Effects of drying conditions on drying kinetics, product quality and retention of carpaine in papaya leaves (Carica papaya Linn.)

Dengue fever causes mortality and morbidity worldwide which is a major concern to governments and the World Health Organization (WHO). It was reported that carpaine, the major active compound extracted from papaya leaves, contributes to the anti-thrombocytopenic activity. Hence, carpaine plays an important role in treating dengue patients by raising the platelet count in the patients’ blood. However, carpaine in papaya leaves could degrade easily when exposed to heat and sunlight during processing and storage. There is no literature reporting on the processing aspects (e.g., preparation, drying and storage) of papaya leaves and the leaves extract to date. This could possibly be due to papaya leaves have no commercial value and the leaves are usually treated as waste. Therefore, this thesis will focus on the effects of drying conditions on drying kinetics, product quality and retention of carpaine in papaya leaves. Extraction and quantification of carpaine from different parts of papaya leaves (young and old) and stalks were carried out. Pale yellow carpaine crystalline powders were successfully extracted and confirmed to have high purity (>95%) by 1H and 13C NMR analyses. Unblended freeze dried samples from young papaya leaves extract showed the highest amount of carpaine, total polyphenol content and DPPH free radical scavenging activities. It is thus recommended to use young leaves to extract carpaine for future drug development in dengue treatment. The drying kinetics and drying rates of papaya leaves using different drying techniques such as hot air drying (60°C, 70°C and 80°C), shade drying and freeze drying were investigated. Typical exponential falling trends were observed, which can be best explained by Fick’s second law of diffusion. The fastest drying rate was observed at high temperature (80°C), followed by at lower temperatures (hot air drying at 60°C and 70°C, and shade drying at averagely 27°C). By using the general solution of Fick’s second law and Arrhenius equation, the effective diffusivities were determined in the range of 2.09 × 10-12 m2/s to 2.18 × 10-12 m2/s, and the activation energy required to initiate moisture diffusion was determined at 2.11 kJ/mol in hot air drying within 60°C to 80°C. Besides, the effects of drying techniques on carpaine retention and antioxidant properties of papaya leaves were investigated to develop a preparation protocol that produces papaya leaves extract with high carpaine retention. Hot air drying at 60°C, 70°C and 80°C are not recommended for the preservation of carpaine in papaya leaves as carpaine is a heat sensitive bioactive compound. Results showed that the carpaine retention in hot air dried samples were significantly lower (p<0.05) than freeze dried and shade dried samples. It is recommended to use freeze drying to remove the moisture in the papaya leaves as it showed the highest retention of carpaine and antioxidant activities. The knowledge on the stability of carpaine during storage is vital as the raw materials used would be mainly in dried form which will be stored in bulk quantity during commercial operation. Studies show that the Weibull model produced the best graphical fit in describing the degradation kinetics of carpaine in all dried samples (freeze dried samples, hot air dried samples at 60°C and 70°C, and shade dried samples), except for hot air dried samples at 80°C, which could be best described by the first order model. Freeze dried samples showed the highest half-life (51.20 months) among all the dried samples. It is thus recommended to select freeze dried samples for extended storage purpose as it is more stable as indicated by the lowest rate constant and the highest half-life

Effects of drying conditions on drying kinetics, product quality and retention of carpaine in papaya leaves (Carica papaya Linn.)

Dengue fever causes mortality and morbidity worldwide which is a major concern to governments and the World Health Organization (WHO). It was reported that carpaine, the major active compound extracted from papaya leaves, contributes to the anti-thrombocytopenic activity. Hence, carpaine plays an important role in treating dengue patients by raising the platelet count in the patients’ blood. However, carpaine in papaya leaves could degrade easily when exposed to heat and sunlight during processing and storage. There is no literature reporting on the processing aspects (e.g., preparation, drying and storage) of papaya leaves and the leaves extract to date. This could possibly be due to papaya leaves have no commercial value and the leaves are usually treated as waste. Therefore, this thesis will focus on the effects of drying conditions on drying kinetics, product quality and retention of carpaine in papaya leaves. Extraction and quantification of carpaine from different parts of papaya leaves (young and old) and stalks were carried out. Pale yellow carpaine crystalline powders were successfully extracted and confirmed to have high purity (>95%) by 1H and 13C NMR analyses. Unblended freeze dried samples from young papaya leaves extract showed the highest amount of carpaine, total polyphenol content and DPPH free radical scavenging activities. It is thus recommended to use young leaves to extract carpaine for future drug development in dengue treatment. The drying kinetics and drying rates of papaya leaves using different drying techniques such as hot air drying (60°C, 70°C and 80°C), shade drying and freeze drying were investigated. Typical exponential falling trends were observed, which can be best explained by Fick’s second law of diffusion. The fastest drying rate was observed at high temperature (80°C), followed by at lower temperatures (hot air drying at 60°C and 70°C, and shade drying at averagely 27°C). By using the general solution of Fick’s second law and Arrhenius equation, the effective diffusivities were determined in the range of 2.09 × 10-12 m2/s to 2.18 × 10-12 m2/s, and the activation energy required to initiate moisture diffusion was determined at 2.11 kJ/mol in hot air drying within 60°C to 80°C. Besides, the effects of drying techniques on carpaine retention and antioxidant properties of papaya leaves were investigated to develop a preparation protocol that produces papaya leaves extract with high carpaine retention. Hot air drying at 60°C, 70°C and 80°C are not recommended for the preservation of carpaine in papaya leaves as carpaine is a heat sensitive bioactive compound. Results showed that the carpaine retention in hot air dried samples were significantly lower (p<0.05) than freeze dried and shade dried samples. It is recommended to use freeze drying to remove the moisture in the papaya leaves as it showed the highest retention of carpaine and antioxidant activities. The knowledge on the stability of carpaine during storage is vital as the raw materials used would be mainly in dried form which will be stored in bulk quantity during commercial operation. Studies show that the Weibull model produced the best graphical fit in describing the degradation kinetics of carpaine in all dried samples (freeze dried samples, hot air dried samples at 60°C and 70°C, and shade dried samples), except for hot air dried samples at 80°C, which could be best described by the first order model. Freeze dried samples showed the highest half-life (51.20 months) among all the dried samples. It is thus recommended to select freeze dried samples for extended storage purpose as it is more stable as indicated by the lowest rate constant and the highest half-life

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology

Structure-Based High-Throughput Epitope Analysis of Hexon Proteins in B and C Species Human Adenoviruses (HAdVs)

Human adenoviruses (HAdVs) are the etiologic agent of many human infectious diseases. The existence of at least 54 different serotypes of HAdVs has resulted in difficulties in clinical diagnosis. Acute respiratory tract disease (ARD) caused by some serotypes from B and C species is particularly serious. Hexon, the main coat protein of HAdV, contains the major serotype-specific B cell epitopes; however, few studies have addressed epitope mapping in most HAdV serotypes. In this study, we utilized a novel and rapid method for the modeling of homologous proteins based on the phylogenetic tree of protein families and built three-dimensional (3D) models of hexon proteins in B and C species HAdVs. Based on refined hexon structures, we used reverse evolutionary trace (RET) bioinformatics analysis combined with a specially designed hexon epitope screening algorithm to achieve high-throughput epitope mapping of all 13 hexon proteins in B and C species HAdVs. This study has demonstrated that all of the epitopes from the 13 hexon proteins are located in the proteins' tower regions; however, the exact number, location, and size of the epitopes differ among the HAdV serotypes

Association of maternal Vitamin D status with glucose tolerance and caesarean section in a multi-ethnic Asian cohort: the growing up in Singapore towards healthy outcomes study

10.1371/journal.pone.0142239PLoS ONE10111-16GUSTO (Growing up towards Healthy Outcomes

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia : The CREAM Consortium

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).Peer reviewe