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  1. Article ; Online: All-Suture Anchor Repair of the Flexor Digitorum Profundus Insertion: A Biomechanical Comparison of 2 Suturing Techniques.

    Belyea, Christopher M / Abbasi, Pooyan / Sanghavi, Kavya K / Giladi, Aviram M / Means, Kenneth R

    The Journal of hand surgery

    2022  Volume 48, Issue 12, Page(s) 1276.e1–1276.e7

    Abstract: ... mattress; group H + K (n = 12) via horizontal mattress with knots thrown and, with each suture tail, 3 ... together. We excluded 2 specimens from the H + K group because of improper anchor placement ... We defined failure as >3-mm gapping.: Results: The H + K group had significantly less gapping during ...

    Abstract Purpose: We compared 2 suturing techniques for reattachment of the flexor digitorum profundus (FDP) via all-suture anchor.
    Methods: We used fresh, matched-pair, cadaveric hands. We disarticulated the fingers at the proximal interphalangeal joints, preserving the proximal FDP. We released the FDPs at their distal insertion and placed an all-suture, 1.0-mm anchor at the center of each FDP footprint. Each anchor's sutures were used to reattach each FDP using 1 of 2 techniques: group H (n = 14) via horizontal mattress; group H + K (n = 12) via horizontal mattress with knots thrown and, with each suture tail, 3 proximal, running-locking, Krackow-type passes on the radial and ulnar FDP sides with the suture ends tied together. We excluded 2 specimens from the H + K group because of improper anchor placement. All other fingers in both groups were individually mounted in an MTS machine for FDP loading in the following sequence for 500 cycles each: (1) to 15 N to simulate passive motion forces; (2) to 19 N for short-arc active motion forces; and (3) to 28 N for full active motion forces. Specimens that had not failed during cyclic testing were then loaded to failure. We measured FDP-to-bone gapping via a digital transducer. We defined failure as >3-mm gapping.
    Results: The H + K group had significantly less gapping during cyclic loading up to 19 N and significantly higher load to failure. The H + K group failed exclusively at the anchor-bone level; the H group failed mostly by suture-tendon pullout.
    Conclusions: The H + K group performed significantly better regarding cyclic and load-to-failure testing after FDP reattachment.
    Clinical relevance: The H + K technique combines the benefits of horizontal-mattress tendon-to-bone apposition and Krackow-tendon locking. It converts the point of failure to the bone level rather than the suture-tendon level.
    MeSH term(s) Humans ; Suture Anchors ; Tendon Injuries/surgery ; Finger Injuries/surgery ; Tendons/surgery ; Suture Techniques ; Biomechanical Phenomena ; Cadaver
    Language English
    Publishing date 2022-06-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605716-0
    ISSN 1531-6564 ; 0363-5023
    ISSN (online) 1531-6564
    ISSN 0363-5023
    DOI 10.1016/j.jhsa.2022.05.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Comparison of 3 Dynamic External Fixation Devices for Proximal Interphalangeal Joint Dorsal Fracture-Dislocations in a Cadaver Model.

    Daniels, Christopher M / Abbasi, Pooyan / Sanghavi, Kavya K / Giladi, Aviram M / Katz, Ryan D / Means, Kenneth R

    The Journal of hand surgery

    2022  Volume 48, Issue 7, Page(s) 736.e1–736.e7

    Abstract: Purpose: Several improvised dynamic external fixation devices are used for treating unstable dorsal proximal interphalangeal (PIP) joint fracture-dislocations. We compared the effectiveness of 3 constructs for simulated dorsal PIP joint fracture- ... ...

    Abstract Purpose: Several improvised dynamic external fixation devices are used for treating unstable dorsal proximal interphalangeal (PIP) joint fracture-dislocations. We compared the effectiveness of 3 constructs for simulated dorsal PIP joint fracture-dislocations in a cadaver model.
    Methods: We tested 30 digits from 10 fresh-frozen, thawed cadaver hands. We aimed to remove the palmar 50% of the base of each digit's middle phalanx (P2), simulating an unstable dorsal PIP joint fracture-dislocation. Each PIP joint was then stabilized via external fixation with either a pins-and-rubber-bands construct, pins-only construct, or tuberculin syringe-pins construct. We allocated 10 digits per fixation group. The finger tendons were secured to a computer-controlled stepper motor-driven linear actuator. Via this mechanism, all PIP joints were taken through 1,400 cycles of flexion-extension. With the PIP joint in neutral extension, we measured the P2 dorsal translation at baseline, after fixator stabilization, and after the motion protocol.
    Results: The actual mean P2 palmar defect created was 48% of the base. All PIP joints were unstable after creating the defect, with a mean initial P2 dorsal displacement of 3.7 mm. After application of the fixators, all PIP joint dislocations were reduced. The median residual P2 dorsal displacements were 0.0 mm for the pins-rubber bands group, 0.1 mm for the pins-only group, and 0.5 mm for the syringe-pins group. There were no cases of PIP joint redislocation after flexion-extension cycling, and the median dorsal P2 displacements were 0.0 mm for the pins-rubber bands group; 0.0 mm for the pins-only group; and 0.5 mm for the syringe-pins group.
    Conclusions: All 3 external fixators restored PIP joint stability following simulated dorsal fracture-dislocation, with all reductions maintained after motion testing. The syringe-pins construct had significantly greater median residual P2 dorsal displacement after the initial reduction and motion testing, which is of unclear clinical importance.
    Clinical relevance: This study informs surgeon decision-making when considering dynamic external fixator options for dorsal PIP joint fracture-dislocations.
    MeSH term(s) Humans ; External Fixators ; Fracture Fixation/methods ; Finger Joint/surgery ; Fracture Dislocation/surgery ; Fractures, Bone/surgery ; Joint Dislocations/surgery ; Cadaver ; Finger Injuries/surgery ; Range of Motion, Articular
    Language English
    Publishing date 2022-03-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605716-0
    ISSN 1531-6564 ; 0363-5023
    ISSN (online) 1531-6564
    ISSN 0363-5023
    DOI 10.1016/j.jhsa.2022.01.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: CaMKK2 as an emerging treatment target for bipolar disorder.

    Kaiser, Jacqueline / Nay, Kevin / Horne, Christopher R / McAloon, Luke M / Fuller, Oliver K / Muller, Abbey G / Whyte, Douglas G / Means, Anthony R / Walder, Ken / Berk, Michael / Hannan, Anthony J / Murphy, James M / Febbraio, Mark A / Gundlach, Andrew L / Scott, John W

    Molecular psychiatry

    2023  Volume 28, Issue 11, Page(s) 4500–4511

    Abstract: Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of ...

    Abstract Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition. The lack of therapeutic innovation in the bipolar disorder field is largely due to a poor understanding of the underlying disease mechanisms and the consequent absence of validated drug targets. A compelling new treatment target is the Ca
    MeSH term(s) Animals ; Humans ; Mice ; Bipolar Disorder/drug therapy ; Bipolar Disorder/genetics ; Calcium-Calmodulin-Dependent Protein Kinase Kinase/genetics ; Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism ; Mutation, Missense
    Chemical Substances Calcium-Calmodulin-Dependent Protein Kinase Kinase (EC 2.7.11.17) ; CAMKK2 protein, human (EC 2.7.11.17) ; Camkk2 protein, mouse (EC 2.7.11.17)
    Language English
    Publishing date 2023-09-20
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-023-02260-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Erratum for Foxall et al., "

    Foxall, Randi L / Means, Jillian / Marcinkiewicz, Ashley L / Schillaci, Christopher / DeRosia-Banick, Kristin / Xu, Feng / Hall, Jeffrey A / Jones, Stephen H / Cooper, Vaughn S / Whistler, Cheryl A

    mBio

    2024  , Page(s) e0102024

    Language English
    Publishing date 2024-04-22
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.01020-24
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Corrigendum to "Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs" [Food Chem. Toxicol. 105 (2017) 448-455].

    Eapen, Alex K / de Cock, Peter / Crincoli, Christine M / Means, Charlotte / Wismer, Tina / Pappas, Christopher

    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

    2017  Volume 110, Page(s) 443

    Language English
    Publishing date 2017-12
    Publishing country England
    Document type Published Erratum
    ZDB-ID 782617-5
    ISSN 1873-6351 ; 0278-6915
    ISSN (online) 1873-6351
    ISSN 0278-6915
    DOI 10.1016/j.fct.2017.08.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The live biotherapeutic SYNB1353 decreases plasma methionine via directed degradation in animal models and healthy volunteers.

    Perreault, Mylène / Means, Jillian / Gerson, Erik / James, Michael / Cotton, Sean / Bergeron, Christopher G / Simon, Mark / Carlin, Dylan Alexander / Schmidt, Nathan / Moore, Theodore C / Blasbalg, Julie / Sondheimer, Neal / Ndugga-Kabuye, Kenneth / Denney, William S / Isabella, Vincent M / Lubkowicz, David / Brennan, Aoife / Hava, David L

    Cell host & microbe

    2024  Volume 32, Issue 3, Page(s) 382–395.e10

    Abstract: Methionine is an essential proteinogenic amino acid, but its excess can lead to deleterious effects. Inborn errors of methionine metabolism resulting from loss of function in cystathionine β-synthase (CBS) cause classic homocystinuria (HCU), which is ... ...

    Abstract Methionine is an essential proteinogenic amino acid, but its excess can lead to deleterious effects. Inborn errors of methionine metabolism resulting from loss of function in cystathionine β-synthase (CBS) cause classic homocystinuria (HCU), which is managed by a methionine-restricted diet. Synthetic biotics are gastrointestinal tract-targeted live biotherapeutics that can be engineered to replicate the benefits of dietary restriction. In this study, we assess whether SYNB1353, an E. coli Nissle 1917 derivative, impacts circulating methionine and homocysteine levels in animals and healthy volunteers. In both mice and nonhuman primates (NHPs), SYNB1353 blunts the appearance of plasma methionine and plasma homocysteine in response to an oral methionine load. A phase 1 clinical study conducted in healthy volunteers subjected to an oral methionine challenge demonstrates that SYNB1353 is well tolerated and blunts plasma methionine by 26%. Overall, SYNB1353 represents a promising approach for methionine reduction with potential utility for the treatment of HCU.
    MeSH term(s) Humans ; Mice ; Animals ; Methionine/metabolism ; Methionine/therapeutic use ; Healthy Volunteers ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Disease Models, Animal ; Homocystinuria/drug therapy ; Homocystinuria/metabolism ; Racemethionine ; Homocysteine/therapeutic use
    Chemical Substances Methionine (AE28F7PNPL) ; Racemethionine (73JWT2K6T3) ; Homocysteine (0LVT1QZ0BA)
    Language English
    Publishing date 2024-02-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2024.01.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Inoviridae

    Foxall, Randi L / Means, Jillian / Marcinkiewicz, Ashely L / Schillaci, Christopher / DeRosia-Banick, Kristin / Xu, Feng / Hall, Jeffrey A / Jones, Stephen H / Cooper, Vaughn S / Whistler, Cheryl A

    mBio

    2023  Volume 15, Issue 1, Page(s) e0285123

    Abstract: Importance: An understanding of the processes that contribute to the emergence of pathogens from environmental reservoirs is critical as changing climate precipitates pathogen evolution and population expansion. Phylogeographic analysis ... ...

    Abstract Importance: An understanding of the processes that contribute to the emergence of pathogens from environmental reservoirs is critical as changing climate precipitates pathogen evolution and population expansion. Phylogeographic analysis of
    MeSH term(s) Prophages ; Vibrio parahaemolyticus/genetics ; Inoviridae ; Ecosystem ; Bacteria ; Bacteriophages/genetics
    Language English
    Publishing date 2023-12-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.02851-23
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  8. Article ; Online: Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs.

    Eapen, Alex K / de Cock, Peter / Crincoli, Christine M / Means, Charlotte / Wismer, Tina / Pappas, Christopher

    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

    2017  Volume 105, Page(s) 448–455

    Abstract: Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating ... ...

    Abstract Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines.
    MeSH term(s) Animals ; Biological Assay ; Dogs ; Erythritol/administration & dosage ; Erythritol/toxicity ; Sweetening Agents/administration & dosage ; Sweetening Agents/toxicity ; Xylitol/administration & dosage ; Xylitol/toxicity
    Chemical Substances Sweetening Agents ; Erythritol (RA96B954X6) ; Xylitol (VCQ006KQ1E)
    Language English
    Publishing date 2017-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 782617-5
    ISSN 1873-6351 ; 0278-6915
    ISSN (online) 1873-6351
    ISSN 0278-6915
    DOI 10.1016/j.fct.2017.04.049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Sphingosine-1-phosphate receptor signalling in the heart.

    Means, Christopher K / Brown, Joan Heller

    Cardiovascular research

    2009  Volume 82, Issue 2, Page(s) 193–200

    Abstract: The five known members of the sphingosine-1-phosphate (S1P) receptor family exhibit diverse tissue expression profiles and couple to distinct G-protein-mediated signalling pathways. S1P1, S1P2, and S1P3 receptors are all present in the heart, but the ... ...

    Abstract The five known members of the sphingosine-1-phosphate (S1P) receptor family exhibit diverse tissue expression profiles and couple to distinct G-protein-mediated signalling pathways. S1P1, S1P2, and S1P3 receptors are all present in the heart, but the ratio of these subtypes differs for various cardiac cells. The goal of this review is to summarize data concerning which S1P receptor subtypes regulate cardiac physiology and pathophysiology, which G-proteins and signalling pathways they couple to, and in which cell types they are expressed. The available information is based on studies using a lamentably limited set of pharmacological agonists/antagonists, but is complemented by work with S1P receptor subtype-specific knockout mice and sphingosine kinase knockout mice. In cardiac myocytes, the S1P1 receptor subtype is the predominant subtype expressed, and the activation of this receptor inhibits cAMP formation and antagonizes adrenergic receptor-mediated contractility. The S1P3 receptor, while expressed at lower levels, mediates the bradycardic effect of S1P agonists. Studies using knockout mice indicate that S1P2 and S1P3 receptors play a major role in mediating cardioprotection from ischaemia/reperfusion injury in vivo. S1P receptors are also involved in remodelling, proliferation, and differentiation of cardiac fibroblasts, a cell type in which the S1P3 receptor predominates. Receptors for S1P are also present in endothelial and smooth muscle cells where they mediate peripheral vascular tone and endothelial responses, but the role of this regulatory system in the cardiac vasculature is unknown. Further understanding of the contributions of each cell and receptor subtype to cardiac function and pathophysiology should expedite consideration of the endogenous S1P signalling pathway as a therapeutic target for cardiovascular disease.
    MeSH term(s) Animals ; Cardiovascular Diseases/physiopathology ; Disease Models, Animal ; GTP-Binding Proteins/physiology ; Heart/physiology ; Heart/physiopathology ; Humans ; Mice ; Muscle, Smooth, Vascular/physiology ; Muscle, Smooth, Vascular/physiopathology ; Receptors, Lysosphingolipid/physiology ; Signal Transduction/physiology
    Chemical Substances Receptors, Lysosphingolipid ; GTP-Binding Proteins (EC 3.6.1.-)
    Language English
    Publishing date 2009-03-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvp086
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  10. Article ; Online: Direct haplotype-resolved 5-base HiFi sequencing for genome-wide profiling of hypermethylation outliers in a rare disease cohort.

    Cheung, Warren A / Johnson, Adam F / Rowell, William J / Farrow, Emily / Hall, Richard / Cohen, Ana S A / Means, John C / Zion, Tricia N / Portik, Daniel M / Saunders, Christopher T / Koseva, Boryana / Bi, Chengpeng / Truong, Tina K / Schwendinger-Schreck, Carl / Yoo, Byunggil / Johnston, Jeffrey J / Gibson, Margaret / Evrony, Gilad / Rizzo, William B /
    Thiffault, Isabelle / Younger, Scott T / Curran, Tom / Wenger, Aaron M / Grundberg, Elin / Pastinen, Tomi

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 3090

    Abstract: Long-read HiFi genome sequencing allows for accurate detection and direct phasing of single nucleotide variants, indels, and structural variants. Recent algorithmic development enables simultaneous detection of CpG methylation for analysis of regulatory ... ...

    Abstract Long-read HiFi genome sequencing allows for accurate detection and direct phasing of single nucleotide variants, indels, and structural variants. Recent algorithmic development enables simultaneous detection of CpG methylation for analysis of regulatory element activity directly in HiFi reads. We present a comprehensive haplotype resolved 5-base HiFi genome sequencing dataset from a rare disease cohort of 276 samples in 152 families to identify rare (~0.5%) hypermethylation events. We find that 80% of these events are allele-specific and predicted to cause loss of regulatory element activity. We demonstrate heritability of extreme hypermethylation including rare cis variants associated with short (~200 bp) and large hypermethylation events (>1 kb), respectively. We identify repeat expansions in proximal promoters predicting allelic gene silencing via hypermethylation and demonstrate allelic transcriptional events downstream. On average 30-40 rare hypermethylation tiles overlap rare disease genes per patient, providing indications for variation prioritization including a previously undiagnosed pathogenic allele in DIP2B causing global developmental delay. We propose that use of HiFi genome sequencing in unsolved rare disease cases will allow detection of unconventional diseases alleles due to loss of regulatory element activity.
    MeSH term(s) Humans ; Haplotypes ; Rare Diseases/genetics ; DNA Methylation/genetics ; Sequence Analysis, DNA ; Base Sequence ; High-Throughput Nucleotide Sequencing ; Nerve Tissue Proteins/genetics
    Chemical Substances DIP2B protein, human ; Nerve Tissue Proteins
    Language English
    Publishing date 2023-05-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-38782-1
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