Apoptosis dan nekrosis sel mukosa rongga mulut akibat radiasi sinar-x dental radiografik konvensional

Background : Despite wide use as a diagnostic tool in medical and dental practice, conventional dental x-ray radiography is a common source of low-dose diagnostic radiation exposure wich may induce DNA damage and the result of cell death (apoptotic and necrotic cells). Purpose : The objective of this study was to examine the effect of conventional dental x-ray radiation on expression of apoptotic and necrotic in oral mucosa cell male rats (rattus norvegicus var. wistar). For this study on experimental laboratories technique was done. Method. Twenty four male wistar rats (150 g) were radiated with 0 mSv, 0,08 mSv, 0,16 mSv, 0,24 mSv of dental x-rays, with the mouth to the source. Oral mucosa cells was collected ten days after radiation were analysed for apopotic cells using immunohistochemistry (Apo-BrdU-IHCTM) and necrotic cells using histology (Hematoxillin Eosin). Apoptotic and necrotic cells examined under light microscope at 1000x magnification. Result. Using test of one way anova showed that conventional dental x-ray radiation to mouth of rat can cause significant differences expression of apoptotic and necrotic on oral mucosa cells. Using correlation test showed a significant influences of positive correlation. Conclusion : Apoptotic and necrotic cell was increase associated with higher dose of conventional dental x-ray radiation in oral mucosa cell

Plasma free choline, betaine and cognitive performance: the Hordaland Health Study

Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70–74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0 v. 61·5, P= 0·004), m-DST (10·5 v. 9·8, P= 0·005) and m-MMSE (11·5 v. 11·4, P= 0·01). A generalised additive regression model showed a positive dose–response relationship between the m-MMSE and choline (P= 0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B12 ( ≤ 257 pmol/l) concentrations (RRKOLT= 2·6, 95 % CI 1·1, 6·1; RRm-MMSE= 2·7, 95 % CI 1·1, 6·6; RRCOWAT= 3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) ( ≥ 3·95 μmol/l) concentrations (RRm-BD= 2·8, 95 % CI 1·3, 6·1). Low betaine ( ≤ 31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RRKOLT= 2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B12 or high MMA on cognitive performance.publishedVersio

CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo KRT12 mutation-specific targeting

CRISPR/Cas9-based therapeutics hold the possibility for permanent treatment of genetic disease. The potency and specificity of this system has been used to target dominantly inherited conditions caused by heterozygous missense mutations through inclusion of the mutated base in the short-guide RNA (sgRNA) sequence. This research evaluates a novel approach for targeting heterozygous single-nucleotide polymorphisms (SNPs) using CRISPR/Cas9. We determined that a mutation within KRT12, which causes Meesmann's epithelial corneal dystrophy (MECD), leads to the occurrence of a novel protospacer adjacent motif (PAM). We designed an sgRNA complementary to the sequence adjacent to this SNP-derived PAM and evaluated its potency and allele specificity both in vitro and in vivo. This sgRNA was found to be highly effective at reducing the expression of mutant KRT12 mRNA and protein in vitro. To assess its activity in vivo we injected a combined Cas9/sgRNA expression construct into the corneal stroma of a humanized MECD mouse model. Sequence analysis of corneal genomic DNA revealed non-homologous end-joining repair resulting in frame-shifting deletions within the mutant KRT12 allele. This study is the first to demonstrate in vivo gene editing of a heterozygous disease-causing SNP that results in a novel PAM, further highlighting the potential for CRISPR/Cas9-based therapeutics

Socioeconomic inequalities in overweight and obesity among 6‐ to 9‐year‐old children in 24 countries from the World Health Organization European region

Childhood overweight and obesity have significant short- and long-term negative impacts on children's health and well-being. These challenges are unequally distributed according to socioeconomic status (SES); however, previous studies have often lacked standardized and objectively measured data across national contexts to assess these differences. This study provides a cross-sectional picture of the association between SES and childhood overweight and obesity, based on data from 123,487 children aged 6–9 years in 24 countries in the World Health Organization (WHO) European region. Overall, associations were found between overweight/obesity and the three SES indicators used (parental education, parental employment status, and family-perceived wealth). Our results showed an inverse relationship between the prevalence of childhood overweight/obesity and parental education in high-income countries, whereas the opposite relationship was observed in most of the middle-income countries. The same applied to family-perceived wealth, although parental employment status appeared to be less associated with overweight and obesity or not associated at all. This paper highlights the need for close attention to context when designing interventions, as the association between SES and childhood overweight and obesity varies by country economic development. Population-based interventions have an important role to play, but policies that target specific SES groups are also needed to address inequalities.The authors gratefully acknowledge support through a grant from the Russian Government in the context of the WHO European Office for the Prevention and Control of NCDs. The Ministries of health of Austria, Croatia, Greece, Italy, Malta, Norway, and the Russian Federation provided financial support for the meetings at which the protocol, data collection procedures, and analyses were discussed. Data collection in the countries was made possible through funding from: Albania: World Health Organization (WHO) Country Office Albania and the WHO Regional Office for Europe. Bulgaria: WHO Regional Office for Europe. Croatia: Ministry of Health, Croatian Institute of Public Health and WHO Regional Office for Europe. Czechia: Ministry of Health of the Czech Republic, grant nr. 17-31670A and MZCR—RVO EU 00023761. Denmark: The Danish Ministry of Health. France: Santé publique France, the French Agency for Public Health. Georgia: WHO. Ireland: Health Service Executive. Italy: Italian Ministry of Health; Italian National Institute of Health (Istituto Superiore di Sanità). Kazakhstan: the Ministry of Health of the Republic of Kazakhstan within the scientific and technical program. Kyrgyzstan: World Health Organization. Latvia: Centre for Disease Prevention and Control, Ministry of Health, Latvia. Lithuania: Science Foundation of Lithuanian University of Health Sciences and Lithuanian Science Council and WHO. Malta: Ministry of Health; Montenegro: WHO and Institute of Public Health of Montenegro. Poland, National Health Program, Ministry of Health. Portugal: Ministry of Health Institutions, the National Institute of Health, Directorate General of Health, Regional Health Directorates and the kind technical support from the Center for Studies and Research on Social Dynamics and Health (CEIDSS). Romania: Ministry of Health; Russian Federation: WHO. San Marino: Health Ministry, Educational Ministry, Social Security Institute and Health Authority. Spain: the Spanish Agency for Food Safety & Nutrition. Tajikistan: WHO Country Office in Tajikistan and Ministry of Health and Social Protection. Turkmenistan: WHO Country Office in Turkmenistan and Ministry of Health. Turkey: Turkish Ministry of Health and World Bank.info:eu-repo/semantics/publishedVersio

Socioeconomic disparities in physical activity, sedentary behavior and sleep patterns among 6- to 9-year-old children from 24 countries in the WHO European region

Physical activity, sedentary behavior, and sleep are important predictors of children's health. This paper aimed to investigate socioeconomic disparities in physical activity, sedentary behavior, and sleep across the WHO European region. This cross-sectional study used data on 124,700 children aged 6 to 9 years from 24 countries participating in the WHO European Childhood Obesity Surveillance Initiative between 2015 and 2017. Socioeconomic status (SES) was measured through parental education, parental employment status, and family perceived wealth. Overall, results showed different patterns in socioeconomic disparities in children's movement behaviors across countries. In general, high SES children were more likely to use motorized transportation. Low SES children were less likely to participate in sports clubs and more likely to have more than 2 h/day of screen time. Children with low parental education had a 2.24 [95% CI 1.94-2.58] times higher risk of practising sports for less than 2 h/week. In the pooled analysis, SES was not significantly related to active play. The relationship between SES and sleep varied by the SES indicator used. Importantly, results showed that low SES is not always associated with a higher prevalence of "less healthy" behaviors. There is a great diversity in SES patterns across countries which supports the need for country-specific, targeted public health interventions.The authors gratefully acknowledge support from a grant from the Russian Government in the context of the WHO European Office for the Prevention and Control of NCDs. Data collection in the countries was made possible through funding from: Croatia: Ministry of Health, Croatian Institute of Public Health and WHO Regional Office for Europe. Albania: World Health Organization (WHO) Country Office Albania and the WHO Regional Office for Europe. Bulgaria: WHO Regional Office for Europe. Czech Republic: Ministry of Health of the Czech Republic, grant nr. AZV MZČR 17-31670 A and MZČR–RVO EÚ 00023761. Denmark: The Danish Ministry of Health. France: Santé publique France, the French Agency for Public Health. Georgia: WHO. Ireland: Health Service Executive. Italy: Italian Ministry of Health; Italian National Institute of Health (Istituto Superiore di Sanità). Kazakhstan: the Ministry of Health of the Republic of Kazakhstan within the scientific and technical program. Kyrgyzstan: World Health Organization. Latvia: Centre for Disease Prevention and Control, Ministry of Health, Latvia. Lithuania: Science Foundation of Lithuanian University of Health Sciences and Lithuanian Science Council and WHO. Malta: Ministry of Health. Montenegro: WHO and Institute of Public Health of Montenegro. Poland: National Health Programme, Ministry of Health. Portugal: Ministry of Health Institutions, the National Institute of Health, Directorate General of Health, Regional Health Directorates and the kind technical support from the Center for Studies and Research on Social Dynamics and Health (CEIDSS). Romania: Ministry of Health. Russian Federation: WHO. San Marino: Health Ministry. Spain: the Spanish Agency for Food Safety & Nutrition. Tajikistan: WHO Country Office in Tajikistan and Ministry of Health and Social Protection; Turkmenistan: WHO Country Office in Turkmenistan and Ministry of Health. Turkey: Turkish Ministry of Health and World Bank. Austria: Federal Ministry of Labor, Social Affairs, Health and Consumer Protection of Austria.info:eu-repo/semantics/publishedVersio

Presence of celiac disease epitopes in modern and old hexaploid wheat varieties: wheat breeding may have contributed to increased prevalence of celiac disease

Gluten proteins from wheat can induce celiac disease (CD) in genetically susceptible individuals. Specific gluten peptides can be presented by antigen presenting cells to gluten-sensitive T-cell lymphocytes leading to CD. During the last decades, a significant increase has been observed in the prevalence of CD. This may partly be attributed to an increase in awareness and to improved diagnostic techniques, but increased wheat and gluten consumption is also considered a major cause. To analyze whether wheat breeding contributed to the increase of the prevalence of CD, we have compared the genetic diversity of gluten proteins for the presence of two CD epitopes (Glia-α9 and Glia-α20) in 36 modern European wheat varieties and in 50 landraces representing the wheat varieties grown up to around a century ago. Glia-α9 is a major (immunodominant) epitope that is recognized by the majority of CD patients. The minor Glia-α20 was included as a technical reference. Overall, the presence of the Glia-α9 epitope was higher in the modern varieties, whereas the presence of the Glia-α20 epitope was lower, as compared to the landraces. This suggests that modern wheat breeding practices may have led to an increased exposure to CD epitopes. On the other hand, some modern varieties and landraces have been identified that have relatively low contents of both epitopes. Such selected lines may serve as a start to breed wheat for the introduction of ‘low CD toxic’ as a new breeding trait. Large-scale culture and consumption of such varieties would considerably aid in decreasing the prevalence of CD

Summary of joint European Hematology Association (EHA) and EuroBloodNet recommendations on diagnosis and treatment of methemoglobinemia

Genetics of disease, diagnosis and treatmen

Recommendations for diagnosis and treatment of methemoglobinemia

Methemoglobinemia is a rare disorder associated with oxidization of divalent ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin (MetHb). Methemoglobinemia can result from either inherited or acquired processes. Acquired forms are the most common, mainly due to the exposure to substances that cause oxidation of the Hb both directly or indirectly. Inherited forms are due either to autosomal recessive variants in the CYB5R3 gene or to autosomal dominant variants in the globin genes, collectively known as HbM disease. Our recommendations are based on a systematic literature search. A series of questions regarding the key signs and symptoms, the methods for diagnosis, the clinical management in neonatal/childhood/adulthood period, and the therapeutic approach of methemoglobinemia were formulated and the relative recommendations were produced. An agreement was obtained using a Delphi-like approach and the experts panel reached a final consensus >75% of agreement for all the questions.Genetics of disease, diagnosis and treatmen