Double trouble: a comprehensive study into unrelated genetic comorbidities in adult patients with Facioscapulohumeral Muscular Dystrophy Type I.

Facioscapulohumeral dystrophy type 1 (FSHD1) displays prominent intra- and interfamilial variability, which complicates the phenotype-genotype correlation. In this retrospective study, we investigated FSHD1 patients classified as category D according to the Comprehensive Clinical Evaluation Form (CCEF), a category defined by FSHD patients showing uncommon clinical features, to identify genetic causes explaining these uncommon phenotypes. Demographics, clinical data and clinical scales of FSHD1 patients were retrospectively evaluated.

Three-dimensional tissue engineered skeletal muscle modelling facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by sporadic misexpression of the transcription factor double homeobox 4 (DUX4) in skeletal muscles. So far, monolayer cultures and animal models have been used to study the FSHD disease mechanism and for FSHD therapy development, but these models do not fully recapitulate the disease and there is a lack of knowledge on how DUX4 misexpression leads to skeletal muscle dysfunction. To overcome these barriers, we have developed a three-dimensional tissue engineered skeletal muscle (3D-TESM) model by generating genetically matched myogenic progenitors (MPs) from human induced pluripotent stem cells of three mosaic FSHD patients.

Target attainment of beta-lactam antibiotics and ciprofloxacin in critically ill patients and its association with 28-day mortality.

Objectives: This study aims to assess pharmacodynamic target attainment in critically ill patients and identify factors influencing target attainment and mortality outcomes.

Methods: We analysed data from the DOLPHIN trial. Beta-lactam and ciprofloxacin peak and trough concentration were measured within the first 36 h (T1) after initiation of treatment.

Emergency Department Triage, Transfer Times, and Hospital Mortality of Patients Admitted to the ICU: A Retrospective Replication and Continuation Study.

Objectives: This study aimed to provide new insights into the impact of emergency department (ED) to ICU time on hospital mortality, stratifying patients by academic and nonacademic teaching (NACT) hospitals, and considering Acute Physiology and Chronic Health Evaluation (APACHE)-IV probability and ED-triage scores.

Design, Setting, And Patients: We conducted a retrospective cohort study (2009-2020) using data from the Dutch National Intensive Care Evaluation registry. Patients directly admitted from the ED to the ICU were included from four academic and eight NACT hospitals.

Best practice guidelines on genetic diagnostics of facioscapulohumeral muscular dystrophy: Update of the 2012 guidelines.

The gold standard for facioscapulohumeral muscular dystrophy (FSHD) genetic diagnostic procedures was published in 2012. With the increasing complexity of the genetics of FSHD1 and 2, the increase of genetic testing centers, and the start of clinical trials for FSHD, it is crucial to provide an update on our knowledge of the genetic features of the FSHD loci and renew the international consensus on the molecular testing recommendations. To this end, members of the FSHD European Trial Network summarized the evidence presented during the 2022 ENMC meeting on Genetic diagnosis, clinical outcome measures, and biomarkers.

Evaluation of the SCAT 5 tool in the assessment of concussion in Para athletes: a Delphi study.

Objectives: To investigate if the sport concussion assessment tool version 5 (SCAT5) could be suitable for application to Para athletes with a visual impairment, a spinal cord injury, or a limb deficiency.

Methods: A 16-member expert panel performed a Delphi technique protocol. The first round encompassed an open-ended questionnaire, with round 2 onwards being composed of a series of closed-ended statements requiring each expert's opinion using a five-point Likert scale.

The first genetically confirmed cohort of Facioscapulohumeral Muscular Dystrophy from Northern India.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of hereditary myopathy. Sixty per cent of the world's population lives in Asia, so a significant percentage of the world's FSHD participants is expected to live there. To date, most FSHD studies have involved individuals of European descent, yet small-scale studies of East-Asian populations suggest that the likelihood of developing FSHD may vary.

Methods behind oncolytic virus-based DC vaccines in cancer: Toward a multiphase combined treatment strategy for Glioblastoma (GBM) patients.

Glioblastoma (GBM) remains an orphan cancer disease with poor outcome. Novel treatment strategies are needed. Immunotherapy has several modes of action.

Development, implementation and impact of an immunoglobulin stewardship programme in Saskatchewan, Canada.

Background And Objectives: Intravenous immunoglobulin (IVIG) is one of the most costly and limited-supply blood products. Judicious use of this therapy is important to ensure a continued supply is available for patients in need. The Saskatchewan IG Stewardship Program was initiated to monitor and reduce inappropriate IG use.

Developmental role of macrophages modeled in human pluripotent stem cell-derived intestinal tissue.

Macrophages populate the embryo early in gestation, but their role in development is not well defined. In particular, specification and function of macrophages in intestinal development remain little explored. To study this event in the human developmental context, we derived and combined human intestinal organoid and macrophages from pluripotent stem cells.

Optical Genome Mapping for the Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy: Advancement and Challenges.

Facioscapulohumeral muscular dystrophy (FSHD) is the second most common muscular dystrophy in adults, and it is associated with local D4Z4 chromatin relaxation, mostly via the contraction of the D4Z4 macrosatellite repeat array on chromosome 4q35. In this study, we aimed to investigate the use of Optical Genome Mapping (OGM) as a diagnostic tool for testing FSHD cases from the UK and India and to compare OGM performance with that of traditional techniques such as linear gel (LGE) and Pulsed-field gel electrophoresis (PFGE) Southern blotting (SB). A total of 6 confirmed and 19 suspected FSHD samples were processed with LGE and PFGE, respectively.

Neurobehavioral consequences of repetitive head impacts in Para swimming: A case report.

Para swimmers with limb deficiency are faced with the particular situation that they must use their head to finish each competition by a hit to the wall. Repetitive head impacts may impair behavioral and brain functions. We therefore investigated neurobehavioral functions of a Para swimmer with dysmelia before and after repetitive head impacts (T1) and without (T2).

Autosomal dominant in cis D4Z4 repeat array duplication alleles in facioscapulohumeral dystrophy.

Facioscapulohumeral dystrophy (FSHD) has a unique genetic aetiology resulting in partial chromatin relaxation of the D4Z4 macrosatellite repeat array on 4qter. This D4Z4 chromatin relaxation facilitates inappropriate expression of the transcription factor DUX4 in skeletal muscle. DUX4 is encoded by a retrogene that is embedded within the distal region of the D4Z4 repeat array.

DUX4 expression in cancer induces a metastable early embryonic totipotent program.

The transcription factor DUX4 regulates a portion of the zygotic gene activation (ZGA) program in the early embryo. Many cancers express DUX4 but it is unknown whether this generates cells similar to early embryonic stem cells. Here we identified cancer cell lines that express DUX4 and showed that DUX4 is transiently expressed in a small subset of the cells.

Utilizing the intelligence edge framework for robotic upper limb rehabilitation in home.

Robotic devices are gaining popularity for the physical rehabilitation of stroke survivors. Transition of these robotic systems from research labs to the clinical setting has been successful, however, providing robot-assisted rehabilitation in home settings remains to be achieved. In addition to ensure safety to the users, other important issues that need to be addressed are the real time monitoring of the installed instruments, remote supervision by a therapist, optimal data transmission and processing.

Neuromuscular disease genetics in under-represented populations: increasing data diversity.

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis.

The Application of Evidence-Based Medicine in Individualized Medicine.

The fundamental aim of healthcare is to improve overall health of the population by providing state-of-the-art healthcare for individuals at an affordable cost. The foundation for this system is largely referred to as "evidence-based medicine". Too often, evidence-based medicine is based solely on so-called "best research evidence", collected through randomized controlled trials while disregarding clinical expertise and patient expectations.

Task-specific training versus usual care to improve upper limb function after stroke: the "Task-AT Home" randomised controlled trial protocol.

Background: Sixty percent of people have non-functional arms 6 months after stroke. More effective treatments are needed. Cochrane Reviews show low-quality evidence that task-specific training improves upper limb function.

-acetylneuraminate pyruvate lyase controls sialylation of muscle glycoproteins essential for muscle regeneration and function.

Deleterious variants in acetylneuraminate pyruvate lyase (NPL) cause skeletal myopathy and cardiac edema in humans and zebrafish, but its physiological role remains unknown. We report generation of mouse models of the disease: , carrying the human p.Arg63Cys variant, and with a 116-bp exonic deletion.

Palliative Care in Severe Neurotrauma Patients in the Intensive Care Unit.

Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide and many patients with TBI require intensive care unit (ICU) management. When facing a life-threatening illness, such as TBI, a palliative care approach that focuses on noncurative aspects of care should always be considered in the ICU. Research shows that neurosurgical patients in the ICU receive palliative care less frequently than the medical patients in the ICU, which is a missed opportunity for these patients.

Clinical response following hypertension induction for clinical delayed cerebral ischemia following subarachnoid hemorrhage: A retrospective, multicenter, cohort study.

Background: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high-quality studies on its efficacy are lacking. We studied immediate and 3-/6-month clinical efficacy of HTI in aSAH patients with clinical DCI.

Methods: A retrospective, multicenter, comparative, observational cohort study in aSAH patients with clinical deterioration due to DCI, admitted to three tertiary referral hospitals in the Netherlands from 2015 to 2019.