Hodgkin's lymphoma and its association with EBV and HIV infection.

Hodgkin's lymphoma (HL) constitutes a clonal expansion of what appears to be malignant B cells. Viruses are involved in its pathogenesis, such as the Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Since these viral infections have been shown to play key roles in the pathogenesis of HL, countries with a prevalence of HIV and EBV represent interesting population targets to study the pathogenesis of HL, linking the evolution of the disease with viral infections. Usually, patients present with late stage disease often involving the bone marrow at the time of diagnosis. The present paper discusses the role of viral infection in African countries, as HL is considered to be a malignant disease characterized by an inflammatory reaction to an aberrant B cell clone that is well known as the Reed-Sternberg cell (HRS).

Determinants of eating at local and western fast-food venues in an urban Asian population: a mixed methods approach.

BACKGROUND: Like several Southeast Asian countries, Singapore has a complex eating-out environment and a rising eating-out prevalence. However the determinants and drivers of eating-out in urban Asian environments are poorly understood. METHODS: We examined the socio-demographic characteristics of persons who frequently ate away from home in local eateries called hawker centres and Western fast-food restaurants, using data from 1647 Singaporean adults participating in the National Nutrition Survey (NNS) 2010. We also assessed the underlying drivers of eating out and evaluated if these were different for eating at local eateries compared to Western fast-food restaurants using 18 focus group discussions of women (130 women). RESULTS: Participants reported a high eating-out frequency with 77.3% usually eating either breakfast, lunch or dinner at eateries. Main venues for eating-out included hawker centres (61.1% usually ate at least 1 of 3 daily meals at this venue) and school/workplace canteens (20.4%). A minority of participants (1.9%) reported usually eating at Western fast-food restaurants. Younger participants and those of Chinese and Malay ethnicity compared to Indians were more likely to eat at Western fast-food restaurants. Chinese and employed persons were more likely to eat at hawker centres. The ready availability of a large variety of affordable and appealing foods appeared to be a primary driver of eating out, particularly at hawker centres. CONCLUSIONS: Our findings highlight the growing importance of eating-out in an urban Asian population where local eating venues play a more dominant role compared with Western fast-food chains. Interventions focusing on improving the food quality at venues for eating out are important to improve the diet of urban Asian populations.

The Alternative Healthy Eating Index Is Associated with a Lower Risk of Fatal and Nonfatal Acute Myocardial Infarction in a Chinese Adult Population.

BACKGROUND: Indexes to quantify adherence to recommended dietary patterns have been developed for Western populations, but it is unclear whether these indexes can predict acute myocardial infarction (AMI) in Asian populations. OBJECTIVES: We aimed to investigate the association between the Alternative Healthy Eating Index (AHEI)-2010 and risk of AMI and to evaluate potential mediation by traditional cardiovascular risk factors in a Chinese population. METHODS: A nested case-control study in 751 incident cases of AMI (564 nonfatal and 288 fatal) and 1443 matched controls was conducted within the prospective Singapore Chinese Health Study, a cohort of ethnic Chinese men and women aged 45-75 y. At baseline, habitual diet was assessed by using a validated, semiquantitative food-frequency questionnaire. AMI cases were ascertained via linkage with nationwide hospital databases (confirmed through medical record review) and the Singapore Birth and Death Registry. We evaluated the association between the AHEI-2010 and cardiovascular risk factors, including glycated hemoglobin, high-sensitivity C-reactive protein, creatinine, plasma lipids (LDL and HDL cholesterol, triglycerides), and blood pressure. ORs and 95% CIs were computed by using multivariable-adjusted conditional logistic regression models. RESULTS: Higher AHEI-2010 scores were associated with a lower risk of AMI (OR for the highest quartile compared with the lowest quartile: 0.62; 95% CI: 0.47, 0.81; P-trend < 0.001), with similar associations for fatal (OR: 0.60; 95% CI: 0.39, 0.94; P-trend = 0.009) and nonfatal (OR: 0.59; 95% CI: 0.43, 0.81; P-trend = 0.002) AMI. This association was only slightly attenuated after adjustment for potential biological intermediates (OR: 0.64; 95% CI: 0.48, 0.86; P-trend = 0.003). CONCLUSIONS: Adherence to dietary recommendations as reflected in the AHEI-2010 was associated with a substantially lower risk of fatal and nonfatal AMI in an Asian population, and this association was largely independent of traditional cardiovascular risk factors.

The role of women in food provision and food choice decision-making in Singapore: a case study.

As countries develop economically and increasing numbers of women enter the workforce, children are partly being cared for by someone other than their mother. Little is known about the impact of this shift in child-care provider on children's nutrition. This study presents findings from a case study of Singapore, a small country that has experienced phenomenal economic growth. Focus groups were conducted with 130 women of varying educational levels and ethnicities to learn about food decisions in their families. The findings showed that Singaporean working women cook infrequently, families eat out frequently, and children exert considerable influence on food choices. Implications for work-family policies and child health are discussed.

Dietary flavonoids and the development of type 2 diabetes and cardiovascular diseases: review of recent findings.

PURPOSE OF REVIEW: This review summarizes the results on flavonoid intakes and the development of type 2 diabetes and cardiovascular diseases. RECENT FINDINGS: Recent advances in food composition databases have allowed the evaluation of a more comprehensive range of flavonoids in epidemiological studies. In addition, the number of randomized trials of flavonoid-rich foods has increased rapidly. Results from both cohort studies and randomized trials suggest that anthocyanidins from berries and flavan-3-ols from green tea and cocoa may lower the risk of type 2 diabetes and cardiovascular diseases. Meta-analyses of randomized trials indicate that the strongest evidence exists for a beneficial effect of green tea on LDL-cholesterol and a beneficial effect of flavan-3-ol-rich cocoa on endothelial function and insulin sensitivity. Few randomized trials had a long duration or evaluated pure flavonoid compounds. SUMMARY: Evidence from cohort studies and randomized trials suggest beneficial effects of food sources of anthocyanidins (berries) and flavan-3-ols (green tea and cocoa) on cardiovascular health. These findings need to be confirmed in long-term randomized trials, and evaluation of pure compounds will be important to establish what specific flavonoids and doses are effective.

Exome sequencing: dual role as a discovery and diagnostic tool.

Recent developments in high-throughput sequence capture methods and next-generation sequencing technologies have now made exome sequencing a viable approach to elucidate the genetic basis of Mendelian disorders with hitherto unknown etiology. In addition, exome sequencing is increasingly being employed as a diagnostic tool for specific genetic diseases, particularly in the context of those disorders characterized by significant genetic and phenotypic heterogeneity, for example, Charcot-Marie-Tooth disease and congenital disorders of glycosylation. Such disorders are challenging to interrogate with conventional polymerase chain reaction-Sanger sequencing methods, because of the inherent difficulty in prioritizing candidate genes for diagnostic testing. Here, we explore the value of exome sequencing as a diagnostic tool and discuss whether exome sequencing can come to serve a dual role in diagnosis and discovery. We summarize the current status of exome sequencing, the technical challenges facing it, and its adaptation to diagnostics, and make recommendations for the use of exome sequencing as a routine diagnostic tool. Finally, we discuss pertinent ethical concerns, such as the use of exome sequencing data, originally generated in a diagnostic context, in research investigations.

Trends in length of stay, functional outcomes, and discharge destination stratified by disease type for inpatient rehabilitation in Singapore community hospitals from 1996 to 2005.

OBJECTIVE: To determine the trends in length of stay (LOS), rehabilitation functional outcome, and discharge destination of patients admitted for inpatient rehabilitation from 1996 to 2005 and stratified by disease in Singapore. DESIGN: Retrospective national data were extracted from medical records of community-based inpatient rehabilitation admissions in Singapore from 1996 to 2005. SETTING: Four community hospitals. PARTICIPANTS: There were 12,506 first admissions for rehabilitation; 40.6% were for stroke, 30.4% for fracture, 2.9% for lower limb (LL) joint replacement, 2.3% for LL amputation, 1.9% for cancer, 1.8% for falls, 1.6% for pneumonia, and 18.5% for other illnesses. The overall mean age ± SD was 73.2±11.5 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: LOS, rehabilitation outcomes (rehabilitation effectiveness [R-effectiveness], rehabilitation efficiency [R-efficiency], relative functional efficiency [Relative-FE]), and discharge destination. RESULTS: The overall median LOS for all disease groups decreased by 16.2% (37 to 31d) from 1996 to 2005. The sharpest decline in LOS among the 8 disease groups was observed in the LL amputation group. The overall mean ± SD admission and discharge activities of daily living scores were 45.6±25.7 and 60.3±28.9, respectively; median R-effectiveness was 28.8%, median R-efficiency was 12.9/30d, and median Relative-FE was 27.7%/30d. From 1996 to 2005, mean R-effectiveness increased by 184% (14% to 40%), R-efficiency increased by 104% (9 to 19 units/30d), and Relative-FE increased by 145% (21% to 51%/30d). Among all inpatient admissions, most were discharged home (78.2%), 10.9% were discharged to an acute hospital, and 9.8% were discharged to nursing or sheltered homes, with no significant change during the 10-year period. CONCLUSIONS: Rehabilitation outcomes of patients admitted to Singapore's community hospitals have improved between 1996 and 2005 despite a decreasing LOS. Discharge destinations have largely remained unchanged over this period.

"Sometimes they'll tell me what they want": family and inter-generational food preferences in the food decisions of Singaporean women.

This study examines responses to questions regarding food choices and decisions from 18 focus groups of women (n=130) age 30-55 years living in Singapore. Focusing on the responses to the questions in the interview protocol closely associated with decision making identified several themes. Food choices and eating decisions are composite phenomenon. These composite food decisions reflect flexible, open systems we refer to here as idiosyncratic regimes in which environmental, social, and intra-personal streams of influence are prioritized as individuals generate possible food decisions. Food decisions represent the imagined and actual presence of the "family" and differing inter-generational food preferences. As women attempt to create harmony from the diversity of food preferences they generate idiosyncratic regimes of food and eating reflecting "triadic streams of influence" manifest in the context of everyday contingencies of family and individual life. Recent concern in Singapore on the part of the Health Promotion Board and the Saw Swee Hock School of Public Health at the National University of Singapore regarding the increasing prevalence of diet-related diseases and obesity among Singaporeans provided the impetus for conducting this qualitative study of food and eating among Singaporean women.

Empirical evidence of the continuing improvement in cost efficiency of an endoscopic surveillance programme for gastric cancer in Singapore from 2004 to 2010.

BACKGROUND: Endoscopic surveillance has been proven effective in prolonging the survival of gastric cancer (GC) patients. However, there is limited evidence on the cost efficiency of delivering this intervention, especially on a national level in spite of cost efficiency being a major determinant of the actual cost-effectiveness of a cancer prevention programme. The Singapore Gastric Cancer Epidemiology Clinical and Genetic Programme (GCEP) is a demonstration project offering scheduled endoscopy to the Chinese population aged 50 years or older in Singapore. By assessing the cost efficiency of the GCEP, this study aimed to provide empirical evidence on the cost structure and mechanisms underlying cost generation in conducting GC surveillance, thus informing resource allocation and programme budgeting for the Singapore government. METHODS: From a societal perspective, we reported on the direct cost (resource consumption) of conducting endoscopic surveillance through the GCEP network. We retrospectively collected individual-level data of 216 subjects recruited at the National University Hospital, Singapore from 01/04/2004 to 31/10/2010. The Overall Cost, Clinical Cost, GCEP Cost and Personal Cost incurred in serving one subject was computed and discounted as 2004 US dollar (US$) per capita for every year. The Generalized Estimation Equation (GEE) was used to model the data. RESULTS: All cost indices continuously declined over the 6.5-year costing period. For the total sample, Overall Cost, Clinical Cost, GCEP Cost and Personal Cost declined by 42.3%, 54.1%, 30% and 25.7% respectively. This downward trend existed for age and gender subgroups and the high risk group only with cost reductions varying between 3.5% and 58.4%. The GEE models confirmed statistical significance of the downward trend and of its association with risk profile, where the moderate risk group had cost indices at most 77% of the high risk group. CONCLUSIONS: Our study offered empirical evidence of improved cost efficiency of a surveillance programme for GC in the early phase of programme implementation. Mechanisms such as economies of scale and self-learning were found to be involved in the cost reduction. Our findings highlighted the importance of assessing the cost efficiency and offered valuable insights for future programme budgeting and policy making.

Diet and endothelial function: from individual components to dietary patterns.

PURPOSE OF REVIEW: Endothelial dysfunction plays an important role in development and progression of atherosclerosis and may also contribute to the pathogenesis of type 2 diabetes. This review summarizes recent findings on the effects of vitamin D, antioxidant vitamins, polyphenols, polyphenol-rich foods, dietary component combinations and healthy diets on endothelial function. RECENT FINDINGS: Dietary patterns rich in fruit, vegetables, fish and nuts appear to have beneficial effects on endothelial function. With regard to specific foods, cacao and green tea consumption have been associated with improvement in endothelial function and this seems to be due to their flavan-3-ol (catechins and epigallocatechin gallate) content. The evidence for beneficial effects of other foods such as citrus fruit, apples and red wine is less consistent. Recent studies have also suggested beneficial effects of vitamin D and anthocyanins on endothelial function and have provided more insight into potential mechanisms underlying the effect of diet on endothelial function. SUMMARY: The currently available evidence supports beneficial effects of various dietary compounds on endothelial function. However, in order to obtain strong evidence for relevant health effects that can be used for specific dietary recommendations, more long-term studies using well characterized diets/supplements in a large number of individuals are needed.

Regions of homozygosity in three Southeast Asian populations.

The genomes of outbred populations were first shown in 2006 to contain regions of homozygosity (ROHs) of several megabases. Further studies have also investigated the characteristics of ROHs in healthy individuals in various populations but there are no studies on Singapore populations to date. This study aims to identify and investigate the characteristics of ROHs in three Singapore populations. A total of 268 samples (96 Chinese, 89 Malays and 83 Indians) are genotyped on Illumina Human 1 M Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We use the PennCNV algorithm to detect ROHs. We report an abundance of ROHs (≥500 kb), with an average of more than one hundred regions per individual. On average, the Indian population has the lowest number of ROHs and smallest total length of ROHs per individual compared with the Chinese and Malay populations. We further investigate the relationship between the occurrence of ROHs and haplotype frequency, regional linkage disequilibrium (LD) and positive selection. Based on the results of this data set, we find that the frequency of occurrence of ROHs is positively associated with haplotype frequency and regional LD. The majority of regions detected for recent positive selection and regions with differential LD between populations overlap with the ROH loci. When we consider both the location of the ROHs and the allelic form of the ROHs, we are able to separate the populations by principal component analysis, demonstrating that ROHs contain information on population structure and the demographic history of a population.

Plasma vitamin E and coenzyme Q10 are not associated with a lower risk of acute myocardial infarction in Singapore Chinese adults.

Vitamin E and coenzyme Q10 (CoQ10) have antioxidant effects that may benefit cardiovascular health. Meta-analyses of randomized controlled trials have not shown a protective effect of supplementation with the vitamin E isomer α-tocopherol on the risk of acute myocardial infarction (AMI), but data on other isomers and CoQ10 are limited. Our objective was to examine the association of the plasma concentrations of vitamin E isomers (α-, γ-, and δ-tocopherol and α-, γ-, and δ-tocotrienol) and CoQ10 (ubiquinol and ubiquinone) with the incidence of AMI. We conducted a nested case-control study with 233 cases of incident AMI and 466 matched controls selected from the Singapore Chinese Health Study, aged 45-74 y at the time of recruitment and free of cardiovascular disease at the time of blood collection. We used conditional logistic regression to examine the association between vitamin E and CoQ10 and the risk of AMI adjusted for other risk factors. In the basic model, higher δ-tocopherol and ubiquinone concentrations were significantly associated with a higher risk of AMI, whereas there were no significant associations for the other vitamin E and CoQ10 isomers. After adjusting for lifestyle and other risk factors, only the association between δ-tocopherol and AMI risk remained significant [OR = 3.09 (95% CI: 1.53, 6.25) highest vs. lowest quintile; P-trend = 0.028]. We did not observe an inverse association between plasma concentrations of vitamin E isomers or CoQ10 and risk of AMI in Singapore Chinese. In contrast, plasma δ-tocopherol concentrations were associated with a higher risk of AMI. Our findings do not support a role of higher vitamin E or CoQ10 intakes in the prevention of AMI.

A comparative population-based study of prostate cancer incidence and mortality rates in Singapore, Sweden and Geneva, Switzerland from 1973 to 2006.

BACKGROUND: Prostate cancer is the most commonly diagnosed malignancy in men in Sweden and Geneva, and the third most common in men in Singapore. This population-based study describes trends in the incidence and mortality rates of prostate cancer in Singapore, Sweden and Geneva (Switzerland) from 1973 to 2006 and explores possible explanations for these different trends. METHODS: Data from patients diagnosed with prostate cancer were extracted from national cancer registries in Singapore (n = 5,172), Sweden (n = 188,783) and Geneva (n = 5,755) from 1973 to 2006. Trends of incidence and mortality were reported using the Poisson and negative binomial regression models. The age, period and birth-cohort were tested as predictors of incidence and mortality rates of prostate cancer. RESULTS: Incidence rates of prostate cancer increased over all time periods for all three populations. Based on the age-period-cohort analysis, older age and later period of diagnosis were associated with a higher incidence of prostate cancer, whereas older age and earlier period were associated with higher mortality rates for prostate cancer in all three countries. CONCLUSIONS: This study demonstrated an overall increase in incidence rates and decrease in mortality rates in Singapore, Sweden and Geneva. Both incidence and mortality rates were much lower in Singapore. The period effect is a stronger predictor of incidence and mortality of prostate cancer than the birth-cohort effect.

Human genetics and genomics a decade after the release of the draft sequence of the human genome.

Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade.

Validation of the functional assessment of cancer therapy-gastric module for the Chinese population.

BACKGROUND: Quality of life (QoL) assessment has become an important aspect of the clinical management of gastric cancer (GC), which poses a greater health threat in Chinese populations around the world. Functional Assessment of Cancer Therapy-Gastric Module (FACT-Ga), a questionnaire developed specifically to measure QoL of patients with GC, has never been validated in Chinese subjects. The current study was designed to examine the psychometric properties of FACT-Ga as a GC specific QoL instrument for its future use in Chinese populations. METHODS: A sample of 67 Chinese patients with GC in the National University Hospital, Singapore was investigated cross-sectionally. The participants independently completed either English or Chinese versions of the FACT-Ga and the European Quality of Life-5 Dimensions (EQ-5D). Reliability was measured as the Cronbach's α for EQ-5D, and five subscale scores and two total scores of FACT-Ga. The sensitivity to patients' clinical status was evaluated by comparing EQ-5D and FACT-Ga scores between clinical subgroups classified by Clinical Stage and Treatment Intent. The construct validity of FACT-Ga was assessed internally by examining the item-to-scale correlations and externally by contrasting the FACT-Ga subscales with the EQ-5D domains. RESULTS: For both FACT-Ga and EQ-5D, patients treated with curative intent rated their QoL higher than those treated for palliation, and early stage patients scored higher than those in the late stage. The sensitivity to clinical status of FACT-Ga scores were differential as four of seven FACT-Ga scores were significant for Treatment Intent while only one subscale score was significant for Clinical Stage. Six FACT-Ga scores had Cronbach's α of 0.8 or above indicating excellent reliability. For construct validity, 45 of 46 items converged about their respective subscales. The monotrait-multimethod correlations between QoL constructs of FACT-Ga and EQ-5D were stronger than the multitrait-multimethod correlations as theoretically hypothesized, suggesting good convergent and discriminant validities. CONCLUSIONS: Given the excellent reliability and good construct validity, FACT-Ga scores are able to distinguish patient groups with different clinical characteristics in the expected direction. Therefore FACT-Ga can be used as a discriminative instrument for measuring QoL of Chinese patients with GC.

Studying the epigenome using next generation sequencing.

The advances in next generation sequencing (NGS) technologies have had a significant impact on epigenomic research. The arrival of NGS technologies has enabled a more powerful sequencing based method--that is, ChIP-Seq--to interrogate whole genome histone modifications, improving on the conventional microarray based method (ChIP-chip). Similarly, the first human DNA methylome was mapped using NGS technologies. More importantly, studies of DNA methylation and histone modification using NGS technologies have yielded new discoveries and improved our knowledge of human biology and diseases. The concept that cytosine methylation was restricted to CpG dinucleotides has only been recently challenged by new data generated from sequencing the DNA methylome. Approximately 25% of all cytosine methylation identified in stem cells was in a non-CG context. The non-CG methylation was more enriched in gene bodies and depleted in protein binding sites and enhancers. The recent developments of third generation sequencing technologies have shown promising results of directly sequencing methylated nucleotides and having the ability to differentiate between 5-methylcytosine and 5-hydroxymethylcytosine. The importance of 5-hydroxymethylcytosine remains largely unknown, but it has been found in various tissues. 5-hydroxymethylcytosine was particularly enriched at promoters and in intragenic regions (gene bodies) but was largely absent from non-gene regions in DNA from human brain frontal lobe tissue. The presence of 5-hydroxymethylcytosine in gene bodies was more positively correlated with gene expression levels. The importance of studying 5-methylcytosine and 5-hydroxymethylcytosine separately for their biological roles will become clearer when more efficient methods to distinguish them are available.

Delays in HIV-1 infant polymerase chain reaction testing may leave children without confirmed diagnoses in the Western Cape province, South Africa.

Background: Early diagnosis and confirmation of HIV infection in newborns is crucial for expedited initiation of antiretroviral therapy. Confirmatory testing must be done for all children with a reactive HIV PCR result. There is no comprehensive data on confirmatory testing and HIV PCR test request rejections at National Health Laboratory Service laboratories in South Africa. Objective: This study assessed the metrics of routine infant HIV PCR testing at the Tygerberg Hospital Virology Laboratory, Cape Town, Western Cape, South Africa, including the proportion of rejected test requests, turn-around time (TAT), and rate of confirmatory testing. Methods: We retrospectively reviewed laboratory-based data on all HIV PCR tests performed on children ≤ 24 months old (n = 43 346) and data on rejected HIV PCR requests (n = 1479) at the Tygerberg virology laboratory over two years (2017-2019). Data from sample collection to release of results were analysed to assess the TAT and follow-up patterns. Results: The proportion of rejected HIV PCR requests was 3.3%; 83.9% of these were rejected for various pre-analytical reasons. Most of the test results (89.2%) met the required 96-h TAT. Of the reactive initial test results, 53.5% had a follow-up sample tested, of which 93.1% were positive. Of the initial indeterminate results, 74.7% were negative on follow-up testing. Conclusion: A high proportion of HIV PCR requests were rejected for pre-analytical reasons. The high number of initial reactive tests without evidence of follow-up suggests that a shorter TAT is required to allow confirmatory testing before children are discharged.

An occupational health survey on health utility and occupational diseases in Chinese university staff to inform cost-utility analysis.

Background: The occupational health of university staff bears great social and economic value for which health utility is an indivisible aspect. Utility is also the primary data for the cost-utility analysis of occupational health programs. Health utility and occupational diseases have not been reported for the university staff in China. In the light of "Healthy China," we conducted this study aiming to (1) estimate the health utility of university staff to inform cost-utility analysis and (2) screen and identify potential occupational diseases for this occupation and examine their impacts on health. Methods: An occupational health survey was conducted in a sample of working-age university staff. Participants were interviewed face-to-face using the WHO Health and Work Performance Questionnaire and the European Quality of Life 5 Dimensions (EQ-5D) instrument to measure health conditions and health utility, respectively. The univariate analysis included the t-test, chi-square test, and correlation techniques. Multivariate generalized linear models were applied to evaluate the significance of each health condition when controlling for other factors. Results: The sample (n = 154) had a mean age of 40.65 years and consisted of slightly more women (51.30%). Participants attained a mean (standard deviation) health utility of 0.945 (0.073). The most affected domain was anxiety/depression with 62 (40.26%) participants reporting problems, followed by pain/discomfort which captured 60 (37.66%) staff with problems. Thus, pain and psychologically related conditions were prevalent. Multivariate models identified two conditions that can significantly reduce the health utility. The psychological/emotional conditions were associated with a utility loss of -0.067 (95%CI: -0.089, -0.045). The pain in body parts other than the head, neck, and back reduced the utility by -0.034 (95%CI: -0.055, -0.014). Conclusion: Working-age staff in Chinese universities may have a lower health utility than the general population. Psychological conditions and musculoskeletal pain appear like occupational diseases. With the health utility data available, economic evaluation of cost-utility should follow up to facilitate the implementation of cost-effective programs.

Revisiting Mendelian disorders through exome sequencing.

Over the past several years, more focus has been placed on dissecting the genetic basis of complex diseases and traits through genome-wide association studies. In contrast, Mendelian disorders have received little attention mainly due to the lack of newer and more powerful methods to study these disorders. Linkage studies have previously been the main tool to elucidate the genetics of Mendelian disorders; however, extremely rare disorders or sporadic cases caused by de novo variants are not amendable to this study design. Exome sequencing has now become technically feasible and more cost-effective due to the recent advances in high-throughput sequence capture methods and next-generation sequencing technologies which have offered new opportunities for Mendelian disorder research. Exome sequencing has been swiftly applied to the discovery of new causal variants and candidate genes for a number of Mendelian disorders such as Kabuki syndrome, Miller syndrome and Fowler syndrome. In addition, de novo variants were also identified for sporadic cases, which would have not been possible without exome sequencing. Although exome sequencing has been proven to be a promising approach to study Mendelian disorders, several shortcomings of this method must be noted, such as the inability to capture regulatory or evolutionary conserved sequences in non-coding regions and the incomplete capturing of all exons.

Regions of homozygosity and their impact on complex diseases and traits.

Regions of homozygosity (ROHs) are more abundant in the human genome than previously thought. These regions are without heterozygosity, i.e. all the genetic variations within the regions have two identical alleles. At present there are no standardized criteria for defining the ROHs resulting in the different studies using their own criteria in the analysis of homozygosity. Compared to the era of genotyping microsatellite markers, the advent of high-density single nucleotide polymorphism genotyping arrays has provided an unparalleled opportunity to comprehensively detect these regions in the whole genome in different populations. Several studies have identified ROHs which were associated with complex phenotypes such as schizophrenia, late-onset of Alzheimer's disease and height. Collectively, these studies have conclusively shown the abundance of ROHs larger than 1 Mb in outbred populations. The homozygosity association approach holds great promise in identifying genetic susceptibility loci harboring recessive variants for complex diseases and traits.