Hypoxia and intra-complex genetic suppressors rescue complex I mutants by a shared mechanism.

The electron transport chain (ETC) of mitochondria, bacteria, and archaea couples electron flow to proton pumping and is adapted to diverse oxygen environments. Remarkably, in mice, neurological disease due to ETC complex I dysfunction is rescued by hypoxia through unknown mechanisms. Here, we show that hypoxia rescue and hyperoxia sensitivity of complex I deficiency are evolutionarily conserved to C. elegans and are specific to mutants that compromise the electron-conducting matrix arm. We show that hypoxia rescue does not involve the hypoxia-inducible factor pathway or attenuation of reactive oxygen species. To discover the mechanism, we use C. elegans genetic screens to identify suppressor mutations in the complex I accessory subunit NDUFA6/nuo-3 that phenocopy hypoxia rescue. We show that NDUFA6/nuo-3(G60D) or hypoxia directly restores complex I forward activity, with downstream rescue of ETC flux and, in some cases, complex I levels. Additional screens identify residues within the ubiquinone binding pocket as being required for the rescue by NDUFA6/nuo-3(G60D) or hypoxia. This reveals oxygen-sensitive coupling between an accessory subunit and the quinone binding pocket of complex I that can restore forward activity in the same manner as hypoxia.

Differences in manifestations of epilepsy and developmental delay in PURA syndrome and 5q31 microdeletions.

PURA is mapped to chromosome 5q31 and plays a vital role in neuronal development and synapse formation. Here, we aim to explore PURA's impact on cognitive development and epilepsy phenotype by comparing patients with single nucleotide variants (SNPs) in the PURA gene (PURA-SNP patients) to those with 5q31 microdeletions including PURA (5q31del + PURA) and those with 5q31 microdeletions not including the PURA gene (5q31del-PURA). A systematic literature search was conducted in PubMed. Two separate searches were performed in order to find patients with PURA SNPs and 5q31 microdeletions. This review includes data from 191 patients collected from a total of 18 articles; 174 of the patients had PURA SNPs, 13 had 5q31 microdeletions involving the PURA gene, and 4 had 5q31 microdeletions without PURA gene implication. All patients exhibited hypotonia, feeding difficulties and dysmorphic features, however epilepsy was primarily present in patients with PURA syndrome, that is, groups PURA-SNP and 5q31del + PURA. Regarding the developmental milestones the 5q31del + PURA group stood out as being the most severe, while the 5q31del-PURA group showed a relatively mild phenotype. Our findings support the hypothesis of PURA being the key contributor of developmental delay and epilepsy among patients with PURA syndrome.

GABRA1-Related Disorders: From Genetic to Functional Pathways.

OBJECTIVE: Variants in GABRA1 have been associated with a broad epilepsy spectrum, ranging from genetic generalized epilepsies to developmental and epileptic encephalopathies. However, our understanding of what determines the phenotype severity and best treatment options remains inadequate. We therefore aimed to analyze the electroclinical features and the functional effects of GABRA1 variants to establish genotype-phenotype correlations. METHODS: Genetic and electroclinical data of 27 individuals (22 unrelated and 2 families) harboring 20 different GABRA1 variants were collected and accompanied by functional analysis of 19 variants. RESULTS: Individuals in this cohort could be assigned into different clinical subgroups based on the functional effect of their variant and its structural position within the GABRA1 subunit. A homogenous phenotype with mild cognitive impairment and infantile onset epilepsy (focal seizures, fever sensitivity, and electroencephalographic posterior epileptiform discharges) was described for variants in the extracellular domain and the small transmembrane loops. These variants displayed loss-of-function (LoF) effects, and the patients generally had a favorable outcome. A more severe phenotype was associated with variants in the pore-forming transmembrane helices. These variants displayed either gain-of-function (GoF) or LoF effects. GoF variants were associated with severe early onset neurodevelopmental disorders, including early infantile developmental and epileptic encephalopathy. INTERPRETATION: Our data expand the genetic and phenotypic spectrum of GABRA1 epilepsies and permit delineation of specific subphenotypes for LoF and GoF variants, through the heterogeneity of phenotypes and variants. Generally, variants in the transmembrane helices cause more severe phenotypes, in particular GoF variants. These findings establish the basis for a better understanding of the pathomechanism and a precision medicine approach in GABRA1-related disorders. Further studies in larger populations are needed to provide a conclusive genotype-phenotype correlation. ANN NEUROL 2023.

Clinical and Molecular Profiling in GNAO1 Permits Phenotype-Genotype Correlation.

BACKGROUND: Defects in GNAO1, the gene encoding the major neuronal G-protein Gαo, are related to neurodevelopmental disorders, epilepsy, and movement disorders. Nevertheless, there is a poor understanding of how molecular mechanisms explain the different phenotypes. OBJECTIVES: We aimed to analyze the clinical phenotype and the molecular characterization of GNAO1-related disorders. METHODS: Patients were recruited in collaboration with the Spanish GNAO1 Association. For patient phenotyping, direct clinical evaluation, analysis of homemade-videos, and an online questionnaire completed by families were analyzed. We studied Gαo cellular expression, the interactions of the partner proteins, and binding to guanosine triphosphate (GTP) and G-protein-coupled receptors (GPCRs). RESULTS: Eighteen patients with GNAO1 genetic defects had a complex neurodevelopmental disorder, epilepsy, central hypotonia, and movement disorders. Eleven patients showed neurological deterioration, recurrent hyperkinetic crisis with partial recovery, and secondary complications leading to death in three cases. Deep brain stimulation improved hyperkinetic crisis, but had inconsistent benefits in dystonia. The molecular defects caused by pathogenic Gαo were aberrant GTP binding and hydrolysis activities, an inability to interact with cellular binding partners, and reduced coupling to GPCRs. Decreased localization of Gαo in the plasma membrane was correlated with the phenotype of "developmental and epileptic encephalopathy 17." We observed a genotype-phenotype correlation, pathogenic variants in position 203 were related to developmental and epileptic encephalopathy, whereas those in position 209 were related to neurodevelopmental disorder with involuntary movements. Milder phenotypes were associated with other molecular defects such as del.16q12.2q21 and I344del. CONCLUSION: We highlight the complexity of the motor phenotype, which is characterized by fluctuations throughout the day, and hyperkinetic crisis with a distinct post-hyperkinetic crisis state. We confirm a molecular-based genotype-phenotype correlation for specific variants. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Recurrent missense variant identified in two unrelated families with MPZL2-related hearing loss, expanding the variant spectrum associated with DFNB111.

MPZL2-related hearing loss is a rare form of autosomal recessive hearing loss characterized by progressive, mild sloping to severe sensorineural hearing loss. Thirty-five previously reported patients had biallelic truncating variants in MPZL2, with the exception of one patient with a missense variant of uncertain significance and a truncating variant. Here, we describe the clinical characteristics and genotypes of five patients from four families with confirmed MPZL2-related hearing loss. A rare missense likely pathogenic variant [NM_005797.4(MPZL2):c.280C>T,p.(Arg94Trp)] located in exon 3 was confirmed to be in trans with a recurrent pathogenic truncating variant that segregated with hearing loss in three of the patients from two unrelated families. This is the first recurrent likely pathogenic missense variant identified in MPZL2. Apparently milder or later-onset hearing loss associated with rare missense variants in MPZL2 indicates that some missense variants in this gene may cause a milder phenotype than that resulting from homozygous or compound heterozygous truncating variants. This study, along with the identification of truncating loss of function and missense MPZL2 variants in several diverse populations, suggests that MPZL2-related hearing loss may be more common than previously appreciated and demonstrates the need for MPZL2 inclusion in hearing loss testing panels.

Efficacy of different 8 h time-restricted eating schedules on visceral adipose tissue and cardiometabolic health: A study protocol.

BACKGROUND AND AIMS: To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. METHODS AND RESULTS: Anticipated 208 adults (50% women) aged 30-60 years, with overweight/obesity (25 ≤ BMI<40 kg/m2) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. CONCLUSION: This study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility.

Small Extracellular Vesicles and Oxidative Pathophysiological Mechanisms in Retinal Degenerative Diseases.

This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related to or modulated by the oxidative burden of retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment, and in some instances, they might also be mediated by autophagy. The fate of these vesicles is diverse: they could end up in circulation being used as markers, or target neighbor cells modulating gene and protein expression, or eventually, in angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles' cargo or free circulating, in the regulation of retinal angiogenesis is also discussed.

Professional experiences of spanish advanced practice nurses: qualitative research.

BACKGROUND: Advanced practice nursing has emerged as a result of the evolution of healthcare systems, the changing needs of the population and the academic development of nursing, as well as sociodemographic and epidemiological changes. The aim of this study is to describe the professional experiences of Spanish advanced practice nurses in specific positions within the healthcare system in order to better understand the development and characteristics of this specialised nursing role. METHODS: A descriptive qualitative study was conducted. Fourteen advanced practice nurses from healthcare centres participated. Semi-structured interviews were carried out. Braun and Clarke's method for reflexive thematic analysis was followed. The Atlas. Ti version 22 program was used for technological support. The COREQ checklist was used to optimise the reporting of this qualitative study. RESULTS: From the analysis of the data collected, three themes and six subthemes were extracted: 1) Advanced practice nursing on the rise: (a) The driving forces in the development of advanced practice nursing, (b) Barriers to the development of advanced practice nursing; 2) Advanced practice nurses as a response to the population's needs: (a) The development of a new professional nursing role, (b) The patient at the centre of care in advanced practice nursing; 3) Training as the foundation for advanced practice nursing: (a) Expert nurses in a specific context, (b) Differences in the level of training depending on the context. CONCLUSION: Advanced practice nurses have faced countless barriers and difficulties that have impeded them from demonstrating their importance and effectiveness within the healthcare system. A stable regulatory framework for the functions of advanced practice nurses is required to promote care, training and research in the field of advanced practice nursing. Health institutions need to promote the role of advanced practice nurses, facilitate the employment of new professionals, and establish new areas of practice. TRIAL REGISTRATION: Not applicable.

A description of risk associated with use of antipsychotics among community dwelling older adults: A descriptive cross-sectional study.

The objective of this research was to analyze the risk of adverse effects in patients older than 65 years with dementia and in concomitant treatment with antidementia and antipsychotic drugs and who are cared for by community nurses. A retrospective cross-sectional descriptive study was carried out. A total of 332 patients who were cared for by primary care teams participated. Most of the patients were women, totally dependent for the basic activities of daily living and residing in the family home. They were polymedicated and there was poor therapeutic adherence. The risk of adverse effects was higher in polymedicated patients who had been taking antipsychotics for longer periods and in those who had a main caregiver. However, those patients who had been assessed by the community nurse were protected from suffering adverse effects. This study demonstrates how integrated and continuous nursing care can reduce adverse effects in this type of patient.

Cultural values, parenting and child adjustment in Italy.

The present study examined the association of mothers' and fathers' individualism, collectivism and conformity values with parenting behaviours and child adjustment during middle childhood in an Italian sample. Children (n = 194; 95 from Naples and 99 from Rome; 49% girls) were 10.93 years old (SD = .61) at the time of data collection. Their mothers (n = 194) and fathers (n = 152) also participated. Mother and father reports were collected about parental individualism and collectivism, conformity values, warmth, family obligations expectations and their children's internalising and externalising problems. Child reports were collected about their parents' warmth, psychological control, rules/limit-setting, family obligations expectations and their own internalising and externalising behaviours. Multiple regressions predicted each of the parenting and child adjustment variables from the value variables, controlling for child gender and parent education. Results showed that maternal collectivism was associated with high psychological control, parental collectivism was associated with high expectations regarding children's family obligations and fathers' conformity values were associated with more child internalising behaviours. Overall, the present study shed light on how parents' cultural values are related to some parenting practices and children's internalising problems in Italy.

Inhibition of altered Orai1 channels in Müller cells protects photoreceptors in retinal degeneration.

The expressions of ion channels by Müller glial cells (MGCs) may change in response to various retinal pathophysiological conditions. There remains a gap in our understanding of MGCs' responses to photoreceptor degeneration towards finding therapies. The study explores how an inhibition of store-operated Ca2+ entry (SOCE) and its major component, Orai1 channel, in MGCs protects photoreceptors from degeneration. The study revealed increased Orai1 expression in the MGCs of retinal degeneration 10 (rd10) mice. Enhanced expression of oxidative stress markers was confirmed as a crucial pathological mechanism in rd10 retina. Inducing oxidative stress in rat MGCs resulted in increasing SOCE and Ca2+ release-activated Ca2+ (CRAC) currents. SOCE inhibition by 2-Aminoethoxydiphenyl borate (2-APB) protected photoreceptors in degenerated retinas. Finally, molecular simulations proved the structural and dynamical features of 2-APB to the target structure Orai1. Our results provide new insights into the physiology of MGCs regarding retinal degeneration and shed a light on SOCE and Orai1 as new therapeutic targets.

Comprehensive Gene Panel Testing for Hearing Loss in Children: Understanding Factors Influencing Diagnostic Yield.

OBJECTIVE: To evaluate factors influencing the diagnostic yield of comprehensive gene panel testing (CGPT) for hearing loss (HL) in children and to understand the characteristics of undiagnosed probands. STUDY DESIGN: This was a retrospective cohort study of 474 probands with childhood-onset HL who underwent CGPT between 2016 and 2020 at a single center. Main outcomes and measures included the association between clinical variables and diagnostic yield and the genetic and clinical characteristics of undiagnosed probands. RESULTS: The overall diagnostic yield was 44% (209/474) with causative variants involving 41 genes. While the diagnostic yield was high in the probands with congenital, bilateral, and severe HL, it was low in those with unilateral, noncongenital, or mild HL; cochlear nerve deficiency; preterm birth; neonatal intensive care unit admittance; certain ancestry; and developmental delay. Follow-up studies on 49 probands with initially inconclusive CGPT results changed the diagnostic status to likely positive or negative outcomes in 39 of them (80%). Reflex to exome sequencing on 128 undiagnosed probands by CGPT revealed diagnostic findings in 8 individuals, 5 of whom had developmental delays. The remaining 255 probands were undiagnosed, with 173 (173/255) having only a single variant in the gene(s) associated with autosomal recessive HL and 28% (48/173) having a matched phenotype. CONCLUSION: CGPT efficiently identifies the genetic etiologies of HL in children. CGPT-undiagnosed probands may benefit from follow-up studies or expanded testing.

Characteristics and outcomes of a Hispanic lupus nephritis cohort from Mexico.

OBJECTIVES: To characterize the clinical presentation and outcomes of LN in a Hispanic cohort from Mexico. METHODS: We studied 440 subjects with systemic lupus erythematosus and biopsy-proven LN followed for >36 months. We obtained demographic, clinical, laboratory, histopathological and treatment variables. All outcomes were analysed by survival analysis and included response to therapy, renal relapses, progression of kidney disease (decline in eGFR ≥ 30%, doubling of serum creatinine, end-stage kidney disease) and patient survival. RESULTS: The median age of the study cohort was 29 years (IQR 23-37) and 96% were female. The median eGFR at inclusion was 81 mL/min/1.73m2 (IQR 48-118) and 24 h-uPCR was 3.4 g/g (IQR 1.9-5.6). Mixed class LN (III/IV+V) was the most frequently observed (69%). Over a median follow-up of 79 months, complete response rates were 22.3%, 40.5% and 51.6%, at 6, 12 and 24 months, respectively. Renal relapse rates were 32.3% and 50.6% at 3 and 5 years. By 3 and 5 years, 20.7% and 31.4% had decline in eGFR ≥30%, 14.4% and 22.5% doubled their serum creatinine, and 9.1% and 17.7% progressed to ESKD. The factors associated with loss of kidney function were age, eGFR at presentation, the histologic chronicity index in the kidney biopsy, and the type of response to therapy. Patient survival was 98.2% and 97.1% at 3 and 5 years. CONCLUSION: Although the response to treatment and patient survival in this Latin American cohort is comparable to that observed in other regions, there is still a high rate of renal relapses and progression to decline in kidney function.

Effect of antimalarials on clinical outcomes in lupus nephritis.

OBJECTIVES: To evaluate the effect of antimalarial drugs in response to therapy, incidence of LN flares, and progression of kidney disease in a large LN cohort. METHODS: We retrospectively studied 424 biopsy-proven LN patients followed for >3 years. We obtained demographic, clinical, laboratory, histopathological, and treatment variables. Antimalarial use was approached as 1) users versus no users, 2) according to prevalent vs incident use regarding the LN flare, and 3) according to the type of antimalarial. All outcomes were evaluated by time-to-event analyses. Adjusted hazard ratios were obtained by Cox regression. RESULTS: The cohort included 424 patients, median age of 29 years (IQR 23-37), 96% female, with a median eGFR of 81 ml/min/1.73m2 (IQR 48-118) and proteinuria of 3.4 g/g (IQR 1.9-5.5). Antimalarial use was associated with higher complete response (aHR 1.57, 1.08-2.27), lower incidence of kidney flares (aHR 0.63, 0.43-0.92), and lower progression to kidney failure (aHR 0.37, 0.23-0.53). The effect on these outcomes was modified by the presentation eGFR, histological class, and/or concomitant initial immunosuppressor. These protective effects were observed in patients with prevalent or incident use regarding the LN flare and patients using hydroxychloroquine. The incidence of toxic retinopathy was 1.7%, 5.7%, and 8.8% by 3-, 5-, and 7 years of continued antimalarial use. CONCLUSION: The use of antimalarial drugs is associated with increased response to therapy, lower incidence of kidney flares, and lower progression to kidney failure in LN patients. Conversely, this population is at high risk of toxic maculopathy, and yearly ophthalmologic examination is recommended.

Experiences and opinions towards baby-led weaning by healthcare professionals. A qualitative study.

BACKGROUND: Baby-led weaning (BLW) is an alternative method to spoon-feeding to introduce solid foods. This study aimed to describe and understand the experiences and opinions of pediatricians and pediatric nurse specialists of the implementation of the BLW approach. METHODS: An interpretive descriptive qualitative research was carried out. A focus group with 7 participants and 13 face-to-face interviews were conducted between February and May 2022 (17 females and 3 males). All were audio-recorded, transcribed, and analyzed with the supported by Atlas.Ti qualitative data analysis software. RESULTS: From the data, two themes developed: (1) BLW as an ideal method of introducing solid food, with the subthemes: "a natural method of introducing complementary feeding" and "BLW is a safe method"; (2) Perceived barriers to the uptake of the BLW method, with the subthemes: "a lack of BLW training prevents the best practice" and "the influence of family and social context on parents." CONCLUSIONS: Healthcare professionals perceive BLW to be a safe and natural weaning approach. The lack of training of healthcare professionals and the influence of family social context on parents may limit the implementation of BLW. IMPACT: Baby-led weaning is perceived by healthcare professionals as a safe complementary feeding method that promotes chewing, improves growth, and the development of fine motor skills. However, lack of training of healthcare professionals and the family social context of the parents hinders the uptake of baby-led weaning. The views of the family and parents' social context about baby-led weaning may restrict their willingness to use the method. Family education delivered by healthcare professionals may avoid risks and allay parental anxieties about safety.

The influence of repeated flares in response to therapy and prognosis in lupus nephritis.

BACKGROUND: Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney and patient prognosis. METHODS: All patients from a biopsy-proven LN cohort between 2008 and 2018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the estimated glomerular filtration rate (eGFR), doubling of serum creatinine, end-stage kidney disease and patient survival. RESULTS: A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria and hematuria among groups. The National Institutes of Health chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups. CONCLUSIONS: A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival.

MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations.

The mammalian mitochondrial proteome is under dual genomic control, with 99% of proteins encoded by the nuclear genome and 13 originating from the mitochondrial DNA (mtDNA). We previously developed MitoCarta, a catalogue of over 1000 genes encoding the mammalian mitochondrial proteome. This catalogue was compiled using a Bayesian integration of multiple sequence features and experimental datasets, notably protein mass spectrometry of mitochondria isolated from fourteen murine tissues. Here, we introduce MitoCarta3.0. Beginning with the MitoCarta2.0 inventory, we performed manual review to remove 100 genes and introduce 78 additional genes, arriving at an updated inventory of 1136 human genes. We now include manually curated annotations of sub-mitochondrial localization (matrix, inner membrane, intermembrane space, outer membrane) as well as assignment to 149 hierarchical 'MitoPathways' spanning seven broad functional categories relevant to mitochondria. MitoCarta3.0, including sub-mitochondrial localization and MitoPathway annotations, is freely available at http://www.broadinstitute.org/mitocarta and should serve as a continued community resource for mitochondrial biology and medicine.

Connexins Biology in the Pathophysiology of Retinal Diseases.

Connexins (Cx) are a family of transmembrane proteins that form gap junction intercellular channels that connect neighboring cells. These channels allow the passage of ions and other biomolecules smaller than 1 kDa, thereby synchronizing the cells both electrically and metabolically. Cxs are expressed in all retinal cell types and the diversity of Cx isoforms involved in the assembly of the channels provides a functional syncytium required for visual transduction. In this chapter, we summarize the status of current knowledge regarding Cx biology in retinal tissues and discuss how Cx dysfunction is associated with retinal disease pathophysiology. Although the contribution of Cx deficiency to retinal degeneration is not well understood, recent findings present Cx as a potential therapeutic target. Therefore, we will briefly discuss pharmacological approaches and gene therapies that are being explored to modulate Cx function and fight sight-threatening eye diseases.

Irregular migrants' experiences of health disparities while living in informal settlements during the COVID-19 pandemic.

AIMS: The objective of this study was to describe and understand irregular migrants' (IMs') experiences of health disparities while living in informal settlements (ISs) during the COVID-19 pandemic. DESIGN: Qualitative descriptive study. METHODS: Thirty-four IMs originating from different African countries living in ISs took part in this study. Data were collected between January and March 2022 through three focus groups and 17 in-depth interviews. Thematic analysis was used to analyse qualitative data with ATLAS.ti computer software. RESULTS: Three main themes emerged: (1) Extreme vulnerability: ISs and abuse; (2) Inequality in health treatment has increased during COVID-19; and (3) The impact of COVID-19 on the health of IMs: help from non-governmental organizations and nurses. CONCLUSION: Irregular migrants are at a higher risk of exposure to COVID-19 due to their precarious living conditions, administrative situation and access to the health system. It is recommended that specific programmes be strengthened to improve health care for this population. IMPACT: What problem did the study address? This study examines IMs' experiences of health disparities during the COVID-19 pandemic. What were the main findings? IMs are at higher risk of exposure to COVID-19 due to social, health, housing and work inequalities. Community health nurses alongside non-governmental organizations have facilitated the implementation of measures to protect this population against COVID-19. Where and on whom will the research have an impact? With the aim of improving care for IMs, strategies have been suggested for health institutions to address problems relating to accessing the health system, and to promote networking between non-governmental organizations and community health nurses.

'I'm still a woman': A qualitative study on sexuality in heterosexual women with Turner Syndrome.

AIM AND OBJECTIVES: The aim of this study was to describe and understand how heterosexual women with Turner Syndrome experience sexuality. BACKGROUND: Turner Syndrome is a genetic condition that is the result of one of the X chromosomes missing or partially missing, and it affects women of all ages. Turner Syndrome may lead to psychological, relational and sex life disorders. DESIGN: This is a qualitative study, and the COREQ checklist was employed to report on the current study. METHODS: The study was conducted in a region of southern Spain. Convenience and snowball sampling were used to recruit 18 women, aged 22-51 years, who had been diagnosed with Turner Syndrome. Participants' experiences were explored through semi-structured interviews between January and May 2021. Thematic analysis was used for data analysis. RESULTS: Three main themes and eight sub-themes emerge from the data analysis: (1) Sexuality linked to corporeality, with the sub-themes: 'Discovering that your body is different', 'Social stigma limits one's sex life' and 'Fear of penetration surpresses sexual desire'. (2) Adapting one's sexuality to Turner Syndrome, with the sub-themes: 'Feeling like a woman' and 'Suffering from and adapting to comorbidities'. (3) When infertility overshadows sexuality, with the sub-themes: 'Prolonging childhood by ignoring sexuality', 'Fertility treatment: always a possibility' and 'Lack of specialised professional knowledge'. CONCLUSION: Heterosexual women with Turner Syndrome suffer from sexual problems, delayed diagnosis and treatment, and lack of information. Unawareness and relational problems may also lead to scarce and late sexual relations, jealousy and a fear of being left. The women with Turner Syndrome refer to little self-exploration or masturbation as well as a fear of penetration. RELEVANCE TO CLINICAL PRACTICE: Understanding the experiences of sexuality in heterosexual women with Turner Syndrome is a challenge for clinical nurses, who could provide quality care to these women in contextualised services.