Publications by authors named "Michael Howell"

Article Synopsis
  • Microglia, the brain's immune cells, are vital for neuron health but may worsen conditions like ALS and FTD, and their exact role in these diseases is still unclear.
  • Researchers created specialized cultures of microglia from human stem cells with VCP mutations to study their behavior and effects on nearby nerve cells and supportive cells, using advanced techniques like RNA sequencing and proteomics.
  • The studies revealed that VCP mutant microglia show immune system and lysosomal issues, react differently to inflammation compared to healthy microglia, and can influence motor neurons and astrocytes through secreted factors, even though certain genetic factors didn't fully address their dysfunction.
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Background And Objectives: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

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A series of biotin-functionalized transition metal complexes was prepared by iClick reaction from the corresponding azido complexes with a novel alkyne-functionalized biotin derivative ([Au(triazolato)(PPh)], [Pt(dpb)(triazolato)], [Pt(triazolato)(terpy)]PF, and [Ir(ppy)(triazolato)(terpy)]PF with dpb = 1,3-di(2-pyridyl)benzene, ppy = 2-phenylpyridine, and terpy = 2,2':6',2''-terpyridine and R = CH, R' = biotin). The complexes were compared to reference compounds lacking the biotin moiety. The binding affinity toward avidin and streptavidin was evaluated with the HABA assay as well as isothermal titration calorimetry (ITC).

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Rare mutations in CARD14 promote psoriasis by inducing CARD14-BCL10-MALT1 complexes that activate NF-κB and MAP kinases. Here, the downstream signalling mechanism of the highly penetrant CARD14E138A alteration is described. In addition to BCL10 and MALT1, CARD14E138A associated with several proteins important in innate immune signalling.

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The capabilities of artificial intelligence (AI) have accelerated over the past year, and they are beginning to impact healthcare in a significant way. Could this new technology help address issues that have been difficult and recalcitrant problems for quality and safety for decades? While we are early in the journey, it is clear that we are in the midst of a fundamental shift in AI capabilities. It is also clear these capabilities have direct applicability to healthcare and to improving quality and patient safety, even as they introduce new complexities and risks.

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Misinformation regarding vaccine science decreased the receptiveness to COVID-19 vaccines, exacerbating the negative effects of the COVID-19 pandemic on society. To mitigate the negative societal impact of the COVID-19 pandemic, impactful and creative science communication was needed, yet little research has explored how to encourage COVID-19 vaccine acceptance and address misconceptions held by non-Science, Technology, Engineering and Mathematics majors (referred to as non-majors). We have previously demonstrated that including expert guest lectures in the vaccine module in the non-major introductory biology course helps combat students' vaccine hesitancy.

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Increasing evidence suggests slow-wave sleep (SWS) dysfunction in Parkinson's disease (PD) is associated with faster disease progression, cognitive impairment, and excessive daytime sleepiness. Beta oscillations (8-35 Hz) in the basal ganglia thalamocortical (BGTC) network are thought to play a role in the development of cardinal motor signs of PD. The role cortical beta oscillations play in SWS dysfunction in the early stage of parkinsonism is not understood, however.

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Importance: Interest in artificial intelligence (AI) has reached an all-time high, and health care leaders across the ecosystem are faced with questions about where, when, and how to deploy AI and how to understand its risks, problems, and possibilities.

Observations: While AI as a concept has existed since the 1950s, all AI is not the same. Capabilities and risks of various kinds of AI differ markedly, and on examination 3 epochs of AI emerge.

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Background And Objectives: REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment. The International RBD Study Group developed the RBD Symptom Severity Scale (RBDSSS) to assess symptom severity for clinical or research use. We assessed the psychometric and clinimetric properties of the RBDSSS in participants enrolled in the North American Prodromal Synucleinopathy (NAPS) Consortium for RBD.

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Article Synopsis
  • RBD is a sleep disorder that can lead to serious brain diseases like Parkinson's, especially in people with past brain injuries or stress.
  • People with both RBD and past trauma had their RBD symptoms start earlier and were more severe than those with just RBD.
  • The study found that those with both RBD and trauma experienced worse mental and physical health, suggesting a possible link to worsening brain problems over time.
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Increasing evidence associates slow-wave sleep (SWS) dysfunction with neurodegeneration. Using a within-subject design in the nonhuman primate model of Parkinson's disease (PD), we found that reduced SWS quantity in mild parkinsonism was accompanied by elevated beta and reduced delta power during SWS in the motor cortex. Our findings support excessive beta oscillations as a mechanism for SWS dysfunction and will inform development of neuromodulation therapies for enhancing SWS in PD.

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Background: Efficacy of ruxolitinib cream, a topical Jak1/Jak2 inhibitor, was demonstrated in a phase 2 trial in patients with vitiligo.

Objective: This study aimed to characterize circulating inflammatory biomarker profiles in patients who demonstrated ≥50% improvement in facial Vitiligo Area Scoring Index scores by week 24 (group 1) and those who did not (group 2).

Design: This was a posthoc analysis of a multicenter, randomized, double-blind, vehicle-controlled, phase 2 study in which screening was conducted between June 7, 2017 and March 21, 2018.

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Importance: Actinic keratosis (AK) is a premalignant lesion that has a1% to 10% potential of progression to squamous cell carcinoma (SCC), but it is not possible to determine which lesions are at higher risk.

Objective: This study examined the epidermal genetic profiles of actinic keratosis and SCC through non-invasive techniques seeking to develop a biopsy-free method for AK monitoring and aid in the early diagnosis of developing SCC.

Design: Ribonucleic acid (RNA) was collected from adhesive tape strips and gene expression levels were measured.

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Article Synopsis
  • - Patients with blood cancers have a weakened immune response to the Omicron variants of SARS-CoV-2.
  • - The study shows that Sotrovimab, a monoclonal antibody treatment, continues to effectively neutralize all examined Omicron subvariants.
  • - These findings highlight the need for close monitoring and potential treatment strategies for immunocompromised patients during the pandemic.
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Highly effective targeted therapies are available to treat noncommunicable chronic inflammatory skin diseases. In contrast, the exact diagnosis of noncommunicable chronic inflammatory skin diseases is complicated by its complex pathogenesis and clinical and histological overlap. Particularly, the differential diagnosis of psoriasis and eczema can be challenging in some cases, and molecular diagnostic tools need to be developed to support a gold standard diagnosis.

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Objective: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment.

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Excessive daytime sleepiness is a recognized non-motor symptom that adversely impacts the quality of life of people with Parkinson's disease (PD), yet effective treatment options remain limited. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for PD motor signs. Reliable daytime sleep-wake classification using local field potentials (LFPs) recorded from DBS leads implanted in STN can inform the development of closed-loop DBS approaches for prompt detection and disruption of sleep-related neural oscillations.

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Introduction: This guideline establishes clinical practice recommendations for the management of rapid eye movement sleep behavior disorder (RBD) in adults.

Methods: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations.

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Unlabelled: This systematic review provides supporting evidence for a clinical practice guideline for the management of rapid eye movement (REM) sleep behavior disorder in adults and children. The American Academy of Sleep Medicine commissioned a task force of 7 experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials and observational studies that addressed interventions for the management of REM sleep behavior disorder in adults and children.

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Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.

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