Occupational Paraquat and Glyphosate Exposure May Decline Renal Functions among Rural Farming Communities in Sri Lanka.

Extensive use of herbicides is common among rural agricultural workers in Sri Lanka. Recent studies have postulated their role in the development of chronic kidney disease of unknown etiology (CKDu). Paraquat and glyphosate are leading herbicides used by sugarcane farmers (SF), hence occupational exposure is inevitable. This study examined the expression of urinary paraquat, glyphosate and biomarkers among residential SF in CKDu emerging regions, Warunagama (WA) and Rahathangama (RH), in the Uva Province with non-endemic Matara (MA) in the Southern Province of Sri Lanka. Urinary glyphosate, Paraquat, kidney injury molecule -1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and ß2-microglobulin (B2M) were determined using enzyme-linked immunosorbent assays (ELISA). Urinary creatinine, microalbumin, serum creatinine (SCr), serum cystatin C, estimated glomerular filtration rate (eGFR), and albumin creatinine ratio (ACR) were also assessed. Generally, herbicide residues and kidney injury biomarkers were higher in SF compared to the non-endemic MA. Creatinine-adjusted urinary glyphosate and paraquat levels were significantly higher in WA compared to MA. ACR in RH (median 14.9; IQR 5.4-393.1 mg/g) and WA (23.7; 11.5-64.6) was significantly higher than MA (4.3; 2.2-6.7). This study reports 39 individuals with impaired kidney function among SF in Sri Lanka for the first time. Urinary NGAL levels were significantly higher in both WA (median 2.14; IQR 1.28-6.15 ng/mg Cr) and RH (3.09; 1.15-9.09) compared to MA (1.28; 0.56-2.81). However, urinary KIM-1 levels in RH (3.2; 1.29-106.1 ng/g Cr) and WA (3.6; 1.94-115.1) were not significantly higher in MA (1.74; 0.76-116.9). Urinary NGAL (r = 0.493), eGFR (r = -0.147) and ACR (r = 0.171) significantly correlated with urinary glyphosate, but not with urinary paraquat levels. Urinary KIM-1 levels did not correlate with either urinary glyphosate or paraquat, while urinary B2M and serum cystatin C levels showed significant correlation with urinary glyphosate levels. The current study reports higher urinary herbicide levels among sugarcane farmers in WA and RH, and that is potentially linked to the subsequent decline in kidney function, as indicated by ACR, eGFR, and NGAL. We posit that these indicators may serve as markers to detect renal injury among herbicide-exposed SF in Rural Sri Lanka.

The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Knowledge, Attitudes, and Practices of Responsive Feeding in Rural Sri Lanka (A Qualitative Study)

Introduction: Responsive Feeding has been proven to be an effective feeding method for children who are at early stages of development. The concept is not popular at the primary health care level and it is reported as a missing link in the current nutrition program in Sri Lanka. Objective: To explore responsive feeding practices among caregivers who have an infant aged between 6 to 12 months and residing in rural Anuradhapura. Methods: A qualitative approach was adopted. The study was carried out in Padaviya Medical Officer of Health area. Study participants were 18 mothers and all ten Public Health Midwives. Diary studies, interviews and focus group discussion were conducted to collect data. The framework approach was used to analyze the data. Results: Pleasant and healthy feeding environment is non-existent. Identification of hunger and satiety cues was poor and hunger sensitive schedule to feed the child was absent. Feeding situations commenced in an emotionally supportive manner, but were not optimally utilized to promote psycho-social stimulation. During the feeding caregivers neglect emotional support and ultimately moves to forceful feeding. Conclusions: The knowledge, attitude and practices are poor on responsive feeding among caregivers and health workers. This may contribute to poor growth and development in children. Action is needed to implement RF practices in the community.

Early renal damage among children living in the region of highest burden of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka.

BACKGROUND: Chronic kidney disease of unknown origin (CKDu) in Sri Lanka is grouped with several other epidemics of similar nature across the world as Chronic Interstitial Nephritis in Agricultural Communities (CINAC). In CKDu endemic countries, the focus has mainly been on adults. We hypothesized that studying distribution and factors associated with elevated urine albumin to creatinine ratio (UACR), an early marker of kidney injury, among children living in a CKDu endemic area may provide important clues about the onset and progression of the disease. METHODS: This cross sectional study was performed in rural primary schools in North Central Province of Sri Lnaka, a CKDu high endemic region. Total of 2880 students aging 5 to 11 years from 67 schools were enrolled for urinalysis in a random spot urine sample. Bedside Schwartz formula was used to measure estimated glomerular filtration rate (eGFR) on all children with UACR > 30 mg/g in Polonnaruwa district and a group of age matched controls. A standard multiple linear regression using log transformed UACR as the dependent variable was performed. Mean eGFR were compared between UACR elevated group and controls using independent sample t test. RESULTS: Median UACR was 10.3 mg/g. Sex, ethnicity, history of having a chronic disease and age uniquely contributed to the multiple regression model which only explained 2.8% of the variance in the log of the UACR (p < 0.001). Only 15 (0.5%) had UACR> 300 mg/g while 8.2% (n = 236) had UACR between 30 to 300 mg/g and 89.8% (n = 203) of them did not have a chronic disease (Chi square 2.21, p = 0.091). Mean eGFR was significantly lower in the group with elevated UACR (88.9 mg/dl/1.73 m2, 95% CI for mean 86.4- 91.3) compared to group with normal UACR (93.7 mg/dl/1.73 m2,95% CI 91.1- 96.3) (t 2.7, p 0.007). Three out of the four students with eGFR less than 60 mg/dl/1.73 m2 had moderately elevated UACR. CONCLUSION: This study provides evidence to suggest that children in CKDu endemic regions are having an early renal damage. This observation needs to be investigated further in order to understand the worldwide epidemic of CKDu.

Genetic and other risk factors for suicidal ideation and the relationship with depression.

BACKGROUND: There is a genetic contribution to the risk of suicide, but sparse prior research on the genetics of suicidal ideation. METHODS: Active and passive suicidal ideation were assessed in a Sri Lankan population-based twin registry (n = 3906 twins) and a matched non-twin sample (n = 2016). Logistic regression models were used to examine associations with socio-demographic factors, environmental exposures and psychiatric symptoms. The heritability of suicidal ideation was assessed using structural equation modelling. RESULTS: The lifetime prevalence of any suicidal ideation was 13.0% (11.7-14.3%) for men; 21.8% (20.3-23.2%) for women, with no significant difference between twins and non-twins. Factors that predicted suicidal ideation included female gender, termination of marital relationship, low education level, urban residence, losing a parent whilst young, low standard of living and stressful life events in the preceding 12 months. Suicidal ideation was strongly associated with depression, but also with abnormal fatigue and alcohol and tobacco use. The best fitting structural equation model indicated a substantial contribution from genetic factors (57%; CI 47-66) and from non-shared environmental factors (43%; CI 34-53) in both men and women. In women this genetic component was largely mediated through depression, but in men there was a significant heritable component to suicidal ideation that was independent of depression. CONCLUSIONS: These are the first results to show a genetic contribution to suicidal ideation that is independent of depression outside of a high-income country. These phenomena may be generalizable, because previous research highlights similarities between the aetiology of mental disorders in Sri Lanka and higher-income countries.

From organophosphate poisoning to diabetes mellitus: The incretin effect.

Organophosphate (OP) poisoning induced disruption of glucose homeostasis is well established. OP poisoning leads to accumulation of acetylcholine (ACh) due to the inhibition of acetylcholinesterases (AChE). On the other hand the incidence of type 2 diabetes mellitus (T2DM) is shown to rise along with the use of pesticides in Southeast Asia. Attenuation of the 'incretin effect' is seen in T2DM. This effect is regulated by a complex loop of mechanism involving ACh driven muscarinic receptors. We hypothesize that OP poisoning leads to disruption of glucose homeostasis by attenuation of the incretin effect. Inhibition of the Glucagon Like Peptide-1 (GLP-1) secretion is our main focus of interest. Positive finding of the hypothesis will open possibility of using incretin based treatment modalities to treat or prevent acute OP induced disruption of glucose homeostasis.

Incidence and risk factors of falls among the elderly in the District of Colombo.

OBJECTIVES: To assess the incidence and risk factors of falls among the elderly in the District of Colombo. METHODS: Incidence of falls was assessed by a community based descriptive study with prospective follow up. Risk factors for falls were assessed by a nested case control study. Participants above 65 years residing in 40 Grama Niladhari Divisions in the Colombo district (n=1200) were assessed for falls and followed up for four months. Those who had falls were selected as cases (n=151), while two controls per case were selected from others. MEASUREMENTS: Tests for gait problems, disability, cognitive impairment and vision. RESULTS: The incidence rate of falls was 492 per 1000 person years (95% CI 448-536). Risk factors for falls identified in the multivariate analysis were falls in the previous year (OR 4.67), high disability level (OR 2.04) and high house risk level (OR 1.68). CONCLUSIONS: The high incidence of falls among the elderly reported in this study and the preventable risk factors identify / indicate the necessity and feasibility of their prevention.

Culture-bound syndromes: the story of dhat syndrome.

BACKGROUND: Culture-bound syndrome is a term used to describe the uniqueness of some syndromes in specific cultures. Dhat (semen-loss anxiety) has been considered to be an exotic 'neurosis of the Orient'. AIMS: To ascertain the presence of similar symptoms and syndromes in different cultures and historical settings. METHOD: Electronic and manual literature searches were used to gather information on the existence and description of semen-loss anxiety in different cultures and settings. RESULTS: Most of the empirical studies on dhat syndrome have emerged from Asia, whereas its concepts have been described historically in other cultures, including Britain, the USA and Australia. The different sources indicate the universality of symptoms and global prevalence of this condition, despite its image as a 'neurosis of the Orient'. CONCLUSIONS: It appears that dhat (semen-loss anxiety) is not as culture-bound as previously thought. We propose that the concept of culture-bound syndromes should be modified in line with DSM-IV recommendations.

Feasibility of using different approaches for recruiting younger twins to establish a population based twin register in Sri Lanka.

Identifying twins for a population-based register can be achieved through birth records or community surveys. We studied the feasibility and effectiveness of different methods of identifying and recruiting twins to establish a population based register. To trace twins a population survey was carried out using an interviewer administered questionnaire. We also inspected the birth registration certificates at a divisional secretariat reported from a specified hospital between the years of 1985-1997 and compared it to the birth register of this same hospital. To recruit twins a random sample of 75 twin pairs (150 twins) identified at the Divisional Secretariat were contacted through the post and 25 twin pairs (50 twins) were personally visited. The prevalence of twins was 6.5 twins per 1000 people in the area surveyed. The twinning rate at the hospital was 18.92 twins per 1000 births. A discrepancy of 38 multiples births between the hospital labour room records and those registered at the DS was noted. The response from the postal invitation for recruitment was 59% and the response from the personal invitation was 68%. (Difference 9.4% 95% CI; 7.06-11.73). Community survey and systematic inspection of birth records either at the hospital or the birth registration office was an effective method to trace twins. Once traced, personal contact was more effective than the postal invitation for recruitment of younger twins. A cost-effective approach would be to use a postal coverage followed by personal contact for non-responders. The alternative method, community coverage, would have financial implications.

Establishing a twin register in Sri Lanka.

Nearly all twin registers are based in developed countries and there is no twin register in the developing world. Our objectives were to initiate the process of establishing a nationwide twin register in Sri Lanka by starting a volunteer register first and working towards a population-based register. Regular newspaper advertisements, feature articles, radio talks, and television programmes were used to publicise a competition for twins, their parents/relatives and friends requesting them to participate by sending in details of twins. The competition ran from 28 March 1997 for a period of 3 months. It offered prizes for three winners selected by drawing lots. Advertisements highlighted the objective of the competition as establishing a twin register for future research and emphasised that informed consent would be obtained for individual research projects. Those who registered comprise 4602 twin pairs (same sex: male--1564, female--1885; different sex--1153), 80 sets of triplets (same sex: male--17, female--31; different sex--42) and two sets of quadruplets (different sex). The oldest twins, triplets, quadruplets are 85, 46, and 5 years old, respectively; 88.0% of twins are less than 30 years old. Although others have previously used media publicity to enrol twins in twin registers, we believe this to be the first time that twins have been enrolled through competition. We have more young twins, and our gender and zygosity proportions after applying Weinburg's rule do not match the proportions expected from a volunteer twin sample. Establishing a twin register for research purposes has proved possible in a developing country.

Cross-cultural adaptation and preliminary validation of a zygosity determination questionnaire for twins in Sri Lanka.

We report the process of adaptation into Sinhala of a questionnaire given to mothers of twins to determine zygosity. Adaptation and validation was carried out in three stages. Firstly, we used a nominal group to translate the English version and to assess the extent of agreement (consensus measurement) on the appropriateness of the translation and resolve disagreement (consensus development). Secondly we used a qualitative interview with 25 mothers of twins. The three main stems of the translated questionnaire were used as a semi-structured interview, and the responses noted verbatim. These were categorised and analysed, and the translated full questionnaire was then presented as closed questions with fixed choice responses. The categorised responses generated during the qualitative interview were compared with the responses to the fixed choices in the full questionnaire. The third stage was the appraisal of the questionnaire by 17 bilingual parents of twins. The source and translated version of the questionnaire were given to them at least 3 days apart. The responses were rated and the total scores were computed to determine the zygosity. This step was carried out to measure the validity and reliability of the Sinhala version. A perfect correlation between the original and adapted version was obtained, with a kappa of 1. The results suggest that the Sinhala version of the questionnaire is conceptually equivalent to the original questionnaire. Comparison of the zygosity determination by using this adapted questionnaire with results from analysis of genetic markers on Sri Lankan twins is needed for final validation of the translated questionnaire.

The prevalence of gestational diabetes in a Sri Lankan antenatal clinic.

INTRODUCTION: Early diagnosis of gestational diabetes mellitus (GDM) is a prerequisite to reducing fetal and neonatal complications of GDM. OBJECTIVES: (a) To ascertain the prevalence of GDM in a Sri Lankan pregnant population. Using the 75 g oral glucose tolerance test (GTT) and WHO criteria. (b) To establish the predictive value of a 50 g glucose challenge test (GCT) compared to the GTT (c) To compare the outcome of pregnancy in GDM with 'non-diabetic pregnancy' (NDP) STUDY DESIGN: Prospective study on a cohort of pregnant women attending antenatal clinics. SETTING: Sri Jayawardenepura General Hospital (SJGH) RESULTS: Of the 721 patients, 131 (18%) had a positive GCT. 40 (5.5%) patients had GDM. If a one-hour GCT of 7.8 mmol/l was considered suspicious of GDM the sensitivity of the glucose challenge test was 63% and the specificity 84%. Statistically significant differences in the prevalence was found when the women were > 35 years [Relative risk (RR) = 3.87 (95% CI-2.06 to 7.27)] or the body mass index > or = 25. (RR = 2.45 (95 CI-1.30 to 4.61) Presence or absence of high parity, family history of diabetes or recurrent abortions had no significant impact on the prevalence of GDM. Mean birth weight was higher (p < 0.05) in GDM (3615 SD 103) than in NDP (2898 SD 143.6). The likelihood of having a caesarean section was higher (p < 0.01, Relative risk (RR) 2.50, 95% CI 1.56-3.95) in GDM when compared to NDP. A higher incidence of hydramnios (p < 0.01 RR 3.41 95% CI 1.44-8.05) was recorded in GDM when compared to NDP. CONCLUSION: The prevalence of GDM in the antenatal clinics at SJGH is 5.5%. Traditional risk factors did not predict GDM. GDM is associated with a higher risk of caesarean section, hydramnios and macrosomia. Hence screening for GDM should be performed in all pregnant women at 24 to 28 weeks of pregnancy using a GCT.

PIP: A prospective cohort study was conducted to ascertain the prevalence of glucose diabetes mellitus (GDM) using the 75 g oral glucose tolerance test (GTT) and WHO criteria, and to compare pregnancy outcomes in GDM with 'nondiabetic pregnancy' (NDP) in Sri Lanka. Furthermore, the study was also aimed to establish the predictive value of a 50 g glucose challenge test (GCT) compared to GTT. The study sample consisted of 721 pregnant women attending antenatal clinics at Sri Jayawardenepura General Hospital. Results revealed that of the 721 patients, 131 (18%) had a positive GCT and 40 (5.5%) patients had GDM. Significant differences in prevalence rates were noted when women were older than 35 years. Moreover, mean birth weight was reportedly higher (p 0.05) in GDM than NDP. Findings also showed that GDM was associated with a higher risk of cesarean section (p 0.01), hydramnios (p 0.01), and macrosomia. Considering the risks of GDM to both maternal and fetal well-being, routine screening of all pregnant women at 24-28 weeks of pregnancy was recommended.

Toluene diisocyanate exposure in a glove manufacturing plant.

CASE REPORT: An accidental exposure due to reuse of containers of toluene diisocyanate to transport nontoxic substances and subsequent occupational toxic exposure caused illness among forty workers in a glove manufacturing plant. Examination and investigation of the patients and factory site inspection were carried out. Toluene diisocyanate-contaminated latex was examined by the infrared spectroscopy. Thirty-two of forty patients had muscle pain and seven had elevated creatine phosphokinase activity. These features have not been reported previously as components of toluene diisocyanate toxicity and their underlying causation remains speculative.