A Stepped-Wedge Cluster-Randomized Trial to Improve Adherence to Evidence-Based Practices for Acute Stroke Management.

Background: There is limited evidence regarding the optimal design and composition of multifaceted quality improvement programs to improve acute stroke care. The researchers aimed to test the effectiveness of a co-designed multifaceted intervention (STELAR: Shared Team Efforts Leading to Adherence Results) directed at hospital clinicians for improving acute stroke care tailored to the local context using feedback of national registry indicator data.

Methods: STELAR was a stepped-wedge cluster trial (partial randomization) using routinely collected Australian Stroke Clinical Registry data from Victorian hospitals segmented in two-month blocks.

PATAS, a First-in-Class Therapeutic Peptide Biologic, Improves Whole-Body Insulin Resistance and Associated Comorbidities In Vivo.

Adipose tissue is a key regulator of whole-body metabolic fitness because of its role in controlling insulin sensitivity. Obesity is associated with hypertrophic adipocytes with impaired glucose absorption, a phenomenon existing in the ultrarare monogenic disorder Alström syndrome consisting of severe insulin resistance. Inactivation of ALMS1 directly inhibits insulin-mediated glucose absorption in the white adipose tissue and induces severe insulin resistance, which leads to type 2 diabetes, accelerated nonalcoholic liver disease, and fibrosis.

Feedback of aggregate patient-reported outcomes (PROs) data to clinicians and hospital end users: findings from an Australian codesign workshop process.

Objectives: Patient-reported outcomes (PROs) are increasingly used to measure the patient's perspective of their outcomes following healthcare interventions. The aim of this study was to determine the preferred formats for reporting service-level PROs data to clinicians, researchers and managers to support greater utility of these data to improve healthcare and patient outcomes.

Setting: Healthcare professionals receiving PRO data feedback at the health service level.

Magnetically Assisted Drug Delivery of Topical Eye Drops Maintains Retinal Function In Vivo in Mice.

Barded-Biedl syndrome (BBS) is a rare genetic disorder with an unmet medical need for retinal degeneration. Small-molecule drugs were previously identified to slow down the apoptosis of photoreceptors in BBS mouse models. Clinical translation was not practical due to the necessity of repetitive invasive intravitreal injections for pediatric populations.

Feedback of patient-reported outcomes to healthcare professionals for comparing health service performance: a scoping review.

Objective: Patient-reported outcomes (PROs) provide self-reported patient assessments of their quality of life, daily functioning, and symptom severity after experiencing an illness and having contact with the health system. Feeding back summarised PROs data, aggregated at the health-service level, to healthcare professionals may inform clinical practice and quality improvement efforts. However, little is known about the best methods for providing these summarised data in a way that is meaningful for this audience.

Relative Adipose Tissue Failure in Alström Syndrome Drives Obesity-Induced Insulin Resistance.

Obesity is a major risk factor for insulin resistance (IR) and its attendant complications. The pathogenic mechanisms linking them remain poorly understood, partly due to a lack of intermediary monogenic human phenotypes. Here, we report on a monogenic form of IR-prone obesity, Alström syndrome (ALMS).

Consensus clinical management guidelines for Alström syndrome.

Alström Syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive variants in the ALMS1 gene, which is located on chromosome 2p13. ALMS is a multisystem, progressive disease characterised by visual disturbance, hearing impairment, cardiomyopathy, childhood obesity, extreme insulin resistance, accelerated non-alcoholic fatty liver disease (NAFLD), renal dysfunction, respiratory disease, endocrine and urologic disorders. Clinical symptoms first appear in infancy with great variability in age of onset and severity.

Tertiary lymphoid structures in cancer - considerations for patient prognosis.

Tertiary lymphoid structures (TLS) are ectopic lymphoid formations that form within nonlymphoid tissue. They share structural and functional characteristics with secondary lymphoid structures such as lymph nodes and can contain B-cell follicles and germinal centers surrounded by a T-cell region. TLS have been described in several types of cancers and are usually associated with positive patient outcomes.

DNAxs/DNAStatistX: Development and validation of a software suite for the data management and probabilistic interpretation of DNA profiles.

The data management, interpretation and comparison of sets of DNA profiles can be complex, time-consuming and error-prone when performed manually. This, combined with the growing numbers of genetic markers in forensic identification systems calls for expert systems that can automatically compare genotyping results within (large) sets of DNA profiles and assist in profile interpretation. To that aim, we developed a user-friendly software program or DNA eXpert System that is denoted DNAxs.

Impact of Local and Systemic Factors on Kidney Dysfunction in Bardet-Biedl Syndrome.

Bardet Biedl syndrome (BBS) is a rare inherited syndromic condition characterized by renal and extra-renal disorders. Renal defect, at either structural or functional level, is one of the cardinal clinical features, and is a major cause of morbidity. However, the pathogenic mechanism underlying its dysfunction remains largely unknown, and to date only symptomatic treatment with no specific therapy is available for these patients.

Knowledge on DNA Success Rates to Optimize the DNA Analysis Process: From Crime Scene to Laboratory.

DNA analysis has become an essential intelligence tool in the criminal justice system for the identification of possible offenders. However, it appears that about half of the processed DNA samples contains too little DNA for analysis. This study looks at DNA success rates within 28 different categories of trace exhibits and relates the DNA concentration to the characteristics of the DNA profile.

Objective data on DNA success rates can aid the selection process of crime samples for analysis by rapid mobile DNA technologies.

Mobile Rapid-DNA devices have recently become available on the market. These devices can perform DNA analyses within 90min with an easy 'sample in-answer out' system, with the option of performing comparisons with a DNA database or reference profile. However, these fast mobile systems cannot yet compete with the sensitivity of the standard laboratory analysis.

Value of MRI olfactory bulb evaluation in the assessment of olfactory dysfunction in Bardet-Biedl syndrome.

Olfactory bulb (OB) volume evaluation by magnetic resonance imaging (MRI) has been demonstrated to be related to olfactory dysfunction in many different diseases. Olfactory dysfunction is often overlooked in Bardet-Biedl syndrome (BBS) patients and is rarely objectively evaluated by MRI. We present a series of 20 BBS patients with olfactory dysfunction.

Exudative pericarditis in the evolution of a diffuse large B-cell lymphoma.

Cardiac involvement in non-Hodgkin's lymphoma is a rare occurrence with a dismal prognosis, which may evolve with different clinical presentations, the most frequent being heart failure. Diagnosis of cardiac involvement is generally made by cardiac ultrasound. We report a case of lymphomatous pericarditis in the evolution of a non-Hodgkin's lymphoma, diagnosed by PET-CT scan, and occurring concomitantly with complete isotopic remission of enlarged mediastinal lymph nodes following chemotherapy.

Comparing the Bbs10 complete knockout phenotype with a specific renal epithelial knockout one highlights the link between renal defects and systemic inactivation in mice.

Background: Bardet-Biedl Syndrome (BBS) is a genetically heterogeneous ciliopathy with clinical cardinal features including retinal degeneration, obesity and renal dysfunction. To date, 20 BBS genes have been identified with BBS10 being a major BBS gene found to be mutated in almost 20 percent of all BBS patients worldwide. It codes for the BBS10 protein which forms part of a chaperone complex localized at the basal body of the primary cilium.

Mutations in TUBGCP4 alter microtubule organization via the γ-tubulin ring complex in autosomal-recessive microcephaly with chorioretinopathy.

We have identified TUBGCP4 variants in individuals with autosomal-recessive microcephaly and chorioretinopathy. Whole-exome sequencing performed on one family with two affected siblings and independently on another family with one affected child revealed compound-heterozygous mutations in TUBGCP4. Subsequent Sanger sequencing was performed on a panel of individuals from 12 French families affected by microcephaly and ophthalmic manifestations, and one other individual was identified with compound-heterozygous mutations in TUBGCP4.

[Bardet-Biedl syndrome: cilia and obesity - from genes to integrative approaches].

The primary cilium is a specialized organelle, present at the surface of most eukaryotic cells, whose main function is to detect, integrate and transmit intra- and extra-cellular signals. Its dysfunction usually results in a group of severe clinical manifestations nowadays termed ciliopathies. The latter can be of syndromic nature with multi-organ dysfunctions and can also be associated with a morbid obese phenotype, like it is the case in the iconic ciliopathy, the Bardet Biedl syndrome (BBS).

Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice.

Aim: Argininosuccinate synthetase (ASS) is essential for recycling L-citrulline, the by-product of NO synthase (NOS), to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice.

Methods And Results: Endothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/- = Ass-KOTie2) were generated by crossing Assfl/fl mice ( = control) with Tie2Cre mice.

Olfaction evaluation and correlation with brain atrophy in Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a well-recognized ciliopathy characterized by cardinal features namely: early onset retinitis pigmentosa, polydactyly, obesity, hypogonadism, renal and cognitive impairment. Recently, disorders of olfaction (anosmia, hyposmia) have been also described in BBS patients. Moreover, morphological brain anomalies have been reported and prompt for further investigations to determine whether they are primary or secondary to peripheral organ involvement (i.

Breast implant-associated anaplastic large-cell lymphoma can be a diagnostic challenge for pathologists.

Background: Primary anaplastic large-cell lymphoma (ALCL) occurring in women with breast implants is very rare. It is usually described as tumor cells infiltrating the periprosthetic capsule. These are most often revealed by a periprosthetic recurrent isolated effusion (seroma cavity), occurring late after implantation of the prosthesis.

Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18).

Background: Bardet-Biedl syndrome (BBS) is a recessive and genetically heterogeneous ciliopathy characterised by retinitis pigmentosa, obesity, kidney dysfunction, postaxial polydactyly, behavioural dysfunction and hypogonadism. 7 of the 17 BBS gene products identified to date assemble together with the protein BBIP1/BBIP10 into the BBSome, a protein complex that ferries signalling receptors to and from cilia.

Methods And Results: Exome sequencing performed on a sporadic BBS case revealed for the first time a homozygous stop mutation (NM_001195306: c.

Hepatic adaptation compensates inactivation of intestinal arginine biosynthesis in suckling mice.

Suckling mammals, including mice, differ from adults in the abundant expression of enzymes that synthesize arginine from citrulline in their enterocytes. To investigate the importance of the small-intestinal arginine synthesis for whole-body arginine production in suckling mice, we floxed exon 13 of the argininosuccinate synthetase (Ass) gene, which codes for a key enzyme in arginine biosynthesis, and specifically and completely ablated Ass in enterocytes by crossing Ass (fl) and Villin-Cre mice. Unexpectedly, Ass (fl/fl) /VilCre (tg/-) mice showed no developmental impairments.