Long-term carcinogenicity of pan masala in Swiss mice

Carcinogenicity of pan masala, a dry powdered chewing mixture of areca nut, catechu, lime, spices and flavoring agents was evaluated by means of the long-term animal bio-assay 6- to 7-week old male and female S/RVCri mice were divided randomly into intermediate and lifetime exposure groups and fed normal diet without pan masala - (zero dose) or diet containing 2.5% and 5% pan masala. Animals in the intermediate-exposure group (n = 10/gender/dose group) were killed after 6, 12 or 18 months of treatment, while those in the lifetime-exposure group (n = 54/gender/dose group) were killed when moribund or at the termination of the experiment at 24 months. Several tissues were processed for histopathological examination. The body weight and survival rate of mice fed pan masala were lower than that of the controls. Histopathological observations of tissues from control animals did not reveal any neoplastic alterations. However, lifetime feeding of pan masala induced adenoma of the liver, stomach, prostate and sebaceous glands, also forestomach papilloma, liver hamartoma, hepatoma and hemangioma, carcinoma of the forestomach, adenocarcinoma of the lung and liver, and testicular lymphoma. Neoplastic lesions appeared mainly in the liver (n = 13), stomach (n = 3) and lung (n = 8). Lung adenocarcinoma, the most frequent malignant tumor type, was observed in 2/120 mice in the intermediate-exposure group and in 8/216 animals in the lifetime-exposure group. Statistical analysis of tumor-induction data revealed a significant dose-related increase in lung adenocarcinomas but not in liver and stomach neoplasms indicating that lung is the major target tissue for the carcinogenic action of pan masala

Evaluating the effectiveness and cost effectiveness of the ‘strengthening families, strengthening communities’ group-based parenting programme: study protocol and initial insights

Background: Up to 20% of UK children experience socio-emotional difficulties which can have serious implications for themselves, their families and society. Stark socioeconomic and ethnic inequalities in children’s well-being exist. Supporting parents to develop effective parenting skills is an important preventive strategy in reducing inequalities. Parenting interventions have been developed, which aim to reduce the severity and impact of these difficulties. However, most parenting interventions in the UK focus on early childhood (0–10 years) and often fail to engage families from ethnic minority groups and those living in poverty. Strengthening Families, Strengthening Communities (SFSC) is a parenting programme designed by the Race Equality Foundation, which aims to address this gap. Evidence from preliminary studies is encouraging, but no randomised controlled trials have been undertaken so far. Methods/design: The TOGETHER study is a multi-centre, waiting list controlled, randomised trial, which aims to test the effectiveness of SFSC in families with children aged 3–18 across seven urban areas in England with ethnically and socially diverse populations. The primary outcome is parental mental well-being (assessed by the Warwick-Edinburgh Mental Well-Being Scale). Secondary outcomes include child socio-emotional well-being, parenting practices, family relationships, self-efficacy, quality of life, and community engagement. Outcomes are assessed at baseline, post intervention, three- and six-months post intervention. Cost effectiveness will be estimated using a cost-utility analysis and cost-consequences analysis. The study is conducted in two stages. Stage 1 comprised a 6-month internal pilot to determine the feasibility of the trial. A set of progression criteria were developed to determine whether the stage 2 main trial should proceed. An embedded process evaluation will assess the fidelity and acceptability of the intervention. Discussion: In this paper we provide details of the study protocol for this trial. We also describe challenges to implementing the protocol and how these were addressed. Once completed, if beneficial effects on both parental and child outcomes are found, the impact, both immediate and longer term, are potentially significant. As the intervention focuses on supporting families living in poverty and those from minority ethnic communities, the intervention should also ultimately have a beneficial impact on reducing health inequalities. Trial registration: Prospectively registered Randomised Controlled Trial ISRCTN15194500

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Parental attachment and depressive symptoms in pregnancies complicated by twin-twin transfusion syndrome: a cohort study

BACKGROUND: Twin-twin transfusion syndrome (TTTS) is a highly morbid condition in which treatment exists, but the pregnancy remains high-risk until delivery. It may have serious sequelae, including fetal death, and in the longer term, neurodevelopmental problems. The aim of this study is to assess antenatal and postnatal parental attachment and depressive symptoms in those with pregnancies affected by TTTS. METHODS: Couples attending for fetoscopic laser ablation treatment of TTTS were asked to complete Condon's Maternal/Paternal Antenatal/Postnatal Attachment Scale as appropriate, and the Edinburgh Depression Scale the day before ablation, 4 weeks post-ablation, and 6-10 weeks postnatally. RESULTS: 25/27 couples completed the pre-ablation questionnaire (median gestational age 19 + 3 weeks [interquartile range 18 + 2-20 + 6]). 8/18 eligible couples returned the post-ablation questionnaire. 5/17 eligible couples returned the postnatal questionnaire. There was no significant difference in parento-fetal attachment when mothers were compared to fathers at each time point, however parento-fetal attachment did increase over time in mothers (p = 0.004), but not fathers. Mothers reported more depressive symptoms antenatally compared to fathers (p < 0.02), but there was no difference postnatally. 50% women reported Edinburgh Depression Scale scores above the cut-off (≥15) 4 weeks post-ablation. Over time maternal depressive symptoms decreased (p = 0.006), however paternal depressive symptoms remained the same. CONCLUSIONS: This is the first attachment and depression study in a UK cohort of parents with pregnancies affected by TTTS. Although this was a small cohort and the questionnaires used had not been validated in these circumstances, the results suggest that centres caring for these couples should be aware of the risk of maternal and paternal antenatal depression, and screen and refer for additional psychological support. Further work is needed in larger cohorts. TRIAL REGISTRATION: ISRCTN 13114861 (retrospectively registered)

Шкала оценки сопутствующих заболеваний у ареактивных пациентов (CoCoS): лингвокультурная адаптация русскоязычной версии (сообщение)

   Identification of complications and control of comorbidities are essential in monitoring the patients with chronic disorders of consciousness and predicting their outcomes. The researchers of the Department of Biotechnological and Applied Clinical Sciences of the University of L'Aquila (Italy) developed the Comorbidities Coma Scale (CoCoS) for a comprehensive assessment of such patients. Lack of an officially validated version of the scale hampers its use in Russia, while using versions which have not been completely validated prevents clinicians from obtaining reliable results when examining patients with chronic disorders of consciousness.   Aim. To develop the official Russian language version of the Comorbidities Coma Scale, considering various linguistic and cultural parameters, as a part of the 1st stage of the validation study.   Material and methods. The first stage of validation was completed: direct and reverse translation of the scale was performed by two independent medical translators. The translated version was assessed by an expert board including an expert translator, neurologists, and critical care specialists. Pilot test and two meetings of the expert board, before and after testing, were arranged to assess the results and approve the final Russian version of the scale.   Results. During the first meeting of the expert board, corrections were made in the Russian language version of the scale in terms of language and cultural adaptation. Pilot testing was carried out based on the inclusion and exclusion criteria. The researchers had no difficulties in understanding and interpreting the instructions for the scale. The second meeting of the expert board was held thereupon, and the final version of the Russian language version of the scale was adopted, which is available on the website of the Center for Validation of Health Status Questionnaires and Scales of the Research Center of Neurology.   Conclusion. The first stage of validation, i. e., linguistic and cultural adaptation, was carried out at the Research Center of Neurology (Moscow, Russia). For the first time, the Russian version of the scale for assessing comorbidities in patients with chronic disorders of consciousness was presented and approved for the practical use. The future publications will address the psychometric results of the scale such as sensitivity, validity, reliability.   Выявление осложнений и контроль над течением сопутствующих заболеваний является важнейшим этапом в отслеживании динамики и прогнозе исходов у пациентов с хроническими нарушениями сознания. Для проведения оценки состояния у данной категории пациентов сотрудниками департамента биотехнологических и прикладных клинических наук университета L'Aquila (Италия) была разработана шкала — Comorbidities Coma Scale (CoCoS). Отсутствие официально валидированной версии данной шкалы затрудняет ее применение в России, а использование версий, не прошедших все необходимые этапы валидации, препятствует получению достоверных результатов при обследовании пациентов с хроническими нарушениями сознания.   Цель. Разработка официальной русскоязычной версии Шкалы оценки сопутствующих заболеваний у ареактивных пациентов с учетом языковых и культурных особенностей ее пользователей в рамках проведения 1-го этапа валидационного исследования.   Материал и методы. Письменное разрешение на адаптацию шкалы CoCoS было получено сотрудниками группы валидации международных шкал и опросников Научного центра неврологии (ФГБНУ НЦН, г. Москва, Россия) у разработчика оригинальной версии Francesca Pistoia. Провели первый этап валидации: выполнен прямой и обратный перевод шкалы двумя независимыми медицинскими переводчиками. Произведена оценка разработанной версии экспертной комиссией с участием переводчика-эксперта, неврологов и анестезиологов-реаниматологов. Провели пилотное тестирование на 15 пациентах с диагнозом хронического нарушения сознания и два заседания экспертной комиссии до и после тестирования для оценки результатов и утверждения окончательной русскоязычной версии шкалы.   Результаты. В ходе первого заседания экспертной комиссии внесли поправки в русскоязычную версию шкалы в рамках языковой и культурной адаптации: были изменены единицы измерения лабораторных показателей с мг/дл на ммоль/л в 7-м и 14-м пунктах (оценка гликемии и концентрации креатинина, соответственно). Изменен термин «надаортальные сосуды» на «брахиоцефальные артерии» в 10-м пункте, сопоставлены предложенные варианты повреждения мягких тканей со стадиями развития пролежней согласно NPUAP — EPUAP [18] в 21-м пункте, добавлен параметр индекс массы тела (ИМТ) для оценки выраженности недостаточности питания. В ходе пилотного тестирования с учетом критериев включения и исключения сложностей при понимании и интерпретации инструкций шкалы у исследователей не возникло. По итогам состоялось второе заседание экспертной комиссии, на котором приняли окончательный вариант русскоязычной версии шкалы. Он доступен для ознакомления на сайте группы валидациимеждународных шкал и опросников ФГБНУ НЦН https://www.neurology.ru/reabilitaciya/centr-validacii-mezhdunarodnyh-shkal-i-oprosnikov, а также по QR-коду.   Заключение. На базе ФГБНУ НЦН выполнили первый этап валидации — лингвокультурную адаптацию. Впервые представили и рекомендовали к использованию русскоязычную версию Шкалы оценки сопутствующих заболеваний у ареактивных пациентов. В последующих публикациях будут представлены результаты оценки психометрических свойств (чувствительность, валидность, надежность) русскоязычной версии данной шкалы

Comorbidities Coma Scale (CoCoS): Linguistic and Cultural Adaptation of the Russian-Language Version

Identification of complications and control of comorbidities are essential in monitoring the patients with chronic disorders of consciousness and predicting their outcomes. The researchers of the Department of Biotechnological and Applied Clinical Sciences of the University of L'Aquila (Italy) developed the Comorbidities Coma Scale (CoCoS) for a comprehensive assessment of such patients. Lack of an officially validated version of the scale hampers its use in Russia, while using versions which have not been completely validated prevents clinicians from obtaining reliable results when examining patients with chronic disorders of consciousness.   Aim. To develop the official Russian language version of the Comorbidities Coma Scale, considering various linguistic and cultural parameters, as a part of the 1st stage of the validation study.   Material and methods. The first stage of validation was completed: direct and reverse translation of the scale was performed by two independent medical translators. The translated version was assessed by an expert board including an expert translator, neurologists, and critical care specialists. Pilot test and two meetings of the expert board, before and after testing, were arranged to assess the results and approve the final Russian version of the scale.   Results. During the first meeting of the expert board, corrections were made in the Russian language version of the scale in terms of language and cultural adaptation. Pilot testing was carried out based on the inclusion and exclusion criteria. The researchers had no difficulties in understanding and interpreting the instructions for the scale. The second meeting of the expert board was held thereupon, and the final version of the Russian language version of the scale was adopted, which is available on the website of the Center for Validation of Health Status Questionnaires and Scales of the Research Center of Neurology.   Conclusion. The first stage of validation, i. e., linguistic and cultural adaptation, was carried out at the Research Center of Neurology (Moscow, Russia). For the first time, the Russian version of the scale for assessing comorbidities in patients with chronic disorders of consciousness was presented and approved for the practical use. The future publications will address the psychometric results of the scale such as sensitivity, validity, reliability

Normative data on regional sweat-sodium concentrations of professional male team-sport athletes

Background: The purpose of this paper was to report normative data on regional sweat sweat-sodium concentrations of various professional male team-sport athletes, and to compare sweat-sodium concentrations among sports. Data to this effect would inform our understanding of athlete sodium requirements, thus allowing for the individualisation of sodium replacement strategies. Accordingly, data from 696 athletes (Soccer, n = 270; Rugby, n = 181; Baseball, n = 133; American Football, n = 60; Basketball, n = 52) were compiled for a retrospective analysis. Regional sweat-sodium concentrations were collected using the pilocarpine iontophoresis method, and compared to self-reported measures collected via questionnaire. Results: Sweat-sodium concentrations were significantly higher (p < 0.05) in American football (50.4 ± 15.3 mmol·L-1), baseball (54.0 ± 14.0 mmol·L-1), and basketball (48.3 ± 14.0 mmol·L-1) than either soccer (43.2 ± 12.0 mmol·L-1) or rugby (44.0 ± 12.1 mmol·L-1), but with no differences among the N.American or British sports. There were strong positive correlations between sweat-sodium concentrations and self-reported sodium losses in American football (rs = 0.962, p < 0.001), basketball (rs = 0.953, p < 0.001), rugby (rs = 0.813, p < 0.001), and soccer (rs = 0.748, p < 0.001). Conclusions: The normative data provided on sweat-sodium concentrations might assist sports science/medicine practitioners in generating bespoke hydration and electrolyte-replacement strategies to meet the sodium demands of professional team-sport athletes. Moreover, these novel data suggest that self-reported measures of sodium loss might serve as an effective surrogate in the absence of direct measures; i.e., those which are more expensive or non-readily available

5-Aza-2′-deoxycytidine stress response and apoptosis in prostate cancer

While studying on epigenetic regulatory mechanisms (DNA methylation at C-5 of –CpG– cytosine and demethylation of methylated DNA) of certain genes (FAS, CLU, E-cadh, CD44, and Cav-1) associated with prostate cancer development and its better management, we noticed that the used in vivo dose of 5-aza-2′-deoxycytidine (5.0 to 10.0 nM, sufficient to inhibit DNA methyltransferase activity in vitro) helped in the transcription of various genes with known (steroid receptors, AR and ER; ER variants, CD44, CDH1, BRCA1, TGFβR1, MMP3, MMP9, and UPA) and unknown (DAZ and Y-chromosome specific) proteins and the respective cells remained healthy in culture. At a moderate dose (20 to 200 nM) of the inhibitor, cells remain growth arrested. Upon subsequent challenge with increased dose (0.5 to 5.0 μM) of the inhibitor, we observed that the cellular morphology was changing and led to death of the cells with progress of time. Analyses of DNA and anti-, pro-, and apoptotic factors of the affected cells revealed that the molecular events that went on are characteristics of programmed cell death (apoptosis)

Effects of male postpartum depression on father-infant interaction: the mediating role of face processing

It is estimated that postpartum depression affects up to 25% of men. Despite such high prevalence, the majority of studies on postpartum depression are focused on mothers, and the role of paternal depression and its effects on infant development have been overlooked by researchers and clinicians. The present study aimed to fill this gap by investigating the effect of paternal postpartum depression on father–infant interactions. In addition, we examined whether differences in face recognition mediated the effects of paternal postpartum depression on father–infant interactions. A total of 61 father–infant dyads (17 postpartum depression, 44 controls) took part in the study. Results revealed that compared to controls, fathers with postpartum depression had a worse pattern of interaction with their infants on measures of responsiveness, mood, and sensitivity; they also had greater difficulty in recognizing happy adult faces, but greater facility in recognizing sad adult faces. Depressed fathers attributed greater intensities to sad adult and infant faces. The tendency to attribute greater intensity to sad adult faces was confirmed as a partial mediator of the effect of paternal postpartum depression on measures of father responsiveness and as a full mediator of the effects of paternal depression on father sensitivity. Clinical implications and suggestions for further studies are discussed

DNA methylation, the early-life social environment and behavioral disorders

One of the outstanding questions in behavioral disorders is untangling the complex relationship between nurture and nature. Although epidemiological data provide evidence that there is an interaction between genetics (nature) and the social and physical environments (nurture) in a spectrum of behavioral disorders, the main open question remains the mechanism. Emerging data support the hypothesis that DNA methylation, a covalent modification of the DNA molecule that is a component of its chemical structure, serves as an interface between the dynamic environment and the fixed genome. We propose that modulation of DNA methylation in response to environmental cues early in life serves as a mechanism of life-long genome adaptation. Under certain contexts, this adaptation can turn maladaptive resulting in behavioral disorders. This hypothesis has important implications on understanding, predicting, preventing, and treating behavioral disorders including autism that will be discussed