The capability approach in rehabilitation: developing capability care.

PURPOSE: To develop a multidisciplinary outpatient rehabilitation intervention for people with neuromuscular diseases (NMD) based on the capability approach: capability care for persons with NMD. MATERIALS AND METHODS: The development process is described using a framework of actions for intervention development. It has been an iterative process consisting of a design phase based on theoretical insights and project group discussions, and a refine phase involving input from relevant stakeholders. RESULTS: Multidisciplinary efforts have resulted in the development of capability care for rehabilitation of persons with NMD. It can focus both on facilitating and achieving functionings (beings and doings), as well as looking for alternative functionings that fulfil the same underlying value, thereby contributing to the persons' well-being. To facilitate a conversation on broader aspects that impact on well-being, persons with NMD receive a preparation letter and healthcare professionals are provided with guiding questions and practical tools to use. CONCLUSIONS: We have shown that it is possible to develop a healthcare intervention based on the capability approach. We hope that rehabilitation professionals will be encouraged to use capability care and that other medical professionals will be inspired to develop capability care in their respective fields. REGISTRATION: Registered at trialregister.nl NL8946.

The capability approach can be used for development of healthcare interventions.Capability care in rehabilitation focuses on realising what is of real value to the person.The capability approach and the ICF are complementary and can both be used in rehabilitation.

Phylogenomics and the rise of the angiosperms.

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.

Treatment Approaches for Altered Facial Expression: A Systematic Review in Facioscapulohumeral Muscular Dystrophy and Other Neurological Diseases.

Background: Facial weakness is a key feature of facioscapulohumeral muscular dystrophy (FSHD) and may lead to altered facial expression and subsequent psychosocial impairment. There is no cure and supportive treatments focus on optimizing physical fitness and compensation of functional disabilities. Objective: We hypothesize that symptomatic treatment options and psychosocial interventions for other neurological diseases with altered facial expression could be applicable to FSHD. Therefore, the aim of this review is to collect symptomatic treatment approaches that target facial muscle function and psychosocial interventions in various neurological diseases with altered facial expression in order to discuss the applicability to FSHD. Methods: A systematic search was performed. Selected studies had to include FSHD, Bell's palsy, Moebius syndrome, myotonic dystrophy type 1, or Parkinson's disease and treatment options which target altered facial expression. Data was extracted for study and patients' characteristics, outcome assessment tools, treatment, outcome of facial expression and or psychosocial functioning. Results: Forty studies met the inclusion criteria, of which only three studies included FSHD patients exclusively. Most, twenty-one, studies were performed in patients with Bell's palsy. Studies included twelve different therapy categories and results were assessed with different outcomes measures. Conclusions: Five therapy categories were considered applicable to FSHD: training of (non-verbal) communication compensation strategies, speech training, physical therapy, conference attendance, and smile restoration surgery. Further research is needed to establish the effect of these therapies in FSHD. We recommend to include outcome measures in these studies that cover at least cosmetic, functional, communication, and quality of life domains.

Trisomy silencing by XIST: translational prospects and challenges.

XIST RNA is heavily studied for its role in fundamental epigenetics and X-chromosome inactivation; however, the translational potential of this singular RNA has been much less explored. This article combines elements of a review on XIST biology with our perspective on the translational prospects and challenges of XIST transgenics. We first briefly review aspects of XIST RNA basic biology that are key to its translational relevance, and then discuss recent efforts to develop translational utility of XIST for chromosome dosage disorders, particularly Down syndrome (DS). Remarkably, it was shown in vitro that expression of an XIST transgene inserted into one chromosome 21 can comprehensively silence that chromosome and "dosage compensate" Trisomy 21, the cause of DS. Here we summarize recent findings and discuss potential paths whereby ability to induce "trisomy silencing" can advance translational research for new therapeutic strategies. Despite its common nature, the underlying biology for various aspects of DS, including cell types and pathways impacted (and when), is poorly understood. Recent studies show that an inducible iPSC system to dosage-correct chromosome 21 can provide a powerful approach to unravel the cells and pathways directly impacted, and the developmental timing, information key to design pharmacotherapeutics. In addition, we discuss prospects of a more far-reaching and challenging possibility that XIST itself could be developed into a therapeutic agent, for targeted cellular "chromosome therapy". A few rare case studies of imbalanced X;autosome translocations indicate that natural XIST can rescue an otherwise lethal trisomy. The potential efficacy of XIST transgenes later in development faces substantial biological and technical challenges, although recent findings are encouraging, and technology is rapidly evolving. Hence, it is compelling to consider the transformative possibility that XIST-mediated chromosome therapy may ultimately be developed, for specific pathologies seen in DS, or other duplication disorders.

A guide to barley mutants.

BACKGROUND: Mutants have had a fundamental impact upon scientific and applied genetics. They have paved the way for the molecular and genomic era, and most of today's crop plants are derived from breeding programs involving mutagenic treatments. RESULTS: Barley (Hordeum vulgare L.) is one of the most widely grown cereals in the world and has a long history as a crop plant. Barley breeding started more than 100 years ago and large breeding programs have collected and generated a wide range of natural and induced mutants, which often were deposited in genebanks around the world. In recent years, an increased interest in genetic diversity has brought many historic mutants into focus because the collections are regarded as valuable resources for understanding the genetic control of barley biology and barley breeding. The increased interest has been fueled also by recent advances in genomic research, which provided new tools and possibilities to analyze and reveal the genetic diversity of mutant collections. CONCLUSION: Since detailed knowledge about phenotypic characters of the mutants is the key to success of genetic and genomic studies, we here provide a comprehensive description of mostly morphological barley mutants. The review is closely linked to the International Database for Barley Genes and Barley Genetic Stocks ( bgs.nordgen.org ) where further details and additional images of each mutant described in this review can be found.

Expand and extend postpartum Medicaid to support maternal and child health.

Most early maternal deaths are preventable, with many occurring within the first year postpartum (we use the terms "maternal" and "mother" broadly to include all individuals who experience pregnancy or postpartum and frame our recognition of need and policy recommendations in gender-neutral terms. To acknowledge limitations inherent in existing policy and the composition of samples in prior research, we use the term "women" when applicable). Black, Hispanic, and Native American individuals are at the most significant risk of pregnancy-related death. They are more commonly covered by Medicaid, highlighting likely contributions of structural racism and consequent social inequities. State-level length and eligibility requirements for postpartum Medicaid vary considerably. Federal policy requires 60 days of Medicaid continuation postpartum, risking healthcare coverage loss during a critical period of heightened morbidity and mortality risk. This policy position paper aims to outline urgent risks to maternal health, detail existing federal and state-level efforts, summarize proposed legislation addressing the issue, and offer policy recommendations for legislative consideration and future study. A team of maternal health researchers and clinicians reviewed and summarized recent research and current policy pertaining to postpartum Medicaid continuation coverage, proposing policy solutions to address this critical issue. Multiple legislative avenues currently exist to support and advance relevant policy to improve and sustain maternal health for those receiving Medicaid during pregnancy, including legislation aligned with the Biden-Harris Maternal Health Blueprint, state-focused options via the American Rescue Plan of 2021 (Public Law 117-2), and recently proposed acts (HR3407, S1542) which were last reintroduced in 2021. Recommendations include (i) reintroducing previously considered legislation requiring states to provide 12 months of continuous postpartum coverage, regardless of pregnancy outcome, and (ii) enacting a revised, permanent federal mandate equalizing Medicaid eligibility across states to ensure consistent access to postpartum healthcare offerings nationwide.

Many maternal deaths happen within the first year postpartum and can be prevented. Black, Hispanic, and Native American mothers are at more risk for many reasons, including unfair systems and insufficient healthcare coverage from government insurance (Medicaid). Rules for getting Medicaid can be very different across states and in postpartum compared to pregnancy. The US government only requires states to continue providing Medicaid for 60 days postpartum, after which it is up to each state. If mothers are required to re-qualify for Medicaid shortly after giving birth, they could lose healthcare when they are at more risk of dying or getting sick. In this policy position paper, a team of maternal health researchers and clinicians reviewed and summarized recent research and current laws related to postpartum Medicaid to propose future laws that could address these issues. Some proposed laws would expand Medicaid coverage during postpartum, but lawmakers have not recently discussed them. This position paper recommends that lawmakers (i) consider laws that require states to provide 12 months of postpartum healthcare coverage and (ii) have the US government make the same rules to qualify for postpartum Medicaid across all states.

Using the Seraph® 100 Microbind® Affinity blood filter under slow flow conditions through 18 G and 16 G central lines.

INTRODUCTION: The Seraph® 100 Microbind® Affinity blood filter (Seraph® 100) has been in use since 2019 for the treatment of fulminant or difficult to treat blood stream infections as an adjunct to pharmacotherapy. In 2020 the device received emergency use authorization by the US Food and Drug Administration for the treatment of critically ill COVID-19 patients with confirmed or imminent respiratory failure. Results of an international registry showed that the Seraph® 100 was operated under blood flow rates of 100-350 mL/min. As those conditions require a large bore central line, a dialysis catheter is currently considered indispensable to operate the Seraph® 100. The use of smaller catheter lumina has neither been evaluated in vitro nor in vivo. METHODS: In vitro pressure data before and after the Seraph® 100 at various blood pump rates (prepump line 16 G, postpump line 18 G) with saline and human plasma were obtained. Further, anecdotal flow and pressure data of two patients treated with the Seraph® 100 for a COVID-19 infection are reported. RESULTS: At a pump speed of 50 mL/min pre-Seraph® pressure using saline was -70 [-70 to -60] mm Hg. In comparison, using plasma pre-Seraph® pressure was lower at -120 [-120 to -105] mm Hg; p < 0.001 (t-test). The post-Seraph® pressure at 50 mL/min using saline of 120 [110-130] mm Hg was not different from plasma at 130 [120-140] mm Hg, p = 0.152 (t-test). Blood flow rates of 50 mL/min did not lead to preAP levels below -250 mm Hg in the two clinical cases. CONCLUSION: Seraph® 100 blood flow rate of 50 mL/min may be achieved using low flow vascular access, allowing to treat a blood volume 72 L in 24 h.

Towards a validated glossary of usability attributes for the evaluation of wearable robotic devices.

BACKGROUND: Despite technical advances in the field of wearable robotic devices (WRD), there is still limited user acceptance of these technologies. While usability often comes as a key factor influencing acceptance, there is a scattered landscape of definitions and scopes for the term. To advance usability evaluation, and to integrate usability features as design requirements during technology development, there is a need for benchmarks and shared terminology. These should be easily accessible and implementable by developers. METHODS: An initial set of usability attributes (UA) was extracted from a literature survey on usability evaluation in WRD. The initial set of attributes was enriched and locally validated with seven developers of WRD through an online survey and a focus group. The locally validated glossary was then externally validated through a globally distributed online survey. RESULTS: The result is the Robotics Usability Glossary (RUG), a comprehensive glossary of 41 UA validated by 70 WRD developers from 17 countries, ensuring its generalizability. 31 of the UA had high agreement scores among respondents and 27 were considered highly relevant in the field, but only 11 of them had been included as design criteria by the respondents. CONCLUSIONS: Multiple UA ought to be considered for a comprehensive usability assessment. Usability remains inadequately incorporated into device development, indicating a need for increased awareness and end-user perspective. The RUG can be readily accessed through an online platform, the Interactive Usability Toolbox (IUT), developed to provide context-specific outcome measures and usability evaluation methods. Overall, this effort is an important step towards improving and promoting usability evaluation practices within WRD. It has the potential to pave the way for establishing usability evaluation benchmarks that further endorse the acceptance of WRD.

External Validation of the 2023 Duke-International Society for Cardiovascular Infectious Diseases Diagnostic Criteria for Infective Endocarditis.

BACKGROUND: The 2023 Duke-International Society of Cardiovascular Infectious Diseases (ISCVID) criteria for infective endocarditis (IE) were introduced to improve classification of IE for research and clinical purposes. External validation studies are required. METHODS: We studied consecutive patients with suspected IE referred to the IE team of Amsterdam University Medical Center (from October 2016 to March 2021). An international expert panel independently reviewed case summaries and assigned a final diagnosis of "IE" or "not IE," which served as the reference standard, to which the "definite" Duke-ISCVID classifications were compared. We also evaluated accuracy when excluding cardiac surgical and pathologic data ("clinical" criteria). Finally, we compared the 2023 Duke-ISCVID with the 2000 modified Duke criteria and the 2015 and 2023 European Society of Cardiology (ESC) criteria. RESULTS: A total of 595 consecutive patients with suspected IE were included: 399 (67%) were adjudicated as having IE; 111 (19%) had prosthetic valve IE, and 48 (8%) had a cardiac implantable electronic device IE. The 2023 Duke-ISCVID criteria were more sensitive than either the modified Duke or 2015 ESC criteria (84.2% vs 74.9% and 80%, respectively; P < .001) without significant loss of specificity. The 2023 Duke-ISCVID criteria were similarly sensitive but more specific than the 2023 ESC criteria (94% vs 82%; P < .001). The same pattern was seen for the clinical criteria (excluding surgical/pathologic results). New modifications in the 2023 Duke-ISCVID criteria related to "major microbiological" and "imaging" criteria had the most impact. CONCLUSIONS: The 2023 Duke-ISCVID criteria represent a significant advance in the diagnostic classification of patients with suspected IE.

Successful percutaneous management of hypothenar hammer syndrome with thrombosuction and catheter-directed intra-arterial thrombolysis.

Hypothenar hammer syndrome (HHS) is a rare vascular disorder leading to ulnar artery thrombosis or aneurysm and causing acute or chronic limb ischemia. The optimal approaches to managing this condition lack a definitive consensus and are essentially empirical, typically necessitating conservative methods for symptomatic relief, with surgical intervention reserved for cases for which conservative measures prove inadequate or when acute limb ischemia ensues. Limited data are available on percutaneous management for this condition. We present the case of a 36-year-old male powerlifter who developed acute digital ischemia due to HHS in the left hand that was managed successfully through an innovative approach using antegrade left brachial artery access and combining percutaneous thrombosuction and intra-arterial thrombolysis. This comprehensive approach resulted in restoration of blood flow and resolution of acute limb ischemia. The patient was subsequently prescribed short-term anticoagulation therapy and remained symptom free at 3 months of follow-up. This innovative strategy challenges traditional surgical approaches in HHS management, underscoring the importance of using minimally invasive techniques as a promising alternative and highlighting potential avenues for further research.

Racial-Ethnic Differences in Receipt of Past-Year Health Care Services Among Suicide Decedents: A Case-Control Study.

OBJECTIVE: Suicide remains an urgent public health crisis. Although some sociodemographic characteristics are associated with greater suicide risk in the general population, it is unclear whether individuals utilizing health care in the United States have similar suicide incidence patterns. The authors examined whether race-ethnicity is associated with suicide death among patients seeking health care and investigated health care utilization patterns. METHODS: Data were collected from electronic health records and government mortality records for patients seeking health care across nine health care systems in the United States. Patients who died by suicide (N=1,935) were matched with patients in a control group (N=19,350) within each health care system. RESULTS: Patients who died by suicide were significantly more likely to be White, older, male, living in low-education areas, living in rural areas, or diagnosed as having mental health conditions or were significantly less likely to have commercial insurance (p<0.05). Among most racial-ethnic groups, those who died by suicide had a higher number of past-year mental health, primary care, and total health care visits; for American Indian/Alaska Native patients, the number of health care visits tended to be lower among suicide decedents. CONCLUSIONS: These findings suggest that higher past-year health care utilization was associated with increased likelihood of suicide death across several racial-ethnic groups. This observation underscores the need for identifying and managing suicide risk in health care settings, including outside of mental health visits, among most racial-ethnic groups.

The Utility of Risk Factors to Define Complicated Staphylococcus aureus Bacteremia in a Setting With Low Methicillin-Resistant S. aureus Prevalence.

INTRODUCTION: Recommended duration of antibiotic treatment of Staphylococcus aureus bacteremia (SAB) is frequently based on distinguishing uncomplicated and complicated SAB, and several risk factors at the onset of infection have been proposed to define complicated SAB. Predictive values of risk factors for complicated SAB have not been validated, and consequences of their use on antibiotic prescriptions are unknown. METHODS: In a prospective cohort, patients with SAB were categorized as complicated or uncomplicated through adjudication (reference definition). Associations and predictive values of 9 risk factors were determined, compared with the reference definition, as was accuracy of Infectious Diseases Society of America (IDSA) criteria that include 4 risk factors, and the projected consequences of applying IDSA criteria on antibiotic use. RESULTS: Among 490 patients, 296 (60%) had complicated SAB. In multivariable analysis, persistent bacteremia (odds ratio [OR], 6.8; 95% confidence interval [CI], 3.9-12.0), community acquisition of SAB (OR, 2.9; 95% CI, 1.9-4.7) and presence of prosthetic material (OR, 2.3; 95% CI, 1.5-3.6) were associated with complicated SAB. Presence of any of the 4 risk factors in the IDSA definition of complicated SAB had a positive predictive value of 70.9% (95% CI, 65.5-75.9) and a negative predictive value of 57.5% (95% CI, 49.1-64.8). Compared with the reference, IDSA criteria yielded 24 (5%) false-negative and 90 (18%) false-positive classifications of complicated SAB. Median duration of antibiotic treatment of these 90 patients was 16 days (interquartile range, 14-19), all with favorable clinical outcome. CONCLUSIONS: Risk factors have low to moderate predictive value to identify complicated SAB and their use may lead to unnecessary prolonged antibiotic use.

Toward an Understanding of GSD5 (McArdle disease): How Do Individuals Learn to Live with the Metabolic Defect in Daily Life.

BACKGROUND: Glycogen storage disease type 5 (GSD) is an autosomal recessive inherited metabolic myopathy caused by a deficiency of the enzyme muscle glycogen phosphorylase. Individuals with GSD5 experience physical activity intolerance. OBJECTIVE: This patient-led study aimed to capture the daily life experiences of GSD5, with a focus on adapting to and coping with their physical activity intolerance. METHODS: An online survey was composed in close collaboration with patient organizations. It consisted of customized and validated questionnaires on demographics, general health and comorbidities, physical activity, psychosocial well-being and functioning, pain, fatigue and adapting to and coping with GSD5. RESULTS: One hundred sixty-two participants (16 countries) participated. The majority, n = 86 (69%) were from the Netherlands, USA or UK. We observed a high rate of misdiagnosis prior to GSD5 diagnosis (49%), surprisingly a relatively high proportion had not been diagnosed by DNA testing which is the gold standard. Being diagnosed had a strong impact on emotional status, daily life activities and important life choices. A large proportion had not received any rehabilitation (41%) nor medical treatment (57%) before diagnosis. Engagement in vigorous and moderate physical activity was reduced. Health related quality of life was low, most likely related to low physical health. The median Fatigue Severity Score was 4.3, indicating moderate to severe fatigue. Participants themselves had found various ways to adapt to and cope with their disability. The adaptations concerned all aspect of their life, including household chores, social and physical activities, and work. In addition to lack of support, participants reported limited availability of information sources. CONCLUSION: Participants have provided guidance for newly diagnosed people, including the advice to accept one's limited abilities and maintain an active lifestyle. We conclude that adequate counseling on ways of adapting and coping is expected to increase both health-related quality of life and physical activity.

Bone quality in LAMA2-related muscular dystrophy and SELENON-related congenital myopathy, a one-year prospective natural history study.

Fragility fractures are frequently reported in neuromuscular diseases and negatively influence functional prognosis, quality of life and survival. In LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related congenital myopathy (SELENON-RM) cross-sectional and prospective natural history studies on bone quality and fragility long bone fractures (LBFs) are lacking. We therefore aim to systematically assess bone quality and provide recommendations for clinical care. We performed a one-year prospective natural history study in 21 LAMA2-MD and 10 SELENON-RM patients including a standardized fracture history and bone quality assessment through dual energy Xray absorptiometry scan (DEXA-scan) and/or bone health index (BHI). Ninety percent of the LAMA2-MD and SELENON-RM patients showed low bone quality. Eight (38%) LAMA2-MD and five (50%) SELENON-RM patients had a history of fragility LBFs. During the one-year follow-up period, one LAMA2-MD patient (female, 3 years) experienced a fragility LBF of the right humerus. We found no difference in bone mineral density between baseline and one-year follow-up. Based on general international guidelines for osteoporosis, we advise adequate vitamin D and calcium intake, and standardized clinical follow-up through a DEXA-scan or BHI in all LAMA2-MD and SELENON-RM patients. On indication, patients should be referred to the pediatrics or internal medicine for consideration of additional treatments.

Mixed methods usability evaluation of an assistive wearable robotic hand orthosis for people with spinal cord injury.

BACKGROUND: Robotic hand orthoses (RHO) aim to provide grasp assistance for people with sensorimotor hand impairment during daily tasks. Many of such devices have been shown to bring a functional benefit to the user. However, assessing functional benefit is not sufficient to evaluate the usability of such technologies for daily life application. A comprehensive and structured evaluation of device usability not only focusing on effectiveness but also efficiency and satisfaction is required, yet often falls short in existing literature. Mixed methods evaluations, i.e., assessing a combination of quantitative and qualitative measures, allow to obtain a more holistic picture of all relevant aspects of device usability. Considering these aspects already in early development stages allows to identify design issues and generate generalizable benchmarks for future developments. METHODS: We evaluated the short-term usability of the RELab tenoexo, a RHO for hand function assistance, in 15 users with tetraplegia after a spinal cord injury through a comprehensive mixed methods approach. We collected quantitative data using the Action Research Arm Test (ARAT), the System Usability Scale (SUS), and timed tasks such as the donning process. In addition, qualitative data were collected through semi-structured interviews and user observations, and analyzed with a thematic analysis to enhance the usability evaluation. All insights were attributed and discussed in relation to specifically defined usability attributes such as comfort, ease of use, functional benefit, and safety. RESULTS: The RELab tenoexo provided an immediate functional benefit to the users, resulting in a mean improvement of the ARAT score by 5.8 points and peaking at 15 points improvement for one user (clinically important difference: 5.7 points). The mean SUS rating of 60.6 represents an adequate usability, however, indicating that especially the RHO donning (average task time = 295 s) was perceived as too long and cumbersome. The participants were generally very satisfied with the ergonomics (size, dimensions, fit) of the RHO. Enhancing the ease of use, specifically in donning, increasing the provided grasping force, as well as the availability of tailoring options and customization were identified as main improvement areas to promote RHO usability. CONCLUSION: The short-term usability of the RELab tenoexo was thoroughly evaluated with a mixed methods approach, which generated valuable data to improve the RHO in future iterations. In addition, learnings that might be transferable to the evaluation and design of other RHO were generated, which have the potential to increase the daily life applicability and acceptance of similar technologies.

Impact of Z chromosome inversions on gene expression in testis and liver tissues in the zebra finch.

Chromosomal inversions have been identified in many natural populations and can be responsible for novel traits and rapid adaptation. In zebra finch, a large region on the Z chromosome has been subject to multiple inversions, which have pleiotropic effects on multiple traits but especially on sperm phenotypes, such as midpiece and flagellum length. To understand the effect, the Z inversion has on these traits, we examined testis and liver transcriptomes of young males at different maturation times. We compared gene expression differences among three inversion karyotypes: AA, B*B* and AB*, where B* denotes the inverted regions on Z with respect to A. In testis, 794 differentially expressed genes were found and most of them were located on chromosome Z. They were functionally enriched for sperm-related traits. We also identified clusters of co-expressed genes that matched with the inversion-related sperm phenotypes. In liver, there were some enriched functions and some overrepresentation on chromosome Z with similar location as in testis. In both tissues, the overrepresented genes were located near the distal end of Z but also in the middle of the chromosome. For the heterokaryotype, we observed several genes with one allele being dominantly expressed, similar to expression patterns in one or the other homokaryotype. This was confirmed with SNPs for three genes, and interestingly one gene, DMGDH, had allele-specific expression originating mainly from one inversion haplotype in the testis, yet both inversion haplotypes were expressed equally in the liver. This karyotype-specific difference in tissue-specific expression suggests a pleiotropic effect of the inversion and thus suggests a mechanism for divergent phenotypic effects resulting from an inversion.

Cardiovascular risk due to diabetes mellitus in patients with chronic kidney disease-prospective data from the German Chronic Kidney Disease cohort.

Background: Diabetes mellitus (DM) and chronic kidney disease (CKD) are well-known cardiovascular and mortality risk factors. To what extent they act in an additive manner and whether the etiology of CKD modifies the risk is uncertain. Methods: The multicenter, prospective, observational German Chronic Kidney Disease study comprises 5217 participants (1868 with DM) with a baseline mean estimated glomerular filtration rate of 30-60 mL/min/1.73 m2 and/or proteinuria >0.5 g/day. We categorized patients whose CKD was caused by cardiovascular or metabolic diseases (CKDcvm) with and without DM, as opposed to genuine CKD (CKDgen) with and without DM. Recorded outcomes were first events of non-cardiovascular and cardiovascular death, 4-point major adverse cardiovascular events (4-point MACE) and hospitalization for heart failure (HHF). Results: During the 6.5-year follow-up 603 (12%) non-cardiovascular and 209 (4%) cardiovascular deaths, 645 (12%) 4-point MACE, and 398 (8%) HHF were observed, most frequently in patients with DM having CKDcvm. DM increased the risk of non-cardiovascular [hazard ratio (HR) 1.92; 95% confidence interval (CI) 1.59-2.32] and cardiovascular (HR 2.25; 95% CI 1.62-3.12) deaths, 4-point MACE (HR 1.93; 95% CI 1.62-2.31) and HHF (HR 1.87; 95% CI 1.48-2.36). Mortality risks were elevated by DM to a similar extent in CKDcvm and CKDgen, but for HHF in CKDcvm only (HR 2.07; 95% CI 1.55-2.77). In patients with DM, CKDcvm (versus CKDgen) only increased the risk for HHF (HR 1.93; 95% CI 1.15-3.22). Conclusions: DM contributes to cardiovascular and mortality excess risk in patients with moderate to severe CKD in both, CKDcvm and CKDgen. Patients with DM and CKDcvm are particularly susceptible to HHF.

Experimental mining plumes and ocean warming trigger stress in a deep pelagic jellyfish.

The deep pelagic ocean is increasingly subjected to human-induced environmental change. While pelagic animals provide important ecosystem functions including climate regulation, species-specific responses to stressors remain poorly documented. Here, we investigate the effects of simulated ocean warming and sediment plumes on the cosmopolitan deep-sea jellyfish Periphylla periphylla, combining insights gained from physiology, gene expression and changes in associated microbiota. Metabolic demand was elevated following a 4 °C rise in temperature, promoting genes related to innate immunity but suppressing aerobic respiration. Suspended sediment plumes provoked the most acute and energetically costly response through the production of excess mucus (at ≥17 mg L-1), while inducing genes related to aerobic respiration and wound repair (at ≥167 mg L-1). Microbial symbionts appeared to be unaffected by both stressors, with mucus production maintaining microbial community composition. If these responses are representative for other gelatinous fauna, an abundant component of pelagic ecosystems, the effects of planned exploitation of seafloor resources may impair deep pelagic biodiversity and ecosystem functioning.

Respiratory function in LAMA2-related muscular dystrophy and SELENON-related congenital myopathy, a 1.5-year natural history study.

INTRODUCTION: LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related congenital myopathy (SELENON-RM) are rare neuromuscular diseases with respiratory impairment from a young age. Prospective natural history studies are needed for prevalence estimations, respiratory characterization, optimizing clinical care and selecting outcome measures for trial readiness. METHODS: Our prospective 1.5-year natural history study included spirometry (forced vital capacity (FVC); difference between upright and supine vital capacity (dVC)), respiratory muscle strength tests (sniff nasal inspiratory pressure (SNIP)) (age≥5 years), and diaphragm ultrasound (thickness; thickening; echogenicity; all ages). RESULTS: Twenty-six LAMA2-MD patients (M = 8, median 21 [9; 31] years) and 11 SELENON-RM patients (M = 8, 20 [10; 33] years) were included. At baseline, 17 (85 %) LAMA2-MD (FVC%: 59 % [33; 68]) and all SELENON-RM patients (FVC%: 34 % [31; 46]) had an impaired respiratory function (FVC%<80 %). Nine (35 %) LAMA2-MD and eight (73 %) SELENON-RM patients received mechanical ventilation at baseline, and two additional SELENON-RM patients started during follow-up. Contrarily to LAMA2-MD, SELENON-RM patients had severe diaphragm atrophy (diaphragm thickness z-score: 2.5 [-3.1; -2.1]) and dysfunction (diaphragm thickness ratio: 1.2 [1.0; 1.7]; dVC: 30 % [7.7; 41]). SNIP was low in both neuromuscular diseases and correlated with motor function. In SELENON-RM, respiratory function decreased during follow-up. CONCLUSION: The majority of LAMA2-MD and all SELENON-RM patients had respiratory impairment. SELENON-RM patients showed lower respiratory function which was progressive, more prevalent mechanical ventilation, and more severe diaphragm atrophy and dysfunction than LAMA2-MD patients. Spirometry (FVC%, dVC) and respiratory muscle strength tests (SNIP) are useful in clinical care and as outcome measure in clinical trials. CLINICAL TRIAL NUMBER: NCT04478981.

Management of rare atlantoaxial synovial cyst case with extension to the cerebellopontine angle: illustrative case.

BACKGROUND: Synovial cysts are a common finding in degenerative spine disease, most frequently involving the facet joints of the lumbar spine. Synovial cysts are less common in the cervical spine and rarely involve the atlantoaxial junction. OBSERVATIONS: In this case report, the authors detail a unique presentation of a left atlantoaxial synovial cyst with large intracranial extension into the cerebellopontine angle causing progressive cranial nerve palsies resulting in tinnitus, vertigo, diminished hearing, gait imbalance, left trigeminal hypesthesia, left facial weakness, and dysarthria. The patient underwent a retromastoid craniectomy for resection of the synovial cyst, resulting in improvement and resolution of symptoms. Follow-up occurred at 6 weeks, 3 months, and 5 months postoperatively without recurrence on imaging. LESSONS: The authors describe acute and long-term management of a unique presentation of an atlantoaxial synovial cyst including retromastoid craniectomy, intervals for follow-up for recurrence, and possible treatment options in cases of recurrence. A systematic literature review was also performed to explore all reported cases of craniocervical junction synovial cysts and subsequent surgical management.