Publications by authors named "Matthew Smith"

1,732 Publications

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Paralytic shellfish toxins associated with Arctic Tern mortalities in Alaska.

Harmful Algae 2022 Aug 9;117:102270. Epub 2022 Jul 9.

U.S. Fish and Wildlife Service, Migratory Bird Management, 1011 East Tudor Road, Anchorage, AK, 99503, USA.

Harmful algal blooms produce biotoxins that can injure or kill fish, wildlife, and humans. These blooms occur naturally but have intensified in many locations globally due to recent climatic changes, including ocean warming. Such changes are especially pronounced in northern regions, where the effects of paralytic shellfish toxins (PSTs) on marine wildlife are of growing concern. In Alaska, seabird mortality events have increased in frequency, magnitude, and duration since 2015 alongside anomalously high ocean temperatures. Although starvation has been implicated as the apparent cause of death in many of these die-offs, saxitoxin (STX) and other PSTs have been identified as possible contributing factors. Here, we describe a mortality event at a nesting colony of Arctic Terns (Sterna paradisaea) near Juneau, Alaska in 2019 and report elevated concentrations of PSTs in bird, forage fish, and mussel samples. Concentrations of STX and other PSTs in tern tissues (2.5-51.2 µg 100g STX-equivalents [STX-eq]) were of similar magnitude to those reported from other PST-induced bird die-offs. We documented high PST concentrations in blue mussels (>11,000 µg 100g STX-eq; Mytilus edulis spp.) collected from nearby beaches, as well as in forage fish (up to 494 µg 100g STX-eq) retrieved from Arctic Tern nests, thereby providing direct evidence of PST exposure via the terns' prey. At maximum concentrations measured in this study, a single 5 g Pacific Sand Lance (Ammodytes personatus) could exceed the median lethal STX dose (LD) currently estimated for birds, offering strong support for PSTs as a likely source of tern mortality. In addition to describing this localized bird mortality event, we used existing energetics data from adult and nestling Arctic Terns to calculate estimated cumulative daily PST exposure based on ecologically relevant concentrations in forage fish. Our estimates revealed potentially lethal levels of PST exposure even at relatively low (≤30 ug 100g STX-eq) toxin concentrations in prey. These findings suggest that PSTs present a significant hazard to Arctic Terns and other northern seabirds and should be included in future investigations of avian mortality events as well as assessments of population health.
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http://dx.doi.org/10.1016/j.hal.2022.102270DOI Listing
August 2022

Afadin couples RAS GTPases to the polarity rheostat Scribble.

Nat Commun 2022 Aug 5;13(1):4562. Epub 2022 Aug 5.

Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, H3T 1J4, Canada.

AFDN/Afadin is required for establishment and maintenance of cell-cell contacts and is a unique effector of RAS GTPases. The biological consequences of RAS complex with AFDN are unknown. We used proximity-based proteomics to generate an interaction map for two isoforms of AFDN, identifying the polarity protein SCRIB/Scribble as the top hit. We reveal that the first PDZ domain of SCRIB and the AFDN FHA domain mediate a direct but non-canonical interaction between these important adhesion and polarity proteins. Further, the dual RA domains of AFDN have broad specificity for RAS and RAP GTPases, and KRAS co-localizes with AFDN and promotes AFDN-SCRIB complex formation. Knockout of AFDN or SCRIB in epithelial cells disrupts MAPK and PI3K activation kinetics and inhibits motility in a growth factor-dependent manner. These data have important implications for understanding why cells with activated RAS have reduced cell contacts and polarity defects and implicate AFDN as a genuine RAS effector.
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http://dx.doi.org/10.1038/s41467-022-32335-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355967PMC
August 2022

Thickness profiling of electron transparent aluminium alloy foil using convergent beam electron diffraction.

J Microsc 2022 Aug 2. Epub 2022 Aug 2.

School of Materials, University of Manchester, Manchester, M13 9PL, United Kingdom.

Convergent beam electron diffraction (CBED) was used to profile the thickness of aluminium alloys foils prepared by using the twinjet electropolishing method. The two-beam CBED condition was obtained by exciting the {200} and {111} aluminium diffracted g-vector. The aluminium alloy foil thicknesses were calculated at different distances from the sample hole edge. In areas where only one Kossel-Mӧllenstedt (K-M) minima fringe was obtained, the thickness was determined by matching the experimental with simulated convergent beam diffraction pattens. In areas far away from the sample edge, the thickness of foils was high enough to generate at least two (K-M) minima fringes, required for linear regression fitting. Samples Being Thin Enough for Achieving Atomic Scale Magnification: To achieve highest possible magnification with the highest resolution and observe the nanometer-scale features of the microstructure in aluminum alloys, it is important to obtain samples which are as thin as we possibly can get to. The samples must be so thin that they can be transparent to the electron beam. To have a clear picture of how profile of a thin sample should look like, advanced microscopes were used where the electrons are concentrated in very narrow areas over the sample. The electron beam going through the sample, experiences a physic phenomenon known as diffraction, which is recorded below the sample, and thickness is calculated out of it. By concentrating the electron beam to different points over the sample, thickness profile was reconstructed. This is imperative for building up reference profiles for check and compare of samples used in transmission electron microscopy. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jmi.13137DOI Listing
August 2022

Association between underlying autoimmune disease and small aneurysm size at rupture.

J Neurosurg 2022 Jul 15:1-8. Epub 2022 Jul 15.

1Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati; and.

Objective: Although the role of inflammation in the development of aneurysms is established, less is known about the development of intracranial aneurysms in the setting of underlying autoimmune disease. The underlying systemic inflammatory characteristics of disorders such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome may influence the development of intracranial aneurysms through common inflammatory pathways. The authors hypothesized that there is an association between underlying autoimmune disease and aneurysm growth and rupture.

Methods: Medical records of patients who underwent cerebral angiography between August 2018 and August 2021 were manually reviewed. Autoimmune diseases as defined for this study are those known to have systemic inflammatory effects on the central nervous system or multiple other organ systems. Statistical analysis, including construction of multivariable linear and logistic regression models, was performed using R version 4.1.0.

Results: Chart review identified 190 patients with 469 ruptured and unruptured saccular intracranial aneurysms. There were 31 patients with 44 aneurysms identified as having an autoimmune disease. The mean size of a ruptured aneurysm was significantly smaller among patients with autoimmune disease compared with patients without autoimmune disease (4.14 mm vs 5.34 mm, p = 0.03). The multivariate logistic regression model did not identify any significant association between rupture and autoimmune disease when controlling for other variables (p = 0.49). In the multivariate linear regression model, autoimmune disease was still significantly associated with a smaller size at rupture (p = 0.04), and smoking was associated with a larger size at rupture (p = 0.03) when controlling for other variables. A second multivariate logistic regression model found autoimmune disease to be independently associated with rupture at a size smaller than 7 mm (p = 0.02), while smoking was independently associated with rupture at a size larger than 7 mm (p = 0.01).

Conclusions: Autoimmune disease is associated with a smaller aneurysm size at rupture, although it is not associated with rupture itself. This association may be due to inflammatory pathways that are common to autoimmune diseases as well as aneurysm wall development. Although the authors were unable to identify any association between rupture status and the presence of autoimmune disease, the association between smaller size at rupture and autoimmune disease warrants further studies, as autoimmune disease may influence the trajectory of aneurysm development and the decision to treat.
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http://dx.doi.org/10.3171/2022.5.JNS22750DOI Listing
July 2022

Seasonality drives the survival landscape of a recovering forest carnivore in a changing world.

Proc Biol Sci 2022 07 27;289(1979):20220833. Epub 2022 Jul 27.

Department of Forest and Wildlife Ecology, University of Wisconsin, Madison, WI 53706, USA.

Ecological heterogeneity promotes species persistence and diversity. Environmental change has, however, eroded patterns of heterogeneity globally, stifling species recovery. To test the effects of seasonal heterogeneity on a reintroduced carnivore, American martens (), we compared metrics of local and season-specific heterogeneity to traditional forest metrics on the survival of 242 individuals across 8 years and predicted a survival landscape for 13 reintroduction sites. We found that heterogeneity-created by forest structure in the growing season and snow in the winter-improved survival and outperformed traditional forest metrics. Spatial variation in heterogeneity created a distinct survival landscape, but seasonal change in heterogeneity generated temporal discordance. All translocation sites possessed high forest heterogeneity but there were greater differences in winter heterogeneity; recovery sites with the poorest snow conditions had the lowest viability. Our work links heterogeneity across seasons to fitness and suggests that management strategies that increase seasonal aspects of heterogeneity may help to recover other sensitive species to continuing environmental change.
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http://dx.doi.org/10.1098/rspb.2022.0833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326265PMC
July 2022

Non-Invasive Spectroscopy for Measuring Cerebral Tissue Oxygenation and Metabolism as a Function of Cerebral Perfusion Pressure.

Metabolites 2022 Jul 20;12(7). Epub 2022 Jul 20.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA.

Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) measure cerebral hemodynamics, which in turn can be used to assess the cerebral metabolic rate of oxygen (CMRO) and cerebral autoregulation (CA). However, current mathematical models for CMRO estimation make assumptions that break down for cerebral perfusion pressure (CPP)-induced changes in CA. Here, we performed preclinical experiments with controlled changes in CPP while simultaneously measuring NIRS and DCS at rest. We observed changes in arterial oxygen saturation (~10%) and arterial blood volume (~50%) with CPP, two variables often assumed to be constant in CMRO estimations. Hence, we propose a general mathematical model that accounts for these variations when estimating CMRO and validate its use for CA monitoring on our experimental data. We observed significant changes in the various oxygenation parameters, including the coupling ratio (CMRO/blood flow) between regions of autoregulation and dysregulation. Our work provides an appropriate model and preliminary experimental evidence for the use of NIRS- and DCS-based tissue oxygenation and metabolism metrics for non-invasive diagnosis of CA health in CPP-altering neuropathologies.
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http://dx.doi.org/10.3390/metabo12070667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323243PMC
July 2022

An algorithm to improve lateralization accuracy of inferior petrosal sinus sampling: procedural nuances for complex patterns of venous drainage. Patient series.

J Neurosurg Case Lessons 2021 Sep 27;2(13):CASE21374. Epub 2021 Sep 27.

Departments of Neurosurgery.

Background: Inferior petrosal sinus sampling (IPSS) is a useful technique in the diagnosis of Cushing's disease (CD) when the imaging finding is negative or equivocal. Different authors have reported considerable variability in the ability to determine tumor laterality with IPSS. Here the authors present a retrospective case series of 7 patients who underwent IPSS using a systematic algorithm to improve lateralization accuracy by identifying optimal sampling sites on the basis of individual cavernous sinus drainage patterns in each patient.

Observations: Of the 7 patients identified, 6 were determined to have CD and subsequently underwent surgery. IPSS was accurate in all patients from whom laterality was predicted. Arterial and venous angiography were used to define cavernous sinus drainage patterns and determine optimal sampling sites. All patients who underwent surgery achieved hormonal cure.

Lessons: All IPSS predictions of lateralization were correct when available, and all patients who underwent surgery achieved hormonal cure. Advances in angiographic techniques for identification of the site of primary drainage from the cavernous sinus and subsequent optimization of microcatheter placement may improve the ability to predict tumor laterality.
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http://dx.doi.org/10.3171/CASE21374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265235PMC
September 2021

Descriptive Characteristics and Outcomes of Patients Undergoing Revision Anterior Cruciate Ligament Reconstruction With and Without Tunnel Bone Grafting.

Am J Sports Med 2022 07;50(9):2397-2409

University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Lytic or malpositioned tunnels may require bone grafting during revision anterior cruciate ligament reconstruction (rACLR) surgery. Patient characteristics and effects of grafting on outcomes after rACLR are not well described.

Purpose: To describe preoperative characteristics, intraoperative findings, and 2-year outcomes for patients with rACLR undergoing bone grafting procedures compared with patients with rACLR without grafting.

Study Design: Cohort study; Level of evidence, 3.

Methods: A total of 1234 patients who underwent rACLR were prospectively enrolled between 2006 and 2011. Baseline revision and 2-year characteristics, surgical technique, pathology, treatment, and patient-reported outcome instruments (International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS], Western Ontario and McMaster Universities Osteoarthritis Index, and Marx Activity Rating Scale [Marx]) were collected, as well as subsequent surgery information, if applicable. The chi-square and analysis of variance tests were used to compare group characteristics.

Results: A total of 159 patients (13%) underwent tunnel grafting-64 (5%) patients underwent 1-stage and 95 (8%) underwent 2-stage grafting. Grafting was isolated to the femur in 31 (2.5%) patients, the tibia in 40 (3%) patients, and combined in 88 patients (7%). Baseline KOOS Quality of Life (QoL) and Marx activity scores were significantly lower in the 2-stage group compared with the no bone grafting group (≤ .001). Patients who required 2-stage grafting had more previous ACLRs ( < .001) and were less likely to have received a bone-patellar tendon-bone or a soft tissue autograft at primary ACLR procedure (≤ .021) compared with the no bone grafting group. For current rACLR, patients undergoing either 1-stage or 2-stage bone grafting were more likely to receive a bone-patellar tendon-bone allograft (≤ .008) and less likely to receive a soft tissue autograft (≤ .003) compared with the no bone grafting group. At 2-year follow-up of 1052 (85%) patients, we found inferior outcomes in the 2-stage bone grafting group (IKDC score = 68; KOOS QoL score = 44; KOOS Sport/Recreation score = 65; and Marx activity score = 3) compared with the no bone grafting group (IKDC score = 77; KOOS QoL score = 63; KOOS Sport/Recreation score = 75; and Marx activity score = 7) (≤ .01). The 1-stage bone graft group did not significantly differ compared with the no bone grafting group.

Conclusion: Tunnel bone grafting was performed in 13% of our rACLR cohort, with 8% undergoing 2-stage surgery. Patients treated with 2-stage grafting had inferior baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting. Patients treated with 1-stage grafting had similar baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting.
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http://dx.doi.org/10.1177/03635465221104470DOI Listing
July 2022

Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis.

EBioMedicine 2022 Jul 8;82:104124. Epub 2022 Jul 8.

Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States.

Background: Intermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data in humans are sparse.

Methods: We conducted a randomised-controlled feeding study of different CR diets in 36 people with MS over 8 weeks. Participants were randomised to 1 of 3 diets: 1) a control diet, in which the participant received 100% of his or her calorie needs 7 days per week, 2) a daily CR diet, in which the participant received 78% of his or her calorie needs 7 days per week, or 3) an intermittent CR diet, in which the participant received 100% of his or her calorie needs on 5 days per week and 25% of his or her calorie needs 2 days per week (i.e., a "5:2" style diet). Untargeted metabolomics was performed on plasma samples at weeks 0, 4 and 8 at Metabolon Inc (Durham, NC). Flow cytometry of cryopreserved peripheral blood mononuclear cells at weeks 0 and 8 were used to identify CD3;CD4 (CD4) and CD3;CD4 (as a proxy for CD8) T cell subsets including effector memory, central memory, and naïve cells.

Findings: 31 (86%) completed the trial. Over time, individuals randomised to intermittent CR had significant reductions in effector memory (for CD4: -3.82%; 95%CI: -7.44, -0.21; for CD4: -6.96%; 95%CI: -11.96, -1.97) and Th1 subsets (-4.26%; 95% CI: -7.11, -1.40) and proportional increases in naïve subsets (for CD4: 10.11%; 95%CI: 3.30, 16.92%). No changes were observed for daily CR or weight-stable diets. Larger within-person changes in lysophospholipid and lysoplasmalogen metabolites in intermittent CR were associated with larger reductions in memory T cell subsets and larger increases in naïve T cell subsets.

Interpretation: In people with MS, an intermittent CR diet was associated with reduction in memory T cell subsets and certain biologically-relevant lipid markers.

Funding: National MS Society, NIH, Johns Hopkins Catalyst Award.
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http://dx.doi.org/10.1016/j.ebiom.2022.104124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283513PMC
July 2022

Local Infiltration Analgesia Versus Interscalene Block for Pain Management Following Shoulder Arthroplasty: A Prospective Randomized Clinical Trial.

J Bone Joint Surg Am 2022 Jul 1. Epub 2022 Jul 1.

Department of Orthopaedic Surgery, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri.

Background: While providing effective analgesia following shoulder arthroplasty, an interscalene block has known complications. Local infiltration analgesia (LIA) using ropivacaine has been successfully employed in other joint arthroplasties, but its efficacy in shoulder arthroplasty has not been studied extensively. The purpose of this study was to compare pain and opioid consumption between LIA and an interscalene block following shoulder arthroplasty.

Methods: Patients undergoing primary shoulder arthroplasty were prospectively randomized into 2 groups: the block group received an interscalene block using liposomal bupivacaine, and the injection group received an LIA injection intraoperatively. The LIA injection included ropivacaine, epinephrine, ketorolac, and normal saline solution. Postoperative visual analog scale pain scores, opioid consumption in morphine milligram equivalents, and complications were compared between the groups. The mean pain scores during the first 24 hours postoperatively were used to test noninferiority of LIA compared with an interscalene block.

Results: The study included 74 patients (52 men and 22 women with a mean age of 69 years; 37 were in the injection group and 37 in the block group). There was no significant difference between the groups with respect to pain scores at any postoperative time points (p > 0.05), except for the 8-hour time point, when the injection group had a significantly higher pain score than the block group (p = 0.01). There was no significant difference in opioid consumption between the groups at any time points postoperatively (p > 0.05). The amount of intraoperative opioid consumption was significantly higher in the injection group (p < 0.001). In noninferiority testing for the mean pain scores during the first 24 hours, the injection group was found to be noninferior to the block group. One patient in the block group developed transient phrenic nerve palsy. One patient in the injection group developed dislocation after reverse arthroplasty related to noncompliance. The mean procedure hospital charge was $1,718 for an interscalene block and $157 for LIA.

Conclusions: LIA and an interscalene block provided similar analgesia during the first 24 hours after primary shoulder arthroplasty. LIA was associated with worse pain at 8 hours postoperatively and more intraoperative opioid consumption but was also substantially less costly.

Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.22.00034DOI Listing
July 2022

Co-optimization of therapeutic antibody affinity and specificity using machine learning models that generalize to novel mutational space.

Nat Commun 2022 07 1;13(1):3788. Epub 2022 Jul 1.

Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.

Therapeutic antibody development requires selection and engineering of molecules with high affinity and other drug-like biophysical properties. Co-optimization of multiple antibody properties remains a difficult and time-consuming process that impedes drug development. Here we evaluate the use of machine learning to simplify antibody co-optimization for a clinical-stage antibody (emibetuzumab) that displays high levels of both on-target (antigen) and off-target (non-specific) binding. We mutate sites in the antibody complementarity-determining regions, sort the antibody libraries for high and low levels of affinity and non-specific binding, and deep sequence the enriched libraries. Interestingly, machine learning models trained on datasets with binary labels enable predictions of continuous metrics that are strongly correlated with antibody affinity and non-specific binding. These models illustrate strong tradeoffs between these two properties, as increases in affinity along the co-optimal (Pareto) frontier require progressive reductions in specificity. Notably, models trained with deep learning features enable prediction of novel antibody mutations that co-optimize affinity and specificity beyond what is possible for the original antibody library. These findings demonstrate the power of machine learning models to greatly expand the exploration of novel antibody sequence space and accelerate the development of highly potent, drug-like antibodies.
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http://dx.doi.org/10.1038/s41467-022-31457-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249733PMC
July 2022

Early-Career Sports Medicine Surgeons Perform a Large Volume of Non-Sports Medicine Procedures: American Board of Orthopaedic Surgery (ABOS) Part-II Data Regarding Orthopaedic Surgeons Specializing in Sports Medicine.

J Bone Joint Surg Am 2022 Jun 30. Epub 2022 Jun 30.

Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, Missouri.

Background: The purpose of this study was to utilize the American Board of Orthopaedic Surgery (ABOS) Part-II Case List database to (1) define the practice patterns of sports medicine-trained ABOS Part- II Oral Examination Candidates and (2) describe the frequency and practice patterns of individuals who are dual fellowship-trained sports medicine candidates.

Methods: The ABOS Part-II Case List database was utilized to define all cases submitted by 3,298 applicants indicating completion of a sports medicine fellowship between January 1, 2003, and January 1, 2020. Cases were classified by subspecialty category and case type. The frequency and practice patterns of candidates pursuing additional fellowship training (i.e., "dual fellowship-trained") were recorded. Descriptive statistical methods were used to describe the annual and overall procedure volume and candidate case mix. Trends in the relative frequency of cases performed and fellowship training patterns were determined using linear regression analysis.

Results: On average, sports medicine-trained candidates submitted 100.6 cases for review during the 6-month case collection period: 59.0 (58.6%) sports medicine/arthroscopy cases, 29.3 (29.1%) trauma/general cases, 4.5 (4.5%) adult reconstruction cases, and 7.8 (7.8%) "other" cases per candidate. Although candidates performed fewer total (r 2 = 0.84, p < 0.001) and sports medicine/arthroscopy (r 2 = 0.85, p < 0.001) cases over the study period, the proportion of sports medicine/arthroscopy cases did not change over the study period (p = 0.18). Dual fellowship training was indicated by 333 individuals (10.1%). The number of dual fellowship-trained candidates pursuing additional fellowship training in pediatrics and adult reconstruction increased over the study period, and the number of dual fellowship-trained candidates pursuing additional fellowship training in trauma decreased over the study period.

Conclusions: Early-career sports medicine candidates are likely to perform >40% of cases outside of the sports medicine subspecialty. Sports medicine trainees are increasingly likely to pursue a second fellowship in pediatrics or adult reconstruction.

Level Of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.21.01129DOI Listing
June 2022

Editorial: Insights in Aging and Public Health: 2021.

Front Public Health 2022 10;10:929418. Epub 2022 Jun 10.

Department of Environmental and Occupational Health, School of Public Health, Texas A&M University, College Station, TX, United States.

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http://dx.doi.org/10.3389/fpubh.2022.929418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226638PMC
June 2022

Definitive treatment choice among Black immigrants with prostate cancer: Analysis of patient surveys distributed at a single safety-net institution.

Prostate 2022 Jun 23. Epub 2022 Jun 23.

Department of Urology, SUNY Downstate College of Medicine, Brooklyn, New York, USA.

Background: Large-scale prostate cancer (PCa) database reviews have found a consistent discrepancy in the mortality rate in Black patients compared to their White counterparts. Furthermore, differences in PCa treatment and outcomes among Black men of different ethnic origins have also been identified. Due to the heterogeneity of PCa-impacted communities and the unclear impact of patient immigration status on treatment outcomes, we sought to determine the demographic factors associated with treatment choice for definitive treatment of PCa in our single institution's patient population of Black immigrants.

Methods: We distributed surveys to all patients in the Kings County Hospital Center urologic oncology clinic from February 2019 to February 2020 and collected relevant health information via EMR. The survey collected demographic information regarding age, education, health insurance, employment status, socioeconomic status, country of birth, and years living in the United States (US).

Results: Out of the 253 patients surveyed, the majority of patients surveyed were Black and foreign born. There were no significant differences in demographic data between US-born and foreign-born patients except number of years living in the United States. In the intermediate risk group, patients living in the United States for <10 years chose surgery significantly more often than US-born patients (90.9% vs. 50.0%, p = 0.036). On multivariate analysis, patients that chose surgery were more likely to be older when diagnosed (odds ratio [OR] = 1.21) and less likely to be born in the United States than in African or Caribbean countries (OR = 0.054).

Conclusions: In our study of a majority-Black population, we found that patients born in the United States were less likely than their foreign counterparts to opt for surgery, as previous studies have shown. The choice of definitive treatment modality for Black men with intermediate risk PCa was found to be influenced by age at diagnosis and immigration status.
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http://dx.doi.org/10.1002/pros.24399DOI Listing
June 2022

SARS-CoV-2 Delta Variant N Gene Mutations Reduce Sensitivity to the TaqPath COVID-19 Multiplex Molecular Diagnostic Assay.

Viruses 2022 06 16;14(6). Epub 2022 Jun 16.

Center for Fundamental and Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.

As the SARS-CoV-2 virus evolves, mutations may result in diminished sensitivity to qRT-PCR diagnostic assays. We investigated four polymorphisms circulating in the SARS-CoV-2 Delta lineage that result in gene target failure (NGTF) on the TaqPath COVID-19 Combo Kit. These mutations were detected from the SARS-CoV-2 genome sequences that matched with the diagnostic assay results of saliva specimens. Full length genes from the samples displaying NGTF were cloned into plasmids and assayed using three SARS-CoV-2 qRT-PCR assays. These constructs resulted in reduced sensitivity to the TaqPath COVID-19 Combo Kit compared to the controls (mean C differences of 3.06, 7.70, 12.46, and 14.12), but were detected equivalently on the TaqPath COVID-19 Fast PCR Combo 2.0 or CDC 2019_nCoV_N2 assays. This work highlights the importance of genomic sequencing to monitor circulating mutations and provide guidance in improving diagnostic assays.
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http://dx.doi.org/10.3390/v14061316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228125PMC
June 2022

Four New Species of : Unravelling the Laurel Wilt Fungal Genus.

J Fungi (Basel) 2022 Jun 8;8(6). Epub 2022 Jun 8.

Institute of Systematic Botany, The New York Botanical Garden, New York, NY 10458, USA.

Symbiosis between beetles and fungi arose multiple times during the evolution of both organisms. Some of the most biologically diverse and economically important are mutualisms in which the beetles cultivate and feed on fungi. Among these are bark beetles and , a fungal genus that produces -like asexual morph and hosts the causal agent of laurel wilt, (formerly ). In this study, we propose four new species of associated with beetles from Belize and Florida (USA). We hope to contribute towards a more robust and inclusive phylogenetic framework for future studies on these beetle-fungi relationships and their potential impact in crops and forests worldwide.
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http://dx.doi.org/10.3390/jof8060613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224673PMC
June 2022

Contributors to Serum NfL Levels in People without Neurologic Disease.

Ann Neurol 2022 Jun 21. Epub 2022 Jun 21.

Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Objective: To assess the effects of demographics, lifestyle factors, and comorbidities on serum neurofilament light chain (sNfL) levels in people without neurologic disease and establish demographic-specific reference ranges of sNfL.

Methods: The National Health and Nutrition Examination Survey (NHANES) is a representative sample of the US population in which detailed information on demographic, lifestyle, routine laboratory tests, and overall health status are systematically collected. From stored serum samples, we measured sNfL levels using a novel high-throughput immunoassay (Siemens Healthineers). We evaluated the predictive capacity of 52 demographic, lifestyle, comorbidity, anthropometric, or laboratory characteristics in explaining variability in sNfL levels. Predictive performance was assessed using cross-validated R (R ) and forward selection was used to obtain a set of best predictors of sNfL levels. Adjusted reference ranges were derived incorporating characteristics using generalized additive models for location, scale, and shape.

Results: We included 1,706 NHANES participants (average age: 43.6 ± 14.8 y; 50.6% male, 35% non-white) without neurological disorders. In univariate models, age explained the most variability in sNfL (R  = 26.8%). Multivariable prediction models for sNfL contained three covariates (in order of their selection): age, creatinine, and glycosylated hemoglobin (HbA1c) (standardized β-age: 0.46, 95% confidence interval [CI]: 0.43, 0.50; creatinine: 0.18, 95% CI: 0.13, 0.22; HbA1c: 0.09, 95% CI: 0.06, 0.11). Adjusted centile curves were derived incorporating identified predictors. We provide an interactive R Shiny application to translate our findings and allow other investigators to use the derived centile curves.

Interpretation: Results will help to guide interpretation of sNfL levels as they relate to neurologic conditions. ANN NEUROL 2022.
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http://dx.doi.org/10.1002/ana.26446DOI Listing
June 2022

Spindle reorientation in response to mechanical stress is an emergent property of the spindle positioning mechanisms.

Proc Natl Acad Sci U S A 2022 06 21;119(26):e2121868119. Epub 2022 Jun 21.

London Centre for Nanotechnology, University College London, London WC1H 0AH, United Kingdom.

Proper orientation of the mitotic spindle plays a crucial role in embryos, during tissue development, and in adults, where it functions to dissipate mechanical stress to maintain tissue integrity and homeostasis. While mitotic spindles have been shown to reorient in response to external mechanical stresses, the subcellular cues that mediate spindle reorientation remain unclear. Here, we used a combination of optogenetics and computational modeling to investigate how mitotic spindles respond to inhomogeneous tension within the actomyosin cortex. Strikingly, we found that the optogenetic activation of RhoA only influences spindle orientation when it is induced at both poles of the cell. Under these conditions, the sudden local increase in cortical tension induced by RhoA activation reduces pulling forces exerted by cortical regulators on astral microtubules. This leads to a perturbation of the balance of torques exerted on the spindle, which causes it to rotate. Thus, spindle rotation in response to mechanical stress is an emergent phenomenon arising from the interaction between the spindle positioning machinery and the cell cortex.
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http://dx.doi.org/10.1073/pnas.2121868119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245638PMC
June 2022

Changes in Dynamic Postural Stability After ACL Reconstruction: Results Over 2 Years of Follow-up.

Orthop J Sports Med 2022 Jun 13;10(6):23259671221098989. Epub 2022 Jun 13.

Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, Missouri, USA.

Background: The anterior cruciate ligament (ACL) is crucial for knee proprioception and postural stability. While ACL reconstruction (ACLR) and rehabilitation improve postural stability, the timing in improvement of dynamic postural stability after ACLR remains relatively unknown.

Purpose: To evaluate changes in dynamic postural stability after ACLR out to 24 months postoperatively.

Study Design: Case series; Level of evidence, 4.

Methods: Patients undergoing ACLR were prospectively enrolled, and dynamic postural stability was assessed within 2 days before surgery, at 3-month intervals postoperatively to 18 months, then at 24 months. Measurements were made on a multidirectional platform tracking the patient's center of mass based on pelvic motion. The amount of time the patient was able to stay on the platform was recorded, and a dynamic motion analysis score, reflecting the patient's ability to maintain one's center of mass, was generated overall and in 6 independent planes of motion.

Results: A total of 44 patients with a mean age of 19.7 ± 6.2 years completed the study protocol. Overall mean dynamic postural stability improved significantly at 3, 6, 9, and 12 months after surgery, with continued improvement out to 24 months. Notable improvements occurred in medial/lateral and anterior/posterior stability from baseline to 6 months postoperatively, while internal/external rotation and flexion/extension stability declined initially after surgery from baseline to 3 months postoperatively before stabilizing to the end of the study period.

Conclusion: Overall dynamic postural stability significantly improved up to 12 months after ACLR. Improvement in postural stability occurred primarily in the medial/lateral and anterior/posterior planes of motion, with initial decreases in the flexion/extension and internal/external rotational planes of motion.
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http://dx.doi.org/10.1177/23259671221098989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201321PMC
June 2022

Multicenter Evaluation of the Idylla GeneFusion in Non-Small-Cell Lung Cancer.

J Mol Diagn 2022 Jun 16. Epub 2022 Jun 16.

Sheffield Teaching Hospitals NHS Foundation Trust, Pathology Laboratory, Royal Hallamshire Hospital, Sheffield, United Kingdom.

Targeted therapy in lung cancer requires the assessment of multiple oncogenic driver alterations, including fusion genes. This retrospective study evaluated the Idylla GeneFusion prototype, an automated and ease-of-use (<2 minutes) test, with a short turnaround time (3 hours) to detect fusions involving ALK, ROS1, RET, and NTRK1/2/3 genes and MET exon 14 skipping. This multicenter study (18 centers) included 313 tissue samples from lung cancer patients with 97 ALK, 44 ROS1, 20 RET, and 5 NTRKs fusions, 32 MET exon 14 skipping, and 115 wild-type samples, previously identified with reference methods (RNA-based next generation sequencing/fluorescence in situ hybridization/quantitative PCR). Valid results were obtained for 306 cases (98%), overall concordance between Idylla and the reference methods was 89% (273/306); overall sensitivity and specificity were 85% (165/193) and 96% (108/113), respectively. Discordances were observed in 28 samples, where Idylla did not detect the alteration identified by the reference methods; and 5 samples where Idylla identified an alteration not detected by the reference methods. All of the ALK-, ROS1-, and RET-specific fusions and MET exon 14 skipping identified by Idylla GeneFusion were confirmed by reference method. To conclude, Idylla GeneFusion is a clinically valuable test that does not require a specific infrastructure, allowing a rapid result. The absence of alteration or the detection of expression imbalance only requires additional testing by orthogonal methods.
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http://dx.doi.org/10.1016/j.jmoldx.2022.05.004DOI Listing
June 2022

Social Support, Sense of Belonging, and Communication Technology Use Among Paid and Unpaid Caregivers of Middle-Aged and Older Adults.

Front Public Health 2022 30;10:898042. Epub 2022 May 30.

Department of Environmental and Occupational Health, School of Public Health, Texas A&M University, College Station, TX, United States.

Objectives: The objectives of this study are to: (1) describe communication technology use among paid and unpaid middle-aged and older caregivers of adults 50 and older in a natural (non-experimental) setting; and (2) examine the association between communication technology use, perceived social support, and sense of belonging in this population.

Methods: Means and standard deviations, or frequencies and percentages, were used to describe study participants. Chi-square tests or independent sample -tests were used to compare sociodemographic characteristics, communication technology use, perceived social support, and sense of belonging to the local community between paid and unpaid caregivers. Multivariable regression analysis was performed to predict each outcome (i.e., sense of belonging and social support) based on the use of texting or communication applications.

Results: The average age of participants was age 64.2 years, and the majority was female (74.8%) and non-Hispanic White (66.9%). Compared to paid caregivers, unpaid caregivers were older (64.5 vs. 62.2 years, = 0.022) and a larger proportion were non-Hispanic White (70.8% vs. 47.7%, < 0.001). Nearly 83% of the study participants reported using texting or communication applications (81.5% among paid caregivers and 83.1% among unpaid caregivers, = 0.718). After adjusting for caregivers' age, sex, race/ethnicity, and education, a significantly higher sense of belonging was observed among paid caregivers than unpaid caregivers ( = 9.40, = 0.009). After adjusting for caregivers' age, sex, race/ethnicity, and education, the use of texting or other communication applications significantly increased caregivers' perceived availability of social support ( = 0.35, = 001).

Conclusions: These study results showed a greater sense of belonging to the local community among paid caregivers compared to unpaid caregivers. The use of communication technology was associated with an increased sense of belonging to their local community among paid caregivers, yet the use of communication technology did not contribute to feelings of belonging among unpaid caregivers. In an aging society, both paid and unpaid caregivers are essential elements of the care system. Research is needed to understand the social support needs of paid and unpaid caregivers and the types of interventions to promote social support and community engagement for both groups.
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http://dx.doi.org/10.3389/fpubh.2022.898042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196896PMC
May 2022

Darolutamide in Metastatic Prostate Cancer. Reply.

Authors:
Matthew R Smith

N Engl J Med 2022 06;386(24):2345

Massachusetts General Hospital, Boston, MA

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http://dx.doi.org/10.1056/NEJMc2205310DOI Listing
June 2022

Corrigendum to "Nitric oxide biosensor uncovers diminished ferrous iron-dependency of cultured cells adapted to physiological oxygen levels" [Redox Biol. 53 (2022) 102319].

Redox Biol 2022 Aug 11;54:102364. Epub 2022 Jun 11.

Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Turkey; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010, Graz, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.redox.2022.102364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287725PMC
August 2022

Precise Quantification of Behavioral Individuality From 80 Million Decisions Across 183,000 Flies.

Front Behav Neurosci 2022 26;16:836626. Epub 2022 May 26.

Center for Brain Science and Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, United States.

Individual animals behave differently from each other. This variability is a component of personality and arises even when genetics and environment are held constant. Discovering the biological mechanisms underlying behavioral variability depends on efficiently measuring individual behavioral bias, a requirement that is facilitated by automated, high-throughput experiments. We compiled a large data set of individual locomotor behavior measures, acquired from over 183,000 fruit flies walking in Y-shaped mazes. With this data set we first conducted a "computational ethology natural history" study to quantify the distribution of individual behavioral biases with unprecedented precision and examine correlations between behavioral measures with high power. We discovered a slight, but highly significant, left-bias in spontaneous locomotor decision-making. We then used the data to evaluate standing hypotheses about biological mechanisms affecting behavioral variability, specifically: the neuromodulator serotonin and its precursor transporter, heterogametic sex, and temperature. We found a variety of significant effects associated with each of these mechanisms that were behavior-dependent. This indicates that the relationship between biological mechanisms and behavioral variability may be highly context dependent. Going forward, automation of behavioral experiments will likely be essential in teasing out the complex causality of individuality.
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http://dx.doi.org/10.3389/fnbeh.2022.836626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178272PMC
May 2022

Prospective Randomized Controlled Clinical Trial Comparing Hyperosmolar Saline to Standard Isotonic Irrigation Fluid for Arthroscopic Knee Surgery: Initial Clinical Outcomes.

J Knee Surg 2022 Jun 10. Epub 2022 Jun 10.

Department of Orthopaedic Surgery, Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri.

Numerous in vitro studies suggest higher osmolarity irrigation fluids potentiate a chondroprotective environment, and a recent clinical study using hyperosmolar saline for shoulder arthroscopy reported potential clinical advantages. This prospective randomized double-blind controlled clinical trial was designed to assess initial clinical outcomes associated with use of a hyperosmolar irrigation solution in patients undergoing arthroscopic knee surgery. With institutional review board approval and informed consent, patients scheduled for arthroscopic knee surgery were randomized to surgery with either isotonic lactated Ringer's (273 mOsm/L) or hyperosmolar saline (593 mOsm/L) irrigation solution. Outcomes included perioperative blood pressure, knee girth, visual analogue scale (VAS) pain scores, and narcotic pain medication consumption. Forty-six patients underwent arthroscopic knee surgery with isotonic ( = 23) or hyperosmolar ( = 23) irrigation fluids. There were 11 males and 12 females (mean age = 44.0 years) in the isotonic cohort and 8 males and 15 females (mean age = 40.2 years) in the hyperosmolar cohort. There were no significant differences with respect to surgical duration (pump time) or amount of irrigation fluid used between the two cohorts. There were no significant differences with respect to change in knee girth, blood pressure, or VAS pain scores. However, patients treated with hyperosmolar saline consumed less narcotic medication on postoperative day 3 (4.0 ± 7.6 vs. 15.5 ± 17.4 mg, = 0.01). The results of this randomized clinical trial suggest that a hyperosmolar irrigation solution is safe and relatively inexpensive for use in patients undergoing arthroscopic knee surgery and contributes to a reduction in initial postoperative narcotic pain medication consumption. A hyperosmolar saline irrigation fluid was not associated with any detrimental effects on the execution of the surgical procedure, postoperative pain, or periarticular fluid extravasation. Taken together with previous basic science, translational, and clinical studies, hyperosmolar saline irrigation fluid is promising alternative to traditional isotonic irrigation fluids for knee arthroscopy. This study is a prospective trial and reflects level of evidence I.
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http://dx.doi.org/10.1055/s-0042-1749655DOI Listing
June 2022

Evaluating the policy of closing bars and restaurants in Cataluña and its effects on mobility and COVID19 incidence.

Sci Rep 2022 06 7;12(1):9132. Epub 2022 Jun 7.

Barcelona Supercomputing Center (BSC), Life Science, 08034, Barcelona, Spain.

The world has gone through unprecedented changes since the global pandemic hit. During the early phase of the pandemic, the absence of known drugs or pharmaceutical treatments forced governments to introduce different policies in order to help reduce contagion rates and manage the economic consequences of the pandemic. This paper analyses the causal impact on mobility and COVID19 incidence from policy makers in Cataluña, Spain. We use anonymized phone-based mobility data together with reported incidence and apply a series of causal impact models frequently used in econometrics and policy evaluation in order to measure the policies impact. We analyse the case of Cataluña and the public policy decision of closing all bars and restaurants down for a 5 week period between 2020-16-10 and 2020-23-11. We find that this decision led to a significant reduction in mobility. It not only led to reductions in mobility but from a behavioural economics standpoint, we highlight how people responded to the policy decision. Moreover, the policy of closing bars and restaurants slowed the incidence rate of COVID19 after a time lag has been taken into account. These findings are significant since governments worldwide want to restrict movements of people in order to slow down COVID19 incidence without infringing on their rights directly.
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http://dx.doi.org/10.1038/s41598-022-11531-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174270PMC
June 2022

Clinical Fate of Glenohumeral Osteoarthritis Following Intraarticular Corticosteroid Injection: An Analysis in 311 Shoulders.

J Shoulder Elb Arthroplast 2022 2;6:24715492221075446. Epub 2022 Feb 2.

Missouri Orthopaedic Institute, University of Missouri, Columbia, MO 65212, USA.

Background: Intraarticular corticosteroid injection is commonly used conservative treatment for glenohumeral osteoarthritis (OA). The purpose of this study was to investigate the clinical fate of symptomatic glenohumeral OA following intraarticular corticosteroid injection and to identify factors associated with undergoing shoulder arthroplasty.

Methods: Glenohumeral OA patients who had undergone at least one glenohumeral corticosteroid injection from 2012 to 2017 were identified. Data for demographics, comorbidities, number of injections, severity of radiographic arthritis, and subsequent treatment were collected up to February 2020. Data were analyzed to compare between patients who had eventually undergone shoulder arthroplasty and those who had not.

Results: A total of 311 shoulders (275 patients) were followed up for 3 to 8 years after the index injection. The mean age of patients was 64.7 years. There were 148 females, and 116 shoulders (37.3%) eventually underwent arthroplasty, 68 (21.9%) further injections only, 104 (33.4%) no further treatment, 14 (4.5%) a non-arthroplasty surgical procedure, and 9 (2.9%) were lost to follow up. Severity of radiographic arthritic changes, female sex, younger age, and nonsmoking status were found to be significantly associated with undergoing arthroplasty (p < 0.001, p = 0.014, p = 0.003, and p = 0.043, respectively).

Conclusion: Approximately one third of glenohumeral OA patients who had received an intraarticular corticosteroid injection eventually elected to undergo shoulder arthroplasty within 3 to 8 years of the injection. High-grade arthritic changes in radiographs, female gender, and younger age were found to be independent factors associated with undergoing arthroplasty. This information may be useful in counseling patients about their future clinical course.Level of Evidence: Level III Retrospective comparative study.
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http://dx.doi.org/10.1177/24715492221075446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163723PMC
February 2022

Severe Rheumatic Mitral Stenosis, Worse Left Atrial Mechanics is Closely Associated with Echo Criteria for Intervention.

J Cardiovasc Echogr 2022 Jan-Mar;32(1):38-46. Epub 2022 Apr 20.

University of Glasgow, Adult Congenital Cardiac Service, Glasgow, Scotland.

Background: Rheumatic mitral valve (MV) stenosis is associated with progressive left atrial (LA) fibrosis and functional impairment, Pulmonary artery systolic pressure (PASP) and right ventricular (RV) dysfunction. The aims of the study were to determine in those patients with severe MV stenosis if LA mechanical function as assessed by speckle tracking echocardiography could identify those with increased PASP, atrial fibrillation (AFib), and RV dysfunction.

Subjects And Methods: Patients with severe MV stenosis were identified from the institutional echo database. Echocardiograms were read off line and measurements included atrial and ventricular strain. Patients were divided into tertiles of LA reservoir strain (LASr) values and data compared between the groups.

Results: Ninety-seven patients, 67 females, mean age 47.4 ± 11.9 years, had MV mean gradient of 8.3 ± 5.1 mmHg, MV area by pressure half time of 1.3 ± 0.3 cm and LASr of 11.18% ± 6.4%. Those patients in the lowest LASr tertile had more AFib (72%, = 0.0001), PASP >50 mm Hg (39%, = 0.005), and worst RV impairment. In multivariable logistic regression analysis, LASr, age, and mean MV gradient were the independent predictors of AFib and PASP >50 mm Hg. Cutoffs, determined by receiver operating characteristic curve analysis had high specificity for the composite outcome of Afib and PASP >50 mmHg (85% for LASr <7.7%).

Conclusion: In severe MV stenosis LASr, age and mean MV gradient, are independent predictors of Afib and PASP >50 mmHg. LASr <7.7% has high sensitivity and specificity in identifying those who meet ESC guideline 2017 criteria for valve intervention, suggesting its potentially helpful addendum to the surveillance of patients with MV stenosis.
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http://dx.doi.org/10.4103/jcecho.jcecho_80_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164921PMC
April 2022

COVID-19 associated disruptions in routine health care of people with mild cognitive impairment or dementia.

Alzheimers Dement (Amst) 2022 1;14(1):e12323. Epub 2022 Jun 1.

Center for Outcomes Research Houston Methodist Houston Texas USA.

Introduction: We report the COVID-19 pandemic's impact on health-care use disruption among people with mild cognitive impairment or Alzheimer's disease and related dementia (MCI/ADRD).

Methods: We compared the pandemic-period health-care use between MCI/ADRD and matched non-MCI/ADRD patients. Using 4-year pre-pandemic data, we modeled three health-care use types (inpatient, outpatient, emergency encounters) to predict pandemic-period use, disaggregated for lockdown and post-lockdown periods. Observed health-care use was compared to the predicted. Proportional differences (confidence intervals) are reported.

Results: Both MCI/ADRD and non-MCI/ADRD patients ( = 5479 each) experienced pandemic-related health-care use disruptions, which were significantly larger for the MCI/ADRD group for outpatient, -13.2% (-16.2%, -10.2%), and inpatient encounters, -12.8% (-18.4%, -7.3%). Large health-care disruptions during lockdown were similar for both groups. However, post-lockdown outpatient, -14.4% (-17.3%, -11.5%), and inpatient, -15.2% (-21.0%, -9.5%), disruptions were significantly greater for MCI/ADRD patients.

Conclusion: MCI/ADRD patients experienced greater and sustained pandemic-related health-care use disruptions, highlighting the need for robust strategies to sustain their essential health care during pandemic-like catastrophes.
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http://dx.doi.org/10.1002/dad2.12323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157405PMC
June 2022

CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice.

J Neuroinflammation 2022 Jun 3;19(1):130. Epub 2022 Jun 3.

Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, MD, 21205, Baltimore, USA.

Background: Multiple sclerosis (MS) is a neurodegenerative disease, wherein aberrant immune cells target myelin-ensheathed nerves. Conventional magnetic resonance imaging (MRI) can be performed to monitor damage to the central nervous system that results from previous inflammation; however, these imaging biomarkers are not necessarily indicative of active, progressive stages of the disease. The immune cells responsible for MS are first activated and sensitized to myelin in lymph nodes (LNs). Here, we present a new strategy for monitoring active disease activity in MS, chemical exchange saturation transfer (CEST) MRI of LNs.

Methods And Results: We studied the potential utility of conventional (T2-weighted) and CEST MRI to monitor changes in these LNs during disease progression in an experimental autoimmune encephalomyelitis (EAE) model. We found CEST signal changes corresponded temporally with disease activity. CEST signals at the 3.2 ppm frequency during the active stage of EAE correlated significantly with the cellular (flow cytometry) and metabolic (mass spectrometry imaging) composition of the LNs, as well as immune cell infiltration into brain and spinal cord tissue. Correlating primary metabolites as identified by matrix-assisted laser desorption/ionization (MALDI) imaging included alanine, lactate, leucine, malate, and phenylalanine.

Conclusions: Taken together, we demonstrate the utility of CEST MRI signal changes in superficial cervical LNs as a complementary imaging biomarker for monitoring disease activity in MS. CEST MRI biomarkers corresponded to disease activity, correlated with immune activation (surface markers, antigen-stimulated proliferation), and correlated with LN metabolite levels.
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http://dx.doi.org/10.1186/s12974-022-02493-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164344PMC
June 2022
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