bims-curels 2026-06-14 papers

bims-curels

Biomed News

on Leigh syndrome

Issue of 2026–06–14
eleven papers selected by
Cure Mito Foundation

Mitochondrial complex I deficiency-associated diseases and models.
Mitochondrial disease: mechanisms, signalling, and therapeutic opportunities.
Effects of an indole chemical, mitochonic acid 5, in a mouse model of mitochondrial disease onset.
Expanding the landscape of tRNA pathogenic variants in mitochondrial DNA.
"If I go down, if I crumble, then everybody does" - identity crisis and emotional strain in parents of children with rare and undiagnosed conditions: a qualitative study.
Associations between adverse childhood experiences, mitochondrial DNA copy number and atopic disease in children.
Training Empathetic Communication Skills in Medical Students With a Role-Prompted GPT-4o Chatbot: Quasi-Experimental Intervention Study.
Mitochondrial mutation status, symptom prevalence, and neuroimaging characteristics in MELAS: a systematic review and meta analysis.
Integrative Literature Review on the Lived Experiences of Parents of Children with a Rare Disease.
How Can I Support a Patient Praying for a Miracle?
Characterizing Parental Use of a HIPAA-Compliant Large Language Model Chatbot in Rare Pediatric Diseases: Insights from Think-Aloud Sessions.

Cell Mol Life Sci. 2026 Jun 10. pii: 249. [Epub ahead of print]83(1):

Mitochondrial complex I deficiency-associated diseases and models.

Lena Jentsch, Natascia Ventura.

  Mitochondrial complex I is the first and largest enzyme of the mitochondrial respiratory chain and thus plays a crucial role in cellular energy metabolism. Defects in the mitochondrial respiratory chain, and in particular CI deficiency, are the primary cause of human mitochondrial associated diseases, which most often presents as severe neurometabolic disorders with fatal outcome. Up to this date the diagnosis and treatment of CI deficiency-associated diseases is challenging, only limited symptomatic therapies exist and no cures are available. This review aims at summarizing current knowledge on the genetic basis of CI deficiency-associated diseases and available experimental disease models. Most common human disorders caused by CI deficiency range from Leigh syndrome to MELAS and LHON, all characterized by genetic and symptomatic heterogeneity. So far, in vivo studies on non-mammalian organisms and mouse models, as well as in vitro studies on patient derived fibroblasts, cybrids and human-induced pluripotent stem cells have mainly facilitated the research of CI deficiency. These model systems provide insights on molecular mechanisms in mitochondrial disease and approaches for potential therapeutic intervention strategies. However, current research is limited by translational relevance of existing disease models, varying degrees of heteroplasmy and tissue specific effects characteristic of mitochondrial diseases, so that basic disease mechanisms still remain poorly understood. To overcome these challenges there is an urgent need for in vivo and in vitro human relevant models to aid the development of effective therapeutic interventions and potential cures of CI deficiency-associated diseases.

Keywords:  Mammalian cell models; Mitochondrial complex I; Mitochondriopathies; Model organisms

DOI:  https://doi.org/10.1007/s00018-026-06169-2
Free Radic Biol Med. 2026 Jun 06. pii: S0891-5849(26)00857-9. [Epub ahead of print]253 749-769

Mitochondrial disease: mechanisms, signalling, and therapeutic opportunities.

Samantha Corrà, Luke Young, Anthony L Moore, Carlo Viscomi.

Mitochondria are central hubs of cellular metabolism and signalling, and their dysfunction underlies a broad spectrum of human diseases, including rare mitochondrial disorders as well as common neurodegenerative and metabolic conditions. Mitochondrial diseases are genetically heterogeneous disorders caused by mutations in nuclear or mitochondrial DNA that impair oxidative phosphorylation (OXPHOS), resulting in reduced ATP production and cellular energy failure. Despite a shared bioenergetic defect, these diseases display marked clinical variability, and the mechanisms underlying this heterogeneity remain poorly understood. At present, no curative therapies are available, although several metabolic and experimental approaches have shown promise in preclinical models. Mitochondrial dysfunction is commonly associated with altered redox homeostasis and increased production of reactive oxygen species (ROS), which can damage mitochondrial components, including mitochondrial DNA, and further impair respiratory chain function. At the same time, ROS also act as context-dependent signalling molecules, with effects that vary according to concentration, localization, and cell type complicating their interpretation in disease mechanisms and therapy development. In this review, we summarize current concepts in mitochondrial disease pathophysiology focusing on unresolved questions that limit mechanistic understanding and clinical translation. We critically evaluate the role of ROS in disease progression and signalling, discuss how the alternative oxidase (AOX) has emerged as a valuable experimental tool to dissect ROS-related mechanisms and reveal unexpected aspects of mitochondrial dysfunction and disease variability.

DOI: https://doi.org/10.1016/j.freeradbiomed.2026.06.013
Sci Rep. 2026 Jun 10.

Effects of an indole chemical, mitochonic acid 5, in a mouse model of mitochondrial disease onset.

Emi Ogasawara, Haruna Tani, Chitose Suzuki, Yuji Owada, Masaki Ogata, Naotada Ishihara, Takaaki Abe, Kazuto Nakada.

  This study tested the effects of mitochonic acid 5 (MA-5) using a mouse model of mitochondrial disease onset (mito-mice∆), with disease resulting from the accumulation of pathogenic mitochondrial DNA harboring a large deletion (∆mtDNA). Administration of MA-5 to mito-mice∆ inhibited the progression of clinical symptoms, such as low body weight and lactic acidosis. In the kidneys, MA-5 protected against mitochondrial respiration defects and subsequent renal failure, even when ∆mtDNA accumulated to > 80%. In the heart, MA-5 also resolved the mitochondrial respiration defects. Our findings suggested that administration of MA-5 would be effective in delaying the progression of some mitochondrial diseases caused by mutant mtDNA and especially in mitochondrial-mediated renal failure.

Keywords:  Mitochondria; Mitochondrial DNA (mtDNA); Mitochondrial diseases; Mitochonic acid 5 (MA-5); Mouse model; Respiratory chain

DOI:  https://doi.org/10.1038/s41598-026-57342-3
Brain Commun. 2026 ;8(3): fcag178

Expanding the landscape of tRNA pathogenic variants in mitochondrial DNA.

Salvatore Loris Siragusa, Santino Blando, Claudio Fiorini, Alberto Pietro Pasti, Danara Ormanbekova, Francesco Casadei, Luca Morandi, Elena Pegoraro, Rocco Liguori, Valerio Carelli, Chiara La Morgia, Leonardo Caporali, Maria Lucia Valentino.

  We present a comprehensive molecular and histopathological characterization of nine patients with mitochondrial myopathy, predominantly manifesting progressive external ophthalmoplegia (PEO), associated with heteroplasmic variants in mitochondrial tRNA genes (mt-tRNA). Among the ten variants identified, four were novel and previously unreported in MITOMAP. Using laser capture microdissection and deep next-generation sequencing, we quantified heteroplasmy at the single-muscle-fibre level, demonstrating that cytochrome c oxidase (COX)-deficient fibres consistently reached near-homoplasmic mutant loads, whereas COX-positive fibres remained heteroplasmic with lower variant fractions. These findings firmly support the pathogenic role of all variants. Furthermore, digital droplet PCR revealed an increased mitochondrial DNA (mtDNA) content in COX-deficient fibres, indicating compensatory mitochondrial biogenesis. Of particular note, one patient harboured two novel heteroplasmic variants, m.10009G > A and m.15961G > A, for which long-read sequencing identified mitogenomes carrying both variants also in cis, suggesting the occurrence of mtDNA recombination in human tissue. By applying refined American College of Medical Genetics and Genomics (ACMG) criteria specific for mt-tRNA, we reclassified several variants as pathogenic or likely pathogenic, including three previously deemed of uncertain significance. Overall, our integrative approach-combining single-fibre molecular dissection, mtDNA quantification, and long-read sequencing-broadens the mutational spectrum of pathogenic mt-tRNA variants, highlights the diagnostic value of single-fibre analyses in confirming pathogenicity, and provides new insights into mitochondrial genome dynamics and compensatory responses in mitochondrial disease.

Keywords:  mitochondrial DNA; mitochondrial myopathy; mt-tRNA variant; mtDNA recombination; single muscle fibre microdissection

DOI:  https://doi.org/10.1093/braincomms/fcag178
Orphanet J Rare Dis. 2026 Jun 09.

"If I go down, if I crumble, then everybody does" - identity crisis and emotional strain in parents of children with rare and undiagnosed conditions: a qualitative study.

Tara Maria Hoffmann, Bettina Friedrich, Celine Lewis.

   BACKGROUND: Caring for a child with a rare condition can significantly impact parents' emotional health, yet research on the emotional impact is limited. This qualitative interview study sought to investigate the lived experiences of parents who are experiencing higher psychological burden. Participants were parents of undiagnosed children undergoing whole genome sequencing (WGS) through the Genomic Medicine Service (GMS) across multiple NHS sites in England. Parents were purposively sampled to select those scoring poorly on validated measures of anxiety, family impact and/or resilience (GAD-7, PedsQL family functioning, BRS). We interviewed 24 parents after testing but prior to the return of WGS results. Questions focused on understanding their lived experience, in particular the emotional impact of their child's condition and how they coped day-to-day.
RESULTS: Semi-structured interviews were transcribed and analysed using reflexive thematic analysis, leading to the generation of the central organising concept: "The construction of a caregiver identity: Torn between being a 'hero(ine)' and being a parent." Parents' experiences as caregivers often involved a significant re-evaluation of their parental role, as they sought to provide love and support while also adjusting to changes in their envisioned family life. Societal expectations, along with the complex challenges of navigating the health and social care systems, contributed to emotional strain. In particular, mothers often adapted their personal identities to embody a 'heroic' caregiving role. The anxiety caused by the uncertainty surrounding their child's condition was also found to affect parents' mental health. Areas for psychological interventions and recommendations to support parents' mental health are identified.
CONCLUSIONS: Further research is needed to explore how the return of genomic sequencing results impacts parents' emotional wellbeing, and whether and which psychological counselling modalities throughout the journey might reduce emotional distress.
CLINICAL TRIAL NUMBER: Not applicable.

Keywords:  Emotional wellbeing; Family dynamics; Genomic sequencing; Mental health; Parent caregivers; Psychological counselling; Psychosocial insights; Rare condition; Uncertainty; Undiagnosed condition

DOI:  https://doi.org/10.1186/s13023-026-04384-5
Psychoneuroendocrinology. 2026 Jun 09. pii: S0306-4530(26)00196-4. [Epub ahead of print]191 107936

Associations between adverse childhood experiences, mitochondrial DNA copy number and atopic disease in children.

Laura M Díaz, Neeta Thakur, Samantha C Lewis, Morgan Ye, David J X González, Nicole R Bush, Dayna Long, Danielle Hessler, Rosemarie de la Rosa.

   BACKGROUND: Exposure to adverse childhood experiences (ACEs) chronically activates the neuroendocrine stress response, which can perturb mitochondrial DNA and may drive risk of atopic disease among children. We sought to examine the association between ACEs and mitochondrial DNA copy number (mtDNAcn), a measure of mitochondrial DNA abundance, and to characterize associations between mtDNAcn and atopic disease (atopic dermatitis, rhinitis and asthma) in a pediatric population.
METHODS: We performed cross-sectional analyses in a sample of 226 children enrolled in the Pediatric ACEs Screening and Resiliency Study who were recruited during well-child visits. Caregivers reported whether their child was exposed to ACEs or ever diagnosed with asthma, atopic dermatitis, or allergic rhinitis. MtDNAcn was measured in buccal swabs using qPCR. Multivariate linear and logistic regression analyses were used to measure associations with ACEs, mtDNAcn and atopic disease.
RESULTS: Children in our study were predominantly non-Hispanic Black, female, with a mean age of 5.6 years (SD = 3.6), and most caregivers had completed high school. We found that greater ACEs exposure was associated with a decrement in children's mtDNAcn. We also observed mtDNAcn was inversely associated with odds of children having atopic dermatitis but not associated with asthma or allergic rhinitis.
CONCLUSION: Our results suggest that greater exposure to ACEs is associated with lower mtDNAcn in children, and that having lower mtDNAcn is associated with greater odds of atopic dermatitis. Future work should measure other biomarkers of mitochondrial stress to understand this potential mechanistic relationship between adverse childhood experiences and atopic disease in children.

Keywords:  Atopic dermatitis; Atopic disease; Childhood adversity; Eczema; Mitochondrial DNA; Psychosocial stress

DOI:  https://doi.org/10.1016/j.psyneuen.2026.107936
JMIR Med Educ. 2026 Jun 12. 12 e88092

Training Empathetic Communication Skills in Medical Students With a Role-Prompted GPT-4o Chatbot: Quasi-Experimental Intervention Study.

Yannik Müller, Hans Lemberg, Paul Gellert, Jan C Zoellick.

   BACKGROUND: There is growing concern that artificial intelligence (AI) may diminish the quality of human relationships. However, in a context of widespread social importance (empathetic conversations between doctors and patients), AI can actually improve human conversational skills, potentially enhancing professional relationships. Recent advances in AI allow for realistically role-prompted counterparts for practicing professional conversations, enabling relational learning without the need for human counterparts.
OBJECTIVE: This study aimed to show the effectiveness of AI chatbots for learning professional communicative skills in medical education. Specifically, we hypothesized that a single conversation with an AI chatbot improves communication skills in medical students across 4 different conversational competencies.
METHODS: We conducted a quasi-experimental intervention study involving 4 distinct role-prompted scenarios (ie, shared decision-making, motivational interviewing, sexually transmitted diseases, and breaking bad news)-each designed to elicit in-depth empathic conversational skills aligned with key learning objectives in medical curricula. Students rated their competence for the 4 scenarios before and after a conversation with GPT-4o (OpenAI) using default settings, without fine-tuning. We expected higher perceived communication competence (PCC) in their conversation topic after the interaction compared with before the interaction in a 2-sided paired t test. Participants received AI-generated feedback, which they rated regarding adequacy. Post hoc analyses addressed gender and case effects, feedback adequacy, and prevalues in PCC.
RESULTS: This study shows that a role-prompted GPT chatbot improves PCC in 162 medical students after a single conversation with mean of 13 (SD 4.8; 95% CI 12-14) prompt-response pairs. We found an increase in PCC with a mean difference of 0.94 (SD 1.64; 95% CI 0.69-1.20; Cohen d=0.58) from 5.89 (95% CI 5.55-6.23; scale 0-10) before the conversation to 6.83 (95% CI 6.55-7.12) after the conversation across 4 different patient role prompts. Furthermore, we found participants rating AI feedback of their conversation to be useful (mean 7.92, SD 1.61; 95% CI 7.67-8.17; scale 0-10), but feedback adequacy did not correspond to PCC increase (r=0.08; P=.32).
CONCLUSIONS: Our results demonstrate how role-prompted GPT increases self-assessed communication competencies, introducing a novel tool for teaching relational learning. Our results present a starting point for using AI in education, particularly teaching communication in professional roles. On the basis of our findings in medical education, we anticipate further studies to investigate conversational training between lawyers and clients, marketers and customers, or managers and employees. Our research thus has implications for any field with a need for conversational training and relational learning.

Keywords:  AI; ChatGPT; artificial intelligence; chatbot; didactic method; educational tool; empathy; feedback; generative pretrained transformer; medical education; simulated patient

DOI:  https://doi.org/10.2196/88092
Orphanet J Rare Dis. 2026 Jun 10.

Mitochondrial mutation status, symptom prevalence, and neuroimaging characteristics in MELAS: a systematic review and meta analysis.

Yanyan Li, Siying Han, Daiyun Huang, Jiayi Chen, Siying Qu, Jinxin Gu, Zhuoyan Xu, Lei Fu, Xiaoyu Tang, Yixue Qiao.

   BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a rare mitochondrial disorder characterized by a wide range of systemic manifestations. MELAS is challenging to diagnose in its early stages and currently lacks targeted treatments. This systematic review and meta-analysis aim to validate the mitochondrial 3243A > G (m.3243A > G) mutation status, symptom prevalence, and neuroimaging characteristics in patients with MELAS. The review also seeks to consolidate and clarify the pathogenic pathways of MELAS while pinpointing potential therapeutic targets.
MAIN BODY: We searched four databases for relevant studies. Study selection, data extraction, and quality assessment using the JBI (Joanna Briggs Institute) scale were performed by two reviewers. We conducted meta-analyses to estimate the pooled proportions for genetic, symptomatic, and imaging features using the random-effects generalized linear mixed model. In addition, seven MELAS-related pathways were researched, and their gene information was expanded through computational retrieval from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. A total of 13 studies involving 988 subjects were included, covering one mutant gene (m.3243A > G), ten clinical symptoms, and four imaging features. The meta-analyses showed a pooled m.3243A > G mutation prevalence of 78% (95% CI: 68%, 86%). The most frequent clinical manifestations were stroke-like episodes (99%; 95% CI: 29%, 100%), seizures (89%; 95% CI: 65%, 97%), and elevated lactate (81%; 95% CI: 50%, 95%). The temporal lobe was the most commonly affected brain region on imaging (87%; 95% CI: 13%, 100%). Pathway analysis revealed mitophagy/autophagy, ROS generation, and energy metabolism as core mechanisms in MELAS, with MNRR1, L-arginine, PI3K-AKT-mTOR, and ETC as potential therapeutic targets.
CONCLUSION: This study collects evidence for the confirmatory diagnosis of MELAS, integrating its genetic, clinical, and neuroimaging spectra. Furthermore, by elucidating the core pathological network, our work provides a potential framework for developing multi-targeted therapeutic strategies.

Keywords:  MELAS; Meta analysis; Neuroimaging; Symptom prevalence; Therapeutic target prediction; m.3243A > G mutation

DOI:  https://doi.org/10.1186/s13023-026-04448-6
Healthcare (Basel). 2026 May 22. pii: 1437. [Epub ahead of print]14(11):

Integrative Literature Review on the Lived Experiences of Parents of Children with a Rare Disease.

Assunta Guillari, Keti Ballfusha, Chiara Palazzo, Maurizio Di Martino, Vincenza Giordano.

   BACKGROUND/OBJECTIVES: Rare diseases have a substantial impact not only on affected individuals but also on their families, particularly parents who assume primary caregiving roles. Despite increasing attention to rare conditions, parents' experiences remain fragmented across the literature. This integrative review aimed to synthesise existing evidence on the experiences and multidimensional impact of caring for a child with a rare disease on parents.
METHODS: An integrative review was conducted following Whittemore and Knafl's methodology and reported according to PRISMA 2020 guidelines. A systematic search was performed across MEDLINE, CINAHL, PsycINFO, PsycARTICLES, and Scopus from 1 November 2025 to 31 January 2026. Twenty-two studies (qualitative, quantitative, mixed-methods, and reviews) were included. Data were analysed using thematic synthesis.
RESULTS: Three interrelated themes were identified: (1) the diagnostic journey, characterised by prolonged uncertainty, fragmented care, and the pivotal role of communication; (2) multidimensional caregiving burden, encompassing emotional, social, economic, and physical impacts, with notable gender differences; and (3) adaptive trajectories, involving dynamic coping processes, parental upskilling, and meaning-making. Across studies, caregiving burden emerged as a cumulative and system-influenced phenomenon, while adaptation was found to coexist with ongoing uncertainty rather than representing a linear resolution.
CONCLUSIONS: Caring for a child with a rare disease profoundly affects parents across multiple domains. The findings highlight the need for integrated, family-centred care models, improved diagnostic communication, and sustained psychosocial support.
IMPLICATIONS FOR NURSING PRACTICE: Nurses play a key role in recognising caregiver burden, supporting adaptive processes, and promoting effective communication throughout the diagnostic and care trajectory.

Keywords:  caregiving burden; coping; diagnostic odyssey; family-centred care; integrative review; parents; rare diseases

DOI:  https://doi.org/10.3390/healthcare14111437
J Christ Nurs. 2026 Jul-Sep 01;43(3):43(3): 192-193

How Can I Support a Patient Praying for a Miracle?

Elizabeth Johnston Taylor.

DOI: https://doi.org/10.1097/CNJ.0000000000001399
Appl Clin Inform. 2026 Jun 09.

Characterizing Parental Use of a HIPAA-Compliant Large Language Model Chatbot in Rare Pediatric Diseases: Insights from Think-Aloud Sessions.

Anna M Kerr, Christine Bereitschaft, Stephanie Milam, James Rudloff, Melanie Bryan, Sally Cohen-Cutler, Min Zhao, Aditi Gupta, Albert Lai, Bryan A Sisk.

BACKGROUND: Parents of children with rare and serious illnesses often have unmet information needs. Large language models (LLMs) can help parents seek medical information. However, few studies have observed parents' use of LLMs or how they would use it in conjunction with their patient portal.
OBJECTIVES: We provided parents of children with cancer or vascular anomalies (VAs) access to a secure HIPAA-compliant chatbot. We characterized how parents used the tool while accessing their child's patient portal and evaluated the chatbot responses.
METHODS: Parents participated in think-aloud sessions (n=48). Parents accessed a HIPAA-compliant GPT 4 Endpoint and entered queries about their child's illness. We examined query length and chatbot response length, accuracy, and readability. We also conducted content analysis on parent queries.
RESULTS: We analyzed 451 queries and 451 responses. Parents' queries ranged from 1 to 104 words. They entered primarily short well-formed questions or phrases/statements. Some entered single words or incomplete phrases. Content was related to diagnosis/etiology, treatment, symptoms/side effects, laboratory values, imaging results, clinician notes/documentation, and supportive resources, with some differences between VA and cancer contexts. Chatbot responses ranged from 9 to 883 words The mean accuracy rating was 4.9±0.5 and the mean Flesch Reading Ease score was 28.4±15.0 (college-graduate level).
CONCLUSIONS: Parents' queries varied in length, complexity, and content, with some differences indicating unique information needs by disease context. Chatbot responses were accurate yet written at a reading level potentially challenging for some users. Future studies should consider these patterns and characteristics when designing health-related chatbot-based tools.

DOI: https://doi.org/10.1055/a-2888-9182