Quantitative Analysis and Diagnostic Significance of Methylated SLC19A3 DNA in the Plasma of Breast and Gastric Cancer Patients

Background: Previously, we have examined the methylation status of SLC19A3 (solute carrier family 19, member 3) promoter and found that SLC19A3 was epigenetically down-regulated in gastric cancer. Here, we aim to develop a new biomarker for cancer diagnosis using methylated SLC19A3 DNA in plasma. Methodology/Principal Findings: SLC19A3 gene expression was examined by RT-qPCR. Methylation status of SLC19A3 promoter was evaluated by methylation-specific qPCR. SLC19A3 expression was significantly down-regulated in 80% (12/15) of breast tumors (P<0.005). Breast tumors had significant increase in methylation percentage when compared to adjacent non-tumor tissues (P<0.005). A robust and simple methylation-sensitive restriction enzyme digestion and real-time quantitative PCR (MSRED-qPCR) was developed to quantify SLC19A3 DNA methylation in plasma. We validated this biomarker in an independent validation cohort of 165 case-control plasma including 60 breast cancer, 45 gastric cancer patients and 60 healthy subjects. Plasma SLC19A3 methylated DNA level was effective in differentiating both breast and gastric cancer from healthy subjects. We further validated this biomarker in another independent blinded cohort of 78 plasma including 38 breast cancer, 20 gastric cancer patients and 20 healthy subjects. The positive predictive values for breast and gastric cancer were 90% and 85%, respectively. The negative predictive value of this biomarker was 85%. Elevated level in plasma has been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 100%. Conclusions: These results suggested that aberrant SLC19A3 promoter hypermethylation in plasma may be a novel biomarker for breast and gastric cancer diagnosis. © 2011 Ng et al.published_or_final_versio

Genetic Testing and Its Clinical Application in Prostate Cancer Management: Consensus Statements from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology

BackgroundIn recent years, indications for genetic testing in prostate cancer (PC) have expanded from patients with a family history of prostate and/or related cancers to those with advanced castration-resistant disease, and even to early PC patients for determination of the appropriateness of active surveillance. The current consensus aims to provide guidance to urologists, oncologists and pathologists working with Asian PC patients on who and what to test for in selected populations.MethodsA joint consensus panel from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology was convened over a series of 5 physical and virtual meetings. A background literature search on genetic testing in PC was performed in PubMed, ClinicalKey, EBSCOHost, Ovid and ProQuest, and three working subgroups were formed to review and present the relevant evidence. Meeting agendas adopted a modified Delphi approach to ensure that discussions proceed in a structured, iterative and balanced manner, which was followed by an anonymous voting on candidate statements. Of 5 available answer options, a consensus statement was accepted if ≥ 75% of the panelists chose “Accept Completely” (Option A) or “Accept with Some Reservation” (Option B).ResultsThe consensus was structured into three parts: indications for testing, testing methods, and therapeutic implications. A list of 35 candidate statements were developed, of which 31 were accepted. The statements addressed questions on the application of PC genetic testing data and guidelines to Asian patients, including patient selection for germline testing, selection of gene panel and tissue sample, provision of genetic counseling, and use of novel systemic treatments in metastatic castration-resistant PC patients.ConclusionThis consensus provides guidance to urologists, oncologists and pathologists working with Asian patients on indications for genetic testing, testing methods and technical considerations, and associated therapeutic implications

Declaração de consenso da seção de psiquiatria geriátrica da Associação Mundial de Psiquiatria sobre ética e capacidade em pessoas idosas com doença mental

BACKGROUND: The World Psychiatric Association (WPA) Section of Old Age Psychiatry, since 1997, has developed Consensus Statements relevant to the practice of Old Age Psychiatry. Since 2006 the Section has worked to develop a Consensus Statement on Ethics and Capacity in older people with mental disorders. METHOD: A Consensus Conference was realized in Prague, September 2008. The meeting was organized by the WPA Section of Old Age Psychiatry, with the participation of International Council of Nurses, Alzheimer Europe and Alzheimer Disease International. Participants who are recognised for their expertise in this area came from 11 countries and include psychiatrists, a neurologist, a nurse and family caregiving representatives. RESULTS: After two days of debate a draft was prepared and submitted to the organizations/associations represented at the meeting. When their respective comments were collected, a final text was prepared and published originally in English. This Portuguese version was prepared by two members of the meeting who came from Portuguese spoken countries. DISCUSSION: This Consensus Statement offers to mental health clinicians caring for older people with mental disorders, caregivers, other health professionals and the general public the setting out of and discourse in ethical principles which can often be complex and challenging, supported by practical guidance in meeting such ethical needs and standards, and to encouraged good clinical practice.CONTEXTO: A Seção de Psiquiatria Geriátrica da Associação Mundial de Psiquiatria (AMP), desde 1997, vem desenvolvendo Declarações de Consenso relevantespara a prática da Psiquiatria Geriátrica. Desde 2006, a Seção vem trabalhando para desenvolver uma Declaração de Consenso sobre Ética e Capacidade em pessoas idosas com transtornos mentais. MÉTODO: Uma Conferência de Consenso foi realizada em Praga em setembro de 2008. Organizada pela Seção de Psiquiatria da Pessoa Idosa da AMP, ela contou com a participação do International Council of Nurses, Alzheimer Europe e Alzheimer Disease International. Os participantes foram reconhecidos pela sua perícia nesse domínio e vieram de 11 países. Incluíam psiquiatras, uma neurologista, um enfermeiro e representantes de cuidadores familiares. RESULTADOS: Após dois dias de reuniões e debate, redigiu-se um rascunho da declaração que foi submetida para análise nas diversas organizações/associações que participaram da reunião. Após as sugestões finais recolhidas, um texto definitivo foi preparado em inglês e publicado. A presente versão em português é da responsabilidade de dois participantes lusófonos da reunião, que são também coautores da declaração de consenso final. CONCLUSÕES: Essa Declaração de Consenso oferece aos clínicos em saúde mental que cuidam de pessoas idosas com transtornos mentais, cuidadores, outros profissionais da saúde e o público em geral as definições e o debate sobre os princípios éticos que podem frequentemente ser complexos e desafiadores, apoiados em orientações práticas para satisfazer tais necessidades e padrões éticos e encorajar a boa prática clínica

Key lifestyles and health outcomes across 16 prevalent chronic diseases: a network analysis of an international observational study

Background: Central and bridge nodes can drive significant overall improvements within their respective networks. We aimed to identify them in 16 prevalent chronic diseases during the coronavirus disease 2019 (COVID-19) pandemic to guide effective intervention strategies and appropriate resource allocation for most significant holistic lifestyle and health improvements. Methods: We surveyed 16 512 adults from July 2020 to August 2021 in 30 territories. Participants self-reported their medical histories and the perceived impact of COVID-19 on 18 lifestyle factors and 13 health outcomes. For each disease subgroup, we generated lifestyle, health outcome, and bridge networks. Variables with the highest centrality indices in each were identified central or bridge. We validated these networks using nonparametric and case-dropping subset bootstrapping and confirmed central and bridge variables' significantly higher indices through a centrality difference test. Findings: Among the 48 networks, 44 were validated (all correlation-stability coefficients >0.25). Six central lifestyle factors were identified: less consumption of snacks (for the chronic disease: anxiety), less sugary drinks (cancer, gastric ulcer, hypertension, insomnia, and pre-diabetes), less smoking tobacco (chronic obstructive pulmonary disease), frequency of exercise (depression and fatty liver disease), duration of exercise (irritable bowel syndrome), and overall amount of exercise (autoimmune disease, diabetes, eczema, heart attack, and high cholesterol). Two central health outcomes emerged: less emotional distress (chronic obstructive pulmonary disease, eczema, fatty liver disease, gastric ulcer, heart attack, high cholesterol, hypertension, insomnia, and pre-diabetes) and quality of life (anxiety, autoimmune disease, cancer, depression, diabetes, and irritable bowel syndrome). Four bridge lifestyles were identified: consumption of fruits and vegetables (diabetes, high cholesterol, hypertension, and insomnia), less duration of sitting (eczema, fatty liver disease, and heart attack), frequency of exercise (autoimmune disease, depression, and heart attack), and overall amount of exercise (anxiety, gastric ulcer, and insomnia). The centrality difference test showed the central and bridge variables had significantly higher centrality indices than others in their networks (P < 0.05). Conclusion: To effectively manage chronic diseases during the COVID-19 pandemic, enhanced interventions and optimised resource allocation toward central lifestyle factors, health outcomes, and bridge lifestyles are paramount. The key variables shared across chronic diseases emphasise the importance of coordinated intervention strategies

Global impacts of Covid-19 on lifestyles and health and preparation preferences: an international survey of 30 countries

Background: The health area being greatest impacted by coronavirus disease 2019 (COVID-19) and residents' perspective to better prepare for future pandemic remain unknown. We aimed to assess and make cross-country and cross-region comparisons of the global impacts of COVID-19 and preparation preferences of pandemic. Methods: We recruited adults in 30 countries covering all World Health Organization (WHO) regions from July 2020 to August 2021. 5 Likert-point scales were used to measure their perceived change in 32 aspects due to COVID-19 (-2 = substantially reduced to 2 = substantially increased) and perceived importance of 13 preparations (1 = not important to 5 = extremely important). Samples were stratified by age and gender in the corresponding countries. Multidimensional preference analysis displays disparities between 30 countries, WHO regions, economic development levels, and COVID-19 severity levels. Results: 16 512 adults participated, with 10 351 females. Among 32 aspects of impact, the most affected were having a meal at home (mean (m) = 0.84, standard error (SE) = 0.01), cooking at home (m = 0.78, SE = 0.01), social activities (m = -0.68, SE = 0.01), duration of screen time (m = 0.67, SE = 0.01), and duration of sitting (m = 0.59, SE = 0.01). Alcohol (m = -0.36, SE = 0.01) and tobacco (m = -0.38, SE = 0.01) consumption declined moderately. Among 13 preparations, respondents rated medicine delivery (m = 3.50, SE = 0.01), getting prescribed medicine in a hospital visit / follow-up in a community pharmacy (m = 3.37, SE = 0.01), and online shopping (m = 3.33, SE = 0.02) as the most important. The multidimensional preference analysis showed the European Region, Region of the Americas, Western Pacific Region and countries with a high-income level or medium to high COVID-19 severity were more adversely impacted on sitting and screen time duration and social activities, whereas other regions and countries experienced more cooking and eating at home. Countries with a high-income level or medium to high COVID-19 severity reported higher perceived mental burden and emotional distress. Except for low- and lower-middle-income countries, medicine delivery was always prioritised. Conclusions: Global increasing sitting and screen time and limiting social activities deserve as much attention as mental health. Besides, the pandemic has ushered in a notable enhancement in lifestyle of home cooking and eating, while simultaneously reducing the consumption of tobacco and alcohol. A health care system and technological infrastructure that facilitate medicine delivery, medicine prescription, and online shopping are priorities for coping with future pandemics