bims-curels 2023-07-30 papers

bims-curels

Biomed News

on Leigh syndrome

Issue of 2023–07–30
seven papers selected by
Cure Mito Foundation

Mitochondrial defects leading to arrested spermatogenesis and ferroptosis in the PARL deficient mouse model of Leigh Syndrome.
Mitochondrial DNA mutations in Medulloblastoma.
Determining the benefits and drawbacks of parents using personal connections and social networks for recruitment in research projects: a qualitative study.
Storytelling for impact: the creation of a storytelling program for patient partners in research.
Using Patient Blogs on Social Media to Assess the Content Validity of Patient-Reported Outcome Measures: Qualitative Analysis of Patient-Written Blogs.
Engaging and informing patients: Health information technology use in community health centers.
The Minimum Data Set for Rare Diseases: Systematic Review.

Elife. 2023 Jul 28. pii: e84710. [Epub ahead of print]12

Mitochondrial defects leading to arrested spermatogenesis and ferroptosis in the PARL deficient mouse model of Leigh Syndrome.

Enrico Radaelli, Charles-Antoine Assenmacher, Jillian Verrelle, Esha Banerjee, Florence Manero, Salim Khiati, Anais Girona, Guillermo Lopez-Lluch, Placido Navas, Marco Spinazzi.

  Impaired spermatogenesis and male infertility are common manifestations of mitochondrial diseases, but the underlying mechanisms are unclear. Here we show that mice deficient for the mitochondrial intra-membrane rhomboid protease PARL, a recently reported model of Leigh syndrome, develop early testicular atrophy caused by a complete arrest of spermatogenesis at meiotic prophase I, followed by germ cell death independently of neurodegeneration. Genetic modifications of PINK1, PGAM5, and TTC19, three major substrates of PARL with important roles in mitochondrial homeostasis, do not reproduce or modify this severe phenotype. PARL deficiency in spermatocytes leads to severe abnormalities in mitochondrial structure associated with prominent electron transfer chain defects, alterations in Coenzyme Q (CoQ) biosynthesis, and metabolic rewiring. These mitochondrial defects are associated with a germ-cell specific decrease in GPX4 expression committing arrested spermatocytes to ferroptosis, a regulated cell death modality characterized by uncontrolled lipid peroxidation. Thus, mitochondrial defects, such as those induced by depletion of PARL, spontaneously initiate ferroptosis in primary spermatocytes in vivo by simultaneous effects on GPX4 and CoQ, the two major ferroptosis-inhibitors. Ferroptosis warrants to be further scrutinized in the pathogenesis of mitochondrial diseases and male infertility.

Keywords:  cell biology; mouse

DOI:  https://doi.org/10.7554/eLife.84710
Acta Neuropathol Commun. 2023 Jul 27. 11(1): 124

Mitochondrial DNA mutations in Medulloblastoma.

Viktoria L E Funke, Sarah Sandmann, Viktoria Melcher, Jochen Seggewiss, Judit Horvath, Natalie Jäger, Marcel Kool, David T W Jones, Stefan M Pfister, Till Milde, Stefan Rutkowski, Martin Mynarek, Julian Varghese, Ronald Sträter, Stephan Rust, Anja Seelhöfer, Janine Reunert, Barbara Fiedler, Ulrich Schüller, Thorsten Marquardt, Kornelius Kerl.

  To date, several studies on genomic events underlying medulloblastoma (MB) biology have expanded our understanding of this tumour entity and led to its division into four groups-WNT, SHH, group 3 (G3) and group 4 (G4). However, there is little information about the relevance of pathogenic mitochondrial DNA (mtDNA) mutations and their consequences across these. In this report, we describe the case of a female patient with MB and a mitochondriopathy, followed by a study of mtDNA variants in MB groups. After being diagnosed with G4 MB, the index patient was treated in line with the HIT 2000 protocol with no indications of relapse after five years. Long-term side effects of treatment were complemented by additional neurological symptoms and elevated lactate levels ten years later, resulting in suspected mitochondrial disease. This was confirmed by identifying a mutation in the MT-TS1 gene which appeared homoplasmic in patient tissue and heteroplasmic in the patient's mother. Motivated by this case, we explored mtDNA mutations across 444 patients from ICGC and HIT cohorts. While there was no statistically significant enrichment of mutations in one MB group, both cohorts encompassed a small group of patients harbouring potentially deleterious mtDNA variants. The case presented here highlights the possible similarities between sequelae caused by MB treatment and neurological symptoms of mitochondrial dysfunction, which may apply to patients across all MB groups. In the context of the current advances in characterising and interpreting mtDNA aberrations, recognising affected patients could enhance our future knowledge regarding the mutations' impact on carcinogenesis and cancer treatment.

Keywords:  DNA mutational analysis; DNA, Mitochondrial; Medulloblastoma; Mitochondrial diseases

DOI:  https://doi.org/10.1186/s40478-023-01602-0
Res Involv Engagem. 2023 Jul 26. 9(1): 58

Determining the benefits and drawbacks of parents using personal connections and social networks for recruitment in research projects: a qualitative study.

Laesa Kim, Carrie Costello, Michael A Golding, Chloé Janse van Rensburg, Jennifer L P Protudjer, Kristy Wittmeier.

   BACKGROUND: It is becoming more common for parents of children with chronic conditions to join research teams as partners. Parent partnerships can help align research with what is relevant and important to families. It is also common for parent partners to be asked to share information about a study through their personal networks, which supports study recruitment. In this parent-led study, we explored parents' experiences when working together with researchers in patient-oriented research studies, in relation to study recruitment.
METHODS: Demographic data were collected through a brief online survey (SurveyMonkey®) and analysed descriptively (n, %, median (interquartile range; IQR)). Qualitative data were collected through focus groups and interviews (July to October 2021), transcribed verbatim, and analysed thematically. Parent co-leads were involved in every stage of the study, including study design, recruitment, data collection, analysis, interpretation, and knowledge mobilization.
RESULTS: Fifteen parents (n = 14 women) who had research partnership experience participated in this study. Most (n = 13) participants self-identified as White or of European descent. The majority (n = 10) had partnered in 1-3 research projects, while five participants had partnered in 4 + projects. Parents had a median of 3 years (IQR: 5) of partnership experience. We identified the following three themes: motivations, authentic partnerships, and learned decision making. Each theme included reflections about recruitment, and about research partnership in general. Motivations included a personal connection to the research topic, a connection to the community impacted by the research topic, and a desire to create change. Authentic partnerships were important for a meaningful experience, and enhanced participant's willingness and ability to share study materials. Learned decision making reflected parents' evolving decisions and practices related to sharing study information or personal information to support research. We provide a summary of participants' recommendations for researchers who work with parent partners, and recommendations for parents as they approach research partnerships.
CONCLUSIONS: Experiences shared by parents who have partnered in research provide valuable information to inform recruitment methods and improve team functioning. Parent partners expressed a willingness to support recruitment and valued a strong research team working together for a common outcome. This study yields a set of recommendations guiding future research that engages parents as team members.

Keywords:  Community networks; Parent partnership; Parents; Patient partner; Patient-oriented research; Qualitative research; Recruitment; Risks & benefits

DOI:  https://doi.org/10.1186/s40900-023-00470-1
Res Involv Engagem. 2023 Jul 25. 9(1): 57

Storytelling for impact: the creation of a storytelling program for patient partners in research.

Leah E Getchell, Marian Reich, Selina Allu, Cathy Woods, Teresa Atkinson, Mary Beaucage, Leanne Stalker, Dwight Sparkes, Catherine Turner, Audrey L'Esperance, Kevin Burns, Meghan J Elliott, Helen Chiu, Norman D Rosenblum, Ruth Sapir-Pichhadze.

  Storytelling is a powerful means to evoke empathy and understanding among people. When patient partners, which include patients, family members, caregivers and organ donors, share their stories with health professionals, this can prompt listeners to reflect on their practice and consider new ways of driving change in the healthcare system. However, a growing number of patient partners are asked to 'share their story' within health care and research settings without adequate support to do so. This may ultimately widen, rather than close, the gap between healthcare practitioners and people affected by chronic disease in this new era of patient and public involvement in research. To better support patient partners with storytelling in the context of a patient-oriented research network, Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) Network adapted an existing in-person storytelling workshop for patient educators within a hospital setting. The result is a 6-week virtual program called Storytelling for Impact, which guides patients, family members, caregivers and organ donors in developing impactful stories and sharing them at health care and research events, e.g., conferences. The online series of synchronous workshops is co-facilitated by story coaches, who are program alumni and Can-SOLVE CKD staff with trained storytelling experience. Each story follows a structure that includes a call to action, which aims to positively impact the priority-setting and delivery of care and research in Canada. The program has been a transformational process for many who have completed it, and numerous other health organizations have expressed interest in sharing this tool with their own patient partners. As result, we have also created an asynchronous online program that can be used by other interested parties outside our network. Patient partners who share their stories can be powerful mediators for inspiring changes in the health care and research landscape, with adequate structured support. We describe two novel programs to support patient partners in impactful storytelling, which are applicable across all health research disciplines. Additional resources are required for sustainability and scale up of training, by having alumni train future storytellers.

Keywords:  Health research; Kidney; Kidney transplant; Living organ donation; Organ donation; Patient and public involvement; Patient engagement; Patient partnerships; Patient-oriented research; Storytelling

DOI:  https://doi.org/10.1186/s40900-023-00471-0
JMIR Form Res. 2023 Jul 28. 7 e43210

Using Patient Blogs on Social Media to Assess the Content Validity of Patient-Reported Outcome Measures: Qualitative Analysis of Patient-Written Blogs.

Diana M J Delnoij, Meggie Derks, Laura Koolen, Shuka Shekary, Jozua Suitela.

   BACKGROUND: Patient-reported outcome measures (PROMs) are questionnaires that measure patient outcomes related to quality of life, health, and functioning, and are increasingly used to assess important outcomes from the patient's perspective. For PROMs to contribute to better health and better care, it is vital that their content validity be adequate. This requires patient involvement in various steps of PROM development. PROM developers not only recognize the benefits of patient involvement but also report difficulties in recruiting patients and experience patient involvement as time-consuming, logistically challenging, and expensive.
OBJECTIVE: This study seeks to explore different strategies for disclosing the experiential knowledge of patients, namely through analyzing patient stories on the web and social media. The research questions are as follows: (1) how do bloggers living with a disease experience their health-related quality of life? (2) How are these experiences reflected in the domains and items of PROMs related to their disease?
METHODS: First, a qualitative analysis of blogs written by patients was performed. Second, subthemes and underlying codes resulting from this qualitative analysis were systematically compared with the domains and items in PROMs for the respective diseases that the bloggers write about. Blogs were identified via the Google search engine between December 2019 and May 2021.
RESULTS: Bloggers describe a wide range of experiences regarding their physical functioning and health; mental well-being; social network and support; daily life, education, work, and leisure; coping; and self-management. Bloggers also write about their positive and negative experiences with health care delivery, the organization of health care, and health care professionals. In general, patients' experiences as described in blogs were reflected in the domains and items of the PROMs related to their disease. However, except for diabetes mellitus, in all the sets of PROMs, potentially missing topics could be identified. Similarly, with the exception of Parkinson disease, all PROMs address issues that patients did not write about in their blogs and that might therefore be redundant.
CONCLUSIONS: Web-based patient stories in the form of blogs reveal how people living with a certain disease experience their health-related quality of life. These stories enable analyses of patients' experiences that can be used to assess the content validity of PROMs. This can be a useful step for researchers who are looking for sets of measuring instruments that match their purposes.

Keywords:  HAQ; Health Assessment Questionnaire; ICHOM; International Consortium for Health Outcome Measurement; NCD; PDQ; PROM; Parkinson Disease Quality of Life Questionnaire; Parkinson disease, diabetes mellitus; blogger; breast cancer; cancer; chronic disease; content analysis; content validity; cross sectional; cross-sectional; data dictionary; diabetes; experience; experiential; inductive; inductive code; narrative; noncommunicable diseases; oncology; patient stories; patient story; patient-reported outcome measure; qualitative; rheumatoid arthritis; social media; storytelling; type II diabetes

DOI:  https://doi.org/10.2196/43210
Int J Med Inform. 2023 Jul 21. pii: S1386-5056(23)00176-4. [Epub ahead of print]177 105158

Engaging and informing patients: Health information technology use in community health centers.

Seongwon Choi, Thomas Powers.

   OBJECTIVE: This paper aims to address the relationship between the community health center (CHC) patient mix and the level of patient engagement health information technology (HIT) comprehensiveness.
PARTICIPANTS: The study was conducted on sample CHCs (n = 3,592 CHC-years) active between 2016 and 2018.
METHODS: Patient engagement HIT comprehensiveness was measured based on a framework of patient engagement through HIT that includes a two-part dichotomy of patient engagement and patient informing. Univariate analysis was used to describe CHC characteristics and multivariable ordered logistic regression analysis was used to test hypothesized relationships.
RESULTS: The study identified four levels of patient engagement HIT comprehensiveness: 1) to neither engage nor inform, 2) to primarily inform, 3) to primarily engage, and 4) to engage and inform. It was found that CHCs serving disproportionate shares of patients with disadvantageous socioeconomic characteristics are less likely to incorporate more comprehensive patient engagement HIT.
CONCLUSION: The results highlight the different levels of patient engagement HIT use among CHCs and a negative association between CHC's higher proportion of patients with a disadvantageous sociodemographic background and patient engagement HIT comprehensiveness.

Keywords:  Community health centers; Digital divide; Health information technology; Patient engagement

DOI:  https://doi.org/10.1016/j.ijmedinf.2023.105158
J Med Internet Res. 2023 Jul 27. 25 e44641

The Minimum Data Set for Rare Diseases: Systematic Review.

Filipe Andrade Bernardi, Bibiana Mello de Oliveira, Diego Bettiol Yamada, Milena Artifon, Amanda Maria Schmidt, Victória Machado Scheibe, Domingos Alves, Têmis Maria Félix.

   BACKGROUND: The minimum data set (MDS) is a collection of data elements to be grouped using a standard approach to allow the use of data for clinical and research purposes. Health data are typically voluminous, complex, and sometimes too ambiguous to generate indicators that can provide knowledge and information on health. This complexity extends further to the rare disease (RD) domain. MDSs are essential for health surveillance as they help provide services and generate recommended population indicators. There is a bottleneck in international literature that reveals a global problem with data collection, recording, and structuring in RD.
OBJECTIVE: This study aimed to identify and analyze the MDSs used for RD in health care networks worldwide and compare them with World Health Organization (WHO) guidelines.
METHODS: The population, concept, and context methodology proposed by the Joanna Briggs Institute was used to define the research question of this systematic review. A total of 4 databases were reviewed, and all the processes were reported using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. The data elements were analyzed, extracted, and organized into 10 categories according to WHO digital health guidelines. The quality assessment used the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist.
RESULTS: We included 20 studies in our review, 70% (n=14) of which focused on a specific health domain and 30% (n=6) of which referred to RD in general. WHO recommends that health systems and networks use standard terminology to exchange data, information, knowledge, and intelligence in health. However, there was a lack of terminological standardization of the concepts in MDSs. Moreover, the selected studies did not follow the same standard structure for classifying the data from their MDSs. All studies presented MDSs with limitations or restrictions because they covered only a specific RD, or their scope of application was restricted to a specific context or geographic region. Data science methods and clinical experience were used to design, structure, and recommend a fundamental global MDS for RD patient records in health care networks.
CONCLUSIONS: Our study highlights the difficulties in standardizing and categorizing findings from MDSs for RD because of the varying structures used in different studies. The fundamental RD MDS designed in this study comprehensively covers the data needs in the clinical and management sectors. These results can help public policy makers support other aspects of their policies. We highlight the potential of our results to help strategic decisions related to RD.
TRIAL REGISTRATION: PROSPERO CRD42021221593; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221593.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.procs.2021.12.034.

Keywords:  health care system; health network; minimum data set; public health; rare disease

DOI:  https://doi.org/10.2196/44641