Valuation of multi-dimensional health states with a "bolt-on": is there a shortcut?

OBJECTIVES: In order to use the EQ-5D questionnaire with bolt-on dimensions in economic evaluation studies, new value sets are needed. In this study, we explored the feasibility of a new approach called scaling factor model, which estimates bolt-on value sets using estimated EQ-5D dimensional weights. METHODS: We designed a two-arm study, inviting university students to value health states with and without bolt-on items using the composite time trade-off (cTTO) method. We selected 25 health states from an orthogonal array and added 5 mildest EQ-5D states in the design. In arm 1, EQ-5D without self-care and standard EQ-5D states were valued, and in arm 2, standard EQ-5D states and EQ-5D with vision were valued. By arm, we compared the mean observed values of health states with and without bolt-on item. Next, by arm, we estimated value sets for the EQ-5D with bolt-on item states using both standard model and scaling factor model. Model performances were compared in terms of prediction accuracy and correlation with likelihood-based mean values. RESULTS: Adding a fifth-level bolt-on to EQ-5D resulted in statistically lower values. This effect is consistent across two arms and bolt-on items. The scaling factor models outperformed the standard models in all statistics. CONCLUSIONS: The scaling factor model offers a methodologically viable and low-cost option for producing value sets for EQ-5D, supplemented with bolt-on items. Future studies should further test this method using other bolt-on items and relevant study populations.

A General Approach to Activate Second-Scale Room Temperature Photoluminescence in Organic Small Molecules.

Organic small molecules that exhibit second-scale phosphorescence at room temperature are of interest for potential applications in sensing, anticounterfeiting, and bioimaging. However, such materials systems are uncommon-requiring millisecond to second-scale triplet lifetimes, efficient intersystem crossing, and slow rates of nonradiative recombination. Here, a simple and scalable approach is demonstrated to activate long-lived phosphorescence in a wide variety of molecules by suspending them in rigid polymer hosts and annealing them above the polymer's glass transition temperature. This process produces submicron aggregates of the chromophore, which suppresses intramolecular motion that leads to nonradiative recombination and minimizes triplet-triplet annihilation that quenches phosphorescence in larger aggregates. In some cases, evidence of excimer-mediated intersystem crossing that enhances triplet generation in aggregated chromophores is found. In short, this approach circumvents the current design rules for long-lived phosphors, which will streamline their discovery and development.

Natural variation in starvation sensitivity maps to a point mutation in phospholipase IPLA2-VIA in Drosophila melanogaster.

Resistance to starvation is a classic complex trait, where genetic and environmental variables can greatly modify an animal's ability to survive without nutrients. In this study, we investigate the genetic basis of starvation resistance using complementary quantitative and classical genetic mapping in Drosophila melanogaster . Using the Drosophila Genetics Reference Panel (DGRP) as a starting point, we queried the genetic basis of starvation sensitivity in one of the most sensitive DGRP lines. We localize a major effect locus modifying starvation resistance to the phospholipase iPLA2-VIA. This finding is consistent with the work of others which demonstrate the importance of lipid regulation in starvation stress. Furthermore, we demonstrate that iPLA2-VIA plays a role in the maintenance of sugar reserves post-starvation, which highlights a key dynamic between lipid remodeling, sugar metabolism and resistance to starvation stress.

Biallelic variants in POPDC2 cause a novel autosomal recessive syndrome presenting with cardiac conduction defects and variable hypertrophic cardiomyopathy.

POPDC2 encodes for the Popeye domain-containing protein 2 which has an important role in cardiac pacemaking and conduction, due in part to its cAMP-dependent binding and regulation of TREK-1 potassium channels. Loss of Popdc2 in mice results in sinus pauses and bradycardia and morpholino knockdown of popdc2 in zebrafish results in atrioventricular (AV) block. We identified bi-allelic variants in POPDC2 in 4 families that presented with a phenotypic spectrum consisting of sinus node dysfunction, AV conduction defects and hypertrophic cardiomyopathy. Using homology modelling we show that the identified POPDC2 variants are predicted to diminish the ability of POPDC2 to bind cAMP. In in vitro electrophysiological studies we demonstrated that, while co-expression of wild-type POPDC2 with TREK-1 increased TREK-1 current density, POPDC2 variants found in the patients failed to increase TREK-1 current density. While patient muscle biopsy did not show clear myopathic disease, it showed significant reduction of the expression of both POPDC1 and POPDC2, suggesting that stability and/or membrane trafficking of the POPDC1-POPDC2 complex is impaired by pathogenic variants in any of the two proteins. Single-cell RNA sequencing from human hearts demonstrated that co-expression of POPDC1 and 2 was most prevalent in AV node, AV node pacemaker and AV bundle cells. Sinoatrial node cells expressed POPDC2 abundantly, but expression of POPDC1 was sparse. Together, these results concur with predisposition to AV node disease in humans with loss-of-function variants in POPDC1 and POPDC2 and presence of sinus node disease in POPDC2, but not in POPDC1 related disease in human. Using population-level genetic data of more than 1 million individuals we showed that none of the familial variants were associated with clinical outcomes in heterozygous state, suggesting that heterozygous family members are unlikely to develop clinical manifestations and therefore might not necessitate clinical follow-up. Our findings provide evidence for POPDC2 as the cause of a novel Mendelian autosomal recessive cardiac syndrome, consistent with previous work showing that mice and zebrafish deficient in functional POPDC2 display sinus and AV node dysfunction.

Salvianolic acid B inhibits thrombosis and directly blocks the thrombin catalytic site.

Background: Salvianolic acid B (SAB) is a major component of Salvia miltiorrhiza root (Danshen), widely used in East/Southeast Asia for centuries to treat cardiovascular diseases. Danshen depside salt, 85% of which is made up of SAB, is approved in China to treat chronic angina. Although clinical observations suggest that Danshen extracts inhibited arterial and venous thrombosis, the exact mechanism has not been adequately elucidated. Objective: To delineate the antithrombotic mechanisms of SAB. Methods: We applied platelet aggregation and coagulation assays, perfusion chambers, and intravital microscopy models. The inhibition kinetics and binding affinity of SAB to thrombin are measured by thrombin enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. We used molecular in silico docking models to predict the interactions of SAB with thrombin. Results: SAB dose-dependently inhibited platelet activation and aggregation induced by thrombin. SAB also reduced platelet aggregation induced by adenosine diphosphate and collagen. SAB attenuated blood coagulation by modifying fibrin network structures and significantly decreased thrombus formation in mouse cremaster arterioles and perfusion chambers. The direct SAB-thrombin interaction was confirmed by enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. Interestingly, SAB shares key structural similarities with the trisubstituted benzimidazole class of thrombin inhibitors, such as dabigatran. Molecular docking models predicted the binding of SAB to the thrombin active site. Conclusion: Our data established SAB as the first herb-derived direct thrombin catalytic site inhibitor, suppressing thrombosis through both thrombin-dependent and thrombin-independent pathways. Purified SAB may be a cost-effective agent for treating arterial and deep vein thrombosis.

Maternal skepticism regarding children's vaccination in Jordan: Investigating the knowledge, attitude, and adherence.

Vaccination is critical to every responsible healthcare system, yielding several health and economic benefits. However, skepticism is a major challenge to vaccination adherence among parents globally. Mothers are primary decision-makers on children's vaccination; therefore, this study aims to assess maternal knowledge, attitudes, and adherence to children's routine vaccination in Jordan, identify the main sources of related information, and explore the awareness and hesitancy related to elective vaccination, which is not incorporated into the national vaccination program (e.g., varicella, flu, meningitis, and meningococcal vaccines). A descriptive, cross-sectional design was conducted to collect data from 533 Jordanian mothers between August and November 2023. Participant mothers completed an online self-administered questionnaire comprising demographics, knowledge, attitudes, and adherence to children's vaccination. The surveyed mothers in general exhibited high levels of knowledge, attitudes, and adherence concerning children's vaccination and a relatively moderate level of adherence concerning elective vaccines. The mothers' perspectives of reluctance towards elective vaccines were explored. The primary healthcare center and physicians were the most prevalent sources of mothers' vaccine-related information. Future efforts should implement tailored health education campaigns that address specific knowledge gaps, such as misconceptions about contraindications and side effects, promote awareness about elective vaccines, and engage healthcare providers to facilitate informed decision-making among Jordanian mothers and improve children's vaccination coverage.

Benchmarking short and long read polishing tools for nanopore assemblies: achieving near-perfect genomes for outbreak isolates.

BACKGROUND: Oxford Nanopore provides high throughput sequencing platforms able to reconstruct complete bacterial genomes with 99.95% accuracy. However, even small levels of error can obscure the phylogenetic relationships between closely related isolates. Polishing tools have been developed to correct these errors, but it is uncertain if they obtain the accuracy needed for the high-resolution source tracking of foodborne illness outbreaks. RESULTS: We tested 132 combinations of assembly and short- and long-read polishing tools to assess their accuracy for reconstructing the genome sequences of 15 highly similar Salmonella enterica serovar Newport isolates from a 2020 onion outbreak. While long-read polishing alone improved accuracy, near perfect accuracy (99.9999% accuracy or ~ 5 nucleotide errors across the 4.8 Mbp genome, excluding low confidence regions) was only obtained by pipelines that combined both long- and short-read polishing tools. Notably, medaka was a more accurate and efficient long-read polisher than Racon. Among short-read polishers, NextPolish showed the highest accuracy, but Pilon, Polypolish, and POLCA performed similarly. Among the 5 best performing pipelines, polishing with medaka followed by NextPolish was the most common combination. Importantly, the order of polishing tools mattered i.e., using less accurate tools after more accurate ones introduced errors. Indels in homopolymers and repetitive regions, where the short reads could not be uniquely mapped, remained the most challenging errors to correct. CONCLUSIONS: Short reads are still needed to correct errors in nanopore sequenced assemblies to obtain the accuracy required for source tracking investigations. Our granular assessment of the performance of the polishing pipelines allowed us to suggest best practices for tool users and areas for improvement for tool developers.

Risperidone-cyclodextrin complex reservoir combined with hydrogel-forming microneedle array patches for enhanced transdermal delivery.

Hydrogel-forming microneedle array patches (HFMAPs) are microneedles that create microconduits upon insertion and swelling in the skin, potentially allowing prolonged drug delivery without generating sharps waste. Delivering hydrophobic drugs using HFMAPs poses challenges, which can be addressed using solubility enhancers such as cyclodextrins (CDs). This study aimed to deliver risperidone (RIS) transdermally using HFMAPs. To enhance the aqueous solubility of RIS hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CD) were utilised and their performance was tested using phase solubility studies. The aqueous solubility of RIS was enhanced by 4.75-fold and 2-fold using HP-ß-CD and HP-γ-CD, respectively. RIS-HP-ß-CD complex (CX) and physical mixture (PM) directly compressed tablets were prepared and combined with HFMAPs. Among the tested formulations, RIS-HP-ß-CD PM reservoirs with 11 x 11 PVA/PVP HFMAPs exhibited the best performance in ex vivo studies and were further evaluated in in vivo experiments using female Sprague Dawley rats. The extended wear time of the MAPs resulted in the sustained release of RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in plasma samples, lasting from 3 to 5 days with a 1-day application and up to 10 days with a 5-day application. For a 1-day application, HFMAPs showed greater systemic exposure to RIS compared to intramuscular control (AUC0-t: 13330.05 ±â€¯2759.95 ng/mL/hour versus 2706 ±â€¯1472 ng/mL/hour). Moreover, RIS exposure was extended to 5 days (AUC0-t: 12292.37 ±â€¯1801.94 ng/mL/hour). In conclusion, HFMAPs could serve as an alternative for delivering RIS in a sustained manner, potentially improving the treatment of schizophrenia.

Neonatal lupus with complete heart block and long term follow up.

We present the case of a 27-year-old pregnant woman, newly diagnosed with Systemic Lupus Erythematosus (SLE) during pregnancy. The patient delivered a newborn at 38 weeks gestation, who, on the first day of life, manifested complete heart block. This case underscores the clinical challenges associated with neonatal lupus, emphasizing the need for collaborative, multidisciplinary management.

Unusual manifestations of Takayasu arteritis: A diagnostic challenge.

Key Clinical Message: Timely recognition of atypical Takayasu arteritis is crucial. Unusual presentations, such as pericardial effusion, can complicate diagnosis. CT angiogram aids in precise diagnosis, guiding targeted immunosuppressive therapy. Multidisciplinary collaboration is vital for comprehensive management, improving patient outcomes in this challenging condition. Abstract: This case study highlights the diagnostic challenges posed by atypical presentations of Takayasu arteritis (TA), focusing on a 42-year-old male presenting with pericardial effusion. Despite inconclusive initial investigations, a CT angiogram revealed large vessel vasculitis, confirming TA. Management with immunosuppressive therapy led to clinical improvement. This case emphasize the importance of recognizing unusual manifestations of TA for timely diagnosis and appropriate treatment, emphasizing the role of multidisciplinary collaboration in optimizing patient outcomes.

Navigating Asymptomatic Mitral Regurgitation: Diagnostic Dilemmas and Treatment Strategies.

This case report explores the complexities involved in the diagnosis and management of asymptomatic mitral regurgitation (MR) in a 64-year-old male presenting with an incidental systolic murmur. Torrential MR with flail mitral valve (MV) segments was identified through comprehensive imaging and clinical evaluation, including echocardiography and catheterization. The discussion highlights the nuances of surgical timing, emphasizing the importance of tailored approaches based on left ventricular (LV) function and dilation. This report sheds light on the evolving landscape of managing asymptomatic MR, underscoring the need for balancing surveillance with proactive intervention to optimize patient outcomes.

A rare case of congenital lobar emphysema presenting as recurrent pneumonia in early adulthood: A case report and literature review.

INTRODUCTION AND SIGNIFICANCE: Congenital lobar emphysema (CLE) is a rare but important lung malformation typically discovered in the newborn period. Some rare cases are reported in adults. It can present with various respiratory symptoms. Diagnosis relies primarily on chest CT scans, and the main treatment is surgery. CASE PRESENTATION: We present a case of a young girl with recurrent respiratory infections who was misdiagnosed with a pneumothorax. A chest tube was inserted. Later, CLE was identified, and the affected lung lobe was surgically removed. CLINICAL DISCUSSION: This case highlights the importance of including CLE in the differential diagnosis for hyperinflation of a lung lobe. A CT scan is crucial for confirmation. CONCLUSION: Congenital lobar emphysema is a rare disease that primarily affects children. Most children with CLE experience symptoms and require surgery. In adults, CLE is uncommon, and surgery is based on the severity of symptoms and radiological findings.

Incidence of Unplanned Readmissions After One-Day Surgery Discharge Among Pediatric Patients: A Retrospective Study From a Tertiary Care Hospital in Saudi Arabia.

Introduction The prevalence of one-day surgery (also known as same-day surgery or outpatient surgery) has been increasing recently among patients and physicians in many countries due to its benefits. The main benefits of one-day surgery are that the patient is not planned to stay overnight before the surgery and can be discharged on the same day of the surgery. The lower cost to the health system can make these surgeries more favorable for both sides. However, unplanned readmission after such surgeries can happen and this has broad implications for patients, their families, and the healthcare system. Therefore, this study primarily aims to identify the incidence of unexpected hospital readmissions following one-day surgery after discharge among children. The study also aims to identify any significant variables that can be identified with the cases of readmissions to allow for further investigations in future studies Methods This study was done at King Abdullah Specialist Children's Hospital in Riyadh, Saudi Arabia. The target population included all pediatric patients who underwent one-day surgeries and were admitted within one week of their discharge from 2017 to 2023 through outpatient clinics and the emergency department. Results The study sample size was 403 patients, with male patients accounting for 241 surgeries (59.8%), and female patients accounting for 162 surgeries (40.1%). The most common American Society of Anesthesiologists (ASA) classification was II, accounting for 169 cases (41.9%). Toddlers and preschoolers (aged 1-6 years) were the age groups with the highest number of patients (n=252, 62.5% combined). Elective surgeries accounted for 382 cases (94.7%). The specialty with the highest number of surgeries was ear, nose, and throat with 284 cases (70.4%) with tonsillectomy with adenoidectomy being the most common surgery with 234 cases (58%). The most common reasons for unplanned readmission were poor oral intake (n=146, 36.2%) and bleeding (n=131, 32.5%). The most common day of readmission was the seventh day in five surgical specialties (45.4%). Conclusion Over the past seven years, 403 patients were readmitted within one week after their one-day surgery at King Abdullah Specialist Children's Hospital. Such a situation may cause dissatisfaction with the medical care that the patients were given and eventually may build an untrusted relationship between the patient and the physician. Future investigations should be established to lower such a condition and develop prevention methods to lower its prevalence.

Study protocol for the development and validation of a questionnaire evaluating predisposition to immunosuppressant medication non-adherence of kidney pre-transplant patients. The KATITA project.

Non-adherence to immunosuppressive medication after kidney transplant is an important cause of graft rejection and loss. Approaches to minimization of non-adherence have focused on the identification of episodes of medication non-adherence, but by then irreparable harm to the graft may already have occurred, and a more effective approach would be to adopt preventive measures in patients who may have difficulty in adhering to medication. The aim of this study protocol is to develop and validate a clinical questionnaire for assessing, in kidney transplant candidate patients in the pre-transplant setting, the predisposition to non-adherence to immunosuppressive medication. In this multicenter, prospective study, a pilot questionnaire in Brazilian Portuguese language, composed of Likert-scaled statements expressing patients' beliefs, behaviors and barriers regarding medication taking will be assembled from a literature review, from focus groups, and an expert panel. The pilot questionnaire will be administered to a minimum of 300 patients in kidney transplant waiting lists and exploratory factor analysis will be used for development of the definitive questionnaire. A random subsample of a minimum of 60 patients will have the scale re-administered after one month for evaluation of test-retest reliability. A multicenter, external validation study will include 364 kidney transplant candidates who will be evaluated immediately before surgery and at months 3, 6 and 12 post-transplant for assessment of concurrent validity, by comparison with two scales that assess medication non-adherence, and for determination of predictive validity using a triangulation method for assessment of medication non-adherence. Structural validity will be assessed with confirmatory factor analysis using structural equation modeling. Cross-cultural generalizability and validity will be assessed by a multicenter study, in which a translation of the scale to another language will be administered to kidney transplant candidate patients from a different culture, with a subsample being selected for test-retest. This study will be conducted in Spain with a Spanish translation of the scale.

Physiotherapists Lack Knowledge in Mental Health: A Survey of Knowledge and Attitudes of Physical Therapists About Their Role in Mental Health.

Purpose: As the number of mental illnesses increases, there is a need to manage it holistically within a multidisciplinary team. The majority of patients with physical disabilities suffer from mental health problems, and physiotherapy can play a role in improving their lifestyle. This study aimed to determine physiotherapists' self-reported knowledge and attitudes regarding their role in treating patients with mental health disorders. Methods: This study adopted a descriptive, cross-sectional, and prospective observational survey design. The sample consisted of 208 physical therapists. Results: The majority of the participants, (48%) had a positive attitude score, with (40%) having a neutral attitude and (12%) having a negative attitude toward treating patients with mental health issues. Most respondents (86%) reported that they need more information regarding patients with mental health disorders and physiotherapists' management of their physical health issues. Conclusion: Many physiotherapists lack knowledge and hold a neutral to negative attitude towards treating patients with mental disorders. This highlights the need for more training to fill the gap in knowledge and guide physiotherapists to build upon their positive attitude towards treating patients with mental disorders.

Extracellular matrices of stromal cell subtypes regulate phenotype and contribute to the stromal microenvironment in vivo.

BACKGROUND: Bone marrow stromal cells (BMSCs) are highly heterogeneous, which may reflect their diverse biological functions, including tissue maintenance, haematopoietic support and immune control. The current understanding of the mechanisms that drive the onset and resolution of heterogeneity, and how BMSCs influence other cells in their environment is limited. Here, we determined how the secretome and importantly the extracellular matrix of BMSCs can influence cellular phenotype. METHODS: We used two immortalised clonal BMSC lines isolated from the same heterogeneous culture as model stromal subtypes with distinct phenotypic traits; a multipotent stem-cell-like stromal line (Y201) and a nullipotent non-stem cell stromal line (Y202), isolated from the same donor BMSC pool. Label-free quantitative phase imaging was used to track cell morphology and migration of the BMSC lines over 96 h in colony-forming assays. We quantified the secreted factors of each cell line by mass spectrometry and confirmed presence of proteins in human bone marrow by immunofluorescence. RESULTS: Transfer of secreted signals from a stem cell to a non-stem cell resulted in a change in morphology and enhanced migration to more closely match stem cell-like features. Mass spectrometry analysis revealed a significant enrichment of extracellular matrix (ECM) proteins in the Y201 stem cell secretome compared to Y202 stromal cells. We confirmed that Y201 produced a more robust ECM in culture compared to Y202. Growth of Y202 on ECM produced by Y201 or Y202 restored migration and fibroblastic morphology, suggesting that it is the deficiency of ECM production that contributes to its phenotype. The proteins periostin and aggrecan, were detected at 71- and 104-fold higher levels in the Y201 versus Y202 secretome and were subsequently identified by immunofluorescence at rare sites on the endosteal surfaces of mouse and human bone, underlying CD271-positive stromal cells. These proteins may represent key non-cellular components of the microenvironment for bona-fide stem cells important for cell maintenance and phenotype in vivo. CONCLUSIONS: We identified plasticity in BMSC morphology and migratory characteristics that can be modified through secreted proteins, particularly from multipotent stem cells. Overall, we demonstrate the importance of specific ECM proteins in co-ordination of cellular phenotype and highlight how non-cellular components of the BMSC microenvironment may provide insights into cell population heterogeneity and the role of BMSCs in health and disease.

Recent Updates of the CRISPR/Cas9 Genome Editing System: Novel Approaches to Regulate Its Spatiotemporal Control by Genetic and Physicochemical Strategies.

The genome editing approach by clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) is a revolutionary advancement in genetic engineering. Owing to its simple design and powerful genome-editing capability, it offers a promising strategy for the treatment of different infectious, metabolic, and genetic diseases. The crystal structure of Streptococcus pyogenes Cas9 (SpCas9) in complex with sgRNA and its target DNA at 2.5 Å resolution reveals a groove accommodating sgRNA:DNA heteroduplex within a bilobate architecture with target recognition (REC) and nuclease (NUC) domains. The presence of a PAM is significantly required for target recognition, R-loop formation, and strand scission. Recently, the spatiotemporal control of CRISPR/Cas9 genome editing has been considerably improved by genetic, chemical, and physical regulatory strategies. The use of genetic modifiers anti-CRISPR proteins, cell-specific promoters, and histone acetyl transferases has uplifted the application of CRISPR/Cas9 as a future-generation genome editing tool. In addition, interventions by chemical control, small-molecule activators, oligonucleotide conjugates and bioresponsive delivery carriers have improved its application in other areas of biological fields. Furthermore, the intermediation of physical control by using heat-, light-, magnetism-, and ultrasound-responsive elements attached to this molecular tool has revolutionized genome editing further. These strategies significantly reduce CRISPR/Cas9's undesirable off-target effects. However, other undesirable effects still offer some challenges for comprehensive clinical translation using this genome-editing approach. In this review, we summarize recent advances in CRISPR/Cas9 structure, mechanistic action, and the role of small-molecule activators, inhibitors, promoters, and physical approaches. Finally, off-target measurement approaches, challenges, future prospects, and clinical applications are discussed.

Antibodies Against ZSCAN1 in Pediatric and Adult Patients With Non-Paraneoplastic ROHHAD Syndrome.

OBJECTIVES: To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor. METHODS: Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls. RESULTS: Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples. DISCUSSION: Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.