The effects of decision aids for genetic counselling among people considering genetic testing: A systematic review.

AIM: To assess the effectiveness of decision aids for genetic counsellees to improve their conflicts in decision-making and psychological well-being when considering genetic tests for inherited genetic diseases, and their knowledge about these tests and their genetic risks. DESIGN: Systematic review. DATA SOURCES: Six electronic databases (PubMed, MEDLINE, OVID Nursing, APA PsycINFO, EMBASE and CINAHL) were searched from inception to May 2022. REVIEW METHODS: Only randomised controlled trials that examined the effect of decision aids for information provision centring genetic testing on outcomes including decisional conflicts, informed choice making, knowledge on genetic risks or genetic tests, and psychological outcomes among participants who had undergone genetic counselling were included. Their risk of bias was assessed using the Version 2 of the Cochrane risk of bias tool for randomised trials. Results were presented narratively. The review was conducted according to the PRISMA checklist. RESULTS: Eight included studies examined the effect of booklet-based, computer-based, film-based or web-based decision aids on individuals considering genetic testing for their increased cancer risks. Despite contrasting findings across studies, they showed that decision aids enable genetic counsellees to feel more informed in decision-making on genetic tests, although most showed no effect on decisional conflict. Knowledge of genetic counsellees on genetic risks and genetic tests were increased after the use of decision aids. Most studies showed no significant effect on any psychological outcomes assessed. CONCLUSIONS: Review findings corroborate the use of decision aids to enhance the effective delivery of genetic counselling, enabling genetic counsellees to gain more knowledge of genetic tests and feel more informed in making decisions to have these tests. RELEVANCE TO CLINICAL PRACTICE: Decision aids can be used to support nurse-led genetic counselling for better knowledge acquisition and decision-making among counsellees. NO PATIENT OR PUBLIC CONTRIBUTION: Patient or public contribution is not applicable as this is a systematic review.

Development and evaluation of a multimedia intervention to promote cervical cancer prevention among South Asian women in Hong Kong.

Objective: The uptake of cervical cancer screening among South Asian ethnic minorities is low, rendering them at higher risk of developing cervical cancer. Interventions should, therefore, be developed to enhance their knowledge of this disease and its prevention. We developed and implemented a Health-Belief-Model-based and culturally sensitive multimedia intervention for South Asian women in Hong Kong, and evaluated its feasibility, acceptability and effectiveness using the Reach-Effectiveness-Adoption-Implementation-Maintenance framework.Design: At post-intervention, a short survey was conducted to assess the participants' perceptions of the acceptability and effectiveness of the intervention. Focus group and/or telephone interviews with persons-in-charge of community organizations were conducted to collect feedback on the intervention's effectiveness and long-term sustainability.Results: The intervention was implemented successfully in partnership with 54 community organizations, of which 51 expressed a willingness to continue doing so at their centers. 1061 South Asian women received the intervention through attendance at the 51 health talks held. Over 90% of them agreed that the intervention was acceptable and effective.Conclusions: The intervention appeared to be feasible, and is potentially effective in enhancing participants' knowledge of cervical cancer and self-efficacy in undergoing screening.

Association of single nucleotide polymorphisms of cytochrome P450 enzymes with experience of vasomotor, vaginal and musculoskeletal symptoms among breast cancer patients: a systematic review.

BACKGROUND: Adjuvant endocrine therapies are known to induce undesirable adverse effects such as vasomotor, vaginal and musculoskeletal symptoms among breast cancer patients. Drugs used in these therapies are often metabolised by cytochrome P450 (CYP) enzymes, in which their metabolising activities can be modified by single nucleotide polymorphisms (SNP) in CYP genes and CYP genotypes. This review aims to explore whether SNPs or genotypes of CYP are associated with the occurrence, frequency and severity of vasomotor, vaginal and musculoskeletal symptoms in breast cancer patients on adjuvant endocrine therapies. METHODS: A literature review was conducted using five electronic databases, resulting in the inclusion of 14 eligible studies, and their findings were presented narratively. Selected items from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist were used for critical appraisal of the reporting quality of the included studies. RESULTS: Most of the included studies showed that SNPs or genotypes of CYP that modify its metabolising activity have no effect on the occurrence, frequency or severity of vasomotor symptoms, including hot flashes. One study showed no correlation of these genetic variations in CYP with musculoskeletal symptoms, and no data were available on the association between such genetic variations and vaginal symptoms. CONCLUSIONS: Overall, genetic variations in CYP have no effect on the experience of hot flashes among breast cancer patients. We recommend exploration of the link between the active metabolites of chemotherapeutic drugs and the molecules shown to affect the occurrence or severity of hot flashes, and the establishment of the relationship between such genetic variations and patients' experience of musculoskeletal and vaginal symptoms. Subgroup analyses based on patients' duration of adjuvant endocrine therapies in such studies are recommended.

Translation and validation of the Traditional Chinese version of the COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (Version 2).

BACKGROUND: Cancer patients often experience severe financial distress due to the high cost of their treatment, and strategies are needed to objectively measure this financial distress. The COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) is one instrument used to measure such financial distress. This study aimed to translate the COST-FACIT (Version 2) [COST-FACIT-v2] instrument into traditional Chinese (COST-FACIT-v2 [TC]) and evaluate its psychometric properties. METHODS: The Functional Assessment of Chronic Illness Therapy (FACIT) translation method was adopted. The translated version was reviewed by an expert panel and by 20 cancer patients for content validity and face validity, respectively, and 640 cancer patients, recruited from three oncology departments, completed the translated scale. Its reliability was evaluated in terms of internal consistency and test-retest reliability. Confirmatory factor analysis has been used to evaluate the one- and two-factor structures of the instrument reported in the literature. The convergent validity was examined by the correlation with health-related quality of life (HRQoL) and psychological distress. Known-group validity was examined by the difference in the COST-FACIT-v2 (TC) total mean score between groups with different income levels and frequency of health care service use. RESULTS: The COST-FACIT-v2 (TC) showed good content and face validity and demonstrated high internal consistency (Cronbach's alpha, 0.86) and acceptable test-retest reliability (intraclass correlation coefficient, 0.71). Confirmatory factor analysis showed that the one- and two-factor structures of the instrument that have been reported in the literature could not be satisfactorily fitted to the data. Psychological distress correlated significantly with the COST-FACIT-v2 (TC) score (r = 0.47; p < 0.001). HRQOL showed a weak to moderate negative correlation with the COST-FACIT-v2 (TC) score (r = - 0.23 to - 0.46; p < 0.001). Significant differences were seen among the COST-FACIT-v2 (TC) scores obtained in groups of different income level and frequency of health care service use. CONCLUSIONS: The COST-FACIT-v2 (TC) showed some desirable psychometric properties to support its validity and reliability for assessing cancer patients' level of financial toxicity.

A family-based multimedia intervention to enhance the uptake of colorectal cancer screening among older South Asian adults in Hong Kong: a study protocol for a cluster randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) screening, such as fecal occult blood test (FOBT), is an effective way to prevent CRC, one of the most common cancers worldwide. However, studies found that South Asian ethnic minorities tend not to utilize CRC screening, whose importance on CRC prevention shall be educated among those from ethnic minorities, especially older adults. The purpose of this study is to develop and implement a family-based, multimedia intervention to augment the knowledge of CRC prevention among older South Asian adults in Hong Kong and enhance their motivation for undergoing FOBT. The acceptability and effectiveness of the intervention will be assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. METHODS: A cluster randomized controlled trial will be carried out. Three hundred and twenty South Asian dyads, comprising an older adult aged between 50 and 75 and a younger family member aged between 18 and 49, will be recruited in ten districts in Hong Kong through community organizations that provide support services for South Asians in local communities. Dyads will be randomly allocated to either the intervention or wait-list control group. Intervention dyads will receive intervention, whose contents are based on the health belief model, via multiple forms of media including PowerPoint presentation, video clip and health information booklet. Control dyads will receive intervention after post-intervention data are collected. For dyads in both groups, an appointment with a family doctor will be arranged for those willing to undergo FOBT. Outcomes will be assessed at baseline and post-intervention. Data will be analysed using the Generalised Linear Models Procedure in an intention-to-treat manner. DISCUSSION: Findings of this study will provide evidence of the benefits of utilizing multimedia and family-based approaches in intervention development to enhance the effectiveness of health promotion interventions for ethnic minorities. Further, the findings would provide reference to the potential incorporation of the intervention in the existing support services for South Asian ethnic minorities in local communities. TRIAL REGISTRATION: This trial is registered at the ISRCTN Registry ( ISRCTN72829325 ) on 19th July 2018.

Novel Strategies on Personalized Medicine for Breast Cancer Treatment: An Update.

Breast cancer is the most common cancer type among women worldwide. With breast cancer patients and survivors being reported to experience a repertoire of symptoms that are detrimental to their quality of life, the development of breast cancer treatment strategies that are effective with minimal side effects is therefore required. Personalized medicine, the treatment process that is tailored to the individual needs of each patient, is recently gaining increasing attention for its prospect in the development of effective cancer treatment regimens. Indeed, recent studies have identified a number of genes and molecules that may be used as biomarkers for predicting drug response and severity of common cancer-associated symptoms. These would provide useful clues not only for the determination of the optimal drug choice/dosage to be used in personalized treatment, but also for the identification of gene or molecular targets for the development of novel symptom management strategies, which ultimately would lead to the development of more personalized therapies for effective cancer treatment. In this article, recent studies that would provide potential new options for personalized therapies for breast cancer patients and survivors are reviewed. We suggest novel strategies, including the optimization of drug choice/dosage and the identification of genetic changes that are associated with cancer symptom occurrence and severity, which may help in enhancing the effectiveness and acceptability of the currently available cancer therapies.

Hypotheses on the Potential of Rice Bran Intake to Prevent Gastrointestinal Cancer through the Modulation of Oxidative Stress.

Previous studies have suggested the potential involvement of oxidative stress in gastrointestinal cancers. In light of this, research efforts have been focused on the potential of dietary antioxidant intake to prevent gastrointestinal cancer through the modulation of oxidative stress. Rice bran, a by-product of rice milling, has been shown to contain an abundance of phytochemicals, which are dietary antioxidants. To date, a number of studies have shown the antioxidative effect of rice bran intake, and some demonstrated that such an effect may contribute to gastrointestinal cancer prevention, largely through the antioxidative properties of rice bran phytochemicals. In addition, these phytochemicals were shown to provide protection against cancer through mechanisms linked to oxidative stress, including ß-catenin-mediated cell proliferation and inflammation. The present article provides an overview of current evidence for the antioxidative properties of rice bran and its phytochemicals, and for the potential of such properties in cancer prevention through the oxidative-stress-linked mechanisms mentioned above. The article also highlights the need for an evaluation of the effectiveness of rice bran dietary interventions among cancer survivors in ameliorating oxidative stress and reducing the level of gastrointestinal cancer biomarkers, thereby establishing the potential of such interventions among these individuals in the prevention of cancer recurrence.

The Utilization of the Immune System in Lung Cancer Treatment: Beyond Chemotherapy.

Lung cancer is ranked first worldwide as one of the main cancers in terms of prevalence and mortality rate. The development of effective treatment strategies against lung cancer is therefore of paramount importance. Traditionally, chemotherapy was employed in the treatment of various cancers. However, the non-specific nature of the actions of chemotherapeutic drugs and the potential for tumors to develop resistance to these drugs may render chemotherapy a less favorable option for cancer treatment. Immunotherapy provides an alternative strategy for this purpose. It involves the utilization of the immune system and the immune effector cells to elicit an immune response to the tumors, thereby eliminating them. Strategies include the administration of pro-inflammatory cytokines for immune stimulation, the removal of immunological checkpoints using monoclonal antibodies, and the use of cancer vaccines to enhance immunity against tumors. This article summarizes the above strategies, highlights the reasons why immunotherapy is superior to chemotherapy for the purpose of tumor removal, and reviews the recent clinical studies comparing the clinical outcomes of patients undergoing immunotherapy and chemotherapy. The article also describes advances in immunotherapeutic strategies for the treatment of lung cancer.

A direct interaction between leucine-rich repeat kinase 2 and specific ß-tubulin isoforms regulates tubulin acetylation.

Mutations in LRRK2, encoding the multifunctional protein leucine-rich repeat kinase 2 (LRRK2), are a common cause of Parkinson disease. LRRK2 has been suggested to influence the cytoskeleton as LRRK2 mutants reduce neurite outgrowth and cause an accumulation of hyperphosphorylated Tau. This might cause alterations in the dynamic instability of microtubules suggested to contribute to the pathogenesis of Parkinson disease. Here, we describe a direct interaction between LRRK2 and ß-tubulin. This interaction is conferred by the LRRK2 Roc domain and is disrupted by the familial R1441G mutation and artificial Roc domain mutations that mimic autophosphorylation. LRRK2 selectively interacts with three ß-tubulin isoforms: TUBB, TUBB4, and TUBB6, one of which (TUBB4) is mutated in the movement disorder dystonia type 4 (DYT4). Binding specificity is determined by lysine 362 and alanine 364 of ß-tubulin. Molecular modeling was used to map the interaction surface to the luminal face of microtubule protofibrils in close proximity to the lysine 40 acetylation site in α-tubulin. This location is predicted to be poorly accessible within mature stabilized microtubules, but exposed in dynamic microtubule populations. Consistent with this finding, endogenous LRRK2 displays a preferential localization to dynamic microtubules within growth cones, rather than adjacent axonal microtubule bundles. This interaction is functionally relevant to microtubule dynamics, as mouse embryonic fibroblasts derived from LRRK2 knock-out mice display increased microtubule acetylation. Taken together, our data shed light on the nature of the LRRK2-tubulin interaction, and indicate that alterations in microtubule stability caused by changes in LRRK2 might contribute to the pathogenesis of Parkinson disease.

Factors affecting HPV vaccine uptake among ethnic minority adolescent girls: A systematic review and meta-analysis.

Objective: Human papillomavirus (HPV) vaccination rates remain low among adolescent girls across ethnic minority groups that experience high incidences of HPV-related cervical cancer with poor outcomes. This systematic review aimed to synthesize the available evidence on the factors affecting HPV vaccination among ethnic minority adolescent girls. Methods: Six databases (PubMed, OVID MEDLINE, EMBASE, CINAHL, PsycINFO, and Scopus) were searched from inception to October 17, 2022. Guided by the conceptual model of vaccine hesitancy, the factors affecting HPV vaccine uptake were descriptively synthesized and analyzed using meta-analyses. Results: This review included 14 studies. The pooled uptake rate of at least one dose of HPV vaccine among ethnic minority adolescent girls was only 38% (95% confidence interval â€‹= â€‹0.22, 0.39). At individual level, age of adolescent girls, knowledge of HPV, perceived importance of HPV vaccination, and perceived risk of HPV infection promoted the vaccine uptake. Beliefs in conspiracy theories and lack of trust in the government and HPV vaccine discouraged the utilization. At social and policy levels, health professionals' recommendations, subjective norms, sexuality-related communication, and vaccine policies such as insurance coverage facilitated HPV vaccination. The religious and moral convictions regarding abstinence from sex until marriage negatively influenced the vaccine acceptance. Conclusions: HPV vaccination among ethnic minority adolescent girls was influenced by multi-level factors that highlighted a combined effort, including culturally sensitive health education programmes, sexuality-related communication skills training, collaboration with religious organizations, debunking conspiracy theories in HPV vaccine, and promoting school-based vaccination programs, to increase the coverage. Systematic review registration: PROSPERO, CRD42022366805.

Factors associated with cervical cancer screening utilisation by people with physical disabilities: A systematic review.

BACKGROUND: Previous studies showed that cervical cancer screening uptake among people with physical disabilities is low. A better understanding of the factors affecting their screening uptake is needed to devise strategies to address this issue. OBJECTIVE: This review explores the factors that impede or enhance cervical cancer screening utilisation by people with physical disabilities, such as mobility, visual and hearing impairments. METHODS: Five electronic databases were searched, resulting in the inclusion of nine studies focusing on people with physical disabilities and their utilisation of cervical cancer screening services. Extracted data from these studies were summarised narratively. Their methodological quality was assessed using the Mixed Methods Appraisal Tool, Version 2018. RESULTS: Three major impeding factors were reported: 1) lack of knowledge of cervical cancer screening and how it can be accessed; 2) difficulties and inconveniences in accessing cancer screening providers and undergoing the screening procedures; and 3) uncomfortable experiences during the screening procedures. The availability of attendant services and wheelchair-accessible facilities and a longer duration of screening procedures enhanced screening utilisation by the subjects. CONCLUSIONS: This review highlights the need to provide training for healthcare professionals on working with people with physical disabilities, enhance supportive services to allow them to access cervical cancer screening and educate them on the importance of screening.

Association of genetic polymorphisms with psychological symptoms in cancer: A systematic review.

Cancer patients suffer from a repertoire of symptoms, including such psychological and psychiatric symptoms as anxiety, depression, and posttraumatic stress. Exploration of genetic factors that modify the risk and severity of these symptoms may facilitate the development of personalised care plans for managing these symptoms. This review aims to provide an overview on the variations in genes that may contribute to the occurrence and severity of anxiety, depression, and posttraumatic stress disorder (PTSD) among cancer patients. Literature search was performed in nine English and Chinese electronic databases, and extracted data are presented narratively. The reporting quality of the included studies was assessed using selected items of The STrengthening the REporting of Genetic Association (STREGA) checklist. Twenty-nine studies were included in the review. Most studies involved breast cancer patients, while patients of other cancer types appeared to be understudied. A number of studies reported the association between genes involved in inflammatory pathways and depression and anxiety. Other genes found to show associations with anxiety, depression, and PTSD among cancer patients are those involved in neurotrophic signalling, serotonergic signalling, regulation of stress response, antioxidation, dopamine catabolism and cellular apoptosis, despite some inconsistencies in findings between studies. Our review highlighted a need for further research for enhancing our knowledge on the association between genetic variations and anxiety, depression, and PTSD of patients of various cancer types. Future studies examining such associations in patients of various cancers should utilise standardised instruments for outcome assessments and stratify the patients based on their age for analysis.

Effect of a family-based multimedia intervention on the uptake of faecal immunohistochemical test among South Asian older adults: A cluster-randomised controlled trial.

BACKGROUND: Colorectal cancer screening, including faecal immunohistochemical test, is an effective method for detecting colorectal cancer early. Nevertheless, faecal immunohistochemical test uptake among South Asian ethnic minorities is low because they have limited knowledge of and face barriers in accessing colorectal cancer screening. Tailored education and appropriate messaging has potential to convey to this population group the importance of colorectal cancer screening. OBJECTIVES: This study aimed to assess the acceptability and effectiveness of a family-based multimedia intervention to raise awareness of colorectal cancer screening and increase the uptake of faecal immunochemical tests among South Asian older adults. DESIGN: A cluster-randomised controlled trial with a wait-list control group. PARTICIPANTS: Three-hundred and twenty dyads of South Asian older adults and their younger family members were recruited at South Asian community centres and non-governmental organisations providing support services to local South Asians in six Hong Kong districts. METHODS: Group allocation of dyads during cluster randomisation was based on the group assignment of the district where they were recruited. The intervention comprised a multimedia health talk, conveying the importance of colorectal cancer screening and support from younger family members in encouraging their older relatives to undergo screening. Site coordinators assisted participants in accessing faecal immunohistochemical test. The primary outcome was increased uptake of faecal immunohistochemical test among South Asian older adults. Secondary outcomes included younger family members' encouragement of their older relatives to undergo faecal immunohistochemical test and their readiness to assist their relatives with the test. Acceptability of the intervention was measured by dyad satisfaction with the intervention. RESULTS: The proportion of older adults participating in faecal immunohistochemical testing was significantly higher among intervention dyads compared with controls (71.8% vs 6.8%, p < 0.001). No significant within-group change was observed on the willingness of younger family members in the intervention group to encourage older adults to undergo faecal immunohistochemical test, nor their readiness to assist older adults in doing so, although a decrease in both outcomes was observed among the control group. Most participants (>86%) were satisfied with the intervention. CONCLUSIONS: Our findings demonstrate the acceptability and effectiveness of the intervention in enhancing faecal immunohistochemical test uptake among South Asian older adults, and the benefit of using a family-based approach in the implementation of cancer screening interventions for these individuals. Implementation of the intervention as a component of usual care within South Asian communities is recommended. Trial registration ISRCTN72829325, 10 July 2018.

Achieving equitable access to cancer screening services to reduce the cancer burden in the Asia-Pacific region: Experience from Hong Kong.

The global burden of cancer can be reduced through early detection by providing people with unrestricted access to cancer screening services. However, health disparities exist within and across countries and regions. This viewpoint article uses the Integrative Multicomponent Programme for Promoting South Asians' Cancer Screening Uptake (IMPACT) project as an example of sharing strategies, such as evidence-based multimedia interventions, community health worker-led interventions, strengthening relationships and building networks, that are being adopted to improve ethnic minorities' access to cancer screening services in Hong Kong. We find that the IMPACT project effectively increased South Asians' cancer screening uptake (e.g. the cervical cancer screening uptake rate saw a 42% increase over 5 years). Future directions for scaling up the IMPACT project have been suggested to contribute to achieving Goal 3 in the United Nations Sustainable Development Goals by 2030, that is, ensuring healthy lives and promoting the well-being of all people at all ages.

A systematic review of the barriers and facilitators influencing the cancer screening behaviour among people with intellectual disabilities.

Individuals with intellectual disabilities (ID) may require assistance in accessing healthcare services, including cancer screening. A better understanding of the factors affecting cancer screening utilisation among these individuals is needed for the development of strategies to promote screening uptake in them. This review aimed to explore the facilitators of and barriers to cancer screening utilisation among people with ID. A literature search was conducted using five databases, and an additional snowball search yielded 16 studies for inclusion in the review. Overall, the methodological quality of these studies was good (43-100%). In this review, we noted barriers to screening among individuals with ID, including perceptions of fear, distress, and embarrassment; unpreparedness for screening; negative interactions with healthcare professionals; a lack of knowledge about cancer screening; mobility issues; a high severity of ID; and a lack of ability to provide consent and communicate verbally. Facilitators to screening among these individuals were also identified, including living in a supervised setting, prior use of other healthcare services, being educated about screening via social media, having carers accompany them to screening appointments, and having dual insurance coverage or a higher income. Our review highlights the current needs of individuals with ID undergoing cancer screening. Strategies should be developed to address these needs, such as the provision of training to healthcare professionals on how to conduct screening for people with ID.

Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent known cause of autosomal dominant Parkinson's disease. The LRRK2 gene encodes a Roco protein featuring a Ras of complex proteins (ROC) GTPase and a kinase domain linked by the C-terminal of ROC (COR) domain. Here, we explored the effects of the Y1699C pathogenic LRRK2 mutation in the COR domain on GTPase activity and interactions within the catalytic core of LRRK2. We observed a decrease in GTPase activity for LRRK2 Y1699C comparable to the decrease observed for the R1441C pathogenic mutant and the T1348N dysfunctional mutant. To study the underlying mechanism, we explored the dimerization in the catalytic core of LRRK2. ROC-COR dimerization was significantly weakened by the Y1699C or R1441C/G mutation. Using a competition assay, we demonstrated that the intra-molecular ROC : COR interaction is favoured over ROC : ROC dimerization. Interestingly, the intra-molecular ROC : COR interaction was strengthened by the Y1699C mutation. This is supported by a 3D homology model of the ROC-COR tandem of LRRK2, showing that Y1699 is positioned at the intra-molecular ROC : COR interface. In conclusion, our data provides mechanistic insight into the mode of action of the Y1699C LRRK2 mutant: the Y1699C substitution, situated at the intra-molecular ROC : COR interface, strengthens the intra-molecular ROC : COR interaction, thereby locally weakening the dimerization of LRRK2 at the ROC-COR tandem domain resulting in decreased GTPase activity.

Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways.

Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process. We report the interaction of LRRK2 with the dishevelled family of phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways important for axon guidance, synapse formation and neuronal maintenance. Interestingly, DVLs can interact with and mediate the activation of small GTPases with structural similarity to the LRRK2 Roc domain. The LRRK2 Roc-COR domain and the DVL1 DEP domain were necessary and sufficient for LRRK2-DVL1 interaction. Co-expression of DVL1 increased LRRK2 steady-state protein levels, an effect that was dependent on the DEP domain. Strikingly, LRRK2-DVL1-3 interactions were disrupted by the familial PARK8 mutation Y1699C, whereas pathogenic mutations at residues R1441 and R1728 strengthened LRRK2-DVL1 interactions. Co-expression of DVL1 with LRRK2 in mammalian cells resulted in the redistribution of LRRK2 to typical cytoplasmic DVL1 aggregates in HEK293 and SH-SY5Y cells and co-localization in neurites and growth cones of differentiated dopaminergic SH-SY5Y cells. This is the first report of the modulation of a key LRRK2-accessory protein interaction by PARK8 Roc-COR domain mutations segregating with Parkinson's disease. Since the DVL1 DEP domain is known to be involved in the regulation of small GTPases, we propose that: (i) DVLs may influence LRRK2 GTPase activity, and (ii) Roc-COR domain mutations modulating LRRK2-DVL interactions indirectly influence kinase activity. Our findings also link LRRK2 to Wnt signalling pathways, suggesting novel pathogenic mechanisms and new targets for genetic analysis in Parkinson's disease.

Perceptions of Chinese Patients Treated for Gynaecological Cancer about Sexual Health and Sexual Information Provided by Healthcare Professionals: A Qualitative Study.

Patients treated for gynaecological cancer (GC) generally experience impaired sexual function. Research on their sexual life experiences and perceptions on the sexuality care they receive is warranted. This study aimed to examine the perceptions of Chinese patients treated for GC regarding the effects of cancer treatment on their sexual function and femininity, their relationships with their partners, and the adequacy of the sexual information received from healthcare professionals during treatment. Individual, semi-structured interviews were conducted with 21 Chinese patients treated for GC, collecting data on their perceptions regarding the effects of cancer treatment on their sexual lives, femininity, and relationships with partners; and their views about the quality of sexuality care received. Data were analysed using content analysis. Participants experienced impaired sexual function, reduced sex drive, and expressed dissatisfaction with their sex lives. They perceived a loss of femininity and poor body image. They desired more information about how to address sexual problems and opted to receive this information from female healthcare professionals in individual counselling sessions during which the professionals could initiate such discussions. Overall, Chinese patients treated for GC have concerns about multiple sexual issues and a strong desire for information about strategies to address these issues. Nurse-led interventions should be implemented via a shared care approach to enhance patients' awareness about managing their sexual and psychological symptoms.

A Community Health Worker-Led Multicomponent Program to Promote Cervical Cancer Screening in South Asian Women: A Cluster RCT.

INTRODUCTION: South Asian women in Hong Kong have low cervical cancer screening uptake because of multiple barriers to utilizing health resources. Interventions that effectively modify the cancer screening behaviors of this population are warranted. This study evaluates the effects of a community health worker-led multicomponent intervention on improving cervical cancer screening uptake among South Asian women in Hong Kong. STUDY DESIGN: This study was an assessor-blind, cluster RCT that included a waitlist control group. SETTING/PARTICIPANTS: Recruitment of eligible subjects took place in 6 nongovernmental organizations; these organizations were randomized into intervention and control groups with a 1:1 allocation ratio. INTERVENTION: Participants in the intervention group received a 3-month multicomponent intervention comprising health education, monthly telephone follow-ups, and navigation assistance. MAIN OUTCOME MEASURES: Participants' cervical cancer screening utilization and beliefs were assessed at baseline, after intervention, and 3 months after intervention. A longitudinal outcome comparison between the 2 groups was performed with generalized estimating equation analysis. Data were collected between September 2018 and January 2020 and were analyzed in 2019-2020. RESULTS: A total of 387 participants completed the intervention. A significantly higher cervical cancer screening uptake was observed among participants in the intervention group (97.9%, 191 of 195) than among participants in the control group (52.6%, 101 of 192) at 3 months after intervention (p=0.005). Significantly greater decrements in perceived barriers to cervical cancer screening were found in the intervention group after intervention (-0.68, 95% CI= -1.35, -0.01, p=0.047) and 3 months after intervention (-0.86, 95% CI= -1.69, -0.04, p=0.041). CONCLUSIONS: A community health worker-led multicomponent intervention is effective in promoting cervical cancer screening uptake and in reducing barriers to cancer screening utilization among South Asian women in Hong Kong. Combining a community health worker-led intervention with multiple intervention components could be an effective strategy for developing interventions to increase cervical cancer screening in underserved populations. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn) ChiCTR1800017227 on July 18, 2018.