in our sample, whereas occupational patterns and ownership of technological goods were poor markers of modernization. With increasing economic development, participants consumed more animal proteins and simple carbohydrates. Physical activity levels were high; most participants were active in gardening, and sports were popular, especially in urban areas. However, urban participants spent more time in sedentary recreation. Men's use of alcohol and tobacco increased with economic development, but we observed marked differences in substance use patterns between two rural islands-one with and one without tourism. CONCLUSIONS: Economic development in Vanuatu is accompanied by nutrition transition and increased sedentary recreation, although physical activity levels remain high. Differences in substance use patterns between rural islands with and without tourism indicate a need for more research in rural areas. These findings might inform research in other communities in the early stages of health transition.

Unusual metastatic presentations of a primary right parapharyngeal acinic cell adenocarcinoma.

Acinic cell adenocarcinoma (ACA) is a malignant epithelial neoplasm of the salivary glands. The patient reported herein presented with an unusual case of a metastatic ACA originating from the right parapharyngeal region, which eventually metastasized to the ipsilateral cavernous sinus and the contralateral mandibular ramus. The trigeminal nerve may have served as a channel for the spread of the cancer from the right parapharyngeal region to the cavernous sinus, and subsequently to the left mandibular ramus. The widening of the left inferior alveolar nerve canal was an early sign of metastasis in this case.

Origins of the Moken Sea Gypsies inferred from mitochondrial hypervariable region and whole genome sequences.

The origins of the Moken 'Sea Gypsies,' a group of traditionally boat-dwelling nomadic foragers, remain speculative despite previous examinations from linguistic, sociocultural and genetic perspectives. We explored Moken origin(s) and affinities by comparing whole mitochondrial genome and hypervariable segment I sequences from 12 Moken individuals, sampled from four islands of the Mergui Archipelago, to other mainland Asian, Island Southeast Asian (ISEA) and Oceanic populations. These analyses revealed a major (11/12) and a minor (1/12) haplotype in the population, indicating low mitochondrial diversity likely resulting from historically low population sizes, isolation and consequent genetic drift. Phylogenetic analyses revealed close relationships between the major lineage (MKN1) and ISEA, mainland Asian and aboriginal Malay populations, and of the minor lineage (MKN2) to populations from ISEA. MKN1 belongs to a recently defined subclade of the ancient yet localized M21 haplogroup. MKN2 is not closely related to any previously sampled lineages, but has been tentatively assigned to the basal M46 haplogroup that possibly originated among the original inhabitants of ISEA. Our analyses suggest that MKN1 originated within coastal mainland SEA and dispersed into ISEA and rapidly into the Mergui Archipelago within the past few thousand years as a result of climate change induced population pressure.