Khon Kaen University

BACKGROUND: Preterm birth is the leading cause of death in children younger than 5 years worldwide. Although preterm survival rates have increased in high-income countries, preterm newborns still die because of a lack of adequate newborn care in many low-income and middle-income countries. We estimated global, regional, and national rates of preterm birth in 2014, with trends over time for some selected countries. METHODS: We systematically searched for data on preterm birth for 194 WHO Member States from 1990 to 2014 in databases of national civil registration and vital statistics (CRVS). We also searched for population-representative surveys and research studies for countries with no or limited CRVS data. For 38 countries with high-quality data for preterm births in 2014, data are reported directly. For countries with at least three data points between 1990 and 2014, we used a linear mixed regression model to estimate preterm birth rates. We also calculated regional and global estimates of preterm birth for 2014. FINDINGS: We identified 1241 data points across 107 countries. The estimated global preterm birth rate for 2014 was 10·6% (uncertainty interval 9·0-12·0), equating to an estimated 14·84 million (12·65 million-16·73 million) live preterm births in 2014. 12· 0 million (81·1%) of these preterm births occurred in Asia and sub-Saharan Africa. Regional preterm birth rates for 2014 ranged from 13·4% (6·3-30·9) in North Africa to 8·7% (6·3-13·3) in Europe. India, China, Nigeria, Bangladesh, and Indonesia accounted for 57·9 million (41×4%) of 139·9 million livebirths and 6·6 million (44×6%) of preterm births globally in 2014. Of the 38 countries with high-quality data, preterm birth rates have increased since 2000 in 26 countries and decreased in 12 countries. Globally, we estimated that the preterm birth rate was 9×8% (8×3-10×9) in 2000, and 10×6% (9×0-12×0) in 2014. INTERPRETATION: Preterm birth remains a crucial issue in child mortality and improving quality of maternal and newborn care. To better understand the epidemiology of preterm birth, the quality and volume of data needs to be improved, including standardisation of definitions, measurement, and reporting. FUNDING: WHO and the March of Dimes.

RATIONALE: This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A two-step approach for the malnutrition diagnosis was selected, i.e., first screening to identify "at risk" status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSION: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re-considered every 3-5 years.

BACKGROUND: This initiative aims to build a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: The Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A 2-step approach for the malnutrition diagnosis was selected, that is, first screening to identify at risk status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among GLIM participants that selected 3 phenotypic criteria (non-volitional weight loss, low body mass index, and reduced muscle mass) and 2 etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least 1 phenotypic criterion and 1 etiologic criterion should be present. Phenotypic metrics for grading severity are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSIONS: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The construct should be re-considered every 3-5 years.

BACKGROUND: A single, high priming dose of tremelimumab (anti-cytotoxic T lymphocyte–associated antigen 4) plus durvalumab (anti–programmed cell death ligand-1), an infusion regimen termed STRIDE (Single Tremelimumab Regular Interval Durvalumab), showed encouraging clinical activity and safety in a phase 2 trial of unresectable hepatocellular carcinoma. METHODS: In this global, open-label, phase 3 trial, the majority of the patients we enrolled with unresectable hepatocellular carcinoma and no previous systemic treatment were randomly assigned to receive one of three regimens: tremelimumab (300 mg, one dose) plus durvalumab (1500 mg every 4 weeks; STRIDE), durvalumab (1500 mg every 4 weeks), or sorafenib (400 mg twice daily). The primary objective was overall survival for STRIDE versus sorafenib. Noninferiority for overall survival for durvalumab versus sorafenib was a secondary objective. RESULTS: In total, 1171 patients were randomly assigned to STRIDE (n=393), durvalumab (n=389), or sorafenib (n=389). The median overall survival was 16.43 months (95% confidence interval [CI], 14.16 to 19.58) with STRIDE, 16.56 months (95% CI, 14.06 to 19.12) with durvalumab, and 13.77 months (95% CI, 12.25 to 16.13) with sorafenib. Overall survival at 36 months was 30.7%, 24.7%, and 20.2%, respectively. The overall survival hazard ratio for STRIDE versus sorafenib was 0.78 (96.02% CI, 0.65 to 0.93; P=0.0035). Overall survival with durvalumab monotherapy was noninferior to sorafenib (hazard ratio, 0.86; 95.67% CI, 0.73 to 1.03; noninferiority margin, 1.08). Median progression-free survival was not significantly different among all three groups. Grade 3/4 treatment-emergent adverse events occurred for 50.5% of patients with STRIDE, 37.1% with durvalumab, and 52.4% with sorafenib. CONCLUSIONS: STRIDE significantly improved overall survival versus sorafenib. Durvalumab monotherapy was noninferior to sorafenib for patients with unresectable hepatocellular carcinoma. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03298451.)

Abstract Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters—fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3′ untranslated region deletion as a mechanism of FGFR2 upregulation. Integration of noncoding promoter mutations with protein–DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores—mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics, and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer. Significance: Integrated whole-genome and epigenomic analysis of CCA on an international scale identifies new CCA driver genes, noncoding promoter mutations, and structural variants. CCA molecular landscapes differ radically by etiology, underscoring how distinct cancer subtypes in the same organ may arise through different extrinsic and intrinsic carcinogenic processes. Cancer Discov; 7(10); 1116–35. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1047

OBJECTIVE: To investigate the risk of adverse pregnancy outcomes among adolescents in 29 countries. DESIGN: Secondary analysis using facility-based cross-sectional data of the World Health Organization Multicountry Survey on Maternal and Newborn Health. SETTING: Twenty-nine countries in Africa, Latin America, Asia and the Middle East. POPULATION: Women admitted for delivery in 359 health facilities during 2-4 months between 2010 and 2011. METHODS: Multilevel logistic regression models were used to estimate the association between young maternal age and adverse pregnancy outcomes. MAIN OUTCOME MEASURES: Risk of adverse pregnancy outcomes among adolescent mothers. RESULTS: A total of 124 446 mothers aged ≤24 years and their infants were analysed. Compared with mothers aged 20-24 years, adolescent mothers aged 10-19 years had higher risks of eclampsia, puerperal endometritis, systemic infections, low birthweight, preterm delivery and severe neonatal conditions. The increased risk of intra-hospital early neonatal death among infants born to adolescent mothers was reduced and statistically insignificant after adjustment for gestational age and birthweight, in addition to maternal characteristics, mode of delivery and congenital malformation. The coverage of prophylactic uterotonics, prophylactic antibiotics for caesarean section and antenatal corticosteroids for preterm delivery at 26-34 weeks was significantly lower among adolescent mothers. CONCLUSIONS: Adolescent pregnancy was associated with higher risks of adverse pregnancy outcomes. Pregnancy prevention strategies and the improvement of healthcare interventions are crucial to reduce adverse pregnancy outcomes among adolescent women in low- and middle-income countries.

Cholangiocarcinoma (CCA) is a highly lethal adenocarcinoma of the hepatobiliary system, which can be classified as intrahepatic, perihilar and distal. Each anatomic subtype has distinct genetic aberrations, clinical presentations and therapeutic approaches. In endemic regions, liver fluke infection is associated with CCA, owing to the oncogenic effect of the associated chronic biliary tract inflammation. In other regions, CCA can be associated with chronic biliary tract inflammation owing to choledocholithiasis, cholelithiasis, or primary sclerosing cholangitis, but most CCAs have no identifiable cause. Administration of the anthelmintic drug praziquantel decreases the risk of CCA from liver flukes, but reinfection is common and future vaccination strategies may be more effective. Some patients with CCA are eligible for potentially curative surgical options, such as resection or liver transplantation. Genetic studies have provided new insights into the pathogenesis of CCA, and two aberrations that drive the pathogenesis of non-fluke-associated intrahepatic CCA, fibroblast growth factor receptor 2 fusions and isocitrate dehydrogenase gain-of-function mutations, can be therapeutically targeted. CCA is a highly desmoplastic cancer and targeting the tumour immune microenvironment might be a promising therapeutic approach. CCA remains a highly lethal disease and further scientific and clinical insights are needed to improve patient outcomes. Cholangiocarcinoma is a highly lethal adenocarcinoma of the hepatobiliary system that can be associated with liver fluke infection but often has no identifiable cause. This Primer reviews the epidemiology, pathophysiological mechanisms, diagnosis and management of cholangiocarcinoma, and highlights the patient experience and future directions.

ISSN:0035-9203

BACKGROUND: Foodborne diseases are globally important, resulting in considerable morbidity and mortality. Parasitic diseases often result in high burdens of disease in low and middle income countries and are frequently transmitted to humans via contaminated food. This study presents the first estimates of the global and regional human disease burden of 10 helminth diseases and toxoplasmosis that may be attributed to contaminated food. METHODS AND FINDINGS: Data were abstracted from 16 systematic reviews or similar studies published between 2010 and 2015; from 5 disease data bases accessed in 2015; and from 79 reports, 73 of which have been published since 2000, 4 published between 1995 and 2000 and 2 published in 1986 and 1981. These included reports from national surveillance systems, journal articles, and national estimates of foodborne diseases. These data were used to estimate the number of infections, sequelae, deaths, and Disability Adjusted Life Years (DALYs), by age and region for 2010. These parasitic diseases, resulted in 48.4 million cases (95% Uncertainty intervals [UI] of 43.4-79.0 million) and 59,724 (95% UI 48,017-83,616) deaths annually resulting in 8.78 million (95% UI 7.62-12.51 million) DALYs. We estimated that 48% (95% UI 38%-56%) of cases of these parasitic diseases were foodborne, resulting in 76% (95% UI 65%-81%) of the DALYs attributable to these diseases. Overall, foodborne parasitic disease, excluding enteric protozoa, caused an estimated 23.2 million (95% UI 18.2-38.1 million) cases and 45,927 (95% UI 34,763-59,933) deaths annually resulting in an estimated 6.64 million (95% UI 5.61-8.41 million) DALYs. Foodborne Ascaris infection (12.3 million cases, 95% UI 8.29-22.0 million) and foodborne toxoplasmosis (10.3 million cases, 95% UI 7.40-14.9 million) were the most common foodborne parasitic diseases. Human cysticercosis with 2.78 million DALYs (95% UI 2.14-3.61 million), foodborne trematodosis with 2.02 million DALYs (95% UI 1.65-2.48 million) and foodborne toxoplasmosis with 825,000 DALYs (95% UI 561,000-1.26 million) resulted in the highest burdens in terms of DALYs, mainly due to years lived with disability. Foodborne enteric protozoa, reported elsewhere, resulted in an additional 67.2 million illnesses or 492,000 DALYs. Major limitations of our study include often substantial data gaps that had to be filled by imputation and suffer from the uncertainties that surround such models. Due to resource limitations it was also not possible to consider all potentially foodborne parasites (for example Trypanosoma cruzi). CONCLUSIONS: Parasites are frequently transmitted to humans through contaminated food. These estimates represent an important step forward in understanding the impact of foodborne diseases globally and regionally. The disease burden due to most foodborne parasites is highly focal and results in significant morbidity and mortality among vulnerable populations.

The authors discuss the molecular pathogenesis of opisthorchiasis and associated cholangiocarcinogenesis, particularly nitrative and oxidative DNA damage and the clinical manifestations of cholangiocarcinoma.

Studies of L2 writing development usually measure T‐units and clausal subordination to assess grammatical complexity, assuming that increased subordination is typical of advanced writing. In this article we challenge this practice by showing that these measures are much more characteristic of conversation than academic writing. The article begins with a critical evaluation of T‐units and clausal subordination as measures of writing development, arguing that they have not proven to be effective discriminators of language proficiency differences. These shortcomings lead to the question of whether these measures actually capture the complexities of professional academic writing, and if not, what alternative measures are better suited? Corpus‐based analyses are undertaken to answer these questions, investigating 28 grammatical features in research articles contrasted with conversation. The results are surprising, showing that most clausal subordination measures are actually more common in conversation than academic writing. In contrast, fundamentally different kinds of grammatical complexity are common in academic writing: complex noun phrase constituents (rather than clause constituents) and complex phrases (rather than clauses). Based on these findings, we hypothesize a sequence of developmental stages for student writing, proposing a radically new approach for the study of complexity in student writing development.

BACKGROUND: There is worldwide debate about the appropriateness of caesarean sections performed without medical indications. In this analysis, we aim to further investigate the relationship between caesarean section without medical indication and severe maternal outcomes. METHODS: This is a multicountry, facility-based survey that used a stratified multistage cluster sampling design to obtain a sample of countries and health institutions worldwide. A total of 24 countries and 373 health facilities participated in this study. Data collection took place during 2004 and 2005 in Africa and the Americas and during 2007 and 2008 in Asia. All women giving birth at the facility during the study period were included and had their medical records reviewed before discharge from the hospital. Univariate and multilevel analysis were performed to study the association between each group's mode of delivery and the severe maternal and perinatal outcome. RESULTS: A total of 286,565 deliveries were analysed. The overall caesarean section rate was 25.7% and a total of 1.0 percent of all deliveries were caesarean sections without medical indications, either due to maternal request or in the absence of other recorded indications. Compared to spontaneous vaginal delivery, all other modes of delivery presented an association with the increased risk of death, admission to ICU, blood transfusion and hysterectomy, including antepartum caesarean section without medical indications (Adjusted Odds Ratio (Adj OR), 5.93, 95% Confidence Interval (95% CI), 3.88 to 9.05) and intrapartum caesarean section without medical indications (Adj OR, 14.29, 95% CI, 10.91 to 18.72). In addition, this association is stronger in Africa, compared to Asia and Latin America. CONCLUSIONS: Caesarean sections were associated with an intrinsic risk of increased severe maternal outcomes. We conclude that caesarean sections should be performed when a clear benefit is anticipated, a benefit that might compensate for the higher costs and additional risks associated with this operation.

Lung function in chronic obstructive pulmonary disease (COPD) can be improved acutely by oral corticosteroids and bronchodilators. Whether clinical improvement can be maintained by subsequent inhaled therapy is unknown. COPD patients (n=1,022, mean prebronchodilator forced expiratory volume in one second (FEV1) 36% predicted) initially received formoterol (9 microg b.i.d.) and oral prednisolone (30 mg o.d.) for 2 weeks. After this time, patients were randomised to b.i.d. inhaled budesonide/formoterol 320/9 microg, budesonide 400 microg, formoterol 9 microg or placebo for 12 months. Postmedication FEV1 improved by 0.21 L and health-related quality of life using the St George's Respiratory Questionnaire (SGRQ) by 4.5 units after run-in. Fewer patients receiving budesonide/formoterol withdrew from the study than those receiving budesonide, formoterol or placebo. Budesonide/formoterol patients had a prolonged time to first exacerbation (254 versus 96 days) and maintained higher FEV1 (99% versus 87% of baseline), both primary variables versus placebo. They had fewer exacerbations (1.38 versus 1.80 exacerbations per patient per year), had higher prebronchodilator peak expiratory flow, and showed clinically relevant improvements in SGRQ versus placebo (-7.5 units). Budesonide/formoterol was more effective than either monocomponent in both primary variables. Budesonide/formoterol in a single inhaler (Symbicort) maintains the benefit of treatment optimisation, stabilising lung function and delaying exacerbations more effectively than either component drug alone or placebo.

BACKGROUND: Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use. METHODS AND FINDINGS: We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown-rump length measured at 8-13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25-31), median height was 162 cm (IQR 157-168), median weight was 61 kg (IQR 55-68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487-2,222). The median pregnancy duration was 39 wk (IQR 38-40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8-16). The median birthweight was 3,300 g (IQR 2,980-3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts. CONCLUSIONS: This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world.

Abstract Application of nanomaterials for agriculture is relatively new as compared to their use in biomedical and industrial sectors. In order to promote sustainable nanoagriculture, biocompatible silver nanoparticles (AgNPs) have been synthesized through green route using kaffir lime leaf extract for use as nanopriming agent for enhancing seed germination of rice aged seeds. Results of various characterization techniques showed the successful formation of AgNPs which were capped with phytochemicals present in the plant extract. Rice aged seeds primed with phytosynthesized AgNPs at 5 and 10 ppm significantly improved germination performance and seedling vigor compared to unprimed control, AgNO 3 priming, and conventional hydropriming. Nanopriming could enhance α-amylase activity, resulting in higher soluble sugar content for supporting seedlings growth. Furthermore, nanopriming stimulated the up-regulation of aquaporin genes in germinating seeds. Meanwhile, more ROS production was observed in germinating seeds of nanopriming treatment compared to unprimed control and other priming treatments, suggesting that both ROS and aquaporins play important roles in enhancing seed germination. Different mechanisms underlying nanopriming-induced seed germination were proposed, including creation of nanopores for enhanced water uptake, rebooting ROS/antioxidant systems in seeds, generation of hydroxyl radicals for cell wall loosening, and nanocatalyst for fastening starch hydrolysis.

ABSTRACT Thirty-one articles on community forestry, encompassing 69 case studies worldwide, were reviewed for systematic data synthesis and hypothesis testing. The meta-study identifies 43 independent variables ranging from internal attributes of the community and resources to external factors. Variables with significant influence on the success of community forestry are tenure security, clear ownership, congruence between biophysical and socioeconomic boundaries of the resources, effective enforcement of rules and regulations, monitoring, sanctioning, strong leadership with capable local organization, expectation of benefits, common interests among community members, and local authority. These variables illustrate community–forest relationships, community ability to organize and continue collective activities, and protection of benefits, rights, and responsibilities in common resource management.

BACKGROUND: This is an update of a Cochrane review first published in 2012, Issue 4. Excessive weight gain during pregnancy is associated with poor maternal and neonatal outcomes including gestational diabetes, hypertension, caesarean section, macrosomia, and stillbirth. Diet or exercise interventions, or both, may reduce excessive gestational weight gain (GWG) and associated poor outcomes; however, evidence from the original review was inconclusive. OBJECTIVES: To evaluate the effectiveness of diet or exercise, or both, interventions for preventing excessive weight gain during pregnancy and associated pregnancy complications. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (5 November 2014), contacted investigators of the previously identified ongoing studies and scanned reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of diet or exercise, or both, interventions for preventing excessive weight gain in pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We organised RCTs according to the type of interventions and pooled data using the random-effects model in the Review Manager software. We also performed subgroup analyses according to the initial risk of adverse effects related to poor weight control. We performed sensitivity analysis to assess the robustness of the findings. MAIN RESULTS: We included 65 RCTs, out of which 49 RCTs involving 11,444 women contributed data to quantitative meta-analysis. Twenty studies were at moderate-to-high risk of bias. Study interventions involved mainly diet only, exercise only, and combined diet and exercise interventions, usually compared with standard care. Study methods varied widely; therefore, we estimated the average effect across studies and performed sensitivity analysis, where appropriate, by excluding outliers and studies at high risk of bias.Diet or exercise, or both, interventions reduced the risk of excessive GWG on average by 20% overall (average risk ratio (RR) 0.80, 95% confidence interval (CI) 0.73 to 0.87; participants = 7096; studies = 24; I² = 52%). This estimate was robust to sensitivity analysis, which reduced heterogeneity, therefore we graded this evidence as high-quality. Interventions involving low glycaemic load diets, supervised or unsupervised exercise only, or diet and exercise combined all led to similar reductions in the number of women gaining excessive weight in pregnancy.Women receiving diet or exercise, or both interventions were more likely to experience low GWG than those in control groups (average RR 1.14, 95% CI 1.02 to 1.27; participants = 4422; studies = 11; I² = 3%; moderate-quality evidence). We found no difference between intervention and control groups with regard to pre-eclampsia (RR 0.95, 95% CI 0.77 to 1.16; participants = 5330; studies = 15; I² = 0%; high-quality evidence); however, maternal hypertension (not a pre-specified outcome) was reduced in the intervention group compared with the control group overall (average RR 0.70, 95% CI 0.51 to 0.96; participants = 5162; studies = 11; I² = 43%; low-quality evidence).There was no clear difference between groups with regard to caesarean delivery overall (RR 0.95, 95% CI 0.88 to 1.03; participants = 7534; studies = 28; I² = 9%; high-quality evidence); although the effect estimate suggested a small difference (5%) in favour of the interventions. In addition, for combined diet and exercise counselling interventions there was a 13% (-1% to 25%) reduction in this outcome (borderline statistical significance).We found no difference between groups with regard to preterm birth overall (average RR 0.91, 95% CI 0.68 to 1.22; participants = 5923; studies = 16; I² = 16%; moderate-quality evidence); however limited evidence suggested that these effect estimates may differ according to the types of interventions, with a trend towards an increased risk for exercise-only interventions.We found no clear difference between intervention and control groups with regard to infant macrosomia (average RR 0.93, 95% CI 0.86 to 1.02; participants = 8598; studies = 27; I² = 0%; high-quality evidence), although the effect estimate suggested a small difference (7% reduction) in favour of the intervention group. The largest effect size occurred in the supervised exercise-only intervention group (RR 0.81, 95% CI 0.64 to 1.02; participants = 2445; studies = 7; I² = 0%), which approached statistical significance (P = 0.07). Furthermore, in subgroup analysis by risk, high-risk women (overweight or obese women, or women with or at risk of gestational diabetes) receiving combined diet and exercise counselling interventions experienced a 15% reduced risk of infant macrosomia (average RR 0.85, 95% CI 0.73 to 1.00; participants = 3252; studies = nine; I² = 0; P = 0.05; moderate-quality evidence)There were no differences in the risk of poor neonatal outcomes including shoulder dystocia, neonatal hypoglycaemia, hyperbilirubinaemia, or birth trauma (all moderate-quality evidence) between intervention and control groups; however, infants of high-risk women had a reduced risk of respiratory distress syndrome if their mothers were in the intervention group (RR 0.47, 95% CI 0.26 to 0.85; participants = 2256; studies = two; I² = 0%; moderate-quality evidence). AUTHORS' CONCLUSIONS: High-quality evidence indicates that diet or exercise, or both, during pregnancy can reduce the risk of excessive GWG. Other benefits may include a lower risk of caesarean delivery, macrosomia, and neonatal respiratory morbidity, particularly for high-risk women receiving combined diet and exercise interventions. Maternal hypertension may also be reduced. Exercise appears to be an important part of controlling weight gain in pregnancy and more research is needed to establish safe guidelines. Most included studies were carried out in developed countries and it is not clear whether these results are widely applicable to lower income settings.

Immunoassays are antibody-based analytical methods for quantitative/qualitative analysis. Since the principle of immunoassays is based on specific antigen-antibody reaction, the assays have been utilized worldwide for diagnosis, pharmacokinetic studies by drug monitoring, and the quality control of commercially available products. Berson and Yalow were the first to develop an immunoassay, known as radioimmunoassay (RIA), for detecting endogenous plasma insulin [1], a development for which Yalow was awarded the Nobel Prize in Physiology or Medicine in 1977. Even today, after half a century, immunoassays are widely utilized with some modifications from the originally proposed system, e.g., radioisotopes have been replaced with enzymes because of safety concerns regarding the use of radioactivity, which is referred to as enzyme immunoassay/enzyme-linked immunosorbent assay (ELISA). In addition, progress has been made in ELISA with the recent advances in recombinant DNA technology, leading to increase in the range of antibodies, probes, and even systems. This review article describes ELISA and its applications for the detection of plant secondary metabolites.

BACKGROUND: Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown. METHODS: We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained. RESULTS: Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering. CONCLUSIONS: Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.).

PURPOSE OF REVIEW: To present the background of liver fluke-associated cholangiocarcinoma in Thailand focusing on recent epidemiological data and pathogenesis of this bile duct cancer. RECENT FINDINGS: More systematic tumor registration in Thailand nowadays uncovers new high-incidence areas that are confined to not only the northeastern part but also some provinces in northern Thailand. The link between the liver fluke, Opisthorchis viverrini, and cholangiocarcinoma, particularly in terms of cellular and molecular pathogenesis, is further elucidated. SUMMARY: Thailand is still the country with the highest incidence of cholangiocarcinoma in the world. Liver fluke induces chronic inflammation leading to oxidative DNA damage of the infected biliary epithelium and malignant transformation. Eradication of the fluke and identification of high-risk populations are urgently needed.