Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: 5-year follow-up results.

Objective: The objective of this study was to evaluate, at 4 and 5 years posttreatment, the long-term safety and efficacy of unilateral MRI-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor in a cohort of patients from a prospective, controlled, multicenter clinical trial.

Methods: Outcomes per the Clinical Rating Scale for Tremor (CRST), including postural tremor scores (CRST Part A), combined hand tremor/motor scores (CRST Parts A and B), and functional disability scores (CRST Part C), were measured by a qualified neurologist. The Quality of Life in Essential Tremor Questionnaire (QUEST) was used to assess quality of life.

An immunogenic cell injury module for the single-cell multiplexed activity metabolomics platform to identify promising anti-cancer natural products.

Natural products constitute and significantly impact many current anti-cancer medical interventions. A subset of natural products induces injury processes in malignant cells that recruit and activate host immune cells to produce an adaptive anti-cancer immune response, a process known as immunogenic cell death. However, a challenge in the field is to delineate forms of cell death and injury that best promote durable antitumor immunity.

A Way Forward in the COVID-19 Pandemic: Making the Case for Narrative Competence in Pulmonary and Critical Care Medicine.

Each surge of the coronavirus disease (COVID-19) pandemic presented new challenges to pulmonary and critical care practitioners. Although some of the initial challenges were somewhat less acute, clinicians now are left to face the physical, emotional, and mental toll of the past 2 years. The pandemic revealed a need for a more varied skillset, including space for reflection, tolerance of uncertainty, and humanism.

Beyond the ICU Rotation: The Importance of Trainee Involvement in Post-Intensive Care Unit Clinics.

Medical learners are vital to the care of critically ill patients in the intensive care unit (ICU). Although these learners are exposed to the challenges and stresses of acute ICU management, they do not typically experience the benefits of following ICU patients and families longitudinally after their ICU rotation. Post-ICU clinics and recovery programs may fill this crucial gap in trainee education.

Oxalate Oxidase for In Situ H O -Generation in Unspecific Peroxygenase-Catalysed Drug Oxyfunctionalisations.

H O -driven enzymes are of great interest for industrial biotransformations. Herein, we show for the first time that oxalate oxidase (OXO) is an efficient in situ source of H O for one of these biocatalysts, which is known as unspecific peroxygenase (UPO). OXO is reasonably robust, produces only CO as a by-product and uses oxalate as a cheap sacrificial electron donor.

Experimental characterization and automatic identification of stridulatory sounds inside wood.

The propagation of animal vocalizations in water and in air is a well-studied phenomenon, but sound produced by bark and wood-boring insects, which feed and reproduce inside trees, is poorly understood. Often being confined to the dark and chemically saturated habitat of wood, many bark- and woodborers have developed stridulatory mechanisms to communicate acoustically. Despite their ecological and economic importance and the unusual medium used for acoustic communication, very little is known about sound production in these insects, or their acoustic interactions inside trees.

Cognitive Capacity Genome-Wide Polygenic Scores Identify Individuals with Slower Cognitive Decline in Aging.

The genetic protective factors for cognitive decline in aging remain unknown. Predicting an individual's rate of cognitive decline-or with better cognitive resilience-using genetics will allow personalized intervention for cognitive enhancement and the optimal selection of target samples in clinical trials. Here, using genome-wide polygenic scores (GPS) of cognitive capacity as the genomic indicators for variations of human intelligence, we analyzed the 18-year records of cognitive and behavioral data of 8511 European-ancestry adults from the Wisconsin Longitudinal Study (WLS), specifically focusing on the cognitive assessments that were repeatedly administered to the participants with their average ages of 64.

Fracture of the Volar Ulnar Index Metacarpal Base: Literature Review.

Information regarding the management of intra-articular base fractures of the index metacarpal is scarce. Fractures of the base of the index metacarpal are rare because of the inherent stability of the joint. Of the handful of case reports on this injury, there appear to be 2 main patterns: fractures of the dorsal radial condyle and fractures of the volar ulnar condyle, which are attached to the extensor carpi radialis longus and flexor carpi radialis tendons, respectively.

Systems Immunology Analyses of Gain-of-Function Immune Phenotypes Reveal Heterogeneous Response to IL-6 and Broad Immunometabolic Roles for STAT1.

Patients with gain-of-function (GOF) pathogenic variants have enhanced or prolonged STAT1 phosphorylation following cytokine stimulation and exhibit increased yet heterogeneous susceptibility to infections, autoimmunity, and cancer. Although disease phenotypes are diverse and other genetic factors contribute, how GOF affects cytokine sensitivity and cell biology remains poorly defined. In this study, we analyzed the immune and immunometabolic profiles of two patients with known pathogenic heterozygous GOF mutation variants.

Optimal LentiCRISPR-Based System for Sequential CRISPR/Cas9 Screens.

The advent of genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening has advanced the understanding of molecular systems within cells. Here, we demonstrate the utility of sequentially performed CRISPR knockout screens that use an existing library to explore a biological question across the human genome, and then the remaining cells are used to examine each gene candidate against one common gene of interest. We call this approach "Many vs One" CRISPR screening, made possible by a modified 7SK promoter in place of the U6 promoter to drive expression of a single guide RNA.

Biocatalytic conversion of sunlight and carbon dioxide to solar fuels and chemicals.

This review discusses the progress in the assembly of photosynthetic biohybrid systems using enzymes and microbes as the biocatalysts which are capable of utilising light to reduce carbon dioxide to solar fuels. We begin by outlining natural photosynthesis, an inspired biomachinery to develop artificial photosystems, and the rationale and motivation to advance and introduce biological substrates to create more novel, and efficient, photosystems. The case studies of various approaches to the development of CO-reducing microbial semi-artificial photosystems are also summarised, showcasing a variety of methods for hybrid microbial photosystems and their potential.

Angiotensin-I-Converting Enzyme Inhibitory Activity of Protein Hydrolysates Generated from the Macroalga (Hudson) JV Lamouroux 1813.

Seaweeds have a long history of use as both food and medicine, especially in Asian cultures. Moreover, there is growing interest in the use of seaweed ingredients and bioactive compounds in pharmaceutical and nutraceutical products. One ailment that seaweed bioactive compounds may impact is hypertension caused by the enzyme Angiotensin Converting Enzyme 1 (ACE-1; EC 3.

Network Approaches to Integrate Analyses of Genetics and Metabolomics Data with Applications to Fetal Programming Studies.

The integration of genetics and metabolomics data demands careful accounting of complex dependencies, particularly when modelling familial omics data, e.g., to study fetal programming of related maternal-offspring phenotypes.

Erosive Tophaceous Gouty Arthropathy of the Hand: A Case Report.

The presence of tophaceous gout in the hand is a classic finding seen in uncontrolled gout. Occasionally gouty tophi can be the initial physical finding in asymptomatic hyperuricemia. Composed of monosodium urate (MSU) crystals, gouty tophi can cause significant soft tissue and joint pathology.

Acute Calcific Tendinitis of the Flexor Carpi Ulnaris Tendon Treated with Lavage and Steroid Injection: A Case Report.

Acute calcific tendinitis (ACT) is a relatively uncommon disorder that can involve the hand and wrist. ACT is frequently misdiagnosed due to a lack of familiarity with the condition and the clinical presentation that can be confused with other conditions. We report a case of acute calcific tendinitis of the flexor carpi ulnaris (FCU) tendon in a 68-year-old woman.

Impact of housing environment and management on pre-/post-weaning piglet productivity.

The complex environment surrounding young pigs reared in intensive housing systems directly influences their productivity and livelihood. Much of the seminal literature utilized housing and husbandry practices that have since drastically evolved through advances in genetic potential, nutrition, health, and technology. This review focuses on the environmental interaction and responses of pigs during the first 8 wk of life, separated into pre-weaning (creep areas) and post-weaning (nursery or wean-finish) phases.

Microscale Purification with Direct Charged Aerosol Detector Quantitation Using Selective Online One- or Two-Dimensional Liquid Chromatography.

The pharmaceutical industry is increasingly faced with challenging separations of complex crude reaction mixtures at the microscale that require the adoption of new platforms for rapid target isolation, impurity determination, and quantitation. In this study, we describe an online microscale one- or two-dimensional liquid chromatography (1D/2D-LC) system with heart-cutting and multi (triple) detector triggering in either dimension to address this need. The advantages of charged aerosol detection (CAD) are discussed for the direct quantitation of limited quantity samples, without utilizing a second analytical instrument or gradient compensation pump.

Optimizing allocation of curricular content across the Undergraduate & Graduate Medical Education Continuum.

Background: Medical educators struggle to incorporate socio-cultural topics into crowded curricula. The "continuum of learning" includes undergraduate and graduate medical education. Utilizing an exemplar socio-cultural topic, we studied the feasibility of achieving expert consensus among two groups of faculty (experts in medical education and experts in social determinants of health) on which aspects of the topic could be taught during undergraduate versus graduate medical education.

Calibrated Regression Models Based on the Risk of Clinical Nodal Metastasis Should be Used as Decision Aids for Prostate Cancer Staging to Reduce Unnecessary Imaging.

Introduction: Radionuclide imaging will change the role of computed tomography and magnetic resonance imaging (CT/MRI) for prostate cancer (CaP) staging. Current guidelines recommend abdominopelvic imaging for new cases of CaP categorized as unfavorable intermediate risk (UIR) or higher. We assessed the performance characteristics of CT/MRI based on the National Comprehensive Cancer Network (NCCN) guidelines and developed a model that predicts cN1 disease using conventional imaging.

How We Review a Medical Education Research Manuscript.

Peer review is a necessary and important component of scholarly publication. When done well, it benefits both the reviewer and authors and improves the science itself. However, the skills of effective peer review are rarely taught.

The Prebiotic Effect of Australian Seaweeds on Commensal Bacteria and Short Chain Fatty Acid Production in a Simulated Gut Model.

Diet is known to affect the composition and metabolite production of the human gut microbial community, which in turn is linked with the health and immune status of the host. Whole seaweeds (WH) and their extracts contain prebiotic components such as polysaccharides (PS) and polyphenols (PP). In this study, the Australian seaweeds, Phyllospora comosa, Ecklonia radiata, Ulva ohnoi, and their PS and PP extracts were assessed for potential prebiotic activities using an in vitro gut model that included fresh human faecal inoculum.

Stress Keratin 17 Expression in Head and Neck Cancer Contributes to Immune Evasion and Resistance to Immune-Checkpoint Blockade.

Purpose: We investigated whether in human head and neck squamous cell carcinoma (HNSCC) high levels of expression of stress keratin 17 (K17) are associated with poor survival and resistance to immunotherapy.

Experimental Design: We investigated the role of K17 in regulating both the tumor microenvironment and immune responsiveness of HNSCC using a syngeneic mouse HNSCC model, MOC2. MOC2 gives rise to immunologically cold tumors that are resistant to immune-checkpoint blockade (ICB).

Functional outcome measures in young, steroid-naïve boys with Duchenne muscular dystrophy.

The purpose of this study was to quantitate motor performance in 196 genetically confirmed steroid-naïve boys with Duchenne muscular dystrophy (DMD), to evaluate the test-retest reliability of measures of motor performance in young DMD boys, and to assess correlations among the different functional outcomes including timed tests. Boys aged 4-7 years were recruited in the FOR-DMD study, a comparative effectiveness study of different steroid regimens in DMD. Eligible boys had to be able to rise from the floor independently and to perform pulmonary function testing consistently.