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Pyruvate dehydrogenase complex (PDHc) is suppressed in some cancer types but overexpressed in others. To understand its contrasting oncogenic roles, there is a need for selective PDHc inhibitors. Its E1-subunit (PDH E1) is a thiamine pyrophosphate (TPP)-dependent enzyme and catalyses the first and rate-limiting step of the complex. In a recent study, we reported a series of ester-based thiamine analogues as selective TPP-competitive PDH E1 inhibitors with low nanomolar affinity. However, when the ester linker was replaced with an amide for stability reasons, the binding affinity was significantly reduced. In this study, we show that an amino-oxetane bioisostere of the amide improves the affinity and maintains stability towards esterase-catalysed hydrolysis.
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Complexo Piruvato Desidrogenase , Tiamina Pirofosfato , Tiamina , Amidas , Ésteres , Oxirredutases , Complexo Piruvato Desidrogenase/antagonistas & inibidores , Complexo Piruvato Desidrogenase/metabolismo , Piruvatos , Tiamina/farmacologia , Tiamina Pirofosfato/metabolismo , Tiamina Pirofosfato/farmacologiaRESUMO
OBJECTIVE: Pulmonary CT angiography (CTA) to detect pulmonary emboli can be performed using conventional dual-source CT with single-energy acquisition at high-pitch (high-pitch conventional CT), which minimizes motion artifacts, or routine-pitch, dual-energy acquisitions (routine-pitch conventional DECT), which maximize iodine signal. We compared iodine signal, radiation dose, and motion artifacts of pulmonary CTA between these conventional CT modalities and dual-source photon-counting detector CT with high-pitch, multienergy acquisitions (high-pitch photon-counting CT). METHODS: Consecutive clinically indicated pulmonary CTA exams were collected. CT number/noise was measured from the main to right lower lobe segmental pulmonary arteries using 120 kV threshold low, 120 kV, and mixed kV (0.6 linear blend) images. Three radiologists reviewed anonymized, randomized exams, rating them using a 4- or 5-point Likert scale (1 = worst, and 4/5 = best) for contrast enhancement in pulmonary arteries, motion artifacts in aortic root to subsegmental pulmonary arteries, lung image quality; pulmonary blood volume (PBV) map image quality (for multienergy or dual-energy exams), and contribution to reader confidence. RESULTS: One hundred fifty patients underwent high-pitch photon-counting CT (n = 50), high-pitch conventional CT (n = 50), and routine-pitch conventional DECT (n = 50). High-pitch photon-counting CT had lower radiation dose (CTDIvol: 8.1 ± 2.5 vs 9.6 ± 6.8 and 16.2 ± 8.5 mGy, respectively; P < 0.001), and routine-pitch conventional DECT had significantly less contrast (P < 0.009). CT number and CNR measurements were significantly greater at high-pitch photon-counting CT (P < 0.001). Across readers, high-pitch photon-counting CT demonstrated significantly higher subjective contrast enhancement in the pulmonary arteries compared to the other modalities (4.7 ± 0.6 vs 4.4 ± 0.7 vs 4.3 ± 0.7; P = 0.011) and lung image quality (3.4 ± 0.5 vs 3.1 ± 0.5 vs 3.1 ± 0.5; P = 0.013). High-pitch photon-counting CT and high-pitch conventional CT had fewer motion artifacts at all levels compared to DECT (P < 0.001). High-pitch photon-counting CT PBV maps had superior image quality (P < 0.001) and contribution to reader confidence (P < 0.001) compared to routine-pitch conventional DECT. CONCLUSION: High-pitch photon-counting pulmonary CTA demonstrated higher contrast in pulmonary arteries at lower radiation doses with improved lung image quality and fewer motion artifacts compared to high-pitch conventional CT and routine-pitch conventional dual-energy CT.
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BACKGROUND: The exploration of discrimination, social acceptance, and their impact on the psychological well-being of older men who have sex with men (MSM) is a critical area of study within the broader field of LGBTQ+ research. This demographic, comprising individuals who identify as both male and homosexual and are aged in the older spectrum of the population, faces unique challenges that intersect age, sexual orientation, and societal attitudes. Objectives This study aimed to explore the relationship between social acceptance and isolation with discrimination and the impact on the psychological well-being of older MSM. METHODS: A cross-sectional survey was administered among older MSM residing in three distinct regions: the People's Republic of China (PRC), Hong Kong, and Taiwan, with a total sample size of N = 453 participants, evenly distributed with N = 151 individuals from each region. The survey included the General Health Questionnaire-12 (GHQ-12), the Discrimination and Self-Stigma Evaluation Scale (DSSES), and the Perceived Acceptance Scale (PAS) which measures the perceived social acceptance from friends, mother, father, and family. The data were analyzed using descriptive statistics, ANOVA, and regression analysis. RESULTS: The mean scores of the GHQ-12 indicated that the participants had a moderate level of psychological distress, with a mean score of 6.38 (SD = 2.55). The DSSES mean score was 27.78 (SD = 8.73), indicating that participants experienced discrimination in their everyday lives. The PAS mean score was 3.08 (SD = 0.48), indicating that participants had a moderate level of perceived social acceptance. These results suggest that discrimination and social acceptance differ among older MSM in different areas in PRC, Hong Kong, and Taiwan. CONCLUSIONS: The study highlights the impact of discrimination and social acceptance on the psychological well-being of older MSM. The findings suggest that interventions aimed at reducing discrimination and promoting social acceptance may improve the psychological well-being of older MSM. These results have important implications for healthcare providers and policymakers in developing strategies to promote social acceptance and reduce discrimination towards older MSM.
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Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Feminino , Idoso , Homossexualidade Masculina , Estudos Transversais , Bem-Estar Psicológico , Status Social , Infecções por HIV/psicologia , Estigma Social , Discriminação SocialRESUMO
A common approach to studying thiamine pyrophosphate (TPP)-dependent enzymes is by chemical inhibition with thiamine/TPP analogues which feature a neutral aromatic ring in place of the positive thiazolium ring of TPP. These are potent inhibitors but their preparation generally involves multiple synthetic steps to construct the central ring. We report efficient syntheses of novel, open-chain thiamine analogues which potently inhibit TPP-dependent enzymes and are predicted to share the same binding mode as TPP. We also report some open-chain analogues that inhibit pyruvate dehydrogenase E1-subunit (PDH E1) and are predicted to occupy additional pockets in the enzyme other than the TPP-binding pockets. This opens up new possibilities for increasing the affinity and selectivity of the analogues for PDH, which is an established anti-cancer target.
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Tiamina Pirofosfato , Tiamina , Tiamina Pirofosfato/farmacologia , Tiamina Pirofosfato/metabolismo , Tiamina/farmacologia , Tiamina/metabolismo , DifosfatosRESUMO
Suppression of pyruvate dehydrogenase complex (PDHc) is a mechanism for cancer cells to manifest the Warburg effect. However, recent evidence suggests that whether PDHc activity is suppressed or activated depends on the type of cancer. The PDHc E1 subunit (PDH E1) is a thiamine pyrophosphate (TPP)-dependent enzyme, catalysing the first and rate-limiting step of PDHc; thus, there is a need for selective PDH E1 inhibitors. There is, however, inadequate understanding of the structure-activity relationship (SAR) and a lack of inhibitors specific for mammalian PDH E1. Our group have reported TPP analogues as TPP-competitive inhibitors to study the family of TPP-dependent enzymes. Most of these TPP analogues cannot be used to study PDHc in cells because (a) they inhibit all members of the family and (b) they are membrane-impermeable. Here we report derivatives of thiamine/TPP analogues that identify elements distinctive to PDH E1 for selectivity. Based on our SAR findings, we developed a series of furan-based thiamine analogues as potent, selective and membrane-permeable inhibitors of mammalian PDH E1. We envision that our SAR findings and inhibitors will aid work on using chemical inhibition to understand the oncogenic role of PDHc.
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Tiamina Pirofosfato , Tiamina , Animais , Tiamina Pirofosfato/metabolismo , Relação Estrutura-Atividade , Piruvato Desidrogenase (Lipoamida)/metabolismo , Difosfatos , Piruvatos , Complexo Piruvato Desidrogenase/metabolismo , Mamíferos/metabolismoRESUMO
Thiamine diphosphate (ThDP), the bioactive form of vitamin B1, is an essential coenzyme needed for processes of cellular metabolism in all organisms. ThDP-dependent enzymes all require ThDP as a coenzyme for catalytic activity, although individual enzymes vary significantly in substrate preferences and biochemical reactions. A popular way to study the role of these enzymes through chemical inhibition is to use thiamine/ThDP analogues, which typically feature a neutral aromatic ring in place of the positively charged thiazolium ring of ThDP. While ThDP analogues have aided work in understanding the structural and mechanistic aspects of the enzyme family, at least two key questions regarding the ligand design strategy remain unresolved: 1) which is the best aromatic ring? and 2) how can we achieve selectivity towards a given ThDP-dependent enzyme? In this work, we synthesise derivatives of these analogues covering all central aromatic rings used in the past decade and make a head-to-head comparison of all the compounds as inhibitors of several ThDP-dependent enzymes. Thus, we establish the relationship between the nature of the central ring and the inhibitory profile of these ThDP-competitive enzyme inhibitors. We also demonstrate that introducing a C2-substituent onto the central ring to explore the unique substrate-binding pocket can further improve both potency and selectivity.
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Tiamina Pirofosfato , Tiamina , Tiamina Pirofosfato/química , Tiamina Pirofosfato/metabolismo , Tiamina/farmacologia , Tiamina/química , Especificidade por Substrato , Coenzimas/química , BiocatáliseRESUMO
BACKGROUND: Hypertension affects more than 1 billion people worldwide. Hypertension management guidelines recommend regular exercise to control blood pressure. Tai Chi is a low-impact, low- to moderate-intensity exercise that has numerous health benefits. OBJECTIVE: The aim of this study is to perform a review of meta-analyses and summarize the existing information on the health benefits of Tai Chi for patients with hypertension. METHODS: This review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Eight health-related databases were systematically searched from their inception to March 2021 to identify the relevant meta-analyses. Two reviewers independently assessed the methodological quality of the evidence. RESULTS: A total of 6 relevant meta-analyses were included in this review: 3 were rated as critically low in quality, 2 were rated low, and 1 was rated high. In the included meta-analyses, Tai Chi showed many benefits for patients with hypertension. In addition to improving blood pressure, the blood lipid profile, blood sugar, body measurements, and quality of life of patients improved significantly after practicing Tai Chi. CONCLUSION: Tai Chi may be considered an effective and safe alternative exercise for patients with hypertension.
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BACKGROUND: High dietary salt consumption is a significant health issue in Chinese populations. This study identified the facilitators for and barriers to salt reduction for prevention of hypertension among Chinese Australians. METHODS: An inductive qualitative study with semi-structured interviews (n = 8) was conducted with convenience samples recruited from social media. Adults who a) were over 18 years old, b) were of Chinese ancestry and c) had lived in Australia for at least 6 months were eligible for participation. Interview transcripts were transcribed and analysed using content analysis. RESULTS: Four facilitators for and eight barriers to reducing salt consumption were synthesised from the narrative materials. The facilitators were: 1) individual perceptions of health benefits, 2) salt alternatives, 3) digital information and 4) increased awareness of negative health impacts from a high-salt diet. The barriers identified were: 1) negative physical changes not apparent, 2) inadequate salt-related health education, 3) hidden salt in food products, 4) inadequate food literacy, 5) pricing, 6) busy lifestyle, 7) low perceived susceptibility and 8) individual food taste preference and cooking habits. Peer and family influence had positive and negative effects on participants' likelihood of reducing salt consumption. CONCLUSIONS: The facilitators for and barriers to maintaining a low-salt diet in Chinese Australians were multifaceted and interrelated. Future salt-reduction strategies should focus on the health benefits of reduced salt consumption and practical interventions such as salt alternatives and education on low-salt food choices and cooking methods and changing perceptions about salt reduction to become a social norm in the Chinese community.
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Individuals within the Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ) community who are diagnosed with cancer experience inequitable treatment in healthcare systems worldwide, resulting in dissatisfaction, communication challenges with healthcare providers, and a deep sense of disappointment. Stigma, discrimination, and perceived homophobia further heighten the risk of psychological and attitudinal disorders, including depression and suicidal tendencies, among LGBTQ cancer patients. To comprehensively assess the discrimination faced by LGBTQ cancer patients and gain deeper insights into their needs and experiences, we conducted a systematic review following PRISMA guidelines. We searched for relevant articles using specific keywords in reputable databases such as PubMed, Google Scholar, and PsycINFO. We rigorously evaluated article quality using the CASP (Critical Appraisal Skills Programme) checklist. From a total of 75 eligible studies, we carefully selected 14 studies, specifically examining LGBTQ cancer patients who were currently undergoing or had previously undergone cancer treatment. The studies revealed various factors, including unmet needs related to anxiety and depression, instances of discrimination, disparities in care, and inadequate support systems. A majority of patients expressed dissatisfaction with their cancer care and continued to encounter discrimination and disparities throughout their treatment journeys. Consequently, this led to heightened levels of anxiety, stress, depression, and negative perceptions of healthcare providers. Based on these findings, we recommend providing specialized training to social workers and healthcare providers. This training will equip them with the necessary skills and knowledge to deliver culturally sensitive care tailored to the unique needs of LGBTQ cancer patients. By addressing discrimination, reducing disparities, and fostering an inclusive environment, healthcare professionals can strive to ensure that LGBTQ cancer patients receive the care they deserve.
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Neoplasias , Minorias Sexuais e de Gênero , Pessoas Transgênero , Feminino , Humanos , Comportamento Sexual/psicologia , Identidade de Gênero , Estigma Social , Neoplasias/terapia , Neoplasias/psicologiaRESUMO
Inhibition of thiamine pyrophosphate (TPP)-dependent enzymes with thiamine/TPP analogues that have the central thiazolium ring replaced with other rings is well established, but a limited number of central rings have been reported. We report a novel analogue, pyrrothiamine, with a central pyrrole ring. We further develop pyrrothiamine derivatives as potent and selective inhibitors of pyruvate dehydrogenase, which might have anti-cancer potential.
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Tiamina Pirofosfato , Tiamina , Tiamina/farmacologia , Tiamina Pirofosfato/farmacologia , Difosfatos , Oxirredutases , Piruvatos , Complexo Piruvato DesidrogenaseRESUMO
INTRODUCTION: The objective of this review is to synthesise and present the best available evidence on the prevalence, predictors and information needs about sexual health among female Arab cancer survivors. METHODS: The databases searched included MEDLINE, Embase and CINAHL from inception of the database until March 2020. The review was undertaken according to the JBI guidelines. Proportional meta-analysis using a random effects model was used for statistical pooling through JBI SUMARI. RESULTS: Seven studies involving female Arab cancer survivors were included in the review. The overall prevalence of sexual dysfunction ranged from 16.7 to 67% (pooled estimate 51%, 95% CIs 21.7% to 80.2%). Dyspareunia and erectile dysfunction were the two main types of sexual dysfunction reported after diagnosis, and the overall prevalence ranged from 42.5% to 65% and 38% to 61%, respectively. The prevalence of vaginal dryness was ranged from 19.8% to 54.2%, and dyspareunia ranged from 22.2% to 65%. The lack of sexuality information and communication with health care providers (HCPs) was also reported in the included studies. CONCLUSION: Cancer and its treatment may result in significant difficulties with sexual activity and sexual functioning among cancer survivor. Communication between the health care professionals and cancer survivors is essential to overcome this problem and improve the quality of life of female Arab cancer survivors.
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Sobreviventes de Câncer , Avaliação das Necessidades , Disfunções Sexuais Fisiológicas , Feminino , Humanos , Árabes , Neoplasias/complicações , Neoplasias/terapia , Prevalência , Qualidade de Vida , Comportamento Sexual , Disfunções Sexuais Fisiológicas/epidemiologiaRESUMO
AIMS: To identify and synthesize the evidence on the perceptions of the health effects of dietary salt consumption and barriers to sustaining a salt-reduced diet for hypertension in Chinese people. DESIGN: A systematic integrated review integrating quantitative and qualitative studies using the PRISMA guidelines. DATA SOURCES: Three databases, MEDLINE, PubMed and CINAHL, were systematically searched for articles published between January 2001 and July 2020. REVIEW METHODS: The quality of the included studies was appraised using the Joanna Briggs Institute's critical appraisal tools for cross-sectional and qualitative studies. Descriptive analysis and constant comparison methods were used to analyse the extracted data. RESULTS: Fourteen studies met the inclusion criteria. The synthesized results identified that (i) adequate salt-related health education had a positive influence on dietary behaviour modifications, (ii) the level of educational exposure to the health benefits of salt reduction influenced Chinese people's perceptions of the health impact associated with high salt intake, (iii) the complexity of salt measurement was a barrier to salt reduction, (iv) salt reduction is a challenge to Chinese food culture, and (v) Chinese migrants may experience linguistic and cultural challenges when they seek appropriate dietary education and advice for hypertension management in their host countries. CONCLUSION: There is room for improvement in recognizing and translating the knowledge of salt-related health issues and the benefits of that knowledge about salt reduction into action. Future nursing interventions should incorporate individuals' cultural needs and the dietary culture of immediate family members. IMPACT: This integrative review reveals that unique Chinese customs and practices reduce the effectiveness of salt reduction campaigns. The effects of education vanish without family support, resulting in suboptimal adherence to dietary salt reduction strategies.
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Hipertensão , Cloreto de Sódio na Dieta , China , Estudos Transversais , Humanos , Hipertensão/prevenção & controle , Pesquisa QualitativaRESUMO
PURPOSE: Nurses play a key role in educating people about a salt-reduced diet to prevent or manage hypertension or cardiac failure. Assessment tools such as the Chinese Determinants of Salt-Restriction Behaviour Questionnaire (DSRBQ) can provide essential evidence to inform education strategies. This study aimed to translate the DSRBQ into English and evaluate the psychometric properties of the Chinese and English versions for people of Chinese ethnicity in Australia. METHODS: A two-phase cross-sectional descriptive study was conducted. Phase 1: The questionnaire was translated into English using the back-translation method. The translation equivalence and content relevance were evaluated by an expert panel. Three items were revised and eight items were removed. Phase 2: Internal consistency and stability of the questionnaires were evaluated by a group of Chinese Australians. RESULTS: Both the English and Chinese versions had satisfactory psychometric properties. In phase 2, 146 participants completed the questionnaire (test), and 49 participants completed the retest. The Cronbach's alpha scores were 0.638 and 0.584 respectively, and the overall intra-class correlation coefficients were 0.820 and 0.688 respectively for the English and Chinese versions. The Item-Content Validity Index (CVI) ranged from 0.50 to 1.00. The Scale-CVI was 0.94. CONCLUSION: The DSRBQ has been translated into English. Both English and Chinese versions have acceptable validity and reliability. The tools can be used in people from a Chinese cultural background living in Australia. Further validation testing may allow the tools to be adapted for use with other Chinese diaspora groups. The validated DSRBQ will support the development of evidence-based salt reduction nursing assessment tool and interventions for Chinese diasporas who reside in a country where Chinese cultural practices are employed by a minority.
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BACKGROUND: An aging population and required hypertension control are global concerns that burden the healthcare system. Text messaging interventions have been developed to support hypertension management, but their effects on the older population are unknown. OBJECTIVES: This review aimed to identify the effects of a text messaging intervention on hypertension management among older adults. METHODS: Four English and two Chinese databases with randomized controlled trials published between January 2010 and December 2020 were searched. The mean age of the participants was 60 years or above. Participants were also diagnosed with hypertension. The Cochrane risk-of-bias tool was used for the critical appraisal. Data in each study were extracted, and a meta-analysis was presented in terms of mean difference (MD) and standardized mean difference (SMD). RESULTS: A total of 1670 records were screened, of which six were included in the final review. The intervention of the included studies lasted up to 6 months, and one-way text messaging was commonly used. Meta-analysis showed that a text messaging intervention significantly reduced systolic blood pressure (MD = -6.11, p < .01) but not diastolic blood pressure. Regarding medication adherence, a moderate effect was noted with the use of text messaging among older adults with hypertension (SMD = 0.65, p = .01). LINKING EVIDENCE TO ACTION: A text messaging intervention can improve hypertension management among older adults. The standardized content of one-way text messaging is suggested to be delivered weekly.
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Telefone Celular , Hipertensão , Envio de Mensagens de Texto , Idoso , Pressão Sanguínea , Humanos , Hipertensão/terapia , Adesão à Medicação , Pessoa de Meia-IdadeRESUMO
Cancer cells are high in heterogeneity and versatility, which can easily adapt to the external stresses via both primary and secondary resistance. Targeting of tumour microenvironment (TME) is a new approach and an ideal therapeutic strategy especially for the multidrug resistant cancer. Recently, we invented AANG, a natural compound formula containing traditional Chinese medicine (TCM) derived Smad3 inhibitor Naringenin (NG) and Smad7 activator Asiatic Acid (AA), for rebalancing TGF-ß/Smad signalling in the TME, and its implication on the multidrug resistance is still unexplored. Here, we observed that an equilibrium shift of the Smad signalling in patients with hepatocellular carcinoma (HCC), which was dramatically enhanced in the recurrent cases showing p-glycoprotein overexpression. We optimized the formula ratio and dosage of AANG that effectively inhibit the proliferation of our unique human multidrug resistant subclone R-HepG2. Mechanistically, we found that AANG not only inhibits Smad3 at post-transcriptional level, but also upregulates Smad7 at transcriptional level in a synergistic manner in vitro. More importantly, AANG markedly suppressed the growth and p-glycoprotein expression of R-HepG2 xenografts in vivo. Thus, AANG may represent a novel and safe TCM-derived natural compound formula for overcoming HCC with p-glycoprotein-mediated multidrug resistance.
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Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Idoso , Animais , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Pessoa de Meia-Idade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: Sex and intimacy are basic needs and important aspects of quality of life among humans. This focus of this review was to synthesise and present the best available qualitative evidence on the sexual life experiences and needs of Chinese adults living with cancer. Moreover, the first-hand experience, meaning and perspective about the sexual life changes and support needs during the survival and extended treatment period were synthesised in this study. METHODS: A systematic review of qualitative studies was undertaken using the Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information (JBI-SUMARI). A comprehensive search of five databases: CINAHL, MEDLINE, PubMed, Scopus and Google Scholar were undertaken from 2010 until February 2020 using defined criteria. Methodological quality and data extraction were undertaken using JBI-SUMARI. RESULTS: Eight studies were included in the review. A total of 39 findings were extracted and aggregated into eight categories based on similarity of meaning. Three synthesised themes were generated: (i) misconceptions and lack of education or information regarding sexual activity exists for patients with cancer, (ii) concerns for overall health and well-being as well as physical and psychological changes can alter sexual desire and behaviours in patients with cancer and (iii) lack of sexual activity and intimacy can create relationship problems. CONCLUSIONS: Sexual relationships are intimate, personal and private in Chinese culture and beliefs. Chinese adults living with cancer report many neglected issues on sexual well-being in various domains. Adequate and consistent education about sexual intimacy issues from health care providers was identified as an important need. Unaddressed needs might affect adults' coping strategies in managing their sexual relations during various stages of cancer treatment and beyond. It must be noted that there are many Chinese ethnic minorities living with cancer outside the Greater China region. The evidence provides valuable recommendations to health care providers globally to consider the specific sexual needs and initiate culturally sensitive sexuality education and care support for Chinese adults living with cancer.
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Neoplasias , Qualidade de Vida , Adulto , China , Humanos , Neoplasias/terapia , Pesquisa Qualitativa , Comportamento SexualRESUMO
BACKGROUND: There are many alternatives to direct journal access, such as podcasts, blogs, and news sites, that allow physicians and the general public to stay up to date with medical literature. However, there is a scarcity of literature that investigates the readership characteristics of open-access medical news sites and how these characteristics may have shifted during the COVID-19 pandemic. OBJECTIVE: This study aimed to assess readership and survey data to characterize open-access medical news readership trends related to the COVID-19 pandemic and overall readership trends regarding pandemic-related information delivery. METHODS: Anonymous, aggregate readership data were obtained from 2 Minute Medicine, an open-access, physician-run medical news organization that has published over 8000 original, physician-written texts and visual summaries of new medical research since 2013. In this retrospective observational study, the average number of article views, number of actions (defined as the sum of the number of views, shares, and outbound link clicks), read times, and bounce rates (probability of leaving a page in <30 s) were compared between COVID-19 articles published from January 1 to May 31, 2020 (n=40) and non-COVID-19 articles (n=145) published in the same time period. A voluntary survey was also sent to subscribed 2 Minute Medicine readers to further characterize readership demographics and preferences, which were scored on a Likert scale. RESULTS: COVID-19 articles had a significantly higher median number of views than non-COVID-19 articles (296 vs 110; U=748.5; P<.001). There were no significant differences in average read times (P=.12) or bounce rates (P=.12). Non-COVID-19 articles had a higher median number of actions than COVID-19 articles (2.9 vs 2.5; U=2070.5; P=.02). On a Likert scale of 1 (strongly disagree) to 5 (strongly agree), our survey data revealed that 65.5% (78/119) of readers agreed or strongly agreed that they preferred staying up to date with emerging literature about COVID-19 by using sources such as 2 Minute Medicine instead of journals. A greater proportion of survey respondents also indicated that open-access news sources were one of their primary sources for staying informed (86/120, 71.7%) compared to the proportion who preferred direct journal article access (61/120, 50.8%). The proportion of readers indicating they were reading one or less full-length medical studies a month were lower following introduction to 2 Minute Medicine compared to prior (21/120, 17.5% vs 38/120, 31.6%; P=.005). CONCLUSIONS: The readership significantly increased for one open-access medical literature platform during the pandemic. This reinforces the idea that open-access, physician-written sources of medical news represent an important alternative to direct journal access for readers who want to stay up to date with medical literature.
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Pesquisa Biomédica/estatística & dados numéricos , COVID-19 , Publicação de Acesso Aberto/estatística & dados numéricos , Leitura , Inquéritos e Questionários , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Adulto JovemRESUMO
Transforming growth factor-ß (TGF-ß) signaling triggers diverse biological actions in inflammatory diseases. In tissue fibrosis, it acts as a key pathogenic regulator for promoting immunoregulation via controlling the activation, proliferation, and apoptosis of immunocytes. In cancer, it plays a critical role in tumor microenvironment (TME) for accelerating invasion, metastasis, angiogenesis, and immunosuppression. Increasing evidence suggest a pleiotropic nature of TGF-ß signaling as a critical pathway for generating fibrotic TME, which contains numerous cancer-associated fibroblasts (CAFs), extracellular matrix proteins, and remodeling enzymes. Its pathogenic roles and working mechanisms in tumorigenesis are still largely unclear. Importantly, recent studies successfully demonstrated the clinical implications of fibrotic TME in cancer. This review systematically summarized the latest updates and discoveries of TGF-ß signaling in the fibrotic TME.
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Fibroblastos Associados a Câncer/patologia , Fibrose/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Fibroblastos Associados a Câncer/metabolismo , Fibrose/metabolismo , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/imunologia , Neovascularização Patológica/patologia , Transdução de Sinais , Microambiente TumoralRESUMO
Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by short open-reading frames (sORF) in mitochondrial DNA that do not necessarily have traditional hallmarks of protein-coding genes. To date, eight MDPs have been identified, all of which have been shown to have various cyto- or metaboloprotective properties. The 12S ribosomal RNA (MT-RNR1) gene harbors the sequence for MOTS-c, whereas the other seven MDPs [humanin and small humanin-like peptides (SHLP) 1-6] are encoded by the 16S ribosomal RNA gene. Here, we review the evidence that endogenous MDPs are sensitive to changes in metabolism, showing that metabolic conditions like obesity, diabetes, and aging are associated with lower circulating MDPs, whereas in humans muscle MDP expression is upregulated in response to stress that perturbs the mitochondria like exercise, some mtDNA mutation-associated diseases, and healthy aging, which potentially suggests a tissue-specific response aimed at restoring cellular or mitochondrial homeostasis. Consistent with this, treatment of rodents with humanin, MOTS-c, and SHLP2 can enhance insulin sensitivity and offer protection against a range of age-associated metabolic disorders. Furthermore, assessing how mtDNA variants alter the functions of MDPs is beginning to provide evidence that MDPs are metabolic signal transducers in humans. Taken together, MDPs appear to form an important aspect of a retrograde signaling network that communicates mitochondrial status with the wider cell and to distal tissues to modulate adaptative responses to metabolic stress. It remains to be fully determined whether the metaboloprotective properties of MDPs can be harnessed into therapies for metabolic disease.
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Metabolismo Energético/fisiologia , Mitocôndrias/metabolismo , Peptídeos/metabolismo , Animais , Metabolismo Energético/genética , Humanos , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Peptídeos/genéticaRESUMO
BACKGROUND: Dental erosion is the dissolution of dental hard tissues caused by acids of a non-bacterial origin. Dietary acids are considered the predominant and most controllable factor. AIM: To synthesise the literature on the effects of dietary acids and habits on dental erosion in the permanent dentition of 10- to 19-year-old adolescents. MATERIALS AND METHODS: An electronic literature search was undertaken in Cochrane, MEDLINE, CINAHL, Dentistry & Oral Sciences Source via EBSCOhost, and Embase with no restriction on the date of publication. RESULTS: The initial search identified 449 articles, and 338 remained after removal of duplicates. Seventy-seven articles remained after screening of titles and abstracts, and 52 were eligible for the full-text review. A considerable variety of beverages, food, and dietary habits were reported as risk factors for dental erosion. The most consistent findings implicated the erosive potential of carbonated beverages and the consumption of acidic drinks at bedtime. CONCLUSIONS: Although results were not consistent between cohort and cross-sectional studies, this review suggests certain dietary risk factors may contribute to dental erosion in adolescents. There is a need for more high-quality cohort studies to establish more conclusive evidence on the role of dietary acids and habits on dental erosion.