Search

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Recurrent miscarriage (RM) represents the spontaneous termination of two or more successive pregnancies. TNFα is a proinflammatory cytokine that is often considered harmful for embryonic development when expressed beyond normal levels., Aim: The study was conducted to assess the association between TNFα-308 polymorphism and RM pathogenesis., Methods: Samples of blood were obtained from patients and controls through venipuncture. The levels of TNFα in serum were measured by ELISA. TNFα gene promoter-associated single-nucleotide polymorphism was investigated with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques with precise primers and the restriction endonuclease, NcoI., Results: Serum TNFα levels in patients were considerably high (p < 0.05) than controls. The genotype and allele frequencies for TNFα gene polymorphism differs significantly (p = 0.0089; p = 0.0043 respectively) between patients and controls. The TNFα-308 SNP exhibited a link with higher RM risk in heterozygous (GG vs. GA; OR: 3.086, 95% CI: 1.475-6.480; p: 0.0027 ), dominant (GG vs. GA + AA; OR: 2.919, 95% CI: 1.410-6.056, p: 0.0038 ), and allelic/codominant (G vs. A; OR: 2.449, 95% CI: 1.313-4.644, p: 0.0064 ) models. However, this SNP showed an insignificant association with higher and lower RM risk in homozygous (GG vs. AA; OR: 1.915, 95% CI: 0.3804-10.99, p: 0.6560) and recessive (AA vs. GA + GG; OR: 0.6596, 95% CI: 0.1152-3.297, p: >0.9999) models, respectively. Further, the TNFα-308G/A genotype frequencies were in concord with HWE both in the controls (χ 2  = 3.235; p = 0.1985) and the patients (χ 2  = 0.0117; p = 0.9942)., Conclusion: The serum TNFα levels were significantly higher in the patients than the controls. The genotyping analysis also demonstrated that TNFα-308G/A SNP significantly increases the overall risk of RM, suggesting that the SNP modulates the TNFα gene expression and thereby increases serum TNFα levels that adversely affect the pregnancy outcome., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Interleukin-17A (IL17A) is a proinflammatory cytokine and is assumed to play an important role in fetal rejection. In order to evaluate the potential role of IL17A polymorphism in the pathogenesis of recurrent miscarriage (RM), serum IL17A levels were estimated by ELISA. Single-nucleotide polymorphism was assessed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) using gene-specific primers and the EcoNI restriction enzyme. Serum IL17A levels were nonsignificantly (p > 0.5) low in RM patients compared with the control group. IL17A gene amplification by PCR yielded the undigested product of 815 bp, and its digestion with EcoNI enzyme produced 815, 529, 286, and 270 bp fragments for the GG genotype; 529, 286, and 270 bp fragments for the GA genotype; and 529 and 286 bp fragments for the AA genotype. The genotype frequency between the RM and control groups exhibited a significant difference (p = 0.001), whereas no significant difference was observed between allele frequencies in the two groups (p = 0.0954). These data suggest that the IL17A gene polymorphism exhibits no significant effect on IL17A gene expression. However, it significantly decreases and increases RM risk in the homozygous and recessive models, suggesting its potential pregnancy-protecting and -harming roles in the AA and GA + GG genotypes, respectively.

More than half of all children in Cambodia experience direct abuse and over 70% experience other traumatic events, which significantly increase their risks for a range of physical and mental health problems. Additionally, Cambodian children face longstanding sociopolitical, intergenerational, and cultural factors that compound the impact of other trauma. As a result, rates of posttraumatic stress symptoms among Cambodian youth are high. However, care providers often rely on Western-based nosology that does not account for culturally specific expressions of trauma. A greater understanding of culturally-salient expressions of distress can help inform diagnostic assessment accuracy and treatment effectiveness and monitoring. The current study utilized a qualitative design to interview 30 Cambodian caregivers of children with trauma experiences and 30 Cambodian children (ages 10-13 years) with trauma experiences to identify key local expressions of trauma. Findings reveal certain PTSD symptoms and culturally-specific frequent and severe trauma-related problems for Cambodian children and domains of functioning impacted by trauma. Certain symptoms seem particularly important to evaluate in this group, such as anger, physical complaints (e.g., headache and palpitations), and cognitive-focused complaints (in particular, "thinking too much"). All caregivers and children reported physical health as impacted by trauma-related problems, highlighting a particularly salient domain of functioning for this population. Expressions of distress explored in the current study are discussed in the context of assessment and intervention development to inform diagnostic and clinical efforts for those working with trauma-exposed Cambodian children.

Child trauma and posttraumatic stress in Cambodia is highly prevalent, perpetuated within a postwar sociocultural context. The examination of locally meaningful expressions of distress is needed to provide culturally sensitive assessment and treatment of trauma-affected Cambodian children. The acceptable, feasible, and sustainable incorporation of expressions of distress into assessment and intervention development relies on key mental health professionals operating in Cambodia, who can provide invaluable perspectives on child trauma experiences in this particular sociocultural context. In this study, qualitative interviews were conducted with 15 Cambodian mental health professionals (MHPs) who work directly with trauma-affected Cambodian children. MHPs were presented with seven key posttraumatic problems derived from previous qualitative interviews with Cambodian children and caregivers, and discussed 1) the causes of these problems, 2) the impact of the problem on the child or those around them, 3) the current treatment for the problem in Cambodia, and 4) recommended treatment. MHPs provided unique insights and perspectives of trauma-affected children in the Cambodian context regarding key target problems, including palpitations, difficulties in school, headache, and thinking too much, and highlighted future directions for assessment and intervention. Recommendations are discussed in regard to programming design and organizational training development to promote culturally salient, feasible, and sustainable mental health service provision in Cambodia.

Schizophrenia often follows a chronic or recurrent course, placing an immense burden on patients and their families. Mental health services in Cambodia are still highly limited, thus there is a major treatment gap. It is common that people consult traditional healers ( Kru Khmer ) and monks. In this culture, people who receive psychiatric medical treatment are expected to exhibit higher mental health literacy, but little is known about this factor. In this study, we interviewed 59 patients with schizophrenia and 59 family caregivers attending psychiatric clinics in Cambodia. Through qualitative analysis using a thematic analysis approach, we extracted eight themes of causal beliefs regarding schizophrenia: (1) spiritual beliefs, (2) cultural symptoms, (3) physical problems, (4) heredity, (5) substance abuse, (6) traumatic events, (7) stress in human relationships or in one's social environment, and (8) socioeconomic position. We found that "thinking too much" ( kit chroeun ) and "worrying too much" ( prouy / barom chroeun ), cultural idioms of distress, were recognized as causal factors of schizophrenia by both parents and family caregivers. Some participants were aware of the possible causal factors in light of the latest psychiatry findings, such as genetic factors and childhood trauma. Our data show that causal beliefs are not a decisive factor in shortening the duration of untreated psychosis (DUP). In Cambodia, where the treatment for schizophrenia is pluralistic, we suggest that it is crucial to embed the meaning of psychiatric treatment into local meaning worlds for better help-seeking behaviors.

Recurrent pregnancy loss (RPL) is a prominent reproductive disease that distresses about 2%-5% of couples. RPL is the loss of two or more successive spontaneous pregnancies prior to the 20th week of embryo development. The commencement of pregnancy necessitates implantation of the embryo into responsive maternal decidua synchronized with the process of placentation, decidual and myometrial trophoblast incursion as well as refashioning of spiral blood arteries of uterus. The collapse of any of the processes fundamental for pregnancy success may result into an array of pregnancy problems including spontaneous pregnancy loss. Endometrium of human female manufactures an extensive range of cytokines during the proliferative and secretory stage of the menstrual cycle. These endometrial cytokines are thought as major players for making the uterus ready for embryo implantation and placental development during pregnancy. Decidual cytokines regulate the invasion of trophoblast and remodeling of spiral arteries as well as take part in immune suppression to accomplish the pregnancy. Deterrence of maternal rejection of embryo needs a regulated milieu, which takes place essentially at the embryo-maternal interface and the tissues of the uterus. The reasons of RPL remain anonymous in a large number of cases that lead to difficulties in management and severe trauma in couples. Cytokine modulatory therapies have been shown promising for preventing RPL. Further study of novel factors is wanted to establish more effective RPL treatment protocols. The present study aims to review the outcome of cytokine breach at materno-embryonic interface and the efficacy of cytokine modulatory therapies in RPL., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The purpose of this study was to evaluate etiology and pregnancy outcome of recurrent miscarriage women. The enrolled patients (280) were evaluated for Triiodothyronine, Thyroxine, Thyroid stimulating hormone, prolactin, chromosomal analysis, Haemoglobin A1C, blood sugar, Magnetic resonance imaging, 3D-ultrasound, auto-antibodies profile (antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, antinuclear antibodies, anti-thyroid antibodies and β2 glycoprotein1), torch profile (Toxoplasmo gondii, rubella, cytomegalo virus and herpes simplex virus), blood vitamin D3 levels, psychological factors, Body mass index and thrombotic factors (protein S and C deficiency, Prothrombin G20210A mutation, anti-thrombin III, Factor V Leiden and Methylenetetrahydrofolate reductase mutation), uterosalpingography (hysteronsalpingography) and hysteroscopy. The therapeutic regimens either singly or combined were employed for the treatment of recurrent miscarriage patients on the basis of etiology (single or multiple) and include intravenous immunoglobulin, low molecular weight heparin, low dose aspirin, levothyroxine, progesterone, folic acid, human chorionic gonadotrophin, vitamin D3, psychotherapy, genetic counselling. However, patients with idiopathic recurrent miscarriage were treated with progesterone supplementation, anticoagulation and/or immune modulatory agents. The incidence of primary recurrent miscarriage was highest and most of the women experienced recurrent miscarriage during first trimester. Endocrinological disorders (39%) were found as the major pathological factor for recurrent miscarriage. Other factors include uterine abnormalities (5.7%), vitamin D3 deficiency (3.5%), psychological factors (3.2%) infection (3.6%), autoimmune abnormalities (1.8%) and protein S deficiency (1.8%). However, 40% cases were idiopathic. The overall live birth rate achieved after the management of recurrent miscarriage patients was 75.7%. Enocrinopathy was the major cause of recurrent miscarriage. The overall live birth rate achieved was 75.7% with highest pregnancy outcome in secondary recurrent miscarriage patients after the management., (© 2020 The Authors.)

Abstract: Immediate post-placental IUD insertion is defined as IUD insertion within 10 min of the expulsion of the placenta. Although the expulsion rate in post-placental insertion is higher than interval insertion, the benefits of highly effective contraception immediately after delivery may outweigh the risks of expulsion., Aims: To compare post-placental IUD (PPIUD) insertion with interval IUD insertion (IIUD) in terms of safety, effect on menstrual cycle, efficacy and satisfaction., Materials and Methods: After meeting all eligibility criteria, the patients were asked to choose between post-placental IUD insertion and interval/delayed IUD insertion. In PPIUD group, insertion was done within 10 min of expulsion of placenta by hand technique. Individuals in IIUD group were asked to return after 6 weeks for IUD insertion by withdrawal technique. Both the groups were followed at 6 weeks, 6 months, 12 months by history, physical examination, per speculum examination and ultrasonography., Observations: 238 patients were allocated to PPIUD group and 273 to IIUD group. In the PPIUD group, there was no bleeding/spotting demonstrable as it was masked by the lochia. Mild pain at insertion was seen in only 11 patients in the PPIUD group. Slight bleeding/spotting was seen in 7.8% patients in the IIUD group, while mild to moderate pain was seen in 39.9% patients. At 6 weeks, 6 months and 1 year follow up with regard to patients complaining of pelvic pain/dysmenorrhea, the difference between the two groups was not statistically significant. Our study found that irregular bleeding or spotting was more in interval insertion than in the post-placental group. The difference in the two groups was statistically significant at 6 weeks and 6 months, but was not significant at 1 year. There was no case of perforation in either group. Our study found a statistically significant difference in expulsion after post-placental compared to delayed insertion. The difference between the two groups was statistically significant ( p  = 0.006) for cumulative expulsion. However, for interval expulsion rate, the difference was not statistically significant ( p  = 0.6). In our study, continuation rates appear to be higher in the PPIUD group, but the difference is not statistically significant., Conclusion: PPIUD is a safe, easy and effective alternative to interval IUD insertion and qualifies to be popularized as a first-line contraceptive agent in eligible patients owing to its immediate and sustained contraceptive benefit, patient comfort, convenience and lower incidence of side effects., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Federation of Obstetric & Gynecological Societies of India 2020.)

Recurrent miscarriage (RM) is defined as two or more consecutive pregnancy losses that affect approximately 5% of conceived women worldwide. RM is a multi-factorial reproductive problem and has been associated with parental chromosomal abnormalities, embryonic chromosomal rearrangements, uterine anomalies, autoimmune disorders, endocrine dysfunction, thrombophilia, life style factors, and maternal infections. However, the exact cause is still undecided in remaining 50% of cases. Immunological rejection of the embryo due to exacerbated maternal immune reaction against paternal embryonic antigens has been set forth as one of the significant reason for RM. The accurate means that shield the embryo during normal pregnancy from the attack of maternal immune network and dismissal are inadequately implicit. However, it is suggested that the genetically irreconcilable embryo escapes maternal immune rejection due to communication among many vital cytokines exuded at maternal-embryonic interface both by maternal and embryonic cells. Previous investigations suggested the Th1/Th2 dominance in altered immunity of RM patients, according to which the allogenic embryo flees maternal T cell reaction by inclining the Th0 differentiation toward Th2 pathway resulting into diminished pro-inflammatory Th1 immunity. However, recently pro-inflammatory Th17 cells and immunoregulatory Treg cells have been discovered as essential immune players in RM besides Th1/Th2 components. Cytokines are believed to develop a complicated regulatory network so as to establish a state of homeostasis between the semi-allogenic embryo and the maternal immune system. However, an adverse imbalance among cytokines at maternal-embryonic interface perhaps due to their gene polymorphisms may render immunoregulatory means not enough to re-establish homeostasis and thus may collapse pregnancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Paper is a versatile, flexible, porous, and eco-friendly substrate that is utilized in the fabrication of low-cost devices and biosensors for rapid detection of analytes of interest. Paper-based sensors provide affordable platforms for simple, accurate, and rapid detection of diseases, in addition to monitoring food quality, environmental and sun exposure, and detection of pathogens. Paper-based devices provide an inexpensive technology for fabrication of simple and portable diagnostic systems that can be immensely useful in resource-limited settings, such as in developing countries or austere environments, where fully-equipped facilities and highly trained medical staff are absent. In this work, we present the different types of paper that are currently utilized in fabrication of paper-based sensors, and common fabrication techniques ranging from wax printing to origami- and kirigami-based approaches. In addition, we present different detection techniques that are employed in paper-based sensors such as colorimetric, electrochemical, and fluorescence detection, chemiluminescence, and electrochemiluminescence, as well as their applications including disease diagnostics, cell cultures, monitoring sun exposure, and analysis of environmental reagents including pollutants. Furthermore, main advantages and disadvantages of different types of paper and future trends for paper-based sensors are discussed.

Vibroarthrography is a radiation-free and inexpensive method of assessing the condition of knee cartilage damage during extension-flexion movements. Acoustic sensors were placed on the patella and medial tibial plateau (two accelerometers) as well as on the lateral tibial plateau (a piezoelectric disk) to measure the structure-borne noise in 59 asymptomatic knees and 40 knees with osteoarthritis. After semi-automatic segmentation of the acoustic signals, frequency features were generated for the extension as well as the flexion phase. We propose simple and robust features based on relative high-frequency components. The normalized nature of these frequency features makes them insusceptible to influences on the signal gain, such as attenuation by fat tissue and variance in acoustic coupling. We analyzed their ability to serve as classification features for detection of knee osteoarthritis, including the effect of normalization and the effect of combining frequency features of all three sensors. The features permitted a distinction between asymptomatic and non-healthy knees. Using machine learning with a linear support vector machine, a classification specificity of approximately 0.8 at a sensitivity of 0.75 could be achieved. This classification performance is comparable to existing diagnostic tests and hence qualifies vibroarthrography as an additional diagnostic tool. Graphical Abstract Acoustic frequency features were used to detect knee osteoarthritis at 80% specificity and 75% sensitivity.

Testimony therapy can provide low-cost, brief, simple, and culturally adaptable psychosocial services in low-income countries (Agger, Raghuvanshi, Khan, Polatin, & Laursen, 2009). Nonetheless, there have been no well-controlled studies of testimony therapy. We report the analyses of a randomized controlled trial designed to assess the effectiveness of testimony therapy plus a culturally adapted ceremony in reducing mental health symptoms among Khmer Rouge torture survivors from across Cambodia. Using multilevel modeling, we compared symptoms of posttraumatic stress disorder, anxiety, and depression between a treatment (n = 45) and a control group (n = 43) at baseline, 3 months, and 6 months. We found that testimony therapy plus ceremony significantly reduced symptoms of posttraumatic stress disorder (d = 0.49), anxiety (d = 0.44), and depression (d = 0.53)., (Copyright © 2017 International Society for Traumatic Stress Studies.)

Background: Pregnancy is associated with multiple skin changes, most of which are physiological in nature, being the direct result of expected modifications of the hormonal, vascular, metabolic or immunologic status in pregnant females. Pregnancy however is also associated with certain pruritic eruptions, which not only cause distress to the pregnant female, but may influence the fetal outcome as well., Objective: The objective of this study was to determine the pattern of skin changes associated with pregnancy and to identify the various clinical types of pregnancy specific dermatoses (PSDs)., Materials and Methods: The study was a cross sectional study carried out at the out-patient Department of Gynecology and obstetrics of our hospital. A total of 650 pregnant females, irrespective of their parity and gestational age were screened for the presence of any dermatological complaint., Results: The age of the study population ranged from 17 to 39 years (mean age: 24 years). The study population included 272 (42%) primigravidae and 378 (58%) multigravidae. Physiological skin changes of pregnancy were seen in all patients, out of which linea nigra was the most common change, seen in 520 (80%) cases. Specific dermatoses of pregnancy were seen in 32 (4.9%) cases, which included (in the decreasing order of frequency) prurigo of pregnancy (50% cases), intrahepatic cholestasis of pregnancy (25% cases), polymorphic eruption of pregnancy (22% cases) and pemphigus gestationis (3% cases)., Conclusion: Skin changes were seen in 100% of pregnant females in this study, the major proportion being formed by physiological skin changes of pregnancy though PSDs were also seen in a significant number.

This study addressed the validity of the prolonged grief (PG) construct in a Cambodian context. Eighty mothers who lost a young adult daughter stemming from a crowd stampede incident during the annual water festival were interviewed at the six-month post-loss point along with a control group of similarly aged women who were not recently bereaved. Both groups were assessed for PG, PTSD, anxiety, and depression symptoms and well as for the number of distal losses experienced during the Khmer Rouge (KR) regime - knowing that all the women were old enough to have lived through the KR regime. Support for the discriminant validity of PG was shown in a factor analysis in which its core symptoms were distinguished from anxiety, depression, and PTSD symptoms. Also, support was found for its incremental validity as shown in the unique sensitivity of PG in distinguishing the two groups when controlling for the other symptoms. Lastly, a positive relationship was found between the number of distal deaths experienced during the KR regime and PG symptom severity among the group of recently bereaved mothers, providing support for the predictive validity of PG. Implications as well as study limitations are discussed., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Azomethine imines can be accessed upon heating appropriate alkynylhydrazide precursors. This simple thermal hydroamination approach allows the formation of five- and six-membered dipoles in modest to excellent yields. The structure of the acyl group is important to minimize side reactions and allow the isolation of the azomethine imines by column chromatography.

Context: To improve the treatment outcomes in women with polycystic ovary syndrome (PCOS), various drugs like glitazones, oral contraceptive pills, or antiandrogens have been combined with metformin., Objective: The aim of the study was to compare the efficacy of the combination of low-dose spironolactone and metformin with either drug alone in the management of women with PCOS., Design and Setting: The present study was an open-label, randomized study conducted at a tertiary care referral center., Patients and Intervention: Of 204 women who met the 2006 Androgen Excess-PCOS criteria for PCOS, 198 were randomized into 3 equal groups to receive metformin (1000 mg/d), low-dose spironolactone (50 mg/d), or a combination of both drugs for a period of 6 months. A total of 169 subjects (n = 56 metformin, 51 spironolactone, 62 combination) completed the study., Main Outcome Measures: Menstrual cycle pattern, Ferriman-Gallwey score, body mass index (BMI), waist-hip ratio, blood pressure, LH, FSH, total T, glucose and insulin sensitivity indices were measured at baseline (0 mo) and 3 and 6 months after the intervention. Recording of adverse events and drug compliance was assessed at each of the visits., Results: The 3 groups had comparable mean age and BMI at baseline. By 6 months, menstrual cycles/y increased, whereas Ferriman-Gallwey score, serum total T, and area under the curve-glucose and -insulin decreased significantly (P < .05) in the combination group as compared to either drug alone. There was no significant change in body weight, BMI, waist-hip ratio, and blood pressure in any of the 3 groups. The combination group had better compliance than either drug alone, and the adverse event rate was not higher., Conclusion: The combination of low-dose spironolactone with metformin seems superior to either drug alone in terms of clinical benefits and compliance in women with PCOS.

Introduction: Normal pregnancy results in a number of important physiological and hormonal changes that alter thyroid function. In pregnancy, the thyroid gland being subjected to physiological stress undergoes several adaptations to maintain sufficient output of thyroid hormones for both mother and fetus. Consequently, pregnant women have been found to be particularly vulnerable to iodine deficiency disorders (IDD), and compromised iodine status during pregnancy has been found to affect the thyroid function and cognition in the neonates., Objectives: Two decades after successful universal salt iodization (USI) in the country, there is scarce data on the iodine status of the pregnant women and their neonates. This is more relevant in areas like Kashmir valley part of sub-Himalayan belt, an endemic region for IDD in the past. The objective was to estimate Urinary Iodine status in pregnant women, the most vulnerable population., Materials and Methods: We studied thyroid function [free T3 (FT3), T3, free T4 (FT4), T4, thyroid stimulating hormone (TSH)] and urinary iodine excretion (UIE) in the 1(st), 2(nd), and 3(rd) trimesters and at early neonatal period in neonates in 81 mother-infant pairs (hypothyroid women on replacement) and compared them with 51 control mother-infant pairs (euthyroid)., Results: Mean age of cases (29.42 + 3.56 years) was comparable to that of controls (29.87 + 3.37 years). The thyroid function evaluation done at baseline revealed the following: FT3 2.92 ± 0.76 versus 3.71 ± 0.54 pg/ml, T3 1.38 ± 0.37 versus 1.70 ± 0.35 ng/dl, FT4 1.22 ± 0.33 versus 1.52 ± 0.21 ng/dl, T4 9.54 ± 2.34 versus 13.55 ± 2.16 μg/dl, and TSH 7.92 ± 2.88 versus 4.14 ± 1.06 μIU/ml in cases versus controls (P > 0.01), respectively. The 2(nd) to 6(th) day thyroid function of neonates born to case and control mothers revealed T3 of 1.46 ± 0.44 versus 1.48 ± 0.36 ng/dl, T4 of 12.92 ± 2.57 versus 11.76 ± 1.78 μg/dl, and TSH of 3.64 ± 1.92 versus 3.82 ± 1.45 μIU/ml, respectively., Discussion: UIE was similar (139.12 ± 20.75 vs. 143.78 ± 17.65 μg/l; P = 0.8), but TSH values were higher in cases (7.92 ± 2.88) as compared to controls (4.14 ± 1.06). Although UIE gradually declined from 1(st) trimester to term, it remained in the sufficient range in both cases and controls. Thyroid function and UIE was similar in both case and control neonates., Conclusion: We conclude that pregnant Kashmiri women and their neonates are iodine sufficient, indicating successful salt iodization in the community. Large community-based studies on thyroid function, autoimmunity, malignancies, etc., are needed to see the long-term impact of iodization.

Background: During the Khmer Rouge (KR) regime from 1975 to 1979 millions of Cambodians were confronted with the death or murder of family members. The long-term psychological consequences of these traumatic losses have not yet been investigated. The purpose of this study was to determine the rate and potential predictors of prolonged grief disorder (PGD) in survivors of the KR regime., Method: The Inventory of Complicated Grief-Revised (ICG-R) was administered in a sample of N=775 Cambodians in face-to-face interviews who had lost at least one family member during the KR regime. Symptoms of PTSD were assessed with the PTSD Checklist-Civilian Version and symptoms of depression and anxiety with the Hopkins Symptom Checklist-25., Results: The prevalence of PGD in the sample was 14.3%. PGD was moderately associated with symptoms of depression, anxiety and PTSD. The loss of a spouse, a child, or a parent was associated with higher symptom severity of PGD than was the loss of a sibling or distant relatives. PGD was predicted by the relationship to the deceased and symptoms of depression and PTSD., Limitations: Limitations of the study include the non-random sampling recruitment. The ICG-R has not been validated for use in Cambodia., Conclusions: The vast majority of Cambodians lost family members during the KR regime. Even three decades later, PGD was prevalent in a substantial proportion of the present sample and related to other psychiatric disorders. The results underline the importance of examining PGD in studies of war-related psychological impairment., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Chromatin immunoprecipitation identifies specific interactions between genomic DNA and proteins, advancing our understanding of gene-level and chromosome-level regulation. Based on chromatin immunoprecipitation experiments using validated antibodies, we define the genome-wide distributions of 19 histone modifications, one histone variant, and eight chromatin-associated proteins in Caenorhabditis elegans embryos and L3 larvae. Cluster analysis identified five groups of chromatin marks with shared features: Two groups correlate with gene repression, two with gene activation, and one with the X chromosome. The X chromosome displays numerous unique properties, including enrichment of monomethylated H4K20 and H3K27, which correlate with the different repressive mechanisms that operate in somatic tissues and germ cells, respectively. The data also revealed striking differences in chromatin composition between the autosomes and between chromosome arms and centers. Chromosomes I and III are globally enriched for marks of active genes, consistent with containing more highly expressed genes, compared to chromosomes II, IV, and especially V. Consistent with the absence of cytological heterochromatin and the holocentric nature of C. elegans chromosomes, markers of heterochromatin such as H3K9 methylation are not concentrated at a single region on each chromosome. Instead, H3K9 methylation is enriched on chromosome arms, coincident with zones of elevated meiotic recombination. Active genes in chromosome arms and centers have very similar histone mark distributions, suggesting that active domains in the arms are interspersed with heterochromatin-like structure. These data, which confirm and extend previous studies, allow for in-depth analysis of the organization and deployment of the C. elegans genome during development.

We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.