Founder effects facilitate the use of a genotyping-based approach to molecular diagnosis in Swedish patients with familial hypercholesterolaemia

Aim To investigate whether genotyping could be used as a cost-effective screening step, preceding next-generation sequencing (NGS), in molecular diagnosis of familial hypercholesterolaemia (FH) in Swedish patients. Methods and results Three hundred patients of Swedish origin with clinical suspicion of heterozygous FH were analysed using a specific array genotyping panel embedding 112 FH-causing mutations in the LDLR, APOB and PCSK9 genes. The mutations had been selected from previous reports on FH patients in Scandinavia and Finland. Mutation-negative cases were further analysed by NGS. In 181 patients with probable or definite FH using the Dutch lipid clinics network (DLCN) criteria (score >= 6), a causative mutation was identified in 116 (64%). Of these, 94 (81%) were detected by genotyping. Ten mutations accounted for more than 50% of the positive cases, with APOB c.10580G>A being the most common. Mutations in LDLR predominated, with (c.2311+1_2312-1)(2514)del (FH Helsinki) and c.259T>G having the highest frequency. Two novel LDLR mutations were identified. In patients with DLCN score A was higher than previously reported in Sweden. The lack of demonstrable mutations in the LDLR, APOB and PCSK9 genes in similar to 1/3 of patients with probable FH strongly suggests that additional genetic mechanisms are to be found in phenotypic FH.Peer reviewe

Inhibition of Intestinal Bile Acid Transporter Slc10a2 Improves Triglyceride Metabolism and Normalizes Elevated Plasma Glucose Levels in Mice

Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2) and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c). Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF) 15 mRNA and normalized bile acid synthesis in Slc10a2−/− mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2 - Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

Neurobiology of eating behavior, nutrition and health

Eating behavior and food-related decision making are among the most complex of the motivated behaviors, and understanding the neurobiology of eating behavior, and its developmental dynamics, is critical to advancing the nutritional sciences and public health. Recent advances from both human and animal studies are revealing that individual capacity to make health-promoting food decisions varies based on biological and physiological variation in the signaling pathways that regulate the homeostatic, hedonic, and executive functions; past developmental exposures and current life-stage; the food environment; and complications of chronic disease that reinforce the obese state. Eating rate drives increased calorie intake, and represents an important opportunity to lower rates of food consumption and energy intake through product reformulation. Understanding human eating behaviors and nutrition in the context of neuroscience can strengthen the evidence base from which dietary guidelines are derived and cam inform policies, practices, and educational programs in a way that increases the likelihood they are adopted and effective for reducing rates of obesity and other diet-related chronic disease

Sustainable Irrigation Requirement Prediction Using Internet of Things and Transfer Learning

Irrigation systems are a crucial research area because it is essential to conserve fresh water and utilize it wisely. As a part of this study, the reliability of predicting the usage of water in the present and future is investigated in order to develop an effective prediction model to communicate demand. In order to improve prediction, we develop a prediction model and share the updated model with nearby farmers. In order to forecast the irrigation requirements, the recommended model utilizes the Internet of Things (IoT), k-nearest neighbours (KNN), cloud storage, long short-term memory (LSTM), and adaptive network fuzzy inference system (ANFIS) techniques. By collecting real-time environmental data, KNN identifies the closest water requirement from the roots and its surrounding. In order to predict short-term requirements, ANFIS is used. To transfer the new requirements for better prediction, transfer learning is used. Time-series-data updates are predicted using LSTM for future forecasting, and the integrated model is shared with other farmers using cloud environments to enhance forecasting and analysis. For implementation, a period of nine to ten months of data was collected from February to December 2021, and banana tree was used to implement the planned strategy. Four farms, with measurements, were considered at varying intervals to determine the minimum and maximum irrigation needs. The requirements of farms were collected over time and compared to the predictions. Future requirements at 8, 16, 24, 32, and 48 h were also anticipated. The results indicated were compared to manual water pouring, and, thus, the entire crop used less water, making our prediction model a real-world option for irrigation. The prediction model was evaluated using R2, MSLE and the average initial prediction value of R2 was 0.945. After using transfer learning, the prediction of the model of Farm-2, 3 and 4 were 0.951, 0.958 and 0.967, respectively

Biomassa de capim-piatã e feijão-guandu consorciados em um sistema integrado com árvores nativas.

Os sistemas de Integração Lavoura-Pecuária-Floresta (ILPF) são métodos de produção sustentável que integram árvores, pastagens e culturas agrícolas

Autophagy is defective in collagen VI muscular dystrophies and its reactivation rescues myofiber degeneration

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Pendampingan Dalam Pembuatan Presentasi Kepada Guru SMAS Kristen Soleman Makassar Menggunakan Platform Canva

Pengabdian masyarakat menjadi fokus utama dalam upaya meningkatkan pendidikan di lingkungan sekolah. Melalui PKM-PM ini bertujuan mengatasi kendala metode pembelajaran tradisional yang dapat menghasilkan kebosanan dan kehilangan minat belajar siswa. Sebagai solusi, kami mengusulkan pemanfaatan teknologi pembelajaran animasi melalui aplikasi Canva dalam pengembangan bahan ajar interaktif, memanfaatkan fasilitas laboratorium sekolah dan memberikan pelatihan serta pendampingan kepada guru-guru. Hasil evaluasi menunjukkan bahwa, meskipun sebagian besar guru belum memiliki pengalaman dengan Canva, setelah pelatihan, mereka menganggap Canva lebih efisien dalam menciptakan bahan ajar yang menarik dan interaktif, yang pada gilirannya meningkatkan efektivitas pembelajaran dan pemahaman materi yang diajarkan. Dari hasil pre-test, kami mencatat bahwa 84,6% dari guru yang kami ajarkan belum pernah menggunakan Canva, sementara 92,3% dari mereka sudah pernah mendengar tentang platform Canva sebelumnya. Hasil post-test juga mengindikasikan perubahan positif dalam persepsi guru terhadap keefisienan Canva dalam pembuatan bahan ajar interaktif, yang dapat memberikan variasi dalam penyajian informasi dalam bahan ajar

Living on social assistance with chronic illness: Buffering and undermining features to well-being

<p>Abstract</p> <p>Background</p> <p>In Sweden, the social security and sickness insurance systems are comprehensive and aim to provide people whose illness prevents them from earning their own living, with either sickness benefits or disability pension. Some, however, are not entitled to these benefits or receive social insurance benefits at a level too low for subsistence, and are referred to social assistance. The purpose of this study was to explore in depth how social assistance recipients with chronic illness perceive and respond to the experience of living on social assistance.</p> <p>Methods</p> <p>Seventeen in-depth interviews were carried out with chronically ill people who had received social assistance for several years. Grounded theory informed the design of the study.</p> <p>Results</p> <p>The study showed that different strategies (living one day at a time, taking steps forwards and backwards and making attempts to find ways out of the situation) were employed by social assistance recipients to maintain or improve their well-being. Contextual features like the prevailing welfare system, public services and the local neighbourhood could buffer or undermine these strategies and their overall well-being. These features together influenced how interviewees perceived their situation, the possible ways out of the situation and the consequences for their well-being.</p> <p>Conclusion</p> <p>From this study it is evident that the way in which individuals on social assistance interact with services and how they are treated by professionals plays an important role in their well-being, in combination with what kind of help and support is available for recipients through the welfare system. In this respect, persons living on social assistance with chronic illness are particularly vulnerable. This study suggests that more effort should be made to find long term solutions concerning income support, rehabilitation and other services provided to this group.</p

Pembelajaran Sex Education dengan Berbagai Media Pembelajaran pada Siswa TK Aisyiyah 1 Tidung

The golden age of early childhood is a critical period for establishing a foundation in intellectual and health understanding, including sex education. According to Article 28 Paragraph 1 of Law Number 20 of 2003 concerning the National Education System, sex education for young children is crucial for advancing the intellectual development of the younger generation. However, observations at Aisyiyah Kindergarten in Makassar City revealed that sex education had never been provided, resulting in a lack of understanding among students. To address this issue, a Community Service activity was conducted at Aisyiyah Kindergarten using robotics-based learning technology, including robot voices, songs, images in PowerPoint format, and teaching books. This program aims to enhance students\u27 knowledge and understanding of sex education through interactive and enjoyable learning methods. Pre-test results showed only 24.4% correct answers from 18 participants, while post-test results after five days of learning showed a significant increase to 88.2% correct answers from 22 participants. These results indicate that the use of robotics technology in education can effectively increase students\u27 learning interest and understanding. This program is expected to serve as a learning model that can be applied in various early childhood education institutions to improve the quality of education and children\u27s understanding in the aspect of sex educationMasa keemasan anak usia dini merupakan periode kritis dalam pembentukan dasar intelektual dan pemahaman kesehatan, termasuk pendidikan seks. Berdasarkan Pasal 28 Ayat 1 dari Undang-Undang Nomor 20 Tahun 2003 tentang Sistem Pendidikan Nasional, pendidikan seks pada anak usia dini sangat penting untuk memajukan intelektual generasi muda. Namun, observasi di TK Aisyiyah, Kota Makassar menunjukkan bahwa pendidikan seks belum pernah diberikan, menyebabkan kurangnya pemahaman di kalangan siswa. Untuk mengatasi masalah ini, dilaksanakan kegiatan Pengabdian kepada Masyarakat dilaksanakan di TK Aisyiyah dengan menggunakan teknologi pembelajaran berbasis robotika, suara robot, lagu, gambar dalam bentuk power point dan buku ajar. Program ini bertujuan untuk meningkatkan pengetahuan dan pemahaman siswa mengenai pendidikan seks melalui metode pembelajaran interaktif dan menyenangkan. Hasil pretes menunjukkan hanya 24.4% jawaban benar dari 18 peserta, sedangkan hasil post-tes setelah pembelajaran selama 5 hari menunjukkan peningkatan signifikan dengan 88.2% jawaban benar dari 22 peserta. Hasil ini menunjukkan bahwa penggunaan teknologi robotika dalam pembelajaran mampu meningkatkan minat belajar dan pemahaman siswa secara efektif. Program ini diharapkan dapat menjadi model pembelajaran yang dapat diterapkan di berbagai institusi pendidikan anak usia dini untuk meningkatkan kualitas pendidikan dan pemahaman anak dalam aspek pendidikan seks